Li Y

General

Full name : Li Yulong

First name : Yulong

Mail : State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871

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Country : China

Email : yulong@gmail.com

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References (592)

Title : Acute effects of exercise intensity on butyrylcholinesterase and ghrelin in young men: A randomized controlled study - Li_2024_J.Exerc.Sci.Fit_22_39
Author(s) : Li Y , Tataka Y , Sakazaki M , Kamemoto K , Nagayama C , Yoshikawa Y , Yamada Y , Miyashita M
Ref : J Exerc Sci Fit , 22 :39 , 2024
Abstract : BACKGROUND/OBJECTIVES: Butyrylcholinesterase (BChE), a liver-derived enzyme that hydrolyzes acylated ghrelin to des-acylated ghrelin, may trigger a potential mechanism responsible for the acute exercise-induced suppression of acylated ghrelin. However, studies examining the effects of an acute bout of high-intensity exercise on BChE and acylated ghrelin have yielded inconsistent findings. This study aimed to examine the acute effects of exercise intensity on BChE, acylated ghrelin and des-acylated ghrelin concentrations in humans. METHODS: Fifteen young men (aged 22.7 +/- 1.8 years, mean +/- standard deviation) completed three, half-day laboratory-based trials (i.e., high-intensity exercise, low-intensity exercise and control), in a random order. In the exercise trials, the participants ran for 60 min (from 09:30 to 10:30) at a speed eliciting 70 % (high-intensity) or 40 % (low-intensity) of their maximum oxygen uptake and then rested for 90 min. In the control trial, participants sat on a chair for the entire trial (from 09:30 to 12:00). Venous blood samples were collected at 09:30, 10:00, 10:30, 11:00, 11:30 and 12:00. RESULTS: The BChE concentration was not altered over time among the three trials. Total acylated and des-acylated ghrelin area under the curve during the first 60 min (i.e., from 0 min to 60 min) of the main trial were lower in the high-intensity exercise trial than in the control (acylated ghrelin, mean difference: 62.6 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 31.4 pg/mL, p = 0.035) and the low-intensity exercise trial (acylated ghrelin, mean difference: 87.7 pg/mL, p < 0.001; des-acylated ghrelin, mean difference: 43.0 pg/mL, p = 0.042). CONCLUSION: The findings suggest that BChE may not be involved in the modulation of ghrelin even though lowered acylated ghrelin concentration was observed after high-intensity exercise.
ESTHER : Li_2024_J.Exerc.Sci.Fit_22_39
PubMedSearch : Li_2024_J.Exerc.Sci.Fit_22_39
PubMedID: 38033619

Title : Facile and selective recognition of sulfonylurea pesticides based on the multienzyme-like activities enhancement of nanozymes combining sensor array - Tian_2024_J.Hazard.Mater_469_133847
Author(s) : Tian T , Song D , Zhang L , Huang H , Li Y
Ref : J Hazard Mater , 469 :133847 , 2024
Abstract : Traditional identification methods based on cholinesterase inhibition are limited to recognizing organic phosphorus and carbamate esters, and their response to sulfonylurea pesticides is weak. Residual sulfonylurea pesticides can pose a threat to human health. So, it is very important to develop an effective, rapid and portable method for sulfonylurea pesticides detection. Herein, we first found that sulfonylurea pesticides have activity-enhancing effects on copper-based nanozymes, and then combined them with the array technology to construct a six-channel sensing array method for selectively identifying sulfonylurea pesticides and detecting total concentration of sulfonylurea pesticides (the limit of detection was 0.03 microg/mL). This method has good selectivity towards sulfonylurea pesticides. In addition, a smartphone-based colorimetric paper sensor analysis method was developed to achieve the on-site detection of the total concentration of sulfonylurea pesticides. And this array can also be used for individual differentiation (1-100 microg/mL). Our work not only investigates the specific responses of copper-based nanozymes to sulfonylurea pesticides, but also develops a simple method that contributes to directly detect sulfonylurea pesticides at the source of pollution, providing insights for further research on sulfonylurea pesticides detection and filling the gap in pesticide residue studies.
ESTHER : Tian_2024_J.Hazard.Mater_469_133847
PubMedSearch : Tian_2024_J.Hazard.Mater_469_133847
PubMedID: 38422731

Title : The m(6)A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN - Jiang_2024_Mol.Cancer_23_55
Author(s) : Jiang T , Qi J , Xue Z , Liu B , Liu J , Hu Q , Li Y , Ren J , Song H , Xu Y , Xu T , Fan R , Song J
Ref : Mol Cancer , 23 :55 , 2024
Abstract : BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m(6)A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.
ESTHER : Jiang_2024_Mol.Cancer_23_55
PubMedSearch : Jiang_2024_Mol.Cancer_23_55
PubMedID: 38491348

Title : DPP-4 inhibitors sitagliptin and PF-00734,200 mitigate dopaminergic neurodegeneration, neuroinflammation and behavioral impairment in the rat 6-OHDA model of Parkinson's disease - Yu_2024_Geroscience__
Author(s) : Yu SJ , Wang Y , Shen H , Bae EK , Li Y , Sambamurti K , Tones MA , Zaleska MM , Hoffer BJ , Greig NH
Ref : Geroscience , : , 2024
Abstract : Epidemiological studies report an elevated risk of Parkinson's disease (PD) in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed dipeptidyl peptidase 4 (DPP-4) inhibitors. With an objective to characterize clinically translatable doses of DPP-4 inhibitors (gliptins) in a well-characterized PD rodent model, sitagliptin, PF-00734,200 or vehicle were orally administered to rats initiated either 7-days before or 7-days after unilateral medial forebrain bundle 6-hydroxydopamine (6-OHDA) lesioning. Measures of dopaminergic cell viability, dopamine content, neuroinflammation and neurogenesis were evaluated thereafter in ipsi- and contralateral brain. Plasma and brain incretin and DPP-4 activity levels were quantified. Furthermore, brain incretin receptor levels were age-dependently evaluated in rodents, in 6-OHDA challenged animals and human subjects with/without PD. Cellular studies evaluated neurotrophic/neuroprotective actions of combined incretin administration. Pre-treatment with oral sitagliptin or PF-00734,200 reduced methamphetamine (meth)-induced rotation post-lesioning and dopaminergic degeneration in lesioned substantia nigra pars compacta (SNc) and striatum. Direct intracerebroventricular gliptin administration lacked neuroprotective actions, indicating that systemic incretin-mediated mechanisms underpin gliptin-induced favorable brain effects. Post-treatment with a threefold higher oral gliptin dose, likewise, mitigated meth-induced rotation, dopaminergic neurodegeneration and neuroinflammation, and augmented neurogenesis. These gliptin-induced actions associated with 70-80% plasma and 20-30% brain DPP-4 inhibition, and elevated plasma and brain incretin levels. Brain incretin receptor protein levels were age-dependently maintained in rodents, preserved in rats challenged with 6-OHDA, and in humans with PD. Combined GLP-1 and GIP receptor activation in neuronal cultures resulted in neurotrophic/neuroprotective actions superior to single agonists alone. In conclusion, these studies support further evaluation of the repurposing of clinically approved gliptins as a treatment strategy for PD.
ESTHER : Yu_2024_Geroscience__
PubMedSearch : Yu_2024_Geroscience__
PubMedID: 38563864

Title : ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2\/STAT3 pathway and interacting with ESM1 - Li_2024_J.Transl.Med_22_46
Author(s) : Li YK , Gao AB , Zeng T , Liu D , Zhang QF , Ran XM , Tang ZZ , Li Y , Liu J , Zhang T , Shi GQ , Zhou WC , Zou WD , Peng J , Zhang J , Li H , Zou J
Ref : J Transl Med , 22 :46 , 2024
Abstract : BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
ESTHER : Li_2024_J.Transl.Med_22_46
PubMedSearch : Li_2024_J.Transl.Med_22_46
PubMedID: 38212795

Title : Biodegradation of Typical Plastics: From Microbial Diversity to Metabolic Mechanisms - Lv_2024_Int.J.Mol.Sci_25_
Author(s) : Lv S , Li Y , Zhao S , Shao Z
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Plastic production has increased dramatically, leading to accumulated plastic waste in the ocean. Marine plastics can be broken down into microplastics (<5 mm) by sunlight, machinery, and pressure. The accumulation of microplastics in organisms and the release of plastic additives can adversely affect the health of marine organisms. Biodegradation is one way to address plastic pollution in an environmentally friendly manner. Marine microorganisms can be more adapted to fluctuating environmental conditions such as salinity, temperature, pH, and pressure compared with terrestrial microorganisms, providing new opportunities to address plastic pollution. Pseudomonadota (Proteobacteria), Bacteroidota (Bacteroidetes), Bacillota (Firmicutes), and Cyanobacteria were frequently found on plastic biofilms and may degrade plastics. Currently, diverse plastic-degrading bacteria are being isolated from marine environments such as offshore and deep oceanic waters, especially Pseudomonas spp. Bacillus spp. Alcanivoras spp. and Actinomycetes. Some marine fungi and algae have also been revealed as plastic degraders. In this review, we focused on the advances in plastic biodegradation by marine microorganisms and their enzymes (esterase, cutinase, laccase, etc.) involved in the process of biodegradation of polyethylene terephthalate (PET), polystyrene (PS), polyethylene (PE), polyvinyl chloride (PVC), and polypropylene (PP) and highlighted the need to study plastic biodegradation in the deep sea.
ESTHER : Lv_2024_Int.J.Mol.Sci_25_
PubMedSearch : Lv_2024_Int.J.Mol.Sci_25_
PubMedID: 38203764

Title : Engineered polymer nanoparticles as artificial chaperones facilitating the selective refolding of denatured enzymes - Li_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2403049121
Author(s) : Li Y , Yin D , Lee SY , Lv Y
Ref : Proc Natl Acad Sci U S A , 121 :e2403049121 , 2024
Abstract : Molecular chaperones assist in protein refolding by selectively binding to proteins in their nonnative states. Despite progress in creating artificial chaperones, these designs often have a limited range of substrates they can work with. In this paper, we present molecularly imprinted flexible polymer nanoparticles (nanoMIPs) designed as customizable biomimetic chaperones. We used model proteins such as cytochrome c, laccase, and lipase to screen polymeric monomers and identify the most effective formulations, offering tunable charge and hydrophobic properties. Utilizing a dispersed phase imprinting approach, we employed magnetic beads modified with destabilized whole-protein as solid-phase templates. This process involves medium exchange facilitated by magnetic pulldowns, resulting in the synthesis of nanoMIPs featuring imprinted sites that effectively mimic chaperone cavities. These nanoMIPs were able to selectively refold denatured enzymes, achieving up to 86.7% recovery of their activity, significantly outperforming control samples. Mechanistic studies confirmed that nanoMIPs preferentially bind denatured rather than native enzymes, mimicking natural chaperone interactions. Multifaceted analyses support the functionality of nanoMIPs, which emulate the protective roles of chaperones by selectively engaging with denatured proteins to inhibit aggregation and facilitate refolding. This approach shows promise for widespread use in protein recovery within biocatalysis and biomedicine.
ESTHER : Li_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2403049121
PubMedSearch : Li_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2403049121
PubMedID: 38691587

Title : PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer - Chen_2024_J.Transl.Med_22_249
Author(s) : Chen M , Zhang C , Li H , Zheng S , Li Y , Yuan M , Chen Y , Wu J , Sun Q
Ref : J Transl Med , 22 :249 , 2024
Abstract : BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.
ESTHER : Chen_2024_J.Transl.Med_22_249
PubMedSearch : Chen_2024_J.Transl.Med_22_249
PubMedID: 38454407

Title : Corrigendum to Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease [Eur. J. Med. Chem. 265 (2024) 116071] -
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , :116169 , 2024
PubMedID: 38290915

Title : Enzymatic Preparation, In-Depth Molecular Analysis, and In Vitro Digestion Simulation of Palmitoleic Acid (-7)-Enriched Fish Oil Triacylglycerols - Ge_2024_J.Agric.Food.Chem__
Author(s) : Ge L , Cheng K , Lu W , Cui Y , Yin X , Jiang J , Li Y , Yao H , Liao J , Xue J , Shen Q
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s(-1), respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.
ESTHER : Ge_2024_J.Agric.Food.Chem__
PubMedSearch : Ge_2024_J.Agric.Food.Chem__
PubMedID: 38564481

Title : The effects of Massa Medicata Fermentata on the digestive function and intestinal flora of mice with functional dyspepsia - Wang_2024_Front.Pharmacol_15_1359954
Author(s) : Wang S , Li Y , Yang X , Hao Y , Zhan X
Ref : Front Pharmacol , 15 :1359954 , 2024
Abstract : Introduction: The purpose of this study was to identify the chemical components of Massa Medicata Fermentata (MMF) in different fermentation methods, analyze its regulatory effects on gastrointestinal propulsion and intestinal flora in mice with food accumulation, and further explore its mechanism of action in the treatment of dyspepsia. Methods: The chemical compositions of three kinds of MMF were identified using the UPLC-Q- Exactive Orbitrap mass spectrometer. A model of spleen deficiency and food accumulation in mice was established. The gastric emptying rate and intestinal propulsion rate were calculated, serum gastrin concentration and cholinesterase activity were measured, and 16S rRNA microbial detection was performed in different groups of mouse feces. Results: The results showed that a total of 95 chemical components were identified from the three MMF extracts, 62 of which were the same, but there were differences in flavonoids and their glycosides, organic acids, and esters. MMF, PFMMF, and commercial MMF could all significantly improve the gastric emptying rate, intestinal propulsion rate, and GAS concentration in the serum of model mice; PFMMF has a better effect, while there was no significant difference in cholinesterase activity among the groups (p > 0.05). The 16S rRNA sequencing results showed that the MMF and PFMMF could increase the content of beneficial bacteria Bacteroidetes and decrease the pathogenic bacteria Verrucomicrobia in the intestines of model mice, while the commercial MMF could not. Discussion: Studies suggest that MMF has a variety of possible mechanisms for improving food accumulation and treating gastrointestinal dyspepsia, which provides reference value for the quality evaluation and clinical application of MMF.
ESTHER : Wang_2024_Front.Pharmacol_15_1359954
PubMedSearch : Wang_2024_Front.Pharmacol_15_1359954
PubMedID: 38495103

Title : Rapid screening of acetylcholinesterase active contaminants in water: A solid phase microextraction-based ligand fishing approach - Huang_2024_Chemosphere_356_141976
Author(s) : Huang Z , He L , Li H , Zhao J , Chen T , Feng Z , Li Y , You J
Ref : Chemosphere , 356 :141976 , 2024
Abstract : Effect-directed analysis (EDA) has been increasingly used for screening toxic contaminants in the environment, but conventional EDA procedures are often time-consuming and labor-extensive. This challenges the use of EDA for toxicant identification in the scenarios when quick answers are demanded. Herein, a solid phase microextraction ligand fishing (SPME-LF) strategy has been proposed as a rapid EDA approach for identifying acetylcholinesterase (AChE) active compounds in water. The feasibility of ligand fishing techniques for screening AChE active chemicals from environmental mixtures was first verified by a membrane separation method. Then, SPME fibers were prepared through self-assembly of boronic acid groups with AChE via co-bonding and applied for SPME-LF. As AChE coated SPME fibers selectively enriched AChE-active compounds from water, comparing sorbing compounds by the SPME fibers with and without AChE coating can quickly distinguish AChE toxicants in mixtures. Compared with conventional EDA, SPME-LF does not require repeating sample separations and bioassays, endowing SPME-LF with the merits of low-cost, labor-saving, and user-friendly. It is believed that cost-efficient and easy-to-use SPME-LF strategy can potentially be a rapid EDA method for screening receptor-specific toxicants in aquatic environment, especially applicable in time-sensitive screening.
ESTHER : Huang_2024_Chemosphere_356_141976
PubMedSearch : Huang_2024_Chemosphere_356_141976
PubMedID: 38608773

Title : DPP8\/9 inhibition attenuates the TGF-beta1-induced excessive deposition of extracellular matrix (ECM) in human mesangial cells via Smad and Akt signaling pathway - Li_2024_Toxicol.Lett__
Author(s) : Li K , Zhang Y , Zhao W , Wang R , Li Y , Wei L , Wang L , Chen X , Chen Z , Liu P , Nie N , Tian X , Fu R
Ref : Toxicol Lett , : , 2024
Abstract : The pathogenesis of glomerular diseases is strongly influenced by abnormal extracellular matrix (ECM) deposition in mesangial cells. Dipeptidyl peptidase IV (DPPIV) enzyme family contains DPP8 and DPP9 involved in multiple diseases. However, the pathogenic roles of DPP8 and DPP9 in mesangial cells ECM deposition remain unclear. In this study, we observed that DPP8 and DPP9 were significantly increased in glomerular mesangial cells and podocytes in CKD patients compared with healthy individuals, and DPP9 levels were higher in the urine of IgAN patients than in control urine. Therefore, we further explored the mechanism of DPP8 and DPP9 in mesangial cells and revealed a significant increase in the expression of DPP8 and DPP9 in human mesangial cells (HMCs) following TGF-beta1 stimulation. Silencing DPP8 and DPP9 by siRNAs alleviated the expression of ECM-related proteins including collagen , collagen , fibronectin, MMP2, in TGF-beta1-treated HMCs. Furthermore, DPP8 siRNA and DPP9 siRNA inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3, as well as the phosphorylation of Akt in HMCs. The findings suggested the inhibition of DPP8/9 may alleviate HMCs ECM deposition induced by TGF-beta1 via suppressing TGF-beta1/Smad and AKT signaling pathway.
ESTHER : Li_2024_Toxicol.Lett__
PubMedSearch : Li_2024_Toxicol.Lett__
PubMedID: 38458339

Title : Discovery, Structure-Based Modification, In Vitro, In Vivo, and In Silico Exploration of m-Sulfamoyl Benzoamide Derivatives as Selective Butyrylcholinesterase Inhibitors for Treating Alzheimer's Disease - Lu_2024_ACS.Chem.Neurosci__
Author(s) : Lu X , Li Y , Guan Q , Yang H , Liu Y , Du C , Wang L , Wang Q , Pei Y , Wu L , Sun H , Chen Y
Ref : ACS Chem Neurosci , : , 2024
Abstract : For the potential therapy of Alzheimer's disease (AD), butyrylcholinesterase (BChE) has gradually gained worldwide interest in the progression of AD. This study used a pharmacophore-based virtual screening (VS) approach to identify Z32439948 as a new BChE inhibitor. Aiding by molecular docking and molecular dynamics, essential binding information was disclosed. Specifically, a subpocket was found and structure-guided design of a series of novel compounds was conducted. Derivatives were evaluated in vitro for cholinesterase inhibition and physicochemical properties (BBB, log P, and solubility). The investigation involved docking, molecular dynamics, enzyme kinetics, and surface plasmon resonance as well. The study highlighted compounds 27a (hBChE IC(50) = 0.078 +/- 0.03 microM) and (R)-37a (hBChE IC(50) = 0.005 +/- 0.001 microM) as the top-ranked BChE inhibitors. These compounds showed anti-inflammatory activity and no apparent cytotoxicity against the human neuroblastoma (SH-SY5Y) and mouse microglia (BV2) cell lines. The most active compounds exhibited the ability to improve cognition in both scopolamine- and Abeta(1-42) peptide-induced cognitive deficit models. They can be promising lead compounds with potential implications for treating the late stage of AD.
ESTHER : Lu_2024_ACS.Chem.Neurosci__
PubMedSearch : Lu_2024_ACS.Chem.Neurosci__
PubMedID: 38453668

Title : Novel polyurethane-degrading cutinase BaCut1 from Blastobotrys sp. G-9 with potential role in plastic bio-recycling - Jiang_2024_J.Hazard.Mater_472_134493
Author(s) : Jiang Z , Chen X , Xue H , Li Z , Lei J , Yu M , Yan X , Cao H , Zhou J , Liu J , Zheng M , Dong W , Li Y , Cui Z
Ref : J Hazard Mater , 472 :134493 , 2024
Abstract : Environmental pollution caused by plastic waste has become global problem that needs to be considered urgently. In the pursuit of a circular plastic economy, biodegradation provides an attractive strategy for managing plastic wastes, whereas effective plastic-degrading microbes and enzymes are required. In this study, we report that Blastobotrys sp. G-9 isolated from discarded plastic in landfills is capable of depolymerizing polyurethanes (PU) and poly (butylene adipate-co-terephthalate) (PBAT). Strain G-9 degrades up to 60% of PU foam after 21 days of incubation at 28 degC by breaking down carbonyl groups via secretory hydrolase as confirmed by structural characterization of plastics and degradation products identification. Within the supernatant of strain G-9, we identify a novel cutinase BaCut1, belonging to the esterase family, that can reproduce the same effect. BaCut1 demonstrates efficient degradation toward commercial polyester plastics PU foam (0.5 mg enzyme/25 mg plastic) and agricultural film PBAT (0.5 mg enzyme/10 mg plastic) with 50% and 18% weight loss at 37 degC for 48 h, respectively. BaCut1 hydrolyzes PU into adipic acid as a major end-product with 42.9% recovery via ester bond cleavage, and visible biodegradation is also identified from PBAT, which is a beneficial feature for future recycling economy. Molecular docking, along with products distribution, elucidates a special substrate-binding modes of BaCut1 with plastic substrate analogue. BaCut1-mediated polyester plastic degradation offers an alternative approach for managing PU plastic wastes through possible bio-recycling.
ESTHER : Jiang_2024_J.Hazard.Mater_472_134493
PubMedSearch : Jiang_2024_J.Hazard.Mater_472_134493
PubMedID: 38696960
Gene_locus related to this paper: 9asco-BaCut1

Title : Sitagliptin elevates plasma and CSF incretin levels following oral administration to nonhuman primates: relevance for neurodegenerative disorders - Li_2024_Geroscience__
Author(s) : Li Y , Vaughan KL , Wang Y , Yu SJ , Bae EK , Tamargo IA , Kopp KO , Tweedie D , Chiang CC , Schmidt KT , Lahiri DK , Tones MA , Zaleska MM , Hoffer BJ , Mattison JA , Greig NH
Ref : Geroscience , : , 2024
Abstract : The endogenous incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) possess neurotrophic, neuroprotective, and anti-neuroinflammatory actions. The dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin reduces degradation of endogenous GLP-1 and GIP, and, thereby, extends the circulation of these protective peptides. The current nonhuman primate (NHP) study evaluates whether human translational sitagliptin doses can elevate systemic and central nervous system (CNS) levels of GLP-1/GIP in naive, non-lesioned NHPs, in line with our prior rodent studies that demonstrated sitagliptin efficacy in preclinical models of Parkinson's disease (PD). PD is an age-associated neurodegenerative disorder whose current treatment is inadequate. Repositioning of the well-tolerated and efficacious diabetes drug sitagliptin provides a rapid approach to add to the therapeutic armamentarium for PD. The pharmacokinetics and pharmacodynamics of 3 oral sitagliptin doses (5, 20, and 100 mg/kg), equivalent to the routine clinical dose, a tolerated higher clinical dose and a maximal dose in monkey, were evaluated. Peak plasma sitagliptin levels were aligned both with prior reports in humans administered equivalent doses and with those in rodents demonstrating reduction of PD associated neurodegeneration. Although CNS uptake of sitagliptin was low (cerebrospinal fluid (CSF)/plasma ratio 0.01), both plasma and CSF concentrations of GLP-1/GIP were elevated in line with efficacy in prior rodent PD studies. Additional cellular studies evaluating human SH-SY5Y and primary rat ventral mesencephalic cultures challenged with 6-hydroxydopamine, established cellular models of PD, demonstrated that joint treatment with GLP-1 + GIP mitigated cell death, particularly when combined with DPP-4 inhibition to maintain incretin levels. In conclusion, this study provides a supportive translational step towards the clinical evaluation of sitagliptin in PD and other neurodegenerative disorders for which aging, similarly, is the greatest risk factor.
ESTHER : Li_2024_Geroscience__
PubMedSearch : Li_2024_Geroscience__
PubMedID: 38532069

Title : Sequence-based design and construction of synthetic nanobody library - Liu_2024_Biotechnol.Bioeng__
Author(s) : Liu C , Li Y , He Q , Fu J , Wei Q , Lin H , Luo Y , Tu Z
Ref : Biotechnol Bioeng , : , 2024
Abstract : Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time-consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S-Library), designed based on the systematic analysis of the next-generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01-IGHJ4*01) and complementary determining regions of constrained diversity. The S-Library containing 2.19 x 10(8) independent clones was constructed by the one-step assembly and rapid electro-transformation. The S-Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naive library (N-Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S-Library. Binders were isolated from both S-Library and N-Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S-Library to be built on conventional reagents and primers.
ESTHER : Liu_2024_Biotechnol.Bioeng__
PubMedSearch : Liu_2024_Biotechnol.Bioeng__
PubMedID: 38548653

Title : Enhanced Biodegradation Rate of Poly(butylene adipate-co-terephthalate) Composites Using Reed Fiber - Xu_2024_Polymers.(Basel)_16_
Author(s) : Xu J , Feng K , Li Y , Xie J , Wang Y , Zhang Z , Hu Q
Ref : Polymers (Basel) , 16 : , 2024
Abstract : To enhance the degradability of poly(butylene adipate-co-terephthalate) (PBAT), reed fiber (RF) was blended with PBAT to create composite materials. In this study, a fifteen day degradation experiment was conducted using four different enzyme solutions containing lipase, cellulase, Proteinase K, and esterase, respectively. The degradation process of the sample films was analyzed using an analytical balance, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). The PBAT/RF composites exhibited an increased surface hydrophilicity, which enhanced their degradation capacity. Among all the enzymes tested, lipase had the most significant impact on the degradation rate. The weight loss of PBAT and PBAT/RF, caused by lipase, was approximately 5.63% and 8.17%, respectively. DSC analysis revealed an increase in the melting temperature and crystallinity over time, especially in the film containing reed fibers. FTIR results indicated a significant weakening of the ester bond peak in the samples. Moreover, this article describes a biodegradation study conducted for three months under controlled composting conditions of PBAT and PBAT/RF samples. The results showed that PBAT/RF degraded more easily in compost as compared to PBAT. The lag phase of PBAT/RF was observed to decrease by 23.8%, while the biodegradation rate exhibited an increase of 11.8% over a period of 91 days. SEM analysis demonstrated the formation of more cracks and pores on the surface of PBAT/RF composites during the degradation process. This leads to an increased contact area between the composites and microorganisms, thereby accelerating the degradation of PBAT/RF. This research is significant for preparing highly degradable PBAT composites and improving the application prospects of biodegradable green materials. PBAT/RF composites are devoted to replacing petroleum-based polymer materials with sustainable, natural materials in advanced applications such as constructional design, biomedical application, and eco-environmental packaging.
ESTHER : Xu_2024_Polymers.(Basel)_16_
PubMedSearch : Xu_2024_Polymers.(Basel)_16_
PubMedID: 38337300

Title : Safety and efficacy of acetylcholinesterase inhibitors for Alzheimer's disease: A systematic review and meta-analysis - Gao_2024_Adv.Clin.Exp.Med__
Author(s) : Gao Y , Liu Y , Li Y
Ref : Adv Clin Exp Med , : , 2024
Abstract : Alzheimer's disease (AD) affects millions of people worldwide. The most commonly used drugs are acetylcholinesterase inhibitors, i.e., donepezil, galantamine and rivastigmine, which increase levels of acetylcholine. However, the exact efficacy and safety of acetylcholinesterase inhibitors in the treatment of AD is still unclear. The main objective of the current study was to determine the exact safety and efficacy profile of acetylcholinesterase inhibitors in the treatment of AD by conducting a systematic review and meta-analysis of clinical trials according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a web-based literature search of PubMed and clinical trial websites using relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (95% CI) using Review Manager software (v. 5.3 for Windows). Heterogeneity was calculated using 2 and I2 tests. The standard mean difference (SMD) was -0.33 [-0.52, -0.13] for donepezil, -0.48 [-0.58, -0.38] for galantamine and -0.65 [-1.06, -0.23] for rivastigmine, indicating a significant effect of these drugs on cognitive outcomes. Here we show the significant effects of all available acetylcholinesterase inhibitors on cognitive function in patients with AD. However, further studies are needed to draw valid conclusions about the effects of acetylcholinesterase inhibitors on functional outcomes and adverse events.
ESTHER : Gao_2024_Adv.Clin.Exp.Med__
PubMedSearch : Gao_2024_Adv.Clin.Exp.Med__
PubMedID: 38439609

Title : P2X(7) receptor-dependent increase in endocannabinoid 2-arachidonoyl glycerol production by neuronal cells in culture: Dynamics and mechanism - Singh_2024_Br.J.Pharmacol__
Author(s) : Singh S , Sarroza D , English A , Whittington D , Dong A , Malamas M , Makriyannis A , van der Stelt M , Li Y , Zweifel L , Bruchas MR , Land BB , Stella N
Ref : British Journal of Pharmacology , : , 2024
Abstract : BACKGROUND AND PURPOSE: Neurotransmission and neuroinflammation are controlled by local increases in both extracellular ATP and the endocannabinoid 2-arachidonoyl glycerol (2-AG). While it is known that extracellular ATP stimulates 2-AG production in cells in culture, the dynamics and molecular mechanisms that underlie this response remain poorly understood. Detection of real-time changes in eCB levels with the genetically encoded sensor, GRAB(eCB2.0), can address this shortfall. EXPERIMENTAL APPROACH: 2-AG and arachidonoylethanolamide (AEA) levels in Neuro2a (N2a) cells were measured by LC-MS, and GRAB(eCB2.0) fluorescence changes were detected using live-cell confocal microscopy and a 96-well fluorescence plate reader. KEY RESULTS: 2-AG and AEA increased GRAB(eCB2.0) fluorescence in N2a cells with EC(50) values of 81 and 58 nM, respectively; both responses were reduced by the cannabinoid receptor type 1 (CB(1)R) antagonist SR141617 and absent in cells expressing the mutant-GRAB(eCB2.0). ATP increased only 2-AG levels in N2a cells, as measured by LC-MS, and induced a transient increase in the GRAB(eCB2.0) signal within minutes primarily via activation of P2X(7) receptors (P2X(7)R). This response was dependent on diacylglycerol lipase beta activity, partially dependent on extracellular calcium and phospholipase C activity, but not controlled by the 2-AG hydrolysing enzyme, alpha/beta-hydrolase domain containing 6 (ABHD6). CONCLUSIONS AND IMPLICATIONS: Considering that P2X(7)R activation increases 2-AG levels within minutes, our results show how these molecular components are mechanistically linked. The specific molecular components in these signalling systems represent potential therapeutic targets for the treatment of neurological diseases, such as chronic pain, that involve dysregulated neurotransmission and neuroinflammation.
ESTHER : Singh_2024_Br.J.Pharmacol__
PubMedSearch : Singh_2024_Br.J.Pharmacol__
PubMedID: 38581262

Title : Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population - Li_2024_Arch.Endocrinol.Metab_68_e230195
Author(s) : Li Y , Cai H , Lin Y , Huang Z , Zhou A , Huang T , Zeng YE , Ye M , Guo G
Ref : Arch Endocrinol Metab , 68 :e230195 , 2024
Abstract : OBJECTIVE: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. SUBJECTS AND METHODS: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. RESULTS: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). CONCLUSION: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.
ESTHER : Li_2024_Arch.Endocrinol.Metab_68_e230195
PubMedSearch : Li_2024_Arch.Endocrinol.Metab_68_e230195
PubMedID: 38530959
Gene_locus related to this paper: human-LPL

Title : Optimization of Extraction Process and Analysis of Biological Activity of Flavonoids from Leaves of Cultivated 'Qi-Nan' Agarwood - Li_2024_Molecules_29_
Author(s) : Li Q , Wei P , Li Y , Fu Y
Ref : Molecules , 29 : , 2024
Abstract : Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids. Subsequently, the composition of the flavonoids, as well as their bioactive abilities, were analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and in vitro activity testing methods. The findings demonstrated that a 1:50 material-to-liquid ratio, 60% ethanol concentration, and ultrasound-assisted extraction time of 30 min were the ideal procedures for extracting flavonoids (flavonoid content: 6.68%). Meanwhile, the 'Qi-Nan' leaves possessed the antioxidant and medicinal potential to prevent diabetes and Alzheimer 's disease, as evidenced by the semi-inhibitory concentrations (IC50 values) of flavonoid extracts for scavenging DPPH() free radicals, scavenging ABTS(+) free radicals, inhibiting acetylcholinesterase, and inhibiting alpha-glucosidase, which were 12.64 microg/mL, 66.58 microg/mL, 102.31 microg/mL, and 38.76 microg/mL, respectively, which indicated that the 'Qi-Nan' leaves possessed the properties of antioxidant and medicinal potential for the prevention of Alzheimer 's disease and diabetes.
ESTHER : Li_2024_Molecules_29_
PubMedSearch : Li_2024_Molecules_29_
PubMedID: 38675648

Title : Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors - Wang_2024_J.Org.Chem__
Author(s) : Wang K , Wang R , Yan Z , Li Y , Shi Y , Ge JY , Bai Y , Chen Z , Zhang L
Ref : J Org Chem , : , 2024
Abstract : Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.
ESTHER : Wang_2024_J.Org.Chem__
PubMedSearch : Wang_2024_J.Org.Chem__
PubMedID: 38720168

Title : Neuroprotection of macamide in a mouse model of Alzheimer's disease involves Nrf2 signaling pathway and gut microbiota - Xia_2024_Eur.J.Pharmacol_975_176638
Author(s) : Xia N , Xu L , Huang M , Xu D , Li Y , Wu H , Mei Z , Yu Z
Ref : European Journal of Pharmacology , 975 :176638 , 2024
Abstract : The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1beta, IL-6, and TNF-alpha in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
ESTHER : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedSearch : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedID: 38734297

Title : A Novel Bacillus Velezensis for Efficient Degradation of Zearalenone - Li_2024_Foods_13_
Author(s) : Li Y , Chen S , Yu Z , Yao J , Jia Y , Liao C , Chen J , Wei Y , Guo R , He L , Ding K
Ref : Foods , 13 : , 2024
Abstract : Zearalenone (ZEN) is considered one of the most serious mycotoxins contaminating grains and their by-products, causing significant economic losses in the feed and food industries. Biodegradation pathways are currently considered the most efficient solution to remove ZEN contamination from foods. However, low degradation rates and vulnerability to environmental impacts limit the application of biodegradation pathways. Therefore, the main research objective of this article was to screen strains that can efficiently degrade ZEN and survive under harsh conditions. This study successfully isolated a new strain L9 which can efficiently degrade ZEN from 108 food ingredients. The results of sequence alignment showed that L9 is Bacillus velezensis. Meanwhile, we found that the L9 degradation rate reached 91.14% at 24 h and confirmed that the primary degradation mechanism of this strain is biodegradation. The strain exhibits resistance to high temperature, acid, and 0.3% bile salts. The results of whole-genome sequencing analysis showed that, it is possible that the strain encodes the key enzyme, such as chitinase, carboxylesterases, and lactone hydrolase, that work together to degrade ZEN. In addition, 227 unique genes in this strain are primarily involved in its replication, recombination, repair, and protective mechanisms. In summary, we successfully excavated a ZEN-degrading, genetically distinct strain of Bacillus velezensis that provides a solid foundation for the detoxification of feed and food contamination in the natural environment.
ESTHER : Li_2024_Foods_13_
PubMedSearch : Li_2024_Foods_13_
PubMedID: 38397507

Title : Decreasing acid value of fatty acid ethyl ester products using complex enzymes - Li_2024_Front.Bioeng.Biotechnol_12_1355009
Author(s) : Li Y , Guo J , Sun S
Ref : Front Bioeng Biotechnol , 12 :1355009 , 2024
Abstract : Recently, enzymatic method has been used to prepare biodiesel using various oils. But the high acid value of the biodiesel product using enzyme as a catalyst has been one issue. In this work, an attempt to reduce the acid value of fatty acid ethyl ester (FAEE) product to satisfy the specified requirement (AV >= 0.5 mgKOH/g), a complex enzyme-catalyzed method was used for the ethanolysis of Semen Abutili seed oil (SASO) (AV = 5.5 +/- 0.3 mgKOH/g). The effects of various variables (constituents of complex enzyme, type and addition of water removal agent, time, temperature, enzyme addition load, substrate ratio) on the enzymatic reaction were investigated. The optimal reaction conditions were: 1% addition of liquid lipase Eversa((a)) Transform 2.0% and 0.8% of enzyme dry powder CALB, reaction temperature 35 degreesC, alcohol-oil ratio 9:1 (mol/mol), 0.8 g/g of 4A-MS and reaction time 24 h. Under the optimal reaction conditions, the FAEE yield was 90.8% +/- 1.5% and its acid value was decreased from 12.0 +/- 0.2 mgKOH/g to 0.39 +/- 0.10 mgKOH/g. In further evaluating the feasibility of preparing FAEE from SASO, the FAEE products obtained under the optimal reaction conditions were purified and evaluated with reference to the ASTM D6751 standard for the main physicochemical indexes. The results obtained were in accordance with the requirements except for the oxidative stability.
ESTHER : Li_2024_Front.Bioeng.Biotechnol_12_1355009
PubMedSearch : Li_2024_Front.Bioeng.Biotechnol_12_1355009
PubMedID: 38390361

Title : Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis - Guo_2023_Mil.Med.Res_10_24
Author(s) : Guo LK , Su Y , Zhang YY , Yu H , Lu Z , Li WQ , Yang YF , Xiao X , Yan H , Lu TL , Li J , Liao YD , Kang ZW , Wang LF , Li Y , Li M , Liu B , Huang HL , Lv LX , Yao Y , Tan YL , Breen G , Everall I , Wang HX , Huang Z , Zhang D , Yue WH
Ref : Mil Med Res , 10 :24 , 2023
Abstract : BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R(2) for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R(2) = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R(2) = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).
ESTHER : Guo_2023_Mil.Med.Res_10_24
PubMedSearch : Guo_2023_Mil.Med.Res_10_24
PubMedID: 37269009

Title : Rhynchophylline relieves nonalcoholic fatty liver disease by activating lipase and increasing energy metabolism - Liu_2023_Int.Immunopharmacol_117_109948
Author(s) : Liu K , Liu S , Wu C , Wang Y , Zhang Y , Yu J , Li X , Qi X , Su S , Zhou L , Li Y
Ref : Int Immunopharmacol , 117 :109948 , 2023
Abstract : Hepatic fat metabolism may be altered in the context of overnutrition and obesity, often resulting in the accumulation of triglycerides in hepatocytes and leading to nonalcoholic fatty liver disease (NAFLD). Natural plant alkaloids have demonstrated great potential for the prevention and treatment of NAFLD. However, the role of rhynchophylline (RHY) in lipid metabolism is not clear. We explored the role of RHY in lipid metabolism in cells treated with oleic and palmitic acids to mimic high-fat diet (HFD) conditions. RHY attenuated oleic and palmitic acid-induced increases in triglyceride accumulation in HepG2, AML12, and LMH cells. RHY also increased energy metabolism and reduced oxidative stress. We further investigated the effect of RHY on hepatic lipid metabolism in mice fed an HFD including 40 mg/kg RHY. RHY alleviated hepatic steatosis, reduced fat deposition, promoted energy metabolism, and improved glucose metabolism. We investigated the mechanism responsible for this activity by docking with key proteins of lipid metabolism disorders using Discovery Studio software, which showed that RHY interacted well with lipases. Finally, we found that adding RHY promoted lipase activity and lipolysis. In conclusion, RHY ameliorated HFD-induced NAFLD and its complications by increasing lipase activity.
ESTHER : Liu_2023_Int.Immunopharmacol_117_109948
PubMedSearch : Liu_2023_Int.Immunopharmacol_117_109948
PubMedID: 37012893

