Wang W

References (189)

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

Title : Prophylactic and therapeutic inhalation of two essential oils ameliorates scopolamine-induced cognitive impairment in mice - Wang_2024_Nat.Prod.Res__1
Author(s) : Wang W , Yang J , Liang D , Yao L , Ma L
Ref : Nat Prod Res , :1 , 2024
Abstract : Clover and lemongrass essential oils of contrasting composition, at three concentration levels (1%, 5%, 10%), were administrated via prophylactic and therapeutic inhalation to scopolamine-treated mice. Chemical analysis showed that clover oil was dominant in eugenol (47.69%) and lemongrass free of eugenol but mainly containing monoterpenoids of comparable proportions. Animal behavioural and brain biochemical tests showed that injection of scopolamine caused memory and learning deficit in mice while prophylactic and therapeutic inhalation of two oils at moderate to high concentrations all obviously reversed the cognitive impairment via inhibiting acetylcholinesterase activities, oxidation and inflammation. Lemongrass essential oil with diverse monoterpenoids can be as effective as or a little bit more potent than eugenol-rich clover essential oil possibly due to the synergistic effect of various monoterpenoids. These findings implied that sniffing of such aroma recipes could be a promising complementary approach for the mitigation of Alzheimer's disease-related cognitive impairment.
ESTHER : Wang_2024_Nat.Prod.Res__1
PubMedSearch : Wang_2024_Nat.Prod.Res__1
PubMedID: 38557211

Title : Quantitative proteomic analysis reveals the mechanism and key esterase of beta-cypermethrin degradation in a bacterial strain from fermented food - Peng_2024_Pestic.Biochem.Physiol_201_105858
Author(s) : Peng C , Tang J , Zhou X , Zhou H , Zhang Y , Wang S , Wang W , Xiang W , Zhang Q , Yu X , Cai T
Ref : Pestic Biochem Physiol , 201 :105858 , 2024
Abstract : Beta-cypermethrin (beta-CY) residues in food are an important threat to human health. Microorganisms can degrade beta-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of beta-CY in a food microorganism was conducted based on proteomics analysis. The beta-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of beta-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of beta-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of beta-CY, which confirmed that this enzyme was the key enzyme in the process of beta-CY degradation. This study reveals the degradation mechanism of beta-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in beta-CY residues.
ESTHER : Peng_2024_Pestic.Biochem.Physiol_201_105858
PubMedSearch : Peng_2024_Pestic.Biochem.Physiol_201_105858
PubMedID: 38685237

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : Soluble epoxide hydrolase inhibitor (TPPU) alleviates ferroptosis by regulating CCL5 after intracerebral hemorrhage in mice - Wu_2024_Biomed.Pharmacother_172_116301
Author(s) : Wu Q , Jiang N , Wang Y , Song G , Li P , Fang Y , Xu L , Wang W , Xie M
Ref : Biomed Pharmacother , 172 :116301 , 2024
Abstract : Soluble epoxide hydrolase (sEH) inhibition has been shown multiple beneficial effects against brain injuries of Intracerebral hemorrhage (ICH). However, the underlying mechanism of its neuroprotective effects after ICH has not been explained fully. Ferroptosis, a new form of iron-dependent programmed cell death, has been shown to be implicated in the secondary injuries after ICH. In this study, We examined whether sEH inhibition can alleviate brain injuries of ICH through inhibiting ferroptosis. Expression of several markers for ferroptosis was observed in the peri-hematomal brain tissues in mice after ICH. lip-1, a ferroptosis inhibitor, alleviated iron accumulation, lipid peroxidation and the secondary damages post-ICH in mice model. Intraperitoneal injection of 1-Trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl)urea (TPPU), a highly selective sEH inhibitor, could inhibit ferroptosis and alleviate brain damages in ICH mice. Furthermore, RNA-sequencing was applied to explore the potential regulatory mechanism underlying the effects of TPPU in ferroptosis after ICH. C-C chemokine ligand 5 (CCL5) may be the key factor by which TPPU regulated ferroptosis after ICH since CCL5 antagonist could mimic the effects of TPPU and CCL5 reversed the inhibitive effect of TPPU on ferroptosis and the neuroprotective effects of TPPU on secondary damage after ICH. Taken together, these data indicate that ferroptosis is a key pathological feature of ICH and Soluble epoxide hydrolase inhibitor can exert neuroprotective effect by preventing ferroptosis after ICH.
ESTHER : Wu_2024_Biomed.Pharmacother_172_116301
PubMedSearch : Wu_2024_Biomed.Pharmacother_172_116301
PubMedID: 38377737

Title : Glucagon-like peptide-1 analogs: Miracle drugs are blooming? - Gong_2024_Eur.J.Med.Chem_269_116342
Author(s) : Gong B , Yao Z , Zhou C , Wang W , Sun L , Han J
Ref : Eur Journal of Medicinal Chemistry , 269 :116342 , 2024
Abstract : Glucagon-like peptide-1 (GLP-1), secreted by L cells in the small intestine, assumes a central role in managing type 2 diabetes mellitus (T2DM) and obesity. Its influence on insulin secretion and gastric emptying positions it as a therapeutic linchpin. However, the limited applicability of native GLP-1 stems from its short half-life, primarily due to glomerular filtration and the inactivating effect of dipeptidyl peptidase-IV (DPP-IV). To address this, various structural modification strategies have been developed to extend GLP-1's half-life. Despite the commendable efficacy displayed by current GLP-1 receptor agonists, inherent limitations persist. A paradigm shift emerges with the advent of unimolecular multi-agonists, such as the recently introduced tirzepatide, wherein GLP-1 is ingeniously combined with other gastrointestinal hormones. This novel approach has captured the spotlight within the diabetes and obesity research community. This review summarizes the physiological functions of GLP-1, systematically explores diverse structural modifications, delves into the realm of unimolecular multi-agonists, and provides a nuanced portrayal of the developmental prospects that lie ahead for GLP-1 analogs.
ESTHER : Gong_2024_Eur.J.Med.Chem_269_116342
PubMedSearch : Gong_2024_Eur.J.Med.Chem_269_116342
PubMedID: 38531211

Title : Molecular, behavioral, and growth responses of juvenile yellow catfish (Tachysurus fulvidraco) exposed to carbamazepine - Chen_2024_Aquat.Toxicol_271_106929
Author(s) : Chen H , Gu X , Mao Z , Zeng Q , Jin M , Wang W , Martyniuk CJ
Ref : Aquat Toxicol , 271 :106929 , 2024
Abstract : Carbamazepine (CBZ) is an anticonvulsant medication used to treat epilepsy and bipolar disorder. Due to its persistence and low removal rate in wastewater treatment plants, it is frequently detected in the environment, raising concerns regarding its potential adverse effects on aquatic organisms and ecosystems. In this study, we aimed to assess the impact of CBZ on the behavior and growth of juvenile yellow catfish Tachysurus fulvidraco, a native and economically important species in China. Fish were exposed to CBZ at three concentrations of 1, 10, or 100 microg/L for 14 days. The fish exposed to 10 and 100 microg/L of CBZ exhibited decreased feeding, and a significant increase in cannibalistic tendencies was observed in fish exposed to 100 microg/L CBZ. Acetylcholinesterase activity was increased in the brain of fish exposed to 100 microg/L CBZ. CBZ also inhibited the growth of yellow catfish. To better elucidate mechanisms of toxicity, transcriptomics was conducted in both the brain and liver. In the brain, gene networks associated with neurotransmitter dysfunction were altered by CBZ, as well as networks associated with mitochondrial dysfunction and metabolism. In the liver, gene networks associated with the immune system were altered by CBZ. The current study improves comprehension of the sub-lethal effects of CBZ and reveals novel insight into molecular and biochemical pathways disrupted by CBZ, identifying putative key events associated with reduced growth and altered behavior. This study emphasizes the necessity for improved comprehension of the effects of pharmaceutical contaminants on fish at environmentally relevant levels.
ESTHER : Chen_2024_Aquat.Toxicol_271_106929
PubMedSearch : Chen_2024_Aquat.Toxicol_271_106929
PubMedID: 38663201

Title : Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase - Kelly_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2314085121
Author(s) : Kelly AG , Wang W , Rothenberger E , Yang J , Gilligan MM , Kipper FC , Attaya A , Gartung A , Hwang SH , Gillespie MJ , Bayer RL , Quinlivan KM , Torres KL , Huang S , Mitsiades N , Yang H , Hammock BD , Panigrahy D
Ref : Proc Natl Acad Sci U S A , 121 :e2314085121 , 2024
Abstract : Cancer therapy, including immunotherapy, is inherently limited by chronic inflammation-induced tumorigenesis and toxicity within the tumor microenvironment. Thus, stimulating the resolution of inflammation may enhance immunotherapy and improve the toxicity of immune checkpoint inhibition (ICI). As epoxy-fatty acids (EpFAs) are degraded by the enzyme soluble epoxide hydrolase (sEH), the inhibition of sEH increases endogenous EpFA levels to promote the resolution of cancer-associated inflammation. Here, we demonstrate that systemic treatment with ICI induces sEH expression in multiple murine cancer models. Dietary omega-3 polyunsaturated fatty acid supplementation and pharmacologic sEH inhibition, both alone and in combination, significantly enhance anti-tumor activity of ICI in these models. Notably, pharmacological abrogation of the sEH pathway alone or in combination with ICI counter-regulates an ICI-induced pro-inflammatory and pro-tumorigenic cytokine storm. Thus, modulating endogenous EpFA levels through dietary supplementation or sEH inhibition may represent a unique strategy to enhance the anti-tumor activity of paradigm cancer therapies.
ESTHER : Kelly_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2314085121
PubMedSearch : Kelly_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2314085121
PubMedID: 38330013

Title : Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy - Panigrahy_2024_bioRxiv__
Author(s) : Panigrahy D , Kelly A , Wang W , Yang J , Hwang SH , Gillespie M , Howard I , Bueno-Beti C , Asimaki A , Penna V , Lavine K , Edin M , Zeldin D , Hammock B , Saffitz J
Ref : Biorxiv , : , 2024
Abstract : Previous studies have implicated persistent innate immune signaling in the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a familial non-ischemic heart muscle disease characterized by life-threatening arrhythmias and progressive myocardial injury. Here, we provide new evidence implicating inflammatory lipid autocoids in ACM. We show that specialized pro-resolving lipid mediators are reduced in hearts of Dsg2mut/mut mice, a well characterized mouse model of ACM. We also found that ACM disease features can be reversed in rat ventricular myocytes expressing mutant JUP by the pro-resolving epoxy fatty acid (EpFA) 14,15-eicosatrienoic acid (14-15-EET), whereas 14,15-EE-5(Z)E which antagonizes actions of the putative 14,15-EET receptor, intensified nuclear accumulation of the desmosomal protein plakoglobin. Soluble epoxide hydrolase (sEH), an enzyme that rapidly converts pro-resolving EpFAs into polar, far less active or even pro-inflammatory diols, is highly expressed in cardiac myocytes in Dsg2mut/mut mice. Inhibition of sEH prevented progression of myocardial injury in Dsg2mut/mut mice and led to recovery of contractile function. This was associated with reduced myocardial expression of genes involved in the innate immune response and fewer pro-inflammatory macrophages expressing CCR2, which mediate myocardial injury in Dsg2mut/mut mice. These results suggest that pro-inflammatory eicosanoids contribute to the pathogenesis of ACM and, further, that inhibition of sEH may be an effective, mechanism-based therapy for ACM patients.
ESTHER : Panigrahy_2024_bioRxiv__
PubMedSearch : Panigrahy_2024_bioRxiv__
PubMedID: 38463975

Title : Isolation, characteristics, and poly(butylene adipate-co-terephthalate) (PBAT) degradation mechanism of a marine bacteria Roseibium aggregatum ZY-1 - Pan_2024_Mar.Pollut.Bull_201_116261
Author(s) : Pan H , Yu T , Zheng Y , Ma H , Shan J , Yi X , Liu Y , Zhan J , Wang W , Zhou H
Ref : Mar Pollut Bull , 201 :116261 , 2024
Abstract : Marine microorganisms have been reported to degrade microplastics. However, the degradation mechanisms are still poorly understood. In this study, a bacterium Roseibium aggregatum ZY-1 was isolated from seawater, which can degrade poly(butylene adipate-co-terephthalate) (PBAT). The PBAT-PLA(polylactic acid, PLA) films, before and after degradation, were characterized by scanning electron microscope (SEM) and Fourier transform infrared spectrometer (FTIR), the weight loss rate and water contact angle were measured. The results indicate that ZY-1 colonized on PBAT-PLA film, changed the functional groups and decreased water contact angle of PBAT-PLA film. Moreover, liquid chromatography mass spectrometry (LC-MS) analysis reveales that PBAT was degraded into its oligomers (TB, BTB) and monomers (T, A) during 10 days, and adipic acid (A) could be used as a sole carbon source. The whole genome sequencing analyses illustrate the mechanisms and enzymes such as PETase, carboxylesterases, arylesterase (PpEst) and genes like pobA, pcaBCDFGHIJKT, dcaAEIJK, paaGHJ involved in PBAT degradation. Therefore, the R. aggregatum ZY-1 will be a promising candidate of PBAT degradation.
ESTHER : Pan_2024_Mar.Pollut.Bull_201_116261
PubMedSearch : Pan_2024_Mar.Pollut.Bull_201_116261
PubMedID: 38537567

Title : Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430 - Wu_2024_J.Nat.Prod__
Author(s) : Wu Z , Wang W , Li J , Ma C , Chen L , Che Q , Zhang G , Zhu T , Li D
Ref : Journal of Natural Products , : , 2024
Abstract : Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster (sla) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key alpha,beta-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin (1), characterized by an N-acylated amino acid structure and demonstrating weak anti-Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.
ESTHER : Wu_2024_J.Nat.Prod__
PubMedSearch : Wu_2024_J.Nat.Prod__
PubMedID: 38447096

Title : GmSABP2-1 encodes methyl salicylate esterase and functions in soybean defense against soybean cyst nematode - Lin_2024_Plant.Cell.Rep_43_138
Author(s) : Lin J , Wang W , Mazarei M , Zhao N , Chen X , Pantalone VR , Hewezi T , Stewart CN, Jr. , Chen F
Ref : Plant Cell Rep , 43 :138 , 2024
Abstract : The soybean gene GmSABP2-1 encodes methyl salicylate esterase and its overexpression led to significant reduction in development of pathogenic soybean cyst nematode. Soybean cyst nematode (SCN, Heterodera glycines) is one of the most devastating pests of soybean (Glycine max L. Merr.). In searching for SCN-defense genes, a soybean gene of the methylesterase (MES) family was found to be upregulated in an SCN-resistant soybean line and downregulated in an SCN-susceptible line upon SCN infection. This gene was designated as GmSABP2-1. Here, we report on biochemical and overexpression studies of GmSABP2-1 to examine its possible function in SCN resistance. The protein encoded by GmSABP2-1 is closely related to known methyl salicylate esterases. To determine the biochemical function of GmSABP2-1, a full-length cDNA of GmSABP2-1 was cloned into a protein expression vector and expressed in Escherichia coli. The resulting recombinant GmSABP2-1 was demonstrated to catalyze the demethylation of methyl salicylate. The biochemical properties of GmSABP2-1 were determined. Its apparent Km value was 46.2+/-2.2 microM for methyl salicylate, comparable to those of the known methyl salicylate esterases. To explore the biological significance of GmSABP2-1 in soybean defense against SCN, we first overexpressed GmSABP2-1 in transgenic hairy roots of an SCN-susceptible soybean line. When infected with SCN, GmSABP2-1-overexpressing hairy roots showed 84.5% reduction in the development of SCN beyond J2 stage. To provide further genetic evidence for the role of GmSABP2-1 in SCN resistance, stable transgenic soybean plants overexpressing GmSABP2-1 were produced. Analysis of the GmSABP2-1-overexpressing lines showed a significant reduction in SCN development compared to non-transgenic plants. In conclusion, we demonstrated that GmSABP2-1 encodes methyl salicylate esterase and functions as a resistance-related gene against SCN.
ESTHER : Lin_2024_Plant.Cell.Rep_43_138
PubMedSearch : Lin_2024_Plant.Cell.Rep_43_138
PubMedID: 38733408
Gene_locus related to this paper: soybn-c6tji9

Title : Efficacy and Safety of Plasma Exchange Combined with Hemoperfusion in the Treatment of Organophosphorus Poisoning: A Meta-Analysis - Yao_2023_Blood.Purif__1
Author(s) : Yao Z , Wang P , Fu Q , Song Q , Wang W , Liu A , Zhang P
Ref : Blood Purif , :1 , 2023
Abstract : INTRODUCTION: The aim of the study was to systematically evaluate the efficacy and safety of plasma exchange combined with hemoperfusion in the treatment of organophosphorus poisoning. METHODS: PubMed, Embase, the Cochrane Library, China National Knowledge Internet, Wanfang database, and Weipu database were searched for articles about this subject. Literature screening and selection were conducted in strict accordance with the inclusion and exclusion criteria. RESULTS: 14 randomized controlled trials with 1,034 participants were included in this meta-analysis study, including 518 cases in plasma exchange combined with hemoperfusion group (the combination treatment group) and 516 cases in hemoperfusion group (the control group). Compared with the control group, the combination treatment group was associated with a higher effective rate (relative risk [RR] = 1.20, 95% confidence interval [CI] [1.11, 1.30], p < 0.00001) and lower fatality rate (RR = 0.28, 95% CI [0.15, 0.52], p< 0.0001); reduced TNF-alpha (standardized mean difference [SMD] = -1.95, 95% CI [-2.42, -1.48], p < 0.00001), IL-6 (SMD = -1.94, 95% CI [-3.08, -0.80], p = 0.0009), and C-reactive protein (CRP) (SMD = -1.94, 95% CI [-2.86, -1.03], p < 0.0001); shorten coma time (SMD = -1.99, 95% CI [-2.75, -1.24], p < 0.00001), recovery time of cholinesterase activity (SMD = -1.71, 95% CI [-1.90, -1.53], p < 0.00001), and hospital stay (SMD = -1.29, 95% CI [-1.59, -0.98], p < 0.00001). The incidence of complications in the combination treatment group such as liver and kidney damage (RR = 0.30, 95% CI [0.18, 0.50], p < 0.00001), pulmonary infection (RR = 0.29, 95% CI [0.18, 0.47], p < 0.00001), and intermediate syndrome (RR = 0.32, 95% CI [0.21, 0.49], p < 0.00001) was lower than that in the control group. CONCLUSIONS: The current evidence suggests that the combination of plasma exchange with hemoperfusion therapy can reduce the mortality of patients with organophosphorus poisoning, shorten the recovery time of cholinesterase activity and the time of coma, reduce the average length of hospital stay, and reduce the levels of IL-6, TNF-alpha, and CRP, but high-quality randomized double-blind controlled trials are still required to confirm the current findings in the future.
ESTHER : Yao_2023_Blood.Purif__1
PubMedSearch : Yao_2023_Blood.Purif__1
PubMedID: 37302392

Title : Perilipin1 deficiency prompts lipolysis in lipid droplets and aggravates the pathogenesis of persistent immune activation in Drosophila - Wang_2023_J.Innate.Immun__
Author(s) : Wang L , Lin J , Yang K , Wang W , Lv Y , Zeng X , Zhao Y , Yu J , Pan L
Ref : J Innate Immun , : , 2023
Abstract : Lipid droplets (LDs) are highly dynamic intracellular organelles, which are involved in lots of biological processes. However, the dynamic morphogenesis and functions of intracellular LDs during persistent innate immune responses remain obscure. In this study, we induce long-term systemic immune activation in Drosophila through genetic manipulation. Then, the dynamic pattern of LDs is traced in the Drosophila fat body. We find that deficiency of Plin1, a key regulator of LDs' reconfiguration, blocks LDs minimization at the initial stage of immune hyperactivation but enhances LDs breakdown at the later stage of sustained immune activation via recruiting the lipase Brummer (Bmm, homologous to human ATGL). The high wasting in LDs shortens the lifespan of flies with high-energy-cost immune hyperactivation. Therefore, these results suggest a critical function of LDs during long-term immune activation and provide a potential treatment for the resolution of persistent inflammation.
ESTHER : Wang_2023_J.Innate.Immun__
PubMedSearch : Wang_2023_J.Innate.Immun__
PubMedID: 37742619

Title : Cell-Dependent Activation of ProTide Prodrugs and Its Implications in Antiviral Studies - Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
Author(s) : Liu Y , Sun S , Li J , Wang W , Zhu HJ
Ref : ACS Pharmacol Transl Sci , 6 :1340 , 2023
Abstract : The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that the activation of ProTide prodrugs varied in different cell lines. In the present study, we investigated the activation profiles of two antiviral prodrugs tenofovir alafenamide (TAF) and sofosbuvir (SOF) in five cell lines commonly used in antiviral research, namely, Vero E6, Huh-7, Calu-3, A549, and Caco-2. We found that TAF and SOF were activated in a cell-dependent manner with Vero E6 being the least efficient and Huh-7 being the most efficient cell line for activating the prodrugs. We also demonstrated that TAF was activated at a significantly higher rate than SOF. We further analyzed the protein expressions of the activating enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding protein 1, and the relevant drug transporters P-glycoprotein and organic anion-transporting polypeptides 1B1 and 1B3 in the cell lines using the proteomics data extracted from the literature and proteome database. The results revealed significant differences in the expression patterns of the enzymes and transporters among the cell lines, which might partially contribute to the observed cell-dependent activation of TAF and SOF. These findings highlight the variability of the abundance of activating enzymes and transporters between cell lines and emphasize the importance of selecting appropriate cell lines for assessing the antiviral efficacy of nucleoside/nucleotide prodrugs.
ESTHER : Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
PubMedSearch : Liu_2023_ACS.Pharmacol.Transl.Sci_6_1340
PubMedID: 37854623

Title : JH degradation pathway participates in hormonal regulation of larval development of Bombyx mori following lambda-cyhalothrin exposure - Su_2023_Chemosphere_349_140871
Author(s) : Su Y , Wang W , Dai Y , Qi R , Gu H , Guo X , Liu X , Ren Y , Li F , Li B , Sun H
Ref : Chemosphere , 349 :140871 , 2023
Abstract : lambda-Cyhalothrin (lambda-cyh), a widely utilized pyrethroid insecticide, poses serious threats to non-target organisms due to its persistence nature in the environment. Exposure to low concentrations of lambda-cyh has been observed to result in prolonged larval development in Bombyx mori, leading to substantial financial losses in sericulture. The present study was undertaken to elucidate the underlying mechanisms for prolonged development caused by lambda-cyh (LC(10)) exposure. The results showed that the JH titer was significantly increased at 24 h of lambda-cyh exposure, and the JH interacting genes Methoprene-tolerant 2, Steroid Receptor Co-activator, Krppel-homolog 1, and JH binding proteins were also up-regulated. Although the target of rapamycin (Tor) genes were induced by lambda-cyh, the biosynthesis of JH in the corpora allata was not promoted. Notably, 13 JH degradation genes were found to be significantly down-regulated in the midgut of B. mori. The mRNA levels and enzyme activity assays indicated that lambda-cyh had inhibitory effects on JH esterase, JH epoxide hydrolase, and JH diol kinase (JHDK). Furthermore, the suppression of JHDK (KWMTBOMO01580) was further confirmed by both western blot and immunohistochemistry. This study has offered a comprehensive perspective on the mechanisms underlying the prolonged development caused by insecticides, and our results also hold significant implications for the safe production of sericulture.
ESTHER : Su_2023_Chemosphere_349_140871
PubMedSearch : Su_2023_Chemosphere_349_140871
PubMedID: 38056714

Title : Efficient decolorization of melanoidin in raw molasses wastewater by thermophilic esterase in actual extreme conditions - Zhang_2023_Bioresour.Technol_382_129191
Author(s) : Zhang Z , Hu W , Xie Q , Shi Y , Zhao Y , Deng Y , He J , Wu X , Zhang Y , Zhang W , Liu P , Yang H , Wang W
Ref : Bioresour Technol , 382 :129191 , 2023
Abstract : This work was developed to explore the versatility of thermophilic esterase for decolorizing raw molasses wastewater at high temperature and acidic pH. Combining covalent crosslinking method with deep eutectic solvent, a thermophilic esterase from Pyrobaculum calidifontis was immobilized on chitosan/macroporous resin composite carrier. The application of this immobilized thermophilic esterase eliminated 92.35% of colorants in raw molasses wastewater, achieving maximal decolorization efficiency across all the enzymes tested. Strikingly, this immobilized thermophilic esterase was capable of engaging in continuous activity for a 5-day period while removing 76.23% of pigments from samples. It effectively and continuously eliminated BOD(5) and COD, effectively and directly facilitating raw molasses wastewater decolorization under extreme conditions more readily than control group. In addition, this thermophilic esterase was believed to achieve decolorization through an addition reaction that disrupted conjugated system of melanoidins. Together, these results highlight an efficient and practical means of achieving enzyme-based molasses wastewater decolorization.
ESTHER : Zhang_2023_Bioresour.Technol_382_129191
PubMedSearch : Zhang_2023_Bioresour.Technol_382_129191
PubMedID: 37196742

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

Title : Role of cholinergic innervation in biliary remnants of patients with biliary atresia - Yang_2023_Front.Pediatr_11_1278978
Author(s) : Yang J , Chen X , Wang W , Su Y , Liu K , Abudusalamu A , Li D , He Y , Wang P , Xiong X , Feng J
Ref : Front Pediatr , 11 :1278978 , 2023
Abstract : OBJECTIVE: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. METHODS: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. RESULTS: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R(2 )= 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). CONCLUSIONS: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
ESTHER : Yang_2023_Front.Pediatr_11_1278978
PubMedSearch : Yang_2023_Front.Pediatr_11_1278978
PubMedID: 38259596

Title : Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon - Wang_2023_Int.J.Mol.Sci_24_4570
Author(s) : Wang W , Wagner KM , Wang Y , Singh N , Yang J , He Q , Morisseau C , Hammock BD
Ref : Int J Mol Sci , 24 :4570 , 2023
Abstract : Aging, which is characterized by enhanced cell senescence and functional decline of tissues, is a major risk factor for many chronic diseases. Accumulating evidence shows that age-related dysfunction in the colon leads to disorders in multiple organs and systemic inflammation. However, the detailed pathological mechanisms and endogenous regulators underlying colon aging are still largely unknown. Here, we report that the expression and activity of the soluble epoxide hydrolase (sEH) enzyme are increased in the colon of aged mice. Importantly, genetic knockout of sEH attenuated the age-related upregulation of senescent markers p21, p16, Tp53, and beta-galactosidase in the colon. Moreover, sEH deficiency alleviated aging-associated endoplasmic reticulum (ER) stress in the colon by reducing both the upstream regulators Perk and Ire1 as well as the downstream pro-apoptotic effectors Chop and Gadd34. Furthermore, treatment with sEH-derived linoleic acid metabolites, dihydroxy-octadecenoic acids (DiHOMEs), decreased cell viability and increased ER stress in human colon CCD-18Co cells in vitro. Together, these results support that the sEH is a key regulator of the aging colon, which highlights its potential application as a therapeutic target for reducing or treating age-related diseases in the colon.
ESTHER : Wang_2023_Int.J.Mol.Sci_24_4570
PubMedSearch : Wang_2023_Int.J.Mol.Sci_24_4570
PubMedID: 36901999

Title : A periplasmic phospholipase that maintains outer membrane lipid asymmetry in Pseudomonas aeruginosa - Guest_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2302546120
Author(s) : Guest RL , Lee MJ , Wang W , Silhavy TJ
Ref : Proc Natl Acad Sci U S A , 120 :e2302546120 , 2023
Abstract : The outer membrane of Gram-negative bacteria is unique in both structure and function. The surface-exposed outer leaflet is composed of lipopolysaccharide, while the inner leaflet is composed of glycerophospholipids. This lipid asymmetry creates mechanical strength, lowers membrane permeability, and is necessary for virulence in many pathogens. Glycerophospholipids that mislocalize to the outer leaflet are removed by the Mla pathway, which consists of the outer membrane channel MlaA, the periplasmic lipid carrier MlaC, and the inner membrane transporter MlaBDEF. The opportunistic pathogen Pseudomonas aeruginosa has two proteins of the MlaA family: PA2800 and PA3239. Here, we show that PA2800 is part of a canonical Mla pathway, while PA3239 functions with the putative lipase PA3238. While loss of either pathway individually has little to no effect on outer membrane integrity, loss of both pathways weakens the outer membrane permeability barrier and increases production of the secondary metabolite pyocyanin. We propose that mislocalized glycerophospholipids are removed from the outer leaflet by PA3239 (renamed MlaZ), transferred to PA3238 (renamed MlaY), and degraded. This pathway streamlines recycling of glycerophospholipid degradation products by removing glycerophospholipids from the outer leaflet prior to degradation.
ESTHER : Guest_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2302546120
PubMedSearch : Guest_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2302546120
PubMedID: 37463202
Gene_locus related to this paper: pseae-PA3238

Title : Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea - Yang_2023_Bioorg.Chem_138_106625
Author(s) : Yang Z , Cao Z , Wang W , Chen Y , Huang W , Jiao S , Chen S , Chen L , Liu Y , Mao J , Zhang L , Li Z
Ref : Bioorg Chem , 138 :106625 , 2023
Abstract : Human carboxylesterase 2 (hCES2A), one of the most important serine hydrolases distributed in the small intestine and colon, plays a crucial role in the hydrolysis of various prodrugs and esters. Accumulating evidence has demonstrated that the inhibition of hCES2A effectively alleviate the side effects induced by some hCES2A-substrate drugs, including delayed diarrhea caused by the anticancer drug irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC(50) = 5.02 +/- 0.67 microM) and high selectivity on hCES2A. Molecular docking and molecular dynamics simulations indicated that LK-44 can formed stable hydrogen bonds with amino acids surrounding the active cavity of hCES2A. The results of inhibition kinetics studies unveiled that LK-44 inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a K(i) value of 5.28 microM. Notably, LK-44 exhibited low toxicity towards HepG2 cells according to the MTT assay. Importantly, in vivo studies showed that LK-44 significantly reduced the side effects of irinotecan-induced diarrhea. These findings suggested that LK-44 is a potent inhibitor of hCES2A with high selectivity against hCES1A, which has potential as a lead compound for the development of more effective hCES2A inhibitors to mitigate irinotecan-induced delayed diarrhea.
ESTHER : Yang_2023_Bioorg.Chem_138_106625
PubMedSearch : Yang_2023_Bioorg.Chem_138_106625
PubMedID: 37300962
Gene_locus related to this paper: human-CES2

Title : Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease - Yang_2023_Phytomedicine_109_154600
Author(s) : Yang M , Zhang X , Qiao O , Ji H , Zhang Y , Han X , Wang W , Li X , Wang J , Guo L , Huang L , Gao W
Ref : Phytomedicine , 109 :154600 , 2023
Abstract : BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A beta oligomer, inhibit the deposition of A beta, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease.
ESTHER : Yang_2023_Phytomedicine_109_154600
PubMedSearch : Yang_2023_Phytomedicine_109_154600
PubMedID: 36610144

