Cheng Y

References (45)

Title : A simple fluorescence detection of acetylcholinesterase with peroxidase-like catalysis from iodide - Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
Author(s) : Huang X , Cheng Y , Zhou Q , Tu Y , Yan J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 313 :124116 , 2024
Abstract : Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01-8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.
ESTHER : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedSearch : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedID: 38490124

Title : Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem - Chi_2024_Plant.Commun__100939
Author(s) : Chi Y , Zhang H , Chen S , Cheng Y , Zhang X , Jia D , Chen Q , Chen H , Wei T
Ref : Plant Commun , :100939 , 2024
Abstract : Plant jasmonoyl-L-isoleucine (JA-Ile) is a major defense signal against insect feeding, but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in plant phloem remains elusive. Insect carboxylesterases (CarEs) are the third major family of detoxification enzymes. Here, we identify a new leafhopper CarE10 that specifically expressed in salivary glands and is secreted into rice phloem as the saliva component. Leafhopper CarE10 directly binds and promotes rice Jasmonate resistant 1 (JAR1) degradation by the proteasome system. Moreover, the direct association of CarE10 with JAR1 obviously impairs JAR1 enzyme activity for JA conversion to JA-Ile in in-vitro JA-Ile synthesis system. A devastating rice reovirus activates and promotes co-secretion of virions and CarE10 by virus-induced vesicles into saliva-stored salivary cavities of leafhopper vectors and ultimately into rice phloem to establish initial infection. Furthermore, virus-mediated increase of CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes the reduced levels of JAR1 and thus suppresses JA-Ile synthesis, thereby promoting host attractiveness to insect vectors and facilitating initial viral transmission. Our findings provide insights into how insect salivary protein CarE10 suppresses host JA-Ile synthesis to benefit initial virus transmission in rice phloem.
ESTHER : Chi_2024_Plant.Commun__100939
PubMedSearch : Chi_2024_Plant.Commun__100939
PubMedID: 38725245

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

Title : Interface chemistry affected the digestion fate of ketogenic diet based on medium- and long-chain triglycerides - Li_2024_Food.Res.Int_180_114059
Author(s) : Li X , Cheng Y , Xu Z , Lin X , Xu B , Wang Z , Li P , Nian B
Ref : Food Res Int , 180 :114059 , 2024
Abstract : Ketogenic diet, characterized by high fat and low carbohydrate content, is gradually becoming a new perspective in the human diet; however, the mechanism of digestion of ketogenic diet remains unknown. In this study, we explored the oil-water interface to elucidate the digestion of a ketogenic diet based on typical representative medium- and long-chain triglycerides. The free fatty acids (FFAs) release indicated that glycerol trioctanoate with a shorter carbon chain (FFA = 920.55 +/- 10.17 micromol) was significantly more digestible than glycerol tripalmitate (851.36 +/- 9.48 micromol) and glycerol tristearate (805.81 +/- 10.03 micromol). Particle size analysis revealed that the length of the carbon chain increased the size of triglycerides, resulting in a decreased contact area with lipase. The interfacial phenomenon indicated that the longer the carbon chain of triglycerides, the greater the reduction in binding capacity with salt ions in the digestive solution. Fluorescence spectroscopy analysis showed that the length of the carbon chain induced the displacement of the lipase peak, suggesting that the carbon chain length could alter the structure of lipase. Molecular dynamics simulation showed that the longer the carbon chain of triglycerides, the easier it was to loosen the structure of lipase. Bond energy analysis showed that the carbon chain length of triglycerides was positively correlated with the bond energy strength of the ester bonding. In conclusion, this study emphasizes that the ketogenic diet should primarily consist of shorter carbon chain triglycerides because carbon chain length can alter the digestion of triglycerides. This provides a new perspective on the quest for more effective ketogenic diet, in line with the current view of healthy diet.
ESTHER : Li_2024_Food.Res.Int_180_114059
PubMedSearch : Li_2024_Food.Res.Int_180_114059
PubMedID: 38395552

Title : Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril\/valsartan in Chinese patients with heart failure - Luo_2023_Eur.J.Clin.Pharmacol__
Author(s) : Luo HY , Gao LC , Long HZ , Zhou ZW , Xu SG , Li FJ , Li HL , Cheng Y , Li CX , Peng XY , Li L , Chen R , Deng P
Ref : European Journal of Clinical Pharmacology , : , 2023
Abstract : OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.
ESTHER : Luo_2023_Eur.J.Clin.Pharmacol__
PubMedSearch : Luo_2023_Eur.J.Clin.Pharmacol__
PubMedID: 36976322

Title : Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C - Kuang_2023_Gen.Physiol.Biophys_42_361
Author(s) : Kuang Y , Wang J , Dong Y , Cheng Y , Li H , Ji Y , Gao H , Cao X
Ref : Gen Physiol Biophys , 42 :361 , 2023
Abstract : Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients were extracted from the Gene Expression Omnibus (GEO) database (GSE130036) and analyzed by weighted gene coexpression network analysis (WGCNA). A total of 31 coexpression modules were identified. The coexpression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packages in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. We further verified the expression of CES1 and CTSC was downregulated in HCM clinical blood and negatively correlated with Maxi LVWT. Finally, we demonstrated that overexpression of CTSC and CES1 could alleviate HCM in an HCM cell model. In summary, the study suggests that CES1 and CTSC negatively regulate the development of HCM and have potential as therapeutic and diagnostic targets for HCM.
ESTHER : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedSearch : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedID: 37449320

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : Anti-human Glioma Cancer Potentials of Neobavaisoflavone as Natural Antioxidant Compound and Its Inhibition Profiles for Acetylcholinesterase and Butyrylcholinesterase Enzymes with Molecular Modeling and Spin Density Distributions Studies - Chen_2022_J.Oleo.Sci_71_277
Author(s) : Chen M , Zhao H , Cheng Y , Wang L , Alotaibi SH , Zhang Y
Ref : J Oleo Sci , 71 :277 , 2022
Abstract : In this study, the carcinogenic potential of Neobavaisoflavone as a natural antioxidant compound and the inhibitory profiles of acetylcholinesterase and butyrylcholinesterase were investigated by molecular modeling and spin density distribution studies. To evaluate the antioxidant properties of neobavaisoflavone, DPPH test was performed in the presence of butyl hydroxytoluene as a control. Neobavaisoflavone cell viability was low compared to normal human glioma cancer cell lines, namely LN-229, U-87 and A-172 cell lines, without any effect of cytotoxicity on normal cell line. Neobavaisoflavone inhibited half of DPPH at 125 microg/mL. The best effects of Neobavaisoflavone antihypertensive glioma against the above cell lines were in the LN-229 cell line. In addition, the significant anti-cancer potential of human glioma Neobavaisoflavone against the popular human glioma cancer cell lines is related in this study. IC(50) values were calculated by Neobavaisoflavone diagrams, 63.87 nM for AChE and 112.98 nM for BuChE, % Activity- [Inhibitor]. According to the above results, Neobavaisoflavone can be used to treat a variety of human glioma cancers in humans. In addition, molecular modeling calculations were performed to compare the biochemical activities of the Neobavaisoflavone molecule with enzymes. After molecular insertion calculations, ADME/T analysis was performed to investigate the properties of the neobavaisoflavone molecule, which will be used as a drug in the future. Then, different parameters for the antioxidant activity of the neobavaisoflavone molecule were calculated.
ESTHER : Chen_2022_J.Oleo.Sci_71_277
PubMedSearch : Chen_2022_J.Oleo.Sci_71_277
PubMedID: 35110469

