He W

References (25)

Title : Elucidating the toxicity mechanisms of organophosphate esters by adverse outcome pathway network - He_2024_Arch.Toxicol_98_233
Author(s) : He W , Ding J , Gao N , Zhu L , Feng J
Ref : Archives of Toxicology , 98 :233 , 2024
Abstract : With the widespread use of organophosphate esters (OPEs), the accumulation and toxicity effect of OPEs in biota are attracting more and more concern. In order to clarify the mechanism of toxicity of OPEs to organisms, this study reviewed the OPEs toxicity and systematically identified the mechanism of OPEs toxicity under the framework of adverse outcome pathway (AOP). OPEs were divided into three groups (alkyl-OPEs, aryl-OPEs, and halogenated-OPEs) and biota was divided into aquatic organism and mammals. The results showed that tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) mainly caused neurotoxicity, reproductive, and hepatotoxicity in different mechanisms. According to the constructed AOP network, the toxicity mechanism of OPEs on aquatic organisms and mammals is different, which is mainly attributed to the different biological metabolic systems of aquatic organisms and mammals. Interestingly, our results indicate that the toxicity effect of the three kinds of OPEs on aquatic organisms is different, while there was no obvious difference in the mechanism of toxicity of OPEs on mammals. This study provides a theoretical basis for OPEs risk assessment in the future.
ESTHER : He_2024_Arch.Toxicol_98_233
PubMedSearch : He_2024_Arch.Toxicol_98_233
PubMedID: 37864630

Title : Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING - Fan_2024_Int.Immunopharmacol_131_111904
Author(s) : Fan C , Du J , Yu Z , Wang J , Yao L , Ji Z , He W , Deng Y , Geng D , Wu X , Mao H
Ref : Int Immunopharmacol , 131 :111904 , 2024
Abstract : Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4alpha. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-beta-gal-positive cells and hindered the manifestation of p16INK4alpha and the inflammatory factor IL-1beta in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.
ESTHER : Fan_2024_Int.Immunopharmacol_131_111904
PubMedSearch : Fan_2024_Int.Immunopharmacol_131_111904
PubMedID: 38518595

Title : Ultra-small magnetic Candida antarctica lipase B nanoreactors for enzyme synthesis of bixin-maltitol ester - Lv_2023_Food.Chem_421_136132
Author(s) : Lv D , Wang M , He W , Wu J , Liu X , Guan Y
Ref : Food Chem , 421 :136132 , 2023
Abstract : Bixin has desirable bioactivities but poor water solubility, which limits its practical applications. Enzymatic transesterification of methyl to alditol groups in bixin by Candida antarctica lipase B (CALB) improves bixin water solubility. Herein, magnetic CALB nanoreactors with diameter of 11.7 nm and CALB layer thickness of 3.5 nm were developed by covalently linking CALB onto silicon covered Fe(3)O(4) nanoparticles. The CALB loading capacity in nanoreactors achieved 30%. The Michaelis constant (Km) and maximum reaction rate of magnetic CALB nanoreactors were 56.1 mmol/L and 0.2 mmol/(L.min). Magnetic CALB nanoreactors could circularly catalyze bixin-maltitol ester synthesis and keep catalytic efficiency of 62.6% after eight repetitive enzymatic reactions. Additionally, the optimal bixin-maltitol ester synthesis procedure was heating bixin-maltitol mixture at molar ratio of 1:7 in anhydrous 2-methyl-2-butanol-dimethylsulfoxide (8:2, v/v) at 50 degreesC for 24 h. Bixin-maltitol ester showed improved water solubility at pH 5.5 and 7.0.
ESTHER : Lv_2023_Food.Chem_421_136132
PubMedSearch : Lv_2023_Food.Chem_421_136132
PubMedID: 37094396

