Liu J


Full name : Liu Junjun

First name : Junjun

Mail : Huazhong University of Science and Technology\; Pharmaceutical Science\; 13 Hangkong Rd.\; Wuhan\; 430030

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Country : China

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Phone : +8615527455184

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References (396)

Title : The Overexpression of Zea mays Strigolactone Receptor Gene D14 Enhances Drought Resistance in Arabidopsis thaliana L - Zhang_2024_Int.J.Mol.Sci_25_
Author(s) : Zhang C , Wang F , Jiao P , Liu J , Zhang H , Liu S , Guan S , Ma Y
Ref : Int J Mol Sci , 25 : , 2024
Abstract : Strigolactones (SLs) represent a recently identified class of plant hormones that are crucial for plant tillering and mycorrhizal symbiosis. The D14 gene, an essential receptor within the SLs signaling pathway, has been well-examined in crops, like rice (Oryza sativa L.) and Arabidopsis (Arabidopsis thaliana L.), yet the research on its influence in maize (Zea mays L.) remains scarce. This study successfully clones and establishes Arabidopsis D14 gene overexpression lines (OE lines). When compared with the wild type (WT), the OE lines exhibited significantly longer primary roots during germination. By seven weeks of age, these lines showed reductions in plant height and tillering, alongside slight decreases in rosette and leaf sizes, coupled with early aging symptoms. Fluorescence-based quantitative assays indicated notable hormonal fluctuations in OE lines versus the WT, implying that D14 overexpression disrupts plant hormonal homeostasis. The OE lines, exposed to cold, drought, and sodium chloride stressors during germination, displayed an especially pronounced resistance to drought. The drought resistance of OE lines, as evident from dehydration-rehydration assays, outmatched that of the WT lines. Additionally, under drought conditions, the OE lines accumulated less reactive oxygen species (ROS) as revealed by the assessment of the related physiological and biochemical parameters. Upon confronting the pathogens Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), post-infection, fluorescence quantitative investigations showed a significant boost in the salicylic acid (SA)-related gene expression in OE lines compared to their WT counterparts. Overall, our findings designate the SL receptor D14 as a key upregulator of drought tolerance and a regulator in the biotic stress response, thereby advancing our understanding of the maize SL signaling pathway by elucidating the function of the pivotal D14 gene.
ESTHER : Zhang_2024_Int.J.Mol.Sci_25_
PubMedSearch : Zhang_2024_Int.J.Mol.Sci_25_
PubMedID: 38279328

Title : The proteomic landscape of fall armyworm oral secretion reveals its role in plant adaptation - Zhang_2024_Pest.Manag.Sci__
Author(s) : Zhang X , Li P , Tang Y , Mu YP , Liu J , Wang MY , Wang W , Mao YB
Ref : Pest Manag Sci , : , 2024
Abstract : BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda (J.E. Smith)) is a polyphagous agricultural pest with rapidly evolving adaptations to host plants. We found the oral secretion (OS) of FAW from different plants influences plant defense response differentially, suggesting its role in adapting to host plants. However, the protein expression profile of FAW OS respond to different plants is largely unknown. RESULTS: Here, from the mass spectrometry assay, we identified a total of 256 proteins in the OS of FAW fed on cotton (Gossypium hirsutum L.), tobacco (Nicotiana benthamiana Domin), maize (Zea mays L.) and artificial diet. The FAW OS primarily comprise of 60 proteases, 32 esterases and 92 non-enzymatic proteins. It displays high plasticity across different diets. We found that more than half of the esterases are lipases which have been reported as insect elicitors to enhance plant defense response. The lipase accumulation in cotton-fed larvae was the highest, followed by maize-fed larvae. In the presence of lipase inhibitors, the enhanced induction on defense genes in wounded leaves by OS was attenuated. On the other hand, the putative effectors were most highly accumulated in the OS from FAW larvae fed on maize compared to those fed on other diets. We identified that one of them (VRLP4) reduces the OS-mediated induction on defense genes in wounded leaves. CONCLUSION: Together, our investigation presents the proteomic landscape of the OS of FAW influenced by different diets and reveals diet-mediated plasticity of OS is involved in FAW adaptation to host plants. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2024_Pest.Manag.Sci__
PubMedSearch : Zhang_2024_Pest.Manag.Sci__
PubMedID: 38587094

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 : Comparison Study of Two Fumonisin-Degrading Enzymes for Detoxification in Piglets - Wang_2024_Toxins.(Basel)_16_3
Author(s) : Wang Z , Lv Z , Czabany T , Nagl V , Krska R , Wang X , Han B , Tao H , Liu J , Wang J
Ref : Toxins (Basel) , 16 :3 , 2024
Abstract : Fumonisins (FBs), particularly fumonisin B1 (FB1) and fumonisin B2 (FB2) produced mainly by Fusarium verticillioide and Fusarium proliferatum, are common contaminants in animal feed and pose a serious threat to both animal and human health. The use of microbial enzymes to efficiently and specifically convert fumonisins into non-toxic or low-toxic metabolites has emerged as the most promising approach. However, most of the available enzymes have only been evaluated in vitro and lack systematic evaluation in vivo. In this study, the detoxification efficacy of two carboxylesterases, FumD (FUMzyme((a))) and FumDSB, was evaluated comparatively in piglets. The results show that feeding piglets 4.4 mg/kg FBs-contaminated diets for 32 days did not significantly affect the average daily gain, organ indices, and immunoglobulins of the piglets. However, a significant reduction (21.2%) in anti-inflammatory cytokine interleukin-4 was observed in the FBs group, and supplementation with FUMzyme((a)) and FumDSB significantly increased interleukin-4 by 62.1% and 28.0%, respectively. In addition, FBs-contaminated diets resulted in a 3-fold increase in the serum sphinganine/sphingosine (Sa/So) ratio, which is a specific biomarker that has been used to accurately reflect fumonisin levels. The serum Sa/So ratio was significantly reduced by 48.8% after the addition of FUMzyme((a)), and was insignificantly reduced by 8.2% in the FumDSB group. These results suggested that FUMzyme was more effective than FumDSB in mitigating FBs toxicity in piglets by down-regulating the Sa/So ratio.
ESTHER : Wang_2024_Toxins.(Basel)_16_3
PubMedSearch : Wang_2024_Toxins.(Basel)_16_3
PubMedID: 38276527
Gene_locus related to this paper: sphmc-FumD , 9sphn-a0a101vlk1

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 : Presence of Multiple Genetic Mutations Related to Insecticide Resistance in Chinese Field Samples of Two Phthorimaea Pest Species - Zhu_2024_Insects_15_
Author(s) : Zhu J , Chen R , Liu J , Lin W , Liang J , Nauen R , Li S , Gao Y
Ref : Insects , 15 : , 2024
Abstract : Potatoes hold the distinction of being the largest non-cereal food crop globally. The application of insecticides has been the most common technology for pest control. The repeated use of synthetic insecticides of the same chemical class and frequent applications have resulted in the emergence of insecticide resistance. Two closely related pests that feed on potato crops are the potato tuber moth, Phthorimaea operculella, and the tomato leafminer, Phthorimaea absoluta (syn. Tuta absoluta). Previous studies indicated the existence of insecticide resistance to various classes of insecticides including organophosphates, carbamates, and pyrethroids in field populations of P. operculella and P. absoluta. However, the exact mechanisms of insecticide resistance in P. operculella and to a lesser extent P. absoluta remain still poorly understood. Detecting resistance genotypes is crucial for the prediction and management of insecticide resistance. In this study, we identified multiple genetic mutations related to insecticide resistance in two species of Phthorimaea. An unexpected genetic divergence on target-site mutations was observed between P. operculella and P. absoluta. Three mutations (A201S, L231V, and F290V) in Ace1 (acetylcholinesterase), four mutations (M918T, L925M, T928I, and L1014F) in VGSC (voltage-gated sodium channel), and one mutation (A301S) in RDL (GABA-gated chloride channel) have been detected with varying frequencies in Chinese P. absoluta field populations. In contrast, P. operculella field populations showed three mutations (F158Y, A201S, and L231V) in Ace1, one mutation (L1014F) in VGSC at a lower frequency, and no mutation in RDL. These findings suggest that pyrethroids, organophosphates, and carbamates are likely to be ineffective in controlling P. absoluta, but not P. operculella. These findings contributed to a deeper understanding of the presence of target-site mutations conferring resistance to commonly used (and cheap) classes of insecticides in two closely related potato pests. It is recommended to consider the resistance status of both pests for the implementation of resistance management strategies in potatoes.
ESTHER : Zhu_2024_Insects_15_
PubMedSearch : Zhu_2024_Insects_15_
PubMedID: 38535389

Title : Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders - Liu_2024_Brain__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev YV , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski MR , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent AL , Siskind CE , Traboulsi EI , Blackstone C , Sisk RA , Miraldi Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Brain , : , 2024
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2024_Brain__
PubMedSearch : Liu_2024_Brain__
PubMedID: 38735647

Title : LET-767 determines lipid droplet protein targeting and lipid homeostasis - Fu_2024_J.Cell.Biol_223_
Author(s) : Fu L , Zhang J , Wang Y , Wu H , Xu X , Li C , Li J , Liu J , Wang H , Jiang X , Li Z , He Y , Liu P , Wu Y , Zou X , Liang B
Ref : Journal of Cell Biology , 223 : , 2024
Abstract : Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.
ESTHER : Fu_2024_J.Cell.Biol_223_
PubMedSearch : Fu_2024_J.Cell.Biol_223_
PubMedID: 38551495

Title : Oligosaccharides from black ginseng innovatively prepared by low temperature steam-heating process ameliorate cognitive impairment in Alzheimer's disease mice via the Keap-1\/Nrf2 pathway - Xu_2024_J.Sci.Food.Agric__
Author(s) : Xu W , Yu P , Shao S , Xie Z , Wu Y , Liu J , Xu T , Cai G , Yang H
Ref : J Sci Food Agric , : , 2024
Abstract : BACKGROUND: Our objective in this study is to evaluate the effectiveness of the oligosaccharides extracted from black ginseng (BG), innovatively prepared by a low-temperature steam-heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS: 8 carbohydrates involving isomaltose and maltotetraose were detected in BG, where the monosaccharide residues including mannose and rhamnose were discovered too. OSBG-treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine (SCO) group. OSBG could decrease acetylcholinesterase (AChE) activity in a tissue-dependent fashion but not in a dose-dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and Kelch-like ECH-associated protein 1 (Keap1), downregulation of malondialdehyde (MDA) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus, Clostridium_XlVb,) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas, compared to the AD mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine-induced intestinal microbiota in mice, providing a homeostasis of gut microbiota and providing evidence for microbiota-regulated therapeutic potentials of it. CONCLUSION: Our results showed for the first time a clear role for OSBG in improving scopolamine-induced memory impairment by inhibiting cholinergic dysfunction in a tissue-dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap-1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in AD patients. This article is protected by copyright. All rights reserved.
ESTHER : Xu_2024_J.Sci.Food.Agric__
PubMedSearch : Xu_2024_J.Sci.Food.Agric__
PubMedID: 38372395

Title : Concentration-dependent effects of lithium on Daphnia magna: Life-history profiles and integrated biomarker response implementation - Chen_2024_Sci.Total.Environ__169866
Author(s) : Chen W , Zhang P , Ye L , Yao J , Wang Z , Liu J , Qin X
Ref : Sci Total Environ , :169866 , 2024
Abstract : The growing use of lithium (Li) in industrial and energy applications and increasing demand worldwide has inevitably resulted in its wide dispersal, representing a significant threat to aquatic systems. Unfortunately, as a ubiquitous emerging contaminant, the comprehensive toxicological information regarding Li at multifarious levels is limited. To diminish this gap, this work was focused to explore Li-induced cascading effects on Daphnia magna as a key species in freshwater ecosystems. Specifically, the organisms were chronically exposed to gradient Li concentrations with emphasis on characterizing life-history traits from individual to population scale, primarily as observed by a markedly concentration-dependent decrease along exposure gradients. In parallel, a robust set of biomarkers relating to energy reserves, antioxidant and biotransformation enzymes, cellular damage, ionoregulation and neurotoxicity were assayed for further understanding potential underlying mechanisms. As a result, biomarker alterations were characterized by significant decreases in energy storage and enzymatic profiles of antioxidant and biotransformation systems, not only triggering an imbalance between reactive oxygen species (ROS) generation and elimination under Li exposure, but compromising the fecundity fitness of phenotypical costs. In contrast, malondialdehyde (MDA) levels were remarkably enhanced as a consequence of inefficient antioxidant and biotransformation capacity leading to lipid peroxidation (LPO). Additionally, Li exerted a dose-dependent biphasic effect on the activities of superoxide dismutase (SOD), Na(+),K(+)-ATPase and acetylcholinesterase (AChE) by interfering with inherent balance. In terms of responsive patterns and dose-effect trends, the integrated biomarker response indices (IBRv2) and star plots were consistent with the differences in biomarker profiles, not only presenting comprehensively biological effects in a visualized form, but signaling the importance of progressive induced changes in an integrative way. Overall, these findings highlighted the need for elucidating Li-produced impacts from a comprehensive perspective, providing valuable insights into better understanding the toxicity of Li in relation to aquatic ecosystem functioning and ecological relevance.
ESTHER : Chen_2024_Sci.Total.Environ__169866
PubMedSearch : Chen_2024_Sci.Total.Environ__169866
PubMedID: 38190914

Title : In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease - Huang_2024_Drug.Des.Devel.Ther_18_133
Author(s) : Huang ST , Luo JC , Zhong GH , Teng LP , Yang CY , Tang CL , Jing L , Zhou ZB , Liu J , Jiang N
Ref : Drug Des Devel Ther , 18 :133 , 2024
Abstract : PURPOSE: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. METHODS: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. RESULTS: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC(50) = 1.57 microM, hBuChE: IC(50) = 0.43 microM) and MAOs (hMAO-A: IC(50) = 2.30 microM, hMAO-B: IC(50) = 4.75 microM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. CONCLUSION: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.
ESTHER : Huang_2024_Drug.Des.Devel.Ther_18_133
PubMedSearch : Huang_2024_Drug.Des.Devel.Ther_18_133
PubMedID: 38283137

Title : Genome-wide association studies of egg production traits by whole genome sequencing of Laiwu Black chicken - Lei_2024_Poult.Sci_103_103705
Author(s) : Lei Q , Zhang S , Wang J , Qi C , Liu J , Cao D , Li F , Han H , Liu W , Li D , Tang C , Zhou Y
Ref : Poult Sci , 103 :103705 , 2024
Abstract : Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 x per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.
ESTHER : Lei_2024_Poult.Sci_103_103705
PubMedSearch : Lei_2024_Poult.Sci_103_103705
PubMedID: 38598913

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 : Frequencies of insecticide resistance mutations detected by the amplicon sequencing in Plutella xylostella (Lepidoptera: Plutellidae) and Spodoptera exigua (Lepidoptera: Noctuidae) from China - Liu_2024_J.Econ.Entomol__
Author(s) : Liu Z , Ma H , Li K , Liu J , Zhu H , Zhou Y , Man Y , Zhou X
Ref : J Econ Entomol , : , 2024
Abstract : The globally prevalent pests, Diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) and Beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), pose significant threats to cruciferous vegetables. They have rapidly developed resistance to a wide range of insecticides, leading to significant yield losses and increased control expenses. In this study, we have established an efficient approach utilizing amplicon sequencing to detect the frequency of 15 target resistance mutant sites in 6 molecular targets, acetylcholinesterase 1 (ACE1), chitin synthase 1 (CHS1), the gamma-aminobutyric acid receptor (GABAR), glutamate-gated chloride channel (GluCl), voltage-gated sodium channels (NaV), and ryanodine receptor (RyR) in P. xylostella and the frequency of 11 mutations in 5 molecular targets (except GluCl) in S. exigua in China. Our findings indicate that P. xylostella exhibits remarkably high frequency (over 88.67%) in pyrethroid resistance-related mutations T929I and L1014F of NaV. In S. exigua, the frequencies of L659F mutation were ranging from 41.92% to 74.89%. In addition, the organophosphorus resistance-related mutations A298S and G324A of ACE1 were detected at frequencies ranging from 34.29% to 75.66%, and these 2 mutations occurred simultaneously (from 29.22% to 65.79%) in P. xylostella. An interannual variation in mutation frequency from 2019 to 2021 was found for P. xylostella in HNCS. The frequency of A298S and G324A mutations steadily increased while the frequency of G4946E and I4790M mutations continuously decreased. These results unveil a worrisome scenario of multiple resistance sites in these 2 pests in China and provide valuable insights for the practical application of pesticides in the field.
ESTHER : Liu_2024_J.Econ.Entomol__
PubMedSearch : Liu_2024_J.Econ.Entomol__
PubMedID: 38748551

Title : Trace Amount of Bi-Doped Core-Shell Pd@Pt Mesoporous Nanospheres with Specifically Enhanced Peroxidase-Like Activity Enable Sensitive and Accurate Detection of Acetylcholinesterase and Organophosphorus Nerve Agents - Lei_2024_Anal.Chem__
Author(s) : Lei M , Ding X , Liu J , Tang Y , Chen H , Zhou Y , Zhu C , Yan H
Ref : Analytical Chemistry , : , 2024
Abstract : The urgent need for sensitive and accurate assays to monitor acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs) arises from the imperative to safeguard human health and protect the ecosystem. Due to its cost-effectiveness, ease of operation, and rapid response, nanozyme-based colorimetry has been widely utilized in the determination of AChE activity and OPs. However, the rational design of nanozymes with high activity and specificity remains a great challenge. Herein, trace amount of Bi-doped core-shell Pd@Pt mesoporous nanospheres (Pd@PtBi(2)) have been successfully synthesized, exhibiting good peroxidase-like activity and specificity. With the incorporation of trace bismuth, there is a more than 4-fold enhancement in the peroxidase-like performance of Pd@PtBi(2) compared to that of Pd@Pt. Besides, no significant improvement of oxidase-like and catalase-like activities of Pd@PtBi(2) was found, which prevents interference from O(2) and undesirable consumption of substrate H(2)O(2). Based on the blocking impact of thiocholine, a colorimetric detection platform utilizing Pd@PtBi(2) was constructed to monitor AChE activity with sensitivity and selectivity. Given the inhibition of OPs on AChE activity, a biosensor was further developed by integrating Pd@PtBi(2) with AChE to detect OPs, capitalizing on the cascade amplification strategy. The OP biosensor achieved a detection limit as low as 0.06 ng mL(-1), exhibiting high sensitivity and anti-interference ability. This work is promising for the construction of nanozymes with high activity and specificity, as well as the development of nanozyme-based colorimetric biosensors.
ESTHER : Lei_2024_Anal.Chem__
PubMedSearch : Lei_2024_Anal.Chem__
PubMedID: 38577757

Title : Depolymerization of the polyester-polyurethane by amidase GatA250 and enhancing the production of 4,4'-methylenedianiline with cutinase LCC - Xin_2024_Biotechnol.J_19_e2300723
Author(s) : Xin K , Lu J , Zeng Q , Zhang T , Liu J , Zhou J , Dong W , Jiang M
Ref : Biotechnol J , 19 :e2300723 , 2024
Abstract : Polyurethane (PU) is a complex polymer synthesized from polyols and isocyanates. It contains urethane bonds that resist hydrolysis, which decreases the efficiency of biodegradation. In this study, we first expressed the amidase GatA250, and then, assessed the enzymatic characterization of GatA250 and its efficiency in degrading the polyester-PU. GatA250 degraded self-synthesized thermoplastic PU film and postconsumption foam with degradation efficiency of 8.17% and 4.29%, respectively. During the degradation, the film released 14.8 microm 4,4'-methylenedianiline (MDA), but 1,4-butanediol (BDO) and adipic acid (AA) were not released. Our findings indicated that GatA250 only cleaved urethane bonds in PU, and the degradation efficiency was extremely low. Hence, we introduced the cutinase LCC, which possesses hydrolytic activity on the ester bonds in PU, and then used both enzymes simultaneously to degrade the polyester-PU. The combined system (LCC-GatA250) had higher degradation efficiency for the degradation of PU film (42.2%) and foam (13.94%). The combined system also showed a 1.80 time increase in the production of the monomer MDA, and a 1.23 and 3.62 times increase in the production of AA and BDO, respectively, compared to their production recorded after treatment with only GatA250 or LCC. This study provides valuable insights into PU pollution control and also proposes applicable solutions to manage PU wastes through bio-recycling.
ESTHER : Xin_2024_Biotechnol.J_19_e2300723
PubMedSearch : Xin_2024_Biotechnol.J_19_e2300723
PubMedID: 38622797
Gene_locus related to this paper: 9bact-g9by57

Title : Hydrogel-involved portable colorimetric sensor based on oxidase mimic Fe\/Co-NC for acetylcholinesterase detection and pesticides inhibition assessment - Zhou_2024_Food.Chem_441_138372
Author(s) : Zhou C , Wang N , Lv Y , Liu J , Su Y , Su X
Ref : Food Chem , 441 :138372 , 2024
Abstract : Herein, we synthesized a novel N-doped carbon layer encapsulated Fe/Co bimetallic nanoparticles (Fe/Co-NC), which exhibited superior oxidase-like activity due to the facilitation of electron penetration and the formation of metal-nitrogen active sites. Fe/Co-NC could catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) to blue oxTMB. Acetylcholinesterase (AChE) could catalyze the hydrolysis of thioacetylcholine to produce reducing thiocholine, which prevented TMB from oxidation. Thus, a portable hydrogel colorimetric sensor was developed for on-site and visual monitoring of AChE with the detection limit of 0.36 U L(-1), and successfully applied to detect AChE in human erythrocyte samples. Furthermore, this platform was used to investigate the inhibition of triazophos on AChE activity.
ESTHER : Zhou_2024_Food.Chem_441_138372
PubMedSearch : Zhou_2024_Food.Chem_441_138372
PubMedID: 38219364

Title : Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation - Liu_2024_Appl.Environ.Microbiol__e0147723
Author(s) : Liu J , Xin K , Zhang T , Wen Y , Li D , Wei R , Zhou J , Cui Z , Dong W , Jiang M
Ref : Applied Environmental Microbiology , :e0147723 , 2024
Abstract : Plastic degradation by biological systems emerges as a prospective avenue for addressing the pressing global concern of plastic waste accumulation. The intricate chemical compositions and diverse structural facets inherent to polyurethanes (PU) substantially increase the complexity associated with PU waste management. Despite the extensive research endeavors spanning over decades, most known enzymes exhibit a propensity for hydrolyzing waterborne PU dispersion (i.e., the commercial Impranil DLN-SD), with only a limited capacity for the degradation of bulky PU materials. Here, we report a novel cutinase (CpCut1) derived from Cladosporium sp. P7, which demonstrates remarkable efficiency in the degrading of various polyester-PU materials. After 12-h incubation at 55 degreesC, CpCut1 was capable of degrading 40.5% and 20.6% of thermoplastic PU film and post-consumer foam, respectively, while achieving complete depolymerization of Impranil DLN-SD. Further analysis of the degradation intermediates suggested that the activity of CpCut1 primarily targeted the ester bonds within the PU soft segments. The versatile performance of CpCut1 against a spectrum of polyester-PU materials positions it as a promising candidate for the bio-recycling of waste plastics.IMPORTANCEPolyurethane (PU) has a complex chemical composition that frequently incorporates a variety of additives, which poses significant obstacles to biodegradability and recyclability. Recent advances have unveiled microbial degradation and enzymatic depolymerization as promising waste PU disposal strategies. In this study, we identified a gene encoding a cutinase from the PU-degrading fungus Cladosporium sp. P7, which allowed the expression, purification, and characterization of the recombinant enzyme CpCut1. Furthermore, this study identified the products derived from the CpCut1 catalyzed PU degradation and proposed its underlying mechanism. These findings highlight the potential of this newly discovered fungal cutinase as a remarkably efficient tool in the degradation of PU materials.
ESTHER : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedSearch : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedID: 38445906
Gene_locus related to this paper: 9pezi-CpCut1

Title : Ameliorative Effect of Natural Sesquiterpene Alcohol Cedrol Against Cerebral Ischemia Infarction-In Vitro and In Vivo Studies - Hu_2024_Appl.Biochem.Biotechnol__
Author(s) : Hu X , Han M , Liu J , Li F , Cui Y
Ref : Appl Biochem Biotechnol , : , 2024
Abstract : Cedrol is a major bioactive compound present in the Cedrus atlantica with numerous biological properties. In this study, we elucidated the neuroprotective properties of cedrol against ischemic infarction in animal and in vitro studies. A cerebral ischemic/reperfusion model was induced in adult Wistar rats, and oxygen-glucose deprivation/reperfusion was induced in SH-SY5Y neuronal cells and treated with different concentrations of cedrol. The percentage of water content, cerebral infarct, and neurological deficit score was assessed in experimental rats. The acetylcholinesterase activity and inflammatory cytokines were quantified to analyze the anti-inflammatory potency of cedrol. Oxidative stress marker malondialdehyde and antioxidants were quantified to evaluate the antioxidant potency of cedrol in an ischemic condition. The neuroprotective potency of cedrol was confirmed by histopathological analysis of the brain tissue of cedrol-treated I/R-induced rats. In in vitro studies, the MTT and LDH assays were performed in cedrol-treated OGD/R SH-SY5Y cells to analyze the cytoprotective effect of cedrol. The anti-inflammatory property of cedrol was confirmed by quantifying the pro-inflammatory cytokine levels in OGD/R-induced cedrol-treated SH-SY5Y cells. The results obtained prove that cedrol significantly prevents brain edema, neurological deficits, acetylcholinesterase activity, and oxidative damage in ischemic-induced rats. It inhibited neuroinflammation in ischemic-induced rats and also in in vitro models. The neuroprotective effect of cedrol during an ischemic condition was authentically established with histological analysis in an animal model and cell survival assays in an in vitro model. Overall, our results confirm that cedrol is a potent alternative drug to treat cerebral ischemia in the future.
ESTHER : Hu_2024_Appl.Biochem.Biotechnol__
PubMedSearch : Hu_2024_Appl.Biochem.Biotechnol__
PubMedID: 38668841

Title : A Versatile Thioesterase Involved in Dimerizationduring Cinnamoyl Lipid Biosynthesis - Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
Author(s) : Deng Z , Liu C , Wang F , Song N , Liu J , Li H , Liu S , Li T , Liu Z , Xiao F , Li W
Ref : Angew Chem Int Ed Engl , :e202402010 , 2024
Abstract : The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatic dimerization remains unknown. In this work, an unusual"gene-within-gene"thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with alpha/beta-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6Pi-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatic dimerization process, possibly via an unprecedent Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6Pi-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.
ESTHER : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedSearch : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedID: 38462490
Gene_locus related to this paper: 9actn-YsfF

Title : Metabolism of host lysophosphatidylcholine in Plasmodium falciparum-infected erythrocytes - Liu_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2320262121
Author(s) : Liu J , Fike KR , Dapper C , Klemba M
Ref : Proc Natl Acad Sci U S A , 121 :e2320262121 , 2024
Abstract : The human malaria parasite Plasmodium falciparum requires exogenous fatty acids to support its growth during the pathogenic, asexual erythrocytic stage. Host serum lysophosphatidylcholine (LPC) is a significant fatty acid source, yet the metabolic processes responsible for the liberation of free fatty acids from exogenous LPC are unknown. Using an assay for LPC hydrolysis in P. falciparum-infected erythrocytes, we have identified small-molecule inhibitors of key in situ lysophospholipase activities. Competitive activity-based profiling and generation of a panel of single-to-quadruple knockout parasite lines revealed that two enzymes of the serine hydrolase superfamily, termed exported lipase (XL) 2 and exported lipase homolog (XLH) 4, constitute the dominant lysophospholipase activities in parasite-infected erythrocytes. The parasite ensures efficient exogenous LPC hydrolysis by directing these two enzymes to distinct locations: XL2 is exported to the erythrocyte, while XLH4 is retained within the parasite. While XL2 and XLH4 were individually dispensable with little effect on LPC hydrolysis in situ, loss of both enzymes resulted in a strong reduction in fatty acid scavenging from LPC, hyperproduction of phosphatidylcholine, and an enhanced sensitivity to LPC toxicity. Notably, growth of XL/XLH-deficient parasites was severely impaired when cultured in media containing LPC as the sole exogenous fatty acid source. Furthermore, when XL2 and XLH4 activities were ablated by genetic or pharmacologic means, parasites were unable to proliferate in human serum, a physiologically relevant fatty acid source, revealing the essentiality of LPC hydrolysis in the host environment and its potential as a target for anti-malarial therapy.
ESTHER : Liu_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2320262121
PubMedSearch : Liu_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2320262121
PubMedID: 38349879

Title : Ruptured organosilica nanocapsules immobilized acetylcholinesterase coupled with MnO(2) nanozyme for screening inhibitors from Inula macrophylla - Liu_2023_Nanoscale__
Author(s) : Liu J , Ha W , Alibekovna EK , Ma R , Shi YP
Ref : Nanoscale , : , 2023
Abstract : Abnormal expression of acetylcholinesterase (AChE) causes Alzheimer's disease (AD). Inhibiting AChE is a common strategy for reducing the degradation of neurotransmitter acetylcholine, in order to treat early-stage AD. Therefore, it is crucial to screen and explore AChE inhibitors which are safer and cause fewer side effects. Our research is focused on establishing a platform of ruptured organosilica nanocapsules (RONs) immobilized AChE coupled with an MnO(2)-OPD colorimetric assay, which could monitor AChE activity and screen AChE inhibitors. The fabricated RONs immobilized AChE possessed excellent pH and thermal stability. Huperzine A was introduced into the established platform to evaluate the inhibition kinetics of the immobilized AChE, which promoted its application in the screening of AChE inhibitors. The satisfactory results of enzyme inhibition kinetics proved the feasibility and applicability of the established method. Thus, the proposed platform was applied to screen AChE inhibitors from 14 compounds isolated from Inula macrophylla, and beta-cyclocostunolide (compound 4) demonstrated the best AChE inhibitory activity among these compounds. This work confirms the existence of chemical components that inhibit AChE activity in Inula macrophylla, and provides a new idea for the application of immobilized enzyme-nanozyme in the field of enzyme inhibitor screening.
ESTHER : Liu_2023_Nanoscale__
PubMedSearch : Liu_2023_Nanoscale__
PubMedID: 37860933

Title : Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function - Lee_2023_J.Biol.Chem__104586
Author(s) : Lee H , Chofflet N , Liu J , Fan S , Lu Z , Rojas M , Penndorf P , Bailey A , Russell W , Machius M , Ren G , Takahashi H , Rudenko G
Ref : Journal of Biological Chemistry , :104586 , 2023
Abstract : MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs) which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III (FN3) domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that wild-type MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1beta, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1:NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.
ESTHER : Lee_2023_J.Biol.Chem__104586
PubMedSearch : Lee_2023_J.Biol.Chem__104586
PubMedID: 36889589

Title : Genome wide identification of GDSL gene family explores a novel GhirGDSL26 gene enhancing drought stress tolerance in cotton - Liu_2023_BMC.Plant.Biol_23_14
Author(s) : Liu J , Wang H , Khan A , Xu Y , Hou Y , Wang Y , Zhou Z , Zheng J , Liu F , Cai X
Ref : BMC Plant Biol , 23 :14 , 2023
Abstract : BACKGROUND: Current climate change scenarios are posing greater threats to the growth and development of plants. Thus, significant efforts are required that can mitigate the negative effects of drought on the cotton plant. GDSL esterase/lipases can offer an imperative role in plant development and stress tolerance. However, thesystematic and functional roles of the GDSL gene family, particularly in cotton under water deficit conditions have not yet been explored. RESULTS: In this study, 103, 103, 99, 198, 203, 239, 249, and 215 GDSL proteins were identified in eight cotton genomes i.e., Gossypium herbaceum (A1), Gossypium arboretum (A2), Gossypium raimondii (D5), Gossypium hirsutum (AD1), Gossypium barbadense (AD2), Gossypium tomentosum (AD3), Gossypium mustelinum (AD4), Gossypium darwinii (AD5), respectively. A total of 198 GDSL genes of Gossypium hirsutum were divided into eleven clades using phylogenetic analysis, and the number of GhirGDSL varied among different clades. The cis-elements analysis showed that GhirGDSL gene expression was mainly related to light, plant hormones, and variable tense environments. Combining the results of transcriptome and RT-qPCR, GhirGDSL26 (Gh_A01G1774), a highly up-regulated gene, was selected for further elucidating its tole in drought stress tolerance via estimating physiological and biochemical parameters. Heterologous expression of the GhirGDSL26 gene in Arabidopsis thaliana resulted in a higher germination and survival rates, longer root lengths, lower ion leakage and induced stress-responsive genes expression under drought stress. This further highlighted that overexpressed plants had a better drought tolerance as compared to the wildtype plants. Moreover, 3, 3'-diaminobenzidine (DAB) and Trypan staining results indicated reduced oxidative damage, less cell membrane damage, and lower ion leakage in overexpressed plants as compared to wild type. Silencing of GhirGDSL26 in cotton via VIGS resulting in a susceptible phenotype, higher MDA and H(2)O(2) contents, lower SOD activity, and proline content. CONCLUSION: Our results demonstrated that GhirGDSL26 plays a critical role in cotton drought stress tolerance. Current findings enrich our knowledge of GDSL genes in cotton and provide theoretical guidance and excellent gene resources for improving drought tolerance in cotton.
ESTHER : Liu_2023_BMC.Plant.Biol_23_14
PubMedSearch : Liu_2023_BMC.Plant.Biol_23_14
PubMedID: 36609252

Title : Developing a Two-Photon AND Logic Probe and Its Application in Alzheimer's Disease Differentiation - Guo_2023_Anal.Chem__
Author(s) : Guo J , Sun J , Liu D , Liu J , Gui L , Luo M , Kong D , Wusiman S , Yang C , Liu T , Yuan Z , Li R
Ref : Analytical Chemistry , : , 2023
Abstract : In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight. In this work, we constructed a two-photon fluorescent probe that recognizes hypochlorous acid and butyrylcholinesterase based on a dual-lock strategy. The thiocarbonyl group is oxidized in the presence of hypochlorous acid, and the hydrolysis occurs at the 7-position ester bond in the existence of butyrylcholinesterase, releasing a strongly fluorescent fluorophore, 4-methylumbelliferone. Excellent imaging was performed in PC12 cells using this probe, and deep two-photon imaging was observed in the brains of AD mice after tail vein injection with this probe. It indicates that the probe can provide a promising tool for the more precise diagnosis of Alzheimer's disease.
ESTHER : Guo_2023_Anal.Chem__
PubMedSearch : Guo_2023_Anal.Chem__
PubMedID: 37947381

