Zhang M

References (152)

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

Title : Pyridostigmine attenuated high-fat-diet induced liver injury by the reduction of mitochondrial damage and oxidative stress via alpha7nAChR and M3AChR - Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
Author(s) : Xue R , Wu Q , Guo L , Ye D , Cao Q , Zhang M , Xian Y , Chen M , Yan K , Zheng J
Ref : J Biochem Mol Toxicol , 38 :e23671 , 2024
Abstract : Obesity is a major cause of nonalcohol fatty liver disease (NAFLD), which is characterized by hepatic fibrosis, lipotoxicity, inflammation, and apoptosis. Previous studies have shown that an imbalance in the autonomic nervous system is closely related to the pathogenesis of NAFLD. In this study, we investigated the effects of pyridostigmine (PYR), a cholinesterase (AChE) inhibitor, on HFD-induced liver injury and explored the potential mechanisms involving mitochondrial damage and oxidative stress. A murine model of HFD-induced obesity was established using the C57BL/6 mice, and PYR (3 mg/kg/d) or placebo was administered for 20 weeks. PYR reduced the body weight and liver weight of the HFD-fed mice. Additionally, the serum levels of IL-6, TNF-alpha, cholesterol, and triglyceride were significantly lower in the PYR-treated versus the untreated mice, corresponding to a decrease in hepatic fibrosis, lipid accumulation, and apoptosis in the former. Furthermore, the mitochondrial morphology improved significantly in the PYR-treated group. Consistently, PYR upregulated ATP production and the mRNA level of the mitochondrial dynamic factors OPA1, Drp1 and Fis1, and the mitochondrial unfolded protein response (UPRmt) factors LONP1 and HSP60. Moreover, PYR treatment activated the Keap1/Nrf2 pathway and upregulated HO-1 and NQO-1, which mitigated oxidative injury as indicated by decreased 8-OHDG, MDA and H(2) O(2) levels, and increased SOD activity. Finally, PYR elevated acetylcholine (ACh) levels by inhibiting AChE, and upregulated the alpha7nAChR and M3AChR proteins in the HFD-fed mice. PYR alleviated obesity-induced hepatic injury in mice by mitigating mitochondrial damage and oxidative stress via alpha7nAChR and M3AChR.
ESTHER : Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
PubMedSearch : Xue_2024_J.Biochem.Mol.Toxicol_38_e23671
PubMedID: 38454809

Title : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : Dipeptidyl peptidase-4 disturbs adipocyte differentiation via the negative regulation of the glucagon-like peptide-1\/adiponectin-cathepsin K axis in mice under chronic stress conditions - Zhang_2024_Faseb.j_38_e23684
Author(s) : Zhang M , Yue X , Xu S , Piao J , Zhao L , Shu S , Kuzuya M , Li P , Hong L , Kim W , Liu B , Cheng XW
Ref : Faseb j , 38 :e23684 , 2024
Abstract : Exposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase-4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress-related adipocyte differentiation, with a focus on the glucagon-like peptide-1 (GLP-1)/adiponectin-CTSK axis in vivo and in vitro. Plasma and inguinal adipose tissue from non-stress wild-type (DPP4(+/+)), DPP4-knockout (DPP4(-/-)) and CTSK-knockout (CTSK(-/-)) mice, and stressed DPP4(+/+), DPP4(-/-), CTSK(-/-), and DPP4(+/+) mice underwent stress exposure plus GLP-1 receptor agonist exenatide loading for 2weeks and then were analyzed for stress-related biological and/or morphological alterations. On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP-1, CTSK, adiponectin, and tumor necrosis factor-alpha proteins and the adipose tissue levels of CTSK, preadipocyte factor-1, fatty acid binding protein-4, CCAAT/enhancer binding protein-alpha, GLP-1 receptor, peroxisome proliferator-activated receptor-gamma, perilipin2, secreted frizzled-related protein-4, Wnt5alpha, Wnt11 and beta-catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP-1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress-induced adipocyte differentiation accompanied with changes in the levels of pref-1, C/EBP-alpha, and PPAR-gamma in 3T3-L1 cells. Thus, these findings indicated that increased DPP4 plays an essential role in stress-related adipocyte differentiation, possibly through a negative regulation of GLP-1/adiponectin-CTSK axis activation in mice under chronic stress conditions.
ESTHER : Zhang_2024_Faseb.j_38_e23684
PubMedSearch : Zhang_2024_Faseb.j_38_e23684
PubMedID: 38795334