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

Title : Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia - Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
Author(s) : Wang S , Cheng Y , Shi Y , Zhao W , Gao L , Fang L , Jin X , Han X , Sun Q , Li G , Zhao J , Xu C
Ref : Front Endocrinol (Lausanne) , 13 :874608 , 2022
Abstract : BACKGROUND: Type I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis. OBJECTIVE: This study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia. METHODS: We conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium. RESULTS: Proband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 +/- 9.46% (p<0.01) and 54.60 +/- 9.03% (p<0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants. CONCLUSIONS: Two novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity.
ESTHER : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedSearch : Wang_2022_Front.Endocrinol.(Lausanne)_13_874608
PubMedID: 35923617
Gene_locus related to this paper: human-LPL

Title : Genome-wide analysis and expression patterns of lipid phospholipid phospholipase gene family in Brassica napus L - Su_2021_BMC.Genomics_22_548
Author(s) : Su W , Raza A , Zeng L , Gao A , Lv Y , Ding X , Cheng Y , Zou X
Ref : BMC Genomics , 22 :548 , 2021
Abstract : BACKGROUND: Lipid phosphate phosphatases (LPP) are critical for regulating the production and degradation of phosphatidic acid (PA), an essential signaling molecule under stress conditions. Thus far, the LPP family genes have not been reported in rapeseed (Brassica napus L.). RESULTS: In this study, a genome-wide analysis was carried out to identify LPP family genes in rapeseed that respond to different stress conditions. Eleven BnLPPs genes were identified in the rapeseed genome. Based on phylogenetic and synteny analysis, BnLPPs were classified into four groups (Group I-Group IV). Gene structure and conserved motif analysis showed that similar intron/exon and motifs patterns occur in the same group. By evaluating cis-elements in the promoters, we recognized six hormone- and seven stress-responsive elements. Further, six putative miRNAs were identified targeting three BnLPP genes. Gene ontology analysis disclosed that BnLPP genes were closely associated with phosphatase/hydrolase activity, membrane parts, phosphorus metabolic process, and dephosphorylation. The qRT-PCR based expression profiles of BnLPP genes varied in different tissues/organs. Likewise, several gene expression were significantly up-regulated under NaCl, PEG, cold, ABA, GA, IAA, and KT treatments. CONCLUSIONS: This is the first report to describe the comprehensive genome-wide analysis of the rapeseed LPP gene family. We identified different phytohormones and abiotic stress-associated genes that could help in enlightening the plant tolerance against phytohormones and abiotic stresses. The findings unlocked new gaps for the functional verification of the BnLPP gene family during stresses, leading to rapeseed improvement.
ESTHER : Su_2021_BMC.Genomics_22_548
PubMedSearch : Su_2021_BMC.Genomics_22_548
PubMedID: 34273948

Title : The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review - Fan_2021_J.Alzheimers.Dis__
Author(s) : Fan F , Liu H , Shi X , Ai Y , Liu Q , Cheng Y
Ref : J Alzheimers Dis , : , 2021
Abstract : BACKGROUND: Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. OBJECTIVE: We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients. METHODS: We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles. RESULTS: Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Abeta agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD. CONCLUSION: Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.
ESTHER : Fan_2021_J.Alzheimers.Dis__
PubMedSearch : Fan_2021_J.Alzheimers.Dis__
PubMedID: 34924395

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

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

Title : Investigation of the transformation and toxicity of trichlorfon at the molecular level during enzymic hydrolysis of apple juice - Li_2020_Food.Chem__128653
Author(s) : Li C , Zhu H , Guo Y , Xie Y , Cheng Y , Yu H , Qian H , Yao W
Ref : Food Chem , :128653 , 2020
Abstract : Trichlorfon is one of the most widely used organophosphorus pesticides in agriculture. In this study, the extent of transformation of trichlorfon to dichlorvos (DDVP), during the polygalacturonase (PG) treatment of apple pulp was monitored. A transformation pathway is proposed for trichlorfon molecules, based on density functional theory (DFT) calculations. The transformation of trichlorfon involves hydroxyl substitution and cleavage, which was confirmed by molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) theory. In addition, the toxicity of trichlorfon and its transformed products was analyzed using Ecological Structure Activity Relationships (ECOSAR) software. The binding sites of the two pesticides are located in the hydrophobic grooves of the acetylcholinesterase (AChE) active site region and both pesticides form hydrophobic interactions and hydrogen bonds with a large number of surrounding amino acid residues. DDVP binds more strongly with AChE, so it is a better AChE inhibitor and more toxic than trichlorfon.
ESTHER : Li_2020_Food.Chem__128653
PubMedSearch : Li_2020_Food.Chem__128653
PubMedID: 33229164

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

Title : Efficient biodegradation of highly crystallized polyethylene terephthalate through cell surface display of bacterial PETase - Chen_2020_Sci.Total.Environ_709_136138
Author(s) : Chen Z , Wang Y , Cheng Y , Wang X , Tong S , Yang H , Wang Z
Ref : Sci Total Environ , 709 :136138 , 2020
Abstract : Polyethylene terephthalate (PET) is one of the most widely used plastics in the world. Accumulation of the discarded PET in the environment is creating a global environmental problem. Recently, a bacterial enzyme named PETase was found to have the novel ability to degrade the highly crystallized PET. However, the enzymatic activity of native PETase is still low limiting its possible use in recycling of PET. In this study, we developed a whole-cell biocatalyst by displaying PETase on the surface of yeast (Pichia pastoris) cell to improve its degradation efficiency. Our data shows that PETase could be functionally displayed on the yeast cell with enhanced pH and thermal stability. The turnover rate of the PETase-displaying yeast whole-cell biocatalyst towards highly crystallized PET dramatically increased about 36-fold compared with that of purified PETase. Furthermore, the whole-cell biocatalyst showed stable turnover rate after seven repeated use and under some chemical/solvent conditions, and its ability to degrade different commercial highly crystallized PET bottles. Our results reveal that PETase-displaying whole-cell biocatalyst affords a promising route for efficient biological recycling of PET.
ESTHER : Chen_2020_Sci.Total.Environ_709_136138
PubMedSearch : Chen_2020_Sci.Total.Environ_709_136138
PubMedID: 31887523