Title : Design, synthesis, and biological evaluation of novel capsaicin-tacrine hybrids as multi-target agents for the treatment of Alzheimer's disease - Long_2023_Bioorg.Chem_143_107026
Author(s) : Long J , Qin F , Luo J , Zhong G , Huang S , Jing L , Yi T , Liu J , Jiang N
Ref : Bioorg Chem , 143 :107026 , 2023
Abstract : A series of novel hybrid compounds were designed, synthesized, and utilized as multi-target drugs to treat Alzheimer's disease (AD) by connecting capsaicin and tacrine moieties. The biological assays indicated that most of these compounds demonstrated strong inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities with IC(50) values in the nanomolar, as well as good blood-brain barrier permeability. Among the synthesized hybrids, compound 5s displayed the most balanced inhibitory effect on hAChE (IC(50) = 69.8 nM) and hBuChE (IC(50) = 68.0 nM), and exhibited promising inhibitory activity against beta-secretase-1 (BACE-1) (IC(50) = 3.6 microM). Combining inhibition kinetics and molecular model analysis, compound 5s was shown to be a mixed inhibitor affecting both the catalytic active site (CAS) and peripheral anionic site (PAS) of hAChE. Additionally, compound 5s showed low toxicity in PC12 and BV2 cell assays. Moreover, compound 5s demonstrated good tolerance at the dose of up to 2500 mg/kg and exhibited no hepatotoxicity at the dose of 3 mg/kg in mice, and it could effectively improve memory ability in mice. Taken together, these findings suggest that compound 5s is a promising and effective multi-target agent for the potential treatment of AD.
ESTHER : Long_2023_Bioorg.Chem_143_107026
PubMedSearch : Long_2023_Bioorg.Chem_143_107026
PubMedID: 38103330

Title : Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension - Guo_2023_Theranostics_13_1826
Author(s) : Guo Y , He Z , Chen Z , Chen F , Wang C , Zhou W , Liu J , Liu H , Shi R
Ref : Theranostics , 13 :1826 , 2023
Abstract : Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.
ESTHER : Guo_2023_Theranostics_13_1826
PubMedSearch : Guo_2023_Theranostics_13_1826
PubMedID: 37064881

Title : Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities - Gan_2023_Chin.J.Nat.Med_21_154
Author(s) : Gan D , Li C , Shu Y , Wang J , Wang C , Zhu L , Yang Y , Liu J , He B , Cai L , Ding Z
Ref : Chin J Nat Med , 21 :154 , 2023
Abstract : The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C(28)-steroid with an unusual beta- and gamma-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC(50) value of 2.61 +/- 0.05 micromol.L(-1). The beta-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 microg.mL(-1). Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 microg.mL(-1), respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC(50) values of 9.2 +/- 0.03 and 13.3 +/- 0.01 micromol.L(-1), respectively.
ESTHER : Gan_2023_Chin.J.Nat.Med_21_154
PubMedSearch : Gan_2023_Chin.J.Nat.Med_21_154
PubMedID: 36871983

Title : Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders - Liu_2023_bioRxiv__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev Y , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski M , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent A , Siskind CE , Traboulsi EI , Blackstone C , Sisk R , Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Biorxiv , : , 2023
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. PNPLA6 encodes Neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a clinical meta-analysis of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 10 variants as likely pathogenic and 36 variants as pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship and the generation of a preclinical animal model pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2023_bioRxiv__
PubMedSearch : Liu_2023_bioRxiv__
PubMedID: 37333224

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 : Novel N(1) or N(9) modified alpha-carboline analogues as potential ligands in Alzheimer's disease therapy: Synthesis and neurobiological activity evaluation - Dan_2023_Bioorg.Chem_133_106378
Author(s) : Dan W , Cao Y , Sun Y , Zhang J , Liu J , Gao J , Han R , Dai J
Ref : Bioorg Chem , 133 :106378 , 2023
Abstract : A series of new alpha-carboline analogues modified at N(1) or N(9) positions by alkyl, benzyl and phenyl were synthesized and characterized as potential ligands for AD therapy. These compounds exhibited multifunctional neurobiological activities including anti-neuroinflammatory, neuroprotective and cholinesterase inhibition. Among them, compound 5d with good drug-like properties and no cytotoxicity, showed potent inhibitory activity against NO production (IC(50) = 1.45 microM), which could suppress the expression levels of iNOS and COX-2 in a dose-dependent manner. Further mechanism exploration indicated that compound 5d could regulate the NF-kappaB signaling pathway by decreasing the phosphorylation of IkappaB-alpha and p65. Notably, compound 5d could effectively decrease the LPS-induced aberrations in zebrafish. Compounds 3b, 4f, 5c, 5g, 5m and 6i exhibited potential neuroprotective activity (cell viability > 70 %) in the H(2)O(2)-induced PC-12 neuronal death model and rescued the SOD activity. In particular, compounds 3b, 4f, and 5g activated the Nrf2 signaling pathway, and improved the expressions of antioxidant proteins NQO-1 and HO-1, which alleviated the head cell apoptosis in zebrafish. Additionally, compound 6i exhibited potential inhibitory activity against BuChE with IC(50) of 0.77 microM. Overall, this work provided some lead compounds based on alpha-carboline used for AD therapy.
ESTHER : Dan_2023_Bioorg.Chem_133_106378
PubMedSearch : Dan_2023_Bioorg.Chem_133_106378
PubMedID: 36736035

Title : Neurodevelopmental toxicity of bisphenol AF in zebrafish larvae and the protective effects of curcumin - Yang_2023_J.Appl.Toxicol__
Author(s) : Yang Q , Liu J , Ding J
Ref : J Appl Toxicol , : , 2023
Abstract : Bisphenol AF (BPAF) is one of the most commonly used alternatives of bisphenol A in the plastics industry. The effects of BPAF on nervous development are unclear. Curcumin (CUR) has been determined to be an anti-inflammatory and antioxidant agent. In this study, the effects of BPAF on neurotoxicity of zebrafish embryos/larvae and whether CUR could reverse effects induced by BPAF were investigated. The results showed that BPAF treatment induced deficits in locomotor behavior, altered the larval brain development, caused aberrant expression of neurogenesis related genes (elavl3, zn5, alpha-tubulin, syn2a, and gap43), decreased acetylcholinesterase (AChE) activity, and induced oxidative stress, cell apoptosis, and neuroinflammation in zebrafish larvae. CUR addition could block the adverse effects of BPAF on nervous development by attenuated oxidative stress and cell apoptosis induced by BPAF in zebrafish, enhanced the activity of AChE, and increased the expression of genes involved in the pro-inflammatory cytokines (IL-6, IL-1beta, TNF-alpha, and IL-8). The results of this study indicate that BPAF could induce aberrant development on nervous system. However, CUR exerts neuroprotective effects on BPAF-induced neurotoxicity in zebrafish larvae.
ESTHER : Yang_2023_J.Appl.Toxicol__
PubMedSearch : Yang_2023_J.Appl.Toxicol__
PubMedID: 37423901

Title : Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients - Liu_2023_Front.Med.(Lausanne)_10_1175089
Author(s) : Liu J , Shao T , Chen H , Ma C , Lu X , Yang X , Song K , Wang L , Lei S , Wang D
Ref : Front Med (Lausanne) , 10 :1175089 , 2023
Abstract : AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.
ESTHER : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedSearch : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedID: 37502364

Title : Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target - Wang_2023_Science_381_eadd5787
Author(s) : Wang K , Zhang Z , Hang J , Liu J , Guo F , Ding Y , Li M , Nie Q , Lin J , Zhuo Y , Sun L , Luo X , Zhong Q , Ye C , Yun C , Zhang Y , Wang J , Bao R , Pang Y , Wang G , Gonzalez FJ , Lei X , Qiao J , Jiang C
Ref : Science , 381 :eadd5787 , 2023
Abstract : A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.
ESTHER : Wang_2023_Science_381_eadd5787
PubMedSearch : Wang_2023_Science_381_eadd5787
PubMedID: 37535747
Gene_locus related to this paper: bactn-BT4193

Title : Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe - Chen_2023_Anal.Chem__
Author(s) : Chen Q , Liu J , Liu S , Zhang J , He L , Liu R , Jiang H , Han X , Zhang K
Ref : Analytical Chemistry , : , 2023
Abstract : Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 microM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 microM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents.
ESTHER : Chen_2023_Anal.Chem__
PubMedSearch : Chen_2023_Anal.Chem__
PubMedID: 36802493

Title : Artificial Intelligence Aided Lipase Production and Engineering for Enzymatic Performance Improvement - Ge_2023_J.Agric.Food.Chem__
Author(s) : Ge F , Chen G , Qian M , Xu C , Liu J , Cao J , Li X , Hu D , Xu Y , Xin Y , Wang D , Zhou J , Shi H , Tan Z
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages. Different neural networks coupled with various algorithms are usually applied to predict the maximum yield of lipase by optimizing the external cultivations for lipase production, while one part is used to predict the molecule variations affecting the properties of lipase. However, few studies have directly utilized AI to engineer lipase by affecting the structure of the enzyme, and a set of research gaps needs to be explored. Additionally, future perspectives of AI application in enzymes, including lipase engineering, are deduced to help the redesign of enzymes and the reform of new functional biocatalysts. This review provides a new horizon for developing effective and innovative AI tools for lipase production and engineering and facilitating lipase applications in the food industry and biomass conversion.
ESTHER : Ge_2023_J.Agric.Food.Chem__
PubMedSearch : Ge_2023_J.Agric.Food.Chem__
PubMedID: 37800676

Title : Acute toxicity of tire wear particles and leachate to Daphnia magna - Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
Author(s) : Liu J , Feng Q , Yang H , Fan X , Jiang Y , Wu T
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109713 , 2023
Abstract : Tire wear particles (TWP) are a new pollutant widely present in the environment, and have been identified as microplastics (MPs), which are receiving increasing attention due to their toxic effects on aquatic organisms. In this study, D. magna was used as test organism, and the leachate from TWP was prepared by hot water extraction for 30 (30-E) and 120 min (120-E). The acute toxic effects of particles and leachate on D. magna were studied under different exposure concentrations. The results showed that zinc and pyrene were the highest detected contaminants in the leachate. The 48 h-LC(50) values for particles and leachate were determined to be 56.99, 461.30 (30-E), and 153.00 mg/L (120-E), respectively. Following a 48 h exposure period, the immobilization of D. magna exposed to the particles and their leachate were increased with the concentration increase. The physical damage of the gut was found to be a possible mechanism for particle-induced biotoxicity. The compounds leached from TWP were responsible for the acute toxicity of leachate. Particles usually demonstrated a greater degree of toxicity in comparison to their leachate, especially at environmentally relevant concentrations. Exposure to particles and leachate resulted in the inhibition of swimming speed, swimming acceleration, filtration rate, and ingestion rate in D. magna. Furthermore, thoracic limb activity was observed to be inhibited. The heart rate of D. magna was significantly increased by the presence of particles at a concentration of 200 mg/L and leachate at concentrations of 400 and 800 mg/L (120-E). The observed alterations in behavior and physiological endpoints may be related to oxidative stress and neurotoxicity in the organism. Reduced superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities indicated that D. magna may suffer from excessive oxidative stress, whereas the increase of acetylcholinesterase (AChE) activity may serve as a biomarker of susceptibility to evaluate the environmental risks of TWP and corresponding leachates as potential aquatic pollutants.. Therefore, a more comprehensive risk assessment of TWP in the environment is necessary.
ESTHER : Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
PubMedSearch : Liu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109713
PubMedID: 37544637

Title : Construction of a ratiometric fluorescent sensing platform based on near-infrared carbon dots for organophosphorus pesticides detection - Xie_2023_Anal.Sci__
Author(s) : Xie W , Liu J , Qu Y , Du F
Ref : Anal Sci , : , 2023
Abstract : In this work, a convenient ratiometric fluorescent platform was designed to measure organophosphorus pesticides (OPs) based on acetylcholinesterase (AChE), acetylthiocholine (ATCh), manganese dioxide nanosheets (MnO(2)), near-infrared carbon dots (RCDs) and o-phenylenediamine (OPD). In this platform, a direct oxidation of OPD by MnO(2) generated the luminescent product 2,3-diaminophenolazine (DAP) through intrinsic oxidase activity, while RCDs served as a fluorescent reference indicator. In the presence of AChE and ATCh, the enzymatic hydrolysate thiocholine (TCh) would reduce MnO(2) nanosheets to Mn(2+), leading to the quenching of DAP fluorescence. On the other hand, OPs can inhibit the catabolism of ATCh by AChE thus acting as a recognizer of OPs. According to these reactions, OPs were quantitatively analyzed by the intensity ratio of fluorescence emitted from RCDs and DAP (F(560)/F(676)). The constructed platform can detect OPs with the range of 0.2-0.6 microM with a detection limit of 4.3 nM. Figure A ratiometric fluorescent probe based on carbon dots was obtained and using it to determine the concentration of organophosphorus pesticides.
ESTHER : Xie_2023_Anal.Sci__
PubMedSearch : Xie_2023_Anal.Sci__
PubMedID: 36944823

Title : Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats - Zeng_2023_Scand.J.Rheumatol__1
Author(s) : Zeng M , Issotina Zibrila A , Li X , Liu X , Wang X , Zeng Z , Wang Z , He Y , Meng L , Liu J
Ref : Scand J Rheumatol , :1 , 2023
Abstract : OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.
ESTHER : Zeng_2023_Scand.J.Rheumatol__1
PubMedSearch : Zeng_2023_Scand.J.Rheumatol__1
PubMedID: 37339380

Title : Do 'Newly Born' orphan proteins resemble 'Never Born' proteins? A study using three deep learning algorithms - Liu_2023_Proteins__
Author(s) : Liu J , Yuan R , Shao W , Wang J , Silman I , Sussman JL
Ref : Proteins , : , 2023
Abstract : "Newly Born" proteins, devoid of detectable homology to any other proteins, known as orphan proteins, occur in a single species or within a taxonomically restricted gene family. They are generated by the expression of novel open reading frames, and appear throughout evolution. We were curious if three recently developed programs for predicting protein structures, namely, AlphaFold2, RoseTTAFold, and ESMFold, might be of value for comparison of such "Newly Born" proteins to random polypeptides with amino acid content similar to that of native proteins, which have been called "Never Born" proteins. The programs were used to compare the structures of two sets of "Never Born" proteins that had been expressed-Group 1, which had been shown experimentally to possess substantial secondary structure, and Group 3, which had been shown to be intrinsically disordered. Overall, although the models generated were scored as being of low quality, they nevertheless revealed some general principles. Specifically, all four members of Group 1 were predicted to be compact by all three algorithms, in agreement with the experimental data, whereas the members of Group 3 were predicted to be very extended, as would be expected for intrinsically disordered proteins, again consistent with the experimental data. These predicted differences were shown to be statistically significant by comparing their accessible surface areas. The three programs were then used to predict the structures of three orphan proteins whose crystal structures had been solved, two of which display novel folds. Surprisingly, only for the protein which did not have a novel fold, and was taxonomically restricted, rather than being a true orphan, did all three algorithms predict very similar, high-quality structures, closely resembling the crystal structure. Finally, they were used to predict the structures of seven orphan proteins with well-identified biological functions, whose 3D structures are not known. Two proteins, which were predicted to be disordered based on their sequences, are predicted by all three structure algorithms to be extended structures. The other five were predicted to be compact structures with only two exceptions in the case of AlphaFold2. All three prediction algorithms make remarkably similar and high-quality predictions for one large protein, HCO_11565, from a nematode. It is conjectured that this is due to many homologs in the taxonomically restricted family of which it is a member, and to the fact that the Dali server revealed several nonrelated proteins with similar folds. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at
ESTHER : Liu_2023_Proteins__
PubMedSearch : Liu_2023_Proteins__
PubMedID: 37092778

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Molluscicidal activity of Nicotiana tabacum extracts on the invasive snail Pomacea canaliculata - Guo_2023_Sci.Rep_13_11597
Author(s) : Guo J , Zhang S , Zeng J , Chen Y , Guo Y , Liu J , He A
Ref : Sci Rep , 13 :11597 , 2023
Abstract : Botanical molluscicides for controlling the invasive snail Pomacea canaliculata have attracted worldwide attention because of their cost and environmental friendliness. Aqueous extracts from discarded tobacco leaf (Nicotiana tobacum) were evaluated for molluscicidal activity against different-sized P. canaliculata under laboratory conditions. The results showed that over 90% of the snails died in 1 g/L tobacco extract within 4 days, and the survival of P. canaliculata was inversely proportional to the snail size, tobacco extract concentration and length of exposure time. Adult males were more susceptible to tobacco extract than females. The snails had few chances to feed or mate in 0.5 g/L tobacco extract, and reproduction was greatly limited in 0.2 g/L. The growth of juvenile snails was inhibited in 0.2 g/L tobacco extract, but adults were unaffected. The antioxidant capacity of P. canaliculata in response to tobacco extract can be size- and sex-dependent, and the activities of superoxide dismutase, catalase, and acetylcholinesterase and the contents of glutathione and malondialdehyde were increased in adult males. These results suggest that discarded tobacco leaves can be useful as a molluscicide for controlling the invasive snail P. canaliculata based on its effects on survival, behaviour, food intake, growth performance and antioxidant capacity.
ESTHER : Guo_2023_Sci.Rep_13_11597
PubMedSearch : Guo_2023_Sci.Rep_13_11597
PubMedID: 37463929

Title : The serum concentration and activity of DPP4 is positively related with the severity of hyperthyroidism in patients with Graves' disease - Chang_2023_Ann.Med_55_2226910
Author(s) : Chang X , Ding X , Wang J , Cai Q , Wang G , Liu J
Ref : Ann Med , 55 :2226910 , 2023
Abstract : OBJECTIVE: Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. METHODS: A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. RESULTS: The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). CONCLUSIONS: The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves' disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves' disease.In patients with Graves 'disease, serum DPP4 activity was positively correlated with TRAb levels.
ESTHER : Chang_2023_Ann.Med_55_2226910
PubMedSearch : Chang_2023_Ann.Med_55_2226910
PubMedID: 37350750

Title : Sphk1 deficiency induces apoptosis and developmental defects and premature death in zebrafish - Huang_2023_Fish.Physiol.Biochem__
Author(s) : Huang L , Han F , Huang Y , Liu J , Liao X , Cao Z , Li W
Ref : Fish Physiol Biochem , : , 2023
Abstract : The sphk1 gene plays a crucial role in cell growth and signal transduction. However, the developmental functions of the sphk1 gene during early vertebrate zebrafish embryo remain not completely understood. In this study, we constructed zebrafish sphk1 mutants through CRISPR/Cas9 to investigate its role in zebrafish embryonic development. Knockout of the sphk1 gene was found to cause abnormal development in zebrafish embryos, such as darkening and atrophy of the head, trunk deformities, pericardial edema, retarded yolk sac development, reduced heart rate, and premature death. The acetylcholinesterase activity was significantly increased after the knockout of sphk1, and some of the neurodevelopmental genes and neurotransmission system-related genes were expressed abnormally. The deletion of sphk1 led to abnormal expression of immune genes, as well as a significant decrease in the number of hematopoietic stem cells and neutrophils. The mRNA levels of cardiac development-related genes were significantly decreased. In addition, cell apoptosis increases in the sphk1 mutants, and the proliferation of head cells decreases. Therefore, our study has shown that the sphk1 is a key gene for zebrafish embryonic survival and regulation of organ development. It deepened our understanding of its physiological function. Our study lays the foundation for investigating the mechanism of the sphk1 gene in early zebrafish embryonic development.
ESTHER : Huang_2023_Fish.Physiol.Biochem__
PubMedSearch : Huang_2023_Fish.Physiol.Biochem__
PubMedID: 37464180

Title : Construction of a Label-Free Ratiometric Biosensor Based on Target Recycling Amplification and Hg-ZnSe QDs for Assay of BChE and OPs - Zhang_2023_J.Agric.Food.Chem_71_11884
Author(s) : Zhang J , Wang M , Liu J , Lv Y , Su X
Ref : Journal of Agricultural and Food Chemistry , 71 :11884 , 2023
Abstract : Herein, we constructed a label-free ratiometric fluorescence biosensing strategy for the determination of butyrylcholinesterase (BChE) activity and organophosphorus (OPs) concentration. BChE promoted the hydrolysis of iodized s-butyrylthiocholine (BTCh) into a reducing substance thiocholine, which can decompose CoOOH nanosheets (CoOOH NSs) to Co(2+). Subsequently, the single-stranded DNA (ssDNA) on the surface of CoOOH NSs was released. Then, ssDNA hybridized with hairpin DNA (h-DNA) and triggered the target recycling amplification process, producing large amounts of G-quadruplex. After adding thioflavin T (ThT), the target BChE was converted into activatable G-quadruplex/ThT with an amplified yellow fluorescence signal. The addition of OPs could significantly inhibit the hydrolysis of BTCh by BChE and thus unable to produce the yellow fluorescence G-quadruplex/ThT complex. Throughout the entire process, the fluorescence intensity of Hg-ZnSe QDs as a reference signal remained unchanged at 630 nm. Furthermore, this work provided an effective approach for detecting the BChE activity in serum samples and OPs in fruits and vegetables.
ESTHER : Zhang_2023_J.Agric.Food.Chem_71_11884
PubMedSearch : Zhang_2023_J.Agric.Food.Chem_71_11884
PubMedID: 37554068

Title : Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH(2)(Fe) - Zhao_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Zhao D , Liu J , Zhou Y , Zhang L , Zhong Y , Yang Y , Zhao B , Yang M , Wang Y
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH(2)(Fe) nanoparticles with a size of -100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH(2)(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
ESTHER : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 36867458

Title : The dynamic changes of genes revealed that persistently overexpressed genes drive the evolution of cyflumetofen resistance in Tetranychus cinnabarinus - Feng_2023_Insect.Sci_30_1129
Author(s) : Feng K , Liu J , Zhao M , Jiang Z , Liu P , Wei P , Dou W , He L
Ref : Insect Sci , 30 :1129 , 2023
Abstract : Changes in gene expression are associated with the evolution of pesticide resistance in arthropods. In this study, transcriptome sequencing was performed in 3 different resistance levels (low, L; medium, M; and high, H) of cyflumetofen-resistant strain (YN-CyR). A total of 1 685 genes, including 97 detoxification enzyme genes, were upregulated in all 3 stages, of which 192 genes, including 11 detoxification enzyme genes, showed a continuous increase in expression level with resistance development (L to H). RNA interference experiments showed that overexpression of 7 genes (CYP392A1, TcGSTd05, CCE06, CYP389A1, TcGSTz01, CCE59, and CYP389C2) is involved in the development of cyflumetofen resistance in Tetranychus cinnabarinus. The recombinant CYP392A1 can effectively metabolize cyflumetofen, while CCE06 can bind and sequester cyflumetofen in vitro. We compared 2 methods for rapid screening of resistance molecular markers, including short-term induction and 1-time high-dose selection. Two detoxification enzyme genes were upregulated in the field susceptible strain (YN-S) by induction with 20% lethal concentration (LC(20) ) of cyflumetofen. However, 16 detoxification enzyme genes were upregulated by 1-time selection with LC(80) of cyflumetofen. Interestingly, the 16 genes were overexpressed in all 3 resistance stages. These results indicated that 1 685 genes that were upregulated at the L stage constituted the basis of cyflumetofen resistance, of which 192 genes in which upregulation continued to increase were the main driving force for the development of resistance. Moreover, the 1-time high-dose selection is an efficient way to rapidly obtain the resistance-related genes that can aid in the development of resistance markers and resistance management in mites.
ESTHER : Feng_2023_Insect.Sci_30_1129
PubMedSearch : Feng_2023_Insect.Sci_30_1129
PubMedID: 36380571
Gene_locus related to this paper: tetur-t1jsk0 , tetur-t1l0m8

Title : Dual functional antioxidant and butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of novel melatonin-alkylbenzylamine hybrids - Liu_2023_Bioorg.Med.Chem_78_117146
Author(s) : Liu P , Cheng M , Guo J , Cao D , Luo J , Wan Y , Fang Y , Jin Y , Xie SS , Liu J
Ref : Bioorganic & Medicinal Chemistry , 78 :117146 , 2023
Abstract : Here, we have designed and synthesized a series of melatonin-alkylbenzylamine hybrids as multitarget agents for the treatment of Alzheimer's disease (AD). Most of them exhibited a potent multifunctional profile involving cholinesterase inhibition and antioxidant effects. Among these compounds, compound 5 was most the potent antioxidant (ORAC =5.13) and also an excellent selective inhibitor of BuChE (huBuChE IC(50)=1.20 microM, huAChE IC(50) = 177.49 microM, SIs= 147.91). Moreover, kinetic study indicated compound 5 was a mixed-type inhibitor for huBuChE. Furthermore, it could induce expression of the Nrf2 as well as its downstream markers at the protein level in cells. More importantly, compound 5 display no acute toxicity in mice at doses up to 2500 mg/kg. And we found compound 5 could improve memory function of scopolamine-induced amnesia mice. These results highlighted compound 5 as a possible hit molecule for further investigation of new anti-AD drugs.
ESTHER : Liu_2023_Bioorg.Med.Chem_78_117146
PubMedSearch : Liu_2023_Bioorg.Med.Chem_78_117146
PubMedID: 36580744

Title : Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase\/monoamine oxidase B inhibitors - Hu_2023_Future.Med.Chem__
Author(s) : Hu Z , Zhou S , Li J , Li X , Zhou Y , Zhu Z , Xu J , Liu J
Ref : Future Med Chem , : , 2023
Abstract : Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC(50) = 0.054 +/- 0.004 microM; MAO-B: IC(50) = 3.25 +/- 0.20 microM), moderate inhibitory effects on self-mediated amyloid-beta (Abeta) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.
ESTHER : Hu_2023_Future.Med.Chem__
PubMedSearch : Hu_2023_Future.Med.Chem__
PubMedID: 37902028

Title : beta-Carbolines norharman and harman change neurobehavior causing neurological damage in Caenorhabditis elegans - Zhang_2023_Food.Funct_14_10031
Author(s) : Zhang L , Liu J , Xu B , Wu D , Wu Y , Li G
Ref : Food Funct , 14 :10031 , 2023
Abstract : beta-Carbolines norharman and harman, belonging to the class of heterocyclic aromatic amines (HAAs), are typical hazardous substances produced during the thermal processing of food. Compared to other HAAs, there have been limited reports on the toxicity of beta-carbolines. Nevertheless, the current studies are concerned with the neurotoxic effects of norharman and harman at high doses. It is still unknown whether the relatively low dose of beta-carbolines in foods induces neurotoxicity and the mechanism of the toxicity. In this study, C. elegans was exposed to a series of gradients of norharman and harman (0, 0.05, 5, and 10 mg L(-1)). The survival rate and indicators of ethology (locomotor behaviors, foraging behavior, and chemotaxis ability) were assessed. The antioxidant system and the contents of neurotransmitters, as well as the activity of acetylcholinesterase (AChE), were evaluated. Additionally, the RNA-seq screening of differentially expressed genes (DEGs) revealed the potential molecular mechanisms of norharman- and harman-induced toxic effects. Our results indicated that the risk of long-term exposure to norharman and harman at low doses (food-related doses) should be emphasized. Moreover, beta-carbolines might induce neurotoxicity by causing oxidative damage, regulating the content of neurotransmitters, and interfering with cytochrome P450 metabolism. This study would provide a toxicological basis for the neurotoxicity of beta-carbolines and lay the foundation for the risk assessment of endogenous pollutants in food.
ESTHER : Zhang_2023_Food.Funct_14_10031
PubMedSearch : Zhang_2023_Food.Funct_14_10031
PubMedID: 37927231

Title : Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones - Yi_2023_Plant.Physiol__
Author(s) : Yi F , An G , Song A , Cheng K , Liu J , Wang C , Wu S , Wang P , Zhu J , Liang Z , Chang Y , Chu Z , Cai C , Zhang X , Chen A , Xu J , Burritt DJ , Herrera-Estrella L , Tran LP , Li W , Cai Y
Ref : Plant Physiol , : , 2023
Abstract : Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.
ESTHER : Yi_2023_Plant.Physiol__
PubMedSearch : Yi_2023_Plant.Physiol__
PubMedID: 36718522

Title : PNPLA6 disorders: what's in a name? - Liu_2023_Ophthalmic.Genet__1
Author(s) : Liu J , Hufnagel RB
Ref : Ophthalmic Genet , :1 , 2023
Abstract : BACKGROUND: Variants in the patatin-like phospholipase domain containing 6 (PNPLA6) gene cause a broad spectrum of neurological disorders characterized by gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. This review examines the clinical, cellular, and biochemical features found across the five PNPLA6-related diseases, with a focus on future questions to be addressed. MATERIALS AND METHODS: A literature review was performed on published clinical reports on patients with PNPLA6 variants. Additionally, in vitro and in vivo models used to study the encoded protein, Neuropathy Target Esterase (NTE), are summarized to lend mechanistic perspective to human diseases. RESULTS: Biallelic pathogenic PNPLA6 variants cause five systemic neurological disorders: spastic paraplegia type 39, Gordon-Holmes, Boucher-Neuhuser, Laurence-Moon, and Oliver-McFarlane syndromes. PNPLA6 encodes NTE, an enzyme involved in maintaining phospholipid homeostasis and trafficking in the nervous system. Retinal disease presents with a unique chorioretinal dystrophy that is phenotypically similar to choroideremia and Leber congenital amaurosis. Animal and cellular models support a loss-of-function mechanism. CONCLUSIONS: Clinicians should be aware of choroideremia-like ocular presentation in patients who also experience growth defects, motor dysfunction, and/or hair anomalies. Although NTE biochemistry is well characterized, further research on the relationship between genotype and the presence or absence of retinopathy should be explored to improve diagnosis and prognosis.
ESTHER : Liu_2023_Ophthalmic.Genet__1
PubMedSearch : Liu_2023_Ophthalmic.Genet__1
PubMedID: 37732399

Title : Adipose triglyceride lipase is a therapeutic target in advanced prostate cancer that promotes metabolic plasticity - Awad_2023_Cancer.Res__
Author(s) : Awad D , Cao PHA , Pulliam TL , Spradlin M , Subramani E , Tellman TV , Ribeiro CF , Muzzioli R , Jewell BE , Pakula H , Ackroyd JJ , Murray MM , Han JJ , Leng M , Jain A , Piyarathna B , Liu J , Song X , Zhang J , Klekers AR , Drake JM , Ittmann MM , Coarfa C , Piwnica-Worms D , Farach-Carson MC , Loda M , L SE , Frigo DE
Ref : Cancer Research , : , 2023
Abstract : Lipid metabolism plays a central role in prostate cancer. To date, the major focus has centered on de novo lipogenesis and lipid uptake in prostate cancer, but inhibitors of these processes have not benefited patients. Better understanding of how cancer cells access lipids once they are created or taken up and stored could uncover more effective strategies to perturb lipid metabolism and treat patients. Here, we identified that expression of adipose triglyceride lipase (ATGL), an enzyme that controls lipid droplet homeostasis and a previously suspected tumor suppressor, correlates with worse overall survival in men with advanced, castration-resistant prostate cancer (CRPC). Molecular, genetic, or pharmacological inhibition of ATGL impaired human and murine prostate cancer growth in vivo and in cell culture or organoids under conditions mimicking the tumor microenvironment. Mass spectrometry imaging demonstrated ATGL profoundly regulates lipid metabolism in vivo, remodeling membrane composition. ATGL inhibition induced metabolic plasticity, causing a glycolytic shift that could be exploited therapeutically by co-targeting both metabolic pathways. Patient-derived phosphoproteomics identified ATGL serine 404 as a target of CAMKK2-AMPK signaling in CRPC cells. Mutation of serine 404 did not alter the lipolytic activity of ATGL but did decrease CRPC growth, migration, and invasion, indicating that non-canonical ATGL activity also contributes to disease progression. Unbiased immunoprecipitation/mass spectrometry suggested that mutation of serine 404 not only disrupts existing ATGL protein interactions but also leads to new protein-protein interactions. Together, these data nominate ATGL as a therapeutic target for CRPC and provide insights for future drug development and combination therapies.
ESTHER : Awad_2023_Cancer.Res__
PubMedSearch : Awad_2023_Cancer.Res__
PubMedID: 38038968

Title : Emodin derivatives as promising multi-aspect intervention agents for amyloid aggregation: molecular docking\/dynamics simulation, bioactivities evaluation, and cytoprotection - Shen_2023_Mol.Divers__2
Author(s) : Shen R , Zhao W , Li X , Liu J , Yang A , Kou X
Ref : Mol Divers , : , 2023
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disease with complex pathogenesis. Despite the pathogenesis is unknown, the misfolding and accumulation of beta-amyloid (Abeta) peptide play the important role in the occurrence and development of AD. Hence, multi-aspect intervention of the misfolded Abeta peptides aggregation is a promising therapy for AD. In previous work, we obtained the emodin derivatives (a-d) with multifunctional anti-AD activities, including metal ions chelation, cholinesterase inhibition, and hydroxyl/superoxide anion radical elimination. In this work, we predicted the interaction of emodin derivatives (a-d) with Abeta by combining molecular docking simulation and molecular dynamics simulation, and evaluated the ability to intervene with the self-, Cu(2+)- and AChE-induced Abeta aggregation via in vitro methods. The results indicated that a-d could act as the potent multi-aspect intervention agents for Abeta aggregation. In addition, a-d could effectively eliminate peroxyl radical, had virtually no neurotoxicity, and protect cells from oxidative and Abeta-induced damage. The prediction results of ADMET properties showed that a-d had suitable pharmacokinetic characteristics. It suggested that a-d could act as the promising multi-targeted directed ligands (MTDLs) for AD. These results may provide meaningful information for the development of the potential MTDLs for AD which are modified from natural-origin scaffolds.
ESTHER : Shen_2023_Mol.Divers__2
PubMedSearch : Shen_2023_Mol.Divers__2
PubMedID: 37737959

Title : Detection of target site mutations in the acetylcholinesterase and voltage-gated sodium channel in field populations of Culex quinquefasciatus and Cx. tritaeniorhynchus from southern Sichuan region of China - Liu_2023_J.Am.Mosq.Control.Assoc__
Author(s) : Liu J , Wang Y , Liu P , Yu X , Tan AI , Zeng J , Li L , Qiu X
Ref : J Am Mosq Control Assoc , : , 2023
Abstract : Culex quinquefasciatus and Cx. tritaeniorhynchus are 2 dominant disease vectors in Neijiang City, Sichuan Province, China. Although there is evidence of confirmed resistance against insecticides in mosquito vectors, nothing is known about the existing insecticide resistance-conferring mutations in Cx. quinquefasciatus and Cx. tritaeniorhynchu in this region so far. In this study, the G119S mutation in the acetylcholinesterase (AChE) was detected in Cx. quinquefasciatus at a very low frequency (0.9%) with no resistant homozygotes being observed. Two resistance mutations in the voltage-gated sodium channel (VGSC) (L1014F and L1014S) were found in Cx. quinquefasciatus with frequencies of 88.7% and 8.3%, respectively. By contrast, the AChE F455W mutation was found to be fixed (with a frequency of 100%) in 3 of the 5 studied populations, with an overall frequency being 98.1%. In addition, 1 resistance-conferring VGSC mutation (L1014F) was detected with an overall frequency of 15.2% in Cx. tritaeniorhynchus. These results indicate that the well-recognized insecticide resistance-conferring mutations in both AChE and VGSC are present in the 2 Culex species in Neijiang. The contrasting patterns in the frequency of resistance alleles indicate that species-customized strategies of insecticide resistance management should be considered for the 2 species.
ESTHER : Liu_2023_J.Am.Mosq.Control.Assoc__
PubMedSearch : Liu_2023_J.Am.Mosq.Control.Assoc__
PubMedID: 36752737