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

Title : Crystal structures of herbicide-detoxifying esterase reveal a lid loop affecting substrate binding and activity - Liu_2023_Nat.Commun_14_4343
Author(s) : Liu B , Wang W , Qiu J , Huang X , Qiu S , Bao Y , Xu S , Ruan L , Ran T , He J
Ref : Nat Commun , 14 :4343 , 2023
Abstract : SulE, an esterase, which detoxifies a variety of sulfonylurea herbicides through de-esterification, provides an attractive approach to remove environmental sulfonylurea herbicides and develop herbicide-tolerant crops. Here, we determined the crystal structures of SulE and an activity improved mutant P44R. Structural analysis revealed that SulE is a dimer with spacious binding pocket accommodating the large sulfonylureas substrate. Particularly, SulE contains a protruding beta hairpin with a lid loop covering the active site of the other subunit of the dimer. The lid loop participates in substrate recognition and binding. P44R mutation altered the lid loop flexibility, resulting in the sulfonylurea heterocyclic ring repositioning to a relative stable conformation thus leading to dramatically increased activity. Our work provides important insights into the molecular mechanism of SulE, and establish a solid foundation for further improving the enzyme activity to various sulfonylurea herbicides through rational design.
ESTHER : Liu_2023_Nat.Commun_14_4343
PubMedSearch : Liu_2023_Nat.Commun_14_4343
PubMedID: 37468532
Gene_locus related to this paper: 9rhiz-g9i933

Title : Low concentration of indoxacarb interferes with the growth and development of silkworm by damaging the structure of midgut cells - Wang_2023_Pestic.Biochem.Physiol_195_105567
Author(s) : Wang W , Su Y , Liu X , Qi R , Li F , Li B , Sun H
Ref : Pestic Biochem Physiol , 195 :105567 , 2023
Abstract : As an important economic insect, Bombyx mori plays an essential role in the development of the agricultural economy. Indoxacarb, a novel sodium channel blocker insecticide, has been widely used for the control of various pests in agriculture and forestry, and its environmental pollution caused by flight control operations has seriously affected the safe production of sericulture in recent years. However, the lethal toxicity and adverse effects of indoxacarb on silkworm remain largely unknown. In this study, the toxicity of indoxacarb on the 5th instar larvae of silkworm was determined, with an LC(50) (72 h) of 2.07 mg/L. Short-term exposure (24 h) to a low concentration of indoxacarb (1/2 LC(50)) showed significantly reduced body weight and survival rate of silkworm larvae. In addition, indoxacarb also led to decreased cocoon weight and cocoon shell weight, but had no significant effects on pupation, adult eclosion, and oviposition. Histopathological and ultrastructural analysis indicated that indoxacarb could severely damage the structure of the midgut epithelial cells, and lead to physiological impairment of the midgut. A total of 3883 differentially expressed genes (DEGs) were identified by midgut transcriptome sequencing and functionally annotated using GO and KEGG. Furthermore, the transcription level and enzyme activity of the detoxification related genes were determined, and our results suggested that esterases (ESTs) might play a major role in metabolism of indoxacarb in the midgut of B. mori. Future studies to examine the detoxification or biotransformation function of candidate genes will greatly enhance our understanding of indoxacarb metabolism in B. mori. The results of this study provide a theoretical basis for elucidating the mechanism of toxic effects of indoxacarb on silkworm by interfering with the normal physiological functions of the midgut.
ESTHER : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedSearch : Wang_2023_Pestic.Biochem.Physiol_195_105567
PubMedID: 37666598

Title : Aflatoxin B(1) Increases Soluble Epoxide Hydrolase in the Brain and Induces Neuroinflammation and Dopaminergic Neurotoxicity - Wang_2023_Int.J.Mol.Sci_24_9938
Author(s) : Wang W , Wang Y , Wagner KM , Lee RD , Hwang SH , Morisseau C , Wulff H , Hammock BD
Ref : Int J Mol Sci , 24 :9938 , 2023
Abstract : Parkinson's disease (PD) is an increasingly common neurodegenerative movement disorder with contributing factors that are still largely unexplored and currently no effective intervention strategy. Epidemiological and pre-clinical studies support the close association between environmental toxicant exposure and PD incidence. Aflatoxin B(1) (AFB(1)), a hazardous mycotoxin commonly present in food and environment, is alarmingly high in many areas of the world. Previous evidence suggests that chronic exposure to AFB(1) leads to neurological disorders as well as cancer. However, whether and how aflatoxin B(1) contributes to the pathogenesis of PD is poorly understood. Here, oral exposure to AFB(1) is shown to induce neuroinflammation, trigger the alpha-synuclein pathology, and cause dopaminergic neurotoxicity. This was accompanied by the increased expression and enzymatic activity of soluble epoxide hydrolase (sEH) in the mouse brain. Importantly, genetic deletion or pharmacological inhibition of sEH alleviated the AFB(1)-induced neuroinflammation by reducing microglia activation and suppressing pro-inflammatory factors in the brain. Furthermore, blocking the action of sEH attenuated dopaminergic neuron dysfunction caused by AFB(1) in vivo and in vitro. Together, our findings suggest a contributing role of AFB(1) to PD etiology and highlight sEH as a potential pharmacological target for alleviating PD-related neuronal disorders caused by AFB(1) exposure.
ESTHER : Wang_2023_Int.J.Mol.Sci_24_9938
PubMedSearch : Wang_2023_Int.J.Mol.Sci_24_9938
PubMedID: 37373086

Title : Discovery of novel carboxylesterase 2 inhibitors for the treatment of delayed diarrhea and ulcerative colitis - Cao_2023_Biochem.Pharmacol__115742
Author(s) : Cao Z , Liu Y , Chen S , Wang W , Yang Z , Chen Y , Jiao S , Huang W , Chen L , Sun L , Li Z , Zhang L
Ref : Biochemical Pharmacology , :115742 , 2023
Abstract : Human carboxylesterase 2 (hCES2) is an enzyme that metabolizes irinotecan to SN-38, a toxic metabolite considered a significant source of side effects (lethal delayed diarrhea). The hCES2 inhibitors could block the hydrolysis of irinotecan in the intestine and thus reduce the exposure of intestinal SN-38, which may alleviate irinotecan-associated diarrhea. However, existing hCES2 inhibitors (except loperamide) are not used in clinical applications due to lack of validity or acceptable safety. Therefore, developing more effective and safer drugs for treating delayed diarrhea is urgently needed. This study identified a lead compound 1 with a novel scaffold by high-throughput screening in our in-house library. After a comprehensive structure-activity relationship study, the optimal compound 24 was discovered as an efficient and highly selective hCES2 inhibitor (hCES2: IC(50) = 6.72 microM; hCES1: IC(50) > 100 microM). Further enzyme kinetics study indicated that compound 24 is a reversible inhibitor of hCES2 with competitive inhibition mode (Ki = 6.28 microM). The cell experiments showed that compound 24 could reduce the level of hCES2 in living cells (IC(50) = 6.54 microM). The modeling study suggested that compound 24 fitted very well with the binding pocket of hCES2 by forming multiple interactions. Notably, compound 24 can effectively treat irinotecan-induced delayed diarrhea and DSS-induced ulcerative colitis, and its safety has also been verified in subtoxic studies. Based on the overall pharmacological and preliminary safety profiles, compound 24 is worthy of further evaluation as a novel agent for irinotecan-induced delayed diarrhea.
ESTHER : Cao_2023_Biochem.Pharmacol__115742
PubMedSearch : Cao_2023_Biochem.Pharmacol__115742
PubMedID: 37567318

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

Title : Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma - Lei_2023_Oxid.Med.Cell.Longev_2023_6811625
Author(s) : Lei K , Liang R , Tan B , Li L , Lyu Y , Wang K , Wang W , Hu X , Wu D , Lin H , Wang M
Ref : Oxid Med Cell Longev , 2023 :6811625 , 2023
Abstract : BACKGROUND: Lipid metabolism reprogramming played an important role in cancer occurrence, development, and immune regulation. The aim of this study was to identify and validate lipid metabolism-related genes (LMRGs) associated with the phenotype, prognosis, and immunological characteristics of lung squamous cell carcinoma (LUSC). METHODS: In the TCGA cohort, bioinformatics and survival analysis were used to identify lipid metabolism-related differentially expressed genes (DEGs) associated with the prognosis of LUSC. PTGIS/HRASLS knockdown and overexpression effects on the LUSC phenotype were analyzed in vitro experiments. Based on the expression distribution of PTGIS/HRASLS, LUSC patients were divided into two clusters by consensus clustering. Clinical information, prognosis, immune infiltration, expression of immune checkpoints, and tumor mutation burden (TMB) level were compared between the TCGA and GSE4573 cohorts. The genes related to clustering and tumor immunity were screened by weighted gene coexpression network analysis (WGCNA), and the target module genes were analyzed by functional enrichment analysis, protein-protein interaction (PPI) analysis, and immune correlation analysis. RESULTS: 191 lipid metabolism-related DEGs were identified, of which 5 genes were independent prognostic genes of LUSC. PTGIS/HRASLS were most closely related to LUSC prognosis and immunity. RT-qPCR, western blot (WB) analysis, and immunohistochemistry (IHC) showed that the expression of PTGIS was low in LUSC, while HRASLS was high. Functionally, PTGIS promoted LUSC proliferation, migration, and invasion, while HRASLS inhibited LUSC proliferation, migration, and invasion. The two clusters' expression and distribution of PTGIS/HRASLS had the opposite trend. Cluster 1 was associated with lower pathological staging (pT, pN, and pTNM stages), better prognosis, stronger immune infiltration, higher expression of immune checkpoints, and higher TMB level than cluster 2. WGCNA found that 28 genes including CD4 and IL10RA were related to the expression of PTGIS/HRASLS and tumor immune infiltration. PTGIS/HRASLS in the GSE4573 cohort had the same effect on LUSC prognosis and tumor immunity as the TCGA cohort. CONCLUSIONS: PTGIS and HRASLS can be used as new therapeutic targets for LUSC as well as biomarkers for prognosis and tumor immunity, which has positive significance for guiding the immunotherapy of LUSC.
ESTHER : Lei_2023_Oxid.Med.Cell.Longev_2023_6811625
PubMedSearch : Lei_2023_Oxid.Med.Cell.Longev_2023_6811625
PubMedID: 36703911

Title : Co-exposure to sodium hypochlorite and cadmium induced locomotor behavior disorder by influencing neurotransmitter secretion and cardiac function in larval zebrafish - Ma_2023_Environ.Pollut_342_123070
Author(s) : Ma L , Yang H , Xiao X , Chen Q , Lv W , Xu T , Jin Y , Wang W , Xiao Y
Ref : Environ Pollut , 342 :123070 , 2023
Abstract : Sodium hypochlorite (NaClO) and cadmium (Cd) are widely co-occurring in natural aquatic environment; however, no study has been conducted on effects of their combined exposure on aquatic organisms. To assess effects of exposure to NaClO and Cd in zebrafish larvae, we designed six treatment groups, as follows: control group, NaClO group (300 microg/L), 1/100 Cd group (48 microg/L), 1/30 Cd group (160 microg/L), NaClO+1/100 Cd group, and NaClO+1/30 Cd group analyzed behavior, neurological function and cardiac function. Results revealed that exposure to 1/30 Cd and NaClO+1/30 Cd caused abnormal embryonic development in larvae by altering body morphology and physiological indicators. Combined exposure to NaClO and 1/30 Cd affected the free-swimming activity and behavior of larvae in response to light-dark transition stimuli. Moreover, exposure to 1/30 Cd or NaClO+1/30 Cd resulted in a significant increase in tyrosine hydroxylase and acetylcholinesterase activities, as well as significant changes of various neurotransmitters. Lastly, exposure to 1/30 Cd or NaClO+1/30 Cd influenced the transcription of cardiac myosin-related genes and disturbed the myocardial contractile function. Altogether, our results suggested that combined exposure to NaClO and Cd induced oxidative damage in larvae, resulting in detrimental effects on nervous system and cardiac function, thus altering their swimming behavior.
ESTHER : Ma_2023_Environ.Pollut_342_123070
PubMedSearch : Ma_2023_Environ.Pollut_342_123070
PubMedID: 38056588

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

Title : Synthesis and Characterization of Epoxidized Silkworm Pupae Oil and Its Application as Polyvinyl Chloride - Ji_2022_Appl.Biochem.Biotechnol_194_1290
Author(s) : Ji Y , Xu L , Xu Q , Liu X , Lin S , Liao S , Wang W , Lan D
Ref : Appl Biochem Biotechnol , 194 :1290 , 2022
Abstract : More and more industries demand environmental friendliness. Silkworm pupae oil (SPO), extracted from the desilked silkworm pupae, can serve as a promising substrate alternative to use in plasticization. This study aimed to prepare epoxidized silkworm pupae oil (ESPO) and investigate their effects on the thermal stability and plasticization of polyvinyl chloride (PVC) films. A chemo-enzymatic method of ESPO was developed in the presence of Lipase SMG1-F278N and H(2)O(2) in natural deep eutectic solvents (DESs). Lipase SMG1-F278N could initiate the epoxidation reaction effectively at room temperature with a negligible loss of activities 10 batches. A maximum oxirane value of 6.94% was obtained. The formation of oxirane ring in ESPO was confirmed by FTIR and (13)C NMR spectra. Moreover, ESPO showed a better thermal stability and lower freezing point than epoxidized soybean oil (ESO). It was demonstrated that ESPO had a good frost resistance. In addition, ESPO showed a significantly improved plasticizing effect on flexible polyvinyl chloride (PVC). Compared with ESO, ESPO could increase the tensile elongation at break effectively. A significantly lower migration rate of plasticizer was observed in PVC plasticized with ESPO.
ESTHER : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedSearch : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedID: 34677760
Gene_locus related to this paper: malgo-a8puy1

Title : Association between Polymorphisms in Telomere-Associated Protein Genes and the Cholinesterase Activity of Omethoate-Exposed Workers -
Author(s) : Fan YH , Li XL , Liu XH , Guo ZF , Yan MQ , Duan XR , Miao WB , Wang W
Ref : Biomedical & Environmental Sciences , 35 :448 , 2022
PubMedID: 35676815

Title : SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice - Xiang_2022_Cell.Death.Dis_13_638
Author(s) : Xiang L , Wu Q , Sun H , Miao X , Lv Z , Liu H , Chen L , Gu Y , Chen J , Zhou S , Jiang H , Du S , Zhou Y , Dong H , Fan Y , Miao S , Lu Q , Chang L , Wang H , Lu Y , Xu X , Wang W , Huang Z
Ref : Cell Death Dis , 13 :638 , 2022
Abstract : Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD.
ESTHER : Xiang_2022_Cell.Death.Dis_13_638
PubMedSearch : Xiang_2022_Cell.Death.Dis_13_638
PubMedID: 35869039

Title : Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase - Li_2022_Molecules_27_6800
Author(s) : Li M , Dai X , Li A , Qi Q , Wang W , Cao J , Jiang Z , Liu R , Suo H , Xu L
Ref : Molecules , 27 :6800 , 2022
Abstract : Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe(3)O(4)@UiO-66-NH(2), was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe(3)O(4)@UiO-66-NH(2)) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) reached 74.4%, which was higher than that of PPL-Fe(3)O(4)@UiO-66-NH(2) (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe(3)O(4)@UiO-66-NH(2) had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe(3)O(4)@UiO-66-NH(2) modified by ionic liquids has great potential for immobilized enzymes.
ESTHER : Li_2022_Molecules_27_6800
PubMedSearch : Li_2022_Molecules_27_6800
PubMedID: 36296392

Title : Evaluation of Antioxidative and Neuroprotective Activities of Total Flavonoids From Sea Buckthorn (Hippophae rhamnoides L.) - Wang_2022_Front.Nutr_9_861097
Author(s) : Wang Z , Wang W , Zhu C , Gao X , Chu W
Ref : Front Nutr , 9 :861097 , 2022
Abstract : The aim of this study was to investigate the antioxidative and neuroprotective activities of total flavonoids from sea buckthorn (Hippophae rhamnoides L.) (TFH). Results indicated that TFH possessed DPPH radicals, hydroxyl radicals and superoxide anions scavenging activities. The neuroprotective potential was assessed with acetylcholinesterase (AChE) and monoamine oxidase A (MAO-A). The inhibition rates of AChE and MAO-A by 50 microg/ml TFH were 75.85 and 51.22%, respectively. The in vivo antioxidative and neuroprotective potential of TFH were explored in Caenorhabditis elegans. In the longevity assay, TFH (50 microg/ml) significantly increased the lifespan of wild-type C. elegans (29.40%). In the hydrogen peroxide-induced oxidative stress challenge, the antioxidant capacity of TFH-treated wild-type C. elegans was significantly enhanced. The C. elegans mutant strain CL4176 was used to study the neuroprotective effect of TFH in vivo. Results showed that TFH significantly delayed paralysis in C. elegans CL4176. Our study suggested total flavonoids from sea buckthorn (Hippophae rhamnoides L.) had the potential as an antioxidative and neuroprotective agent to extend aging and treat neurodegenerative diseases.
ESTHER : Wang_2022_Front.Nutr_9_861097
PubMedSearch : Wang_2022_Front.Nutr_9_861097
PubMedID: 35799585

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

Title : Effect of thiamethoxam on the behavioral profile alteration and toxicity of adult zebrafish at environmentally relevant concentrations - Yang_2022_Sci.Total.Environ_858_159883
Author(s) : Yang J , Guo C , Luo Y , Fan J , Wang W , Yin X , Xu J
Ref : Sci Total Environ , 858 :159883 , 2022
Abstract : Thiamethoxam (THM) is a commercial neonicotinoid insecticide with broad-spectrum insecticidal activity. It has been widely detected in the aquatic environment, but its behavioral toxicity on aquatic organisms received limited attention. In this study, adult zebrafish were exposed to THM at three levels (0.1, 10, and 1000 g/L) for 45 days to investigate its effect on their ecological behavior, histopathology, bioaccumulation, and stress response. The bioconcentration factor in zebrafish brain was significantly higher (p < 0.05) at low concentration of THM (0.1 g/L) than in other treatment groups. In terms of individual behavior, the locomotor activity, aggregation, and social activity of fish were enhanced after THM exposure, but the memory of the food zone was disturbed and abnormal swimming behavior was observed. THM exposure caused brain tissue necrosis, erythrocyte infiltration, cloudy swelling, and other pathological changes in brain tissue and affected the concentrations of acetylcholinesterase and cortisol related to neurotoxicity. The condition factor and organ coefficients (brain, heart, and intestine) of zebrafish were markedly impacted by THM treatment at 0.1 and 1000 g/L, respectively. This finding showed that THM was more harmful to fish behavior than lethality, reproduction, and growth, and a behavioral study can be a useful tool for ecological risk assessment.
ESTHER : Yang_2022_Sci.Total.Environ_858_159883
PubMedSearch : Yang_2022_Sci.Total.Environ_858_159883
PubMedID: 36356732

Title : Hydrolysis Mechanism of Carbamate Methomyl by a Novel Esterase PestE: A QM\/MM Approach - Wang_2022_Int.J.Mol.Sci_24_
Author(s) : Wang Z , Zhang Q , Wang G , Wang W , Wang Q
Ref : Int J Mol Sci , 24 : , 2022
Abstract : Methomyl is one of the most important carbamates that has caused potential hazardous effects on both human beings and the environment. Here, we systematically investigated the hydrolysis mechanism of methomyl catalyzed by esterase PestE using molecular dynamics simulations (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. The hydrolysis mechanism involves two elementary steps: () serine-initiated nucleophilic attack and () C-O bond cleavage. Our work elicits the atomic level details of the hydrolysis mechanism and free energy profiles along the reaction pathway. The Boltzmann-weighted average potential barriers are 19.1 kcal/mol and 7.5 kcal/mol for steps and , respectively. We identified serine-initiated nucleophilic attack as the rate determining-step. The deep learning-based k(cat) prediction model indicated that the barrier of the rate-determining step is 15.4 kcal/mol, which is in good agreement with the calculated results using Boltzmann-weighted average method. We have elucidated the importance of the protein-substrate interactions and the roles of the key active site residues during the hydrolysis process through noncovalent interactions analysis and electrostatic potential (ESP) analysis. The results provide practical value for achieving efficient degradation of carbamates by hydrolases.
ESTHER : Wang_2022_Int.J.Mol.Sci_24_
PubMedSearch : Wang_2022_Int.J.Mol.Sci_24_
PubMedID: 36613879

Title : Aflatoxin B(1) exposure disrupts the intestinal immune function via a soluble epoxide hydrolase-mediated manner - Wang_2022_Ecotoxicol.Environ.Saf_249_114417
Author(s) : Wang W , Wang Y , Yang J , Wagner KM , Hwang SH , Cheng J , Singh N , Edwards P , Morisseau C , Zhang G , Panigrahy D , Hammock BD
Ref : Ecotoxicology & Environmental Safety , 249 :114417 , 2022
Abstract : Aflatoxin B(1) (AFB(1)) contamination in food and feed leads to severe global health problems. Acting as the frontier immunological barrier, the intestinal mucosa is constantly challenged by exposure to foodborne toxins such as AFB(1) via contaminated diets, but the detailed toxic mechanism and endogenous regulators of AFB(1) toxicity are still unclear. Here, we showed that AFB(1) disrupted intestinal immune function by suppressing macrophages, especially M2 macrophages, and antimicrobial peptide-secreting Paneth cells. Using an oxylipinomics approach, we identified that AFB(1) immunotoxicity is associated with decreased epoxy fatty acids, notably epoxyeicosatrienoic acids, and increased soluble epoxide hydrolase (sEH) levels in the intestine. Furthermore, sEH deficiency or inhibition rescued the AFB(1)-compromised intestinal immunity by restoring M2 macrophages as well as Paneth cells and their-derived lysozyme and alpha-defensin-3 in mice. Altogether, our study demonstrates that AFB(1) exposure impairs intestinal immunity, at least in part, in a sEH-mediated way. Moreover, the present study supports the potential application of pharmacological intervention by inhibiting the sEH enzyme in alleviating intestinal immunotoxicity and associated complications caused by AFB(1) global contamination.
ESTHER : Wang_2022_Ecotoxicol.Environ.Saf_249_114417
PubMedSearch : Wang_2022_Ecotoxicol.Environ.Saf_249_114417
PubMedID: 36525946

Title : PRDX6: A protein bridging S-palmitoylation and diabetic neuropathy - Cao_2022_Front.Endocrinol.(Lausanne)_13_992875
Author(s) : Cao Y , Wang W , Zhan X , Zhang Y
Ref : Front Endocrinol (Lausanne) , 13 :992875 , 2022
Abstract : Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes. It can affect both the peripheral and central nervous systems, leading to pain, decreased motility, cognitive decline, and dementia. S-palmitoylation is a reversible posttranslational lipid modification, and its dysregulation has been implicated in metabolic syndrome, cancers, neurological disorders, and infections. However, the role of S-palmitoylation in diabetic neuropathy remains unclear. Here we demonstrate a potential association between activating protein palmitoylation and diabetic neuropathy. We compared the proteomic data of lumbar dorsal root ganglia (DRG) of diabetes mice and palmitoylome profiling data of the HUVEC cell line. The mapping results identified peroxiredoxin-6 (PRDX6) as a novel target in diabetic neuropathy, whose biological mechanism was associated with S-palmitoylation. Bioinformatic prediction revealed that PRDX6 had two palmitoylation sites, Cys47 and Cys91. Immunofluorescence results indicated PRDX6 translocating between the cytoplasm and cell membrane. Protein function analysis proposed that increased palmitoylation could competitively inhibit the formation of disulfide-bond between Cys47 and Cys91 and change the spatial topology of PRDX6 protein. Cl(-)HCO3(-) anion exchanger 3 (AE3) was one of the AE family members, which was proved to express in DRG. AE3 activity evoked Cl(-) influx in neurons which was generally associated with increased excitability and susceptibility to pain. We demonstrated that the S-palmitoylation status of Cys47 could affect the interaction between PRDX6 and the C-terminal domain of AE3, thereby regulating the activity of AE3 anion exchanger enzyme in the nervous system. The results highlight a central role for PRDX6 palmitoylation in protection against diabetic neuropathy.
ESTHER : Cao_2022_Front.Endocrinol.(Lausanne)_13_992875
PubMedSearch : Cao_2022_Front.Endocrinol.(Lausanne)_13_992875
PubMedID: 36120430

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

Title : Analysis of transcript-wide profile regulated by microsatellite instability of colorectal cancer - Xu_2022_Ann.Transl.Med_10_169
Author(s) : Xu Y , Wang X , Chu Y , Li J , Wang W , Hu X , Zhou F , Zhang H , Zhou L , Kuai R , Jin Y , Yang D , Peng H
Ref : Ann Transl Med , 10 :169 , 2022
Abstract : BACKGROUND: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. METHODS: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). RESULTS: A total of 237 significantly differentially expressed genes (P(adj)<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. CONCLUSIONS: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
ESTHER : Xu_2022_Ann.Transl.Med_10_169
PubMedSearch : Xu_2022_Ann.Transl.Med_10_169
PubMedID: 35280417

Title : An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase - Zhao_2022_EMBO.Rep__e52669
Author(s) : Zhao X , Wang W , Yao Y , Li X , Huang X , Wang Y , Ding M
Ref : EMBO Rep , :e52669 , 2022
Abstract : The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high-fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet-resident protein Plin2 and the RDH/CG2064-Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH-Plin2 axis modulates lipid droplet size.
ESTHER : Zhao_2022_EMBO.Rep__e52669
PubMedSearch : Zhao_2022_EMBO.Rep__e52669
PubMedID: 35132760

Title : Monoacylglycerol lipase from marine Geobacillus sp. showing lysophospholipase activity and its application in efficient soybean oil degumming - Liu_2022_Food.Chem_406_134506
Author(s) : Liu X , Wang W , Zhao Z , Xu L , Yang B , Lan D , Wang Y
Ref : Food Chem , 406 :134506 , 2022
Abstract : Enzymatic degumming is an essential refining process to improve oil quality. In this study, a monoacylglycerol lipase GMGL was derived from marine Geobacillus sp., and was found that not only took monoacylglycerol (MAG) as substrate, but also had activity toward lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and glycerolphosphatidylcholine (GPC). Binding free energy showed LPC and LPE could bind with enzyme stably as MAG. It presented great potential in the field of enzymatic degumming. The phosphorus content in crude soybean oil decreased from 680.50 to 2.01 mg/kg and the yield of oil reached to 98.80 % after treating with phospholipase A1 (Lecitase Ultra) combined with lipase GMGL. An ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was developed to identify 21 differential phospholipids between crude soybean oil and enzymatic treatment. This work might shed some light on understanding the catalytic mechanism of monoacylglycerol lipase and provide an effective strategy for enzymatic degumming.
ESTHER : Liu_2022_Food.Chem_406_134506
PubMedSearch : Liu_2022_Food.Chem_406_134506
PubMedID: 36463594

Title : Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities - Zang_2021_Molecules_26_
Author(s) : Zang Y , Liu K , Wang W , Li C , Ma J , Yang J , Chen X , Wang X , Zhang D
Ref : Molecules , 26 : , 2021
Abstract : The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC(50)) 1.63-4.62 microM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
ESTHER : Zang_2021_Molecules_26_
PubMedSearch : Zang_2021_Molecules_26_
PubMedID: 33671020

Title : Improving the catalytic efficiency and substrate affinity of a novel esterase from marine Klebsiella aerogenes by random and site-directed mutation - Gao_2021_World.J.Microbiol.Biotechnol_37_106
Author(s) : Gao H , Zhu R , Li Z , Wang W , Liu Z , Hu N
Ref : World J Microbiol Biotechnol , 37 :106 , 2021
Abstract : A novel esterase (EstKa) from marine Klebsiella aerogenes was characterized with hydrolytic activity against p-nitrophenyl caprylate (pNPC, C(8)) under optimum conditions (50 degreesC and pH 8.5). After two rounds of mutagenesis, two highly potential mutants (I6E9 and L7B11) were obtained with prominent activity, substrate affinity and thermostability. I6E9 (L90Q/P96T) and L7B11 (A37S/Q100L/S133G/R138C/Q156R) were 1.56- and 1.65-fold higher than EstKa in relative catalytic efficiency. The influence of each amino acid on enzyme activity was explored by site-directed mutation. The mutants Pro96Thr and Gln156Arg showed 1.29- and 1.48-fold increase in catalytic efficiency (Kcat/Km) and 54.4 and 36.2% decrease in substrate affinity (Km), respectively. The compound mutant Pro96Thr/Gln156Arg exhibited 68.9% decrease in Km and 1.41-fold increase in Kcat/Km relative to EstKa. Homology model structure analysis revealed that the replacement of Gln by hydrophilic Arg on the esterase surface improved the microenvironment stability and the activity. The replacement of Pro by Thr enabled the esterase enzyme to retain 90% relative activity after 3 h incubation at 45 degreesC. Structural analysis confirmed that the formation of a hydrogen bond leads to a notable increase of catalytic efficiency under high temperature conditions.
ESTHER : Gao_2021_World.J.Microbiol.Biotechnol_37_106
PubMedSearch : Gao_2021_World.J.Microbiol.Biotechnol_37_106
PubMedID: 34037848

Title : Structure and biomolecular recognition of nitro-BODIPY-andrographolide assembles for cancer treatment - Ali_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_263_120180
Author(s) : Ali AM , Wang W , Chen QY
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 263 :120180 , 2021
Abstract : Andrographolide (Andro) derivatives can interfere with a variety of enzymes. To increase the cancer cell absorption of Andro and to enhance the therapeutic effect of breast cancer, nitro group substituted boron dipyrromethene (NBDP) was used as the carrier of Andro. Two NBDP based assemblies (NBDP-Andro and nano NBDPAndro@PEG) were synthesized and characterized by spectroscopic methods. The affinity of Andro with NBDP enhanced the emission of NBDP. The interaction of the compounds with lipase was also studied. NBDP-Andro can bind with lipase and form new species with an emission at 360 nm. Results demonstrate that the Andro of NBDP-Andro drives the interaction of compounds with protein (BSA) and lipase by inter-molecular forces. The large red shift emission at 611 nm of the NBDPAndro@PEG is observed and discussed. Also, the MTT assay confirms that Nano NBDPAndro@PEG can enhance the inhibition rate of the proliferation of MCF-7 breast cancer cells. Therefore, nitro substituted BODIPY can be a carrier of andrographolide for cancer treatment.
ESTHER : Ali_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_263_120180
PubMedSearch : Ali_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_263_120180
PubMedID: 34303221

Title : Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice - Tian_2021_Neurochem.Int_150_105197
Author(s) : Tian Y , Yuan X , Wang Y , Wu Q , Fang Y , Zhu Z , Song G , Xu L , Wang W , Xie M
Ref : Neurochem Int , 150 :105197 , 2021
Abstract : Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH.
ESTHER : Tian_2021_Neurochem.Int_150_105197
PubMedSearch : Tian_2021_Neurochem.Int_150_105197
PubMedID: 34592333

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
Gene_locus related to this paper: malgo-a8puy1

Title : NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation - Zhao_2021_J.Orthop.Surg.Res_16_364
Author(s) : Zhao T , Meng Y , Wang Y , Wang W
Ref : J Orthop Surg Res , 16 :364 , 2021
Abstract : BACKGROUND: Cancer stem cells (CSCs) are mainly contributed to malignancy metastatic potential and resistant therapy of osteosarcoma (OS). The mitochondria-related apoptosis was generally accepted as the target of tumor therapy. However, the effect of N-myc downstream-regulated gene 1 (NDRG1) on CSCs and mitochondrial health in OS is still unknown. METHODS: In OS cells, MG63 and U2OS, the siRNA of NDRG1 were conducted. Transwell, western blot, RT-qPCR, and mitochondria isolation were used to identify the effect of NDRG on OS cells and mitochondria. Moreover, the differentiation-related factors of CSCs were determined. RESULTS: After downregulation of NDRG1, the cell viability, invasion ability decreased whereas cell apoptosis increased. The expressions profiles of fibronectin, vimentin, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP) 2, MMP9, and MMP13 were downregulated, but E-cadherin expression level was upregulated by NDRG1 siRNA. At the same time, cytochrome (Cyt) C levels were increased in cytosol with the decreasing in mitochondria after siRNA treatment. The mitochondrial membrane potential (MMPs) was declined, and the function of mitochondria was impeded. The expressions of uncoupling proteins (UCP) 2, voltage dependent anion channel (VDAC), peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha, and cyclooxygenase (COX) 2 were downregulated by NDRG1 silencing. Moreover, NDRG performed its function primarily through the Wnt pathway and could regulate the differentiation of osteosarcoma stem cells. CONCLUSION: Silencing of NDRG1 could damage the function of mitochondria, promote the CSCs differentiation, alleviating OS progression.
ESTHER : Zhao_2021_J.Orthop.Surg.Res_16_364
PubMedSearch : Zhao_2021_J.Orthop.Surg.Res_16_364
PubMedID: 34099022