Title : Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality - Chen_2024_J.Med.Chem__
Author(s) : Chen Y , Sun J , Tong H , Wang J , Cao R , Xu H , Chen L , Morisseau C , Zhang M , Shi Y , Han C , Zhuang J , Jing Y , Liu Z , Hammock BD , Chen G
Ref : Journal of Medicinal Chemistry , : , 2024
Abstract : Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.
ESTHER : Chen_2024_J.Med.Chem__
PubMedSearch : Chen_2024_J.Med.Chem__
PubMedID: 38236416

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

Title : Habitual feeding patterns impact polystyrene microplastic abundance and potential toxicity in edible benthic mollusks - Wang_2023_Sci.Total.Environ_866_161341
Author(s) : Wang S , Zheng L , Shen M , Zhang L , Wu Y , Li G , Guo C , Hu C , Zhang M , Sui Y , Dong X , Lv L
Ref : Sci Total Environ , 866 :161341 , 2023
Abstract : That increasing microplastics (MPs, <5 mm) eventually end up in the sediment which may become a growing menace to diverse benthic lives is worthy of attention. In this experiment, three edible mollusks including one deposit-feeding gastropod (Bullacta exarate) and two filter-feeding bivalves (Cyclina sinensis and Mactra veneriformis) were exposed to polystyrene microplastic (PS-MP) for 7 days and depurated for 3 days. PS-MP numbers in the digestive system and non-digestive system, digestive enzymes, oxidative stress indexes, and a neurotoxicity index of three mollusks were determined at day 0, 3, 7, 8 and 10. After seven-day exposure, the PS-MP were found in all three mollusks' digestive and non-digestive systems. And PS-MP in M. veneriformis (9.57 +/- 2.19 items/individual) was significantly higher than those in C. sinensis (3.00 +/- 2.16 items/individual) and B. exarate (0.83 +/- 1.07 items/individual) at day 7. Three-day depuration could remove most of the PS-MP in the mollusks, and higher PS-MP clearance rates were found in filter-feeding C. sinensis (77.78 %) and M. veneriformis (82.59 %) compared to surface deposit-feeding B. exarate (50.00 %). The digestive enzymes of B. exarate significantly reacted to PS-MP exposure, while oxidative responses were found in C. sinensis. After three-day depuration, the changes of digestive enzymes and the oxidative states were fixed, but neurotoxicity induced by PS-MP was not recoverable. Besides, it is noteworthy that changes of digestive enzymes and acetylcholinesterase are related to feeding patterns.
ESTHER : Wang_2023_Sci.Total.Environ_866_161341
PubMedSearch : Wang_2023_Sci.Total.Environ_866_161341
PubMedID: 36603620

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

Title : [Structure-guided engineering for improving the thermal stability of zearalenone hydrolase] - Guan_2023_Sheng.Wu.Gong.Cheng.Xue.Bao_39_3336
Author(s) : Guan A , Zhang M , Xu F
Ref : Sheng Wu Gong Cheng Xue Bao , 39 :3336 , 2023
Abstract : Zearalenone is one of the most widely polluted Fusarium toxins in the world, seriously endangering livestock and human health. Zearalenone hydrolase (ZHD) derived from Clonostachys rosea can effectively degrade zearalenone. However, the high temperature environment in feed processing hampers the application of this enzyme. Structure-based rational design may provide guidance for engineering the thermal stability of enzymes. In this paper, we used the multiple structure alignment (MSTA) to screen the structural flexibility regions of ZHD. Subsequently, a candidate mutation library was constructed by sequence conservation scoring and conformational free energy calculation, from which 9 single point mutations based on residues 136 and 220 were obtained. The experiments showed that the thermal melting temperature (T(m)) of the 9 mutants increased by 0.4-5.6 degC. The S220R and S220W mutants showed the best thermal stability, the T(m) of which increased by 5.6 degC and 4.0 degC compared to that of the wild type. Moreover, the thermal half-inactivation time at 45 degC were 15.4 times and 3.1 times longer, and the relative activities were 70.6% and 57.3% of the wild type. Molecular dynamics simulation analysis showed that the interaction force at and around the mutation site was enhanced, contributing to the improved thermal stability of ZHD. The probability of 220-K130 hydrogen bond of the mutants S220R and S220W increased by 37.1% and 19.3%, and the probability of K130-D223 salt bridge increased by 30.1% and 12.5%, respectively. This work demonstrated the feasibility of thermal stability engineering strategy where the structural and sequence alignment as well as free energy calculation of natural enzymes were integrated, and obtained ZHD variants with enhanced thermal stability, which may facilitate the industrial application of ZHD.
ESTHER : Guan_2023_Sheng.Wu.Gong.Cheng.Xue.Bao_39_3336
PubMedSearch : Guan_2023_Sheng.Wu.Gong.Cheng.Xue.Bao_39_3336
PubMedID: 37622364
Gene_locus related to this paper: biooc-ZHD101