Title : Design and construction of Carboxylesterase 2c Gene knockout Rats by CRISPR\/Cas9 - Liu_2023_Curr.Drug.Metab__
Author(s) : Liu J , Shang X , Yao B , Zhang Y , Huang S , Guo Y , Wang X
Ref : Curr Drug Metab , : , 2023
Abstract : BACKGROUND: Carboxylesterase 2 (CES2) is mainly distributed in the human liver and gut, and plays an active role in the metabolic activation of many prodrugs and lipid metabolism. Although CES2 is of great significance, there are still few animal models related to CES2. OBJECTIVES: This research aims to construct Ces2c gene knockout (KO) rats and further study the function of CES2. METHODS: CRISPR/Cas9 gene editing technology was used to target and cleave the rat Ces2c gene. Compensatory effects of major CES subtypes both in the liver and small intestine of KO rats were detected at mRNA levels. Meanwhile, diltiazem and aspirin were used as substrates to test the metabolic capacity of Ces2c in KO rats. RESULTS: This Ces2c KO rat model showed normal growth and breeding without off-target effects. The metabolic function of Ces2c KO rats was verified by the metabolic study of CES2 substrates in vitro. The results showed that the metabolic capacity of diltiazem in KO rats was weakened, while the metabolic ability of aspirin did not change significantly. In addition, the serum physiological indexes showed that the Ces2c deletion did not affect the liver function of rats. CONCLUSION: The Ces2c KO rat model was successfully constructed by CRISPR/Cas9 system. This rat model can not only be used as an important tool to study the drug metabolism mediated by Ces2, but also as an important animal model to study the physiological function of Ces2.
ESTHER : Liu_2023_Curr.Drug.Metab__
PubMedSearch : Liu_2023_Curr.Drug.Metab__
PubMedID: 36694315
Gene_locus related to this paper: ratno-pbcxe

Title : The effects of carvacrol on development and gene expression profiles in Spodoptera frugiperda - Liu_2023_Pestic.Biochem.Physiol_195_105539
Author(s) : Liu J , Lin Y , Huang Y , Liu L , Cai X , Lin J , Shu B
Ref : Pestic Biochem Physiol , 195 :105539 , 2023
Abstract : The fall armyworm, Spodoptera frugiperda, is a highly polyphagous agricultural pest that is widely distributed around the world and causes severe crop yield loss. Carvacrol showed adverse effects on many pests, such as larval death and growth inhibition. While the effects of carvacrol on S. frugiperda larvae are not yet known. In this study, the effects of carvacrol on S. frugiperda, including larval growth inhibition and mortality induction, were observed. The detoxification and digestive enzyme activities of larvae with 1.0 and 2.0 g/kg carvacrol treatments were analyzed. Carvacrol boosted the enzyme activities of carboxylesterase (CarE) and glutathione S-transferase (GST) while decreasing the activities of alpha-amylase (AMS), lipase (LIP), and trypsin. A total of 3422 differentially expressed genes were identified in the larvae treated with 2.0 g/kg carvacrol, of which the DEGs involved in xenobiotic detoxification, food digestion, and insecticidal targets were further examined. These results suggest that carvacrol could regulate growth and development by affecting the process of food digestion, and exert its toxicity on the larvae through interaction with a variety of insecticidal targets. While the altered expressions of detoxification enzymes might be related to the detoxification and metabolism of carvacrol. Our findings offer a theoretical foundation for the use of carvacrol for S. frugiperda control in the field.
ESTHER : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedSearch : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedID: 37666589

Title : Protective effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in aging mice - Guo_2022_Front.Pharmacol_13_992269
Author(s) : Guo Y , Qu Y , Li W , Shen H , Cui J , Liu J , Li J , Wu D
Ref : Front Pharmacol , 13 :992269 , 2022
Abstract : The aging process of human beings is accompanied by the decline of learning and memory ability and progressive decline of brain function, which induces Alzheimer's Disease (AD) in serious cases and seriously affects the quality of patient's life. In recent years, more and more studies have found that natural plant antioxidants can help to improve the learning and memory impairment, reduce oxidative stress injury and aging lesions in tissues. This study aimed to investigate the effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in D-galactose-induced aging mice and its molecular mechanism. The composition of Monarda didymaL. essential oil was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). A mouse aging model was established by the subcutaneous injection of D-galactose in mice. The behavior changes of the mice were observed by feeding the model mice with essential oil, thymol and donepezil, and the histopathological changes of the hippocampus were observed by HE staining. And the changes of acetylcholinesterase (AchE), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and the content of malondialdehyde (MDA) in hippocampal tissues were detected by corresponding kits. The expression of mitogen activated protein kinase (MAPK) and nuclear factor E2 related factor 2 (Nrf2) pathways related proteins were detected by western blot. Animal experimental results showed that compared with model group, the above indexes in Monarda didymaL. essential oil and thymol groups improved significantly in a dose-dependent manner. Monarda didymaL. essential oil and its main active component thymol can improve the learning and memory impairment of aging mice to some extent, and Nrf2 and MAPK pathways may be involved in its action process.
ESTHER : Guo_2022_Front.Pharmacol_13_992269
PubMedSearch : Guo_2022_Front.Pharmacol_13_992269
PubMedID: 36105199

Title : FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis - Du_2022_Cell.Death.Dis_13_488
Author(s) : Du Q , Liu P , Zhang C , Liu T , Wang W , Shang C , Wu J , Liao Y , Chen Y , Huang J , Tan H , Zhao Y , Xia M , Liu J , Yao S
Ref : Cell Death Dis , 13 :488 , 2022
Abstract : Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.
ESTHER : Du_2022_Cell.Death.Dis_13_488
PubMedSearch : Du_2022_Cell.Death.Dis_13_488
PubMedID: 35597782

Title : Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1H)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease - Guo_2022_Drug.Des.Devel.Ther_16_1495
Author(s) : Guo J , Xu A , Cheng M , Wan Y , Wang R , Fang Y , Jin Y , Xie SS , Liu J
Ref : Drug Des Devel Ther , 16 :1495 , 2022
Abstract : BACKGROUND: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports. PURPOSE: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate. METHODS: All compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo. RESULTS: Most compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC(50)=0.28 microM to eeAChE; IC(50)=0.34 microM to hAChE; IC(50)=2.81 microM to hMAO-B; IC(50)=0.91 microM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 microM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.). CONCLUSION: This work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.
ESTHER : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedSearch : Guo_2022_Drug.Des.Devel.Ther_16_1495
PubMedID: 35611357

Title : Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) - Li_2022_BMC.Genomics_23_185
Author(s) : Li Z , Wu L , Wang C , Wang Y , He L , Wang Z , Ma X , Bai F , Feng G , Liu J , Jiang Y , Song F
Ref : BMC Genomics , 23 :185 , 2022
Abstract : BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
ESTHER : Li_2022_BMC.Genomics_23_185
PubMedSearch : Li_2022_BMC.Genomics_23_185
PubMedID: 35249536

Title : Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression - Zhou_2022_Cancers.(Basel)_14_
Author(s) : Zhou X , Zhong F , Yan Y , Wu S , Wang H , Liu J , Li F , Cui D , Xu M
Ref : Cancers (Basel) , 14 : , 2022
Abstract : Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer.
ESTHER : Zhou_2022_Cancers.(Basel)_14_
PubMedSearch : Zhou_2022_Cancers.(Basel)_14_
PubMedID: 36230535
Gene_locus related to this paper: human-ABHD11

Title : Acquisition of T6SS Effector TseL Contributes to the Emerging of Novel Epidemic Strains of Pseudomonas aeruginosa - Ren_2022_Microbiol.Spectr__e0330822
Author(s) : Ren A , Jia M , Liu J , Zhou T , Wu L , Dong T , Cai Z , Qu J , Liu Y , Yang L , Zhang Y
Ref : Microbiol Spectr , :e0330822 , 2022
Abstract : Pseudomonas aeruginosa is an opportunistic pathogen with multiple strategies to interact with other microbes and host cells, gaining fitness in complicated infection sites. The contact-dependent type VI secretion system (T6SS) is one critical secretion apparatus involved in both interbacterial competition and pathogenesis. To date, only limited numbers of T6SS-effectors have been clearly characterized in P. aeruginosa laboratory strains, and the importance of T6SS diversity in the evolution of clinical P. aeruginosa remains unclear. Recently, we characterized a P. aeruginosa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. Bioinformatic analysis has revealed a putative type VI secretion system (T6SS) dependent lipase effector in LYSZa7, which is a homologue of TseL in Vibrio cholerae and is widely distributed in pathogens. We experimentally validated that this TseL homologue belongs to the Tle2, a subfamily of T6SS-lipase effectors; thereby, we name this effector TseL (TseL(PA) in this work). Further, we showed the lipase-dependent bacterial toxicity of TseL(PA), which primarily targets bacterial periplasm. The toxicity of TseL(PA) can be neutralized by two immunity proteins, TsiP1 and TsiP2, which are encoded upstream of tseL. In addition, we proved this TseL(PA) contributes to bacterial pathogenesis by promoting bacterial internalization into host cells. Our study suggests that clinical bacterial strains employ a diversified group of T6SS effectors for interbacterial competition and might contribute to emerging of new epidemic clonal lineages. IMPORTANCE Pseudomonas aeruginosa is one predominant pathogen that causes hospital-acquired infections and is one of the commonest coinfecting bacteria in immunocompromised patients and chronic wounds. This bacterium harbors a diverse accessory genome with a high frequency of gene recombination, rendering its population highly heterogeneous. Numerous Pa lineages coexist in the biofilm, where successful epidemic clonal lineage or strain-specific type commonly acquires genes to increase its fitness over the other organisms. Current studies of Pa genomic diversity commonly focused on antibiotic resistant genes and novel phages, overlooking the contribution of type VI secretion system (T6SS). We characterized a Pa clinical strain LYSZa7 from a COVID-19 patient, which adopted complex genetic adaptations toward chronic infections. We report, in this study, a novel T6SS-lipase effector that is broadly distributed in Pa clinical isolates and other predominant pathogens. The study suggests that hospital transmission may raise the emergence of new epidemic clonal lineages with specified T6SS effectors.
ESTHER : Ren_2022_Microbiol.Spectr__e0330822
PubMedSearch : Ren_2022_Microbiol.Spectr__e0330822
PubMedID: 36546869
Gene_locus related to this paper: pseae-T6SSTseL

Title : A hemicyanine-based fluorescent probe for simultaneous imaging of Carboxylesterases and Histone deacetylases in hepatocellular carcinoma - Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
Author(s) : Shu Y , Huang C , Liu H , Hu F , Wen H , Liu J , Wang X , Shan C , Li W
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 281 :121529 , 2022
Abstract : Carboxylesterases (CESs) and Histone deacetylases (HDACs) are regarded as important signaling enzymes highly associated with the development and progression of multiple cancers, including hepatocellular carcinoma (HCC). In this work, a near-infrared (NIR) fluorescent probe named Lys-HXPI was designed and synthesized, which linked a hemicyanine dye and 6-acetamidohexanoic acid via an ester bond. Lys-HXPI displayed a remarkable increase with a NIR emission at 720 nm, a low detection limit (<10 nM) for HDAC1, HDAC 6, CES1 and CES2, as well as a high selectivity for the target enzymes over other relevant analytes. Furthermore, Lys-HXPI was used to image endogenous target enzymes in living cells, tumor-bearing nude mice and tissue slices. The ability of Lys-HXPI to simultaneous image CESs and HDACs was demonstrated with RT-qPCR and the confocal imaging in Hep G2 and MDA-MB-231. Taking advantage of NIR emission, the probe was also successfully applied to imaging Hep G2 tumor mice and tissue slices. Lys-HXPI is expected to be useful for the effective detecting of CESs and HDACs in complex biosystems.
ESTHER : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedSearch : Shu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_281_121529
PubMedID: 35797949

Title : Emerging role of carboxylesterases in nonalcoholic fatty liver disease - Liu_2022_Biochem.Pharmacol__115250
Author(s) : Liu J , Yao B , Gao L , Zhang Y , Huang S , Wang X
Ref : Biochemical Pharmacology , :115250 , 2022
Abstract : Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a global public health problem. Carboxylesterases (CESs), as potential influencing factors of NAFLD, are very important to improve clinical outcomes. This review aims to deeply understand the role of CESs in the progression of NAFLD and proposes that CESs can be used as potential targets for NAFLD treatment. We first introduced CESs and analyzed the relationship between CESs and hepatic lipid metabolism and inflammation. Then, we further reviewed the regulation of nuclear receptors on CESs, including PXR, CAR, PPARalpha, HNF4alpha and FXR, which may influence the progression of NAFLD. Finally, we evaluated the advantages and disadvantages of existing NAFLD animal models and summarized the application of CES-related animal models in NAFLD research. In general, this review provides an overview of the relationship between CESs and NAFLD and discusses the role and potential value of CESs in the treatment and prevention of NAFLD.
ESTHER : Liu_2022_Biochem.Pharmacol__115250
PubMedSearch : Liu_2022_Biochem.Pharmacol__115250
PubMedID: 36130649

Title : Transcriptome-wide association study reveals cholesterol metabolism gene Lpl is a key regulator of cognitive dysfunction - Hu_2022_Front.Mol.Neurosci_15_1044022
Author(s) : Hu W , Liu J , Hu Y , Xu Q , Deng T , Wei M , Lu L , Mi J , Bergquist J , Xu F , Tian G
Ref : Front Mol Neurosci , 15 :1044022 , 2022
Abstract : Cholesterol metabolism in the brain plays a crucial role in normal physiological function, and its aberrations are associated with cognitive dysfunction. The present study aimed to determine which cholesterol-related genes play a vital role in cognitive dysfunction and to dissect its underlying molecular mechanisms using a systems genetics approach in the BXD mice family. We first systematically analyzed the association of expression of 280 hippocampal genes related to cholesterol metabolism with cognition-related traits and identified lipoprotein lipase (Lpl) as a critical regulator. This was further confirmed by phenome-wide association studies that indicate Lpl associated with hippocampus volume residuals and anxiety-related traits. By performing expression quantitative trait locus mapping, we demonstrate that Lpl is strongly cis-regulated in the BXD hippocampus. We also identified -3,300 genes significantly (p < 0.05) correlated with the Lpl expression. Those genes are mainly involved in the regulation of neuron-related traits through the MAPK signaling pathway, axon guidance, synaptic vesicle cycle, and NF-kappa B signaling pathway. Furthermore, a protein-protein interaction network analysis identified several direct interactors of Lpl, including Rab3a, Akt1, Igf1, Crp, and Lrp1, which indicates that Lpl involves in the regulation of cognitive dysfunction through Rab3a-mediated synaptic vesicle cycle and Akt1/Igf1/Crp/Lrp1-mediated MAPK signaling pathway. Our findings demonstrate the importance of the Lpl, among the cholesterol-related genes, in regulating cognitive dysfunction and highlighting the potential signaling pathways, which may serve as novel therapeutic targets for the treatment of cognitive dysfunction.
ESTHER : Hu_2022_Front.Mol.Neurosci_15_1044022
PubMedSearch : Hu_2022_Front.Mol.Neurosci_15_1044022
PubMedID: 36590920

Title : Polyketide Derivatives from the Endophytic Fungus Phaeosphaeria sp. LF5 Isolated from Huperzia serrata and Their Acetylcholinesterase Inhibitory Activities - Xiao_2022_J.Fungi.(Basel)_8_
Author(s) : Xiao Y , Liang W , Zhang Z , Wang Y , Zhang S , Liu J , Chang J , Ji C , Zhu D
Ref : J Fungi (Basel) , 8 : , 2022
Abstract : The secondary metabolites of Phaeosphaeria sp. LF5, an endophytic fungus with acetylcholinesterase (AChE) inhibitory activity isolated from Huperzia serrata, were investigated. Their structures and absolute configurations were elucidated by means of extensive spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses, and calculations of electronic circular dichroism (ECD). A chemical study on the solid-cultured fungus LF5 resulted in 11 polyketide derivatives, which included three previously undescribed derivatives: aspilactonol I (4), 2-(1-hydroxyethyl)-6-methylisonicotinic acid (7), and 6,8-dihydroxy-3-(1'R, 2'R-dihydroxypropyl)-isocoumarin (9), and two new natural-source-derived aspilactonols (G, H) (2, 3). Moreover, the absolute configuration of de-O-methyldiaporthin (11) was identified for the first time. Compounds 4 and 11 exhibited inhibitory activity against AChE with half maximal inhibitory concentration (IC(50)) values of 6.26 and 21.18 microM, respectively. Aspilactonol I (4) is the first reported furanone AChE inhibitor (AChEI). The results indicated that Phaeosphaeria is a good source of polyketide derivatives. This study identified intriguing lead compounds for further research and development of new AChEIs.
ESTHER : Xiao_2022_J.Fungi.(Basel)_8_
PubMedSearch : Xiao_2022_J.Fungi.(Basel)_8_
PubMedID: 35330234

Title : Novel inhibitors of AChE and Abeta aggregation with neuroprotective properties as lead compounds for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_235_114305
Author(s) : Liu Y , Uras G , Onuwaje I , Li W , Yao H , Xu S , Li X , Phillips J , Allen S , Gong Q , Zhang H , Zhu Z , Liu J , Xu J
Ref : Eur Journal of Medicinal Chemistry , 235 :114305 , 2022
Abstract : A series of sulfone analogs of donepezil were designed and synthesized as novel acetylcholinesterase (AChE) inhibitors with the potent inhibiting Abeta aggregation and providing neuroprotective effects as potential modalities for Alzheimer's disease (AD). Most of the target compounds displayed effective inhibition of AChE, especially compound 24r which displayed powerful inhibitory activity (IC(50) = 2.4 nM). Kinetic and docking studies indicated that compound 24r was a mixed-type inhibitor. Furthermore, in glyceraldehyde (GA)-exposed SH-SY5Y differentiated neuronal cells, compound 24r could potently inhibit AChE, reduce tau phosphorylation at S396 residue, provide neuroprotection by rescuing neuronal morphology and increasing cell viability. It was also found to reduce amyloid aggregation in the presence of AChE. In addition, compound 24r showed evident protections from mitochondrial membrane dysfunction and oxidative stress in okadaic acid-induced pharmacological models. Moreover, compound 24r exhibited more effective treatment prospects in vivo than donepezil, including a moderate blood-brain barrier permeability, a more potent AChE inhibitory activity and behavioral improvement in scopolamine-induced cognition-impaired mice model at a much lower dose. Collectively, compound 24r is a promising lead compound for further investigation to discovery and development of new anti-AD agents.
ESTHER : Liu_2022_Eur.J.Med.Chem_235_114305
PubMedSearch : Liu_2022_Eur.J.Med.Chem_235_114305
PubMedID: 35339839

Title : Development and validation of a LC-MS\/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice - Yuan_2022_Biomed.Chromatogr__e5380
Author(s) : Yuan M , Hu W , Feng Y , Tong Y , Wang X , Tan B , Xu H , Liu J
Ref : Biomedical Chromatography , :e5380 , 2022
Abstract : Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. RDV is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5'-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an ACQUITY HSS T(3) column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1000 ng/mL for RDV, 5-10000 ng/mL for both RM-442 and RN, respectively. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442, and RSD < 7.2% for RN) and accuracy (91.0%-106.3% for RDV, 92.5%-98.6% for RM-442, and 87.5%-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in blood of normal and diabetic nephropathy DBA/2J mice after intravenous injection of RDV 20 mg/kg. The AUC(0-t) of RN between the normal and diabetic nephropathy mice had significant difference (P < 0.01).
ESTHER : Yuan_2022_Biomed.Chromatogr__e5380
PubMedSearch : Yuan_2022_Biomed.Chromatogr__e5380
PubMedID: 35373846

Title : Characterization of the synergistic inhibitory effect of cyanidin-3-O-glucoside and catechin on pancreatic lipase - Wang_2022_Food.Chem_404_134672
Author(s) : Wang Y , Chen L , Liu H , Xie J , Yin W , Xu Z , Ma H , Wu W , Zheng M , Liu M , Liu J
Ref : Food Chem , 404 :134672 , 2022
Abstract : This study aimed to identify novel pancreatic lipase (PL) inhibitors using affinity ultrafiltration combined with spectroscopy and molecular docking. Cyanidin-3-O-glucoside (C3G; IC(50): 0.268 mg/mL) and catechin (IC(50): 0.280 mg/mL) were shown to be potent PL inhibitors extracted from black rice and adzuki bean coat extracts. Isobologram analysis revealed that the combined use of C3G and catechin at a ratio of 2:3 had a remarkable synergistic effect (IC(50) of the mixture: 0.201 mg/mL). The inhibitory mechanism of C3G-catechin mixture was of mixed type. The C3G-catechin mixture had a great impact on PL secondary structures. Molecular docking analysis further demonstrated that these polyphenols formed hydrophobic interactions and hydrogen bonds with amino acid residues in the binding pocket of PL. Collectively, C3G and catechin were shown to inhibit PL in a synergistic manner and can be potentially used for the development of food supplements for obesity prevention.
ESTHER : Wang_2022_Food.Chem_404_134672
PubMedSearch : Wang_2022_Food.Chem_404_134672
PubMedID: 36323025

Title : Highly Selective Detection of Paraoxon in Food Based on the Platform of Cu Nanocluster\/MnO(2) Nanosheets - Liu_2022_Nanomaterials.(Basel)_12_
Author(s) : Liu S , Zhang P , Miao Y , Li C , Shi YE , Liu J , Lv YK , Wang Z
Ref : Nanomaterials (Basel) , 12 : , 2022
Abstract : Selective and sensitive identification of paraoxon residue in agricultural products is greatly significant for food safety but remains a challenging task. Herein, a detection platform was developed by integrating Cu nanoclusters (Cu NCs) with MnO(2) nanosheets, where the fluorescence of Cu NCs was effectively quenched. Upon introducing butyrylcholinesterase and butyrylcholine into the system, their hydrolysate, thiocholine, leads to the decomposition of the platform through a reaction between the MnO(2) nanosheets and thiol groups on thiocholine. The electron-rich groups on thiocholine can further promote the fluorescence intensity of Cu NCs through host-guest interactions. Adding paraoxon results in the failure of fluorescence recovery and further promotion, which could be utilized for the quantitative detection of paraoxon, and a limit of detection as low as 0.22 ng/mL can be achieved. The detection platform shows strong tolerance to common interference species, which endows its applications for the detection of paraoxon in vegetables and fruit. These presented results not only open a new door for the functionalization of metal nanoclusters but also offer an inspiring strategy for analytic techniques in nanomedicine and environmental science.
ESTHER : Liu_2022_Nanomaterials.(Basel)_12_
PubMedSearch : Liu_2022_Nanomaterials.(Basel)_12_
PubMedID: 35564138

Title : Role of epoxyeicosatrienoic acids in cardiovascular diseases and cardiotoxicity of drugs - Zhang_2022_Life.Sci_310_121122
Author(s) : Zhang Y , Gao L , Yao B , Huang S , Liu J , Liu Z , Wang X
Ref : Life Sciences , 310 :121122 , 2022
Abstract : Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs. Therefore, the regulation of CYP and sEH enzymes on EETs points out the direction for exploring EET-mediated cardiac protection. The metabolic pathway of EETs is not only an important target for the development of new drugs for CVD but also an important factor in preventing drug cardiotoxicity. The development and clinical application of sEH inhibitors and EETs analogues provide broad prospects for the treatment of CVD.
ESTHER : Zhang_2022_Life.Sci_310_121122
PubMedSearch : Zhang_2022_Life.Sci_310_121122
PubMedID: 36309225

Title : Novel AP2238-clorgiline hybrids as multi-target agents for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation - Zhong_2022_Bioorg.Chem_130_106224
Author(s) : Zhong G , Guo J , Pang C , Su D , Tang C , Jing L , Zhang F , He P , Yan Y , Chen Z , Liu J , Jiang N
Ref : Bioorg Chem , 130 :106224 , 2022
Abstract : Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC(50) = 4.03 +/- 0.03 microM, eqBuChE: IC(50) = 5.64 +/- 0.53 microM; hAChE: IC(50) = 8.30 +/- 0.04 microM, hBuChE: IC(50) = 1.91 +/- 0.06 microM) and hMAO-B (IC(50) = 3.29 +/- 0.09 microM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 microM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.
ESTHER : Zhong_2022_Bioorg.Chem_130_106224
PubMedSearch : Zhong_2022_Bioorg.Chem_130_106224
PubMedID: 36332315

Title : Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus - Sun_2022_Andrology__
Author(s) : Sun T , Xu W , Wang J , Wang T , Wang S , Liu K , Liu J
Ref : Andrology , : , 2022
Abstract : BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved.
ESTHER : Sun_2022_Andrology__
PubMedSearch : Sun_2022_Andrology__
PubMedID: 36113503

Title : Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals - Yang_2022_ACS.Omega_7_30720
Author(s) : Yang Y , Liu J , Liu L , Zhou Y , Zhang L , Zhong Y , Zhao D , Wang Y
Ref : ACS Omega , 7 :30720 , 2022
Abstract : A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.
ESTHER : Yang_2022_ACS.Omega_7_30720
PubMedSearch : Yang_2022_ACS.Omega_7_30720
PubMedID: 36092617

Title : Hollow urchin-shaped manganese dioxide microspheres immobilized acetylcholinesterase for rapid screening inhibitors from traditional herbal medicines - Liu_2022_J.Chromatogr.A_1665_462824
Author(s) : Liu J , Ha W , Zhang HX , Shi YP
Ref : Journal of Chromatography A , 1665 :462824 , 2022
Abstract : Acetylcholinesterase (AChE) is generally considered to be a valuable therapeutic target for Alzheimer's disease (AD). To rapidly screen novel AChE inhibitors from Traditional Chinese medicines (TCMs), polydopamine (PDA) coated hollow urchin-shaped manganese dioxide microspheres (h-MnO(2)@PDA) were fabricated in this work. AChE was immobilized onto the surface of h-MnO(2)@PDA for the first time, and the prepared h-MnO(2)@PDA immobilized AChE coupled with capillary electrophoresis (CE) was applied to AChE inhibitor screening. The enzyme catalytic activity and kinetic performances of the immobilized AChE were determined by measuring the peak areas of 5-thio-2-nitrobenzoic acid (TNB), which was produced by the reaction of thiocholine (TCh) with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB). Inhibition kinetics for the immobilized AChE was performed by employing huperzine A as model inhibitor, and its inhibition constant and IC(50) were determined. The constructed AChE immobilized h-MnO(2)@PDA presented outstanding pH, thermal and storage stability. Ultimately, the constructed strategy was applied to screen AChE inhibitors from 7 TCMs and Schisandrae Chinensis Fructus was screened out for its superior AChE inhibitory activity. Therefore, our work not only established a platform for efficiently screening novel AChE inhibitors from TCMs, but also provided inspiration for further exploration of Schisandrae Chinensis Fructus as a potential drug for AD.
ESTHER : Liu_2022_J.Chromatogr.A_1665_462824
PubMedSearch : Liu_2022_J.Chromatogr.A_1665_462824
PubMedID: 35051752

Title : Design, synthesis and insecticidal activity and mechanism research of Chasmanthinine derivatives - Song_2022_Sci.Rep_12_15290
Author(s) : Song Z , Li X , Xu K , Sun G , Yang L , Huang L , Liu J , Yin P , Huang S , Gao F , Zhou X , Chen L
Ref : Sci Rep , 12 :15290 , 2022
Abstract : Unrestricted reproduction and spread of pest had caused great damage to the quality and yield of crops in recent years. Besides the use of traditional chemical pesticides, natural products also make a huge contribution against pests. Chasmanthinine, a diterpenoid alkaloid isolated from Aconitum franchetii var. villosulum, shown extremely antifeedant activity against Spodoptera exigua. Therefore, a series of novel Chasmanthinine derivatives were synthesized and their biological activity was studied in this work. Compound 33 showed the strongest antifeedant activity (EC(50) = 0.10 mg/cm(2)) among all the test compounds. The mechanism research of 33 revealed that its antifeedant effect was related to the inhibition of carboxylesterase (CES), and proved the thiophene acyl group could form a strong binding effect with CES by molecular docking. Moreover, compound 10 exhibited the strongest cytotoxicity (IC(50) = 12.87 microM) against Sf9 cell line and moderate contact toxicity. The mechanism research indicated that compound 10 could induce Sf9 cells apoptosis. In summary, the results lay a foundation for the application of diterpene alkaloids in plant protection.
ESTHER : Song_2022_Sci.Rep_12_15290
PubMedSearch : Song_2022_Sci.Rep_12_15290
PubMedID: 36088472

Title : The suppression of pancreatic lipase-related protein 2 ameliorates experimental hepatic fibrosis in mice - Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
Author(s) : Ding Z , Cheng R , Liu J , Zhao Y , Ge W , Yang Y , Xu X , Wang S , Zhang J
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , 1867 :159102 , 2022
Abstract : Quiescent hepatic stellate cells (HSCs) store vitamin A as lipid droplets in the cytoplasm. When activated, these cells lose vitamin A and exhibit an increased capacity for proliferation, mobility, contractility, and the synthesis of collagen and other components of the extracellular matrix. Our previous work demonstrated that the lipid hydrolytic gene pancreatic lipase-related protein 2 (mPlrp2) is involved in the hydrolysis of retinyl esters (REs) in the liver. Here, we showed that bile duct ligation (BDL)-induced liver injury triggered the conditional expression of mPlrp2 in livers and describe evidence of a strong relationship between the expression of mPlrp2 and Acta-2, a marker for activated HSCs. RNA interference targeting mPlrp2 inhibited HSC activation and ameliorated hepatic fibrosis induced by BDL in mice. Liver BDL markedly reduced the adenosine level and increased the ratio between S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH). Chromatin immunoprecipitation (ChIP) analysis demonstrated an increase in trimethylated histone H3K4 at the mPlrp2 promoter in BDL mice, which was associated with the conditional expression of mPlrp2 in the liver. SAM, a well-known hepatoprotective substance, inhibited mPlrp2 expression and reduced RE hydrolysis in mice with hepatic fibrosis induced by chronic CCl(4) treatment. Liver fibrosis induced by CCl(4) or BDL was improved in Plrp2(-/-) mice. Our results reveal that mPlrp2 suppression is a potential approach for treating hepatic fibrosis.
ESTHER : Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
PubMedSearch : Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
PubMedID: 34995790
Gene_locus related to this paper: mouse-LIPR2

Title : Microplastics induce neurotoxicity in aquatic animals at environmentally realistic concentrations: A meta-analysis - Xiong_2022_Environ.Pollut_318_120939
Author(s) : Xiong F , Liu J , Xu K , Huang J , Wang D , Li F , Wang S , Zhang J , Pu Y , Sun R
Ref : Environ Pollut , 318 :120939 , 2022
Abstract : Microplastics (MPs) draw international attention owing to their widespread distribution in water ecosystems, but whether MPs cause neurotoxic effects in aquatic animals at environmentally realistic concentrations is still controversial. This meta-analysis recompiled 35 studies to determine whether MPs could change the levels of brain (in vivo) neurotransmitters in aquatic animals at environmentally realistic concentrations (>=1smg/L, median = 0.100 mg/L). Then, a group comparison was conducted to compare the effects of different factors on the effect size and to explore the significant factors affecting the neurotoxicity of MPs. The results demonstrated that MP exposure could considerably decrease the levels of acetylcholinesterase (AchE) in the brain of aquatic animals by 16.2%. However, the effects of MPs on cholinesterase (CHE), acetylcholine (ACh), dopamine (DA) and gamma-aminobutyric acid (GABA) were not statistically significant due to the small number of studies and samples. The neurotoxicity of MPs was closely linked with particle size and exposure time but independent of animal species, MP compositions, MP morphology and MP concentrations. Further literatures review indicated that MP-induced neurotoxicity and behavioral changes are related with multiple biological processes, including nerve damage, oxidative stress, intestinal flora disturbance and metabolic disorder. Furthermore, some factors influencing MP neurotoxicity in the real environment (e.g. the aging of MPs, the release of MP additives, and the co-exposure of MPs and pollutants) were discussed. Overall, this study preliminarily explored whether MPs induced changes in neurotoxicity-related indicators in aquatic animals through meta-analysis and provided scientific evidence for evaluating the health risks and neurotoxicity of MPs at the environmental level.
ESTHER : Xiong_2022_Environ.Pollut_318_120939
PubMedSearch : Xiong_2022_Environ.Pollut_318_120939
PubMedID: 36581239

Title : Two-Stage SN38 Release from a Core-Shell Nanoparticle Enhances Tumor Deposition and Antitumor Efficacy for Synergistic Combination with Immune Checkpoint Blockade - Jiang_2022_ACS.Nano__
Author(s) : Jiang X , Lee M , Xia J , Luo T , Liu J , Rodriguez M , Lin W
Ref : ACS Nano , : , 2022
Abstract : Long-circulating nanomedicines efficiently deliver chemotherapies to tumors to reduce general toxicity. However, extended blood circulation of nanomedicines can increase drug exposure to leukocytes and lead to hematological toxicity. Here, we report a two-stage release strategy to enhance the drug deposition and antitumor efficacy of OxPt/SN38 core-shell nanoparticles with a hydrophilic oxaliplatin (OxPt) prodrug coordination polymer core and a lipid shell containing a hydrophobic cholesterol-conjugated SN38 prodrug (Chol-SN38). By conjugating cholesterol to the phenol group of SN38 via an acetal linkage and protecting the 20-hydroxy position with a trimethylsilyl (TMS) group, Chol-SN38 releases SN38 in two stages via esterase-catalyzed cleavage of the acetal linkage in the liver followed by acid-mediated hydrolysis of the TMS group to preferentially release SN38 in tumors. Compared to irinotecan, OxPt/SN38 reduces SN38 blood exposure by 9.0 times and increases SN38 tumor exposure by 4.7 times. As a result, OxPt/SN38 inhibits tumor growth on subcutaneous, spontaneous, and metastatic tumor models by causing apoptotic and immunogenic cell death. OxPt/SN38 exhibits strong synergy with the immune checkpoint blockade to regress subcutaneous colorectal and pancreatic tumors with 33-50% cure rates and greatly inhibits tumor growth and invasion in a spontaneous prostate cancer model and a liver metastasis model of colorectal cancer without causing side effects. Mechanistic studies revealed important roles of enhanced immunogenic cell death and upregulated PD-L1 expression by OxPt/SN38 in activating the tumor immune microenvironment to elicit potent antitumor immunity. This work highlights the potential of combining innovative prodrug design and nanomedicine formulation to address unmet needs in cancer therapy.
ESTHER : Jiang_2022_ACS.Nano__
PubMedSearch : Jiang_2022_ACS.Nano__
PubMedID: 36382721

