Zhang J

General

Full name : Zhang Jun

First name : Jun

Mail : Human BioMolecular Research Institute\; 5310 Eastgate Mall\; San Diego\; CA 92121-2804

Zip Code :

City :

Country : USA

Email : jzhang@hbri.org

Phone : +18584589305

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References (430)

Title : Characterization and validation of fatty acid metabolism-related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer - Li_2024_Biotechnol.Appl.Biochem__
Author(s) : Li H , Zhou T , Zhang Q , Yao Y , Hua T , Zhang J , Wang H
Ref : Biotechnol Appl Biochem , : , 2024
Abstract : Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis. The tumor immune microenvironment was analyzed using the CIBERSORT algorithm, followed by functional analysis and immunotherapy efficacy prediction by gene set variation analysis. The role of model genes in regulating endometrial cancer in vitro was verified by CCK-8, colony formation, wound healing, and transabdominal invasion assays, and verified in vivo by subcutaneous tumor transplantation in nude mice. A prognostic model containing 14 genes was constructed and validated in 3 cohorts and clinical samples. The results showed differences in the infiltration of immune cells between the high-risk and low-risk groups, and that the high-risk group may respond better to immunotherapy. Experiments in vitro confirmed that knockdown of epoxide hydrolase 2 (EPHX2) and acyl-CoA oxidase like (ACOXL) had an inhibitory effect on EC cells, as did overexpression of hematopoietic prostaglandin D synthase (HPGDS). The same results were obtained in experiments in vivo. Prognostic models related to fatty acid metabolism can be used for the risk assessment of endometrial cancer patients. Experiments in vitro and in vivo confirmed that the key genes HPGDS, EPHX2, and ACOXL in the prognostic model may affect the development of endometrial cancer.
ESTHER : Li_2024_Biotechnol.Appl.Biochem__
PubMedSearch : Li_2024_Biotechnol.Appl.Biochem__
PubMedID: 38616327

Title : Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity - Zhang_2024_Sci.Immunol_9_eadh2334
Author(s) : Zhang T , Yu W , Cheng X , Yeung J , Ahumada V , Norris PC , Pearson MJ , Yang X , van Deursen W , Halcovich C , Nassar A , Vesely MD , Zhang Y , Zhang J , Ji L , Flies DB , Liu L , Langermann S , LaRochelle WJ , Humphrey R , Zhao D , Zhang Q , Gu R , Schalper KA , Sanmamed MF , Chen L
Ref : Sci Immunol , 9 :eadh2334 , 2024
Abstract : T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.
ESTHER : Zhang_2024_Sci.Immunol_9_eadh2334
PubMedSearch : Zhang_2024_Sci.Immunol_9_eadh2334
PubMedID: 38669316

Title : Inhibition of cannabinoid degradation enhances hippocampal contextual fear memory and exhibits anxiolytic effects - Zhang_2024_iScience_27_108919
Author(s) : Zhang J , Yuan R , Han W , Chang Y , Kong L , Wei C , Zheng Q , Zhu X , Liu Z , Ren W , Han J
Ref : iScience , 27 :108919 , 2024
Abstract : Recent studies have demonstrated the pivotal involvement of endocannabinoids in regulating learning and memory, but the conclusions obtained from different paradigms or contexts are somewhat controversial, and the underlying mechanisms remain largely elusive. Here, we show that JZL195, a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase, can enhance the performance of mice in a contextual fear conditioning task and increase the time spent in open arms in the elevated zero maze (EZM). Although the effect of JZL195 on fear memory could not be inhibited by antagonists of cannabinoid receptors, the effect on the EZM seems to be mediated by CB1R. Simultaneously, hippocampal neurons are hyperactive, and theta oscillation power is significantly increased during the critical period of memory consolidation upon treatment with JZL195. These results suggest the feasibility of targeting the endocannabinoid system for the treatment of various mental disorders.
ESTHER : Zhang_2024_iScience_27_108919
PubMedSearch : Zhang_2024_iScience_27_108919
PubMedID: 38318362

Title : Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on Enucleation or Nucleus-Retaining of Cornus officinalis Fruits - Zhang_2024_Molecules_29_
Author(s) : Zhang J , Niu P , Li M , Wang Y , Ma Y , Wang P
Ref : Molecules , 29 : , 2024
Abstract : The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, alpha-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better alpha-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.
ESTHER : Zhang_2024_Molecules_29_
PubMedSearch : Zhang_2024_Molecules_29_
PubMedID: 38611753

Title : Biodegradation of poly(ethylene terephthalate) through PETase surface-display: From function to structure - Han_2024_J.Hazard.Mater_461_132632
Author(s) : Han W , Zhang J , Chen Q , Xie Y , Zhang M , Qu J , Tan Y , Diao Y , Wang Y , Zhang Y
Ref : J Hazard Mater , 461 :132632 , 2024
Abstract : Polyethylene terephthalate (PET) is one of the most used plastics which has caused some environmental pollution and social problems. Although many newly discovered or modified PET hydrolases have been reported at present, there is still a lack of comparison between their hydrolytic capacities, as well as the need for new biotechnology to apply them for the PET treatment. Here, we systematically studied the surface-display technology for PET hydrolysis using several PET hydrolases. It is found that anchoring protein types had little influence on the surface-display result under T7 promoter, while the PET hydrolase types were more important. By contrast, the newly reported FAST-PETase showed the strongest hydrolysis effect, achieving 71.3% PET hydrolysis in 24 h by pGSA-FAST-PETase. Via model calculation, FAST-PETase indeed exhibited higher temperature tolerance and catalytic capacity. Besides, smaller particle size and lower crystallinity favored the hydrolysis of PET pellets. Through protein structure comparison, we summarized the common characteristics of efficient PET-hydrolyzing enzymes and proposed three main crystal structures of PET enzymes via crystal structural analysis, with ISPETase being the representative and main structure. Surface co-display of FAST-PETase and MHETase can promote the hydrolysis of PET, and the C-terminal of the fusion protein is crucial for PET hydrolysis. The results of our research can be helpful for PET contamination removal as well as other areas involving the application of enzymes. SYNOPSIS: This research can promote the development of better PET hydrolase and its applications in PET pollution treatment via bacteria surface-display.
ESTHER : Han_2024_J.Hazard.Mater_461_132632
PubMedSearch : Han_2024_J.Hazard.Mater_461_132632
PubMedID: 37804764

Title : A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease - Shan_2024_ACS.Nano__
Author(s) : Shan X , Lu Y , Luo Z , Zhao X , Pang M , Yin H , Guo X , Zhou H , Zhang J , Huang J , Shi Y , Lou J , Luo L , You J
Ref : ACS Nano , : , 2024
Abstract : Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Abeta accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.
ESTHER : Shan_2024_ACS.Nano__
PubMedSearch : Shan_2024_ACS.Nano__
PubMedID: 38517764

Title : Computer-aided rational design strategy based on protein surface charge to improve the thermal stability of a novel esterase from Geobacillus jurassicus - Song_2024_Biotechnol.Lett__
Author(s) : Song R , Zhang J , Zhu M , Lin L , Wei W , Wei D
Ref : Biotechnol Lett , : , 2024
Abstract : OBJECTIVES: Although Geobacillus are significant thermophilic bacteria source, there are no reports of thermostable esterase gene in Geobacillus jurassicus or rational design strategies to increase the thermal stability of esterases. RESULTS: Gene gju768 showed a highest similarity of 15.20% to esterases from Geobacillus sp. with detail enzymatic properties. Using a combination of Gibbs Unfolding Free Energy (deltadeltaG) calculator and the distance from the mutation site to the catalytic site (Ds(Calpha-Calpha)) to screen suitable mutation sites with elimination of negative surface charge, the mutants (D24N, E221Q, and E253Q) displayed stable mutants with higher thermal stability than the wild-type (WT). Mutant E253Q exhibited the best thermal stability, with a half-life (T(1/2)) at 65 degreesC of 32.4 min, which was 1.8-fold of the WT (17.9 min). CONCLUSION: Cloning of gene gju768 and rational design based on surface charge engineering contributed to the identification of thermostable esterase from Geobacillus sp. and the exploration of evolutionary strategies for thermal stability.
ESTHER : Song_2024_Biotechnol.Lett__
PubMedSearch : Song_2024_Biotechnol.Lett__
PubMedID: 38523202

Title : Establishment of transgenic fluorescent mice for labeling synapses and screening synaptogenic adhesion molecules - Yang_2024_Elife_13_
Author(s) : Yang L , Zhang J , Liu S , Zhang Y , Wang L , Wang X , Wang S , Li K , Wei M , Zhang C
Ref : Elife , 13 : , 2024
Abstract : Synapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Due to the diversity of synapses in different brain areas, circuits and neurons, although many synaptic CAMs, such as Neurexins (NRXNs), Neuroligins (NLGNs), Synaptic cell adhesion molecules (SynCAMs), Leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) and SLIT and NTRK-like protein (SLITRKs) have been identified as synaptogenic molecules, how these molecules determine specific synapse formation and whether other molecules driving synapse formation remain undiscovered are unclear. Here, to providing a tool for synapse labeling and synaptic CAMs screening by artificial synapse formation (ASF) assay, we generated synaptotagmin-1-tdTomato (Syt1-tdTomato) transgenic mice by inserting the tdTomato-fused synaptotagmin-1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-tdTomato transgenic mice, the tdTomato-fused synaptotagmin-1 (SYT1-tdTomato) signals were widely observed in different areas and overlapped with synapsin-1, a widely-used synaptic marker. In olfactory bulb, the SYT1-tdTomato signals are highly enriched in glomerulus. In the cultured hippocampal neurons, the SYT1-tdTomato signals showed colocalization with several synaptic markers. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-tdTomato transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-tdTomato transgenic mice could form synaptic connections with HEK293T cells expressing NLGN2, LRRTM2, and SLITRK2 without immunostaining. Therefore, our work suggested that the Syt1-tdTomato transgenic mice with the ability to label synapses by tdTomato, and it will be a convenient tool for screening synaptogenic molecules.
ESTHER : Yang_2024_Elife_13_
PubMedSearch : Yang_2024_Elife_13_
PubMedID: 38450720

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 : Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea - Wang_2024_J.Agric.Food.Chem__
Author(s) : Wang Q , Wang X , Cai D , Yu J , Chen X , Niu W , Wang S , Liu X , Zhou D , Yin F , Wang T , Shi X , Wu Z , Zhang J , Hao J , Liu P
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.
ESTHER : Wang_2024_J.Agric.Food.Chem__
PubMedSearch : Wang_2024_J.Agric.Food.Chem__
PubMedID: 38226868 || 38634420

Title : The acute neurotoxicity of inorganic mercury in Mactra chinensis philippi - Ma_2024_Aquat.Toxicol_270_106896
Author(s) : Ma B , Zhao X , Zhang X , Yang B , Cai Z , Xing Z , Xu M , Mi L , Zhang J , Wang L , Zhao Y , Liu X
Ref : Aquat Toxicol , 270 :106896 , 2024
Abstract : Inorganic mercury (IHg) is hazardous to marine organisms especially resulting in neurotoxicity, bivalves are sensitive to pollutants as "ocean sentinel", but data on the neurotoxicity of IHg in bivalves are sparse. So we chosed M. chinensis philippi with typical neural structures in bivalves to investigate the neurotoxicity of IHg, which could be helpful to understand the specificity of neural regulation and the response characteristics of bivalves. After acute exposed to IHg (HgCl(2)) for 24 h, the metabolites of ganglion tissues in M. chinensis philippi were evaluated using (1)H-nuclear magnetic resonance based metabolomics; Ca(2+), neurotransmitters (nitric oxide, glutamate, acetylcholine) and related enzymes (calcineurin, nitric oxide synthase and acetylcholinesterase) were measured using biochemical detection. Compared to the control group, the levels of the nitric oxide (81.04 +/- 12.84 micromol/g prot) and acetylcholine (30.93 +/- 12.57 microg/mg prot) in M. chinensis philippi of IHg-treated were decreased, while glutamate (2.11 +/- 0.61 mmol/L) increased significantly; the activity of nitric oxide synthase (679.34 +/- 135.33 U/mg prot) was increased, while acetylcholinesterase (1.39 +/- 0.44 U/mg prot) decreased significantly, and the activity of calcineurin (0.52 +/- 0.02 U/mg prot) had a statistically insignificant increasing tendency. The concentration of Ca(2+) (0.92 +/- 0.46 mmol/g prot) in the IHg-treated group was significantly higher than that in the control group. OPLS-DA was performed to reveal the difference in metabolites between the control and IHg-challenged groups, the metabolites of glucose, glutamine, inosine, succinate, glutamate, homarine, and alanine were sensitive to IHg, subsequently metabolic pathways that were affected including glucose metabolism, glutamine metabolism, nucleotide metabolism, Krebs cycle, amino acid metabolism and osmotic regulation. In our study, IHg interfered with metabolites in M. chinensis philippi, thus the corresponding metabolic pathways were changed, which influenced the neurotransmitters subsequently. Furthermore, Ca(2+)overload affected the synthesis or degradation of the neurotransmitters, and then the altered neurotransmitters involved in changes in metabolic pathways again. Overall, we hypothesized that the neurotoxic effects of IHg on bivalve were in close contact with metabolism, neurotransmitters, related enzymes and Ca(2+), which could be effective neurotoxic biomarkers for marine environmental quality assessment, and also provide effective data for the study of the regulatory mechanism of the nervous system in response to IHg in bivalves.
ESTHER : Ma_2024_Aquat.Toxicol_270_106896
PubMedSearch : Ma_2024_Aquat.Toxicol_270_106896
PubMedID: 38490093

Title : Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles - Tang_2024_Mater.Today.Bio_25_100988
Author(s) : Tang X , Zhang J , Sui D , Xu Z , Yang Q , Wang T , Li X , Liu X , Deng Y , Song Y
Ref : Mater Today Bio , 25 :100988 , 2024
Abstract : The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.
ESTHER : Tang_2024_Mater.Today.Bio_25_100988
PubMedSearch : Tang_2024_Mater.Today.Bio_25_100988
PubMedID: 38379935

Title : Personalized venlafaxine dose prediction using artificial intelligence technology: a retrospective analysis based on real-world data - Liu_2024_Int.J.Clin.Pharm__
Author(s) : Liu Y , Yu Z , Ye X , Zhang J , Hao X , Gao F , Yu J , Zhou C
Ref : Int J Clin Pharm , : , 2024
Abstract : BACKGROUND: Venlafaxine dose regimens vary considerably between individuals, requiring personalized dosing. AIM: This study aimed to identify dose-related influencing factors of venlafaxine through real-world data analysis and to construct a personalized dose model using advanced artificial intelligence techniques. METHOD: We conducted a retrospective study on patients with depression treated with venlafaxine. Significant variables were selected through a univariate analysis. Subsequently, the predictive performance of seven models (XGBoost, LightGBM, CatBoost, GBDT, ANN, TabNet, and DT) was compared. The algorithm that demonstrated optimal performance was chosen to establish the dose prediction model. Model validation used confusion matrices and ROC analysis. Additionally, a dose subgroup analysis was conducted. RESULTS: A total of 298 patients were included. TabNet was selected to establish the venlafaxine dose prediction model, which exhibited the highest performance with an accuracy of 0.80. The analysis identified seven crucial variables correlated with venlafaxine daily dose, including blood venlafaxine concentration, total protein, lymphocytes, age, globulin, cholinesterase, and blood platelet count. The area under the curve (AUC) for predicting venlafaxine doses of 75 mg, 150 mg, and 225 mg were 0.90, 0.85, and 0.90, respectively. CONCLUSION: We successfully developed a TabNet model to predict venlafaxine doses using real-world data. This model demonstrated substantial predictive accuracy, offering a personalized dosing regimen for venlafaxine. These findings provide valuable guidance for the clinical use of the drug.
ESTHER : Liu_2024_Int.J.Clin.Pharm__
PubMedSearch : Liu_2024_Int.J.Clin.Pharm__
PubMedID: 38733475

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 : Dynamic metabolism of endothelial triglycerides protects against atherosclerosis in mice - Boutagy_2024_J.Clin.Invest__
Author(s) : Boutagy NE , Gamez-Mendez A , Fowler JW , Zhang H , Chaube BK , Esplugues E , Lee S , Horikami D , Zhang J , Citrin KM , Singh AK , Coon BG , Suarez Y , Fernandez-Hernando C , Sessa WC
Ref : J Clinical Investigation , : , 2024
Abstract : Blood vessels are continually exposed to circulating lipids and elevations of ApoB containing lipoproteins cause atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FA) into triglyceride (TG) rich lipid droplets (LD) is not known. In this study, we showed that deletion of the enzyme, adipose triglyceride lipase (ATGL) in the endothelium, led to neutral lipid accumulation in vessels and impaired endothelial dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD impacts endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.
ESTHER : Boutagy_2024_J.Clin.Invest__
PubMedSearch : Boutagy_2024_J.Clin.Invest__
PubMedID: 38175710

Title : Huperzine A injection ameliorates motor and cognitive abnormalities via regulating multiple pathways in a murine model of Parkinson's disease - Guo_2023_Eur.J.Pharmacol__175970
Author(s) : Guo X , Wu Y , Wang Q , Zhang J , Sheng X , Zheng L , Wang Y
Ref : European Journal of Pharmacology , :175970 , 2023
Abstract : As a common progressive neurodegenerative disorder, the satisfied therapies for Parkinson's disease (PD) are still unavailable. As a natural acetylcholinesterase inhibitor, the neuroprotective characteristic of Huperzine A (HupA) was supported by previous studies. However, questions remain on whether HupA injection (HAI, a main preparation of HupA) intervention conduces to PD treatment and if so, the potential molecular mechanisms. In this study, the efficacies of HAI treatment on PD-like pathological phenotypes were evaluated in a MPTP-induced PD murine model. The network pharmacology, transcriptome sequencing and experimental verification were integrated to comprehensively reveal the primary molecular mechanisms. Therapeutically, HAI intervention significantly improved the impaired locomotor behaviors as well as learning and memory abilities, and prevented the degeneration of dopaminergic neurons of PD mice. The network pharmacology analysis combined with experimental results showed that HAI treatment could effectively restore the disordered transcriptional levels of inflammatory factors and apoptosis related genes in the SNpc and striatum tissues of PD mice. Transcriptome sequencing results found that inflammation and oxidative phosphorylation served as significant functional mechanisms involved in HAI administration. The experimental verification indicated that HAI treatment effectively regulated the abnormal transcription levels of inflammation and oxidative phosphorylation related hub genes in the hippocampal samples of PD mice. In addition, molecular docking suggested strong affinity between HupA and the above core targets. Overall, this work displayed the reliable therapeutic effects of HAI on ameliorating the pathological symptoms of PD mice via modulating multiple pathways. The current findings were expected to provide a potential anti-PD agent.
ESTHER : Guo_2023_Eur.J.Pharmacol__175970
PubMedSearch : Guo_2023_Eur.J.Pharmacol__175970
PubMedID: 37549727

Title : Biotransformation, metabolic response, and toxicity of UV-234 and UV-326 in larval zebrafish (Danio rerio) - Zhang_2023_Environ.Int_174_107896
Author(s) : Zhang J , Huang Y , Pei Y , Wang Y , Li M , Chen H , Liang X , Martyniuk CJ
Ref : Environ Int , 174 :107896 , 2023
Abstract : Benzotriazole ultraviolet stabilizers (BUVSs) are emerging pollutants that are widely detected in aquatic ecosystems. While structure-dependent effects of BUVSs are reported, the relationship between biotransformation and toxicity outcomes remains unclear. In this study, zebrafish embryos were exposed to two common BUVSs (UV-234 and UV-326) at 1, 10, and 100 microg/L for up to 7 days. Comparison of their uptake and biotransformation revealed that the bioaccumulation capacity of UV-234 was higher than that of UV-326, while UV-326 was more extensively biotransformed with additional conjugation reactions. However, UV-326 showed low metabolism due to inhibited phase II enzymes, which may result in the comparable internal concentrations of both BUVSs in larval zebrafish. Both BUVSs induced oxidative stress while decreased MDA, suggesting the disturbance of lipid metabolism. The subsequent metabolomic profiling revealed that UV-234 and UV-326 exerted different effects on arachidonic acid, lipid, and energy metabolism. However, both BUVSs negatively impacted the cyclic guanosine monophosphate / protein kinase G pathway. This converged metabolic change resulted in comparable toxicity of UV-234 and UV-326, which was confirmed by the induction of downstream apoptosis, neuroinflammation, and abnormal locomotion behavior. These data have important implications for understanding the metabolism, disposition, and toxicology of BUVSs in aquatic organisms.
ESTHER : Zhang_2023_Environ.Int_174_107896
PubMedSearch : Zhang_2023_Environ.Int_174_107896
PubMedID: 36966637

Title : Discovery of anthraquinones as DPP-IV inhibitors: Structure-activity relationships and inhibitory mechanism - Ma_2023_Fitoterapia__105549
Author(s) : Ma HH , Zhang J , Li CQ , Zou LW
Ref : Fitoterapia , :105549 , 2023
Abstract : Dipeptidyl peptidase IV (DPP-IV) is an integrated type II transmembrane protein that reduces endogenous insulin contents and increases plasma glucose levels by hydrolyzing glucagon-like peptide-1 (GLP-1). Inhibition of DPP-IV regulates and maintains glucose homeostasis, making it an attractive drug target for the treatment of diabetes II. Natural compounds have tremendous potential to regulate glucose metabolism. In this study, we examined the DPP-IV inhibitory activity of a series of natural anthraquinones and synthetic structural analogues on DPP-IV using fluorescence-based biochemical assays. The inhibitory efficiency differed among anthraquinone compounds with different structures. Alizarin (7), aloe emodin (11), emodin (13) emerged the outstanding inhibitory potential for DPP-IV with IC(50) values lower than 5 microM. To clarifying the inhibitory mechanism, inhibitory kinetics were performed, which showed that alizarin red S (8) and 13 were effective non-competitive inhibitors of DPP-IV, while alizarin complexone (9), rhein (12), and anthraquinone-2-carboxylic acid (23) were mixed inhibitors. Emodin was determined as inhibitor with the strongest DPP-IV-binding affinity determined via molecular docking. Structure-activity relationship (SAR) demonstrated that hydroxyl group at C-1 and C-8 sites and hydroxyl, hydroxymethyl or carboxyl group at the C-2 or C-3 site were very essential for DPP-IV inhibition, replacement of hydroxyl group with amino group at C-1 could led to an increase of the inhibitory potential. Further fluorescence imaging showed that both compounds 7 and 13 significantly inhibited DPP-IV activity in RTPEC cells. Overall, the results indicated that anthraquinones would be a natural functional ingredient for inhibiting DPP-IV and provided new ideas for searching and developing potential antidiabetic compounds.
ESTHER : Ma_2023_Fitoterapia__105549
PubMedSearch : Ma_2023_Fitoterapia__105549
PubMedID: 37244503

Title : Efficient polyethylene terephthalate biodegradation by an engineered Ideonella sakaiensis PETase with a fixed substrate-binding W156 residue - ?Yin_2023_Green.Chemistry__
Author(s) : Yin Q , Zhang J , Ma S , Gu T , Wang M , You S , Ye S , Su R , Wang Y , Qi W
Ref : Green Chemistry , : , 2023
Abstract : Ideonella sakaiensis PETase (IsPETase) is a unique polyethylene terephthalate (PET) hydrolase that displays great potential for mitigating PET waste at moderate temperatures. Although IsPETase exhibits greater specific activity towards PET, rapid activity loss limits its commercial application. Herein, semi-saturation mutation was carried out to stabilize the most flexible region in IsPETase and a thermostable S92P/D157A variant with a Tm value of 70.8 degreesC (deltaTm = 24.1 degreesC) was constructed, which enabled a 109.3-fold increase in products released from amorphous PET depolymerization at 40 degreesC. The further depolymerization of untreated post-consumer PET obtained 17.34 mM products (95.0% TPA). The crystal structure indicated that the ""wobbling"" W156 residue in IsPETaseWT was fixed in the substrate-binding conformation in the S92P/D157A variant, which contributed to an increase in thermostability and could provide steady interaction with the substrate. Previous studies emphasized that the W156 residue exhibiting a ""wobbling effect"" is critical to substrate binding, while the different structure-function relationship of the S92P/D157A variant indicated that the wobbling of W156 may not be a pre-requisite for efficient PET biodegradation. Instead, engineering PET hydrolases for fixing the conserved W156 residue in the substrate-binding conformation was proposed. The S92P/D157A variant exhibited a preference for PET in the gauche conformation, which is consistent with its efficiency towards the degradation of low crystallinity PET, further cementing the importance of conformation selection and providing complementary evidence for the function of the fixed W156 residue in PET binding and catalytic processes. Collectively, our results could contribute to the understanding and engineering of more effective PET hydrolases, promoting the industrial application of the enzymatic PET recycling process.
ESTHER : ?Yin_2023_Green.Chemistry__
PubMedSearch : ?Yin_2023_Green.Chemistry__
PubMedID:
Gene_locus related to this paper: idesa-peth

Title : Elucidation of Carboxylesterase Mediated Pharmacokinetic Interactions between Irinotecan and Oroxylin A in Rats via Physiologically Based Pharmacokinetic Modeling - Zhang_2023_Pharm.Res__
Author(s) : Zhang J , Zhang Y , Lai YS , Song Q , Xiao M , Ji X , Yan X , Zuo Z
Ref : Pharm Res , : , 2023
Abstract : PURPOSE: Our previous screening studies identified Oroxylin A (OXA) as a strong inhibitor on the carboxyolesterase mediated hydrolysis of irinotecan to SN-38. The current study employed a whole-body physiologically based pharmacokinetic (PBPK) modeling approach to investigate the underlying mechanisms of the carboxylesterase-mediated pharmacokinetics interactions between irinotecan and OXA in rats. METHODS: Firstly, rats received irinotecan intravenous treatment at 35 micromol/kg without or with oral OXA pretreatment (2800 micromol/kg) daily for 5 days. On day 5, blood and tissues were collected for analyses of irinotecan/SN-38 concentrations and carboxylesterase expression. In addition, effects of OXA on the enzyme kinetics of irinotecan hydrolysis and unbound fractions of irinotecan and SN-38 in rat plasma, liver and intestine were also determined. Finally, a PBPK model that integrated the physiological parameters, enzyme kinetics, and physicochemical properties of irinotecan and OXA was developed. RESULTS: Our PBPK model could accurately predict the pharmacokinetic profiles of irinotecan/SN-38, with AUC(0-6h) and C(max) values within +/-27% of observed values. When OXA was included as a carboxylesterase inhibitor, the model could also predict the irinotecan/SN-38 plasma concentrations within twofold of those observed. In addition, the PBPK model indicated inhibition of carboxylesterase-mediated hydrolysis of irinotecan in the intestinal mucosa as the major underlying mechanism for the pharmacokinetics interactions between irinotecan and OXA. CONCLUSION: A whole-body PBPK model was successfully developed to not only predict the impact of oral OXA pretreatment on the pharmacokinetics profiles of irinotecan but also reveal its inhibition on the intestinal carboxylesterase as the major underlying mechanism.
ESTHER : Zhang_2023_Pharm.Res__
PubMedSearch : Zhang_2023_Pharm.Res__
PubMedID: 37667147

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

Title : Clinical characteristics and high risk factors of patients with Omicron variant strain infection in Hebei, China - Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
Author(s) : Wang L , Liu T , Yue H , Zhang J , Sheng Q , Wu L , Wang X , Zhang M , Wang J , Yu W
Ref : Front Cell Infect Microbiol , 13 :1294904 , 2023
Abstract : OBJECTIVE: The Omicron variant has a weaker pathogenicity compared to the Delta variant but is highly transmissible and elderly critically ill patients account for the majority. This study has significant implications for guiding clinical personalized treatment and effectively utilizing healthcare resources. METHODS: The study focuses on 157 patients infected with the novel coronavirus Omicron variant, from December, 2022, to February, 2023. The objective is to analyze the baseline data, test results, imaging findings and identify risk factors associated with severe illness. RESULTS: Among the 157 included patients, there were 55 cases in the non-severe group (all were moderate cases) and 102 cases in the severe group (including severe and critical cases). Infection with the Omicron variant exhibits significant differences between non-severe and severe cases (baseline data, blood routine, coagulation, inflammatory markers, cardiac, liver, kidney functions, Chest CT, VTE score, etc.). A multifactorial logistic regression analysis showed that neutrophil percentage >75%, eosinophil percentage <0.4%, D-dimer >0.55 mg/L, PCT >0.25 ng/mL, LDH >250 U/L, albumin <40 g/L, A/G ratio <1.2, cholinesterase<5100 U/L, uric acid >357 mole/L and blood calcium<2.11 mmol/L were the most likely independent risk factors for severe novel coronavirus infection. CONCLUSION: Advanced age, low oxygenation index, elevated neutrophil percentage, decreased eosinophil percentage, elevated PCT, elevated LDH, decreased albumin, decreased A/G ratio, elevated uric acid, decreased blood calcium, and elevated D-dimer are independent prognostic risk factors for non-severe patients progressing to severe illness. These factors should be closely monitored and actively treated to prevent or minimize the occurrence of severe illness.
ESTHER : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedSearch : Wang_2023_Front.Cell.Infect.Microbiol_13_1294904
PubMedID: 38145047

Title : Monitoring acetylcholinesterase level changes under oxidative stress through ESIPT-ICT-based near-infrared fluorescent probe - Wei_2023_Sens.Actuators.B.Chem_380_133392
Author(s) : Wei X , Zhu T , Ma Y , Sun J , Zheng G , Ma T , Yang X , Song Z , Lv Y , Zhang J , Yan M
Ref : Sensors and Actuators B: Chemical , 380 :133392 , 2023
Abstract : Oxidative stress plays an important role in pathology, and contributes to a variety of diseases, including inflammation, neurodegenerative diseases, and cancer. Research studies have shown that acetylcholinesterase (AChE) plays a key role in regulating oxidative stress. However, an effective analytical method for real-time monitoring of AChE under oxidative stress is still lacking. Currently, fluorescent probes based on dual sensing mechanisms have attracted great attention by combining and amplifying the advantages of both mechanisms. In this work, two NIR fluorescent probes (SNCN-AE and SNC-AE) that combined ESIPT and ICT processes were designed and synthesized for accurate detection of AChE activity. After the probes reacted with AChE, the strong electron push-pull effect enhanced the ICT process, which further synergized with the ESIPT effect, resulting in a distinct NIR fluorescence signal accompanied by a large Stokes shift. In particular, SNCN-AE showed better detection performance of fast response, good photostability and low cytotoxicity, which was highly suitable for imaging of endogenous AChE in living system. Importantly, SNCN-AE had been successfully applied for monitoring AChE under oxidative stress in PC12 cells and zebrafish model. These excellent properties made probes the promising tools for studying oxidative stress and related diseases.
ESTHER : Wei_2023_Sens.Actuators.B.Chem_380_133392
PubMedSearch : Wei_2023_Sens.Actuators.B.Chem_380_133392
PubMedID:

Title : Ferulic acid production from wheat bran by integration of enzymatic pretreatment and a cold-adapted carboxylesterase catalysis - Cao_2023_Bioresour.Technol__129435
Author(s) : Cao L , Xue D , Liu X , Wang C , Fang D , Zhang J , Gong C
Ref : Bioresour Technol , :129435 , 2023
Abstract : High-value chemical production from natural lignocellulose transformation is a reliable waste utilization approach. A gene encoding cold-adapted carboxylesterase in Arthrobacter soli Em07 was identified. The gene was cloned and expressed in Escherichia coli to obtain a carboxylesterase enzyme with a molecular weight of 37.2 KDa. The activity of the enzyme was determined using alpha-naphthyl acetate as substrate. Results showed that the optimum enzyme activity of carboxylesterase was at 10 degreesC and pH 7.0. It was also found that the enzyme could degrade 20 mg enzymatic pretreated de-starched wheat bran (DSWB) to produce 235.8 microg of ferulic acid under the same conditions, which was 5.6 times more than the control. Compared to the chemical strategy, enzymatic pretreatment is advantageous because it is environmentally friendly, and the by-products can be easily treated. Therefore, this strategy provides an effective method for high-value utilization of biomass waste in agriculture and industry.
ESTHER : Cao_2023_Bioresour.Technol__129435
PubMedSearch : Cao_2023_Bioresour.Technol__129435
PubMedID: 37399964

Title : Identification, Characterization, and Computer-Aided Rational Design of a Novel Thermophilic Esterase from Geobacillus subterraneus, and Application in the Synthesis of Cinnamyl Acetate - Zhang_2023_Appl.Biochem.Biotechnol__
Author(s) : Zhang J , Lin L , Wei W , Wei D
Ref : Appl Biochem Biotechnol , : , 2023
Abstract : Investigation of a novel thermophilic esterase gene from Geobacillus subterraneus DSMZ 13552 indicated a high amino acid sequence similarity of 25.9% to a reported esterase from Geobacillus sp. A strategy that integrated computer-aided rational design tools was developed to select mutation sites. Six mutants were selected from four criteria based on the simulated saturation mutation (including 19 amino acid residues) results. Of these, the mutants Q78Y and G119A were found to retain 87% and 27% activity after incubation at 70 degreesC for 20 min, compared with the 19% activity for the wild type. Subsequently, a double-point mutant (Q78Y/G119A) was obtained and identified with optimal temperature increase from 65 to 70 degreesC and a 41.51% decrease in K(m). The obtained T(1/2) values of 42.2 min (70 degreesC) and 16.9 min (75 degreesC) for Q78Y/G119A showed increases of 340% and 412% compared with that in the wild type. Q78Y/G119A was then employed as a biocatalyst to synthesize cinnamyl acetate, for which the conversion rate reached 99.40% with 0.3 M cinnamyl alcohol at 60 degreesC. The results validated the enhanced enzymatic properties of the mutant and indicated better prospects for industrial application as compared to that in the wild type. This study reported a method by which an enzyme could evolve to achieve enhanced thermostability, thereby increasing its potential for industrial applications, which could also be expanded to other esterases.
ESTHER : Zhang_2023_Appl.Biochem.Biotechnol__
PubMedSearch : Zhang_2023_Appl.Biochem.Biotechnol__
PubMedID: 37713064

Title : Comparative study on inhibitory effects of ginsenosides on human pancreatic lipase and porcine pancreatic lipase: structure-activity relationships and inhibitory mechanism - Wang_2023_Nat.Prod.Res__1
Author(s) : Wang AQ , Wang YJ , Zhang J , Fan YM , Li SY , Zou LW
Ref : Nat Prod Res , :1 , 2023
Abstract : The inhibitory effects of twenty-six ginsenosides on human pancreatic lipase (hPL) and porcine pancreatic lipase (pPL) were studied. Study reveals that nine ginsenosides have moderate inhibitory effects against hPL, and good selectivity over pPL. By contrast, (S)-Rh2 showed good inhibitory effects on pPL over hPL. SAR analysis indicated that introduction of the O-glycosyl group(s) at C-3/C-7 site is unbeneficial for hPL inhibition, ginsenosides with A-skeleton is more beneficial than ginsenosides with B-/C-skeleton. Inhibition kinetic analysis indicated that Rg3 and (S)-Rh2 inhibited hPL-catalyzed DDAO-ol hydrolysis in a mixed manner. Molecular docking studies have confirmed that Rg3 and (S)-Rh2 inhibit hPL via many Pi-hydrogen interactions and hydrogen bonds with catalytic residues of hPL. These results indicated that pPL as an enzyme source could not fully represent the inhibitory effect of the tested compounds on hPL, and hPL should be used as far as possible to evaluate the inhibitory effect of PL.
ESTHER : Wang_2023_Nat.Prod.Res__1
PubMedSearch : Wang_2023_Nat.Prod.Res__1
PubMedID: 37471672

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

Title : Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury - Zhang_2023_Int.J.Biol.Sci_19_294
Author(s) : Zhang J , Luan ZL , Huo XK , Zhang M , Morisseau C , Sun CP , Hammock BD , Ma XC
Ref : Int J Biol Sci , 19 :294 , 2023
Abstract : Acute kidney injury (AKI) is a pathological condition characterized by a rapid decrease in glomerular filtration rate and nitrogenous waste accumulation during hemodynamic regulation. Alisol B, from Alisma orientale, displays anti-tumor, anti-complement, and anti-inflammatory effects. However, its effect and action mechanism on AKI is still unclear. Herein, alisol B significantly attenuated cisplatin (Cis)-induced renal tubular apoptosis through decreasing expressions levels of cleaved-caspase 3 and cleaved-PARP and the ratio of Bax/Bcl-2 depended on the p53 pathway. Alisol B also alleviated Cis-induced inflammatory response (e.g. the increase of ICAM-1, MCP-1, COX-2, iNOS, IL-6, and TNF-alpha) and oxidative stress (e.g. the decrease of SOD and GSH, the decrease of HO-1, GCLC, GCLM, and NQO-1) through the NF-kappaB and Nrf2 pathways. In a target fishing experiment, alisol B bound to soluble epoxide hydrolase (sEH) as a direct cellular target through the hydrogen bond with Gln384, which was further supported by inhibition kinetics and surface plasmon resonance (equilibrium dissociation constant, K (D) = 1.32 microM). Notably, alisol B enhanced levels of epoxyeicosatrienoic acids and decreased levels of dihydroxyeicosatrienoic acids, indicating that alisol B reduced the sEH activity in vivo. In addition, sEH genetic deletion alleviated Cis-induced AKI and abolished the protective effect of alisol B in Cis-induced AKI as well. These findings indicated that alisol B targeted sEH to alleviate Cis-induced AKI via GSK3beta-mediated p53, NF-kappaB, and Nrf2 signaling pathways and could be used as a potential therapeutic agent in the treatment of AKI.
ESTHER : Zhang_2023_Int.J.Biol.Sci_19_294
PubMedSearch : Zhang_2023_Int.J.Biol.Sci_19_294
PubMedID: 36594097