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

Title : Glimepiride Use is Associated with Reduced Cardiovascular Mortality in Patients with Type 2 Diabetes and Chronic Heart Failure: A Prospective Cohort Study - He_2022_Eur.J.Prev.Cardiol__
Author(s) : He W , Yuan G , Han Y , Yan Y , Li G , Zhao C , Shen J , Jiang X , Chen C , Ni L , Wang DW
Ref : Eur J Prev Cardiol , : , 2022
Abstract : BACKGROUND: Glimepiride has good cardiovascular safety. However, whether glimepiride benefits clinical cardiovascular outcomes is unclear. METHODS: A total of 21,451 inpatients with type 2 diabetes (T2D) and chronic heart failure (CHF) were analyzed, including 638 who received glimepiride treatment and 20,813 who did not. Propensity score matching yielded 509 pairs (glimepiride and non-glimepiride groups), and both groups were followed up. Kaplan-Meier and Cox regression analyses were used to compare all-cause mortality, cardiovascular mortality, hospitalizations and emergency visits for heart failure, and hospitalizations for acute myocardial infarction or stroke. RESULTS: During follow-up, the all-cause mortality (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.35-0.63; P < 0.001), cardiovascular mortality (adjusted HR, 0.34; 95% CI, 0.24-0.48; P < 0.001), and number of hospitalizations and emergency visits for heart failure (adjusted HR, 0.42; 95% CI, 0.36-0.50; P < 0.001) and hospitalizations for acute myocardial infarction or stroke (adjusted HR, 0.53; 95% CI, 0.38-0.73; P < 0.001) were significantly lower in the glimepiride group; the conclusion remained similar in all subgroups. Furthermore, high-dose glimepiride use (2-4mg/day) was associated with lower cardiovascular mortality than low-dose (1mg/day) (adjusted HR, 0.55; 95% CI, 0.31-0.99; P = 0.047). Glimepiride exhibited good molecular docking with soluble epoxide hydrolase (sEH) and increased the level epoxyeicosatrienoic acid (EET). CONCLUSIONS: Long-term continuous glimepiride use is associated with better survival, fewer hospitalizations and emergency visits for heart failure, and fewer hospitalizations for acute myocardial infarction or stroke in patients with T2D and CHF. High-dose glimepiride has greater cardiovascular protective advantages than low-dose glimepiride. The cardiovascular protective effect of glimepiride may be related to the EET level increase through sEH inhibition.
ESTHER : He_2022_Eur.J.Prev.Cardiol__
PubMedSearch : He_2022_Eur.J.Prev.Cardiol__
PubMedID: 36573717

Title : IL-6 downregulates hepatic carboxylesterases via NF-kappaB activation in dextran sulfate sodium-induced colitis - Li_2021_Int.Immunopharmacol_99_107920
Author(s) : Li M , Lan L , Zhang S , Xu Y , He W , Xiang D , Liu D , Ren X , Zhang C
Ref : Int Immunopharmacol , 99 :107920 , 2021
Abstract : Ulcerative colitis (UC) is associated with increased levels of inflammatory factors, which is attributed to the abnormal expression and activity of enzymes and transporters in the liver, affecting drug disposition in vivo. This study aimed to examine the impact of intestinal inflammation on the expression of hepatic carboxylesterases (CESs) in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Two major CESs isoforms, CES1 and CES2, were down-regulated, accompanied by decreases in hepatic microsomal metabolism of clopidogrel and irinotecan. Meanwhile, IL-6 levels significantly increased compared with other inflammatory factors in the livers of UC mice. In contrast, using IL-6 antibody simultaneously reversed the down-regulation of CES1, CES2, pregnane X receptor (PXR), and constitutive androstane receptor (CAR), as well as the nuclear translocation of NF-kappaB in the liver. We further confirmed that treatment with NF-kappaB inhibitor abolished IL-6-induced down-regulation of CES1, CES2, PXR, and CAR in vitro. Thus, it was concluded that IL-6 represses hepatic CESs via the NF-kappaB pathway in DSS-induced colitis. These findings indicate that caution should be exercised concerning the proper and safe use of therapeutic drugs in patients with UC.
ESTHER : Li_2021_Int.Immunopharmacol_99_107920
PubMedSearch : Li_2021_Int.Immunopharmacol_99_107920
PubMedID: 34217990