Title : Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease - Liu_2023_Eur.J.Med.Chem_265_116071
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , 265 :116071 , 2023
Abstract : In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC(50) = 30.35 +/- 2.07 nM) and human butyrylcholinesterase (hBuChE, IC(50) = 48.03 +/- 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H(2)O(2)-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Abeta(1-42) and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.
ESTHER : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedSearch : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedID: 38157596

Title : Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice - Zhang_2023_J.Ethnopharmacol__117416
Author(s) : Zhang Q , Li Y , Fan B , Wang F , Li Z , Carlos Pires Dias A , Liu X , Wang Q
Ref : J Ethnopharmacol , :117416 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.
ESTHER : Zhang_2023_J.Ethnopharmacol__117416
PubMedSearch : Zhang_2023_J.Ethnopharmacol__117416
PubMedID: 37981114

Title : Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids - Zhou_2023_J.Agric.Food.Chem_71_18359
Author(s) : Zhou H , Jian Y , Shao Q , Guo F , Zhang M , Wan F , Yang L , Liu Y , Li Y , Yang P , Li Z , Li S , Ding W
Ref : Journal of Agricultural and Food Chemistry , 71 :18359 , 2023
Abstract : Plants employ abundant toxic secondary metabolites to withstand insect attack, while pollinators can tolerate some natural defensive compounds. Coumarins, as promising green alternatives to chemical insecticides, possess wide application prospects in the crop protection field. Herein, the bioactivities of 30 natural coumarin derivatives against Aphis gossypii were assessed and revealed that 6-methylcoumarin exhibited potent aphicidal activity against aphids but displayed no toxicity to honeybees. Additionally, using biochemical, bioinformatic, and molecular assays, we confirmed that the action mode of 6-methylcoumarin against aphids was by inhibiting acetylcholinesterase (AChE). Meanwhile, functional assays revealed that the difference in action site, which located in Lys585 in aphid AChE (equivalent to Val548 in honeybee AChE), was the principal reason for 6-methylcoumarin being toxic to aphids but safe to pollinators. This action site was further validated by mutagenesis data, which uncovered how 6-methylcoumarin was unique selective to the aphid over honeybee or mammalian AChE. Furthermore, a 2D-QSAR model was established, revealing that the central structural feature was H3m, which offers guidance for the future design of more potent coumarin compounds. This work provides a sustainable strategy to take advantage of coumarin analogues for pest management while protecting nontarget pollinators.
ESTHER : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedSearch : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedID: 37965968

Title : Acaricidal activities of paeonol from Moutan Cortex, dried bark of Paeonia suffruticosa, against the grain pest mite Aleuroglyphus ovatus (Acari: Acaridae) - Zou_2023_Exp.Appl.Acarol__
Author(s) : Zou M , Xue Q , Teng Q , Zhang Q , Liu T , Li Y , Zhao J
Ref : Exp Appl Acarol , : , 2023
Abstract : Aleuroglyphus ovatus (Acari: Acaridae) is a major pest mite of stored grains that is distributed worldwide. Paeonol, a phenolic component of the essential oil extracted from the Chinese herb Paeonia moutan, possesses a range of biological activities, including antiviral, antifungal and acaricidal activity. This study investigated the bioactivity of paeonol against A. ovatus and its effect on the activity of detoxification enzymes. The bioactivity of paeonol against A. ovatus was determined by contact, fumigation and repellency bioassays, and the mechanism was preliminarily explored via morphological observation of the color changes of mite epidermis and determination of the changing trend of some important enzymes associated with acaricidal efficacy in the mites. The results showed that the median lethal concentration (LC(50)) in the contact and fumigation bioassays was 9.832 microg/cm(2) and 14.827 microg/cm(3), respectively, and the acaricidal activity of paeonol was higher under direct contact than under fumigation. Dynamic symptomatology studies registered typical neurotoxicity symptoms including excitation, convulsion and paralysis in A. ovatus treated with paeonol. The enzyme activity of catalase (CAT), nitric oxide synthase (NOS) and glutathione-S-transferase (GST) was higher, whereas the activity of superoxide dismutase (SOD) and acetylcholinesterase (AChE) was lower, compared to the control group. CAT, NOS and GST were activated, whereas SOD and AChE activities were inhibited after paeonol intervention. Our findings suggest paeonol has potent acaricidal activity against A. ovatus and thus may be used as an agent to control the stored-product mite A. ovatus.
ESTHER : Zou_2023_Exp.Appl.Acarol__
PubMedSearch : Zou_2023_Exp.Appl.Acarol__
PubMedID: 37979065

Title : Palmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating beta-catenin palmitoylation - Gu_2023_Nat.Commun_14_6682
Author(s) : Gu M , Jiang H , Tan M , Yu L , Xu N , Li Y , Wu H , Hou Q , Dai C
Ref : Nat Commun , 14 :6682 , 2023
Abstract : palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases. However, the role and mechanisms for protein palmitoylation in renal fibrosis have not been elucidated. Here we show protein palmitoylation and DHHC9 were downregulated in the fibrotic kidneys of mouse models and chronic kidney disease (CKD) patients. Ablating DHHC9 in tubular cells aggravated, while inducing DHHC9 overexpression with adeno-DHHC9 transfection or iproniazid treatment protected against kidney fibrosis in male mouse models. Mechanistically, DHHC9 palmitoylated beta-catenin, thereby promoted its ubiquitination and degradation. Additionally, acyl protein thioesterase 1 (APT1) was induced in the fibrotic kidneys, which depalmitoylated beta-catenin, increased its abundance and nuclear translocation. Ablating tubular APT1 or inhibiting APT1 with ML348 markedly protected against unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)-induced kidney fibrosis in male mice. This study reveals the regulatory mechanism of protein palmitoylation in kidney fibrosis.
ESTHER : Gu_2023_Nat.Commun_14_6682
PubMedSearch : Gu_2023_Nat.Commun_14_6682
PubMedID: 37865665
Gene_locus related to this paper: human-LYPLA1

Title : Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93 - Li_2023_Front.Microbiol_13_1081094
Author(s) : Li Y , Rong Z , Li Z , Cui H , Li J , Xu XW
Ref : Front Microbiol , 13 :1081094 , 2023
Abstract : Introduction: CPT11 (Irinotecan; 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) is an important camptothecin-based broad-spectrum anticancer prodrug. The activation of its warhead, SN38 (7-ethyl-10-hydroxycamptothecin), requires hydrolysis by carboxylesterases. NPC (7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin) is a metabolic derivative of CPT11 and is difficult to be hydrolyzed by human carboxylesterase. Microbial carboxylesterase with capability on both CPT11 and NPC hydrolysis is rarely reported. A marine microbial carboxylesterase, E93, was identified to hydrolyze both substrates in this study. This enzyme was an appropriate subject for uncovering the catalytic mechanism of carboxylesterases to CPT11 and NPC hydrolysis. Methods: X-ray diffraction method was applied to obtain high-resolution structure of E93. Molecular docking was adopted to analyze the interaction of E93 with p -NP ( p -nitrophenyl), CPT11, and NPC substrates. Mutagenesis and enzymatic assay were adopted to verify the binding pattern of substrates. Results: Three core regions (Region A, B, and C) of the catalytic pocket were identified and their functions on substrates specificity were validated via mutagenesis assays. The Region A was involved in the binding with the alcohol group of all tested substrates. The size and hydrophobicity of the region determined the binding affinity. The Region B accommodated the acyl group of p -NP and CPT11 substrates. The polarity of this region determined the catalytic preference to both substrates. The Region C specifically accommodated the acyl group of NPC. The interaction from the acidic residue, E428, contributed to the binding of E93 with NPC. Discussion: The study analyzed both unique and conserved structures of the pocket in E93, for the first time demonstrating the discrepancy of substrate-enzyme interaction between CPT11 and NPC. It also expanded the knowledge about the substrate specificity and potential application of microbial Family VII carboxylesterases.
ESTHER : Li_2023_Front.Microbiol_13_1081094
PubMedSearch : Li_2023_Front.Microbiol_13_1081094
PubMedID: 36756200
Gene_locus related to this paper: 9sphn-E93

Title : Nanoplasmonic biosensors for multicolor visual analysis of acetylcholinesterase activity and drug inhibitor screening in point-of-care testing - Li_2023_Biosens.Bioelectron_247_115912
Author(s) : Li Y , Chen L , Li CY , Zhang J , Zhao Y , Yang YH , Yang T
Ref : Biosensors & Bioelectronics , 247 :115912 , 2023
Abstract : The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the alpha-FeOOH nanorods (NRs) to release amounts of Fe(2+), which was regarded as Fenton reagent to efficiently catalyze H(2)O(2) to produce .OH. Then, the as-formed .OH can further largely shorten the gold nanobipyramids (Au NBPs), generating a series of palpable color variations. The linear range for AChE activity was 0.01-500.0 U/L with the limit of detection as low as 0.0074 U/L. The vivid visual effects could be easily distinguished for the multicolor assay of AChE activity by naked eye in visible light. To achieve the point-of-care testing, Au NBPs were further assembled on polymeric electrospun nanofibrous films (ENFs) surface as test strips for the easy-to-use test of AChE activity by RGB values with a smartphone. Fascinatingly, this proposed strategy can be used for the visual screening AChE inhibitors or non-inhibitors. Comparing with the clinical drugs (rivastigmine tartrate, and donepezil), some natural alkaloids such as evodiamine, caffeine, camptothecin, and berberine hydrochloride were selected as inhibitor modes to confirm the drug screening capability of this method. This proposed strategy may have great potential in the other disease-related enzymatic biomarkers assay and the rapid screening of drug therapy.
ESTHER : Li_2023_Biosens.Bioelectron_247_115912
PubMedSearch : Li_2023_Biosens.Bioelectron_247_115912
PubMedID: 38096721

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : Strigolactone regulates adventitious root formation via the MdSMXL7-MdWRKY6-MdBRC1 signaling cascade in apple - Fan_2023_Plant.J_113_772
Author(s) : Fan X , Li Y , Deng CH , Wang S , Wang Z , Wang Y , Qiu C , Xu X , Han Z , Li W
Ref : Plant J , 113 :772 , 2023
Abstract : Propagation through stem cuttings is a popular method worldwide for species such as fruit tree rootstocks and forest trees. Adventitious root (AR) formation from stem cuttings is crucial for effective and successful clonal propagation of apple rootstocks. Strigolactones (SLs) are newly identified hormones involved in AR formation. However, the regulatory mechanisms underpinning this process remain elusive. In the present study, weighted gene co-expression network analysis, as well as rooting assays using stable transgenic apple materials, revealed that MdBRC1 served as a key gene in the inhibition of AR formation by SLs. We have demonstrated that MdSMXL7 and MdWRKY6 synergistically regulated MdBRC1 expression, depending on the interactions of MdSMXL7 and MdWRKY6 at the protein level downstream of SLs as well as the direct promoter binding on MdBRC1 by MdWRKY6. Furthermore, biochemical studies and genetic analysis revealed that MdBRC1 inhibited AR formation by triggering the expression of MdGH3.1 in a transcriptional activation pathway. Finally, the present study not only proposes a component, MdWRKY6, that enables MdSMXL7 to regulate MdBRC1 during the process of SL-controlled AR formation in apple, but also provides prospective target genes to enhance AR formation capacity using CRISPR (i.e. clustered regularly interspaced short palindromic repeats) technology, particularly in woody plants.
ESTHER : Fan_2023_Plant.J_113_772
PubMedSearch : Fan_2023_Plant.J_113_772
PubMedID: 36575587

Title : Phosphoproteome reveals long-term potentiation deficit following treatment of ultra-low dose soman exposure in mice - Long_2023_J.Hazard.Mater_459_132211
Author(s) : Long Q , Zhang Z , Li Y , Zhong Y , Liu H , Chang L , Ying Y , Zuo T , Wang Y , Xu P
Ref : J Hazard Mater , 459 :132211 , 2023
Abstract : Soman, a warfare nerve agent, poses a significant threat by inducing severe brain damage that often results in death. Nonetheless, our understanding of the biological changes underlying persistent neurocognitive dysfunction caused by low dosage of soman remains limited. This study used mice to examine the effects of different doses of soman over time. Phosphoproteomic analysis of the mouse brain is the first time to be used to detect toxic effects of soman at such low or ultra-low doses, which were undetectable based on measuring the activity of acetylcholinesterase at the whole-animal level. We also found that phosphoproteome alterations could accurately track the soman dose, irrespective of the sampling time. Moreover, phosphoproteome revealed a rapid and adaptive cellular response to soman exposure, with the points of departure 8-38 times lower than that of acetylcholinesterase activity. Impaired long-term potentiation was identified in phosphoproteomic studies, which was further validated by targeted quantitative proteomics, immunohistochemistry, and immunofluorescence analyses, with significantly increased levels of phosphorylation of protein phosphatase 1 in the hippocampus following soman exposure. This increase in phosphorylation inhibits long-term potentiation, ultimately leading to long-term memory dysfunction in mice.
ESTHER : Long_2023_J.Hazard.Mater_459_132211
PubMedSearch : Long_2023_J.Hazard.Mater_459_132211
PubMedID: 37572605

Title : Improving pesticide residue detection: Immobilized enzyme microreactor embedded in microfluidic paper-based analytical devices - Zhang_2023_Food.Chem_439_138179
Author(s) : Zhang J , Li Y , Zhang T , Zheng Z , Jing H , Liu C
Ref : Food Chem , 439 :138179 , 2023
Abstract : Orientationally immobilized enzyme microreactors (OIMERs), embedded in microfluidic paper-based analytical devices (microPADs) were developed for improved detection of pesticide residues in food. Acetylcholinesterase (AChE) was orientationally immobilized on the reusable Part I of the microPADs, using the specific affinity binding of concanavalin A (Con A) to a glycosyl group on AChE. Using the disposable Part II, facile colorimetric quantification was performed with a smartphone and software, or qualitative detection by a naked-eye visual test. The AChE immobilized in OIMERs not only had improved activity and stability, but also high sensitivity, with a limit of detection as low as (0.007 +/- 0.003) microg/mL. The method was used to detect pesticides residues in real vegetable samples; the recovery (88.6-102.7%) showed high reliability for pesticide residues detection in foods. A molecular docking study and an enzyme kinetic analysis were conducted to characterize the mechanism of action of the OIMERs.
ESTHER : Zhang_2023_Food.Chem_439_138179
PubMedSearch : Zhang_2023_Food.Chem_439_138179
PubMedID: 38091789

Title : Enantioselectivity and origin of enhanced efficiency in polyethylene terephthalate hydrolases catalyzed depolymerization - Zheng_2023_J.Hazard.Mater_452_131295
Author(s) : Zheng M , Li Y , Dong W , Zhang Q , Wang W
Ref : J Hazard Mater , 452 :131295 , 2023
Abstract : Biotechnology is one of the most promising strategies to resolve the global crisis of plastic pollution. A clear understanding of the core enzyme mechanisms in the biotransformation process is critical for rational enzyme engineering and for practical, industrial-scale applications. Herein, we systematically examined and evidenced a largely unexplored piece in the depolymerization mechanism catalyzed by polyethylene terephthalate (PET) hydrolases: their enantioselectivity. We found that all the short-lived tetrahedron intermediates (IM3 and IM8) possess S-type chirality in six representative PET hydrolases. For instance, the binding percentage ratio of pro-S:pro-R is 57:21 in FAST-PETase, while pro-S binding leads to a much lower average energy barrier (5.2 kcal/mol) than pro-R binding (33.1 kcal/mol). Key structural features (e.g. the angle for Ser@H1-His@N1-PET@O2 and distance for His@N1-PET@O2) that significantly modulate the enantioselectivity were identified. The origin of the energy landscape variation between wild-type IsPETase and mutant FAST-PETase was also unveiled via analysis of key features, the distortion/interaction energy, and non-covalent bond interactions. This study supplies the missing piece in the mechanism for depolymerization catalyzed by PET hydrolases, and will aid in the rational design of enzymes for industrial recycling of PET plastic waste.
ESTHER : Zheng_2023_J.Hazard.Mater_452_131295
PubMedSearch : Zheng_2023_J.Hazard.Mater_452_131295
PubMedID: 36989777

Title : Polystyrene nanoplastics induce lipid metabolism disorder and alter fatty acid composition in the hepatopancreas of Pacific whiteleg shrimp (Litopenaeus vannamei) - Li_2023_Sci.Total.Environ__167616
Author(s) : Li Y , Ye Y , Rihan N , Zhu B , Jiang Q , Liu X , Zhao Y , Che X
Ref : Sci Total Environ , :167616 , 2023
Abstract : The impact of nanoplastics (NPs) on environmental pollution and aquatic organisms has gradually attracted attention, but there are relatively few reports of the effects of NPs on the lipid metabolism of crustaceans. In this study, we exposed Pacific whiteleg shrimp (Litopenaeus vannamei) to different concentrations of polystyrene NPs (0, 0.1, 1, 5, and 10 mg/L) for 28 days. We then evaluated the effects of NP exposure on metabolite content, histology, lipid metabolism-related enzyme activity, and gene expression. Our results showed that with increasing NPs concentrations and exposure time, (1) the crude protein and crude fat content decreased and fatty acid composition changed; (2) the tissue structure was destroyed and the number of lipid droplets increased in the hepatopancreas; (3) the activities of acetyl-CoA carboxylase, fatty acid synthase, carnitine palmitoyl transferase-1, pyruvate kinase and low-density lipoprotein content tended to decrease and that of lipase and high-density lipoprotein content first increased and then decreased; the content of triglycerides and total carbohydrate first decreased and then increased; (4) the expression of fatty acid synthesis-related genes (Fas, SREBP, and FAD), fatty acid transport-related genes (FATP, FABP, and ACBP), and fatty acid decomposition-related genes (Ampk and lip1) first increased and then decreased. These results indicate that exposure to NPs can cause physiological disorders of fat metabolism in L. vannamei and that high concentrations of NPs have a negative impact on lipid metabolism. These results of this study provide valuable ecotoxicological data for better interpretation of the mechanism of action of NPs in crustaceans.
ESTHER : Li_2023_Sci.Total.Environ__167616
PubMedSearch : Li_2023_Sci.Total.Environ__167616
PubMedID: 37832676

Title : Metagenomic exploration of microbial and enzymatic traits involved in microplastic biodegradation - Hu_2023_Chemosphere_348_140762
Author(s) : Hu X , Gu H , Sun X , Wang Y , Liu J , Yu Z , Li Y , Jin J , Wang G
Ref : Chemosphere , 348 :140762 , 2023
Abstract : Agricultural mulch films are frequently applied to achieve high yield, resulting in large quantities of microplastic (MP) pollution in agroecosystem. However, studies focusing specifically on the diversity of MP-degrading enzymes and related microbial communities have yet to be conducted. Here, we established a soil microcosmic incubation with addition of 5% (w/w) conventional (low-density polyethylene (LDPE)) and biodegradable (blend of polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT)) MPs for incubation 90 days. The DNA samples extracted from soils and plastisphere of MPs were examined by metagenomics and genome binning methods, specifically targeting carbohydrate-active enzymes (CAZymes) and plastic-degrading enzymes (PDZymes). The results revealed that plastisphere of MPs exhibited significantly distinct patterns of CAZymes and PDZymes from soils, and abundances of all examined exoenzymes were higher in plastisphere than those in soils. Plastisphere of LDPE-MPs selectively enriched proteases and alkane monooxygenase (alkB), and required families of carbohydrate-binding module (CBM) to increase the binding of CAZymes with MPs. Dissimilarly, diverse CAZymes with high abundances were observed in the plastisphere of PBAT-PLA MPs and esterases were important indicative PDZymes for PBAT-PLA degradation. The enriched exoenzymes in plastisphere of LDPE-MPs were mainly assigned to Actinobacteria while Proteobacteria with higher abundance in plastisphere of PBAT-PLA MPs containing most indicative exoenzymes. Moreover, a high-quality genome classified as Amycolatopsis japonica was reconstructed and found to contain one or more gene copies of indicative exoenzymes for polyethylene. Two novel genomes classified as Sphingomonas were selectively enriched in plastisphere of PBAT-PLA MPs and contained diverse genes encoding degrading exoenzymes. Taken together, our study highlighted the CAZymes and PDZymes can be exploited as potent microbial strategies for solving MPs pollution in croplands.
ESTHER : Hu_2023_Chemosphere_348_140762
PubMedSearch : Hu_2023_Chemosphere_348_140762
PubMedID: 38006912

Title : Oxymetazoline Hydrochloride Eye-Drops as Treatment for Myasthenia Gravis-Related Ptosis: A Description of Two Cases - Taha_2023_Cureus_15_e36351
Author(s) : Taha M , Li Y , Morren J
Ref : Cureus , 15 :e36351 , 2023
Abstract : In this article, we described two patients with myasthenia gravis-related ptosis who experienced sustained improvement with the use of oxymetazoline hydrochloride ophthalmic solution 0.1%. Despite the commonly used treatments for ptosis in myasthenia gravis (MG), such as acetylcholinesterase inhibitors and corticosteroids, complete remission of ptosis is not always achieved, and these treatments are often accompanied by systemic side effects. Our case report suggests the long-term efficacy of daily use of oxymetazoline eye drops in improving ptosis, providing a potential alternative or adjunctive treatment option without significant adverse effects. Further research is necessary to confirm these observations across larger cohorts of MG patients and establish the effectiveness of oxymetazoline eye drops in MG-related ptosis.
ESTHER : Taha_2023_Cureus_15_e36351
PubMedSearch : Taha_2023_Cureus_15_e36351
PubMedID: 37082493

Title : A novel and controllable method for simultaneous preparation of human milk fat substitutes (OPL, OPO and LPL): two-step enzymatic ethanolysis-esterification strategy - Li_2023_Food.Res.Int_163_112168
Author(s) : Li Y , Zhang Y , Zhou Y , Zheng M
Ref : Food Res Int , 163 :112168 , 2023
Abstract : A novel and effective approach based on the two-step ethanolysis-esterification strategy was proposed for the controllable and simultaneous preparation of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL), 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and 1,3-dilinoleoyl-2-palmitoyl-glycerol (LPL) with adjustable proportions. Enzymatic ethanolysis of fractionated palm stearin was carried out to yield 2-monopalmitoylglycerol (79.4s+/-s0.6s%) with over 91.0s% purity at the optimal conditions. The immobilized Candida sp. lipase (CSL) on octyl-functionalized ordered mesoporous silica (OMS-C(8)) was applied to re-esterify 2-monopalmitoylglycerol with oleic acid and linoleic acid for the simultaneous production of OPL, OPO, and LPL. The total content in the final products was 81.5s%, with 91.3s% of palmitic acid (PA) content at the sn-2 position. Besides, OPL/OPO/LPL was conveniently prepared with suitable proportions for worldwide infants by adjusting the ratio of acyl donors. This paper provides a novel and effective two-step ethanolysis-esterification strategy for the development of human milk fat substitutes (HMFS).
ESTHER : Li_2023_Food.Res.Int_163_112168
PubMedSearch : Li_2023_Food.Res.Int_163_112168
PubMedID: 36596114

Title : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : Associations of per- and polyfluoroalkyl substances, polychlorinated biphenyl, organochlorine pesticides, and polybrominated diphenyl ethers with oxidative stress markers: A systematic review and meta-analysis - Chen_2023_Environ.Res__117308
Author(s) : Chen JC , Baumert BO , Li Y , Pan S , Robinson S , Rubbo B , Costello E , He J , Hampson H , Beglarian E , Rock S , Goodrich J , Eckel SP , Aung MT , McConnell R , Conti DV , Chatzi L
Ref : Environ Research , :117308 , 2023
Abstract : BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps. OBJECTIVE: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies. METHODS: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to July 12, 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis. RESULTS: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of alpha-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all beta [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (p(one-tailed) = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (p(one-tailed) = 0.02) and paraoxonase-1 (p(one-tailed) = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase. CONCLUSIONS: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity.
ESTHER : Chen_2023_Environ.Res__117308
PubMedSearch : Chen_2023_Environ.Res__117308
PubMedID: 37813138

Title : Smartphone-assisted sensor array constructed by copper-based laccase-like nanozymes for specific identification and discrimination of organophosphorus pesticides - Song_2023_Food.Chem_424_136477
Author(s) : Song D , Tian T , Yang X , Wang L , Sun Y , Li Y , Huang H
Ref : Food Chem , 424 :136477 , 2023
Abstract : Accurate pesticide identification is of great importance for regulating food safety. However, the discrimination between organophosphorus pesticides (OPs) and carbamate pesticides (CPs) is still a challenge for existing analytical methods based on cholinesterase inhibition. It mainly because of the similar inhibitory effect of OPs and CPs on cholinesterase. Herein, we found that OPs and CPs differentially affected nanozymes with laccase-like activity, which would be interfered by OPs in different degrees rather than CPs. Thus, we fabricated a nanozyme sensor array and successfully achieved the OPs identification and similar individual discrimination, ignoring the interference from CPs or other potential interferents (antibiotics, ions, other pesticides). On the basis of nanozyme sensor array, a portable method using smartphone was constructed and utilized to determine OPs in fruits and vegetables. This work would contribute to the development of portable sensors and the highly selective identification and discrimination of OPs in complex samples.
ESTHER : Song_2023_Food.Chem_424_136477
PubMedSearch : Song_2023_Food.Chem_424_136477
PubMedID: 37263094

Title : How Closely Does Induced Agarwood's Biological Activity Resemble That of Wild Agarwood? - Ma_2023_Molecules_28_
Author(s) : Ma S , Huang M , Fu Y , Qiao M , Li Y
Ref : Molecules , 28 : , 2023
Abstract : Continuous innovation in artificially-induced agarwood technology is increasing the amount of agarwood and substantially alleviating shortages. Agarwood is widely utilized in perfumes and fragrances; however, it is unclear whether the overall pharmacological activity of induced agarwood can replace wild agarwood for medicinal use. In this study, the volatile components, total chromone content, and the differences in the overall activities of wild agarwood and induced agarwood, including the antioxidant, anti-acetylcholinesterase, and anti-glucosidase activity were all determined. The results indicated that both induced and wild agarwood's chemical makeup contains sesquiterpenes and 2-(2-phenylethyl)chromones. The total chromone content in generated agarwood can reach 82.96% of that in wild agarwood. Induced agarwood scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)) radicals and inhibited acetylcholinesterase activity and alpha-glucosidase activity with IC(50) values of 0.1873 mg/mL, 0.0602 mg/mL, 0.0493 mg/mL, and 0.2119 mg/mL, respectively, reaching 80.89%, 93.52%, 93.52%, and 69.47% of that of wild agarwood, respectively. Accordingly, the results distinguished that induced agarwood has the potential to replace wild agarwood in future for use in medicine because it has a similar chemical makeup to wild agarwood and has comparable antioxidant, anti-acetylcholinesterase, and anti-glucosidase capabilities.
ESTHER : Ma_2023_Molecules_28_
PubMedSearch : Ma_2023_Molecules_28_
PubMedID: 37049682

Title : Alcoholic Setdb1 suppression promotes hepatosteatosis in mice by strengthening Plin2 - Zhang_2023_Metabolism__155656
Author(s) : Zhang Y , Li Y , Liu Y , Wang H , Chen Y , Zhang B , Song M , Song L , Ding Q , Qiu J , Fan M , Qu L , Wang Z
Ref : Metabolism , :155656 , 2023
Abstract : BACKGROUND AND AIMS: Hepatosteatosis is one of the early features of alcoholic liver disease (ALD) and pharmaceutical or genetic interfering of the development of hepatosteatosis will efficiently alleviate the progression of ALD. Currently, the role of histone methyltransferase Setdb1 in ALD is not yet well understood. METHOD: Lieber-De Carli diet mice model and NIAAA mice model were constructed to confirm the expression of Setdb1. The hepatocyte-specific Setdb1-knockout (Setdb1-HKO) mice was established to determine the effects of Setdb1 in vivo. Adenovirus-Setdb1 were produced to rescue the hepatic steatosis in both Setdb1-HKO and Lieber-De Carli mice. The enrichment of H3k9me3 in the upstream sequence of Plin2 and the chaperone-mediated autophagy (CMA) of Plin2 were identified by ChIP and co-IP. Dual-luciferase reporter assay was used to detect the interaction of Setdb1 3'UTR and miR216b-5p in AML12 or HEK 293 T cells. RESULTS: We found that Setdb1 was downregulated in the liver of alcohol-fed mice. Setdb1 knockdown promoted lipid accumulation in AML12 hepatocytes. Meanwhile, hepatocyte-specific Setdb1-knockout (Setdb1-HKO) mice exhibited significant lipid accumulation in the liver. Overexpression of Setdb1 was performed with an adenoviral vector through tail vein injection, which ameliorated hepatosteatosis in both Setdb1-HKO and alcoholic diet-fed mice. Mechanistically, downregulated Setdb1 promoted the mRNA expression of Plin2 by desuppressing H3K9me3-mediated chromatin silencing in its upstream sequence. Pin2 acts as a critical membrane surface-associated protein to maintain lipid droplet stability and inhibit lipase degradation. The downregulation of Setdb1 also maintained the stability of Plin2 protein through inhibiting Plin2-recruited chaperone-mediated autophagy (CMA). To explore the reasons for Setdb1 suppression in ALD, we found that upregulated miR-216b-5p bound to the 3'UTR of Setdb1 mRNA, disturbed its mRNA stability, and eventually aggravated hepatic steatosis. CONCLUSIONS: Setdb1 suppression plays an important role in the progression of alcoholic hepatosteatosis via elevating the expression of Plin2 mRNA and maintaining the stability of Plin2 protein. Targeting hepatic Setdb1 might be a promising diagnostic or therapeutic strategy for ALD.
ESTHER : Zhang_2023_Metabolism__155656
PubMedSearch : Zhang_2023_Metabolism__155656
PubMedID: 37419179

Title : Discovery of seven-membered ring berberine analogues as highly potent and specific hCES2A inhibitors - Yang_2023_Chem.Biol.Interact_378_110501
Author(s) : Yang Y , Xiong Y , Zhu G , Sun M , Zou K , Zhao Y , Zhang Y , Xu Z , Li Y , Zhu W , Jia Q , Li B , Ge G
Ref : Chemico-Biological Interactions , 378 :110501 , 2023
Abstract : Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC(50) = 1.66 microM) and excellent selectivity over hCES1A (IC(50) > 100 microM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K(i) value of 1.035 microM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
ESTHER : Yang_2023_Chem.Biol.Interact_378_110501
PubMedSearch : Yang_2023_Chem.Biol.Interact_378_110501
PubMedID: 37080375

Title : Regulation of NLGN3 and the synaptic Rho-GEF signaling pathway by CDK5 - Jeong_2023_J.Neurosci__
Author(s) : Jeong J , Han W , Hong E , Pandey S , Li Y , Lu W , Roche KW
Ref : Journal of Neuroscience , : , 2023
Abstract : Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that are involved in synapse assembly and function. The NLGN gene family consists of 5 genes (NLGN1-3, 4X, and 4Y). NLGN3 forms heterodimers with other NLGNs and is expressed at both excitatory and inhibitory synapses, although the distinct role at different synapses is not fully understood. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that targets various neuronal substrates to impact neuronal migration, neurite outgrowth, synaptic transmission, and plasticity. Both NLGNs and their presynaptic binding partners neurexins are highly associated with neurodevelopmental disorders. The NLGN3 gene is on the X chromosome and variants in NLGN3 have been linked to the pathophysiology in neurodevelopmental disorders. To better understand the endogenous modulation of NLGN3, we generated an HA-tagged knock-in (KI) mouse. We found that Cdk5 associates with NLGN3 in vivo and phosphorylates NLGN3 on serine 725 (S725) in the KI mouse of either sex. The phosphorylation affects the NLGN3 association with Kalirin-7, a postsynaptic guanine nucleotide exchange factors (GEFs) for Rho GTPase family proteins. We further observed that the phosphorylation modulates NLGN3 surface expression and NLGN3-mediated synaptic currents in cultured rat neurons. Thus, we characterized NLGN3 as a novel Cdk5 substrate and revealed the functional consequences of NLGN3 S725 phosphorylation in neurons. Our study provides a novel molecular mechanism underlying Cdk5-mediated regulation of postsynaptic cell adhesion molecules.Significance StatementNLGN3 is involved in synapse assembly and function at both excitatory and inhibitory synapses and has been associated with the pathophysiology of neurodevelopmental disorders. Cdk5 has a brain-specific activity and involved in neuronal transmission, synapse function and plasticity. Here, we characterize NLGN3 as a Cdk5 substrate for the first time and show Cdk5-mediated phosphorylation regulates NLGN3 function. We demonstrate NLGN3 S725 is a Cdk5 phosphorylation site and reveal the site is important for NLGN3 association with Kalirin-7, NLGN3 surface expression, and NLGN3-mediated synaptic transmission.
ESTHER : Jeong_2023_J.Neurosci__
PubMedSearch : Jeong_2023_J.Neurosci__
PubMedID: 37699715

Title : Green-emitting carbon dots as a turn on fluorescence bio-probe for highly sensitive and selective detection of lipase in human serum - Al-Mashriqi_2023_Anal.Bioanal.Chem__
Author(s) : Al-Mashriqi HS , Sanga P , Chen J , Li X , Xiao J , Li Y , Qiu H
Ref : Anal Bioanal Chem , : , 2023
Abstract : Enzyme activity assays play a crucial role in numerous fields, including biotechnology, the food industry, and clinical diagnostics. Lipases are particularly important enzymes due to their widespread use in lipid metabolism and esterification reactions. Here, we present a pioneering method for the sensitive and selective determination of lipase activity using green carbon dots (G-CDs) for first time. G-CDs are a fascinating class of carbon nanomaterials with unique optical properties and biocompatibility, making them ideal candidates for enzyme activity assays. This approach eliminates the need for traditional fluorophores or chromogenic substrates, reducing costs, fast response time (1 min), and environmental impact with a quantum yield (QY) of 7.42%. As designed, the G-CDs fluorescent probe turn-on demonstrated a reliable linear detection range from 0 to 9 mg/mL under ideal conditions, with detection limit of 0.01 mg/mL and limit of quantification (LOQ) of 0.045 mg/mL, respectively. Furthermore, the G-CDs system was thoroughly evaluated in human serum samples, showing recoveries ranging from 100.0 to 105.0%. These findings highlight the promising applicability of the G-CDs probe for lipase detection, yielding highly favorable results.
ESTHER : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedSearch : Al-Mashriqi_2023_Anal.Bioanal.Chem__
PubMedID: 38082135

Title : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : CES1-Triggered Liver-Specific Cargo Release of CRISPR\/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration - Zhao_2023_Adv.Sci.(Weinh)__e2300502
Author(s) : Zhao Y , Li Y , Wang F , Gan X , Zheng T , Chen M , Wei L , Chen J , Yu C
Ref : Adv Sci (Weinh) , :e2300502 , 2023
Abstract : The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9-mRNA/ single-guide RNA (Cas9-mRNA/sgRNA) in vitro and vivo, using carboxylesterase-responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG-b-P(Met/n-PMA). The copolymer can self-assemble with Cas9-mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG-b-P(Met/n-PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low-density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed-point release, which expand the application of CRISPR delivery systems.
ESTHER : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedSearch : Zhao_2023_Adv.Sci.(Weinh)__e2300502
PubMedID: 37083231

Title : Bidirectional selection of the functional properties and environmental friendliness of organophosphorus (OP) pesticide derivatives: Design, screening, and mechanism analysis - Wang_2023_Sci.Total.Environ__163043
Author(s) : Wang Z , Pu Q , Li Y
Ref : Sci Total Environ , :163043 , 2023
Abstract : Organophosphorus pesticides (OPs) are widely used in agricultural production, but the resulting pollution and drug resistance have sparked widespread concern. Therefore, this paper built a model to design OP substitute molecules with high functionality and environmental friendliness, as well as conducted various human health and ecological environment evaluations, synthetic accessibility screening, and easy detection screening. The functionality of the two OP substitute molecules, DIM-100 and DIM-164, increased by 22.79 % and 22.18 %, respectively, and the environmental friendliness increased by 18.07 % and 24.02 %, respectively. The human health risk and ecological, environmental risks were significantly reduced. Both molecules are easy to synthesize, and their detection sensitivity is 9.85 % and 11.24 % higher than that of the target molecule, respectively. Furthermore, significant changes in the distribution of electrons and holes near the C8 and S1 atoms of the OP substitute molecule resulted in easier breakage of the C8-S1 bond, enhancing its photodegradation ability. The charge transfer ability between the atoms of the molecule (as increasing the electron-withdrawing group led to an increase in charge of the P atom) and the volume of the cholinesterase active pocket both affect the functionality of the DIM substitute molecule. That is, the volume of the cholinesterase active pocket of the bee is smaller than that of the brown planthopper and is more affected by the volume of the OP molecule. Furthermore, the mutual verification analysis of the bidirectional selectivity effect of OP substitute molecules between the BayesianRidge model and the 3D-QS(A(2) + (3))R model reveals that the overall charge transfer degree of DIM substitute molecules is the main reason for the increase in the bidirectional selectivity effect.
ESTHER : Wang_2023_Sci.Total.Environ__163043
PubMedSearch : Wang_2023_Sci.Total.Environ__163043
PubMedID: 36963678

Title : Discovering metabolic vulnerability using spatially resolved metabolomics for antitumor small molecule-drug conjugates development as a precise cancer therapy strategy - Wang_2023_J.Pharm.Anal_13_776
Author(s) : Wang X , Zhang J , Zheng K , Du Q , Wang G , Huang J , Zhou Y , Li Y , Jin H , He J
Ref : J Pharm Anal , 13 :776 , 2023
Abstract : Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy. However, metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity. Herein, choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types, and a choline-modified strategy for small molecule-drug conjugates (SMDCs) design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy, instead of directly inhibiting choline metabolism. As a proof-of-concept, choline-modified SMDCs were designed, screened, and investigated for their druggability in vitro and in vivo. This strategy improved tumor targeting, preserved tumor inhibition and reduced toxicity of paclitaxel, through targeted drug delivery to tumor by highly expressed choline transporters, and site-specific release by carboxylesterase. This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
ESTHER : Wang_2023_J.Pharm.Anal_13_776
PubMedSearch : Wang_2023_J.Pharm.Anal_13_776
PubMedID: 37577390