Title : Plasma cholinesterase activity is influenced by interactive effect between omethoate exposure and CYP2E1 polymorphisms - Wang_2021_J.Environ.Sci.Health.B__1
Author(s) : Wang T , Zhang H , Li L , Zhang W , Wang Q , Wang W
Ref : J Environ Sci Health B , :1 , 2021
Abstract : The aim of this study was to explore the association between metabolizing enzyme gene polymorphisms and the decrease in cholinesterase activity induced by omethoate exposure. A total of 180 workers exposed to omethoate over an extended period were recruited along with 115 healthy controls. Cholinesterase activity in whole blood, erythrocyte, and plasma was detected using acetylthiocholine and the dithio-bis-(nitrobenzoic acid) method. Six polymorphic loci of GSTT1(+/-), GSTM1(+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867, and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The gene-environment interactions were analyzed using the generalized linear model method. The cholinesterase activity of erythrocyte and plasma in the exposure group was significantly lower than that in the control group (P < 0.001) in general. The plasma cholinesterase activity in the TT + AT genotype in CYP2E1 rs6413432 was lower than that in the AA genotype in the exposure group (P = 0.016). Interaction between the AA genotype in CYP2E1 rs6413432 and omethoate exposure had a significant effect on plasma cholinesterase activity (P = 0.079). The decrease in plasma cholinesterase activity was associated with interaction between the AA genotypes in rs6413432 and omethoate exposure.
ESTHER : Wang_2021_J.Environ.Sci.Health.B__1
PubMedSearch : Wang_2021_J.Environ.Sci.Health.B__1
PubMedID: 33872129

Title : Protective effects of pretreatment with Fe(2+), Cu(2+), and Rb(+) on phoxim poisoning in silkworm, Bombyx mori - Guo_2021_J.Trace.Elem.Med.Biol_68_126844
Author(s) : Guo J , Wang X , Wang W , Jia L , Guo W , Wu G
Ref : J Trace Elem Med Biol , 68 :126844 , 2021
Abstract : BACKGROUND: Phoxim is a widely used organophosphorus pesticide in agriculture. People are paying more and more attention to its toxicity. At present, there is no appropriate way to solve the phoxim poisoning of silkworm, which severely affected the development of sericulture. Fe(2+), Cu(2+), Rb(+) exerted their biological effects through various forms in vivo. METHODS: To evaluate the effect of Fe(2+)/Cu(2+)/Rb(+) on phoxim poisoning in silkworm, Bombyx mori were treated with fresh mulberry leaves soaked in 2.5 mg/L phoxim for 2 min with 50 mg/L FeCl(2), 150 mg/L CuCl(2), or 0.5 mg/L RbCl from 5 days of the fifth-instar silkworm. RESULTS: Fe(2+), Cu(2+), and Rb(+) pretreatments significantly inhibited the phoxim-induced reduction of survival rate and alleviated the phoxim-induced poisoning symptoms. The protective effects of Fe(2+), Cu(2+), and Rb(+) on phoxim poisoning might be due to their enhancement of superoxide dismutase (SOD), catalase (CAT), and carboxylesterase (CarE) in the hemolymph and fat body of silkworm. This enhancement might reduce reactive oxygen species (ROS) accumulation and oxidative stress (OS) caused by phoxim poisoning. Thereby it reduced the damage to silkworm tissues and cells. CONCLUSIONS: These results showed that Fe(2+), Cu(2+), and Rb(+) treatments protected the silkworm from phoxim poisoning by directly enhancing the activity of SOD, CAT, and CarE enzymes and reducing oxidative stress, but not dependent on the high expression of CYP genes. The use of Fe(2+), Cu(2+), and Rb(+) to enhance the activity of SOD, CAT, and CarE enzymes may be an underlying effective way to solve phoxim poisoning in the silkworm industry.
ESTHER : Guo_2021_J.Trace.Elem.Med.Biol_68_126844
PubMedSearch : Guo_2021_J.Trace.Elem.Med.Biol_68_126844
PubMedID: 34425455

Title : Tracing the genetic footprints of vertebrate landing in non-teleost ray-finned fishes - Bi_2021_Cell_184_1377
Author(s) : Bi X , Wang K , Yang L , Pan H , Jiang H , Wei Q , Fang M , Yu H , Zhu C , Cai Y , He Y , Gan X , Zeng H , Yu D , Zhu Y , Qiu Q , Yang H , Zhang YE , Wang W , Zhu M , He S , Zhang G
Ref : Cell , 184 :1377 , 2021
Abstract : Rich fossil evidence suggests that many traits and functions related to terrestrial evolution were present long before the ancestor of lobe- and ray-finned fishes. Here, we present genome sequences of the bichir, paddlefish, bowfin, and alligator gar, covering all major early divergent lineages of ray-finned fishes. Our analyses show that these species exhibit many mosaic genomic features of lobe- and ray-finned fishes. In particular, many regulatory elements for limb development are present in these fishes, supporting the hypothesis that the relevant ancestral regulation networks emerged before the origin of tetrapods. Transcriptome analyses confirm the homology between the lung and swim bladder and reveal the presence of functional lung-related genes in early ray-finned fishes. Furthermore, we functionally validate the essential role of a jawed vertebrate highly conserved element for cardiovascular development. Our results imply the ancestors of jawed vertebrates already had the potential gene networks for cardio-respiratory systems supporting air breathing.
ESTHER : Bi_2021_Cell_184_1377
PubMedSearch : Bi_2021_Cell_184_1377
PubMedID: 33545088
Gene_locus related to this paper: atrsp-a0a8j7tiu5

Title : Protection studies of an excretory-secretory protein HcABHD against Haemonchus contortus infection - Lu_2021_Vet.Res_52_3
Author(s) : Lu M , Tian X , Zhang Y , Wang W , Tian AL , Aimulajiang K , Liu L , Li C , Yan R , Xu L , Song X , Li X
Ref : Vet Res , 52 :3 , 2021
Abstract : Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus alpha/beta-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory-secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus.
ESTHER : Lu_2021_Vet.Res_52_3
PubMedSearch : Lu_2021_Vet.Res_52_3
PubMedID: 33407892
Gene_locus related to this paper: haeco-CDJ88804

Title : [Serum C-reactive protein, cholinesterase and prealbumin are correlated with prognosis of severe coronavirus disease 2019 patients] - Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
Author(s) : Wang H , Hu L , Bai GQ , Liu Z , Yu GG , Wang W , Sun L
Ref : Zhonghua Nei Ke Za Zhi , 60 :134 , 2021
Abstract : Objective: To retrospectively analyze the relationship between serum C-reactive protein (CRP), serum cholinesterase (ChE), prealbumin (PA) and mortality in severe patients with coronavirus disease 2019 (COVID-19). Methods: During the period from January 29 to March 30, 2020, a total of 344 COVID-19 patients were admitted to west branch of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. One-hundred and ninety-two patients were diagnosed with common type and excluded, and 34 patients were transferred to LeiShenShan or other medical units. The remaining 118 patients were severe cases, and 18 cases were excluded due to incomplete data. A total of 100 severe COVID-19 patients were finally collected. According to the outcome, the patients were divided into death group (37 cases) and survival group(63 cases), and the levels of serum CRP, ChE and PA were compared. Statistical analysis were performed by SPSS25.0. Results: There were 53 male patients in this study. The level of CRP in death group was significantly more elevated compare to the survival group [(95.72+/-39.56) mg/L vs. (22.21+/-20.75) mg/L, P<0.01]. On the contrary, serum ChE in death group was remarkably decreased [(5 082+/-1 566) U/L vs. (7 075+/-1 680) U/L, P<0.01]. Also, serum PA in death group was significantly lower [(86.18+/-47.94) mg/L vs. (167.40+/-57.82) mg/L, P<0.01]. Univariate analysis showed that CRP and PA had an impact on the survival of critical patients, but multivariate Cox regression analysis suggested that CRP was the independent factor affecting the survival of critical patients. Conclusions: CRP is generally elevated in severe patients with COVID-19, and serum ChE and PA accordingly decrease. CRP and PA have influence on patients' survival, but only CRP demonstrates predictive value for prognosis in critical patients with COVID-19.
ESTHER : Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
PubMedSearch : Wang_2021_Zhonghua.Nei.Ke.Za.Zhi_60_134
PubMedID: 33503724

Title : A Valuable Product of Microbial Cell Factories: Microbial Lipase - Yao_2021_Front.Microbiol_12_743377
Author(s) : Yao W , Liu K , Liu H , Jiang Y , Wang R , Wang W , Wang T
Ref : Front Microbiol , 12 :743377 , 2021
Abstract : As a powerful factory, microbial cells produce a variety of enzymes, such as lipase. Lipase has a wide range of actions and participates in multiple reactions, and they can catalyze the hydrolysis of triacylglycerol into its component free fatty acids and glycerol backbone. Lipase exists widely in nature, most prominently in plants, animals and microorganisms, among which microorganisms are the most important source of lipase. Microbial lipases have been adapted for numerous industrial applications due to their substrate specificity, heterogeneous patterns of expression and versatility (i.e., capacity to catalyze reactions at the extremes of pH and temperature as well as in the presence of metal ions and organic solvents). Now they have been introduced into applications involving the production and processing of food, pharmaceutics, paper making, detergents, biodiesel fuels, and so on. In this mini-review, we will focus on the most up-to-date research on microbial lipases and their commercial and industrial applications. We will also discuss and predict future applications of these important technologies.
ESTHER : Yao_2021_Front.Microbiol_12_743377
PubMedSearch : Yao_2021_Front.Microbiol_12_743377
PubMedID: 34616387

Title : Ric8 acts as a regulator of G-protein signaling required for nematode-trapping lifecycle of Arthrobotrys oligospora - Bai_2021_Environ.Microbiol__
Author(s) : Bai N , Zhang G , Wang W , Feng H , Yang X , Zheng Y , Yang L , Xie M , Zhang KQ , Yang J
Ref : Environ Microbiol , : , 2021
Abstract : Resistance to inhibitors of cholinesterase 8 (Ric8) is a conserved guanine nucleotide exchange factor that is involved in the regulation of G-protein signaling in filamentous fungi. Here, we characterized an orthologous Ric8 (AoRic8) in Arthrobotrys oligospora by multi-omics analyses. The Aoric8 deletion (deltaAoric8) mutants lost an ability to produce traps essential for nematode predation, accompanied by a marked reduction in cAMP level. Yeast two-hybrid assay revealed that AoRic8 interacted with G-protein subunit Galpha1. Moreover, the mutants were compromised in mycelia growth, conidiation, stress resistance, endocytosis, cellular components, and intrahyphal hyphae. Revealed by transcriptomic analysis differentially upregulated genes in the absence of Aoric8 were involved in cell cycle, DNA replication, and recombination during trap formation while downregulated genes were primarily involved in organelles, carbohydrate metabolism, and amino acid metabolism. Metabolomic analysis showed that many compounds were markedly downregulated in deltaAoric8 mutants versus the wild-type strain. Our results demonstrated a crucial role for AoRic8 in the fungal growth, environmental adaption, and nematode predation through control of cell cycle, organelle, and secondary metabolism by G-protein signaling. This article is protected by copyright. All rights reserved.
ESTHER : Bai_2021_Environ.Microbiol__
PubMedSearch : Bai_2021_Environ.Microbiol__
PubMedID: 34431203

Title : Chemical Constituents and their Antioxidant, Anti-Inflammatory and Anti-Acetylcholinesterase Activities from Pholidota cantonensis - Liu_2021_Plant.Foods.Hum.Nutr_76_105
Author(s) : Liu L , Zou M , Zeng K , Ye X , Wang R , Wang W , Zhang X
Ref : Plant Foods Hum Nutr , 76 :105 , 2021
Abstract : Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC(50) = 0.72 +/- 0.08 microM) than the positive control quercetin (IC(50) = 12.94 +/- 0.08 microM). Compound 13 also had a higher inhibitory rate (99.59 +/- 0.43%) on AChE than that of the positive control galantamine (78.32 +/- 1.16%) at the concentrate of 50 microg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs.
ESTHER : Liu_2021_Plant.Foods.Hum.Nutr_76_105
PubMedSearch : Liu_2021_Plant.Foods.Hum.Nutr_76_105
PubMedID: 33620638

Title : Kinetics-Driven Drug Design Strategy for Next-Generation Acetylcholinesterase Inhibitors to Clinical Candidate - Zhou_2021_J.Med.Chem_64_1844
Author(s) : Zhou Y , Fu Y , Yin W , Li J , Wang W , Bai F , Xu S , Gong Q , Peng T , Hong Y , Zhang D , Liu Q , Xu Y , Xu HE , Zhang H , Jiang H , Liu H
Ref : Journal of Medicinal Chemistry , 64 :1844 , 2021
Abstract : The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.
ESTHER : Zhou_2021_J.Med.Chem_64_1844
PubMedSearch : Zhou_2021_J.Med.Chem_64_1844
PubMedID: 33570950
Gene_locus related to this paper: human-ACHE

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

Title : Carboxylesterases from bacterial enrichment culture degrade strobilurin fungicides - Wang_2021_Sci.Total.Environ__152751
Author(s) : Wang W , Zhao Z , Yan H , Zhang H , Li QX , Liu X
Ref : Sci Total Environ , :152751 , 2021
Abstract : Strobilurin fungicides are a class of persistent fungicides frequently detected in the environment. Microbes can effectively degrade strobilurins, but the mechanisms are complex and diverse. Compared with isolated strains, bacterial consortia are more robust in terms of the degradation of multiple pollutants. The enrichment culture XS19 is a group of bacterial strains enriched from soil and degrades six strobilurins at 50 mg/L within 8 d, including azoxystrobin, picoxystrobin, trifloxystrobin, kresoxim-methyl, pyraclostrobin and enestroburin. LC-Q-TOF-MS analysis confirmed that XS19 can demethylate these strobilurins via hydrolysis of the methyl ester group. Analysis of the bacterial communities suggested that Pseudomonas (69.8%), Sphingobacterium (21.2%), Delftia (6.3%), and Achromobacter (1.6%) spp. were highly associated with the removal of strobilurins in the system. Metagenomics-based comprehensive analysis of XS19 suggested that carboxylesterases in Pseudomonas and Sphingobacterium play a central role in the catabolism of strobilurins. Moreover, the carboxylesterase inhibitor bis-p-nitrophenyl phosphate inhibited the degradation activity of strobilurins in XS19. This work proved that XS19 or carboxylesterases can effectively hydrolyze strobilurins, providing a reliable bioremediation paradigm.
ESTHER : Wang_2021_Sci.Total.Environ__152751
PubMedSearch : Wang_2021_Sci.Total.Environ__152751
PubMedID: 34979227

Title : A GRN Autocrine-Dependent FAM135B\/AKT\/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression - Dong_2021_Cancer.Res_81_910
Author(s) : Dong D , Zhang W , Xiao W , Wu Q , Cao Y , Gao X , Huang L , Wang Y , Chen J , Wang W , Zhan Q
Ref : Cancer Research , 81 :910 , 2021
Abstract : Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B (FAM135B) was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo, likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. Patients with ESCC with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for patients with ESCC. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. In addition, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for patients with ESCC. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC. SIGNIFICANCE: These findings investigate the mechanisms of FAM135B in promoting ESCC progression and suggest new potential prognostic biomarkers and therapeutic targets in patients with ESCC.
ESTHER : Dong_2021_Cancer.Res_81_910
PubMedSearch : Dong_2021_Cancer.Res_81_910
PubMedID: 33323378
Gene_locus related to this paper: human-FAM135B

Title : Clinical significance of EPHX2 deregulation in prostate cancer - Liu_2021_Asian.J.Androl_23_109
Author(s) : Liu MS , Zhao H , Xu CX , Xie PB , Wang W , Yang YY , Lee WH , Jin Y , Zhou HQ
Ref : Asian J Androl , 23 :109 , 2021
Abstract : The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.
ESTHER : Liu_2021_Asian.J.Androl_23_109
PubMedSearch : Liu_2021_Asian.J.Androl_23_109
PubMedID: 32687069

Title : Pyrethroid Carboxylesterase PytH from Sphingobium faniae JZ-2: Structure and Catalytic Mechanism - Xu_2020_Appl.Environ.Microbiol_86_e02971
Author(s) : Xu D , Gao Y , Sun B , Ran T , Zeng L , He J , Wang W
Ref : Applied Environmental Microbiology , 86 :e02971 , 2020
Abstract : Carboxylesterase PytH, isolated from a pyrethroid degrading bacterium Sphingobium faniae JZ-2, could rapidly hydrolyze the ester bond of a wide range of pyrethroid pesticides, including permethrin, fenpropathrin, cypermethrin, fenvalerate, deltamethrin, cyhalothrin and bifenthrin. To elucidate the catalytic mechanism of PytH, here we report the crystal structures of PytH with bifenthrin (BIF) and phenylmethylsulfonyl fluoride (PMSF) and two PytH mutants. Though PytH shares low sequence identity with reported alpha/beta-hydrolase fold proteins, the typical triad catalytic center with Ser-His-Asp triad (Ser78, His230 and Asp202) is present and vital for the hydrolase activity. However, no contact was found between Ser78 and His230 in the structures we solved, which may be due to the fact that the PytH structures we determined are in their inactive or low activity forms. The structure of PytH is composed of a core domain and a lid domain; some hydrophobic amino acid residues surrounding the substrate from both domains form a deeper and wider hydrophobic pocket than its homologous structures. This indicates that the larger hydrophobic pocket makes PytH fit for its larger substrates binding; both lid and core domains are involved in substrate binding and the lid domain induced core domain movement may make the active center correctly positioned with substrates.IMPORTANCE Pyrethroid pesticides are widely applied in agriculture and household, however, extensive use of these pesticides also causes serious environmental and health problems. The hydrolysis of pyrethroids by carboxylesterases is the major pathway of microbial degradation of pyrethroids, but the structure of carboxylesterases and its catalytic mechanism are still unknown. Carboxylesterase PytH from Sphingobium faniae JZ-2 could effectively hydrolyze a wide range of pyrethroid pesticides. The crystal structures of PytH are solved in this study. It showed that it belongs to the alpha/beta-hydrolase fold proteins with typical catalytic Ser-His-Asp triad though PytH has a low sequence identity (about 20%) with them. The special large hydrophobic binding pocket endowed PytH binding bigger pyrethroids family substrates. Our structures shed light on the substrate selectivity and the future application of PytH and deeper the understanding of alpha/beta-hydrolase members.
ESTHER : Xu_2020_Appl.Environ.Microbiol_86_e02971
PubMedSearch : Xu_2020_Appl.Environ.Microbiol_86_e02971
PubMedID: 32303545
Gene_locus related to this paper: sphwj-c0la90

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

Title : Soluble epoxide hydrolase is an endogenous regulator of obesity-induced intestinal barrier dysfunction and bacterial translocation - Wang_2020_Proc.Natl.Acad.Sci.U.S.A_117_8431
Author(s) : Wang Y , Yang J , Wang W , Sanidad KZ , Cinelli MA , Wan D , Hwang SH , Kim D , Lee KSS , Xiao H , Hammock BD , Zhang G
Ref : Proc Natl Acad Sci U S A , 117 :8431 , 2020
Abstract : Intestinal barrier dysfunction, which leads to translocation of bacteria or toxic bacterial products from the gut into bloodstream and results in systemic inflammation, is a key pathogenic factor in many human diseases. However, the molecular mechanisms leading to intestinal barrier defects are not well understood, and there are currently no available therapeutic approaches to target intestinal barrier function. Here we show that soluble epoxide hydrolase (sEH) is an endogenous regulator of obesity-induced intestinal barrier dysfunction. We find that sEH is overexpressed in the colons of obese mice. In addition, pharmacologic inhibition or genetic ablation of sEH abolishes obesity-induced gut leakage, translocation of endotoxin lipopolysaccharide or bacteria, and bacterial invasion-induced adipose inflammation. Furthermore, systematic treatment with sEH-produced lipid metabolites, dihydroxyeicosatrienoic acids, induces bacterial translocation and colonic inflammation in mice. The actions of sEH are mediated by gut bacteria-dependent mechanisms, since inhibition or genetic ablation of sEH fails to attenuate obesity-induced gut leakage and adipose inflammation in mice lacking gut bacteria. Overall, these results support that sEH is a potential therapeutic target for obesity-induced intestinal barrier dysfunction, and that sEH inhibitors, which have been evaluated in human clinical trials targeting other human disorders, could be promising agents for prevention and/or treatment.
ESTHER : Wang_2020_Proc.Natl.Acad.Sci.U.S.A_117_8431
PubMedSearch : Wang_2020_Proc.Natl.Acad.Sci.U.S.A_117_8431
PubMedID: 32220957
Gene_locus related to this paper: human-EPHX2

Title : Cortical ChAT(+) neurons co-transmit acetylcholine and GABA in a target- and brain-region-specific manner - Granger_2020_Elife_9_
Author(s) : Granger AJ , Wang W , Robertson K , El-Rifai M , Zanello AF , Bistrong K , Saunders A , Chow BW , Nunez V , Turrero Garcia M , Harwell CC , Gu C , Sabatini BL
Ref : Elife , 9 : , 2020
Abstract : The mouse cerebral cortex contains neurons that express choline acetyltransferase (ChAT) and are a potential local source of acetylcholine. However, the neurotransmitters released by cortical ChAT(+) neurons and their synaptic connectivity are unknown. We show that the nearly all cortical ChAT(+) neurons in mice are specialized VIP(+) interneurons that release GABA strongly onto other inhibitory interneurons and acetylcholine sparsely onto layer 1 interneurons and other VIP(+)/ChAT(+) interneurons. This differential transmission of ACh and GABA based on the postsynaptic target neuron is reflected in VIP(+)/ChAT(+) interneuron pre-synaptic terminals, as quantitative molecular analysis shows that only a subset of these are specialized to release acetylcholine. In addition, we identify a separate, sparse population of non-VIP ChAT(+) neurons in the medial prefrontal cortex with a distinct developmental origin that robustly release acetylcholine in layer 1. These results demonstrate both cortex-region heterogeneity in cortical ChAT(+) interneurons and target-specific co-release of acetylcholine and GABA.
ESTHER : Granger_2020_Elife_9_
PubMedSearch : Granger_2020_Elife_9_
PubMedID: 32613945

Title : Eicosanoids: The Overlooked Storm in Coronavirus Disease 2019 (COVID-19)? - Hammock_2020_Am.J.Pathol_190_1782
Author(s) : Hammock BD , Wang W , Gilligan MM , Panigrahy D
Ref : American Journal of Pathology , 190 :1782 , 2020
Abstract : Severe coronavirus disease 2019 (COVID-19) symptoms, including systemic inflammatory response and multisystem organ failure, are now affecting thousands of infected patients and causing widespread mortality. Coronavirus infection causes tissue damage, which triggers the endoplasmic reticulum stress response and subsequent eicosanoid and cytokine storms. Although proinflammatory eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, are critical mediators of physiological processes, such as inflammation, fever, allergy, and pain, their roles in COVID-19 are poorly characterized. Arachidonic acid-derived epoxyeicosatrienoic acids could alleviate the systemic hyperinflammatory response in COVID-19 infection by modulating endoplasmic reticulum stress and stimulating the resolution of inflammation. Soluble epoxide hydrolase (sEH) inhibitors, which increase endogenous epoxyeicosatrienoic acid levels, exhibit potent anti-inflammatory activity and inhibit various pathologic processes in preclinical disease models, including pulmonary fibrosis, thrombosis, and acute respiratory distress syndrome. Therefore, targeting eicosanoids and sEH could be a novel therapeutic approach in combating COVID-19. In this review, we discuss the predominant role of eicosanoids in regulating the inflammatory cascade and propose the potential application of sEH inhibitors in alleviating COVID-19 symptoms. The host-protective action of omega-3 fatty acid-derived epoxyeicosanoids and specialized proresolving mediators in regulating anti-inflammation and antiviral response is also discussed. Future studies determining the eicosanoid profile in COVID-19 patients or preclinical models are pivotal in providing novel insights into coronavirus-host interaction and inflammation modulation.
ESTHER : Hammock_2020_Am.J.Pathol_190_1782
PubMedSearch : Hammock_2020_Am.J.Pathol_190_1782
PubMedID: 32650004

Title : Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM\/MM study - Zhou_2020_Sci.Total.Environ_709_135897
Author(s) : Zhou J , Zhu L , Chen J , Wang W , Zhang R , Li Y , Zhang Q
Ref : Sci Total Environ , 709 :135897 , 2020
Abstract : The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals.
ESTHER : Zhou_2020_Sci.Total.Environ_709_135897
PubMedSearch : Zhou_2020_Sci.Total.Environ_709_135897
PubMedID: 31887512
Gene_locus related to this paper: 9euro-a0a0d2ilk1

Title : Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial - Wang_2020_Curr.Med.Res.Opin_36_1107
Author(s) : Wang W , Yao J , Guo X , Guo Y , Yan C , Liu K , Zhang Y , Wang X , Li H , Wen Z , Li S , Xiao X , Liu W , Li Z , Zhang L , Shao S , Ye S , Qin G , Li Y , Li F , Zhang X , Li X , Peng Y , Deng H , Xu X , Zhou L , Huang Y , Cao M , Xia X , Shi M , Dou J , Yuan J
Ref : Curr Med Res Opin , 36 :1107 , 2020
Abstract : Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
ESTHER : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedSearch : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedID: 32338063

Title : The association between polymorphisms in miRNA and the cholinesterase activity of workers in an omethoate-exposed environment - Zou_2020_Int.J.Environ.Health.Res__1
Author(s) : Zou K , Zhou X , Wang W , Shi L , Fu X
Ref : Int J Environ Health Res , :1 , 2020
Abstract : To explore the association between polymorphisms in microRNAs (miRNAs) and the cholinesterase (ChE) activity in omethoate-exposed workers, we recruited 180 omethoate-exposed workers and 115 controls to measure their ChE activity using acetylcholine and dithio-bis-(nitrobenzoic acid) and genotype susceptible SNPs in their miRNA by time-of-flight mass spectrometry. ChE activity in the exposure group was lower than that in the control group (P < 0.001). The analysis of covariance result showed that ChE activity was lower in the (- -/- T) genotype in miR-30a rs111456995 (1.97 +/- 0.47) than in the TT genotype (2.23 +/- 0.59) of the exposure group (P = 0.004). Multivariate linear regression was performed to find influencing factors on ChE activity, and variables kept in the model included omethoate exposure (b = -1.094, P < 0.001), gender (b = -0.381, P < 0.001), miR-30a rs111456995 (- -/- T)(b = -0.248, P < 0.001), and drinking (b = 0.258, P =0.019). The results suggest that individuals carrying a (- -/- T) genotype in miR-30a rs111456995 were more susceptible to damage in their cholinesterase induced by omethoate exposure.
ESTHER : Zou_2020_Int.J.Environ.Health.Res__1
PubMedSearch : Zou_2020_Int.J.Environ.Health.Res__1
PubMedID: 32962420

Title : Neurological effects of subchronic exposure to dioctyl phthalate (DOP), lead, and arsenic, individual and mixtures, in immature mice - Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
Author(s) : Feng W , Wu X , Mao G , Zhao T , Wang W , Chen Y , Zhang M , Yang L
Ref : Environ Sci Pollut Res Int , 27 :9247 , 2020
Abstract : Dioctyl phthalate (DOP) (200, 500, and 1000 mg kg(-1) bw, i.g.), Pb (Ac)(2) (50 mg L(-1), p.o.), and NaAsO(2) (10 mg L(-1), p.o.) were administered individually and as mixtures to weanling male mice for 8 weeks. It was observed that Pb, As, and DOP exposure could significantly inhibit the growth and development of mice. Compared with the Pb, As, and Pb + As groups, the activities of iNOS and TNOS were significantly increased, the levels of AChE and SOD were significantly decreased, and the level of MDA was significantly increased in the Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups. The factorial analysis shows that the iNOS, TNOS, and AChE present synergistic effects on Pb, As, and DOP. A significant increase of escape latency and a significant decrease of original platform quadrant stops were observed between Pb + As + DOP-H and Pb + As groups. The factorial analysis shows that there was a synergistic effect on Pb, As, and DOP. Compared with that of the control group, the expression levels of caspase-3 and Bax expression in Pb + As, DOP-H, Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups were significantly increased in the hippocampus. The expression levels of Bcl-2 expression decreased significantly and the Bax/Bcl-2 ratio increased significantly. Pathological alterations on the hippocampus were found in exposed groups. This result shows that combined exposure of Pb, As, and DOP could induce neurotoxicity, of which possible mechanism is hippocampal neuronal apoptosis. Graphical abstract This study shows that there were three components with eigenvalues greater than 1, which together explained 89.40% of total variance. The first component (PC1) showed high loadings on B-SOD, L-SOD, B-MDA, L-MDA, K-MDA, iNOS, tNOS, and AChE and accounted for 46.55% of the total variance after Varimax rotation. PC2 accounted for 23.81% of the total variance with high loadings on B-As, L-As, K-As, and K-SOD, whereas PC3 showed high loadings on B-Pb, L-Pb, and K-Pb and accounted for 19.04% of the total variance.
ESTHER : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedSearch : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedID: 31916164

Title : Discovery and development of a novel short-chain fatty acid ester synthetic biocatalyst under aqueous phase from Monascus purpureus isolated from Baijiu - Xu_2020_Food.Chem_338_128025
Author(s) : Xu Y , Wang X , Liu X , Li X , Zhang C , Li W , Sun X , Wang W , Sun B
Ref : Food Chem , 338 :128025 , 2020
Abstract : Short-chain fatty acid esters are important flavor chemicals in Chinese traditional fermented Baijiu. Monascus purpureus was recognized as an important microorganism contributing to ester synthesis. However, the molecular basis for ester synthesis was still lacking. The present work combined genome sequencing, transcriptome sequencing, gene library construction, and enzyme engineering to discover a novel catalyst from M. purpureus (isolated from Baijiu fermentation starter). Enzyme LIP05, belonging to the alpha/beta hydrolase family, was identified to synthesize short-chain fatty acid esters under aqueous phase. After deleting the lid domain of LIP05, the synthesis of ethyl pentanoate, ethyl hexanoate, ethyl octanoate, or ethyl decanoate was achieved. Ethyl octanoate with the highest conversion ratio of 93.7% was obtained with the assistance of ultrasound. The study reveals the molecular basis for synthesizing short-chain fatty acid esters by M. purpureus and will promote the application of the species or the enzyme in food industry.
ESTHER : Xu_2020_Food.Chem_338_128025
PubMedSearch : Xu_2020_Food.Chem_338_128025
PubMedID: 32927200
Gene_locus related to this paper: monpu-a0a507qkl5