Title : Frameshift coding sequence variants in the LPL gene: identification of two novel events and exploration of the genotype-phenotype relationship for variants reported to date - Zhang_2023_Lipids.Health.Dis_22_128
Author(s) : Zhang G , Hu Y , Yang Q , Pu N , Li G , Zhang J , Tong Z , Masson E , Cooper DN , Chen JM , Li W
Ref : Lipids Health Dis , 22 :128 , 2023
Abstract : BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme for triglyceride hydrolysis. Homozygous or compound heterozygous LPL variants cause autosomal recessive familial chylomicronemia syndrome (FCS), whereas simple heterozygous LPL variants are associated with hypertriglyceridemia (HTG) and HTG-related disorders. LPL frameshift coding sequence variants usually cause complete functional loss of the affected allele, thereby allowing exploration of the impact of different levels of LPL function in human disease. METHODS: All exons and flanking intronic regions of LPL were Sanger sequenced in patients with HTG-related acute pancreatitis (HTG-AP) or HTG-AP in pregnancy. Previously reported LPL frameshift coding sequence variants were collated from the Human Gene Mutation Database and through PubMed keyword searching. Original reports were manually evaluated for the following information: zygosity status of the variant, plasma LPL activity of the variant carrier, disease referred for genetic analysis, patient's age at genetic analysis, and patient's disease history. SpliceAI was employed to predict the potential impact of collated variants on splicing. RESULTS: Two novel rare variants were identified, and 53 known LPL frameshift coding sequence variants were collated. Of the 51 variants informative for zygosity, 30 were simple heterozygotes, 12 were homozygotes, and 9 were compound heterozygotes. Careful evaluation of the 55 variants with respect to their clinical and genetic data generated several interesting findings. First, we conclude that 6-7% residual LPL function could significantly delay the age of onset of FCS and reduce the prevalence of FCS-associated syndromes. Second, whereas a large majority of LPL frameshift coding sequence variants completely disrupt gene function through their "frameshift" nature, a small fraction of these variants may act wholly or partly as "in-frame" variants, leading to the generation of protein products with some residual LPL function. Third, we identified two candidate LPL frameshift coding sequence variants that may retain residual function based on genotype-phenotype correlation or SpliceAI-predicted data. CONCLUSIONS: This study reported two novel LPL variants and yielded new insights into the genotype-phenotype relationship as it pertains to LPL frameshift coding sequence variants.
ESTHER : Zhang_2023_Lipids.Health.Dis_22_128
PubMedSearch : Zhang_2023_Lipids.Health.Dis_22_128
PubMedID: 37568214
Gene_locus related to this paper: human-LPL

Title : Diketopyrrolopyrrole-based fluorescent probe for visualizing over-expressed carboxylesterase in fever via ratiometric imaging - Zhang_2023_Talanta_266_124971
Author(s) : Zhang B , Qin S , Wang N , Lu X , Jiao J , Zhang J , Zhao W
Ref : Talanta , 266 :124971 , 2023
Abstract : Fever is the result of inflammation and the innate self-defense response of organisms, can cause abnormal changes in the activity of many enzymes in organisms, including the important carboxylesterase (CE). Monitoring the activity changes of CE in vivo during a fever will help to understand heat-related pathological mechanisms. In this paper, we designed diketopyrrolopyrrole-based ratiometric fluorescent probes DPP-FBC-P and DPP-FBO-P containing alkyl chain and diethylene glycol monomethyl ether chain respective for detection of CE. Both probes could realized fast response to CE and displayed good selectivity and high sensitivity. Compared with DPP-FBO-P, DPP-FBC-P had better biocompatibility, larger signal to noise ratio (225-fold vs 125-fold) and lower detection limit (1.6 x 10(-5) U/mL vs 4.2 x 10(-5) U/mL). Moreover, the probe DPP-FBC-P had been successfully applied to image the endogenous CE in HepG2 cells and solid tumors, and also visualized the over expressed CE in fever cells. Most importantly, the changes of CE level in the liver of fever mice model induced by LPS were monitored with the assistance of DPP-FBC-Pvia dual channel ratio imaging for the first time. In addition, fluorescence color signal in solution was captured by smart phone, and the linear relationship between RGB ratio (G/R) and CE concentration was established. This work will provide a potential approach for investigating the physiological and pathological processes of heat related diseases.
ESTHER : Zhang_2023_Talanta_266_124971
PubMedSearch : Zhang_2023_Talanta_266_124971
PubMedID: 37480822

Title : Identification and Functions of JHE 6 Specifically Expressed in Bombyx mori Silk Gland - Zhang_2023_Insects_14_
Author(s) : Zhang X , Zhang J , Wu K , Yang H , Cheng T , Liu C
Ref : Insects , 14 : , 2023
Abstract : Juvenile hormone esterase (JHE) is the specific enzyme that degrades juvenile hormone (JH) and regulates the JH titer in insects. JH also regulates the development of the silk gland and the synthesis and secretion of silk proteins in Bombyx mori. Here, we identified nine possible JHE family members, Bmjhe1-9. Notably, Bmjhe6 is specifically expressed in the silk gland. Using semi-quantitative, quantitative real-time RT-PCR and Western blot, it was confirmed that Bmjhe6 was specifically expressed in the middle silk gland (MSG) with high levels in the anterior region of the MSG (A-MSG). The immunofluorescence localization analysis revealed that Bmjhe6 is produced within cells, secreted into the gland lumen, and co-transported with silk proteins into the anterior silk gland (ASG). In vitro hormone induction experiments demonstrated that Bmjhe6 responds to a JH analog, increasing its expression after 12-24 h, whereas 20-hydroxyecdysone inhibited it. In addition, Bmjhe6 knockdown using dsBmjhe6 injections accelerated larval development, resulting in increased larval body and silk gland weight. This induced disordered sericin genes (Ser2, Ser3) expression, and key genes in the JH synthesis pathway (BmKr-h1 and BmMet1) were significantly upregulated along with the transcription factors (SGF-1 and Sage). These results indicate that Bmjhe6 plays an important role in silk gland growth and silk protein synthesis by modulating JH signal.
ESTHER : Zhang_2023_Insects_14_
PubMedSearch : Zhang_2023_Insects_14_
PubMedID: 38132582

Title : Exploring the binding effects and inhibiting mechanism of hyperoside to lipase using multi-spectroscopic approaches, isothermal titration calorimetry, inhibition kinetics and molecular dynamics - Zeng_2023_RSC.Adv_13_6507
Author(s) : Zeng Z , Wu D , Tang L , Hu X , Zhang J , Geng F
Ref : RSC Adv , 13 :6507 , 2023
Abstract : Hyperoside (HYP) is a flavonoid with various physiological activities. The present study examined the interaction mechanism between HYP and lipase using multi-spectrum and computer-aided techniques. Results demonstrated that the force type of HYP on lipase was mainly hydrogen bond, hydrophobic interaction force, and van der Waals force, and HYP had an excellent binding affinity with lipase at 1.576 x 10(5) M(-1). HYP dose-dependently inhibited lipase in the inhibition experiment, and its IC(50) value was 1.92 x 10(-3) M. Moreover, the results suggested that HYP could inhibit the activity by binding to essential groups. Conformational studies indicated that the conformation and microenvironment of lipase were slightly changed after the addition of HYP. Computational simulations further confirmed the structural relationships of HYP to lipase. The interaction between HYP and lipase can provide ideas for the development of functional foods related to weight loss. The results of this study help comprehend the pathological significance of HYP in biological systems, as well as its mechanism.
ESTHER : Zeng_2023_RSC.Adv_13_6507
PubMedSearch : Zeng_2023_RSC.Adv_13_6507
PubMedID: 36845588

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 : Inhibition effect of 1-acetoxy-6alpha-(2-methylbutyryl)eriolanolide toward soluble epoxide hydrolase: Multispectral analysis, molecular dynamics simulation, biochemical, and in vitro cell-based studies - Zhang_2023_Int.J.Biol.Macromol__123911
Author(s) : Zhang J , Yang FY , Zhu QM , Zhang WH , Zhang M , Yi J , Wang Y , Zhang HL , Yan JK , Liang GB , Sun CP
Ref : Int J Biol Macromol , :123911 , 2023
Abstract : Soluble epoxide hydrolase (sEH) serves as a potential target in inflammation-related diseases. Based on the bioactivity-guided separation, a new sesquiterpenoid inulajaponoid A (1) was isolated from Inula japonica with a sEH inhibitory effect, together with five known compounds, such as 1-O-acetyl-6-O-isobutyrylbritannilactone (2), 6beta-hydroxytomentosin (3), 1beta,8beta-dihydroxyeudesma-4(15),11(13)-dien-12,6alpha-olide (4), (4S,6S,7S,8R)-1-O-acetyl-6-O-(3-methylvaleryloxy)-britannilactone (5), and 1-acetoxy-6alpha-(2-methylbutyryl)eriolanolide (6). Among them, compounds 1 and 6 were assigned as mixed and uncompetitive inhibitors, respectively. The result of immunoprecipitation (IP)-MS demonstrated the specific binding of compound 6 to sEH in the complex system, which was further confirmed by the fluorescence-based binding assay showing its equilibrium dissociation constant (K(d) = 2.43 microM). The detail molecular stimulation revealed the mechanism of action of compound 6 with sEH through the hydrogen bond of amino acid residue Gln384. Furthermore, this natural sEH inhibitor (6) could suppress the MAPK/NF-kappaB activation to regulate inflammatory mediators, such as NO, TNF-alpha, and IL-6, which confirmed the anti-inflammatory effect of inhibition of sEH by 6. These findings provided a useful insight to develop sEH inhibitors upon the sesquiterpenoids.
ESTHER : Zhang_2023_Int.J.Biol.Macromol__123911
PubMedSearch : Zhang_2023_Int.J.Biol.Macromol__123911
PubMedID: 36878397

Title : N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor - Mao_2023_Anal.Chem__
Author(s) : Mao YW , Zhang J , Zhang R , Li JQ , Wang AJ , Zhou XC , Feng JJ
Ref : Analytical Chemistry , : , 2023
Abstract : Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (.OH) in the H(2)O(2) system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive colorimetric sensor was built for detection of AChE with a broader linear range of 0.1-30 U L(-1) and a lower limit of detection (LOD, 0.066 U L(-1)), combined with its feasible analysis in human serum samples. Also, this platform was applied for measuring huperzine A inhibitor with a wide linear scope of 5-500 nM and a LOD down to 4.17 nM. This strategy provides a low-cost and convenient approach for early clinical diagnosis and drug development.
ESTHER : Mao_2023_Anal.Chem__
PubMedSearch : Mao_2023_Anal.Chem__
PubMedID: 37220384

Title : Near-infrared ratiometric fluorescent strategy for butyrylcholinesterase activity and its application in the detection of pesticide residue in food samples and biological imaging - Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
Author(s) : Yuan W , Wan C , Zhang J , Li Q , Zhang P , Zheng K , Zhang Q , Ding C
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 297 :122719 , 2023
Abstract : Butyrylcholinesterase (BChE) is an essential esterase synthesized by the liver, and its level is considered as a vital index for health evaluation. Therefore, it is of great need to develop a highly sensitive and selective tool to monitor BChE activity, which remains a considerable challenge on account of its usage in complex biological systems. A near-infrared (NIR) fluorescent probe was elaborated in this work, employing cyanine backbone to provide the intrinsic NIR fluorescence and avoid interference from bioluminescence. There presented an intriguing structural transformation upon the sensing event to shrink the conjugation in this protocol, leading to an eye-catching fluorescence change from NIR (816 nm) to red (637 nm) region, which gave rise to the proposed ratiometric assay. After an overall investigation, this receptor was verified to be applicable in a wide bio-area with ratiometric pattern, including the cellular level and slice platform. It was worth mentioning that this receptor was also discovered to be capable of monitoring pesticide dichlorvos (DDVP) residue in food samples with high sensitivity and accuracy, with significant potential to be developed as an alternative candidate for monitoring environmental pollution.
ESTHER : Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
PubMedSearch : Yuan_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_297_122719
PubMedID: 37043836

Title : Effects of walnut seed coat polyphenols on walnut protein hydrolysates: Structural alterations, hydrolysis efficiency, and acetylcholinesterase inhibitory capacity - Su_2023_Food.Chem_437_137905
Author(s) : Su G , Chen J , Huang L , Zhao M , Huang Q , Zhang J , Zeng X , Zhang Y , Deng L , Zhao T
Ref : Food Chem , 437 :137905 , 2023
Abstract : The walnut meal is rich in nutrients such as protein from the kernel and polyphenolic compounds from the seed coat. However, the influences of seed coat polyphenols on walnut protein (WP) hydrolysis remained unclear. In this study, our findings indicated that polyphenols induced alterations in the secondary structure and amino acid composition of WP. These changes resulted in both a hindrance of hydrolysis and an enhancement of acetylcholinesterase (AChE) inhibition. Furthermore, four peptides of 119 identified peptides (LR, SF, FQ, and FR) were synthesized based on higher predicted bioactivity and Vinascores in silico. Among them, FQ showed interaction with amino acid residues in AChE through the formation of four Pi-Pi stacking bonds and two hydrogen bonds, resulting in the highest AChE inhibitory capacity. The combination index showed that chlorogenic acid derived from the seed coat and FQ at the molar ratio of 1:4 exhibited synergistic effects of AChE inhibition.
ESTHER : Su_2023_Food.Chem_437_137905
PubMedSearch : Su_2023_Food.Chem_437_137905
PubMedID: 37922803

Title : Enhancement degradation efficiency of pyrethroid-degrading esterase (Est816) through rational design and its application in bioremediation - Fan_2023_Chemosphere_319_138021
Author(s) : Fan X , Zhao M , Wen H , Zhang Y , Zhang J , Liu X
Ref : Chemosphere , 319 :138021 , 2023
Abstract : The pervasive use of pyrethroids is seriously hazardous to the environment and even human health. Enzymatic bioremediation is potentially a rapid and environmentally friendly technology to combat the pollution of pyrethroid pesticides. The hydrolysis of ester linkages is the initial and critical enzymatic step in microbial degradation pathways. Here, the versatile and thermostable esterase Est816 was cloned and its new function, pyrethroid-hydrolysis activity, was expanded. To further improve its pyrethroid-hydrolysis ability, Est816 was modified by rational design. After two rounds of mutation, the best-performing mutant, Est816(A216V/K238N/M97V,) was obtained, which could completely degrade 1 mg/L lambda-cyhalothrin, cypermethrin, and deltamethrin within 20 min, and efficiently degrade fenvalerate, reaching over 80% conversion. Degradation activity analyses showed that three substitutions (A216V, K238 N and M97V) were beneficial for enhancing the activity of Est816. Enzymatic characterization showed that Est816(A216V/K238N/M97V) inherited broad substrate specificity and possessed excellent stability and adaptability over wide ranges of temperature and pH, which is essential for bioremediation in frequently changing conditions. Furthermore, Est816(A216V/K238N/M97V) had the best degradation effect on all four pyrethroid residues in Panax notoginseng root, with more than 87% conversion after 24 h. Pyrethroid residues in tea, cucumber, and soil were reduced by more than 76%, 80%, and 76%, respectively. Taken together, these findings highlight the great potential of Est816(A216V/K238N/M97V) in the bioremediation of pyrethroid-contaminated soil and agricultural products.
ESTHER : Fan_2023_Chemosphere_319_138021
PubMedSearch : Fan_2023_Chemosphere_319_138021
PubMedID: 36731665
Gene_locus related to this paper: 9bact-i6yrg4

Title : Systemic effects of nanoplastics on multi-organ at the environmentally relevant dose: The insights in physiological, histological, and oxidative damages - Meng_2023_Sci.Total.Environ__164687
Author(s) : Meng X , Ge L , Zhang J , Xue J , Gonzalez-Gil G , Vrouwenvelder JS , Li Z
Ref : Sci Total Environ , :164687 , 2023
Abstract : Nanoplastics (NPs) are ubiquitous contaminants that have adverse effects on human health. Previous research has explored the toxicity of NPs on specific organs at high doses, but this is insufficient for accurate health risk assessments. In the present study, a systematic study of NPs toxicity in the liver, kidney, and intestine was performed on mice at an equivalent dose of potential human exposure and toxic dose for four weeks. The results revealed that NPs penetrated the intestinal barrier and accumulated in various organs including liver, kidney, and intestine via the clathrin-mediated endocytosis, phagocytosis, and paracellular pathways. At the toxic dose, damage scores on physiology, morphology, and redox balance were more than twice that at the environmentally relevant dose, which was dose-depended. The jejunum experienced the most severe damage compared to the liver and kidney. In addition, a significant correlation between biomarkers was found, such as TNF-alpha and cholinesterase levels, indicating a close connection between the intestine and liver. Remarkably, the NPs exposed mice had an approximate double reactive oxygen species content compared to the control. This study promotes comprehensive understanding of health risks caused by NPs throughout the body and informs future policies and regulations to mitigate NPs-related health concerns.
ESTHER : Meng_2023_Sci.Total.Environ__164687
PubMedSearch : Meng_2023_Sci.Total.Environ__164687
PubMedID: 37290651

Title : Computational Modeling Study of the Binding of Aging and Non-Aging Inhibitors with Neuropathy Target Esterase - Wu_2023_Molecules_28_
Author(s) : Wu W , Huang J , Han P , Zhang J , Wang Y , Jin F , Zhou Y , Wang P
Ref : Molecules , 28 : , 2023
Abstract : Neuropathy target esterase (NTE) is a serine hydrolase with phospholipase B activity, which is involved in maintaining the homeostasis of phospholipids. It can be inhibited by aging inhibitors such as some organophosphorus (OP) compounds, which leads to delayed neurotoxicity with distal degeneration of axons. However, the detailed binding conformation of aging and non-aging inhibitors with NTE is not known. In this study, new computational models were constructed by using MODELLER 10.3 and AlphaFold2 to further investigate the inhibition mechanism of aging and non-aging compounds using molecular docking. The results show that the non-aging compounds bind the hydrophobic pocket much deeper than aging compounds and form the hydrophobic interaction with Phe1066. Therefore, the unique binding conformation of non-aging compounds may prevent the aging reaction. These important differences of the binding conformations of aging and non-aging inhibitors with NTE may help explain their different inhibition mechanism and the protection of non-aging NTE inhibitors against delayed neuropathy.
ESTHER : Wu_2023_Molecules_28_
PubMedSearch : Wu_2023_Molecules_28_
PubMedID: 38005352 || 38067477

Title : Combination of two-photon fluorescent probes for carboxylesterase and ONOO(-) to visualize the transformation of nonalcoholic fatty liver to nonalcoholic steatohepatitis in liver orthotopic imaging - Jiao_2023_Talanta_270_125521
Author(s) : Jiao X , Wang Y , Zhang J , Wang X
Ref : Talanta , 270 :125521 , 2023
Abstract : As the most common cause of liver diseases, nonalcoholic fatty liver disease (NAFLD) can be classified into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). While NAFL is generally benign, the transition from NAFL to NASH is a cardinal feature of the non-benign liver disease that leads to cirrhosis and cancer, which indicates that tracking the transformation of NAFL to NASH timely is significant for precision management of liver diseases. Therefore, two fluorescent probes (CNFCl and DRNO) have been developed to visualize this pathological event. alpha-Fluorochloroacetamide and alpha-ketoamide was employed as the recognition site for carboxylesterase (CE) in CNFCl and peroxynitrite (ONOO(-)) in DRNO, respectively. CNFCl (lambda(em) = 445 nm) and DRNO (lambda(em) = 560 nm) showed high specificity and sensitivity towards CE and ONOO(-) respectively. By incubating with CE/ONOO(-) for 0.5 h respectively, both the emission intensity of CNFCl (linear range: 0-0.2 U/mL) and DRNO (linear range: 0-17.5 microM) displayed significant enhancement. As a result, the detection limit of CNFCl and DRNO for CE and ONOO(-) was calculated as 4.2 mU/L and 0.05 microM respectively. More importantly, the emission spectra of CNFCl and DRNO in the presence of CE and ONOO(-) respectively were cross-talk free under the two-photon excitation of 720 nm. This greatly facilitated the simultaneous detection of CE and ONOO(-) at distinctive channel, thus ensuring the high fidelity of the detection. These two probes were combined to image the fluctuation of CE and ONOO(-) during the conversion of NAFL to NASH in vitro and in vivo. It was found that while CE displayed a tendency to rise and then reduce during the transition from NAFL to NASH, ONOO(-) increased continuously, confirming that the combined imaging by CNFCl and DRNO might visualize the transformation of NAFL to NASH. The results provide robust visual tool to decipher the relationship between the stage of NAFLD and the level of CE/ONOO(-). We anticipate this study may open new avenues to distinguish NASH from NAFL, which may further promote the study of intracellular biological activities of CE and the development of NAFLD diagnostic methods.
ESTHER : Jiao_2023_Talanta_270_125521
PubMedSearch : Jiao_2023_Talanta_270_125521
PubMedID: 38091750

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 : In-vitro metabolism of LXY18, an orally available, potent blocker of AURKB relocation in mitosis - Li_2023_J.Pharm.Biomed.Anal_232_115415
Author(s) : Li J , Choudhry N , Lv G , Nimishetti N , Reddy MC , Liu H , Allen TD , Zhang J , Yang D
Ref : J Pharm Biomed Anal , 232 :115415 , 2023
Abstract : This study investigated the metabolism of LXY18, a quinolone-based compound that suppresses tumorigenesis by blocking AURKB localization. Metabolite profiling of LXY18 in liver microsomes from six species and human S9 fractions revealed that LXY18 undergoes various conserved metabolic reactions, such as N-hydroxylation, N-oxygenation, O-dealkylation, and hydrolysis, resulting in ten metabolites. These metabolites were produced through a combination of CYP450 enzymes, and non-CYP450 enzymes including CES1, and AO. Two metabolites, M1 and M2 were authenticated by chemically synthesized standards. M1 was the hydrolyzed product catalyzed by CES1 whereas M2 was a mono-N-oxidative derivative catalyzed by a CYP450 enzyme. AO was identified as the enzyme responsible for the formation of M3 with the help of AO-specific inhibitors and LXY18 analogs, 5b and 5c. M1 was the intermediate of LXY18 to produce M7, M8, M9, and M10. LXY18 potently inhibited 2C19 with an IC(50) of 290 nM but had a negligible impact on the other CYP450s, indicating a low risk of drug-drug interaction. Altogether, the study provides valuable insights into the metabolic process of LXY18 and its suitability as a drug candidate. The data generated serves as a significant reference point for conducting further safety assessments and optimizing drug development.
ESTHER : Li_2023_J.Pharm.Biomed.Anal_232_115415
PubMedSearch : Li_2023_J.Pharm.Biomed.Anal_232_115415
PubMedID: 37120975

Title : Computational design of highly efficient thermostable MHET hydrolases and dual enzyme system for PET recycling - Zhang_2023_Commun.Biol_6_1135
Author(s) : Zhang J , Wang H , Luo Z , Yang Z , Zhang Z , Wang P , Li M , Zhang Y , Feng Y , Lu D , Zhu Y
Ref : Commun Biol , 6 :1135 , 2023
Abstract : Recently developed enzymes for the depolymerization of polyethylene terephthalate (PET) such as FAST-PETase and LCC-ICCG are inhibited by the intermediate PET product mono(2-hydroxyethyl) terephthalate (MHET). Consequently, the conversion of PET enzymatically into its constituent monomers terephthalic acid (TPA) and ethylene glycol (EG) is inefficient. In this study, a protein scaffold (1TQH) corresponding to a thermophilic carboxylesterase (Est30) was selected from the structural database and redesigned in silico. Among designs, a double variant KL-MHETase (I171K/G130L) with a similar protein melting temperature (67.58 degreesC) to that of the PET hydrolase FAST-PETase (67.80 degreesC) exhibited a 67-fold higher activity for MHET hydrolysis than FAST-PETase. A fused dual enzyme system comprising KL-MHETase and FAST-PETase exhibited a 2.6-fold faster PET depolymerization rate than FAST-PETase alone. Synergy increased the yield of TPA by 1.64 fold, and its purity in the released aromatic products reached 99.5%. In large reaction systems with 100 g/L substrate concentrations, the dual enzyme system KL36F achieved over 90% PET depolymerization into monomers, demonstrating its potential applicability in the industrial recycling of PET plastics. Therefore, a dual enzyme system can greatly reduce the reaction and separation cost for sustainable enzymatic PET recycling.
ESTHER : Zhang_2023_Commun.Biol_6_1135
PubMedSearch : Zhang_2023_Commun.Biol_6_1135
PubMedID: 37945666
Gene_locus related to this paper: geost-est30

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : RhlA Exhibits Dual Thioesterase and Acyltransferase Activities during Rhamnolipid Biosynthesis - Tang_2023_ACS.Catal_13_5759
Author(s) : Ting Tang T , Fu L , Xie W , Luo Y , Zhang Y , Zhang J , Si T
Ref : ACS Catal , 13 :5759 , 2023
Abstract : Rhamnolipids (RLs) are a desirable class of biosurfactants originating from Pseudomonas aeruginosa. Rhamnosyltransferase 1 chain A (RhlA) catalyzes the formation of -3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs) to constitute the RL lipid moiety, and the molecular structure of this moiety exerts major impacts on the physiochemical and biological properties of corresponding RLs. However, the catalytic mechanism and sequence-structurefunction relationship of RhlA remain elusive. Here, we report the X-ray crystal structure of P. aeruginosa RhlA with an a/-hydrolase fold and a canonical nucleophile/histidine/acidic catalytic triad. Unexpectedly, free 3-hydroxy fatty acids within a secondary ligand-binding pocket were observed in the crystal of RhlA, which is traditionally considered an acyltransferase that acts only on acyl carrier protein (ACP)-bound substrates. In vitro isotopic labeling, enzyme kinetics experiments, and QM/MM simulations confirmed that free -hydroxy fatty acids are a reaction intermediate during HAA synthesis. Moreover, first-shell residue mutations that targeted different ligand-binding pockets resulted in distinct modulation patterns for the two acyl chain lengths of HAAs. In conclusion, the revealed biosynthetic mechanism may guide future engineering for the biosynthesis of designer RLs.
ESTHER : Tang_2023_ACS.Catal_13_5759
PubMedSearch : Tang_2023_ACS.Catal_13_5759
PubMedID:
Gene_locus related to this paper: pseae-rhla

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

Title : In silico identification of novel stilbenes analogs for potential multi-targeted drugs against Alzheimer's disease - Firdoos_2023_J.Mol.Model_29_209
Author(s) : Firdoos S , Dai R , Tahir RA , Khan ZY , Li H , Zhang J , Ni J , Quan Z , Qing H
Ref : J Mol Model , 29 :209 , 2023
Abstract : CONTEXT: Alzheimer's disease (AD) is a chronic progressive neurodegenerative syndrome, which adversely disturbs cognitive abilities as well as intellectual processes and frequently occurs in the elderly. Inhibition of cholinesterase is a valuable approach to upsurge acetylcholine concentrations in the brain and persuades the development of multi-targeted ligands against cholinesterases. METHODS: The current study aims to determine the binding potential accompanied by antioxidant and anti-inflammatory activities of stilbenes-designed analogs against both cholinesterases (Acetylcholinesterase and butyrylcholinesterase) and neurotrophin targets for effective AD therapeutics. Docking results have shown that the WS6 compound exhibited the least binding energy - 10.1 kcal/mol with Acetylcholinesterase and - 7.8 kcal/mol with butyrylcholinesterase. The WS6 also showed a better binding potential with neurotrophin targets that are Brain-derived Neurotrophic Factor, Neurotrophin 4, Nerve Growth Factor, and Neurotrophin 3. The tested compounds particularly WS6 revealed significant antioxidant and anti-inflammatory activities through the comparative docking analysis with Fluorouracil and Melatonin as control drugs of antioxidants while Celecoxib and Anakinra as anti-inflammatory. The bioinformatics approaches including molecular docking calculations followed by the pharmacokinetics analysis and molecular dynamic simulations were accomplished to explore the capabilities of designed stilbenes as effective and potential leads. Root mean square deviation, root mean square fluctuations, and MM-GBSA calculations were performed through molecular dynamic simulations to extract the structural and residual variations and binding free energies through the 50-ns time scale.
ESTHER : Firdoos_2023_J.Mol.Model_29_209
PubMedSearch : Firdoos_2023_J.Mol.Model_29_209
PubMedID: 37314512

Title : Influence of Five Drying Methods on Active Compound Contents and Bioactivities of Fresh Flowers from Syringa pubescens Turcz - Xu_2023_Molecules_28_
Author(s) : Xu W , Zhang J , Wu Y , Zhang Z , Wang X , Ma J
Ref : Molecules , 28 : , 2023
Abstract : The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against alpha-amylase, alpha-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC(50) values with 0.118 +/- 0.004 mg/mL for DPPH radical, 1.538 +/- 0.0972 for hydroxyl radical and 0.886 +/- 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H(2)O(2)-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1beta and TNF-alpha expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC(50) values of inhibitory activity on alpha-glucosidase and alpha-amylase from SHD sample were 2.516 +/- 0.024 and 0.734 +/- 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC(50) values of 3.443 +/- 0.060 and 1.732 +/- 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.
ESTHER : Xu_2023_Molecules_28_
PubMedSearch : Xu_2023_Molecules_28_
PubMedID: 38067533

Title : Platinum nanoflowers stabilized with aloe polysaccharides for detection of organophosphorus pesticides in food - Zhao_2023_Int.J.Biol.Macromol__126552
Author(s) : Zhao H , Li R , Zhang T , Zhou L , Wang L , Han Z , Liu S , Zhang J
Ref : Int J Biol Macromol , :126552 , 2023
Abstract : Organophosphorus pesticides can inhibit the activity of acetylcholinesterase and cause neurological diseases. Therefore, it is crucial to establish an efficient and sensitive platform for organophosphorus pesticide detection. In this work, we extracted aloe polysaccharide (AP) from aloe vera with the number average molecular weight of 29,271 Da and investigated its reducing property. We prepared aloe polysaccharide stabilized platinum nanoflowers (AP-Pt(n) NFs), their particle size ranges were 29.4-67.3 nm. Furthermore, AP-Pt(n) NFs exhibited excellent oxidase-like activity and the catalytic kinetics followed the typical Michaelis-Menten equation. They showed strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of organophosphorus pesticides in food using biocompatible AP-Pt(n) NFs. The detection range was 0.5 microg/L - 140 mg/L, which was wider than many previously reported nanozyme detection systems. This colorimetric biosensor had good selectivity and good promise for bioassay analysis.
ESTHER : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedSearch : Zhao_2023_Int.J.Biol.Macromol__126552
PubMedID: 37660849

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

Title : Macrophage Inactivation by Small Molecule Wedelolactone via Targeting sEH for the Treatment of LPS-Induced Acute Lung Injury - Zhang_2023_ACS.Cent.Sci_9_440
Author(s) : Zhang J , Zhang M , Huo XK , Ning J , Yu ZL , Morisseau C , Sun CP , Hammock BD , Ma XC
Ref : ACS Cent Sci , 9 :440 , 2023
Abstract : Soluble epoxide hydrolase (sEH) plays a critical role in inflammation by modulating levels of epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs). Here, we investigate the possible role of sEH in lipopolysaccharide (LPS)-mediated macrophage activation and acute lung injury (ALI). In this study, we found that a small molecule, wedelolactone (WED), targeted sEH and led to macrophage inactivation. Through the molecular interaction with amino acids Phe362 and Gln384, WED suppressed sEH activity to enhance levels of EETs, thus attenuating inflammation and oxidative stress by regulating glycogen synthase kinase 3beta (GSK3beta)-mediated nuclear factor-kappa B (NF-kappaB) and nuclear factor E2-related factor 2 (Nrf2) pathways in vitro. In an LPS-stimulated ALI animal model, pharmacological sEH inhibition by WED or sEH knockout (KO) alleviated pulmonary damage, such as the increase in the alveolar wall thickness and collapse. Additionally, WED or sEH genetic KO both suppressed macrophage activation and attenuated inflammation and oxidative stress in vivo. These findings provided the broader prospects for ALI treatment by targeting sEH to alleviate inflammation and oxidative stress and suggested WED as a natural lead candidate for the development of novel synthetic sEH inhibitors.
ESTHER : Zhang_2023_ACS.Cent.Sci_9_440
PubMedSearch : Zhang_2023_ACS.Cent.Sci_9_440
PubMedID: 36968547

Title : Inhibition of 2-arachidonoylglycerol degradation enhances glial immunity by single-cell transcriptomic analysis - Zhu_2023_J.Neuroinflammation_20_17
Author(s) : Zhu D , Zhang J , Hashem J , Gao F , Chen C
Ref : J Neuroinflammation , 20 :17 , 2023
Abstract : BACKGROUND: 2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid. Inhibition of 2-AG metabolism by inactivation of monoacylglycerol lipase (MAGL), the primary enzyme that degrades 2-AG in the brain, produces anti-inflammatory and neuroprotective effects in neurodegenerative diseases. However, the molecular mechanisms underlying these beneficial effects are largely unclear. METHODS: Hippocampal and cortical cells were isolated from cell type-specific MAGL knockout (KO) mice. Single-cell RNA sequencing was performed by 10 x Genomics platform. Cell Ranger, Seurat (v3.2) and CellChat (1.1.3) packages were used to carry out data analysis. RESULTS: Using single-cell RNA sequencing analysis, we show here that cell type-specific MAGL KO mice display distinct gene expression profiles in the brain. Inactivation of MAGL results in robust changes in expression of immune- and inflammation-related genes in microglia and astrocytes. Remarkably, upregulated expression of chemokines in microglia is more pronounced in mice lacking MAGL in astrocytes. In addition, expression of genes that regulate other cellular functions and Wnt signaling in astrocytes is altered in MAGL KO mice. CONCLUSIONS: Our results provide transcriptomic evidence that cell type-specific inactivation of MAGL induces differential expression of immune-related genes and other fundamental cellular pathways in microglia and astrocytes. Upregulation of the immune/inflammatory genes suggests that tonic levels of immune/inflammatory vigilance are enhanced in microglia and astrocytes, particularly in microglia, by inhibition of 2-AG metabolism, which likely contribute to anti-inflammatory and neuroprotective effects produced by inactivation of MAGL in neurodegenerative diseases.
ESTHER : Zhu_2023_J.Neuroinflammation_20_17
PubMedSearch : Zhu_2023_J.Neuroinflammation_20_17
PubMedID: 36717883

Title : Sublethal effects of halofenozide on larval development and detoxification in Phaedon brassicae (Coleoptera: Chrysomelidae) - Ma_2023_J.Econ.Entomol__
Author(s) : Ma L , Xu C , Peng Y , Zhang J , Zhang W
Ref : J Econ Entomol , : , 2023
Abstract : The brassica leaf beetle, Phaedon brassicae, is a serious defoliator of cruciferous crops. Halofenozide (Hal), an ecdysone agonist, is a new class of insect growth-regulating insecticide. Our preliminary experiment revealed the outstanding larval toxicity of Hal against P. brassicae. However, the metabolic degradation of this compound in insects remains unclear. In this study, oral administration of Hal at LC10 and LC25 caused severe separation of the cuticle and epidermis, leading to larval molting failure. Sublethal dose exposure also significantly reduced the larval respiration rate as well as their pupation rates and pupal weights. Conversely, the activities of the multifunctional oxidase, carboxylesterase (CarE), and glutathione S-transferase (GST) were significantly enhanced in Hal-treated larvae. Further analysis using RNA sequencing identified 64 differentially expressed detoxifying enzyme genes, including 31 P450s, 13 GSTs, and 20 CarEs. Among the 25 upregulated P450s, 22 genes were clustered into the CYP3 clan, and the other 3 genes belonged to the CYP4 clan. Meanwhile, 3 sigma class GSTs and 7 epsilon class GSTs were dramatically increased, accounting for the majority of the upregulated GSTs. Moreover, 16 of the 18 overexpressed CarEs were clustered into the coleopteran xenobiotic-metabolizing group. These results showed the augmented expression of detoxification genes in P. brassicae after exposed to sublethal dose of Hal, and helped to better understand the potential metabolic pathways that could contribute to the reduced sensitivity to Hal in this pest. Overall, a deep insight into the detoxification mechanisms would provide practical guidance for the field management of P. brassicae.
ESTHER : Ma_2023_J.Econ.Entomol__
PubMedSearch : Ma_2023_J.Econ.Entomol__
PubMedID: 37338416