Title : Exploration of the SIRT1-mediated BDNF-TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis - Wang_2023_Front.Public.Health_11_1247294
Author(s) : Wang F , Li Y , Tang D , Yang B , Tian T , Tian M , Meng N , Xie W , Zhang C , He Z , Zhu X , Ming D , Liu Y
Ref : Front Public Health , 11 :1247294 , 2023
Abstract : INTRODUCTION: Fluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF-TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments. METHODS: This study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting. RESULTS: All rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities. DISCUSSION: Currently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.
ESTHER : Wang_2023_Front.Public.Health_11_1247294
PubMedSearch : Wang_2023_Front.Public.Health_11_1247294
PubMedID: 37711250

Title : Genome-wide association study of 17 serum biochemical indicators in a chicken F(2) resource population - Song_2023_BMC.Genomics_24_98
Author(s) : Song H , Li W , Li Y , Zhai B , Guo Y , Chen Y , Han R , Sun G , Jiang R , Li Z , Yan F , Li G , Liu X , Zhang Y , Tian Y , Kang X
Ref : BMC Genomics , 24 :98 , 2023
Abstract : BACKGROUND: Serum biochemical indicators are often regarded as direct reflections of animal metabolism and health. The molecular mechanisms underlying serum biochemical indicators metabolism of chicken (Gallus Gallus) have not been elucidated. Herein, we performed a genome-wide association study (GWAS) to identify the variation associated with serum biochemical indicators. The aim of this research was to broaden the understanding of the serum biochemical indicators in chickens. RESULTS: A GWAS of serum biochemical indicators was carried out on 734 samples from an F2 Gushix Anka chicken population. All chickens were genotyped by sequencing, 734 chickens and 321,314 variants were obtained after quality control. Based on these variants, a total of 236 single-nucleotide polymorphisms (SNPs) on 9 chicken chromosomes (GGAs) were identified to be significantly (-log(10)(P) > 5.72) associated with eight of seventeen serum biochemical indicators. Ten novel quantitative trait locis (QTLs) were identified for the 8 serum biochemical indicator traits of the F2 population. Literature mining revealed that the ALPL, BCHE, GGT2/GGT5 genes at loci GGA24, GGA9 and GGA15 might affect the alkaline phosphatase (AKP), cholinesterase (CHE) and gamma-glutamyl transpeptidase (GGT) traits, respectively. CONCLUSION: The findings of the present study may contribute to a better understanding of the molecular mechanisms of chicken serum biochemical indicator regulation and provide a theoretical basis for chicken breeding programs.
ESTHER : Song_2023_BMC.Genomics_24_98
PubMedSearch : Song_2023_BMC.Genomics_24_98
PubMedID: 36864386

Title : Transcriptome reveals the toxicity difference of dimethyl disulfide by contact and fumigation on Meloidogyne incognita through calcium channel-mediated oxidative phosphorylation - Wang_2023_J.Hazard.Mater_460_132268
Author(s) : Wang Q , Wang X , Zhang D , Fang W , Li Y , Cao A , Yan D
Ref : J Hazard Mater , 460 :132268 , 2023
Abstract : The prevention and control of root-knot nematode disease has been posing a severe challenge worldwide. Fumigant dimethyl disulfide (DMDS) has excellent biological activity against nematodes. However, DMDS displays significant differences in contact and fumigation toxicity on nematodes. The specific regulatory mechanisms of DMDS on nematodes were investigated by characterizing the ultrastructure of nematodes, examining the physiological and biochemical indicators, and conducting transcriptome high-throughput sequencing. As indicated by the results, DMDS fumigation exhibited the biological activity of against M. incognita 121 times higher than DMDS contact. DMDS contact destroyed nematode body wall cells. Besides, DMDS fumigation destroyed the structure of pseudocoelom. DMDS treatment expedited the oxygen consumption of nematode while inhibiting acetylcholinesterase activity. As indicated by the analysis of vital signaling pathways based on transcriptome, DMDS based on the contact mode penetrated directly into the nematode through the body wall and subsequently affected calcium channels in the body wall and muscle, disrupting their structure; it serves as an uncoupling agent to interfere with ATP synthase. Moreover, DMDS based on the fumigation mode entered the body through the respiratory pathway of olfactory perception-oxygen exchange and subsequently affected calcium channels in the nerve; eventually, DMDS acted on complex IV or complex I.
ESTHER : Wang_2023_J.Hazard.Mater_460_132268
PubMedSearch : Wang_2023_J.Hazard.Mater_460_132268
PubMedID: 37619272

Title : Synthesis and biological evaluation of substituted acetamide derivatives as potential butyrylcholinestrase inhibitors - Yu_2023_Sci.Rep_13_4877
Author(s) : Yu D , Yang C , Liu Y , Lu T , Li L , Chen G , Liu Z , Li Y
Ref : Sci Rep , 13 :4877 , 2023
Abstract : Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC(50) values of 3.94 microM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor.
ESTHER : Yu_2023_Sci.Rep_13_4877
PubMedSearch : Yu_2023_Sci.Rep_13_4877
PubMedID: 36966194

Title : Sequence-Responsive Multifunctional Supramolecular Nanomicelles Act on the Regression of TNBC and Its Lung Metastasis via Synergic Pyroptosis-Mediated Immune Activation - Wang_2023_Small__e2305101
Author(s) : Wang X , Li Y , Hasrat K , Yang L , Qi Z
Ref : Small , :e2305101 , 2023
Abstract : Design of effective nanodrugs to modulate the immunosuppression of tumor microenvironment is a desirable approach to boost the clinical tumor-therapeutic effect. Supramolecular nanomicelles PolyMN-TO-8, which are constructed by self-assembling supramolecular host MTX-MPEG2000, guest NPX-2S, and TO-8 through hydrophobic forces, have excellent stability and responsiveness to carboxylesterase and glutathione in turn. In vivo studies validate that PolyMN-TO-8 enable to trigger pyroptosis-mediated immunogenic cell death under laser, avoiding the occurrence of immune dysregulation simultaneously. This therapeutic mode strengthens dendritic cells' maturation and accelerates the infiltration of CD8(+) T cells into tumors through moderate activation of pro-inflammatory factors with elimination of immune-escape, ultimately making the tumor inhibition rate as high as 87.44% via synergistic functions of photodynamic therapy, photothermal therapy, chemotherapy, etc. The loss of immune-escape quickens the infiltration of CD8(+) T cells into lungs, and further eschews the generation of tumor nodules in it. Chemotherapy, the release of interferon-gamma, and immune memory effect also strengthen the defense against metastasis. The generation of O(2) catalyzed by PolyMN-TO-8 under laser is indispensable for tumor metastasis inhibition undoubtedly.
ESTHER : Wang_2023_Small__e2305101
PubMedSearch : Wang_2023_Small__e2305101
PubMedID: 37635105

Title : Two-Site Enhanced Porphyrinic Metal-Organic Framework Nanozymes and Nano-\/Bioenzyme Confined Catalysis for Colorimetric\/Chemiluminescent Dual-Mode Visual Biosensing - Chai_2023_Anal.Chem__
Author(s) : Chai H , Li Y , Yu K , Yuan Z , Guan J , Tan W , Ma J , Zhang X , Zhang G
Ref : Analytical Chemistry , : , 2023
Abstract : The rational design of efficient nanozymes and the immobilization of enzymes are of great significance for the construction of high-performance biosensors based on nano-/bioenzyme catalytic systems. Herein, a novel V-TCPP(Fe) metal-organic framework nanozyme with a two-dimensional nanosheet morphology is rationally designed by using V(2)CT(x) MXene as a metal source and iron tetrakis(4-carboxyphenyl)porphine (FeTCPP) ligand as an organic linker. It exhibits enhanced peroxidase- and catalase-like activities and luminol-H(2)O(2) chemiluminescent (CL) behavior. Based on the experimental and theoretical results, these excellent enzyme-like activities are derived from the two-site synergistic effect between V nodes and FeTCPP ligands in V-TCPP(Fe). Furthermore, a confined catalytic system is developed by zeolitic imidazole framework (ZIF) coencapsulation of the V-TCPP(Fe) nanozyme and bioenzyme. Using the acetylcholinesterase (AChE) as a model, our constructed V-TCPP(Fe)/AChE@ZIF confined catalytic system was successfully used for the colorimetric/CL dual-mode visual biosensing of organophosphorus pesticides. This work is expected to provide new insights into the design of efficient nanozymes and confined catalytic systems, encouraging applications in catalysis and biosensing.
ESTHER : Chai_2023_Anal.Chem__
PubMedSearch : Chai_2023_Anal.Chem__
PubMedID: 37881841

Title : Monovalent SARS-COV-2 mRNA vaccine using optimal UTRs and LNPs is highly immunogenic and broadly protective against Omicron variants - Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
Author(s) : Ye Z , Bonam SR , McKay LGA , Plante JA , Walker J , Zhao Y , Huang C , Chen J , Xu C , Li Y , Liu L , Harmon J , Gao S , Song D , Zhang Z , Plante KS , Griffiths A , Hu H , Xu Q
Ref : Proc Natl Acad Sci U S A , 120 :e2311752120 , 2023
Abstract : The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4(+) and CD8(+) T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3beta (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs.
ESTHER : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedSearch : Ye_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2311752120
PubMedID: 38134199

Title : Screening of Acetylcholinesterase Inhibitors by Capillary Electrophoresis with Oriented-Immobilized Enzyme Microreactors Based on Gold Nanoparticles - Zhang_2023_Molecules_29_
Author(s) : Zhang J , Li Y , Chen L , Zheng Z , Liu C
Ref : Molecules , 29 : , 2023
Abstract : A facial and efficient method for the screening of acetylcholinesterase (AChE) inhibitors by capillary electrophoresis was developed. Based on the specific affinity of concanavalin A (Con A) for binding to the glycosyl group of AChE, enzyme molecules were oriented-immobilized on the surface of gold nanoparticles (AuNPs@Con A@AChE). Then, these modified nanoparticles were bounded to the capillary inlet (about 1.0 cm) by electrostatic self-assembly to obtain the oriented-immobilized enzyme microreactor (OIMER). Compared to an IMER with a free enzyme, the peak area of the product obtained by the OIMER increased by 52.6%. The Michaelis-Menten constant (K(m)) was as low as (0.061 +/- 0.003) mmol/L. The method exhibits good repeatability with a relative standard deviation (RSD) of 1.3% for 100 consecutive runs. The system was successfully applied to detect the IC(50) values of donepezil and four components from Chinese medicinal plants. This work demonstrates the potential of this method as a low cost, simple, and accurate screening method for other enzyme inhibitors.
ESTHER : Zhang_2023_Molecules_29_
PubMedSearch : Zhang_2023_Molecules_29_
PubMedID: 38202701

Title : A portable acetylcholinesterase-based electrochemical sensor for field detection of organophosphorus - Wen_2023_RSC.Adv_13_6389
Author(s) : Wen L , Wang J , Liu Z , Tao CA , Rao J , Hang J , Li Y
Ref : RSC Adv , 13 :6389 , 2023
Abstract : A portable acetylcholinesterase (AChE)-based electrochemical sensor based on a screen-printed carbon electrode (SPCE) and a miniature potentiostat was constructed for the rapid field detection of organophosphorus pesticides (OPs). Graphene (GR) and gold nanoparticles (AuNPs) were successively introduced onto SPCE for surface modification. Due to the synergistic effect of the two nanomaterials, the signal of the sensor has a significant enhancement. Take isocarbophos (ICP) as a model for chemical warfare agents (CAWs) and Ops; the SPCE/GR/AuNPs/AChE/Nafion sensor shows a wider linear range (0.1-2000 microg L(-1)), and a lower limit of detection (0.012 microg L(-1)) than SPCE/AChE/Nafion and SPCE/GR/AChE/Nafion sensors. Tests in actual fruit and tap water samples also yielded satisfactory results. Therefore, the proposed method can be used as a simple and cost-effective strategy for construction of portable electrochemical sensors for OP field detection.
ESTHER : Wen_2023_RSC.Adv_13_6389
PubMedSearch : Wen_2023_RSC.Adv_13_6389
PubMedID: 36874943

Title : Mechanism of the Change in the Intestinal Microbiota of C-Strain Spodoptera frugiperda (Lepidoptera: Noctuidae) after an Interspecific Transference between Rice and Corn - Di_2023_Microorganisms_11_
Author(s) : Di T , Li Y , Du G , He Y , Wang W , Shen Y , Meng J , Xiao W , Xiao G , Chen B
Ref : Microorganisms , 11 : , 2023
Abstract : Spodoptera frugiperda (J.E.Smith) (Lepidoptera: Noctuidae) was first found in 2019 in Yunnan, China, and it was characterized as a corn strain; it was also found on rice strains there, and it damages rice in China, but little is known about the effect of host plant transfer on the intestinal microbiota and the activities of detoxification enzymes in the C-strain (corn strain) S. frugiperda. The intestinal microbiota and the protective enzyme activity of S. frugiperda that were transferred from rice plants were assessed, and the fourth generation of insects transferred from corn were studied; the gene types of S. frugiperda that were transferred from rice plants were tested using mitochondrial Tpi gene sequences. The results showed that the intestinal microbiota in the C-strain S. frugiperda were changed after the host transference, and the diversity and richness of the intestinal bacterial communities of the S. frugiperda feeding on rice were significantly reduced after the transfer of the host from corn. The predominant species of intestinal bacteria of the S. frugiperda on rice transferred from corn were Enterococcus and Enterobacter, with relative abundances of 28.7% and 66.68%; the predominant species of intestinal bacteria of the S. frugiperda that were transferred from rice and feeding on corn were Enterococcus (22.35%) and Erysipelatoclostridium (73.92%); and the predominant species of intestinal bacteria of S. frugiperda feeding on corn was Enterococcus, with a relative abundance of 61.26%. The CAT (catalase) activity of the S. frugiperda transferred from corn onto rice from corn was reduced, the POD (peroxidase) activity was significantly increased after the transfer from corn, and no significant variations were found for the SOD (superoxide dismutase), CarE (carboxylesterase), and GST (glutathione S-transferase) activities of S. frugiperda after the host plant transfer. The results showed that after feeding on rice, the activities of CAT and POD in the in S. frugiperda body changed in order to resist plant secondary metabolites from corn or rice, but there was no significant change in the detoxification enzymes in the body. In summary, switching the host plant between corn and rice induced variations in the intestinal microbiota in C-strain S. frugiperda owing to the strain difference between the C-strain and the R-strain (rice strain), and this was consistent with the results of the activities of detoxification enzymes. The results indicat that changes in intestinal microbiota and physiological enzymes may be important reasons for the adaptive capacity of C-strain S. frugiperda to rice.
ESTHER : Di_2023_Microorganisms_11_
PubMedSearch : Di_2023_Microorganisms_11_
PubMedID: 37894172

Title : Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase - Zhao_2023_Bioorg.Med.Chem_91_117413
Author(s) : Zhao Y , Zhang M , Hou X , Han J , Qin X , Yang Y , Song Y , Liu Z , Zhang Y , Xu Z , Jia Q , Li Y , Chen K , Li B , Zhu W , Ge G
Ref : Bioorganic & Medicinal Chemistry , 91 :117413 , 2023
Abstract : Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
ESTHER : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedSearch : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedID: 37490786

Title : Sitagliptin Extends Lifespan of Caenorhabditis elegans by Inhibiting IIS and Activating DR-like Signaling Pathways - Ye_2023_Gerontology__
Author(s) : Ye Q , Li Y , Wang C , Zheng J , Qiao J , Yang J , Wan QL
Ref : Gerontology , : , 2023
Abstract : INTRODUCTION: The discovery of longevity molecules that delay aging and prolong lifespan has always been a dream of humanity. Sitagliptin phosphate (SIT), an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, is an oral drug commonly used in the treatment of type 2 diabetes (T2D). In addition to being anti-diabetic, previous studies have reported that SIT has shown potential to improve health. However, whether SIT plays a role in the amelioration of aging and the underlying molecular mechanism remain undetermined. METHODS: Caenorhabditis elegans (C. elegans) was used as a model of aging. Lifespan assays were performed with adult-stage worms on NGM plates containing FUDR with or without the specific concentration of SIT. The period of fast body movement, body bending rates and pharyngeal pumping rates were recorded to assess the health-span of C. elegans. Gene expression was confirmed by GFP fluorescence signal of transgenic worms and qPCR. In addition, the intracellular ROS levels were measured using a free radical sensor H2DCF-DA. RESULTS: We found that SIT significantly extended lifespan and health-span of C. elegans. Mechanistically, we found that several age-related pathways and genes were involved in SIT-induced lifespan extension. The transcription factors DAF-16/FOXO, SKN-1/NRF2 and HSF-1 played important roles in SIT-induced longevity. Moreover, our findings illustrated that SIT induced survival benefits by inhibiting the insulin/insulin-like signaling (IIS) pathway and activating the dietary restriction (DR)-related and mitochondrial function-related signaling pathways. CONCLUSION: Our work may provide a theoretical basis for the development of anti-T2D drugs as anti-aging drugs, especially for the treatment of age-related disease in diabetic patients.
ESTHER : Ye_2023_Gerontology__
PubMedSearch : Ye_2023_Gerontology__
PubMedID: 37952525

Title : Impact of Donepezil Supplementation on Alzheimer's Disease-like Pathology and Gut Microbiome in APP\/PS1 Mice - Li_2023_Microorganisms_11_
Author(s) : Li Y , Wu M , Kong M , Sui S , Wang Q , He Y , Gu J
Ref : Microorganisms , 11 : , 2023
Abstract : Based on published information, the occurrence and development of Alzheimer's disease (AD) are potentially related to gut microbiota changes. Donepezil hydrochloride (DH), which enhances cholinergic activity by blocking acetylcholinesterase (AChE), is one of the first-line drugs for AD treatment approved by the Food and Drug Administration (FDA) of the USA. However, the potential link between the effects of DH on the pathophysiological processes of AD and the gut microbiota remains unclear. In this study, pathological changes in the brain and colon, the activities of superoxide dismutase (SOD) and AChE, and changes in intestinal flora were observed. The results showed that Abeta deposition in the prefrontal cortex and hippocampus of AD mice was significantly decreased, while colonic inflammation was significantly alleviated by DH treatment. Concomitantly, SOD activity was significantly improved, while AChE was significantly reduced after DH administration. In addition, the gut microbiota community composition of AD mice was significantly altered after DH treatment. The relative abundance of Akkermansia in the AD group was 54.8% higher than that in the N group. The relative abundance of Akkermansia was increased by 18.3% and 53.8% in the AD_G group and the N_G group, respectively. Interestingly, Akkermansia showed a potential predictive value and might be a biomarker for AD. Molecular docking revealed the binding mode and major forces between DH and membrane proteins of Akkermansia. The overall results suggest a novel therapeutic mechanism for treating AD and highlight the critical role of gut microbiota in AD pathology.
ESTHER : Li_2023_Microorganisms_11_
PubMedSearch : Li_2023_Microorganisms_11_
PubMedID: 37764150

Title : Cholinesterase inhibitors-associated torsade de pointes\/QT prolongation: a real-world pharmacovigilance study - Zhang_2023_Front.Pharmacol_14_1343650
Author(s) : Zhang N , Gan L , Xiang G , Xu J , Jiang T , Li Y , Wu Y , Ni R , Liu Y
Ref : Front Pharmacol , 14 :1343650 , 2023
Abstract : Objective: Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer's disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation. Methods: All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs. Results: 557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within 1 month after taking ChEIs. The drug with the highest frequency of combination with donepezil and galantamine is citalopram, and the drug with the highest frequency of combination with rivastigmine is atorvastatin. Conclusion: The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in elderly women, the initial stage after taking ChEIs, and when ChEIs combining with drugs that could prolong the QT interval.
ESTHER : Zhang_2023_Front.Pharmacol_14_1343650
PubMedSearch : Zhang_2023_Front.Pharmacol_14_1343650
PubMedID: 38273821

Title : Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis - Xu_2023_World.J.Gastroenterol_29_3534
Author(s) : Xu YF , Hao YX , Ma L , Zhang MH , Niu XX , Li Y , Zhang YY , Liu TT , Han M , Yuan XX , Wan G , Xing HC
Ref : World J Gastroenterol , 29 :3534 , 2023
Abstract : BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.
ESTHER : Xu_2023_World.J.Gastroenterol_29_3534
PubMedSearch : Xu_2023_World.J.Gastroenterol_29_3534
PubMedID: 37389241

Title : Improving the Efficiency of Precise Genome Editing with CRISPR\/Cas9 to Generate Goats Overexpressing Human Butyrylcholinesterase - Wang_2023_Cells_12_
Author(s) : Wang JH , Wu SJ , Li Y , Zhao Y , Liu ZM , Deng SL , Lian ZX
Ref : Cells , 12 : , 2023
Abstract : The CRISPR/Cas9 system is widely used for genome editing in livestock production, although off-target effects can occur. It is the main method to produce genome-edited goats by somatic cell nuclear transfer (SCNT) of CRISPR/Cas9-mediated genome-edited primary goat fetal fibroblast cells (GFFs). Improving the double-strand break (DSB) efficiency of Cas9 in primary cells would improve the homologous repair (HR) efficiency. The low efficiency of HR remains a major hurdle in CRISPR/Cas9-mediated precise genome editing, increasing the work required to screen the genome-edited primary cell clones. In this study, we modified several essential parameters that affect the efficiency of the CRISPR/Cas9-mediated knock-in GFF cloning system, including establishing a high-efficiency transfection system for primary cells via nucleofection and optimizing homology arm (HA) length during HR. Here, we specifically inserted a recombinant human butyrylcholinesterase gene (rhBChE) into the goat fibroblast growth factor (FGF)-5 locus through the CRISPR/Cas9 system, thereby achieving simultaneous rhBChE insertion and FGF5 knock-out. First, this study introduced the Cas9, FGF5 knock-out small guide RNA, and rhBChE knock-in donors into GFFs by electroporation and obtained positive cell clones without off-target effects. Then, we demonstrated the expression of rhBChE in GFF clones and verified its function. Finally, we obtained a CRISPR/Cas9-mediated rhBChE-overexpression goat.
ESTHER : Wang_2023_Cells_12_
PubMedSearch : Wang_2023_Cells_12_
PubMedID: 37508483

Title : Neuroligins facilitate the development of bone cancer pain via regulating synaptic transmission: an experimental study - Xie_2023_Braz.J.Anesthesiol__
Author(s) : Xie X , Li Y , Su S , Li X , Xu X , Gao Y , Peng M , Ke C
Ref : Braz J Anesthesiol , : , 2023
Abstract : BACKGROUND: The underlying mechanism of chronic pain involves the plasticity in synaptic receptors and neurotransmitters. This study aimed to investigate potential roles of Neuroligins (NLs) within the spinal dorsal horn of rats in a newly established Bone Cancer Pain (BCP) model. The objective was to explore the mechanism of neuroligin involved in the occurrence and development of bone cancer pain. METHODS: Using our rat BCP model, we assessed pain hypersensitivity over time. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to investigate NL expression, and NLs were overexpressed in the rat spinal cord using lentiviral vectors. Immunofluorescence staining and whole-cell patch-clamp recordings were deployed to investigate the role of NLs in the development of BCP. RESULTS: We observed reduced expression levels of NL1 and NL2, but not of NL3, within the rat spinal cord, which were found to be associated with and essential for the development of BCP in our model. Accordingly, NL1 or NL2 overexpression in the spinal cord alleviated mechanical hypersensitivity of rats. Electrophysiological experiments indicated that NL1 and NL2 are involved in BCP via regulating gamma-aminobutyric acid-ergic interneuronal synapses and the activity of glutamatergic interneuronal synapses, respectively. CONCLUSIONS: Our observations unravel the role of NLs in cancer-related chronic pain and further suggest that inhibitory mechanisms are central features of BCP in the spinal dorsal horn. These results provide a new perspective and basis for subsequent studies elucidating the onset and progression of BCP.
ESTHER : Xie_2023_Braz.J.Anesthesiol__
PubMedSearch : Xie_2023_Braz.J.Anesthesiol__
PubMedID: 36841430

Title : Soluble epoxide hydrolase deficiency attenuates airway inflammation in COPD via IRE1alpha\/JNK\/AP-1 signaling pathway - Yu_2023_J.Inflamm.(Lond)_20_36
Author(s) : Yu Y , Yang A , He X , Wu B , Wu Y , Li Y , Nie S , Xu B , Wang H , Yu G
Ref : J Inflamm (Lond) , 20 :36 , 2023
Abstract : BACKGROUND: Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown. METHOD: 16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD. Human epithelial cells were used in vitro to determine the regulation mechanism of sEH in endoplasmic reticulum stress induced by cigarette smoke. RESULTS: sEH deficiency helps reduce emphysema formation after smoke exposure by alleviating endoplasmic reticulum stress response. sEH deficiency effectively reverses the upregulation of phosphorylation IRE1alpha and JNK and the nuclear expression of AP-1, alleviating the secretion of inflammatory factors induced by cigarette smoke extract. Furthermore, the treatment with endoplasmic reticulum stress and IRE1alpha inhibitor downregulated cigarette smoke extract-induced sEH expression and the secretion of inflammatory factors. CONCLUSION: sEH probably alleviates airway inflammatory response and endoplasmic reticulum stress via the IRE1alpha/JNK/AP-1 pathway, which might attenuate lung injury caused by long-term smoking and provide a new pharmacological target for preventing and treating COPD.
ESTHER : Yu_2023_J.Inflamm.(Lond)_20_36
PubMedSearch : Yu_2023_J.Inflamm.(Lond)_20_36
PubMedID: 37915073

Title : Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Abeta damage and targeting the ERK pathway - Li_2023_J.Ethnopharmacol__117564
Author(s) : Li Y , Wu H , Liu M , Zhang Z , Ji Y , Xu L , Liu Y
Ref : J Ethnopharmacol , :117564 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect beta-amyloid (Abeta) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Abeta deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Abeta damage and targeting the ERK pathway.
ESTHER : Li_2023_J.Ethnopharmacol__117564
PubMedSearch : Li_2023_J.Ethnopharmacol__117564
PubMedID: 38081400

Title : Impacts of QM region sizes and conformation numbers on modelling enzyme reactions: a case study of polyethylene terephthalate hydrolase - Zheng_2023_Phys.Chem.Chem.Phys__
Author(s) : Zheng M , Li Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , : , 2023
Abstract : A quantum mechanics/molecular mechanics (QM/MM) approach is a broadly used tool in computational enzymology. Treating the QM region with a high-level DFT method is one of the important branches. Here, taking leaf-branch compost cutinase-catalyzed polyethylene terephthalate depolymerization as an example, the convergence behavior of energy barriers as well as key structural and charge features with respect to the size of the QM region (up to 1000 atoms) is systematically investigated. BP86/6-31G(d)//CHARMM and M06-2X/6-311G(d,p)//CHARMM level of theories were applied for geometry optimizations and single-point energy calculations, respectively. Six independent enzyme conformations for all the four catalytic steps (steps (i)-(iv)) were considered. Most of the twenty-four cases show that at least 500 QM atoms are needed while only two rare cases show that -100 QM atoms are sufficient for convergence when only a single conformation was considered. This explains why most previous studies showed that 500 or more QM atoms are required while a few others showed that -100 QM atoms are sufficient for DFT/MM calculations. More importantly, average energy barriers and key structural/charge features from six conformations show an accelerated convergence than that in a single conformation. For instance, to reach energy barrier convergence (within 2.0 kcal mol(-1)) for step (ii), only -100 QM atoms are required if six conformations are considered while 500 or more QM atoms are needed with a single conformation. The convergence is accelerated to be more rapid if hundreds and thousands of conformations were considered, which aligns with previous findings that only several dozens of QM atoms are required for convergence with semi-empirical QM/MM MD simulations.
ESTHER : Zheng_2023_Phys.Chem.Chem.Phys__
PubMedSearch : Zheng_2023_Phys.Chem.Chem.Phys__
PubMedID: 37917137

Title : Coupling multifactor dominated the biochemical response and the alterations of intestinal microflora of earthworm Pheretima guillelmi due to typical herbicides - Chang_2023_Environ.Sci.Pollut.Res.Int__
Author(s) : Chang X , Fu F , Sun Y , Zhao L , Li X , Li Y
Ref : Environ Sci Pollut Res Int , : , 2023
Abstract : The excessive application of herbicides on farmlands can substantially reduce labor costs and increase crop yields, but can also have undesirable effects on terrestrial ecosystems. To evaluate the ecological toxicity of herbicides, metolachlor and fomesafen, two typical herbicides that are extensively used worldwide were chosen as target pollutants, and the endogeic earthworm Pheretima guillelmi, which is widely distributed in China, was selected as the test organism. A laboratory-scale microcosmic experiment was set, and energy resources, enzymes, and the composition and connections of intestinal microorganisms in earthworms were determined. Both herbicides depleted the energy resources of the earthworms, especially glycogen contents; increased the levels of antioxidant enzymes; and inhibited acetylcholinesterase. Moreover, the richness and diversity of the intestinal bacterial community of the earthworms were suppressed. Additionally, the bacterial composition at the genus level changed greatly and the connections between dominant bacteria increased dramatically. Most interactions among the bacterial genera belonging to the same and different phyla showed mutualism and competition, respectively. Importantly, metolachlor with higher toxicity had a transitory effect on these indicators in earthworms, whereas fomesafen, with lower toxicity but stronger bioaccumulation potential, exerted a sustaining impact on earthworms. Collectively, these results indicate that the toxic effects of herbicides on terrestrial organisms should be comprehensively considered in combination with biological toxicity, persistence, bioaccumulation potential, and other factors.
ESTHER : Chang_2023_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Chang_2023_Environ.Sci.Pollut.Res.Int__
PubMedID: 37526832

Title : Network pharmacology combined with an animal model to reveal the material basis and mechanism of Amomum villosum in alleviating constipation in mice - Liu_2023_Gene_897_148064
Author(s) : Liu S , Zhao Y , Li S , Li Y , Liu L , Sheng J , Tian Y , Gao X
Ref : Gene , 897 :148064 , 2023
Abstract : Constipation is a prevalent gastrointestinal disorder, with its prevalence showing an annual upward trend. There are many factors involved in the occurrence of constipation, such as abnormal smooth muscle contraction and disorders of gastrointestinal hormone secretion. Amomum villosum (A. villosum) has been proven to be effective in improving digestive system diseases, but there is no report on improving constipation. Therefore, we used network pharmacology prediction combined with animal experiments to explore the key active components of A. villosum and their pharmacological mechanisms. The results of network pharmacological prediction showed that beta-sitosterol was the key laxative compound of A. villosum, which may play a laxative role by activating the adrenoceptor alpha 1 A-myosin light chain (ADRA1A-MLC) pathway. Further animal experiments showed that beta-sitosterol could significantly shorten the time to first black stool; increase faecal weight, faecal number, and faecal water content; and promote gastrointestinal motility. beta-sitosterol may promote intestinal motility by upregulating the expression of ADRA1A and myosin light chain 9 (Myl9) mRNA and protein in the colon, thereby activating the ADRA1A-MLC signalling pathway. In addition, it is possible to improve constipation symptoms by regulating serum neurotransmitters and gastrointestinal motility-related factors, such as the serum content of 5-hydroxytryptamine (5-HT) and acetylcholinesterase (AchE) and the mRNA expression of 5-hydroxytryptamine receptor 4 (5-HT4), stem cell factor (SCF), stem cell factor receptor (c-Kit) and smooth muscle myosin light chain kinase (smMLCK) in the colon. These results lay a foundation for the application of A. villosum and beta-sitosterol in constipation.
ESTHER : Liu_2023_Gene_897_148064
PubMedSearch : Liu_2023_Gene_897_148064
PubMedID: 38065427

Title : Characteristics of CXE family of Salvia miltiorrhiza and identification of interactions between SmGID1s and SmDELLAs - Li_2023_Plant.Physiol.Biochem_206_108140
Author(s) : Li Y , Pang Q , Li B , Fu Y , Guo M , Zhang C , Tian Q , Hu S , Niu J , Wang S , Wang D , Wang Z
Ref : Plant Physiol Biochem , 206 :108140 , 2023
Abstract : Carboxylesterase (CXE) is a class of hydrolases that contain an alpha/beta folding domain, which plays critical roles in plant growth, development, and stress responses. Based on the genomic and transcriptomic data of Salvia miltiorrhiza, the SmCXE family was systematically analyzed using bioinformatics. The results revealed 34 SmCXE family members in S. miltiorrhiza, and the SmCXE family could be divided into five groups (Group I, Group II, Group III, Group IV, and Group V). Cis-regulatory elements indicated that the SmCXE promoter region contained tissue-specific and development-related, hormone-related, stress-related, and photoresponsive elements. Transcriptome analysis revealed that the expression levels of SmCXE2 were highest in roots and flowers (SmCXE8 was highest in stems and SmCXE19 was highest in leaves). Further, two GA receptors SmCXE1 (SmGID1A) and SmCXE2 (SmGID1B) were isolated from the SmCXE family, which are homologous to other plants. SmGID1A and SmGID1B have conserved HGGSF motifs and active amino acid sites (Ser-Asp-Val/IIe), which are required to maintain their GA-binding activities. SmGID1A and SmGID1B were significantly responsive to gibberellic acid (GA(3)) and methyl jasmonate (MeJA) treatment. A subcellular assay revealed that SmCXE1 and SmCXE2 resided within the nucleus. SmGID1B can interact with SmDELLAs regardless of whether GA(3) exists, whereas SmGID1A can only interact with SmDELLAs in the presence of GA(3). A Further assay showed that the GRAS domain mediated the interactions between SmGID1s and SmDELLAs. This study lays a foundation for further elucidating the role of SmCXE in the growth and development of S. miltiorrhiza.
ESTHER : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedSearch : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedID: 38134738
Gene_locus related to this paper: salmi-SmCXE1 , salmi-SmCXE2 , salmi-SmCXE3 , salmi-SmCXE4 , salmi-SmCXE5 , salmi-SmCXE6 , salmi-SmCXE7 , salmi-SmCXE8 , salmi-SmCXE9 , salmi-SmCXE10 , salmi-SmCXE11 , salmi-SmCXE12 , salmi-SmCXE13 , salmi-SmCXE14 , salmi-SmCXE15 , salmi-SmCXE16 , salmi-SmCXE17 , salmi-SmCXE18 , salmi-SmCXE19 , salmi-SmCXE20 , salmi-SmCXE21 , salmi-SmCXE22 , salmi-SmCXE23 , salmi-SmCXE24 , salmi-SmCXE25 , salmi-SmCXE26 , salmi-SmCXE27 , salmi-SmCXE28 , salmi-SmCXE29 , salmi-SmCXE30 , salmi-SmCXE31 , salmi-SmCXE32 , salmi-SmCXE33 , salmi-SmCXE34

Title : Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038 - Li_2023_Nat.Prod.Res__1
Author(s) : Li H , Long J , Wang X , She J , Liu Y , Li Y , Yang B
Ref : Nat Prod Res , :1 , 2023
Abstract : Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.
ESTHER : Li_2023_Nat.Prod.Res__1
PubMedSearch : Li_2023_Nat.Prod.Res__1
PubMedID: 37129009

Title : Feed-forward activation of habenula cholinergic neurons by acetylcholine - Chung_2023_Neurosci__
Author(s) : Chung L , Jing M , Li Y , Tapper AR
Ref : Neuroscience , : , 2023
Abstract : While the functional and behavioral role of the medial habenula (MHb) is still emerging, recent data indicate an involvement of this nuclei in regulating mood, aversion, and addiction. Unique to the MHb is a large cluster of cholinergic neurons that project to the interpeduncular nucleus and densely express acetylcholine receptors (AChRs) suggesting that the activity of these cholinergic neurons may be regulated by ACh itself. Whether endogenous ACh from within the habenula regulates cholinergic neuron activity has not been demonstrated. Supporting a role for ACh in modulating MHb activity, acetylcholinesterase inhibitors (ACEIs) increased the firing rate of MHb cholinergic neurons in mouse habenula slices, an effect blocked by AChR antagonists and mediated by ACh which was detected via expressing fluorescent ACh sensors in MHbin vivo. To test if cholinergic afferents innervate MHb cholinergic neurons, we used anterograde and retrograde viral tracing to identify cholinergic inputs. Surprisingly, tracing experiments failed to detect cholinergic inputs into the MHb, including from the septum, suggesting that MHb cholinergic neurons may release ACh within the MHb to drive cholinergic activity. To test this hypothesis, we expressed channelrhodopsin in a portion ofMHb cholinergic neurons while recording from non-opsin-expressing neurons. Light pulses progressively increased activity of MHb cholinergic neurons indicating feed-forward activation driven by MHb ACh release. These data indicate MHb cholinergic neurons may utilize a unique feed-forward mechanism to synchronize and increase activity by releasing local ACh.
ESTHER : Chung_2023_Neurosci__
PubMedSearch : Chung_2023_Neurosci__
PubMedID: 37572877

Title : Fluorescent assay for acetylcholinesterase activity and inhibitor screening based on lanthanide organic\/inorganic hybrid materials - Zhang_2023_Anal.Methods__
Author(s) : Zhang B , Wang Y , Wu D , Zhao Q , Chen Y , Li Y , Sun J , Yang X
Ref : Anal Methods , : , 2023
Abstract : It is of great significance for the clinical diagnosis of Alzheimer's disease (AD) to achieve the on-site activity evaluation of acetylcholinesterase (AChE), the hydrolase of acetylcholine (ACh). Herein, we have developed a biosensing method endowed with considerable superiority based on the organic-inorganic hybrid composite Eu(DPA)(3)@Lap with excellent stability and fluorescent properties for this purpose by loading Eu(3+) ions and 2,6-dipicolinic acid (DPA) into LAPONITE(a) (Lap). Through the comprehensive consideration of the specific hydrolysis of acetylthiocholine (ATCh) into thiocholine (TCh) by AChE, the high binding affinity of TCh to copper ion (Cu(2+)), and the selective fluorescence quenching ability of Cu(2+), a simple Eu(DPA)(3)@Lap-based assay was developed to realize the rapid and convenient evaluation of AChE activity. Owning to the facile signal on-off-on response mode with a clear PET-based sensing mechanism, our assay presents favorable selectivity and sensitivity (LOD of 0.5 mU mL(-1)). Furthermore, the fluorescent assay was successfully applied for assessing AChE activity in human serum samples and screening potential AChE inhibitors, showing potential for application in the early diagnosis and drug screening of AD, as a new development path of AD therapy.
ESTHER : Zhang_2023_Anal.Methods__
PubMedSearch : Zhang_2023_Anal.Methods__
PubMedID: 38116865