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 : BCHE as a Prognostic Biomarker in Endometrial Cancer and Its Correlation with Immunity - Liu_2022_J.Immunol.Res_2022_6051092
Author(s) : Liu J , Tian T , Liu X , Cui Z
Ref : J Immunol Res , 2022 :6051092 , 2022
Abstract : BACKGROUND: In developed countries, the most common gynecologic malignancy is endometrial carcinoma (EC), making the identification of EC biomarkers extremely essential. As a natural enzyme, butyrylcholinesterase (BCHE) is found in hepatocytes and plasma. There is a strong correlation between BCHE gene mutations and cancers and other diseases. The aim of this study was to analyze the role of BCHE in patients with EC. METHODS: A variety of analyses were conducted on The Cancer Genome Atlas (TCGA) data, including differential expression analysis, enrichment analysis, immunity, clinicopathology, and survival analysis. The Gene Expression Omnibus (GEO) database was used to validate outcomes. Using R tools, Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) analyses revealed the potential mechanisms of BCHE in EC. Sangerbox tools were used to delve into the relations between BCHE expression and tumor microenvironment, including microsatellite instability (MSI), tumor neoantigen count (TNC), and tumor mutation burden (TMB). BCHE's genetic alteration analysis was conducted by cBioPortal. In addition, the Human Protein Atlas (HPA) was used to validate the outcomes by immunohistochemistry, and an analysis of the protein-protein interaction network (PPI) was performed with the help of the STRING database. RESULTS: Based on our results, BCHE was a significant independent prognostic factor for patients with EC. The prognosis with EC was affected by age, stage, grade, histological type, and BCHE. GSEA showed that BCHE was closely related to pathways regulating immune response, including transforming growth factor-beta (TGF-beta) signaling pathways and cancer immunotherapy through PD1 blockade pathways. The immune analysis revealed that CD4+ regulatory T cells (Tregs) were negatively correlated with BCHE expression and the immune checkpoint molecules CD28, ADORA2A, BTNL2, and TNFRSF18 were all significantly related to BCHE. BCHE expression was also associated with TMB by genetic alteration analysis. CONCLUSIONS: Identifying BCHE as a biomarker for EC might help predict its prognosis and could have important implications for immunotherapy.
ESTHER : Liu_2022_J.Immunol.Res_2022_6051092
PubMedSearch : Liu_2022_J.Immunol.Res_2022_6051092
PubMedID: 35915658

Title : Biological activities and gene expression of detoxifying enzymes in Tribolium castaneum induced by Moutan cortex essential oil - Li_2022_J.Toxicol.Environ.Health.A__1
Author(s) : Li X , Xu Y , Liu J , Yu X , Zhang W , You C
Ref : J Toxicol Environ Health A , :1 , 2022
Abstract : Tribolium castaneum is one of the most harmful storage pests in the world. The aim of this study was to determine the chemical composition, repellent, and contact activities of Moutan cortex essential oil against this insect pest. In addition, the effects of Moutan cortex were examined on the expressions of three major detoxifying enzyme genes in T. castaneum. Four components were identified in this essential oil by gas chromatography-mass spectrometry (GC-MS), which was predominantly paeonol (99.13%). Paeonol exerted significant repellent activity against T. castaneum, which was more potent than the positive control N.N-diethyl-meta-toluamide (DEET). The most significant contact toxicity was observed at 24 h after exposure to paeonol. Further, quantitative real-time PCR (qRT-PCR) was used to assess expression changes in three detoxification enzyme genes in T. castaneum, including carboxylesterase (CarE), glutathione S-transferase (Gst) and cytochrome P4506BQ8 (Cyp6bq8). Among these, Gst was most highly up-regulated after treatment with paeonol with the highest expression level of 4.9-fold (Rps18 as internal reference gene) greater than control at 24 h following treatment. Data indicated that Gst might play a critical role in metabolic detoxification of toxic xenobiotics. Taken together, our findings might lay a foundation for development of paeonol as a potential natural repellent or pesticide to control storage pests.
ESTHER : Li_2022_J.Toxicol.Environ.Health.A__1
PubMedSearch : Li_2022_J.Toxicol.Environ.Health.A__1
PubMedID: 35435144

Title : Tissue-specific accumulation, depuration, and effects of perfluorooctanoic acid on fish: Influences of aqueous pH and sex - Dong_2022_Sci.Total.Environ__160567
Author(s) : Dong H , Lu G , Wang X , Zhang P , Yang H , Yan Z , Liu J , Jiang R
Ref : Sci Total Environ , :160567 , 2022
Abstract : Perfluorooctanoic acid (PFOA) is widely distributed in nature, particularly in aquatic environments. Its bioaccumulation and toxicity in aquatic organisms can be affected by both the chemical status of PFOA in water and the physiology of the organism. However, research on the patterns of these effects is scarce. In this study, we investigated the influence of aqueous pH (pH 6, acidic; pH 7.5, neutral; pH 9, basic) and fish sex on PFOA uptake, clearance, and biochemical effects in crucian carp (C. auratus) using flow-through exposure. In the 17-d kinetic experiment, PFOA bioaccumulation adhered to a uniform first-order model in which PFOA uptake rates from water to blood and liver in acidic conditions were faster than those in other conditions, indicating possible acidic pH influence on PFOA uptake. PFOA clearance rates in these compartments of males were slower than in females, which was attributed to the notably stronger expression of Oat2 (organic anion transporter 2, responsible for reabsorption) in the kidneys of males. Similar responses were observed for peroxisome proliferation-related biomarkers at different pH levels and in different sexes. These biochemical responses were driven by the internal concentrations of PFOA. The inhibition acetylcholinesterase activity in the fish brain was closely linked to changes in P-glycoprotein content, demonstrating a protective relationship. Collectively, an aqueous pH lower than 7.5 might affect the uptake of PFOA by fish. The clearance discrepancies between the sexes highlight the importance of anion carriers for ionizable organic compounds in aquatic organisms.
ESTHER : Dong_2022_Sci.Total.Environ__160567
PubMedSearch : Dong_2022_Sci.Total.Environ__160567
PubMedID: 36455738

Title : The Cell-Cell Communication Signal Indole Controls the Physiology and Interspecies Communication of Acinetobacter baumannii - Cui_2022_Microbiol.Spectr__e0102722
Author(s) : Cui B , Chen X , Guo Q , Song S , Wang M , Liu J , Deng Y
Ref : Microbiol Spectr , :e0102722 , 2022
Abstract : Many bacteria utilize quorum sensing (QS) to control group behavior in a cell density-dependent manner. Previous studies have demonstrated that Acinetobacter baumannii employs an N-acyl-L-homoserine lactone (AHL)-based QS system to control biological functions and virulence. Here, we report that indole controls biological functions, virulence and AHL signal production in A. baumannii. The biosynthesis of indole is performed by A1S_3160 (AbiS, Acinetobacter baumannii indole synthase), which is a novel indole synthase annotated as an alpha/beta hydrolase in A. baumannii. Heterologous expression of AbiS in an Escherichia coli indole-deficient mutant also rescued the production of indole by using a distinct biosynthetic pathway from the tryptophanase TnaA, which produces indole directly from tryptophan in E. coli. Moreover, we revealed that indole from A. baumannii reduced the competitive fitness of Pseudomonas aeruginosa by inhibiting its QS systems and type III secretion system (T3SS). As A. baumannii and P. aeruginosa usually coexist in human lungs, our results suggest the crucial roles of indole in both the bacterial physiology and interspecies communication. IMPORTANCE Acinetobacter baumannii is an important human opportunistic pathogen that usually causes high morbidity and mortality. It employs the N-acyl-L-homoserine lactone (AHL)-type quorum sensing (QS) system, AbaI/AbaR, to regulate biological functions and virulence. In this study, we found that A. baumannii utilizes another QS signal, indole, to modulate biological functions and virulence. It was further revealed that indole positively controls the production of AHL signals by regulating abaI expression at the transcriptional levels. Furthermore, indole represses the QS systems and type III secretion system (T3SS) of P. aeruginosa and enhances the competitive ability of A. baumannii. Together, our work describes a QS signaling network where a pathogen uses to control the bacterial physiology and pathogenesis, and the competitive ability in microbial community.
ESTHER : Cui_2022_Microbiol.Spectr__e0102722
PubMedSearch : Cui_2022_Microbiol.Spectr__e0102722
PubMedID: 35862954
Gene_locus related to this paper: acicp-AbiS

Title : Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors - Tian_2022_Bioorg.Chem_127_105898
Author(s) : Tian Y , Li S , Dong K , Su X , Fu S , Lv X , Duan M , Yang T , Han Y , Hu G , Liu J , Sun Y , Yue H , Zhang H , Du Z , Miao Z , Tong M , Liu Y , Qin M , Gong P , Hou Y , Gao Z , Zhao Y
Ref : Bioorg Chem , 127 :105898 , 2022
Abstract : The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC(50) value of 0.04 +/- 0.01 nM and a K(i) value of 0.2 +/- 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.
ESTHER : Tian_2022_Bioorg.Chem_127_105898
PubMedSearch : Tian_2022_Bioorg.Chem_127_105898
PubMedID: 35792317

Title : A multi-target directed ligands strategy for the treatment of Alzheimer's disease: Dimethyl fumarate plus Tranilast modified Dithiocarbate as AChE inhibitor and Nrf2 activator - Guo_2022_Eur.J.Med.Chem_242_114630
Author(s) : Guo J , Cheng M , Liu P , Cao D , Luo J , Wan Y , Fang Y , Jin Y , Xie SS , Liu J
Ref : Eur Journal of Medicinal Chemistry , 242 :114630 , 2022
Abstract : Alzheimer's disease (AD) possessed intricate pathogenesis. Currently, multi-targeted drugs were considered to have the potential to against AD by simultaneously triggering molecules in functionally complementary pathways. Hence, a series of molecules based on the pharmacophoric features of Dimethyl fumarate, Tranilast, and Dithiocarbate were designed and synthesized. These compounds showed significant AChE inhibitory activity in vitro. Among them, compound 4c(2) displayed the mighty inhibitory activity to hAChE (IC(50) = 0.053 microM) and held the ability to cross the BBB. Kinetic study and molecular docking pointed out that 4c(2) bound well into the active sites of hAChE, forming steady and sturdy interactions with key residues in hAChE. Additionally, 4c(2) as an Nrf2 activator could promote the nuclear translocation of Nrf2 protein and induce the expressions of Nrf2-dependent enzymes HO-1, NQO1, and GPX4. Moreover, 4c(2) rescued BV-2 cells from H(2)O(2)-induced injury and inhibited ROS accumulation. For the anti-neuroinflammatory potential of 4c(2), we observed that 4c(2) could lower the levels of pro-inflammatory cytokines (NO, IL-6 and TNF-alpha) and suppressed the expressions of iNOS and COX-2. In particular, 4c(2) was well tolerated in mice (2500 mg/kg, p.o.) and efficaciously recovered the memory impairment in a Scopolamine-induced mouse model. Overall, these results highlighted that 4c(2) was a promising multi-targeted agent for treating AD.
ESTHER : Guo_2022_Eur.J.Med.Chem_242_114630
PubMedSearch : Guo_2022_Eur.J.Med.Chem_242_114630
PubMedID: 35987018

Title : Zeaxanthin remodels cytoplasmic lipid droplets via beta3-adrenergic receptor signaling and enhances perilipin 5-mediated lipid droplet-mitochondrion interactions in adipocytes - Xie_2022_Food.Funct__
Author(s) : Xie J , Liu H , Yin W , Ge S , Jin Z , Zheng M , Cai D , Liu M , Liu J
Ref : Food Funct , : , 2022
Abstract : Cytoplasmic lipid droplets (LDs), which are remarkably dynamic, neutral lipid storage organelles, play fundamental roles in lipid metabolism and energy homeostasis. Both the dynamic remodeling of LDs and LD-mitochondrion interactions in adipocytes are effective mechanisms to ameliorate obesity and related comorbidities. Zeaxanthin (ZEA) is a natural carotenoid and has beneficial effects on anti-obesity. However, the underlying mechanisms of ZEA on LD modulation are still unclear. In the present study, ZEA efficiently inhibited LD accumulation and attenuated adipocyte proliferation by arresting the cell cycle. ZEA drove transcriptional alterations to reprogram a lipid oxidative metabolism phenotype in mature 3T3-L1 adipocytes. ZEA significantly decreased the TAG and FA content and modulated the dynamic alterations of LDs by upregulating the expression of lipases and the LD-mitochondrion contact site protein, perilipin 5 (PLIN5), and downregulating the LD fusion protein, fat-specific protein 27 (FSP27). Mechanistically, ZEA stimulated LD remodeling and ameliorated mitochondrial defects caused by large and unilocular LD accumulation by activating beta3-adrenergic receptor (beta3-AR) signaling. Furthermore, the knockdown of PLIN5 impaired the LD-mitochondrion interactions, thereby disrupting the role of ZEA in promoting mitochondrial fatty acid oxidation and respiratory chain operation. Collectively, the present study demonstrates that ZEA induces LD structural and metabolic remodeling by activating beta3-AR signaling and enhances PLIN5-mediated LD-mitochondrion interactions in hypertrophic white adipocytes, thereby enhancing oxidative capacity, and has the potential as a nutritional intervention for the prevention and treatment of obesity and associated metabolic syndrome.
ESTHER : Xie_2022_Food.Funct__
PubMedSearch : Xie_2022_Food.Funct__
PubMedID: 35924967

Title : Novel and Potent Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease from Natural (+\/-)-7,8-Dihydroxy-3-methyl-isochroman-4-one - Li_2022_Molecules_27_3090
Author(s) : Li X , Jia Y , Li J , Zhang P , Li T , Lu L , Yao H , Liu J , Zhu Z , Xu J
Ref : Molecules , 27 :3090 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline as well as behavioral problems. It is a progressive and well recognized complex disease; therefore, it is very urgent to develop novel and effective anti-AD drugs. In this study, a series of novel isochroman-4-one derivatives from natural (+/-)-7,8-dihydroxy-3-methyl-isochroman-4-one [(+/-)-XJP] were designed and synthesized, and their anti-AD potential was evaluated. Among them, compound 10a [(Z)-3-acetyl-1-benzyl-4-((6,7-dimethoxy-4-oxoisochroman-3-ylidene)methyl)pyridin-1-ium bromide] possessed potent anti-acetylcholinesterase (AChE) activity as well as modest antioxidant activity. Further molecular modeling and kinetic investigations revealed that compound 10a was a dual-binding inhibitor that binds to both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the enzyme AChE. In addition, compound 10a exhibited low cytotoxicity and moderate anti-Abeta aggregation efficacy. Moreover, the in silico screening suggested that these compounds could pass across the blood-brain barrier with high penetration. These findings show that compound 10a was a promising lead from a natural product with potent AChE inhibitory activity and deserves to be further developed for the prevention and treatment of AD.
ESTHER : Li_2022_Molecules_27_3090
PubMedSearch : Li_2022_Molecules_27_3090
PubMedID: 35630563

Title : Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors - Tian_2022_Bioorg.Med.Chem.Lett_70_128805
Author(s) : Tian Y , Li S , Yang P , Su X , Liu J , Lv X , Dong K , Yang T , Duan M , Hu G , Yue H , Sun Y , Zhang H , Du Z , Miao Z , Tong M , Hou Y , Gao Z , Zhao Y
Ref : Bioorganic & Medicinal Chemistry Lett , 70 :128805 , 2022
Abstract : The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC(50) value of 0.03 +/- 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.
ESTHER : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedSearch : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedID: 35598794

Title : Preparation, characterization and bioactivities of selenized polysaccharides from Lonicera caerulea L. fruits - Shao_2022_Int.J.Biol.Macromol__
Author(s) : Shao C , Zhong J , Liu J , Yang Y , Li M , YangYu , Xu Y , Wang L
Ref : Int J Biol Macromol , : , 2022
Abstract : Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO(3)-Na(2)SeO(3) method, where the selenium (Se) contents were 228 +/-24 and 353 +/- 36 microg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 10(4), 5.6 10(4), and 5.1 10(4) kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE.
ESTHER : Shao_2022_Int.J.Biol.Macromol__
PubMedSearch : Shao_2022_Int.J.Biol.Macromol__
PubMedID: 36403769

Title : Leveraging a Fluorescent Fatty Acid Probe to Discover Cell-Permeable Inhibitors of Plasmodium falciparum Glycerolipid Biosynthesis - Dapper_2022_Microbiol.Spectr__e0245622
Author(s) : Dapper C , Liu J , Klemba M
Ref : Microbiol Spectr , :e0245622 , 2022
Abstract : A sensitive and quantitative fluorescence-based approach is presented for characterizing fatty acid acquisition and lipid biosynthesis by asexually replicating, intraerythrocytic Plasmodium falciparum. We show that a BODIPY-containing, green-fluorescent fatty acid analog is efficiently and rapidly incorporated into parasite neutral lipids and phospholipids. Prelabeling with a red-fluorescent ceramide analog permits normalization and enables reliable quantitation of glycerolipid labeling. Inhibition of lipid labeling by competition with natural fatty acids and by acyl-coenzyme A synthetase and diacylglycerol acyltransferase inhibitors demonstrates that the fluorescent fatty acid probe is acquired, activated, and transferred to lipids through physiologically-relevant pathways. To assess its utility in discovering small molecules that block parasite lipid biosynthesis, the lipid labeling assay was used to screen a panel of mammalian lipase inhibitors and a selection of compounds from the "Malaria Box" anti-malarial collection. Several compounds were identified that inhibited the incorporation of the fluorescent fatty acid probe into lipids in cultured parasites at low micromolar concentrations. Two contrasting profiles of suppression of neutral lipid and phospholipid synthesis were observed, which implies the inhibition of distinct pathways. IMPORTANCE The human malaria parasite Plasmodium falciparum relies on fatty acid scavenging to supply this essential precursor of lipid synthesis during its asexual replication cycle in human erythrocytes. This dependence on host fatty acids represents a potential vulnerability that can be exploited to develop new anti-malarial therapies. The quantitative experimental approach described here provides a platform for simultaneously interrogating multiple facets of lipid metabolism- fatty acid uptake, fatty acyl-CoA synthesis, and neutral lipid and phospholipid biosynthesis- and of identifying cell-permeable inhibitors that are active in situ.
ESTHER : Dapper_2022_Microbiol.Spectr__e0245622
PubMedSearch : Dapper_2022_Microbiol.Spectr__e0245622
PubMedID: 36314974

Title : The efficacy of Azotobacter chroococcum in altering maize plant-defense responses to armyworm at elevated CO(2) concentration - Song_2022_Ecotoxicol.Environ.Saf_248_114296
Author(s) : Song Y , Liu J , Fu M , Liu H , Wang W , Wang S , Chen F
Ref : Ecotoxicology & Environmental Safety , 248 :114296 , 2022
Abstract : Elevated atmospheric carbon dioxide (eCO(2)) concentrations can alter the carbon:nitrogen ratio and palatability of host plants for herbivorous insects, but rhizobacteria likely mitigate the alteration and influence physiological adaptation of insects. In this study, we conducted transcriptomic analysis of maize (Zea mays) response to Azotobacter chroococcum (AC) inoculation under eCO(2) conditions in contrast to ambient CO(2) (aCO(2)), and studied the effects of plant-defense change of maize under eCO(2) on the oriental armyworm, Mythimna separata. Results showed that there were 16, 14, 16 and 135 differentially expressed genes that were associated with plant-defense response in maize leaves between aCO(2)-CK and aCO(2)-AC, eCO(2)-CK and eCO(2)-AC, aCO(2)-CK and eCO(2)-CK, aCO(2)-AC and eCO(2)-AC, respectively. Moreover, A. chroococcum inoculation and eCO(2) influenced plant hormone signal transduction of maize. Interestingly, A. chroococcum inoculation significantly decreased the contents of JA (jasmonic acid) and JA-Ile (isoleucine conjugate of JA) in leaves, but eCO(2) markedly increased contents of JA-Ile, JA and SA (salicylic acid). Compared to aCO(2), eCO(2) significantly decreased activity of protective enzyme (catalase), and increased activities of digestive (lipase and protease), protective (peroxidase) and detoxifying enzymes (carboxylesterase, Mixed-functional oxidase and glutathione s-transferase), prolonged developmental time, and decreased survival rate and body weight of larvae (P<0.05). A. chroococcum inoculation significantly increased the activity of protective enzyme (catalase), and decreased the activities of detoxifying enzymes (carboxylesterase, glutathione s-transferase and mixed-functional oxidase), thus increased the growth rate and body weight of larvae in comparison with no-inoculation of A. chroococcum (P<0.05). The indices of M. separata were significantly correlated with the foliar contents of JA, JA-Ile and SA (|r| = 0.44-0.85, P<0.05), indicating that A. chroococcum inoculation altered the physiological adaptation of M. separata under eCO(2) by disturbing defense substances in maize. Our results in understanding effects of A. chroococcum inoculation on maize resistance to herbivorous insects will be valuable for agricultural pest control in the future at eCO(2) conditions.
ESTHER : Song_2022_Ecotoxicol.Environ.Saf_248_114296
PubMedSearch : Song_2022_Ecotoxicol.Environ.Saf_248_114296
PubMedID: 36399994

Title : Populus euphratica Phospholipase Ddelta Increases Salt Tolerance by Regulating K(+)\/Na(+) and ROS Homeostasis in Arabidopsis - Zhang_2022_Int.J.Mol.Sci_23_4911
Author(s) : Zhang Y , Yao J , Yin K , Liu Z , Deng C , Liu J , Hou S , Zhang H , Yu D , Zhao N , Zhao R , Chen S
Ref : Int J Mol Sci , 23 :4911 , 2022
Abstract : Phospholipase Dalpha (PLDalpha), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Ddelta (PLDdelta) can mediate the salt response in higher plants. PePLDdelta was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDdelta-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDdelta-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H(2)O(2) levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDdelta-overexpressed plants increased the transcription of genes encoding the plasma membrane Na(+)/H(+) antiporter (AtSOS1) and H(+)-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na(+) extrusion and reduce K(+) loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K(+)/Na(+) homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDdelta. PePLDdelta-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2), 36:5 (18:2-18:3) and 36:6 (18:3-18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0-18:2), 34:3 (16:0-18:3), 36:4 (18:2-18:2) and 36:5 (18:2-18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDdelta-derived PA enhanced the salinity tolerance by regulating ROS and K(+)/Na(+) homeostasis in Arabidopsis.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_4911
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_4911
PubMedID: 35563299

Title : Application of a novel fluorogenic polyurethane analogue probe in polyester-degrading microorganisms screening by microfluidic droplet - Xu_2022_Microb.Biotechnol__
Author(s) : Xu A , Liu J , Cao S , Xu B , Guo C , Yu Z , Chen X , Zhou J , Dong W , Jiang M
Ref : Microb Biotechnol , : , 2022
Abstract : Application of polyester-degrading microorganisms or enzymes should be considered as an eco-friendly alternative to chemical recycling due to the huge plastic waste disposal nowadays. However, current impranil DLN-based screening of polyester-degrading microorganisms is time-consuming, labour-intensive and unable to distinguish polyesterases from other protease- or amidase-like enzymes. Herein, we present an approach that combined a novel synthetic fluorescent polyurethane analogue probe (FPAP), along with the droplet-based microfluidics to screen polyurethane-degrading microorganisms through fluorescence-activated droplet sorting (FADS) pipeline. The fluorescent probe FPAP exhibited a fluorescence enhancement effect once hydrolysed by polyesterases, along with a strong specificity in discriminating polyesterases from other non-active enzymes. Application of FPAP in a microfluidic droplet system demonstrated that this probe exhibited high sensitivity and efficiency in selecting positive droplets containing leaf-branch compost cutinase (LCC) enzymes. This novel fluorogenic probe, FPAP, combined with the droplet microfluidic system has the potential to be used in the exploitation of novel PUR-biocatalysts for biotechnological and environmental applications.
ESTHER : Xu_2022_Microb.Biotechnol__
PubMedSearch : Xu_2022_Microb.Biotechnol__
PubMedID: 35881631
Gene_locus related to this paper: 9bact-g9by57

Title : Inhibition of Dipeptidyl Peptidase-4 by Flavonoids: Structure-Activity Relationship, Kinetics and Interaction Mechanism - Pan_2022_Front.Nutr_9_892426
Author(s) : Pan J , Zhang Q , Zhang C , Yang W , Liu H , Lv Z , Liu J , Jiao Z
Ref : Front Nutr , 9 :892426 , 2022
Abstract : With the aim to establish a structure-inhibitory activity relationship of flavonoids against dipeptidyl peptidase-4 (DPP-4) and elucidate the interaction mechanisms between them, a pannel of 70 structurally diverse flavonoids was used to evaluate their inhibitory activities against DPP-4, among which myricetin, hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin showed higher inhibitory activities in a concentration-dependent manner. Structure-activity relationship analysis revealed that introducing hydroxyl groups to C3', C4', and C6 of the flavonoid structure was beneficial to improving the inhibitory efficacy against DPP-4, whereas the hydroxylation at position 3 of ring C in the flavonoid structure was unfavorable for the inhibition. Besides, the methylation of the hydroxyl groups at C3', C4', and C7 of the flavonoid structure tended to lower the inhibitory activity against DPP-4, and the 2,3-double bond and 4-carbonyl group on ring C of the flavonoid structure was essential for the inhibition. Glycosylation affected the inhibitory activity diversely, depending on the structure of flavonoid aglycone, type of glycoside, as well as the position of substitution. Inhibition kinetic analysis suggested that myricetin reversibly inhibited DPP-4 in a non-competitive mode, whereas hyperoside, narcissoside, cyanidin 3-O-glucoside, and isoliquiritigenin all reversibly inhibited DPP-4 in a mixed type. Moreover, the fluorescence quenching analysis indicated that all the five flavonoid compounds could effectively quench the intrinsic fluorescence of DPP-4 by spontaneously binding with it to form an unstable complex. Hydrogen bonds and van der Waals were the predominant forces to maintain the complex of myricetin with DPP-4, and electrostatic forces might play an important role in stabilizing the complexes of the remaining four flavonoids with DPP-4. The binding of the tested flavonoids to DPP-4 could also induce the conformation change of DPP-4 and thus led to inhibition on the enzyme. Molecular docking simulation further ascertained the binding interactions between DPP-4 and the selected five flavonoids, among which hyperoside, narcissoside, cyaniding 3-O-glucoside, and isoliquiritigenin inserted into the active site cavity of DPP-4 and interacted with the key amino acid residues of the active site, whereas the binding site of myricetin was located in a minor cavity close to the active pockets of DPP-4.
ESTHER : Pan_2022_Front.Nutr_9_892426
PubMedSearch : Pan_2022_Front.Nutr_9_892426
PubMedID: 35634373

Title : Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA - Liu_2022_Plant.Cell_34_3301
Author(s) : Liu T , Zhang X , Zhang H , Cheng Z , Liu J , Zhou C , Luo S , Luo W , Li S , Xing X , Chang Y , Shi C , Ren Y , Zhu S , Lei C , Guo X , Wang J , Zhao Z , Wang H , Zhai H , Lin Q , Wan J
Ref : Plant Cell , 34 :3301 , 2022
Abstract : Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
ESTHER : Liu_2022_Plant.Cell_34_3301
PubMedSearch : Liu_2022_Plant.Cell_34_3301
PubMedID: 35670739

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 : Biodegradation and up-cycling of polyurethanes: Progress, challenges, and prospects - Liu_2021_Biotechnol.Adv_48_107730
Author(s) : Liu J , He J , Xue R , Xu B , Qian X , Xin F , Blank LM , Zhou J , Wei R , Dong W , Jiang M
Ref : Biotechnol Adv , 48 :107730 , 2021
Abstract : Polyurethanes (PUR) are ranked globally as the 6th most abundant synthetic polymer material. Most PUR materials are specifically designed to ensure long-term durability and high resistance to environmental factors. As the demand for diverse PUR materials is increasing annually in many industrial sectors, a large amount of PUR waste is also being generated, which requires proper disposal. In contrast to other mass-produced plastics such as PE, PP, and PET, PUR is a family of synthetic polymers, which differ considerably in their physical properties due to different building blocks (for example, polyester- or polyether-polyol) used in the synthesis. Despite its xenobiotic properties, PUR has been found to be susceptible to biodegradation by different microorganisms, albeit at very low rate under environmental and laboratory conditions. Discovery and characterization of highly efficient PUR-degrading microbes and enzymes capable of disassembling PUR polymer chains into oligo- and monomeric compounds is of fundamental importance for a circular plastic economy. In this review, the main methods used for screening PUR-degrading microbes and enzymes are summarized and compared in terms of their catalytic mechanisms. Furthermore, recycling and upcycling strategies of waste PUR polymers, including microbial conversion of PUR monomers into value added products, are presented.
ESTHER : Liu_2021_Biotechnol.Adv_48_107730
PubMedSearch : Liu_2021_Biotechnol.Adv_48_107730
PubMedID: 33713745

Title : Mitochondrial homeostasis and redox status in cardiovascular diseases: Protective role of the vagal system - He_2021_Free.Radic.Biol.Med_178_369
Author(s) : He X , Liu J , Zang WJ
Ref : Free Radic Biol Med , 178 :369 , 2021
Abstract : Mitochondria participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular Ca(2+) handling, apoptosis, and cell fate determination. Disruption of mitochondrial homeostasis under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and energy insufficiency, which further disturb mitochondrial and cellular homeostasis in a deleterious loop. Mitochondrial redox status has therefore become a potential target for therapy against cardiovascular diseases. In this review, we highlight recent progress in determining the roles of mitochondrial processes in regulating mitochondrial redox status, including mitochondrial dynamics (fusion-fission pathways), mitochondrial cristae remodeling, mitophagy, biogenesis, and mitochondrion-organelle interactions (endoplasmic reticulum-mitochondrion interactions, nucleus-mitochondrion communication, and lipid droplet-mitochondrion interactions). The strategies that activate vagal system include direct vagal activation (electrical vagal stimulation and administration of vagal neurotransmitter acetylcholine) and pharmacological modulation (choline and cholinesterase inhibitors). The vagal system plays an important role in maintaining mitochondrial homeostasis and suppressing mitochondrial oxidative stress by promoting mitochondrial biogenesis and mitophagy, moderating mitochondrial fusion and fission, strengthening mitochondrial cristae stabilization, regulating mitochondrion-organelle interactions, and inhibiting mitochondrial Ca(2+) overload. Therefore, enhancement of vagal activity can maintain mitochondrial homeostasis and represents a promising therapeutic strategy for cardiovascular diseases.
ESTHER : He_2021_Free.Radic.Biol.Med_178_369
PubMedSearch : He_2021_Free.Radic.Biol.Med_178_369
PubMedID: 34906725

Title : A Roadmap to the Structure-Related Metabolism Pathways of Per- and Polyfluoroalkyl Substances in the Early Life Stages of Zebrafish (Danio rerio) - Han_2021_Environ.Health.Perspect_129_77004
Author(s) : Han J , Gu W , Barrett H , Yang D , Tang S , Sun J , Liu J , Krause HM , Houck KA , Peng H
Ref : Environmental Health Perspectives , 129 :77004 , 2021
Abstract : BACKGROUND: Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear. OBJECTIVES: To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. Environmental Protection Agency's PFAS screening library. METHODS: Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied high-resolution mass spectrometry-based nontargeted analysis to identify metabolites of PFAS in zebrafish larvae after 5 d of exposure by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFAS. RESULTS: Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS were highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of beta-oxidation or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis was identified as a major metabolism pathway for diverse PFAS, and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences toward perfluoroalkyl carboxamides. CONCLUSIONS: We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS.
ESTHER : Han_2021_Environ.Health.Perspect_129_77004
PubMedSearch : Han_2021_Environ.Health.Perspect_129_77004
PubMedID: 34288731

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 : Influence of suspended sediment on the bioavailability of benzophenone-3: Focus on accumulation and multi-biological effects in Daphnia magna - Yang_2021_Chemosphere_275_129974
Author(s) : Yang H , Lu G , Yan Z , Liu J
Ref : Chemosphere , 275 :129974 , 2021
Abstract : The UV-filter benzophenone-3 (BP3) tends to associate with suspended sediment (SPS) due to hydrophobicity, which could alter its toxicological effects on non-target aquatic organisms. In this study, the freshwater cladoceran Daphnia magna (D. magna) was selected as a model organism to investigate the impacts of the source and composition of SPS on the accumulation and multiple toxicological effects (from the molecular level to individual level) of BP3. Among the three components of SPS, amorphous organic carbon (AOC) and minerals promoted the body burden of BP3, while black carbon (BC) inhibited the bioaccumulation. The inhibition effects of BP3 on swimming and feeding behaviors of D. magna were also enhanced due to the presence of AOC and BC. Compared with BP3 exposure alone, higher oxidative stress and neurotoxicity were observed in the presence of SPS containing AOC, BC and minerals, corresponding to that superoxide dismutase, catalase and glutathione-S-transferase activities were further induced, and acetylcholinesterase activity was inhibited. Furthermore, BP3 induced mRNA expression levels of the endocrine system (ecdysone receptor, cytochrome P450 CYP314) and metabolic system (toxicant nuclear receptor HR96, P-glycoprotein), and the presence of SPS containing AOC, BC and minerals exhibited an enhanced effect. Combined with all endpoints, evident relationship was observed between the bioaccumulation level and the response of individual behavior and molecular biomarkers. The results demonstrated that the effects of SPS compositions on bioaccumulation and toxicological effects of organic UV-filters should be considered in aquatic environments.
ESTHER : Yang_2021_Chemosphere_275_129974
PubMedSearch : Yang_2021_Chemosphere_275_129974
PubMedID: 33639549

Title : Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE\/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease - Yao_2021_J.Med.Chem__
Author(s) : Yao H , Uras G , Zhang P , Xu S , Yin Y , Liu J , Qin S , Li X , Allen S , Bai R , Gong Q , Zhang H , Zhu Z , Xu J
Ref : Journal of Medicinal Chemistry , : , 2021
Abstract : Based on a multitarget strategy, a series of novel tacrine-pyrimidone hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation results demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and glycogen synthase kinase 3 (GSK-3). The optimal compound 27g possessed excellent dual AChE/GSK-3 inhibition both in terms of potency and equilibrium (AChE: IC(50) = 51.1 nM; GSK-3beta: IC(50) = 89.3 nM) and displayed significant amelioration on cognitive deficits in scopolamine-induced amnesia mice and efficient reduction against phosphorylation of tau protein on Ser-199 and Ser-396 sites in glyceraldehyde (GA)-stimulated differentiated SH-SY5Y cells. Furthermore, compound 27g exhibited eligible pharmacokinetic properties, good kinase selectivity, and moderate neuroprotection against GA-induced reduction in cell viability and neurite damage in SH-SY5Y-derived neurons. The multifunctional profiles of compound 27g suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.
ESTHER : Yao_2021_J.Med.Chem__
PubMedSearch : Yao_2021_J.Med.Chem__
PubMedID: 34024109

Title : One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase - Liu_2021_J.Org.Chem__
Author(s) : Liu C , Wang Y , Liu J , Chen A , Xu J , Zhang R , Wang F , Nie K , Deng L
Ref : J Org Chem , : , 2021
Abstract : 4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.
ESTHER : Liu_2021_J.Org.Chem__
PubMedSearch : Liu_2021_J.Org.Chem__
PubMedID: 34085515