Title : Integration of clinical demographics and routine laboratory analysis parameters for early prediction of gestational diabetes mellitus in the Chinese population - Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
Author(s) : Zhang H , Dai J , Zhang W , Sun X , Sun Y , Wang L , Li H , Zhang J
Ref : Front Endocrinol (Lausanne) , 14 :1216832 , 2023
Abstract : Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy, impairing both maternal and fetal health in short and long term. As early interventions are considered desirable to prevent GDM, this study aims to develop a simple-to-use nomogram based on multiple common risk factors from electronic medical health records (EMHRs). A total of 924 pregnant women whose EMHRs were available at Peking University International Hospital from January 2022 to October 2022 were included. Clinical demographics and routine laboratory analysis parameters at 8-12 weeks of gestation were collected. A novel nomogram was established based on the outcomes of multivariate logistic regression. The nomogram demonstrated powerful discrimination (the area under the receiver operating characteristic curve = 0.7542), acceptable agreement (Hosmer-Lemeshow test, P = 0.3214) and favorable clinical utility. The C-statistics of 10-Fold cross validation, Leave one out cross validation and Bootstrap were 0.7411, 0.7357 and 0.7318, respectively, indicating the stability of the nomogram. A novel nomogram based on easily-accessible parameters was developed to predict GDM in early pregnancy, which may provide a paradigm for repurposing clinical data and benefit the clinical management of GDM. There is a need for prospective multi-center studies to validate the nomogram before employing the nomogram in real-world clinical practice.
ESTHER : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedSearch : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedID: 37900122

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 : An ultrasensitive and selective near-infrared fluorescent probe for tracking carboxylesterases with large Stokes shift in living cells and mice - Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
Author(s) : Zhang W , Qi C , Wang X , Fu Z , Zhang J , Zhou Y , Wang Y
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 308 :123708 , 2023
Abstract : Carboxylesterases (CEs) play great role in CEs-related diseases and drug metabolism. Selectively monitoring its activity is important to explore its role in CEs-related diseases and drug combination. Herein, a new "turn-on" near-infrared (NIR) fluorescent probe (CHY-1) was reported with large Stokes shift (145 nm) for CEs detection. Dicyanoisophorone-based derivative was chosen as NIR fluorophore and 4-bromobutyrate was the identifying group. What's more, CHY-1 exhibited ultra-sensitivity (LOD - 9.2 x 10(-5) U/mL), high selectivity against Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE) and Chymotrypsin for CEs fluorescence detection under physiological pH and temperature. Furthermore, CHY-1 showed little effect on cell viability at high concentration and featured good optical imaging character for the slight change of CEs activity induced by 5-Fu (5-Fluorouridine, anti-tumor drug) and CEs inhibitor in living cells. Moreover, CHY-1 was also used to detect the activity and distribution of CEs in mice. Taken together, CHY-1 had widely applicable value in the diagnosis of CEs-related diseases and drug combination.
ESTHER : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedSearch : Zhang_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_308_123708
PubMedID: 38042124

Title : Multi- and trans-generational effects of di-n-octyl phthalate on behavior, lifespan and reproduction of Caenorhabditis elegans through neural regulation and lipid metabolism - Zhang_2023_Sci.Total.Environ__165268
Author(s) : Zhang J , Wang L , Liu M , Yu Z
Ref : Sci Total Environ , :165268 , 2023
Abstract : Di-n-octyl phthalate (DOP) is one important phthalate analog whose toxicities need comprehensive investigation to fully demonstrate phthalates health risks. In the present study, apical effects of DOP on behavior, lifespan and reproduction and the underlying mechanisms were explored in Caenorhabditis elegans for four consecutive generations (F1 to F4) and the trans-generational effects were also measured in the great-grand-children (T4 and T4') of F1 and F4. Multi-generational results showed that DOP caused both stimulation and inhibition on head swing, body bending, reverse, Omega steering, pharyngeal pump and satiety quiescence. The stimulation and inhibition altered over concentrations and across generations, and the alteration was the greatest in reverse locomotion which showed both concentration-dependent hormesis and trans-hormesis. DOP stimulated lifespan and inhibited reproduction, showing trade-off relationships. Significant trans-generational residual effects were found in T4 and T4' where the exposure was completed eliminated. Moreover, both similar and different effects were found in comparisons between F1 and F4, between F1 and T4, between F4 and T4' and also between T4 and T4'. Further analysis showed close connections between effects of DOP on neurotransmitters (including dopamine, acetylcholine, gamma-aminobutyric acid and serotonin) and enzymes in lipid metabolism (including lipase, acetyl CoA carboxylase, fatty acid synthetase, carnitine palmitoyl-transferase, glycerol phosphate acyltransferase and acetyl CoA synthetase). Moreover, the close connections were also found between biochemical and apical effects. Notably, the connections were different in multi- and trans-generational effects, which urged further studies to reveal the response strategies underlying the exposure scenarios.
ESTHER : Zhang_2023_Sci.Total.Environ__165268
PubMedSearch : Zhang_2023_Sci.Total.Environ__165268
PubMedID: 37406686

Title : Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase attenuated particulate matter 2.5 exposure mediated lung injury - Zhang_2023_J.Hazard.Mater_458_131890
Author(s) : Zhang J , Zhang WH , Morisseau C , Zhang M , Dong HJ , Zhu QM , Huo XK , Sun CP , Hammock BD , Ma XC
Ref : J Hazard Mater , 458 :131890 , 2023
Abstract : Air pollution represented by particulate matter 2.5 (PM2.5) is closely related to diseases of the respiratory system. Although the understanding of its mechanism is limited, pulmonary inflammation is closely correlated with PM2.5-mediated lung injury. Soluble epoxide hydrolase (sEH) and epoxy fatty acids play a vital role in the inflammation. Herein, we attempted to use the metabolomics of oxidized lipids for analyzing the relationship of oxylipins with lung injury in a PM2.5-mediated mouse model, and found that the cytochrome P450 oxidases/sEH mediated metabolic pathway was involved in lung injury. Furthermore, the sEH overexpression was revealed in lung injury mice. Interestingly, sEH genetic deletion or the selective sEH inhibitor TPPU increased levels of epoxyeicosatrienoic acids (EETs) in lung injury mice, and inactivated pulmonary macrophages based on the MAPK/NF-kappaB pathway, resulting in protection against PM2.5-mediated lung injury. Additionally, a natural sEH inhibitor luteolin from Inula japonica displayed a pulmonary protective effect towards lung injury mediated by PM2.5 as well. Our results are consistent with the sEH message and protein being both a marker and mechanism for PM2.5-induced inflammation, which suggest its potential as a pharmaceutical target for treating diseases of the respiratory system.
ESTHER : Zhang_2023_J.Hazard.Mater_458_131890
PubMedSearch : Zhang_2023_J.Hazard.Mater_458_131890
PubMedID: 37406527

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 : Rapid screening for acetylcholinesterase inhibitors in Selaginella doederleinii Hieron by using functionalized magnetic Fe(3)O(4) nanoparticles - Zhang_2022_Talanta_243_123284
Author(s) : Zhang F , Li S , Liu C , Fang K , Jiang Y , Zhang J , Lan J , Zhu L , Pang H , Wang G
Ref : Talanta , 243 :123284 , 2022
Abstract : Insufficient acetylcholine (ACh) can cause cognitive and memory dysfunction, clinically known as, Alzheimer's disease (AD). Acetylcholinesterase (AChE) can hydrolyze ACh into acetic acid and inactivate choline. Therefore, inhibiting the activity of AChE would help to improve the effectiveness of AD treatment. Currently, the methods for rapid screening of AChE inhibitors are limited. This study reports the application of AChE-immobilized magnetic nanoparticles as a drug screening tool to screen AChE inhibitors for natural products. First, AChE was immobilized on a surface of amino-modified magnetic nanoparticles using covalent binding and the AChE concentration, and the pH as well as time was optimized to obtain the maximum enzyme immobilization yield (61.4 microg/mg), and the kinetic model indicated that AChE-immobilized magnetic nanoparticles and the substrate had the high affinity and specificity. Then, a ligand fishing experiment was carried out using a mixed model of tacrine (an inhibitor of AChE) and caffeic acid (a non-inhibitor of AChE) to verify the specificity of the immobilized AChE, and the conditions for ligand fishing were further optimized. Finally, the optimized immobilized AChE was combined with UPLC-MS to screen for AChE inhibitors in Selaginella doederleinii Hieron extracts. Four compounds were confirmed to be potent AChE inhibitors. Among the four compounds, amentoflavone had a stronger AChE inhibitory effect than tacrine (positive control) with an IC(50) of 0.73 +/- 0.009 micromol/L. The results showed that AChE-functionalized magnetic nanoparticles can be used in the discovery of target drugs from complex matrices.
ESTHER : Zhang_2022_Talanta_243_123284
PubMedSearch : Zhang_2022_Talanta_243_123284
PubMedID: 35255433

Title : Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor - Zhang_2022_PLoS.One_17_e0266608
Author(s) : Zhang C , Li W , Li X , Wan D , Mack S , Zhang J , Wagner K , Wang C , Tan B , Chen J , Wu CW , Tsuji K , Takeuchi M , Chen Z , Hammock BD , Pinkerton KE , Yang J
Ref : PLoS ONE , 17 :e0266608 , 2022
Abstract : Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.
ESTHER : Zhang_2022_PLoS.One_17_e0266608
PubMedSearch : Zhang_2022_PLoS.One_17_e0266608
PubMedID: 35443010

Title : Inhibition of Radix Scutellariae flavones on carboxylesterase mediated activations of prodrugs - Zhang_2022_Life.Sci_305_120743
Author(s) : Zhang J , Xiao M , Ji X , Lai YS , Song Q , Zhang Y , Ip CM , Ng WL , Zuo Z
Ref : Life Sciences , 305 :120743 , 2022
Abstract : AIMS: Carboxylesterase (CES) plays an essential role in the hydrolysis of ester prodrugs. Our study explored the inhibitions of Radix Scutellariae flavones, including baicalein (B), baicalin (BG), wogonin (W), wogonoside (WG), oroxylin A (OXA) and oroxylin A-7-O-glucuronide (OAG), on CES-mediated hydrolysis of seven prodrugs (capecitabine, clopidogrel, mycophenolate mofetil, dabigatran etexilate, acetylsalicylic acid, prasugrel and irinotecan). MAIN METHODS: In vitro screenings were developed by incubating the flavones with prodrugs in rat plasma, intestine S9 and liver S9. Docking simulations were conducted using AMDock v1.5.2. In vivo evaluations were performed in rats co-administered with the selected flavone and prodrug via oral gavage/intravenous administration for five consecutive days. KEY FINDINGS: The in vitro investigation showed that B and OXA demonstrated strongest inhibitions on the hydrolysis of irinotecan followed by dabigatran in rat plasma, intestine S9 and liver S9. Consistent results showed in the molecular docking analyses. Additionally, in rats receiving irinotecan, B/OXA intravenous and oral pre-treatments both led to reduction trends on the active metabolite SN-38 formation in plasma. Besides, significant decreases of SN-38/irinotecan plasma concentration ratios were found in the B/OXA oral pre-treatment group with quicker and stronger inhibition potential in OXA pre-treatment than that from B pre-treatment. OXA oral pre-treatment was also found to be able to significantly inhibit intestinal CES2 activities at 0.5 h and 5 h after irinotecan administration. SIGNIFICANCE: Our current findings for the first time alert on potential CES-mediated HDIs between RS flavones and prodrugs, which provide a constructive information referring to rational drug combinations in clinical practice.
ESTHER : Zhang_2022_Life.Sci_305_120743
PubMedSearch : Zhang_2022_Life.Sci_305_120743
PubMedID: 35780840

Title : Discovery of triterpenoids as potent dual inhibitors of pancreatic lipase and human carboxylesterase 1 - Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
Author(s) : Zhang J , Pan QS , Qian XK , Zhou XL , Wang YJ , He RJ , Wang LT , Li YR , Huo H , Sun CG , Sun L , Zou LW , Yang L
Ref : J Enzyme Inhib Med Chem , 37 :629 , 2022
Abstract : Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure-activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC(50) of 0.75 microM and 0.014 microM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC(50) of 2.13 microM and 0.055 microM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.
ESTHER : Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
PubMedSearch : Zhang_2022_J.Enzyme.Inhib.Med.Chem_37_629
PubMedID: 35100926

Title : Enhancement of the polyethylene terephthalate and mono-(2-hydroxyethyl) terephthalate degradation activity of Ideonella sakaiensis PETase by an electrostatic interaction-based strategy - Yin_2022_Bioresour.Technol_364_128026
Author(s) : Yin Q , You S , Zhang J , Qi W , Su R
Ref : Bioresour Technol , 364 :128026 , 2022
Abstract : The serious environmental pollution that came up with the continuously growing demand for polyethylene terephthalate (PET) has attracted global concern. The IsPETase which has shown the highest PET degradation activity under ambient temperature is a promising enzyme for PET biodegradation, while poor thermostability limited its practical application. Herein, an electrostatic interaction-based strategy was applied for rational design of IsPETase towards enhanced thermostability. The IsPETase(I139R) variant displayed the highest T(m) value of 56.4s degreesC and 3.6-times higher PET degradation activity. Molecular simulations demonstrated that the introduction of salt bridges stabilized the local structures, resulting in robust thermostability. Meanwhile, the IsPETase(S92K/D157E/R251A) not only exhibited higher thermostability but also showed a 1.74-fold k(cat) increase towards mono-(2-hydroxyethyl) terephthalate, which ultimately achieved PET depolymerization to complete monomer TPA. Collectively, the electrostatic interaction-based strategy, together with the derived IsPETase variants, could help promote the bio-recycle of PET, reducing the severe global burden of PET waste.
ESTHER : Yin_2022_Bioresour.Technol_364_128026
PubMedSearch : Yin_2022_Bioresour.Technol_364_128026
PubMedID: 36174890

Title : UHPLC-QTOF\/MS-based comparative metabolomics in pectoralis major of fast- and slow-growing chickens at market ages - Zhang_2022_Food.Sci.Nutr_10_487
Author(s) : Zhang J , Cao J , Geng A , Wang H , Chu Q , Yan Z , Zhang X , Zhang Y , Liu H
Ref : Food Sci Nutr , 10 :487 , 2022
Abstract : The molecular regulatory mechanism underlying meat quality between different chicken genotypes remains elusive. This study aimed to identify the differences in metabolites and pathways in pectoralis major (breast muscle) between a commercial fast-growing chicken genotype (Cobb500) and a slow-growing Chinese native chicken genotype (Beijing-You chickens, BYC) at market ages respectively based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF/MS). Eighteen metabolites were identified as potential biomarkers between BYC and Cobb500 at market ages. Among them, L-cysteine exhibited a higher relative intensity in BYC compared with Cobb500 and was enriched into 10 potential flavor-associated KEGG pathways. In addition, the glycerophospholipid metabolism pathway was found to be associated with chicken meat flavor and the accumulation of sn-glycerol 3-phosphate and acetylcholine was more predominant in BYC than that in Cobb500, which were catalyzed by glycerophosphocholine phosphodiesterase (GPCPD1, EC:3.1.4.2), choline O-acetyltransferase (CHAT, EC:2.3.1.6), and acetylcholinesterase (ACHE, EC:3.1.1.7). Overall, the present study provided some metabolites and pathways for further investigating the roles of the differences in meat flavor quality in breast muscle between Cobb500 and BYC at market ages.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_487
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_487
PubMedID: 35154685

Title : Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae - Li_2022_Front.Microbiol_13_853744
Author(s) : Li W , Liu X , Tsui W , Xu A , Li D , Zhang X , Li P , Bian X , Zhang J
Ref : Front Microbiol , 13 :853744 , 2022
Abstract : Klebsiella pneumoniae is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of K. pneumoniae pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of K. pneumoniae have not been fully elucidated. Among these mechanisms, the secretion systems encoded by strains of the bacteria confer adaptive advantages depending on the niche occupied. The type VI secretion system (T6SS) is a multi-protein complex that delivers effector proteins to the extracellular environment or directly to eukaryotic or prokaryotic cells. T6SSs are widely distributed in Gram-negative bacteria and play an important role in bacterial virulence and the interactions between bacteria and other microorganisms or the environment. This study aimed to enhance the understanding of the characteristics of T6SSs in K. pneumoniae through an in-depth comparative genomic analysis of the T6SS in 241 sequenced strains of K. pneumoniae. We identified the T6SS loci, the synteny of the loci in different species, as well as the effectors and core T6SS-related genes in K. pneumoniae. The presence of a T6SS was a common occurrence in K. pneumoniae, and two T6SS clusters are the most prevalent. The variable region downstream of the gene vgrG usually encodes effector proteins. Conserved domain analysis indicated that the identified putative effectors in K. pneumoniae had the functions of lipase, ribonuclease, deoxyribonuclease, and polysaccharide hydrolase. However, some effectors did not contain predicted functional domains, and their specific functions have yet to be elucidated. This in silico study represents a detailed analysis of T6SS-associated genes in K. pneumoniae and provides a foundation for future studies on the mechanism(s) of T6SSs, especially effectors, which may generate new insights into pathogenicity and lead to the identification of proteins with novel antimicrobial properties.
ESTHER : Li_2022_Front.Microbiol_13_853744
PubMedSearch : Li_2022_Front.Microbiol_13_853744
PubMedID: 35633723

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 : Circadian Rhythm and Neurotransmitters Are Potential Pathways through Which Ocean Acidification and Warming Affect the Metabolism of Thick-Shell Mussels - Tang_2022_Environ.Sci.Technol__
Author(s) : Tang Y , Du X , Sun S , Shi W , Han Y , Zhou W , Zhang J , Teng S , Ren P , Liu G
Ref : Environ Sci Technol , : , 2022
Abstract : Although the impacts of ocean acidification and warming on marine organisms have been increasingly documented, little is known about the affecting mechanism underpinning their interactive impacts on physiological processes such as metabolism. Therefore, the effects of these two stressors on metabolism were investigated in thick-shell mussel Mytilus coruscus in this study. In addition, because metabolism is primarily regulated by circadian rhythm and neurotransmitters, the impacts of acidification and warming on these two regulatory processes were also analyzed. The data obtained demonstrated that the metabolism of mussels (indicated by the clearance rate, oxygen consumption rate, ammonia excretion rate, O:N ratio, ATP content, activity of pyruvate kinase, and expression of metabolism-related genes) were significantly affected by acidification and warming, resulting in a shortage of energy supply (indicated by the in vivo content of ATP). In addition, exposure to acidification and warming led to evident disruption in circadian rhythm (indicated by the heartrate and the expression rhythm of Per2, Cry, and BMAL1) and neurotransmitters (indicated by the activity of acetyl cholinesterase and in vivo contents of ACh, GABA, and DA). These findings suggest that circadian rhythms and neurotransmitters might be potential routes through which acidification and warming interactively affect the metabolism of mussels.
ESTHER : Tang_2022_Environ.Sci.Technol__
PubMedSearch : Tang_2022_Environ.Sci.Technol__
PubMedID: 35293730

Title : Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model - Sun_2022_Proc.Natl.Acad.Sci.U.S.A_119_
Author(s) : Sun CP , Zhou JJ , Yu ZL , Huo XK , Zhang J , Morisseau C , Hammock BD , Ma XC
Ref : Proc Natl Acad Sci U S A , 119 : , 2022
Abstract : Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.
ESTHER : Sun_2022_Proc.Natl.Acad.Sci.U.S.A_119_
PubMedSearch : Sun_2022_Proc.Natl.Acad.Sci.U.S.A_119_
PubMedID: 35217618
Gene_locus related to this paper: human-EPHX2

Title : Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity - Cao_2022_Toxicol.Lett_361_1
Author(s) : Cao C , Wang L , Zhang J , Liu Z , Li M , Xie S , Chen G , Xu X
Ref : Toxicol Lett , 361 :1 , 2022
Abstract : The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)- 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity.
ESTHER : Cao_2022_Toxicol.Lett_361_1
PubMedSearch : Cao_2022_Toxicol.Lett_361_1
PubMedID: 35331841

Title : Toxic effects of waterborne benzylparaben on the growth, antioxidant capacity and lipid metabolism of Nile tilapia (Oreochromis niloticus) - Lin_2022_Aquat.Toxicol_248_106197
Author(s) : Lin H , Jia Y , Han F , Xia C , Zhao Q , Zhang J , Li E
Ref : Aquat Toxicol , 248 :106197 , 2022
Abstract : Benzylparaben (BzP) is a potential endocrine disruptor; however, its antioxidant defense, lipotoxicity and underlying mechanism of BzP in aquatic organisms are unknown. This study investigated the impacts of waterborne low-, environmental-related and high-level benzylparaben on the growth, antioxidant capacity, lipid metabolism and lipidomic response of Nile tilapia (Oreochromis niloticus). Juvenile tilapia (0.60 +/- 0.11 g) were exposed to 0, 5, 50, 500 and 5000 ng/L benzylparaben for 8 weeks in quadruplicate for each group. Benzylparaben increased the body crude fat content but decreased brain acetylcholinesterase activity in O. niloticus. Benzylparaben caused oxidative stress, leading to hepatic morphology damage and lipid metabolism disorders in fish. Lipidomic analysis identified 13 lipid classes in fish liver. Benzylparaben exposure induced metabolic disorders of glycerol phospholipids, glycerolipids and sphingomyelins in fish liver. These findings indicate that environmentally related benzylparaben levels (5 to 50 ng/L) could induce an antioxidant response, result in triglyceride accumulation, and increase adipocyte formation and fatty acid intake in tilapia. However, high benzylparaben concentrations inhibit lipid deposition, presumably due to the effects of the antioxidant system, and induce tissue inflammation. Therefore, this study provides new insights into the toxic effects and potential mechanism of benzylparaben in fish, especially from the aspect of lipid metabolism.
ESTHER : Lin_2022_Aquat.Toxicol_248_106197
PubMedSearch : Lin_2022_Aquat.Toxicol_248_106197
PubMedID: 35623196

Title : Single-atom Ce-N-C nanozyme bioactive paper with a 3D-printed platform for rapid detection of organophosphorus and carbamate pesticide residues - Song_2022_Food.Chem_387_132896
Author(s) : Song G , Zhang J , Huang H , Wang X , He X , Luo Y , Li JC , Huang K , Cheng N
Ref : Food Chem , 387 :132896 , 2022
Abstract : Rapid detection of pesticide residues based on enzyme mimics has recently attracted much interest. However, most nanozymes have low activity. Herein, a "single-atom Ce-N-C nanozyme" (SACe-N-C nanozyme) was rationally devised and verified to mimic peroxidase (POD-like) with superior activity. Based on its high POD-like activities and cascaded catalytic reactions with acetylcholinesterase (AChE), we constructed a bioactive paper for the detection of pesticide residues, which offered a portable approach to monitor fruits and vegetables within 30 min. More importantly, a 3D printed platform was integrated on the basis of SACe-N-C bioactive paper to achieve on-site portable testing of omethoate, methamidophos, carbofuran, and carbosulfan, showing limits of detection (LODs) of 55.83, 71.51, 81.81, and 74.98 ng/mL, respectively. The recovery rates were 84.09-104.68%. This study provided new insight into the design of novel single-atom nanozymes for cascaded catalytic detection and other rapid detection applications with high efficiency and low cost.
ESTHER : Song_2022_Food.Chem_387_132896
PubMedSearch : Song_2022_Food.Chem_387_132896
PubMedID: 35421648

Title : Identification and characterization of two types of triacylglycerol lipase genes from Neocaridina denticulata sinensis - Liang_2022_Fish.Shellfish.Immunol__
Author(s) : Liang M , Ma L , Li X , Feng D , Zhang J , Sun Y
Ref : Fish Shellfish Immunol , : , 2022
Abstract : Triacylglycerol lipases (TGLs) can catalyze the hydrolysis reaction of triacylglycerol serving multiple functions in most organisms. Based on the genomic and transcriptomic databases of Neocaridina denticulata sinensis, two TGL genes from N. denticulata sinensis designated NdTGL1 and NdTGL2 were identified and characterized. NdTGL1 showed the highest expression in the stomach, followed by the testis and hepatopancreas, and NdTGL2 exhibited the maximum expression in the hepatopancreas, followed by the stomach and heart. Under the stimulation of copper ion, the expression of NdTGL1 peaked at 12 h and the expression of NdTGL2 elevated significantly at 24 h after stimulation (P < 0.05). It is speculated that NdTGLs may play an important role in the stress response of N. denticulata sinensis. Challenged with Vibrio parahaemolyticus, the expression profiles of NdTGL1 and NdTGL2 in the hepatopancreas was different, which indicates that the immune response of the V. parahaemolyticus challenge might lead to changes in triglyceride metabolism. The recombinant NdTGL (recNdTGL1 and recNdTGL2) were obtained and the enzymatic characterization of recNdTGL1 and recNdTGL2 were determined. The common maximum activity and stability of the recNdTGL1 and recNdTGL2 were observed at 45 C and 10 C, respectively. Both recNdTGL1 and recNdTGL2 exhibited the highest activity at pH 10.0. Furthermore, the recNdTGL1 and recNdTGL2 displayed the maximum stability at pH 5.0 and pH 8.0, respectively. In presence of different metal ions, the enzyme activity of recNdTGL1 and recNdTGL2 were inhibited by Cu(2+) and Zn(2+), and decreased by about 25%. Studies on the triacylglycerol lipases of N. denticulata sinensis provide theoretical support for studies related to fat metabolism in crustaceans and studies on response mechanism of digestive enzymes to microbial pathogens.
ESTHER : Liang_2022_Fish.Shellfish.Immunol__
PubMedSearch : Liang_2022_Fish.Shellfish.Immunol__
PubMedID: 36379446

Title : Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour - Chen_2022_Phytochemistry_196_113089
Author(s) : Chen SQ , Jia J , Hu JY , Wu J , Sun WT , Zheng M , Wang X , Zhu KK , Jiang CS , Yang SP , Zhang J , Wang SB , Cai YS
Ref : Phytochemistry , 196 :113089 , 2022
Abstract : Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC(50) values of 2.61, 1.19, and 1.74 microM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 microg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC(50) of 20.06 microM) and alpha-glycosidase inhibitor (IC(50) of 17.18 microM), while tabernamine, ervahanine B, and ervadivaricatine B only showed alpha-glycosidase inhibitory activities with IC(50) values in the range of 0.95-4.61 microM.
ESTHER : Chen_2022_Phytochemistry_196_113089
PubMedSearch : Chen_2022_Phytochemistry_196_113089
PubMedID: 35074605

Title : Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) - Zhang_2022_Pest.Manag.Sci__
Author(s) : Zhang L , Wang L , Chen J , Zhang J , He Y , Lu Y , Cai J , Chen X , Wen X , Xu Z , Wang C
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2022_Pest.Manag.Sci__
PubMedSearch : Zhang_2022_Pest.Manag.Sci__
PubMedID: 35192738

Title : GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis - Zhang_2022_J.Clin.Lipidol__
Author(s) : Zhang G , Yang Q , Mao W , Hu Y , Pu N , Deng H , Yu X , Zhang J , Zhou J , Ye B , Li G , Li B , Ke L , Tong Z , Murakami M , Kimura T , Nakajima K , Cao W , Liu Y , Li W
Ref : J Clin Lipidol , : , 2022
Abstract : BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.
ESTHER : Zhang_2022_J.Clin.Lipidol__
PubMedSearch : Zhang_2022_J.Clin.Lipidol__
PubMedID: 36064883

Title : Conceptual framework for the insect metamorphosis from larvae to pupae by transcriptomic profiling, a case study of Helicoverpa armigera (Lepidoptera: Noctuidae) - Gao_2022_BMC.Genomics_23_591
Author(s) : Gao X , Zhang J , Wu P , Shu R , Zhang H , Qin Q , Meng Q
Ref : BMC Genomics , 23 :591 , 2022
Abstract : BACKGROUND: Insect metamorphosis from larvae to pupae is one of the most important stages of insect life history. Relatively comprehensive information related to gene transcription profiles during lepidopteran metamorphosis is required to understand the molecular mechanism underlying this important stage. We conducted transcriptional profiling of the brain and fat body of the cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) during its transition from last instar larva into pupa to explore the physiological processes associated with different phases of metamorphosis. RESULTS: During metamorphosis, the differences in gene expression patterns and the number of differentially expressed genes in the fat body were found to be greater than those in the brain. Each stage had a specific gene expression pattern, which contributed to different physiological changes. A decrease in juvenile hormone levels at the feeding stage is associated with increased expression levels of two genes (juvenile hormone esterase, juvenile hormone epoxide hydrolase). The expression levels of neuropeptides were highly expressed at the feeding stage and the initiation of the wandering stage and less expressed at the prepupal stage and the initiation of the pupal stage. The transcription levels of many hormone (or neuropeptide) receptors were specifically increased at the initiation of the wandering stage in comparison with other stages. The expression levels of many autophagy-related genes in the fat body were found to be gradually upregulated during metamorphosis. The activation of apoptosis was probably related to enhanced expression of many key genes (Apaf1, IAP-binding motif 1 like, cathepsins, caspases). Active proliferation might be associated with enhanced expression levels in several factors (JNK pathway: jun-D; TGF-beta pathway: decapentaplegic, glass bottom boat; insulin pathway: insulin-like peptides from the fat body; Wnt pathway: wntless, TCF/Pangolin). CONCLUSIONS: This study revealed several vital physiological processes and molecular events of metamorphosis and provided valuable information for illustrating the process of insect metamorphosis from larvae to pupae.
ESTHER : Gao_2022_BMC.Genomics_23_591
PubMedSearch : Gao_2022_BMC.Genomics_23_591
PubMedID: 35963998

Title : Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry - Hu_2022_Lab.Med__
Author(s) : Hu C , Zhuang X , Zhang J , Wang T , Du S , Wang J , Peng X , Cao Q , Zhang M , Jiang Y
Ref : Lab Med , : , 2022
Abstract : OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. METHODS: Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. RESULTS: A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. CONCLUSION: The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM.
ESTHER : Hu_2022_Lab.Med__
PubMedSearch : Hu_2022_Lab.Med__
PubMedID: 35075477

Title : Association of the Cholinergic Anti-Inflammatory Pathway Activity with Proinflammatory Factors and Prognosis of Patients with Acute Respiratory Distress Syndrome - Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
Author(s) : Yang Y , Zhang J , Yang X , Yang J
Ref : Evid Based Complement Alternat Med , 2022 :8302701 , 2022
Abstract : OBJECTIVE: The cholinergic anti-inflammatory pathway (CAP) has been shown to modulate cytokine release by activating alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) in monocytes/macrophages. However, their association with proinflammatory factors and prognosis in patients with acute respiratory distress syndrome (ARDS) has not been clarified. Here, we explored the correlation between CAP activity, proinflammatory factors, and the prognosis of ARDS patients. METHODS: The data of patients with ARDS (n = 65; underwent treatment) and healthy individuals (the control group; n = 65; underwent routine physical examination) at the Chongqing People's Hospital were investigated. Based on the survival status, ARDS patients were divided into a death ARDS group (n = 22) and a survival ARDS group (n = 43), and based on the diagnostic criteria of ARDS, the patients were also divided into a severe ARDS group (n = 30) and a mild-to-moderate ARDS group (n = 35). The levels of acetylcholine (ACh), acetylcholinesterase (AChE), and alpha7nAChR mRNA in peripheral blood monocytes were assessed. The levels of TNF-alpha and IL-6 in peripheral serum and peripheral monocytes were detected by ELISA and Western blot tests. The association between alpha7nAChR and inflammatory factors and prognosis was analyzed. The receiver-operating characteristic (ROC) curve was used to evaluate the reliability of CAP-related factors in predicting the survival status of ARDS patients. RESULTS: Compared with the control group, the levels of ACh, AChE, and alpha7nAChR mRNA of the ARDS group were significantly decreased. And, the ACh, AChE, and alpha7nAChR mRNA levels in the death/severe ARDS group were significantly lower than in the survival/mild-to-moderate ARDS group. However, the levels of TNF-alpha and IL-6 were significantly higher in the severe/death ARDS group. Furthermore, we observed that CAP-related factors were negatively correlated with the levels of IL-6 and TNF-alpha in peripheral serum in the ARDS group. The ROC curve showed that CAP-related factors were reliable markers for predicting the survival status of ARDS patients. CONCLUSION: The related factors of the cholinergic anti-inflammatory pathway were significantly decreased in patients with ARDS, suggesting the ACh, AChE, and alpha7nAChR levels as potential indicators to evaluate the severity and prognosis status of ARDS patients.
ESTHER : Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
PubMedSearch : Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
PubMedID: 35664939

Title : Concurrent production of ferulic acid and glucose from wheat bran by catalysis of a putative bifunctional enzyme - Fang_2022_Bioresour.Technol__128393
Author(s) : Fang D , Xue D , Liu X , Cao L , Zhang J , Gong C
Ref : Bioresour Technol , :128393 , 2022
Abstract : The aim of this work is to study a bifunctional endoglucanase/carboxylesterase in Sphingobacterium soilsilvae Em02 and express it in soluble form in engineered Escherichia coli. The molecular weight of the recombinant protein of the bifunctional enzyme was 41 KDa. This research also determined the enzymatic activities of the bifunctional enzymes using microcrystalline cellulose and p-nitrophenyl butyrate as substrates and found 40 degreesC as the optimum temperature for their enzymatic activities. The optimal pH in dual function was 6.0 for endoglucanase and 7.0 for carboxylesterase. The bifunctional enzyme also exhibited enzymatic activities on the natural biomass by generating up to 3.94 mg of glucose and 49.4 microg of ferulic acid from 20 mg of destarched wheat bran. This indicates the broad application prospects of the bifunctional enzyme in agriculture and industry.
ESTHER : Fang_2022_Bioresour.Technol__128393
PubMedSearch : Fang_2022_Bioresour.Technol__128393
PubMedID: 36442604

Title : Effects of spinetoram and glyphosate on physiological biomarkers and gut microbes in Bombus terrestris - Tang_2022_Front.Physiol_13_1054742
Author(s) : Tang QH , Li WL , Wang JP , Li XJ , Li D , Cao Z , Huang Q , Li JL , Zhang J , Wang ZW , Guo J
Ref : Front Physiol , 13 :1054742 , 2022
Abstract : The sublethal effects of pesticide poisoning will have significant negative impacts on the foraging and learning of bees and bumblebees, so it has received widespread attention. However, little is known about the physiological effects of sublethal spinetoram and glyphosate exposure on bumblebees. We continuously exposed Bombus terrestris to sublethal (2.5 mg/L) spinetoram or glyphosate under controlled conditions for 10 days. The superoxide dismutase, glutathione-S-transferase, carboxylesterase, prophenoloxidase, alpha-amylase and protease activities, and changes in gut microbes were measured to understand the effects of sublethal pesticide exposure on the physiology and gut microbes of bumblebees. Sublethal pesticide exposure to significantly increased superoxide dismutase activity and significantly decreased gut alpha-amylase activity in bumblebees but had no significant effect on glutathione-S-transferase, carboxylesterase or gut protease activities. In addition, glyphosate increased the activity of prophenoloxidase. Interestingly, we observed that neither of the two pesticides had a significant effect on dominant gut bacteria, but glyphosate significantly altered the structure of the dominant gut fungal community, and reduced the relative abundance of Zygosaccharomyces associated with fat accumulation. These results suggest that sublethal spinetoram and glyphosate do not significantly affect the detoxification system of bumblebees, but may affect bumblebee health by inhibiting energy acquisition. Our results provide information on the sublethal effects of exposure to low concentrations of glyphosate and spinetoram on bumblebees in terms of physiology and gut microbes.
ESTHER : Tang_2022_Front.Physiol_13_1054742
PubMedSearch : Tang_2022_Front.Physiol_13_1054742
PubMedID: 36699673