Title : CARD8 inflammasome activation triggers pyroptosis in human T cells - Linder_2020_EMBO.J__e105071
Author(s) : Linder A , Bauernfried S , Cheng Y , Albanese M , Jung C , Keppler OT , Hornung V
Ref : EMBO Journal , :e105071 , 2020
Abstract : Inflammasomes execute a unique type of cell death known as pyroptosis. Mostly characterized in myeloid cells, caspase-1 activation downstream of an inflammasome sensor results in the cleavage and activation of gasdermin D (GSDMD), which then forms a lytic pore in the plasma membrane. Recently, CARD8 was identified as a novel inflammasome sensor that triggers pyroptosis in myeloid leukemia cells upon inhibition of dipeptidyl-peptidases (DPP). Here, we show that blocking DPPs using Val-boroPro triggers a lytic form of cell death in primary human CD4 and CD8 T cells, while other prototypical inflammasome stimuli were not active. This cell death displays morphological and biochemical hallmarks of pyroptosis. By genetically dissecting candidate components in primary T cells, we identify this response to be dependent on the CARD8-caspase-1-GSDMD axis. Moreover, DPP9 constitutes the relevant DPP restraining CARD8 activation. Interestingly, this CARD8-induced pyroptosis pathway can only be engaged in resting, but not in activated T cells. Altogether, these results broaden the relevance of inflammasome signaling and associated pyroptotic cell death to T cells, central players of the adaptive immune system.
ESTHER : Linder_2020_EMBO.J__e105071
PubMedSearch : Linder_2020_EMBO.J__e105071
PubMedID: 32840892
Gene_locus related to this paper: human-DPP9

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

Title : Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease - Bai_2019_Eur.J.Med.Chem_183_111737
Author(s) : Bai P , Wang K , Zhang P , Shi J , Cheng X , Zhang Q , Zheng C , Cheng Y , Yang J , Lu X , Sang Z
Ref : Eur Journal of Medicinal Chemistry , 183 :111737 , 2019
Abstract : A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase (IC50=1.3+/-0.01muM) and butyrylcholinesterase (IC50=1.2+/-0.09muM). Besides, 23c exhibited selective MAO-B inhibitory activity with IC50 value of 0.57+/-0.01muM. Compound 23c was also a potential antioxidant and neuroprotectant. In addition, compound 23c could inhibit self-induced Abeta1-42 aggregation. Moreover, compound 23c was a selective metal chelator, and could inhibit and disaggregate Cu(2+)-induced Abeta1-42 aggregation, which was supported by the further transmission electron microscopy images. Furthermore, 23c could cross the blood-brain barrier in vitro, and improved scopolamine-induced memory impairment in vivo assay. Molecular modeling studies showed that 23c could bind to the active site of AChE, BuChE, Abeta1-42 and MAO-B. Taken together, these results suggested that compound 23c might be a potential multifunctional agent for the treatment of AD.
ESTHER : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedSearch : Bai_2019_Eur.J.Med.Chem_183_111737
PubMedID: 31581002

Title : Copper exposure enhances Spodoptera litura larval tolerance to beta-cypermethrin - Lu_2019_Pestic.Biochem.Physiol_160_127
Author(s) : Lu K , Li W , Cheng Y , Ni H , Chen X , Li Y , Tang B , Sun X , Liu T , Qin N , Chen D , Zeng R , Song Y
Ref : Pestic Biochem Physiol , 160 :127 , 2019
Abstract : Environmental xenobiotics can influence the tolerance of insects to chemical insecticides. Heavy metals are widespread distributed, can be easily bio-accumulated in plants and subsequently within phytophagous insects via the food chains. However, less attention has been paid to the effect of heavy metal exposure on their insecticide tolerance. In this study, pre-exposure of copper (Cu, 25-100mgkg(-1)) significantly enhanced the subsequent tolerance of Spodoptera litura to beta-cypermethrin, a widely used pyrethroid insecticide in crop field. Cytochrome P450 monooxygenases (CYPs) activities were cross-induced in larvae exposed to Cu and beta-cypermethrin, while the activities of glutathione S-transferase (GST) and carboxylesterase (CarE) were not affected. Application of piperonyl butoxide (PBO), a P450 synergist, effectively impaired the tolerance to beta-cypermethrin in Cu-exposed S. litura larvae with a synergistic ratio of 1.72, indicating that P450s contribute to larval tolerance to beta-cypermethrin induced by Cu exposure. Among the four CYP6AB family genes examined, only larval midgut-specific CYP6AB12 was found to be cross-induced by Cu and beta-cypermethrin. RNA interference (RNAi)-mediated silencing of CYP6AB12 effectively decreased the mRNA levels of the target gene, and significantly reduced the larval tolerance to beta-cypermethrin following exposure to Cu. These results showed that pre-exposure of heavy metal Cu enhanced larval tolerance to beta-cypermethrin in S. litura, possibly through the cross-induction of P450s. Our findings provide new insights on the relationship between heavy metals and chemical insecticides that may benefit both the risk evaluation of heavy metal contamination and development of pest management strategies.
ESTHER : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedSearch : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedID: 31519247

Title : Carboxylesterase, a de-esterification enzyme, catalyzes the degradation of chlorimuron-ethyl in Rhodococcus erythropolis D310-1 - Zang_2019_J.Hazard.Mater__121684
Author(s) : Zang H , Wang H , Miao L , Cheng Y , Zhang Y , Liu Y , Sun S , Wang Y , Li C
Ref : J Hazard Mater , :121684 , 2019
Abstract : Microbial degradation is considered to be the most acceptable method for degradation of chlorimuron-ethyl, a typical long-term residual sulfonylurea herbicide, but the underlying mechanism at the genetic and biochemical levels is unclear. In this work, the genome sequence of the chlorimuron-ethyl-degrading bacterium Rhodococcus erythropolis D310-1 was completed, and the gene clusters responsible for the degradation of chlorimuron-ethyl in D310-1 were predicted. A carboxylesterase gene, carE, suggested to be responsible for carboxylesterase de-esterification, was cloned from D310-1. CarE was expressed in Escherichia coli BL21 and purified to homogeneity. The active site of the chlorimuron-ethyl-degrading enzyme CarE and the biochemical activities of CarE were elucidated. The results demonstrated that CarE is involved in catalyzing the de-esterification of chlorimuron-ethyl. A carE deletion mutant strain, D310-1DeltacarE, was constructed, and the chlorimuron-ethyl degradation rate in the presence of 100mgL(-1) chlorimuron-ethyl within 120h decreased from 86.5 % (wild-type strain D310-1) to 58.2 % (mutant strain D310-1DeltacarE). Introduction of the plasmid pNit-carE restored the ability of the mutant strain to utilize chlorimuron-ethyl. This study is the first to demonstrate that carboxylesterase can catalyze the de-esterification reaction of chlorimuron-ethyl and provides new insights into the mechanism underlying the degradation of sulfonylurea herbicides and a theoretical basis for the utilization of enzyme resources.
ESTHER : Zang_2019_J.Hazard.Mater__121684
PubMedSearch : Zang_2019_J.Hazard.Mater__121684
PubMedID: 31784128
Gene_locus related to this paper: rhoe4-c1a280