Title : Toxic effects of subacute exposure to acrylamide on motor endplates of the gastrocnemius in rats - Yanxian_2021_Toxicology__152934
Author(s) : Yanxian B , Gu Z , Zhang T , Luo Y , Zhang C , Luo L , Ma Y , Liu J
Ref : Toxicology , :152934 , 2021
Abstract : Acrylamide (ACR) is a recognized toxin that is known to induce neurotoxicity in humans and experimental animals. This study aimed to investigate the toxic effects of subacute exposure of the motor endplate (MEP) of the gastrocnemius in rats to ACR. All rats were randomly divided into control, 9, 18, and 36 mg/kg ACR groups, and ACR was administered by gastric gavage for 21 days. The behavioral tests were performed weekly. On the 22(nd) day, the wet weight of the gastrocnemius was measured. The changes in muscle fiber structure, nerve endings, and MEP in the gastrocnemius were examined by hematoxylin-eosin (HE) and gold chloride staining. Acetylcholinesterase (AChE) content in the gastrocnemius was detected by AChE staining. The expression of AChE and calcitonin gene-related peptide was detected by immunohistochemistry and western blot. Rats exposed to ACR showed a significant increase in gait scores and hind limb splay distance compared with the control group, and the wet weight of the gastrocnemius was reduced, HE staining showed that the muscle fiber structure of the gastrocnemius became thin and the arrangement was dense with nuclear aggregation, gold chloride staining showed that nerve branches decreased and became thin, nerve fibers became short and light, the number of MEPs was decreased, the staining became light, and the structure was not clear. AChE staining showed that the number of MEPs was significantly reduced after exposure to ACR, the shape became small, and the AChE content decreased in a dose-dependent manner. Immunohistochemistry and western blot analysis results of the expression levels of AchE and CGRP showed a decreasing trend as compared to the control group with increasing ACR exposure dose. The reduction in protein levels may be the mechanism by which ACR has a toxic effect on the MEP in the gastrocnemius of rats.
ESTHER : Yanxian_2021_Toxicology__152934
PubMedSearch : Yanxian_2021_Toxicology__152934
PubMedID: 34509579

Title : Association of EPHX1 polymorphisms with plasma concentration of carbamazepine in epileptic patients: Systematic review and meta-analysis - Hu_2021_J.Clin.Neurosci_91_159
Author(s) : Hu T , Zeng X , Tian T , Liu J
Ref : J Clin Neurosci , 91 :159 , 2021
Abstract : BACKGROUND: Carbamazepine (CBZ) is a wildly used anti-epileptic drug (AED). Increasing evidence suggested that polymorphisms in Epoxide Hydrolase1 (EPHX1) gene are associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of CBZ, albeit the results were inconsistent. METHODS: A literature search on PubMed, Embase, and Cochrane Library was conducted to identify eligible studies published between 1974 and 2020. A meta-analysis was performed and the standardized mean difference (SMD) and 95% confidence interval (95% CI) were estimated using a random-effects model. The heterogeneity and leave-one-study-out sensitivity analyses of each article and the publication bias were also performed. All the statistical analyses were performed using STATA 14.0. RESULTS: A total of 6 articles with 1746 subjects were included in this meta-analysis. A significant correlation was detected between EPHX1 rs1051740 T > C polymorphisms and decreased plasma concentration of CBZ (TT vs CC: SMD = 0.34, P < 0.001; TC vs CC: SMD = 0.35, P = 0.009). However, similar results were not detected in the comparison of TT vs. TC in the EPHX1 rs1051740 T > C variation (P = 0.637), while subgroup analyses showed an association with plasma CBZ concentration in the non-Asian group (P < 0.001, I(2) = 0.0%, Ph = 0.400). Although the association of EPHX1 rs2234922 A > G polymorphisms with plasma CBZ concentration was not detected (AA vs GG:SMD = 0.54, P = 0.102; AA vs AG:SMD = -0.05, P = 0.670; AG vs GG: SMD = 0.86, P = 0.107), subgroup analyses showed that the GG genotype EPHX1 rs2234922 was associated with increased plasma CBZ concentration in the Asian group (P = 0.005, I(2) = 48.6%, Ph = 0.143). CONCLUSION: EPHX1 rs1051740 T > C and rs2234922 A > G are important genetic variants associated with plasma CBZ concentration. The role of EPHX1 polymorphisms in the interindividual variability of plasma CBZ concentration varied significantly among different ethnic groups, which should be considered during clinical validation and in future studies.
ESTHER : Hu_2021_J.Clin.Neurosci_91_159
PubMedSearch : Hu_2021_J.Clin.Neurosci_91_159
PubMedID: 34373022

Title : Dose- and time-related effects of acute diisopropylfluorophosphate intoxication on forced swim behavior and sucrose preference in rats - Liu_2021_Neurotoxicol_82_82
Author(s) : Liu J , Hester K , Pope C
Ref : Neurotoxicology , 82 :82 , 2021
Abstract : Acute intoxication by organophosphorus anticholinesterases (OPs) has been associated with depression and other neuropsychiatric disorders. We previously reported that adult male rats treated with diisopropylfluorophosphate (2.5 mg/kg, sc) showed acute cholinergic signs followed by changes (increased immobility/decreased swimming) in the forced swim test (a measure of behavioral despair) for at least one month. This study was conducted to evaluate the further persistence of changes in the forced swim test out to 4 months and to compare responses in a sucrose preference test, a measure of anhedonia. Adult male rats were treated with vehicle (peanut oil, 1 mL/kg, sc) or DFP (2.0, 2.25 or 2.5 mg/kg) followed by sacrifice 4 h later for measurement of OP-sensitive serine hydrolases (cholinesterase [ChE], fatty acid amide hydrolase [FAAH], and monoacylglycerol lipase [MAGL]) in hippocampus. Additional rats were treated similarly and evaluated for functional signs of acute toxicity from 30 min to 6 days, and then motor activity, forced swim behavior and sucrose preference at approximately 1 week, 1 month and 4 months after dosing. All dosages of DFP elicited serine hydrolase inhibition (ChE, 92-96 %; FAAH, 46-63 %; MAGL, 26-33 %). Body weight was reduced in all DFP-treated groups during the first two weeks, and lethality was noted with the higher dosages. Involuntary movements were elicited in all DFP treatment groups during the first week, but both time of onset and rate of recovery were dose-related. There was a significant reduction in ambulation at one week after the highest dosage (2.5 mg/kg), but no other significant locomotor changes were noted. Immobility was increased and swimming was decreased in the forced swim test at all three time-points by 2.25 mg/kg DFP, and at 2 of 3 time-points by the other dosages. While length of water deprivation and time after DFP dosing affected sucrose preference, DFP treatment had no main effect. We conclude that the forced swim test (a measure of behavioral despair/coping mechanism for inescapable stress) is a robust and persistent neurobehavioral consequence of acute DFP intoxication while sucrose preference, a measure of anhedonia and a common symptom of major clinical depression, is not affected.
ESTHER : Liu_2021_Neurotoxicol_82_82
PubMedSearch : Liu_2021_Neurotoxicol_82_82
PubMedID: 33232745

Title : Resistance of Bemisia tabaci Mediterranean (Q-biotype) to pymetrozine: resistance risk assessment, cross-resistance to six other insecticides and detoxification enzyme assay - Wang_2021_Pest.Manag.Sci_77_2114
Author(s) : Wang F , Liu J , Shuai S , Miao C , Chi B , Chen P , Wang K , Li H , Liu Y
Ref : Pest Manag Sci , 77 :2114 , 2021
Abstract : BACKGROUND: The whitefly Bemisia tabaci (Gennadius) is a severe pest that affects many field and glasshouse crops worldwide and has developed resistance to insecticides in most chemical classes. Pymetrozine, a neuroactive pyridine azomethine, is selective towards piercing-sucking pests in Hemiptera. The aim of this study was to assess the resistance of B. tabaci Mediterranean (MED) to pymetrozine in the laboratory. RESULTS: After successive selection of 18 generations of MED in the presence of using pymetrozine, there was an 11.28-fold increase in the median lethal concentration (LC(50) ). When the realized heritability (h(2) ) of B. tabaci to pymetrozine in the field was assumed to be the value estimated in the laboratory (h(2) = 0.1360) and the mortality was 70-90%, only 7.2-15.9 generations were estimated to be needed to obtain a ten-fold increase in resistance to pymetrozine. Compared with the susceptible populations (G(0) ), the Pyme-SEL strain (G(18) ) showed a low level of cross-resistance to neonicotinoids (nitenpyram, imidacloprid, acetamiprid, and thiamethoxam) and no cross-resistance to chlorpyrifos or abamectin. With the G(0) and the Pyme-SEL strains (G(11) and G(18) ) as test strains, the activity of multifunctional oxidase exhibited the greatest increase during selection, while the activities of carboxylesterase and glutathione-S-transferase did not change significantly. CONCLUSION: This study show that a potential risk of development of resistance to pymetrozine exists in B. tabaci after continuous application. During the application of pymetrozine to control B. tabaci in the field, the frequency of its use in combination with neonicotinoids should be used with caution. 2020 Society of Chemical Industry.
ESTHER : Wang_2021_Pest.Manag.Sci_77_2114
PubMedSearch : Wang_2021_Pest.Manag.Sci_77_2114
PubMedID: 33332688

Title : Trelagliptin ameliorates IL-1beta-impaired chondrocyte function via the AMPK\/SOX-9 pathway - Liu_2021_Mol.Immunol_140_70
Author(s) : Liu J , Zuo Q , Li Z , Chen J , Liu F
Ref : Mol Immunol , 140 :70 , 2021
Abstract : Chondrocyte dysregulation plays a critical role in the development of osteoarthritis (OA). The pro-inflammatory cytokine interleukin-1beta (IL-1beta) activates chondrocytes and degrades the structural extracellular matrix (ECM). These events are the important mechanism of OA. Trelagliptin, a selective inhibitor of dipeptidyl Peptidase 4 (DPP-4) used for the treatment of type 2 diabetes mellitus (T2DM), has displayed a wide range of anti-inflammatory capacities. The effects of Trelagliptin in OA and chondrocytes have not been tested before. Here, we show that Trelagliptin mitigates IL-1beta-induced production of inflammatory cytokines such as interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in human chondrocytes. Trelagliptin ameliorates IL-1beta-induced oxidative stress by reducing the generation of reactive oxygen species (ROS). Particularly, the presence of Trelagliptin prevents IL-1beta-induced reduction of Acan genes and the protein Aggrecan. Moreover, we show that Trelagliptin restores IL-1beta-induced reduction of SOX-9 and that the knockdown of SOX-9 abolishes the protective effects of Trelagliptin. Mechanistically, we demonstrate that AMPK is required for the amelioration of Trelagliptin on SOX-9- reduction by IL-1beta. Collectively, our study demonstrates that the DPP-4 inhibitor Trelagliptin has a protective effect on chondrocyte function. Trelagliptin may have the potential role to antagonize chondrocyte-derived inflammation in OA.
ESTHER : Liu_2021_Mol.Immunol_140_70
PubMedSearch : Liu_2021_Mol.Immunol_140_70
PubMedID: 34666245

Title : Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects - Issotina_2021_J.Hypertens__
Author(s) : Issotina Zibrila A , Wang Z , Ali MA , Osei JA , Sun Y , Zafar S , Liu K , Li C , Kang Y , Liu J
Ref : J Hypertens , : , 2021
Abstract : OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.
ESTHER : Issotina_2021_J.Hypertens__
PubMedSearch : Issotina_2021_J.Hypertens__
PubMedID: 34232157

Title : Chemical composition of essential oils from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare and their acaricidal effects on Haemaphysalis longicornis (Acari: Ixodidae) - Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
Author(s) : Qiao Y , Yu Z , Bai L , Li H , Zhang S , Liu J , Gao Z , Yang X
Ref : Ecotoxicology & Environmental Safety , 224 :112672 , 2021
Abstract : Chemical acaricides are mainly used in traditional tick control, which leads to the emergence of tick resistance and concurrently results in environmental pollution. In the present study, the chemical constituents of essential oils (EOs) from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare was analyzed, and their potential application was evaluated to control the vector tick Haemaphysalis longicornis, which is widely distributed over vast areas of Eurasia, Australia, and New Zealand. Gas chromatography-mass spectrometry analysis revealed that the phenols thymol and carvacrol accounted for 34.66% and 75.72% of the EOs of T. mongolicus and O. vulgare, respectively, whereas trans-cinnamaldehyde (49.42%) was the main constituent of C. verum EO. Immersion tests showed that the EOs of C. verum and O. vulgare had significant acaricidal activity against larval H. longicornis, with the 50% lethal concentration (LC(50)) being 16.07 and 18.02 mg/mL, respectively, and the 95% lethal concentration (LC(95)) being 120.37 and 130.09 mg/mL, respectively. The EOs of O. vulgare and T. mongolicus showed significant acaricidal activity against unfed adult H. longicornis, with LC(50) being 43.50 and 44.21 mg/mL, respectively, and LC(95) being 113.66 and 137.99 mg/mL, respectively. The fumigant toxicity test showed significant acaricidal activity of the three EOs against both unfed and engorged nymphal and adult H. longicornis. Enzyme assays revealed that the EOs of both C. verum and O. vulgare significantly inhibited glutathione S-transferase activity (P < 0.05). In contrast, the activities of carboxylesterase and multifunction oxidases were significantly inhibited by EOs extracted from all three plants (P < 0.05). Taken together, these findings suggest that plant EOs may serve as an environment-friendly alternative for synthetic acaricides in future tick control.
ESTHER : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedSearch : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedID: 34416637

Title : Development and validation of an ultrasensitive LC-MS\/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial - Bai_2021_Biomed.Chromatogr_35_e4994
Author(s) : Bai H , Lu J , Cheng X , Liu L , Zhang W , Wei Y , Wang Y , Liu J , Ding J , Yu Q , Zhang Y , Chen G , Fan Y , Wang X
Ref : Biomedical Chromatography , 35 :e4994 , 2021
Abstract : This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C(18) analytical column (50x2.1mm, 5microm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.
ESTHER : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedSearch : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedID: 32986878

Title : Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease - Zhang_2021_Eur.J.Med.Chem_213_113154
Author(s) : Zhang Z , Guo J , Cheng M , Zhou W , Wan Y , Wang R , Fang Y , Jin Y , Liu J , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 213 :113154 , 2021
Abstract : In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC(50) values 0.85 microM and 0.59 microM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu(2+) and Al(3+) at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
ESTHER : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedSearch : Zhang_2021_Eur.J.Med.Chem_213_113154
PubMedID: 33476932

Title : Endophytic Fungal Community of Huperzia serrata: Diversity and Relevance to the Production of Huperzine A by the Plant Host - Cui_2021_Molecules_26_
Author(s) : Cui L , Noushahi HA , Zhang Y , Liu J , Cosoveanu A , Liu Y , Yan L , Zhang J , Shu S
Ref : Molecules , 26 : , 2021
Abstract : As the population ages globally, there seem to be more people with Alzheimer's disease. Unfortunately, there is currently no specific treatment for the disease. At present, Huperzine A (HupA) is one of the best drugs used for the treatment of Alzheimer's disease and has been used in clinical trials for several years in China. HupA was first separated from Huperzia serrata, a traditional medicinal herb that is used to cure fever, contusions, strains, hematuria, schizophrenia, and snakebite for several hundreds of years in China, and has been confirmed to have acetylcholinesterase inhibitory activity. With the very slow growth of H. serrata, resources are becoming too scarce to meet the need for clinical treatment. Some endophytic fungal strains that produce HupA were isolated from H. serrate in previous studies. In this article, the diversity of the endophytic fungal community within H. serrata was observed and the relevance to the production of HupA by the host plant was further analyzed. A total of 1167 strains were obtained from the leaves of H. serrata followed by the stems (1045) and roots (824). The richness as well as diversity of endophytic fungi within the leaf and stem were higher than in the root. The endophytic fungal community was similar within stems as well as in leaves at all taxonomic levels. The 11 genera (Derxomyces, Lophiostoma, Cyphellophora, Devriesia, Serendipita, Kurtzmanomyces, Mycosphaerella, Conoideocrella, Brevicellicium, Piskurozyma, and Trichomerium) were positively correlated with HupA content. The correlation index of Derxomyces with HupA contents displayed the highest value (CI = 0.92), whereas Trichomerium showed the lowest value (CI = 0.02). Through electrospray ionization mass spectrometry (ESI-MS), it was confirmed that the HS7-1 strain could produce HupA and the total alkaloid concentration was 3.7 ug/g. This study will enable us to screen and isolate the strain that can produce HupA and to figure out the correlation between endophytic fungal diversity with HupA content in different plant organs. This can provide new insights into the screening of strains that can produce HupA more effectively.
ESTHER : Cui_2021_Molecules_26_
PubMedSearch : Cui_2021_Molecules_26_
PubMedID: 33567664

Title : A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China - Qian_2021_Parasit.Vectors_14_169
Author(s) : Qian W , Liu N , Yang Y , Liu J , He J , Chen Z , Li M , Qiu X
Ref : Parasit Vectors , 14 :169 , 2021
Abstract : BACKGROUND: Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides. METHODS: A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing. RESULTS: The G119S mutation in AChE was detected at high frequencies (0.40-0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets. CONCLUSIONS: Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy.
ESTHER : Qian_2021_Parasit.Vectors_14_169
PubMedSearch : Qian_2021_Parasit.Vectors_14_169
PubMedID: 33743789

Title : Effects of exogenous GR24 on biogas upgrading and nutrient removal by co-culturing microalgae with fungi under mixed LED light wavelengths - Zhang_2021_Chemosphere_281_130791
Author(s) : Zhang W , Zhao C , Liu J , Sun S , Zhao Y , Wei J
Ref : Chemosphere , 281 :130791 , 2021
Abstract : To realize the synchronous purification of raw biogas and biogas slurry, the algal-fungal symbiont pellets were cultivated by supplementing strigolactone (GR24) under different mixed LED light wavelengths. The optimal light intensity was proved to be red and blue in the ratio of 5:5. The symbionts treated with 10(-9) M GR24 had the highest growth rate and mean daily productivity. The extracellular carbonic anhydrase activity and the content of chlorophyll were also affected by GR24 concentrations and mixed light wavelengths. With the induction of 10(-9) M GR24, the maximum removal efficiency of chemical oxygen demand, total nitrogen, and total phosphorus reached 76.35 +/- 6.87%, 78.77 +/- 7.13% and 79.49 +/- 7.43%, respectively. Besides, the CO(2) removal efficiency reached 59.32 +/- 5.19% when the concentration of GR24 was 10(-7) M. This work will be beneficial for large-scale biogas slurry purification and biogas upgrading using co-cultivation of microalgae and fungi.
ESTHER : Zhang_2021_Chemosphere_281_130791
PubMedSearch : Zhang_2021_Chemosphere_281_130791
PubMedID: 34020195

Title : Construction and characterization of CRISPR\/Cas9 knockout rat model of carboxylesterase 2a gene - Liu_2021_Mol.Pharmacol__2
Author(s) : Liu J , Shang X , Huang S , Xu Y , Lu J , Zhang Y , Liu Z , Wang X
Ref : Molecular Pharmacology , : , 2021
Abstract : Carboxylesterase 2 (CES2), an important metabolic enzyme, plays a critical role in drug biotransformation and lipid metabolism. Although CES2 is very important, few animal models have been generated to study its properties and functions. Rat Ces2 is similar to human CES2A-CES3A-CES4A gene cluster, with highly similar gene structure, function and substrate. In this report, CRISPR/Cas9 technology was firstly used to knock out rat Ces2a, a main subtype of Ces2 mostly distributed in liver and intestine. This model showed the absence of CES2A protein expression in liver. Further pharmacokinetic studies of diltiazem, a typical substrate of CES2A, confirmed the loss of function of CES2A both in vivo and in vitro. At the same time, the expression of CES2C and CES2J protein in liver decreased significantly. The body and liver weight of Ces2a knockout rats also increased, but the food intake did not change. Moreover, the deficiency of Ces2a led to obesity, insulin resistance and liver fat accumulation, which are consistent with the symptoms of nonalcoholic fatty liver disease (NAFLD). Therefore, this rat model is not only a powerful tool to study drug metabolism mediated by CES2, but also a good disease model to study NAFLD. Significance Statement Human CES2 plays a key role in the first-pass hydrolysis metabolism of most oral prodrugs as well as lipid metabolism. In this study, CRISPR/Cas9 technology was used to knock out Ces2a gene in rats for the first time. This model can be used not only in the study of drug metabolism and pharmacokinetics, but also as a disease model of NAFLD and other metabolic disorder.
ESTHER : Liu_2021_Mol.Pharmacol__2
PubMedSearch : Liu_2021_Mol.Pharmacol__2
PubMedID: 34503976
Gene_locus related to this paper: ratno-LOC246252

Title : Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites - Hu_2021_Sci.Rep_11_21639
Author(s) : Hu Y , Chen R , Gao H , Lin H , Wang J , Wang X , Liu J , Zeng Y
Ref : Sci Rep , 11 :21639 , 2021
Abstract : Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model's outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783-0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784-0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP.
ESTHER : Hu_2021_Sci.Rep_11_21639
PubMedSearch : Hu_2021_Sci.Rep_11_21639
PubMedID: 34737270

Title : Insecticidal Terpenes From the Essential Oils of Artemisia nakaii and Their Inhibitory Effects on Acetylcholinesterase - Liu_2021_Front.Plant.Sci_12_720816
Author(s) : Liu J , Hua J , Qu B , Guo X , Wang Y , Shao M , Luo S
Ref : Front Plant Sci , 12 :720816 , 2021
Abstract : Essential oils (EOs) are often the source of insecticidal substances of high efficiency and low toxicity. From gas chromatograph-mass spectrometer, column chromatography, and nuclear magnetic resonance spectra analyses, twenty terpenes were identified from the EOs of Artemisia nakaii. These comprised mostly monoterpenes (49.01%) and sesquiterpenes (50.76%). The terpenes at the highest concentrations in the EOs of A. nakaii were feropodin (200.46 +/- 1.42 microg/ml), (+)-camphor (154.93 +/- 9.72 microg/ml), beta-selinene (57.73 +/- 2.48 microg/ml), and 1,8-cineole (17.99 +/- 1.06 microg/ml), calculated using area normalization and external standards. The EOs were tested for biological activity and showed strong fumigant toxicity and significant antifeedant activity against the larvae of Spodoptera litura. Furthermore, the monoterpenes 1,8-cineole and (+)-camphor displayed significant fumigant activity against S. litura, with LC(50) values of 7.00 +/- 0.85 and 18.16 +/- 2.31 microl/L, respectively. Antifeedant activity of the sesquiterpenes feropodin and beta-selinene was obvious, with EC(50) values of 12.23 +/- 2.60 and 10.46 +/- 0.27 microg/cm(2), respectively. The EOs and beta-selinene were also found to inhibit acetylcholinesterase, with IC(50) values of 37.75 +/- 3.59 and 6.88 +/- 0.48 microg/ml, respectively. These results suggest that monoterpenes and sesquiterpenes from the EOs of A. nakaii could potentially be applied as a botanical pesticides in the control of S. litura.
ESTHER : Liu_2021_Front.Plant.Sci_12_720816
PubMedSearch : Liu_2021_Front.Plant.Sci_12_720816
PubMedID: 34456959

Title : Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials - Li_2021_Medicine.(Baltimore)_100_e26662
Author(s) : Li X , Wang Y , Liu J , Xiong Y , Chen S , Han J , Xie W , Wu Q
Ref : Medicine (Baltimore) , 100 :e26662 , 2021
Abstract : BACKGROUND: Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD. METHODS: The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay. RESULTS: Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P<.0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P=.002). Seventeen studies showed that perioperative sedation with alpha2-adrenergic receptor agonists prevented POD (P=.0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P=.002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P<.00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay. CONCLUSION: Measures including intraoperative monitoring of bispectral index, supplemental analgesia, alpha2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium.
ESTHER : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedSearch : Li_2021_Medicine.(Baltimore)_100_e26662
PubMedID: 34398027

Title : The protonation state of Glu202 in acetylcholinesterase - Wang_2021_Proteins__
Author(s) : Wang J , Lai S , Kong Y , Yao W , Chen X , Liu J
Ref : Proteins , : , 2021
Abstract : Acetylcholinesterase (AChE) is the crucial enzyme in the central nervous system. It is the target of various organophosphorus nerve agents and pesticides, and the inhibition of AChE is a therapeutic strategy for the treatment of various neurological-related diseases. The Glu202 is a key residue adjacent to the catalytic His447 and plays important role in catalysis. Although the Glu202 has long been considered as negatively charged in many studies, more and more evidences support a protonated Glu202. However, Glu202 is freely accessible by solvent, and thus it seems more reasonable for Glu202 to majorly take the deprotonated state. In the present work, we carried out a series of molecular dynamics simulations with the Glu202 adopting different protonation states. Our results show that the protonated Glu202 is important in maintaining the key hydrogen bond network that supports the catalytic triad, whereas the deprotonated Glu202 results in the collapse of the key hydrogen bond network which consequently destabilizes the catalytic His447. We also notice that different protonation states of Glu202 merely alters the binding mode of ACh. However, since the catalytic His447 is disrupted if Glu202 is deprotonated, His447 can not facilitate the nucleophilic attack performed by Ser203. Therefore, the catalytic efficiency of ACh hydrolysis should be remarkably decreased if Glu202 is deprotonated. Our findings suggest that, when designing and developing highly active AChE inhibitors or proposing mechanistic hypotheses for AChE-catalyzed reactions, the protonated state of Glu202 should be considered. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Proteins__
PubMedSearch : Wang_2021_Proteins__
PubMedID: 34546589

Title : Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents - Zhao_2021_Inorg.Chem__
Author(s) : Zhao D , Liu J , Zhang L , Zhou Y , Zhong Y , Yang Y , Huang C , Wang Y
Ref : Inorg Chem , : , 2021
Abstract : Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), -potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.
ESTHER : Zhao_2021_Inorg.Chem__
PubMedSearch : Zhao_2021_Inorg.Chem__
PubMedID: 34969248

Title : IRREGULAR POLLEN EXINE2 Encodes a GDSL Lipase Essential for Male Fertility in Maize - Huo_2020_Plant.Physiol_184_1438
Author(s) : Huo Y , Pei Y , Tian Y , Zhang Z , Li K , Liu J , Xiao S , Chen H
Ref : Plant Physiol , 184 :1438 , 2020
Abstract : Anther cuticle and pollen exine are two physical barriers protecting plant reproductive cells against environmental stresses; defects in either often cause male sterility. Here, we report the characterization of a male-sterile mutant irregular pollen exine2 (ipe2) of maize (Zea mays), which displays shrunken anthers and no starch accumulation in mature pollen grains. We cloned the causal gene IPE2 and confirmed its role in male fertility in maize with a set of complementary experiments. IPE2 is specifically expressed in maize developing anthers during stages 8 to 9 and encodes an endoplasmic-reticulum-localized GDSL lipase. Dysfunction of IPE2 resulted in delayed degeneration of tapetum and middle layer, leading to defective formation of anther cuticle and pollen exine, and complete male sterility. Aliphatic metabolism was greatly altered, with the contents of lipid constituents, especially C16/C18 fatty acids and their derivatives, significantly reduced in ipe2 developing anthers. Our study elucidates GDSL function in anther and pollen development and provides a promising genetic resource for breeding hybrid maize.
ESTHER : Huo_2020_Plant.Physiol_184_1438
PubMedSearch : Huo_2020_Plant.Physiol_184_1438
PubMedID: 32913046

Title : Development of a practical prediction scoring system for severe acute organophosphate poisoning - Dong_2020_J.Appl.Toxicol__
Author(s) : Dong N , Liu J , Wang Z , Gao N , Pang L , Xing J
Ref : J Appl Toxicol , : , 2020
Abstract : Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 x 10(9) /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital.
ESTHER : Dong_2020_J.Appl.Toxicol__
PubMedSearch : Dong_2020_J.Appl.Toxicol__
PubMedID: 32030807

Title : Synergistic Degradation of Pyrethroids by the Quorum Sensing-Regulated Carboxylesterase of Bacillus subtilis BSF01 - Xiao_2020_Front.Bioeng.Biotechnol_8_889
Author(s) : Xiao Y , Lu Q , Yi X , Zhong G , Liu J
Ref : Front Bioeng Biotechnol , 8 :889 , 2020
Abstract : The well-studied quorum sensing (QS) mechanism has established a complex knowledge system of how microorganisms behave collectively in natural ecosystems, which contributes to bridging the gap between the ecological functions of microbial communities and the molecular mechanisms of cell-to-cell communication. In particular, the ability of agrochemical degradation has been one most attractive potential of functional bacteria, but the interaction and mutual effects of intracellular degradation and intraspecific behavior remained unclear. In this study, we establish a connection between QS regulation and biodegradation by harnessing the previously isolated Bacillus subtilis BSF01 as a template which degrades various pyrethroids. First, we characterize the genetic and transcriptional basis of comA-involved QS system in B. subtilis BSF01 since the ComQXPA circuit coordinates group behaviors in B. subtilis isolates. Second, the genetic and transcriptional details of pyrethroid-degrading carboxylesterase CesB are defined, and its catalytic capacity is evaluated under different conditions. More importantly, we adopt DNA pull-down and yeast one-hybrid techniques to reveal that the enzymatic degradation of pyrethroids is initiated through QS signal regulator ComA binding to carboxylesterase gene cesB, highlighting the synergistic effect of QS regulation and pyrethroid degradation in B. subtilis BSF01. Taken together, the elucidated mechanism provides novel details on the intercellular response of functional bacteria against xenobiotic exposure, which opens up possibilities to facilitate the in-situ contaminant bioremediation via combining the QS-mediated strategies.
ESTHER : Xiao_2020_Front.Bioeng.Biotechnol_8_889
PubMedSearch : Xiao_2020_Front.Bioeng.Biotechnol_8_889
PubMedID: 32850741

Title : Extradural Contralateral C7 Nerve Root Transfer in a Cervical Posterior Approach for Treating Spastic Limb Paralysis: A Cadaver Feasibility Study - Yang_2020_Spine.(Phila.Pa.1976)_45_E608
Author(s) : Yang K , Jiang F , Zhang S , Zhao H , Shi Z , Liu J , Cao X
Ref : Spine (Phila Pa 1976) , 45 :E608 , 2020
Abstract : STUDY DESIGN: Anatomic study in nine fresh-frozen cadavers. OBJECTIVE: To confirm the anatomical feasibility of transferring the extradural ventral roots (VRs) and dorsal roots (DRs) of contralateral C7 nerves to those of the ipsilateral C7 nerves respectively through a cervical posterior approach. SUMMARY OF BACKGROUND DATA: The contralateral C7 nerve root transfer technique makes breakthrough for treating spastic limb paralysis. However, its limitations include large surgical trauma and limited indications. METHODS: Nine fresh-frozen cadavers (four females and five males) were placed prone, and the feasibility of exposing the bilateral extradural C7 nerve roots, separation of the extradural C7 VR and DR, and transfer of the VR and DR of the contralateral C7 to those of the ipsilateral C7 on the dural mater were assessed. The pertinent distances and the myelography results of each specimen were analyzed. The acetylcholinesterase (AChE) and antineurofilament 200 (NF200) double immunofluorescent staining were preformed to determine the nerve fiber properties. RESULTS: A cervical posterior midline approach was made and the laminectomy was performed to expose the bilateral extradural C7 nerve roots. After the extradural C7 VR and DR are separated, the VR and DR of the contralateral C7 have sufficient lengths to be transferred to those of the ipsilateral C7 on the dural mater. The myelography results showed that the spinal cord is not compressed after the nerve anastomosis. The AChE and NF200 double immunofluorescent staining showed the distal ends of the contralateral C7 VRs were mostly motor nerve fibers, and the distal ends of the contralateral C7 DRs were mostly sensory nerve fibers. CONCLUSION: Extradural contralateral C7 nerve root transfer in a cervical posterior approach for treating spastic limb paralysis is anatomically feasible. LEVEL OF EVIDENCE: 5.
ESTHER : Yang_2020_Spine.(Phila.Pa.1976)_45_E608
PubMedSearch : Yang_2020_Spine.(Phila.Pa.1976)_45_E608
PubMedID: 31770316

Title : Biological uptake, depuration and biochemical effects of diclofenac and carbamazepine in Carassius carassius - Nkoom_2020_Ecotoxicol.Environ.Saf_205_111106
Author(s) : Nkoom M , Lu G , Liu J , Dong H
Ref : Ecotoxicology & Environmental Safety , 205 :111106 , 2020
Abstract : The uptake and depuration kinetics of diclofenac and carbamazepine alone at an environmentally relevant nominal concentration of 2 mug/L and in combination at a concentration ratio of 1:1 with total concentration of 4 mug/L were evaluated in Carassius carassius after 7 d uptake and depuration. Also, the biochemical effects of both drugs alone at nominal concentrations of 2 and 10 mug/L as well as in combination with total concentrations of 4 and 20 mug/L were investigated in Carassius carassius after 7 d exposure followed by 10 d recovery. In the single treatments, steady-state BCFs measured after the 7 d exposure were 73.05, 49.71, 38.01 and 24.93 L/kg for diclofenac and 9.25, 8.99, 5.29 and 4.11 L/kg for carbamazepine in the liver, brain, gill and muscle of Carassius carassius, respectively. Comparatively lower BCFs were measured in the tissues of Carassius carassius for both drugs in the combined treatments. Acetylcholinesterase activity in the brain was significantly induced by diclofenac while carbamazepine and the mixtures significantly inhibited it during all the exposure days as well as after the 10 d recovery in all treatments. This indicates that Carassius carassius could not recover from the neurotoxic effects caused by carbamazepine unlike the inductive effect caused by diclofenac which was recoverable after 10 days. A significant increase in the activities of 7-ethoxyresorufin O-deethylase and glutathione s-transferase for individual and mixed pharmaceuticals suggest that metabolism and detoxification of both drugs took place in the liver of Carassius carassius. Also, a significant increase in the activities of superoxide dismutase, catalase, glutathione reductase and malondialdehyde contents in the individual and mixture treatments mean that the antioxidant defence system of Carassius carassius was triggered to fight against oxidative stress but lipid peroxidation still occurred. However, Carassius carassius recovered from all these increases (superoxide dismutase, catalase, glutathione reductase and malondialdehyde) after the 10 d recovery, suggesting that oxidative damage is reversible. Our results indicate that both drugs at environmentally relevant concentrations might cause adverse effects in Carassius carassius and other fish species.
ESTHER : Nkoom_2020_Ecotoxicol.Environ.Saf_205_111106
PubMedSearch : Nkoom_2020_Ecotoxicol.Environ.Saf_205_111106
PubMedID: 32818877

Title : Identification of key residues of carboxylesterase PxEst-6 involved in pyrethroid metabolism in Plutella xylostella (L.) - Li_2020_J.Hazard.Mater_407_124612
Author(s) : Li Y , Sun H , Tian Z , Ye X , Li R , Li X , Zheng S , Liu J , Zhang Y
Ref : J Hazard Mater , 407 :124612 , 2020
Abstract : The long-term and excessive use of insecticides has led to severe environmental problems and the evolution of insecticide resistance in insects. Carboxylesterases (CarEs) are important detoxification enzymes conferring insecticide resistance on insects. Herein, the detoxification process of Plutella xylostella (L.) carboxylesterase 6 (PxEst-6), one representative P. xylostella carboxylesterase, is investigated with cypermethrin, bifenthrin, cyfluthrin and lambda-cyhalothrin. RT-qPCR shows that PxEst-6 is highly expressed in the midgut and cuticles of the third instar larvae. Exposure to pyrethroid insecticides resulted in PxEst-6 up-regulation in a short time. Metabolic assays indicate that PxEst-6 has the capacity to metabolize these pyrethroid insecticides. The combination of molecular docking, binding mode analyses and alanine mutations demonstrated that His451, Lys458 and Gln431 were key residues of PxEst-6 for metabolizing pyrethroids and the acetate groups derived from pyrethroids were key sites for being metabolized by PxEst-6. H451- and K458-derived hydrogen bond (H-bond) interactions with the pyrethroid acetate groups and the polar interactions with the pyrethroid acetate group provided by the Q431 sidechain were crucial to the pyrethroids' metabolism by PxEst-6. Our study contributes to revealing the reasons for pyrethroid resistance in P. xylostella, and provides a fundamental basis for the development of novel pyrethroid insecticides.
ESTHER : Li_2020_J.Hazard.Mater_407_124612
PubMedSearch : Li_2020_J.Hazard.Mater_407_124612
PubMedID: 33338816
Gene_locus related to this paper: pluxy-f1c4b8