Title : Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression - He_2021_Cell.Death.Dis_12_992
Author(s) : He W , Huang J , Liu Y , Xie C , Zhang K , Zhu X , Chen J , Huang H
Ref : Cell Death Dis , 12 :992 , 2021
Abstract : Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.
ESTHER : He_2021_Cell.Death.Dis_12_992
PubMedSearch : He_2021_Cell.Death.Dis_12_992
PubMedID: 34689162

Title : Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats - Wang_2021_Front.Psychiatry_12_638328
Author(s) : Wang Q , Dong L , Wang M , Chen S , Li S , Chen Y , He W , Zhang H , Zhang Y , Pires Dias AC , Yang S , Liu X
Ref : Front Psychiatry , 12 :638328 , 2021
Abstract : Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.
ESTHER : Wang_2021_Front.Psychiatry_12_638328
PubMedSearch : Wang_2021_Front.Psychiatry_12_638328
PubMedID: 33841208

Title : Ultra-highly sensitive organophosphorus biosensor based on chitosan\/tin disulfide and British housefly acetylcholinesterase - Liu_2020_Food.Chem_324_126889
Author(s) : Liu X , Sakthivel R , Liu WC , Huang CW , Li J , Xu C , Wu Y , Song L , He W , Chung RJ
Ref : Food Chem , 324 :126889 , 2020
Abstract : Pesticides have been extensively applied worldwide to protect crops from worms and insects; however, the continuous use of pesticides affects ecosystems, agricultural product safety, nontarget organisms, and human health. In this paper, we report a highly sensitive biosensor for the determination of pesticides based on tin sulfide (SnS2) and chitosan (CHIT) nanocomposites decorated with a unique British housefly acetylcholinesterase (AChE). The hydrothermally synthesized nano-SnS2 mixed with chitosan solution (CHIT-SnS2) was drop-casted onto a glassy carbon electrode (GCE). Subsequently, the British housefly AChE was immobilized on the CHIT/SnS2-coated GCE that was then employed for pesticide detection. The developed biosensor showed an ultra-high sensitivity and wide linear detection range from 0.02 nM to 20000 nM with a detection limit of 0.02 nM for the detection of chlorpyrifos as the model pesticide. Furthermore, the AChE/CHIT-SnS2/GCE exhibited acceptable storage stability, good reproducibility, and selectivity.
ESTHER : Liu_2020_Food.Chem_324_126889
PubMedSearch : Liu_2020_Food.Chem_324_126889
PubMedID: 32353659

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

Title : Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2\/CES1 Signaling Pathway - He_2019_Dig.Dis.Sci_64_3182
Author(s) : He W , Xu Y , Ren X , Xiang D , Lei K , Zhang C , Liu D
Ref : Digestive Diseases & Sciences , 64 :3182 , 2019
Abstract : BACKGROUND: Vitamin E has been reported to have a beneficial effect on nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism of action has not yet been clearly defined. AIM: We aimed to evaluate the effects and mechanisms of vitamin E on lipid and glucose homeostasis both in vivo and in vitro. METHODS: An NAFLD model was established in C57BL/6 mice fed a 30% fructose solution for 8 weeks. Subsequently, NAFLD mice were given vitamin E (70 mg/kg) for 2 weeks. In addition, L02 cells were treated with 5 mM fructose and 100 nM vitamin E to explore the potential mechanisms of action. RESULTS: Vitamin E reversed the impaired glucose tolerance of fructose-treated mice. Histopathological examination showed that liver steatosis was significantly relieved in vitamin E-treated mice. These effects may be attributed to the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2), carboxylesterase 1 (CES1), and downregulated proteins involved in lipid synthesis by vitamin E treatment. In vivo, vitamin E also significantly reduced lipid accumulation in fructose-treated L02 cells, and the Nrf2 inhibitor ML385 reversed the protective effects of vitamin E. CONCLUSION: These data indicated that the therapeutic effects of vitamin E on lipid and glucose homeostasis may be associated with activation of the Nrf2/CES1 signaling pathway.
ESTHER : He_2019_Dig.Dis.Sci_64_3182
PubMedSearch : He_2019_Dig.Dis.Sci_64_3182
PubMedID: 31076985