Title : Therapeutic potential of aromatic plant extracts in Alzheimer's disease: Comprehensive review of their underlying mechanisms - Ma_2023_CNS.Neurosci.Ther__
Author(s) : Ma Y , Li Y , Yin R , Guo P , Lei N , Li G , Xiong L , Xie Y
Ref : CNS Neurosci Ther , : , 2023
Abstract : AIMS: The aim of this review is to outline recent advancements in the application and mechanistic studies of aromatic plant extracts in Alzhermer`s disease (AD) to demonstrate their value in the management of this disease. BACKGROUND: AD is a neurodegenerative disease with a complex pathogenesis characterized by severe cognitive impairment. Currently, there are very few drugs available for the treatment of AD, and treatments are primarily focused on symptom relief. Aromatherapy is a traditional complementary alternative therapy that focuses on the prevention and treatment of the disease through the inhalation or transdermal administration of aromatic plant extracts. Over the past few years, studies on the use of aromatic plant extracts for the treatment of AD have been increasing and have demonstrated a definitive therapeutic effect. METHODS: We systematically summarized in vitro, in vivo, and clinical studies focusing on the potential use of aromatic plant extracts in the treatment of AD in PubMed, ScienceDirect, Google Scholar, and the Chinese National Knowledge Infrastructure from 2000 to 2022. RESULTS: Our literature survey indicates that aromatic plant extracts exert anti-AD effects by modulating pathological changes through anti-amyloid, anti-tau phosphorylation, anti-cholinesterase, anti-inflammation, and anti-oxidative stress mechanisms (Figure 1). CONCLUSION: This review provides a future strategy for the research of novel anti-AD drugs from aromatic plant extracts.
ESTHER : Ma_2023_CNS.Neurosci.Ther__
PubMedSearch : Ma_2023_CNS.Neurosci.Ther__
PubMedID: 37122144

Title : Fermentation of Lactobacillus fermentum NB02 with feruloyl esterase production increases the phenolic compounds content and antioxidant properties of oat bran - Li_2023_Food.Chem_437_137834
Author(s) : Li Y , Zhang Y , Dong L , Liu Y , Liu L
Ref : Food Chem , 437 :137834 , 2023
Abstract : In this study, strains producing feruloyl esterase were screened by Oxford Cup clear zones method and by evaluating the ability to decompose hydroxycinnamoyl esters. The strain was identified by 16S rDNA molecular biology. The contents of dietary fiber, reducing sugar, water-extractable arabinoxylans, phytic acid, total phenolics, total flavonoid, phenolic compounds composition, microstructure and antioxidant activity in bran before and after fermentation were studied. Eight strains producing feruloyl esterase were screened, among which strain P1 had the strongest ability to decompose hydroxycinnamoyl esters. The strain was identified and named L. fermentum NB02. Compared with unfermented bran, fermented bran exhibited higher contents of soluble dietary fiber, reducing sugar, water-extractable arabinoxylans, total phenolics, total flavonoid, and lower insoluble dietary fiber and phytic acid content. The dense surface structure of bran was destroyed, forming a porous structure. The release of phenolic compounds increased significantly. L. fermentum NB02 fermentation improved the antioxidant capacity of bran.
ESTHER : Li_2023_Food.Chem_437_137834
PubMedSearch : Li_2023_Food.Chem_437_137834
PubMedID: 37897817

Title : In vitro deacetylation of N-acetylserotonin by arylacetamide deacetylase - Huang_2023_J.Pineal.Res_75_e12870
Author(s) : Huang Z , Li Y , Konishi K , Sakai Y , Tashiro K , Fukami T , Borjigin J
Ref : J Pineal Res , 75 :e12870 , 2023
Abstract : Arylacetamide deacetylase (AADAC) is a deacetylation enzyme present in the mammalian liver, gastrointestinal tract, and brain. During our search for mammalian enzymes capable of metabolizing N-acetylserotonin (NAS), AADAC was identified as having the ability to convert NAS to serotonin. Both human and rodent recombinant AADAC proteins can deacetylate NAS in vitro, although the human AADAC shows markedly higher activity compared with rodent enzyme. The AADAC-mediated deacetylation reaction can be potently inhibited by eserine in vitro. In addition to NAS, recombinant hAADAC can deacetylate melatonin (to form 5-methoxytryptamine) and N-acetyltryptamine (NAT) (to form tryptamine). In addition to the in vitro deacetylation of NAS by the recombinant AADAC proteins, liver (mouse and human) and brain (human) extracts were able to deacetylate NAS; these activities were sensitive to eserine. Taken together, these results demonstrate a new role for AADAC and suggest a novel pathway for the AADAC-mediated metabolism of pineal indoles in mammals.
ESTHER : Huang_2023_J.Pineal.Res_75_e12870
PubMedSearch : Huang_2023_J.Pineal.Res_75_e12870
PubMedID: 37002641

Title : Dinotefuran induces oxidative stress and autophagy on Bombyx mori silk gland: Toxic effects and implications for nontarget organisms - Huang_2023_Environ.Pollut_336_122470
Author(s) : Huang Y , Zou S , Zhan P , Hao Z , Lu Q , Jing W , Li Y , Xu Y , Wang H
Ref : Environ Pollut , 336 :122470 , 2023
Abstract : Dinotefuran, a third-generation neonicotinoid insecticide, is widely utilized in agriculture for pest control; however, its environmental consequences and risks to non-target organisms remain largely unknown. Bombyx mori is an economically important insect and a good toxic detector for environmental assessments. In this study, ultrastructure analysis showed that dinotefuran exposure caused an increase in autophagic vesicles in the silk gland. Dinotefuran exposure triggered elevated levels of oxidative stress in silk glands. Reactive oxygen species, oxidized glutathione disulfide, glutathione peroxidase, the activities of UDP glucuronosyl-transferase and carboxylesterase were induced in the middle silk gland, while malondialdehyde, reactive oxygen species, superoxide dismutase oxidized glutathione disulfide were increased in the posterior silk gland. Global transcription patterns revealed the physiological responses were induced by dinotefuran. Dinotefuran exposure substantially induced the expression levels of many genes involved in the mTOR and PI3K - Akt signaling pathways in the middle silk gland, whereas many differentially expressed genes involved in fatty acid and pyrimidine metabolism were found in the posterior silk gland. Additionally, functional, ultrastructural, and transcriptomic analysis indicate that dinotefuran exposure induced an increase of autophagy in the silk gland. This study illuminates the toxicity effects of dinotefuran exposure on silkworms and provides new insights into the underlying molecular toxicity mechanisms of dinotefuran to nontarget organisms.
ESTHER : Huang_2023_Environ.Pollut_336_122470
PubMedSearch : Huang_2023_Environ.Pollut_336_122470
PubMedID: 37657723

Title : Characterization of the metabolism of eupalinolide A and B by carboxylesterase and cytochrome P450 in human liver microsomes - Li_2023_Front.Pharmacol_14_1093696
Author(s) : Li Y , Liu X , Li L , Zhang T , Gao Y , Zeng K , Wang Q
Ref : Front Pharmacol , 14 :1093696 , 2023
Abstract : Eupalinolide A (EA; Z-configuration) and eupalinolide B (EB; E-configuration) are bioactive cis-trans isomers isolated from Eupatorii Lindleyani Herba that exert anti-inflammatory and antitumor effects. Although one pharmacokinetic study found that the metabolic parameters of the isomers were different in rats, metabolic processes relevant to EA and EB remain largely unknown. Our preliminary findings revealed that EA and EB are rapidly hydrolyzed by carboxylesterase. Here, we investigated the metabolic stability and enzyme kinetics of carboxylesterase-mediated hydrolysis and cytochrome P450 (CYP)-mediated oxidation of EA and EB in human liver microsomes (HLMs). We also explored differences in the hydrolytic stability of EA and EB in human liver microsomes and rat liver microsomes (RLMs). Moreover, cytochrome P450 reaction phenotyping of the isomers was performed via in silico methods (i.e., using a quantitative structure-activity relationship model and molecular docking) and confirmed using human recombinant enzymes. The total normalized rate approach was considered to assess the relative contributions of five major cytochrome P450s to EA and EB metabolism. We found that EA and EB were eliminated rapidly, mainly by carboxylesterase-mediated hydrolysis, as compared with cytochrome P450-mediated oxidation. An inter-species difference was observed as well, with faster rates of EA and EB hydrolysis in rat liver microsomes. Furthermore, our findings confirmed EA and EB were metabolized by multiple cytochrome P450s, among which CYP3A4 played a particularly important role.
ESTHER : Li_2023_Front.Pharmacol_14_1093696
PubMedSearch : Li_2023_Front.Pharmacol_14_1093696
PubMedID: 36762117

Title : Comparative expression profiles of carboxylesterase orthologous CXE14 in two closely related tea geometrid species, Ectropis obliqua Prout and Ectropis grisescens Warren - Yang_2023_Front.Physiol_14_1194997
Author(s) : Yang F , Li Y , Gao M , Xia Q , Wang Q , Tang M , Zhou X , Guo H , Xiao Q , Sun L
Ref : Front Physiol , 14 :1194997 , 2023
Abstract : Insect carboxylesterases (CXEs) can be expressed in multiple tissues and play crucial roles in detoxifying xenobiotic insecticides and degrading olfactory cues. Therefore, they have been considered as an important target for development of eco-friendly insect pest management strategies. Despite extensive investigation in most insect species, limited information on CXEs in sibling moth species is currently available. The Ectropis obliqua Prout and Ectropis grisescens Warren are two closely related tea geometrid species, which share the same host of tea plant but differ in geographical distribution, sex pheromone composition, and symbiotic bacteria abundance, providing an excellent mode species for studies of functional diversity of orthologous CXEs. In this study, we focused on EoblCXE14 due to its previously reported non-chemosensory organs-biased expression. First, the EoblCXE14 orthologous gene EgriCXE14 was cloned and sequence characteristics analysis showed that they share a conserved motif and phylogenetic relationship. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to compare the expression profiles between two Ectropis spp. The results showed that EoblCXE14 was predominately expressed in E. obliqua larvae, whereas EgriCXE14 was abundant in E. grisescens at multiple developmental stages. Interestingly, both orthologous CXEs were highly expressed in larval midgut, but the expression level of EoblCXE14 in E. obliqua midgut was significantly higher than that of EgriCXE14 in E. grisescens midgut. In addition, the potential effect of symbiotic bacteria Wolbachia on the CXE14 was examined. This study is the first to provide comparative expression profiles of orthologous CXE genes in two sibling geometrid moth species and the results will help further elucidate CXEs functions and identify a potential target for tea geometrid pest control.
ESTHER : Yang_2023_Front.Physiol_14_1194997
PubMedSearch : Yang_2023_Front.Physiol_14_1194997
PubMedID: 37293262

Title : Rescuing yeast from cell death enables overproduction of fatty acids from sole methanol - Gao_2022_Nat.Metab__
Author(s) : Gao J , Li Y , Yu W , Zhou YJ
Ref : Nat Metab , : , 2022
Abstract : Methanol is an ideal feedstock for biomanufacturing that can be beneficial for global carbon neutrality; however, the toxicity of methanol limits the efficiency of methanol metabolism toward biochemical production. We here show that engineering production of free fatty acids from sole methanol results in cell death with decreased cellular levels of phospholipids in the methylotrophic yeast Ogataea polymorpha, and cell growth is restored by adaptive laboratory evolution. Whole-genome sequencing of the adapted strains reveals that inactivation of LPL1 (encoding a putative lipase) and IZH3 (encoding a membrane protein related to zinc metabolism) preserve cell survival by restoring phospholipid metabolism. Engineering the pentose phosphate pathway and gluconeogenesis enables high-level production of free fatty acid (15.9 g l(-1)) from sole methanol. Preventing methanol-associated toxicity underscores the link between lipid metabolism and methanol tolerance, which should contribute to enhancing methanol-based biomanufacturing.
ESTHER : Gao_2022_Nat.Metab__
PubMedSearch : Gao_2022_Nat.Metab__
PubMedID: 35817856

Title : MiR-181a-5p facilitates proliferation, invasion, and glycolysis of breast cancer through NDRG2-mediated activation of PTEN\/AKT pathway - Zhai_2022_Bioengineered_13_83
Author(s) : Zhai Z , Mu T , Zhao L , Li Y , Zhu D , Pan Y
Ref : Bioengineered , 13 :83 , 2022
Abstract : Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of breast cancer. In this research, we explored the involvement of miR-181a-5p in the progression of breast cancer and investigated potential molecular mechanisms. Firstly, the miR-181a-5p and N-myc downstream-regulated gene (NDRG) 2 expression was detected by real-time quantitative polymerase chain reaction. Cellular processes were assessed using Cell Counting Kit 8, Bromodeoxyuridine, colony formation and transwell assays. HK2, PKM2 and LDHA activities were assessed by ELISA. The combination between miR-181a-5p was assessed by dual-luciferase reporter assay and RNA pull-down assay. The results indicated that miR-181a-5p levels were upregulated and NDRG2 levels were downregulated in breast cancer, leading to poor prognosis. Silencing of miR-181a-5p inhibited cell proliferation, invasion, glycolysis, and xenograft tumor growth, while enhanced miR-181a-5p got the opposite results. Furthermore, NDRG2 acts as a target of miR-181a-5p. Knockout of NDRG2 facilitated biological behaviors and meanwhile enhanced phosphorylation (p)-PTEN and p-AKT levels. Rescue experiments showed that restoring NDRG2 abolished the effects caused by miR-181a-5p in breast cancer cells. In conclusion, miR-181a-5p facilitated tumor progression through NDRG2-induced activation of PTEN/AKT signaling pathway of breast cancer, suggesting that focusing on miR-181a-5p may provide new insight for breast cancer therapy.Abbreviations Brdu: Bromodeoxyuridine; CCK-8: Cell Counting Kit-8; miRNA: microRNAs; mut: mutant; RT-qPCR: real-time quantitative polymerase chain reaction; UTR: untranslated region; WT: wild-type.
ESTHER : Zhai_2022_Bioengineered_13_83
PubMedSearch : Zhai_2022_Bioengineered_13_83
PubMedID: 34951340
Gene_locus related to this paper: human-NDRG2

Title : Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population - Bai_2022_Microbiome_10_147
Author(s) : Bai X , Sun Y , Li Y , Li M , Cao Z , Huang Z , Zhang F , Yan P , Wang L , Luo J , Wu J , Fan D , Chen H , Zhi M , Lan P , Zeng Z , Wu X , Miao Y , Zuo T
Ref : Microbiome , 10 :147 , 2022
Abstract : BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.
ESTHER : Bai_2022_Microbiome_10_147
PubMedSearch : Bai_2022_Microbiome_10_147
PubMedID: 36100953

Title : Biochemical toxicity and transcriptome aberration induced by dinotefuran in Bombyx mori - Xu_2022_Environ.Pollut__119562
Author(s) : Xu S , Hao Z , Li Y , Zhou Y , Shao R , Chen R , Zheng M , Xu Y , Wang H
Ref : Environ Pollut , :119562 , 2022
Abstract : Dinotefuran is a third-generation neonicotinoid pesticide and is increasingly used in agricultural production, which has adverse effects on nontarget organisms. However, the research on the impact of dinotefuran on nontarget organisms is still limited. Here the toxic effects of dinotefuran on an economic lepidopteran model insect, Bombyx mori, were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. Cytochrome P450, glutathione S-transferase, carboxylesterase, and UDP glycosyl-transferase activities were induced in the fat body at early stages after dinotefuran exposure. By contrast, only glutathione S-transferase activity was increased in the midgut. To overcome the lack of sensitivity of the biological assays at the individual organism level, RNA sequencing was performed to measure differential expressions of mRNA from silkworm larvae after dinotefuran exposure. Differential gene expression profiling revealed that various detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with the upregulation of the detoxifying enzyme. The global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved multiple cellular processes, including energy metabolism, oxidative stress, detoxification, and other fundamental physiological processes. Many metabolism processes, such as carbon metabolism, fatty acid biosynthesis, pyruvate metabolism, and the citrate cycle, were partially repressed in the midgut or fat body. Furthermore, dinotefuran significantly activated the MAPK/CREB, CncC/Keap1, PI3K/Akt, and Toll/IMD pathways. The links between physiological, biochemical toxicity and comparative transcriptomic analysis facilitated the systematic understanding of the integrated biological toxicity of dinotefuran. This study provides a holistic view of the toxicity and detoxification metabolism of dinotefuran in silkworm and other organisms.
ESTHER : Xu_2022_Environ.Pollut__119562
PubMedSearch : Xu_2022_Environ.Pollut__119562
PubMedID: 35659910

Title : Biological evaluation, molecular modeling and dynamics simulation of phenanthrenes isolated from Bletilla striata as butyrylcholinesterase inhibitors - Liu_2022_Sci.Rep_12_13649
Author(s) : Liu Y , Tu Y , Kang Y , Zhu C , Wu C , Chen G , Liu Z , Li Y
Ref : Sci Rep , 12 :13649 , 2022
Abstract : As part of our continuous studies on natural cholinesterase inhibitors from plant kingdom, the 95% ethanol extract from tubers of Bletilla striata showed promising butyrylcholinesterase (BChE) inhibition (IC(50) = 8.6 microg/mL). The extracts with different polarities (petroleum ether, ethyl acetate, n-butanol, and water) were prepared and evaluated for their inhibition of cholinesterases. The most active ethyl acetate extract was subjected to a bioassay-guided isolation and afforded twenty-two bibenzyls and phenanthrenes (1-22). All isolates were further evaluated for their BChE inhibition activity, and five phenanthrenes presented promising capacity (IC(50) < 10 microM). Further kinetic studies indicated their modes of inhibition. Compounds 6, 8, and 14 were found to be mixed-type inhibitors, while compounds 10 and 12 could be classified as non-competitive inhibitors. The potential interaction mechanism of them with BChE was demonstrated by molecular docking and molecular dynamics simulation, showing that they could interact with catalytic active site and peripheral anionic site of BChE. These natural phenanthrenes provide new scaffold for the further design and optimization, with the aim to discover new selective BChE inhibitors for the treatment of AD.
ESTHER : Liu_2022_Sci.Rep_12_13649
PubMedSearch : Liu_2022_Sci.Rep_12_13649
PubMedID: 35953511

Title : A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells - Moore_2022_ACS.Chem.Biol_17_2595
Author(s) : Moore KP , Schwaid AG , Tudor M , Park S , Beshore DC , Converso A , Shipe WD , Anand R , Lan P , Moningka R , Rothman DM , Sun W , Chi A , Cornella-Taracido I , Adam GC , Bahnck-Teets C , Carroll SS , Fay JF , Goh SL , Lusen J , Quan S , Rodriguez S , Xu M , Andrews CL , Song C , Filzen T , Li J , Hollenstein K , Klein DJ , Lammens A , Lim UM , Fang Z , McHale C , Li Y , Lu M , Diamond TL , Howell BJ , Zuck P , Balibar CJ
Ref : ACS Chemical Biology , 17 :2595 , 2022
Abstract : Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells. Tool compounds ICeD-1 and ICeD-2 ("inducer of cell death-1 and 2"), optimized for potency and selectivity from screening hits, were used to deconvolute the mechanism of action using a combination of chemoproteomic, biochemical, pharmacological, and genetic approaches. We determined that these compounds function by modulating dipeptidyl peptidase 9 (DPP9) and activating the caspase recruitment domain family member 8 (CARD8) inflammasome. Efficacy of ICeD-1 and ICeD-2 was dependent on HIV-1 protease activity and synergistic with efavirenz, which promotes premature activation of HIV-1 protease at high concentrations in infected cells. This in vitro synergy lowers the efficacious cell kill concentration of efavirenz to a clinically relevant dose at concentrations of ICeD-1 or ICeD-2 that do not result in complete DPP9 inhibition. These results suggest engagement of the pyroptotic pathway as a potential approach to eliminate HIV-1 infected cells.
ESTHER : Moore_2022_ACS.Chem.Biol_17_2595
PubMedSearch : Moore_2022_ACS.Chem.Biol_17_2595
PubMedID: 36044633
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202 - Shao_2022_Molecules_27_
Author(s) : Shao S , Wang X , She J , Zhang H , Pang X , Lin X , Zhou X , Liu Y , Li Y , Yang B
Ref : Molecules , 27 : , 2022
Abstract : Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3-11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC(50) value of 1.31 microM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC(50) value of 2.32 microM.
ESTHER : Shao_2022_Molecules_27_
PubMedSearch : Shao_2022_Molecules_27_
PubMedID: 35335187

Title : Rebuilding the lid region from conformational and dynamic features to engineering applications of lipase in foods: Current status and future prospects - Chen_2022_Compr.Rev.Food.Sci.Food.Saf__
Author(s) : Chen G , Khan IM , He W , Li Y , Jin P , Campanella OH , Zhang H , Huo Y , Chen Y , Yang H , Miao M
Ref : Compr Rev Food Sci Food Saf , : , 2022
Abstract : The applications of lipases in esterification, amidation, and transesterification have broadened their potential in the production of fine compounds with high cumulative values. Mostly, the catalytic triad of lipases is covered by either one or two mobile peptides called the "lid" that control the substrate channel to the catalytic center. The lid holds unique conformational allostery via interfacial activation to regulate the dynamics and catalytic functions of lipases, thereby highlighting its importance in redesigning these enzymes for industrial applications. The structural characteristic of lipase, the dynamics of lids, and the roles of lid in lipase catalysis were summarized, providing opportunities for rebuilding lid region by biotechniques (e.g., metagenomic technology and protein engineering) and enzyme immobilization. The review focused on the advantages and disadvantages of strategies rebuilding the lid region. The main shortcomings of biotechnologies on lid rebuilding were discussed such as negative effects on lipase (e.g., a decrease of activity). Additionally, the main shortcomings (e.g., enzyme desorption at high temperatre) in immobilization on hydrophobic supports via interfacial action were presented. Solutions to the mentioned problems were proposed by combinations of computational design with biotechnologies, and improvements of lipase immobilization (e.g., immobilization protocols and support design). Finally, the review provides future perspectives about designing hyperfunctional lipases as biocatalysts in the food industry based on lid conformation and dynamics.
ESTHER : Chen_2022_Compr.Rev.Food.Sci.Food.Saf__
PubMedSearch : Chen_2022_Compr.Rev.Food.Sci.Food.Saf__
PubMedID: 35470946

Title : A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase - Xia_2022_Biosensors.(Basel)_12_
Author(s) : Xia M , Li C , Liu L , He Y , Li Y , Jiang G , Wang J
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.
ESTHER : Xia_2022_Biosensors.(Basel)_12_
PubMedSearch : Xia_2022_Biosensors.(Basel)_12_
PubMedID: 35884287

Title : Mechanism and Structural Insights Into a Novel Esterase, E53, Isolated From Erythrobacter longus - Ding_2022_Front.Microbiol_12_798194
Author(s) : Ding Y , Nie L , Yang XC , Li Y , Huo YY , Li Z , Gao Y , Cui HL , Li J , Xu XW
Ref : Front Microbiol , 12 :798194 , 2022
Abstract : Esterases are a class of enzymes that split esters into an acid and an alcohol in a chemical reaction with water, having high potential in pharmaceutical, food and biofuel industrial applications. To advance the understanding of esterases, we have identified and characterized E53, an alkalophilic esterase from a marine bacterium Erythrobacter longus. The crystal structures of wild type E53 and three variants were solved successfully using the X-ray diffraction method. Phylogenetic analysis classified E53 as a member of the family IV esterase. The enzyme showed highest activity against p-nitrophenyl butyrate substrate at pH 8.5 9.5 and 40 C. Based on the structural feature, the catalytic pocket was defined as R1 (catalytic center), R2 (pocket entrance), and R3 (end area of pocket) regions. Nine variants were generated spanning R1-R3 and thorough functional studies were performed. Detailed structural analysis and the results obtained from the mutagenesis study revealed that mutations in the R1 region could regulate the catalytic reaction in both positive and negative directions; expanding the bottleneck in R2 region has improved the enzymatic activity; and R3 region was associated with the determination of the pH pattern of E53. N166A in R3 region showed reduced activity only under alkaline conditions, and structural analysis indicated the role of N166 in stabilizing the loop by forming a hydrogen bond with L193 and G233. In summary, the systematic studies on E53 performed in this work provide structural and functional insights into alkaliphilic esterases and further our knowledge of these enzymes.
ESTHER : Ding_2022_Front.Microbiol_12_798194
PubMedSearch : Ding_2022_Front.Microbiol_12_798194
PubMedID: 35069500
Gene_locus related to this paper: erylo-E53

Title : Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease - Wu_2022_Bioorg.Chem_122_105760
Author(s) : Wu D , Chen J , Luo K , Li H , Liu T , Li L , Dai Z , Li Y , Zhao Y , Fu X
Ref : Bioorg Chem , 122 :105760 , 2022
Abstract : In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD.
ESTHER : Wu_2022_Bioorg.Chem_122_105760
PubMedSearch : Wu_2022_Bioorg.Chem_122_105760
PubMedID: 35349945

Title : Insight into the uptake and metabolism of a new insecticide cyetpyrafen in plants - Li_2022_Environ.Int_169_107522
Author(s) : Li R , Wang S , Chang J , Pan X , Dong F , Li Z , Zheng Y , Li Y
Ref : Environ Int , 169 :107522 , 2022
Abstract : As new agrochemicals are continuously introduced into agricultural systems, it is essential to investigate their uptake and metabolism by plants to better evaluate their fate and accumulation in crops and the subsequent risks to human exposure. In this study, the uptake and elimination kinetics and transformation of a novel insecticide, cyetpyrafen, in two model crops (lettuce and rice) were first evaluated by hydroponic experiments. Cyetpyrafen was rapidly taken up by plant roots and reached a steady state within 24 h, and it was preferentially accumulated in root parts with root concentration factors up to 2670 mL/g. An uptake mechanism study suggested that root uptake of cyetpyrafen was likely to be dominated by passive diffusion and was difficult to transport via xylem and phloem. Ten phase I and three phase II metabolites of cyetpyrafen were tentatively identified in the hydroponic-plant system through a nontarget screening strategy. The structures of two main metabolites (M-309 and M-391) were confirmed by synthesized standards. The metabolic pathways were proposed including hydroxylation, hydrolysis, dehydrogenation, dehydration and conjugation, which were assumed to be regulated by cytochrome P450, carboxylesterase, glycosyltransferase, glutathione S-transferases and peroxidase. Cyetpyrafen and its main metabolites (M-409, M-309 and M-391) were estimated to be harmful/toxic toward nontarget organisms by theoretical calculation. The high bioaccumulation and extensive transformation of cyetpyrafen highlighted the necessity for systematically assessing the crop uptake and metabolism of new agrochemicals.
ESTHER : Li_2022_Environ.Int_169_107522
PubMedSearch : Li_2022_Environ.Int_169_107522
PubMedID: 36137426

Title : Activation of GPR55 attenuates cognitive impairment, oxidative stress, neuroinflammation, and synaptic dysfunction in a streptozotocin-induced Alzheimer's mouse model - Xiang_2022_Pharmacol.Biochem.Behav__173340
Author(s) : Xiang X , Wang X , Wu Y , Hu J , Li Y , Jin S , Wu X
Ref : Pharmacol Biochem Behav , :173340 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cascading changes in cognition and behavior. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for the treatment of diabetes, but its function in AD is unclear. The objective of this study was to investigate the neuroprotective effects of O-1602, a GPR55 agonist, on the streptozotocin (STZ)-induced AD mouse model. A single intracerebroventricular (i.c.v.) injection of STZ into the brains of mice significantly induced cognitive impairment. In contrast, O-1602 (2.0 or 4.0 microg/mouse, i.c.v.) can improve the cognitive dysfunction caused by STZ in the Morris water maze (MWM) and novel object recognition (NOR) tests. Importantly, O-1602 treatment reversed STZ-induced GPR55 down-regulation, reduced the activity of beta-secretase 1 (BACE1) and the level of Abeta(1-42), and abolished the up-regulation of acetylcholinesterase (AChE) activity in the hippocampus and frontal cortex. Besides, O-1602 markedly suppressed STZ-induced oxidative stress, characterized by decreased malondialdehyde (MDA) level, and increased the levels of glutathione (GSH), superoxide dismutases (SOD), and catalase (CAT), as well as attenuated neuroinflammation as indicated by decreased series of pro-inflammatory cytokines and microglia activation. O-1602 treatment also ameliorated synaptic dysfunction by promoting the up-regulation of PSD-95 protein in the STZ-treated mice. Our results suggest that O-1602 has potent neuroprotective effects against STZ-induced neurotoxicity. Meanwhile, these findings suggest that GPR55 might be a novel and promising target for the treatment of AD.
ESTHER : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedSearch : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedID: 35090841

Title : Evaluation of the toxicity effects of microplastics and cadmium on earthworms - Liang_2022_Sci.Total.Environ__155747
Author(s) : Liang X , Zhou D , Wang J , Li Y , Liu Y , Ning Y
Ref : Sci Total Environ , :155747 , 2022
Abstract : Microplastics (MPs) and heavy metal pollution have become research hotspots in recent years. This study focused on the comprehensive evaluation of the toxicity effect on Eisenia fetida under combined exposure to MPs and the heavy metal cadmium (Cd). With Cd concentration, MPs concentration and MPs partical size as stress factors, the TOPSIS model was constructed to explore the toxicity levels of the stress factors. A short-term co-exposure test and a long-term co-exposure test were designed by orthogonal combination tests with equivalent toxicity levels. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione peroxidase (GPX), glutathione S transferase (GST), and acetylcholinesterase (AChE) and the contents of protein (TP), glutathione (GSH), and malondialdehyde (MDA) in earthworms were determined. Integrated biological responses version 2 (IBRv2) was used to evaluate the toxicity of MPs and Cd combined exposure on earthworms. The results showed that the toxicity ratio of Cd concentration, MPs concentration and MPs partical size was 46 to 29 to 25. Combined exposure to MPs and Cd enhanced the activities of SOD, POD, CAT, GPX and GST, MDA and GSH contents also increased, while the AChE activities were inhibited. SOD, GPX and GST play important roles in the resistance of earthworms to pollutant stress. During short-term co-exposure, Cd concentration had antagonistic effects with on MPs concentration and MPs partical size, while they showed synergistic effects during long-term co-exposure.
ESTHER : Liang_2022_Sci.Total.Environ__155747
PubMedSearch : Liang_2022_Sci.Total.Environ__155747
PubMedID: 35533859

Title : The metabolic resistance of Nilaparvata lugens to chlorpyrifos is mainly driven by the carboxylesterase CarE17 - Lu_2022_Ecotoxicol.Environ.Saf_241_113738
Author(s) : Lu K , Li Y , Xiao T , Sun Z
Ref : Ecotoxicology & Environmental Safety , 241 :113738 , 2022
Abstract : The involvement of carboxylesterases (CarEs) in resistance to chlorpyrifos has been confirmed by the synergism analysis in Nilaparvata lugens. However, the function of specific CarE gene in chlorpyrifos resistance and the transcriptional regulatory mechanism are obscure. Herein, the expression patterns of 29 CarE genes in the susceptible and chlorpyrifos-resistant strains were analyzed. Among them, CarE3, CarE17 and CarE19 were overexpressed in the resistant strain, and knockdown of either CarE gene by RNA interference significantly increased the susceptibility to chlorpyrifos. Remarkably, knockdown of CarE17 reduced the enzymatic activity of CarE by 88.63 % and showed a much greater effect on increasing chlorpyrifos toxicity than silencing other two CarE genes. Overexpression of CarE17 in Drosophila melanogaster decreased the toxicity of chlorpyrifos to transgenic fruit flies. Furthermore, the region between - 205 to + 256 of CarE17 promoter sequence showed the highest promoter activity, and 16 transcription factors (TFs) were predicted from this region. Among these TFs, Lim1beta and C15 were overexpressed in the resistant strain. Knockdown of either TF resulted in reduced CarE17 expression and a decrease in resistance of N. lugens to chlorpyrifos. These results indicate that the constitutive overexpression of Lim1beta and C15 induces CarE17 expression thus conferring chlorpyrifos resistance in N. lugens.
ESTHER : Lu_2022_Ecotoxicol.Environ.Saf_241_113738
PubMedSearch : Lu_2022_Ecotoxicol.Environ.Saf_241_113738
PubMedID: 35679727

Title : Case Report: Next-Generation Sequencing Identified a Novel Pair of Compound-Heterozygous Mutations of LPL Gene Causing Lipoprotein Lipase Deficiency - Li_2022_Front.Genet_13_831133
Author(s) : Li Y , Hu M , Han L , Feng L , Yang L , Chen X , Du T , Yao H
Ref : Front Genet , 13 :831133 , 2022
Abstract : Lipoprotein lipase deficiency (LPLD) is a rare disease characterized by the accumulation of chylomicronemia with early-onset. Common symptoms are abdominal pain, hepatosplenomegaly, eruptive xanthomas and lipemia retinalis. Serious complications include acute pancreatitis. Gene LPL is one of causative factors of LPLD. Here, we report our experience on an asymptomatic 3.5-month-old Chinese girl with only milky blood. Whole-exome sequencing was performed and identified a pair of compound-heterozygous mutations in LPL gene, c.862G>A (p.A288T) and c.461A>G (p.H154R). Both variants are predicted "deleterious" and classified as "likely pathogenic". This study expanded the LPL mutation spectrum of disease LPLD, thereby offering exhaustive and valuable experience on early diagnosis and proper medication of LPLD.
ESTHER : Li_2022_Front.Genet_13_831133
PubMedSearch : Li_2022_Front.Genet_13_831133
PubMedID: 35309119
Gene_locus related to this paper: human-LPL

Title : Negative correlation between early recovery and lipoprotein-associated phospholipase A2 levels after intravenous thrombolysis - Li_2022_J.Int.Med.Res_50_3000605221093303
Author(s) : Li Y , Wang W , Yang H , Guo W , Feng J , Yang D , Guo L , Tan G
Ref : J Internal Medicine Res , 50 :3000605221093303 , 2022
Abstract : OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered a biomarker for systemic inflammation and the risk of myocardial infarction and stroke. However, little is known about the effect of acute vascular events on marker levels. The purpose of this study was to assess the potential association of early recovery with Lp-PLA2 levels in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: Forty-three consecutive AIS patients who had their first stroke and were hospitalized within 5 hours of the onset of stroke were enrolled. All patients were treated with IVT using alteplase or urokinase. Plasma Lp-PLA2 levels were measured within 24 hours after IVT. Variables that showed a significant association with Lp-PLA2 in univariate analysis were included in the multivariate ordered logistic regression model. RESULTS: Early recovery was associated with Lp-PLA2 levels after IVT, and Lp-PLA2 levels tended to decrease with increased probability of early recovery. This study is the first to report a negative correlation between early recovery and Lp-PLA2 levels after IVT. CONCLUSION: Early recovery after IVT was negatively correlated with Lp-PLA2 A2 levels.
ESTHER : Li_2022_J.Int.Med.Res_50_3000605221093303
PubMedSearch : Li_2022_J.Int.Med.Res_50_3000605221093303
PubMedID: 35441552

Title : Identification of Host Molecules Involved in the Proliferation of Nucleopolyhedrovirus in Bombyx mori - Xu_2022_J.Agric.Food.Chem__
Author(s) : Xu J , Xie X , Ma Q , Zhang L , Li Y , Chen Y , Li K , Xiao Y , Tettamanti G , Xu H , Tian L
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : The Bombyx mori nucleopolyhedrovirus (BmNPV), a foodborne infectious virus, is the pathogen causing nuclear polyhedrosis and high lethality in the silkworm. In this study, we characterized the molecules involved in BmNPV-silkworm interaction by RNA sequencing of the fat body isolated from the virus-susceptible strain P50. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that the upregulated differentially expressed genes (DEGs) were mainly involved in translation, signal transduction, folding, sorting, and degradation, as well as transport and catabolism, while the downregulated DEGs were predominantly enriched in the metabolism of carbohydrates, amino acids, and lipids at 72 h post BmNPV infection. Knockout of the upregulated somatomedin-B and thrombospondin type-1 domain-containing protein, probable allantoicase, trifunctional purine biosynthetic protein adenosine-3, and Psl and pyoverdine operon regulator inhibited the proliferation of BmNPV, while knockout of the downregulated clip domain serine protease 3 and carboxylesterase clade H, member 1 promoted it. The molecules herein identified provide a foundation for developing strategies and designing drugs against BmNPV.
ESTHER : Xu_2022_J.Agric.Food.Chem__
PubMedSearch : Xu_2022_J.Agric.Food.Chem__
PubMedID: 36321811

Title : Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment - Ye_2022_Nanomedicine__102581
Author(s) : Ye Z , Gao L , Cai J , Wang Y , Li Y , Tong S , Yan T , Sun Q , Qi Y , Xu Y , Jiang H , Zhang S , Zhao L , Chen Q
Ref : Nanomedicine , :102581 , 2022
Abstract : Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.
ESTHER : Ye_2022_Nanomedicine__102581
PubMedSearch : Ye_2022_Nanomedicine__102581
PubMedID: 35811067

Title : Nanobodies as binding-chaperones stabilize the recombinant Bombyx mori acetylcholinesterase and protect the enzyme activity in pesticide detection - Cai_2022_Enzyme.Microb.Technol_155_109992
Author(s) : Cai J , Romao E , Wu G , Li J , Li L , Wang Z , Li Y , Yang J , Shen Y , Xu Z , Muyldermans S , Wang H
Ref : Enzyme Microb Technol , 155 :109992 , 2022
Abstract : In our previous study, the recombinant type II acetylcholinesterase from Bombyx mori (rBmAChE) presented outstanding sensitivity to pesticides, which exhibited great potential in pesticides detection. However, the poor stability of rBmAChE and also the unclear mechanism of its sensitivity hindered the applications in on-site testing of pesticides residues. In this study, we constructed an immune nanobody library, in which we obtained 48 rBmAChE-specific nanobodies. Among them, Nb4 and Nb9 were verified as the most prominent enhancers of the enzyme activity and stabilizers under thermal stress, which indicated their usage as protective reagents for rBmAChE. The simultaneously addition of the two Nbs enhanced the thermal-stability of rBmAChE against exposure to 50-70 degreesC, and also remained 100% residual activity after 30 days storage at - 20 degreesC or 4 degreesC, whereas 80% and 62% at - 80 degreesC and 25 degreesC. The homologous modeling and docking of Nb4 and Nb9 to rBmAChE indicated the stabilization of Nb4 to the peripheral anion site (PAS) of rBmAChE while Nb9 protected the C-terminal structure. Substrate docking demonstrated the importance of electrostatic attraction during catalytic process, that might be enhanced by Nbs. As a result, Nb4 and Nb9 were proved to have great potential on rBmAChE applications due to their regulation on enzyme activity and protection against thermal-inactivation and long-term storage of rBmAChE.
ESTHER : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedSearch : Cai_2022_Enzyme.Microb.Technol_155_109992
PubMedID: 35114480

Title : Ancestral sequence reconstruction and spatial structure analysis guided alteration of longer-chain substrate catalysis for Thermomicrobium roseum lipase - Ma_2022_Enzyme.Microb.Technol_156_109989
Author(s) : Ma D , Xin Y , Guo Z , Shi Y , Zhang L , Li Y , Gu Z , Ding Z , Shi G
Ref : Enzyme Microb Technol , 156 :109989 , 2022
Abstract : Thermomicrobium roseum DSM 5159 lipase (TrLip) is an enzyme with marked thermostability and excellent solvent resistance. However, TrLip reveals relatively high catalytic efficiency on short-chain substrates but poor activity against mid-long or long-chain fatty acids, which would limit its industrial application. In this study, ancestral sequence reconstruction (ASR), a common engineering tool for the evolutionary history of protein families, was employed to identify the natural evolutionary trends within 5 A around the catalytic center. Two mutation libraries were constructed, one for the catalytic center and the other for the pocket flexibility. A total of 69 mutants were expressed and purified in the Escherichia coli expression system to determine the kinetic parameters, and W219G could significantly enhance the catalytic efficiency against substrates with 12-, 16- and 18-carbon side chains. In addition, the double mutant W219G/F265M could further catalyze the breakdown of the above three substrates up to 6.34-, 4.21- and 4.86-folds compared to the wild-type TrLip, while the initial pH and thermostability were maintained. Through bioinformatics analysis, the significantly enhanced catalytic efficiency against longer-side chain substrates should be associated with the reduction of steric hindrance. With the outstanding stability and the promoted activity, TrLip should be of great potential in chemical and food industry.
ESTHER : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedSearch : Ma_2022_Enzyme.Microb.Technol_156_109989
PubMedID: 35134708
Gene_locus related to this paper: therp-b9l0x7