Title : Comparative transcriptome reveals the potential modulation mechanisms of estradiol affecting ovarian development of female Portunus trituberculatus - Liu_2019_PLoS.One_14_e0226698
Author(s) : Liu M , Pan J , Dong Z , Cheng Y , Gong J , Wu X
Ref : PLoS ONE , 14 :e0226698 , 2019
Abstract : Estradiol is an important sex steroid hormone that is involved in the regulation of crustacean ovarian development. However, the molecular regulatory mechanisms of estradiol on ovarian development are largely unknown. This study performed transcriptome sequencing of ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ of crabs after estradiol treatment (0.1mug g-1 crab weight). A total of 23, 806 genes were annotated, and 316, 1300, 669, 142, 383 genes were expressed differently in ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ respectively. Differentially expressed gene enrichment analysis revealed several crucial pathways including protein digestion and absorption, pancreatic secretion, insect hormone biosynthesis, drug metabolism-cytochrome P450 and signal transduction pathway. Through this study, some key genes in correlation with the ovarian development and nutrition metabolism were significantly affected by estradiol, such as vitelline membrane outer layer 1-like protein, heat shock protein 70, Wnt5, JHE-like carboxylesterase 1, cytochrome P302a1, crustacean hyperglycemic hormone, neuropeptide F2, trypsin, carboxypeptidase B, pancreatic triacylglycerol lipase-like, and lipid storage droplet protein. Moreover, RT-qPCR validation demonstrated that expression of transcripts related to ovarian development (vitelline membrane outer layer 1-like protein and cytochrome P302a1) and nutrition metabolism (trypsin, glucose dehydrogenase and lipid storage droplet protein) were significantly affected by estradiol treatment. This study not only has identified relevant genes and several pathways that are involved in estradiol regulation on ovarian development of P. trituberculatus, but also provided new insight into the understanding of the molecular function mechanisms of estradiol in crustacean.
ESTHER : Liu_2019_PLoS.One_14_e0226698
PubMedSearch : Liu_2019_PLoS.One_14_e0226698
PubMedID: 31856263

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

Title : Global transcriptomic analysis of Rhodococcus erythropolis D310-1 in responding to chlorimuron-ethyl - Cheng_2018_Ecotoxicol.Environ.Saf_157_111
Author(s) : Cheng Y , Zang H , Wang H , Li D , Li C
Ref : Ecotoxicology & Environmental Safety , 157 :111 , 2018
Abstract : Chlorimuron-ethyl is a typical long-term residual sulfonylurea herbicide whose long period of residence poses a serious hazard to rotational crops. Microbial degradation is considered to be the most acceptable method for its removal, but the degradation mechanism is not clear. In this work, we investigated gene expression changes during the degradation of chlorimuron-ethyl by an effective chlorimuron-ethyl-degrading bacterium, Rhodococcus erythropolis D310-1. The genes that correspond to this degradation and their mode of action were identified using RNA-Seq and qRT-PCR. The RNA-Seq results revealed that 500 genes were up-regulated during chlorimuron-ethyl degradation by strain D310-1. KEGG annotation showed that the dominant metabolic pathways were "Toluene degradation" and "Aminobenzoate degradation". Combining GO and KEGG classification with the relevant literature, we predicted that cytochrome P-450, carboxylesterase, and monooxygenase were involved in metabolic chlorimuron-ethyl biodegradation and that the enzyme active site and mode of action coincided with the degradation pathway proposed in our previous study. qRT-PCR experiments suggested that the R. erythropolis D310-1 carboxylesterase, cytochrome P-450 and glycosyltransferase genes were the key genes expressed during chlorimuron-ethyl biodegradation. To the best of our knowledge, this report is the first to describe the transcriptome analysis of a Rhodococcus species during the degradation of chlorimuron-ethyl.
ESTHER : Cheng_2018_Ecotoxicol.Environ.Saf_157_111
PubMedSearch : Cheng_2018_Ecotoxicol.Environ.Saf_157_111
PubMedID: 29614448

Title : Assessment of the oxidative and genotoxic effects of the glyphosate-based herbicide roundup on the freshwater shrimp, Macrobrachium nipponensis - Hong_2018_Chemosphere_210_896
Author(s) : Hong Y , Yang X , Huang Y , Yan G , Cheng Y
Ref : Chemosphere , 210 :896 , 2018
Abstract : In the present study, an acute toxic test was performed to assess the oxidative stress and genotoxic effects of the herbicide on the freshwater shrimp Macrobrachium nipponensis. The results showed that the 48-h and 96-h LC50 values of Roundup to M. nipponensis were 57.684mg/L and 11.237mg/L, respectively. For further investigation, the shrimps were exposed to sublethal concentrations of 0.35, 0.70, 1.40, 2.80 and 5.60mg/L for 96h. A significant decrease in total haemocytes count (THC) was observed at concentration of 5.60mg/L throughout the experiment. The level of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in all the treatments decreased in a dose- and time-dependent manner except for the concentration group of 0.35mg/L. The malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum increased significantly at concentrations of 2.80mg/L and 5.60mg/L. A significant decrease in acetylcholinesterase (AChE) activity was observed at each concentration (P0.05). In addition, the micronucleus (MN) frequency of haemocytes significantly increased (P0.05) at concentrations of 1.40, 2.80 and 5.60mg/L, whereas the comet ratio and %DNA in the tails exhibited a clear time- and dose-dependent response during the exposure. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants, and this dose-dependent relation suggests the sensitivity and availability of all the biomarkers. These results revealed that Roundup had a prominent toxic effect on M. nipponensis based on the antioxidative response inhibition and genotoxicity.
ESTHER : Hong_2018_Chemosphere_210_896
PubMedSearch : Hong_2018_Chemosphere_210_896
PubMedID: 30208549

Title : Triglyceride metabolism in exercising muscle - Watt_2017_Biochim.Biophys.Acta_1862_1250
Author(s) : Watt MJ , Cheng Y
Ref : Biochimica & Biophysica Acta , 1862 :1250 , 2017
Abstract : Triglycerides are stored within lipid droplets in skeletal muscle and can be hydrolyzed to produce fatty acids for energy production through beta-oxidation and oxidative phosphorylation. While there was some controversy regarding the quantitative importance of intramyocellular triglyceride (IMTG) as a metabolic substrate, recent advances in proton magnetic resonance spectroscopy and confocal microscopy support earlier tracer and biopsy studies demonstrating a substantial contribution of IMTG to energy production, particularly during moderate-intensity endurance exercise. This review provides an update on the understanding of IMTG utilization during exercise, with a focus on describing the key regulatory proteins that control IMTG breakdown and how these proteins respond to acute exercise and in the adaptation to exercise training. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.
ESTHER : Watt_2017_Biochim.Biophys.Acta_1862_1250
PubMedSearch : Watt_2017_Biochim.Biophys.Acta_1862_1250
PubMedID: 28652193