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 : 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 : The Effect of Longwave Ultraviolet Light Radiation on Dendrolimus tabulaeformis Antioxidant and Detoxifying Enzymes - Wang_2019_Insects_11_
Author(s) : Wang W , Gao C , Ren L , Luo Y
Ref : Insects , 11 : , 2019
Abstract : Longwave ultraviolet (UVA) light, in the range of 315-400 nm, has been widely used as a light source in the light trapping of insect pests. Previous studies have demonstrated the oxidative stress and lethal effect of UV radiation on insects. In this study, we evaluated the influence of UVA radiation on the antioxidant and detoxifying enzymes of Dendrolimus tabulaeformis. We tested the contents of malondialdehyde (MDA), hydroxyl radical (.OH), hydrogen peroxide (H2O2), reduced glutathione (GSH), and oxidized glutathione (GSSH) following different exposure time periods of UVA light irradiation on D. tabulaeformis adults. In addition, we investigated how the activities of antioxidant and detoxifying enzymes responded to UVA radiation by determining the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO), glutathione S-transferase (GST), glutathione reductase (GR), acetylcholinesterase (AChE), carboxylesterase (CarE), alkaline phosphatase (ALP), and acid phosphatase (ACP). Adults were exposed to UVA light for different time periods (0, 5, 15, 30, 60, and 120 min). We found that exposure to UVA light for 5 min resulted in rapid variation in the activities of the antioxidant and detoxification enzyme systems. However, the antioxidant capacity of females was incongruous with that of males following UVA irradiation. Our results confirmed that UVA light irradiation increased the level of oxidative stress and disturbed physiological detoxification in D. tabulaeformis adults. Based on the above results, we anticipated that further research of the mechanism of UVA irradiation on the antioxidant and detoxifying enzymes of D. tabulaeformis would gain more importance, allowing to develop and use new, less toxic and environmentally friendly pesticides.
ESTHER : Wang_2019_Insects_11_
PubMedSearch : Wang_2019_Insects_11_
PubMedID: 31861292

Title : Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease - Zhu_2019_Int.J.Colorectal.Dis_34_255
Author(s) : Zhu T , Sun X , Wei M , Yi B , Zhao X , Wang W , Feng J
Ref : Int J Colorectal Dis , 34 :255 , 2019
Abstract : OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age <= 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR <=3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.
ESTHER : Zhu_2019_Int.J.Colorectal.Dis_34_255
PubMedSearch : Zhu_2019_Int.J.Colorectal.Dis_34_255
PubMedID: 30368570

Title : Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity - Feng_2019_Fitoterapia__104378
Author(s) : Feng Z , Chen S , Wang W , Feng L , Dong Y , Zou Y , Ke C , Tang C , Yao S , Zhang H , Gan L , Ye Y , Lin L
Ref : Fitoterapia , :104378 , 2019
Abstract : Five previously undescribed lycodine-type alkaloids, named huperzine Y (1), 8,15-epoxy-N-demethylhuperzinine (2), 7-hydroxyl-huperzinine (3), huperzine Z (4), and huperzine D N-oxide (5), were isolated from the whole plants of Lycopodiastrum casuarinoides (Lycopodiaceae), along with ten known analogues. The structures of the new compounds were elucidated by means of spectroscopic technique (IR, UV, MS and NMR). The absolute configurations of the new compounds were established on the basis of comparison of their experimental and TD-DFT (time-dependent density functional theory) calculated ECD spectra. Moreover, all the isolates were evaluated for acetylcholinesterase (AChE) inhibitory activity. Only huperzine C showed moderate activity, with an IC50 value of 0.525+/-0.140muM, which was comparable with the positive control, huperzine A (IC50=0.143+/-0.029muM).
ESTHER : Feng_2019_Fitoterapia__104378
PubMedSearch : Feng_2019_Fitoterapia__104378
PubMedID: 31676395

Title : A rat model of organophosphate-induced status epilepticus and the beneficial effects of EP2 receptor inhibition - Rojas_2019_Neurobiol.Dis__104399
Author(s) : Rojas A , Ganesh T , Wang W , Wang J , Dingledine R
Ref : Neurobiol Dis , :104399 , 2019
Abstract : This review describes an adult rat model of status epilepticus (SE) induced by diisopropyl fluorophosphate (DFP), and the beneficial outcomes of transient inhibition of the prostaglandin-E2 receptor EP2 with a small molecule antagonist, delayed by 2-4h after SE onset. Administration of six doses of the selective EP2 antagonist TG6-10-1 over a 2-3day period accelerates functional recovery, attenuates hippocampal neurodegeneration, neuroinflammation, gliosis and blood-brain barrier leakage, and prevents long-term cognitive deficits without blocking SE itself or altering acute seizure characteristics. This work has provided important information regarding organophosphate-induced seizure related pathologies in adults and revealed the effectiveness of delayed EP2 inhibition to combat these pathologies.
ESTHER : Rojas_2019_Neurobiol.Dis__104399
PubMedSearch : Rojas_2019_Neurobiol.Dis__104399
PubMedID: 30818067

Title : One-step orientated immobilization of nanobodies and its application for immunoglobulin purification - Fu_2019_J.Chromatogr.A_1603_15
Author(s) : Fu J , Li J , Wang W , Wu H , Zhou P , Li Y , He Q , Tu Z
Ref : Journal of Chromatography A , 1603 :15 , 2019
Abstract : Affinity chromatography technologies play an important role in the purification of antibodies. To prepare affinity materials, prior isolation and purification of affinity ligands are required before coupling onto solid supports, which is quite expensive and laborious in large-scale applications. In this study, a one-step approach which circumvents the ligand purification procedures was developed to fabricate affinity gel for purifying immunoglobulin G (IgG). A self-labeling tag, haloalkane dehalogenase, was fused to the C-terminal of an anti-Fc variable domain of the heavy chain of the heavy-chain antibody (AFV) which was isolated in previous work. The AFV binds to various sources of IgG and is highly thermal stable. The fusion protein, namely HAFV, was expressed in Escherichia coli as a soluble protein. The binding affinity of HAFV to the Fc region of IgG was characterized and compared with the untagged anti-Fc nanobody. Next, the HAFV was immobilized directly from the crude cell lysate of isopropylthio-beta-D-galactoside (IPTG) induced E. coli. The effects of NaCl concentrations and pH on the capacity of the HAFV resin were investigated. In addition, the one-step coupled HAFV resin was compared with the AFV resin and commercial resins (Protein A and Protein G) by evaluating the static capacity and stability. Though the Protein A (8.34+/-0.37mg/ml) and Protein G (9.19+/-0.28mg/ml) showed higher static capacity, the static capacity of HAFV resin (8.21+/-0.30mg/ml) was better than that of the untagged AFV gel (6.48+/-0.56mg/ml). The recovery results calculated for the reusability and stability show that there is no significant difference between the results obtained for the HAFV gel with those of the untagged AFV gel and commercial Protein A and G. After stored at 37 for 7 days and recycled 10 times, the static capacity of HAFV gel remains above 78%. Our strategy is site-specific, cost-effective, reproducible, and has the potential to dramatically cut down the costs of affinity materials for IgG purification.
ESTHER : Fu_2019_J.Chromatogr.A_1603_15
PubMedSearch : Fu_2019_J.Chromatogr.A_1603_15
PubMedID: 31213362
Gene_locus related to this paper: xanau-halo1

Title : Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts - Zhang_2019_Cancer.Lett_465_36
Author(s) : Zhang L , Zhou J , Yan Y , Zhou X , Zhou Q , Du R , Hu S , Ge W , Huang Y , Xu H , Kong Y , Zheng H , Ding Y , Shen Y , Wang W
Ref : Cancer Letters , 465 :36 , 2019
Abstract : Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients.
ESTHER : Zhang_2019_Cancer.Lett_465_36
PubMedSearch : Zhang_2019_Cancer.Lett_465_36
PubMedID: 31479691

Title : Proteomic and metabolomic responses in hepatopancreas of whiteleg shrimp Litopenaeus vannamei infected by microsporidian Enterocytozoon hepatopenaei - Ning_2019_Fish.Shellfish.Immunol_87_534
Author(s) : Ning M , Wei P , Shen H , Wan X , Jin M , Li X , Shi H , Qiao Y , Jiang G , Gu W , Wang W , Wang L , Meng Q
Ref : Fish Shellfish Immunol , 87 :534 , 2019
Abstract : Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. HPM is not normally associated with shrimp mortality, but is associated with significant growth retardation. In this study, the responses induced by EHP were investigated in hepatopancreas of shrimp Litopenaeus vannamei using proteomics and metabolomics. Among differential proteins identified, several (e.g., peritrophin-44-like protein, alpha2 macroglobulin isoform 2, prophenoloxidase-activating enzymes, ferritin, Rab11A and cathepsin C) were related to pathogen infection and host immunity. Other proteomic biomarkers (i.e., farnesoic acid o-methyltransferase, juvenile hormone esterase-like carboxylesterase 1 and ecdysteroid-regulated protein) resulted in a growth hormone disorder that prevented the shrimp from molting. Both proteomic KEGG pathway (e.g., "Glycolysis/gluconeogenesis" and "Glyoxylate and dicarboxylate metabolism") and metabolomic KEGG pathway (e.g., "Galactose metabolism" and "Biosynthesis of unsaturated fatty acids") data indicated that energy metabolism pathway was down-regulated in the hepatopancreas when infected by EHP. More importantly, the changes of hormone regulation and energy metabolism could provide much-needed insight into the underlying mechanisms of stunted growth in shrimp after EHP infection. Altogether, this study demonstrated that proteomics and metabolomics could provide an insightful view into the effects of microsporidial infection in the shrimp L. vannamei.
ESTHER : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedSearch : Ning_2019_Fish.Shellfish.Immunol_87_534
PubMedID: 30721776

Title : Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells - Tang_2018_Gene_667_95
Author(s) : Tang L , Wang G , Jiang L , Chen P , Wang W , Chen J , Wang L
Ref : Gene , 667 :95 , 2018
Abstract : OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. MATERIALS AND METHODS: 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. RESULTS: sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. CONCLUSION: Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study.
ESTHER : Tang_2018_Gene_667_95
PubMedSearch : Tang_2018_Gene_667_95
PubMedID: 29665449
Gene_locus related to this paper: human-EPHX2

Title : The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas - Liu_2018_Front.Immunol_9_284
Author(s) : Liu Z , Wang L , Lv Z , Zhou Z , Wang W , Li M , Yi Q , Qiu L , Song L
Ref : Front Immunol , 9 :284 , 2018
Abstract : It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a "nervous-hemocyte"-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system. After hemocytes were exposed to lipopolysaccharide (LPS) stimulation, acetylcholine (ACh), and norepinephrine (NE) in the cell supernatants, both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05) comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase and dopamine beta-hydroxylase in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase and monoamine oxidase, two enzymes essential in the metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF) genes, the activities of superoxide dismutase, catalase and lysosome, and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that oyster hemocyte could de novo synthesize and release cholinergic and adrenergic neurotransmitters, and the hemocyte-derived ACh/NE could then execute a negative regulation on hemocyte phagocytosis and synthesis of immune effectors with similar autocrine/paracrine signaling pathway identified in vertebrate macrophages. Findings in the present study demonstrated that the immune and neuroendocrine system evolved from a common origin and enriched our knowledge on the evolution of NEI system.
ESTHER : Liu_2018_Front.Immunol_9_284
PubMedSearch : Liu_2018_Front.Immunol_9_284
PubMedID: 29535711

Title : Highly Efficient Deacidification of High-Acid Rice Bran Oil Using Methanol as a Novel Acyl Acceptor - Li_2018_Appl.Biochem.Biotechnol_184_1061
Author(s) : Li D , Faiza M , Ali S , Wang W , Tan CP , Yang B , Wang Y
Ref : Appl Biochem Biotechnol , 184 :1061 , 2018
Abstract : A highly efficient process for reducing the fatty acid (FA) content of high-acid rice bran oil (RBO) was developed by immobilized partial glycerides-selective lipase SMG1-F278N-catalyzed esterification/transesterification using methanol as a novel acyl acceptor. Molecular docking simulation indicated that methanol was much closer to the catalytic serine (Ser-171) compared with ethanol and glycerol, which might be one of the reasons for its high efficiency in the deacidification of high-acid RBO. Additionally, the reaction parameters were optimized to minimize the FA content of high-acid RBO. Under the optimal conditions (substrate molar ratio of methanol to FAs of 1.8:1, enzyme loading of 40sU/g, and at 30s degreesC), FA content decreased from 25.14 to 0.03% after 6sh of reaction. Immobilized SMG1-F278N exhibited excellent methanol tolerance and retained almost 100% of its initial activity after being used for ten batches. After purification by molecular distillation, the final product contained 97.86% triacylglycerol, 2.10% diacylglycerol, and 0.04% FA. The acid value of the final product was 0.09smg KOH/g, which reached the grade one standard of edible oil. Overall, methanol was a superior acyl acceptor for the deacidification of high-acid RBO and the high reusability of immobilized SMG1-F278N indicates an economically attractive process.
ESTHER : Li_2018_Appl.Biochem.Biotechnol_184_1061
PubMedSearch : Li_2018_Appl.Biochem.Biotechnol_184_1061
PubMedID: 28948493
Gene_locus related to this paper: malgo-a8puy1

Title : CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells - Feng_2018_Biomed.Pharmacother_107_1496
Author(s) : Feng X , Zhang D , Li X , Ma S , Zhang C , Wang J , Li Y , Liang L , Zhang P , Qu Y , Zhang Z , Yang Z , Xiang Y , Zhang W , Wang S , Shao W , Wang W
Ref : Biomed Pharmacother , 107 :1496 , 2018
Abstract : CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC.
ESTHER : Feng_2018_Biomed.Pharmacother_107_1496
PubMedSearch : Feng_2018_Biomed.Pharmacother_107_1496
PubMedID: 30257367

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro - Liu_2018_J.Insect.Sci_18_
Author(s) : Liu R , Wang W , Liu X , Lu Y , Xiang T , Zhou W , Wan Y
Ref : J Insect Sci , 18 : , 2018
Abstract : To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25 degrees C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.
ESTHER : Liu_2018_J.Insect.Sci_18_
PubMedSearch : Liu_2018_J.Insect.Sci_18_
PubMedID: 30395292

Title : Genomic Analysis of Microbulbifer sp. Strain A4B-17 and the Characterization of Its Metabolic Pathways for 4-Hydroxybenzoic Acid Synthesis - Tian_2018_Front.Microbiol_9_3115
Author(s) : Tian J , Zhu L , Wang W , Zhang L , Li Z , Zhao Q , Xing K , Feng Z , Peng X
Ref : Front Microbiol , 9 :3115 , 2018
Abstract : The marine bacterium Microbulbifer sp. A4B-17 produces secondary metabolites such as 4-hydroxybenzoic acid (4HBA) and esters of 4HBA (parabens). 4HBA is a useful material in the synthesis of the liquid crystal. Parabens are man-made compounds that have been extensively used since the 1920s in the cosmetic, pharmaceutical, and food industries for their effective antimicrobial activity. In this study, we completed the sequencing and annotation of the A4B-17 strain genome and found all genes for glucose utilization and 4HBA biosynthesis. Strain A4B-17 uses the Embden-Meyerhof-Parnas (EMP), hexose monophosphate (HMP), and Entner-Doudoroff (ED) pathways to utilize glucose. Other sugars such as fructose, sucrose, xylose, arabinose, galactose, mannitol, and glycerol supported cell growth and 4HBA synthesis. Reverse transcriptional analysis confirmed that the key genes involved in the glucose metabolism were functional. Paraben concentrations were proportionally increased by adding alcohols to the culture medium, indicating that strain A4B-17 synthesizes the 4HBA and the alcohols separately and an esterification reaction between them is responsible for the paraben synthesis. A gene that codes for a carboxylesterase was proposed to catalyze this reaction. The temperature and NaCl concentration for optimal growth were determined to be 35 degrees C and 22.8 g/L.
ESTHER : Tian_2018_Front.Microbiol_9_3115
PubMedSearch : Tian_2018_Front.Microbiol_9_3115
PubMedID: 30619190

Title : Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane - Wang_2018_Phys.Chem.Chem.Phys_20_20540
Author(s) : Wang J , Tang X , Li Y , Zhang R , Zhu L , Chen J , Sun Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , 20 :20540 , 2018
Abstract : The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts.
ESTHER : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedSearch : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedID: 30051124

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

Title : The Prognostic Value of Lipoprotein-Associated Phospholipase A(2) in the Long-Term Care of Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention - Yang_2018_Clin.Appl.Thromb.Hemost_24_822
Author(s) : Yang L , Wang H , Zhang Y , Han T , Wang W
Ref : Clin Appl Thromb Hemost , 24 :822 , 2018
Abstract : Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor for cardiovascular disease. Accordingly, studies from many countries around the world have shown an association between Lp-PLA(2) and cardiovascular events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), but this association has not been documented among the Chinese. The aim of this study was to assess the use of Lp-PLA(2) as a useful marker for predicting the long-term prognosis of Chinese patients with ACS undergoing PCI. A total of 651 consecutive patients undergoing PCI between September 2013 and January 2015 were divided into 2 groups: the high Lp-PLA(2) group (n = 262, Lp-PLA(2) > 138 nmol/L) and the low Lp-PLA(2) group (n = 389, Lp-PLA(2) >= 138 nmol/L). The end point was all-cause mortality and rehospitalization. The median follow-up was 24 months. Multivariate analysis showed that high Lp-PLA(2) was an independent predictor of all-cause mortality and rehospitalization (hazard ratio: 1.429, 95% confidence interval [CI]: 1.411-1.448; P < .05). The Lp-PLA(2) had good accuracy for predicting all-cause mortality and rehospitalization among patients with ACS undergoing PCI (area under the receiver-operating characteristic curve: 0.858, 95% CI: 0.819-0.898; P < .05), and a good correlation with the Global Registry of Acute Coronary Event score ( r = 0.525, P < .05). This study provided evidence that Lp-PLA(2) could predict all-cause mortality and rehospitalization risk among patients with ACS undergoing PCI.
ESTHER : Yang_2018_Clin.Appl.Thromb.Hemost_24_822
PubMedSearch : Yang_2018_Clin.Appl.Thromb.Hemost_24_822
PubMedID: 29121808
Gene_locus related to this paper: human-PLA2G7

Title : Effects of soil acidification on the toxicity of organophosphorus pesticide on Eisenia fetida and its mechanism - Zou_2018_J.Hazard.Mater_359_365
Author(s) : Zou X , Xiao X , Zhou H , Chen F , Zeng J , Wang W , Feng G , Huang X
Ref : J Hazard Mater , 359 :365 , 2018
Abstract : Organophosphorus pesticides (OPs) have been widely used to control agricultural insects. Soil acidification is a major problem in soil of intensive agricultural systems, especially in red soil with a low pH buffer capacity. However, the effects of soil acidification on the toxicity of pesticides are still unclear. In the present study, the toxicity of three OPs on E. fetida was determined at individual (14-day lethal test) and biochemical levels (antioxidative defence enzymes) by using acidified soils (pH=5.5, 4.3 and 3.1). The results showed that the toxicity of tested OPs was slightly increased with the decrease of soil pH. To interpret the phenomena, an optimum Quantitative Structure Activity Relationship (QSAR) model was developed based on the toxicity mechanism and the partial least squares regression (PLS) method. The model indicated bioavailability and toxicodynamics are key factors of soil acidification affecting the toxicity of the OPs. Further results revealed the bioavailability of the OPs was strongly related to their hydrolysis and biodegradation character, whereas the effects of soil acidification on toxicodynamics were mainly caused by the interaction between the acetylcholinesterase (AchE) and the OPs. Results will increase understanding of the effects of soil acidification on the toxicity of pesticides and its mechanism.
ESTHER : Zou_2018_J.Hazard.Mater_359_365
PubMedSearch : Zou_2018_J.Hazard.Mater_359_365
PubMedID: 30048951

Title : Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate - Duan_2018_R.Soc.Open.Sci_5_172357
Author(s) : Duan X , Yang Y , Wang S , Feng X , Wang T , Wang P , Yao W , Cui L , Wang W
Ref : R Soc Open Sci , 5 :172357 , 2018
Abstract : Cholinesterase activity (ChA), the effective biomarker for organophosphate pesticide exposure, is possibly affected by single nucleotide polymorphisms (SNPs) in cell-cycle-related genes. One hundred and eighty workers with long-term exposure to omethoate and 115 healthy controls were recruited to explore the gene-gene and gene-environment interactions. The acetylthiocholine and dithio-bis-(nitrobenzoic acid) method was used to detect the cholinesterase activities in whole blood, erythrocytes and plasma. Genetic polymorphisms were determined by the PCR-RFLP and direct PCR electrophoresis methods. Statistical results showed that the cholinesterase activities of whole blood, erythrocytes and plasma in the exposure group were significantly lower than those in the control group (p < 0.001), and erythrocyte cholinesterase activities were associated with gender, smoking and drinking in the exposure group (p < 0.05). Single-locus analyses showed that there is a statistically significant difference in the ChA among the genotypes CC, CA and AA of the p21 rs1801270 locus in the control group (p = 0.033), but not in the exposure group. A significant interaction between genes and environmental factors (i.e. p53, p21, mdm2, gender, smoking and drinking) affecting ChA was found through a generalized multifactor dimensionality reduction analysis. These obtained markers will be useful in further marker-assisted selection in workers with exposure to omethoate.
ESTHER : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedSearch : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedID: 29892419

Title : Novel acetylcholinesterase inhibitors from Zijuan tea and biosynthetic pathway of caffeoylated catechin in tea plant - Wang_2017_Food.Chem_237_1172
Author(s) : Wang W , Fu XW , Dai XL , Hua F , Chu GX , Chu MJ , Hu FL , Ling TJ , Gao LP , Xie ZW , Wan XC , Bao GH
Ref : Food Chem , 237 :1172 , 2017
Abstract : Zijuan tea is a special cultivar of Yunnan broad-leaf tea (Camellia sinensis var. assamica) with purple buds, leaves, and stems. Phytochemical study on this tea led to the discovery of three hydroxycinnamoylated catechins (HCCs) (1-3), seven other catechins (4-10), three proanthocyanidins (11-13), five flavones and flavone glycosides (14-18), two alkaloids (19, 20), one steroid (21), and one phenylpropanoid glycoside (22). The isolation and structural elucidation of the caffeoylated catechin (1) by means of spectroscopic techniques were described. We also provide the first evidence that 1 is synthesized via a two-step pathway in tea plant. The three HCCs (1-3) were investigated on their bioactivity through molecular modeling simulation and biochemical experiments. Our results show that they bind acetylcholinesterase (AChE) tightly and have strong AChE inhibitory activity with IC50 value at 2.49, 11.41, 62.26muM, respectively.
ESTHER : Wang_2017_Food.Chem_237_1172
PubMedSearch : Wang_2017_Food.Chem_237_1172
PubMedID: 28763966

Title : Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM\/MM study - Tang_2017_Bioorg.Chem_73_16
Author(s) : Tang X , Zhang R , Li Y , Zhang Q , Wang W
Ref : Bioorg Chem , 73 :16 , 2017
Abstract : The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.
ESTHER : Tang_2017_Bioorg.Chem_73_16
PubMedSearch : Tang_2017_Bioorg.Chem_73_16
PubMedID: 28527381

Title : Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species - He_2017_Parasit.Vectors_10_383
Author(s) : He P , Wang W , Sanogo B , Zeng X , Sun X , Lv Z , Yuan D , Duan L , Wu Z
Ref : Parasit Vectors , 10 :383 , 2017
Abstract : BACKGROUND: Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms.
METHODS: In this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy.
RESULTS: 5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in hepatopancreas tissues, including degeneration of the endoplasmic reticulum and vacuolization in mitochondria. In addition, transcriptional levels of superoxide dismutase (SOD), acid phosphatase (ACP) and NOS in the hepatopancreas were significantly downregulated as shown by real-time quantitative polymerase chain reaction (RT-PCR). These results indicated that the hepatopancreas is a primary target organ of salicylanilidate.
CONCLUSIONS: Salicylanilidate not only had deleterious effects on Biomphalaria species and S. mansoni cercariae but also showed very low toxicity to D. rerio, suggesting that it has broad potential applications.
ESTHER : He_2017_Parasit.Vectors_10_383
PubMedSearch : He_2017_Parasit.Vectors_10_383
PubMedID: 28793917

Title : Deep Brain Magnetic Stimulation Promotes Neurogenesis and Restores Cholinergic Activity in a Transgenic Mouse Model of Alzheimer's Disease - Zhen_2017_Front.Neural.Circuits_11_48
Author(s) : Zhen J , Qian Y , Fu J , Su R , An H , Wang W , Zheng Y , Wang X
Ref : Front Neural Circuits , 11 :48 , 2017
Abstract : Alzheimer's disease (AD) is characterized by progressive decline of memory and cognitive functions. Deep magnetic stimulation (DMS), a noninvasive and nonpharmacological brain stimulation, has been reported to alleviate stress-related cognitive impairment in neuropsychiatric disorders. Our previous study also discovered the preventive effect of DMS on cognitive decline in an AD mouse model. However, the underlying mechanism must be explored further. In this study, we investigated the effect of DMS on spatial learning and memory functions, neurogenesis in the dentate gyrus (DG), as well as expression and activity of the cholinergic system in a transgenic mouse model of AD (5XFAD). Administration of DMS effectively improved performance in spatial learning and memory of 5XFAD mice. Furthermore, neurogenesis in the hippocampal DG of DMS-treated 5XFAD mice was clearly enhanced. In addition, DMS significantly raised the level of acetylcholine and prevented the increase in acetylcholinesterase activity as well as the decrease in acetyltransferase activity in the hippocampus of 5XFAD mice. These findings indicate that DMS may be a promising noninvasive tool for treatment and prevention of AD cognitive impairment by promoting neurogenesis and enhancing cholinergic system function.
ESTHER : Zhen_2017_Front.Neural.Circuits_11_48
PubMedSearch : Zhen_2017_Front.Neural.Circuits_11_48
PubMedID: 28713248

Title : Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation - Li_2017_ACS.Chem.Neurosci_8_2708
Author(s) : Li X , Wang H , Xu Y , Liu W , Gong Q , Wang W , Qiu X , Zhu J , Mao F , Zhang H , Li J
Ref : ACS Chem Neurosci , 8 :2708 , 2017
Abstract : Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3.319 +/- 0.708 muM), 5-HT1A agonist (EC50 = 107 +/- 37 nM), and 5-HT reuptake inhibition (IC50 = 76.3 +/- 33 nM). Compound 1e displayed tolerable hepatotoxicity and moderate hERG inhibition activity, and could penetrate the blood-brain barrier in vivo. Furthermore, an oral intake of 30 mg/kg 1e.HCl could significantly improve the cognitive function of scopolamine-induced amnesia mice and alleviate the depressive symptom in tail suspension test. The effectivity of 1e validates the rationality of our design strategy.
ESTHER : Li_2017_ACS.Chem.Neurosci_8_2708
PubMedSearch : Li_2017_ACS.Chem.Neurosci_8_2708
PubMedID: 28872831

Title : Annotinolide F and lycoannotines A-I, further Lycopodium alkaloids from Lycopodium annotinum - Tang_2017_Phytochemistry_143_1
Author(s) : Tang Y , Xiong J , Zou Y , Wang W , Huang C , Zhang HY , Hu JF
Ref : Phytochemistry , 143 :1 , 2017
Abstract : Seven lycopodine-type (annotinolide F and lycoannotines A-F), two lycodine-type (lycoannotines G and H), and one fawcettimine-type (lycoannotine I) previously undescribed naturally occurring Lycopodium alkaloids together with thirteen known ones were isolated from the whole plant of Lycopodium annotinum. Their structures and absolute configurations were determined by extensive spectroscopic methods, single-crystal X-ray diffraction, chemical transformation, and electronic circular dichroism (ECD) calculations. Among the isolates, annotinolide F, lycoannotines A and B are unusual 7,8-seco-lycopodane derivatives, and annotinolide F even further possesses a rare 8,5-lactone framework through a lactonization after the C-7/C-8 bond cleavage. Lycoannotine C is an uncommon 8,15-seco lycopodine-type alkaloid, whereas lycoannotine I represents the first example of a naturally occurring C-9/N bond cleavage product of fawcettimine-type alkaloid. Among them, only lycoannotine I was found to show considerable anti-butyrylcholinesterase (anti-BuChE) activity.
ESTHER : Tang_2017_Phytochemistry_143_1
PubMedSearch : Tang_2017_Phytochemistry_143_1
PubMedID: 28738241

Title : Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (NSCLC) - Tang_2017_Int.J.Cancer_140_1620
Author(s) : Tang Z , Li J , Shen Q , Feng J , Liu H , Wang W , Xu L , Shi G , Ye X , Ge M , Zhou X , Ni S
Ref : International Journal of Cancer , 140 :1620 , 2017
Abstract : Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT). The epithelial markers E-cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis-associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA-IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non-cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5-year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.
ESTHER : Tang_2017_Int.J.Cancer_140_1620
PubMedSearch : Tang_2017_Int.J.Cancer_140_1620
PubMedID: 27943262

Title : The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke - Raju_2017_Am.J.Respir.Cell.Mol.Biol_56_99
Author(s) : Raju SV , Lin VY , Liu L , McNicholas CM , Karki S , Sloane PA , Tang L , Jackson PL , Wang W , Wilson L , Macon KJ , Mazur M , Kappes JC , DeLucas LJ , Barnes S , Kirk K , Tearney GJ , Rowe SM
Ref : American Journal of Respiratory Cellular & Molecular Biology , 56 :99 , 2017
Abstract : Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-mum resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.
ESTHER : Raju_2017_Am.J.Respir.Cell.Mol.Biol_56_99
PubMedSearch : Raju_2017_Am.J.Respir.Cell.Mol.Biol_56_99
PubMedID: 27585394

Title : Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice - Chen_2017_Sci.Rep_7_7758
Author(s) : Chen Y , Tian H , Yao E , Tian Y , Zhang H , Xu L , Yu Z , Fang Y , Wang W , Du P , Xie M
Ref : Sci Rep , 7 :7758 , 2017
Abstract : Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype "combination therapy" targeting multiple mechanisms of stroke injury with a single agent. However, its role in the pathological process after WMLs has not been clarified. The present study was to investigate the role of a potent sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on multiple elements in white matter of mice brain after chronic hypoperfusion. Adult male C57BL/6 mice were subjected to bilateral carotid artery stenosis (BCAS) to induce WMLs. Administration of TPPU significantly inhibited microglia activation and inflammatory response, increased M2 polarization of microglial cells, enhanced oligodendrogenesis and differentiation of oligodendrocytes, promoted white matter integrity and remyelination following chronic hypoperfusion. Moreover, these cellular changes were translated into a remarkable functional restoration. The results suggest that sEH inhibition could exert multi-target protective effects and alleviate cognitive impairment after chronic hypoperfusion induced WMLs in mice.
ESTHER : Chen_2017_Sci.Rep_7_7758
PubMedSearch : Chen_2017_Sci.Rep_7_7758
PubMedID: 28798352

Title : Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3 - Yao_2017_Neurochem.Res_42_446
Author(s) : Yao Y , Wang W , Jing L , Wang Y , Li M , Hou X , Wang J , Peng T , Teng J , Jia Y
Ref : Neurochem Res , 42 :446 , 2017
Abstract : microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke.
ESTHER : Yao_2017_Neurochem.Res_42_446
PubMedSearch : Yao_2017_Neurochem.Res_42_446
PubMedID: 27812761