Title : HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture - Hu_2020_J.Neuroimmune.Pharmacol_15_538
Author(s) : Hu G , Niu F , Liao K , Periyasamy P , Sil S , Liu J , Dravid SM , Buch S
Ref : J Neuroimmune Pharmacol , 15 :538 , 2020
Abstract : Although combination antiretroviral therapy (cART) has improved the health of millions of those living with HIV-1 (Human Immunodeficiency Virus, Type 1), the penetration into the central nervous system (CNS) of many such therapies is limited, thereby resulting in residual neurocognitive impairment commonly referred to as NeuroHIV. Additionally, while cART has successfully suppressed peripheral viremia, cytotoxicity associated with the presence of viral Transactivator of transcription (Tat) protein in tissues such as the brain, remains a significant concern. Our previous study has demonstrated that both HIV-1 Tat as well as opiates such as morphine, can directly induce synaptic alterations via independent pathways. Herein, we demonstrate that exposure of astrocytes to HIV-1 protein Tat mediates the induction and release of extracellular vesicle (EV) microRNA-7 (miR-7) that is taken up by neurons, leading in turn, to downregulation of neuronal neuroligin 2 (NLGN2) and ultimately to synaptic alterations. More importantly, we report that these impairments could be reversed by pretreatment of neurons with a neurotrophic factor platelet-derived growth factor-CC (PDGF-CC). Graphical Abstract.
ESTHER : Hu_2020_J.Neuroimmune.Pharmacol_15_538
PubMedSearch : Hu_2020_J.Neuroimmune.Pharmacol_15_538
PubMedID: 31401755

Title : Optimization of chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone to sigma-caprolactone using response surface methodology - Zhang_2020_Biotechnol.Prog_36_e2901
Author(s) : Zhang Y , Jiang W , Lv K , Sun Y , Gao X , Zhao Q , Ren W , Wang F , Liu J
Ref : Biotechnol Prog , 36 :e2901 , 2020
Abstract : sigma-Caprolactone (sigma-CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of sigma-CL synthesis through chemoenzymatic Baeyer-Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of sigma-CL was 98.06% with about 1.2 M sigma-CL concentration that has a substantial increase mainly due to both better stability of the cross-linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5 degreesC. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R(2) value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of sigma-CL (p < .0006).
ESTHER : Zhang_2020_Biotechnol.Prog_36_e2901
PubMedSearch : Zhang_2020_Biotechnol.Prog_36_e2901
PubMedID: 31465150

Title : Design, synthesis and evaluation of quinolinone derivatives containing dithiocarbamate moiety as multifunctional AChE inhibitors for the treatment of Alzheimer's disease - Fu_2020_J.Enzyme.Inhib.Med.Chem_35_118
Author(s) : Fu J , Bao F , Gu M , Liu J , Zhang Z , Ding J , Xie SS
Ref : J Enzyme Inhib Med Chem , 35 :118 , 2020
Abstract : A series of novel quinolinone derivatives bearing dithiocarbamate moiety were designed and synthesised as multifunctional AChE inhibitors for the treatment of AD. Most of these compounds exhibited strong and clearly selective inhibition to eeAChE. Among them, compound 4c was identified as the most potent inhibitor to both eeAChE and hAChE (IC50 = 0.22 muM for eeAChE; IC50 = 0.16 muM for hAChE), and it was also the best inhibitor to AChE-induced Abeta aggregation (29.02% at 100 muM) and an efficient inhibitor to self-induced Abeta aggregation (30.67% at 25 muM). Kinetic and molecular modelling studies indicated that compound 4c was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4c had good ability to cross the BBB, showed no toxicity on SH-SY5Y neuroblastoma cells and was well tolerated in mice at doses up to 2500 mg/kg (po).
ESTHER : Fu_2020_J.Enzyme.Inhib.Med.Chem_35_118
PubMedSearch : Fu_2020_J.Enzyme.Inhib.Med.Chem_35_118
PubMedID: 31694418

Title : Simulated revelation of the adsorption behaviours of acetylcholinesterase on charged self-assembled monolayers - Yang_2020_Nanoscale__
Author(s) : Yang S , Liu J , Zheng H , Zhong J , Zhou J
Ref : Nanoscale , : , 2020
Abstract : An acetylcholinesterase (AChE)-based electrochemical biosensor, as a promising alternative to detect organophosphates (OPs) and carbamate pesticides, has gained considerable attention in recent years, due to the advantages of simplicity, rapidity, reliability and low cost. The bio-activity of AChE immobilized on the surface and the direct electron transfer (DET) rate between an enzyme and an electrode directly determined the analytical performances of the AChE-based biosensor, and experimental studies have shown that the charged surfaces have a strong impact on the detectability of the AChE-based biosensor. Therefore, it is very important to reveal the behaviour of AChE in bulk solution and on charged surfaces at the molecular level. In this work, the adsorption orientation and conformation of AChE from Torpedo californica (TcAChE) on oppositely charged self-assembled monolayers (SAMs), COOH-SAM and NH2-SAM with different surface charge densities, were investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics simulations (AAMD). Simulation results show that TcAChE could spontaneously and stably adsorb on two oppositely charged surfaces by the synergy of an electric dipole and charged residue patch, and opposite orientations were observed. The active-site gorge of TcAChE is oriented toward the surface with the "end-on" orientation and the active sites are close to the surface when it is adsorbed on the positively charged surface and the tunnel cost for the substrate is lower than that on the negatively charged surface and in bulk solution, while for TcAChE adsorbed on the negatively charged surface, the active site of TcAChE is far away from the surface and the active-site gorge is oriented toward the solution with a "back-on" orientation. It suggests that the positively charged surface could provide a better microenvironment for the efficient bio-catalytic reaction and quick DET between TcAChE and the electrode surface. Moreover, the RMSD, RMSF, dipole moment, gyration radius, eccentricity and superimposed structures show that only a slight conformational change occurred on the relatively flexible structure of TcAChE during simulations, and the native conformation is well preserved after adsorption. This work helps us better comprehend the adsorption mechanism of TcAChE on charged surfaces and might provide some guidelines for the development of new TcAChE-based amperometric biosensors for the detection of organophosphorus pesticides.
ESTHER : Yang_2020_Nanoscale__
PubMedSearch : Yang_2020_Nanoscale__
PubMedID: 32022070

Title : The Chromosome-Based Rubber Tree Genome Provides New Insights into Spurge Genome Evolution and Rubber Biosynthesis - Liu_2020_Mol.Plant_13_336
Author(s) : Liu J , Shi C , Shi CC , Li W , Zhang QJ , Zhang Y , Li K , Lu HF , Zhu ST , Xiao ZY , Nan H , Yue Y , Zhu XG , Wu Y , Hong XN , Fan GY , Tong Y , Zhang D , Mao CL , Liu YL , Hao SJ , Liu WQ , Lv MQ , Zhang HB , Liu Y , Hu-Tang GR , Wang JP , Wang JH , Sun YH , Ni SB , Chen WB , Zhang XC , Jiao YN , Eichler EE , Li GH , Liu X , Gao LZ
Ref : Mol Plant , 13 :336 , 2020
Abstract : The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the -1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by -65.88% (-970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains -15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.
ESTHER : Liu_2020_Mol.Plant_13_336
PubMedSearch : Liu_2020_Mol.Plant_13_336
PubMedID: 31838037
Gene_locus related to this paper: hevbr-a0a6a6mdr9

Title : Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review - Wang_2020_Curr.Vasc.Pharmacol_18_358
Author(s) : Wang Z , Yang Y , Liu M , Wei Y , Liu J , Pei H , Li H
Ref : Curr Vasc Pharmacol , 18 :358 , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.
ESTHER : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedSearch : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedID: 31291876

Title : Identification and molecular docking study of fish roe-derived peptides as potent BACE 1, AChE, and BChE inhibitors - Yu_2020_Food.Funct_11_6643
Author(s) : Yu Z , Ji H , Shen J , Kan R , Zhao W , Li J , Ding L , Liu J
Ref : Food Funct , 11 :6643 , 2020
Abstract : Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE 1) play vital roles in the development and progression of Alzheimer's disease (AD). The objective of the present study was to identify fish roe-derived anti-AD peptides with activities against AChE, BChE, and BACE 1. Fish roe proteins were cleaved in silico by gastrointestinal proteases, and the released peptides were collected. Subsequently, the toxicity, solubility, and biological properties of these novel di- and tri-peptides were predicted and validated. Finally, potential anti-AD peptides were docked to targets, i.e., AChE, BChE, and BACE 1. A novel anti-AD tripeptide WIR with potent inhibition of AChE and BACE 1 was identified, with IC(50) values of 43.32 +/- 1.22 microM and 2.27 +/- 0.35 mM, respectively. In addition, the inhibition rate of WIR (at a concentration of 1.06 +/- 0.87 microM) against BChE was 33.5%, and the peptide WIR was able to simultaneously interact with AChE, BChE, and BACE 1. Residues Ser286 of AChE, Asp70 of BChE, and Thr231, Arg235 of BACE 1 played key roles in the interaction with peptide WIR. In summary, peptide WIR exhibits the potential to be an effective treatment for AD.
ESTHER : Yu_2020_Food.Funct_11_6643
PubMedSearch : Yu_2020_Food.Funct_11_6643
PubMedID: 32656560

Title : Genetic Manipulation of an Aminotransferase Family Gene dtlA Activates Youssoufenes in Marine-Derived Streptomyces youssoufiensis - Li_2020_Org.Lett_22_729
Author(s) : Li H , Liu J , Deng Z , Li T , Liu Z , Che Q , Li W
Ref : Org Lett , 22 :729 , 2020
Abstract : Disruption of an aminotransferase family gene dtlA activated the production of a novel dimeric benzoic polyene acids (BPAs), named youssoufene A1 (1), along with four new (2-5, youssoufenes B1-B4) and a known (6) monomeric BPA in the marine-derived Streptomyces youssoufiensis OUC6819. The structures of 1-5 were elucidated by extensive spectroscopic and computational approaches. Youssoufene A1 (1) exhibited notably increased growth inhibition (MIC = 12.5 microg/mL) against multidrug resistant Enterococcus faecalis compared to monomeric structures (2-6).
ESTHER : Li_2020_Org.Lett_22_729
PubMedSearch : Li_2020_Org.Lett_22_729
PubMedID: 31891272
Gene_locus related to this paper: 9actn-YsfF

Title : Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro -
Author(s) : Wang M , Cao R , Zhang L , Yang X , Liu J , Xu M , Shi Z , Hu Z , Zhong W , Xiao G
Ref : Cell Res , 30 :269 , 2020
PubMedID: 32020029

Title : Enzymology, Histological and Ultrastructural Effects of Ar-Turmerone on Culex pipiens pallens Larvae - Liu_2020_Insects_11_
Author(s) : Liu J , Fernandez D , Gao Y , Pierre S , Dai G
Ref : Insects , 11 : , 2020
Abstract : Our previous article demonstrated that ar-turmerone ((6S)-2-methyl-6-(4-methylphenyl)-2-hepten-4-one) extracted from Curcuma longa L. has a significant larvicidal activity against the fourth instar larvae of Culex pipiens pallens. To reveal the effects of ar-turmerone on C. pipiens pallens larvae, light microscopy and transmission electron microscopy were used to observe the histological and ultrastructure changes in muscle and digestive tissues of fourth instar larvae. It was also revealed by detecting the activity of the acetylcholinesterase (AChE) enzyme and three detoxifying enzymes, including carboxylesterase (CarE), glutathione-S-transferase (GST) and Cytochrome P450 monooxidases (P450). The observation under the light microscope showed that the larvae displayed a disruption of myofibril in ventral muscle cells, the disappearance of nucleolus in the malpighian tubule cells, and the exfoliation of the brush border in midgut epithelial cells, 24 h after treatment. The observation under the transmission electron microscope displayed disorganized Z-lines in the ventral muscle cells, and dissolved membrane of mitochondria, nuclear and endoplasmic reticulum in abdominal cells. The enzymatic activity results showed that ar-turmerone significantly increased the level of detoxifying enzymes, while the activity of AChE was not obviously affected. All the results suggest that the larvicidal mechanism of ar-turmerone is estimated to be stomach poison and the active sites might be the muscle and digestive tissues, and the mode of action of ar-turmerone may be unrelated to AChE.
ESTHER : Liu_2020_Insects_11_
PubMedSearch : Liu_2020_Insects_11_
PubMedID: 32486189

Title : Bemisia tabaci (Hemiptera: Aleyrodidae) Insecticide Resistance in Shandong Province, China - Wang_2020_J.Econ.Entomol_113_911
Author(s) : Wang F , Liu J , Chen P , Li HY , Ma JJ , Liu YJ , Wang K
Ref : J Econ Entomol , 113 :911 , 2020
Abstract : The Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex comprises important pests and virus vectors in agricultural crops worldwide. In China, B. tabaci has spread to more than 20 provinces and caused severe losses of vegetables, fruits, and ornamental plants. However, B. tabaci has developed resistance to many insecticidal classes in Shandong Province, eastern China. In this study, we investigated the cryptic species, insecticide resistance and detoxifying enzymes of B. tabaci from six representative locations exhibiting severe damage in Shandong. At four of the six locations, B. tabaci Mediterranean (MED) comprised 100% of the samples collected. In a further two locations, species composition was predominantly (>94%) MED with B. tabaci Middle East-Asia Minor 1 (MEAM1), comprising a low proportion (<6%) of the samples collected. For all field populations, avermectin was the most effective insecticide against adult B. tabaci, pyriproxyfen had a significant effect on B. tabaci eggs and field populations were susceptible to pymetrozine. Six field populations of B. tabaci have developed low-to-moderate resistance to neonicotinoids. The detoxifying enzyme activity of carboxylesterase, glutathione S-transferase, and multifunctional oxidase were quantified. Multifunctional oxidase and glutathione S-transferase activity were positively correlated with insecticide resistance in several B. tabaci populations.
ESTHER : Wang_2020_J.Econ.Entomol_113_911
PubMedSearch : Wang_2020_J.Econ.Entomol_113_911
PubMedID: 31800055

Title : Thiol-suppressed I(2)-etching of AuNRs: acetylcholinesterase-mediated colorimetric detection of organophosphorus pesticides - Qing_2020_Mikrochim.Acta_187_497
Author(s) : Qing Z , Li Y , Luo G , Hu J , Zou Z , Lei Y , Liu J , Yang R
Ref : Mikrochim Acta , 187 :497 , 2020
Abstract : For the first time it is demonstrated that sulfhydryl compounds can suppress longitudinal etching of gold nanorods via consuming oxidizers, which provides a new signaling mechanism for colorimetric sensing. As a proof of concept, a colorimetric assay is developed for detecting organophosphorus pesticides, which are most widely used in modern agriculture to improve food production but with high toxicity to animals and the ecological environment. Triazophos was selected as a model organophosphorus pesticide. In the absence of triazophos, the active acetylcholinesterase can catalyze the conversion of acetylthiocholine iodide to thiocholine whose thiol group can suppress the I(2)-induced etching of gold nanorods. When triazophos is present, the activity of AchE is inhibited, and I(2)-induced etching of gold nanorods results in triazophos concentration-dependent color change from brown to blue, pink, and red. The aspect ratio of gold nanorods reduced with gradually blue-shifted longitudinal absorption. There was a linear detection range from 0 to 117 nM (R(2) = 0.9908), the detection limit was 4.69 nM, and a good application potential was demonstrated by the assay of real water samples. This method will not only contribute to public monitoring of organophosphorus pesticides but also has verified a new signaling mechanism which will open up a new path to develop colorimetric detection methods. It has been first found that sulfhydryl compounds can suppress longitudinal etching of gold nanorods (AuNRs) via consuming oxidizers, which provides a new signaling mechanism for colorimetric sensing. As a proof of concept, a colorimetric assay is developed for sensitively detecting organophosphorus pesticides (OPs). It will not only contribute to public monitoring of OPs but also has verified a new signaling mechanism which will open up a new path to develop multicolor colorimetric methods.
ESTHER : Qing_2020_Mikrochim.Acta_187_497
PubMedSearch : Qing_2020_Mikrochim.Acta_187_497
PubMedID: 32803418

Title : A De Novo Designed Esterase with p-Nitrophenyl Acetate Hydrolysis Activity - Li_2020_Molecules_25_4658
Author(s) : Li G , Xu L , Zhang H , Liu J , Yan J , Yan Y
Ref : Molecules , 25 :4658 , 2020
Abstract : Esterases are a large family of enzymes with wide applications in the industry. However, all esterases originated from natural sources, limiting their use in harsh environments or newly- emerged reactions. In this study, we designed a new esterase to develop a new protocol to satisfy the needs for better biocatalysts. The ideal spatial conformation of the serine catalytic triad and the oxygen anion hole at the substrate-binding site was constructed by quantum mechanical calculation. The catalytic triad and oxygen anion holes were then embedded in the protein scaffold using the new enzyme protocol in Rosetta 3. The design results were subsequently evaluated, and optimized designs were used for expression and purification. The designed esterase had significant lytic activities towards p-nitrophenyl acetate, which was confirmed by point mutations. Thus, this study developed a new protocol to obtain novel enzymes that may be useful in unforgiving environments or novel reactions.
ESTHER : Li_2020_Molecules_25_4658
PubMedSearch : Li_2020_Molecules_25_4658
PubMedID: 33066055
Gene_locus related to this paper: aspor-cutas , fusso-cutas , hevbr-hnl

Title : Identification of ovalbumin-derived peptides as multi-target inhibitors of AChE, BChE and BACE1 - Yu_2020_J.Sci.Food.Agric__
Author(s) : Yu Z , Dong W , Wu S , Shen J , Zhao W , Ding L , Liu J , Zheng F
Ref : J Sci Food Agric , : , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that occurs to the elderly. But there is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin. RESULTS: The potential tripeptides IEK, LYR and CIK were selected for molecular docking. The '-CDOCKER_Energy' value of the best docking position of the tripeptide IEK, LYR and CIK interacting with acetylcholinesterase (AChE) were - 93.8119, -86.9556 and - 73.6370 kcal/mol, respectively. The '-CDOCKER_Energy' values for interaction with butyrylcholinesterase (BChE) were - 96.6386, -80.8392 and - 87.4341 kcal/mol, respectively. Most importantly, the '-CDOCKER_Energy' values for interaction with beta-site amyloid precursor protein cleavage enzyme1 (BACE1) were - 85.5903, -71.3342 and - 68.4290 kcal/mol, respectively. Overall, in vitro assays results demonstrated that peptide CIK exhibited impressive inhibitory activities against AChE, BChE, and BACE1, with the IC50 value of 6.76, 7.72, and 34.48 muM, respectively. Especially, CIK can be contacted with some peripheral anion sites (PAS) and catalytic sites on AChE, BChE and BACE1. CONCLUSION: Tripeptide CIK can effectively inhibit the activities of AChE, BChE and BACE1. Therefore, tripeptide CIK has the potential to effectively treat AD. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2020_J.Sci.Food.Agric__
PubMedSearch : Yu_2020_J.Sci.Food.Agric__
PubMedID: 31997357

Title : Multilevel ecotoxicity assessment of environmentally relevant bisphenol F concentrations in Daphnia magna - Liu_2020_Chemosphere_240_124917
Author(s) : Liu J , Shen J , Lu G , Xu X , Yang H , Yan Z , Chen W
Ref : Chemosphere , 240 :124917 , 2020
Abstract : With the pressure to ban or limit the use of Bisphenol A (BPA), substitutes such as bisphenol F (BPF) are applied to various commodities and generally detected in aquatic systems worldwide. To understand the potential ecological risk of BPF, the acute toxicity as well as behavioural, physiological and biochemical parameters of the water flea Daphnia magna were assessed. Following BPF exposure at concentrations ranging from 0.1mugL(-1) to 100mugL(-1), phenotypic traits including growth development, fecundity and swimming activity were significantly inhibited in response to exposure to sublethal concentrations (1-100mugL(-1)) of BPF, which had a positive relationship with the activity of antioxidant enzymes. Moreover, the acetylcholinesterase (AChE) activity, which was strictly associated with the behavioural changes, was clearly inhibited, which was also obviously related to the heart rate and thoracic limb activity. Compared to the toxicity of BPA, BPF induces similar toxic effects, and the health concerns regarding the use of these alternatives should be highlighted.
ESTHER : Liu_2020_Chemosphere_240_124917
PubMedSearch : Liu_2020_Chemosphere_240_124917
PubMedID: 31726617

Title : Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line - Sun_2020_Proteomics.Clin.Appl_14_e1900080
Author(s) : Sun R , Dong C , Li R , Chu H , Liu J , Hao D , Zhang L , Zhao B , Wang L , Zhang Y
Ref : Proteomics Clin Appl , 14 :e1900080 , 2020
Abstract : PURPOSE: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with HCC. EXPERIMENTAL DESIGN: In this study, proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent are performed. Then the expression level and function of differentially expressed plasma membrane proteins are verified. RESULTS: In total, 25 plasma membrane proteins are shown differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 are upregulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 is closely related to the chemoresistance of Bel/5Fu to 5-Fu. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with HCC.
ESTHER : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedSearch : Sun_2020_Proteomics.Clin.Appl_14_e1900080
PubMedID: 32067389
Gene_locus related to this paper: human-EPHX1

Title : HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure - Wu_2019_J.Viral.Hepat_26_1334
Author(s) : Wu J , Guo N , Zhang X , Xiong C , Liu J , Xu Y , Fan J , Yu J , Zhao X , Liu B , Wang W , Zhang J , Cao H , Li L
Ref : J Viral Hepat , 26 :1334 , 2019
Abstract : A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.
ESTHER : Wu_2019_J.Viral.Hepat_26_1334
PubMedSearch : Wu_2019_J.Viral.Hepat_26_1334
PubMedID: 31294523

Title : Novel chromanone-dithiocarbamate hybrids as multifunctional AChE inhibitors with beta-amyloid anti-aggregation properties for the treatment of Alzheimer's disease - Jiang_2019_Bioorg.Chem_89_103027
Author(s) : Jiang N , Ding J , Liu J , Sun X , Zhang Z , Mo Z , Li X , Yin H , Tang W , Xie SS
Ref : Bioorg Chem , 89 :103027 , 2019
Abstract : By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Abeta aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC50=0.10muM) and AChE-induced Abeta aggregation (33.02% at 100muM), and could effectively inhibit self-induced Abeta aggregation (38.25% at 25muM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors.
ESTHER : Jiang_2019_Bioorg.Chem_89_103027
PubMedSearch : Jiang_2019_Bioorg.Chem_89_103027
PubMedID: 31176237

Title : A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review - Li_2019_Gene_704_113
Author(s) : Li T , Feng Y , Liu Y , He C , Liu J , Chen H , Deng Y , Li M , Li W , Song J , Niu Z , Sang S , Wen J , Men M , Chen X , Li J , Liu X , Ling J
Ref : Gene , 704 :113 , 2019
Abstract : Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.
ESTHER : Li_2019_Gene_704_113
PubMedSearch : Li_2019_Gene_704_113
PubMedID: 30974196
Gene_locus related to this paper: human-ABHD12

Title : Pediatric reference intervals of liver and renal function tests from birth to adolescence in Chinese children as performed on the Olympus AU5400 - Liu_2019_Clin.Chim.Acta_490_142
Author(s) : Liu J , Dai Y , Lee Y , Yuan E , Wang Q , Wang L , Su Y
Ref : Clinica Chimica Acta , 490 :142 , 2019
Abstract : BACKGROUND: The growth and development of children and adolescents influence values of liver and renal function tests. The purpose of this study was to determine age- and gender-specific reference intervals for liver and renal function tests in apparently healthy Chinese children and adolescents. METHODS: A total of 63,086 apparently healthy children and adolescents (0-15 y) were chosen as reference individuals in this study. The 15 biochemical analytes relating to liver and renal function were measured using an Olympus AU5400 analyzer. Reference intervals were partitioned according to age and/or gender subgroups using the Harris and Boyd's method and established using non-parametric methods. RESULTS: Our results showed that all analytes except for cholinesterase (ChE) and alpha1-microglobulin (alpha1-MG) required partitioning by age. Gender partitions were also required for alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), creatinine (Cre), and uric acid (UA). Age- and gender-appropriate reference intervals for liver and renal function tests were established for apparently healthy Chinese children and adolescents. CONCLUSIONS: When establishing pediatric reference intervals, partitioning by age and/or gender is essential. Those reference intervals can be adopted in other clinical laboratories after appropriate validation.
ESTHER : Liu_2019_Clin.Chim.Acta_490_142
PubMedSearch : Liu_2019_Clin.Chim.Acta_490_142
PubMedID: 30611730

Title : Pharmacological treatment of apathy in Lewy body disorders: A systematic review - Liu_2019_Parkinsonism.Relat.Disord_60_14
Author(s) : Liu J , Cooper CA , Weintraub D , Dahodwala N
Ref : Parkinsonism Relat Disord , 60 :14 , 2019
Abstract : INTRODUCTION: There are no approved treatments for apathy, a frequent and incapacitating symptom in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We reviewed the literature on the pharmacological treatment of apathy in PD and DLB to inform practice and future research. METHOD: We searched PubMed and PsycINFO using the terms "apathy", "treatment", and "Parkinson" or "Lewy body (bodies)." The results were filtered for "clinical trials" and "case reports." We included articles if apathy was measured as an outcome measure, before and after treatment. References of included articles were also reviewed. RESULTS: The PD search identified 19 articles: 13 randomized control trials (RCTs), 4 open-label studies, 1 case series, and 1 case report. Apathy was the primary outcome in 11 out of 19 studies. A decrease in apathy ratings was seen in 14 of the 19 studies. Of these 14 studies, 9 investigated medications with some dopaminergic effect. Three investigated acetylcholinesterase inhibitors (AChEIs) and found benefit in improving apathy. The DLB search identified 4 articles: 1 RCT, 2 open-label studies, and 1 case series. All 4 studies demonstrated decreased apathy and investigated AChEIs. CONCLUSIONS: We identified 23 studies that assessed the pharmacological treatment of apathy. In PD, agents with dopaminergic activity were the most studied and appeared to have the most benefit. AChEIs also appeared to have benefit in both PD and DLB but were less studied. Future studies of apathy treatment would benefit from larger samples and standardized assessments of apathy to define study populations and endpoints.
ESTHER : Liu_2019_Parkinsonism.Relat.Disord_60_14
PubMedSearch : Liu_2019_Parkinsonism.Relat.Disord_60_14
PubMedID: 30470658

Title : HFIP-Functionalized Co3 O4 Micro-Nano-Octahedra\/rGO as a Double-Layer Sensing Material for Chemical Warfare Agents - Alali_2019_Chemistry_25_11892
Author(s) : Alali KT , Liu J , Chen R , Liu Q , Zhang H , Li J , Hou J , Li R , Wang J
Ref : Chemistry , 25 :11892 , 2019
Abstract : Semiconductor metal oxides (SMO)-based gas-sensing materials suffer from insufficient detection of a specific target gas. Reliable selectivity, high sensitivity, and rapid response-recovery times under various working conditions are the main requirements for optimal gas sensors. Chemical warfare agents (CWA) such as sarin are fatal inhibitors of acetylcholinesterase in the nerve system. So, sensing materials with high sensitivity and selectivity toward CWA are urgently needed. Herein, micro-nano octahedral Co3 O4 functionalized with hexafluoroisopropanol (HFIP) were deposited on a layer of reduced graphene oxide (rGO) as a double-layer sensing materials. The Co3 O4 micro-nano octahedra were synthesized by direct growth from electrospun fiber templates calcined in ambient air. The double-layer rGO/Co3 O4 -HFIP sensing materials presented high selectivity toward DMMP (sarin agent simulant, dimethyl methyl phosphonate) versus rGO/Co3 O4 and Co3 O4 sensors after the exposure to various gases owing to hydrogen bonding between the DMMP molecules and Co3 O4 -HFIP. The rGO/Co3 O4 -HFIP sensors showed high stability with a response signal around 11.8 toward 0.5 ppm DMMP at 125 degrees C, and more than 75 % of the initial response was maintained under a saturated humid environment (85 % relative humidity). These results prove that these double-layer inorganic-organic composite sensing materials are excellent candidates to serve as optimal gas-sensing materials.
ESTHER : Alali_2019_Chemistry_25_11892
PubMedSearch : Alali_2019_Chemistry_25_11892
PubMedID: 31309626

Title : Hepatoprotective Potential of Partially Hydrolyzed Guar Gum against Acute Alcohol-Induced Liver Injury in Vitro and Vivo - Wu_2019_Nutrients_11_
Author(s) : Wu C , Liu J , Tang Y , Li Y , Yan Q , Jiang Z
Ref : Nutrients , 11 : , 2019
Abstract : Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by beta-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kgday). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IkappaBalpha, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury.
ESTHER : Wu_2019_Nutrients_11_
PubMedSearch : Wu_2019_Nutrients_11_
PubMedID: 31035540

Title : Bisphenol F-Induced Neurotoxicity toward Zebrafish Embryos - Yuan_2019_Environ.Sci.Technol_53_14638
Author(s) : Yuan L , Qian L , Qian Y , Liu J , Yang K , Huang Y , Wang C , Li Y , Mu X
Ref : Environ Sci Technol , 53 :14638 , 2019
Abstract : In this study, the influence of bisphenol F (BPF) toward central nervous system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity toward zebrafish embryos, including inhibited locomotion, reduced moving distance, and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. Peripheral motor neuron development was significantly inhibited by BPF at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-seq assay implied that the transcriptional changes were not mediated by ERalpha. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, and acetylcholine) or acetylcholinesterase (Ache) enzyme activity after BPF exposure, indicating that BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentration.
ESTHER : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedSearch : Yuan_2019_Environ.Sci.Technol_53_14638
PubMedID: 31702913

Title : Fluevirines E and F, two new alkaloids from Flueggea virosa - Yang_2019_Nat.Prod.Res__1
Author(s) : Yang X , Liu J , Huo Z , Yuwen H , Li Y , Zhang Y
Ref : Nat Prod Res , :1 , 2019
Abstract : Two new alkaloids, fluevirines E (1) and F (2), along with six known Securinega alkaloids, were isolated from the methanol extract of the twigs and leaves of Flueggea virosa. The structures and absolute configurations of the new compounds were elucidated by means of MS, NMR, and ECD analyses. Compound 1 is a new dimeric indole alkaloid while 2 is a new securinega-type alkaloid. The in vitro cytotoxic activities of the isolated alkaloids against several human cancer cell lines and their acetylcholinesterase inhibitory activity were also evaluated.
ESTHER : Yang_2019_Nat.Prod.Res__1
PubMedSearch : Yang_2019_Nat.Prod.Res__1
PubMedID: 30721084

Title : Different durations of cognitive stimulation therapy for Alzheimer's disease: a systematic review and meta-analysis - Chen_2019_Clin.Interv.Aging_14_1243
Author(s) : Chen J , Duan Y , Li H , Lu L , Liu J , Tang C
Ref : Clin Interv Aging , 14 :1243 , 2019
Abstract : Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of cognitive stimulation therapy (CST) of different durations for Alzheimer's disease (AD). Methods: A comprehensive search was carried out in three databases. The primary outcome was Mini-Mental State Examination (MMSE) score. We conducted a meta-analysis with Review Manager, version 5.3 and assessed the methodological quality of the included studies using the Cochrane Collaboration Recommendations assessment tool. Results: Treatment effects from the meta-analysis showed that CST plus acetylcholinesterase inhibitors (ChEIs) was better than the control assessed by MMSE. In addition, the meta-analysis indicated that long-term CST was better than short-term or maintenance CST. Conclusion: Our study confirmed that the combination of CST and drug treatment for AD is effective in AD, regardless of whether short-term CST, maintenance CST, or long-term CST is used. The long-term CST appears to be more effective.
ESTHER : Chen_2019_Clin.Interv.Aging_14_1243
PubMedSearch : Chen_2019_Clin.Interv.Aging_14_1243
PubMedID: 31371930

Title : Kinetic model of the enzymatic Michael addition for synthesis of mitomycin analogs catalyzed by immobilized lipase from T. laibacchii - Zhang_2019_Mol.Catal_466_146
Author(s) : Zhang Y , Zhao Y , Gao X , Jiang W , Li Z , Yao Q , Yang F , Wang F , Liu J
Ref : Molecular Catalysis , 466 :146 , 2019
Abstract : The present study investigates the kinetic model of the enzymatic Michael addition of butylamine to 2-methyl-1,4-benzoquinone to form 2-methyl-3-n-butylaminoyl-1-hydro-4-quinone in citrate buffer solution (pH 7.0). The yield of the product of 98% was achieved, mainly due to the excellent regioselectivity of immobilized lipase from T. laibacchii. The immobilized preparation used here was obtained by a method of purification and in situ immobilization. Through the purification using a PEG 4000/ K2HPO4 aqueous two-phase system (ATPS), the T. laibacchii lipase was partitioned predominantly in the PEG-rich top phase where diatomite was added to achieve in situ immobilization via interfacial activation on the hydrophobic support. A proposed reaction mechanism of the Michael addition involves (1) the oxyanion hole polarizes the alpha,beta-unsaturated carbonyl of 2-methyl-1,4 -benzoquinone, increasing its electrophilic ability, (2) the catalytic histidine deprotonates the nucleophile n-butyl amine. A modified sequential mechanism including ordered and random sequential bi-bi was proposed for the first, and it is beneficial to add these modification mechanisms to the family of enzyme complex reaction mechanism because the mechanism is partly expanded. The kinetic parameters were directly obtained by combining the numerical integration toolbox ode45 to solve differential equations and the nonlinear optimization toolbox fmincon for error minimizing objective function. A very satisfactory agreement between experimental data and model results was obtained based on the modified random bi-bi mechanism, implying that the enzymatic Michael addition may follow the modified random bi-bi mechanism. The mass transfer limitations were investigated, and it is found that both internal and external mass transfer limitations could be ignored.
ESTHER : Zhang_2019_Mol.Catal_466_146
PubMedSearch : Zhang_2019_Mol.Catal_466_146