Title : Glycyrrhetinic Acid Liposomes Containing Mannose-Diester Lauric Diacid-Cholesterol Conjugate Synthesized by Lipase-Catalytic Acylation for Liver-Specific Delivery - Chen_2017_Molecules_22_E1598
Author(s) : Chen J , Chen Y , Cheng Y , Gao Y
Ref : Molecules , 22 : , 2017
Abstract : Mannose-diester lauric diacid-cholesterol (Man-DLD-Chol), as a liposomal target ligand, was synthesized by lipase catalyzed in a non-aqueous medium. Its chemical structure was confirmed by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Glycyrrhetinic acid (GA) liposomes containing Man-DLD-Chol (Man-DLD-Chol-GA-Lp) were prepared by the film-dispersion method. We evaluated the characterizations of liposomes, drug-release in vitro, the hemolytic test, cellular uptake, pharmacokinetics, and the tissue distributions. The cellular uptake in vitro suggested that the uptake of Man-DLD-Chol-modified liposomes was significantly higher than that of unmodified liposomes in HepG2 cells. Pharmacokinetic parameters indicated that Man-DLD-Chol-GA-Lp was eliminated more rapidly than GA-Lp. In tissue distributions, the targeting efficiency (Te) of Man-DLD-Chol-GA-Lp on liver was 54.67%, relative targeting efficiency (RTe) was 3.39, relative uptake rate (Re) was 4.78, and peak concentration ratio (Ce) was 3.46. All these results supported the hypothesis that Man-DLD-Chol would be an efficient liposomal carrier, and demonstrated that Man-DLD-Chol-GA-Lp has potential as a drug delivery for liver-targeting therapy.
ESTHER : Chen_2017_Molecules_22_E1598
PubMedSearch : Chen_2017_Molecules_22_E1598
PubMedID: 28946644

Title : Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation - Xu_2017_Brain.Behav_7_e00793
Author(s) : Xu X , Hu Z , Zhang L , Liu H , Cheng Y , Xia K , Zhang X
Ref : Brain Behav , 7 :e00793 , 2017
Abstract : INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing.
METHODS: In this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK293 cells expressing wild-type and mutant neuroligin.
RESULTS: We found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1-neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms. CONCLUSION: Our data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
ESTHER : Xu_2017_Brain.Behav_7_e00793
PubMedSearch : Xu_2017_Brain.Behav_7_e00793
PubMedID: 28948087
Gene_locus related to this paper: human-NLGN4X

Title : Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score - Wu_2016_Exp.Ther.Med_11_806
Author(s) : Wu X , Xie W , Cheng Y , Guan Q
Ref : Exp Ther Med , 11 :806 , 2016
Abstract : The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis.
ESTHER : Wu_2016_Exp.Ther.Med_11_806
PubMedSearch : Wu_2016_Exp.Ther.Med_11_806
PubMedID: 26997996

Title : Synthesis of stable isotopically labelled 3-methylfuran-2(5H)-one and the corresponding strigolactones - Cheng_2015_J.Labelled.Comp.Radiopharm_58_355
Author(s) : Cheng Y , Ding WH , Long Q , Zhao M , Yang J , Li XQ
Ref : J Labelled Comp Radiopharm , 58 :355 , 2015
Abstract : Conventional synthetic procedures of strigolactones (SLs) involve the independent synthesis of ring ABC and ring D, followed by a coupling of the two fragments. Here we prepared three kinds of stable, isotopically labelled D-ring analogues productively using a facile protocol. Then, a coupling of the D-rings to ring ABC produced three isotope-labelled SL derivatives. Moreover, (+)-D3-2'-epi-1A and (-)-ent-D3-2'-epi-1A with high enantiomeric purity were obtained via chiral resolution.
ESTHER : Cheng_2015_J.Labelled.Comp.Radiopharm_58_355
PubMedSearch : Cheng_2015_J.Labelled.Comp.Radiopharm_58_355
PubMedID: 26179068

Title : Analysis of essential amino acid residues for catalytic activity of cis-epoxysuccinate hydrolase from Bordetella sp. BK-52 - Bao_2014_Appl.Microbiol.Biotechnol_98_1641
Author(s) : Bao W , Pan H , Zhang Z , Cheng Y , Xie Z , Zhang J , Li Y
Ref : Applied Microbiology & Biotechnology , 98 :1641 , 2014
Abstract : cis-Epoxysuccinate hydrolase (CESH) from Bordetella sp. BK-52, an epoxide hydrolase (EH), catalyzes the stereospecific hydrolysis of cis-epoxysuccinate to D(-)-tartrate. The enzyme, which shows no homology to other reported EHs, belongs to the DUF849 superfamily of prokaryotic proteins, which have unknown function. Metal composition analysis revealed that the CESH is a Zn(2+)-dependent enzyme with an approximately 1:1 molar ratio of zinc to enzyme. The results of an (18)O-labeling study suggest that the enzyme catalyzes epoxide hydrolysis by means of a one-step mechanism. We evaluated the relationship between the structure and function of the enzyme by means of sequence alignment, modeling, substrate binding, and reaction kinetics studies. The CESH has a canonical (beta/alpha)8 TIM barrel fold, and we used site-directed mutagenesis to identify eight residues (H47, H49, R51, T82, Y138, N140, W164, and D251) as being localized to the active site or highly conserved. On the basis of these results and theoretical considerations, we identified H47 and H49 as zinc-binding ligands, and we propose that a zinc atom and R51, T82, Y138, N140, W164, and D251 are the catalytic residues and participate in substrate binding. In summary, the structure and catalytic mechanism of the CESH from Bordetella sp. BK-52 differ from those of classic EHs, which have an alpha/beta hydrolase fold, act via a two-step catalytic mechanism, and do not require cofactors, prosthetic groups, or metal ions.
ESTHER : Bao_2014_Appl.Microbiol.Biotechnol_98_1641
PubMedSearch : Bao_2014_Appl.Microbiol.Biotechnol_98_1641
PubMedID: 23764769

Title : Cloning, homology modeling, and reaction mechanism analysis of a novel cis-epoxysuccinate hydrolase from Klebsiella sp - Cheng_2014_Biotechnol.Lett_36_2537
Author(s) : Cheng Y , Pan H , Bao W , Sun W , Xie Z , Zhang J , Zhao Y
Ref : Biotechnol Lett , 36 :2537 , 2014
Abstract : The gene encoding a novel cis-epoxysuccinate hydrolase, which hydrolyzes cis-epoxysuccinate to L (+)-tartaric acid, was cloned from Klebsiella sp. BK-58 and expressed in Escherichia coli. The ORF was 825 bp encoding a mature protein of 274 amino acids with a molecular mass of 30.1 kDa. Multiple sequence alignment showed that the enzyme belonged to the haloacid dehalogenase-like super family. Homology modeling and site-directed mutagenesis were performed to investigate the structural characteristics of the enzyme. Its overall structure consisted of a core domain formed by six-stranded parallel beta-sheets flanked by seven alpha-helices and a subdomain that had a four helix bundle structure. Residues D48, T52, R85, N165, K195, Y201, A219, H221, and D224 were catalytically important forming the active pocket between the two domains. An (18)O-labeling study suggested that the catalytic reaction of the enzyme proceeded through a two-step mechanism.
ESTHER : Cheng_2014_Biotechnol.Lett_36_2537
PubMedSearch : Cheng_2014_Biotechnol.Lett_36_2537
PubMedID: 25216644