Title : Effects of monocrotophos pesticide on cholinergic and dopaminergic neurotransmitter systems during early development in the sea urchin Hemicentrotus pulcherrimus - Zhang_2017_Toxicol.Appl.Pharmacol_328_46
Author(s) : Zhang X , Li S , Wang C , Tian H , Wang W , Ru S
Ref : Toxicol Appl Pharmacol , 328 :46 , 2017
Abstract : During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae. At the blastula stages, MCP disrupted DA metabolism but not 5-HT metabolism, resulting in abnormal development. High ChAT and AChE activity were observed at the gastrulation-completed stage and the two-armed pluteus stage, respectively, MCP inhibited ChAT activity and AChE activity/distribution and resulted in developmental defects of the plutei. From the gastrula stage to the two-armed pluteus stage, we found ubiquitous disrupting effects of MCP on ACh, DA, and 5-HT metabolism, particularly at critical periods during the development of these neurotransmitter systems. Therefore, we propose that this disruption is one of the main mechanisms of MCP-related developmental neurotoxicity, which would contribute better understanding insight into the mechanism of MCP pesticide's toxic effects.
ESTHER : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedSearch : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedID: 28479505

Title : Identification of lysophospholipase protein from Spiroplasma eriocheiris and verification of its function - Zhu_2017_Microbiology_163_175
Author(s) : Zhu H , Liu P , Du J , Wang J , Jing Y , Zhang J , Gu W , Wang W , Meng Q
Ref : Microbiology , 163 :175 , 2017
Abstract : Spiroplasma eriocheiris is known to cause tremor disease in the Chinese mitten crab Eriocheir sinensis; however, the molecular characterization of this pathogen is still unclear. S. eriocheiris has the ability to invade and survive within mouse 3T6 cells. The invasion process may require causing damage to the host cell membrane by chemical, physical or enzymatic means. In this study, we systematically characterized a novel lysophospholipase (lysoPL) of S. eriocheiris TDA-040725-5T. The gene that encodes lysoPL in S. eriocheiris (SE-LysoPL) was cloned, sequenced and expressed in Escherichia coli BL21 (DE3). Enzymatic assays revealed that the purified recombinant SE-LysoPL hydrolysed long-chain acyl esterases at pH 7 and 30 degrees C. SE-LysoPL was detected in the membrane and cytoplasmic protein fractions using the SE-LysoPL antibody in Western blot. The virulence ability of S. eriocheiris was effectively reduced at the early stage of infection (m.o.i.=100) by the SE-LysoPL antibody neutralization test. To the best of our knowledge, this is the first study to identify and characterize a gene from S. eriocheiris encoding a protein exhibiting lysoPL and esterase activities. Our findings indicate that SE-LysoPL plays important roles in the pathogenicity of S. eriocheiris.
ESTHER : Zhu_2017_Microbiology_163_175
PubMedSearch : Zhu_2017_Microbiology_163_175
PubMedID: 27926815
Gene_locus related to this paper: 9molu-a0a0h3xm88

Title : Autotransporter domain-dependent enzymatic analysis of a novel extremely thermostable carboxylesterase with high biodegradability towards pyrethroid pesticides - Cai_2017_Sci.Rep_7_3461
Author(s) : Cai X , Wang W , Lin L , He D , Huang G , Shen Y , Wei W , Wei D
Ref : Sci Rep , 7 :3461 , 2017
Abstract : The EstPS1 gene, which encodes a novel carboxylesterase of Pseudomonas synxantha PS1 isolated from oil well-produced water, was cloned and sequenced. EstPS1 has an open reading frame of 1923 bp and encodes the 640-amino acid carboxylesterase (EstPS1), which contains an autotransporter (AT) domain (357-640 amino acids). Homology analysis revealed that EstPS1 shared the highest identity (88%) with EstA from Pseudomonas fluorescens A506 (NCBI database) and belonged to the carboxylesterase family (EC The optimum pH and temperature of recombinant EstPS1 were found to be 8.0 and 60 degrees C, respectively. EstPS1 showed high thermostability, and the half-lives (T1/2 thermal inactivation) at 60, 70, 80, 90, and 100 degrees C were 14 h, 2 h, 31 min, 10 min, and 1 min, respectively. To understand the role of the AT domain in carboxylesterase, AT domain-truncated carboxylesterase (EstPS1DeltaAT) was generated. EstPS1DeltaAT showed a clearly decreased secretion rate, owing to the AT domain strongly improved secretory expression in the heterogeneous system. EstPS1 degraded various pyrethroid pesticides, and hydrolysis efficiencies were dependent on the pyrethroid molecular structure. EstPS1 degraded all the tested pyrethroid pesticides and hydrolysed the p-nitrophenyl esters of medium-short-chain fatty acids, indicating that EstPS1 is an esterase with broad specificity.
ESTHER : Cai_2017_Sci.Rep_7_3461
PubMedSearch : Cai_2017_Sci.Rep_7_3461
PubMedID: 28615636

Title : Simplified Enzymatic Upgrading of High-Acid Rice Bran Oil Using Ethanol as a Novel Acyl Acceptor - Li_2016_J.Agric.Food.Chem_64_6730
Author(s) : Li D , Wang W , Durrani R , Li X , Yang B , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 64 :6730 , 2016
Abstract : One of the major challenges in the upgrading of high-acid rice bran oil (RBO) is to efficiently reduce the amount of free fatty acids. Here we report a novel method for upgrading high-acid RBO using ethanol as a novel acyl acceptor in combination with a highly selective lipase from Malassezia globosa (SMG1-F278N). This process enabled an unprecedented deacidification efficiency of up to 99.80% in a short time (6 h); the immobilized SMG1-F278N used in deacidification exhibited excellent operational stability and could be used for at least 10 consecutive batches without detectable loss in activity. Scale-up was performed under optimized conditions to verify the applicability of this process, and low-acid (0.08%) RBO with a high level of gamma-oryzanol (27.8 g/kg) and gamma-oryzanol accumulation fold (1.5) was obtained after molecular distillation at lower temperature (120 degreesC). Overall, we report a simplified and efficient procedure for the production of edible RBO from high-acid RBO.
ESTHER : Li_2016_J.Agric.Food.Chem_64_6730
PubMedSearch : Li_2016_J.Agric.Food.Chem_64_6730
PubMedID: 27571030
Gene_locus related to this paper: malgo-a8puy1

Title : A Novel Process for the Synthesis of Highly Pure n-3 Polyunsaturated Fatty Acid (PUFA)-Enriched Triglycerides by Combined Transesterification and Ethanolysis - Li_2016_J.Agric.Food.Chem_64_6533
Author(s) : Li D , Wang W , Qin X , Li X , Yang B , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 64 :6533 , 2016
Abstract : In this study, a novel two-step enzymatic reaction was developed for the synthesis of highly pure triacylglycerols (TAGs) with a high content of n-3 polyunsaturated fatty acids (PUFAs). Glyceride mixtures were primarily synthesized by Novozym 435-catalyzed transesterification of glycerol and DHA/EPA-rich ethyl esters (EEs), followed by removal of partial glycerides, for the first time, by immobilized mono- and diacylglycerol lipase SMG1-F278N-catalyzed ethanolysis. TAG yield as high as 98.66% was achieved under the optimized conditions, and highly pure (98.75%) n-3 PUFA-enriched TAGs with 88.44% of n-3 PUFA was obtained after molecular distillation at lower temperature (140 degreesC). In addition, the EEs produced during ethanolysis had a FA composition similar to that of the original EEs, making them feasible for cyclic utilization. This was the first study reporting removal of partial glycerides by ethanolysis. Through ethanolysis, a higher purity product could be easily obtained at a relatively low temperature compared with the conventional high-temperature molecular distillation.
ESTHER : Li_2016_J.Agric.Food.Chem_64_6533
PubMedSearch : Li_2016_J.Agric.Food.Chem_64_6533
PubMedID: 27540752
Gene_locus related to this paper: malgo-a8puy1

Title : Soluble epoxide hydrolase inhibition provides multi-target therapeutic effects in rats after spinal cord injury - Chen_2016_Mol.Neurobiol_53_1565
Author(s) : Chen X , Huang X , Qin C , Fang Y , Liu Y , Zhang G , Pan D , Wang W , Xie M
Ref : Molecular Neurobiology , 53 :1565 , 2016
Abstract : Multiple players are involved in motor and sensory dysfunctions after spinal cord injury (SCI). Therefore, therapeutic approaches targeting these various players in the damage cascade hold considerable promise for the treatment of traumatic spinal cord injury. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). sEH inhibition has been shown to provide neuroprotective effects upon multiple elements of neurovascular unit under cerebral ischemia. However, its role in the pathological process after SCI remains unclear. In this study, we tested the hypothesis that sEH inhibition may have therapeutic effects in preventing secondary damage in rats after traumatic SCI. sEH was widely expressed in spinal cord tissue, mainly confined to astrocytes, and neurons. Administration of sEH inhibitor AUDA significantly suppressed local inflammatory responses as indicated by the reduced microglia activation and IL-1 beta expression, as well as the decreased infiltration of neutrophils and T lymphocytes. Meanwhile, reactive astrogliosis was remarkably attenuated. Furthermore, treatment of AUDA improved angiogenesis, inhibited neuron cells apoptosis, alleviated demyelination and formation of cavity and improved motor recovery. Together, these results provide the first in vivo evidence that sEH inhibition could exert multiple targets protective effects after SCI in rats. sEH may thereby serve as a promising multi-mechanism therapeutic target for the treatment of SCI.
ESTHER : Chen_2016_Mol.Neurobiol_53_1565
PubMedSearch : Chen_2016_Mol.Neurobiol_53_1565
PubMedID: 25663200

Title : Comparative transcriptome analyses of deltamethrin-susceptible and -resistant Culex pipiens pallens by RNA-seq - Lv_2016_Mol.Genet.Genomics_291_309
Author(s) : Lv Y , Wang W , Hong S , Lei Z , Fang F , Guo Q , Hu S , Tian M , Liu B , Zhang D , Sun Y , Ma L , Shen B , Zhou D , Zhu C
Ref : Mol Genet Genomics , 291 :309 , 2016
Abstract : The widespread and improper use of pyrethroid insecticides, such as deltamethrin, has resulted in the evolution of resistance in many mosquito species, including Culex pipiens pallens. With the development of high-throughput sequencing, it is possible to massively screen pyrethroid resistance-associated gene. In this study, we used Illumina-Solexa transcriptome sequencing to identify genes that are expressed differently in deltamethrin-susceptible and -resistant strains of Culex pipiens pallens as a critical knowledge base for further studies. A total of 4,961,197,620 base pairs and 55,124,418 reads were sequenced, mapped to the Culex quinquefasciatus genome and assembled into 17,679 known genes. We recorded 1826 significantly differentially expressed genes (DEGs). Among them, 1078 genes were up-regulated and 748 genes were down-regulated in the deltamethrin-resistant strain compared to -susceptible strain. These DEGs contained cytochrome P450 s, cuticle proteins, UDP-glucuronosyltransferases, lipases, serine proteases, heat shock proteins, esterases and others. Among the 1826 DEGs, we found that the transcriptional levels of CYP6AA9 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Moreover, the expression levels of the CYP6AA9 were significantly higher in the resistant strains than the susceptible strains in three different field populations. We further confirmed the association between the CYP6AA9 gene and deltamethrin resistance in mosquitoes by RNA interfering (RNAi). Altogether, we explored massive potential pyrethroid resistance-associated genes and demonstrated that CYP6AA9 participated in the pyrethroid resistance in mosquitoes.
ESTHER : Lv_2016_Mol.Genet.Genomics_291_309
PubMedSearch : Lv_2016_Mol.Genet.Genomics_291_309
PubMedID: 26377942

Title : Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07 - Ji_2016_Sci.Rep_6_21863
Author(s) : Ji K , Wang W , Zeng B , Chen S , Zhao Q , Chen Y , Li G , Ma T
Ref : Sci Rep , 6 :21863 , 2016
Abstract : Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis.
ESTHER : Ji_2016_Sci.Rep_6_21863
PubMedSearch : Ji_2016_Sci.Rep_6_21863
PubMedID: 26911736
Gene_locus related to this paper: 9entr-a0a127l3e1

Title : Genomic Analysis Reveals Multi-Drug Resistance Clusters in Group B Streptococcus CC17 Hypervirulent Isolates Causing Neonatal Invasive Disease in Southern Mainland China - Campisi_2016_Front.Microbiol_7_1265
Author(s) : Campisi E , Rosini R , Ji W , Guidotti S , Rojas-Lopez M , Geng G , Deng Q , Zhong H , Wang W , Liu H , Nan C , Margarit I , Rinaudo CD
Ref : Front Microbiol , 7 :1265 , 2016
Abstract : Neonatal invasive disease caused by group B Streptococcus (GBS) represents a significant public health care concern globally. However, data related to disease burden, serotype distribution, and molecular epidemiology in China and other Asian countries are very few and specifically relative to confined regions. The aim of this study was to investigate the genetic characteristics of GBS isolates recovered from neonates with invasive disease during 2013-2014 at Guangzhou and Changsha hospitals in southern mainland China. We assessed the capsular polysaccharide type, pilus islands (PIs) distribution and hvgA gene presence in a panel of 26 neonatal clinical isolates, of which 8 were recovered from Early Onset Disease and 18 from Late Onset Disease (LOD). Among 26 isolates examined, five serotypes were identified. Type III was the most represented (15 cases), particularly among LOD strains (n = 11), followed by types Ib (n = 5), V (n = 3), Ia (n = 2) and II (n = 1). We performed whole-genome sequencing analysis and antimicrobial susceptibility testing on the 14 serotype III isolates belonging to the hypervirulent Clonal Complex 17 (serotype III-CC17). The presence of PI-2b alone was associated with 13 out of 14 serotype III-CC17 strains. Genome analysis led us to identify two multi-drug resistance gene clusters harbored in two new versions of integrative and conjugative elements (ICEs), carrying five or eight antibiotic resistance genes, respectively. These ICEs replaced the 16 kb-locus that normally contains the PI-1 operon. All isolates harboring the identified ICEs showed multiple resistances to aminoglycoside, macrolide, and tetracycline antibiotic classes. In conclusion, we report the first whole-genome sequence analysis of 14 GBS serotype III-CC17 strains isolated in China, representing the most prevalent lineage causing neonatal invasive disease. The acquisition of newly identified ICEs conferring multiple antibiotic resistance could in part explain the spread of this specific clone among Chinese neonatal isolates and underlines the need for a constant epidemiological surveillance.
ESTHER : Campisi_2016_Front.Microbiol_7_1265
PubMedSearch : Campisi_2016_Front.Microbiol_7_1265
PubMedID: 27574519

Title : Fibroblast growth factor 21 protects mouse brain against d-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation - Yu_2015_Pharmacol.Biochem.Behav_133_122
Author(s) : Yu Y , Bai F , Wang W , Liu Y , Yuan Q , Qu S , Zhang T , Tian G , Li S , Li D , Ren G
Ref : Pharmacol Biochem Behav , 133 :122 , 2015
Abstract : Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that FGF21-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal ( for 8weeks and administered simultaneously with FGF21 (1, 2 or Our results showed that administration of FGF21 significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, FGF21 also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting IkappaBalpha degradation and NF-kappaB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6, decreased significantly. In conclusion, these results suggest that FGF21 protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation.
ESTHER : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedSearch : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedID: 25871519

Title : Over-transcription of genes in a parathion-resistant strain of mosquito Culex pipiens quinquefasciatus - Wang_2015_Insect.Sci_22_150
Author(s) : Wang W , Liu SL , Liu YY , Qiao CL , Chen SL , Cui F
Ref : Insect Sci , 22 :150 , 2015
Abstract : Insecticide resistance is an evolutionary adaptation that develops quite quickly in mosquitoes because of the high selection pressure of chemical insecticides, rapid generation time and large population size. Identification of genes associated with insecticide resistance is fundamental to understand the complex processes responsible for resistance. We compared the gene transcriptional profiles of parathion-resistant and -susceptible Culex pipiens quinquefasciatus using a combination of suppression subtractive hybridization and complementary DNA (cDNA) microarray techniques. A total of 278 colonies were selected from the resistant-susceptible mosquito subtractive library, 38 of which showed more than two fold stronger immunoblotting signals in the resistant strain than in the susceptible strain using cDNA microarray selection. The sequencing results showed that the 38 colonies can be matched to 12 genes of C. p. quinquefasciatus. Eight genes were confirmed to be overexpressed by more than two fold in the resistant strain. These genes encode chymotrypsin-1, theta glutathione S-transferase, lipase 3, larval serum protein 1 beta chain, cytochrome b, mitochondrial ribosomal large subunit, 28S rRNA, and a protein with unknown function. This study serves as a preliminary attempt to identify new genes associated with organophosphate resistance in this mosquito species and provides insights into the complicated physiological phenomenon of insecticide resistance.
ESTHER : Wang_2015_Insect.Sci_22_150
PubMedSearch : Wang_2015_Insect.Sci_22_150
PubMedID: 24431295

Title : Protein Depalmitoylation Is Induced by Wnt5a and Promotes Polarized Cell Behavior - Wang_2015_J.Biol.Chem_290_15707
Author(s) : Wang W , Runkle KB , Terkowski SM , Ekaireb RI , Witze ES
Ref : Journal of Biological Chemistry , 290 :15707 , 2015
Abstract : Wnt5a signaling regulates polarized cell behavior, but the downstream signaling events that promote cell polarity are not well understood. Our results show that Wnt5a promotes depalmitoylation of the melanoma cell adhesion molecule (MCAM) at cysteine 590. Mutation of Cys-590 to glycine is sufficient to polarize MCAM localization, similar to what is observed with Wnt5a stimulation. Inhibition of the depalmitoylating enzyme APT1 blocks Wnt5a-induced depalmitoylation, asymmetric MCAM localization, and cell invasion. Directly altering expression of the basal protein palmitoylation machinery is sufficient to promote cell invasion. Additionally, cancer mutations in palmitoyltransferases decrease MCAM palmitoylation and have impaired ability to suppress cell invasion. Our results provide evidence that Wnt5a induces protein depalmitoylation, which promotes polarized protein localization and cell invasion.
ESTHER : Wang_2015_J.Biol.Chem_290_15707
PubMedSearch : Wang_2015_J.Biol.Chem_290_15707
PubMedID: 25944911

Title : Engineering of Glarea lozoyensis for exclusive production of the pneumocandin B0 precursor of the antifungal drug caspofungin acetate - Chen_2015_Appl.Environ.Microbiol_81_1550
Author(s) : Chen L , Yue Q , Li Y , Niu X , Xiang M , Wang W , Bills GF , Liu X , An Z
Ref : Applied Environmental Microbiology , 81 :1550 , 2015
Abstract : Pneumocandins produced by the fungus Glarea lozoyensis are acylated cyclic hexapeptides of the echinocandin family. Pneumocandin B0 is the starting molecule for the first semisynthetic echinocandin antifungal drug, caspofungin acetate. In the wild-type strain, pneumocandin B0 is a minor fermentation product, and its industrial production was achieved by a combination of extensive mutation and medium optimization. The pneumocandin biosynthetic gene cluster was previously elucidated by a whole-genome sequencing approach. Knowledge of the biosynthetic cluster suggested an alternative way to produce exclusively pneumocandin B0. Disruption of GLOXY4, encoding a nonheme, alpha-ketoglutarate-dependent oxygenase, confirmed its involvement in l-leucine cyclization to form 4S-methyl-l-proline. The absence of 4S-methyl-l-proline abolishes pneumocandin A0 production, and 3S-hydroxyl-l-proline occupies the hexapeptide core's position 6, resulting in exclusive production of pneumocandin B0. Retrospective analysis of the GLOXY4 gene in a previously isolated pneumocandin B0-exclusive mutant (ATCC 74030) indicated that chemical mutagenesis disrupted the GLOXY4 gene function by introducing two amino acid mutations in GLOXY4. This one-step genetic manipulation can rationally engineer a high-yield production strain.
ESTHER : Chen_2015_Appl.Environ.Microbiol_81_1550
PubMedSearch : Chen_2015_Appl.Environ.Microbiol_81_1550
PubMedID: 25527531
Gene_locus related to this paper: glal2-glon

Title : Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products - Wang_2015_BMC.Genomics_16_28
Author(s) : Wang X , Zhang X , Liu L , Xiang M , Wang W , Sun X , Che Y , Guo L , Liu G , Wang C , Yin WB , Stadler M , Liu X
Ref : BMC Genomics , 16 :28 , 2015
Abstract : BACKGROUND: In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics.
RESULTS: Here, we report the genome sequence of the endophytic fungus of tea Pestalotiopsis fici W106-1/CGMCC3.15140. The abundant carbohydrate-active enzymes especially significantly expanding pectinases allow the fungus to utilize the limited intercellular nutrients within the host plants, suggesting adaptation of the fungus to endophytic lifestyle. The P. fici genome encodes a rich set of secondary metabolite synthesis genes, including 27 polyketide synthases (PKSs), 12 non-ribosomal peptide synthases (NRPSs), five dimethylallyl tryptophan synthases, four putative PKS-like enzymes, 15 putative NRPS-like enzymes, 15 terpenoid synthases, seven terpenoid cyclases, seven fatty-acid synthases, and five hybrids of PKS-NRPS. The majority of these core enzymes distributed into 74 secondary metabolite clusters. The putative Diels-Alderase genes have undergone expansion. CONCLUSION: The significant expansion of pectinase encoding genes provides essential insight in the life strategy of endophytes, and richness of gene clusters for secondary metabolites reveals high potential of natural products of endophytic fungi.
ESTHER : Wang_2015_BMC.Genomics_16_28
PubMedSearch : Wang_2015_BMC.Genomics_16_28
PubMedID: 25623211
Gene_locus related to this paper: 9pezi-w3wud0 , 9pezi-w3xja3 , pesfw-w3wz53 , pesfw-w3x341 , pesfw-w3whp0 , pesfw-w3xc39 , pesfw-w3wrn9 , pesfw-pfmab , pesfw-pfmae

Title : Outbred genome sequencing and CRISPR\/Cas9 gene editing in butterflies - Li_2015_Nat.Commun_6_8212
Author(s) : Li X , Fan D , Zhang W , Liu G , Zhang L , Zhao L , Fang X , Chen L , Dong Y , Chen Y , Ding Y , Zhao R , Feng M , Zhu Y , Feng Y , Jiang X , Zhu D , Xiang H , Feng X , Li S , Wang J , Zhang G , Kronforst MR , Wang W
Ref : Nat Commun , 6 :8212 , 2015
Abstract : Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system.
ESTHER : Li_2015_Nat.Commun_6_8212
PubMedSearch : Li_2015_Nat.Commun_6_8212
PubMedID: 26354079
Gene_locus related to this paper: papxu-a0a194pj15 , papxu-a0a194q254 , papma-a0a194rdx2 , papxu-a0a194q858 , papxu-a0a194pyl3 , papxu-a0a194q337 , papma-a0a194r1p9 , papma-a0a194r6h1 , papxu-a0a194q1w8 , papma-a0a194ql80 , papma-a0a0n1ipl3 , papma-a0a194qm14

Title : Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication - Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
Author(s) : Yang K , Tian Z , Chen C , Luo L , Zhao B , Wang Z , Yu L , Li Y , Sun Y , Li W , Chen Y , Zhang Y , Ai D , Zhao J , Shang C , Ma Y , Wu B , Wang M , Gao L , Sun D , Zhang P , Guo F , Wang W , Wang J , Varshney RK , Ling HQ , Wan P
Ref : Proc Natl Acad Sci U S A , 112 :13213 , 2015
Abstract : Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean.
ESTHER : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedSearch : Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213
PubMedID: 26460024
Gene_locus related to this paper: phaan-a0a0l9ttq5 , phaan-a0a0l9vh69 , phaan-a0a0l9vh89 , phaan-a0a0s3tc53 , vigrr-a0a1s3v914 , phaan-a0a0s3s998 , phaan-a0a0s3siv8 , phaan-a0a0l9uys5 , phaan-a0a0s3rp07 , phaan-a0a0s3rbq0 , vigrr-a0a1s3tul4 , phaan-a0a0s3smk7 , phaan-a0a0s3slm9 , phaan-a0a0l9ujf5 , phaan-a0a0l9til9 , phaan-a0a0l9uqr2 , phaan-a0a0l9v1m8 , phaan-a0a0l9uc60 , phaan-a0a0l9ucr8

Title : Overexpression of miR-155 in the Liver of Transgenic Mice Alters the Expression Profiling of Hepatic Genes Associated with Lipid Metabolism - Lin_2015_PLoS.One_10_e0118417
Author(s) : Lin X , Jia J , Du T , Li W , Wang X , Wei J , Zeng H , Yao L , Chen X , Zhuang J , Weng J , Liu Y , Lin J , Wu Q , Wang W , Yao K , Xu K , Xiao D
Ref : PLoS ONE , 10 :e0118417 , 2015
Abstract : Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice.
ESTHER : Lin_2015_PLoS.One_10_e0118417
PubMedSearch : Lin_2015_PLoS.One_10_e0118417
PubMedID: 25799309

Title : Deciphering the venomic transcriptome of killer-wasp Vespa velutina - Liu_2015_Sci.Rep_5_9454
Author(s) : Liu Z , Chen S , Zhou Y , Xie C , Zhu B , Zhu H , Liu S , Wang W , Chen H , Ji Y
Ref : Sci Rep , 5 :9454 , 2015
Abstract : Wasp stings have been arising to be a severe public health problem in China in recent years. However, molecular information about lethal or toxic factors in wasp venom is extremely lacking. In this study, we used two pyrosequencing platforms to analyze the transcriptome of Vespa velutina, the most common wasp species native in China. Besides the substantial amount of transcripts encoding for allergens usually regarded as the major lethal factor of wasp sting, a greater abundance of hemostasis-impairing toxins and neurotoxins in the venom of V. velutina were identified, implying that toxic reactions and allergic effects are envenoming strategy for the dangerous outcomes. The pattern of differentially expressed genes before and after venom extraction clearly indicates that the manifestation of V. velutina stings depends on subtle regulations in the metabolic pathway required for toxin recruitment. This comparative analysis offers timely clues for developing clinical treatments for wasp envenoming in China and around the world.
ESTHER : Liu_2015_Sci.Rep_5_9454
PubMedSearch : Liu_2015_Sci.Rep_5_9454
PubMedID: 25896434
Gene_locus related to this paper: vesve-pa1

Title : Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like effects and enhances adult hippocampal neurogenesis and synaptic plasticity - Zhang_2015_Hippocampus_25_16
Author(s) : Zhang Z , Wang W , Zhong P , Liu SJ , Long JZ , Zhao L , Gao HQ , Cravatt BF , Liu QS
Ref : Hippocampus , 25 :16 , 2015
Abstract : The endocannabinoid ligand 2-arachidonoylglycerol (2-AG) is inactivated primarily by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments with MAGL inhibitor JZL184 produce antidepressant- and anxiolytic-like effects in a chronic unpredictable stress (CUS) model of depression in mice. However, the underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis has been implicated in animal models of anxiety and depression and behavioral effects of antidepressants. We tested whether CUS and chronic JZL184 treatments affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of mouse hippocampus. We report that CUS induced depressive-like behaviors and decreased the number of bromodeoxyuridine-labeled neural progenitor cells and doublecortin-positive immature neurons in the DG, while chronic JZL184 treatments prevented these behavioral and cellular deficits. We also investigated the effects of CUS and chronic JZL184 on a form long-term potentiation (LTP) in the DG known to be neurogenesis-dependent. CUS impaired LTP induction, whereas chronic JZL184 treatments restored LTP in CUS-exposed mice. These results suggest that enhanced adult neurogenesis and long-term synaptic plasticity in the DG of the hippocampus might contribute to antidepressant- and anxiolytic-like behavioral effects of JZL184.
ESTHER : Zhang_2015_Hippocampus_25_16
PubMedSearch : Zhang_2015_Hippocampus_25_16
PubMedID: 25131612
Gene_locus related to this paper: human-MGLL

Title : Reproductive Mode and the Evolution of Genome Size and Structure in Caenorhabditis Nematodes - Fierst_2015_PLoS.Genet_11_e1005323
Author(s) : Fierst JL , Willis JH , Thomas CG , Wang W , Reynolds RM , Ahearne TE , Cutter AD , Phillips PC
Ref : PLoS Genet , 11 :e1005323 , 2015
Abstract : The self-fertile nematode worms Caenorhabditis elegans, C. briggsae, and C. tropicalis evolved independently from outcrossing male-female ancestors and have genomes 20-40% smaller than closely related outcrossing relatives. This pattern of smaller genomes for selfing species and larger genomes for closely related outcrossing species is also seen in plants. We use comparative genomics, including the first high quality genome assembly for an outcrossing member of the genus (C. remanei) to test several hypotheses for the evolution of genome reduction under a change in mating system. Unlike plants, it does not appear that reductions in the number of repetitive elements, such as transposable elements, are an important contributor to the change in genome size. Instead, all functional genomic categories are lost in approximately equal proportions. Theory predicts that self-fertilization should equalize the effective population size, as well as the resulting effects of genetic drift, between the X chromosome and autosomes. Contrary to this, we find that the self-fertile C. briggsae and C. elegans have larger intergenic spaces and larger protein-coding genes on the X chromosome when compared to autosomes, while C. remanei actually has smaller introns on the X chromosome than either self-reproducing species. Rather than being driven by mutational biases and/or genetic drift caused by a reduction in effective population size under self reproduction, changes in genome size in this group of nematodes appear to be caused by genome-wide patterns of gene loss, most likely generated by genomic adaptation to self reproduction per se.
ESTHER : Fierst_2015_PLoS.Genet_11_e1005323
PubMedSearch : Fierst_2015_PLoS.Genet_11_e1005323
PubMedID: 26114425
Gene_locus related to this paper: caere-e3mmc6

Title : Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites - Zhou_2014_BMC.Genomics_15_42
Author(s) : Zhou D , Zhang D , Ding G , Shi L , Hou Q , Ye Y , Xu Y , Zhou H , Xiong C , Li S , Yu J , Hong S , Yu X , Zou P , Chen C , Chang X , Wang W , Lv Y , Sun Y , Ma L , Shen B , Zhu C
Ref : BMC Genomics , 15 :42 , 2014
Abstract : BACKGROUND: Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.
RESULTS: We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.
CONCLUSIONS: The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
ESTHER : Zhou_2014_BMC.Genomics_15_42
PubMedSearch : Zhou_2014_BMC.Genomics_15_42
PubMedID: 24438588
Gene_locus related to this paper: anoga-Q7PVF9 , 9dipt-a0a084vlt1 , 9dipt-a0a084vdq2 , 9dipt-sime3xf.a , 9dipt-sime3xf.b , 9dipt-a0a084vbj8 , 9dipt-a0a084wan7 , 9dipt-a0a084wik4 , 9dipt-a0a084wk64 , 9dipt-a0a084wez8 , 9dipt-a0a084vji7 , 9dipt-a0a084vlc2 , 9dipt-a0a084vsa5 , 9dipt-a0a084wlk0 , 9dipt-a0a084wah8 , 9dipt-a0a084wln4 , 9dipt-a0a084we78 , 9dipt-a0a084wjm6 , 9dipt-a0a084wjm7 , 9dipt-a0a084we77 , 9dipt-a0a084wlk1 , 9dipt-a0a084we80 , 9dipt-a0a084wjm4 , 9dipt-a0a084w1n7 , 9dipt-a0a084we79 , 9dipt-a0a084wev9 , 9dipt-a0a084vlc3 , 9dipt-a0a084vdq4 , 9dipt-a0a084vdq5 , 9dipt-a0a084vdq1 , 9dipt-a0a084wah9 , 9dipt-a0a084wan6 , 9dipt-a0a084wlj8 , 9dipt-a0a084wk45 , 9dipt-a0a084wk46 , 9dipt-a0a084wlj9 , 9dipt-a0a084vsa4 , 9dipt-a0a084vs93 , 9dipt-a0a084wl93 , anosi-a0a0f7kyf5 , anosi-a0a0f7l1f2 , anosi-a0a084wum0 , anost-a0a182xxz0 , anosi-a0a084vn28 , anosi-a0a084vpt0 , anoga-q7q887