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

Title : Physiological vs. pharmacological signalling to myosin phosphorylation in airway smooth muscle - Gao_2017_J.Physiol_595_6231
Author(s) : Gao N , Tsai MH , Chang AN , He W , Chen CP , Zhu M , Kamm KE , Stull JT
Ref : Journal de Physiologie , 595 :6231 , 2017
Abstract : KEY POINTS: Smooth muscle myosin regulatory light chain (RLC) is phosphorylated by Ca(2+) /calmodulin-dependent myosin light chain kinase and dephosphorylated by myosin light chain phosphatase (MLCP). Tracheal smooth muscle contains significant amounts of myosin binding subunit 85 (MBS85), another myosin phosphatase targeting subunit (MYPT) family member, in addition to MLCP regulatory subunit MYPT1. Concentration/temporal responses to carbachol demonstrated similar sensitivities for bovine tracheal force development and phosphorylation of RLC, MYPT1, MBS85 and paxillin. Electrical field stimulation releases ACh from nerves to increase RLC phosphorylation but not MYPT1 or MBS85 phosphorylation. Thus, nerve-mediated muscarinic responses in signalling modules acting on RLC phosphorylation are different from pharmacological responses with bath added agonist. The conditional knockout of MYPT1 or the knock-in mutation T853A in mice had no effect on muscarinic force responses in isolated tracheal tissues. MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction. ABSTRACT: Ca(2+) /calmodulin activation of myosin light chain kinase (MLCK) initiates myosin regulatory light chain (RLC) phosphorylation for smooth muscle contraction with subsequent dephosphorylation for relaxation by myosin light chain phosphatase (MLCP) containing regulatory (MYPT1) and catalytic (PP1cdelta) subunits. RLC phosphorylation-dependent force development is regulated by distinct signalling modules involving protein phosphorylations. We investigated responses to cholinergic agonist treatment vs. neurostimulation by electric field stimulation (EFS) in bovine tracheal smooth muscle. Concentration/temporal responses to carbachol demonstrated tight coupling between force development and RLC phosphorylation but sensitivity differences in MLCK, MYPT1 T853, MYPT1 T696, myosin binding subunit 85 (MBS85), paxillin and CPI-17 (PKC-potentiated protein phosphatase 1 inhibitor protein of 17 kDa) phosphorylations. EFS increased force and phosphorylation of RLC, CPI-17 and MLCK. In the presence of the cholinesterase inhibitor neostigmine, EFS led to an additional increase in phosphorylation of MYPT1 T853, MYPT1 T696, MBS85 and paxillin. Thus, there were distinct pharmacological vs. physiological responses in signalling modules acting on RLC phosphorylation and force responses, probably related to degenerate G protein signalling networks. Studies with genetically modified mice were performed. Expression of another MYPT1 family member, MBS85, was enriched in mouse, as well as bovine tracheal smooth muscle. Carbachol concentration/temporal-force responses were similar in trachea from MYPT1(SM+/+) , MYPT1(SM-/-) and the knock-in mutant mice containing nonphosphorylatable MYPT1 T853A with no differences in RLC phosphorylation. Thus, MYPT1 T853 phosphorylation was not necessary for regulation of RLC phosphorylation in tonic airway smooth muscle. Furthermore, MLCP activity may arise from functionally shared roles between MYPT1 and MBS85, resulting in minimal effects of MYPT1 knockout on contraction.
ESTHER : Gao_2017_J.Physiol_595_6231
PubMedSearch : Gao_2017_J.Physiol_595_6231
PubMedID: 28749013