Title : Multi-Scale Continuum Modeling of Biological Processes: From Molecular Electro-Diffusion to Sub-Cellular Signaling Transduction - Cheng_2012_Comput.Sci.Discov_5_
Author(s) : Cheng Y , Kekenes-Huskey P , Hake J , Holst M , McCammon JA , Michailova A
Ref : Comput Sci Discov , 5 : , 2012
Abstract : This article provides a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http:\/\/mccammon.ucsd.edu/smol/, http:\/\/FETK.org) by numerical solution of time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally-validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times with increasing ionic strength and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a non-linear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally-derived rodent ventricular myocyte geometries. Results reveal the important role for mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that the alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate subcellular Ca2+ signals. Model predicts that reduced off-rate in whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for integration of molecular-scale information into simulations of cellular-scale systems.
ESTHER : Cheng_2012_Comput.Sci.Discov_5_
PubMedSearch : Cheng_2012_Comput.Sci.Discov_5_
PubMedID: 23505398

Title : Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population - Li_2011_Ann.Hum.Genet_75_605
Author(s) : Li L , Qi L , Lv N , Gao Q , Cheng Y , Wei Y , Ye J , Yan X , Dang A
Ref : Ann Hum Genet , 75 :605 , 2011
Abstract : The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.
ESTHER : Li_2011_Ann.Hum.Genet_75_605
PubMedSearch : Li_2011_Ann.Hum.Genet_75_605
PubMedID: 21834908
Gene_locus related to this paper: human-PLA2G7

Title : Site-directed mutagenesis of epoxide hydrolase to probe catalytic amino acid residues and reaction mechanism - Pan_2011_FEBS.Lett_585_2545
Author(s) : Pan H , Xie Z , Bao W , Cheng Y , Zhang J , Li Y
Ref : FEBS Letters , 585 :2545 , 2011
Abstract : Epoxide hydrolase from Rhodococcus opacus catalyzes the stereospecific hydrolysis of cis-epoxysuccinate to L(+)-tartrate. It shows low but significant similarity to haloacid dehalogenase and haloacetate dehalogenase (16-23% identity). To identify catalytically important residues, we mutated 29 highly conserved charged and polar amino acid residues (except for one alanine). The replacement of D18, D193, R55, K164, H190, T22, Y170, N134 and A188 led to a significant loss in the enzyme activity, indicating their involvement in the catalysis. Single and multiple turnover reaction studies show that the enzyme reaction proceeded through the two-step mechanism involving the formation of a covalent intermediate. We discuss the roles of these residues and propose its possible reaction mechanism.
ESTHER : Pan_2011_FEBS.Lett_585_2545
PubMedSearch : Pan_2011_FEBS.Lett_585_2545
PubMedID: 21763314

Title : 1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia - Anandan_2011_Bioorg.Med.Chem.Lett_21_983
Author(s) : Anandan SK , Webb HK , Chen D , Wang YX , Aavula BR , Cases S , Cheng Y , Do ZN , Mehra U , Tran V , Vincelette J , Waszczuk J , White K , Wong KR , Zhang LN , Jones PD , Hammock BD , Patel DV , Whitcomb R , MacIntyre DE , Sabry J , Gless R
Ref : Bioorganic & Medicinal Chemistry Lett , 21 :983 , 2011
Abstract : 1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents.
ESTHER : Anandan_2011_Bioorg.Med.Chem.Lett_21_983
PubMedSearch : Anandan_2011_Bioorg.Med.Chem.Lett_21_983
PubMedID: 21211973

Title : Genetic and epigenetic inactivation of LPL gene in human prostate cancer - Kim_2009_Int.J.Cancer_124_734
Author(s) : Kim JW , Cheng Y , Liu W , Li T , Yegnasubramanian S , Zheng SL , Xu J , Isaacs WB , Chang BL
Ref : International Journal of Cancer , 124 :734 , 2009
Abstract : Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p=0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.
ESTHER : Kim_2009_Int.J.Cancer_124_734
PubMedSearch : Kim_2009_Int.J.Cancer_124_734
PubMedID: 19004026