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 : Novel donepezil-chalcone-rivastigmine hybrids as potential multifunctional anti-Alzheimer's agents: Design, synthesis, in vitro biological evaluation, in vivo and in silico studies - Sang_2022_Bioorg.Chem_127_106007
Author(s) : Sang Z , Bai P , Ban Y , Wang K , Wu A , Mi J , Hu J , Xu R , Zhu G , Wang J , Zhang J , Wang C , Tan Z , Tang L
Ref : Bioorg Chem , 127 :106007 , 2022
Abstract : Alzheimer's disease (AD) is a chronic, progressive brain neurodegenerative disorder. Up to now, there is no effective drug to halt or reverse the progress of AD. Given the complex pathogenesis of AD, the multi-target-directed ligands (MTDLs) strategy is considered as the promising therapy. Herein, a series of novel donepezil-chalone-rivastigmine hybrids was rationally designed and synthesized by fusing donepezil, chalone and rivastigmine. The in vitro bioactivity results displayed that compound 10c was a reversible huAChE (IC(50) = 0.87 microM) and huBuChE (IC(50) = 3.3 microM) inhibitor. It also presented significant anti-inflammation effects by suppressing the level of IL-6 and TNF-alpha production, and significantly inhibited self-mediated Abeta(1-42) aggregation (60.6%) and huAChE-mediated induced Abeta(1-40) aggregation (46.2%). In addition, 10c showed significant neuroprotective effect on Abeta(1-42)-induced PC12 cell injury and activated UPS pathway in HT22 cells to degrade tau and amyloid precursor protein (APP). Furthermore, compound 10c presented good stabilty in artificial gastrointestinal fluids and liver microsomes in vitro. The pharmacokinetic study showed that compound 10c was rapidly absorbed in rats and distributed in rat brain after intragastric administration. The PET-CT imaging demonstrated that [(11)C]10c could quickly enter the brain and washed out gradually in vivo. Further, compound 10c at a dose of 5 mg/kg improved scopolamine-induced memory impairment, deserving further investigations.
ESTHER : Sang_2022_Bioorg.Chem_127_106007
PubMedSearch : Sang_2022_Bioorg.Chem_127_106007
PubMedID: 35849893

Title : The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos - Yu_2022_Chemosphere_307_135751
Author(s) : Yu H , Zhang J , Chen Y , Chen J , Qiu Y , Zhao Y , Li H , Xia S , Chen S , Zhu J
Ref : Chemosphere , 307 :135751 , 2022
Abstract : Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.
ESTHER : Yu_2022_Chemosphere_307_135751
PubMedSearch : Yu_2022_Chemosphere_307_135751
PubMedID: 35863420

Title : The dipeptidyl peptidase-4 inhibitor linagliptin ameliorates LPS-induced acute lung injury by maintenance of pulmonary microvascular barrier via activating the Epac1\/AKT pathway - Zhang_2022_Biomed.Pharmacother_155_113704
Author(s) : Zhang N , Tang S , Zhang J , Pei B , Pang T , Sun G
Ref : Biomed Pharmacother , 155 :113704 , 2022
Abstract : Pulmonary microvascular endothelial cells (PMVECs) barrier dysfunction is a main pathophysiological feature of sepsis-related acute lung injury (ALI). This study aimed to investigate whether the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin could protect against LPS-induced PMVECs barrier disruption and its underlying molecular mechanisms. A classical ALI animal model and LPS-treated PMVECs were applied and all were treated with or without linagliptin. Cellular experiments demonstrated that linagliptin could mitigate LPS-induced PMVECs hyperpermeability and intercellular junction (VE-cadherin, beta-catenin, and ZO-1) disruption in a dose-dependent manner. Correspondingly, it was observed that linagliptin pretreatment distinctly relieved LPS-induced lung injury, oxidative stress, and pulmonary edema in vivo. Furthermore, we found that the inhibition of oxidative stress by linagliptin may be achieved by reversing impaired mitochondrial function. Mechanistically, linagliptin administration promoted the activation of the Epac1 pathway and its downstream AKT pathway, while inhibition of the Epac1/Akt signaling pathway significantly alleviated the above-mentioned protective effect of linagliptin on the PMVECs barrier. Taken together, these data suggest that linagliptin can effectively reserve PMVECs barrier dysfunction and inhibit oxidative stress to protect against ALI via activating the Epac1/AKT signaling pathway, and thus may become a potential clinical therapeutic strategy for ALI.
ESTHER : Zhang_2022_Biomed.Pharmacother_155_113704
PubMedSearch : Zhang_2022_Biomed.Pharmacother_155_113704
PubMedID: 36115114

Title : Biodegradation Pathway and Detoxification of beta-cyfluthrin by the Bacterial Consortium and Its Bacterial Community Structure - Li_2022_J.Agric.Food.Chem_70_7626
Author(s) : Li H , Ma Y , Yao T , Ma L , Zhang J , Li C
Ref : Journal of Agricultural and Food Chemistry , 70 :7626 , 2022
Abstract : In the process of microbial degradation of pyrethroid pesticides, the synergistic effect of the microbial community is more conducive to the complete degradation of toxic compounds than a single strain. At present, the degradation pathway of pyrethroids in a single strain has been well revealed, but the synergistic metabolism at the community level has not been well explained. This study elucidated the bacterial community succession, metabolic pathway, and phytotoxicity assessment during beta-cyfluthrin biodegradation by a novel bacterial consortium enriched from contaminated soil. The results showed that the half-life of beta-cyfluthrin at different initial concentrations of 0.25, 0.5, 0.75, and 1.0 mg mL(-1) were 4.16, 7.34, 12.81, and 22.73 days, respectively. Enterobacter was involved in beta-cyfluthrin degradation metabolism in the initial stage, and other bacterial genera (Microbacterium, Ochrobactrum, Pseudomonas, Hyphomicrobiaceae, Achromobacter, etc.) significantly contribute to the degradation of intermediate metabolites in the later stages. Functional gene prediction and metabolite analysis showed that xenobiotic biodegradation and metabolism, especially benzoate degradation and metabolism by cytochrome P450 were the major means of beta-cyfluthrin degradation. Further, two degradation pathways of beta-cyfluthrin were proposed, which were mainly ester hydrolysis and oxidation to degrade beta-cyfluthrin through the production of carboxylesterase and oxidoreductase. In addition, the inoculated bacterial consortium could degrade beta-cyfluthrin residues in water and soil and reduce its phytotoxicity in Medicago sativa. Hence, this novel bacterial consortium has important application in the remediation environments polluted by beta-cyfluthrin.
ESTHER : Li_2022_J.Agric.Food.Chem_70_7626
PubMedSearch : Li_2022_J.Agric.Food.Chem_70_7626
PubMedID: 35698868

Title : Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation - Li_2022_Mol.Metab__101597
Author(s) : Li H , Chen R , Zhou Y , Wang H , Sun L , Yang Z , Bai L , Zhang J
Ref : Mol Metab , :101597 , 2022
Abstract : OBJECTIVE: Contextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. METHODS: We applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA-CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. RESULTS: In the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. CONCLUSIONS: Together, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention.
ESTHER : Li_2022_Mol.Metab__101597
PubMedSearch : Li_2022_Mol.Metab__101597
PubMedID: 36096452

Title : Role of Natural Compounds and Target Enzymes in the Treatment of Alzheimer's Disease - Wang_2022_Molecules_27_
Author(s) : Wang S , Kong X , Chen Z , Wang G , Zhang J , Wang J
Ref : Molecules , 27 : , 2022
Abstract : Alzheimer's disease (AD) is a progressive neurological condition. The rising prevalence of AD necessitates the rapid development of efficient therapy options. Despite substantial study, only a few medications are capable of delaying the disease. Several substances with pharmacological activity, derived from plants, have been shown to have positive benefits for the treatment of AD by targeting various enzymes, such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), beta-secretase, gamma-secretase, and monoamine oxidases (MAOs), which are discussed as potential targets. Medicinal plants have already contributed a number of lead molecules to medicine development, with many of them currently undergoing clinical trials. A variety of medicinal plants have been shown to diminish the degenerative symptoms associated with AD, either in their raw form or as isolated compounds. The aim of this review was to provide a brief summary of AD and its current therapies, followed by a discussion of the natural compounds examined as therapeutic agents and the processes underlying the positive effects, particularly the management of AD.
ESTHER : Wang_2022_Molecules_27_
PubMedSearch : Wang_2022_Molecules_27_
PubMedID: 35807418

Title : In Silico Investigation on KAR Signaling Reveals the Significant Dynamic Change of Its Receptor's Structure - Liu_2022_J.Chem.Inf.Model_62_1933
Author(s) : Liu X , Zhang J
Ref : J Chem Inf Model , 62 :1933 , 2022
Abstract : Karrikins (KARs) have been identified as a class of smoke-derived plant growth regulators widely functioning among angiosperms. However, little is known about the mechanism by which these molecules trigger the relevant signal transduction. In this research, conventional molecular dynamics simulations were used to investigate the dynamical behavior of the apo- and holo-forms of the KAR receptor KAI2. The results show that the dynamic binding conformation of KAR(1) in the active site is not completely consistent with that in the static crystal and is largely affected by the residue segment of the receptor, Tyr150-Asn180. The binding of the ligand with KAI2 changes the distribution of the electrostatic potential near the active site and drives the conformational transition of the Tyr150-Asn180 segment with strong internal positive correlation. A 'dual induction' signaling mechanism is proposed in view of the present calculations. Our work paves way for in-depth understanding of the KAR signal transduction mechanism and sheds light on further experimental and theoretical exploration.
ESTHER : Liu_2022_J.Chem.Inf.Model_62_1933
PubMedSearch : Liu_2022_J.Chem.Inf.Model_62_1933
PubMedID: 35389657

Title : Synthesis, insecticidal activity, and mode of action of novel imidazopyridine mesoionic derivatives containing an amido group - Liu_2022_Pest.Manag.Sci__
Author(s) : Liu Z , Song R , Zhang D , Wu R , Liu T , Wu Z , Zhang J , Hu D
Ref : Pest Manag Sci , : , 2022
Abstract : BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate-to-good insecticidal activity against Sogatella furcifera, and some exhibited good-to-excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC(50) values of 10.5 and 2.09 microg mL(-1) , respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system-related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real-time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the alpha4 and beta1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode-of-action of imidazopyridine mesoionic derivatives. 2022 Society of Chemical Industry.
ESTHER : Liu_2022_Pest.Manag.Sci__
PubMedSearch : Liu_2022_Pest.Manag.Sci__
PubMedID: 36054072

Title : 5-Methyltetrahydrofolate Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Induced by D-Galactose and Aluminum Chloride - Zhang_2022_Int.J.Environ.Res.Public.Health_19_
Author(s) : Zhang Z , Wu H , Qi S , Tang Y , Qin C , Liu R , Zhang J , Cao Y , Gao X
Ref : Int J Environ Research Public Health , 19 : , 2022
Abstract : The effects of 5-methyltetrahydrofolate (5-MTHF) on a rat model of Alzheimer's disease (AD) induced by D-galactose (D-gal) and aluminum chloride (AlCl(3)) were investigated. Wistar rats were given an i.p. injection of 60 mg/kg D-gal and 10 mg/kg AlCl(3) to induce AD and three doses of 1 mg/kg, 5 mg/kg or 10 mg/kg 5-MTHF by oral gavage. A positive control group was treated with 1 mg/kg donepezil by gavage. Morris water maze performance showed that 5 and 10 mg/kg 5-MTHF significantly decreased escape latency and increased the number of platform crossings and time spent in the target quadrant for AD rats. The administration of 10 mg/kg 5-MTHF decreased the brain content of amyloid beta-protein 1-42 (Abeta(1-42)) and phosphorylated Tau protein (p-Tau) and decreased acetylcholinesterase and nitric oxide synthase activities. Superoxide dismutase activity, vascular endothelial growth factor level and glutamate concentration were increased, and malondialdehyde, endothelin-1, interleukin-6, tumor necrosis factor-alpha and nitric oxide decreased. The administration of 10 mg/kg 5-MTHF also increased the expression of disintegrin and metallopeptidase domain 10 mRNA and decreased the expression of beta-site amyloid precursor protein cleavage enzyme 1 mRNA. In summary, 5-MTHF alleviates memory impairment in a D-gal- and AlCl(3)-exposed rat model of AD. The inhibition of Abeta(1-42) and p-Tau release, reduced oxidative stress, the regulation of amyloid precursor protein processing and the release of excitatory amino acids and cytokines may be responsible.
ESTHER : Zhang_2022_Int.J.Environ.Res.Public.Health_19_
PubMedSearch : Zhang_2022_Int.J.Environ.Res.Public.Health_19_
PubMedID: 36554305

Title : Genome-Wide Analysis of the GDSL Genes in Pecan (Carya illinoensis K. Koch): Phylogeny, Structure, Promoter Cis-Elements, Co-Expression Networks, and Response to Salt Stresses - Jiao_2022_Genes.(Basel)_13_
Author(s) : Jiao Y , Zhang J , Pan C
Ref : Genes (Basel) , 13 : , 2022
Abstract : The Gly-Asp-Ser-Leu (GDSL)-lipase family is a large subfamily of lipolytic enzymes that plays an important role in plant growth and defense against environmental stress. However, little is known about their function in pecans (Carya illinoensis K. Koch). In this study, 87 CilGDSLs were identified and divided into 2 groups and 12 subgroups using phylogenetic analysis; members of the same sub-branch had conserved gene structure and motif composition. The majority of the genes had four introns and were composed of an alpha-helix and a beta-strand. Subcellular localization analysis revealed that these genes were localized in the extracellular matrix, chloroplasts, cytoplasm, nucleus, vacuole, and endoplasmic reticulum, and were validated by transient expression in tobacco mesophyll cells. Furthermore, the analysis of the promoter cis-elements for the CilGDSLs revealed the presence of plant anaerobic induction regulatory, abscisic acid response, light response elements, jasmonic acid (JA) response elements, etc. The qRT-PCR analysis results in "Pawnee" with salt treatment showed that the CilGDSL42.93 (leaf) and CilGDSL39.88 (root) were highly expressed in different tissues. After salt stress treatment, isobaric tags for relative and absolute quantitation (iTRAQ) analysis revealed the presence of a total of ten GDSL proteins. Moreover, the weighted gene co-expression network analysis (WGCNA) showed that one set of co-expressed genes (module), primarily CilGDSL41.11, CilGDSL39.49, CilGDSL34.85, and CilGDSL41.01, was significantly associated with salt stress in leaf. In short, some of them were shown to be involved in plant defense against salt stress in this study.
ESTHER : Jiao_2022_Genes.(Basel)_13_
PubMedSearch : Jiao_2022_Genes.(Basel)_13_
PubMedID: 35885886

Title : Recent advances of chemosensors for nerve agents - Wang_2022_Chem.Asian.J__
Author(s) : Wang X , Feng R , Fu T , Zhang J , Sun X
Ref : Chem Asian J , : , 2022
Abstract : Nerve agents are a branch of organophosphorus (OP) compounds that chemically cause irreversible inhibition of acetylcholinesterase, thereby failing the hydrolysis of acetylcholine, resulting in severe neurological disease and death in organisms. Thus, the unreasonable use of such compounds threatens public and national security, so it is a high demand to establish portable, low-cost, sensitive, and highly selective methods for their precise detection. In this review, we introduced the recent development of spectroscopy-based optical chemosensors that aimed for the detection of nerve agent, focusing on the progress made in the molecular design, sensing principle and applications. We also conclude this Review by highlighting the current challenges associated with the future development and outlook.
ESTHER : Wang_2022_Chem.Asian.J__
PubMedSearch : Wang_2022_Chem.Asian.J__
PubMedID: 35599234

Title : Effects of ABCG1 knockout on proteomic composition of HDL in mice on a chow diet and a high-fat diet - Wu_2022_Proteomics__e2100028
Author(s) : Wu Y , Chen L , Xie Z , Wang C , Zhang J , Yan X
Ref : Proteomics , :e2100028 , 2022
Abstract : ATP-binding cassette transporter G1 (ABCG1) is a cellular transmembrane protein that transports oxysterol efflux from cells to high-density lipoprotein (HDL) particles in the plasma. Previous studies have demonstrated that an ABCG1 deficiency exerts an antiatherosclerotic function through the effects of oxysterol accumulation in cells to enhance apoptosis and regulate inflammatory processes. However, whether the deficiency of ABCG1 and the corresponding changes in the efflux of oxysterols could take a series of impacts on the proteomic composition of HDL remains unclear. Here, plasma HDL of ABCG1(-/-) mice and their wild-type controls on a normal chow diet (NCD) or a high-fat diet (HFD) were isolated by ultracentrifugation. The proportion of 7-ketocholesterol and the proteomic composition of samples were comparatively analyzed by LC-MS/MS. In NCD-fed mice, lipid metabolism-related protein (arachidonate 12-lipoxygenase) and antioxidative protein (pantetheinase) exhibited increased accumulation, and inflammatory response protein (alpha-1-antitrypsin) was decreased in accumulation in ABCG1(-/-) mice HDL. In HFD-fed mice, fewer proteins were detected than that of NCD-fed mice. The ABCG1(-/-) mice HDL exhibited increased accumulation of lipid metabolism-related proteins (e.g., carboxylesterase 1C, apolipoprotein (apo)C-4) and decreased accumulation of alpha-1-antitrypsin, as well as significantly reduced proportion of 7-ketocholesterol. Additionally, positive correlations were found between 7-ketocholesterol and some essential proteins on HDL, such as alpha-1-antitrypsin, apoA-4, apoB-100, and serum amyloid A (SAA). These results suggest a detrimental impact of oxysterols on HDL composition, which might affect the antiatherosclerotic properties of HDL.
ESTHER : Wu_2022_Proteomics__e2100028
PubMedSearch : Wu_2022_Proteomics__e2100028
PubMedID: 35234362

Title : Biological responses of Eisenia fetida towards the exposure and metabolism of tris (2-butoxyethyl) phosphate - Wu_2021_Sci.Total.Environ__152285
Author(s) : Wu X , Zhu Y , Yang M , Zhang J , Lin D
Ref : Sci Total Environ , :152285 , 2021
Abstract : The toxicity of various organophosphorus flame retardants (OPFRs) is of increasing concern. However, there is still a lack of research on the toxicity of OPFRs to terrestrial invertebrates and its metabolism in vivo. Herein, earthworms (Eisenia fetida) were exposed to soil spiked with 0, 0.05, 0.5, and 5 mg/kg tris(2-butoxyethyl) phosphate (TBOEP, a typical alkyl OPFRs) for 28 d to study the biological responses to the exposure and metabolism of TBOEP. TBOEP exposure inhibited the activity of acetyl-cholinesterase (64.4-68.6% of that in the control group), increased the energy consumption level, and affected calcium-dependent pathways of E. fetida, which caused a 3.6-12.4% reduction in the weight gain rate (developmental toxicity), a 10.6-69.4% reduction in the number of juveniles (reproduction toxicity), and neurotoxicity to E. fetida. The 5 mg/kg TBOEP exposure caused a significant accumulation of malondialdehyde (1.68 times higher than that in the control group) in E. fetida, which indicated that the balance of oxidation and anti-oxidation of E. fetida was broken. Meanwhile, E. fetida maintained the absorption and metabolic abilities to TBOEP under the environmental condition. The removal rate of soil TBOEP was increased by 25.1-35.5% by the presence of E. fetida. Importantly, TBOEP could accumulate in E. fetida (0.09-76.0 microg/kg) and the activation of cytochrome P450 and glutathione detoxification pathway promoted the metabolism of TBOEP in E. fetida. These findings link the biological responses and metabolic behavior of earthworms under pollution stress and provide fundamental data for the environmental risk assessment and pollution removal of OPFRs in soil.
ESTHER : Wu_2021_Sci.Total.Environ__152285
PubMedSearch : Wu_2021_Sci.Total.Environ__152285
PubMedID: 34933047

Title : Butyrylcholinesterase nanodepots with enhanced prophylactic and therapeutic performance for acute organophosphorus poisoning management - Yu_2021_J.Mater.Chem.B__
Author(s) : Yu C , Zhao M , Pan Z , Bo Y , Zhao W , He X , Zhang J
Ref : J Mater Chem B , : , 2021
Abstract : Acute organophosphorus pesticide poisoning (AOPP) is a worldwide health concern that has threatened human lives for decades, which attacks acetylcholinesterase (AChE) and causes nervous system disorders. Classical treatment options are associated with short in vivo half-life and side effects. As a potential alternative, delivery of mammalian-derived butyrylcholinesterase (BChE) offers a cost-effective way to block organophosphorus attack on acetylcholinesterase, a key enzyme in the neurotransmitter cycle. Yet the use of exotic BChE as a prophylactic or therapeutic agent is compromised by short plasma residence, immune response and unfavorable biodistribution. To overcome these obstacles, BChE nanodepots (nBChE) composed of a BChE core/polymorpholine shell structure were prepared via in situ polymerization, which showed enhanced stability, prolonged plasma circulation, attenuated antigenicity and reduced accumulation in non-targeted tissues. In vivo administration of nBChE pre- or post-organophosphorus exposure in a BALB/C mouse model resulted in potent prophylactic and therapeutic efficiency. To our knowledge, this is the first systematic delivery of non-human BChE to tackle AOPP. In addition, this work also opens up a new avenue for real applications in both research and clinical settings to cope with acute intoxication-related diseases.
ESTHER : Yu_2021_J.Mater.Chem.B__
PubMedSearch : Yu_2021_J.Mater.Chem.B__
PubMedID: 33533366

Title : A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma - Zhang_2021_Anal.Methods_13_2671
Author(s) : Zhang J , Qian XK , Song PF , Li XD , Wang AQ , Huo H , Yao JC , Zhang GM , Zou LW
Ref : Anal Methods , 13 :2671 , 2021
Abstract : Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescent probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN) for DPP-IV detection with high specificity and sensitivity. In this study, a high-throughput screening (HTS) method for DPP-IV inhibitors using human plasma as the enzyme source was established and optimized. Further investigations demonstrate that the IC50 value of sitagliptin (listed as the DPP-IV inhibitor) determined with human recombinant DPP-IV (36.22 nM) is very similar to that in human plasma (39.18 nM), and sitagliptin acts as a competitive inhibitor against human plasma DPP-IV-mediated GP-BAN hydrolysis. These results indicate that expensive human recombinant DPP-IV can be replaced by human plasma in this GP-BAN-based assay. On this basis, GP-AMC (commercial probe) was used as a comparison to verify this method, and the catalytic efficacy (Vmax/Km) for GP-AMC (0.09 min-1) hydrolysis in human plasma is lower than that for GP-BAN (0.21 min-1). Further analysis of inhibition kinetics (sitagliptin) and molecular docking (GP-BAN and GP-AMC) showed that GP-BAN has better specificity and affinity for enzymes than GP-AMC. Finally, the optimized method was used for the HTS of DPP-IV inhibitors in 69 natural alkaloids.
ESTHER : Zhang_2021_Anal.Methods_13_2671
PubMedSearch : Zhang_2021_Anal.Methods_13_2671
PubMedID: 34036983

Title : [Propeptide-mediated protein folding: mechanism and its impact on lipase] - Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
Author(s) : Tian M , Zhang J , Luo W , Wang Z , Fu J , Huang S , Lu P
Ref : Sheng Wu Gong Cheng Xue Bao , 37 :88 , 2021
Abstract : The formation of most proteins consists of two steps: the synthesis of precursor proteins and the synthesis of functional proteins. In these processes, propeptides play important roles in assisting protein folding or inhibiting its activity. As an important polypeptide chain coded by a gene sequence in lipase gene, propeptide usually functions as an intramolecular chaperone, assisting enzyme molecule folding. Meanwhile, some specific sites on propeptide such as glycosylated sites, have important effect on the activity, stability in extreme environment, methanol resistance and the substrate specificity of the lipase. Studying the mechanism of propeptide-mediated protein folding, as well as the influence of propeptide on lipases, will allow to regulate lipase by alternating the propeptide folding behavior and in turn pave new ways for protein engineering research.
ESTHER : Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
PubMedSearch : Tian_2021_Sheng.Wu.Gong.Cheng.Xue.Bao_37_88
PubMedID: 33501792

Title : Neuroprotective Effects of Isoquercetin: An In Vitro and In Vivo Study - Yang_2021_Cell.J_23_355
Author(s) : Yang Q , Kang ZH , Zhang J , Qu F , Song B
Ref : Cell J , 23 :355 , 2021
Abstract : OBJECTIVE: Alzheimer's disease (AD) is considered a neurodegenerative disease that affects the cognitive function of elderly individuals. In this study, we aimed to analyze the neuroprotective potential of isoquercetin against the in vitro and in vivo models of AD and investigated the possible underlying mechanisms. MATERIALS AND METHODS: The experimental study was performed on PC12 cells treated with lipopolysaccharide (LPS). Reactive oxygen species (ROS), antioxidant parameters, and pro-inflammatory cytokines were measured. In an in vivo approach, Wistar rats were used and divided into different groups. We carried out the Morris water test to determine the cognitive function. Biochemical parameters, antioxidant parameters, and pro-inflammatory parameters were examined. RESULTS: The non-toxic effect on PC12 cells was shown by isoquercetin. Isoquercetin significantly reduced the production of nitrate and ROS, along with the altered levels of antioxidants. Isoquercetin significantly (P<0.001) down-regulated proinflammatory cytokines in PC12 cells treated with LPS. In the in vivo approach, isoquercetintreated groups considerably showed the up-regulation in the latency and transfer latency time, as compared with AD groups. Isoquercetin significantly reduced Abeta-peptide, protein carbonyl, while enhanced the production of brainderived neurotrophic factor (BDNF) and acetylcholinesterase (AChE). Isoquercetin significantly (P<0.001) reduced pro-inflammatory cytokines and inflammatory mediators, as compared with AD groups. CONCLUSION: Based on the results, we may infer that, through antioxidant and anti-inflammatory systems, isoquercetin prevented neurochemical and neurobehavioral modifications against the model of colchicine-induced AD rats.
ESTHER : Yang_2021_Cell.J_23_355
PubMedSearch : Yang_2021_Cell.J_23_355
PubMedID: 34308580

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

Title : Chlorogenic acid alleviates thioacetamide-induced toxicity and promotes liver development in zebrafish (Danio rerio) through the Wnt signaling pathway - Liu_2021_Aquat.Toxicol_242_106039
Author(s) : Liu Y , Guo J , Zhang J , Deng Y , Xiong G , Fu J , Wei L , Lu H
Ref : Aquat Toxicol , 242 :106039 , 2021
Abstract : Chlorogenic acid (CGA) is a phenylpropanoid compound that is well known to improve the antioxidant capacity and other biological activities. However, the roles of CGA in the liver development of organisms are unclear. In the present study, we aimed to investigate the function of CGA in the hepatic development in thioacetamide (TAA)-induced zebrafish embryos. We found that CGA exerted certain beneficial effects on zebrafish larvae from TAA-exposed zebrafish embryos, such as increasing the liver size, body length, heart rate, acetylcholinesterase activity, and motor ability. In addition, CGA displayed an antioxidant effect on TAA-induced zebrafish embryos by enhancing the activities of superoxide dismutase (SOD), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH), and decreasing of the contents of malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO). The results of western blotting analysis showed that CGA inhibited cell apoptosis by increasing the levels of Bcl2 apoptosis regulator and decreasing the levels of Bcl2 associated X (Bax), apoptosis regulator and tumor protein P53. Moreover, CGA promoted cell proliferation in TAA-induced zebrafish larvae, as detected using proliferating cell nuclear antigen fluorescence immunostaining. In addition, CGA inhibited the expression of Wnt signaling pathway genes Dkk1 (encoding Dickkopf Wnt signaling pathway inhibitors), and promoted the expression of Lef1 (encoding lymphoid enhancer binding factor 1) and Wnt2bb (encoding wingless-type MMTV integration site family, member 2Bb). When the Wnt signal inhibitor IWR-1 was added, there was no significant change in liver development in the IWR-1 + TAA group compared with the IWR-1 + TAA + CGA group (p <0.05), which suggested that CGA regulates liver development via Wnt signaling pathway. Overall, our results suggested that CGA might alleviate TAA-induced toxicity in zebrafish and promote liver development through the Wnt signaling pathway, which provides a basis for the therapeutic effect of CGA on liver dysplasia.
ESTHER : Liu_2021_Aquat.Toxicol_242_106039
PubMedSearch : Liu_2021_Aquat.Toxicol_242_106039
PubMedID: 34856462

Title : Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer's disease - Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
Author(s) : Zhang J , Liu R , Zhang D , Zhang Z , Zhu J , Xu L , Guo Y
Ref : Colloids Surf B Biointerfaces , 200 :111584 , 2021
Abstract : Nanopeptide assembled from peptide-anchored nanoparticles possess an enormous research potential in the field of cellular medicine and disease treatment. The aim of this study was to explore the neuroprotective effects of maize tetrapeptide anchored gold nanoparticles against l-glutamic acid-induced PC12 cell apoptosis and a murine Alzheimer's disease model induced by aluminum chloride and d-galactose. The results revealed that the nanopeptide antioxidant inhibited intracellular ROS accumulation and promoted cell differentiation than that of maize bioactive tetrapeptide. Compared with untreated Alzheimer's disease model mice, nanopeptide administration shortened the escape latency time in a water maze test and improved the movements in the autonomic activity test. After 16 days of nanopeptide administration, the central cholinergic system function of acetylcholine and cholineacetyltransferase were enhanced, and the level of acetylcholinesterase was reduced. It also increased superoxide dismutase and glutathione peroxidase activity in sera and hypothalami. Moreover, nanopeptide treatment upregulated cerebral nuclear factor erythroid 2-related factor 2 and heme-oxygenase-1 and downregulated kelch-like ECH-associated protein 1 relative to untreated Alzheimer's disease model mice. Thus, the novel nanopeptide is expected to be used as the neuroprotective agent to prevent Alzheimer's disease.
ESTHER : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedSearch : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedID: 33508658

Title : Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism - Chen_2021_Chemosphere_286_131866
Author(s) : Chen X , Zheng J , Teng M , Zhang J , Qian L , Duan M , Cheng Y , Zhao W , Wang Z , Wang C
Ref : Chemosphere , 286 :131866 , 2021
Abstract : Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.
ESTHER : Chen_2021_Chemosphere_286_131866
PubMedSearch : Chen_2021_Chemosphere_286_131866
PubMedID: 34391112

Title : The protective effects of Omarigliptin against Lipopolysaccharide (LPS)- induced inflammatory response and expression of mucin 5AC (MUC5AC) in human bronchial epithelial cells - Ma_2021_Mol.Immunol_141_108
Author(s) : Ma L , Chang E , Ruan X , Zhang B , Tang F , Zhang J
Ref : Mol Immunol , 141 :108 , 2021
Abstract : The epidemic of chronic inflammatory lung diseases such as asthma, bronchitis, and chronic obstructive pulmonary disease (COPD) has become a global public health problem. Oxidative stress, inflammation, and overproduction of airway mucus play critical roles in the progression of these diseases. Omarigliptin, an oral dipeptidyl peptidase 4 (DPP-4) inhibitor, has been demonstrated to have anti-inflammatory effects in patients with type II diabetes. However, its role in chronic inflammatory lung diseases remains enigmatic. This study is to investigate whether Omarigliptin possesses a beneficial effect against Lipopolysaccharide (LPS)-induced injuries in human BEAS-2B bronchial epithelial cells. Our results show that Omarigliptin suppressed LPS-induced oxidative stress by attenuating the generation of mitochondrial reactive oxygen species (ROS) and decrease in reduced glutathione (GSH) in BEAS-2B cells. Additionally, Omarigliptin mitigated inflammatory response by inhibiting the expression of pro-inflammatory mediators, including interleukin-1beta (IL-1beta), interleukin-12 (IL-12), and macrophage chemoattractant protein-1 (MCP-1) in LPS-challenged BEAS-2B cells. Moreover, Omarigliptin mitigated the LPS-induced overproduction of MUC5AC by rescuing the expression of the suppressor of cytokine signaling 1(SOCS1). Importantly, we found that this process is mediated by the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Based on these findings, we conclude that Omarigliptin might be a promising agent for the treatment of chronic inflammatory lung diseases.
ESTHER : Ma_2021_Mol.Immunol_141_108
PubMedSearch : Ma_2021_Mol.Immunol_141_108
PubMedID: 34871838

Title : Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis - Zhang_2021_Front.Med__
Author(s) : Zhang J , Song Y , Shi Q , Fu L
Ref : Front Med , : , 2021
Abstract : Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. They can also regulate the immune microenvironment, participate in epithelial-mesenchymal transition, and then regulate tumor invasion and metastasis. Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion. This article introduces the structures and functions of FASN and MGLL, their relationship with abnormal lipid metabolism, and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.
ESTHER : Zhang_2021_Front.Med__
PubMedSearch : Zhang_2021_Front.Med__
PubMedID: 33973101
Gene_locus related to this paper: human-FASN , human-MGLL

Title : Insecticidal and acetylcholine esterase inhibition activity of Rhododendron thymifolium essential oil and its main constituent against two stored product insects - Liang_2021_J.Environ.Sci.Health.B__1
Author(s) : Liang JY , Yang YY , An Y , Shao YZ , He CY , Zhang J , Jia LY
Ref : J Environ Sci Health B , :1 , 2021
Abstract : In this work, we investigated the bioactivities of the essential oil (EO) extracted from the Rhododendron thymifolium and its principal germacrone against Lasioderma serricorne and Tribolium castaneum. The EO was obtained by steam distillation. Germacrone was obtained by cryogenic crystallization. The bioactivity of EO and germacrone was tested via contact and repellent activity assays. The results showed that EO and germacrone possessed contact and repellent activities against two species of insects. EO exhibited obvious contact activity against the L. serricorn adults, larvae and T. castaneum larvae with LD(50) values of 29.15 microg/adult, 42.73 microg/larva, 19.65 microg/larva respectively. Germacrone exhibited excellent contact activity against the L. serricorne adults, larvae and the T. castaneum larvae with LD(50) values of 17.18 microg/adult, 20.94 microg/larva, 20.93 microg/larva respectively. And at the highest testing concentrations (78.63 and 15.73 nL/cm(2)), the repellent activity of EO and germacrone on two target insects was comparable to that of the positive control (DEET) after 30 h exposure. In especially, in the treatment of the 120 h after the repellent activity of EO and germacrone against T.castaneum adults and larvae were still very significant and showed the same level percentage repellency as DEET. Meanwhile, germacrone exhibited inhibition of acetylcholinesterase activity with IC(50) values of 3%. The results indicated that the EO of R. thymifolium and germacrone had the potential to be developed as natural insecticides and repellents for the control of T. castaneum and L. serricorne.
ESTHER : Liang_2021_J.Environ.Sci.Health.B__1
PubMedSearch : Liang_2021_J.Environ.Sci.Health.B__1
PubMedID: 33678144

Title : Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis - Wang_2021_Front.Immunol_12_753247
Author(s) : Wang S , Yang H , Guo R , Wang L , Zhang Y , Lv J , Zhao X , Zhang J , Fang H , Zhang Q , Yang J , Cui X , Gao P , Chang T , Gao F
Ref : Front Immunol , 12 :753247 , 2021
Abstract : This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.
ESTHER : Wang_2021_Front.Immunol_12_753247
PubMedSearch : Wang_2021_Front.Immunol_12_753247
PubMedID: 34956185

Title : Biodegradation of erythromycin by Delftia lacustris RJJ-61 and characterization of its erythromycin esterase - Ren_2021_J.Basic.Microbiol_61_55
Author(s) : Ren J , Wang Z , Deng L , Niu D , Fan B , Huhe T , Li Z , Zhang J , Li C
Ref : J Basic Microbiol , 61 :55 , 2021
Abstract : The residual erythromycin in fermentation waste can pollute the environment and threaten human health. However, there are no effective approaches to remedy this issue. In this study, an erythromycin-degrading bacterium named RJJ-61 was isolated and identified as a strain of Delftia lacustris based on morphological and phylogenetic analyses. The degradation ability of this strain was also evaluated; it could degrade 45.18% of erythromycin at 35 degreesC in 120h. Furthermore, the key degradation gene ereA was cloned from strain RJJ-61 and expressed in Escherichia coli BL21; the molecular weight of the expressed protein was ~45kDa. The enzyme activity of EreA was 108.0mUml(-1) at 35 degreesC and pH 7.0. Finally, the EreA protein was used to degrade erythromycin from mycelial dregs and 50% diluted solution, and the removal rates in them were 41.42% and 69.78%, respectively. In summary, D. lacustris RJJ-61 is a novel erythromycin-degrading strain that has great potential to remove erythromycin pollutants from the environment.
ESTHER : Ren_2021_J.Basic.Microbiol_61_55
PubMedSearch : Ren_2021_J.Basic.Microbiol_61_55
PubMedID: 33332633