Title : Novel ferulic amide derivatives with tertiary amine side chain as acetylcholinesterase and butyrylcholinesterase inhibitors: The influence of carbon spacer length, alkylamine and aromatic group - Liu_2016_Eur.J.Med.Chem_126_810
Author(s) : Liu H , Liu L , Gao X , Liu Y , Xu W , He W , Jiang H , Tang J , Fan H , Xia X
Ref : Eur Journal of Medicinal Chemistry , 126 :810 , 2016
Abstract : Based on our recent investigations on chalcone derivatives as AChE inhibitors, a series of ferulic acid (FA) tertiary amine derivatives similar to chalcone compounds were designed and synthesized. The results of bioactivity evaluation revealed that most of new synthesized compounds had comparable or more potent AChE inhibitory activity than the control drug Rivastigmine. The alteration of carbon chain linking tertiary amine groups and ferulic acid scaffold markedly influenced the inhibition activity against AChE. Among them the inhibitory activity of compound 6d (IC50: 0.71 +/- 0.09 mumol/L) and 6e (IC50: 1.11 +/- 0.17 mumol/L) was equal to 15-fold and 9-fold than that of Rivastigmine against AChE (IC50: 10.54 +/- 0.86 mumol/L), respectively. Moreover, compound 6d shows the highest selectivity for AChE over butyrylcholinesterase(BuChE) (ratio: 18.3). The kinetic study suggested that compound 6d revealed a mixed-type inhibition against AChE. The result of molecular docking showed that compound 6d combines to AChE with three amino acid sites(Trp84, Tyr334 and Trp279), while combines to BuChE with two amino acid sites (Tyr67 and Gly66) in enzyme domains, respectively. Compound 6d might act as a potential agent for the treatment of Alzheimer's diseases (AD).
ESTHER : Liu_2016_Eur.J.Med.Chem_126_810
PubMedSearch : Liu_2016_Eur.J.Med.Chem_126_810
PubMedID: 27951489

Title : DWARF14 is a non-canonical hormone receptor for strigolactone - Yao_2016_Nature_536_469
Author(s) : Yao R , Ming Z , Yan L , Li S , Wang F , Ma S , Yu C , Yang M , Chen L , Li Y , Yan C , Miao D , Sun Z , Yan J , Sun Y , Wang L , Chu J , Fan S , He W , Deng H , Nan F , Li J , Rao Z , Lou Z , Xie D
Ref : Nature , 536 :469 , 2016
Abstract : Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
ESTHER : Yao_2016_Nature_536_469
PubMedSearch : Yao_2016_Nature_536_469
PubMedID: 27479325
Gene_locus related to this paper: arath-AtD14

Title : Regulations of Xenobiotics and Endobiotics on Carboxylesterases: A Comprehensive Review - Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
Author(s) : Xu Y , Zhang C , He W , Liu D
Ref : Eur J Drug Metab Pharmacokinet , 41 :321 , 2016
Abstract : Carboxylesterases (CESs) play major roles in catalyzing the hydrolysis of a wide range of ester- and amide-containing compounds. CESs dominate both the biotransformation of numerous therapeutic drugs and the detoxification of environmental toxicants, and the activity alteration of CESs may be a determinant reason for modification of the resultant pharmacokinetic/pharmacodynamic profile when two or more drugs are concurrently used. Herein, we provide a comprehensive review of the current literature involving of induction and inhibition on CESs by both exogenous and endogenous compounds. In particular, the inhibition constant and inhibition pattern of inhibitors on CESs in studies using animal microsomes or human recombinant CESs are summarized. Further studies are needed to clarify the underlying regulation mechanism, and alterations in CESs activity should be taken into consideration for safe clinical therapy.
ESTHER : Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
PubMedSearch : Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
PubMedID: 26914100