Title : The genome sequence of taurine cattle: a window to ruminant biology and evolution - Elsik_2009_Science_324_522
Author(s) : Elsik CG , Tellam RL , Worley KC , Gibbs RA , Muzny DM , Weinstock GM , Adelson DL , Eichler EE , Elnitski L , Guigo R , Hamernik DL , Kappes SM , Lewin HA , Lynn DJ , Nicholas FW , Reymond A , Rijnkels M , Skow LC , Zdobnov EM , Schook L , Womack J , Alioto T , Antonarakis SE , Astashyn A , Chapple CE , Chen HC , Chrast J , Camara F , Ermolaeva O , Henrichsen CN , Hlavina W , Kapustin Y , Kiryutin B , Kitts P , Kokocinski F , Landrum M , Maglott D , Pruitt K , Sapojnikov V , Searle SM , Solovyev V , Souvorov A , Ucla C , Wyss C , Anzola JM , Gerlach D , Elhaik E , Graur D , Reese JT , Edgar RC , McEwan JC , Payne GM , Raison JM , Junier T , Kriventseva EV , Eyras E , Plass M , Donthu R , Larkin DM , Reecy J , Yang MQ , Chen L , Cheng Z , Chitko-McKown CG , Liu GE , Matukumalli LK , Song J , Zhu B , Bradley DG , Brinkman FS , Lau LP , Whiteside MD , Walker A , Wheeler TT , Casey T , German JB , Lemay DG , Maqbool NJ , Molenaar AJ , Seo S , Stothard P , Baldwin CL , Baxter R , Brinkmeyer-Langford CL , Brown WC , Childers CP , Connelley T , Ellis SA , Fritz K , Glass EJ , Herzig CT , Iivanainen A , Lahmers KK , Bennett AK , Dickens CM , Gilbert JG , Hagen DE , Salih H , Aerts J , Caetano AR , Dalrymple B , Garcia JF , Gill CA , Hiendleder SG , Memili E , Spurlock D , Williams JL , Alexander L , Brownstein MJ , Guan L , Holt RA , Jones SJ , Marra MA , Moore R , Moore SS , Roberts A , Taniguchi M , Waterman RC , Chacko J , Chandrabose MM , Cree A , Dao MD , Dinh HH , Gabisi RA , Hines S , Hume J , Jhangiani SN , Joshi V , Kovar CL , Lewis LR , Liu YS , Lopez J , Morgan MB , Nguyen NB , Okwuonu GO , Ruiz SJ , Santibanez J , Wright RA , Buhay C , Ding Y , Dugan-Rocha S , Herdandez J , Holder M , Sabo A , Egan A , Goodell J , Wilczek-Boney K , Fowler GR , Hitchens ME , Lozado RJ , Moen C , Steffen D , Warren JT , Zhang J , Chiu R , Schein JE , Durbin KJ , Havlak P , Jiang H , Liu Y , Qin X , Ren Y , Shen Y , Song H , Bell SN , Davis C , Johnson AJ , Lee S , Nazareth LV , Patel BM , Pu LL , Vattathil S , Williams RL, Jr. , Curry S , Hamilton C , Sodergren E , Wheeler DA , Barris W , Bennett GL , Eggen A , Green RD , Harhay GP , Hobbs M , Jann O , Keele JW , Kent MP , Lien S , McKay SD , McWilliam S , Ratnakumar A , Schnabel RD , Smith T , Snelling WM , Sonstegard TS , Stone RT , Sugimoto Y , Takasuga A , Taylor JF , Van Tassell CP , Macneil MD , Abatepaulo AR , Abbey CA , Ahola V , Almeida IG , Amadio AF , Anatriello E , Bahadue SM , Biase FH , Boldt CR , Carroll JA , Carvalho WA , Cervelatti EP , Chacko E , Chapin JE , Cheng Y , Choi J , Colley AJ , de Campos TA , De Donato M , Santos IK , de Oliveira CJ , Deobald H , Devinoy E , Donohue KE , Dovc P , Eberlein A , Fitzsimmons CJ , Franzin AM , Garcia GR , Genini S , Gladney CJ , Grant JR , Greaser ML , Green JA , Hadsell DL , Hakimov HA , Halgren R , Harrow JL , Hart EA , Hastings N , Hernandez M , Hu ZL , Ingham A , Iso-Touru T , Jamis C , Jensen K , Kapetis D , Kerr T , Khalil SS , Khatib H , Kolbehdari D , Kumar CG , Kumar D , Leach R , Lee JC , Li C , Logan KM , Malinverni R , Marques E , Martin WF , Martins NF , Maruyama SR , Mazza R , McLean KL , Medrano JF , Moreno BT , More DD , Muntean CT , Nandakumar HP , Nogueira MF , Olsaker I , Pant SD , Panzitta F , Pastor RC , Poli MA , Poslusny N , Rachagani S , Ranganathan S , Razpet A , Riggs PK , Rincon G , Rodriguez-Osorio N , Rodriguez-Zas SL , Romero NE , Rosenwald A , Sando L , Schmutz SM , Shen L , Sherman L , Southey BR , Lutzow YS , Sweedler JV , Tammen I , Telugu BP , Urbanski JM , Utsunomiya YT , Verschoor CP , Waardenberg AJ , Wang Z , Ward R , Weikard R , Welsh TH, Jr. , White SN , Wilming LG , Wunderlich KR , Yang J , Zhao FQ
Ref : Science , 324 :522 , 2009
Abstract : To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
ESTHER : Elsik_2009_Science_324_522
PubMedSearch : Elsik_2009_Science_324_522
PubMedID: 19390049
Gene_locus related to this paper: bovin-2neur , bovin-a0jnh8 , bovin-a5d7b7 , bovin-ACHE , bovin-balip , bovin-dpp4 , bovin-dpp6 , bovin-e1bi31 , bovin-e1bn79 , bovin-est8 , bovin-f1mbd6 , bovin-f1mi11 , bovin-f1mr65 , bovin-f1n1l4 , bovin-g3mxp5 , bovin-q0vcc8 , bovin-q2kj30 , bovin-q3t0r6 , bovin-thyro

Title : Cold acclimation induces physiological cardiac hypertrophy and increases assimilation of triacylglycerol metabolism through lipoprotein lipase - Cheng_2008_Biochim.Biophys.Acta_1781_618
Author(s) : Cheng Y , Hauton D
Ref : Biochimica & Biophysica Acta , 1781 :618 , 2008
Abstract : The contribution of triacylglycerol to energy provision in the hypertrophied heart, mediated through lipoprotein lipase (LPL) is largely unknown and the contribution of very-low-density lipoprotein (VLDL) receptor to control of LPL presentation at the endothelium is unclear. For isolated perfused rat hearts, cold acclimation (CA) induced volume-overload hypertrophy, with decreased developed pressure (P<0.01), increased end-diastolic volume of the left ventricle (P<0.001) and a loss of contractile reserve in response to dobutamine challenge (P<0.01). Oleate utilisation by perfused hearts was unchanged by CA, however uptake of intralipid emulsion increased 3-fold (P<0.01). CA increased the proportion of lipid deposited in tissue lipids from 10% in euthermic controls to 40% (P<0.01) although the overall contribution of individual lipid classes was unaffected. Cold acclimation significantly increased heparin-releasable LPL (P<0.05) and tissue residual LPL (P<0.01). Western blot analysis indicated preserved expression of proteins coding for SERCA2, muscle-CPT1 and VLDL-receptor following CA, while AMPKalpha2 and phospho-AMPKalpha2 were unaffected. These observations indicate that for physiological hypertrophy AMPK phosphorylation does not mediate the enhanced translocation of LPL to cardiac endothelium.
ESTHER : Cheng_2008_Biochim.Biophys.Acta_1781_618
PubMedSearch : Cheng_2008_Biochim.Biophys.Acta_1781_618
PubMedID: 18722549

Title : Genome biology of Actinobacillus pleuropneumoniae JL03, an isolate of serotype 3 prevalent in China - Xu_2008_PLoS.One_3_e1450
Author(s) : Xu Z , Zhou Y , Li L , Zhou R , Xiao S , Wan Y , Zhang S , Wang K , Li W , Jin H , Kang M , Dalai B , Li T , Liu L , Cheng Y , Zhang L , Xu T , Zheng H , Pu S , Wang B , Gu W , Zhang XL , Zhu GF , Wang S , Zhao GP , Chen H
Ref : PLoS ONE , 3 :e1450 , 2008
Abstract : Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae.
ESTHER : Xu_2008_PLoS.One_3_e1450
PubMedSearch : Xu_2008_PLoS.One_3_e1450
PubMedID: 18197260
Gene_locus related to this paper: actp2-a3n347 , actp7-b3h2v1 , actp7-b3h2x2 , actpj-b0bpm3 , actpj-b0bqd8 , actpj-b0brq2