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 : Key Metabolic Enzymes Involved in Remdesivir Activation in Human Lung Cells - Li_2021_Antimicrob.Agents.Chemother__AAC0060221
Author(s) : Li R , Liclican A , Xu Y , Pitts J , Niu C , Zhang J , Kim C , Zhao X , Soohoo D , Babusis D , Yue Q , Ma B , Murray BP , Subramanian R , Xie X , Zou J , Bilello JP , Li L , Schultz BE , Sakowicz R , Smith BJ , Shi PY , Murakami E , Feng JY
Ref : Antimicrobial Agents & Chemotherapy , :AAC0060221 , 2021
Abstract : Remdesivir (RDV; GS-5734; Veklury(a)), the first FDA-approved antiviral to treat COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. RDV is taken up in the target cells and metabolized in multiple steps to form the active nucleoside triphosphate (TP) (GS-443902), which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. In this report, we profiled the key enzymes involved in the RDV metabolic pathway with multiple parallel approaches: (1) bioinformatic analysis of nucleoside/tide metabolic enzyme mRNA expression using public human tissue and lung single-cell RNAseq datasets; (2) protein and mRNA quantification of enzymes in human lung tissue and primary lung cells; (3) biochemical studies on the catalytic rate of key enzymes; (4) effects of specific enzyme inhibitors on the GS-443902 formation; and (5) the effects of these inhibitors on RDV antiviral activity against SARS-CoV-2 in cell culture. Our data collectively demonstrated that carboxylesterase 1 (CES1) and cathepsin A (CatA) are enzymes involved in hydrolyzing RDV to its alanine intermediate Met X, which is further hydrolyzed to the monophosphate form by histidine triad nucleotide-binding protein 1 (HINT1). The monophosphate is then consecutively phosphorylated to diphosphate and triphosphate by cellular phosphotransferases. Our data support the hypothesis that the unique properties of RDV prodrug not only allow lung-specific accumulation critical for the treatment of respiratory viral infection such as COVID-19, they also enable efficient intracellular metabolism of RDV and its Met X to monophosphate and successive phosphorylation to form the active TP in disease-relevant cells.
ESTHER : Li_2021_Antimicrob.Agents.Chemother__AAC0060221
PubMedSearch : Li_2021_Antimicrob.Agents.Chemother__AAC0060221
PubMedID: 34125594

Title : Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors against Pancreatic Lipase - Bao_2021_ChemMedChem__
Author(s) : Bao X , Zhang J , Yang Y , Qian XK , Song PF , Zhao YS , Guan XQ , Zou LW , Wang H
Ref : ChemMedChem , : , 2021
Abstract : Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones were synthesized and their inhibitory effects against PL were assayed using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones brought us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor against PL (IC50 0.30 microM). In addition, P32 displayed some selectivity over other known serine hydrolase. Molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the Pi-Pi interactions of 2-naphthyl unit (R1) and hydrophobic interactions of phenyl moiety (R3) with the active site of PL, respectively. Thus, P32 could serve as promising lead compound for the development of more efficacious and selective pyrazolones-type PL inhibitors for biomedical applications.
ESTHER : Bao_2021_ChemMedChem__
PubMedSearch : Bao_2021_ChemMedChem__
PubMedID: 33527731

Title : Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis - Yi_2021_Front.Physiol_12_674023
Author(s) : Yi J , Wang S , Wang Z , Wang X , Li G , Zhang X , Pan Y , Zhao S , Zhang J , Zhou JJ , Wang J , Xi J
Ref : Front Physiol , 12 :674023 , 2021
Abstract : Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela.
ESTHER : Yi_2021_Front.Physiol_12_674023
PubMedSearch : Yi_2021_Front.Physiol_12_674023
PubMedID: 34566671

Title : Whole-genome sequencing to detect mutations associated with resistance to insecticides and Bt proteins in Spodoptera frugiperda - Guan_2021_Insect.Sci_28_627
Author(s) : Guan F , Zhang J , Shen H , Wang X , Padovan A , Walsh TK , Tay WT , Gordon KHJ , James W , Czepak C , Otim MH , Kachigamba D , Wu Y
Ref : Insect Sci , 28 :627 , 2021
Abstract : The fall armyworm (FAW), Spodoptera frugiperda, is a major pest native to the Americas that has recently invaded the Old World. Point mutations in the target-site proteins acetylcholinesterase-1 (ace-1), voltage-gated sodium channel (VGSC) and ryanodine receptor (RyR) have been identified in S. frugiperda as major resistance mechanisms to organophosphate, pyrethroid and diamide insecticides respectively. Mutations in the adenosine triphosphate-binding cassette transporter C2 gene (ABCC2) have also been identified to confer resistance to Cry1F protein. In this study, we applied a whole-genome sequencing (WGS) approach to identify point mutations in the target-site genes in 150 FAW individuals collected from China, Malawi, Uganda and Brazil. This approach revealed three amino acid substitutions (A201S, G227A and F290V) of S. frugiperda ace-1, which are known to be associated with organophosphate resistance. The Brazilian population had all three ace-1 point mutations and the 227A allele (mean frequency = 0.54) was the most common. Populations from China, Malawi and Uganda harbored two of the three ace-1 point mutations (A201S and F290V) with the 290V allele (0.47-0.58) as the dominant allele. Point mutations in VGSC (T929I, L932F and L1014F) and RyR (I4790M and G4946E) were not detected in any of the 150 individuals. A novel 12-bp insertion mutation in exon 15 of the ABCC2 gene was identified in some of the Brazilian individuals but absent in the invasive populations. Our results not only demonstrate robustness of the WGS-based genomic approach for detection of resistance mutations, but also provide insights for improvement of resistance management tactics in S. frugiperda.
ESTHER : Guan_2021_Insect.Sci_28_627
PubMedSearch : Guan_2021_Insect.Sci_28_627
PubMedID: 32558234
Gene_locus related to this paper: spolt-ACHE2 , spolt-ACHE1

Title : Novel cannabidiol-carbamate hybrids as selective BuChE inhibitors: Docking-based fragment reassembly for the development of potential therapeutic agents against Alzheimer's disease - Jiang_2021_Eur.J.Med.Chem_223_113735
Author(s) : Jiang X , Zhang Z , Zuo J , Wu C , Zha L , Xu Y , Wang S , Shi J , Liu XH , Zhang J , Tang W
Ref : Eur Journal of Medicinal Chemistry , 223 :113735 , 2021
Abstract : Cannabidiol (CBD) and rivastigmine have been launched as drugs for treating dementia and cholinesterases (ChEs) are ideal drug targets. This study focused on developing novel ChE inhibitors as drug leads against dementia through molecular modeling and fragment reassembly approaches. A potent carbamate fragment binding to active site gorge of BuChE was found via a docking-based structural splicing approach, thus, 17 novel compounds were designed by structural reassembly. Compound C16 was identified as a highly selective potent BuChE inhibitor (IC(50) = 5.3 nM, SI > 4000), superior to CBD (IC(50) = 0.67 microM). C16 possessed BBB penetrating ability, benign safety, neuroprotection, antioxidant and pseudo-irreversible BuChE inhibition (K(d) = 13 nM, k(2) = 0.26 min(-1)), showing good drug-like properties. In vivo studies confirmed that C16 significantly ameliorated the scopolamine-induced cognition impairment, almost entirely recovered the Abeta(1-42) (icv)-impaired cognitive function to the normal level, showed better behavioral performance than donepezil and good anti-amyloidogenic effect. Hence, the potential BuChE inhibitor C16 can be developed as a promising disease-modifying treatment of AD.
ESTHER : Jiang_2021_Eur.J.Med.Chem_223_113735
PubMedSearch : Jiang_2021_Eur.J.Med.Chem_223_113735
PubMedID: 34371367

Title : Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure - Zhou_2021_J.Hazard.Mater_416_126142
Author(s) : Zhou W , Li X , Wang Y , Wang J , Zhang J , Wei H , Peng C , Wang Z , Li G , Li D
Ref : J Hazard Mater , 416 :126142 , 2021
Abstract : 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.
ESTHER : Zhou_2021_J.Hazard.Mater_416_126142
PubMedSearch : Zhou_2021_J.Hazard.Mater_416_126142
PubMedID: 34492931

Title : Co-Expression of a Thermally Stable and Methanol-Resistant Lipase and Its Chaperone from Burkholderia cepacia G63 in Escherichia coli - Zhang_2021_Appl.Biochem.Biotechnol_193_717
Author(s) : Zhang J , Tian M , Chen X , Lv P , Luo W , Wang Z , Xu J
Ref : Appl Biochem Biotechnol , 193 :717 , 2021
Abstract : Biodiesel biosynthesis with enzymatic transesterification is considered green, sustainable, and environmentally friendly method. Lipase from Burkholderia cepacia G63 has excellent catalytic properties in biodiesel production. Lipase chaperones promote secretion and folding of enzymes, thereby enhancing enzymatic activity. In the current study, heterologous co-expression of lipase (lipA) and chaperone (lipB) was achieved in Escherichia coli through codon optimization. The enzymatic activity of purified and renatured lipAB was 2080.23 +/- 19.18 U/g at 50 degreesC and pH 8.0. Moreover, lipAB showed increased resistance to pH and temperature changes, and lipAB retained stable catalytic properties after treatment with metal ions, organic solvents, and surfactants, namely Mg(2+), methanol, and Triton-100X. Besides, using recombinant lipase lipAB as catalysts, biodiesel was synthesized using rapeseed oil under 50 degreesC for 72 h with a yield of 90.23%. Thus, the current study confirmed that co-expression of lipase and its chaperone is an effective strategy to enhance enzyme activity and improve the biochemical profile, meanwhile, showing that lipAB is a promising biocatalyst for biodiesel production.
ESTHER : Zhang_2021_Appl.Biochem.Biotechnol_193_717
PubMedSearch : Zhang_2021_Appl.Biochem.Biotechnol_193_717
PubMedID: 33184764

Title : Concurrent urinary organophosphate metabolites and acetylcholinesterase activity in Ecuadorian adolescents - Skomal_2021_Environ.Res__112163
Author(s) : Skomal AE , Zhang J , Yang K , Yen J , Tu X , Suarez-Torres J , Lopez-Paredes D , Calafat AM , Ospina M , Martinez D , Suarez-Lopez JR
Ref : Environ Research , :112163 , 2021
Abstract : BACKGROUND: Organophosphates are insecticides that inhibit the enzymatic activity of acetylcholinesterase (AChE). Because of this, AChE is considered a physiological marker of organophosphate exposure in agricultural settings. However, limited research exists on the associations between urinary organophosphate metabolites and AChE activity in children. METHODS: This study included 526 participants from 2 exams (April and July-October 2016) of ages 12-17 years living in agricultural communities in Ecuador. AChE activity was measured at both examinations, and organophosphate metabolites, including para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), and malathion dicarboxylic acid (MDA) were measured in urine collected in July-October. We used generalized estimating equation generalized linear model (GEEGLM), adjusting for hemoglobin, creatinine, and other demographic and anthropometric covariates, to estimate associations of urinary metabolite concentrations with AChE activity (July-October) and AChE % change between April and July-October. RESULTS: The mean (SD) of AChE and AChE % change (April vs July-October) were 3.67 U/mL (0.54) and -2.5 % (15.4 %), respectively. AChE activity was inversely associated with PNP concentration, whereas AChE % change was inversely associated with PNP and MDA. There was evidence of a threshold: difference was only significant above the 80th percentile of PNP concentration (AChE difference per SD increase of metabolite = -0.12 U/mL [95 %CI: 0.20, -0.04]). Likewise, associations with AChE % change were significant only above the 80th percentile of TCPy (AChE % change per SD increase of metabolite = -1.38 % [95 %CI: 2.43 %, -0.32 %]) and PNP -2.47 % [95 %CI: 4.45 %, -0.50 %]). PNP concentration at <=80th percentile was associated with elevated ORs for low AChE activity of 2.9 (95 % CI: 1.5, 5.7) and for AChE inhibition of >= -10 % of 3.7 (95 % CI: 1.4, 9.8). CONCLUSIONS: Urinary organophosphate metabolites, including PNP, TCPy and MDA, particularly at concentrations above the 80th percentile, were associated with lower AChE activity among adolescents. These findings bring attention to the value of using multiple constructs of pesticide exposure in epidemiologic studies.
ESTHER : Skomal_2021_Environ.Res__112163
PubMedSearch : Skomal_2021_Environ.Res__112163
PubMedID: 34627797

Title : The enhancement of rice bran oil quality through a novel moderate biorefining process - Li_2021_LWT_151_112118
Author(s) : Li D , Zhang J , Faiza M , Shi L , Wang W , Liu N , Wang Y
Ref : LWT , 151 :112118 , 2021
Abstract : Edible grade rice bran oil (RBO) rich in ?-oryzanol and phytosterol but without glycidyl esters (GEs) and monochloropropanediol esters (MCPDEs) was obtained from rice bran by moderate biorefining. High-acid RBO (acid value of 51.22mg KOH/g) was firstly extracted from rice bran and was then moderately biorefined by combining improved enzymatic degumming, dewaxing, enzymatic deacidification, bleaching, and low-temperature purification (120C). Through monitoring the refining process, results showed that the improved enzymatic degumming by combining partial glyceride lipase SMG1-F278N and phospholipase A1 enabled the phosphorus content to quickly decrease to 4.56mg/kg after optimization by response surface methodology. After biorefining, the final RBO with the acid and peroxide value of 0.10mg KOH/g and 2.05mmol/kg reached the grade-one standard of edible oil. Additionally, the final RBO contained 20.66mg/kg ?-oryzanol and 20.63mg/kg phytosterol with the retention rate of 71.67% and 59.2% but with undetectable GEs and MCPDEs. The environmental friendliness of the novel moderate biorefining process and superior product quality of the final product point toward a promising viable process for RBO refining in the further.
ESTHER : Li_2021_LWT_151_112118
PubMedSearch : Li_2021_LWT_151_112118
PubMedID:
Gene_locus related to this paper: malgo-a8puy1

Title : Research Progress on Dipeptidyl Peptidase Family: Structure, Function and Xenobiotic Metabolism - Qian_2021_Curr.Med.Chem__
Author(s) : Qian XK , Zhang J , Li XD , Song PF , Zou LW
Ref : Curr Med Chem , : , 2021
Abstract : Prolyl-specific peptidases or proteases, including Dipeptidyl Peptidase 2, 4, 6, 8, 9, 10, Fibroblast Activation Protein, prolyl endopeptidase and prolyl carboxypeptidase, belong to the dipeptidyl peptidase family. In human physiology and anatomy, they have homology amino acid sequences, similarities in structure, but play distinct functions and roles. Some of them also play important roles in the metabolism of drugs containing endogenous peptides, xenobiotics containing peptides, and exogenous peptides. The major functions of these peptidases in both the metabolism of human health and bioactive peptides are of significant importance in the development of effective inhibitors to control the metabolism of endogenous bioactive peptides. The structural characteristics, distribution of tissue, endogenous substrates, and biological functions were summarized in this review. Furthermore, the xenobiotics metabolism of the dipeptidyl peptidase family is illustrated. All the evidence and information summarized in this review would be very useful for researchers to extend the understanding of the proteins of these families and offer advice and assistance in physiology and pathology studies.
ESTHER : Qian_2021_Curr.Med.Chem__
PubMedSearch : Qian_2021_Curr.Med.Chem__
PubMedID: 34525910

Title : Expression and kinetic analysis of carboxylesterase LmCesA1 from Locusta migratoria - Yin_2021_Biotechnol.Lett__
Author(s) : Yin F , Ma W , Li D , Zhang X , Zhang J
Ref : Biotechnol Lett , : , 2021
Abstract : OBJECTIVE: To investigate the biochemical characterization of the carboxylesterase LmCesA1 from Locusta migratoria. RESULTS: We expressed recombinant LmCesA1 in Sf9 cells by using the Bac-to-bac baculovirus expression system. Enzyme kinetic assays showed that the K(m) values of LmCesA1 for alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA) were 0.08 +/- 0.01 mM and 0.22 +/- 0.03 mM, respectively, suggesting that LmCesA1 has a higher affinity for alpha-NA. LmCesA1 retained its enzymatic activity during incubations at pH 7-10 and at 10-30 degreesC. In an inhibition experiment, two organophosphate pesticides (malaoxon and malathion) and one pyrethroid pesticide (deltamethrin) showed different inhibition profiles against purified LmCesA1. Recombinant LmCesA1 activity was significantly inhibited by malaoxon in vitro. UPLC analysis showed that no metabolites were detected. CONCLUSIONS: These results suggest that overexpression of LmCesA1 enhances malathion sequestration to confer malathion tolerance in L. migratoria.
ESTHER : Yin_2021_Biotechnol.Lett__
PubMedSearch : Yin_2021_Biotechnol.Lett__
PubMedID: 33511494
Gene_locus related to this paper: locmi-l7su46

Title : PubChem in 2021: new data content and improved web interfaces - Kim_2021_Nucleic.Acids.Res_49_D1388
Author(s) : Kim S , Chen J , Cheng T , Gindulyte A , He J , He S , Li Q , Shoemaker BA , Thiessen PA , Yu B , Zaslavsky L , Zhang J , Bolton EE
Ref : Nucleic Acids Research , 49 :D1388 , 2021
Abstract : PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
ESTHER : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedSearch : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedID: 33151290

Title : DECR1 directly activates HSL to promote lipolysis in cervical cancer cells - Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
Author(s) : Zhou H , Zhang J , Yan Z , Qu M , Zhang G , Han J , Wang F , Sun K , Wang L , Yang X
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159090 , 2021
Abstract : Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth.
ESTHER : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedSearch : Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090
PubMedID: 34896618

Title : A stable biosensor based on chitosan-modified graphene for detecting organophosphorus pesticides - Zhang_2021_Biotechnol.Appl.Biochem__
Author(s) : Zhang J , Hu H , Wang P , Zhang C , Wuma J , Yang L
Ref : Biotechnol Appl Biochem , : , 2021
Abstract : An acetylcholinesterase (AChE) biosensor was successfully fabricated with a stable structure and high detection accuracy. Graphene (Gra) nano-fragments modified with chitosan and acetylcholinesterase were successively drip-coated on the surface of a glassy carbon electrode via a layer-by-layer assembly method. The concentration range of the sensor to detect dichlorvos was 0.1 nM to 100000 nM, and the limit of detection was 54 pM. Chitosan (CS) was used to modify graphene for the first time, which enhanced the mechanical flexibility of these graphene nanostructures, significantly improving the stability and detection accuracy of this sensor. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedSearch : Zhang_2021_Biotechnol.Appl.Biochem__
PubMedID: 33660328

Title : Inhibition of 2-Arachidonoylglycerol Metabolism Alleviates Neuropathology and Improves Cognitive Function in a Tau Mouse Model of Alzheimer's Disease - Hashem_2021_Mol.Neurobiol__
Author(s) : Hashem J , Hu M , Zhang J , Gao F , Chen C
Ref : Molecular Neurobiology , : , 2021
Abstract : Alzheimer's disease (AD) is the most common cause of dementia, which affects more than 5 million individuals in the USA. Unfortunately, no effective therapies are currently available to prevent development of AD or to halt progression of the disease. It has been proposed that monoacylglycerol lipase (MAGL), the key enzyme degrading the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, is a therapeutic target for AD based on the studies using the APP transgenic models of AD. While inhibition of 2-AG metabolism mitigates beta-amyloid (Abeta) neuropathology, it is still not clear whether inactivation of MAGL alleviates tauopathies as accumulation and deposition of intracellular hyperphosphorylated tau protein are the neuropathological hallmark of AD. Here we show that JZL184, a potent MAGL inhibitor, significantly reduced proinflammatory cytokines, astrogliosis, phosphorylated GSK3beta and tau, cleaved caspase-3, and phosphorylated NF-kB while it elevated PPARgamma in P301S/PS19 mice, a tau mouse model of AD. Importantly, tau transgenic mice treated with JZL184 displayed improvements in spatial learning and memory retention. In addition, inactivation of MAGL ameliorates deteriorations in expression of synaptic proteins in P301S/PS19 mice. Our results provide further evidence that MAGL is a promising therapeutic target for AD.
ESTHER : Hashem_2021_Mol.Neurobiol__
PubMedSearch : Hashem_2021_Mol.Neurobiol__
PubMedID: 33939165

Title : Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots - Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
Author(s) : Chen M , Zhang J , Chang J , Li H , Zhai Y , Wang Z
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 269 :120756 , 2021
Abstract : Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay.
ESTHER : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedSearch : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedID: 34952437

Title : Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve - Wang_2021_J.Affect.Disord_292_565
Author(s) : Wang S , Ishima T , Qu Y , Shan J , Chang L , Wei Y , Zhang J , Pu Y , Fujita Y , Tan Y , Wang X , Ma L , Wan X , Hammock BD , Hashimoto K
Ref : J Affect Disord , 292 :565 , 2021
Abstract : BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice. METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed. RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium. LIMITATIONS: Detailed mechanisms are unclear. CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.
ESTHER : Wang_2021_J.Affect.Disord_292_565
PubMedSearch : Wang_2021_J.Affect.Disord_292_565
PubMedID: 34147969

Title : Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells - Qian_2021_Bioorg.Med.Chem_40_116187
Author(s) : Qian XK , Zhang J , Song PF , Zhao YS , Ma HY , Jin Q , Wang DD , Guan XQ , Li SY , Bao X , Zou LW
Ref : Bioorganic & Medicinal Chemistry , 40 :116187 , 2021
Abstract : Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids. In this study, we synthesized a series of pyrazolones and assayed their inhibitory effects against CES2 in vitro. Structure-activity relationship analysis of these pyrazolones reveals that the introduction of 4-methylphenyl unit (R(1)), 4-methylbenzyl (R(2)) and cyclohexyl (R(3)) moieties are beneficial for CES2 inhibition. Guided by these SARs results, 1-cyclohexyl-4-(4-methylbenzyl)-3-p-tolyl-1H- pyrazol-5(4H)-one (27) was designed and synthesized. Further investigations demonstrated that the compound 27 exhibited stronger CES2 inhibition activity with a lower IC(50) value (0.13 microM). The inhibition kinetic study demonstrated that compound 27 inhibited the hydrolysis of CES2-fluorescein diacetate (FD) through non-competitive inhibition. In addition, the molecular docking showed that the core of pyrazolone, the cyclohexane moiety, 4-methylbenzyl and 4-methylphenyl groups in compound 27 all played important roles with the amino acid residues of CSE2. Also, compound 27 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. In brief, we designed and synthesized a novel pyrazolone compound with a strong inhibitory ability on CES2 and could inhibit the adipogenesis induced by mouse preadipocytes, which can be served as a promising lead compound for the development of more potent pyrazolone-type CES2 inhibitors, and also used as a potential tool for exploring the biological functions of CES2 in human being.
ESTHER : Qian_2021_Bioorg.Med.Chem_40_116187
PubMedSearch : Qian_2021_Bioorg.Med.Chem_40_116187
PubMedID: 33965840

Title : Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K\/Akt\/m-TOR signaling pathway in the brains of mice - Zhang_2021_Int.Immunopharmacol_99_108035
Author(s) : Zhang Y , Ding C , Cai Y , Chen X , Zhao Y , Liu X , Zhang J , Sun S , Liu W
Ref : Int Immunopharmacol , 99 :108035 , 2021
Abstract : An increasing amount of evidence has shown that injection of D-galactose (D-gal) can mimic natural aging that typically is associated with brain injury. Oxidative stress and apoptosis has been shown to play an essential role in aging process. The purpose of this study was to investigate the protective effectsof astilbin (ASB) on D-Gal-induced agingin miceand to further explore the underlying mechanisms. We randomly divided 50 mice into 5 groups.To establish this model of aging, 40micewere intraperitoneally administered D-Gal (500 mg/kg). The mice in the treatmentgroupswere intragastricaly administratedASB at doses of 40 and 80 mg/kg. H&E and TUNEL staining were used to determine the effect of ASB on the number of apoptotic cells in the brain. Furthermore, biochemical indices of serum, oxidative stress factors, and apoptosis factors were determined to clarify the underlying mechanism using reagent test kits and western blotting. The results showed that varying doses of ASB could improve D-Gal-induced histopathological damageand significantly alleviatedthe aging induced by D-Galin mice. ASB remarkably decreased the activities of malondialdehyde (MDA)(p < 0.01)and Acetyl cholinesterase (AChE)(p < 0.05) and markedlyincreased the content of catalase (CAT)(p < 0.01)and superoxide dismutase (SOD)(p < 0.01), respectively. In addition, Western blotting revealed thatASB treatment (40 mg/kg)attenuated the D-gal-induced Bax and Caspase 3 protein expression(p < 0.01) and reversed the increase in Bcl-2protein expressionin brain. Moreover, ASB treatment significantly upregulated the protein expression ofp-PI3K/PI3K and altered the p-Akt/Akt ratio (p < 0.05), while inhibiting the expression of p-m-TOR relative to m-TOR(p < 0.05). Moreover, the expression of P53 tended to decreasein the low ASB treatmentgroup (40 mg/kg), whereas no change was observed in the high ASB treatmentgroup (80 mg/kg). In the intestinal flora, the richness of the normal group and the ASB group was higher than that of the D-Gal group. Heat map analysis also showed that ASB promoted Lactobacillus and other probiotics and also confirmed the advantages of ASB. The observed changes in intestinal flora further verified the efficacy of ASB.
ESTHER : Zhang_2021_Int.Immunopharmacol_99_108035
PubMedSearch : Zhang_2021_Int.Immunopharmacol_99_108035
PubMedID: 34435579

Title : Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene - Luo_2021_Front.Pediatr_9_679342
Author(s) : Luo X , Wang C , Lin L , Yuan F , Wang S , Wang Y , Wang A , Wu S , Lan X , Xu Q , Yin R , Cheng H , Zhang Y , Xi J , Zhang J , Sun X , Yan J , Zeng F , Chen Y
Ref : Front Pediatr , 9 :679342 , 2021
Abstract : The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14-15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14-15 deletion could cause CMS.
ESTHER : Luo_2021_Front.Pediatr_9_679342
PubMedSearch : Luo_2021_Front.Pediatr_9_679342
PubMedID: 34912755

Title : Assessing the Single and Combined Toxicity of Chlorantraniliprole and Bacillus thuringiensis (GO33A) against Four Selected Strains of Plutella xylostella (Lepidoptera: Plutellidae), and a Gene Expression Analysis - Shabbir_2021_Toxins.(Basel)_13_
Author(s) : Shabbir MZ , He L , Shu C , Yin F , Zhang J , Li ZY
Ref : Toxins (Basel) , 13 : , 2021
Abstract : Concerns about resistance development to conventional insecticides in diamondback moth (DBM) Plutella xylostella (L.), the most destructive pest of Brassica vegetables, have stimulated interest in alternative pest management strategies. The toxicity of Bacillus thuringiensis subsp. aizawai (Bt GO33A) combined with chlorantraniliprole (Chl) has not been documented. Here, we examined single and combined toxicity of chlorantraniliprole and Bt to assess the levels of resistance in four DBM strains. Additionally, enzyme activities were tested in field-original highly resistant (FOH-DBM), Bt-resistant (Bt-DBM), chlorantraniliprole-resistant (CL-DBM), and Bt + chlorantraniliprole-resistant (BtC-DBM) strains. The Bt product had the highest toxicity to all four DBM strains followed by the mixture of insecticides (Bt + Chl) and chlorantraniliprole. Synergism between Bt and chlorantraniliprole was observed; the combination of Bt + (Bt + Chl) (1:1, LC(50):LC(50)) was the most toxic, showing a synergistic effect against all four DBM strains with a poison ratio of 1.35, 1.29, 1.27, and 1.25. Glutathione S-transferase (GST) and carboxyl-esterase (CarE) activities showed positive correlations with chlorantraniliprole resistance, but no correlation was observed with resistance to Bt and Bt + Chl insecticides. Expression of genes coding for PxGST, CarE, AChE, and MFO using qRT-PCR showed that the PxGST and MFO were significantly overexpressed in Bt-DBM. However, AChE and CarE showed no difference in the four DBM strains. Mixtures of Bt with chlorantraniliprole exhibited synergistic effects and may aid the design of new combinations of pesticides to delay resistance in DBM strains substantially.
ESTHER : Shabbir_2021_Toxins.(Basel)_13_
PubMedSearch : Shabbir_2021_Toxins.(Basel)_13_
PubMedID: 33809820

Title : Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota - Zhang_2021_Environ.Pollut_277_116767
Author(s) : Zhang J , Meng H , Kong X , Cheng X , Ma T , He H , Du W , Yang S , Li S , Zhang L
Ref : Environ Pollut , 277 :116767 , 2021
Abstract : Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 microm and 9-Nitroanthracene (9-NAnt, 5 and 500 microg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works.
ESTHER : Zhang_2021_Environ.Pollut_277_116767
PubMedSearch : Zhang_2021_Environ.Pollut_277_116767
PubMedID: 33640823

Title : Cholinesterase is Associated With Prognosis and Response to Chemotherapy in Advanced Gastric Cancer - Bi_2021_Pathol.Oncol.Res_27_580800
Author(s) : Bi Y , Zhang J , Zeng D , Chen L , Ye W , Yang Q , Ling Y
Ref : Pathol Oncol Res , 27 :580800 , 2021
Abstract : Background: Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Methods: Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). Results: A total of 150 advanced GC patients were included and divided into serum level <=5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141-2.243; p = 0.006), poorer OS (HR, 1.76; 95% CI, 1.228-2.515; p = 0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272-1.129; p = 0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response (p < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28-2.57; p = 0.0002). The medium OS was 13.1 months in patients with increased post-treatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29-2.71; p = 0.0002). Conclusion: Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC.
ESTHER : Bi_2021_Pathol.Oncol.Res_27_580800
PubMedSearch : Bi_2021_Pathol.Oncol.Res_27_580800
PubMedID: 34257526

Title : Dual-fiber optic bioprobe system for triglyceride detection using surface plasmon resonance sensing and lipase-immobilized magnetic bead hydrolysis - Zhou_2021_Biosens.Bioelectron_196_113723
Author(s) : Zhou S , Li X , Zhang J , Yuan H , Hong X , Chen Y
Ref : Biosensors & Bioelectronics , 196 :113723 , 2021
Abstract : The rapid and accurate detection of triglyceride (TG) plays a valuable role in the prevention and control of dyslipidemia. In this paper, a novel method for TG detection using a dual-fiber optic bioprobe system, which can accurately detect different levels of TG concentration in serum, is proposed. The system employs disposable microprobe-type fiber optic surface plasmon resonance (SPR) biosensors for signal acquisition, providing high stability and portability while avoiding cross-contamination caused by repeated use. The proposed biosensor with a high sensitivity of 1.25 nm/(mg/mL) for TG detection in serum and a tiny diameter of 125 microm, was fabricated using a novel multimode fiber-single-mode fiber-reflector (MSR) structure, which has been scarcely ever reported to the best of our knowledge. In the process of TG detection, lipase-immobilized magnetic beads were introduced to specifically hydrolyze TG, and the relationship between the TG content and the SPR differential signal was obtained from dual-fiber optic bioprobe measurements of the TG sample before and after hydrolysis. The proposed method achieved TG detection in the concentration range of 0-8 mg/mL (including healthy and unhealthy levels of TG concentration in the human body). Additionally, the miniaturized fiber optic biosensors used in this work have the advantages of low sample consumption, high sensitivity, simple operation, label-free measurement, high selectivity, and low cost. This method provides a new pathway for rapid and reliable TG detection and has potential applications in medical research and clinical diagnosis.
ESTHER : Zhou_2021_Biosens.Bioelectron_196_113723
PubMedSearch : Zhou_2021_Biosens.Bioelectron_196_113723
PubMedID: 34688110

Title : Specific immobilization of lipase on functionalized 3D printing scaffolds via enhanced hydrophobic interaction for efficient resolution of racemic 1-indanol - Zhang_2021_Biochem.Biophys.Res.Commun_546_111
Author(s) : Zhang J , Gao B , Lv K , Kumissay L , Wu B , Chu J , He B
Ref : Biochemical & Biophysical Research Communications , 546 :111 , 2021
Abstract : Lipase immobilization with hydrophobic interaction is of interesting exploration, and some functionalized groups on supports are special for activity increasing. To achieved a good performance of cost-effective immobilization on macro-supports for feasible usage and recycle, eco-friendly PLA-based 3D printing macro-scaffolds with fabrication was designed, and phenyl groups with different length of linkers and combined two kinds of groups were anchored for lipase YCJ01 binding with improving payload, the highest enzyme expression of 2227.5 U/g, activity recovery of 137.3%, and increasing specific activity of 815.9 U/mg were attained by using PLA@AMTS-C7-Ph/PLA@AMTS-C9-Ph scaffolds as carries. The immobilized lipase YCJ01 on bifunctionalized 3D printing scaffolds was further applied to the efficient resolution of racemic 1-indanol (267 mM) with high stereoselectivity using a binary solvent system. The immobilized lipase YCJ01 could control the over transesterification of (S)-1-indanol and exhibit good operational stability of repetitive usage for 9 cycles. This is beneficial to obtain the high enantiomerical pure product by feasible separation of immobilized biocatalyst without rigorous operation.
ESTHER : Zhang_2021_Biochem.Biophys.Res.Commun_546_111
PubMedSearch : Zhang_2021_Biochem.Biophys.Res.Commun_546_111
PubMedID: 33582553

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

Title : Endothelial Lipase Exerts its Anti-Atherogenic Effect through Increased Catabolism of beta-VLDLs - Yan_2020_J.Atheroscler.Thromb__
Author(s) : Yan H , Niimi M , Wang C , Chen Y , Zhou H , Matsuhisa F , Nishijima K , Kitajima S , Zhang B , Yokomichi H , Nakajima K , Murakami M , Zhang J , Chen YE , Fan J
Ref : J Atheroscler Thromb , : , 2020
Abstract : AIM: Endothelial lipase (EL) plays an important role in lipoprotein metabolism. Our recent study showed that increased hepatic expression of EL attenuates diet-induced hypercholesterolemia, thus subsequently reducing atherosclerosis in transgenic (Tg) rabbits. However, it is yet to be determined whether increased EL activity itself per se is anti-atherogenic or whether the anti-atherogenic effect of EL is exclusively dependent on its lipid-lowering effect. METHODS: To determine the mechanisms underlying EL-mediated anti-atherogenic effect, we fed Tg and non-Tg rabbits diets containing different amounts of cholesterol to make their plasma cholesterol levels similarly high. Sixteen weeks later, we examined their lipoprotein profiles and compared their susceptibility to atherosclerosis. RESULTS: With Tg and non-Tg rabbits having hypercholesterolemia, the plasma lipids and lipoprotein profiles were observed to be similar, while pathological examinations revealed that lesion areas of both aortic and coronary atherosclerosis of Tg rabbits were not significantly different from non-Tg rabbits. Moreover, Tg rabbits exhibited faster clearance of DiI-labeled beta-VLDLs than non-Tg rabbits. CONCLUSION: The results of our study suggest that the enhancement of beta-VLDL catabolism is the major mechanism for atheroprotective effects of EL in Tg rabbits.
ESTHER : Yan_2020_J.Atheroscler.Thromb__
PubMedSearch : Yan_2020_J.Atheroscler.Thromb__
PubMedID: 32448826

Title : Colonization of Beauveria bassiana 08F04 in root-zone soil and its biocontrol of cereal cyst nematode (Heterodera filipjevi) - Zhang_2020_PLoS.One_15_e0232770
Author(s) : Zhang J , Fu B , Lin Q , Riley IT , Ding S , Chen L , Cui J , Yang L , Li H
Ref : PLoS ONE , 15 :e0232770 , 2020
Abstract : Cereal cyst nematodes cause serious yield losses of wheat in Hunaghuai winter wheat growing region in China. Beauveria bassiana 08F04 isolated from the surface of cysts is a promising biological control agent for cereal cyst nematodes. As the colonization capacity is a crucial criteria to assess biocontrol effectiveness for a microbial agent candidate, we aimed to label B. bassiana 08F04 for efficient monitoring of colonization in the soil. The binary pCAM-gfp plasmid containing sgfp and hph was integrated into B. bassiana 08F04 using the Agrobacterium tumefaciens-mediated transformation. The transformation caused a significant change in mycelial and conidial yields, and in extracellular chitinase activity in some transformants. The cultural filtrates of some transformants also decreased acetylcholinesterase activity and the survival of Heterodera filipjevi second-stage juveniles relative to the wild-type strain. One transformant (G10) had a growth rate and biocontrol efficacy similar to the wild-type strain, so it was used for a pilot study of B. bassiana colonization conducted over 13 weeks. Real-time PCR results and CFU counts revealed that the population of G10 increased quickly over the first 3 weeks, then decreased slowly over the following 4 weeks before stabilizing. In addition, the application of wild-type B. bassiana 08F04 and transformant G10 significantly reduced the number of H. filipjevi females in roots by 64.4% and 60.2%, respectively. The results of this study have practical applications for ecological, biological and functional studies of B. bassiana 08F04 and for bionematicide registration.
ESTHER : Zhang_2020_PLoS.One_15_e0232770
PubMedSearch : Zhang_2020_PLoS.One_15_e0232770
PubMedID: 32369513