Title : Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase - Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
Author(s) : Tarver JE, Jr. , Pabba PK , Barbosa J , Han Q , Gardyan MW , Brommage R , Thompson AY , Schmidt JM , Wilson AG , He W , Lombardo VK , Carson KG , Wilson AGE
Ref : Bioorganic & Medicinal Chemistry Lett , 26 :1525 , 2016
Abstract : A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3-d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4-yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified.
ESTHER : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
PubMedSearch : Tarver_2016_Bioorg.Med.Chem.Lett_26_1525
PubMedID: 26897593
Gene_locus related to this paper: human-NOTUM

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : Try113His and His139Arg polymorphisms in the microsomal epoxide hydrolase gene are not associated with risk of breast cancer - Gong_2014_Tumour.Biol_35_8087
Author(s) : Gong WF , He W , Zhang QM , Xiang BD , Ma L , Huang S , Bai T , Zhong JH , Li LQ
Ref : Tumour Biol , 35 :8087 , 2014
Abstract : Breast cancer may be caused by several factors, including polymorphisms in the microsomal epoxide hydrolase (mEH) gene. Previous work suggested an association between mEH polymorphism and risk of breast cancer, but the results have been inconsistent. PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure database were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphisms and susceptibility to breast cancer. Odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to assess the strength of the association. Seven studies involving 6,357 cases and 8,089 controls were included in this study. The Tyr113His mEH polymorphism did not affect breast cancer risk in the allelic contrast model (OR = 0.99, 95 % CI = 0.94-1.04, P = 0.58), the dominant genetic model (OR = 1.14, 95 % CI = 0.88-1.48, P = 0.33), or the recessive genetic model (OR = 1.03, 95 % CI = 0.96-1.10, P = 0.43). Similarly, the His139Arg mEH polymorphism was not associated with breast cancer risk in the allelic contrast model (OR = 0.97, 95 % CI = 0.91-1.04, P = 0.44), the dominant genetic model (OR = 1.01, 95 % CI = 0.84-1.21, P = 0.94), or the recessive genetic model (OR = 1.04, 95 % CI = 0.96-1.12, P = 0.35). The mEH polymorphisms Tyr113His and His139Arg are not risk factors for breast cancer. Further, large and well-designed studies are required to confirm this conclusion.
ESTHER : Gong_2014_Tumour.Biol_35_8087
PubMedSearch : Gong_2014_Tumour.Biol_35_8087
PubMedID: 24840637

Title : Population genomics reveal recent speciation and rapid evolutionary adaptation in polar bears - Liu_2014_Cell_157_785
Author(s) : Liu S , Lorenzen ED , Fumagalli M , Li B , Harris K , Xiong Z , Zhou L , Korneliussen TS , Somel M , Babbitt C , Wray G , Li J , He W , Wang Z , Fu W , Xiang X , Morgan CC , Doherty A , O'Connell MJ , McInerney JO , Born EW , Dalen L , Dietz R , Orlando L , Sonne C , Zhang G , Nielsen R , Willerslev E , Wang J
Ref : Cell , 157 :785 , 2014
Abstract : Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
ESTHER : Liu_2014_Cell_157_785
PubMedSearch : Liu_2014_Cell_157_785
PubMedID: 24813606
Gene_locus related to this paper: ursma-a0a384cw87 , ursma-a0a384cqm7 , ursma-a0a452vbh6 , ursma-a0a384cyu0