Title : Effects of Chlorpyrifos on Cholinesterase and Serine Lipase Activities and Lipid Metabolism in Brains of Rainbow Trout (Oncorhynchus mykiss) - Greer_2019_Toxicol.Sci_172_146
Author(s) : Greer JB , Magnuson JT , Hester K , Giroux M , Pope C , Anderson T , Liu J , Dang V , Denslow ND , Schlenk D
Ref : Toxicol Sci , 172 :146 , 2019
Abstract : Chlorpyrifos is an organophosphorus insecticide that elicits acute toxicity through inhibition of acetylcholinesterase (AChE), leading to acetylcholine accumulation and prolonged stimulation of cholinergic receptors throughout the central and peripheral nervous systems. Previous studies have indicated that neurodevelopment may also be impaired through alternative pathways, including reduction of cAMP catalyzed downstream events. The upstream initiating events that underlie non-cholinergic neurological actions of chlorpyrifos and other organophosphorus compounds remain unclear. To investigate the potential role of disruption of fatty acid signaling as a mechanism of toxicity, lipid metabolism and fatty acid profiles were examined to identify alterations that may play a critical role in upstream signaling in the CNS. Juvenile rainbow trout were treated for 7 days with nominal chlorpyrifos concentrations previously reported to diminish olfactory responses (10, 20, and 40 microg/L). While lethality was noted higher doses, measured chlorpyrifos concentrations of 1.38 microg/L (nominal concentration 10 microg/L) significantly reduced the activity of AChE and two serine lipases, monoacylglycerol lipase and fatty acid amide hydrolase in the brain. Reductions in lysophosphatidylethanolamines (16:0; 18:0, 18:1, and 22:6) derived from the phosphatidylethanolamines and free fatty acids (Palmitic acid16:0; Linolenic acid18:3; Eicosadienoic acid 20:2; Arachidonic acid 20:4; and Docosahexaenoic acid 22:6) were also noted, suggesting that chlorpyrifos inhibited the metabolism of selected phospholipid signaling precursors at sublethal concentrations. These results indicate that in addition to AChE inhibition, environmentally relevant chlorpyrifos exposure alters serine lipase activity and lipid metabolites in the trout brain, which may compromise neuronal signaling and impact neurobehavioral responses in aquatic animals.
ESTHER : Greer_2019_Toxicol.Sci_172_146
PubMedSearch : Greer_2019_Toxicol.Sci_172_146
PubMedID: 31359069

Title : Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection - Zhang_2019_Antiviral.Res__104693
Author(s) : Zhang H , Liu J , Zhu X , Li X , Jin W , Chen H , Wu M , Li C , Liu C , JunqiNiu , Ding Y
Ref : Antiviral Res , :104693 , 2019
Abstract : BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224.
ESTHER : Zhang_2019_Antiviral.Res__104693
PubMedSearch : Zhang_2019_Antiviral.Res__104693
PubMedID: 31838002

Title : Systematic exploration of Astragalus membranaceus and Panax ginseng as immune regulators: Insights from the comparative biological and computational analysis - Liu_2019_Phytomedicine__153077
Author(s) : Liu J , Nile SH , Xu G , Wang Y , Kai G
Ref : Phytomedicine , :153077 , 2019
Abstract : BACKGROUND: Immune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) as immune booster and help to control diseases with their healthy synergistic effect on immune system. PURPOSE: This study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study. METHODS: Computational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis. RESULTS: AM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups. CONCLUSION: A novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.
ESTHER : Liu_2019_Phytomedicine__153077
PubMedSearch : Liu_2019_Phytomedicine__153077
PubMedID: 31477352

Title : Latrophilin mediates insecticides susceptibility and fecundity through two carboxylesterases, esterase4 and esterase6, in Tribolium castaneum - Wei_2019_Bull.Entomol.Res__1
Author(s) : Wei L , Gao S , Xiong W , Liu J , Mao J , Lu Y , Song X , Li B
Ref : Bull Entomol Res , :1 , 2019
Abstract : Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
ESTHER : Wei_2019_Bull.Entomol.Res__1
PubMedSearch : Wei_2019_Bull.Entomol.Res__1
PubMedID: 30789108

Title : Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model - Shen_2019_Brain.Behav.Immun_81_535
Author(s) : Shen Y , Peng W , Chen Q , Hammock BD , Liu J , Li D , Yang J , Ding J , Wang X
Ref : Brain Behavior & Immunity , 81 :535 , 2019
Abstract : PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127mg/kg) and pilocarpine (40mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1mg/kg/d) was intragastrically given for 4weeks from the 21st day after SE induction in the SRS+0.1 TPPU group. The SRS+PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). RESULTS: The frequency of SRS was significantly decreased at 6weeks and 7weeks after SE induction in the 0.1TPP U group compared with the SRS+PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-alpha, IL-1beta, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS+PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed. The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS+PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. CONCLUSION: TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviours in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression.
ESTHER : Shen_2019_Brain.Behav.Immun_81_535
PubMedSearch : Shen_2019_Brain.Behav.Immun_81_535
PubMedID: 31306773

Title : Bioconcentration of the antiepileptic drug carbamazepine and its physiological and biochemical effects on Daphnia magna - Nkoom_2019_Ecotoxicol.Environ.Saf_172_11
Author(s) : Nkoom M , Lu G , Liu J , Yang H , Dong H
Ref : Ecotoxicology & Environmental Safety , 172 :11 , 2019
Abstract : Owing to its persistence, carbamazepine an antiepileptic drug is regularly detected in the aquatic environment. The motive for our research was to assess the bioconcentration, physiological and biochemical effects of carbamazepine in Daphnia magna. A 48h aqueous exposure of carbamazepine yielded bioconcentration factors of 202.56 and 19.95 in Daphnia magna for the respective nominal treatments of 5 and 100microg/L. Apparently, the inhibition of the capability of Daphnia magna to obtain food attributable to carbamazepine exposure will reduce their fitness to reproduce as well as to grow. Also, a significant alteration in the phototactic behaviour of Daphnia magna exposed to carbamazepine is maladaptive since it will increase their chance of being preyed upon in the surface water during daylight. Again, a significant decline in the acetylcholinesterase activity observed herein brings to light the neurotoxicity of carbamazepine to Daphnia magna. Moreover, significant inhibition of the superoxide dismutase, catalase and glutathione reductase activities coupled with the simultaneous induction of the malondialdehyde content imply that carbamazepine evoked a life-threatening oxidative stress that overpowered the antioxidant defence system of Daphnia magna. These observations confirm that carbamazepine can accumulate and consequently cause negative physiological and biochemical changes to wild Daphnia magna populations.
ESTHER : Nkoom_2019_Ecotoxicol.Environ.Saf_172_11
PubMedSearch : Nkoom_2019_Ecotoxicol.Environ.Saf_172_11
PubMedID: 30669069

Title : Myasthenia gravis and specific immunotherapy: monoclonal antibodies - Cai_2019_Ann.N.Y.Acad.Sci_1452_18
Author(s) : Cai XJ , Li ZW , Xi JY , Song HZ , Liu J , Zhu WH , Guo Y , Jiao Z
Ref : Annals of the New York Academy of Sciences , 1452 :18 , 2019
Abstract : Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.
ESTHER : Cai_2019_Ann.N.Y.Acad.Sci_1452_18
PubMedSearch : Cai_2019_Ann.N.Y.Acad.Sci_1452_18
PubMedID: 31393614

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells - Wan_2019_FASEB.J__fj201802675R
Author(s) : Wan L , Xia T , Du Y , Liu J , Xie Y , Zhang Y , Guan F , Wu J , Wang X , Shi C
Ref : FASEB Journal , :fj201802675R , 2019
Abstract : The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed via electron microscopy, Western blot analysis, and acetylcholinesterase activity. Confocal microscopy was used to measure the uptake of exosomes by quiescent HSCs, Kupffer cells (KCs), and liver sinusoidal endothelial cells (LSECs). Hif-1alpha was inhibited via 2-ME or specific small interfering RNAs to investigate its role in exosomes derived from HSCs. It was determined that glucose transporter 1 and pyruvate kinase M2 were increasingly expressed in fibrotic liver samples, cell lysates, and exosomes derived from activated HSCs. Exosomes released from HSCs were associated with activation and glucose uptake of HSCs. Delivery of exosomes from activated HSCs induced glycolysis of quiescent HSCs, KCs, and LSECs. Disruption of Hif-1 expression suppressed the glycolysis effect delivered by exosomes. Conclusively, our results demonstrated that exosomes secreted by activated HSCs affect the metabolic switch of liver nonparenchymal cells via delivery of glycolysis-related proteins. These findings represent a novel mechanism that contributes to liver fibrosis and has significant implications for new diagnosis and treatment of liver diseases.-Wan, L., Xia, T., Du, Y., Liu, J., Xie, Y., Zhang, Y., Guan, F., Wu, J., Wang, X., Shi, C. Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exomes in metabolic switch of liver nonparenchymal cells.
ESTHER : Wan_2019_FASEB.J__fj201802675R
PubMedSearch : Wan_2019_FASEB.J__fj201802675R
PubMedID: 30970216

Title : Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest - Hai_2019_Crit.Care.Med_47_e144
Author(s) : Hai K , Chen G , Gou X , Jang H , Gong D , Cheng Y , Gong C , Li X , Liu Y , Li H , Zhang G , Yang L , Ke B , Liu J
Ref : Critical Care Medicine , 47 :e144 , 2019
Abstract : OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.
ESTHER : Hai_2019_Crit.Care.Med_47_e144
PubMedSearch : Hai_2019_Crit.Care.Med_47_e144
PubMedID: 30431495

Title : Molecular and phenotypic responses of male crucian carp (Carassius auratus) exposed to perfluorooctanoic acid - Dong_2019_Sci.Total.Environ_653_1395
Author(s) : Dong H , Lu G , Yan Z , Liu J , Ji Y
Ref : Sci Total Environ , 653 :1395 , 2019
Abstract : Perfluorooctanoic acid (PFOA) has long been produced and widely used due to its excellent water and oil repellent properties. However, this trend has facilitated to the ubiquitous existence of PFOA in environmental matrix, and the potential ecotoxicity on aquatic organisms has not been fully elucidated. To study the tissue-specific bioconcentration and the nervous system- and energy-related biochemical effects of PFOA, as well as the phenotypic alterations by this chemical, male crucian carp (Carassius auratus) were exposed to gradient concentrations of PFOA (nominal 0.2, 10, 500 and 25,000mug/L) in a flow-through apparatus for 7days. PFOA was enriched in tissues following an order of blood>kidney>/=liver>gill>brain>muscle. The bioconcentration factors ranged from 0.1 to 60.4. Acetylcholinesterase activity in the fish brain was inhibited, while liver carboxylesterase was induced in most cases and attenuated with time. The acyl-CoA oxidase activity was dose-dependently elevated and accompanied by a decline of ATP contents. PFOA treatments also inhibited the activity of the electron transport system (ETS). At the transcriptional level, ETS component complexes II and IV were concordantly depressed, and ATP synthesis was also downregulated. The mRNA level of peroxisome proliferator activated receptor alpha was increasingly upregulated, with related downstream genes upregulated in varying degrees. The phenotypes showed patterns of increased liver pathology and reduced swimming activity. In summary, PFOA leads to adverse effects in Carassius auratus related to multiple aspects, which may be associated with the nervous system, fundamental energy metabolism and other unpredictable factors. The results obtained in this study are expected to help clarify the PFOA toxic mechanisms on energy relevance.
ESTHER : Dong_2019_Sci.Total.Environ_653_1395
PubMedSearch : Dong_2019_Sci.Total.Environ_653_1395
PubMedID: 30759578

Title : A Review of Danshen Combined with Clopidogrel in the Treatment of Coronary Heart Disease - Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
Author(s) : Zhang Z , Wang Y , Tan W , Wang S , Liu J , Liu X , Wang X , Gao X
Ref : Evid Based Complement Alternat Med , 2019 :2721413 , 2019
Abstract : Objective: Danshen, the root of Salvia miltiorrhiza Bunge, is a traditional herbal medicine in China, which has been used to treat irregular menstruation, cold hernia, and abdominal pain for thousands of years. Danshen is frequently used in combination with drugs to treat cardiovascular diseases. Clopidogrel is a commonly used drug for treating coronary heart disease, but clopidogrel resistance restricts its development. Therefore, the clinical efficacy of Danshen combined with clopidogrel treats coronary heart disease and the relationship between Danshen and clopidogrel metabolism enzymes is suggested for future investigations. Materials and Methods: The information was collected by searching online databases, and the RevMan 5.3 software was used to perform meta-analysis. Results: Twenty-two articles, including 2587 patients, were enrolled after the evaluation. Meta-analysis showed that Danshen combined with clopidogrel was more effective than clopidogrel alone in treating coronary heart disease by improving clinical curative effect, reducing the frequency of angina pectoris, improving electrocardiogram results, shortening the duration of angina pectoris, and easing adverse reactions. Danshen inhibited carboxylesterase 1 and most enzyme of cytochrome P450, especially cytochrome P450 1A2, which may affect the metabolism of clopidogrel. Conclusion: Danshen combined with clopidogrel may compensate for individual differences of clopidogrel resistance among individuals in the treatment of coronary heart disease. Meanwhile, the inhibitory effect of Danshen on cytochrome P450 and carboxylesterase 1 could be partly responsible for the synergistic and attenuating effects of Danshen combined with clopidogrel.
ESTHER : Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
PubMedSearch : Zhang_2019_Evid.Based.Complement.Alternat.Med_2019_2721413
PubMedID: 30911318

Title : Tacrine-Hydrogen Sulfide Donor Hybrid Ameliorates Cognitive Impairment in the Aluminum Chloride Mouse Model of Alzheimer's Disease - Cheng_2019_ACS.Chem.Neurosci_10_3500
Author(s) : Cheng XJ , Gu JX , Pang YP , Liu J , Xu T , Li XR , Hua YZ , Newell KA , Huang XF , Yu Y , Liu Y
Ref : ACS Chem Neurosci , 10 :3500 , 2019
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive loss of memory and cognitive function, and is associated with the deficiency of synaptic acetylcholine, as well as chronic neuroinflmmation. Tacrine, a potent acetylcholinesterase (AChE) inhibitor, was previously a prescribed clinical therapeutic agent for AD, but it was recently withdrawn because it caused widespread hepatotoxicity. Hydrogen sulfide (H2S) has neuroprotective, hepatoprotective, and anti-inflammatory effects. In this study, we synthesized a new compound, a tacrine-H2S donor hybrid (THS) by introducing H2S-releasing moieties (ACS81) to tacrine. Subsequently, pharmacological and biological evaluations of THS were conducted in the aluminum trichloride (AlCl3)-induced AD mice model. We found that THS (15 mmol/kg) improved cognitive and locomotor activity in AD mice in the step-through test and open field test, respectively. THS showed strong AChE inhibitory activity in the serum and hippocampus of AD mice and induced increased hippocampal H2S levels. Furthermore, THS reduced mRNA expression of the proinflammatory cytokines, TNF-alpha, IL-6, and IL-1beta and increased synapse-associated proteins (synaptophysin and postsynaptic density protein 95) in the hippocampus of AD mice. Importantly, THS, unlike tacrine, did not increase liver transaminases (alanine transaminase and aspartate transaminase) or proinflammatory cytokines, indicating THS is much safer than tacrine. Therefore, the multifunctional effects of this new hybrid compound of tacrine and H2S indicate it is a promising compound for further research into the treatment of AD.
ESTHER : Cheng_2019_ACS.Chem.Neurosci_10_3500
PubMedSearch : Cheng_2019_ACS.Chem.Neurosci_10_3500
PubMedID: 31244052

Title : NOTUM inhibition increases endocortical bone formation and bone strength - Brommage_2019_Bone.Res_7_2
Author(s) : Brommage R , Liu J , Vogel P , Mseeh F , Thompson AY , Potter DG , Shadoan MK , Hansen GM , Jeter-Jones S , Cui J , Bright D , Bardenhagen JP , Doree DD , Moverare-Skrtic S , Nilsson KH , Henning P , Lerner UH , Ohlsson C , Sands AT , Tarver JE , Powell DR , Zambrowicz B , Liu Q
Ref : Bone Res , 7 :2 , 2019
Abstract : The disability, mortality and costs caused by non-vertebral osteoporotic fractures are enormous. Existing osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral fractures. Cortical bone is a major determinant of non-vertebral bone strength. To identify novel osteoporosis drug targets, we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable genes. Cortical bone thickness was substantially elevated in Notum (-/-) mice. NOTUM is a secreted WNT lipase and we observed high NOTUM expression in cortical bone and osteoblasts but not osteoclasts. Three orally active small molecules and a neutralizing antibody inhibiting NOTUM lipase activity were developed. They increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone formation. Thus, inhibition of NOTUM activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.
ESTHER : Brommage_2019_Bone.Res_7_2
PubMedSearch : Brommage_2019_Bone.Res_7_2
PubMedID: 30622831
Gene_locus related to this paper: human-NOTUM

Title : Bioconcentration, behavioral, and biochemical effects of the non-steroidal anti-inflammatory drug diclofenac in Daphnia magna - Nkoom_2019_Environ.Sci.Pollut.Res.Int_26_5704
Author(s) : Nkoom M , Lu G , Liu J , Dong H , Yang H
Ref : Environ Sci Pollut Res Int , 26 :5704 , 2019
Abstract : The non-steroidal anti-inflammatory drug (NSAID) diclofenac is one of the most frequently studied as well as controversially discussed pharmaceutically active drug on the subject of its relevance to the environment. This study was conducted to assess the bioconcentration potential of diclofenac and its behavioral and biochemical effects in Daphnia magna. The bioconcentration factors of diclofenac determined after 48 h of aqueous exposure in Daphnia magna were 70.94 and 8.02 for the nominal exposure concentrations of 5 and 100 mug/L, respectively. Diclofenac exposure obviously decreased the filtration and ingestion rates of the daphnids. A significant increase of the acetylcholinesterase activity that was observed in this study indicates that diclofenac might not have neurobehavioral toxicity in Daphnia magna. Significant induction of malondialdehyde content is an indication of overproduction of reactive oxygen species leading to oxidative damage in daphnids after diclofenac exposure. Moreover, significant inhibition of the superoxide dismutase, catalase, and glutathione reductase activities implies that the antioxidant defense system of Daphnia magna was overwhelmed. Also, significant inhibition of glutathione s-transferase activity might point to the fact that the enzyme was not capable to detoxify diclofenac in Daphnia magna. These findings indicate that diclofenac can accumulate and consequently stimulate behavioral and biochemical disturbances in Daphnia magna.
ESTHER : Nkoom_2019_Environ.Sci.Pollut.Res.Int_26_5704
PubMedSearch : Nkoom_2019_Environ.Sci.Pollut.Res.Int_26_5704
PubMedID: 30612359

Title : Urinary biomarkers for assessment of human exposure to monomeric aryl phosphate flame retardants - Zhao_2019_Environ.Int_124_259
Author(s) : Zhao F , Kang Q , Zhang X , Liu J , Hu J
Ref : Environ Int , 124 :259 , 2019
Abstract : While monomeric aryl organophosphate flame retardants (m-aryl-OPFRs) are used worldwide in a variety of consumer products, specific biomarkers for epidemiologic studies are lacking. To explore the potential of urinary hydroxylated metabolites of m-aryl-OPFRs as the biomarkers, we detected triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP) in 259 whole blood samples and their 5 hydroxylated and 2 diester metabolites in the paired urine samples from the general population. 2-Ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), and 3-hydroxy-4-methylphenyl di-p-tolyl phosphate (3-OH-MDTP) were detected in >80% of urine samples after enzymatic hydrolysis of conjugates, and their concentrations showed significant positive correlations with the blood concentrations of their corresponding parent compounds, respectively. To characterize the temporal reliability, the m-aryl-OPFRs metabolites were also determined in urine samples repeated nine times from six volunteers over 3 months. Urinary 5-OH-EHDPP showed strong temporal reliability (creatinine-corrected intraclass correlation coefficients (ICCs), 0.77; 95% confidence interval [CI], 0.58 to 0.90), and urinary 3-OH-MDTP (creatinine-corrected ICC, 0.52; 95% CI, 0.37 to 0.87) and 4-OH-TPHP (0.56; 95% CI, 0.32 to 0.80) showed moderate-to-strong temporal reliability, while relatively weak temporal reliability was found for urinary DPHP (creatinine-corrected ICC, 0.37; 95% CI, 0.12 to 0.62). This study confirmed specific, reliable, and frequently detected biomarkers for TPHP and EHDPP and developed new biomarker of TCrP for future epidemiological research on health effects of m-aryl-OPFRs.
ESTHER : Zhao_2019_Environ.Int_124_259
PubMedSearch : Zhao_2019_Environ.Int_124_259
PubMedID: 30660026

Title : Bioconcentration and effects of hexabromocyclododecane exposure in crucian carp (Carassius auratus) - Dong_2018_Ecotoxicology_27_313
Author(s) : Dong H , Lu G , Yan Z , Liu J , Yang H , Nkoom M
Ref : Ecotoxicology , 27 :313 , 2018
Abstract : As a cycloaliphatic brominated flame retardant, hexabromocyclododecane (HBCD) has been widely used in building thermal insulation and fireproof materials. However, there is little information on the bioconcentration as well as effects with respect to HBCD exposure in the aquatic environment. To investigate the bioconcentration of HBCD in tissues (muscle and liver) and its biochemical and behavioural effects, juvenile crucian carp (Carassius auratus) were exposed to different concentrations of technical HBCD (nominal concentrations, 2, 20, 200 mug/L) for 7 days, using a flow-through exposure system. HBCD was found to concentrate in the liver and muscle with a terminal concentration of 0.60 +/- 0.22 mug/g lw (lipid weight) and 0.18 +/- 0.02 mug/g lw, respectively, at an environmentally-relevant concentration (2 mug/L). The total thyroxine and total triiodothyronine in the fish plasma were lowered as a result of exposure to the HBCD. Acetylcholinesterase activity in the brain was increased, while swimming activity was inhibited and shoaling inclination was enhanced after exposure to 200 mug/L HBCD. Feeding rate was suppressed in the 20 and 200 mug/L treatment groups. In summary, HBCD concentrations 10-100x higher than the current environmentally-relevant exposures induced adverse effects in the fish species tested in this study. These results suggest that increasing environmental concentrations and/or species with higher sensitivity than carp might be adversely affected by HBCD.
ESTHER : Dong_2018_Ecotoxicology_27_313
PubMedSearch : Dong_2018_Ecotoxicology_27_313
PubMedID: 29404869

Title : Predicting plant immunity gene expression by identifying the decoding mechanism of calcium signatures - Lenzoni_2018_New.Phytol_217_1598
Author(s) : Lenzoni G , Liu J , Knight MR
Ref : New Phytol , 217 :1598 , 2018
Abstract : Calcium plays a key role in determining the specificity of a vast array of signalling pathways in plants. Cellular calcium elevations with different characteristics (calcium signatures) carry information on the identity of the primary stimulus, ensuring appropriate downstream responses. However, the mechanism for decoding calcium signatures is unknown. To determine this, decoding of the salicylic acid (SA)-mediated plant immunity signalling network controlling gene expression was examined. A dynamic mathematical model of the SA-mediated plant immunity network was developed. This model was used to predict responses to different calcium signatures; these were validated empirically using quantitative real-time PCR to measure gene expression. The mechanism for decoding calcium signatures to control expression of plant immunity genes enhanced disease susceptibility 1 (EDS1) and isochorismate synthase 1 (ICS1) was identified. Calcium, calmodulin, calmodulin-binding transcription activators (CAMTA)3 and calmodulin binding protein 60g (CBP60g) together amplify each calcium signature into three active signals, simultaneously regulating expression. The time required for calcium to return to steady-state level also quantitatively regulates gene expression. Decoding of calcium signatures occurs via nonlinear interactions between these active signals, producing a unique response in each case. Key properties of the calcium signatures are not intuitive, exemplifying the importance of mathematical modelling approaches. This approach can be applied to identifying the decoding mechanisms of other plant calcium signalling pathways.
ESTHER : Lenzoni_2018_New.Phytol_217_1598
PubMedSearch : Lenzoni_2018_New.Phytol_217_1598
PubMedID: 29218709

Title : Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II) - Wang_2018_Chem.Biol.Drug.Des_91_756
Author(s) : Wang J , Wang C , Wu Z , Li X , Xu S , Liu J , Lan Q , Zhu Z , Xu J
Ref : Chemical Biology Drug Des , 91 :756 , 2018
Abstract : A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC50 value of 0.15 nm and high AChE/BuChE selectivity (SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti-Alzheimer's disease agents.
ESTHER : Wang_2018_Chem.Biol.Drug.Des_91_756
PubMedSearch : Wang_2018_Chem.Biol.Drug.Des_91_756
PubMedID: 29112799

Title : Comparative in vitro and in vivo effects of chlorpyrifos oxon in the outbred CD-1 mouse (Mus musculus) and great plains toad (Anaxyrus cognatus) - Anderson_2018_Environ.Toxicol.Chem_37_1898
Author(s) : Anderson T , Liu J , McMurry S , Pope C
Ref : Environ Toxicol Chem , 37 :1898 , 2018
Abstract : We compared biochemical, functional, and behavioral responses to the organophosphorus anticholinesterase chlorpyrifos oxon (CPO) in mice (Mus musculus, CD-1) and toads (Anaxyrus cognatus, Great Plains toad). Toads were substantially less sensitive to acute lethality of CPO based on the maximum tolerated (nonlethal) dose (toads, 77 mg/kg; mice, 5.9 mg/kg). Sublethal exposures led to classical signs of toxicity (increased involuntary movements, autonomic secretions) in mice but hypoactivity in toads. Motor performance in an inclined plane test was not affected by CPO in mice but was altered at the highest dosage in toads. Acetylcholinesterase (AChE), butyrylcholinesterase, monoacylglycerol lipase, and fatty acid amide hydrolase activities in brain were inhibited in mice but not in toads, and fatty acid amide hydrolase activity in the liver was inhibited in both species. Toad brain AChE was less sensitive to in vitro inhibition by CPO (50% inhibitory concentration [IC50; 20 min, 37 degrees C], 101 vs 7.8 nM; IC50 [20 min, 26 degrees C], 149 vs 6.2 nM), and studies of inhibitor kinetics indicated substantially lower anticholinesterase potency of CPO against the toad brain enzyme. Using an in vitro indirect inhibition assay, preincubation of CPO with toad brain homogenate was more effective than an equivalent mouse brain homogenate at reducing CPO potency. These data suggest that the relatively low sensitivity of toads to cholinergic toxicity is based on the low sensitivity of brain AChE, which in turn may be attributable to more effective target-site detoxification. Environ Toxicol Chem 2018;37:1898-1906. (c) 2018 SETAC.
ESTHER : Anderson_2018_Environ.Toxicol.Chem_37_1898
PubMedSearch : Anderson_2018_Environ.Toxicol.Chem_37_1898
PubMedID: 29573455

Title : Lipase-mediated direct in situ ring-opening polymerization of E-caprolactone formed by a chemo-enzymatic method - Zhang_2018_J.Biotechnol_281_74
Author(s) : Zhang Y , Lu P , Sun Q , Li T , Zhao L , Gao X , Wang F , Liu J
Ref : J Biotechnol , 281 :74 , 2018
Abstract : A novel method to synthesize poly(sigma-caprolactone) (PCL) through a three-step, lipase-mediated chemo-enzymatic reaction from cyclohexanone using an immobilized lipase from Trichosporon laibacchii (T. laibacchii) CBS5791 was developed. The immobilized preparation with 1280 U. g(-1) used here was obtained by a method of purification and in situ immobilization where the crude intracellular lipase (cell homogenate) was subjected to partial purification by an aqueous two-phase system (ATPS) consisting of 12% (w/w) polyethylene glycol (PEG) 4000 and 13% (w/w) potassium phosphate (K(2)HPO(4)) and then in situ immobilization directly on diatomite from the top PEG-rich phase of ATPS. In this multi-step process, the sigma-caprolactone (sigma-CL) produced by lipase-mediated one-pot two-step chemo-enzymatic oxidation of cyclohexanone was directly subjected to in situ ring-opening polymerization (ROP) started by adding highly hydrophobic solvents. It is necessary to note that sigma-CL synthesis and its subsequent ROP were catalyzed by the same lipase. The impact of various reaction parameters, e.g., solvent, cyclohexanone: hydrogen peroxide molar ratio, hydrogen peroxide forms and reaction temperature were investigated. Toluene was selected as a preferred solvent due to supporting the highest molecular weight (M(n) = 2168) and moderate sigma-CL conversion (65.42%). Through the optimization of reaction conditions, PCL was produced with a M(n) of 2283 at 50 degreesC for 24 h. These results reveal that this lipase-mediated direct ring-opening polymerization of in situ formed sigma-CL is an alternative route to the conventional synthesis of PCL.
ESTHER : Zhang_2018_J.Biotechnol_281_74
PubMedSearch : Zhang_2018_J.Biotechnol_281_74
PubMedID: 29908204

Title : Molecular cloning and expression analysis of a prawn (Macrobrachium rosenbergii) juvenile hormone esterase-like carboxylesterase following immune challenge - Zhu_2018_Fish.Shellfish.Immunol_80_10
Author(s) : Zhu XJ , Xiong Y , He W , Jin Y , Qian YQ , Liu J , Dai ZM
Ref : Fish Shellfish Immunol , 80 :10 , 2018
Abstract : Methyl farnesoate (MF), the crustacean juvenile hormone (JH), plays critical roles in various physiological processes in crustaceans. The titer of MF is precisely regulated by specific carboxylesterase. Here, we report for the first time that the cloning and expression analysis of a JH esterase-like carboxylesterase from the prawn Macrobrachium rosenbergii (named as MrCXE). MrCXE contained a 1935-bp open reading frame (ORF) conceptually translated into a 644-amino acids protein. MrCXE protein shared the highest identity (36%) with JH esterase-like carboxylesterase from the swimming crab, Portunus trituberculatus and exhibited the typical motifs of JH esterase-like carboxylesterases. MrCXE was most abundantly expressed in hepatopancreas, the major tissue for MF metabolism. MrCXE was expressed at a low level in gut and was not detected in other tissues. Additionally, MrCXE expression was upregulated in hepatopancreas by eyestalk ablation to increase MF level. Furthermore, the mRNA level of MrCXE was significantly increased in the hepatopancreas when challenged by the bacterial pathogens Aeromonas hydrophila and Vibrio parahaemolyticus. To our knowledge, this is the first report that the JH esterase-like carboxylesterase is involved in the innate immune response of the crustaceans.
ESTHER : Zhu_2018_Fish.Shellfish.Immunol_80_10
PubMedSearch : Zhu_2018_Fish.Shellfish.Immunol_80_10
PubMedID: 29803663

Title : Design, synthesis and biological evaluation of new coumarin-dithiocarbamate hybrids as multifunctional agents for the treatment of Alzheimer's disease - Jiang_2018_Eur.J.Med.Chem_146_287
Author(s) : Jiang N , Huang Q , Liu J , Liang N , Li Q , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 146 :287 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's Disease (AD). The biological assays indicated that most of them showed potent inhibition and excellent selectivity towards acetylcholinesterase (AChE), and could inhibit self-induced beta-amyloid (Abeta) aggregation. Especially, compound 4n presented the highest ability to inhibit AChE (IC50, 0.027muM for hAChE) and good inhibition of Abeta aggregation (40.19% at 25muM). Kinetic and molecular modeling studies revealed that 4n was a mixed-type inhibitor, which could interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, it also possessed specific metal-chelating ability, good BBB permeability and low toxicity on SH-SY5Y neuroblastoma cells. Moreover, compound 4n did not exhibit any acute toxicity in mice at doses up to 1000mg/kg, and could reverse the cognitive dysfunction of scopolamine-induced AD mice. As far as we know, 4n was the first reported dithiocarbamate derivative with multifunctional activity. Its excellent profiles in vitro and effectivity in vivo highlight this structurally distinct compound as a potential lead compound in the research of innovative multifunctional drugs for AD.
ESTHER : Jiang_2018_Eur.J.Med.Chem_146_287
PubMedSearch : Jiang_2018_Eur.J.Med.Chem_146_287
PubMedID: 29407958

Title : Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum - Guo_2018_Org.Biomol.Chem_16_8130
Author(s) : Guo Y , Zhang N , Sun W , Duan X , Zhang Q , Zhou Q , Chen C , Zhu H , Luo Z , Liu J , Li XN , Xue Y , Zhang Y
Ref : Org Biomol Chem , 16 :8130 , 2018
Abstract : Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
ESTHER : Guo_2018_Org.Biomol.Chem_16_8130
PubMedSearch : Guo_2018_Org.Biomol.Chem_16_8130
PubMedID: 30334059

Title : Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae - Shi_2018_Aquat.Toxicol_203_80
Author(s) : Shi Q , Wang M , Shi F , Yang L , Guo Y , Feng C , Liu J , Zhou B
Ref : Aquat Toxicol , 203 :80 , 2018
Abstract : Triphenyl phosphate (TPhP), a typical organophosphate ester, is frequently detected in the environment and biota samples. It has been implicated as a neurotoxin as its structure is similar to neurotoxic organophosphate pesticides. The purpose of the present study was to investigate its potential developmental neurotoxicity in fish by using zebrafish larvae as a model. Zebrafish (Danio rerio) embryos were exposed to 0.8, 4, 20 and 100 mug/L of TPhP from 2 until 144 h post-fertilization. TPhP was found to have high bioconcentrations in zebrafish larvae after exposure. Further, it significantly reduced locomotor activity as well as the heart rate at the 100 mug/L concentration. TPhP exposure significantly altered the content of the neurotransmitters gamma-aminobutyric and histamine. Downregulation of the genes related to central nervous system development (e.g., alpha1-tubulin, mbp, syn2a, shha, and elavl3) as well as the corresponding proteins (e.g., alpha1-tubulin, mbp, and syn2a) was observed, but the gap-43 protein was found to upregulated. Finally, marked inhibition of total acetylcholinesterase activity, which is considered as a biomarker of neurotoxicant exposure, was also observed in the larvae. Our results indicate that exposure to environmentally relevant concentrations of TPhP can affect different parameters related to center nervous system development, and thus contribute to developmental neurotoxicity in early developing zebrafish larvae.
ESTHER : Shi_2018_Aquat.Toxicol_203_80
PubMedSearch : Shi_2018_Aquat.Toxicol_203_80
PubMedID: 30096480

Title : Study protocol for a randomised, double-blind, placebo-controlled 12-week pilot phase II trial of Sailuotong (SLT) for cognitive function in older adults with mild cognitive impairment - Steiner_2018_Trials_19_522
Author(s) : Steiner GZ , Bensoussan A , Liu J , Hohenberg MI , Chang DH
Ref : Trials , 19 :522 , 2018
Abstract : BACKGROUND: Mild cognitive impairment (MCI) is a syndrome characterised by a decline in cognition but relatively intact activities of daily living. People with MCI have an increased risk of developing dementia, and MCI is often referred to as a transitional stage between healthy ageing and dementia. Currently, there are no pharmaceutical therapies approved by the US Federal Drug Administration for MCI. Randomised controlled trials on the two major classes of anti-dementia pharmaceuticals, cholinesterase inhibitors and glutamate receptor antagonists, have produced poor results in MCI cohorts. There is a need to test and evaluate new and promising treatments for MCI that target multiple aspects of the syndrome's multi-faceted pathophysiology. The primary aim of this study is to evaluate the efficacy of 12 weeks of treatment with a standardised herbal formula, Sailuotong (SLT), compared to placebo, on cognition in older adults with MCI. Secondary aims are to assess SLT's mechanisms of action via electroencephalography (EEG), autonomic function, brain blood flow, and inflammation, as well as its safety in this cohort. METHODS/DESIGN: The target cohort for this trial is community-dwelling older adults over the age of 60 years who meet the National Institute of Aging-Alzheimer's Association working group core clinical criteria for MCI due to Alzheimer's disease. Eighty participants will be recruited and randomly allocated via a permuted block strategy at a 1:1 ratio to either the treatment or placebo group. The co-primary cognitive outcome measures are Logical Memory Story A delayed recall (episodic memory), Letter Number Sequencing (perceptual processing speed), and both the Trail Making Test and Rey Complex Figure Test (executive function). Secondary outcome measures are EEG activity, autonomic function (via electrocardiogram, skin conductance, and peripheral pulse pressure), brain blood flow (via common carotid artery ultrasound), and serum concentrations of inflammatory cytokines. Analyses will be performed blind to group allocation. DISCUSSION: This study is a 12-week, randomised, double-blind, placebo-controlled trial. Primary and secondary outcome measures will be compared between treatment and placebo groups at baseline and endpoint. Data from this pilot study will inform a larger, more highly powered clinical trial if the findings are positive. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000371392 Registered on 10 March 2017.
ESTHER : Steiner_2018_Trials_19_522
PubMedSearch : Steiner_2018_Trials_19_522
PubMedID: 30253809