Title : Strategy of In Situ Electrochemical Regulation for Highly Enhanced Nonenzymatic Sensing of Carbaryl - Lv_2023_Anal.Chem__
Author(s) : Lv Y , Zhang Y , Yang Y , Li J , Wang J , Xiao X , Zhang M
Ref : Analytical Chemistry , : , 2023
Abstract : Specific and sensitive sensing of most pesticide residues relies on enzymes such as acetylcholinesterase and advanced materials, which need to be loaded on the surface of working electrodes, leading to instability, uneven surface, tedious process, and high cost. Meanwhile, employing certain potential or current in electrolyte solution could also modify the surface in situ and overcome these drawbacks. However, this method is only regarded as electrochemical activation widely applied in the pretreatment of electrodes. In this paper, by means of regulating the electrochemical technique and its parameters, we prepared a proper sensing interface and derivatized the carbaryl (a carbamate pesticide) hydrolyzed form (1-naphthol) to enhance sensing by 100 times within several minutes. After regulation I by chronopotentiometry with 0.2 mA for 20 s or chronoamperometry with 2 V for 10 s, abundant oxygen-containing groups form and the ordered carbon structure is destroyed. Sweeping from -0.5 to 0.9 V through cyclic voltammetry for only one segment, following regulation II, the composition of oxygen-containing groups changes and the disordered structure is alleviated. Finally, on the constructed sensing interface, test by regulation III through differential pulse voltammetry from 0.8 to -0.4 V, resulting in derivatization of 1-naphthol during 0.8-0 V, followed by electroreduction of the derivative at around -0.17 V. Compared with the electro-oxidation peak at 0.5 V in previous reports, it is essential to improve specificity, even toward several other carbamate pesticides with similar structures. Hence, the in situ electrochemical regulation strategy has demonstrated great potential for effective sensing of electroactive molecules.
ESTHER : Lv_2023_Anal.Chem__
PubMedSearch : Lv_2023_Anal.Chem__
PubMedID: 36802553

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

Title : The miRNAs let-7b and miR-141 Coordinately Regulate Vitellogenesis by Modulating Methyl Farnesoate Degradation in the Swimming Crab Portunus trituberculatus - Yu_2023_Int.J.Mol.Sci_25_279
Author(s) : Yu X , Zhang M , Liu P , Li J , Gao B , Meng X
Ref : Int J Mol Sci , 25 : , 2023
Abstract : Methyl farnesoate (MF), a crucial sesquiterpenoid hormone, plays a pivotal role in the reproduction of female crustaceans, particularly in the vitellogenesis process. Despite extensive research on its functions, the molecular mechanisms that regulate MF levels during the vitellogenic phase remain largely elusive. This study investigates the roles of microRNAs (miRNAs), significant post-transcriptional regulators of gene expression, in controlling MF levels in the swimming crab Portunus trituberculatus. Through bioinformatic analysis, four miRNAs were identified as potential regulators targeting two genes encoding Carboxylesterases (CXEs), which are key enzymes in MF degradation. Dual luciferase reporter assays revealed that let-7b and miR-141 suppress CXE1 and CXE2 expression by directly binding to their 3' UTRs. In vivo overexpression of let-7b and miR-141 significantly diminished CXE1 and CXE2 levels, consequently elevating hemolymph MF and enhancing vitellogenin expression. Spatiotemporal expression profile analysis showed that these two miRNAs and their targets exhibited generally opposite patterns during ovarian development. These findings demonstrate that let-7b and miR-141 collaboratively modulate MF levels by targeting CXEs, thus influencing vitellogenesis in P. trituberculatus. Additionally, we found that the expression of let-7b and miR-141 were suppressed by MF, constituting a regulatory loop for the regulation of MF levels. The findings contribute novel insights into miRNA-mediated ovarian development regulation in crustaceans and offer valuable information for developing innovative reproduction manipulation techniques for P. trituberculatus.
ESTHER : Yu_2023_Int.J.Mol.Sci_25_279
PubMedSearch : Yu_2023_Int.J.Mol.Sci_25_279
PubMedID: 38203450
Gene_locus related to this paper: portr-a0a1i9kj57 , portr-a0a1i9ky23