Title : Molecular cloning of a novel bioH gene from an environmental metagenome encoding a carboxylesterase with exceptional tolerance to organic solvents - Shi_2013_BMC.Biotechnol_13_13
Author(s) : Shi Y , Pan Y , Li B , He W , She Q , Chen L
Ref : BMC Biotechnol , 13 :13 , 2013
Abstract : ABSTRACT: BACKGROUND: BioH is one of the key enzymes to produce the precursor pimeloyl-ACP to initiate biotin biosynthesis de novo in bacteria. To date, very few bioH genes have been characterized. In this study, we cloned and identified a novel bioH gene, bioHx, from an environmental metagenome by a functional metagenomic approach. The bioHx gene, encoding an enzyme that is capable of hydrolysis of p-nitrophenyl esters of fatty acids, was expressed in Escherichia coli BL21 using the pET expression system. The biochemical property of the purified BioHx protein was also investigated.
RESULTS: Screening of an unamplified metagenomic library with a tributyrin-containing medium led to the isolation of a clone exhibiting lipolytic activity. This clone carried a 4,570-bp DNA fragment encoding for six genes, designated bioF, bioHx, fabG, bioC, orf5 and sdh, four of which were implicated in the de novo biotin biosynthesis. The bioHx gene encodes a protein of 259 aa with a calculated molecular mass of 28.60 kDa, displaying 24-39% amino acid sequence identity to a few characterized bacterial BioH enzymes. It contains a pentapeptide motif (Gly76-Trp77-Ser78-Met79-Gly80) and a catalytic triad (Ser78-His230-Asp202), both of which are characteristic for lipolytic enzymes. BioHx was expressed as a recombinant protein and characterized. The purified BioHx protein displayed carboxylesterase activity, and it was most active on p-nitrophenyl esters of fatty acids substrate with a short acyl chain (C4). Comparing BioHx with other known BioH proteins revealed interesting diversity in their sensitivity to ionic and nonionic detergents and organic solvents, and BioHx exhibited exceptional resistance to organic solvents, being the most tolerant one amongst all known BioH enzymes. This ascribed BioHx as a novel carboxylesterase with a strong potential in industrial applications.
CONCLUSIONS: This study constituted the first investigation of a novel bioHx gene in a biotin biosynthetic gene cluster cloned from an environmental metagenome. The bioHx gene was successfully cloned, expressed and characterized. The results demonstrated that BioHx is a novel carboxylesterase, displaying distinct biochemical properties with strong application potential in industry. Our results also provided the evidence for the effectiveness of functional metagenomic approach for identifying novel bioH genes from complex ecosystem.
ESTHER : Shi_2013_BMC.Biotechnol_13_13
PubMedSearch : Shi_2013_BMC.Biotechnol_13_13
PubMedID: 23413993

Title : Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients - Shi_2012_Stem.Cells.Transl.Med_1_725
Author(s) : Shi M , Zhang Z , Xu R , Lin H , Fu J , Zou Z , Zhang A , Shi J , Chen L , Lv S , He W , Geng H , Jin L , Liu Z , Wang FS
Ref : Stem Cells Transl Med , 1 :725 , 2012
Abstract : Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients.
ESTHER : Shi_2012_Stem.Cells.Transl.Med_1_725
PubMedSearch : Shi_2012_Stem.Cells.Transl.Med_1_725
PubMedID: 23197664