Title : Analysis of virulence proteins in pathogenic Acinetobacter baumannii to provide early warning of zoonotic risk - Zou_2022_Microbiol.Res_266_127222
Author(s) : Zou D , Chang J , Lu S , Xu J , Hu P , Zhang K , Sun X , Guo W , Li Y , Liu Z , Ren H
Ref : Microbiol Res , 266 :127222 , 2022
Abstract : Acinetobacter baumannii is a ubiquitous opportunistic pathogen usually with low virulence. In recent years, reports of increased pathogenicity of A. baumannii in livestock due to the migratory behaviour of wildlife have attracted public health attention. Our previous study reported that an A. baumannii strain isolated from dead chicks, CCGGD201101, showed enhanced pathogenicity, but the mechanism for increased virulence is not understood. Here, to screen potential virulence factors, the proteomes of the isolated strain CCGGD201101 and the standard strain ATCC19606 of A. baumannii were compared, and the possible virulence-enhancing mechanisms were further analysed. The 50 % lethal dose (LD(50)) values of CCGGD201101 and standard strain ATCC19606 in ICR mice were determined to verify their bacterial toxicity. 2D fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) and quantitative real-time PCR (RTqPCR) were applied to screen and identify differentially expressed proteins or genes that may be related to virulence enhancement. Bioinformatics analyses based on proteinprotein interaction (PPI) networks were used to explore the function of potential virulence proteins. The pathogenicity of potential virulence factors was assessed by phylogenetic analyses and an animal infection model. The results showed that the LD(50) of CCGGD201101 for mice was 1.186 x 10(6) CFU/mL, and the virulence was increased by 180.5-fold compared to ATCC19606. Forty-seven protein spots were significantly upregulated for the A. baumannii CCGGD201101 strain (fold change <=1.5, p < 0.05). In total, 14 upregulated proteins were identified using proteomic analysis, and the mRNA expression levels of these proteins were nearly identical, with few exceptions. According to the PPI network and phylogenetic analyses, the I78 family peptidase inhibitor, 3-oxoacyl-ACP reductase FabG, and glycine zipper were screened as being closely related to the pathogenicity of bacteria. Furthermore, the I78 overexpression strains exhibited higher lethality in mouse infection models, which indicated that the I78 family peptidase inhibitor was a potential new virulence factor to enhance the pathogenicity of the A. baumannii CCGGD201101 strain. The present study helped us to better understand the mechanisms of virulence enhancement and provided a scientific basis for establishing an early warning system for enhanced virulence of A. baumannii from animals.
ESTHER : Zou_2022_Microbiol.Res_266_127222
PubMedSearch : Zou_2022_Microbiol.Res_266_127222
PubMedID: 36306681
Gene_locus related to this paper: aciba-YdeN

Title : Toxicological effects of trace amounts of pyriproxyfen on the midgut of non-target insect silkworm - Xu_2022_Pestic.Biochem.Physiol_188_105266
Author(s) : Xu K , Lan H , He C , Wei Y , Lu Q , Cai K , Yu D , Yin X , Li Y , Lv J
Ref : Pestic Biochem Physiol , 188 :105266 , 2022
Abstract : Pyriproxyfen is an insect growth regulator that is widely used in public health and pest control in agriculture. Our previous studies have shown that trace amounts of pyriproxyfen in the environment can cause serious toxic effects in the non-target insect silkworm, including failing to pupate, metamorphose and spin cocoons. However, it is unknown why pyriproxyfen not only has no lethal effects on fifth instar larvae but also tend to increase their body weight. The midgut is the main digestive organs of the silkworm, our results showed that the residual of pyriproxyfen in the silkworm at 24sh after 1sxs10(-4)smg/L pyriproxyfen treatment caused severe damage to the midgut microvilli, goblet cells, and nuclei of the silkworm, but body weight and digestibility of the larval were both increased. In addition, pyriproxyfen significantly (ps
ESTHER : Xu_2022_Pestic.Biochem.Physiol_188_105266
PubMedSearch : Xu_2022_Pestic.Biochem.Physiol_188_105266
PubMedID: 36464371

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : The Detoxification Enzymatic Responses of Plutella xylostella (Lepidoptera: Plutellidae) to Cantharidin - Sun_2022_J.Econ.Entomol__
Author(s) : Sun H , Wang P , Wei C , Li Y , Zhang Y
Ref : J Econ Entomol , : , 2022
Abstract : Plutella xylostella (L.) (Lepidoptera: Plutellidae) is one of the most destructive pests of Brassicaceae vegetables. Cantharidin is an insect-derived defensive toxin, which has been reported to have toxicity to a variety of pests and especially lepidopteran pests. Although the toxicity of cantharidin on P. xylostella has been demonstrated, there is little information available on the specific detoxification response of P. xylostella against cantharidin. This study investigates the enzymatic response (including serine/threonine phosphatases [PSPs], carboxylesterases [CarEs], glutathione-S-transferases [GSTs], and cytochrome P450 monooxygenases [P450]) in P. xylostella to the sublethal and low lethal concentrations of cantharidin (LC10 and LC25). Results showed that the inhibitory activity of PSPs was increased and then decreased in vivo, while PSPs activity could be almost completely inhibited in vitro. Interestingly, the activities of detoxification enzymes (GST, CarE, and P450) in P. xylostella displayed a trend of decreasing and then increasing after exposure to the two concentrations of cantharidin. Notably, the increase in P450 enzyme activity was the most significant. The increasing trend of detoxification enzyme activity was congruent with the recovery trend of PSPs activity. This study contributes to our understanding of the detoxification mechanism of cantharidin in P. xylostella and helps in the further development of biogenic agents.
ESTHER : Sun_2022_J.Econ.Entomol__
PubMedSearch : Sun_2022_J.Econ.Entomol__
PubMedID: 36073195

Title : Emerging Mosquito Resistance to Piperonyl Butoxide-Synergized Pyrethroid Insecticide and Its Mechanism - Zhou_2022_J.Med.Entomol__
Author(s) : Zhou G , Li Y , Jeang B , Wang X , Cummings RF , Zhong D , Yan G
Ref : Journal of Medical Entomology , : , 2022
Abstract : Piperonyl butoxide (PBO)-synergized pyrethroid products are widely available for the control of pyrethroid-resistant mosquitoes. To date, no study has examined mosquito resistance after pre-exposure to PBO and subsequent enzymatic activity when exposed to PBO-synergized insecticides. We used Culex quinquefasciatus Say (Diptera: Culicidae), an important vector of arboviruses and lymphatic filariasis, as a model to examine the insecticide resistance mechanisms of mosquitoes to PBO-synergized pyrethroid using modified World Health Organization tube bioassays and biochemical analysis of metabolic enzyme expressions pre- and post-PBO exposure. Mosquito eggs and larvae were collected from three cities in Orange County in July 2020 and reared in insectary, and F0 adults were used in this study. A JHB susceptible strain was used as a control. Mosquito mortalities and metabolic enzyme expressions were examined in mosquitoes with/without pre-exposure to different PBO concentrations and exposure durations. Except for malathion, wild strain Cx quinquefasciatus mosquitoes were resistant to all insecticides tested, including PBO-synergized pyrethroids (mortality range 3.7 +/- 4.7% to 66.7 +/- 7.7%). Wild strain mosquitoes had elevated levels of carboxylesterase (COE, 3.8-fold) and monooxygenase (P450, 2.1-fold) but not glutathione S-transferase (GST) compared to susceptible mosquitoes. When wild strain mosquitoes were pre-exposed to 4% PBO, the 50% lethal concentration of deltamethrin was reduced from 0.22% to 0.10%, compared to 0.02% for a susceptible strain. The knockdown resistance gene mutation (L1014F) rate was 62% in wild strain mosquitoes. PBO pre-exposure suppressed P450 enzyme expression levels by 25~34% and GST by 11%, but had no impact on COE enzyme expression. Even with an optimal PBO concentration (7%) and exposure duration (3h), wild strain mosquitoes had significantly higher P450 enzyme expression levels after PBO exposure compared to the susceptible laboratory strain. These results further demonstrate other studies that PBO alone may not be enough to control highly pyrethroid-resistant mosquitoes due to multiple resistance mechanisms. Mosquito resistance to PBO-synergized insecticide should be closely monitored through a routine resistance management program for effective control of mosquitoes and the pathogens they transmit.
ESTHER : Zhou_2022_J.Med.Entomol__
PubMedSearch : Zhou_2022_J.Med.Entomol__
PubMedID: 35050361

Title : Knockdown of GmD53a confers strigolactones mediated rhizobia interaction and promotes nodulation in soybean - Rehman_2022_PeerJ_10_e12815
Author(s) : Rehman N , Khan FU , Imran M , Rajput SA , Li Y , Ullah I , Akhtar RW , Al-Huqail AA , Askary AE , Khalifa AS , Azhar MT
Ref : PeerJ , 10 :e12815 , 2022
Abstract : BACKGROUND: Strigolactones (SLs) play a key role in modulating plant root growth, shoot branching, and plant-symbiont interaction. However, despite their significance, the components of SL biosynthesis and signaling in soybean and their role in soybean-rhizobia interaction is unknown. METHODS: In this study, we identified and functionally characterized the GmD53a from soybean. The GmD53a ORFs were amplified from root cDNA using primers for GmD53a RNA interference. To induce transgenic hairy roots of soybean, electric shock was used to transform pB7WG1WG2 vectors containing GmD53a knockdown and GUS into K599 strains of Agrobacterium rhizogenes. The hairy roots and nodules were collected and examined for root nodules ratio and RNA was extracted after 4 weeks of rhizobia inoculation. RESULTS: A tissue-specific expression assay showed that GmD53a was differentially expressed in plant parts, predominantly in the stem and nodule. Furthermore, its expression was significantly up-regulated during rhizobia infection and varied with nodule formation. The GmD53a-knockdown chimerical plants were produced to further check its role in soybean nodulation in comparison with control GUS. In knockdown lines, the GmD53a (suppressor of strigolactone MAX2) has a higher number of nodules compared to control lines. Furthermore, the expression levels of several nodulation genes essential for initiation and formation of nodules were altered in GmD53a-knockdown lines. CONCLUSION: The results revealed that SL biosynthesis and signaling are not conserved but also have close interaction between SL and legume rhizobia.
ESTHER : Rehman_2022_PeerJ_10_e12815
PubMedSearch : Rehman_2022_PeerJ_10_e12815
PubMedID: 35116200

Title : Phenolic and bisamide derivatives from Aglaia odorata and their biological activities - Yang_2022_Nat.Prod.Res__1
Author(s) : Yang X , Yu Y , Wu P , Liu J , Li Y , Tao L , Tan R , Hao X , Yuan C , Yi P
Ref : Nat Prod Res , :1 , 2022
Abstract : Three new compounds (1-3), including two bisamide derivatives (1 and 2) and a lignin (3), along with 15 known compounds were isolated from Aglaia odorata. Compound 2 was a pair of enantiomers and successfully resolved into the anticipated enantiomers. Their structures were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, and X-ray crystallography. Three compounds showed excellent inhibitory activities on alpha-glucosidase with IC(50) values ranging from 54.48 to 240.88 microM, better than that of the positive control (acarbose, IC(50) = 590.94 microM). Moreover, compounds 3, 13, and 15 presented moderate inhibitory activities against butyrylcholinesterase. Compound 17 exhibited potent PTP1B inhibitory activity with an IC(50) value of 179.45 microM. Representative active compounds were performed for the molecular docking study. Herein, we described the isolation, structure elucidation, the inhibitory effects on three enzymes, and molecular docking of the isolates from the title plant.
ESTHER : Yang_2022_Nat.Prod.Res__1
PubMedSearch : Yang_2022_Nat.Prod.Res__1
PubMedID: 36580570

Title : Molecular Basis of the Reinforced Effect of Berberine against Cutinase from Colletotrichum capsisi by Supplying Sodium Stearate as Dispersant - Li_2022_ACS.Appl.Bio.Mater__
Author(s) : Li Y , He R , Cui Y , Ge X
Ref : ACS Appl Bio Mater , : , 2022
Abstract : Berberine (BBR) is a promising botanical pesticide that can reduce the enzyme activity of secreted cutinase from fungal pathogens. However, only less than 15% of total activity was prohibited. Herein we researched BBR's self-aggregation in water via molecular dynamics simulations, and further investigated the effect of dispersant on blocking the aggregation together with the impact on cutinase. Strong hydrophobic interactions were found between adjacent BBR molecules, and these molecules formed clustered conformations at different BBR concentrations. Interestingly, one of the tested dispersants, sodium stearate (ST), is able to insert into BBR clusters and form stable interaction until the end of simulation, resulting in decreased hydrophobic strength in the BBR-ST cluster. More importantly, supply of ST with BBR resulted in BBR's reinforced hydrophobic interactions between BBR and the catalytic center of cutinase, which led to the inactivated mode of cutinase. Finally, wet experiments demonstrated that combined application of BBR and ST indeed resulted in a synergy-like effect on reducing the activity of cutinase. Overall, our findings revealed the mechanism of the reinforced effect of BBR against cutinase when supplying ST as dispersant, suggesting an undiscovered role of ST in enhancing the efficiency of this botanical pesticide.
ESTHER : Li_2022_ACS.Appl.Bio.Mater__
PubMedSearch : Li_2022_ACS.Appl.Bio.Mater__
PubMedID: 35114082

Title : Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition - Li_2022_Elife_11_e79736
Author(s) : Li Y , Balakrishnan VK , Rowse M , Wu CG , Bravos AP , Yadav VK , Ivarsson Y , Strack S , Novikova IV , Xing Y
Ref : Elife , 11 : , 2022
Abstract : Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme-PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores.
ESTHER : Li_2022_Elife_11_e79736
PubMedSearch : Li_2022_Elife_11_e79736
PubMedID: 35924897
Gene_locus related to this paper: human-PPME1

Title : Portable hydrogel test kit integrated dual-emission coordination polymer nanocomposite for on-site detection of organophosphate pesticides - Li_2022_Biosens.Bioelectron_220_114890
Author(s) : Li Y , Huang Z , Liu B , Huang ZZ , Yang H , Tan H
Ref : Biosensors & Bioelectronics , 220 :114890 , 2022
Abstract : It is of great significance to on-site detection of organophosphate pesticides (OPs) for pollution monitoring and poisoning estimation. Herein, we developed a portable hydrogel test kit for on-site detection of OPs, which is based on the integration of agarose hydrogel with dual-emission coordination polymers (CPs) nanocomposite comprised of Ru(bpy)(3)(2+) and zinc (II)-based CPs (ZnCPs) loaded with thioflavin T (ThT). Different from Ru(bpy)(3)(2+) with stable fluorescence in acidic environment, ThT@ZnCPs is highly sensitive to H(+), which destroys the structure of ZnCPs as a host and quenches ThT@ZnCPs fluorescence. The distinct fluorescence behaviors of Ru(bpy)(3)(2+) and ThT@ZnCPs in acidic environment enable the hydrogel test kit to exhibit ratiometric fluorescence responses to acetylcholinesterase (AChE), which hydrolyzes acetylcholine to acetic acid and provides H(+). On this basis, combining the inhibition effect of OPs to AChE activity, a ratiometric fluorescence method for OPs detection was established with the hydrogel test kit, and satisfactory results have been achieved in buffered aqueous solutions and apple juice samples. Attractively, by employing smartphone as a signal readout, on-site quantitation of OPs was accomplished with the features of easy to use, portability and low cost, demonstrating a great promising for point-of-care testing in food safety monitoring.
ESTHER : Li_2022_Biosens.Bioelectron_220_114890
PubMedSearch : Li_2022_Biosens.Bioelectron_220_114890
PubMedID: 36395730

Title : Characterization of feruloyl esterases from Pecoramyces sp. F1 and the synergistic effect in biomass degradation - Ma_2022_World.J.Microbiol.Biotechnol_39_17
Author(s) : Ma J , Ma Y , Li Y , Sun Z , Sun X , Padmakumar V , Cheng Y , Zhu W
Ref : World J Microbiol Biotechnol , 39 :17 , 2022
Abstract : Feruloyl esterase (FAE; EC 3.1.1.73)cleaves the ester bondbetween ferulic acid (FA) and sugar, to assist the release of FAs and degradation of plant cell walls. In this study, two FAEs (Fae13961 and Fae16537) from the anaerobic fungus Pecoramyces sp. F1 were heterologously expressed in Pichia pastoris (P. pastoris). Compared with Fae16537, Fae13961 had higher catalytic efficiency. The optimum temperature and pH of both the FAEs were 45 and 7.0, respectively. They showed good stability-Fae16537 retained up to 80% activity after incubation at 37 for 24h. The FAEs activity was enhanced by Ca(2+) and reduced by Zn(2+), Mn(2+), Fe(2+) and Fe(3+). Additionally, the effect of FAEs on the hydrolytic efficiency of xylanase and cellulase was also determined. The FAE Fae13961 had synergistic effect with xylanase and it promoted the degradation of xylan substrates by xylanase, but it did not affect the degradation of cellulose substrates by cellulase. When Fae13961 was added in a mixture of xylanase and cellulase to degrade complex agricultural biomass, it significantly enhanced the mixture's ability to disintegrate complex substrates. These FAEs could serve as superior auxiliary enzymes for other lignocellulosic enzymes in the process of degradation of agricultural residues for industrial applications.
ESTHER : Ma_2022_World.J.Microbiol.Biotechnol_39_17
PubMedSearch : Ma_2022_World.J.Microbiol.Biotechnol_39_17
PubMedID: 36409385

Title : Effect of lentivirus-mediated peroxiredoxins 6 gene silencing on the phenotype of human gastric cancer BGC-823 cells - Mu_2022_J.Cancer.Res.Ther_18_411
Author(s) : Mu R , Li Y , Xing J , Lin R , Ye S , Zhang Y , Mu H , Guo X , An L
Ref : J Cancer Research Ther , 18 :411 , 2022
Abstract : AIMS: Peroxiredoxins (PRDX6) regulates the occurrence and progression of cancer. The aim of this study is to investigate the effect of PRDX6 knockdown on the biological behavior of human gastric cancer cell line BGC-823 cells. SETTINGS AND DESIGN: Research article. SUBJECTS AND METHODS: The differential expression of PRDX6 in gastric cancer and normal gastric tissues was tested by immunohistochemistry. Ribonucleic acid plasmid of PRDX6 gene was packaged using a lentivirus, and BGC-823 cells were transfected with the lentivirus to obtain a BGC-823 cell line in which the expression of PRDX6 was stably silenced. STATISTICAL ANALYSIS USED: The proliferation activity of BGC-823 cells was detected using the cell counting kit-8 method. The effect of PRDX6 on the migration and invasion of BGC-823 cells was evaluated using the scratch test and Transwell assay, and the expression of related proteins was detected by western blot. RESULTS: The expression of PRDX6 in gastric cancer was significantly increased (P < 0.05). Compared with those in the untransfected and negative control groups. The proliferation, migration, and invasion of gastric cancer BGC-823 cells were significantly inhibited, and the apoptotic rates were significantly increased in the lentivirus-transfected (short hairpin-PRDX6) group. Western blot analysis showed that the expression of Bax protein increased, whereas that of proliferating cell nuclear antigen, Bcl-2, PI3K, phospho (p-Akt), and phosphorylated-mammalian target of rapamycin (mTOR) decreased significantly compared with that in WT and vector groups (P < 0.05). CONCLUSION: The knockdown of PRDX6 gene expression in BGC-823 cells can inhibit the proliferation, migration, and invasion of gastric cancer cells and promote apoptosis, thereby affecting gastric cancer cells.
ESTHER : Mu_2022_J.Cancer.Res.Ther_18_411
PubMedSearch : Mu_2022_J.Cancer.Res.Ther_18_411
PubMedID: 35645108

Title : The diagnosis of immune-related pancreatitis disguised as multifocal lesions on MRI by endoscopic ultrasound-guided fine-needle biopsy: A case report - Shi_2022_Front.Immunol_13_933595
Author(s) : Shi W , Tan B , Li Y , Zhu L , Feng Y , Jiang Q , Qian J
Ref : Front Immunol , 13 :933595 , 2022
Abstract : Immune checkpoint inhibitor (ICI)-related acute pancreatitis (irAP) is a rare, potentially life-threatening immune-related adverse event. Whereas CT and MRI remain first-line diagnostic imaging modalities, more patients are presenting with atypical irAP as ICI use increases. To appropriately manage these events, it is important to catalog these presentations and provide comprehensive clinical, radiological, and pathological descriptions to guide evidence-based practice. Here, we present the case of a 66-year-old man with advanced lung adenocarcinoma who, after the fifth course of toripalimab, developed epigastric discomfort and elevated serum amylase and lipase. irAP was suspected, but MRI revealed atypical, multifocal pancreatic lesions. To exclude metastases, an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed. EUS revealed a slightly swollen pancreas with heterogeneous echoic signals and scattered hyperechoic areas in the parenchyma without an obvious mass. Histopathological examination of the FNB revealed retention of the normal lobular pancreatic architecture with focal acinar atrophy associated with a CD8(+) T lymphocyte-predominant infiltrate, further confirming the diagnosis of irAP. After starting glucocorticoids, his symptoms resolved, serum amylase and lipase rapidly decreased to normal, and the abnormal MRI features diminished. irAP can, therefore, present as multifocal lesions on MRI, and, when metastatic disease requires exclusion, EUS-FNB is an effective way to establish a definitive diagnosis. Refining the histopathological and immunopathological criteria for the diagnosis of irAP is now warranted.
ESTHER : Shi_2022_Front.Immunol_13_933595
PubMedSearch : Shi_2022_Front.Immunol_13_933595
PubMedID: 36177047

Title : The Molecular Brakes of Adipose Tissue Lipolysis - Li_2022_Front.Physiol_13_826314
Author(s) : Li Y , Li Z , Ngandiri DA , Llerins Perez M , Wolf A , Wang Y
Ref : Front Physiol , 13 :826314 , 2022
Abstract : Adaptation to changes in energy availability is pivotal for the survival of animals. Adipose tissue, the body's largest reservoir of energy and a major source of metabolic fuel, exerts a buffering function for fluctuations in nutrient availability. This functional plasticity ranges from energy storage in the form of triglycerides during periods of excess energy intake to energy mobilization via lipolysis in the form of free fatty acids for other organs during states of energy demands. The subtle balance between energy storage and mobilization is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance, type 2 diabetes and cancer cachexia. As a result, adipocyte lipolysis is tightly regulated by complex regulatory mechanisms involving lipases and hormonal and biochemical signals that have opposing effects. In thermogenic brown and brite adipocytes, lipolysis stimulation is the canonical way for the activation of non-shivering thermogenesis. Lipolysis proceeds in an orderly and delicately regulated manner, with stimulation through cell-surface receptors via neurotransmitters, hormones, and autocrine/paracrine factors that activate various intracellular signal transduction pathways and increase kinase activity. The subsequent phosphorylation of perilipins, lipases, and cofactors initiates the translocation of key lipases from the cytoplasm to lipid droplets and enables protein-protein interactions to assemble the lipolytic machinery on the scaffolding perilipins at the surface of lipid droplets. Although activation of lipolysis has been well studied, the feedback fine-tuning is less well appreciated. This review focuses on the molecular brakes of lipolysis and discusses some of the divergent fine-tuning strategies in the negative feedback regulation of lipolysis, including delicate negative feedback loops, intermediary lipid metabolites-mediated allosteric regulation and dynamic protein-protein interactions. As aberrant adipocyte lipolysis is involved in various metabolic diseases and releasing the brakes on lipolysis in thermogenic adipocytes may activate thermogenesis, targeting adipocyte lipolysis is thus of therapeutic interest.
ESTHER : Li_2022_Front.Physiol_13_826314
PubMedSearch : Li_2022_Front.Physiol_13_826314
PubMedID: 35283787

Title : Combined effects of chlorpyrifos and cyfluthrin on neurobehavior and neurotransmitter levels in larval zebrafish - Zhang_2022_J.Appl.Toxicol__
Author(s) : Zhang W , Fan R , Luo S , Liu Y , Jin Y , Li Y , Xiong M , Chen Y , Jia L , Yuan X
Ref : J Appl Toxicol , : , 2022
Abstract : Chlorpyrifos and cyfluthrin are insecticides commonly used in agriculture. The mixed residues of chlorpyrifos and cyfluthrin in the aquatic environment may have combined effects on non-target species. Therefore, studying the combined toxic effects and mechanisms of pesticide mixtures is of great significance to environmental risk assessment. To evaluate the risk of combined exposure, we examined the effects of both compounds, separately and together, on motor activity, acetylcholinesterase (AChE) activity, and neurotransmitter levels in larval zebrafish. Chlorpyrifos exposure significantly reduced functional motor capacity (swim distance and velocity) and enhanced meandering, while cyfluthrin exposure alone had no significant effects on swim parameters. However, combined exposure significantly reduced total swimming distance and mean velocity, and increased meandering. Both compounds alone and the combination significantly reduced AChE activity, and the combined effect was antagonistic. Combined exposure also significantly altered the concentrations of serotonin, serotonin precursors, and dopamine precursors, as well as concentrations of the amino acid neurotransmitters glycine, alanine, and aspartic acid. Combined exposure to chlorpyrifos and cyfluthrin exhibited distinct joint action modes in terms of neurobehavior, AChE activity, and neurotransmitter levels, thereby providing an experimental basis for assessing the combined exposure to chlorpyrifos and cyfluthrin's environmental risk.
ESTHER : Zhang_2022_J.Appl.Toxicol__
PubMedSearch : Zhang_2022_J.Appl.Toxicol__
PubMedID: 35470462

Title : Cardiomyocyte-specific disruption of soluble epoxide hydrolase limits inflammation to preserve cardiac function - Sosnowski_2022_Am.J.Physiol.Heart.Circ.Physiol__
Author(s) : Sosnowski DK , Jamieson KL , Gruzdev A , Li Y , Valencia R , Yousef A , Kassiri Z , Zeldin DC , Seubert JM
Ref : American Journal of Physiology Heart Circ Physiol , : , 2022
Abstract : Endotoxemia elicits a multi-organ inflammatory response which results in cardiac dysfunction and often leads to death. Inflammation-induced metabolism of endogenous N-3 and N-6 polyunsaturated fatty acids generate numerous lipid mediators, such as epoxy fatty acids (EpFAs), which protect the heart. However, EpFAs are hydrolyzed by soluble epoxide hydrolase (sEH), which attenuates their cardioprotective actions. Global genetic disruption of sEH preserves EpFA levels and attenuates cardiac dysfunction in mice following acute lipopolysaccharide (LPS)-induced inflammatory injury. In leukocytes, EpFAs modulate the innate immune system through the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. However, the mechanisms by which both EpFAs and sEH inhibition exert their protective effects in the cardiomyocyte are still elusive. This study investigated whether cardiomyocyte-specific sEH disruption attenuates inflammation and cardiac dysfunction in acute LPS inflammatory injury via modulation of the NLRP3 inflammasome. We employ a novel genetic mouse model using tamoxifen-inducible CreER recombinase technology to target sEH genetic disruption to the cardiomyocyte. Primary cardiomyocyte studies provide mechanistic insight into inflammasome signaling. For the first time, we demonstrate that cardiomyocyte-specific sEH disruption preserves cardiac function and attenuates inflammatory response by limiting local cardiac inflammation and activation of the systemic immune response. Mechanistically, inhibition of cardiomyocyte-specific sEH activity or exogenous EpFA treatment do not prevent upregulation of NLRP3 inflammasome machinery in cardiomyocytes. Rather, they limit downstream activation of the pathway leading to release of fewer chemoattractant factors and recruitment of immune cells to the heart. These data emphasize that cardiomyocyte-specific sEH is vital for mediating detrimental systemic inflammation.
ESTHER : Sosnowski_2022_Am.J.Physiol.Heart.Circ.Physiol__
PubMedSearch : Sosnowski_2022_Am.J.Physiol.Heart.Circ.Physiol__
PubMedID: 35985007

Title : Evodiamine-A Privileged Structure with Broad-Ranging Biological Activities - Li_2022_Mini.Rev.Med.Chem__
Author(s) : Li D , Li Y , Jiang X , Liu W , Zhao Q
Ref : Mini Rev Med Chem , : , 2022
Abstract : Evodiamine (EVO) is a natural quinolone alkaloid firstly isolated from the fruit of Evodia rutaecarpa, which is one of the most frequently used traditional Chinese herb for treating a variety of ailments including headaches, abdominal pain, vomiting, diarrhea, amenorrhea difficult menstruation, postpartum hemorrhage, and other diseases. Latest pharmacological studies showed that EVO possesses a broad spectrum of pharmacological activities through different mechanisms. However, its moderate activities and poor physicochemical properties hampered its clinical application. In this regard, the modification of EVO aiming at seeking derivatives with more potency and better physicochemical properties has been extensively emerging. These derivatives exhibit diverse biological activities including antitumor, anti-Alzheimer's disease, anti-pulmonary hypertension, anti-fungi, and thermogenic activities via a variety of mechanisms. Moreover, they were described to act as single, dual, or multiple inhibitors or agonists of many proteins such as topoisomerase I, topoisomerase II, tubulin, histone deacetylase, sirtuins, butyrylcholinesterase, phosphodiesterase 5, and transient receptor potential vanilloid 1. However, hitherto, there is no comprehensive review to systematically summarize the derivatives of EVO. In this perspective, this paper aims to provide a comprehensive description of them focused on their diverse biological activities. For each biological activity, the mechanisms and the main structure-activity relationships (SARs) will be presented in cases where adequate information is available. Finally, future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration of EVO.
ESTHER : Li_2022_Mini.Rev.Med.Chem__
PubMedSearch : Li_2022_Mini.Rev.Med.Chem__
PubMedID: 35379148

Title : Improved liver lipid catabolism and utilization in growth hormone transgenic common carp (Cyprinus carpio L.) through enhanced lipolytic and fatty acid beta-oxidation pathways - Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
Author(s) : Wu Y , Li R , Wu X , Guo W , Li Y , Song Y , Tao B , Chen J , Han D , Xie S , Wang Y , Zhu Z , Hu W
Ref : Front Endocrinol (Lausanne) , 13 :982488 , 2022
Abstract : Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid beta-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 +/- 0.32 g) and WT (initial weight 3.30 +/- 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 +/- 0.33 g) and WT (initial weight 3.27 +/- 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid beta-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.
ESTHER : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedSearch : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedID: 36171901

Title : Chlorophyll Inhibits the Digestion of Soybean Oil in Simulated Human Gastrointestinal System - Wang_2022_Nutrients_14_
Author(s) : Wang X , Li Y , Shen S , Yang Z , Zhang H , Zhang Y
Ref : Nutrients , 14 : , 2022
Abstract : Nowadays, much available processed and highly palatable food such as cream products and fried and convenient food, which usually showed a high energy density, had caused an increase in the intake of dietary lipids, further leading to significant growth in the prevalence of obesity. Chlorophyll, widespread in fruits and vegetables, was proven to have beneficial effects on alleviating obesity. This study investigated the effects of chlorophyll on the digestive characteristics of lipids under in vitro simulated adult and infant gastrointestinal systems. Chlorophyll decreased the release rate of free fatty acid (FFA) during in vitro adult and infant intestinal digestion by 69.2% and 60.0%, respectively. Meanwhile, after gastrointestinal digestion, chlorophyll changed the FFA composition of soybean oil emulsion and increased the particle size of oil droplets. Interestingly, with the addition of chlorophyll, the activity of pancreatic lipase was inhibited during digestion, which may be related to pheophytin (a derivative of chlorophyll after gastric digestion). Therefore, the results obtained from isothermal titration calorimetry and molecular docking further elucidated that pheophytin could bind to pancreatic lipase with a strong affinity of (4.38 +/- 0.76) x 10(7) M(-1) (K(a)), while the binding site was amino acid residue Trp253. The investigation not only explained why chlorophyll inhibited digestive enzyme activity to reduce lipids digestion but also provided exciting opportunities for developing novel chlorophyll-based healthy products for dietary application in preventing obesity.
ESTHER : Wang_2022_Nutrients_14_
PubMedSearch : Wang_2022_Nutrients_14_
PubMedID: 35565719

Title : Spleen volume-based non-invasive tool for predicting hepatic decompensation in people with compensated cirrhosis (CHESS1701) - Yu_2022_JHEP.Rep_4_100575
Author(s) : Yu Q , Xu C , Li Q , Ding Z , Lv Y , Liu C , Huang Y , Zhou J , Huang S , Xia C , Meng X , Lu C , Li Y , Tang T , Wang Y , Song Y , Qi X , Ye J , Ju S
Ref : JHEP Rep , 4 :100575 , 2022
Abstract : BACKGROUND & AIMS: Non-invasive stratification of the liver decompensation risk remains unmet in people with compensated cirrhosis. This study aimed to develop a non-invasive tool (NIT) to predict hepatic decompensation. METHODS: This retrospective study recruited 689 people with compensated cirrhosis (median age, 54 years; 441 men) from 5 centres from January 2016 to June 2020. Baseline abdominal computed tomography (CT), clinical features, and liver stiffness were collected, and then the first decompensation was registered during the follow-up. The spleen-based model was designed for predicting decompensation based on a deep learning segmentation network to generate the spleen volume and least absolute shrinkage and selection operator (LASSO)-Cox. The spleen-based model was trained on the training cohort of 282 individuals (Institutions I-III) and was validated in 2 external validation cohorts (97 and 310 individuals from Institutions IV and V, respectively) and compared with the conventional serum-based models and the Baveno VII criteria. RESULTS: The decompensation rate at 3 years was 23%, with a 37.6-month median (IQR 21.1-52.1 months) follow-up. The proposed model showed good performance in predicting decompensation (C-index <=0.84) and outperformed the serum-based models (C-index comparison test p <0.05) in both the training and validation cohorts. The hazard ratio (HR) for decompensation in individuals with high risk was 7.3 (95% CI 4.2-12.8) in the training and 5.8 (95% CI 3.9-8.6) in the validation (log-rank test, p <0.05) cohorts. The low-risk group had a negligible 3-year decompensation risk (>=1%), and the model had a competitive performance compared with the Baveno VII criteria. CONCLUSIONS: This spleen-based model provides a non-invasive and user-friendly method to help predict decompensation in people with compensated cirrhosis in diverse healthcare settings where liver stiffness is not available. LAY SUMMARY: People with compensated cirrhosis with larger spleen volume would have a higher risk of decompensation. We developed a spleen-based model and validated it in external validation cohorts. The proposed model might help predict hepatic decompensation in people with compensated cirrhosis when invasive tools are unavailable.
ESTHER : Yu_2022_JHEP.Rep_4_100575
PubMedSearch : Yu_2022_JHEP.Rep_4_100575
PubMedID: 36204707

Title : Effects of Peroxiredoxin 6 and Its Mutants on the Isoproterenol Induced Myocardial Injury in H9C2 Cells and Rats - Mu_2022_Oxid.Med.Cell.Longev_2022_2576310
Author(s) : Mu R , Ye S , Lin R , Li Y , Guo X , An L
Ref : Oxid Med Cell Longev , 2022 :2576310 , 2022
Abstract : BACKGROUND: Peroxiredoxin 6 (PRDX6) is an important antioxidant enzyme, with a potential application value in the treatment of diseases caused by oxidative damage. METHODS: PRDX6 and a mutant (mPRDX6) were heterologously expressed by using an E.coli expression system and purified by Ni-affinity chromatography. Isoproterenol (ISO) was used to induce a myocardial cell injury model and an animal myocardial injury model. After the treatment with PRDX6 and mPRDX6, the proliferation activity of H9C2 cells was detected by Cell Counting Kit-8 (CCK8) method; the apoptosis was evaluated by flow cytometry, and the histological changes of myocardial cells were observed by hematoxylin and eosin (H&E) staining, the levels of catalase (CAT), glutathione peroxidase (GPX), malondialdehyde (MDA), and superoxide dismutase (SOD) in ISO-treated H9C2 cells as well as in the heart tissue and serum of rats treated with ISO were detected, and the expression levels of Bax, Bcl-2 and peroxisome proliferators-activated receptors-gamma (PPAR-gamma) proteins were detected by Western blot. RESULTS: PRDX6 and mPRDX6 were successfully expressed and purified. The results of efficacy study showed that the mutant mPRDX6, in which the phospholipaseA2 (PLA2) activity of PRDX6 was deleted by site directed mutation, had a better protective effect against the myocardial injury than PRDX6. CCK8 results showed that compared with that in ISO group, the proliferation activity of H9C2 cells was significantly enhanced (P < 0.01), the apoptosis rate was significantly decreased (P < 0.01), and the fluorescence intensity of reactive oxygen species (ROS) was significantly decreased (P < 0.01) in mPRDX6 group. The results of H&E staining showed that the myocardial injury was alleviated to a certain extent in mPRDX6 group. Compared with those in ISO group, the activities of CAT, GPX, and SOD in H9C2 cells and the heart tissue and serum of rats were significantly increased (P < 0.05), while the contents of MDA were significantly decreased (P < 0.05). Western blot analysis showed that the expression level of Bcl-2 in H9C2 cells was significantly decreased (P < 0.01), and that of Bax and PPAR-gamma was significantly increased (P < 0.05). CONCLUSION: mPRDX6 has a protective effect against the myocardial injury induced by ISO, and the mechanism may be related to its antioxidation. This study may provide a theoretical basis for the research and development of drugs used for the treatment of myocardial injury.
ESTHER : Mu_2022_Oxid.Med.Cell.Longev_2022_2576310
PubMedSearch : Mu_2022_Oxid.Med.Cell.Longev_2022_2576310
PubMedID: 35378825