Title : Increased expression of soluble epoxide hydrolase in the brain and liver from patients with major psychiatric disorders: A role of brain - liver axis - Zhang_2020_J.Affect.Disord_270_131
Author(s) : Zhang J , Tan Y , Chang L , Hammock BD , Hashimoto K
Ref : J Affect Disord , 270 :131 , 2020
Abstract : BACKGROUND: Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids might play a role in the pathogenesis of major psychiatric disorders. Here we studied whether expression of sEH protein is altered in the postmortem samples (parietal cortex, and liver) from patients with major psychiatric disorders. METHODS: Protein expression of sEH in the parietal cortex and liver from control, major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) groups was measured. RESULTS: Levels of sEH in the parietal cortex and liver from MDD, BD, and SZ groups were significantly higher than the control group. Interestingly, there was a positive correlation between sEH protein in the parietal cortex and sEH protein the liver in all groups. LIMITATIONS: The small number in each group may limit our interpretation. CONCLUSIONS: This study shows that the increased expression of sEH in the brain and liver might play a role in the pathogenesis of major psychiatric disorders, suggesting a role of brain - liver axis in major psychiatric disorders.
ESTHER : Zhang_2020_J.Affect.Disord_270_131
PubMedSearch : Zhang_2020_J.Affect.Disord_270_131
PubMedID: 32339103

Title : Biochemical Characterization and Mutational Analysis of a Lactone Hydrolase from Phialophora americana - Yu_2020_J.Agric.Food.Chem_68_2570
Author(s) : Yu X , Tu T , Luo H , Huang H , Su X , Wang Y , Zhang J , Bai Y , Yao B
Ref : Journal of Agricultural and Food Chemistry , 68 :2570 , 2020
Abstract : The mycotoxin zearalenone (ZEN) is a secondary metabolite produced mainly by Fusarium species. ZEN poses health hazards both for humans and animals, as a major contaminant in the food and feed industries. Currently, there is no effective technique for degrading ZEN during industrial processes. In this study, we isolated and biochemically characterized a novel lactone hydrolase, ZHD607, isolated from Phialophora americana, cloned, and exogenously expressed in Pichia pastoris. ZHD607 was characterized as a mesophilic lactone hydrolase having a neutral pH and showing optimal activity at 35 degreesC and pH 8.0. Two mutants, ZHDM1 and I160Y, generated from ZHD607 based on structure and sequence alignment analyses, exhibited 2.9- and 3.4-fold higher activity towards ZEN than did ZHD607. Molecular dynamics simulation revealed diverse mechanisms driving this improved catalytic activity. These findings enrich our knowledge about ZHD enzyme family and represent an important step toward industrialization of ZEN-detoxifying lactone hydrolases.
ESTHER : Yu_2020_J.Agric.Food.Chem_68_2570
PubMedSearch : Yu_2020_J.Agric.Food.Chem_68_2570
PubMedID: 31760747
Gene_locus related to this paper: 9euro-a0a0d2e8j6

Title : Protostane-type triterpenoids as natural soluble epoxide hydrolase inhibitors: Inhibition potentials and molecular dynamics - Sun_2020_Bioorg.Chem_96_103637
Author(s) : Sun CP , Zhang J , Zhao WY , Yi J , Yan JK , Wang YL , Morisseau C , Liu ZB , Hammock BD , Ma XC
Ref : Bioorg Chem , 96 :103637 , 2020
Abstract : The inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic approach to treat inflammation and other disorders. In our present investigation on searching for sEH inhibitors from traditional Chinese medicines, we found that Alisma orientale displayed inhibition of sEH. We constructed a small library of protostane-type triterpenoids (1-25) isolated from A. orientale, and screened their inhibitory activities. Alismanin B (1), 11-deoxy-25-anhydro alisol E (4), 11-deoxy alisol B (5), and 25-O-ethyl alisol A (15) displayed concentration-dependently inhibitory activities against sEH with IC50 values from 3.40 +/- 0.57 muM to 9.57 +/- 0.88 muM. 11-Deoxy-25-anhydro alisol E (4) and 11-deoxy alisol B (5) were defined as mixed-type competitive inhibitors with Ki values of 12.6 and 3.48 muM, respectively, based on the result of inhibition kinetics. The potential interaction mechanism of 11-deoxy alisol B (5) with sEH was analyzed by molecular docking and molecular dynamics, revealing that amino acid residues Trp336 and Tyr466 were vital for its inhibitory activity.
ESTHER : Sun_2020_Bioorg.Chem_96_103637
PubMedSearch : Sun_2020_Bioorg.Chem_96_103637
PubMedID: 32032849

Title : Microchamber arrays made of biodegradable polymers for enzymatic release of small hydrophilic cargos - Zhang_2020_Soft.Matter_16_2266
Author(s) : Zhang J , Sun R , DeSouza-Edwards AO , Frueh J , Sukhorukov GB
Ref : Soft Matter , 16 :2266 , 2020
Abstract : The encapsulation of small hydrophilic molecules and response to specific biological triggers in a controlled manner have become two of the significant challenges in biomedical research, in particular in the field of localized drug delivery and biosensing. This work reports the fabrication of free-standing microchamber array films made of biodegradable polymers for the encapsulation and enzymatically triggered release of small hydrophilic molecules. Polycaprolactone (PCL) microchamber arrays were demonstrated to fully biodegrade within 5 hours of exposure to lipase from Pseudomonas cepacia (lipase PS) at a concentration of 0.5 mg ml-1, with lower concentrations producing correspondingly longer degradation times. The gradual process of deterioration was real-time monitored utilising laser Fraunhofer diffraction patterns. Additionally, a small hydrophilic molecule, 5(6)-carboxyfluorescein (CF), was loaded into the PCL microchamber arrays in a dry state; however, the substantial permeability of the PCL film led to leakage of the dye molecules. Consequently, polylactic acid (PLA) was blended with PCL to reduce its permeability, enabling blended PCL-PLA (1 : 2 ratio correspondingly) microchamber arrays to trap the small hydrophilic molecule CF. PCL-PLA (1 : 2) microchamber arrays hold potential for controlled release under the catalysis of lipase within 26 hours. Additionally, it is calculated that approximately 11 pg of CF dye crystals was loaded into individual microchambers of 10 microm size, indicating that the microchamber array films could yield a highly efficient encapsulation.
ESTHER : Zhang_2020_Soft.Matter_16_2266
PubMedSearch : Zhang_2020_Soft.Matter_16_2266
PubMedID: 32039413

Title : Low Mismatch Rate between Double-Stranded RNA and Target mRNA Does Not Affect RNA Interference Efficiency in Colorado Potato Beetle - He_2020_Insects_11_
Author(s) : He W , Xu W , Fu K , Guo W , Zhang J
Ref : Insects , 11 : , 2020
Abstract : RNA interference (RNAi)-based technology has been proven as a novel approach for insect pest control. However, whether insects could evolve resistance to RNAi and the underlying mechanism is largely unknown. The target gene mutations were thought to be one of the potential ways to develop the resistance. Here we predicted the effective siRNA candidates that could be derived from dsRNA against the Colorado potato beetle (CPB) beta-Actin gene (dsACT). By site-directed mutagenesis, we synthesized the dsRNAs with the defect in generation of effective siRNAs (and thus were supposed to have comparable low RNAi efficacy). We showed that, with mismatches to the target gene, all the dsRNA variants caused similar levels of silencing of target gene, mortality and larval growth retardation of CPB. Our results suggest that when the mismatch rate of dsACT and target beta-Actin mRNA is less than 3%, the RNAi efficiency is not impaired in CPB, which might imply the low possibility of RNAi resistance evolving through the sequence mismatches between dsRNA and the target gene.
ESTHER : He_2020_Insects_11_
PubMedSearch : He_2020_Insects_11_
PubMedID: 32708568

Title : Left atrial appendage thrombus formation in a patient with atrial fibrillation on dabigatran therapy associated with CES1 and ABCB1 genetic polymorphisms: A case report - Wu_2020_Medicine.(Baltimore)_99_e22084
Author(s) : Wu T , Xia X , Fu J , Chen W , Zhang J
Ref : Medicine (Baltimore) , 99 :e22084 , 2020
Abstract : RATIONALE: Dabigatran is a direct thrombin inhibitor that is widely used to prevent the formation of thrombus formation. Amiodarone can increase the plasma concentration of dabigatran. CES1 (carboxylesterase 1) and ABCB1 (ATP-binding cassette subfamily B member 1) genetic polymorphisms associate with the pharmacokinetics of dabigatran. PATIENT CONCERNS: A 62-year-old woman was admitted to the hospital due to chest tightness, fatigue, and discomfort despite long-term anticoagulation with dabigatran 110 mg twice daily for 6 months, with concomitant use of amiodarone. DIAGNOSES: Left atrial appendage thrombus formation with a history of atrial fibrillation. INTERVENTIONS: The clinician changed dabigatran to warfarin. To explore the causes of insufficient anticoagulation using dabigatran in this patient, we examined the ABCB1 and CES1 genes. Results showed that she carried ABCB1 variant alleles with 3 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs1045642, rs2032582) and CES1 variant alleles with 2 heterozygote SNPs (rs2244613, rs4580160). OUTCOMES: The left atrial appendage thrombus disappeared. LESSONS: Multiple mutations in the ABCB1 and CES1 genes may influence the pharmacokinetics of dabigatran and could have contributed to the thrombus formation in the left atrial appendage.
ESTHER : Wu_2020_Medicine.(Baltimore)_99_e22084
PubMedSearch : Wu_2020_Medicine.(Baltimore)_99_e22084
PubMedID: 32899083

Title : Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase - Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
Author(s) : Pu Y , Yang J , Chang L , Qu Y , Wang S , Zhang K , Xiong Z , Zhang J , Tan Y , Wang X , Fujita Y , Ishima T , Wan D , Hwang SH , Hammock BD , Hashimoto K
Ref : Proc Natl Acad Sci U S A , : , 2020
Abstract : Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.
ESTHER : Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
PubMedSearch : Pu_2020_Proc.Natl.Acad.Sci.U.S.A__
PubMedID: 32398374

Title : High-efficiency expression of the thermophilic lipase from Geobacillus thermocatenulatus in Escherichia coli and its application in the enzymatic hydrolysis of rapeseed oil - Zhang_2020_3.Biotech_10_523
Author(s) : Zhang J , Tian M , Lv P , Luo W , Wang Z , Xu J
Ref : 3 Biotech , 10 :523 , 2020
Abstract : Long-chain fatty acids are widely used in food and chemical industries, and the enzymatic preparation of fatty acids is considered an environmentally friendly process. In the present study, long-chain fatty acids were prepared by the enzymatic hydrolysis of rapeseed oil with a genetically engineered lipase. Because thermophilic lipase has strong stability at higher temperatures, it was more suitable for the industrial production of long-chain fatty acids. Therefore, the thermophilic lipase BTL2 from Geobacillus thermocatenulatus was efficiently expressed in E. coli BL21(DE3) cells with an enzyme activity of 39.50 U/mg followed by gene codon optimisation. Experimental results showed that the recombinant lipase BTL2 exhibited excellent resistance to certain organic solvents (n-hexane, benzene, ethanol, and butanol). The metal cation Ca(2+) and the non-ionic surfactant Triton-100X enhanced enzyme activity by 7.36% and 56.21% respectively. Moreover, the acid value of the liberated long-chain fatty acids by hydrolysing rapeseed oil was approximately 161.64 mg KOH/g at 50 degreeC in 24 h, the hydrolytic conversion rate was 91.45%, and the productivity was approximately 6.735 mg KOH/g h. These results suggested that the recombinant lipase BTL2 has excellent hydrolytic performance for rapeseed oil and showed great potential for the enzymatic preparation of long-chain fatty acids.
ESTHER : Zhang_2020_3.Biotech_10_523
PubMedSearch : Zhang_2020_3.Biotech_10_523
PubMedID: 33194527

Title : Soluble epoxide hydrolase as a therapeutic target for obesity-induced disorders: roles of gut barrier function involved - Zhang_2020_Prostaglandins.Leukot.Essent.Fatty.Acids_162_102180
Author(s) : Zhang J , Tu M , Liu Z , Zhang G
Ref : Prostaglandins Leukot Essent Fatty Acids , 162 :102180 , 2020
Abstract : Emerging research supports that soluble epoxide hydrolase (sEH), an enzyme involved in eicosanoid metabolism, could be a promising target for obesity-associated disorders. The sEH enzyme is overexpressed in many tissues of obese animals. Genetic ablation or pharmacological inhibition of sEH attenuates the development of a wide range of obesity-induced disorders, including endoplasmic reticulum stress, metabolic syndrome, kidney diseases, insulin resistance, fatty liver, hepatic steatosis, inflammation, and endothelial dysfunction. Furthermore, our recent research showed that genetic ablation or inhibition of sEH attenuated obesity-induced intestinal barrier dysfunction and its resulted bacterial translocation, which is widely regarded to be a central mechanism for the pathogenesis of various obesity-induced disorders. Together, these results support that targeting sEH could be a promising strategy to reduce risks of obesity-induced disorders, at least in part through blocking obesity-induced leaky gut syndrome.
ESTHER : Zhang_2020_Prostaglandins.Leukot.Essent.Fatty.Acids_162_102180
PubMedSearch : Zhang_2020_Prostaglandins.Leukot.Essent.Fatty.Acids_162_102180
PubMedID: 33038829

Title : Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse - Leembruggen_2020_Autism.Res_13_691
Author(s) : Leembruggen AJL , Balasuriya GK , Zhang J , Schokman S , Swiderski K , Bornstein JC , Nithianantharajah J , Hill-Yardin EL
Ref : Autism Res , 13 :691 , 2020
Abstract : Gastrointestinal (GI) dysfunction is commonly reported by people diagnosed with autism spectrum disorder (ASD; autism) but the cause is unknown. Mutations in genes encoding synaptic proteins including Neuroligin-3 are associated with autism. Mice lacking Neuroligin-3 (Nlgn3(-/-) ) have altered brain function, but whether the enteric nervous system (ENS) is altered remains unknown. We assessed for changes in GI structure and function in Nlgn3(-/-) mice. We found no significant morphological differences in villus height or crypt depth in the jejunum or colon between wildtype (WT) and Nlgn3(-/-) mice. To determine whether deletion of Nlgn3 affects enteric neurons, we stained for neural markers in the myenteric plexus. Nlgn3(-/-) mice had similar numbers of neurons expressing the pan-neuronal marker Hu in the jejunum, proximal mid, and distal colon regions. We also found no differences in the number of neuronal nitric oxide synthase (nNOS+) or calretinin (CalR+) motor neurons and interneurons between WT and Nlgn3(-/-) mice. We used ex vivo video imaging analysis to assess colonic motility under baseline conditions and observed faster colonic migrating motor complexes (CMMCs) and an increased colonic diameter in Nlgn3(-/-) mice, although CMMC frequency was unchanged. At baseline, CMMCs were faster in Nlgn3(-/-) mice compared to WT. Although the numbers of neuronal subsets are conserved in Nlgn3(-/-) mice, these findings suggest that Neuroligin-3 modulates inhibitory neural pathways in the ENS and may contribute to mechanisms underlying GI disorders in autism. Autism Res 2020, 13: 691-701. 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gut problems. Many gene mutations associated with autism affect neuronal activity. We studied mice in which the autism-associated Neuroligin-3 gene is deleted to determine whether this impacts gut neuronal numbers or motility. We found that although mutant mice had similar gut structure and numbers of neurons in all gut regions examined, they had distended colons and faster colonic muscle contractions. Further work is needed to understand how Neuroligin-3 affects neuron connectivity in the gastrointestinal tract.
ESTHER : Leembruggen_2020_Autism.Res_13_691
PubMedSearch : Leembruggen_2020_Autism.Res_13_691
PubMedID: 31002480

Title : RMS2 encoding a GDSL lipase mediates lipid homeostasis in anthers to determine rice male fertility - Zhao_2020_Plant.Physiol__
Author(s) : Zhao J , Long T , Wang Y , Tong X , Tang J , Li J , Wang H , Tang L , Li Z , Shu Y , Liu X , Li S , Liu H , Wu Y , Zhang J
Ref : Plant Physiol , : , 2020
Abstract : Plant male gametogenesis is a coordinated effort involving both reproductive tissues and sporophytic tissues, in which lipid metabolism plays an essential role. Although GDSL esterases/lipases have been well known as key enzymes for many plant developmental processes and stress responses, their functions in reproductive development remain unclear. Here, we report the identification of a rice male sterile 2 (rms2) mutant in rice (Oryza sativa), which is completely male sterile due to the defects in tapetum degradation, cuticle formation in sporophytic tissues, and impaired exine and central vacuole development in pollen grains. RMS2 was map-based cloned as an endoplasmic reticulum-localized GDSL lipase gene, which is predominantly transcribed during early anther development. In rms2, a three-nucleotides deletion and one base substitution (TTGT to A) occurred within the GDSL domain, which reduced the lipid hydrolase activity of the resulting protein and led to significant changes in the content of 16 lipid components and numerous other metabolites as revealed by a comparative metabolic analysis. Furthermore, RMS2 is directly targeted by male fertility regulators Undeveloped Tapetum 1 (UDT1) and Persistent Tapetal Cell 1 (PTC1) both in vitro and in vivo, suggesting that RMS2 may serve as a key node in the rice male fertility regulatory network. These findings shed light on the function of GDSLs in reproductive development and provide a promising gene resource for hybrid rice breeding.
ESTHER : Zhao_2020_Plant.Physiol__
PubMedSearch : Zhao_2020_Plant.Physiol__
PubMedID: 32029522

Title : Exploration of the Molecular Mechanism for Lipoprotein Lipase Expression Variations in SH-SY5Y Cells Exposed to Different Doses of Amyloid-Beta Protein - Zhang_2020_Front.Aging.Neurosci_12_132
Author(s) : Zhang J , Liu Y , Wang S , Que R , Zhao W , An L
Ref : Front Aging Neurosci , 12 :132 , 2020
Abstract : Progressive accumulation of amyloid-beta (Abeta) plaques in the brain is a characteristic pathological change in Alzheimer's disease (AD). We previously found the expression of lipoprotein lipase (LPL) was increased in SH-SY5Y cells exposed to low-dose Abeta and decreased in cells with high-dose Abeta exposure, but the molecular mechanism is still unclear. Based on previous studies, the opposite regulation of histone deacetylase2 (HDAC2) and HDAC3 on LPL expression probably explain the above molecular mechanism, in which microRNA-29a and peroxisome proliferator-activated receptor gamma (PPARgamma) may be involved. This study further revealed the mechanism of HDAC2 and HDAC3 on conversely regulating LPL expression. The results showed that HDAC2 down-regulated microRNA-29a by decreasing histone acetylation (Ace-H3K9) level in its promoter region, subsequently increasing LPL expression directly or through PPARgamma/LPL pathway; HDAC3 decreased LPL expression through inhibiting Ace-H3K9 levels in LPL and PPARgamma promoter regions and up-regulating microRNA-29a. This study also found that with increasing concentrations of Abeta in cells, HDAC2 and HDAC3 expression were gradually increased, and Ace-H3K9 levels in LPL and PPARgamma promoter region regulated by HDAC3 were decreased correspondingly, while Ace-H3K9 levels in microRNA-29a promoter region modulated by HDAC2 were not decreased gradually but presented a U-shaped trend. These may lead to the results that a U-shaped alteration in microRNA-29a expression, subsequently leading to an inverse U-shaped alteration in PPARgamma or LPL expression. In conclusion, HDAC2 and HDAC3 at least partly mediate LPL expression variations in different concentrations of Abeta exposed SH-SY5Y cells, in which microRNA-29a and PPARgamma are involved, and the histone acetylation level in microRNA-29a promoter region plays a key role.
ESTHER : Zhang_2020_Front.Aging.Neurosci_12_132
PubMedSearch : Zhang_2020_Front.Aging.Neurosci_12_132
PubMedID: 32477101

Title : PTUPB ameliorates high-fat diet-induced non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in mice - Sun_2020_Biochem.Biophys.Res.Commun__
Author(s) : Sun CC , Zhang CY , Duan JX , Guan XX , Yang HH , Jiang HL , Hammock BD , Hwang SH , Zhou Y , Guan CX , Liu SK , Zhang J
Ref : Biochemical & Biophysical Research Communications , : , 2020
Abstract : Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global adult population, and no effective pharmacological treatment has been found. Products of arachidonic acid metabolism have been developed into a novel therapy for metabolic syndrome and diabetes. It has been demonstrated that protective actions of a novel dual cyclooxygenase-2 (COX-2) and soluble epoxide hydrolase (sEH) inhibitor, PTUPB, on the metabolic abnormalities. Here, we investigated the effects of PTUPB on hepatic steatosis in high-fat diet (HFD)-induced obese mice, as well as in hepatocytes in vitro. We found that PTUPB treatment reduced body weight, liver weight, liver triglyceride and cholesterol content, and the expression of lipolytic/lipogenic and lipid uptake related genes (Acc, Cd36, and Cidec) in HFD mice. In addition, PTUPB treatment arrested fibrotic progression with a decrease of collagen deposition and expression of Col1a1, Col1a3, and alpha-SMA. In vitro, PTUPB decreased palmitic acid-induced lipid deposition and downregulation of lipolytic/lipogenic genes (Acc and Cd36) in hepatocytes. Additionally, we found that PTUPB reduced the production of pro-inflammatory cytokines and suppressed the NLRP3 inflammasome activation in HFD mice and hepatocytes. In conclusion, dual inhibition of COX-2/sEH attenuates hepatic steatosis by inhibiting the NLRP3 inflammasome activation. PTUPB might be a promising potential therapy for liver steatosis associated with obesity.
ESTHER : Sun_2020_Biochem.Biophys.Res.Commun__
PubMedSearch : Sun_2020_Biochem.Biophys.Res.Commun__
PubMedID: 31973813

Title : Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases - Li_2020_Eur.J.Med.Chem_185_111862
Author(s) : Li Q , Xing S , Chen Y , Liao Q , Liu Y , He S , Feng F , Zhang J , Liu W , Guo Q , Sun Y , Sun H
Ref : Eur Journal of Medicinal Chemistry , 185 :111862 , 2020
Abstract : Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases.
ESTHER : Li_2020_Eur.J.Med.Chem_185_111862
PubMedSearch : Li_2020_Eur.J.Med.Chem_185_111862
PubMedID: 31735576

Title : miR-132 improves the cognitive function of rats with Alzheimer's disease by inhibiting the MAPK1 signal pathway - Deng_2020_Exp.Ther.Med_20_159
Author(s) : Deng Y , Zhang J , Sun X , Ma G , Luo G , Miao Z , Song L
Ref : Exp Ther Med , 20 :159 , 2020
Abstract : Alzheimer's disease (AD) is a common worldwide progressive neurodegenerative disease. The dysregulation of miRNA is crucial in neurodegenerative diseases and neuron apoptosis during AD and is closely associated with the MAPK pathway. By bioinformatic website, we found that there was target inhibiting relationship between microRNA (miR)-132 and MAPK1. Therefore, the current study speculated that miR-132 could improve the cognitive function of rats with AD by inhibiting MAPK1 expression. To verify our hypothesis, 10 normal rats and 60 rats with AD were selected and divided into model, Ad-miR-132 negative control (NC), Ad-miR-132, Ad-small interfering (si)MAPK1 NC, Ad-siMAPK1 and Ad-miR-132 + Ad-MAPK1 groups. Rats were evaluated for learning by performing morris water maze tests and pathological changes of the hippocampus were assessed via HE staining. Additionally, hippocampus cell apoptosis was determined using a TUNEL assay and levels of acetylcholinesterase (AChE), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in sera via ELISA. The mRNA and protein expression of miR-132, iNOS, MAPK1 and phosphorylated (p)-MAPK1 was determined in hippocampus tissues via reverse transcription-quantitative PCR and western blotting, respectively. Compared with normal mice, rats with AD had significantly decreased learning abilities, increased cell apoptosis rates, increased levels of AChE, iNOS, ROS, MDA, MAPK1 and p-MAPK1 and decreased levels of SOD, GSH-Px and miR-132. Upregulation of miR-132 group improved the above indictors and silencing MAKP1 worsened the condition of rats. miR-132 upregulation therefore reversed the negative effects caused by MAPK1 silencing in rats with AD. In conclusion, miR-132 inhibited hippocampal iNOS expression and oxidative stress by inhibiting MAPK1expression to improve the cognitive function of rats with AD.
ESTHER : Deng_2020_Exp.Ther.Med_20_159
PubMedSearch : Deng_2020_Exp.Ther.Med_20_159
PubMedID: 33093897

Title : Neurotoxicity of perfluorooctanoic acid and post-exposure recovery due to blueberry anthocyanins in the planarians Dugesia japonica - Zhang_2020_Environ.Pollut_263_114471
Author(s) : Zhang J , Shao X , Zhao B , Zhai L , Liu N , Gong F , Ma X , Pan X , Yuan Z , Zhang X
Ref : Environ Pollut , 263 :114471 , 2020
Abstract : Perfluorooctanoic acid (PFOA) is a widely used synthetic industrial chemical which accumulates in ecosystems and organisms. Our study have investigated the neurobehavioral effects of PFOA and the alleviation effects of PFOA-induced neurotoxicity by blueberry anthocyanins (ANT) in Dugesia japonica. The planarians were exposed to PFOA and ANT for ten days. Researchs showed that exposure to PFOA affected locomotor behavior and ANT significantly alleviated the reduction in locomotion induced by PFOA. The regeneration of eyespots and auricles was suppressed by PFOA and was promoted by ANT. Following exposure to PFOA, acetylcholinesterase activity continually decreased and was unaffected in the ANT group, but was elevated after combined administration of PFOA and ANT. Oxidative DNA damage was found in planarians exposed to PFOA and was attenuated after administration of ANT by the alkaline comet assay. Concentrations of three neurotransmitters increased following exposure to PFOA and decreased after administration of ANT. Furthermore, ANT promoted and PFOA inhibited neuronal regeneration. DjotxA, DjotxB, DjFoxG, DjFoxD and Djnlg associated with neural processes were up-regulated following exposure to PFOA. Our findings indicate that PFOA is a neurotoxicant while ANT can attenuate these detrimental effects.
ESTHER : Zhang_2020_Environ.Pollut_263_114471
PubMedSearch : Zhang_2020_Environ.Pollut_263_114471
PubMedID: 32268227

Title : N-methoxy-beta-carboline alkaloids with inhibitory activities against Abeta42 aggregation and acetylcholinesterase from the stems of Picrasma quassioides - Zhang_2020_Bioorg.Chem_101_104043
Author(s) : Zhang J , Zhao SS , Xie J , Yang J , Chen GD , Hu D , Zhang WG , Wang CX , Yao XS , Gao H
Ref : Bioorg Chem , 101 :104043 , 2020
Abstract : Nine new N-methoxy-beta-carboline alkaloids (NMCAs) (1a/1b-3a/3b and 4-6) and two known NMCAs (7 and 8) were isolated from the stems of Picrasma quassioides. Their structures were elucidated by spectroscopic data analyses, quantum chemical calculations, and single-crystal X-ray crystallographic data. An analysis of the (13)C NMR chemical shifts of the N-methoxy groups in these NMCAs and 41 gathered known compounds reveals the phenomenon that the chemical shifts of all these N-methoxy groups are greater than deltaC 62, which can be used to recognize the N-methoxy group rapidly. In addition, the acetylcholinesterase (AChE) and Abeta42 aggregation inhibitory activities of 1-8 were evaluated. Compounds 1, 2, 7, and 8 displayed AChE inhibitory activity with IC50 values of 14.9, 13.2, 17.6, and 43.9 muM, respectively. Compound 2 showed inhibition activity against Abeta42 aggregation with an IC50 value of 10.1 muM.
ESTHER : Zhang_2020_Bioorg.Chem_101_104043
PubMedSearch : Zhang_2020_Bioorg.Chem_101_104043
PubMedID: 32629286

Title : Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated From Anemarrhena asphodeloides Bunge: A Review - Lin_2020_Front.Pharmacol_11_764
Author(s) : Lin Y , Zhao WR , Shi WT , Zhang J , Zhang KY , Ding Q , Chen XL , Tang JY , Zhou ZY
Ref : Front Pharmacol , 11 :764 , 2020
Abstract : Anemarrhena asphodeloides Bunge is a famous Chinese Materia Medica and has been used in traditional Chinese medicine for more than two thousand years. Steroidal saponins are important active components isolated from A. asphodeloides Bunge. Among which, the accumulation of numerous experimental studies involved in Timosaponin AIII (Timo AIII) draws our attention in the recent decades. In this review, we searched all the scientific literatures using the key word "timosaponin AIII" in the PubMed database update to March 2020. We comprehensively summarized the pharmacological activity, pharmacokinetics, and toxicity of Timo AIII. We found that Timo AIII presents multiple-pharmacological activities, such as anti-cancer, anti-neuronal disorders, anti-inflammation, anti-coagulant, and so on. And the anti-cancer effect of Timo AIII in various cancers, especially hepatocellular cancer and breast cancer, is supposed as its most potential activity. The anti-inflammatory activity of Timo AIII is also beneficial to many diseases. Moreover, VEGFR, X-linked inhibitor of apoptosis protein (XIAP), B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), thromboxane (Tx) A2 receptor, mTOR, NF-kappaB, COX-2, MMPs, acetylcholinesterase (AChE), and so on are identified as the crucial pharmacological targets of Timo AIII. Furthermore, the hepatotoxicity of Timo AIII was most concerned, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. In conclusion, Timo AIII is potent as a compound or leading compound for further drug development while still needs in-depth studies.
ESTHER : Lin_2020_Front.Pharmacol_11_764
PubMedSearch : Lin_2020_Front.Pharmacol_11_764
PubMedID: 32581782

Title : Decreased T-cell mediated hepatic injury in concanavalin A-treated PLRP2-deficient mice - Ge_2020_Int.Immunopharmacol_85_106604
Author(s) : Ge W , Gao Y , Zhao Y , Yang Y , Sun Q , Yang X , Xu X , Zhang J
Ref : Int Immunopharmacol , 85 :106604 , 2020
Abstract : Concanavalin A (Con A) activates innate immunity and causes liver damage mediated by cytotoxic T lymphocytes (CTL) in mice. The Pancreatic lipase-related protein 2 (PLRP2) is induced by interleukin (IL)-4 in vitro in CTLs and associated with CTL functions. We examined the role of PLRP2 in a mouse model of Con A-induced T cell-mediated hepatitis. PLRP2-knockout and wild-type (WT) mice were inoculated with 20 mg/kg Con A. Mice lacking PLRP2 reduced Con A-induced hepatitis, which was manifested by a decrease in serum aminotransferase and histopathological assessment. The expression and secretion of cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon (IFN)-gamma, IL-6, and IL-1beta were suppressed in Con A-treated PLRP2-knockout mice. In PLRP2 knockout mice, Con A-induced liver chemokines and adhesion molecules (such as MIP-1alpha, MIP-1beta, ICAM-1 and MCP-1) were also down regulated. In the WT liver treated with Con A, the number of T cells (CD4(+) and CD8(+)) and macrophages (CD11b(+) F4/80(+)) increased significantly, while the lack of PLRP2 reduced the number of T cells in the liver, but had no effect on macrophages. The shift of the metabolic profiles was impaired in Con A-treated PLRP2-knockout mice compared to WT mice. In conclusion, these results indicate that PLRP2 deficiency reduces T-cell mediated Con A-induced hepatitis, and suggest PLRP2 is a potential target of anti-inflammatory and immunomodulatory drugs to treat immune-mediated hepatitis.
ESTHER : Ge_2020_Int.Immunopharmacol_85_106604
PubMedSearch : Ge_2020_Int.Immunopharmacol_85_106604
PubMedID: 32428799
Gene_locus related to this paper: mouse-LIPR2

Title : Biochemical and behavior effects induced by diheptyl phthalate (DHpP) and Diisodecyl phthalate (DIDP) exposed to zebrafish - Poopal_2020_Chemosphere_252_126498
Author(s) : Poopal RK , Zhang J , Zhao R , Ramesh M , Ren Z
Ref : Chemosphere , 252 :126498 , 2020
Abstract : Both Diheptyl-phthalate (DHpP) and Diisodecyl-phthalate (DIDP) were used extensively as plasticizers. Recently, their occurrence in the environmental matrices and human body fluids have been reported. Unfortunately, these phthalate congeners are without basic toxicity profiles. Hence, we studied the toxic effects of both DHpP and DIDP in the median lethal concentration (LC50 96-h) on zebrafish (Danio rerio). We assessed swimming behavior strength and tissues biomarker responses including total antioxidants capacity (TAOC), transaminases, and acetylcholinesterase (AChE) enzyme. Fish exposed to phthalate congeners (Treatment-I and-II) for 15-days showed alterations on fish swimming behavior and circadian rhythm. At the end of the exposure period, both liver and heart tissue transaminases activities were found to be accelerated in DHpP and DIDP treated fish, when compared to control group. TAOC and AChE activities were found to be decreased in brain, gills, intestine, and muscle tissues of phthalate congeners treated fish than the control group. Alterations observed in the studied biomarkers were concentration-based response. Among treatment groups DHpP showed higher effects. Comparative studies on swimming behavior and biochemical activities were reasonable to know the swimming responses are mediated due to external stress or internal stress. More studies on molecular and biomarkers assessments are warranted on toxicity of emerging contaminants.
ESTHER : Poopal_2020_Chemosphere_252_126498
PubMedSearch : Poopal_2020_Chemosphere_252_126498
PubMedID: 32197170

Title : Immobilized angiotensin II type I receptor: A powerful method of high throughput screening for antihypertensive compound identification through binding interaction analysis - Liang_2020_J.Chromatogr.A__461003
Author(s) : Liang Q , Fu X , Zhang J , Hao J , Feng G , Wang J , Li Q , Ahmad F , Zhao X
Ref : Journal of Chromatography A , :461003 , 2020
Abstract : The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0mum microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 +/- 0.003, 0.05142 +/- 0.003, 0.07547 +/- 0.004 and 0.01310 +/- 0.005 min(-1) by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12x10(4) and 1.5x10(4)/M) and slower kinetics (kd: 0.6864 +/- 0.03 and 0.3005 +/- 0.01 min(-1)) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds.
ESTHER : Liang_2020_J.Chromatogr.A__461003
PubMedSearch : Liang_2020_J.Chromatogr.A__461003
PubMedID: 32156458

Title : [Determination of gastrodin activity inhibition on acetylcholinesterase by capillary electrophoresis] - Zhang_2020_Se.Pu_38_1102
Author(s) : Zhang J , Zhang B , He M , Han L , Gao D , Liu C
Ref : Se Pu , 38 :1102 , 2020
Abstract : Alzheimer's disease (AD) is the most common cause of dementia in elderly individuals. Currently, acetylcholinesterase inhibitors (AChEI) are the most effective clinical treatment for AD. AChEIs in natural products may have therapeutic potential and should be screened for use in AD treatment. The authors describe a simple and reliable method for AChEI screening by capillary electrophoresis (CE). A hexadimethrine bromide (HDB) solution was pushed into a capillary (0.015 MPax10 s) and incubated for 5 min. The capillary was flushed with deionized water for 5 min to remove free HDB, followed by plugging with an acetylcholinesterase (AChE) solution. After a 5 min incubation, the AChE was immobilized on the positively charged coating by ion binding, and the micro-reactor was created. The substrate solution, acetylthiocholine iodide (AThC), was injected into the capillary and incubated in the micro-reactor for 1 min. The unreacted substrate and the enzymolysis product were separated by CE. Gastrodin, an important component of Gastrodia elata, can inhibit AChE activity. After a certain amount of gastrodin was spiked into the substance solution, the peak area of the product decreased. Greater peak area reduction indicated stronger inhibition of AChEI. We observed good reproducibility of the product peak, with relative standard deviation (RSD) values less than 5.3%. The micro-reactor can be reused up to 300 times, which greatly improves efficiency. When the concentration of gastrodin was 5.24 micromol/L, the inhibition rate of AChE reached 64.8%. The IC(50) of gastrodin was (2.26+/-0.14) micromol/L (R(2)=0.9983), which was consistent with the result of traditional UV method (2.09+/-0.18 micromol/L). If the function of the micro-reactor deteriorates, it can be conveniently renewed by flushing the column to remove the enzyme and repeating the AChE immobilization protocol. The proposed method is simple, efficient, and low cost, and can be used to screen AChEI from natural products, thus contributing to the improvement of AD treatment.
ESTHER : Zhang_2020_Se.Pu_38_1102
PubMedSearch : Zhang_2020_Se.Pu_38_1102
PubMedID: 34213277

Title : Characterization and Genome Analysis of a Zearalenone-Degrading Bacillus velezensis Strain ANSB01E - Guo_2020_Curr.Microbiol_77_273
Author(s) : Guo Y , Zhou J , Tang Y , Ma Q , Zhang J , Ji C , Zhao L
Ref : Curr Microbiol , 77 :273 , 2020
Abstract : Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.
ESTHER : Guo_2020_Curr.Microbiol_77_273
PubMedSearch : Guo_2020_Curr.Microbiol_77_273
PubMedID: 31748861
Gene_locus related to this paper: 9baci-QBK11187

Title : Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines - Zhang_2020_J.Pharm.Anal_10_253
Author(s) : Zhang J , Wang D , Zou L , Xiao M , Zhang Y , Li Z , Yang L , Ge G , Zuo Z
Ref : J Pharm Anal , 10 :253 , 2020
Abstract : In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 activities in human blood and kidney should be considered. In summary, a selective and sensitive bioluminescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.
ESTHER : Zhang_2020_J.Pharm.Anal_10_253
PubMedSearch : Zhang_2020_J.Pharm.Anal_10_253
PubMedID: 32612872