Title : Genetic organization of transposase regions surrounding blaKPC carbapenemase genes on plasmids from Klebsiella strains isolated in a New York City hospital - Gootz_2009_Antimicrob.Agents.Chemother_53_1998
Author(s) : Gootz TD , Lescoe MK , Dib-Hajj F , Dougherty BA , He W , Della-Latta P , Huard RC
Ref : Antimicrobial Agents & Chemotherapy , 53 :1998 , 2009
Abstract : Carbapenem-resistant Klebsiella strains carrying Klebsiella pneumoniae carbapenemases (KPC) are endemic to New York City and are spreading across the United States and internationally. Recent studies have indicated that the KPC structural gene is located on a 10-kb plasmid-borne element designated Tn4401. Fourteen Klebsiella pneumoniae strains and one Klebsiella oxytoca strain isolated at a New York City hospital in 2005 carrying either bla(KPC-2) or bla(KPC-3) were examined for isoforms of Tn4401. Ten of the Klebsiella strains contained a 100-bp deletion in Tn4401, corresponding to the Tn4401a isoform. The presence of this deletion adjacent to the upstream promoter region of bla(KPC) in Tn4401a resulted in a different -35 promoter sequence of TGGAGA than that of CTGATT present in isoform Tn4401b. Complete sequencing of one plasmid carrying bla(KPC) from each of three nonclonal isolates indicated the presence of genes encoding other types of antibiotic resistance determinants. The 70.6-kb plasmid from K. pneumoniae strain S9 carrying bla(KPC-2) revealed two identical copies of Tn4401b inserted in an inverse fashion, but in this case, one of the elements disrupted a group II self-splicing intron. In K. pneumoniae strain S15, the Tn4401a element carrying bla(KPC-2) was found on both a large 120-kb plasmid and a smaller 24-kb plasmid. Pulsed-field gel electrophoresis results indicate that the isolates studied represent a heterogeneous group composed of unrelated as well as closely related Klebsiella strains. Our results suggest that endemic KPC-positive Klebsiella strains constitute a generally nonclonal population comprised of various alleles of bla(KPC) on several distinct plasmid genetic backgrounds. This study increases our understanding of the genetic composition of the evolving and expanding role of KPC-producing, healthcare-associated, gram-negative pathogens.
ESTHER : Gootz_2009_Antimicrob.Agents.Chemother_53_1998
PubMedSearch : Gootz_2009_Antimicrob.Agents.Chemother_53_1998
PubMedID: 19258268
Gene_locus related to this paper: klepn-b6uyy9

Title : [Molecular cloning and characterization of an acetylcholinesterase gene Dd-ace-2 from sweet potato stem nematode Ditylenchus destructor] - Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
Author(s) : Ding Z , Peng D , Huang W , He W , Gao B
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :239 , 2008
Abstract : A cDNA, named Dd-ace-2, encoding an acetylcholinesterase (AChE, EC3.1.1.7), was isolated from sweet-potato-stem nematode, Ditylenchus destructor. The nucleotide and amino acid sequences among different nematode species were compared and analyzed with DNAMAN5.0, MEGA3.0 softwares. The results showed that the complete nucleotide sequence of Dd-ace-2 gene of Ditylenchus destructor contains 2425 base pairs from which deduced 734 amino acids (GenBank accession No. EF583058). The homology rates of amino acid sequences of Dd-ace-2 gene between Ditylenchus destructor and Meloidogyne incognita, Caenorhabditis elegans, Dictyocaulus viviparous were 48.0%, 42.7%, 42.1% respectively. The mature acetylcholinesterase sequences of Ditylenchus destructor may encode by the first 701 residues of deduced 734 amino acids.The conserved motifs involved in the catalytic triad, the choline binding site and 10 aromatic residues lining the catalytic gorge were present in the Dd-ace-2 deduced protein. Phylogenetic analysis based on AChEs of other nematodes and species showed that the deduced AChE formed the same cluster with ACE-2s.
ESTHER : Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
PubMedSearch : Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
PubMedID: 18464607

Title : Co-expression of Gbeta5 enhances the function of two Ggamma subunit-like domain-containing regulators of G protein signaling proteins - Kovoor_2000_J.Biol.Chem_275_3397
Author(s) : Kovoor A , Chen CK , He W , Wensel TG , Simon MI , Lester HA
Ref : Journal of Biological Chemistry , 275 :3397 , 2000
Abstract : Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta5. The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K(+) (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of Gbeta5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of Gbeta1, and co-expression of Gbeta5 alone had no effect on GIRK channel kinetics. Gbeta5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by Gbeta5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.
ESTHER : Kovoor_2000_J.Biol.Chem_275_3397
PubMedSearch : Kovoor_2000_J.Biol.Chem_275_3397
PubMedID: 10652332