Title : Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Chronic Ethanol-Induced Cardiac Fibrosis by Restoring Autophagic Flux - Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
Author(s) : Zhou C , Huang J , Li Q , Zhan C , He Y , Liu J , Wen Z , Wang DW
Ref : Alcohol Clin Exp Res , 42 :1970 , 2018
Abstract : BACKGROUND: Chronic drinking leads to myocardial contractile dysfunction and dilated cardiomyopathy, and cardiac fibrosis is a consequence of these alcoholic injuries. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) to less bioactive diols, and EETs have cardioprotective properties. However, the effects of sEH inhibition in ethanol (EtOH)-induced cardiac fibrosis are unknown. METHODS: This study was designed to investigate the role and underlying mechanisms of sEH inhibition in chronic EtOH feeding-induced cardiac fibrosis. C57BL/6J mice were fed a 4% Lieber-DeCarli EtOH diet for 8 weeks, and the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered throughout the experimental period. RESULTS: The results showed that chronic EtOH intake led to cardiac dilatation, collagen deposition, and autophagosome accumulation, while TPPU administration ameliorated these effects. In vitro, treating primary cardiac fibroblasts (CFs) with EtOH resulted in CF activation, including alpha smooth muscle actin overexpression, collagen synthesis, and cell migration. Moreover, EtOH disturbed CF autophagic flux, as evidenced by the increased LC3 II/I ratio and SQSTM1 expression, and by the enhanced autophagosome accumulation. TPPU treatment prevented the activation of CF induced by EtOH and restored the impaired autophagic flux by suppressing mTOR activation. CONCLUSIONS: Taken together, these findings suggest that sEH pharmacological inhibition may be a unique therapeutic strategy for treating EtOH-induced cardiac fibrosis.
ESTHER : Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
PubMedSearch : Zhou_2018_Alcohol.Clin.Exp.Res_42_1970
PubMedID: 30047995

Title : [Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases] - Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
Author(s) : Liu ZM , Fang F , Ding CH , Zhang WH , Deng J , Chen CH , Wang X , Liu J , Li Z , Jia XL , Zeng JS , Qian SY
Ref : Zhonghua Er Ke Za Zhi , 56 :216 , 2018
Abstract : Objective: To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT) Methods: The clinical data of 2 patients with congenital myasthenia syndrome were collected, and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital, Capital Medical University. The clinical features and gene mutation characteristics were analyzed, and the patients were followed-up for therapeutic efficacy. Results: The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively. The two patients were admitted to the PICU due to dyspnea, cyanotic episodes that required intubation. The patients had repeated apnea and became ventilator dependent. Case 1 died due to refusal of any treatment. Case 2 had a tracheotomy, and gradually weaned from ventilator after using pyridostigmine. The hospitalization of case 2 lasted 162 days. Case 2 was followed up to the age of 3 years and 4 months, and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation. Both cases were negative for anti-AChR, anti-acetylcholinesterase, anti-MuSK antibodies. Neostigmine test was negative in case 1 and suspiciously positive in case 2. Low-frequency repetitive nerve stimulation testing of case 2 was negative. Cranial MRI scans of both cases showed brain atrophy-like change. Genetic testing showed compound heterozygous deletions (exon 4, 5, 6) and pathogenic variant c.914T>C (p.I305T) in CHAT in case 1, compound heterozygous variants c.1007T>C (p.I336T) and c.64C>T (p.Q22X) in CHAT in case 2. To our knowledge, compound heterozygous deletions (exon 4, 5, 6) and p.Q22X were novel, previously unreported variants. Conclusion: CMS-EA usually presents at birth or in the neonatal period with hypotonia, ptosis, dysphagia due to severe bulbar weakness, and respiratory insufficiency with cyanosis and apnea. Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.
ESTHER : Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
PubMedSearch : Liu_2018_Zhonghua.Er.Ke.Za.Zhi_56_216
PubMedID: 29518833

Title : Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers - Ding_2018_Ecotoxicol.Environ.Saf_161_563
Author(s) : Ding M , Yang Y , Duan X , Wang S , Feng X , Wang T , Wang P , Liu S , Li L , Liu J , Tang L , Niu X , Zhang Y , Li G , Yao W , Cui L , Wang W
Ref : Ecotoxicology & Environmental Safety , 161 :563 , 2018
Abstract : Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P<0.001). Multivariate analysis indicates that exposure group (b=-1.016, P<0.001), agender (b=0.365, P<0.001), drinking (b=0.271, P=0.004) and TERF1rs3863242 (b=-0.368, P=0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate.
ESTHER : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedSearch : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedID: 29929132

Title : Unexpected protonation state of Glu197 discovered from simulations of tacrine in butyrylcholinesterase - Wan_2018_Phys.Chem.Chem.Phys_20_14938
Author(s) : Wan X , Yao Y , Fang L , Liu J
Ref : Phys Chem Chem Phys , 20 :14938 , 2018
Abstract : Butyrylcholinesterase (BChE) has been actively involved in drug discoveries from many fields for decades. In the crystal structure of the BChE-tacrine complex, there is an unanticipated formyl-proline molecule resolved very close to tacrine, raising an essential question on how reliable it is to apply the binding pose in a crystal structure to analyze related experimental observations, in which no formyl-proline is actually involved. In this study, by performing a series of 100 ns molecular dynamics simulations, we demonstrate that it is safe to employ the structural information from this crystal structure to analyze related experimental observations. Surprisingly, Glu197 needs to be protonated to have the structures simulated appropriately. It should be noted that Glu197 has been commonly considered as deprotonated in diverse analyses due to its low pKa in aqueous solution, for which some interpretations are inconsistent or unclear. Our further investigation shows that the protonated Glu197 plays a very important role in preserving His438 within the catalytic triad through stabilizing a highly conserved water molecule. Interestingly, the catalytic triad and Glu197 have been long recognized for possibly deviating largely from the crystal structure, which might be catalytically deficient and is generally considered to result from the difference between the crystal and aqueous environment. Herein, our results suggest that the large deviations of the catalytic triad and Glu197 from the crystal structure are caused by the inappropriate protonation state of Glu197. This finding shall provide an important clue that has been long missing for a better understanding of BChE-related puzzles or even reconsideration of some BChE-catalyzed reaction mechanisms.
ESTHER : Wan_2018_Phys.Chem.Chem.Phys_20_14938
PubMedSearch : Wan_2018_Phys.Chem.Chem.Phys_20_14938
PubMedID: 29786716

Title : Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase - Zeng_2018_ACS.Catal_8_8856
Author(s) : Zeng S , Liu J , Anankanbil S , Chen M , Guo Z , Adams JP , Snajdrova R , Li Z
Ref : ACS Catal , 8 :8856 , 2018
Abstract : A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a-g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h-j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2-4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.
ESTHER : Zeng_2018_ACS.Catal_8_8856
PubMedSearch : Zeng_2018_ACS.Catal_8_8856
Gene_locus related to this paper: sphmc-SpL

Title : Quorum Sensing System of Ruegeria mobilis Rm01 Controls Lipase and Biofilm Formation - Su_2018_Front.Microbiol_9_3304
Author(s) : Su Y , Tang K , Liu J , Wang Y , Zheng Y , Zhang XH
Ref : Front Microbiol , 9 :3304 , 2018
Abstract : Quorum sensing (QS) promotes in situ extracellular enzyme (EE) activity via the exogenous signal N-acylhomoserine lactone (AHL), which facilitates marine particle degradation, but the species that engage in this regulatory mechanism remain unclear. Here, we obtained AHL-producing and AHL-degrading strains from marine particles. The strain Ruegeria mobilis Rm01 of the Roseobacter group (RBG), which was capable of both AHL producing and degrading, was chosen to represent these strains. We demonstrated that Rm01 possessed a complex QS network comprising AHL-based QS and quorum quenching (QQ) systems and autoinducer-2 (AI-2) perception system. Rm01 was able to respond to multiple exogenous QS signals through the QS network. By applying self-generated AHLs and non-self-generated AHLs and AI-2 QS signal molecules, we modulated biofilm formation and lipase production in Rm01, which reflected the coordination of bacterial metabolism with that of other species via eavesdropping on exogenous QS signals. These results suggest that R. mobilis might be one of the participators that could regulate EE activities by responding to QS signals in marine particles.
ESTHER : Su_2018_Front.Microbiol_9_3304
PubMedSearch : Su_2018_Front.Microbiol_9_3304
PubMedID: 30687283

Title : Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides against AChE and BChE - Yu_2018_Food.Funct_9_1173
Author(s) : Yu Z , Wu S , Zhao W , Ding L , Fan Y , Shiuan D , Liu J , Chen F
Ref : Food Funct , 9 :1173 , 2018
Abstract : Alzheimer's disease (AD) is a global health issue affecting millions of elderly people worldwide. The aim of the present study was to identify novel anti-AD peptides isolated from albumin. Anti-AD activities of the peptides were evaluated via inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results revealed that peptide KLPGF could effectively inhibit AChE with an inhibition rate of 61.23% at a concentration of 50 mug mL(-1). In addition, the peptide KLPGF came in contact with acylation sites and peripheral anion sites of AChE. The present study demonstrates that the peptide KLPGF could become a potential functional food intervention in AD.
ESTHER : Yu_2018_Food.Funct_9_1173
PubMedSearch : Yu_2018_Food.Funct_9_1173
PubMedID: 29363710

Title : Two birds, one stone: hesperetin alleviates chemotherapy-induced diarrhea and potentiates tumor inhibition - Yu_2018_Oncotarget_9_27958
Author(s) : Yu Y , Kong R , Cao H , Yin Z , Liu J , Nan X , Phan AT , Ding T , Zhao H , Wong STC
Ref : Oncotarget , 9 :27958 , 2018
Abstract : Chemotherapy-induced diarrhea (CID), with clinical high incidence, adversely affects the efficacy of cancer treatment and patients' quality of life. Our study demonstrates that the citrus flavonoid hesperetin (Hst) has a superior potential as a new agent to prevent and alleviate CID. In the animal model for irinotecan (CPT-11) induced CID, Hst could selectively inhibit intestinal carboxylesterase (CES2) and thus reduce the local conversion of CPT-11 to cytotoxic SN-38 which causes intestinal toxicity. Oral administration of Hst manifested an excellent anti-diarrhea efficacy, prohibiting 80% of severe and 100% of mild diarrhea in the CPT-11 administered tumor-bearing mice. In addition, a significant attenuation of intestinal inflammation contributed to the anti-diarrhea effect of Hst. Moreover, Hst was found to work synergistically with CPT-11 in tumor inhibition by suppressing the tumor's STAT3 activity and recruiting tumoricidal macrophages into the tumor microenvironment. The anti-intestinal inflammation and anti-STAT3 properties of Hst would contribute its broad benefits to the management of diarrhea caused by other chemo or targeted agents, and more importantly, enhance and reinforce the anti-tumor effects of these agents, to improve patient outcomes.
ESTHER : Yu_2018_Oncotarget_9_27958
PubMedSearch : Yu_2018_Oncotarget_9_27958
PubMedID: 29963254

Title : Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation - He_2018_Bioorg.Chem_81_512
Author(s) : He Q , Liu J , Lan JS , Ding J , Sun Y , Fang Y , Jiang N , Yang Z , Sun L , Jin Y , Xie SS
Ref : Bioorg Chem , 81 :512 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
ESTHER : He_2018_Bioorg.Chem_81_512
PubMedSearch : He_2018_Bioorg.Chem_81_512
PubMedID: 30245233

Title : ANNALS EXPRESS: Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China - Dai_2017_Ann.Clin.Biochem__4563217738801
Author(s) : Dai Y , Liu J , Yuan E , Lee Y , Wang Q , Jia L , Wang L , Su Y
Ref : Annals of Clinical Biochemistry , :4563217738801 , 2017
Abstract : AIMS: Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish essential to establish reference intervals for a range of analytes during pregnancy.
METHODS: The cross-sectional study was performed in 13656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analyzed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon's test. Reference intervals were established using a non-parametric method.
RESULTS: Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid, and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, beta2-microglobulin, and cystatin-C fell significantly during the first trimestersand then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established.
CONCLUSIONS: The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.
ESTHER : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedSearch : Dai_2017_Ann.Clin.Biochem__4563217738801
PubMedID: 29153025

Title : Polyionic complexes of butyrylcholinesterase and poly-l-lysine-g-poly(ethylene glycol): Comparative kinetics of catalysis and inhibition and in vitro inactivation by proteases and heat - Hester_2017_Chem.Biol.Interact_275_86
Author(s) : Hester K , Liu J , Flynn N , Sultatos LG , Geng L , Brimijoin S , Ramsey JD , Hartson S , Ranjan A , Pope C
Ref : Chemico-Biological Interactions , 275 :86 , 2017
Abstract : We previously reported that recombinant human butyrylcholinesterase (rhBChE) complexed with a series of copolymers of poly-l-lysine (PLL) with grafted (polyethylene) glycol (PEG) (i.e., PLL-g-PEG) showed reduced catalytic activity but relatively similar concentration-dependent inactivation of the organophosphorus inhibitor paraoxon. Herein, we compared the kinetics of catalysis (using butyrylthiocholine as the substrate) and inhibition (using four different inhibitors) of free and copolymer-complexed rhBChE. Using scanning electron microscopy, polyionic complexes of rhBChE with three different PLL-g-PEG copolymers (based on PLL size) appeared as spheroid-shaped particles with relatively similar particle sizes (median diameter = 35 nm). Relatively similar particle sizes were also noted using dynamic light scattering (mean = 26-35 nm). The three copolymer-complexed enzymes exhibited reduced kcat (30-33% reduction), but no significant changes in Km. Inhibitory potency (as reflected by the bimolecular rate constant, ki) was similar among the free and copolymer-complexed enzymes when paraoxon was the inhibitor, whereas statistically significant reductions in ki (16-60%) were noted with the other inhibitors. Sensitivity to inactivation by proteases and heat was also compared. Copolymer-complexed enzymes showed lesser time-dependent inactivation by the proteases trypsin and pronase and by heat compared to the free enzyme. Understanding the unique properties of PLL-g-PEG-BChE complexes may lead to enhanced approaches for use of BChE and other protein bioscavengers.
ESTHER : Hester_2017_Chem.Biol.Interact_275_86
PubMedSearch : Hester_2017_Chem.Biol.Interact_275_86
PubMedID: 28756151

Title : Biological effects of citalopram in a suspended sediment-water system on Daphnia magna - Yang_2017_Environ.Sci.Pollut.Res.Int_24_21180
Author(s) : Yang H , Lu G , Yan Z , Liu J , Ma B , Dong H
Ref : Environ Sci Pollut Res Int , 24 :21180 , 2017
Abstract : Suspended sediment (SPS) plays an important role in the aquatic ecosystems. Selective serotonin uptake inhibitors (SSRIs) are commonly used antidepressants and are frequently detected in aquatic environments. However, the biological effects of SSRIs in the presence of SPS are not well understood. To fill this gap, an SPS-water system was constructed to investigate the effects of citalopram (CIT) on Daphnia magna in the presence of SPS with different concentrations (0.1, 0.5, 1 g l(-1)) and organic carbon contents (0.5, 1, 1.5, 2%). A dialysis bag was applied in the exposure system to control the same dissolved concentration of CIT and prevent SPS from entering into the bag. The dissolved CIT concentration obviously decreased in the SPS-water system during the exposure period. The presence of SPS significantly increased the immobilization of D. magna, and the immobilization rates were positively correlated with the SPS concentration and negatively correlated with the organic carbon content in SPS. For a single exposure, CIT significantly increased superoxide dismutase (SOD) activity and inhibited acetylcholinesterase (AChE) activity in D. magna, while SPS itself did not change the SOD and AChE activities. In the SPS-water system, SOD activity was significantly suppressed, indicating that the SPS-CIT combination could result in oxidative damage. However, SPS did not enhance the neurotoxicity of D. magna that was induced by CIT. These results suggest that SPS exerts a vital role on the biological effects of CIT and the contaminants sorbed on SPS should be taken into consideration.
ESTHER : Yang_2017_Environ.Sci.Pollut.Res.Int_24_21180
PubMedSearch : Yang_2017_Environ.Sci.Pollut.Res.Int_24_21180
PubMedID: 28733820

Title : Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system - Liu_2017_Food.Chem_226_165
Author(s) : Liu Y , Zhang Q , Guo Y , Liu J , Xu J , Li Z , Wang J , Wang Y , Xue C
Ref : Food Chem , 226 :165 , 2017
Abstract : The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages.
ESTHER : Liu_2017_Food.Chem_226_165
PubMedSearch : Liu_2017_Food.Chem_226_165
PubMedID: 28254008

Title : Acetylcholinesterase Inhibitory Alkaloids from the Whole Plants of Zephyranthes carinata - Zhan_2017_J.Nat.Prod_80_2462
Author(s) : Zhan G , Zhou J , Liu J , Huang J , Zhang H , Liu R , Yao G
Ref : Journal of Natural Products , 80 :2462 , 2017
Abstract : Eleven new alkaloids (1-11), classified as the 12-acetylplicamine (1), N-deformyl-seco-plicamine (2), plicamine (3-6), 4a-epi-plicamine (7), seco-plicamine (8), and lycorine (9-11) framework types, along with 15 known alkaloids (12-26) were isolated from the whole plants of Zephyranthes carinata. The structures of the new alkaloids 1-11 were established by extensive spectroscopic data interpretation. The absolute configurations of 9 and 10 were defined by single-crystal X-ray diffraction analysis. Zephycarinatines A (1), B (2), and G (7) represent the first examples of 12-acetylplicamine, N-deformyl-seco-plicamine, and 4a-epi-plicamine alkaloids, respectively. Alkaloids 6, 11, 17, and 20-23 exhibited AChE inhibitory activities with IC50 values ranging from 1.21 to 184.05 muM, and a preliminary structure-activity relationship is discussed.
ESTHER : Zhan_2017_J.Nat.Prod_80_2462
PubMedSearch : Zhan_2017_J.Nat.Prod_80_2462
PubMedID: 28898076

Title : Application of hemoperfusion in severe acute organophosphorus pesticide poisoning - Li_2017_Turk.J.Med.Sci_47_1277
Author(s) : Li Z , Wang G , Zhen G , Zhang Y , Liu J , Liu S
Ref : Turk J Med Sci , 47 :1277 , 2017
Abstract : Background/aim: The aim of this research is to investigate the clinical efficacy of hemoperfusion in the treatment of severe acute organophosphorus pesticide poisoning (AOPP). Materials and methods: Patients meeting the inclusion criteria were divided into Groups 1 and 2 according to whether hemoperfusion was applied or not. Group 2 was observed as the control group. Conventional therapy for AOPP was given to Groups 1 and 2. Besides conventional treatment, patients in Group 1 were also treated with hemoperfusion therapy. Cholinesterase activity and blood glucose concentration were tested before hemoperfusion and for the first 3 days afterwards. The recovery time of 50% cholinesterase was recorded. At the same time, the incidence and mortality of intermediate syndrome was observed and compared. Results: The incidence and mortality of intermediate syndrome in Group 1 was obviously decreased, and the recovery time of cholinesterase activity was significantly shortened compared with Group 2. Conclusion: Hemoperfusion, used for treating severe AOPP, contributes to the improvement of cholinesterase activity, low incidence and mortality of intermediate syndrome, and increase in curative rate.
ESTHER : Li_2017_Turk.J.Med.Sci_47_1277
PubMedSearch : Li_2017_Turk.J.Med.Sci_47_1277
PubMedID: 29156874

Title : Crystal structure of a lipase from Streptomyces sp. strain W007 - implications for thermostability and regiospecificity - Zhao_2017_FEBS.J_284_3506
Author(s) : Zhao Z , Hou S , Lan D , Wang X , Liu J , Khan FI , Wang Y
Ref : Febs J , 284 :3506 , 2017
Abstract : MAS1 from marine Streptomyces sp. strain W007 belongs to the bacterial lipase I.7 subfamily and is characterized as a thermostable and nonregiospecific lipase. To shed light on the catalytic mechanism of MAS1, we determined its crystal structure with closed conformation in two crystal forms at 2.3 A resolution. MAS1 adopts the canonical alpha/beta hydrolase core fold with its catalytic triad being formed by S109, D200 and H232. Structural analysis and biochemical assays revealed that disulfide bonds and salt bridges play a vital role in the thermostability of MAS1. In addition, we discovered that the replacement of H108 with a tryptophan converts MAS1 from a nonregiospecific to an sn-1,3-specific lipase, suggesting the functional importance of the second position from the conserved pentapeptide motif in defining the regiospecificity of MAS1. Our present study provides insights into the molecular basis for the thermostability and regiospecificity of MAS1, and it may aid in the rational design of thermostable or regiospecific lipases for potential industrial applications. DATABASE: Structural data are available in the Protein Data Bank database under the accession numbers 5H6B and 5H6G.
ESTHER : Zhao_2017_FEBS.J_284_3506
PubMedSearch : Zhao_2017_FEBS.J_284_3506
PubMedID: 28857479
Gene_locus related to this paper: 9actn-h0b8d4

Title : Clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning and prognosis analysis after rescue - Dong_2017_Medicine.(Baltimore)_96_e7237
Author(s) : Dong H , Weng YB , Zhen GS , Li FJ , Jin AC , Liu J
Ref : Medicine (Baltimore) , 96 :e7237 , 2017
Abstract : This study reports the clinical emergency treatment of 68 critical patients with severe organophosphorus poisoning, and analyzes the prognosis after rescue.The general data of 68 patients with severe organophosphorus poisoning treated in our hospital were retrospectively analyzed. These patients were divided into 2 groups: treatment group, and control group. Patients in the control group received routine emergency treatment, while patients in the treatment group additionally received hemoperfusion plus hemodialysis on the basis of routine emergency treatment. The curative effects in these 2 groups and the prognosis after rescue were compared.Compared with the control group, atropinization time, recovery time of cholinesterase activity, recovery time of consciousness, extubation time, and length of hospital stay were shorter (P < .05); the total usage of atropine was significantly lower (P < .05); Glasgow Coma Score was significantly higher (P < .05); acute physiology and chronic health score (APACHE II) was significantly lower (P < .05); and mortality and poisoning rebound rate was significantly lower (P < .05) in the treatment group.Hemoperfusion and hemodialysis on the basis of routine emergency treatment for critical patients with organophosphorus poisoning can improve rescue outcomes and improve the prognosis of patients, which should be popularized.
ESTHER : Dong_2017_Medicine.(Baltimore)_96_e7237
PubMedSearch : Dong_2017_Medicine.(Baltimore)_96_e7237
PubMedID: 28640122

Title : Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum perforatum - Guo_2017_J.Nat.Prod_80_1493
Author(s) : Guo Y , Zhang N , Chen C , Huang J , Li XN , Liu J , Zhu H , Tong Q , Zhang J , Luo Z , Xue Y , Zhang Y
Ref : Journal of Natural Products , 80 :1493 , 2017
Abstract : The new polyprenylated acylphloroglucinol derivatives 1-15 and the known furohyperforin (16) were isolated from the stems and leaves of Hypericum perforatum. Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G (10) and H (11) are similarly the first examples of naturally occurring [3.3.1]-type polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory activities and cytotoxic activities against a panel of human tumor cell lines. Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC50 3.98-9.13 muM) against AChE.
ESTHER : Guo_2017_J.Nat.Prod_80_1493
PubMedSearch : Guo_2017_J.Nat.Prod_80_1493
PubMedID: 28445039

Title : Synthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: A review - Liu_2017_Carbohydr.Polym_174_999
Author(s) : Liu J , Pu H , Liu S , Kan J , Jin C
Ref : Carbohydr Polym , 174 :999 , 2017
Abstract : In recent years, increasing attention has been paid to the grafting of phenolic acid onto chitosan in order to enhance the bioactivity and widen the application of chitosan. Here, we present a comprehensive overview on the recent advances of phenolic acid grafted chitosan (phenolic acid-g-chitosan) in many aspects, including the synthetic method, structural characterization, biological activity, physicochemical property and potential application. In general, four kinds of techniques including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods are frequently used for the synthesis of phenolic acid-g-chitosan. The structural characterization of phenolic acid-g-chitosan can be determined by several instrumental methods. The physicochemical properties of chitosan are greatly altered after grafting. As compared with chitosan, phenolic acid-g-chitosan exhibits enhanced antioxidant, antimicrobial, antitumor, anti-allergic, anti-inflammatory, anti-diabetic and acetylcholinesterase inhibitory activities. Notably, phenolic acid-g-chitosan shows potential applications in many fields as coating agent, packing material, encapsulation agent and bioadsorbent.
ESTHER : Liu_2017_Carbohydr.Polym_174_999
PubMedSearch : Liu_2017_Carbohydr.Polym_174_999
PubMedID: 28821158

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Bioconcentration and multi-biomarkers of organic UV filters (BM-DBM and OD-PABA) in crucian carp - Ma_2017_Ecotoxicol.Environ.Saf_141_178
Author(s) : Ma B , Lu G , Liu J , Yan Z , Yang H , Pan T
Ref : Ecotoxicology & Environmental Safety , 141 :178 , 2017
Abstract : Organic UV filters (OUV-Fs) are increasingly used in sunscreens and personal care products. In the present work, the bioconcentration and multi-biomarker effects of butyl methoxydibenzoylmethane (BM-DBM) and ethylhexyl dimethyl p-aminobenzoate (OD-PABA) were investigated in crucian carp (Carassius auratus). The fish were exposed to various concentrations of BM-DBM (3.88, 35.61, 181.85 and 337.15mug/L), OD-PABA (4.66, 53.83, 264.22 and 459.32mug/L) and their mixture (2.31+2.79, 23.69+26.18, 97.37+134.81 and 193.93+246.08mug/L) for 28 days. The maximal concentrations of two OUV-Fs were detected in the fish liver, followed by the brain, kidney, gill and muscle in most cases. The maximal BCF values of OD-PABA calculated in various exposure concentrations were 0.37 - 101.21 in single exposure groups and 0.11 - 31.09 in mixed exposure groups. Acetylcholinesterase (AChE) activity was significantly inhibited by BM-DBM as well as the mixtures at all of the exposure concentrations and by OD-PABA at higher concentrations (>/=264.22mug/L) during 28 days of exposure. The maximal inhibition rates of AChE activity reached 64.04% for BM-DBM, 41.05% for OD-PABA and 61.50% for the mixtures at the highest concentration, which indicated that these two OUV-Fs might damage the central nervous system. Concerning oxidative stress status, BM-DBM and the mixtures significantly increased superoxide dismutase (SOD) and glutathione reductase (GR) activities and inhibited catalase (CAT) activity, while OD-PABA caused a significant increase of GR and CAT activities. AChE and GR activities seemed to be more sensitive biomarkers for BM-DBM and OD-PABA.
ESTHER : Ma_2017_Ecotoxicol.Environ.Saf_141_178
PubMedSearch : Ma_2017_Ecotoxicol.Environ.Saf_141_178
PubMedID: 28343007

Title : Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest - Cheng_2017_Nat.Ecol.Evol_1_1747
Author(s) : Cheng T , Wu J , Wu Y , Chilukuri RV , Huang L , Yamamoto K , Feng L , Li W , Chen Z , Guo H , Liu J , Li S , Wang X , Peng L , Liu D , Guo Y , Fu B , Li Z , Liu C , Chen Y , Tomar A , Hilliou F , Montagne N , Jacquin-Joly E , d'Alencon E , Seth RK , Bhatnagar RK , Jouraku A , Shiotsuki T , Kadono-Okuda K , Promboon A , Smagghe G , Arunkumar KP , Kishino H , Goldsmith MR , Feng Q , Xia Q , Mita K
Ref : Nat Ecol Evol , 1 :1747 , 2017
Abstract : The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
ESTHER : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedSearch : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedID: 28963452

Title : A new facet of NDRG1 in pancreatic ductal adenocarcinoma: Suppression of glycolytic metabolism - Liu_2017_Int.J.Oncol_50_1792
Author(s) : Liu W , Zhang B , Hu Q , Qin Y , Xu W , Shi S , Liang C , Meng Q , Xiang J , Liang D , Ji S , Liu J , Hu P , Liu L , Liu C , Long J , Ni Q , Yu X , Xu J
Ref : Int J Oncol , 50 :1792 , 2017
Abstract : N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1alpha level. Moreover, NDRG1 has a unique role in modulating cancer metabolism of pancreatic ductal adenocarcinoma (PDAC). The mechanism accounting for NDRG1 in modulating aerobic glycolysis, at least partly, relied on its regulation of glycolysis genes including GLUT1, HK2, LDHA and PDK1. Additionally, NDRG1 is shown to suppress the activity of HIF1alpha, which is responsible for regulation of glycolysis enzymes. The current study is the first to elucidate a unique facet of the potent tumor/metastasis suppressor NDRG1 in the regulation of PDAC glycolysis, leading to important insights into the mechanism by which NDRG1 exert inhibitory function in PDAC.
ESTHER : Liu_2017_Int.J.Oncol_50_1792
PubMedSearch : Liu_2017_Int.J.Oncol_50_1792
PubMedID: 28350132

Title : Malassezia globosa MgMDL2 lipase: Crystal structure and rational modification of substrate specificity - Lan_2017_Biochem.Biophys.Res.Commun_488_259
Author(s) : Lan D , Xu H , Xu J , Dubin G , Liu J , Iqbal Khan F , Wang Y
Ref : Biochemical & Biophysical Research Communications , 488 :259 , 2017
Abstract : Lipases play an important role in physiological metabolism and diseases, and also have multiple industrial applications. Rational modification of lipase specificity may increase the commercial utility of this group of enzymes, but is hindered by insufficient mechanistic understanding. Here, we report the 2.0 A resolution crystal structure of a mono- and di-acylglycerols lipase from Malassezia globosa (MgMDL2). Interestingly, residues Phe278 and Glu282 were found to involve in substrate recognition because mutation on each residue led to convert MgMDL2 to a triacylglycerol (TAG) lipase. The Phe278Ala and Glu282Ala mutants also acquired ability to synthesize TAGs by esterification of glycerol and fatty acids. By in silicon analysis, steric hindrance of these residues seemed to be key factors for the altered substrate specificity. Our work may shed light on understanding the unique substrate selectivity mechanism of mono- and di-acylglycerols lipases, and provide a new insight for engineering biocatalysts with desired catalytic behaviors for biotechnological application.
ESTHER : Lan_2017_Biochem.Biophys.Res.Commun_488_259
PubMedSearch : Lan_2017_Biochem.Biophys.Res.Commun_488_259
PubMedID: 28433636
Gene_locus related to this paper: malgo-a8puy5

Title : Amaryllidaceae alkaloids with new framework types from Zephyranthes candida as potent acetylcholinesterase inhibitors - Zhan_2017_Eur.J.Med.Chem_127_771
Author(s) : Zhan G , Liu J , Zhou J , Sun B , Aisa HA , Yao G
Ref : Eur Journal of Medicinal Chemistry , 127 :771 , 2017
Abstract : Three new Amaryllidaceae alkaloids, named zephycandidines I-III (1-3), were isolated from Zephyranthes candida. The structures of 1-3 were elucidated by spectroscopic analyses including HRESIMS, 1H NMR, 13C NMR, DEPT, HSQC, 1H-1H COSY, HMBC, ROESY, and electronic circular dichroism (ECD), as well as ECD calculation. The absolute configuration of 1 was finally established by single crystal X-ray diffraction using Cu Kalpha radiation. Zephycandidines I (1) and III (3) with new framework types represent the first example of 7-phenyl-hexahydroindole and 5,2'-dimethyl-biphenyl-2-ylamine alkaloids, respectively, and their plausible biosynthetic pathway are proposed. Zephycandidine II (2) is the first C3a-phenyl-hexahydroindole type alkaloid isolated from the genus of Zephyranthes. These new alkaloids 1-3 were evaluated for their acetylcholinesterase (AChE) inhibitory activities, and 3 showed potent AChE inhibitory activity with an IC50 value of 8.82 muM, suggesting that the framework of 5,2'-dimethyl-biphenyl-2-ylamine in 3 may be a potential group for the AChE inhibitory activity. The docking studies of 1-3 and galanthamine with AChE revealed that interactions with W286 and Y337 are necessary for the AChE inhibitory activity.
ESTHER : Zhan_2017_Eur.J.Med.Chem_127_771
PubMedSearch : Zhan_2017_Eur.J.Med.Chem_127_771
PubMedID: 27823880

Title : Interaction of erythromycin and ketoconazole on the neurological, biochemical and behavioral responses in crucian carp - Liu_2017_Environ.Toxicol.Pharmacol_55_14
Author(s) : Liu J , Cai Y , Lu G , Dan X , Wu D , Yan Z
Ref : Environ Toxicol Pharmacol , 55 :14 , 2017
Abstract : The presence of pharmaceuticals in the aquatic environment has received great attention due to their potential impacts on public health. The single, as well as the combined toxicities of erythromycin (ERY) and ketoconazole (KCZ) on the bioaccumulation, biochemical and behavioral responses, were examined in crucian carp. This study focused on the uptake of contaminants, acetylcholinesterase (AChE) activity in the brain, swimming and shoaling behavior of fish. After 14days of binary exposure, the addition of KCZ at nominal concentrations of 0.2, 2 and 20mug/L significantly increased the accumulation of ERY in the brain of the fish and the bioconcentration factor of 2.08 was 2.6-fold higher than that calculated from the ERY-alone exposure. The brain AChE activity was significantly inhibited by ERY and KCZ with a significant correlation with respect to the accumulative concentration of the contaminants. The inhibition rates of swimming activity to KCZ were increased with a corresponding increase in the exposure concentration of KCZ in the single exposure. However, this manner was altered by the combined exposure. In addition, shoaling was significantly enhanced by KCZ-alone exposure, which was significantly correlated with the swimming activity. This study indicates that the mixture of the contaminants may cause endocrine disrupting effects and behavior modification especially in fish with known ecological and evolutionary consequences.
ESTHER : Liu_2017_Environ.Toxicol.Pharmacol_55_14
PubMedSearch : Liu_2017_Environ.Toxicol.Pharmacol_55_14
PubMedID: 28802958

Title : The impacts of pesticide and nicotine exposures on functional brain networks in Latino immigrant workers - Bahrami_2017_Neurotoxicol_62_138
Author(s) : Bahrami M , Laurienti PJ , Quandt SA , Talton J , Pope CN , Summers P , Burdette JH , Chen H , Liu J , Howard TD , Arcury TA , Simpson SL
Ref : Neurotoxicology , 62 :138 , 2017