Title : ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis - Liu_2020_Front.Cell.Dev.Biol_8_570
Author(s) : Liu G , Ruan Y , Zhang J , Wang X , Wu W , He P , Wang J , Xiong J , Cheng Y , Liu L , Yang Y , Tian Y , Jian R
Ref : Front Cell Developmental Biology , 8 :570 , 2020
Abstract : Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function.
ESTHER : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedSearch : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedID: 32733886
Gene_locus related to this paper: human-ABHD11

Title : Catalytic Hydrolysis Mechanism of Cocaine by Human Carboxylesterase 1: An Orthoester Intermediate Slows Down the Reaction - Yan_2019_Molecules_24_
Author(s) : Yan M , Zhang Z , Liu Z , Zhang C , Zhang J , Fan S , Yang Z
Ref : Molecules , 24 : , 2019
Abstract : Human carboxylesterase 1 (hCES1) is a major carboxylesterase in the human body and plays important roles in the metabolism of a wide variety of substances, including lipids and drugs, and therefore is attracting more and more attention from areas including lipid metabolism, pharmacokinetics, drug-drug interactions, and prodrug activation. In this work, we studied the catalytic hydrolysis mechanism of hCES1 by the quantum mechanics computation method, using cocaine as a model substrate. Our results support the four-step theory of the esterase catalytic hydrolysis mechanism, in which both the acylation stage and the deacylation stage include two transition states and a tetrahedral intermediate. The roles and cooperation of the catalytic triad, S221, H468, and E354, were also analyzed in this study. Moreover, orthoester intermediates were found in hCES1-catalyzed cocaine hydrolysis reaction, which significantly elevate the free energy barrier and slow down the reaction. Based on this finding, we propose that hCES1 substrates with beta-aminocarboxylester structure might form orthoester intermediates in hCES1-catalyzed hydrolysis, and therefore prolong their in vivo half-life. Thus, this study helps to clarify the catalytic mechanism of hCES1 and elucidates important details of its catalytic process, and furthermore, provides important insights into the metabolism of hCES1 substrates and drug designing.
ESTHER : Yan_2019_Molecules_24_
PubMedSearch : Yan_2019_Molecules_24_
PubMedID: 31717501
Gene_locus related to this paper: human-CES1

Title : Synthesis and biological evaluation of calycanthaceous alkaloid analogs - Zheng_2019_Bioorg.Med.Chem__115088
Author(s) : Zheng S , Zhu R , Zhou X , Chen L , Bai H , Zhang J
Ref : Bioorganic & Medicinal Chemistry , :115088 , 2019
Abstract : Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81microgmL(-1), respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63microgmL(-1). Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1ngmL(-1), respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4A. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
ESTHER : Zheng_2019_Bioorg.Med.Chem__115088
PubMedSearch : Zheng_2019_Bioorg.Med.Chem__115088
PubMedID: 31521458

Title : Role of esterase mediated hydrolysis of simvastatin in human and rat blood and its impact on pharmacokinetic profiles of simvastatin and its active metabolite in rat - Li_2019_J.Pharm.Biomed.Anal_168_13
Author(s) : Li Z , Zhang J , Zhang Y , Zuo Z
Ref : J Pharm Biomed Anal , 168 :13 , 2019
Abstract : Simvastatin is known as a pro-drug, which could be hydrolyzed by esterases to its active form, simvastatin acid. Although pharmacokinetics of simvastatin and simvastatin acid have been widely studied, hydrolysis of simvastatin to simvastatin acid during blood sampling and plasma preparation has been overlooked in the previous studies, leading to underestimation of simvastatin concentration and overestimation of simvastatin acid concentration in plasma. Since both efficacy and adverse drug reaction of simvastatin are highly dependent on simvastatin and simvastatin acid concentrations in vivo, accurate assessment of the two compounds are critical in their pharmacokinetic and pharmacodynamic studies. The current study was proposed aiming to investigate the esterase mediated hydrolysis of simvastatin in human and rat blood and its impact on the pharmacokinetic study of simvastatin and simvastatin acid. Using various esterase inhibitors including potassium florid (KF), bis(4-nitrophenyl) phosphate (BNPP), and ethylenediaminetetraacetic acid (EDTA), carboxylesterase was found to be the major esterase that hydrolyzed simvastatin in rat blood, while carboxylesterase and paraoxonase were the major esterases mediating the hydrolysis of simvastatin in human blood. Further studies using human recombinant enzymes identified simvastatin as substrates of PON1, CES1b, PON3 and CES1c with Clint of 8.75, 5.77, 3.93, and 2.45 muL/min/mg protein. Therefore, inhibition treatments with 20 mM BNPP and 50 mM KF/ 10 mM EDTA were developed to efficiently prevent the hydrolysis of simvastatin during blood sampling and plasma preparation in rat/human. The subsequent pharmacokinetics of orally administered simvastatin at 8.66 mg/kg in rats found that the Cmax and AUC0-infinity of simvastatin in absence of such esterase inhibitors in the blood sampling process were only 17.04 +/- 6.60% and 15.30 +/- 6.76% of those in presence of the inhibitors, whereas the Cmax and AUC0-infinity of simvastatin acid were 1.60 +/- 0.30 and 1.80 +/- 0.22 times of that obtained in presence of the inhibitors. Nevertheless, T1/2 of simvastatin and simvastatin acid remained the same regardless of the blood sampling method. Our current study for the first time demonstrated the importance for assessment of simvastatin stability during the blood sampling and plasma preparation process, which may be applicable to therapeutic drug monitoring of not only simvastatin but also other pro-drugs/compounds sharing similar metabolic properties.
ESTHER : Li_2019_J.Pharm.Biomed.Anal_168_13
PubMedSearch : Li_2019_J.Pharm.Biomed.Anal_168_13
PubMedID: 30776567

Title : Biodegradability and biodegradation pathway of di-(2-ethylhexyl) phthalate by Burkholderia pyrrocinia B1213 - Li_2019_Chemosphere_225_443
Author(s) : Li J , Zhang J , Yadav MP , Li X
Ref : Chemosphere , 225 :443 , 2019
Abstract : This study was conducted to investigate the biodegradation of di-(2-ethylhexyl) phthalate (DEHP) by Burkholderia pyrrocinia B1213. The results showed that DEHP at concentration of 500 mg/L in a mineral salt medium containing 1.0% yeast extract can be almost completely degraded (98.05%) by strain B1213. The optimal condition for DEHP degradation was pH 7.0, temperature 30 degreesC. Moreover, B1213 shows better degradation effect on long-chain PAEs, such as DEHP, which provides a great potential for its use in bioremediation of soils contaminated with PAEs. The kinetic studies showed that DEHP depletion curves fit well to the modified Gompertz model. The mono(2-ethylhexyl) phthalate (MEHP), mono-dibutyl phthalate (MBP), phthalic acid (PA) and 4-oxo-hexanoic acid were identified as the metabolites of DEHP by HPLC-ESI-QTOFMS. The detection of MBP and 4-oxo-hexanoic acid as intermediates prompted us to propose a novel and more complete DEHP biodegradation pathway compared to the classic pathway: DEHP is first degraded to MEHP by esterases, which is then converted to MBP through beta-oxidation. Then MBP is degraded to PA by esterases, which is then converted to protocatechuate (PCA) under aerobic conditions rapidly. PCA is ultimately cleaved to generate CO(2) and H(2)O via 4-oxo-hexanoic acid.
ESTHER : Li_2019_Chemosphere_225_443
PubMedSearch : Li_2019_Chemosphere_225_443
PubMedID: 30897469

Title : Cholinesterase inhibitory isoquinoline alkaloids from Corydalis mucronifera - Zhang_2019_Phytochemistry_159_199
Author(s) : Zhang J , Zhang C , Xu FC , Quesheng , Zhang QY , Tu PF , Liang H
Ref : Phytochemistry , 159 :199 , 2019
Abstract : Eight previously undescribed isoquinoline alkaloids, mucroniferanines H-M, together with 16 known isoquinoline alkaloids, were isolated from Corydalis mucronifera Maxim.. The structures of the previously undescribed compounds were elucidated by interpretation of 1D and 2D NMR spectroscopic and HRMS data, and their absolute configurations were established by computational electronic circular dichroism (ECD) calculations and X-ray diffraction data. Mucroniferanine L is reported as the first natural amide bond linked isoquinoline alkaloid dimer. The isolated compounds were evaluated for AChE and BuChE inhibitory activities and mucroniferanine H showed significant activities with IC50 values of 2.31muM and 36.71muM, respectively.
ESTHER : Zhang_2019_Phytochemistry_159_199
PubMedSearch : Zhang_2019_Phytochemistry_159_199
PubMedID: 30634082

Title : Improvement of the alkali stability of Penicillium cyclopium lipase by error-prone PCR, - Huang_2018_Electron.J.Biotechnol_39_91
Author(s) : Huang L , Zheng D , Zhao Y , Ma J , Li Y , Xu Z , Shan M , Shao S , Guo Q , Zhang J , Fuping Lu F , Yihan Liu Y
Ref : Electronic Journal of Biotechnology , 39 :91 , 2019
Abstract : Background Lipases are extensively exploited in lots of industrial fields; cold-adapted lipases with alkali-resistance are especially desired in detergent industry. Penicillium cyclopium lipase I (PCL) might be suitable for applications of detergent industry due to its high catalytic efficiency at low temperature and relatively good alkali stability. In this study, to better meet the requirements, the alkali stability of PCL was further improved via directed evolution with error-prone PCR. Results The mutant PCL (N157F) with an improved alkali stability was selected based on a high-throughput activity assay. After incubating at pH11.0 for 120min, N157F retained 70% of its initial activity, which was 23% higher than that of wild type PCL. Combined with the three-dimensional structure analysis, N157F exhibited an improved alkali stability under the high pH condition due to the interactions of hydrophilicity and -strand propensity. Conclusions This work provided the theoretical foundation and preliminary data for improving alkali stability of PCL to meet the industrial requirements, which is also beneficial to improving alkali-tolerance ability of other industrial enzymes via molecular modification. How to cite: Huang L, Zheng D, Zhao Y, et al. Improvement of the alkali stability of Penicillium cyclopium lipase by error-prone PCR.
ESTHER : Huang_2018_Electron.J.Biotechnol_39_91
PubMedSearch : Huang_2018_Electron.J.Biotechnol_39_91
PubMedID:
Gene_locus related to this paper: penex-Q9HFW6

Title : Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents - Xu_2019_ACS.Chem.Neurosci_10_482
Author(s) : Xu Y , Zhang J , Wang H , Mao F , Bao K , Liu W , Zhu J , Li X , Zhang H , Li J
Ref : ACS Chem Neurosci , 10 :482 , 2019
Abstract : Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC50 = 0.032 +/- 0.007 muM) and MAO-B (IC50 = 2.117 +/- 0.061 muM), along with the improved blood-brain barrier (BBB) permeability, antioxidant ability, and good copper chelating property in vitro. Animal studies showed that compound 1c.HCl could inhibit the cerebral AChE/MAO-B activities and alleviate scopolamine-induced cognitive impairment in mice. Combined with good oral bioavailability ( F = 45.55%), these findings demonstrated that compound 1c may be a potent brain permeable multifunctional candidate for the treatment of AD.
ESTHER : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedSearch : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedID: 30110536

Title : Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice - Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
Author(s) : Zhang J , Wang J , Zhou GS , Tan YJ , Tao HJ , Chen JQ , Pu ZJ , Ma JY , She W , Kang A , Zhu Y , Liu P , Zhu ZH , Shi XQ , Tang YP , Duan JA
Ref : Oxid Med Cell Longev , 2019 :8636835 , 2019
Abstract : Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer's disease (AD). The aim of the study was undertaken to investigate the antiamnesic effects of the two drugs alone and in combination through in vivo models of the Morris water maze along with in vitro antioxidants, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The potential mechanisms were speculated by the activities of acetylcholine (ACh), AChE, superoxide dismutase (SOD), and malondialdehyde (MDA) and the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine protein kinase B (TrkB). The combination group showed a concentration-dependent inhibition of cholinesterase and antioxidation. As far as its mechanism was concerned, the combination of two drugs exerted excellent effects on oxidative stress, cholinergic pathway damage, and inactivation of the BDNF-TrkB signaling pathway. Additionally, to elucidate the binding mechanism of GT active ingredients into the structure of AChE, the results of molecular docking studies indicated that hydrogen and/or hydrophobic bonds might play an important role in their binding process. Thus, the combination of drugs could treat AD perfectly and further verify the scientific rationality of clinical medication.
ESTHER : Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
PubMedSearch : Zhang_2019_Oxid.Med.Cell.Longev_2019_8636835
PubMedID: 30911351

Title : Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation - Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
Author(s) : Gan L , Guo M , Si J , Zhang J , Liu Z , Zhao J , Wang F , Yan J , Li H , Zhang H
Ref : Artif Cells Nanomed Biotechnol , 47 :4202 , 2019
Abstract : Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 muM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.
ESTHER : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedSearch : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedID: 31713449

Title : The Structures and Bioactivities of Fatty Acid Synthase Inhibitors - Jiang_2019_Curr.Med.Chem_26_7081
Author(s) : Jiang H , Gan T , Zhang J , Ma Q , Liang Y , Zhao Y
Ref : Curr Med Chem , 26 :7081 , 2019
Abstract : BACKGROUND: Fatty Acid Synthase (FAS or FASN) is a vital enzyme which catalyzes the de novo synthesis of long chain fatty acids. A number of studies have recently been reported that FAS was combined targets for the discovery of anti-obesity and anti-cancer drugs. Great interest has been developed in finding novel FAS inhibitors, and result in more than 200 inhibitors being reported. METHODS: The reported research literature about the FAS inhibitors was collected and analyzedsised through major databases including Web of Science, and PubMed. Then the chemical stractures, FAS inhibitory activities, and Structure-Activity Relationships (SAR) were summarized focused on all these reported FAS inhibitors. RESULTS: The 248 FAS inhibitors, which were reported during the past 20 years, could be divided into thiolactone, butyrolactone and butyrolactam, polyphenols, alkaloids, terpenoids, and other structures, in view of their structure characteristics. And the SAR of high inhibitory structures of each type was proposed in this paper. CONCLUSION: A series of synthetic quinolinone derivatives show strongest inhibitory activity in the reported FAS inhibitors. Natural polyphenols, existing in food and herbs, show more adaptive in medicine exploration because of their safety and efficiency. Moreover, screening the FAS inhibitors from microorganism and marine natural products could be the hot research directions in the future.
ESTHER : Jiang_2019_Curr.Med.Chem_26_7081
PubMedSearch : Jiang_2019_Curr.Med.Chem_26_7081
PubMedID: 31538883

Title : Rational design of a Yarrowia lipolytica derived lipase for improved thermostability - Zhang_2019_Int.J.Biol.Macromol_137_1190
Author(s) : Zhang H , Sang J , Zhang Y , Sun T , Liu H , Yue R , Zhang J , Wang H , Dai Y , Lu F , Liu F
Ref : Int J Biol Macromol , 137 :1190 , 2019
Abstract : To improve the thermostability of the lipase LIP2 from Yarrowia lipolytica, molecular dynamics (MD) simulations at various temperatures were used to investigate the common fluctuation sites of the protein, which are considered to be thermally weak points. Two of these residues were selected for mutations to improve the enzyme's thermostability, and the variants predicted by MD simulations to have improved thermostability were expressed in Pichia pastoris GS115 for further investigations. According to the proline rule, the high fluctuation site S115 or V213 was replaced with proline residue, the two lipase mutants S115P and V213P were obtained. The mutant V213P exhibited evidently enhanced thermostability with an approximately 70% longer half-life at 50 degrees C than that of the parent LIP2 expressed in P. pastoris. The temperature optimum of V213P was 42 degrees C, which was about 5.0 degrees C higher than that of the parent LIP2, while its specific catalytic activity was comparable to that of the parent and reached 876.5U/mg. The improved thermostability of V213P together with its high catalytic efficiency indicated that the rational design strategy employed here can be efficiently applied for structure optimization of industrially important enzymes.
ESTHER : Zhang_2019_Int.J.Biol.Macromol_137_1190
PubMedSearch : Zhang_2019_Int.J.Biol.Macromol_137_1190
PubMedID: 31299254
Gene_locus related to this paper: yarli-lip2

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 : Preventive Effects of Different Fermentation Times of Shuidouchi on Diphenoxylate-Induced Constipation in Mice - Chen_2019_Foods_8_
Author(s) : Chen L , Zhang J , Suo H , Wang W , Wang H , Zhang Y , Hu Q , Zhao X , Li J
Ref : Foods , 8 : , 2019
Abstract : This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product. By improving its processing technology, it can incur better biological activity and become a health food. The Shuidouchi-treated mice were evaluated using constipation-related kits, quantitative polymerase chain reaction (qPCR), and Western blot assays. After the mice were fed 72-h-fermented Shuidouchi (72-SDC) for 9 d, the defecation time to excrete the first black stool was lower than that of the control and 24-SDC and 48-SDC groups, but was much higher than that of the normal group. The gastrointestinal (GI) transit of the small intestine of the 72-SDC group was higher than that of the control and the 24-SDC and 48-SDC groups, but lower that of the normal group. Meanwhile, 72-SDC could significantly increase the levels of ghrelin, endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE) in the serum of constipated mice compared to the levels in mice in the control group. Moreover, 72-SDC could raise c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GNDF), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression levels, and reduce transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels in small-intestinal tissue compared to the levels in the control group. Meanwhile, 72-SDC also raised ghrelin mRNA expression in gastric tissue and transient receptor potential ankyrin 1 (TRPA1) mRNA expression in colon tissue compared to the control group mice; these effects were stronger than those of 24-SDC and 48-SDC. Shuidouchi has good preventative effects on constipation and performs best when fermented for at least 72 h.
ESTHER : Chen_2019_Foods_8_
PubMedSearch : Chen_2019_Foods_8_
PubMedID: 30832248

Title : Linarin improves the dyskinesia recovery in Alzheimer's disease zebrafish by inhibiting the acetylcholinesterase activity - Pan_2019_Life.Sci_222_112
Author(s) : Pan H , Zhang J , Wang Y , Cui K , Cao Y , Wang L , Wu Y
Ref : Life Sciences , 222 :112 , 2019
Abstract : BACKGROUND: Due to complex pathogenesis of Alzheimer's disease (AD), currently there is no effective disease-modifying treatment. Acetylcholinesterase (AChE) has introduced itself as an important target for AD therapy. Linarin as the representative active ingredient of flavonoid glycoside in Flos chrysanthemi indici has been found to have anti-acetylcholinesterase effect. AIMS: The present study intended to explore the potential effect of linarin for treatment of AD. MAIN METHODS: In this study, molecular docking simulation was used to evaluate whether linarin could dock with AChE and decipher the mechanism of linarin as an AChE inhibitor. After molecular docking simulation, AlCl3-induced Alzheimer's disease zebrafish model was established. Effects of linarin on treating AD zebrafish dyskinesia and AChE inhibition were compared with donepezil (DPZ) which was used as a positive control drug. KEY FINDINGS: Molecular docking simulation showed that linarin plays a critical role in AChE inhibition by binding AChE active sites. The experiments illustrated that the dyskinesia recovery rate of AD zebrafish could be significantly improved by linarin. The dyskinesia recovery and AChE inhibition rate were 88.0% and 74.5% respectively, while those of DPZ were 79.3% and 43.6%. SIGNIFICANCE: These findings provide evidences for supporting linarin to be developed into an AD drug by inhibiting the activity of AChE.
ESTHER : Pan_2019_Life.Sci_222_112
PubMedSearch : Pan_2019_Life.Sci_222_112
PubMedID: 30802512

Title : Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice - Yi_2019_J.Med.Food_22_1208
Author(s) : Yi R , Peng P , Zhang J , Du M , Lan L , Qian Y , Zhou J , Zhao X
Ref : J Med Food , 22 :1208 , 2019
Abstract : This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.
ESTHER : Yi_2019_J.Med.Food_22_1208
PubMedSearch : Yi_2019_J.Med.Food_22_1208
PubMedID: 31621475

Title : Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis - Li_2019_Eur.J.Neurol_26_1296
Author(s) : Li M , Han J , Zhang Y , Lv J , Zhang J , Zhao X , Ren L , Fang H , Yang J , Cui X , Zhang Q , Li Q , Du Y , Gao F
Ref : Eur Journal of Neurology , 26 :1296 , 2019
Abstract : BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved.
ESTHER : Li_2019_Eur.J.Neurol_26_1296
PubMedSearch : Li_2019_Eur.J.Neurol_26_1296
PubMedID: 31050101

Title : Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo - Guo_2019_Bioorg.Chem_92_103258
Author(s) : Guo E , Hu Y , Du T , Zhu H , Chen L , Qu W , Zhang J , Xie N , Liu W , Feng F , Xu J
Ref : Bioorg Chem , 92 :103258 , 2019
Abstract : Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Abeta25-35-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-beta peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Abeta1-42 deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six beta-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four beta-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE).
ESTHER : Guo_2019_Bioorg.Chem_92_103258
PubMedSearch : Guo_2019_Bioorg.Chem_92_103258
PubMedID: 31520892

Title : Aster glehni Extract Ameliorates Scopolamine-Induced Cognitive Impairment in Mice - Liao_2019_J.Med.Food_22_685
Author(s) : Liao Y , Bae HJ , Park JH , Zhang J , Koo B , Lim MK , Han EH , Lee SH , Jung SY , Lew JH , Ryu JH
Ref : J Med Food , 22 :685 , 2019
Abstract : The leaves of Aster glehni Fr. Schm. (Asteraceae) have been used to treat insomnia in Korea. Insomnia is a common adverse effect of therapeutic agents for Alzheimer's disease (AD), and the control of sleep disturbance may prevent dementia. We hypothesized that the leaves of A. glehni can attenuate cognitive dysfunctions observed in AD. We observed the ameliorating effects of the ethanolic extract of leaves of A. glehni (AG-D) on memory dysfunction through the Morris water maze test, the passive avoidance test, and the Y-maze test. We performed acetylcholinesterase (AChE) activity assay and Western blotting to determine the mechanism of action of AG-D. AG-D significantly attenuated memory dysfunction observed in the above behavior studies and inhibited the activity of AChE. AG-D also increased the levels of phosphorylation extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase 3beta (GSK-3beta) and the expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampi. These results suggest that AG-D ameliorates memory impairments by AChE inhibition and activation of ERK-CREB-BDNF and PI3K-Akt-GSK-3beta signaling pathways. Taken together, this study suggests that AG-D could be used as a potential treatment for cognitive dysfunction.
ESTHER : Liao_2019_J.Med.Food_22_685
PubMedSearch : Liao_2019_J.Med.Food_22_685
PubMedID: 31225769

Title : Single and joint oxidative stress-related toxicity of sediment-associated cadmium and lead on Bellamya aeruginosa - Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
Author(s) : Liu X , Chen Q , Ali N , Zhang J , Wang M , Wang Z
Ref : Environ Sci Pollut Res Int , 26 :24695 , 2019
Abstract : The biotoxicity of heavy metals in sediments toward benthic organisms has evoked great concern for the health of freshwater ecosystems. This study applied a sediment toxicity testing protocol to investigate the single and joint toxicity of cadmium (Cd) and lead (Pb) on Bellamya aeruginosa. B. aeruginosa were exposed to different concentrations of Cd (5, 25, and 100 mg/kg), Pb (20, 100, and 400 mg/kg), and their different concentration combinations. A suite of biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), metallothionein (MT), malondialdehyde (MDA), and acetylcholinesterase (AChE), were measured after 7, 14, 21, and 28 days of exposure to evaluate their oxidative stress status. Cell apoptosis of soft tissue was also determined after exposure. Results revealed that these endpoints represented sensitive biomarkers for the characterization of the oxidative stress response induced by these metals. Specifically, a decrease of SOD and GPx and an increase of MDA were indicative of the potential failure of the antioxidant defense system in neutralizing the reactive oxygen species (ROS) generated in the exposure of the Pb-treated group. The integrated biomarker response (IBR) index revealed the most significant sub-lethal toxicity for Pb-spiked sediments, leading to the highest rate of cell apoptosis (70.8%). Exposure to Cd resulted in a time- and dose-dependent effect on MT levels, which suggested active detoxification of this metal. Exposure to the mixture resulted in amelioration of Pb toxicity, likely due to the competitive binding of Cd to active enzyme, with the result of an observed antagonistic interaction. This study indicated that B. aeruginosa represents a good biomonitor for assessing Cd and Pb contamination of sediments, and laid the foundation for their potential risk assessments in freshwater ecosystems.
ESTHER : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedSearch : Liu_2019_Environ.Sci.Pollut.Res.Int_26_24695
PubMedID: 31240645

Title : Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer's Disease - Ma_2019_Front.Neurosci_13_1400
Author(s) : Ma X , Sun Z , Han X , Li S , Jiang X , Chen S , Zhang J , Lu H
Ref : Front Neurosci , 13 :1400 , 2019
Abstract : Background: Alzheimer's disease (AD) and diabetes mellitus (DM) often coexist in patients because having one of these conditions increases risk for the other. These two diseases share several pathophysiological mechanisms, such as specific inflammatory signaling pathways, oxidative stress, and cell apoptosis. It is still unclear exactly which mechanisms associated with DM are responsible for increased AD risk. Studies have found that even transient elevation of brain Abeta levels can allow T2DM to slightly disrupt the neural milieu in a way that encourages pathologies associated with the onset of memory deficits and AD. A recent study argues that a potential common pathogenetic mechanism underlying both DM and AD is evidenced by the cooccurrence of amyloid brain legions and deposits containing both tau and Abeta in pancreatic beta cells. Given these links, an investigation detailing disease mechanisms as well as treatment options for patients with cooccurring DM and AD is urgently needed. The biological effects of resveratrol relevant to DM and AD treatment include its abilities to modulate oxidative stress and reduce inflammation. A rat model of DM and concomitant AD was created for this study using intraperitoneal injection of streptozotocin and hippocampal injection of Abeta1-40 to characterize resveratrol's potential protective action. Results: Resveratrol significantly increased the Sirt1 expression, inhibited the memory impairment, the increased acetylcholinesterase, malondialdehyde, interleukin-1beta and interleukin 6 levels, and the decreased levels of choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione in this rat model of diabetes and concomitant AD. The Sirt 1 inhibitor EX527 partially reversed the effects of resveratrol. Conclusion: This study suggests that resveratrol may have a neuroprotective action through activation of Sirt1 signaling in diabetes and AD with concurrent onset.
ESTHER : Ma_2019_Front.Neurosci_13_1400
PubMedSearch : Ma_2019_Front.Neurosci_13_1400
PubMedID: 32038127

Title : Development of a long-acting Fc-fused cocaine hydrolase with improved yield of protein expression - Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
Author(s) : Chen X , Deng J , Zheng X , Zhang J , Zhou Z , Wei H , Zhan CG , Zheng F
Ref : Chemico-Biological Interactions , 306 :89 , 2019
Abstract : Human butyrylcholinesterase (BChE) is known as a safe and effective protein for detoxification of organophosphorus (OP) nerve agents. Its rationally designed mutants with considerably improved catalytic activity against cocaine, known as cocaine hydrolases (CocHs), are recognized as the most promising drug candidates for the treatment of cocaine abuse. However, it is a grand challenge to efficiently produce active recombinant BChE and CocHs with a sufficiently long biological half-life. In the present study, starting from a promising CocH, known as CocH3 (i.e. A199S/F227A/S287G/A328W/Y332G mutant of human BChE), which has a approximately 2000-fold improved catalytic activity against cocaine compared to wild-type BChE, we designed an N-terminal fusion protein, Fc(M3)-(PAPAP)2-CocH3, which was constructed by fusing Fc of human IgG1 to the N-terminal of CocH3 and further optimized by inserting a linker between the two protein domains. Without lowering the enzyme activity, Fc(M3)-(PAPAP)2-CocH3 expressed in Chinese hamster ovary (CHO) cells has not only a long biological half-life of 105+/-7h in rats, but also a high yield of protein expression. Particularly, Fc(M3)-(PAPAP)2-CocH3 has a approximately 21-fold increased protein expression yield in CHO cells compared to CocH3 under the same experimental conditions. Given the observations that Fc(M3)-(PAPAP)2-CocH3 has not only a high catalytic activity against cocaine and a long biological half-life, but also a high yield of protein expression, this new protein entity reported in this study would be a more promising candidate for therapeutic treatment of cocaine overdose and addiction.
ESTHER : Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
PubMedSearch : Chen_2019_Chem.Biol.Interact_13ChEPon_306_89
PubMedID: 30986387

Title : Highly Selective Synthesis of Monolaurin via Enzymatic Transesterification under Batch and Continuous Flow Conditions - Chen_2019_J.Oleo.Sci_68_1125
Author(s) : Chen F , Zhang G , Liu C , Zhang J , Zhao F , Xu B
Ref : J Oleo Sci , 68 :1125 , 2019
Abstract : This study aimed to investigate the highly selective production of monolaurin via enzymatic transesterification of methyl laurate and glycerol. It was determined that a binary solvent system (tert-butanol/iso-propanol, 20:80, wt./wt.) was suitable for the enzymatic production of monolaurin, especially in the continuous process. The highest mass fraction of monolaurin in the product mixture (80.8 wt.%) was achieved in a batch mode under the following conditions: a methyl laurate-to-glycerol molar ratio of 1:6, a substrate concentration (methyl laurate in the binary solvent) of 15 wt.%, an enzyme dosage of 6 wt.% of the amount of methyl laurate, and a reaction time of 1.5 h at 50 degC. Compared with the results under the batch conditions, a slightly higher yield of monolaurin (82.5 +/- 2.5 wt.%) was obtained in a continuous flow system at a flow rate of 0.1 mL/min, while the mass fraction of dilaurin in the product mixture was only 0.7 +/- 0.6 wt.%. In addition, the yield of monolaurin remained almost unchanged during the 18 tested days of the continuous experiment.
ESTHER : Chen_2019_J.Oleo.Sci_68_1125
PubMedSearch : Chen_2019_J.Oleo.Sci_68_1125
PubMedID: 31611516

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 : Ambient temperature-mediated enzymic activities and intestinal microflora in Lymantria dispar larvae - Zeng_2019_Arch.Insect.Biochem.Physiol__e21597
Author(s) : Zeng J , Shi Z , Shi J , Guo J , Zhang G , Zhang J
Ref : Archives of Insect Biochemistry & Physiology , :e21597 , 2019
Abstract : To understand how ambient temperature affect the gypsy moth larvae, and provide a theoretical basis for pest control in different environments. Fourth instar gypsy moth larvae were incubating for 3 hr at 15, 20, 25, 30, 35, and 40, respectively. Afterward, digestive and antioxidant enzyme activities, total antioxidant capacity, and intestinal microflora community were analyzed to reveal how the caterpillars respond to ambient temperature stress. Results showed that both digestive and antioxidant enzymes were regulated by the ambient temperature. The optimum incubation temperatures of protease, amylase, trehalase, and lipase in gypsy moth larvae were 30, 25, and 20, respectively. When the incubation temperature was deviated optimum temperatures, digestive enzyme activities would be downregulated depending on the extent of temperature stress. In addition, glutathione S-transferase, peroxidase, catalase, and polyphenol oxidase would be activated under a sufferable temperature stress, but superoxide dismutase and carboxylesterase (CarE) would be inhibited. In addition, results showed that the top two abundant phyla were Proteobacteria and Firmicutes. The phylum Firmicutes abundance was decreased and phylum Proteobacteria abundance was increased by ambient temperature stress. Moreover, it suggested that gypsy moth caterpillars at different ambient temperature mainly differed from each other by Escherichia-Shigella and Bifidobacterium in control, Acinetobacter in T15, and Lactobacillus in T40, respectively.
ESTHER : Zeng_2019_Arch.Insect.Biochem.Physiol__e21597
PubMedSearch : Zeng_2019_Arch.Insect.Biochem.Physiol__e21597
PubMedID: 31328829

Title : Whole Genome Sequencing and Analysis of Chlorimuron-Ethyl Degrading Bacteria Klebsiella pneumoniae 2N3 - Zhang_2019_Int.J.Mol.Sci_20_
Author(s) : Zhang C , Hao Q , Zhang Z , Zhang X , Pan H , Zhang J , Zhang H , Sun F
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Klebsiella pneumoniae 2N3 is a strain of gram-negative bacteria that can degrade chlorimuron-ethyl and grow with chlorimuron-ethyl as the sole nitrogen source. The complete genome of Klebsiella pneumoniae 2N3 was sequenced using third generation high-throughput DNA sequencing technology. The genomic size of strain 2N3 was 5.32 Mb with a GC content of 57.33% and a total of 5156 coding genes and 112 non-coding RNAs predicted. Two hydrolases expressed by open reading frames (ORFs) 0934 and 0492 were predicted and experimentally confirmed by gene knockout to be involved in the degradation of chlorimuron-ethyl. Strains of DeltaORF 0934, DeltaORF 0492, and wild type (WT) reached their highest growth rates after 8-10 hours in incubation. The degradation rates of chlorimuron-ethyl by both DeltaORF 0934 and DeltaORF 0492 decreased in comparison to the WT during the first 8 hours in culture by 25.60% and 24.74%, respectively, while strains DeltaORF 0934, DeltaORF 0492, and the WT reached the highest degradation rates of chlorimuron-ethyl in 36 hours of 74.56%, 90.53%, and 95.06%, respectively. This study provides scientific evidence to support the application of Klebsiella pneumoniae 2N3 in bioremediation to control environmental pollution.
ESTHER : Zhang_2019_Int.J.Mol.Sci_20_
PubMedSearch : Zhang_2019_Int.J.Mol.Sci_20_
PubMedID: 31234527
Gene_locus related to this paper: klep7-a6tb98 , klep7-mhpc

Title : Pharmacological Effects of Verticine: Current Status - Yin_2019_Evid.Based.Complement.Alternat.Med_2019_2394605
Author(s) : Yin Z , Zhang J , Guo Q , Chen L , Zhang W , Kang W
Ref : Evid Based Complement Alternat Med , 2019 :2394605 , 2019
Abstract : Verticine is the major bioactive constituent of Fritillaria as a kind of Traditional Chinese Medicine. Pharmacological researches have reported various benefits of verticine, including anticancer, anti-inflammatory, protecting against acute lung injury, tracheobronchial relaxation, antitussive, expectorant, sedative, and analgesic activities, in addition to inhibiting proliferation of cultured orbital fibroblast, angiotensin converting enzyme (ACE), and acetylcholinesterase (AChE) and inhibiting hERG potassium channels. The underlying mechanisms of verticine are still under investigation. This review will comprehensively summarize the metabolism, biological activities, and possible mechanism of verticine.
ESTHER : Yin_2019_Evid.Based.Complement.Alternat.Med_2019_2394605
PubMedSearch : Yin_2019_Evid.Based.Complement.Alternat.Med_2019_2394605
PubMedID: 30956677

Title : Synthesis and evaluation of coumarin\/1,2,4-oxadiazole hybrids as selective BChE inhibitors with neuroprotective activity - Zhang_2018_J.Asian.Nat.Prod.Res__1
Author(s) : Zhang J , Li JC , Song JL , Cheng ZQ , Sun JZ , Jiang CS
Ref : J Asian Nat Prod Res , :1 , 2018
Abstract : A series of new coumarin/1,2,4-oxadiazole hybrids were synthesized and evaluated for cholinesterase inhibitory and neuroprotective activities. Among them, enantiomers 5u and 5v showed potent hBChE inhibitory activity with IC50 values of 8.17 and 9.56 muM, respectively, and also exhibited good selectivity for hBChE over hAChE by 9.49- and 7.58-fold, respectively. In addition, both compounds could protect SH-SY5Y cells against Abeta25-35-induced neurotoxicity. The preliminary bioassay results provided a new chemotype for multifunctional anti-Alzheimer's disease agents and continuing investigation into compounds 5u and 5v is warranted.
ESTHER : Zhang_2018_J.Asian.Nat.Prod.Res__1
PubMedSearch : Zhang_2018_J.Asian.Nat.Prod.Res__1
PubMedID: 29991292