Title : Acetylcholinesterase: mechanisms of covalent inhibition of wild-type and H447I mutant determined by computational analyses - Cheng_2007_J.Am.Chem.Soc_129_6562
Author(s) : Cheng Y , Cheng X , Radic Z , McCammon JA
Ref : Journal of the American Chemical Society , 129 :6562 , 2007
Abstract : The reaction mechanisms of two inhibitors TFK+ and TFK0 binding to both the wild-type and H447I mutant mouse acetylcholinesterase (mAChE) have been investigated by using a combined ab initio quantum mechanical/molecular mechanical (QM/MM) approach and classical molecular dynamics (MD) simulations. In the wild-type mAChE, the binding reactions of TFK+ and TFK0 are both spontaneous processes, which proceed through the nucleophilic addition of the Ser203-Ogamma to the carbonyl-C of TFK+ or TFK0, accompanied with a simultaneous proton transfer from Ser203 to His447. No barrier is found along the reaction paths, consistent with the experimental reaction rates approaching the diffusion-controlled limit. By contrast, TFK+ binding to the H447I mutant may proceed with a different reaction mechanism. A water molecule takes over the role of His447 and participates in the bond breaking and forming as a "charge relayer". Unlike in the wild-type mAChE case, Glu334, a conserved residue from the catalytic triad, acts as a catalytic base in the reaction. The calculated energy barrier for this reaction is about 8 kcal/mol. These predictions await experimental verification. In the case of the neutral ligand TFK0, however, multiple MD simulations on the TFK0/H447I complex reveal that none of the water molecules can be retained in the active site as a "catalytic" water. Furthermore, our alchemical free energy calculation also suggests that the binding of TFK0 to H447I is much weaker than that of TFK+. Taken together, our computational studies confirm that TFK0 is almost inactive in the H447I mutant and also provide detailed mechanistic insights into the experimental observations.
ESTHER : Cheng_2007_J.Am.Chem.Soc_129_6562
PubMedSearch : Cheng_2007_J.Am.Chem.Soc_129_6562
PubMedID: 17461584

Title : Finite element analysis of the time-dependent Smoluchowski equation for acetylcholinesterase reaction rate calculations - Cheng_2007_Biophys.J_92_3397
Author(s) : Cheng Y , Suen JK , Zhang D , Bond SD , Zhang Y , Song Y , Baker NA , Bajaj CL , Holst MJ , McCammon JA
Ref : Biophysical Journal , 92 :3397 , 2007
Abstract : This article describes the numerical solution of the time-dependent Smoluchowski equation to study diffusion in biomolecular systems. Specifically, finite element methods have been developed to calculate ligand binding rate constants for large biomolecules. The resulting software has been validated and applied to the mouse acetylcholinesterase (mAChE) monomer and several tetramers. Rates for inhibitor binding to mAChE were calculated at various ionic strengths with several different time steps. Calculated rates show very good agreement with experimental and theoretical steady-state studies. Furthermore, these finite element methods require significantly fewer computational resources than existing particle-based Brownian dynamics methods and are robust for complicated geometries. The key finding of biological importance is that the rate accelerations of the monomeric and tetrameric mAChE that result from electrostatic steering are preserved under the non-steady-state conditions that are expected to occur in physiological circumstances.
ESTHER : Cheng_2007_Biophys.J_92_3397
PubMedSearch : Cheng_2007_Biophys.J_92_3397
PubMedID: 17307827

Title : In-situ synthesis of a tacrine-triazole-based inhibitor of acetylcholinesterase: configurational selection imposed by steric interactions - Senapati_2006_J.Med.Chem_49_6222
Author(s) : Senapati S , Cheng Y , McCammon JA
Ref : Journal of Medicinal Chemistry , 49 :6222 , 2006
Abstract : Recently, researchers have used acetylcholinesterase (AChE) as a reaction vessel to synthesize its own inhibitors. Thus, 1 (syn-TZ2PA6), a femtomolar AChE inhibitor, which is formed in a 1:1 mixture with its anti-isomer by solution phase reaction from 3 (TZ2) and 4 (PA6), can be synthesized exclusively inside the AChE gorge. Our computational approach based on quantum mechanical/molecular mechanical (QM/MM) calculations, molecular dynamics (MD), and targeted molecular dynamics (TMD) studies answers why 1 is the sole product in the AChE environment. Ab initio QM/MM results show that the reaction in the AChE gorge occurs when 3/azide and 4/acetylene are extended in a parallel orientation. An MD simulation started from the final structure of QM/MM calculations keeps the azide's and acetylene's parallel orientations intact for 10 ns of simulation time. A TMD simulation applied on an antiparallel azide-acetylene conformation flips the acetylene easily to bring it to a position that is parallel to azide. A second set of QM/MM calculations performed on this flipped structure generates a similar minimum-energy path as obtained previously. Even a TMD simulation carried out on a parallel azide-acetylene conformation could not deform their parallel arrangement. All of these results, thus, imply that inside the AChE gorge, the azide group of 3 and the acetylene group of 4 always remain parallel, with the consequence that 1 is the only product. The architecture of the gorge plays an important role in this selective formation of 1.
ESTHER : Senapati_2006_J.Med.Chem_49_6222
PubMedSearch : Senapati_2006_J.Med.Chem_49_6222
PubMedID: 17034128

Title : Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats - Feng_2004_J.Pineal.Res_37_198
Author(s) : Feng Z , Cheng Y , Zhang JT
Ref : J Pineal Res , 37 :198 , 2004
Abstract : Melatonin is an endogenously generated potent antioxidant. Our previous studies indicate that melatonin improved learning and memory deficits in APP695 transgenic mouse of Alzheimer's disease. An ovariectomized (OVX) rat model which is characterized by progressive memory deficits, central cholinergic nerve system degeneration and differentiation/apoptosis imbalance is the ideal in vivo model in which to test the neuroprotective effects of melatonin. OVX Sprague-Dawley rats received daily injections of melatonin (5, 10 and 20 mg/kg) or 17 beta-estradiol (E2, 80 microg/kg) or sesame oil for 16 wk. Morris water maze results showed that ovarian steroid deprivation resulted in spatial memory impairment, while melatonin and E2 significantly ameliorated spatial memory deficits in OVX rats. The latency to find the hidden platform and the distance to reach the platform become shorter in both melatonin and E2-treated rats compared with those that were only OVX. Four months after OVX, the choline acetyltransferase activity in the frontal cortex and hippocampus were greatly decreased in comparison with the controls. Melatonin and E2 antagonized the effects induced by OVX. Interestingly, the activity of the acetylcholinesterase was not altered in any group of rats. DNA fragmentation was presented in the front cortex of the OVX rats. Melatonin and E2 reduced the number of apoptotic neurons. These findings demonstrate the important effects of melatonin and E2 on cholinergic neurons and support the potential application of melatonin in the treatment of dementia in postmenopausal women. Our results indicate that neuroprotection by melatonin partly correlated to modulation of apoptosis and protection of the cholinergic system. Early long-term melatonin application is a promising strategy which could potentially be applied in a clinic setting.
ESTHER : Feng_2004_J.Pineal.Res_37_198
PubMedSearch : Feng_2004_J.Pineal.Res_37_198
PubMedID: 15357665