Title : Extraction and preparation of 5-lipoxygenase and acetylcholinesterase inhibitors from Astragalus membranaceus stems and leaves - Liu_2022_J.Sep.Sci__
Author(s) : Liu R , Zhang Y , Li S , Liu C , Zhuang S , Zhou X , Li Y , Liang J
Ref : J Sep Sci , : , 2022
Abstract : In this study, an efficient method that employs 5-lipoxygenase and acetylcholinesterase as biological target molecules in receptor-ligand affinity ultrafiltration-liquid chromatography was developed for the screening of enzyme inhibitors derived from the Astragalus membranaceus stems and leaves. The effects of the extraction time, number of extraction cycles, ethanol concentration, and liquid-solid ratio on the total yield of the target compounds were investigated using response surface methodology, and the bioactive components were isolated using a combination of semi-preparative high-performance liquid chromatography and high-speed countercurrent chromatography via a two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (1:6:2:6, v/v/v/v). Subsequently, ten naturally-occurring bioactive components in the Astragalus membranaceus stems and leaves, including wogonin, ononin, isoquercitrin, calycosin-7-glucoside, 3-hydroxy-9,10-dimethoxyptercarpan, hyperoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, baicalein, calycosin, and soyasaponin, were screened using affinity ultrafiltration to determine their potential effects against Alzheimer's disease. Consequently, all target compounds had purities higher than 95.0%, and the potential anti-Alzheimer's disease effect of the obtained bioactive compounds was verified using molecular docking analysis. Based on the results, the back-to-back screening of complex enzyme inhibitors and separation of the target bioactive compounds using complex chromatography could provide a new approach for the discovery and preparation of natural active ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2022_J.Sep.Sci__
PubMedSearch : Liu_2022_J.Sep.Sci__
PubMedID: 36502278

Title : Hesperidin methyl chalcone ameliorates lipid metabolic disorders by activating lipase activity and increasing energy metabolism - Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
Author(s) : Liu S , Liu K , Wang Y , Wu C , Xiao Y , Yu J , Ma Z , Liang H , Li X , Li Y , Zhou L
Ref : Biochimica & Biophysica Acta Mol Basis Dis , :166620 , 2022
Abstract : Obesity has become an increasingly serious health issue with the continuous improvement in living standards. Its prevalence has become an economic burden on health care systems worldwide. Flavonoids have been shown to be beneficial in the prevention and treatment of obesity. Here, we evaluated the therapeutic potential of the flavonoid hesperidin methyl chalcone (HMC) on mice with high-fat diet (HFD)-induced hepatic steatosis in vivo and in vitro. Treatment with HMC reduced oleic and palmitic acid-induced increases in intracellular triglyceride accumulation in HepG2, AML12 and LMH cells. HMC also enhanced energy metabolism and lowered oxidative stress. We used Discovery studio to dock key proteins associated with lipid metabolism disorders to HMC, and found that HMC interacted with lipase. Furthermore, we demonstrated that HMC improved lipase activity and lipolysis. In addition, we found that HMC promoted glucose absorption, alleviated lipid metabolic disorders, improved HFD-induced liver injury, and regulated HFD-induced changes in energy metabolism. In conclusion, our study demonstrated that HMC ameliorated HFD-induced obesity and its complications by promoting lipase activity, and provides a novel approach for the prevention and treatment of obesity and related diseases.
ESTHER : Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
PubMedSearch : Liu_2022_Biochim.Biophys.Acta.Mol.Basis.Dis__166620
PubMedID: 36494040

Title : An in vitro nerve agent brain poisoning transwell model for convenient and accurate antidote evaluation - Huang_2022_Toxicol.In.Vitro__105541
Author(s) : Huang L , Li Y , Zhang Z , Huang J , Xing H , Wang L , Sui X , Luo Y , Wang Y , Yang J
Ref : Toxicol In Vitro , :105541 , 2022
Abstract : Nerve agent (NA) can inhibit acetylcholinesterase (AChE) causing seriously injury at extremely low doses. However, the cruel reality is that the lack of effective cerebral antidotes for treatment of NA poisoning. There is an urgent requirement for the large-scale evaluation and screening of antidotes. An effective NA antidote should include two characteristics: a) to permeate the blood-brain barrier (BBB); 2) to reactivate the inhibited AChE in brain. Existing methods for evaluating reactivators in vitro can only examine the reactivation effect, while the current Transwell model can only evaluate the drug penetration performance for crossing the barrier. In this work, brain microvascular endothelial cells (RBMECs) were inoculated to establish a Transwell model. AChE, NAs and antidotes of reactivators were added into the different chambers to simulate central poisoning and peripheral drug administration. This method can evaluate the reactivation ability and brain penetration ability of compounds at same time, which is a rapidly and accurately way for drug preliminary screening. In addition to small-molecule drugs, a liposomal nanoantidote loaded with the reactivator Asoxime chloride (HI-6)was prepared. This nanoantidote show high reactivation rate against the NA (sarin), evaluated by both this modified model in vitro and animal test, gaining the consistence results.
ESTHER : Huang_2022_Toxicol.In.Vitro__105541
PubMedSearch : Huang_2022_Toxicol.In.Vitro__105541
PubMedID: 36572320

Title : Employing Engineered Enolase Promoter for Efficient Expression of Thermomyces lanuginosus Lipase in Yarrowia lipolytica via a Self-Excisable Vector - Jiao_2022_Int.J.Mol.Sci_24_
Author(s) : Jiao L , Li W , Li Y , Zhou Q , Zhu M , Zhao G , Zhang H , Yan Y
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Yarrowia lipolytica is progressively being employed as a workhouse for recombinant protein expression. Here, we expanded the molecular toolbox by engineering the enolase promoter (pENO) and developed a new self-excisable vector, and based on this, a combined strategy was employed to enhance the expression of Thermomyces lanuginosus lipase (TLL) in Y. lipolytica. The strength of 11 truncated enolase promoters of different length was first identified using eGFP as a reporter. Seven of the truncated promoters were selected to examine their ability for driving TLL expression. Then, a series of enolase promoters with higher activities were developed by upstream fusing of different copies of UAS1B, and the recombinant strain Po1f/hp16e(100)-tll harboring the optimal promoter hp16e(100) obtained a TLL activity of 447 U/mL. Additionally, a new self-excisable vector was developed based on a Cre/loxP recombination system, which achieved efficient markerless integration in Y. lipolytica. Subsequently, strains harboring one to four copies of the tll gene were constructed using this tool, with the three-copy strain Po1f/3tll showing the highest activity of 579 U/mL. The activity of Po1f/3tll was then increased to 720 U/mL by optimizing the shaking flask fermentation parameters. Moreover, the folding-related proteins Hac1, Pdi, and Kar2 were employed to further enhance TLL expression, and the TLL activity of the optimal recombinant strain Po1f/3tll-hac1-pdi-kar2 reached 1197 U/mL. By using this combined strategy, TLL activity was enhanced by approximately 39.9-fold compared to the initial strain. Thus, the new vector and the combined strategy could be a useful tool to engineer Y. lipolytica for high-level expression of heterologous protein.
ESTHER : Jiao_2022_Int.J.Mol.Sci_24_
PubMedSearch : Jiao_2022_Int.J.Mol.Sci_24_
PubMedID: 36614159

Title : Response of xenobiotic biodegradation and metabolic genes in Tribolium castaneum following eugenol exposure - Zhang_2022_Mol.Genet.Genomics__
Author(s) : Zhang Y , Gao S , Zhang P , Sun H , Lu R , Yu R , Li Y , Zhang K , Li B
Ref : Mol Genet Genomics , : , 2022
Abstract : Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control.
ESTHER : Zhang_2022_Mol.Genet.Genomics__
PubMedSearch : Zhang_2022_Mol.Genet.Genomics__
PubMedID: 35419714

Title : Comparative Genome Analysis Reveals Phylogenetic Identity of Bacillus velezensis HNA3 and Genomic Insights into Its Plant Growth Promotion and Biocontrol Effects - Zaid_2022_Microbiol.Spectr__e0216921
Author(s) : Zaid DS , Cai S , Hu C , Li Z , Li Y
Ref : Microbiol Spectr , :e0216921 , 2022
Abstract : Bacillus velezensis HNA3, a potential plant growth promoter and biocontrol rhizobacterium, was isolated from plant rhizosphere soils in our previous work. Here, we sequenced the entire genome of the HNA3 strain and performed a comparative genome analysis. We found that HNA3 has a 3,929-kb chromosome with 46.5% GC content and 4,080 CDSs. We reclassified HNA3 as a Bacillus velezensis strain by core genome analysis between HNA3 and 74 previously defined Bacillus strains in the evolutionary tree. A comparative genomic analysis among Bacillus velezensis HNA3, Bacillus velezensis FZB42, Bacillus amyloliquefaciens DSM7, and Bacillus subtilis 168 showed that only HNA3 has one predicated secretory protein feruloyl esterase that catalyzes the hydrolysis of plant cell wall polysaccharides. The analysis of gene clusters revealed that whole biosynthetic gene clusters type Lanthipeptide was exclusively identified in HNA3 and might lead to the synthesis of new bioactive compounds. Twelve gene clusters were detected in HNA3 responsible for the synthesis of 14 secondary metabolites including Bacillaene, Fengycin, Bacillomycin D, Surfactin, Plipastatin, Mycosubtilin, Paenilarvins, Macrolactin, Difficidin, Amylocyclicin, Bacilysin, Iturin, Bacillibactin, Paenibactin, and others. HNA3 has 77 genes encoding for possible antifungal and antibacterial secreting carbohydrate active enzymes. It also contains genes involved in plant growth promotion, such as 11 putative indole acetic acid (IAA)-producing genes, spermidine and polyamine synthase genes, volatile compound producing genes, and multiple biofilm related genes. HNA3 also has 19 phosphatase genes involved in phosphorus solubilization. Our results provide insights into the genetic characteristics responsible for the bioactivities and potential application of HNA3 as plant growth-promoting strain in ecological agriculture. IMPORTANCE This study is the primary initiative to identify Bacillus velezensis HNA3 whole genome sequence and reveal its genomic properties as an effective biocontrol agent against plant pathogens and a plant growth stimulator. HNA3 genetic profile can be used as a reference for future studies that can be applied as a highly effective biofertilizer and biofungicide inoculum to improve agriculture productivity. HNA3 reclassified in the phylogenetic tree which may be helpful for highly effective strain engineering and taxonomy. The genetic comparison among HNA3 and closely similar species B. velezensis FZB42, B. amyloliquefaciens DSM7, and B. subtilis 168 demonstrates some distinctive genetic properties of HNA3 and provides a basis for the genetic diversity of the Bacillus genus, which allows developing more effective eco-friendly resources for agriculture and separation of Bacillus velezensis as distinct species in the phylogenetic tree.
ESTHER : Zaid_2022_Microbiol.Spectr__e0216921
PubMedSearch : Zaid_2022_Microbiol.Spectr__e0216921
PubMedID: 35107331

Title : Characterization of 4 deletion mutants of Pseudomonas plecoglossicida and their potential for live attenuated vaccines in large yellow croaker (Larimichthys crocea) - Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
Author(s) : Li Y , Chi Y , Li S , Jia T , Mao Z
Ref : Fish Shellfish Immunol , : , 2022
Abstract : To search for live attenuated vaccines (LAV) candidates against Pseudomonas plecoglossicida, the causative agent of the visceral granulomas disease in farmed large yellow croaker (Larimichthys crocea), two type VI secretion systems (T6SS) and a predicted alpha/beta fold family hydrolase encoding gene, ORF4885 were targeted to construct deletion mutants. The biological profiles of 4 mutants were characterized; LD50 to the croakers detected, in vivo survival post-infection investigated relative percent of survival (RPS) of the croakers 28d post-vaccination determined, and transcription of five immunity-related genes of the treated fish was quantified. On comparison to the WT, the mutants revealed similar growth curves in 11h; swarming motility of delta4885 declined significantly at 72h post-incubation (P < 0.05); deltaS1delta4885 showed significantly poor biofilm formation and weak resistance to fish serum bactericidal activity (P < 0.05). LD50 of the mutants were much higher than the WT, indication of strong virulence attenuation; in vivo survival test showed the mutant deltaS1delta4885 and deltaS1deltaS3 were eliminated by the host 10d post-infection, demonstration of the safety and potentiality to be LAV candidates. Immunization with the mutant deltaS1delta4885 provided higher RPS than deltaS1deltaS3. Transcription of IgT was significant in all immunized groups while IgM increased only in intraperitoneally injected groups. This study successfully searched a quite safe and strong immunogenic LAV candidate to defeat P. plecoglossicida infection.
ESTHER : Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
PubMedSearch : Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
PubMedID: 35752370
Gene_locus related to this paper: 9psed-s2k464

Title : A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: findings from the UK Biobank - Zhu_2022_Gene_822_146340
Author(s) : Zhu X , Li Y , Yu T , Li S , Chen M
Ref : Gene , :146340 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are protective factors against cardiovascular diseases (CVDs) because of their vasodilatory, cholesterol-lowering, and anti-inflammatory effects. Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, degrades EETs into less biologically active metabolites. EPHX2 is highly polymorphic, and genetic polymorphisms in EPHX2 have been linked to various types of CVDs, such as coronary heart disease, essential hypertension, and atrial fibrillation recurrence. METHODS: Based on a priori hypothesis that EPHX2 genetic polymorphisms play an important role in the pathogenesis of CVDs, we comprehensively investigated the associations between 210 genetic polymorphisms in the EPHX2 gene and an array of 118 diseases in the circulatory system using a large sample from the UK Biobank (N=307,516). The diseases in electronic health records were mapped to the phecode system, which was more representative of independent phenotypes. Survival analyses were employed to examine the effects of EPHX2 variants on CVD incidence, and a phenome-wide association study was conducted to study the impact of EPHX2 polymorphisms on 62 traits, including blood pressure, blood lipid levels, and inflammatory indicators. RESULTS: A novel association between the intronic variant rs116932590 and the phenotype "aneurysm and dissection of heart" was identified. In addition, the rs149467044 and rs200286838 variants showed nominal evidence of association with arterial aneurysm and cerebrovascular disease, respectively. Furthermore, the variant rs751141, which was linked with a lower hydrolase activity of sEH, was significantly associated with metabolic traits, including blood levels of triglycerides, creatinine, and urate. CONCLUSIONS: Multiple novel associations observed in the present study highlight the important role of EPHX2 genetic variation in the pathogenesis of CVDs.
ESTHER : Zhu_2022_Gene_822_146340
PubMedSearch : Zhu_2022_Gene_822_146340
PubMedID: 35183688

Title : The strigolactone receptor SlDWARF14 plays a role in photosynthetic pigment accumulation and photosynthesis in tomato - Li_2022_Plant.Cell.Rep_41_2089
Author(s) : Li Z , Pi Y , Zhai C , Xu D , Ma W , Chen H , Li Y , Wu H
Ref : Plant Cell Rep , 41 :2089 , 2022
Abstract : Tomato DWARF14 regulates the development of roots, shoot branches and leaves, and also plays a role in photosynthetic pigment accumulation and photosynthetic capacity. Strigolactones (SLs) are a novel class of plant hormones. DWARF14 (D14) is the only SL receptor identified to date, but it is not functionally analyzed in tomato (Solanum lycopersicum). In the present study, we identified the potential SL receptor in tomato by bioinformatic analysis, which was designated as SlD14. SlD14 was expressed in roots, stems, flowers and developing fruits, with the highest expression level in leaves. sld14 mutant plants produced by the CRISPR/Cas9 system displayed reduced plant height and root biomass, increased shoot branching and altered leaf shape comparing with WT plants. The cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE 3 (SlIPT3), auxin biosynthetic genes FLOOZY (SlFZY) and TRYPTOPHAN AMINOTRANSFERASE RELATED 1 (SlTAR1) and several auxin transport genes SlPINs, which are involved in branch formation, showed higher expression levels in the sld14 plant stem. In addition, sld14 plants exhibited light-green leaves, reduced chlorophyll and carotenoid contents, abnormal chloroplast structure and reduced photosynthetic capacity. Transcriptomic analysis showed that the transcript levels of six chlorophyll biosynthetic genes, three carotenoid biosynthetic genes and numerous chlorophyll a/b-binding protein genes were decreased in sld14 plants. These results suggest that tomato SL receptor gene SlD14 not only regulates the development of roots, shoot branches and leaves, but also plays a role in regulating photosynthetic pigment accumulation and photosynthetic capacity.
ESTHER : Li_2022_Plant.Cell.Rep_41_2089
PubMedSearch : Li_2022_Plant.Cell.Rep_41_2089
PubMedID: 35907035

Title : Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93 - Li_2022_Front.Microbiol_13_1081094
Author(s) : Li Y , Rong Z , Li Z , Cui H , Li J , Xu XW
Ref : Front Microbiol , 13 :1081094 , 2022
Abstract : INTRODUCTION: CPT11 (Irinotecan; 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) is an important camptothecin-based broad-spectrum anticancer prodrug. The activation of its warhead, SN38 (7-ethyl-10-hydroxycamptothecin), requires hydrolysis by carboxylesterases. NPC (7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin) is a metabolic derivative of CPT11 and is difficult to be hydrolyzed by human carboxylesterase. Microbial carboxylesterase with capability on both CPT11 and NPC hydrolysis is rarely reported. A marine microbial carboxylesterase, E93, was identified to hydrolyze both substrates in this study. This enzyme was an appropriate subject for uncovering the catalytic mechanism of carboxylesterases to CPT11 and NPC hydrolysis. METHODS: X-ray diffraction method was applied to obtain high-resolution structure of E93. Molecular docking was adopted to analyze the interaction of E93 with p-NP (p-nitrophenyl), CPT11, and NPC substrates. Mutagenesis and enzymatic assay were adopted to verify the binding pattern of substrates. RESULTS: Three core regions (Region A, B, and C) of the catalytic pocket were identified and their functions on substrates specificity were validated via mutagenesis assays. The Region A was involved in the binding with the alcohol group of all tested substrates. The size and hydrophobicity of the region determined the binding affinity. The Region B accommodated the acyl group of p-NP and CPT11 substrates. The polarity of this region determined the catalytic preference to both substrates. The Region C specifically accommodated the acyl group of NPC. The interaction from the acidic residue, E428, contributed to the binding of E93 with NPC. DISCUSSION: The study analyzed both unique and conserved structures of the pocket in E93, for the first time demonstrating the discrepancy of substrate-enzyme interaction between CPT11 and NPC. It also expanded the knowledge about the substrate specificity and potential application of microbial Family VII carboxylesterases.
ESTHER : Li_2022_Front.Microbiol_13_1081094
PubMedSearch : Li_2022_Front.Microbiol_13_1081094
PubMedID: 36756200

Title : Characteristics of a recombinant Fusarium verticillioides cutinase and its effects on enzymatic hydrolysis of rice straw - Gu_2021_Int.J.Biol.Macromol_171_382
Author(s) : Gu S , Liu C , Zhang W , Qu M , Li Y , Zang Y , Xiong X , Pan K , Zhao X
Ref : Int J Biol Macromol , 171 :382 , 2021
Abstract : The current study heterologously expressed a cutinase from Fusarium verticillioides by Pichia pastoris and investigated its properties and effects on the hydrolysis of rice straw. The optimal pH and temperature for F. verticillioides cutinase were 8.0 and 50 degreesC, respectively. F. verticillioides cutinase had poor thermal stability and could be inhibited by some metal ions, inhibitors, and detergents (5 mM), including Ni(2+), Zn(2+), Cu(2+), Ca(2+), Mn(2+), sodium dodecyl sulfate, EDTA, and Tween-20. F. verticillioides cutinase could tolerate 15% methanol and dimethyl sulfoxide but was significantly repressed by 15% ethanol and acetone with 48% and 63% residual activity, respectively. F. verticillioides cutinase could degrade the cuticle of rice straw with palmitic acid and stearic acid as the main products. However, the dissolving sugars released from the rice straw treated with F. verticillioides cutinase were significantly reduced by 29.2 microg/mL compared with the control (107.9 microg/mL). Similarly, the reducing sugars produced from the cellulase hydrolysis of rice straw pretreated with F. verticillioides cutinase were reduced by 63.5 microg/mL relative to the control (253.6 microg/mL). Scanning electron microscopy results showed that numerous tuberculate or warty protrusions were present nearly everywhere on the surface of rice straw treated with F. verticillioides cutinase, and some protrusions even covered and blocked the stomata of the rice straw surface. Current limited data indicate that F. verticillioides cutinase might not be an appropriate choice for improving the utilization of agricultural straws.
ESTHER : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedSearch : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedID: 33434547
Gene_locus related to this paper: gibm7-w7lbp5

Title : Acetylcholinesterase inhibition with Pyridostigmine attenuates hypertension and neuroinflammation in the paraventricular nucleus in rat model for Preeclampsia - Issotina_2021_Int.Immunopharmacol__108365
Author(s) : Issotina Zibrila A , Li Y , Wang Z , Zhao G , Liu H , Leng J , Ahasan Ali M , Ampofo Osei J , Kang YM , Liu J
Ref : Int Immunopharmacol , :108365 , 2021
Abstract : Preeclampsia (PE) is characterized by hypertension, autonomic imbalance and inflammation. The subfornical organ (SFO) reportedly relays peripheral inflammatory mediator's signals to the paraventricular nucleus (PVN), a brain autonomic center shown to mediate hypertension in hypertensive rat but not yet in PE rat models. Additionally, we previously showed that Pyridostigmine (PYR), an acetylcholinesterase inhibitor, attenuated placental inflammation and hypertension in PE models. In this study, we investigated the effect of PYR on the activities of these brain regions in PE model. PYR (20 mg/kg/day) was administered to reduced uterine perfusion pressure (RUPP) Sprague-Dawley rat from gestational day (GD) 14 to GD19. On GD19, the mean arterial pressure (MAP) was recorded and samples were collected for analysis. RUPP rats exhibited increased MAP (P = 0.0025), elevated circulating tumor necrosis factor-alpha (TNF-alpha, P = 0.0075), reduced baroreflex sensitivity (BRS), increased neuroinflammatory markers including TNF-alpha, interleukin-1beta (IL-1beta), microglial activation (P = 0.0039), oxidative stress and neuronal excitation within the PVN and the SFO. Changes in MAP, in molecular and cellular expression induced by RUPP intervention were improved by PYR. The ability of PYR to attenuate TNF-alpha mediated central effect was evaluated in TNF-alpha-infused pregnant rats. TNF-alpha infusion-promoted neuroinflammation in the PVN and SFO in dams was abolished by PYR. Collectively, our data suggest that PYR improves PE-like symptoms in rat by dampening placental ischemia and TNF-alpha-promoted inflammation and pro-hypertensive activity in the PVN. This broadens the therapeutical potential of PYR in PE.
ESTHER : Issotina_2021_Int.Immunopharmacol__108365
PubMedSearch : Issotina_2021_Int.Immunopharmacol__108365
PubMedID: 34815190

Title : Stilbenoids isolated from the roots of Rheum lhasaense under the guidance of the acetylcholinesterase inhibition activity - Liu_2021_J.Nat.Med__
Author(s) : Liu Q , Shen J , Li P , Li Y , He C , Xiao P
Ref : J Nat Med , : , 2021
Abstract : Four unknown stilbenoids, including one dimer, namely 4'-methoxy-scirpusin A (5) and three monomeric stilbene glycosides, namely piceatannol-3'-O-[2''-(3,5-dihydroxy-4-methoxybenzoyl)]-beta-D-glucopyranoside (13), piceatannol-3'-O-(2''-galloyl)-beta-D-glucopyranoside (14) and piceatannol-3'-O-(6''-p-coumaroyl)-beta-D-glucopyranoside (16) together with 15 described compounds, were isolated from the ethyl acetate fraction of the ethanol extract of roots of Rheum lhasaense based on the guidance of the inhibitory effect on acetylcholinesterase. The structures of the unknown compounds were established by combined spectroscopic analysis and comparing their spectral data with compounds with similar structures. Some selected components were also investigated for their inhibitory abilities on acetylcholinesterase (AChE), indicating that compound 13 may be responsible for higher inhibitory activity of the ethyl acetate fraction on AChE.
ESTHER : Liu_2021_J.Nat.Med__
PubMedSearch : Liu_2021_J.Nat.Med__
PubMedID: 33411157

Title : Magnetic covalent organic framework immobilized gold nanoparticles with high-efficiency catalytic performance for chemiluminescent detection of pesticide triazophos - Ma_2021_Talanta_235_122798
Author(s) : Ma Y , Zhao Y , Xu X , Ding S , Li Y
Ref : Talanta , 235 :122798 , 2021
Abstract : Covalent organic frameworks (COFs) are considered to be a promising support material for catalyst due to their highly ordered porous structure. Here, a core-shell structured Fe(3)O(4) magnetic covalent organic framework (Fe(3)O(4)@COF) was synthesized and employed to provide basic sites for immobilization of gold nanoparticles (AuNPs). The AuNPs was in-situ immobilized on the shell of Fe(3)O(4)@COF via a citrate reducing method. The Fe(3)O(4)@COF-AuNP had convenient magnetic separability and exhibited excellent mimicking peroxidase-like activity in catalyzing chemiluminescence (CL) reaction of luminol with hydrogen peroxide (H(2)O(2)). With acetylcholine chloride (ACh) as substrate of acetylcholinesterase (AChE), a CL method was exploited for sensitive detection of organophosphorus pesticide triazophos due to its irreversible inhibiting effect on the AChE activity and subsequently influences the production of H(2)O(2) under the condition of choline oxidase (ChOx). This method gave a good linearity for triazophos in the range of 5.0-300.0 nmol L(-1), and a limit of detection (LOD) of 1 nmol L(-1) was acquired. The applicability of this method was verified by the determination of triazophos in different spiked vegetable samples.
ESTHER : Ma_2021_Talanta_235_122798
PubMedSearch : Ma_2021_Talanta_235_122798
PubMedID: 34517656

Title : Platelet activating-factor acetylhydrolase II: A member of phospholipase A2 family that hydrolyzes oxidized phospholipids - Dong_2021_Chem.Phys.Lipids_239_105103
Author(s) : Dong L , Li Y , Wu H
Ref : Chemistry & Physic of Lipids , 239 :105103 , 2021
Abstract : Intracellular platelet activating-factor acetylhydrolase type II (PAF-AH II) is a 40-kDa monomeric enzyme. It was originally identified as an enzyme that hydrolyzes the acetyl group of PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). As a member of phospholipase A2 super family, PAF-AH II has broad substrate specificity. It can hydrolyze phospholipids with relatively short-length or oxidatively modified sn-2 chains which endows it with various functions such as protection against oxidative stress, transacetylase activity and producing lipid mediators. PAF-AH II has been proven to be involved in several diseases such as allergic diseases, oxidative stress-induced injury and ischemia injury, thus it has drawn more attention from researchers. In this paper, we outline an entire summary of PAF-AH II, including its structure, substrate specificity, activity assay, inhibitors and biological activities.
ESTHER : Dong_2021_Chem.Phys.Lipids_239_105103
PubMedSearch : Dong_2021_Chem.Phys.Lipids_239_105103
PubMedID: 34116047
Gene_locus related to this paper: human-PAFAH2

Title : Adsorption mechanism of two pesticides on polyethylene and polypropylene microplastics: DFT calculations and particle size effects - Mo_2021_Environ.Pollut_291_118120
Author(s) : Mo Q , Yang X , Wang J , Xu H , Li W , Fan Q , Gao S , Yang W , Gao C , Liao D , Li Y , Zhang Y
Ref : Environ Pollut , 291 :118120 , 2021
Abstract : Polyethylene (PE) and polypropylene (PP) microplastics (MPs), as carriers, can bind with pesticides, which propose harmful impacts to aqueous ecosystems. Meanwhile, carbofuran and carbendazim (CBD), two widely used carbamate pesticides, are toxic to humans because of the inhibition of acetylcholinesterase activity. The interaction between two MPs and two pesticides could start in farmland and be maintained during transportation to the ocean. Herein, the adsorption behavior and mechanism of carbofuran and carbendazim (CBD) by PE and PP MPs were investigated via characterization and density functional theory (DFT) simulation. The adsorption kinetic and thermodynamic data were best described by pseudo-second-order kinetics and the Freundlich models. The adsorption behaviors of individual carbofuran/CBD on both MPs were very similar. The CBD adsorption rate and capacity of PE and PP MPs were higher than those of carbofuran. This phenomenon explained the lower negative effects of DOM (oxalic acid, glycine (Gly)) on CBD adsorption relative to those of carbofuran. The presence of oxalic acid and Gly decreased the PE adsorption by 20.40-48.02% and the PP adsorption by 19.27-42.11%, respectively. It indicated the significance of DOM in carbofuran cycling. The adsorption capacities were negatively correlated with MPs size, indicating the importance of specific surficial area. Fourier transformation infrared spectroscopy before and after adsorption suggested that the adsorption process did not produce any new covalent bond. Instead, intermolecular van der Waals forces were one of the primary adsorption mechanisms of carbofuran and CBD by MPs, as evidenced by DFT calculations. Based on the zeta potential, the electrostatic interaction explained the higher adsorption CBD by MPs than carbofuran.
ESTHER : Mo_2021_Environ.Pollut_291_118120
PubMedSearch : Mo_2021_Environ.Pollut_291_118120
PubMedID: 34520951

Title : Enteral Nutrition Combined with Improved-Sijunzi Decoction Shows Positive Effect in Precachexia Cancer Patients: A Retrospective Analysis - Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
Author(s) : Li Y , Chen Y , Zeng Y , Dong J , Li C , Jia Y , Zhao Y , Wang K
Ref : Evid Based Complement Alternat Med , 2021 :7357521 , 2021
Abstract : BACKGROUND: Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. METHODS: A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. RESULTS: ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001, PG-SGA: p=0.019, dietary intake: p=0.0001, TCMS: p=0.0001). The levels of HGB (p=0.006), PAlb (p=0.001), Alb (p=0.0001), TP (p=0.008), and ChE (p=0.0001) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB (p=0.028) and CRP/PALB (p=0.005) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. CONCLUSIONS: Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).
ESTHER : Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
PubMedSearch : Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
PubMedID: 34603476

Title : Biogenetic cantharidin is a promising leading compound to manage insecticide resistance of Mythimna separata (Lepidoptera: Noctuidae) - Li_2021_Pestic.Biochem.Physiol_172_104769
Author(s) : Li Y , Sun H , Yasoob H , Tian Z , Li R , Zheng S , Liu J , Zhang Y
Ref : Pestic Biochem Physiol , 172 :104769 , 2021
Abstract : Cantharidin (CTD) is a natural toxin with effective toxicity to lepidopteran pests. Nevertheless, little information is available on whether pests develop resistance to CTD. After being exposed to CTD (50 mg/L to 90 mg/L) or 10 generations, the resistance ratio of laboratory selected cantharidin-resistant Mythimna separata (Cantharidin-SEL) strain was only elevated 1.95-fold. Meanwhile, the developmental time for M. separata was prolonged (delayed1.65 in males and 1.84 days in females). The reported CTD target, the serine/threonine phosphatases (PSPs), have not been shown significant activity variation during the whole process of CTD-treatment. The activity of detoxification enzymes (cytochrome monooxygenase P450, glutathione-S-transferase (GST) and carboxylesterase) were affected by CTD selection, but this change was not mathematically significant. More importantly, no obvious cross-resistance with other commonly used insecticides was observed in the M. separata population treated with CTD for 10 generations (resistance ratios were all lower 2.5). Overall, M. separata is unlikely to produce target-site insensitivity resistance, metabolic resistance to CTD. Meanwhile, cantharidin-SEL is not prone to develop cross-resistance with other insecticides. These results indicate that CTD is a promising biogenetic lead compound which can be applied in the resistance management on M. separata.
ESTHER : Li_2021_Pestic.Biochem.Physiol_172_104769
PubMedSearch : Li_2021_Pestic.Biochem.Physiol_172_104769
PubMedID: 33518040

Title : Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells - Zhang_2021_Pharmacol.Res_169_105630
Author(s) : Zhang Y , Li K , Li Y , Zhao W , Wang L , Chen Z , Ma X , Yao T , Wang J , Dong W , Li X , Tian X , Fu R
Ref : Pharmacol Res , 169 :105630 , 2021
Abstract : BACKGROUND: DPP8 and DPP9 have been demonstrated to play important roles in multiple diseases. Evidence for increased gene expression of DPP8 and DPP9 in tubulointerstitium was found to be associated with the decline of kidney function in chronic kidney disease (CKD) patients, which was observed in the Nephroseq human database. To examine the role of DPP8 and DPP9 in the tubulointerstitial injury, we determined the efficacy of DPP8 and DPP9 on epithelial-to-mesenchymal transition (EMT) and tubulointerstitial fibrosis (TIF) as well as the underlying mechanisms. METHODS: We conducted the immunofluorescence of DPP8 and DPP9 in kidney biopsy specimens of CKD patients, established unilateral ureteral obstruction (UUO) animal model, treated with TC-E5007 (a specific inhibitor of both DPP8 and DPP9) or Saxagliptin (positive control) or saline, and HK-2 cells model. RESULTS: We observed the significantly increased expression of DPP8 and DPP9 in the renal proximal tubule epithelial cells of CKD patients compared to the healthy control subjects. DPP8/DPP9 inhibitor TC-E5007 could significantly attenuate the EMT and extracellular matrix (ECM) synthesis in UUO mice, all these effects were mediated via interfering with the TGF-beta1/Smad signaling. TC-E5007 treatment also presented reduced renal inflammation and improved renal function in the UUO mice compared to the placebo-treated UUO group. Furthermore, the siRNA for DPP8 and DPP9, and TC-E5007 treatment decreased EMT- and ECM-related proteins in TGF-beta1-treated HK-2 cells respectively, which could be reversed significantly by transduction with lentivirus-DPP8 and lentivirus-DPP9. CONCLUSION: These data obtained provide evidence that the DPP8 and DPP9 could be potential therapeutic targets against TIF.
ESTHER : Zhang_2021_Pharmacol.Res_169_105630
PubMedSearch : Zhang_2021_Pharmacol.Res_169_105630
PubMedID: 33932609
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Risk Factors and a Nomogram Model Establishment for Postoperative Delirium in Elderly Patients Undergoing Arthroplasty Surgery: A Single-Center Retrospective Study - Chen_2021_Biomed.Res.Int_2021_6607386
Author(s) : Chen D , Li Y , Li Q , Gao W , Li J , Wang S , Cao J
Ref : Biomed Res Int , 2021 :6607386 , 2021
Abstract : OBJECTIVE: To explore the related risk factors of postoperative delirium (POD) after hip or knee arthroplasty in elderly orthopedic patients and the predictive value of related risk factors. Material and Methods. In total, 309 patients (<=60 years) who received knee and hip arthroplasty between January 2017 and May 2020 were consecutively selected into the POD and nonpostoperative delirium (NPOD) groups. Group bias was eliminated through propensity score matching. Univariate and multivariable logistic analysis was used to determine the risk factors for POD. The nomogram was made by R. RESULTS: 58 patients were included in each group after propensity score matching; multivariable analysis demonstrated that LDH (OR = 4.364, P = 0.017), CHE (OR = 4.640, P = 0.004), Cystatin C (OR = 5.283, P = 0.006), arrhythmia (OR = 5.253, P = 0.002), and operation duration (OR = 1.017, P = 0.050) were independent risk factors of POD. LDH, CHE, Cystatin C, and arrhythmia were used to construct a nomogram to predict the POD. The nomogram was well calibrated and had moderate discriminative ability (AUC = 0.821, 95% CI: 0.760~0.883). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Our study revealed that arrhythmia, operation duration, the increase of lactate dehydrogenase and Cystatin C, and the decrease of cholinesterase were reliable factors for predicting postoperative delirium after elderly hip and knee arthroplasty. Meanwhile, the nomogram we developed can assist the clinician to filtrate potential patients with postoperative delirium.
ESTHER : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedSearch : Chen_2021_Biomed.Res.Int_2021_6607386
PubMedID: 34901277

Title : Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney - Luo_2021_J.Biol.Chem__100667
Author(s) : Luo J , Hu S , Fu M , Luo L , Li Y , Li W , Cai Y , Dong R , Yang Y , Tu L , Xu X
Ref : Journal of Biological Chemistry , :100667 , 2021
Abstract : The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was used to treat mice (1 mg/kg/d) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) were markedly upregulated in the kidneys of mice fed a HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2, and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knock-down or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the IKKalpha/beta/NF-kappaB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by a HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression due to inactivation of the IKKalpha/beta/NF-kappaB-induced inflammatory response.
ESTHER : Luo_2021_J.Biol.Chem__100667
PubMedSearch : Luo_2021_J.Biol.Chem__100667
PubMedID: 33864813

Title : Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 GAG knock-in mice - Yokoi_2021_IBRO.Neurosci.Rep_11_1
Author(s) : Yokoi F , Dang MT , Zhang L , Dexter KM , Efimenko I , Krishnaswamy S , Villanueva M , Misztal CI , Gerard M , Lynch P , Li Y
Ref : IBRO Neurosci Rep , 11 :1 , 2021
Abstract : DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous deltaGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.
ESTHER : Yokoi_2021_IBRO.Neurosci.Rep_11_1
PubMedSearch : Yokoi_2021_IBRO.Neurosci.Rep_11_1
PubMedID: 34189496

Title : Genome-Wide Identification of Tannase Genes and Their Function of Wound Response and Astringent Substances Accumulation in Juglandaceae - Wang_2021_Front.Plant.Sci_12_664470
Author(s) : Wang J , Wang K , Lyu S , Huang J , Huang C , Xing Y , Wang Y , Xu Y , Li P , Hong J , Xi J , Si X , Ye H , Li Y
Ref : Front Plant Sci , 12 :664470 , 2021
Abstract : Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes (TAs) responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that TA genes and neighboring clade genes (TA-like genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of TA genes produced by tandem repeat. TA genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene GGTs and the hydrolase gene TAs was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the CcGGTs' expression was higher than CiGGTs in the initiation of development, but CcTAs continued to be down-regulated while CiTA2a and CiTA2b were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of TAs in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae.
ESTHER : Wang_2021_Front.Plant.Sci_12_664470
PubMedSearch : Wang_2021_Front.Plant.Sci_12_664470
PubMedID: 34079571
Gene_locus related to this paper: camsi-CsTA

Title : Reduced neuropathy target esterase in pre-eclampsia suppresses tube formation of HUVECs via dysregulation of phospholipid metabolism - Li_2021_J.Cell.Physiol_236_4435
Author(s) : Li M , Shen X , Liu H , Yang B , Lu S , Tang M , Ling Y , Li Y , Kuang H
Ref : Journal of Cellular Physiology , 236 :4435 , 2021
Abstract : Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism.
ESTHER : Li_2021_J.Cell.Physiol_236_4435
PubMedSearch : Li_2021_J.Cell.Physiol_236_4435
PubMedID: 33184906

Title : Combined use of GABA and sitagliptin promotes human beta-cell proliferation and reduces apoptosis - Liu_2021_J.Endocrinol_248_133
Author(s) : Liu W , Lau HK , Son DO , Jin T , Yang Y , Zhang Z , Li Y , Prud'homme GJ , Wang Q
Ref : J Endocrinol , 248 :133 , 2021
Abstract : gamma-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent beta-cell survival and function. In human beta-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic beta-cell protective effect in mice islets. However, it remains unclear whether this combination has similar effects on human beta-cell. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-gamma mice with streptozotocin-induced diabetes, and then treated them with GABA, Sita, or both. The oral administration of either GABA or Sita ameliorated blood glucose levels, increased transplanted human beta-cell counts and plasma human insulin levels. Importantly, the combined administration of the drugs generated significantly superior results in all these responses, as compared to the monotherapy with either one of them. The proliferation and/or regeneration, improved by the combination, were demonstrated by increased Ki67+, PDX-1+, or Nkx6.1+ beta-cell numbers. Protection against apoptosis was also significantly improved by the drug combination. The expression level of alpha-Klotho, a protein with protective and stimulatory effects on beta cells, was also augmented. Our study indicates that combined use of GABA and Sita produced greater therapeutic benefits, which are likely due to an enhancement of beta-cell proliferation and a decrease in apoptosis.
ESTHER : Liu_2021_J.Endocrinol_248_133
PubMedSearch : Liu_2021_J.Endocrinol_248_133
PubMedID: 33258801