Title : Oil degradation and biosurfactant production by the deep sea bacterium Dietzia maris As-13-3 - Wang_2014_Front.Microbiol_5_711
Author(s) : Wang W , Cai B , Shao Z
Ref : Front Microbiol , 5 :711 , 2014
Abstract : Recent investigations of extreme environments have revealed numerous bioactive natural products. However, biosurfactant-producing strains from deep sea extreme environment are largely unknown. Here, we show that Dietzia maris As-13-3 isolated from deep sea hydrothermal field could produce di-rhamnolipid as biosurfactant. The critical micelle concentration (CMC) of the purified di-rhamnolipid was determined to be 120 mgL(-1), and it lowered the surface tension of water from 74 +/- 0.2 to 38 +/- 0.2 mN m(-1). Further, the alkane metabolic pathway-related genes and di-rhamnolipid biosynthesis-related genes were also analyzed by the sequencing genome of D. maris As-13-3 and quantitative real-time PCR (Q-PCR), respectively. Q-PCR analysis showed that all these genes were induced by n-Tetradecane, n-Hexadecane, and pristane. To the best of our knowledge, this is first report about the complete pathway of the di-rhamnolipid synthesis process in the genus Dietzia. Thus, our study provided the insights into Dietzia in respects of oil degradation and biosurfactant production, and will help to evaluate the potential of Dietzia in marine oil removal.
ESTHER : Wang_2014_Front.Microbiol_5_711
PubMedSearch : Wang_2014_Front.Microbiol_5_711
PubMedID: 25566224
Gene_locus related to this paper: burcj-b4ehi9

Title : Galanthamine, an acetylcholine inhibitor, prevents prepulse inhibition deficits induced by adolescent social isolation or MK-801 treatment - Shao_2014_Brain.Res_1589_105
Author(s) : Shao S , Li M , Du W , Shao F , Wang W
Ref : Brain Research , 1589 :105 , 2014
Abstract : Adolescence is a critical period for neurodevelopment. MK-801 treatment and social isolation are important animal models for various neurodevelopmental disorders. Dysfunctions in the central cholinergic system are involved in creating the cognitive deficits observed in neurological diseases. In the present study, we aimed to investigate whether the acetylcholinesterase inhibitor galanthamine could reverse pre-cognitive prepulse inhibition (PPI) deficits and spatial learning deficits of adult rats in the Morris water maze. We induced these effects using either adolescent MK-801 treatment or social isolation from postnatal day (PND) 38-51. Our results showed that both adolescent social isolation and MK-801 treatment impaired PPI in adult rats, but neither had an effect on spatial learning. Furthermore, galanthamine injections over 7 days significantly enhanced PPI of normal rats and improved PPI disruption induced by adolescent pharmacological and rearing interventions. The results suggest that acetylcholinesterase inhibitors, such as galanthamine, might have the potential to improve pre-cognition in neurodevelopmental diseases by improving auditory sensory gating.
ESTHER : Shao_2014_Brain.Res_1589_105
PubMedSearch : Shao_2014_Brain.Res_1589_105
PubMedID: 25281804

Title : Enhanced production of lipstatin from Streptomyces toxytricini by optimizing fermentation conditions and medium - Zhu_2014_J.Gen.Appl.Microbiol_60_106
Author(s) : Zhu T , Wang L , Wang W , Hu Z , Yu M , Wang K , Cui Z
Ref : J Gen Appl Microbiol , 60 :106 , 2014
Abstract : This paper is concerned with optimization of fermentation conditions for lipstatin production with Streptomyces toxytricini zjut011 by the single factor and orthogonal tests. Five single factors of important effects on lipstatin production were explored. L-Leucine was identified to be the most suitable precursor for lipstatin biosynthesis and for the first time the divalent cations Mg(2+), Co(2+) and Zn(2+) were found to have significant effect on enhancing lipstatin fermentation titer. The effects of the additives on the lipstatin production were in the order of L-leucine Mg(2+) Co(2+) Zn(2+) octanoic acid. The optimized conditions for lipstatin production were determined as 45.72 mmol/L of L-leucine (added on the 4 th day), 31.1985 mmol/L of octanoic acid (added on the 6th day), 12 mmol/L of Mg(2+), 1 mmol/L of Co(2+) and 0.25 mmol/L of Zn(2+). Under these conditions, a maximum lipstatin of 4.208 g/ml was achieved in verification experiments in 500 ml shake flasks.
ESTHER : Zhu_2014_J.Gen.Appl.Microbiol_60_106
PubMedSearch : Zhu_2014_J.Gen.Appl.Microbiol_60_106
PubMedID: 25008166

Title : Comparative genomic analysis shows that Streptococcus suis meningitis isolate SC070731 contains a unique 105K genomic island - Wu_2014_Gene_535_156
Author(s) : Wu Z , Wang W , Tang M , Shao J , Dai C , Zhang W , Fan H , Yao H , Zong J , Chen D , Wang J , Lu C
Ref : Gene , 535 :156 , 2014
Abstract : Streptococcus suis (SS) is an important swine pathogen worldwide that occasionally causes serious infections in humans. SS infection may result in meningitis in pigs and humans. The pathogenic mechanisms of SS are poorly understood. Here, we provide the complete genome sequence of S. suis serotype 2 (SS2) strain SC070731 isolated from a pig with meningitis. The chromosome is 2,138,568bp in length. There are 1933 predicted protein coding sequences and 96.7% (57/59) of the known virulence-associated genes are present in the genome. Strain SC070731 showed similar virulence with SS2 virulent strains HA9801 and ZY05719, but was more virulent than SS2 virulent strain P1/7 in the zebrafish infection model. Comparative genomic analysis revealed a unique 105K genomic island in strain SC070731 that is absent in seven other sequenced SS2 strains. Further analysis of the 105K genomic island indicated that it contained a complete nisin locus similar to the nisin U locus in S. uberis strain 42, a prophage similar to S. oralis phage PH10 and several antibiotic resistance genes. Several proteins in the 105K genomic island, including nisin and RelBE toxin-antitoxin system, contribute to the bacterial fitness and virulence in other pathogenic bacteria. Further investigation of newly identified gene products, including four putative new virulence-associated surface proteins, will improve our understanding of SS pathogenesis.
ESTHER : Wu_2014_Gene_535_156
PubMedSearch : Wu_2014_Gene_535_156
PubMedID: 24316490
Gene_locus related to this paper: strej-e8uk64

Title : Health hazard assessment of occupationally di-(2-ethylhexyl)-phthalate-exposed workers in China - Wang_2014_Chemosphere_120C_37
Author(s) : Wang W , Xu X , Fan CQ
Ref : Chemosphere , 120C :37 , 2014
Abstract : Di-(2-ethylhexyl)-phthalate (DEHP) is a potential hazard to human health. The effects of occupational high level DEHP exposure on human health were evaluated by measuring the plasma cholinesterase, residues, renal and hepatic biochemical markers. The study was conducted in three representative polyvinyl chloride manufacturing facilities from large size (S1), medium side (S2) to small size (S3). Total 456 adult males including 352 exposed workers (occupational) and 104 control workers (background) were selected. The average DEHP concentrations in respirable particulate matter were 233, 291, and 707mugm-3 for S1-S3, respectively, compared with 0.26mugm-3 in the background atmosphere (labeled by S4). The results showed significant decreases in post exposure plasma cholinesterase (PChE) levels (<30%) from the exposed workers as compared to baseline. These exposed workers had been evaluated for plasma DEHP residues. Regression analyses explored that PChE decreased significantly with increasing plasma DEHP residues. Serum aspartate aminotransferase, alanine aminotransferase, creatinine, urea, gamma glutamyltransferase, malondialdehyde, total antioxidant and C-reactive protein were significantly raised as compared to the controls. Of the 352 exposed workers, 116 (33.0%) had a daily DEHP intake 22.7mugkgbw-1d-1 , which is more than 20mugkgbw-1d-1 specified by the US Environmental Protection Agency. The study demonstrated that occupational phthalate exposure produces health hazards.
ESTHER : Wang_2014_Chemosphere_120C_37
PubMedSearch : Wang_2014_Chemosphere_120C_37
PubMedID: 24974312

Title : Monoacylglycerol lipase inhibition blocks chronic stress-induced depressive-like behaviors via activation of mTOR signaling - Zhong_2014_Neuropsychopharmacology_39_1763
Author(s) : Zhong P , Wang W , Pan B , Liu X , Zhang Z , Long JZ , Zhang HT , Cravatt BF , Liu QS
Ref : Neuropsychopharmacology , 39 :1763 , 2014
Abstract : The endocannabinoid (eCB) system regulates mood, emotion, and stress coping, and dysregulation of the eCB system is critically involved in pathophysiology of depression. The eCB ligand 2-arachidonoylglycerol (2-AG) is inactivated by monoacylglycerol lipase (MAGL). Using chronic unpredictable mild stress (CUS) as a mouse model of depression, we examined how 2-AG signaling in the hippocampus was altered in depressive-like states and how this alteration contributed to depressive-like behavior. We report that CUS led to impairment of depolarization-induced suppression of inhibition (DSI) in mouse hippocampal CA1 pyramidal neurons, and this deficiency in 2-AG-mediated retrograde synaptic depression was rescued by MAGL inhibitor JZL184. CUS induced depressive-like behaviors and decreased mammalian target of rapamycin (mTOR) activation in the hippocampus, and these biochemical and behavioral abnormalities were ameliorated by chronic JZL184 treatments. The effects of JZL184 were mediated by cannabinoid CB1 receptors. Genetic deletion of mTOR with adeno-associated viral (AAV) vector carrying the Cre recombinase in the hippocampus of mTORf/f mice recapitulated depressive-like behaviors induced by CUS and abrogated the antidepressant-like effects of chronic JZL184 treatments. Our results suggest that CUS decreases eCB-mTOR signaling in the hippocampus, leading to depressive-like behaviors, whereas MAGL inhibitor JZL184 produces antidepressant-like effects through enhancement of eCB-mTOR signaling.
ESTHER : Zhong_2014_Neuropsychopharmacology_39_1763
PubMedSearch : Zhong_2014_Neuropsychopharmacology_39_1763
PubMedID: 24476943

Title : Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas - Tang_2013_PLoS.Genet_9_e1003923
Author(s) : Tang H , Wang L , Wang W , Yu H , Zhang K , Yao Y , Xu P
Ref : PLoS Genet , 9 :e1003923 , 2013
Abstract : Microorganisms such as Pseudomonas putida play important roles in the mineralization of organic wastes and toxic compounds. To comprehensively and accurately elucidate key processes of nicotine degradation in Pseudomonas putida, we measured differential protein abundance levels with MS-based spectral counting in P. putida S16 grown on nicotine or glycerol, a non-repressive carbon source. In silico analyses highlighted significant clustering of proteins involved in a functional pathway in nicotine degradation. The transcriptional regulation of differentially expressed genes was analyzed by using quantitative reverse transcription-PCR. We observed the following key results: (i) The proteomes, containing 1,292 observed proteins, provide a detailed view of enzymes involved in nicotine metabolism. These proteins could be assigned to the functional groups of transport, detoxification, and amino acid metabolism. There were significant differences in the cytosolic protein patterns of cells growing in a nicotine medium and those in a glycerol medium. (ii) The key step in the conversion of 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine was catalyzed by a multi-enzyme reaction consisting of a molybdopeterin binding oxidase (spmA), molybdopterin dehydrogenase (spmB), and a (2Fe-2S)-binding ferredoxin (spmC) with molybdenum molybdopterin cytosine dinucleotide as a cofactor. (iii) The gene of a novel nicotine oxidoreductase (nicA2) was cloned, and the recombinant protein was characterized. The proteins and functional pathway identified in the current study represent attractive targets for degradation of environmental toxic compounds.
ESTHER : Tang_2013_PLoS.Genet_9_e1003923
PubMedSearch : Tang_2013_PLoS.Genet_9_e1003923
PubMedID: 24204321

Title : Draft Genome Sequence of a Benzothiophene-Desulfurizing Bacterium, Gordona terrae Strain C-6 - Wang_2013_Genome.Announc_1_e00381
Author(s) : Wang W , Ma T , Ren Y , Li G
Ref : Genome Announc , 1 : , 2013
Abstract : Gordona terrae strain C-6 was isolated from oil-contaminated soil and is capable of desulfurizing benzothiophene (BT). Here we report the draft genome sequence of G. terrae strain C-6, which may help to reveal the genetic basis of the BT biodesulfurization pathway.
ESTHER : Wang_2013_Genome.Announc_1_e00381
PubMedSearch : Wang_2013_Genome.Announc_1_e00381
PubMedID: 23788548
Gene_locus related to this paper: 9acto-h5ue78 , 9acto-h5ujj3 , 9acto-j9rte6 , 9acto-j9rnp4 , 9acto-h5ui26 , 9actn-r7y6f1 , 9actn-r7ybz2

Title : An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo - Tang_2013_J.Biol.Chem_288_1307
Author(s) : Tang J , Majeti J , Sudom A , Xiong Y , Lu M , Liu Q , Higbee J , Zhang Y , Wang Y , Wang W , Cao P , Xia Z , Johnstone S , Min X , Yang X , Shao H , Yu T , Sharkov N , Walker N , Tu H , Shen W , Wang Z
Ref : Journal of Biological Chemistry , 288 :1307 , 2013
Abstract : Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). Small molecule DPP-IV inhibitors have been used as treatments for type 2 diabetes to improve glucose tolerance. However, each of the marketed small molecule drugs has its own limitation in terms of efficacy and side effects. To search for an alternative strategy of inhibiting DPP-IV activity, we generated a panel of tight binding inhibitory mouse monoclonal antibodies (mAbs) against rat DPP-IV. When tested in vitro, these mAbs partially inhibited the GLP-1 cleavage activity of purified enzyme and rat plasma. To understand the partial inhibition, we solved the co-crystal structure of one of the mAb Fabs (Ab1) in complex with rat DPP-IV. Although Ab1 does not bind at the active site, it partially blocks the side opening, which prevents the large substrates such as GLP-1 from accessing the active site, but not small molecules such as sitagliptin. When Ab1 was tested in vivo, it reduced plasma glucose and increased plasma GLP-1 concentration during an oral glucose tolerance test in rats. Together, we demonstrated the feasibility of using mAbs to inhibit DPP-IV activity and to improve glucose tolerance in a diabetic rat model.
ESTHER : Tang_2013_J.Biol.Chem_288_1307
PubMedSearch : Tang_2013_J.Biol.Chem_288_1307
PubMedID: 23184939
Gene_locus related to this paper: ratno-dpp4

Title : Genetic variability of mutans streptococci revealed by wide whole-genome sequencing - Song_2013_BMC.Genomics_14_430
Author(s) : Song L , Wang W , Conrads G , Rheinberg A , Sztajer H , Reck M , Wagner-Dobler I , Zeng AP
Ref : BMC Genomics , 14 :430 , 2013
Abstract : BACKGROUND: Mutans streptococci are a group of bacteria significantly contributing to tooth decay. Their genetic variability is however still not well understood.
RESULTS: Genomes of 6 clinical S. mutans isolates of different origins, one isolate of S. sobrinus (DSM 20742) and one isolate of S. ratti (DSM 20564) were sequenced and comparatively analyzed. Genome alignment revealed a mosaic-like structure of genome arrangement. Genes related to pathogenicity are found to have high variations among the strains, whereas genes for oxidative stress resistance are well conserved, indicating the importance of this trait in the dental biofilm community. Analysis of genome-scale metabolic networks revealed significant differences in 42 pathways. A striking dissimilarity is the unique presence of two lactate oxidases in S. sobrinus DSM 20742, probably indicating an unusual capability of this strain in producing H2O2 and expanding its ecological niche. In addition, lactate oxidases may form with other enzymes a novel energetic pathway in S. sobrinus DSM 20742 that can remedy its deficiency in citrate utilization pathway.Using 67 S. mutans genomes currently available including the strains sequenced in this study, we estimates the theoretical core genome size of S. mutans, and performed modeling of S. mutans pan-genome by applying different fitting models. An "open" pan-genome was inferred.
CONCLUSIONS: The comparative genome analyses revealed diversities in the mutans streptococci group, especially with respect to the virulence related genes and metabolic pathways. The results are helpful for better understanding the evolution and adaptive mechanisms of these oral pathogen microorganisms and for combating them.
ESTHER : Song_2013_BMC.Genomics_14_430
PubMedSearch : Song_2013_BMC.Genomics_14_430
PubMedID: 23805886
Gene_locus related to this paper: strrt-j3jp47

Title : Toxicological effects of multi-walled carbon nanotubes adsorbed with nonylphenol on earthworm Eisenia fetida - Hu_2013_Environ.Sci.Process.Impacts_15_2125
Author(s) : Hu C , Cai Y , Wang W , Cui Y , Li M
Ref : Environ Sci Process Impacts , 15 :2125 , 2013
Abstract : The high surface area of multi-walled carbon nanotubes (MWCNTs) tends to adsorb a large variety of toxic chemicals, which may enhance the toxicity of both MWCNTs and chemicals to organisms. In order to evaluate the combined toxicity of nonylphenol (NP) and MWCNTs to the earthworm Eisenia fetida in soil, artificial soil systems containing distilled water, 0.1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs absorbed 5 mg kg(-1) NP, and 10 mg kg(-1) NP alone were prepared and exposed to earthworms for 7 days. Antioxidative responses, and activities of cellulase, Na(+), K(+)-ATPase and acetylcholinesterase (TChE) as well as DNA damage were chosen as toxicological endpoints. The results showed that 1 g kg(-1) MWCNTs adsorbed 5 mg kg(-1) NP from the soil which caused much more adverse effects on the earthworms than each chemical alone, evident from the responses of cellulase, Na(+), K(+)-ATPase and comet assay. This study indicated that MWCNTs facilitated the bioavailability of NP to the earthworm and increased the harmful effects of NP.
ESTHER : Hu_2013_Environ.Sci.Process.Impacts_15_2125
PubMedSearch : Hu_2013_Environ.Sci.Process.Impacts_15_2125
PubMedID: 24104387

Title : The Capsella rubella genome and the genomic consequences of rapid mating system evolution - Slotte_2013_Nat.Genet_45_831
Author(s) : Slotte T , Hazzouri KM , Agren JA , Koenig D , Maumus F , Guo YL , Steige K , Platts AE , Escobar JS , Newman LK , Wang W , Mandakova T , Vello E , Smith LM , Henz SR , Steffen J , Takuno S , Brandvain Y , Coop G , Andolfatto P , Hu TT , Blanchette M , Clark RM , Quesneville H , Nordborg M , Gaut BS , Lysak MA , Jenkins J , Grimwood J , Chapman J , Prochnik S , Shu S , Rokhsar D , Schmutz J , Weigel D , Wright SI
Ref : Nat Genet , 45 :831 , 2013
Abstract : The shift from outcrossing to selfing is common in flowering plants, but the genomic consequences and the speed at which they emerge remain poorly understood. An excellent model for understanding the evolution of self fertilization is provided by Capsella rubella, which became self compatible <200,000 years ago. We report a C. rubella reference genome sequence and compare RNA expression and polymorphism patterns between C. rubella and its outcrossing progenitor Capsella grandiflora. We found a clear shift in the expression of genes associated with flowering phenotypes, similar to that seen in Arabidopsis, in which self fertilization evolved about 1 million years ago. Comparisons of the two Capsella species showed evidence of rapid genome-wide relaxation of purifying selection in C. rubella without a concomitant change in transposable element abundance. Overall we document that the transition to selfing may be typified by parallel shifts in gene expression, along with a measurable reduction of purifying selection.
ESTHER : Slotte_2013_Nat.Genet_45_831
PubMedSearch : Slotte_2013_Nat.Genet_45_831
PubMedID: 23749190
Gene_locus related to this paper: arath-CGEP , 9bras-r0h1k6 , 9bras-r0gvg3 , 9bras-r0gv62 , 9bras-r0g5k5 , 9bras-r0f1u1 , 9bras-r0guy4 , 9bras-r0ien7 , 9bras-r0i2r7 , 9bras-r0fbh7 , 9bras-r0fnq1 , 9bras-r0hae6 , 9bras-r0gwt8 , 9bras-r0ewe4 , 9bras-r0gsz7 , 9bras-r0ij26 , 9bras-r0h783 , 9bras-r0i5w1 , 9bras-r0fgs3 , 9bras-r0h1e1 , 9bras-r0fme4 , 9bras-r0ieh8 , 9bras-r0f5l9 , 9bras-r0ffy6

Title : Enzymatic synthesis of extremely pure triacylglycerols enriched in conjugated linoleic acids - Cao_2013_Molecules_18_9704
Author(s) : Cao Y , Wang W , Xu Y , Yang B , Wang Y
Ref : Molecules , 18 :9704 , 2013
Abstract : This work was objectively targeted to synthesize extremely pure triacylglycerols (TAG) enriched in conjugated linoleic acids (CLAs) for medical and dietetic purposes. Extremely pure CLA-enriched TAG was successfully synthesized by using the multi-step process: TAG was primarily synthesized by lipase-catalyzed esterification of CLA and glycerol and then the lower glycerides [monoacylglycerol (MAG) and diacylglycerol (DAG)] in the esterification mixtures was hydrolyzed to free fatty acids (FFAs) by a mono- and di-acylglycerol lipase (lipase SMG1), finally, the FFAs were further separated from TAG by low temperature (150 degreesC) molecular distillation. The operation parameters for the lipase SMG1-catalyzed hydrolysis were optimized using response surface methodology based on the central composite rotatable design (CCRD). The operation parameters included water content, pH and reaction temperature and all of these three parameters showed significant effects on the hydrolysis of lower glycerides. The optimal conditions were obtained with a water content of 66.4% (w/w, with respect to oil mass), pH at 5.7 and 1 h of reaction time at 19.6 degreesC. Under these conditions, the content of lower glycerides in the reaction mixture decreased from 45.2% to 0.3% and the purity of CLA-enriched TAG reached 99.7%. Further purification of TAG was accomplished by molecular distillation and the final CLA-enriched TAG product yielded 99.8% of TAG. These extremely pure CLA-enriched TAG would be used for in vivo studies in animals and humans in order to get specic information concerning CLA metabolism.
ESTHER : Cao_2013_Molecules_18_9704
PubMedSearch : Cao_2013_Molecules_18_9704
PubMedID: 23945644

Title : Complete Genome Sequence of the Industrial Strain Gluconobacter oxydans H24 - Ge_2013_Genome.Announc_1_e00003
Author(s) : Ge X , Zhao Y , Hou W , Zhang W , Chen W , Wang J , Zhao N , Lin J , Wang W , Chen M , Wang Q , Jiao Y , Yuan Z , Xiong X
Ref : Genome Announc , 1 : , 2013
Abstract : Gluconobacter oxydans is characterized by its ability to incompletely oxidize carbohydrates and alcohols. The high yields of its oxidation products and complete secretion into the medium make it important for industrial use. We report the finished genome sequence of Gluconobacter oxydans H24, an industrial strain with high l-sorbose productivity.
ESTHER : Ge_2013_Genome.Announc_1_e00003
PubMedSearch : Ge_2013_Genome.Announc_1_e00003
PubMedID: 23472221
Gene_locus related to this paper: gluth-t1e0l0 , gluoy-k7si88 , gluoy-k7smm7

Title : Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]py ridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778) - Devasthale_2013_J.Med.Chem_56_7343
Author(s) : Devasthale P , Wang Y , Wang W , Fevig J , Feng J , Wang A , Harrity T , Egan D , Morgan N , Cap M , Fura A , Klei HE , Kish K , Weigelt C , Sun L , Levesque P , Moulin F , Li YX , Zahler R , Kirby MS , Hamann LG
Ref : Journal of Medicinal Chemistry , 56 :7343 , 2013
Abstract : Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.
ESTHER : Devasthale_2013_J.Med.Chem_56_7343
PubMedSearch : Devasthale_2013_J.Med.Chem_56_7343
PubMedID: 23964740
Gene_locus related to this paper: human-DPP4

Title : NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation - Pietiainen_2013_J.Cell.Sci_126_3961
Author(s) : Pietiainen V , Vassilev B , Blom T , Wang W , Nelson J , Bittman R , Back N , Zelcer N , Ikonen E
Ref : Journal of Cell Science , 126 :3961 , 2013
Abstract : N-myc downstream-regulated gene 1 (NDRG1) mutations cause Charcot-Marie-Tooth disease type 4D (CMT4D). However, the cellular function of NDRG1 and how it causes CMT4D are poorly understood. We report that NDRG1 silencing in epithelial cells results in decreased uptake of low-density lipoprotein (LDL) due to reduced LDL receptor (LDLR) abundance at the plasma membrane. This is accompanied by the accumulation of LDLR in enlarged EEA1-positive endosomes that contain numerous intraluminal vesicles and sequester ceramide. Concomitantly, LDLR ubiquitylation is increased but its degradation is reduced and ESCRT (endosomal sorting complex required for transport) proteins are downregulated. Co-depletion of IDOL (inducible degrader of the LDLR), which ubiquitylates the LDLR and promotes its degradation, rescues plasma membrane LDLR levels and LDL uptake. In murine oligodendrocytes, Ndrg1 silencing not only results in reduced LDL uptake but also in downregulation of the oligodendrocyte differentiation factor Olig2. Both phenotypes are rescued by co-silencing of Idol, suggesting that ligand uptake through LDLR family members controls oligodendrocyte differentiation. These findings identify NDRG1 as a novel regulator of multivesicular body formation and endosomal LDLR trafficking. The deficiency of functional NDRG1 in CMT4D might impair lipid processing and differentiation of myelinating cells.
ESTHER : Pietiainen_2013_J.Cell.Sci_126_3961
PubMedSearch : Pietiainen_2013_J.Cell.Sci_126_3961
PubMedID: 23813961

Title : Genome sequence of Gallaecimonas xiamenensis type strain 3-C-1 - Lai_2012_J.Bacteriol_194_6937
Author(s) : Lai Q , Wang L , Wang W , Shao Z
Ref : Journal of Bacteriology , 194 :6937 , 2012
Abstract : Gallaecimonas xiamenensis 3-C-1(T) was isolated from a crude-oil-degrading consortium enriched from the surface seawater around Xiamen Island. Here, we present the draft genome of strain 3-C-1(T), which contains 4,062,282 bp with a G+C content of 60.58% and contains 3,798 protein-coding genes and 65 tRNAs.
ESTHER : Lai_2012_J.Bacteriol_194_6937
PubMedSearch : Lai_2012_J.Bacteriol_194_6937
PubMedID: 23209203
Gene_locus related to this paper: 9gamm-k2ikd5 , 9gamm-k2ijf5

Title : Genome sequence of Idiomarina xiamenensis type strain 10-D-4 - Lai_2012_J.Bacteriol_194_6938
Author(s) : Lai Q , Wang L , Wang W , Shao Z
Ref : Journal of Bacteriology , 194 :6938 , 2012
Abstract : Idiomarina xiamenensis strain 10-D-4(T) was isolated from an oil-degrading consortium enriched from surface seawater around the Xiamen island. Here, we present the draft genome of strain 10-D-4(T), which contains 2,899,282 bp with a G+C content of 49.48% and contains 2,673 protein-coding genes and 43 tRNA genes.
ESTHER : Lai_2012_J.Bacteriol_194_6938
PubMedSearch : Lai_2012_J.Bacteriol_194_6938
PubMedID: 23209204
Gene_locus related to this paper: 9gamm-k2kal0 , 9gamm-k2kmn4

Title : Systematic review and meta-analysis of the relationship between EPHX1 polymorphisms and colorectal cancer risk - Liu_2012_PLoS.One_7_e43821
Author(s) : Liu F , Yuan D , Wei Y , Wang W , Yan L , Wen T , Xu M , Yang J , Li B
Ref : PLoS ONE , 7 :e43821 , 2012
Abstract : BACKGROUND: Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.
METHODS: Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.
RESULTS: This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83-0.98; dominant model, OR = 0.92, 95%CI = 0.85-0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies' publication time, the results were persistent and robust. CONCLUSION: This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.
ESTHER : Liu_2012_PLoS.One_7_e43821
PubMedSearch : Liu_2012_PLoS.One_7_e43821
PubMedID: 22928041

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : On-line immobilized acetylcholinesterase microreactor for screening of inhibitors from natural extracts by capillary electrophoresis - Min_2012_Anal.Bioanal.Chem_404_2397
Author(s) : Min W , Wang W , Chen J , Wang A , Hu Z
Ref : Anal Bioanal Chem , 404 :2397 , 2012
Abstract : In this study we developed a simple capillary electrophoresis (CE) method with an on-line acetylcholinesterase (AChE) microreactor at the inlet of capillary for inhibitor screening. The fused-silica capillary surface was modified with a polycationic polyethylenimine coating. Solutions of the enzyme and chitosan were then injected to immobilize the enzyme in approximately 2.9 cm of the capillary inlet (total length of capillary 60.2 cm) by electrostatic interaction and the film overlay technique. Separation of enzyme reaction product (thiocholine, ThCh) and unreacted substrate (acetylthiocholine, AThCh) was achieved within 3.0 min. The conditions affecting the efficiency of reaction of the enzyme were optimized by measuring the peak area of ThCh. Under the optimum conditions, using Huperzine-A as model inhibitor, K (i) and IC (50) were 0.551 mumol L(-1) and 1.52 mumol L(-1), respectively, for immobilized AChE. Finally, screening of a small compound library containing two known AChE inhibitors and 30 natural extracts was conducted, and species with inhibition activity were directly identified. Compared with previous publications on screening for AChE inhibitors in natural products based on CE methods, the method developed in this work has the advantages of lower cost per analysis, less leakage, and better bioaffinity for the immobilized enzyme because of the unique properties of sodium alginate and chitosan.
ESTHER : Min_2012_Anal.Bioanal.Chem_404_2397
PubMedSearch : Min_2012_Anal.Bioanal.Chem_404_2397
PubMedID: 22932810

Title : Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups - Tu_2012_Bioorg.Med.Chem_20_4422
Author(s) : Tu Z , Wang W , Cui J , Zhang X , Lu X , Xu J , Parsons SM
Ref : Bioorganic & Medicinal Chemistry , 20 :4422 , 2012
Abstract : To identify selective high-affinity ligands for the vesicular acetylcholine transporter (VAChT), we have incorporated a carbonyl group into the structures of trozamicol and prezamicol scaffolds, and also converted the secondary amines of the piperidines of trozamicols and prezamicols into amides. Of 18 new racemic compounds, 4 compounds displayed high affinity for VAChT (K(i)=10-20 nM) and greater than 300-fold selectivity for VAChT over sigma(1) and sigma(2) receptors, namely (4-(4-fluorobenzoyl)-4'-hydroxy-[1,3'-bipiperidin]-1'-yl)(3-methylthiophen-2-yl)m ethanone oxalate (9g) (K(i-VAChT)=11.4 nM, VAChT/sigma(1)=1063, VAChT/sigma(2)=370), (1'-benzoyl-4'-hydroxy-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10c) (K(i-VAChT)=15.4 nM, VAChT/sigma(1)=374, VAChT/sigma(2)=315), (4'-hydroxy-1'-(thiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)me thanone oxalate (10e) (K(i-VAChT)=19.0 nM, VAChT/sigma(1)=1787, VAChT/sigma(2)=335), and (4'-hydroxy-1'-(3-methylthiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyp henyl)methanone oxalate (10g) (K(i-VAChT)=10.2 nM, VAChT/sigma(1)=1500, VAChT/sigma(2)=2030). These four compounds can be radiosynthesized with C-11 or F-18 to validate their possibilities of serving as PET probes for quantifying the levels of VAChT in vivo.
ESTHER : Tu_2012_Bioorg.Med.Chem_20_4422
PubMedSearch : Tu_2012_Bioorg.Med.Chem_20_4422
PubMedID: 22739089