Title : Antioxidative status, immunological responses, and heat shock protein expression in hepatopancreas of Chinese mitten crab, Eriocheir sinensis under the exposure of glyphosate - Hong_2018_Fish.Shellfish.Immunol_86_840
Author(s) : Hong Y , Huang Y , Yan G , Pan C , Zhang J
Ref : Fish Shellfish Immunol , 86 :840 , 2018
Abstract : As a broad-spectrum herbicide, glyphosate was extensively utilised in China for several decades. The contradiction between glyphosate spraying and crab breeding in the rice-crab co-culture system has become more obvious. In this study, the antioxidative status and immunological responses of Chinese mitten crab, Eriocheir sinensis, under sublethal exposure of glyphosate were investigated by detecting the antioxidative and immune-related enzyme activity, acetylcholinesterase (AChE) activity and relative mRNA expression of heat shock proteins (HSPs) in hepatopancreas. The results showed that high concentrations of glyphosate (44 and 98mg/L) could induce significant alteration of superoxide dismutase (SOD), peroxidase (POD), acid phosphatase (ACP), alkaline phosphatase (AKP), and phenoloxidase (PO) activities by first rising then falling during the exposure. However, AChE activity in all treatments including 4.4mg/L was inhibited markedly after 6h of exposure. In addition, the relative mRNA expression of HSP 60, HSP 70, and HSP 90 was significantly upregulated at both 48h and 96h. These results revealed that glyphosate has a prominent toxic effect on E. sinensis based on antioxidative and immunological response inhibition and AChE activity reduction even at the lowest concentration of 4.4mg/L, and a protective response by upregulation of HSPs was carried out by the species to ease the environmental stress.
ESTHER : Hong_2018_Fish.Shellfish.Immunol_86_840
PubMedSearch : Hong_2018_Fish.Shellfish.Immunol_86_840
PubMedID: 30572127

Title : The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study - Liu_2018_Lancet.Neurol_17_309
Author(s) : Liu SY , Wile DJ , Fu JF , Valerio J , Shahinfard E , McCormick S , Mabrouk R , Vafai N , McKenzie J , Neilson N , Perez-Soriano A , Arena JE , Cherkasova M , Chan P , Zhang J , Zabetian CP , Aasly JO , Wszolek ZK , McKeown MJ , Adam MJ , Ruth TJ , Schulzer M , Sossi V , Stoessl AJ
Ref : Lancet Neurol , 17 :309 , 2018
Abstract : BACKGROUND: Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. METHODS: Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N-(11)C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. FINDINGS: We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0.009, default mode network-related regions p=0.006, limbic network-related regions p=0.020) and the thalamus (p=0.008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0.046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0.043, default mode network-related regions p=0.021) and the thalamus (thalamus p=0.004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. INTERPRETATION: LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. FUNDING: Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.
ESTHER : Liu_2018_Lancet.Neurol_17_309
PubMedSearch : Liu_2018_Lancet.Neurol_17_309
PubMedID: 29456161

Title : Preventive Effect of Lactobacillus fermentum CQPC03 on Activated Carbon-Induced Constipation in ICR Mice - Zhang_2018_Medicina.(Kaunas)_54_
Author(s) : Zhang J , Chen B , Liu B , Zhou X , Mu J , Wang Q , Zhao X , Yang Z
Ref : Medicina (Kaunas) , 54 : , 2018
Abstract : Background and objectives: Paocai (pickled cabbage), which is fermented by lactic acid bacteria, is a traditional Chinese food. The microorganisms of Paocai were isolated and identified, and the constipation inhibition effect of one of the isolated Lactobacillus was investigated. Materials and Methods: The 16S rDNA technology was used for microbial identification. A mouse constipation model was established using activated carbon. After intragastric administration of Lactobacillus (10(8) CFU/mL), the mice were dissected to prepare pathological sections of the small intestine. Serum indicators were detected using kits, and the expression of small intestine-related mRNAs was detected by qPCR assay. Results: One strain of Lactobacillus was identified and named Lactobacillus fermentum CQPC03 (LF-CQPC03). Body weight and activated carbon propulsion rate were all higher in mice intragastrically administered with LF-CQPC03 compared with the control group, while the time to the first black stool in treated mice was lower than that in the control group. Serum assays showed that gastrin (Gas), endothelin (ET), and acetylcholinesterase (AchE) levels were significantly higher in the LF-CQPC03-treated mice than in the control group, while somatostatin (SS) levels were significantly lower than in the control mice. Mouse small intestine tissue showed that c-Kit, stem cell factor (SCF), and glial cell-derived neurotrophic factor (GDNF) mRNA expression levels were significantly higher in the LF-CQPC03 treated mice than in control mice, while transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels were significantly lower in the LF-CQPC03 treated mice than in control mice. Conclusions: There is a better effect with high-dose LF-CQPC03, compared to the lower dose (LF-CQPC03-L), showing good probiotic potential, as well as development and application value.
ESTHER : Zhang_2018_Medicina.(Kaunas)_54_
PubMedSearch : Zhang_2018_Medicina.(Kaunas)_54_
PubMedID: 30463207

Title : VHL and Hypoxia Signaling: Beyond HIF in Cancer - Zhang_2018_Biomedicines_6_
Author(s) : Zhang J , Zhang Q
Ref : Biomedicines , 6 : , 2018
Abstract : Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor alpha (including HIF1alpha and HIF2alpha) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-kappaB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.
ESTHER : Zhang_2018_Biomedicines_6_
PubMedSearch : Zhang_2018_Biomedicines_6_
PubMedID: 29562667

Title : Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) - Ni_2018_ACS.Chem.Neurosci_9_1625
Author(s) : Ni W , Wang H , Li X , Zheng X , Wang M , Zhang J , Gong Q , Ling D , Mao F , Zhang H , Li J
Ref : ACS Chem Neurosci , 9 :1625 , 2018
Abstract : On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven this method was feasible in AD mouse models. In this study, our work focused on exploring alternative novel tadalafil derivatives (3a-s). Among the 19 analogues, compound 3c exhibited good selective dual-target AChE/PDE5 inhibition and good blood-brain barrier (BBB) permeability. Moreover, its citrate (3c.Cit) possessed improved water solubility and good effects against scopolamine-induced cognitive impairment with inhibition of cortical AChE activities and enhancement of cAMP response element-binding protein (CREB) phosphorylation ex vivo.
ESTHER : Ni_2018_ACS.Chem.Neurosci_9_1625
PubMedSearch : Ni_2018_ACS.Chem.Neurosci_9_1625
PubMedID: 29616790

Title : Molecular-docking-guided design and synthesis of new IAA-tacrine hybrids as multifunctional AChE\/BChE inhibitors - Cheng_2018_Bioorg.Chem_83_277
Author(s) : Cheng ZQ , Zhu KK , Zhang J , Song JL , Muehlmann LA , Jiang CS , Liu CL , Zhang H
Ref : Bioorg Chem , 83 :277 , 2018
Abstract : A series of new indole-3-acetic acid (IAA)-tacrine hybrids as dual acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitors were designed and prepared based on the molecular docking mode of AChE with an IAA derivative (1a), a moderate AChE inhibitor identified by screening our compound library for anti-Alzheimer's disease (AD) drug leads. The enzyme assay results revealed that some hybrids, e.g. 5d and 5e, displayed potent dual in vitro inhibitory activities against AChE/BChE with IC50 values in low nanomolar range. Molecular modeling studies in tandem with kinetic analysis suggest that these hybrids target both catalytic active site and peripheral anionic site of cholinesterase (ChE). Molecular dynamic simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations indicate that 5e has more potent binding affinity than hit 1a, which may explain the stronger inhibitory effect of 5e on AChE. Furthermore, their predicted pharmacokinetic properties and in vitro influences on mouse brain neural network electrical activity were discussed. Taken together, compound 5e can be highlighted as a lead compound worthy of further optimization for designing new anti-AD drugs.
ESTHER : Cheng_2018_Bioorg.Chem_83_277
PubMedSearch : Cheng_2018_Bioorg.Chem_83_277
PubMedID: 30391700

Title : Design, synthesis and biological evaluation of tricyclic pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one scaffolds as selective BuChE inhibitors - Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
Author(s) : Qiu GL , He SS , Chen SC , Li B , Wu HH , Zhang J , Tang WJ
Ref : J Enzyme Inhib Med Chem , 33 :1506 , 2018
Abstract : Based on the structural analysis of tricyclic scaffolds as butyrylcholinesterase (BuChE) inhibitors, a series of pyrazolo[1,5-c][1,3]benzoxazin-5(5H)-one derivatives were designed, synthesized and evaluated for their acetylcholinesterase (AChE) and BuChE inhibitory activity. Compounds with 5-carbonyl and 7- or/and 9-halogen substitutions showed potential BuChE inhibitory activity, among which compounds 6a, 6c and 6g showed the best BuChE inhibition (IC50 = 1.06, 1.63 and 1.63 microM, respectively). The structure-activity relationship showed that the 5-carbonyl and halogen substituents significantly influenced BuChE activity. Compounds 6a and 6g were found nontoxic, lipophilic and exhibited remarkable neuroprotective activity and mixed-type inhibition against BuChE (Ki = 7.46 and 3.09 microM, respectively). Docking studies revealed that compound 6a can be accommodated into BuChE via five hydrogen bonds, one Pi-Sigma interaction and three Pi-Alkyl interactions.
ESTHER : Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
PubMedSearch : Qiu_2018_J.Enzyme.Inhib.Med.Chem_33_1506
PubMedID: 30284486

Title : Detoxification of diphenyl ether herbicide lactofen by Bacillus sp. Za and enantioselective characteristics of an esterase gene lacE - Zhang_2018_J.Hazard.Mater_341_336
Author(s) : Zhang J , Lu L , Chen F , Chen L , Yin J , Huang X
Ref : J Hazard Mater , 341 :336 , 2018
Abstract : A bacterial strain Za capable of degrading diphenyl ether herbicide lactofen was isolated and identified as Bacillus sp. This strain could degrade 94.8% of 50mgL-1 lactofen after 4days of inoculation in flasks. It was revealed that lactofen was initially hydrolyzed to desethyl lactofen, which was further transformed to acifluorfen, followed by the reduction of the nitro group to yield aminoacifluorfen. The phytotoxicity of the transformed product aminoacifluorfen to maize was decreased significantly compared with the lactofen. A gene lacE, encoding an esterase responsible for lactofen hydrolysis to desethyl lactofen and acifluorfen continuously, was cloned from Bacillus sp. Za. The deduced amino acid belonging to the esterase family VII contained a typical Ser-His-Asp/Glu catalytic triad and the conserved motifs GXSXG. The purified recombinant protein LacE displayed maximal esterase activity at 40 degrees C and pH 7.0. Additionally, LacE had broad substrate specificity and was capable of hydrolyzing p-nitrophenyl esters. The enantioselectivity of LacE during lactofen degradation was further studied, and the results indicated that the (S)-(+)-lactofen was degraded faster than the (R)-(-)-lactofen, which could illustrate the reported phenomenon that (S)-(+)-lactofen was preferentially degraded in soil and sediment.
ESTHER : Zhang_2018_J.Hazard.Mater_341_336
PubMedSearch : Zhang_2018_J.Hazard.Mater_341_336
PubMedID: 28802244
Gene_locus related to this paper: bacsu-pnbae

Title : IL-6 release of Rv0183 antigen-stimulated whole blood is a potential biomarker for active tuberculosis patients - Liu_2018_J.Infect_76_376
Author(s) : Liu Y , Li X , Liu W , Zhong Z , Wang L , Ge S , Zhang J , Xia N
Ref : J Infect , 76 :376 , 2018
Abstract : OBJECTIVE: New tests for diagnosing active tuberculosis (aTB) are urgently needed, and TB antigen-specific cell-mediated immunity can be expected to develop new testing methods of aTB. MATERIALS AND METHODS: Rv0183 protein, the only monoglyceride lipase identified in mycobacteria, was used to stimulate freshly heparin-treated whole blood. The Rv0183-specific cytokines/chemokines response associated with aTB was screened firstly with 4 aTB patients and 4 LTBIs, and further evaluated in 192 suspected aTB patients and 372 healthy individuals. RESULTS: Out of 71 cytokines/chemokines, the response of IL-6 against Rv0183 protein was found to be associated with aTB. The Rv0183-specific IL-6 response was significantly higher in aTB patients (n = 128) than in those with non-TB lung disease (n = 64) and in healthy individuals (n = 327) (p < 0.0001), and not affected by latent TB infection. In IGRA+ suspected active TB patients, the sensitivity, specificity, PPV and NPV of IL-6 response (with cutoff of 235.2 pg/ml) were 85.7%, 100%, 100% and 51.5% for diagnosing aTB, respectively. While in IGRA- ones, they were 87.5%, 80.5%, 60.9% and 95.0% with 174.2 pg/ml IL-6 response as cutoff, respectively. CONCLUSIONS: These results clearly show that the Rv0183 antigen-specific IL-6 response has the potential to be used as an immune-diagnosis test for active TB in clinical practice.
ESTHER : Liu_2018_J.Infect_76_376
PubMedSearch : Liu_2018_J.Infect_76_376
PubMedID: 29174965
Gene_locus related to this paper: myctu-rv0183

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans - Yang_2018_Arch.Toxicol_92_2779
Author(s) : Yang S , Zhang H , Zhang J , Li Y , Jin Y , Zhang S , De Saeger S , Zhou J , Sun F , De Boevre M
Ref : Archives of Toxicology , 92 :2779 , 2018
Abstract : Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry. Additionally, in vivo metabolism of ZEN-14G was conducted in model animals, rats, by oral administration. As a result, 29 phase I metabolites and 6 phase II metabolites were identified and significant inter-species metabolic differences were observed as well. What is more, ZEN-14G could be considerably deglucosidated into its free form of ZEN after the incubation with animals and human liver microsomes in the absence of NADPH, which was mainly metabolized by human carboxylesterase CES-I and II. Furthermore, results showed that the major metabolic pathways of ZEN-14G were deglucosylation, hydroxylation, hydrogenation and glucuronidation. Although interspecies differences in the biotransformation of ZEN-14G were observed, ZEN, alpha-ZEL-14G, beta-ZEL-14G, alpha-ZEL, ZEN-14G-16GlcA and ZEN-14GlcA were the major metabolites of ZEN-14G. Additionally, a larger yield of 6-OH-ZEN-14G and 8-OH-ZEN-14G was also observed in human liver microsomes. The obtained data would be of great importance for the safety assessment of modified mycotoxin, ZEN-14G, and provide another perspective for risk assessment of mycotoxin.
ESTHER : Yang_2018_Arch.Toxicol_92_2779
PubMedSearch : Yang_2018_Arch.Toxicol_92_2779
PubMedID: 30019167

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract : Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.
ESTHER : Qi_2018_Org.Biomol.Chem_16_9046
PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

Title : Xylarianins A-D from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2 - Zhang_2018_Bioorg.Chem_81_350
Author(s) : Zhang J , Liang JH , Zhao JC , Wang YL , Dong PP , Liu XG , Zhang TY , Wu YY , Shang DJ , Zhang YX , Sun CP
Ref : Bioorg Chem , 81 :350 , 2018
Abstract : Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1-4), three new natural products, 6-methoxycarbonyl-2'-methyl-3,5,4',6'-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2'-rnethyl-3,5,4',6'-tetramethoxy-diphenyl ether (6), and 2-chlor-4'-hydroxy-6-methoxy carbonyl-2'-methyl-3,5,6'-trimethoxy-diphenyl ether (7), and eleven known compounds (8-18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh2(OCOCF3)4-induced electronic circular dichroism (ECD) spectra analyses. The integrated (1)H and (13)C NMR data of three new natural products 5-7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5-9, and 18 displayed significant inhibitory activities against hCE 2 with IC50 values of 10.43+/-0.51, 6.69+/-0.85, 12.36+/-1.27, 18.25+/-1.78, 29.78+/-0.48, 18.86+/-1.87, and 20.72+/-1.51microM, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.
ESTHER : Zhang_2018_Bioorg.Chem_81_350
PubMedSearch : Zhang_2018_Bioorg.Chem_81_350
PubMedID: 30193143

Title : Mucroniferanines A-G, Isoquinoline Alkaloids from Corydalis mucronifera - Zhang_2018_J.Nat.Prod_81_364
Author(s) : Zhang J , Zhang QY , Tu PF , Xu FC , Liang H
Ref : Journal of Natural Products , 81 :364 , 2018
Abstract : Five pairs of isoquinoline alkaloid enantiomers, mucroniferanines A-E (1-5), two inseparable epimeric pairs, mucroniferanines F and G (6, 7), and 10 known isoquinoline alkaloids (8-17) were obtained from Corydalis mucronifera. The structures were characterized using spectroscopic data analysis, and the absolute configurations were established by ECD and X-ray data analysis. The new compounds except for 3 possess a rare 9-methyl group in the isoquinoline alkaloids, and compounds 2 and 3 possess rare benzo[1,2-d:3,4-d]bis[1,3]dioxole moieties. It is the first report of stereoisomerism involving the 9-methyl phthalideisoquinoline alkaloids. Compounds (-)-4, 6, and 7 exhibited acetylcholinesterase inhibitory activities with IC50 values of 28.3, 12.2, and 11.3 muM, respectively.
ESTHER : Zhang_2018_J.Nat.Prod_81_364
PubMedSearch : Zhang_2018_J.Nat.Prod_81_364
PubMedID: 29400966

Title : Ag(+) -Gated Surface Chemistry of Gold Nanoparticles and Colorimetric Detection of Acetylcholinesterase - Zhang_2018_Small__e1801680
Author(s) : Zhang J , Zheng W , Jiang X
Ref : Small , :e1801680 , 2018
Abstract : Chemical regulation of enzyme-mimic activity of nanomaterials is challenging because it requires a precise understanding of the surface chemistry and mechanism, and rationally designed applications. Herein, Ag(+) -gated peroxidase activity is demonstrated by successfully modulating surface chemistry of cetyltrimethylammonium bromide-capped gold nanoparticles (CTAB-AuNPs). A surface blocking effect of long-chain molecules on surfaces of AuNPs that inhibit peroxidase activity of AuNPs is found. Ag(+) ions can selectively bind on the surfaces of AuNPs and competitively destroy CTAB membrane forming Ag(+) @CTAB-AuNPs complexes to result in enhanced peroxidase activity. Ag(+) @CTAB-AuNPs show the highest peroxidase activity compared to similar-sized citrate-capped and ascorbic acid-capped AuNPs. Ag(+) @CTAB-AuNPs can potentially develop into analyte-responsive systems and exhibit advantages in the optical sensing field. For example, the Ag(+) @CTAB-AuNPs system shows an enhanced sensitivity and selectivity for acetylcholinesterase activity sensing compared to other methods.
ESTHER : Zhang_2018_Small__e1801680
PubMedSearch : Zhang_2018_Small__e1801680
PubMedID: 29971910

Title : Pharmacological Basis for the Use of Evodiamine in Alzheimer's Disease: Antioxidation and Antiapoptosis - Zhang_2018_Int.J.Mol.Sci_19_
Author(s) : Zhang Y , Wang J , Wang C , Li Z , Liu X , Zhang J , Lu J , Wang D
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Evodiamine (Evo), a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus, has a wide range of pharmacological activities. The present study sought to explore the neuroprotective effects of Evo in l-glutamate (l-Glu)-induced apoptosis of HT22 cells, and in a d-galactose and aluminum trichloride-developed Alzheimer’s disease (AD) mouse model. Evo significantly enhanced cell viability, inhibited the accumulation of reactive oxygen species, ameliorated mitochondrial function, increased the B-cell lymphoma-2 protein content, and inhibited the high expression levels of Bax, Bad, and cleaved-caspase-3 and -8 in l-Glu-induced HT22 cells. Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the l-Glu-induced HT22 cells. In the AD mouse model, Evo reduced the aimless and chaotic movements, reduced the time spent in the central area in the open field test, and decreased the escape latency time in the Morris water maze test. Evo reduced the deposition of amyloid beta 42 (Aβ42) in the brain, and increased the serum level of Aβ42, but showed no significant effects on Aβ40. In addition, six weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels. In the central cholinergic system of AD mice, Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum, hypothalamus, and brain. Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases.
ESTHER : Zhang_2018_Int.J.Mol.Sci_19_
PubMedSearch : Zhang_2018_Int.J.Mol.Sci_19_
PubMedID: 29883380

Title : Hydrogels Incorporating Au@Polydopamine Nanoparticles: Robust Performance for Optical Sensing - Zhang_2018_Anal.Chem_90_11423
Author(s) : Zhang J , Mou L , Jiang X
Ref : Analytical Chemistry , 90 :11423 , 2018
Abstract : Stimuli-responsive hydrogels (SRhG) that undergo response to physicochemical stimuli have been broadly applied in separation, biosensing, and drug delivery. Since, most of the SRhG are based on the structural behaviors (swelling or collapse). Herein, we describe a more simple and convenient colorimetric SRhG of polydopamine-coated gold nanoparticles (Au@PDA NPs) hydrogel. The newly developed SRhG is based on the in situ surface chemistry of Au@PDA NPs with core-shell structure embedding in agarose hydrogel. Silver ions can in situ form Ag NPs on surfaces of Au@PDA NPs (Ag_Au@PDA NPs with core-satellites like structure) at ambient conditions, which shift the localized surface plasmon resonance (LSPR) absorption peak and result in color change. The solid sensing phase of SRhG shows greatly improved stability and anti-interference ability comparing to that of solution phase sensing. With rational designs, Au@PDA NPs hydrogel shows great potential in optical sensing, for example, biothiol detection, and coupled with enzyme-cascade reaction for acetylcholinesterase activity detection and inhibitor assays with excellent sensitivity and selectivity.
ESTHER : Zhang_2018_Anal.Chem_90_11423
PubMedSearch : Zhang_2018_Anal.Chem_90_11423
PubMedID: 30191718

Title : Total Synthesis of Pulmonarin B and Design of Brominated Phenylacetic Acid\/Tacrine Hybrids: Marine Pharmacophore Inspired Discovery of New ChE and Abeta Aggregation Inhibitors - Cheng_2018_Mar.Drugs_16_
Author(s) : Cheng ZQ , Song JL , Zhu K , Zhang J , Jiang CS , Zhang H
Ref : Mar Drugs , 16 : , 2018
Abstract : A marine natural product, pulmonarin B (1), and a series of related tacrine hybrid analogues were synthesized and evaluated as cholinesterase (ChE) inhibitors. The in vitro ChE assay results revealed that 1 showed moderate dual acetylcholinesterase (AChE)/ butyrylcholinesterase (BChE) inhibitory activity, while the hybrid 12j proved to be the most potent dual inhibitor among the designed derivatives, being almost as active as tacrine. Molecular modeling studies together with kinetic analysis suggested that 12j interacted with both the catalytic active site and peripheral anionic site of AChE. Compounds 1 and 12j could also inhibit self-induced and AChE-induced Abeta aggregation. In addition, the cell-based assay against the human hepatoma cell line (HepG2) revealed that 1 and 12j did not show significant hepatotoxicity compared with tacrine and donepezil. Taken together, the present study confirmed that compound 1 was a potential anti-Alzheimer's disease (AD) hit, and 12j could be highlighted as a multifunctional lead compound for anti-AD drug development.
ESTHER : Cheng_2018_Mar.Drugs_16_
PubMedSearch : Cheng_2018_Mar.Drugs_16_
PubMedID: 30134630

Title : Ethanolic Extract of Opuntia ficus-indica var. saboten Ameliorates Cognitive Dysfunction Induced by Cholinergic Blockade in Mice - Kwon_2018_J.Med.Food_21_971
Author(s) : Kwon Y , Liao Y , Koo B , Bae H , Zhang J , Han EH , Yun SM , Lim MK , Lee SH , Jung SY , Ryu JH
Ref : J Med Food , 21 :971 , 2018
Abstract : The stem of Opuntia ficus-indica var. saboten is edible and has been used as a medicinal herb on Jeju Island in Korea. We previously reported that the butanolic extract of O. ficus-indica var. saboten exerts the enhancement of long-term memory in mice. However, the antiamnesic effects of O. ficus-indica var. saboten and its mode of action has not been clearly elucidated. In the present study, we explored the effects of the ethanolic extract of stems of O. ficus-indica var. saboten (EOFS) on cognitive performance in mouse and attempted to delineate its mechanism of action. We used the passive avoidance, Y-maze, and novel object recognition tests to assess its effects on cognitive functions in scopolamine-induced memory-impaired mice. We observed that EOFS (100, 200, and 400 mg/kg) ameliorated scopolamine-induced cognitive dysfunction. We also explored its mechanism of action by conducting an acetylcholinesterase (AChE) activity assay using the mouse whole brain and Western blot using the mouse hippocampal tissue. Western blot analysis and the ex vivo study revealed that EOFS increased the levels of phosphorylated extracellular signal-regulated kinase and cAMP response element-binding protein (CREB) and the levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus. It also inhibited AChE activity in the brain. Our findings suggest that EOFS would be useful for the treatment of cholinergic blockade-induced cognitive dysfunction.
ESTHER : Kwon_2018_J.Med.Food_21_971
PubMedSearch : Kwon_2018_J.Med.Food_21_971
PubMedID: 30044674

Title : Effect of Telmisartan on Preventing Learning and Memory Deficits Via Peroxisome Proliferator-Activated Receptor-gamma in Vascular Dementia Spontaneously Hypertensive Rats - Gao_2018_J.Stroke.Cerebrovasc.Dis_27_277
Author(s) : Gao Y , Li W , Liu Y , Wang Y , Zhang J , Li M , Bu M
Ref : J Stroke Cerebrovasc Dis , 27 :277 , 2018
Abstract : BACKGROUND: This study aimed to explore the effect of telmisartan (TEL), as a partial peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, in vascular dementia (VaD) rats induced by middle cerebral artery occlusion (MCAO). METHODS: Spontaneously hypertensive rats were divided into 6 groups: the sham group, model group, TEL-treated groups (1, 5, and 10 mg/kg), and TEL + GW9662 (10 mg/kg + 1 mg/kg). Using the MCAO method established the VaD rat model. Cognitive function was detected through the Morris water maze test, and matrix metalloproteinase 2 (MMP2) or matrix metalloproteinase 9 (MMP9), acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and synaptophysin (SYN) in the hippocampus of rats were measured by the immunohistochemical method. RESULTS: In the Morris water maze test, the spatial memory ability was significantly impaired in the model group and improved in the TEL groups (1, 5, and 10 mg/kg), but the improvement effect of TEL on spatial memory was inhibited by GW9662, a PPAR-gamma antagonist. Compared with the sham group, the expression levels of MMP2, MMP9, and AChE increased and the expression levels of ChAT and SYN decreased significantly in the model group. Interestingly, TEL (1, 5, and 10 mg/kg) significantly reduced the expression levels of MMP2, MMP9, and AChE and significantly improved the expression levels of ChAT and SYN in a dose-dependent manner. However, cotreatment with GW9662 inhibited the TEL-mediated improvement effects on MMPs, the cholinergic system, and SYN. CONCLUSION: This study suggested that TEL had improvement effects in VaD rats via the PPAR-gamma pathway.
ESTHER : Gao_2018_J.Stroke.Cerebrovasc.Dis_27_277
PubMedSearch : Gao_2018_J.Stroke.Cerebrovasc.Dis_27_277
PubMedID: 29241675

Title : Ophiosphaerellins A-I, Polyketide-Derived Compounds from the Endolichenic Fungus Ophiosphaerella korrae - Li_2018_ACS.Omega_3_176
Author(s) : Li Y , Zhu R , Zhang J , Xie F , Wang X , Xu K , Qiao Y , Zhao Z , Lou H
Ref : ACS Omega , 3 :176 , 2018
Abstract : Ophiosphaerellins A-I (1-9), the first example of bicyclo[4.1.0]heptenones, as well as their biosynthetic relatives ophiosphaerekorrins A-B (10-11) were isolated from the endolichenic fungus Ophiosphaerella korrae. Biosynthetically, they were derived from the polyketide pathway, and their absolute configurations were determined on the basis of the combination analysis of spectral data, circular dichroism calculations, and single-crystal X-ray diffraction measurement. Preliminary test with thin-layer chromatography bioautography found that this type of compounds showed moderate acetylcholinesterase (AChE) inhibitory effects.
ESTHER : Li_2018_ACS.Omega_3_176
PubMedSearch : Li_2018_ACS.Omega_3_176
PubMedID: 30023771

Title : Perfluorooctane sulfonate induced neurotoxicity responses associated with neural genes expression, neurotransmitter levels and acetylcholinesterase activity in planarians Dugesia japonica - Yuan_2018_Chemosphere_206_150
Author(s) : Yuan Z , Shao X , Miao Z , Zhao B , Zheng Z , Zhang J
Ref : Chemosphere , 206 :150 , 2018
Abstract : As a persistent and widespread toxic organic pollutant in the environment, perfluorooctane sulfonate (PFOS) has the potential to cause great harm to wildlife. In our study, the effects of PFOS on neurodevelopment gene expression, neurotransmitter content, neuronal morphology, acetylcholinesterase (AChE) activity were examined, and the potential neurotoxicity mechanisms of PFOS were also investigated in planarians, Dugesia japonica. Using quantitative real-time PCR analysis, five neurodevelopmental related genes were measured, among which, DjotxA, DjotxB, DjFoxD, and DjFoxG were found to be down-regulated, while Djnlg was found to be up-regulated, following exposure to PFOS for 10 days compared with control groups. In addition, the neurotransmitters including dopamine, serotonin, and gamma-aminobutyricacid as well as the acitivity of AChE were altered by PFOS exposure. Furthermore, PFOS exposure altered brain morphology as well as smaller cephalic ganglia which displayed reduced nerve fiber density decreased brain branches compared to controls. Our results demonstrate that neurotransmission was disturbed after exposure to PFOS and that exposure to this pollutant can cause neurotoxic defects. Results from this study provide valuable information regarding the neuro- and ecological toxicity of PFOS in aquatic animals and aquatic environments.
ESTHER : Yuan_2018_Chemosphere_206_150
PubMedSearch : Yuan_2018_Chemosphere_206_150
PubMedID: 29738904

Title : Correlation Between Liver Stiffness Measured by Shear Wave Elastography and Child-Pugh Classification - Wang_2018_J.Ultrasound.Med_37_2191
Author(s) : Wang J , Wang Q , Yu G , She Q , Zhang W , Zhang J
Ref : Journal of Ultrasound in Medicine , 37 :2191 , 2018
Abstract : OBJECTIVES: To explore the association between liver stiffness and the Child-Pugh classification of liver function by shear wave elastography (SWE). METHODS: A total of 116 patients with liver cirrhosis were divided into 3 groups according to the Child-Pugh classification prospectively. Conventional ultrasound imaging and SWE were performed for all patients. The associations of liver stiffness measured by SWE with ultrasound measurements, serum biochemical indicators, and the Child-Pugh classification were analyzed. Receiver operating characteristic curves were analyzed and compared to determine the ability of liver stiffness to diagnose cirrhosis. RESULTS: Liver stiffness measured by SWE increased with an increasing Child-Pugh classification, internal diameter of the hepatic portal and splenic veins, spleen thickness, spleen length, total bilirubin level, and prothrombin time, which were positively correlated with the Child-Pugh classification (all P < .05). The albumin level and liver stiffness showed higher areas under the curve in comparison with other parameters for evaluating the Child-Pugh classification. Albumin and cholinesterase levels were negatively correlated with the Child-Pugh classification (P < .05). All of these indicators were significantly different between each pair of groups (all P < .05), except for the internal diameter of the hepatic portal vein, prothrombin time, and total bilirubin, and cholinesterase levels between groups B and C (P > 0.05) and the thickness and length of spleen and internal diameter of the splenic vein between groups A and B (P > 0.05). There were no differences among the groups for alanine aminotransferase, aspartate aminotransferase, and globulin levels. CONCLUSIONS: Liver stiffness measured by SWE was correlated with the Child-Pugh classification, and it may be able to help evaluate liver function in patients with cirrhosis.
ESTHER : Wang_2018_J.Ultrasound.Med_37_2191
PubMedSearch : Wang_2018_J.Ultrasound.Med_37_2191
PubMedID: 29476558

Title : Oxoisoaporphine Alkaloids: Prospective Anti-Alzheimer's Disease, Anticancer, and Antidepressant Agents - Zhang_2018_ChemMedChem_13_1262
Author(s) : Zhang J , Chen L , Sun J
Ref : ChemMedChem , 13 :1262 , 2018
Abstract : Oxoisoaporphine alkaloids are a family of oxoisoquinoline-derived alkaloids that were first isolated from the rhizome of Menispermum dauricum DC. (Menispermaceae). It has been demonstrated that oxoisoaporphine alkaloids possess various biological properties, such as cholinesterase and beta-amyloid inhibition, acting as a topoisomerase intercalator, monoamine oxidase A inhibition, and are expected to become anti-Alzheimer's disease, anticancer, and antidepressant drugs. This review provides an overview of natural sources, synthetic routes, bioactivities, structure-function relationship, and modification investigations into oxoisoaporphine alkaloids, with the aim of providing references to the structure-activity relationships for the design and development of oxoisoaporphine derivatives with higher efficacy and therapeutic potential.
ESTHER : Zhang_2018_ChemMedChem_13_1262
PubMedSearch : Zhang_2018_ChemMedChem_13_1262
PubMedID: 29696800

Title : The memory ameliorating effects of DHP1402, an herbal mixture, on cholinergic blockade-induced cognitive dysfunction in mice - Kim_2018_J.Ethnopharmacol_211_38
Author(s) : Kim H , Lee HE , Jung IH , Jeon SJ , Zhang J , Kwon Y , Jang DS , Ryu JH
Ref : J Ethnopharmacol , 211 :38 , 2018
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F Chow (Rhamnaceae) and the roots of Codonopsis lanceolata (Siedbold & Zucc.) Benth. & Hook. f ex Trautv. (Campanulaceae), contained in the DHP1402, have long been used for treating dementia or hypomnesia as folk medicine. AIM OF THE STUDY: It has been reported that Z. jujuba var. spinosa and C. lanceolata are effective in improving cognitive function, but via different mechanisms. Therefore, in the present study, we evaluated the synergistic effects of Z. jujuba var. spinosa and C. lanceolata on scopolamine-induced memory impairment. MATERIALS AND METHODS: Scopolamine, a cholinergic muscarinic receptor antagonist, was used to induce cognitive dysfunction. We employed several behavioral tasks to estimate the synergistic effect of the seeds of Z. jujuba var. spinosa and the roots of C. lanceolata. In addition, we introduced the Western blotting, the antagonism passive avoidance task to investigate a synergistic effect of an herbal formulation. RESULTS: Synergistic effects of a combination of Z. jujuba var. spinosa and C. lanceolata at a 5:1 ratio [(w/w), DHP1402] were observed against cognitive dysfunction in the passive avoidance and Y-maze tasks. DHP1402 also ameliorated memory deficits in a dose-dependent manner in these behavioral tasks, as well as in the Morris water maze task. According to the Western blot results, the phosphorylation levels of protein kinase A (PKA), extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus were also increased in a synergistic manner after the administration of DHP1402. In addition, we found that the effects of DHP1402 on cognitive function were mediated by N-methyl-D-aspartate (NMDA) receptor signalling, based on the antagonism studies. Furthermore, we found that DHP1402 has inhibitory activity against acetylcholinesterase (AChE). CONCLUSION: DHP1402 attenuates cholinergic blockade-induced cognitive dysfunction through NMDA receptor modulation, PKA-ERK-CREB pathway activation, and AChE inhibition. Therefore, DHP1402 could be a candidate for alleviating cognitive dysfunction.
ESTHER : Kim_2018_J.Ethnopharmacol_211_38
PubMedSearch : Kim_2018_J.Ethnopharmacol_211_38
PubMedID: 28917975

Title : Terpenoids from the Soft Coral Sinularia sp. Collected in Yongxing Island - Qin_2018_Mar.Drugs_16_
Author(s) : Qin GF , Tang XL , Sun YT , Luo XC , Zhang J , van Ofwegen L , Sung PJ , Li PL , Li GQ
Ref : Mar Drugs , 16 : , 2018
Abstract : Three new sesquiterpenoids (sinuketal (1), sinulins A and B (2 and 3)) and two new cembranoids (sinulins C and D (4 and 5)), as well as eight known sesquiterpenoids (6–13) and eight known cembranoids (14–21), were isolated from the Xisha soft coral Sinularia sp. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 possesses an unprecedented isopropyl-branched bicyclo [6.3.0] undecane carbon skeleton with unique endoperoxide moiety, and a plausible biosynthetic pathway of it was postulated. According to the reported biological properties of endoperoxide, the antimalarial, cytotoxic, antiviral, and target inhibitory activities of 1 were tested. Compound 1 showed mild in vitro antimalarial activity against Plasmodium falciparum 3D7, weak cytotoxic activities toward Jurkat, MDA-MB-231, and U2OS cell lines, inhibitory effects against influenza A viruses H1N1 and PR8, as well as mild target inhibitory activity against acetylcholinesterase. The other compounds were evaluated for cytotoxicities against HeLa, HCT-116, and A549 tumor cell lines and target inhibitory activities against protein tyrosine phosphatase 1B (PTP1B). Compound 20 exhibited cytotoxicities against HeLa and HCT-116, and compounds 5, 11, and 15 showed mild target inhibitory activities against PTP1B.
ESTHER : Qin_2018_Mar.Drugs_16_
PubMedSearch : Qin_2018_Mar.Drugs_16_
PubMedID: 29652789