Title : Activation of the NR2E nuclear receptor HR83 leads to metabolic detoxification-mediated chlorpyrifos resistance in Nilaparvata lugens - Lu_2021_Pestic.Biochem.Physiol_173_104800
Author(s) : Lu K , Li Y , Cheng Y , Li W , Song Y , Zeng R , Sun Z
Ref : Pestic Biochem Physiol , 173 :104800 , 2021
Abstract : Increased production of detoxification enzymes appears to be the primary route for insecticide resistance in many crop pests. However, the mechanisms employed by resistant insects for overexpression of detoxification genes involved in insecticide resistance remain obscure. We report here that the NR2E nuclear receptor HR83 plays a critical role in chlorpyrifos resistance by regulating the expression of detoxification genes in the brown planthopper (BPH), Nilaparvata lugens. HR83 was highly expressed in the fat body and ovary of adult females in chlorpyrifos-resistant BPHs. Knockdown of HR83 by RNA interference showed no effect on female fecundity, whereas caused a decrease of resistance to chlorpyrifos. This treatment also led to a dramatic reduction in the expression of multiple detoxification genes, including four UDP-glycosyltransferases (UGTs), three cytochrome P450 monooxygenases (P450s) and four carboxylesterases (CarEs). Among these HR83-regulated genes, UGT-1-3, UGT-2B10, CYP6CW1, CYP4CE1, CarE and Esterase E4-1 were over-expressed both in the fat body and ovary of the resistant BPHs. Functional analyses revealed that UGT-2B10, CYP4CE1, CarE and Esterase E4-1 are essential for the resistance of BPH to chlorpyrifos. Generally, this study implicates HR83 in the metabolic detoxification-mediated chlorpyrifos resistance and suggests that the regulation of detoxification genes may be an ancestral function of the NR2E nuclear receptor subfamily.
ESTHER : Lu_2021_Pestic.Biochem.Physiol_173_104800
PubMedSearch : Lu_2021_Pestic.Biochem.Physiol_173_104800
PubMedID: 33771269

Title : Isolation and Functional Analysis of Effector Proteins of Magnaporthe oryzae - Dai_2021_Methods.Mol.Biol_2356_199
Author(s) : Dai MD , Li Y , Sun LX , Lin FC , Liu XH
Ref : Methods Mol Biol , 2356 :199 , 2021
Abstract : In nature, plants have evolved a myriad of preformed and induced defenses to protect themselves from microbes. Upon microbial infection, the recognition of the microbe-associated molecular patterns (MAMPs) by the pattern recognition receptors (PRRs) triggers the first stage of defense response (Dodds and Rathjen, Nat Rev Genet 11:539-548, 2010). However, in order to develop microbial delivery, effectors target PRRs for deregulating immune responses and facilitating host colonization (Thomma et al., Plant Cell 23:4-15, 2011). Here, we contribute a protocol for the screening system of Magnaporthe oryzae effectors and construct a fluorescent system to trace secretory proteins in the sheath infection samples. Using the tobacco rattle virus (TRV) system, the proteins including LysM, Chitin, Cutinase, and CFEM domains were selected and divided into two kinds according to the results of cell death induced or inhibited test in Nicotiana benthamiana. Then, candidate effectors can be deleted or overexpressed in M. oryzae. The barley or rice infection with M. oryzae, rice leaf sheath inoculation, and subcellular localization during infection can be performed to explore the functions of these effectors.
ESTHER : Dai_2021_Methods.Mol.Biol_2356_199
PubMedSearch : Dai_2021_Methods.Mol.Biol_2356_199
PubMedID: 34236688

Title : Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1 - Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
Author(s) : Hu S , Luo J , Fu M , Luo L , Cai Y , Li W , Li Y , Dong R , Yang Y , Tu L , Xu X
Ref : American Journal of Physiology Heart Circ Physiol , : , 2021
Abstract : Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2(-/-)) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2(-/-) mice without NAM treatment. However, the arterial protective effects were gone in Ephx2(-/-) mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation.
ESTHER : Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
PubMedSearch : Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
PubMedID: 34142887

Title : A ratiometric fluorescence strategy based on inner filter effect for Cu(2+)-mediated detection of acetylcholinesterase - Li_2021_Mikrochim.Acta_188_385
Author(s) : Li Y , Liang H , Lin B , Yu Y , Wang Y , Zhang L , Cao Y , Guo M
Ref : Mikrochim Acta , 188 :385 , 2021
Abstract : A novel ratiometric fluorescence strategy for detection of acetylcholestinerase (AChE) is proposed based on carbon nitride quantum dots (g-CNQD) and the complex (PA) formed between phenylboronic acid (PBA) and alizarin red S (ARS). PA showed fluorescence at 598 nm and quenched the fluorescence of g-CNQD at 438 nm. Through UV-visible absorption, fluorescence, and fluorescence lifetime measurements, the quenching effect was demonstrated as inner filter effect (IFE). When Cu(2+) was added, the coordination of ARS and Cu(2+) decreased the fluorescence of PA at 598 nm and recovered that of g-CNQD at 438 nm. In the presence of AChE it catalyzed the hydrolysis of acetylthiocholine (ATCh) to produce thiocholine (TCh) which competed with ARS for binding to Cu(2+); thus, the fluorescence at 598 nm increased and that at 438 nm decreased again. Under the mediation of Cu(2+), the fluorescence ratio F(598)/F(438) of PA-CNQD probe had good linear relationship with AChE concentration in the range 0.5-15 mU/mL with a detection limit of 0.36 mU/mL. The method was successfully applied to the determination of AChE in human serum and the screening of inhibitors.
ESTHER : Li_2021_Mikrochim.Acta_188_385
PubMedSearch : Li_2021_Mikrochim.Acta_188_385
PubMedID: 34664146

Title : Prognostic Significance of Hematopoietic-cell Serglycin for the Survival of Hepatocellular Carcinoma: A Single-center Retrospective Study - Li_2021_Comb.Chem.High.Throughput.Screen_24_986
Author(s) : Li Y , Chen H , Lu H , Zou Z
Ref : Comb Chem High Throughput Screen , 24 :986 , 2021
Abstract : AIM AND OBJECTIVE: Inflammation-related changes in peripheral blood cells and blood proteins are prognostic factors for survival in hepatocellular carcinoma (HCC), but their usefulness is limited by an active bacterial infection. This study investigated whether infection interfered with the predictive value of serglycin, a proteoglycan found in hematopoietic cells, on survival in HCC. MATERIALS AND METHODS: Patients with hepatitis B virus (HBV)-induced HCC, 100 without and 30 with a bacterial infection, and 30 healthy adult controls were enrolled retrospectively. Baseline clinical data collected before treatment with transarterial chemoembolization (TACE) was evaluated, and serglycin expression was assayed by flow cytometry. Receiver operating characteristic (ROC) curve analysis identified serglycin cutoff values for patient stratification. Cox regression and Kaplan-Meier analyses were performed to identify predictors of overall survival (OS). RESULTS: Serglycin levels in peripheral blood cells were higher in both groups of HCC patients than in the control group. Cholinesterase, lung metastasis, average neutrophil serglycin fluorescence intensity, and aspartate aminotransferase levels were associated with survival risk. Barcelona Clinic Liver Cancer stage A was associated with a good prognosis of OS. CONCLUSION: The intensity of serglycin fluorescence in peripheral neutrophils was independently predictive of survival in HCC, and its value was not limited by a bacterial infection. The method presented here is a simple and feasible way to predict prognosis in HCC patients with TACE.
ESTHER : Li_2021_Comb.Chem.High.Throughput.Screen_24_986
PubMedSearch : Li_2021_Comb.Chem.High.Throughput.Screen_24_986
PubMedID: 33081679

Title : Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry - Zhao_2021_Bioorg.Chem_108_104656
Author(s) : Zhao S , Xu J , Zhang S , Han M , Wu Y , Li Y , Hu L
Ref : Bioorg Chem , 108 :104656 , 2021
Abstract : In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).
ESTHER : Zhao_2021_Bioorg.Chem_108_104656
PubMedSearch : Zhao_2021_Bioorg.Chem_108_104656
PubMedID: 33548731

Title : Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development - Li_2021_Plant.J__
Author(s) : Li S , Li Y , Chen L , Zhang C , Wang F , Li H , Wang M , Wang Y , Nan F , Xie D , Yan J
Ref : Plant J , : , 2021
Abstract : Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.
ESTHER : Li_2021_Plant.J__
PubMedSearch : Li_2021_Plant.J__
PubMedID: 33860570

Title : Broad-spectrum pesticide screening by multiple cholinesterases and thiocholine sensors assembled high-throughput optical array system - Chen_2021_J.Hazard.Mater_402_123830
Author(s) : Chen L , Tian X , Li Y , Lu L , Nie Y , Wang Y
Ref : J Hazard Mater , 402 :123830 , 2021
Abstract : Accurate screening of organophosphorus and carbamates pesticides from the complex real sample is crucial for water quality analysis and food safety control. Herein, a simple, low-cost and accurate pesticides screening method based on a high-throughput optical array system assembled by multiple cholinesterases (ChE) and thiocholine (TCh) sensors is described. The detection mechanism is that the inhibition of ChE activity by pesticides reduces the TCh produced by the hydrolysis of butyryl/acetylthiocholine iodide, thus changing the fluorescence intensity of TCh sensor. The diverse response of ChEs to pesticides and different affinity of sensors to TCh ensure the high-throughput and distinguishable signal output, which allow the establishment of high discrete pesticide database with intra-cluster agglomeration and inter-cluster dispersion. By using the database, the screening of unknown real contaminated samples were successfully operated, and the screened pesticide species and concentrations were consistent with high-performance liquid chromatography. This screening strategy demonstrates the feasibility of replacing existing complex mass spectrometry-based screening strategy with simple optical analysis, providing a new idea for the development of simple accurate screening technologies for widespread organic pollutants including pesticides.
ESTHER : Chen_2021_J.Hazard.Mater_402_123830
PubMedSearch : Chen_2021_J.Hazard.Mater_402_123830
PubMedID: 33254811

Title : A dual-signal sensor for the analysis of parathion-methyl using silver nanoparticles modified with graphitic carbon nitride - Li_2021_J.Pharm.Anal_11_183
Author(s) : Li Y , Wan M , Yan G , Qiu P , Wang X
Ref : J Pharm Anal , 11 :183 , 2021
Abstract : A highly sensitive and selective method was developed for both UV-vis spectrophotometric and fluorimetric determination of organophosphorus pesticides (OPs). This method used silver nanoparticles (AgNPs) modified with graphitic carbon nitride (g-C(3)N(4)). The AgNPs reduced the fluorescence intensity of g-C(3)N(4). Acetylthiocholine (ATCh) could be catalytically hydrolyzed by acetylcholinesterase (AChE) to form thiocholine, which induces aggregation of the AgNPs. This aggregation led to the recovery of the blue fluorescence of g-C(3)N(4), with excitation/emission peaks at 310/460 nm. This fluorescence intensity could be reduced again in the presence of OPs because of the inhibitory effect of OPs on the activity of AChE. The degree of reduction was found to be proportional to the concentration of OPs, and the limit of fluorometric detection was 0.0324 microg/L (S/N = 3). In addition, the absorption of the g-C(3)N(4)/AgNPs at 390 nm decreased because of the aggregation of the AgNPs, but was recovered in presence of OPs because of the inhibition of enzyme activity by OPs. This method was successfully applied to the analysis of parathion-methyl in real samples.
ESTHER : Li_2021_J.Pharm.Anal_11_183
PubMedSearch : Li_2021_J.Pharm.Anal_11_183
PubMedID: 34012694

Title : Characterization of a novel sn1,3 lipase from Ricinus communis L. suitable for production of oleic acid-palmitic acid-glycerol oleate - Li_2021_Sci.Rep_11_6913
Author(s) : Li Y , Li G , Sun H , Chen Y
Ref : Sci Rep , 11 :6913 , 2021
Abstract : The hydrolysis properties of lipase in castor was evaluated using two different substrate forms (tripalmitic glycerides and trioleic glycerides) to catalyze the reaction under different operational conditions. RcLipase was obtained from castor seeds and results show that RcLipase is a conservative serine lipase with a conserved catalytic center (SDH) and a conserved pentapeptide (GXSXG). This enzyme exhibited the greatest activity and tolerance to chloroform and toluene when it was expressed in Pichia pastoris GS115 at 40 degC and pH 8.0. Zn and Cu ions exerted obvious inhibitory effects on the enzyme, and displayed good hydrolytic activity for long-chain natural and synthetic lipids. HPLC analysis showed that this enzyme has 1,3 regioselectivity when glycerol tripalmitate and oleic acid are used as substrates. The fatty acid composition in the reaction product was 21.3% oleic acid and 79.1% sn-2 palmitic acid.
ESTHER : Li_2021_Sci.Rep_11_6913
PubMedSearch : Li_2021_Sci.Rep_11_6913
PubMedID: 33767251
Gene_locus related to this paper: ricco-a0a0d3l472

Title : mTOR and ERK1\/2 signaling participate in the process of acetate regulating lipid metabolism and HSL expression - Li_2021_Anim.Biosci__
Author(s) : Li Y , Fu C , Liu L , Liu Y , Li F
Ref : Anim Biosci , : , 2021
Abstract : OBJECTIVE: Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. METHODS: The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 (ERK1/2) activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. RESULTS: It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. CONCLUSION: Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition.
ESTHER : Li_2021_Anim.Biosci__
PubMedSearch : Li_2021_Anim.Biosci__
PubMedID: 34727637

Title : Impaired cholesterol efflux in retinal pigment epithelium of individuals with juvenile macular degeneration - Tsai_2021_Am.J.Hum.Genet__
Author(s) : Tsai YT , Li Y , Ryu J , Su PY , Cheng CH , Wu WH , Li YS , Quinn PMJ , Leong KW , Tsang SH
Ref : American Journal of Human Genetics , : , 2021
Abstract : Macular degeneration (MD) is characterized by the progressive deterioration of the macula and represents one of the most prevalent causes of blindness worldwide. Abnormal intracellular accumulation of lipid droplets and pericellular deposits of lipid-rich material in the retinal pigment epithelium (RPE) called drusen are clinical hallmarks of different forms of MD including Doyne honeycomb retinal dystrophy (DHRD) and age-related MD (AMD). However, the appropriate molecular therapeutic target underlying these disorder phenotypes remains elusive. Here, we address this knowledge gap by comparing the proteomic profiles of induced pluripotent stem cell (iPSC)-derived RPEs (iRPE) from individuals with DHRD and their isogenic controls. Our analysis and follow-up studies elucidated the mechanism of lipid accumulation in DHRD iRPE cells. Specifically, we detected significant downregulation of carboxylesterase 1 (CES1), an enzyme that converts cholesteryl ester to free cholesterol, an indispensable process in cholesterol export. CES1 knockdown or overexpression of EFEMP1(R345W), a variant of EGF-containing fibulin extracellular matrix protein 1 that is associated with DHRD and attenuated cholesterol efflux and led to lipid droplet accumulation. In iRPE cells, we also found that EFEMP1(R345W) has a hyper-inhibitory effect on epidermal growth factor receptor (EGFR) signaling when compared to EFEMP1(WT) and may suppress CES1 expression via the downregulation of transcription factor SP1. Taken together, these results highlight the homeostatic role of cholesterol efflux in iRPE cells and identify CES1 as a mediator of cholesterol efflux in MD.
ESTHER : Tsai_2021_Am.J.Hum.Genet__
PubMedSearch : Tsai_2021_Am.J.Hum.Genet__
PubMedID: 33909993

Title : Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection - Yu_2021_Fish.Shellfish.Immunol__
Author(s) : Yu C , Xu W , Li X , Jin J , Zhao X , Wang S , Zhang Z , Wei Y , Chen Q , Li Y
Ref : Fish Shellfish Immunol , : , 2021
Abstract : Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Dierential gene expression analysis revealed 896 signicantly dierently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
ESTHER : Yu_2021_Fish.Shellfish.Immunol__
PubMedSearch : Yu_2021_Fish.Shellfish.Immunol__
PubMedID: 34303835

Title : Metabolism and Interspecies Variation of IMMH-010, a Programmed Cell Death Ligand 1 Inhibitor Prodrug - Wang_2021_Pharmaceutics_13_
Author(s) : Wang Y , Liu X , Zou X , Wang S , Luo L , Liu Y , Dong K , Yao X , Li Y , Chen X , Sheng L
Ref : Pharmaceutics , 13 : , 2021
Abstract : IMMH-010 is an ester prodrug of YPD-29B, a potent programmed cell death ligand 1 (PD-L1) inhibitor. The metabolism of IMMH-010 was investigated and compared in various species. Four metabolites of IMMH-010 were identified, and the major metabolite was the parent compound, YPD-29B, which was mainly catalyzed by carboxylesterase 1 (CES1). We observed IMMH-010 metabolism in the plasma of various species. IMMH-010 was rapidly metabolized to YPD-29B in rat and mouse plasma, whereas it remained stable in human and monkey plasma. In the liver S9 fractions of human, monkey, dog, and rat, IMMH-010 was quickly transformed to YPD-29B with no obvious differences among species. In addition, the transformation ratio of IMMH-010 to YPD-29B was low in rat and human intestines, which indicated that the intestine was not an important site for IMMH-010 hydrolysis. Moreover, we demonstrated the remarkable antitumor efficacy of IMMH-010 in B16F10 melanoma and MC38 colon carcinoma xenograft mouse models. We also compared the pharmacokinetic profiles of IMMH-010 in rodents and primates. After oral administration of IMMH-010, the general exposure of active metabolite YPD-29B was slightly lower in primates than in rodents, suggesting that data should be extrapolated cautiously from rodents to humans.
ESTHER : Wang_2021_Pharmaceutics_13_
PubMedSearch : Wang_2021_Pharmaceutics_13_
PubMedID: 33919384

Title : The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis - Li_2021_Chemosphere_263_128238
Author(s) : Li Y , Fang R , Liu Z , Jiang L , Zhang J , Li H , Liu C , Li F
Ref : Chemosphere , 263 :128238 , 2021
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.
ESTHER : Li_2021_Chemosphere_263_128238
PubMedSearch : Li_2021_Chemosphere_263_128238
PubMedID: 33297185

Title : Screening and identification of acetylcholinesterase inhibitors from Terminalia chebula fruits by immobilized enzyme on cellulose filter paper coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and molecular docking - Li_2021_J.Chromatogr.A_1663_462784
Author(s) : Li YJ , He FQ , Zhao HH , Li Y , Chen J
Ref : Journal of Chromatography A , 1663 :462784 , 2021
Abstract : With the increasing demand of new drugs for the treatment of Alzheimer's disease (AD), screening acetylcholinesterase (AChE) inhibitors from traditional Chinese medicines (TCMs) has been proved to be an effective strategy for drug discovery. In present study, a novel strategy was developed to fish out AChE inhibitors from Terminalia chebula fruits based on immobilized AChE coupled with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and molecular docking. For AChE immobilization, cellulose filter paper (CFP) as the carrier was modified with chitosan to be introduced to amino groups, and then AChE was modified on the amino-modified CFP through a Schiff base reaction with glutaraldehyde as a cross-linking agent. The CPF-immobilized AChE possessed advantages of a wider range for pH and temperature endurance, better storage stability, excellent reproducibility and reusability. The CPF-immobilized AChE was incubated with the extract of T. chebula fruits, and then the active components would form complexes with immobilized AChE. The complexes were further conveniently separated with inactive components by virtue of the instantaneous separation characteristic of CFP. Eventually, 25 (1-11, 13-26) potential AChE inhibitors were fished out and their structures were further identified by UPLC-QTOF-MS. Moreover, molecular docking was performed to discriminate non-specific compounds to AChE and explore binding mechanisms between potential inhibitors and AChE, and 25 compounds could be well embedded into active sites of AChE with affinities ranging from -9.9 to -6.4 kcal/mol. Inhibitory activities of screened active components on AChE were evaluated in vitro, and punicalagin, 1,3,6-tri-O-galloyl-beta-D-glucose (1,3,6-TGG), chebulinic acid and geraniin exhibited excellent AChE-inhibitory properties with IC(50) values of 0.43 +/- 0.03, 0.46 +/- 0.02, 0.50 +/- 0.03 and 0.51 +/- 0.03 mM, respectively. The results indicated that the developed method was simple and efficient, and could be utilized to screen and identify potential AChE inhibitors from TCMs.
ESTHER : Li_2021_J.Chromatogr.A_1663_462784
PubMedSearch : Li_2021_J.Chromatogr.A_1663_462784
PubMedID: 34974370

Title : Hydrogen-bonded lipase-hydrogel microspheres for esterification application - Qin_2021_J.Colloid.Interface.Sci_606_1229
Author(s) : Qin Z , Feng N , Li Y , Fei X , Tian J , Xu L , Wang Y
Ref : J Colloid Interface Sci , 606 :1229 , 2021
Abstract : Lipase is the most widely used enzyme in industry. Due to its unique "lid" structure, lipase can only show high activity at the oil-water interface, which means that water is needed in the catalytic esterification process. However, the traditional lipase catalytic system cannot effectively control "micro-water" in the esterification environment, resulting in the high content of free water, which hinders the esterification reaction and reduces the yield. In this paper, a promising strategy of esterification catalyzed by polyacrylamide hydrogel immobilized lipase is reported. The porous polyacrylamide hydrogel microspheres (PHM) prepared by inverse emulsion polymerization are used as carrier to adsorb lipase by hydrogen bonding interaction. These hydrogel microspheres provide a "micro-water environment" for lipase in the anhydrous reaction system, and further provide an oil-water interface for "interface activation" of lipase. The obtained lipase-porous polyacrylamide hydrogel microspheres (L-PHMs) exhibit higher temperature and pH stability compared with free lipase, and the optimum enzymatic activity reach 1350 U/g (pH 6, 40 degreesC). L-PHMs can still remain about 49% of their original activity after 20 reuses. Furthermore, L-PHMs have been successfully applied to catalyze the synthesis of conjugated linoleic acid ethyl ester. The results suggest that this immobilization method opens up a new way for the application of lipase in ester synthesis.
ESTHER : Qin_2021_J.Colloid.Interface.Sci_606_1229
PubMedSearch : Qin_2021_J.Colloid.Interface.Sci_606_1229
PubMedID: 34492461

Title : MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1 - Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
Author(s) : Luo Z , Fan Y , Liu X , Liu S , Kong X , Ding Z , Li Y , Wei L
Ref : Technol Cancer Research Treat , 20 :15330338211033074 , 2021
Abstract : BACKGROUND: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. METHODS: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. RESULTS: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3'UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. CONCLUSIONS: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.
ESTHER : Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
PubMedSearch : Luo_2021_Technol.Cancer.Res.Treat_20_15330338211033074
PubMedID: 34355586
Gene_locus related to this paper: human-NDRG1

Title : Substrate Engineering in Lipase-Catalyzed Selective Polymerization of d-\/l-Aspartates and Diols to Prepare Helical Chiral Polyester - Zhang_2021_Biomacromolecules__
Author(s) : Zhang Y , Xia B , Li Y , Lin X , Wu Q
Ref : Biomacromolecules , : , 2021
Abstract : The synthesis of optically pure polymers is one of the most challenging tasks in polymer chemistry. Herein, Novozym 435 (Lipase B from Candida antarctica, immobilized on Lewatit VP OC 1600)-catalyzed polycondensation between d-/l-aspartic acid (Asp) diester and diols for the preparation of helical chiral polyesters was reported. Compared with d-Asp diesters, the fast-reacting l-Asp diesters easily reacted with diols to provide a series of chiral polyesters containing N-substitutional l-Asp repeating units. Besides amino acid configuration, N-substituent side chains and the chain length of diols were also investigated and optimized. It was found that bulky acyl N-substitutional groups like N-Boc and N-Cbz were more favorable for this polymerization than small ones probably due to competitively binding of these small acyl groups into the active site of Novozym 435. The highest molecular weight can reach up to 39.5 x 10(3) g/mol (M(w,) D = 1.64). Moreover, the slow-reacting d-Asp diesters were also successfully polymerized by modifying the substrate structure to create a "nonchiral" condensation environment artificially. These enantiocomplementary chiral polyesters are thermally stable and have specific helical structures, which was confirmed by circular dichroism (CD) spectra, scanning electron microscope (SEM), and molecular calculation.
ESTHER : Zhang_2021_Biomacromolecules__
PubMedSearch : Zhang_2021_Biomacromolecules__
PubMedID: 33427463

Title : Safety and pharmacokinetic interaction between fotagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin in healthy subjects - Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
Author(s) : Ding Y , Zhang H , Li C , Zheng W , Wang M , Li Y , Sun H , Wu M
Ref : Expert Opin Drug Metab Toxicol , 17 :725 , 2021
Abstract : BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have significant clinical efficacy for type 2 diabetes mellitus (T2DM). The combination of fotagliptin (FOT) with metformin (MET) is a promising therapeutic approach in MET-resistant patients. The aim of the present study was to evaluate the pharmacokinetic (PK) interaction between FOT and MET in healthy subjects after multiple-dose administration. METHODS: Eighteen participants received a randomized open-label, three period treatment that included MET 1000 mg alone, co-administration of FOT 24 mg and MET, followed by FOT 24 mg alone. Serial blood samples were collected for PK analysis, which included geometric mean ratios (GMRs) with 90% confidence intervals (CIs), area under the concentration-time curve (AUC), and maximum plasma concentration (C(max)). RESULTS: Analysis results showed that for FOT alone or combination therapy, the 90% CIs of the GMR for AUC(0-24,ss) and C(max,ss) were 102.08% (98.9%, 105.36%) and 110.65% (102.19%, 119.82%), respectively. For MET, they were 113.41% (100.32%, 128.22%) and 97.11% (83.80%, 112.55%) for AUC(0-12,ss) and C(max,ss), respectively. FOT or MET monotherapy and the combination therapy with both drugs were well tolerated. CONCLUSIONS: No PK drug-drug interactions were found in the combination therapy with FOT and MET. Therefore, FOT can be co-administered with MET without dose adjustment. TRIAL REGISTRATION: The trial is registered at http://www.chinadrugtrials.org.cn/(Registration No. CTR20190221).
ESTHER : Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
PubMedSearch : Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
PubMedID: 33899649

Title : A Unique Sulfotransferase-Involving Strigolactone Biosynthetic Route in Sorghum - Wu_2021_Front.Plant.Sci_12_793459
Author(s) : Wu S , Li Y
Ref : Front Plant Sci , 12 :793459 , 2021
Abstract : LOW GERMINATION STIMULANT 1 (LGS1) plays an important role in strigolactones (SLs) biosynthesis and Striga resistance in sorghum, but the catalytic function remains unclear. Using the recently developed SL-producing microbial consortia, we examined the activities of sorghum MORE AXILLARY GROWTH1 (MAX1) analogs and LGS1. Surprisingly, SbMAX1a (cytochrome P450 711A enzyme in sorghum) synthesized 18-hydroxy-carlactonoic acid (18-hydroxy-CLA) directly from carlactone (CL) through four-step oxidations. The further oxidated product orobanchol (OB) was also detected in the microbial consortium. Further addition of LGS1 led to the synthesis of both 5-deoxystrigol (5DS) and 4-deoxyorobanchol (4DO). Further biochemical characterization found that LGS1 functions after SbMAX1a by converting 18-hydroxy-CLA to 5DS and 4DO possibly through a sulfonation-mediated pathway. The unique functions of SbMAX1 and LGS1 imply a previously unknown synthetic route toward SLs.
ESTHER : Wu_2021_Front.Plant.Sci_12_793459
PubMedSearch : Wu_2021_Front.Plant.Sci_12_793459
PubMedID: 34970291

Title : Reducing alcohol and\/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform - Kong_2021_Mol.Psychiatry__
Author(s) : Kong Q , Li Y , Yue J , Wu X , Xu M
Ref : Mol Psychiatry , : , 2021
Abstract : Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.
ESTHER : Kong_2021_Mol.Psychiatry__
PubMedSearch : Kong_2021_Mol.Psychiatry__
PubMedID: 33619338

Title : Soluble ligands as drug targets for treatment of inflammatory bowel disease - Tong_2021_Pharmacol.Ther__107859
Author(s) : Tong X , Zheng Y , Li Y , Xiong Y , Chen D
Ref : Pharmacol Ther , :107859 , 2021
Abstract : Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by persistent inflammation in a hereditarily susceptible host. In addition to gastrointestinal symptoms, patients with IBD frequently suffer from extra-intestinal complications such as fibrosis, stenosis or cancer. Mounting evidence supports the targeting of cytokines for effective treatment of IBD. Cytokines can be included in a newly proposed classification "soluble ligands" that has become the third major target of human protein therapeutic drugs after enzymes and receptors. Soluble ligands have potential significance for research and development of anti-IBD drugs. Compared with traditional drug targets for IBD treatment, such as receptors, at least three factors contribute to the increasing importance of soluble ligands as drug targets. Firstly, cytokines are the main soluble ligands and targeting of them has demonstrated efficacy in patients with IBD. Secondly, soluble ligands are more accessible than receptors, which are embedded in the cell membrane and have complex tertiary membrane structures. Lastly, certain potential target proteins that are present in membrane-bound forms can become soluble following cleavage, providing further opportunities for intervention in the treatment of IBD. In this review, 49 drugs targeting 25 distinct ligands have been evaluated, including consideration of the characteristics of the ligands and drugs in respect of IBD treatment. In addition to approved drugs targeting soluble ligands, we have also assessed drugs that are in preclinical research and drugs inhibiting ligand-receptor binding. Some new types of targetable soluble ligands/proteins, such as epoxide hydrolase and p-selectin glycoprotein ligand-1, are also introduced. Targeting soluble ligands not only opens a new field of anti-IBD drug development, but the circulating soluble ligands also provide diagnostic insights for early prediction of treatment response. In conclusion, soluble ligands serve as the third-largest protein target class in medicine, with much potential for the drugs targeting them.
ESTHER : Tong_2021_Pharmacol.Ther__107859
PubMedSearch : Tong_2021_Pharmacol.Ther__107859
PubMedID: 33895184

Title : Backbone Conformation Shifts in X-ray Structures of Human Acetylcholinesterase upon Covalent Organophosphate Inhibition - Luedtke_2021_Crystals_11_1270
Author(s) : Luedtke S , Bojo C , Li Y , Luna E , Bianca Pomar , Radic Z
Ref : Crystals , 11 :1270 , 2021
Abstract : Conformations of Calpha backbones in X-ray structures of most organophosphate (OP)-inhibited human acetylcholinesterases (hAChEs) have been previously shown to be similar to that of the native hAChE. One of the exceptions is the structure of the diethylphosphoryl-hAChE conjugate, where stabilization of a large ethoxy group into the acyl pocket (AP) of hAChE-triggered notable loop distortions and consequential dissociation of the hAChE homodimer. Recently, six X-ray structures of hAChE conjugated with large OP nerve agents of the A-type, Novichoks, have been deposited to PDB. In this study we analyzed backbone conformation shifts in those structures, as well as in OP-hAChE conjugates formed by Paraoxon, Soman, Tabun, and VX. A Java-based pairwise alpha carbon comparison tool (PACCT 3) was used for analysis. Surprisingly, despite the snug fit of large substituents on phosphorus, inside Novichok-conjugated hAChEs only minor conformational changes were detected in their backbones. Small magnitudes of observed changes were due to a 1.2-2.4 A shift of the entire conjugated OP away from the AP. It thus appears that the small AP of AChEs can accommodate, without distortion, substituents of the size of ethoxy or butyryl groups, provided that conjugated OP is "pulled" away from the AP. This observation has practical consequences in the structure-based design of nucleophilic reactivation antidotes as well as in the definition of the AChE specificity that relies on the size of its AP
ESTHER : Luedtke_2021_Crystals_11_1270
PubMedSearch : Luedtke_2021_Crystals_11_1270
PubMedID:

Title : Responses of Asian clams (Corbicula fluminea) to low concentration cadmium stress: Whether the depuration phase restores physiological characteristics - Wang_2021_Environ.Pollut_284_117182
Author(s) : Wang Z , Kong F , Fu L , Li Y , Li M , Yu Z
Ref : Environ Pollut , 284 :117182 , 2021
Abstract : The effect of low concentration Cd stress on bivalves is unclear. In this study, Asian clams (Corbicula fluminea) were continuously exposed to 0, 0.05, 0.10, and 0.20 mg/L Cd for 14 d (exposure phase) and to artificial freshwater for 7 d (depuration phase). A total of 16 variables were measured to explore the toxic effects on C. fluminea. All physiological characteristics were significantly inhibited in the treatments (p < 0.05), and the negative effects of Cd did not return to normal levels in the short term. Tissue damage was found in the feet and gills of C. fluminea in all the treatments. On the 7th day (D7), enzyme activity in all the treatments was significantly higher (p < 0.05) than in the control group. Acetylcholinesterase, superoxide dismutase, and catalase activities were enhanced on D14 in all the treatments. However, only glutathione S-transferase activity was significantly higher in all the treatments (p < 0.05) than in the control group on D21. The instability of the enzymes indicated that the adaptability of C. fluminea became stronger throughout the experiment. In each group, the maximum bioaccumulation of Cd followed the order: 0.20 mg/L > 0.05 mg/L > 0.10 mg/L, which might be caused by the filtration capacity of C. fluminea in the 0.05-mg/L group, which was higher than that of the 0.10-mg/L group. Thus, low Cd concentrations effect the physiological characteristics, tissue health, and antioxidant system of C. fluminea and may require a long recovery time to be restored to normal levels.
ESTHER : Wang_2021_Environ.Pollut_284_117182
PubMedSearch : Wang_2021_Environ.Pollut_284_117182
PubMedID: 33901982

Title : Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology - Li_2021_Drug.Des.Devel.Ther_15_1883
Author(s) : Li S , Wang Y , Li C , Yang N , Yu H , Zhou W , Chen S , Yang S , Li Y
Ref : Drug Des Devel Ther , 15 :1883 , 2021
Abstract : BACKGROUND: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. METHODS: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. RESULTS: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. CONCLUSION: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
ESTHER : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedSearch : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedID: 33976539

Title : Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE\/GSK3beta inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine - Jiang_2021_Eur.J.Med.Chem_223_113663
Author(s) : Jiang X , Liu C , Zou M , Xie H , Lin T , Lyu W , Xu J , Li Y , Feng F , Sun H , Liu W
Ref : Eur Journal of Medicinal Chemistry , 223 :113663 , 2021
Abstract : Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3beta (Glycogen synthase kinase 3beta) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3beta inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD.
ESTHER : Jiang_2021_Eur.J.Med.Chem_223_113663
PubMedSearch : Jiang_2021_Eur.J.Med.Chem_223_113663
PubMedID: 34198150

Title : Synthesis, Characterization, and Simulation of Four-Armed Megamolecules - Zhou_2021_Biomacromolecules__
Author(s) : Zhou S , He P , Dhindwal S , Grum-Tokars VL , Li Y , Parker K , Modica JA , Bleher R , Dos Reis R , Zuchniarz J , Dravid VP , Voth GA , Roux B , Mrksich M
Ref : Biomacromolecules , : , 2021
Abstract : This paper describes the synthesis, characterization, and modeling of a series of molecules having four protein domains attached to a central core. The molecules were assembled with the "megamolecule" strategy, wherein enzymes react with their covalent inhibitors that are substituted on a linker. Three linkers were synthesized, where each had four oligo(ethylene glycol)-based arms terminated in a para-nitrophenyl phosphonate group that is a covalent inhibitor for cutinase. This enzyme is a serine hydrolase and reacts efficiently with the phosphonate to give a new ester linkage at the Ser-120 residue in the active site of the enzyme. Negative-stain transmission electron microscopy (TEM) images confirmed the architecture of the four-armed megamolecules. These cutinase tetramers were also characterized by X-ray crystallography, which confirmed the active-site serine-phosphonate linkage by electron-density maps. Molecular dynamics simulations of the tetracutinase megamolecules using three different force field setups were performed and compared with the TEM observations. Using the Amberff99SB-disp + pH7 force field, the two-dimensional projection distances of the megamolecules were found to agree with the measured dimensions from TEM. The study described here, which combines high-resolution characterization with molecular dynamics simulations, will lead to a comprehensive understanding of the molecular structures and dynamics for this new class of molecules.
ESTHER : Zhou_2021_Biomacromolecules__
PubMedSearch : Zhou_2021_Biomacromolecules__
PubMedID: 33979120
Gene_locus related to this paper: fusso-cutas

Title : Computational biotransformation of polyethylene terephthalate by depolymerase: A QM\/MM approach - Zheng_2021_J.Hazard.Mater_423_127017
Author(s) : Zheng M , Li Y , Dong W , Feng S , Zhang Q , Wang W
Ref : J Hazard Mater , 423 :127017 , 2021
Abstract : Despite increasing environmental concerns on ever-lasting Polyethylene Terephthalate (PET), its global production is continuously growing. Effective strategies that can completely remove PET from environment are urgently desired. Here biotransformation processes of PET by one of the most effective enzymes, leaf-branch compost cutinase (LCC), were systematically explored with Molecular Dynamics and Quantum Mechanics/Molecular Mechanics approaches. We found that four concerted steps are required to complete the whole catalytic cycle. The last concerted step, deacylation, was determined as the rate-determining step with Boltzmann-weighted average barrier of 13.6 kcal/mol and arithmetic average of 16.1 +/- 2.9 kcal/mol. Interestingly, unprecedented fluctuations of hydrogen bond length during LCC catalyzed transformation process toward PET were found. This fluctuation was also observed in enzyme IsPETase, indicating that it may widely exist in other catalytic triad (Ser-His-Asp) containing enzymes as well. In addition, possible features (bond, angle, dihedral angle and charge) that influence the catalytic reaction were identified and correlations between activation energies and key features were established. Our results present new insights into catalytic mechanism of hydrolases and shed light on the efficient recycling of the ever-lasting PET.
ESTHER : Zheng_2021_J.Hazard.Mater_423_127017
PubMedSearch : Zheng_2021_J.Hazard.Mater_423_127017
PubMedID: 34464862
Gene_locus related to this paper: 9bact-g9by57

Title : Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds - Zhang_2021_J.Control.Release_329_1117
Author(s) : Zhang Y , He J , Shen L , Wang T , Yang J , Li Y , Wang Y , Quan D
Ref : J Control Release , 329 :1117 , 2021
Abstract : Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.
ESTHER : Zhang_2021_J.Control.Release_329_1117
PubMedSearch : Zhang_2021_J.Control.Release_329_1117
PubMedID: 33096123