Title : Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors - Wu_2012_Chem.Biol.Drug.Des_79_897
Author(s) : Wu D , Jin F , Lu W , Zhu J , Li C , Wang W , Tang Y , Jiang H , Huang J , Liu G , Li J
Ref : Chemical Biology Drug Des , 79 :897 , 2012
Abstract : Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design.
ESTHER : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedSearch : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedID: 22381062

Title : Production of extremely pure diacylglycerol from soybean oil by lipase-catalyzed glycerolysis - Wang_2011_Enzyme.Microb.Technol_49_192
Author(s) : Wang W , Li T , Ning Z , Wang Y , Yang B , Yang X
Ref : Enzyme Microb Technol , 49 :192 , 2011
Abstract : Research work was objectively targeted to synthesize highly pure diacylglycerol (DAG) with glycerolysis of soybean oil in a solvent medium of t-butanol. Three commercial immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) were screened, and Novozym 435 was the best out of three candidates. Batch reaction conditions of the enzymatic glycerolysis, the substrate mass ratio, the reaction temperature and the substrate concentration, were studied. The optimal reaction conditions were achieved as 6.23:1 mass ratio of soybean oil to glycerol, 40% (w/v) of substrate concentration in t-butanol and reaction temperature of 50 degreeC. A two-stage molecular distillation was employed for purification of DAG from reaction products. Scale-up was attempted based on the optimized reaction conditions, 98.7% (24 h) for the conversion rate of soybean oil, 48.5% of DAG in the glycerolysis products and 96.1% for the content of DAG in the final products were taken in account as the results.
ESTHER : Wang_2011_Enzyme.Microb.Technol_49_192
PubMedSearch : Wang_2011_Enzyme.Microb.Technol_49_192
PubMedID: 22112408

Title : The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line - Xu_2011_Nat.Biotechnol_29_735
Author(s) : Xu X , Nagarajan H , Lewis NE , Pan S , Cai Z , Liu X , Chen W , Xie M , Wang W , Hammond S , Andersen MR , Neff N , Passarelli B , Koh W , Fan HC , Wang J , Gui Y , Lee KH , Betenbaugh MJ , Quake SR , Famili I , Palsson BO
Ref : Nat Biotechnol , 29 :735 , 2011
Abstract : Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of the assembled scaffolds with 21 chromosomes isolated by microfluidics to identify chromosomal locations of genes. Furthermore, we investigate genes involved in glycosylation, which affect therapeutic protein quality, and viral susceptibility genes, which are relevant to cell engineering and regulatory concerns. Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
ESTHER : Xu_2011_Nat.Biotechnol_29_735
PubMedSearch : Xu_2011_Nat.Biotechnol_29_735
PubMedID: 21804562
Gene_locus related to this paper: crigr-g3hfm0 , crigr-g3h894 , crigr-a0a061hy43 , crigr-g3h3f6 , crigr-g3i9k7 , crigr-g3i9k8 , crigr-g3grm1 , crigr-g3in33 , crigr-g3i1j5 , crigr-a0a061ika1 , crigr-g3hqj0 , crigr-g3hh02 , crigr-g3h083 , crigr-a0a3l7ib08 , crigr-a0a061ihy9 , crigr-g3ifk5 , crigr-g3ily8 , crigr-g3hvc7 , crigr-g3gtp1 , crigr-g3h7k6 , crigr-g3hkm8

Title : Alterations of endocannabinoid signaling, synaptic plasticity, learning, and memory in monoacylglycerol lipase knock-out mice - Pan_2011_J.Neurosci_31_13420
Author(s) : Pan B , Wang W , Zhong P , Blankman JL , Cravatt BF , Liu QS
Ref : Journal of Neuroscience , 31 :13420 , 2011
Abstract : Endocannabinoid (eCB) signaling is tightly regulated by eCB biosynthetic and degradative enzymes. The eCB 2-arachidonoylglycerol (2-AG) is hydrolyzed primarily by monoacylglycerol lipase (MAGL). Here, we investigated whether eCB signaling, synaptic function, and learning behavior were altered in MAGL knock-out mice. We report that MAGL(-)/(-) mice exhibited prolonged depolarization-induced suppression of inhibition (DSI) in hippocampal CA1 pyramidal neurons, providing genetic evidence that the inactivation of 2-AG by MAGL determines the time course of the eCB-mediated retrograde synaptic depression. CB(1) receptor antagonists enhanced basal IPSCs in CA1 pyramidal neurons in MAGL(-)/(-) mice, while the magnitude of DSI or CB(1) receptor agonist-induced depression of IPSCs was decreased in MAGL(-)/(-) mice. These results suggest that 2-AG elevations in MAGL(-)/(-) mice cause tonic activation and partial desensitization of CB(1) receptors. Genetic deletion of MAGL selectively enhanced theta burst stimulation (TBS)-induced long-term potentiation (LTP) in the CA1 region of hippocampal slices but had no significant effect on LTP induced by high-frequency stimulation or long-term depression induced by low-frequency stimulation. The enhancement of TBS-LTP in MAGL(-)/(-) mice appears to be mediated by 2-AG-induced suppression of GABA(A) receptor-mediated inhibition. MAGL(-)/(-) mice exhibited enhanced learning as shown by improved performance in novel object recognition and Morris water maze. These results indicate that genetic deletion of MAGL causes profound changes in eCB signaling, long-term synaptic plasticity, and learning behavior.
ESTHER : Pan_2011_J.Neurosci_31_13420
PubMedSearch : Pan_2011_J.Neurosci_31_13420
PubMedID: 21940435
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : The HindIII polymorphism in the lipoprotein lipase gene predicts type 2 diabetes risk among Chinese adults - Qi_2011_Clin.Chim.Acta_412_1229
Author(s) : Qi Y , Liu J , Wang W , Wang M , Sun JY , Li Y , Wu ZS , Zhao D
Ref : Clinica Chimica Acta , 412 :1229 , 2011
Abstract : OBJECTIVE: We aimed to investigate the polymorphism HindIII of the lipoprotein lipase (LPL) gene to explore whether it had a potential role in susceptibility to type 2 diabetes mellitus (T2DM) among Han Chinese, and whether this effect was influenced by regulating LPL or other risk factors. METHODS: Overall, 654 Han Chinese adults were selected from a community-based cross-sectional study using a stratified cluster random sampling. Genotyping was performed using the PCR-RFLP technique, and the metabolic variables were measured using standard methods. RESULTS: Individuals with the HindIII H-/H- genotype tended to have higher pre-heparin LPL (PrLPL) and lower triglyceride levels but an unexpected higher prevalence of T2DM compared with the H+/H+ genotype carriers. The association between the H-/H- genotype and T2DM risk remained unchanged across all subgroups of lipids/glucose-related RF. In a recessive model, the H-/H- genotype conferred a 2.12-fold increased risk [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.18-8.27] for T2DM after controlling for age and sex, and increased further after additionally adjusting for traditional RFs, and PrLPL (OR=4.45; 95% CI=1.51-13.07). CONCLUSIONS: This study indicated that Chinese adults with the LPL gene HindIII H-/H- genotype had a significantly increased risk of T2DM, even if they had favorable lipid profiles.
ESTHER : Qi_2011_Clin.Chim.Acta_412_1229
PubMedSearch : Qi_2011_Clin.Chim.Acta_412_1229
PubMedID: 21419757

Title : Synthesis and in vitro biological evaluation of carbonyl group-containing analogues for sigma1 receptors - Wang_2011_J.Med.Chem_54_5362
Author(s) : Wang W , Cui J , Lu X , Padakanti PK , Xu J , Parsons SM , Luedtke RR , Rath NP , Tu Z
Ref : Journal of Medicinal Chemistry , 54 :5362 , 2011
Abstract : To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1) (K(i) = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K(i) > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K(i) = 44.2 nM). The compound [1'-(4-fluorobenzyl)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanon e (14a) displayed very high affinity and selectivity for sigma(1) receptor (K(i) = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.
ESTHER : Wang_2011_J.Med.Chem_54_5362
PubMedSearch : Wang_2011_J.Med.Chem_54_5362
PubMedID: 21732626

Title : Molluscicidal activity of cardiac glycosides from Nerium indicum against Pomacea canaliculata and its implications for the mechanisms of toxicity - Dai_2011_Environ.Toxicol.Pharmacol_32_226
Author(s) : Dai L , Wang W , Dong X , Hu R , Nan X
Ref : Environ Toxicol Pharmacol , 32 :226 , 2011
Abstract : Cardiac glycosides from fresh leaves of Nerium indicum were evaluated for its molluscicidal activity against Pomacea canaliculata (golden apple snail: GAS) under laboratory conditions. The results showed that LC(50) value of cardiac glycosides against GAS was time dependent and the LC(50) value at 96 h was as low as 3.71 mg/L, which was comparable with that of metaldehyde at 72 h (3.88 mg/L). These results indicate that cardiac glycosides could be an effective molluscicide against GAS. The toxicological mechanism of cardiac glucosides on GAS was also evaluated through changes of selected biochemical parameters, including cholinesterase (ChE) and esterase (EST) activities, glycogen and protein contents in hepatopancreas tissues of GAS. Exposure to sublethal concentrations of cardiac glycosides, GAS showed lower activities of EST isozyme in the later stages of the exposure period as well as drastically decreased glycogen content, although total protein content was not affected at the end of 24 and 48 h followed by a significant depletion at the end of 72 and 96 h. The initial increase followed by a decline of ChE activity was also observed during the experiment. These results suggest that cardiac glycosides seriously impair normal physiological metabolism, resulting in fatal alterations in major biochemical constituents of hepatopancreas tissues of P. canaliculata.
ESTHER : Dai_2011_Environ.Toxicol.Pharmacol_32_226
PubMedSearch : Dai_2011_Environ.Toxicol.Pharmacol_32_226
PubMedID: 21843803

Title : 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site - Wang_2011_Bioorg.Med.Chem.Lett_21_6646
Author(s) : Wang W , Devasthale P , Wang A , Harrity T , Egan D , Morgan N , Cap M , Fura A , Klei HE , Kish K , Weigelt C , Sun L , Levesque P , Li YX , Zahler R , Kirby MS , Hamann LG
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :6646 , 2011
Abstract : Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 muM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 mumol/kg in ob/ob mice.
ESTHER : Wang_2011_Bioorg.Med.Chem.Lett_21_6646
PubMedSearch : Wang_2011_Bioorg.Med.Chem.Lett_21_6646
PubMedID: 21996520
Gene_locus related to this paper: human-DPP4

Title : Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques - Yan_2011_Nat.Biotechnol_29_1019
Author(s) : Yan G , Zhang G , Fang X , Zhang Y , Li C , Ling F , Cooper DN , Li Q , Li Y , van Gool AJ , Du H , Chen J , Chen R , Zhang P , Huang Z , Thompson JR , Meng Y , Bai Y , Wang J , Zhuo M , Wang T , Huang Y , Wei L , Li J , Wang Z , Hu H , Yang P , Le L , Stenson PD , Li B , Liu X , Ball EV , An N , Huang Q , Fan W , Zhang X , Wang W , Katze MG , Su B , Nielsen R , Yang H , Wang X
Ref : Nat Biotechnol , 29 :1019 , 2011
Abstract : The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.
ESTHER : Yan_2011_Nat.Biotechnol_29_1019
PubMedSearch : Yan_2011_Nat.Biotechnol_29_1019
PubMedID: 22002653
Gene_locus related to this paper: macfa-BCHE , macfa-g7nzc0 , macfa-g7nze2 , macfa-g7p4b9 , macfa-g7pa87 , macfa-g7pd01 , macfa-g7q259 , macfa-3neur , macfa-g8f585 , macfa-KANSL3 , macfa-q4r8p0 , macfa-SPG21 , macfa-TEX30 , macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6sz31 , macmu-f6the6 , macmu-f6zkq5 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-g7npb8 , macmu-g7nq39 , macmu-KANSL3 , macmu-TEX30 , macfa-g7pgg6 , macmu-g7n4x3 , macfa-g7nzx2 , macfa-g8f4f7 , macmu-f7ba84 , macfa-g7psx7 , macmu-h9er02 , macfa-g8f3k0 , macfa-a0a2k5w1n7 , macmu-g7mxj6 , macfa-g7pbk1 , macfa-a0a2k5urk5 , macfa-a0a2k5wye4 , macfa-g7pe14 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macfa-g7nxn9 , macmu-a0a1d5rh04 , macmu-h9fud6 , macfa-g8f3e1 , macfa-i7gcw6 , macmu-f6qwx1 , macmu-f7h4t2 , macfa-a0a2k5wkd0 , macfa-a0a2k5v7v4 , macfa-g7p7y3 , macfa-a0a2k5uqq3 , macmu-i2cu80 , macfa-g8f5i1 , macmu-f7h550 , macmu-f7gkb9 , macfa-a0a2k5tui1

Title : The sheep genome reference sequence: a work in progress - Archibald_2010_Anim.Genet_41_449
Author(s) : Archibald AL , Cockett NE , Dalrymple BP , Faraut T , Kijas JW , Maddox JF , McEwan JC , Hutton Oddy V , Raadsma HW , Wade C , Wang J , Wang W , Xun X
Ref : Anim Genet , 41 :449 , 2010
Abstract : Until recently, the construction of a reference genome was performed using Sanger sequencing alone. The emergence of next-generation sequencing platforms now means reference genomes may incorporate sequence data generated from a range of sequencing platforms, each of which have different read length, systematic biases and mate-pair characteristics. The objective of this review is to inform the mammalian genomics community about the experimental strategy being pursued by the International Sheep Genomics Consortium (ISGC) to construct the draft reference genome of sheep (Ovis aries). Component activities such as data generation, sequence assembly and annotation are described, along with information concerning the key researchers performing the work. This aims to foster future participation from across the research community through the coordinated activities of the consortium. The review also serves as a 'marker paper' by providing information concerning the pre-publication release of the reference genome. This ensures the ISGC adheres to the framework for data sharing established at the recent Toronto International Data Release Workshop and provides guidelines for data users.
ESTHER : Archibald_2010_Anim.Genet_41_449
PubMedSearch : Archibald_2010_Anim.Genet_41_449
PubMedID: 20809919
Gene_locus related to this paper: sheep-cauxin , sheep-thyro , sheep-BCHE , sheep-w5p985 , sheep-w5q8g9 , sheep-w5phz5 , sheep-w5q544 , sheep-w5puc7 , sheep-w5p5z7 , sheep-w5qa37 , sheep-w5qa61 , sheep-w5nxa2 , sheep-w5nxc9 , sheep-w5nx87 , sheep-w5q8e4 , sheep-w5p609 , sheep-w5p6d2 , sheep-w5pcd7 , sheep-w5p0t3 , sheep-w5p0x1 , sheep-w5p121 , sheep-w5pq36 , sheep-w5qi65 , sheep-w5q4j6 , sheep-w5q5i2 , sheep-w5q6h9 , sheep-w5qet9 , sheep-w5p1i2 , sheep-w5p871 , sheep-w5pji8 , sheep-w5qd48 , sheep-w5q5g0 , sheep-w5pr16 , sheep-w5pzj7 , sheep-w5q716 , sheep-w5pxj8 , sheep-w5qh96 , sheep-w5q4p1

Title : Pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV inhibitor after oral administration in rats - Wang_2010_Xenobiotica_40_707
Author(s) : Wang X , Zhang D , Xu W , Liu H , Wang W
Ref : Xenobiotica , 40 :707 , 2010
Abstract : The pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV (DPP IV) inhibitor, was studied in rats after oral administration for developing it as an antidiabetic agent. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to determine lipoyl vildagliptin in rat plasma. After an overnight fasting, rats were orally given lipoyl vildagliptin. Following a single oral dose of 25, 50, and 100 mg x kg(-1), T(max) values were from 1.25 to 1.84 h, CL/F values were around 100 l h(-1) kg(-1). In the dose range, C(max) values (63.9-296 mug x l(-1)) and AUC(0-infinity)values (260-1214 mug x h x l(-1)) were proportional to the doses. In conclusion, this LC-MS/MS method for the determination of lipoyl vildagliptin in rat plasma was selective and sensitive. In rats, lipoyl vildagliptin displayed linear pharmacokinetics after a single oral dose in the range of 25-100 mg x kg(-1). Lipoyl vildagliptin might have very high CL/F values and V(d)/F values, which indicated that the bioavailability of this drug might be low or lipoyl vildagliptin might distribute extensively or accumulate in tissues in view of its high liposolubility.
ESTHER : Wang_2010_Xenobiotica_40_707
PubMedSearch : Wang_2010_Xenobiotica_40_707
PubMedID: 20735236

Title : Influence of alcohol treatments on the activity of lipases immobilized on methyl-modified silica aerogels - Gao_2010_Bioresour.Technol_101_7231
Author(s) : Gao S , Wang W , Wang Y , Luo G , Dai Y
Ref : Bioresour Technol , 101 :7231 , 2010
Abstract : The effects of alcohol treatment on the activity and loading amount of Candida rugosa lipase (CRL), Candida Antarctica lipase B (CALB) and Porcine Pancreas lipase (PPL) immobilized on methyl-modified silica aerogels were investigated, and the fluorescent analysis was used to explore the change of lipase hydrophobicity in aqueous solution caused by alcohols. It is found that alcohol types and the stages at which alcohol was added significantly influenced the performance of immobilized lipases through changing the hydrophobicity of the molecules. For CRL and PPL, five kinds of alcohol were added in the adsorption process, and n-butanol and isopropanol improved the apparent activity of CRL and PPL up to 2.5 times and 2 times those of the untreated ones, respectively; however, for CALB, it is better to activate the immobilized CALB after the adsorption process, and the apparent activity of CALB increased up to 2.76 times through n-butanol treatment.
ESTHER : Gao_2010_Bioresour.Technol_101_7231
PubMedSearch : Gao_2010_Bioresour.Technol_101_7231
PubMedID: 20576560

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Novel features of the polysaccharide-digesting gliding bacterium Flavobacterium johnsoniae as revealed by genome sequence analysis - McBride_2009_Appl.Environ.Microbiol_75_6864
Author(s) : McBride MJ , Xie G , Martens EC , Lapidus A , Henrissat B , Rhodes RG , Goltsman E , Wang W , Xu J , Hunnicutt DW , Staroscik AM , Hoover TR , Cheng YQ , Stein JL
Ref : Applied Environmental Microbiology , 75 :6864 , 2009
Abstract : The 6.10-Mb genome sequence of the aerobic chitin-digesting gliding bacterium Flavobacterium johnsoniae (phylum Bacteroidetes) is presented. F. johnsoniae is a model organism for studies of bacteroidete gliding motility, gene regulation, and biochemistry. The mechanism of F. johnsoniae gliding is novel, and genome analysis confirms that it does not involve well-studied motility organelles, such as flagella or type IV pili. The motility machinery is composed of Gld proteins in the cell envelope that are thought to comprise the "motor" and SprB, which is thought to function as a cell surface adhesin that is propelled by the motor. Analysis of the genome identified genes related to sprB that may encode alternative adhesins used for movement over different surfaces. Comparative genome analysis revealed that some of the gld and spr genes are found in nongliding bacteroidetes and may encode components of a novel protein secretion system. F. johnsoniae digests proteins, and 125 predicted peptidases were identified. F. johnsoniae also digests numerous polysaccharides, and 138 glycoside hydrolases, 9 polysaccharide lyases, and 17 carbohydrate esterases were predicted. The unexpected ability of F. johnsoniae to digest hemicelluloses, such as xylans, mannans, and xyloglucans, was predicted based on the genome analysis and confirmed experimentally. Numerous predicted cell surface proteins related to Bacteroides thetaiotaomicron SusC and SusD, which are likely involved in binding of oligosaccharides and transport across the outer membrane, were also identified. Genes required for synthesis of the novel outer membrane flexirubin pigments were identified by a combination of genome analysis and genetic experiments. Genes predicted to encode components of a multienzyme nonribosomal peptide synthetase were identified, as were novel aspects of gene regulation. The availability of techniques for genetic manipulation allows rapid exploration of the features identified for the polysaccharide-digesting gliding bacteroidete F. johnsoniae.
ESTHER : McBride_2009_Appl.Environ.Microbiol_75_6864
PubMedSearch : McBride_2009_Appl.Environ.Microbiol_75_6864
PubMedID: 19717629
Gene_locus related to this paper: flaj1-a5fb12 , flaj1-a5fmd7 , flaj1-a5fns3

Title : Novel 16-substituted bifunctional derivatives of huperzine B: multifunctional cholinesterase inhibitors - Shi_2009_Acta.Pharmacol.Sin_30_1195
Author(s) : Shi YF , Zhang HY , Wang W , Fu Y , Xia Y , Tang XC , Bai DL , He XC
Ref : Acta Pharmacol Sin , 30 :1195 , 2009
Abstract : AIM: To design novel bifunctional derivatives of huperzine B (HupB) based on the concept of dual binding site of acetylcholinesterase (AChE) and evaluate their pharmacological activities for seeking new drug candidates against Alzheimer's disease (AD).
METHODS: Novel 16-substituted bifunctional derivatives of HupB were synthesized through chemical reactions. The inhibitory activities of the derivatives toward AChE and butyrylcholinesterase (BCHE) were determined in vitro by modified Ellman's method. Cell viability was quantified by the reduction of MTT.
RESULTS: A new preparative method was developed for the generation of 16-substituted derivatives of HupB, and pharmacological trials indicated that the derivatives were multifunctional cholinesterase inhibitors targeting both AChE and BCHE. Among the derivatives tested, 9c, 9e, 9f, and 9i were 480 to 1360 times more potent as AChE inhibitors and 370 to 1560 times more potent as BCHE inhibitors than the parent HupB. Further preliminary pharmacological trials of derivatives 9c and 9i were performed, including examining the mechanism of AChE inhibition, the substrate kinetics of the enzyme inhibition, and protection against hydrogen peroxide (H2O2)-induced cytotoxicity in PC12 cells. CONCLUSION: Preliminary pharmacological evaluation indicated that 16-substituted derivatives of HupB, particularly 9c and 9i, would be potentially valuable new drug candidates for AD therapy, and further exploration is needed to evaluate their pharmacological and clinical efficacies.
ESTHER : Shi_2009_Acta.Pharmacol.Sin_30_1195
PubMedSearch : Shi_2009_Acta.Pharmacol.Sin_30_1195
PubMedID: 19578388

Title : Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase - Zhu_2009_Bioorg.Med.Chem_17_1600
Author(s) : Zhu Y , Xiao K , Ma L , Xiong B , Fu Y , Yu H , Wang W , Wang X , Hu D , Peng H , Li J , Gong Q , Chai Q , Tang X , Zhang H , Shen J
Ref : Bioorganic & Medicinal Chemistry , 17 :1600 , 2009
Abstract : To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC(50)=0.567 microM; AChE: IC(50)=1.83 microM), and also showed excellent inhibitory effects on Abeta production of APP transfected HEK293 cells (IC(50)=98.7 nM) and mild protective effect against hydrogen peroxide (H(2)O(2))-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of Abeta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients.
ESTHER : Zhu_2009_Bioorg.Med.Chem_17_1600
PubMedSearch : Zhu_2009_Bioorg.Med.Chem_17_1600
PubMedID: 19162488

Title : Cholinergic alterations following alcohol exposure in the frontal cortex of Aldh2-deficient mice models - Jamal_2009_Brain.Res_1295_37
Author(s) : Jamal M , Ameno K , Miki T , Wang W , Kumihashi M , Isse T , Kawamoto T , Kitagawa K , Nakayama K , Ijiri I , Kinoshita H
Ref : Brain Research , 1295 :37 , 2009
Abstract : We investigated the effects of alcohol (EtOH) and acetaldehyde (ACe) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the frontal cortex of Aldh2-/- (KO) mice. KO mice were used as models of Aldh2-deficient humans to examine ACe effects. Brain samples were analyzed at 40 and 120 min after 2- and 4-g/kg intraperitoneal EtOH administration by RT-PCR and Western blot. Wild-type (WT) mice exhibited a remarkable decrease in ChAT and AChE mRNA expression at both time points only after 4-g/kg EtOH treatment compared with the naive control, whereas KO mice showed a considerable reduction in cholinergic markers after 2- and 4-g/kg EtOH treatment. The 4-g/kg EtOH-induced decrease in ChAT and AChE RNA expression at both time points was significantly greater than that in obtained with the administration of 2-g/kg at 40 min in WT mice. KO mice showed a significant difference in ChAT mRNA at 40 min between the EtOH groups. The findings regarding the ChAT mRNA levels are consistent with the results of Western blot in both types of mice, with some exceptions. EtOH-induced ChAT and AChE expression in KO mice was significantly lower than that in WT mice. This genotype effect occurred mostly at 40 min after EtOH dosing. Only ACe was quantified in the brains of KO mice, whereas EtOH was detected in both types of mice in vivo. These results suggest that EtOH and ACe combined or high EtOH alone alters cholinergic markers expression via changes in presynaptic and postsynaptic processes in the mice frontal cortex, thus indicating that central cholinergic neurons may be sensitive to EtOH and ACe.
ESTHER : Jamal_2009_Brain.Res_1295_37
PubMedSearch : Jamal_2009_Brain.Res_1295_37
PubMedID: 19664611

Title : Leptin replacement restores supraspinal cholinergic antinociception in leptin-deficient obese mice - Wang_2009_J.Pain_10_836
Author(s) : Wang W , Baghdoyan HA , Lydic R
Ref : J Pain , 10 :836 , 2009
Abstract : A single gene deletion causes lack of leptin and obesity in B6.V-Lep(ob) (obese; ob) mice compared with wild-type C57BL/6J (B6) mice. This study compared the phenotype of nociception and supraspinal antinociception in obese and B6 mice by testing 2 hypotheses: (1) microinjection of cholinomimetics or an adenosine receptor agonist, but not morphine, into the pontine reticular formation (PRF) is antinociceptive in B6 but not obese mice, and (2) leptin replacement in obese mice attenuates differences in nociceptive responses between obese and B6 mice. Adult male mice (n = 22) were implanted with microinjection guide tubes aimed for the PRF. The PRF was injected with neostigmine, carbachol, nicotine, N(6)-p-sulfophenyladenosine (SPA), morphine, or saline (control), and latency to paw withdrawal (PWL) from a thermal stimulus was recorded. B6 and ob mice did not differ in PWL after saline microinjection into the PRF. Neostigmine, carbachol, and SPA caused PWL to increase significantly in B6 but not obese mice. An additional 15 obese mice were implanted with osmotic pumps that delivered leptin for 7 days. Leptin replacement in obese mice restored the analgesic effect of PRF neostigmine to the level displayed by B6 mice. The results show for the first time that leptin significantly alters supraspinal cholinergic antinociception. PERSPECTIVE: This study specifies a brain region (the pontine reticular formation), cholinergic neurotransmission, and a protein (leptin) modulating thermal nociception. The results are relevant for efforts to understand the association between obesity, disordered sleep, and hyperalgesia.
ESTHER : Wang_2009_J.Pain_10_836
PubMedSearch : Wang_2009_J.Pain_10_836
PubMedID: 19380255

Title : Suppression of N-myc downstream-regulated gene 2 is associated with induction of Myc in colorectal cancer and correlates closely with differentiation - Shi_2009_Biol.Pharm.Bull_32_968
Author(s) : Shi H , Jin H , Chu D , Wang W , Zhang J , Chen C , Xu C , Fan D , Yao L
Ref : Biol Pharm Bull , 32 :968 , 2009
Abstract : NDRG2, a new member of the N-Myc downstream-regulated gene (NDRG) family, is a focus for study at present. Up to now, its expression and function in carcinoma remain to be elucidated. In this study, using a colorectal cancer tissue array and a series of 213 colorectal cancer samples, the relationship between Ndrg2 and c-MYC expression and tumor differentiation level was investigated. Immunohistochemistry showed that Ndrg2 expression was reduced and that c-Myc was increased in colorectal carcinomas. In addition, Ndrg2 protein levels increased from poorly differentiated to well-differentiated carcinomas (p=0.005). Real-time polymerase chain reaction and Western blots demonstrated quantitatively that NDRG2 mRNA and protein levels were lower in colorectal carcinomas compared to the adjacent tissue and normal tissue from the same individual (p=3x10(-8)). Also, the NDRG2 expression level in adjacent carcinoma tissue was lower than that of normal tissue. However, the expression pattern of c-MYC was the inverse (p=5x10(-8)). Finally, we induced the differentiation of the colorectal carcinoma cell lines HT29, SW480 and SW620 and found that NDRG2 expression increased and that c-MYC expression declined with increasing differentiation. These novel data show a disparity in both the mRNA and protein expression levels of Ndrg2 and c-Myc between colorectal cancers and normal tissues. Taken together, NDRG2 may play a role during the differentiation of colorectal cancer cells, and the function of NDRG2 in the development of colorectal cancer should be further investigated.
ESTHER : Shi_2009_Biol.Pharm.Bull_32_968
PubMedSearch : Shi_2009_Biol.Pharm.Bull_32_968
PubMedID: 19483300

Title : NDRG3 is an androgen regulated and prostate enriched gene that promotes in vitro and in vivo prostate cancer cell growth - Wang_2009_Int.J.Cancer_124_521
Author(s) : Wang W , Li Y , Hong A , Wang J , Lin B , Li R
Ref : International Journal of Cancer , 124 :521 , 2009
Abstract : NDRG3 belongs to the N-myc down-regulated gene (NDRG) family that contains 4 paralogs: NDRG1, -2, -3 and -4. The function of NDRG3 and its relationship to cancer has not been studied. We herein report our examination of the expression and biological roles of NDRG3 in prostate cancers. We showed that NDRG3 expression is enriched in testis and prostate using gene expression data derived from massively parallel signature sequencing from 33 different human organs. We further showed that NDRG3 is expressed in both epithelial prostate cancer cells and prostatic stromal cells at both mRNA and proteins levels. We demonstrated that NDRG1 is significantly up-regulated by androgen in LNCaP cells. Over-expression of NDRG3 in stably transfected PC-3 cells increased their growth rates and migration capabilities when compared to parental or mock empty vector transfected PC-3 cells. In addition, we found that overexpresson of NDRG3 promoted the growth of xenograft tumors in nude mice. Finally, we found that NDRG3 expression was detected in 58.6% (41/70) of prostate cancer specimens compared to 13.2% (5/38) of benign prostatic hyperplasia specimens by immunohistochemistry. We showed by microarray and by RT-PCR that NDRG3 overexpression up-regulates the expression of many angiogenic chemokines including CXCL1 (chemokine ligand 1), CXCL3 (chemokine ligand 3) and CXCL5 (chemokine ligand 5), which may increase angiogenesis of tumors. Taken together, these results demonstrate that NDRG3 is a tumor promoter, the overexpression of which may contribute to the malignant phenotype of tumors.
ESTHER : Wang_2009_Int.J.Cancer_124_521
PubMedSearch : Wang_2009_Int.J.Cancer_124_521
PubMedID: 18975380

Title : Blockade of 2-arachidonoylglycerol hydrolysis by selective monoacylglycerol lipase inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) Enhances retrograde endocannabinoid signaling - Pan_2009_J.Pharmacol.Exp.Ther_331_591
Author(s) : Pan B , Wang W , Long JZ , Sun D , Hillard CJ , Cravatt BF , Liu QS
Ref : Journal of Pharmacology & Experimental Therapeutics , 331 :591 , 2009
Abstract : Endocannabinoid (eCB) signaling mediates depolarization-induced suppression of excitation (DSE) and inhibition (DSI), two prominent forms of retrograde synaptic depression. N-Arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), two known eCBs, are degraded by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective blockade of FAAH and MAGL is critical for determining the roles of the eCBs in DSE/DSI and understanding how their action is regulated. 4-Nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) is a recently developed, highly selective, and potent MAGL inhibitor that increases 2-AG but not AEA concentrations in mouse brain. Here, we report that JZL184 prolongs DSE in Purkinje neurons in cerebellar slices and DSI in CA1 pyramidal neurons in hippocampal slices. The effect of JZL184 on DSE/DSI is mimicked by the nonselective MAGL inhibitor methyl arachidonyl fluorophosphonate. In contrast, neither the selective FAAH inhibitor cyclohexylcarbamic acid 3'-carbomoylbiphenyl-3-yl ester (URB597) nor FAAH knockout has a significant effect on DSE/DSI. JZL184 produces greater enhancement of DSE/DSI in mouse neurons than that in rat neurons. The latter finding is consistent with biochemical studies showing that JZL184 is more potent in inhibiting mouse MAGL than rat MAGL. These results indicate that the degradation of 2-AG by MAGL is the rate-limiting step that determines the time course of DSE/DSI and that JZL184 is a useful tool for the study of 2-AG-mediated signaling.
ESTHER : Pan_2009_J.Pharmacol.Exp.Ther_331_591
PubMedSearch : Pan_2009_J.Pharmacol.Exp.Ther_331_591
PubMedID: 19666749

Title : Clinical, experimental, and genomic differences between intermediately pathogenic, highly pathogenic, and epidemic Streptococcus suis - Ye_2009_J.Infect.Dis_199_97
Author(s) : Ye C , Zheng H , Zhang J , Jing H , Wang L , Xiong Y , Wang W , Zhou Z , Sun Q , Luo X , Du H , Gottschalk M , Xu J
Ref : J Infect Dis , 199 :97 , 2009
Abstract : BACKGROUND: Streptococcus suis emerged to cause an unusual outbreak of streptococcal toxic-shock-like syndrome (STSLS) in 2005. The mechanisms involved are unknown. METHODS: Clinical, laboratory, and epidemiologic data on patients infected with culture-confirmed S. suis were analyzed. The strain involved in the outbreak, "epidemic" strain ST7, was compared with both a classical highly pathogenic strain, ST1, and an intermediately pathogenic strain, ST25, to determine both its capacity to induce cytokines in experimentally infected mice and its genomic difference. RESULTS: Of 38 patients infected with culture-confirmed S. suis, 14 presented with STSLS. During the early phase of the disease, serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, interferon-gamma, and tumor necrosis factor-alpha were more elevated in patients with STSLS than in those with meningitis only. Serum levels of proinflammatory cytokines were significantly higher in mice infected with ST7 than in those infected with either ST1 or ST25. Genomic comparisons with ST25 showed that ST1 had acquired 132 genomic islands, including 5 pathogenicity islands, and that ST7, the epidemic strain, had acquired an additional 5 genomic islands. CONCLUSION: Intermediately pathogenic strain ST25 has evolved to become highly pathogenic strain ST1, which, in turn, has more recently evolved to become epidemic strain ST7. ST7 has the ability to stimulate the production of massive amounts of proinflammatory cytokines, leading to STSLS.
ESTHER : Ye_2009_J.Infect.Dis_199_97
PubMedSearch : Ye_2009_J.Infect.Dis_199_97
PubMedID: 19016627
Gene_locus related to this paper: strsu-a4vws4 , strsu-q673u2 , strsy-a4vus4

Title : Epoxy functionalised poly(epsilon-caprolactone): synthesis and application - Zhou_2008_Chem.Commun.(Camb)__5806
Author(s) : Zhou J , Wang W , Villarroya S , Thurecht KJ , Howdle SM
Ref : Chem Commun (Camb) , :5806 , 2008
Abstract : Glycidol is used as an initiator for ring-opening polymerisation of epsilon-caprolactone (epsilon-CL) to synthesise epoxy-functionalised poly(epsilon-caprolactone) (PCL) in a reaction catalysed by lipase, and the epoxy-functionalised PCL was further copolymerised with carbon dioxide or anhydride to produce novel graft or hyperbranched copolymers.
ESTHER : Zhou_2008_Chem.Commun.(Camb)__5806
PubMedSearch : Zhou_2008_Chem.Commun.(Camb)__5806
PubMedID: 19009088

Title : Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters - Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
Author(s) : Wang F , Wang W , Wahala K , Adlercreutz H , Ikonen E , Tikkanen MJ
Ref : American Journal of Physiology Endocrinol Metab , 295 :E1455 , 2008
Abstract : Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) belong to a unique family of naturally occurring hydrophobic steroid hormone derivatives that are transported in circulating lipoproteins and may act as a source of dehydroepiendrosterone (DHEA) and other biologically active steroid hormones in cells. Here, we studied the metabolic fate of low-density lipoprotein-associated [(3)H]DHEA-FAE ([(3)H]DHEA-FAE-LDL) and the possible role of lysosomal acid lipase (LAL) in the hydrolysis of DHEA-FAE in cultured human cells. When HeLa cells were incubated with [(3)H]DHEA-FAE-LDL, the accumulation of label in the cellular fraction increased with incubation time and could be inhibited by excess unlabeled LDL, suggesting LDL receptor or LDL receptor-related receptor-dependent uptake. During 48 h of chase, decreasing amounts of [(3)H]DHEA-FAE were found in the cellular fraction, while in the medium increasing amounts of unesterified [(3)H]DHEA and its two metabolites, [(3)H]-5alpha-androstanedione (5alpha-adione) and [(3)H]androstenedione (4-adione), appeared. As LDL-cholesteryl ester hydrolysis is dependent on LAL activity, we depleted LAL from HeLa cells using small interfering RNAs and compared the hydrolysis of [(3)H]DHEA-FAE-LDL and [(3)H]cholesteryl-FAE-LDL. The results demonstrated a more modest but significant reducing effect on the hydrolysis of [(3)H]DHEA-FAE compared with [(3)H]cholesteryl-FAE. Moreover, experiments in LAL-deficient human fibroblasts (Wolman disease patient cells) showed that [(3)H]DHEA-FAE hydrolysis was not completely dependent on LAL activity. In summary, LDL-transported [(3)H]DHEA-FAE entered cells via LDL receptor or LDL receptor-related receptor-mediated uptake, followed by intracellular hydrolysis and further metabolism into 5alpha-adione and 4-adione that were excreted from cells. Although LAL contributed to the deesterification of DHEA-FAE, it was not solely responsible for the hydrolysis.
ESTHER : Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
PubMedSearch : Wang_2008_Am.J.Physiol.Endocrinol.Metab_295_E1455
PubMedID: 18796546

Title : Human differentiation-related gene NDRG1 is a Myc downstream-regulated gene that is repressed by Myc on the core promoter region - Zhang_2008_Gene_417_5
Author(s) : Zhang J , Chen S , Zhang W , Liu X , Shi H , Che H , Wang W , Li F , Yao L
Ref : Gene , 417 :5 , 2008
Abstract : N-Myc downstream-regulated gene 1 (ndrg1) is up-regulated in N-Myc knockout mouse embryos. The human NDRG family consists of 4 highly homologous members and human Ndrg1 exhibits approximately 94% homology with mouse ndrg1. However, the regulatory mechanism of NDRG1 via Myc repression is as yet unknown. We previously identified human NDRG2 and demonstrated that this gene is transcriptionally down-regulated by Myc via Miz-1-dependent interaction with the core promoter region of NDRG2. Here, we provide evidence that human NDRG1 is regulated by Myc in a manner similar to NDRG2. We found that Ndrg1 expression levels were enhanced as Myc expression declined in differentiated cells, but were down-regulated following Myc induction. The data revealed that both N-Myc and c-Myc can repress human NDRG1 at the transcriptional level. We further determined that the core promoter region of human NDRG1 is required for Myc repression, and verified the interaction of Myc with the core promoter region. However, the presence of the protein synthesis inhibitor cycloheximide could reverse the repression of Myc, indicating the indirect repression of human NDRG1 by Myc. Moreover, we found that c-Myc-mediated repression can be inhibited by TSA, an HDACs inhibitor, which suggests the involvement of HDACs in the repression process. Taken together, our results demonstrate that, in common with NDRG2, human NDRG1 can be indirectly transcriptionally down-regulated by Myc via interaction with the NDRG1 core promoter.
ESTHER : Zhang_2008_Gene_417_5
PubMedSearch : Zhang_2008_Gene_417_5
PubMedID: 18455888

Title : Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population - Zhang_2008_Pharmacogenet.Genomics_18_45
Author(s) : Zhang L , Ding H , Yan J , Hui R , Wang W , Kissling GE , Zeldin DC , Wang DW
Ref : Pharmacogenet Genomics , 18 :45 , 2008
Abstract : OBJECTIVE: Epoxyeicosatrienoic acids have been recognized for their protective effects on the cardiovascular system. This study investigated whether two common polymorphisms in genes believed to be influential in regulating circulating levels of epoxyeicosatrienoic acids, namely cytochrome P450 2J2 (CYP2J2) G-50T and soluble epoxide hydrolase (EPHX2) G860A, were associated with ischemic stroke risk in a Chinese population. METHODS AND RESULTS: Screening of 200 patients with ischemic stroke and 350 control participants revealed that CYP2J2-50T allele frequency was not significantly different in ischemic stroke cases versus controls. In contrast, EPHX2 860A allele frequency was 16.8% in ischemic stroke cases versus 21.7% in controls (P=0.047), and the presence of this variant allele was associated with a significantly lower risk of ischemic stroke after adjustment for sex, age and multiple cardiovascular risk factors (adjusted odds ratio=0.50, 95% confidence interval 0.29-0.86). Moreover, there was a significant interaction between the EPHX2 G860A polymorphism, smoking and ischemic stroke risk such that nonsmokers carrying the EPHX2 G860A variant allele were at the lowest risk of ischemic stroke (odds ratio=0.33, 95% confidence interval, 0.17-0.67, P=0.002), whereas no significant association was observed in smokers. CONCLUSIONS: Collectively, these data indicate a protective influence of the G860A polymorphism of EPHX2 on ischemic stroke in Chinese nonsmokers.
ESTHER : Zhang_2008_Pharmacogenet.Genomics_18_45
PubMedSearch : Zhang_2008_Pharmacogenet.Genomics_18_45
PubMedID: 18216721

Title : A recalibrated molecular clock and independent origins for the cholera pandemic clones - Feng_2008_PLoS.One_3_e4053
Author(s) : Feng L , Reeves PR , Lan R , Ren Y , Gao C , Zhou Z , Cheng J , Wang W , Wang J , Qian W , Li D , Wang L
Ref : PLoS ONE , 3 :e4053 , 2008
Abstract : Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6(th) (1899-1923) and 7(th) (1961-present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7(th) pandemic clone, while the 6(th) pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6(th) pandemic isolate, and compared them with the published 7(th) pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7(th) pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed. We then used this to estimate the divergence date of the 6(th) and 7(th) pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000-50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens.
ESTHER : Feng_2008_PLoS.One_3_e4053
PubMedSearch : Feng_2008_PLoS.One_3_e4053
PubMedID: 19115014
Gene_locus related to this paper: vibch-VC1974 , vibch-VC2610 , vibch-VC2718 , vibch-y1892 , vibch-y2276

Title : Changes in cholinergic function in the frontal cortex and hippocampus of rat exposed to ethanol and acetaldehyde - Jamal_2007_Neurosci_144_232
Author(s) : Jamal M , Ameno K , Ameno S , Morishita J , Wang W , Kumihashi M , Ikuo U , Miki T , Ijiri I
Ref : Neuroscience , 144 :232 , 2007
Abstract : Our previous microdialysis study demonstrated that both ethanol (EtOH) and acetaldehyde (ACe) decrease in vivo acetylcholine (ACh) release in the medial frontal cortex of freely moving rats. To better understand the mechanisms of EtOH and ACe's effects on the cholinergic system in the brain, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) expression was examined at 40 and 240 min after a dose of EtOH (1 g/kg) in the rat frontal cortex and hippocampus. The control group was treated with 0.9% saline, and other groups received EtOH or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) and 60 min later by EtOH intraperitoneally. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed that ChAT mRNA levels were decreased by 72.8% and 71.6% in the EtOH and CY+EtOH groups, respectively, at 40 min after EtOH injection compared with saline in the frontal cortex. The hippocampal ChAT levels were reduced by 76.5% and 53.0% in the EtOH and CY+EtOH groups, respectively, at this time. CY+EtOH-induced depletion in ChAT mRNA levels was markedly higher than EtOH in the hippocampus. A similar decrease pattern of ChAT was observed at protein levels as determined by Western blot, but the reduced ChAT levels were significantly higher in the CY+EtOH group as compared with the EtOH group both in the frontal cortex and hippocampus. At 240 min after EtOH injection, the EtOH group had no effect on ChAT at mRNA levels, as compared with saline, whereas CY+EtOH group induced a significant decrease in ChAT mRNA expression to 62.0% and 65.5% in the frontal cortex and hippocampus, respectively. These data were consistent with the results of the Western blot analysis. AChE expression at mRNA levels was not changed at either 40 or 240 min after EtOH dosing in either of these groups in the frontal cortex and hippocampus. Within 40 and 240 min, a statistically significant difference in ChAT expression at mRNA and protein levels was found in the EtOH and CY+EtOH groups both in the frontal cortex and hippocampus. The data obtained from this study demonstrate that EtOH and ACe concentrations decreased ChAT expression at 40 and 240 min after EtOH administration in the frontal cortex and hippocampus, and this result suggests that reduced ChAT expression is strongly related to a decrease in ACh release in the rat brain.
ESTHER : Jamal_2007_Neurosci_144_232
PubMedSearch : Jamal_2007_Neurosci_144_232
PubMedID: 17045751

Title : Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice - Lei_2007_Int.J.Obes.(Lond)_31_1023
Author(s) : Lei F , Zhang XN , Wang W , Xing DM , Xie WD , Su H , Du LJ
Ref : Int J Obes (Lond) , 31 :1023 , 2007
Abstract : OBJECTIVE: To investigate the anti-obesity effects of the pomegranate leaf extract (PLE) in a mouse model of high-fat diet induced obesity and hyperlipidemia. DESIGN: For the anti-obesity experiment, male and female ICR mice were fed with a high-fat diet to induce obesity. When the weight of the high-fat diet group was 20% higher than the normal diet group, the animals were treated with 400 or 800 mg/kg/day of PLE for 5 weeks. Body weight and daily food intake were measured regularly during the experimental period. The various adipose pads were weighed and serum total cholesterol (TC), triglyceride (TG), glucose and high-density lipoprotein cholesterol (HDL-C) were measured after 5 weeks, treatment with PLE. In the fat absorption experiment, both the normal and obese mice were given 0.5 ml lipid emulsion and PLE at a dose of 800 mg/kg at the same time. Serial serum TG levels were measured at times 1, 2, 3, 4 and 6 h after the treatment. TGs in fecal excretions were measured after the mice were orally given a lipid emulsion. Effects of PLE and its isolated compounds (ellagic acid and tannic acid) on pancreatic lipase activity were examined in vitro. RESULTS: The PLE-treated groups showed a significant decrease in body weight, energy intake and various adipose pad weight percents and serum, TC, TG, glucose levels and TC/HDL-C ratio after 5 weeks treatment. Furthermore, PLE significantly attenuated the raising of the serum TG level and inhibited the intestinal fat absorption in mice given a fat emulsion orally. PLE showed a significant difference in decreasing the appetite of obese mice fed a high-fat diet, but showed no effect in mice fed a normal diet. CONCLUSION: PLE can inhibit the development of obesity and hyperlipidemia in high-fat diet induced obese mice. The effects appear to be partly mediated by inhibiting the pancreatic lipase activity and suppressing energy intake. PLE may be a novel appetite suppressant that only affects obesity owing to a high-fat diet.
ESTHER : Lei_2007_Int.J.Obes.(Lond)_31_1023
PubMedSearch : Lei_2007_Int.J.Obes.(Lond)_31_1023
PubMedID: 17299386

Title : Ethanol and acetaldehyde: in vivo quantitation and effects on cholinergic function in rat brain - Jamal_2007_Novartis.Found.Symp_285_137
Author(s) : Jamal M , Ameno K , Ikuo U , Kumihashi M , Wang W , Ijiri I
Ref : Novartis Found Symp , 285 :137 , 2007
Abstract : First, ethanol (EtOH) and acetaldehyde levels were determined simultaneously in the striatum of free-moving rats after administration of their major oxidative enzyme inhibitors followed by EtOH. The results showed that acetaldehyde was present in the cyanamide (CY) + EtOH, CY + 4-methylpyrazole (4-MP) + EtOH and CY + sodium azide + EtOH groups. The CY + EtOH-induced peak acetaldehyde level was 195.2 +/- 19.4 microM, and this value was significantly higher than those in the other groups. The peak EtOH level was 25.9 +/- 2.3mM in the CY + 4-MP + EtOH group, and this level was considerably higher than the value in EtOH. No significant difference in brain EtOH levels was found in any of the other groups studied. Second, the effects of EtOH and acetaldehyde on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were investigated in the frontal cortex and hippocampus of high acetaldehyde-producing rats using RT-PCR and Western blot. The results showed that EtOH and acetaldehyde decreased ChAT expression at 40 and 240 min after EtOH dosing in the brain. The acetaldehyde-induced reduction in ChAT expression was significantly higher than that induced by EtOH. No remarkable alteration of AChE expression was observed. The study suggested that catalase made a significant contribution to acetaldehyde formation in the rat brain, and that EtOH and acetaldehyde decreased ChAT expression at 40 and 240 min after EtOH dosing.
ESTHER : Jamal_2007_Novartis.Found.Symp_285_137
PubMedSearch : Jamal_2007_Novartis.Found.Symp_285_137
PubMedID: 17590992

Title : Genome and proteome of long-chain alkane degrading Geobacillus thermodenitrificans NG80-2 isolated from a deep-subsurface oil reservoir - Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
Author(s) : Feng L , Wang W , Cheng J , Ren Y , Zhao G , Gao C , Tang Y , Liu X , Han W , Peng X , Liu R , Wang L
Ref : Proc Natl Acad Sci U S A , 104 :5602 , 2007
Abstract : The complete genome sequence of Geobacillus thermodenitrificans NG80-2, a thermophilic bacillus isolated from a deep oil reservoir in Northern China, consists of a 3,550,319-bp chromosome and a 57,693-bp plasmid. The genome reveals that NG80-2 is well equipped for adaptation into a wide variety of environmental niches, including oil reservoirs, by possessing genes for utilization of a broad range of energy sources, genes encoding various transporters for efficient nutrient uptake and detoxification, and genes for a flexible respiration system including an aerobic branch comprising five terminal oxidases and an anaerobic branch comprising a complete denitrification pathway for quick response to dissolved oxygen fluctuation. The identification of a nitrous oxide reductase gene has not been previously described in Gram-positive bacteria. The proteome further reveals the presence of a long-chain alkane degradation pathway; and the function of the key enzyme in the pathway, the long-chain alkane monooxygenase LadA, is confirmed by in vivo and in vitro experiments. The thermophilic soluble monomeric LadA is an ideal candidate for treatment of environmental oil pollutions and biosynthesis of complex molecules.
ESTHER : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedSearch : Feng_2007_Proc.Natl.Acad.Sci.U.S.A_104_5602
PubMedID: 17372208
Gene_locus related to this paper: geotd-g3jwz2 , geoka-q5l1n0 , geotn-a4ijt0 , geotn-a4ilq0 , geotn-a4is13 , geotn-a4isp0 , geotn-a4isp3

Title : Sodium selenite induces apoptosis in cultured cortical neurons with special concomitant changes in expression of the apoptosis-related genes - Xiao_2006_Neurotoxicol_27_478
Author(s) : Xiao R , Qiao JT , Zhao HF , Liang J , Yu HL , Liu J , Guo AM , Wang W
Ref : Neurotoxicology , 27 :478 , 2006
Abstract : Sodium selenite was used to examine whether selenium compound is able to trigger apoptotic degeneration in cultured cortical neurons in vitro and to explore the detailed changes in expression of the related genes during the apoptotic processes using molecular biological and flow cytometric examinations. The results indicated that: (1) cortical neurons treated with sodium selenite with different dosages (0.0008, 0.004, 0.0200, 0.1000, and 0.5000 microM) and different exposure times (2, 4, 24, and 48 h) exhibited dose- and time-dependent apoptotic processes as revealed by typical DNA ladder formation detected by agarose gel electrophoresis; (2) the internucleosomal DNA fragmentation detected by flow cytometric examination showed a prominent peak of hypodiploid DNA contents as early as 4h after exposure of 0.1 microM sodium selenite; (3) the DNA fragmentation induced by sodium selenite as revealed by the above two examinations could be blocked by aurintricarboxylic acid; (4) the transcriptions of mRNAs related to bcl-2, bax, c-fos, p53, and acetylcholinesterase (AChE) genes, as detected by RT-PCR assays, showed down-regulation for bcl-2 and up-regulation for bax, c-fos, p53, and AChE genes after exposure of sodium selenite. This study suggests that the sodium selenite is effective for inducing apoptosis in cultured cortical neurons and that relevant changes in expression of several apoptosis-related genes might further our understanding of the mechanism(s) that initiates and maintains the apoptotic processes.
ESTHER : Xiao_2006_Neurotoxicol_27_478
PubMedSearch : Xiao_2006_Neurotoxicol_27_478
PubMedID: 16542727

Title : [Progress of study on brain protective effect and mechanism of Polygonum multiflorum] - Wang_2005_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_25_955
Author(s) : Wang W , Wang DQ
Ref : Zhongguo Zhong Xi Yi Jie He Za Zhi , 25 :955 , 2005
Abstract : This paper reviews the brain protective effect and mechanism of Polygonum multiflorum (PM), its extracts and active component, tetrahydroxystilbene-glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside) published in recent decade. They have major effects as calcium channel antagonists, antioxidant, cholinomimetic drugs and cholinesterase inhibitors, as well as actions in regulating cell apoptosis and prolonging the ageing. The brain protective mechanism of PM is multi-target, multi-link and multi-way. Therefore, PM has great applicative value in prevention and treatment of senile neuropathies, such as Alzheimer's disease, Parkinson's disease and vascular dementia, etc.
ESTHER : Wang_2005_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_25_955
PubMedSearch : Wang_2005_Zhongguo.Zhong.Xi.Yi.Jie.He.Za.Zhi_25_955
PubMedID: 16313126

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Can block copolymers be synthesized by a single-step chemoenzymatic route in supercritical carbon dioxide? - Duxbury_2005_J.Am.Chem.Soc_127_2384
Author(s) : Duxbury CJ , Wang W , de Geus M , Heise A , Howdle SM
Ref : Journal of the American Chemical Society , 127 :2384 , 2005
Abstract : We demonstrate the single-step one-pot synthesis of block copolymers by simultaneous enzymatic ring-opening polymerization and chemically catalyzed atom transfer radical polymerization in supercritical carbon dioxide. Both catalyst systems function simultaneously under these conditions, providing a simple route to the formation of block copolymers of dissimilar monomers.
ESTHER : Duxbury_2005_J.Am.Chem.Soc_127_2384
PubMedSearch : Duxbury_2005_J.Am.Chem.Soc_127_2384
PubMedID: 15724980

Title : Presynaptic glycine receptors on GABAergic terminals facilitate discharge of dopaminergic neurons in ventral tegmental area - Ye_2004_J.Neurosci_24_8961
Author(s) : Ye JH , Wang F , Krnjevic K , Wang W , Xiong ZG , Zhang J
Ref : Journal of Neuroscience , 24 :8961 , 2004
Abstract : GABA-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic (DA) neurons of the ventral tegmental area (VTA) of rats, in acute brain slices, and from enzymatically or mechanically dissociated neurons. In young rats (3-10 d of age), where GABA is excitatory, glycine (1-3 microm) and taurine (10-30 microm) increased the amplitude of evoked IPSCs (eIPSCs) and the frequency of spontaneous IPSCs (sIPSCs) but had minimal postsynaptic effects. Strychnine (1 microm) blocked the action of glycine; when applied alone, it reduced the amplitude of eIPSCs and the frequency of sIPSCs, indicating a tonic facilitation of GABAergic excitation by some endogenous glycine agonist(s). In medium containing no Ca2+, or with Cd2+ or tetrodotoxin added, the amplitude and especially the frequency of sIPSCs greatly diminished. In many cells, glycine had no effect on remaining miniature IPSCs, suggesting a preterminal site of glycine receptors (GlyRs). Fura-2 fluorescent imaging showed a glycine-induced increase of [Ca2+] in nerve terminals (on DA neurons), which was suppressed by strychnine or 3 microm omega-conotoxin MVIIA. Therefore, the presynaptic GlyR-mediated facilitation of GABAergic transmission seems to be mediated by N- and/or P/Q-type Ca2+ channels. In older rats (22-30 d of age), where GABA causes inhibition, the effect of strychnine on GABAergic IPSCs was reversed to facilitation, indicating a tonic glycinergic inhibition of GABA release. Furthermore, glycine (1-3 microm) reduced the amplitude of eIPSCs and the frequency of sIPSCs. Hence, the overall effect of the presynaptic action of glycine is to enhance the firing of DA cells, both in very young and older rats.
ESTHER : Ye_2004_J.Neurosci_24_8961
PubMedSearch : Ye_2004_J.Neurosci_24_8961
PubMedID: 15483115

Title : Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms - Jin_2003_Toxicon_42_539
Author(s) : Jin Y , Lu Q , Zhou X , Zhu S , Li R , Wang W , Xiong Y
Ref : Toxicon , 42 :539 , 2003
Abstract : Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes.
ESTHER : Jin_2003_Toxicon_42_539
PubMedSearch : Jin_2003_Toxicon_42_539
PubMedID: 14529736

Title : Cloning and expression pattern of the human NDRG3 gene - Zhao_2001_Biochim.Biophys.Acta_1519_134
Author(s) : Zhao W , Tang R , Huang Y , Wang W , Zhou Z , Gu S , Dai J , Ying K , Xie Y , Mao Y
Ref : Biochimica & Biophysica Acta , 1519 :134 , 2001
Abstract : We report the cloning and expression pattern of a novel N-myc downstream-regulated gene 3 (NDRG3), located on human chromosome 20q11.21-11.23. The NDRG3 cDNA is 2588 base pair in length, encoding a 363 amino acid polypeptide highly related to mouse Ndr3 protein. Northern blot reveals that NDRG3 is highly expressed in testis, prostate and ovary. By in situ hybridization, the NDRG3 mRNA was localized to the outer layers of seminiferous epithelium, indicating that it may play a role in spermatogenesis.
ESTHER : Zhao_2001_Biochim.Biophys.Acta_1519_134
PubMedSearch : Zhao_2001_Biochim.Biophys.Acta_1519_134
PubMedID: 11406283

Title : Activation and Ca2+ permeation of stably transfected alpha3\/beta4 neuronal nicotinic acetylcholine receptor - Zhang_1999_Mol.Pharmacol_55_970
Author(s) : Zhang J , Xiao Y , Abdrakhmanova G , Wang W , Cleemann L , Kellar KJ , Morad M
Ref : Molecular Pharmacology , 55 :970 , 1999
Abstract : The alpha3/beta4 rat neuronal nicotinic acetylcholine receptor, stably transfected in human embryonic kidney cells, was examined using the whole-cell-clamp technique and 2-dimensional confocal imaging. Application of agonists (nicotine, cytisine, epibatidine) activated a large (100-200 pA/pF) inwardly rectifying monovalent current, with little current at voltages between 0 and +40 mV. Rapid application of nicotine and cytisine indicated EC50 values of congruent with22 and congruent with64 microM, respectively, and suggested second order binding kinetics (Hill coefficient approximately 2). The time constant of desensitization (decay) of nicotine-activated current was concentration-dependent (typically approximately 10 s at 30 microM versus approximately 1.0 s at 100-1000 microM), but not voltage-dependent and was significantly smaller than the approximately 200 s reported for the alpha3/beta4 receptor expressed in Xenopus oocytes. Nicotine-activated current was rapidly and reversibly blocked by coapplication of mecamylamine and d-tubocurarine. At -80 mV holding potentials, the current was also suppressed by approximately 25% either upon complete removal or elevation of Ca2+ to 10 mM. Total replacement of Na+ by Ca2+ also completely blocked the current. On the other hand, evidence for permeation of Ca2+ was indicated by increased inward current at -40 mV upon elevation of Ca2+ from 2 to 10 mM, as well as a rise in the cytosolic Ca2+ proportional to the current carried by the receptor. These findings are consistent with the idea that Ca2+, in addition to its channel-permeating properties, may also regulate the receptor from an extracellular site. Our results suggest that the alpha3/beta4 neuronal nicotinic acetylcholine receptor, when stably expressed in human embryonic kidney 293 cells, has desensitization kinetics and Ca2+ regulatory mechanisms somewhat different from those described for the receptor expressed in Xenopus oocytes.
ESTHER : Zhang_1999_Mol.Pharmacol_55_970
PubMedSearch : Zhang_1999_Mol.Pharmacol_55_970
PubMedID: 10347237

Title : Expression of an atrial G-protein-activated potassium channel in Xenopus oocytes - Dascal_1993_Proc.Natl.Acad.Sci.U.S.A_90_6596
Author(s) : Dascal N , Lim NF , Schreibmayer W , Wang W , Davidson N , Lester HA
Ref : Proc Natl Acad Sci U S A , 90 :6596 , 1993
Abstract : Injection of rat atrial RNA into Xenopus oocytes resulted in the expression of guanine nucleotide binding (G) protein-activated K+ channel. Current through the channel could be activated by acetylcholine or, if RNA encoding a neuronal 5HT1A receptor was coinjected with atrial RNA, by serotonin (5HT). A 5HT-evoked current (I5HT) was observed in oocytes injected with ventricle RNA fractions (of 2.5-5.5 kb) and 5HT1A receptor RNA. I5HT displayed strong inward rectification with very little conductance above the K+ equilibrium potential, was highly selective for K+ over Na+, and was blocked by 5-300 microM Ba2+. I5HT was suppressed by intracellular injection of the nonhydrolyzable analog of GDP, guanosine 5'-[beta-thio]diphosphate, but not by treatment with pertussis toxin (PTX), suggesting coupling of the receptor to the G-protein-activated K+ channel via a PTX-insensitive G protein, possibly endogenously present in the oocyte. Coexpression of the alpha subunit of a PTX-sensitive G protein, G(i2), rendered I5HT sensitive to PTX inhibition. Native oocytes displayed a constitutively active inwardly rectifying K+ current with a lower sensitivity to Ba2+ block; expression of a similar current was also directed by atrial or ventricle RNA of 1.5-3 kb. Xenopus oocytes may be employed for cloning of the G-protein-activated K+ channel cDNA and for studying the coupling between this channel and G proteins.
ESTHER : Dascal_1993_Proc.Natl.Acad.Sci.U.S.A_90_6596
PubMedSearch : Dascal_1993_Proc.Natl.Acad.Sci.U.S.A_90_6596
PubMedID: 8341673