Title : An ABHD17-like hydrolase screening system to identify de-S-acylation enzymes of protein substrates in plant cells - Liu_2021_Plant.Cell__
Author(s) : Liu X , Li M , Li Y , Chen Z , Zhuge C , Ouyang Y , Zhao Y , Lin Y , Xie Q , Yang C , Lai J
Ref : Plant Cell , : , 2021
Abstract : Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of ABHD17 (Alpha/Beta Hydrolase Domain-containing Protein 17)-like Acyl Protein Thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RIN4 (RPM1 Interacting Protein 4), which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation.
ESTHER : Liu_2021_Plant.Cell__
PubMedSearch : Liu_2021_Plant.Cell__
PubMedID: 34338800
Gene_locus related to this paper: arath-AT1G66900 , arath-AT2G24320 , arath-AT4G31020 , arath-AT5G20520 , arath-AT5G38220 , arath-F3C3.3 , arath-AT1G13610 , arath-At5g14390 , arath-F22K18.40 , arath-At3g01690 , arath-Q9LI62

Title : A glyoxylate-containing benzene derivative and butenolides from a marine algicolous fungus Aspergillus sp. SCSIO 41304 - Qi_2021_Nat.Prod.Res__1
Author(s) : Qi X , Chen WH , Lin XP , Liao SR , Yang B , Zhou XF , Liu YH , Wang JF , Li Y
Ref : Nat Prod Res , :1 , 2021
Abstract : A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2-11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH(3), which is rare in natural sources. All the isolated compounds (1-11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC(50) values of 25.95 and 47.06 microM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL.
ESTHER : Qi_2021_Nat.Prod.Res__1
PubMedSearch : Qi_2021_Nat.Prod.Res__1
PubMedID: 34542359

Title : Early enteral nutrition combined with PSS-based nursing in the treatment of organophosphorus pesticide poisoning - Sun_2021_Am.J.Transl.Res_13_9315
Author(s) : Sun Y , Yang Y , Zhang Z , Li Y , Hu Y , Wang N
Ref : Am J Transl Res , 13 :9315 , 2021
Abstract : OBJECTIVE: To investigate the administration of early enteral nutrition combined with poisoning severity score (PSS)-based nursing in the treatment of organophosphorus pesticide poisoning (OPP). METHODS: A total of 99 OPP patients treated in our hospital between June 2019 and June 2020 were enrolled in this study and were divided into the conventional group (n=46, early enteral nutrition support + routine care) and the combined group (n=53, PSS-based nursing + early enteral nutrition support + routine care). The nutritional status indicators, the hemoglobin (Hb) and blood glucose levels, the Glasgow coma scale (GCS) scores, and the complications were compared between the two groups. RESULTS: The total protein (TP), albumin (ALB), and prealbumin (PAB) levels were reduced in the conventional group after the intervention (P<0.05) but were significantly lower than they were in the combined group (P<0.05). The Hb and blood glucose levels were decreased in the conventional group after the intervention (P<0.05) and were significantly higher than they were in the combined group (P<0.05). The GCS scores increased significantly as the treatment progressed (P<0.05), and the GCS scores in the combined group were significantly higher than the GCS scores in the conventional group at 3 and 5 days after the treatment (P<0.05). The time to the recovery of 60% cholinesterase (CHE) activity, the durations of the mechanical ventilation, the lengths of the hospital stays, and the hospital costs in the combined group were significantly lower than they were in the conventional group (P<0.05). The complication rate in the combined group (9.43%) was significantly lower than the complication rate in the conventional group (32.61%) (P<0.05). CONCLUSION: Early enteral nutrition combined with PSS-based nursing can effectively control the blood glucose, improve the nutritional disorders, promote recovery, and reduce complications in OPP patients.
ESTHER : Sun_2021_Am.J.Transl.Res_13_9315
PubMedSearch : Sun_2021_Am.J.Transl.Res_13_9315
PubMedID: 34540048

Title : Congenital myasthenic syndrome in China: genetic and myopathological characterization - Zhao_2021_Ann.Clin.Transl.Neurol__
Author(s) : Zhao Y , Li Y , Bian Y , Yao S , Liu P , Yu M , Zhang W , Wang Z , Yuan Y
Ref : Ann Clin Transl Neurol , : , 2021
Abstract : OBJECTIVE: We aimed to summarize the clinical, genetic, and myopathological features of a cohort of Chinese patients with congenital myasthenic syndrome, and follow up on therapeutic outcomes. METHODS: The clinical spectrum, mutational frequency of genes, and pathological diagnostic clues of various subtypes of patients with congenital myasthenic syndrome were summarized. Therapeutic effects were followed up. RESULTS: Thirty-five patients from 29 families were recruited. Ten genes were identified: GFPT1 (27.6%), AGRN (17.2%), CHRNE (17.2%), COLQ (13.8%), GMPPB (6.9%), CHAT, CHRNA1, DOK7, COG7, and SLC25A1 (3.4% each, respectively). Sole limb-girdle weakness was found in patients with AGRN (1/8) and GFPT1 (7/8) mutations, whereas distal weakness was all observed in patients with AGRN (6/8) mutations. Tubular aggregates were only found in patients with GFPT1 mutations (5/6). The patients with GMPPB mutations (2/2) had decreased alpha-dystroglycan. Acetylcholinesterase inhibitor therapy resulted in no response or worsened symptoms in patients with COLQ mutations, a diverse response in patients with AGRN mutations, and a good response in patients with other subtypes. Albuterol therapy was effective or harmless in most subtypes. Therapy effects became attenuated with long-term use in patients with COLQ or AGRN mutations. INTERPRETATION: The genetic distribution of congenital myasthenic syndrome in China is distinct from that of other ethnic origins. The appearance of distal weakness, selective limb-girdle myasthenic syndrome, tubular aggregates, and decreased alpha-dystroglycan were indicative of the specific subtypes. Based on the follow-up findings, we suggest cautious evaluation of the long-term efficacy of therapeutic agents in congenital myasthenic syndrome.
ESTHER : Zhao_2021_Ann.Clin.Transl.Neurol__
PubMedSearch : Zhao_2021_Ann.Clin.Transl.Neurol__
PubMedID: 33756069

Title : Molecular dynamics investigation of the interaction between Colletotrichum capsici cutinase and berberine suggested a mechanism for reduced enzyme activity - Li_2021_PLoS.One_16_e0247236
Author(s) : Li Y , Wei J , Yang H , Dai J , Ge X
Ref : PLoS ONE , 16 :e0247236 , 2021
Abstract : Berberine is a promising botanical pesticide against fungal plant pathogens. However, whether berberine inhibits the invasion of fungal pathogen across plant surface remains unclear. Here we demonstrated that the enzyme activities of purified cutinase from fungal pathogen Colletotrichum capsici were partially inhibited in presence of berberine toward different substrates. Molecular dynamics simulation results suggested the rigidity of cutinase was decreased with berberine added into the system. Interestingly, aggregations of berberine to the catalytic center of cutinase were observed, and stronger hydrophobic interactions were detected between key residue His 208 and berberine with concentrations of berberine increased. More importantly, this hydrophobic interaction conferred conformational change of the imidazole ring of His 208, which swung out of the catalytic center to an inactive mode. In summary, we provided the molecular mechanism of the effect of berberine on cutinase from C. capsici.
ESTHER : Li_2021_PLoS.One_16_e0247236
PubMedSearch : Li_2021_PLoS.One_16_e0247236
PubMedID: 33606796

Title : Chemical Constituents from the Wild Atractylodes macrocephala Koidz and Acetylcholinesterase Inhibitory Activity Evaluation as Well as Molecular Docking Study - Zhu_2021_Molecules_26_
Author(s) : Zhu Q , Lin M , Zhuo W , Li Y
Ref : Molecules , 26 : , 2021
Abstract : Screening the lead compounds which could interact both with PAS and CAS of acetylcholinesterase (AChE) is an important trend in finding innovative drugs for Alzheimer's disease (AD). In this paper, four sesquiterpenes, i.e., atractylenolide III (1), atractylenolide IV (2), 3-acetyl-atractylon (3) and beta-eudesmol (4), were obtained from the wild Atractylode macrocephala grown in Qimen for the first time. Their structures were elucidated mainly by NMR spectroscopy. To screen the potential dual site inhibitors of AChE, the compounds 1, 2, 3, as well as a novel and rare bisesquiterpenoid lactone, biatractylenolide II (5), which was also obtained from the tilted plant in our previous investigation, were evaluated their AChE inhibitory activities by using Ellman's colorimetric method. The results showed that biatractylenolide II displayed moderate inhibitory activity (IC(50) = 19.61 +/- 1.11 microg/mL) on AChE. A further molecular docking study revealed that biatractylenolide II can interact with both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. These data suggest that biatractylenolide II can be considered a new lead compound to research and develop more potential dual site inhibitors of AChE.
ESTHER : Zhu_2021_Molecules_26_
PubMedSearch : Zhu_2021_Molecules_26_
PubMedID: 34885880

Title : Two novel Mutations of the LPL Gene in two Chinese family cases with Familial Chylomicronemia Syndrome - Wang_2021_Clin.Chim.Acta__
Author(s) : Wang M , Zhou Y , He X , Deng C , Liu X , Li J , Zhou L , Li Y , Zhang Y , Liu H , Li L
Ref : Clinica Chimica Acta , : , 2021
Abstract : The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429+1G>T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.
ESTHER : Wang_2021_Clin.Chim.Acta__
PubMedSearch : Wang_2021_Clin.Chim.Acta__
PubMedID: 34324844
Gene_locus related to this paper: human-LPL

Title : Discovery, biological evaluation and molecular dynamic simulations of butyrylcholinesterase inhibitors through structure-based pharmacophore virtual screening - Lu_2021_Future.Med.Chem_13_769
Author(s) : Lu T , Liu Y , Chen H , Han C , Feng X , Zhou H , Li Y
Ref : Future Med Chem , 13 :769 , 2021
Abstract : Aim: Butyrylcholinesterase (BChE) is a crucial therapeutic target because it is associated with multiple pathological elements of Alzheimer's disease (AD). An integrated computational strategy was employed to exploit effective BChE inhibitors. Methods & results: Ten compounds derived from the Enamine database by structure-based pharmacophore virtual screening were further evaluated for biological activity; out of the ten, only five had an IC(50) of less than 100 microM. Among these five compounds, a new molecule, 970180, presented the most potency against BChE, with an IC(50) of 4.24 +/- 0.16 microM, and acted as a mixed-type inhibitor. Molecular dynamic simulations and absorption, distribution, metabolism and excretion prediction further confirmed its high potential as a good candidate of BChE inhibitor. Furthermore, cytotoxicity of molecule 970180 was not observed at concentrations up to 50 microM, and the molecule also showed a prominent neuroprotective effect compared with tacrine at 25 and 50 microM. Conclusion: This study provides an effective structure-based pharmacophore virtual screening method to discover BChE inhibitors and provide new choices for the development of BChE inhibitors, which may be beneficial for AD patients.
ESTHER : Lu_2021_Future.Med.Chem_13_769
PubMedSearch : Lu_2021_Future.Med.Chem_13_769
PubMedID: 33759552

Title : Genome-wide analysis of the serine carboxypeptidase-like protein family in Triticum aestivum reveals TaSCPL184-6D is involved in abiotic stress response - Xu_2021_BMC.Genomics_22_350
Author(s) : Xu X , Zhang L , Zhao W , Fu L , Han Y , Wang K , Yan L , Li Y , Zhang XH , Min DH
Ref : BMC Genomics , 22 :350 , 2021
Abstract : BACKGROUND: The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. RESULTS: In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. CONCLUSIONS: We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat.
ESTHER : Xu_2021_BMC.Genomics_22_350
PubMedSearch : Xu_2021_BMC.Genomics_22_350
PubMedID: 33992092

Title : Thifluzamide exposure induced neuro-endocrine disrupting effects in zebrafish (Danio rerio) - Yang_2021_Arch.Toxicol__
Author(s) : Yang Y , Chang J , Wang D , Ma H , Li Y , Zheng Y
Ref : Archives of Toxicology , : , 2021
Abstract : Thifluzamide is widely used fungicide and frequently detected in aquatic system. In this study, the toxicity of fungicide thifluzamide to non-targeted aquatic organisms was investigated for neuroendocrine disruption potentials. Here, zebrafish embryos were exposed to a series of concentrations of thifluzamide for 6 days. The results showed that both the development of embryos/larvae and the behavior of hatched larvae were significantly affected by thifluzamide. Importantly, the decreased activity of acetylcholinesterase (AchE) and the increased contents of neurotransmitters such as serotonin (5-HT) and norepinephrine (NE), along with transcriptional changes of nervous system related genes were observed following 4 days exposure to thifluzamide. Besides, the decreased contents of triiodothyronine (T3) and thyroxine (T4) in whole body, as well as significant expression alteration in hypothalamic-pituitary-thyroid (HPT) axis associated genes were discovered in zebrafish embryos after 4 days of exposure to thifluzamide. Our results clearly demonstrated that zebrafish embryos exposed to thifluzamide could disrupt neuroendocrine, compromise behavior and induce developmental abnormality, suggesting impact of this fungicide on developmental programming in zebrafish.
ESTHER : Yang_2021_Arch.Toxicol__
PubMedSearch : Yang_2021_Arch.Toxicol__
PubMedID: 34635929

Title : Analysis of Differentially Expressed Transcripts in Apolygus lucorum (Meyer-Dur) Exposed to Different Temperature Coefficient Insecticides - An_2020_Int.J.Mol.Sci_21_658
Author(s) : An J , Liu C , Dou Y , Gao Z , Dang Z , Yan X , Pan W , Li Y
Ref : Int J Mol Sci , 21 :658 , 2020
Abstract : The existence of a temperature effect of insecticides frustrated the control of the green plant bug Apolygus lucorum (Meyer-Dur). Previous studies mostly focused on the application of insecticides, but the underlying mechanism remains incompletely understood. Here, we report a transcriptome profiling of A. lucorum treated by three kinds of temperature coefficient insecticides (TCIs) (positive TCI: imidacloprid, negative TCI: b-cypermethrin and non-effect TCI: phoxim) at 15 degrees C, 25 degrees C and 35 degrees C by using next- and third-generation RNA-Seq methods. A total of 34,739 transcripts were annotated from 277.74 Gb of clean data. There were more up-regulated transcripts than down-regulated transcripts in all three kinds of TCI treatments. Further Venn diagrams indicate the regulatory transcripts and regulatory modes were different at the three temperatures. The responses to imidacloprid involved more detox and stress response transcripts such as cytochrome P450 (CYP450), carboxylesterase (CarE) and catalase (CAT) at 35 degrees C, which was the case for beta-cypermethrin at 15 degrees C. UDP-glucuronyltransferase (UGT) and heat shock protein (HSP) transcripts were heavily involved, and thus deserve particular note in the temperature effect of insecticides. This high-confidence transcriptome atlas provides improved gene information for further study on the insecticide temperature effect related physiological and biochemical processes of A. lucorum.
ESTHER : An_2020_Int.J.Mol.Sci_21_658
PubMedSearch : An_2020_Int.J.Mol.Sci_21_658
PubMedID: 31963875

Title : A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y - Nguyen_2020_Neuron_106_759
Author(s) : Nguyen TA , Wu K , Pandey S , Lehr AW , Li Y , Bemben MA , Badger JD, 2nd , Lauzon JL , Wang T , Zaghloul KA , Thurm A , Jain M , Lu W , Roche KW
Ref : Neuron , 106 :759 , 2020
Abstract : Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing approximately 97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.
ESTHER : Nguyen_2020_Neuron_106_759
PubMedSearch : Nguyen_2020_Neuron_106_759
PubMedID: 32243781
Gene_locus related to this paper: human-NLGN4X

Title : The Comparative Efficacy of Multiple Interventions for Mild Cognitive Impairment in Alzheimer's Disease: A Bayesian Network Meta-Analysis - Lai_2020_Front.Aging.Neurosci_12_121
Author(s) : Lai X , Wen H , Li Y , Lu L , Tang C
Ref : Front Aging Neurosci , 12 :121 , 2020
Abstract : Background: Mild cognitive impairment (MCI) is the early phase of Alzheimer's disease (AD). The aim of early intervention for MCI is to decrease the rate of conversion from MCI to AD. However, the efficacy of multiple interventions in MCI, and the optimal methods of delivery, remain controversial. We aimed to compare and rank the treatment methods for MCI in AD, in order to find an optimal intervention for MCI and a way to prevent or delay the occurrence of AD. Methods: Pair-wise and network meta-analysis were conducted to integrate the treatment effectiveness through direct and indirect evidence. Four English databases and three Chinese databases were searched for international registers of eligible published, single or double blind, randomized controlled trials up to September 31st 2019. We included nine comparative interventions: pharmacological therapies which incorporated cholinesterase inhibitors (ChEI), ginkgo, nimodipine, and Chinese medicine; non-pharmacological therapies comprising of acupuncture, music therapy, exercise therapy, and nutrition therapy; and a placebo group. The primary outcome was the Mini-Mental State Examination (MMSE) score. The secondary outcome was the AD Assessment Scale-cognitive subscale (ADAS-cog). Results: Twenty-eight trials were eligible, including 6,863 participants. In the direct meta-analysis, as for the Mini-Mental State Examination scale, the ChEIs (MD: -0.38; 95% CI: -0.74, -0.01), Chinese medicine (MD: -0.31; 95% CI: -0.75, 0.13), exercise therapy (MD: -0.50; 95% CI: -0.65, -0.35), music therapy (MD: -1.71; 95% CI: -4.49, 1.07), were statistically more efficient than placebo. For AD Assessment Scalecognitive subscale outcome, ChEIs (MD: 1.20; 95% CI: 0.73, 1.68), Acupuncture (MD: 1.36; 95% CI: 1.28, 1.44), Chinese medicine (MD: 0.61; 95% CI: 0.49, 0.73) and exercise (MD: 0.61; 95% CI: 0.49, 0.73) were better than placebo. In the network meta-analysis, the MMSE outcome ranked music therapy (59%) as the best and Acupuncture (26%) as second. Nutrition and Ginkgo treatment had the lowest rank among all interventions. For ADAS-cog outcome, acupuncture (52) ranked the best. Conclusion: Among the nine treatments studied, music therapy appears to be the best treatment for MCI, followed by acupuncture. Our study provides new insights into potential clinical treatments for MCI due to AD, and may aid the development of guidelines for MCI in AD.
ESTHER : Lai_2020_Front.Aging.Neurosci_12_121
PubMedSearch : Lai_2020_Front.Aging.Neurosci_12_121
PubMedID: 32581760

Title : Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry - Xu_2020_Int.J.Biol.Macromol_150_1184
Author(s) : Xu J , Zhao S , Zhang S , Pei J , Li Y , Zhang Y , He X , Hu L
Ref : Int J Biol Macromol , 150 :1184 , 2020
Abstract : In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride.
ESTHER : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedSearch : Xu_2020_Int.J.Biol.Macromol_150_1184
PubMedID: 31758986

Title : Prolonged Soluble Epoxide Hydrolase Reactivity in Brain Endothelial Cells Is Associated with Long Cognitive Deficits in Sepsis - Wang_2020_Mol.Neurobiol__
Author(s) : Wang P , Wang W , Hu Y , Li Y
Ref : Molecular Neurobiology , : , 2020
Abstract : Sepsis-associated encephalopathy (SAE) is known to cause long-term cognitive deficits which are related to sustained microglial activation, but the mechanisms are unclear. Recently, studies have shown soluble epoxide hydrolase (sEH) affects the chronic cognitive function or participates in long-term neuropsychiatric illness. We hypothesized that sEH may be involved in the long-term cognitive deficits of SAE. Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) and were administered vehicle or sEH inhibitor TPPU. CLP induced prolonged endothelial sEH reactivity and sustained activation of microglia in close vicinity to blood vessels at 14 days. We also observed that persistent loss of endothelial BBB function at 14 days following CLP. However, TPPU-treated septic mice exhibited improved BBB function and declined neuro-inflammation. We confirmed these beneficial effects in vitro, which indicated TPPU resulted in a significant improvement in IL-1beta-induced loss of BBB integrity on hCMEC/D3 cell monolayers. Animals were also given a behavior test at 14 days after CLP. Mice showed normal basal locomotor activity in the open field compared with sham-operated animals, but performed fewer entries to the center zone, indicating increased anxiety-like behavior as avoidance of the center. TPPU-treated CLP mice showed normal crossing into the center zone during an open-field test and improved recovery of the ability to learn the novel object recognition (NOR) task compared with saline-treated CLP animals. Our data indicated that prolonged sEH reactivity in brain endothelial cells is associated with long cognitive deficits in sepsis. sEHIs such as TPPU can improve the endothelial barrier function and decrease CLP-induced long-term encephalopathy, at least in part, through anti-inflammatory effects.
ESTHER : Wang_2020_Mol.Neurobiol__
PubMedSearch : Wang_2020_Mol.Neurobiol__
PubMedID: 32378122

Title : Design, synthesis and evaluation of phthalide alkyl tertiary amine derivatives as promising acetylcholinesterase inhibitors with high potency and selectivity against Alzheimer's disease - Luo_2020_Bioorg.Med.Chem__115400
Author(s) : Luo L , Song Q , Li Y , Cao Z , Qiang X , Tan Z , Deng Y
Ref : Bioorganic & Medicinal Chemistry , :115400 , 2020
Abstract : A series of phthalide alkyl tertiary amine derivatives were designed, synthesized and evaluated as potential multi-target agents against Alzheimer's disease (AD). The results indicated that almost all the compounds displayed significant AChE inhibitory and selective activities. Besides, most of the derivatives exhibited increased self-induced Abeta1-42 aggregation inhibitory activity compared to the lead compound dl-NBP, and some compounds also exerted good antioxidant activity. Specifically, compound I-8 showed the highest inhibitory potency toward AChE (IC50=2.66nM), which was significantly better than Donepezil (IC50=26.4nM). Moreover, molecular docking studies revealed that compound I-8 could bind to both the catalytic active site and peripheral anionic site of AChE. Furthermore, compound I-8 displayed excellent BBB permeability in vitro. Importantly, the step-down passive avoidance test indicated that I-8 significantly reversed scopolamine-induced memory deficit in mice. Collectively, these results suggested that I-8 might be a potent and selective AChE inhibitor for further anti-AD drug development.
ESTHER : Luo_2020_Bioorg.Med.Chem__115400
PubMedSearch : Luo_2020_Bioorg.Med.Chem__115400
PubMedID: 32146060

Title : Adipokinetic hormone enhances CarE-mediated chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens - Tang_2020_Insect.Mol.Biol_29_511
Author(s) : Tang B , Cheng Y , Li Y , Li W , Ma Y , Zhou Q , Lu K
Ref : Insect Molecular Biology , 29 :511 , 2020
Abstract : Adipokinetic hormone (AKH), the principal stress-responsive neurohormone in insects, has been implicated in insect responses to insecticides. However, the functionality of AKH and its mode of signalling in insecticide resistance are unknown. Herein, we demonstrated that the enhanced activity of carboxylesterases (CarEs) is involved in the chlorpyrifos resistance in Nilaparvata lugens [brown planthopper (BPH)]. Chlorpyrifos exposure significantly induced the expression of AKH and its receptor AKHR in the susceptible BPH (Sus), and these two AKH signalling genes were over-expressed in the chlorpyrifos-resistant strain (Res) compared to Sus. RNA interference (RNAi) against AKH or AKHR decreased the CarE activity and suppressed the BPH's resistance to chlorpyrifos in Res. Conversely, AKH peptide injection elevated the CarE activity and enhanced the BPH's survival against chlorpyrifos in Sus. Furthermore, five CarE genes were identified to be positively affected by the AKH pathway using RNAi and AKH injection. Among these CarE genes, CarE and Esterase E4-1 were found to be over-expressed in Res compared to Sus, and knockdown of either gene decreased the BPH's resistance to chlorpyrifos. In conclusion, AKH plays a role in enhancing chlorpyrifos resistance in the BPH through positive influence on the expression of CarE genes and CarE enzyme activity.
ESTHER : Tang_2020_Insect.Mol.Biol_29_511
PubMedSearch : Tang_2020_Insect.Mol.Biol_29_511
PubMedID: 32686884

Title : Resveratrol oligomers from Paeonia suffruticosa protect mice against cognitive dysfunction by regulating cholinergic, antioxidant and anti-inflammatory pathways - Liu_2020_J.Ethnopharmacol__112983
Author(s) : Liu S , Li Y , Yi F , Liu Q , Chen N , He X , He C , Xiao P
Ref : J Ethnopharmacol , :112983 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia suffruticosa Andr. has been widely used in traditional Chinese medicine as an anti-tumour, anti-oxidant, anti-inflammatory and neuroprotective agent. Resveratrol oligomers are the main components of the seed coat extracts of Paeonia suffruticosa (PSCE) and have DPPH free radical scavenging and beta-secretase inhibitory activity. However, studies of its effect on ameliorating cognitive deficits are limited, and analyses of the underlying mechanisms are insufficient. AIM OF STUDY: This study aimed to investigate the cholinesterase inhibitory activities of resveratrol oligomers from P. suffruticosa in vitro and their effects on diminishing the oxygen-glucose deprivation/reoxygenation (OGD/R) -induced cytotoxicity in PC12cells and scopolamine-induced cognitive deficits in mice. Moreover, the underlying mechanisms were further explored. MATERIALS AND METHODS: In vitro, the inhibitory effects of PSCE and its 10 stilbenes on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated using the Ellmann assay, and its protective effects on normal and OGD/R-injured PC12cells were evaluated using the MTT assay. For the in vivo assay, C57BL/6 mice were orally administered PSCE at doses of 150 and 600mg/kg for 28 days, and injected with scopolamine (1.5mg/kg) to induce cognitive deficits. The memory behaviours were evaluated using the novel object recognition, Morris water maze and inhibitory avoidance test. Levels of various biochemical markers were also examined, including AChE, choline acetyltransferase (ChAT), acetylcholine (ACh), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) in the mouse brain and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) in serum. RESULTS: PSCE and its 10 stilbenes display good inhibition of AChE and BuChE activities and significantly increase the viability of normal and OGD/R-injured PC12cells. PSCE improves the cognitive performance of scopolamine-treated mice in behavioural tests. Meanwhile, PSCE increases AChE, ChAT, SOD, and CAT activities and ACh, GSH, IL-4 levels, and decreases IL-1beta, IL-6, TNF-alpha levels in the model animals. CONCLUSIONS: Resveratrol oligomers from P. suffruticosa show neuroprotective effect in vitro and in vivo by regulating cholinergic, antioxidant and anti-inflammatory pathways, may have promising application in the treatment of Alzheimer's disease.
ESTHER : Liu_2020_J.Ethnopharmacol__112983
PubMedSearch : Liu_2020_J.Ethnopharmacol__112983
PubMedID: 32442589

Title : Protein Surface Printer for Exploring Protein Domains - Li_2020_J.Chem.Inf.Model_60_5255
Author(s) : Li Y , Qiao B , Olvera de la Cruz M
Ref : J Chem Inf Model , 60 :5255 , 2020
Abstract : The surface of proteins is vital in determining protein functions. Herein, a program, Protein Surface Printer (PSP), is built that performs multiple functions in quantifying protein surface domains. Two proteins, PETase and cytochrome P450, are used to validate that the program supports atomistic simulations with different combinations of programs and force fields. A case study is conducted on the structural analysis of the spike proteins of SARS-CoV-2 and SARS-CoV and the human cell receptor ACE2. Although the surface domains of both spike proteins are highly similar, their receptor-binding domains (RBDs) and the O-linked glycan domains are structurally different. The O-linked glycan domain of SARS-CoV-2 is highly positively charged, which may promote binding to negatively charged human cells.
ESTHER : Li_2020_J.Chem.Inf.Model_60_5255
PubMedSearch : Li_2020_J.Chem.Inf.Model_60_5255
PubMedID: 32846088

Title : Role of penehyclidine in acute organophosphorus pesticide poisoning - Yu_2020_World.J.Emerg.Med_11_37
Author(s) : Yu SY , Gao YX , Walline J , Lu X , Zhao LN , Huang YX , Tao J , Yu AY , Ta N , Xiao RJ , Li Y
Ref : World J Emerg Med , 11 :37 , 2020
Abstract : BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients. METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR). RESULTS: Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine- or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS. CONCLUSION: Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.
ESTHER : Yu_2020_World.J.Emerg.Med_11_37
PubMedSearch : Yu_2020_World.J.Emerg.Med_11_37
PubMedID: 31893002

Title : Geographic variation in sexual communication in the cotton bollworm, Helicoverpa armigera - Gao_2020_Pest.Manag.Sci_76_3596
Author(s) : Gao K , Torres-Vila LM , Zalucki MP , Li Y , Griepink F , Heckel DG , Groot AT
Ref : Pest Manag Sci , 76 :3596 , 2020
Abstract : BACKGROUND: Geographic variation in male response to sex pheromone lures has been studied in the field in a number of moth species. However, only a few studies have investigated geographic variation in female calling and sex pheromone under field conditions. For an effective field implementation of sex pheromone lures, it is essential to know the local sex pheromone blend and local timing of sexual communication. We investigated the level and extent of geographic variation in the sexual communication of the important agricultural pest Helicoverpa armigera (Lepidoptera, Noctuidae) in three continents. RESULTS: We found there is no genetic variation in the calling behavior of H. armigera. In the female sex pheromone, we found more between-population variation than within-population variation. In male response experiments, we found geographic variation as well. Strikingly, when adding the antagonistic compound Z11-16:OAc to the pheromone blend of H. armigera, significantly fewer males were caught in Australia and China, but not in Spain. This variation is likely not only due to local environmental conditions, such as photoperiod and temperature, but also to the presence of other closely related species with which communication interference may occur. CONCLUSION: Finding geographic variation in both the female sexual signal and the male response in this pest calls for region-specific pheromone lures. Our study shows that the analysis of geographic variation in moth female sex pheromones as well as male responses is important for effectively monitoring pest species that occur around the globe. 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
ESTHER : Gao_2020_Pest.Manag.Sci_76_3596
PubMedSearch : Gao_2020_Pest.Manag.Sci_76_3596
PubMedID: 32406164

Title : Positive correlation between human exposure to organophosphate esters and gastrointestinal cancer in patients from Wuhan, China - Li_2020_Ecotoxicol.Environ.Saf_196_110548
Author(s) : Li Y , Fu Y , Hu K , Zhang Y , Chen J , Zhang S , Zhang B , Liu Y
Ref : Ecotoxicology & Environmental Safety , 196 :110548 , 2020
Abstract : As kinds of endocrine disruptors, organophosphate esters (OPEs) pollution in the environment had received increasing attention recently. Food and water intake were two important exposure pathways for OPEs. However, the studies about the potential association between OPEs and gastrointestinal cancer were limited. This study investigated the possible association between OPEs and gastrointestinal cancer. All cancer patients were diagnosed with gastrointestinal cancer from a Grade 3 A hospital in Wuhan, China, while the control group was non-cancer healthy persons. The results showed that 6 OPEs were found in the control samples, while 8 in the samples from patients with gastrointestinal cancer. The detection frequencies of OPEs in gastrointestinal cancer patients were significantly higher than those in the control group (p < 0.05 or p < 0.01), except for triethyl phosphate (TEP) and tris (methylphenyl) phosphate (TMPP) in the gastric cancer group. The concentrations of OPEs in the control group were significantly lower than those in the gastric cancer group and colorectal cancer group (p < 0.01). In the control group and gastrointestinal cancer group, TEP was the dominant pollutant. Correlation analysis found that concentrations of TEP, tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), TMPP, tris(2-ethylhexyl) phosphate (TEHP), and 2-ethylhexyl diphenyl phosphate (EHDPP) were associated with gastric cancer (p < 0.01), and concentrations of TEP, TCIPP, TPHP, TMPP and TEHP were associated with colorectal cancer (p < 0.01). A cluster analysis divided the 34 patients with gastric cancer and 40 patients with colorectal cancer in four groups. The results showed that the elderly male patients with gastric cancer were more sensitive to the exposure of EHDPP, while the TEP exposure was more sensitive to the relatively young gastrointestinal cancer patients. These findings indicated that OPEs might play a role in developing gastrointestinal cancer.
ESTHER : Li_2020_Ecotoxicol.Environ.Saf_196_110548
PubMedSearch : Li_2020_Ecotoxicol.Environ.Saf_196_110548
PubMedID: 32278140

Title : Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia - Li_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158873
Author(s) : Li Y , Torp MK , Norheim F , Khanal P , Kimmel A , Stenslokken KO , Vaage J , Dalen KT
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :158873 , 2020
Abstract : Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5(+/+) and Plin5(-/-) mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5(-/-) mice cultured with oleic acid stored less LDs than Plin5(+/+), but comparable levels to Plin5(+/+) cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO(2) was similar between Plin5(+/+) and Plin5(-/-) cardiomyocytes, but Plin5(-/-) cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids, Plin5(-/-) cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared to Plin5(+/+). In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. Old Plin5(-/-) mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chain Myh7 and the fatty acid transporter Cd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.
ESTHER : Li_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158873
PubMedSearch : Li_2020_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__158873
PubMedID: 33373698

Title : Functional Characterization of two Carboxylesterase Genes Involved in Pyrethroid Detoxification in Helicoverpa armigera - Li_2020_J.Agric.Food.Chem_68_3390
Author(s) : Li Y , Bai L , Zhao C , Xu J , Sun Z , Dong Y , Li D , Liu XL , Ma ZQ
Ref : Journal of Agricultural and Food Chemistry , 68 :3390 , 2020
Abstract : Insect carboxylesterases are major enzymes involved in metabolism of xenobiotics including insecticides. Two carboxylesterase genes, CarE001A and CarE001H, were cloned from the destructive agricultural pest Helicoverpa armigera. Quantitative Real-Time PCR showed that CarE001A and CarE001H were predominantly expressed in fat body and midgut, respectively; developmental expression analyses found that the expression levels of both CarEs were significantly higher in fifth- instar larvae than in other life stages. Recombinant CarE001A and CarE001H expressed in the Escherichia coli exhibited high enzymatic activity toward alpha-naphthyl acetate. Inhibition assays showed that organophosphates had strong inhibition on CarEs activity compared to pyrethroids. Metabolism assays indicated that CarE001A and CarE001H were able to metabolize beta-cypermethrin and lambda-cyhalothrin. Homology modeling and molecular docking analyses demonstrated that beta-cypermethrin could fit nicely into the active pocket of both carboxylesterases. These results suggested that CarE001A and CarE001H could play important roles in the detoxification of pyrehtroids in H. armigera.
ESTHER : Li_2020_J.Agric.Food.Chem_68_3390
PubMedSearch : Li_2020_J.Agric.Food.Chem_68_3390
PubMedID: 32096985
Gene_locus related to this paper: helam-d5g3d5 , helam-d9iv61

Title : Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish - Ma_2020_ACS.Sens_5_83
Author(s) : Ma J , Si T , Yan C , Li Y , Li Q , Lu X , Guo Y
Ref : ACS Sens , 5 :83 , 2020
Abstract : Acetylcholinesterase (AChE) plays crucial roles in numerous physiological processes such as cell differentiation, cell apoptosis, and nerve tissue developments. Hence, it is highly necessary to design a fluorescent probe for monitoring AChE activity in complex living organisms. In this work, a near-infrared (NIR) off-on probe (CyN) was developed for AChE detection. CyN was exactly synthesized by introducing an N,N-dimethyl carbamyl moiety to hemicyanine (CyOH). AChE can "light up" strong NIR fluorescence through a cleavage special ester bond and transform CyN into CyOH. Moreover, CyN was qualified for imaging the dynamic change of AChE activity in PC12 cells with retinoic acid or hypoxia stimulation. In particular, the probe has been successfully applied for in situ tracing the intact distribution of AChE in living zebrafish. The observations indicate that major occurrence sites of endogenic AChE on zebrafish are the yolk sac and neuromasts. Overall, CyN shows great potential for use in AChE-related physiological studies.
ESTHER : Ma_2020_ACS.Sens_5_83
PubMedSearch : Ma_2020_ACS.Sens_5_83
PubMedID: 31875385
Gene_locus related to this paper: danre-ACHE

Title : A dual-mode nanoprobe for the determination of parathion methyl based on graphene quantum dots modified silver nanoparticles - Li_2020_Anal.Bioanal.Chem_412_5583
Author(s) : Li Y , Chen S , Lin D , Chen Z , Qiu P
Ref : Anal Bioanal Chem , 412 :5583 , 2020
Abstract : We developed a highly sensitive and selective method for double-signal analysis (fluorescence and ultraviolet-visible spectrophotometry) of organophosphorus pesticides (OPs), based on reversible quenching of graphene quantum dots (GQDs; fluorophores) with silver nanoparticles (AgNPs; absorbers). We used acetylcholinesterase to catalytically convert acetylthiocholine into thiocholine. In turn, by competitive binding to the AgNPs, the produced thiocholine displaces AgNPs from the GQDs and thus induces fluorescence recovery. However, OP analytes inhibit the activity of acetylcholinesterase and, in so doing, retain the silver-graphene nanoparticle complex and fluorescence quenching. The degree of quenching is proportional to the concentration of OPs; the detection limit is as low as 0.017 microg/L. The ultraviolet-visible absorption of GQDs/AgNPs at 390 nm decreases-because of AgNP aggregation that occurs after desorption from the GQDs-and the absorbance is linearly proportional to the OP concentration. Our system has good selectivity to substances that are commonly present in water and vegetables. We successfully applied our method to OP analysis in water, apple, and carrot samples.
ESTHER : Li_2020_Anal.Bioanal.Chem_412_5583
PubMedSearch : Li_2020_Anal.Bioanal.Chem_412_5583
PubMedID: 32572544

Title : Hepatocyte-specific Expression of Human Carboxylesterase 2 Attenuates Non-alcoholic Steatohepatitis in Mice - Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Xu Y , Pan X , Hu S , Zhu Y , Cassim Bawa F , Li Y , Yin L , Zhang Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2020
Abstract : Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were i.v. injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced non-alcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD.
ESTHER : Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Xu_2020_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 33325808

Title : Acetylcholinesterase electrochemical biosensors with graphene-transition metal carbides nanocomposites modified for detection of organophosphate pesticides - Wang_2020_PLoS.One_15_e0231981
Author(s) : Wang B , Li Y , Hu H , Shu W , Yang L , Zhang J
Ref : PLoS ONE , 15 :e0231981 , 2020
Abstract : An acetylcholinesterase biosensor modified with graphene and transition metal carbides was prepared to detect organophosphorus pesticides. Cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy were used to characterize the electrochemical catalysis of the biosensor: acetylcholinesterase/chitosan-transition metal carbides/graphene/glassy carbon electrode. With the joint modification of graphene and transition metal carbides, the biosensor has a good performance in detecting dichlorvos with a linear relationship from 11.31 muM to 22.6 nM and the limit of detection was 14.45 nM. Under the premise of parameter optimization, the biosensor showed a good catalytic performance for acetylcholine. Compared to the biosensors without modification, it expressed a better catalytic performance due to the excellent electrical properties, biocompatibility and high specific surface area of graphene, transition metal carbides. Finally, the biosensor exhibits good stability, which can be stored at room temperature for one month without significant performance degradation, and has practical potential for sample testing.
ESTHER : Wang_2020_PLoS.One_15_e0231981
PubMedSearch : Wang_2020_PLoS.One_15_e0231981
PubMedID: 32348360