Title : Characterization of caffeoyl shikimate esterase gene family identifies CsCSE5 as a positive regulator of Podosphaera xanthii and Corynespora cassiicola pathogen resistance in cucumber - Yu_2023_Plant.Cell.Rep__
Author(s) : Yu Y , He J , Liu L , Zhao H , Zhang M , Hong J , Meng X , Fan H
Ref : Plant Cell Rep , : , 2023
Abstract : CsCSE genes might be involved in the tolerance of cucumber to pathogens. Silencing of the CsCSE5 gene resulted in attenuated resistance of cucumber to Podosphaera xanthii and Corynespora cassiicola. Caffeoyl shikimate esterase (CSE), a key enzyme in the lignin biosynthetic pathway, has recently been characterized to play a key role in defense against pathogenic infection in plants. However, a systematic analysis of the CSE gene family in cucumber (Cucumis sativus) has not yet been conducted. Here, we identified eight CsCSE genes from the cucumber genome via bioinformatic analyses, and these genes were unevenly distributed on chromosomes 1, 3, 4, and 5. Results from multiple sequence alignment indicated that the CsCSE proteins had domains required for CSE activity. Phylogenetic analysis of gene structure and protein motifs revealed the conservation and diversity of the CsCSE gene family. Collinearity analysis showed that CsCSE genes had high homology with CSE genes in wax gourd (Benincasa hispida). Cis-acting element analysis of the promoters suggested that CsCSE genes might play important roles in growth, development, and stress tolerance. Expression pattern analysis indicated that CsCSE5 might be involved in regulating the resistance of cucumber to pathogens. Functional verification data confirmed that CsCSE5 positively regulates the resistance of cucumber to powdery mildew pathogen Podosphaera xanthii and target leaf spot pathogen Corynespora cassiicola. The results of our study provide information that will aid the genetic improvement of resistant cucumber varieties.
ESTHER : Yu_2023_Plant.Cell.Rep__
PubMedSearch : Yu_2023_Plant.Cell.Rep__
PubMedID: 37823975

Title : Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase - Zhao_2023_Bioorg.Med.Chem_91_117413
Author(s) : Zhao Y , Zhang M , Hou X , Han J , Qin X , Yang Y , Song Y , Liu Z , Zhang Y , Xu Z , Jia Q , Li Y , Chen K , Li B , Zhu W , Ge G
Ref : Bioorganic & Medicinal Chemistry , 91 :117413 , 2023
Abstract : Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
ESTHER : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedSearch : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedID: 37490786

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

Title : Identification of the Flavone-Inducible Counter-Defense Genes and Their cis-Elements in Helicoverpa armigera - Deng_2023_Toxins.(Basel)_15_
Author(s) : Deng Z , Zhang Y , Fang L , Zhang M , Wang L , Ni X , Li X
Ref : Toxins (Basel) , 15 : , 2023
Abstract : Flavone is widely found in plants and plays an important role in plant defense against pests. Many pests, such as Helicoverpa armigera, use flavone as a cue to upregulate counter-defense genes for detoxification of flavone. Yet the spectrum of the flavone-inducible genes and their linked cis-regulatory elements remains unclear. In this study, 48 differentially expressed genes (DEGs) were found by RNA-seq. These DEGs were mainly concentrated in the retinol metabolism and drug metabolism-cytochrome P450 pathways. Further in silico analysis of the promoter regions of 24 upregulated genes predicted two motifs through MEME and five previously characterized cis-elements including CRE, TRE, EcRE, XRE-AhR and ARE. Functional analysis of the two predicted motifs and two different versions of ARE (named ARE1 and ARE2) in the promoter region of the flavone-inducible carboxylesterase gene CCE001j verified that the two motifs and ARE2 are not responsible for flavone induction of H. armigera counter-defense genes, whereas ARE1 is a new xenobiotic response element to flavone (XRE-Fla) and plays a decisive role in flavone induction of CCE001j. This study is of great significance for further understanding the antagonistic interaction between plants and herbivorous insects.
ESTHER : Deng_2023_Toxins.(Basel)_15_
PubMedSearch : Deng_2023_Toxins.(Basel)_15_
PubMedID: 37368666

Title : Responses and detoxification mechanisms of earthworm Amynthas hupeiensis to metal contaminated soils of North China - Liu_2023_Environ.Pollut__121584
Author(s) : Liu Y , Chen M , Mu X , Wang X , Zhang M , Yin Y , Wang K
Ref : Environ Pollut , :121584 , 2023
Abstract : Metal contamination is widespread, but only a few studies have evaluated the toxicological risks of metals (Cd, Cu, and Pb) in earthworms from farmlands in North China (Hebei province). Amynthas hupeiensis, the dominant species in the study area, was used to determine the responses and detoxification mechanisms of uncontaminated (CK), and low (LM)-, and high (HM)-metal-contaminated soils following 7-, 14-, and 28-days exposure. Metal toxicity in LM and HM soils inhibited the biomass of A. hupeiensis. The concentrations of Cd in A. hupeiensis bodies indicated accumulated Cd appeared to remain steady with prolonged exposure, while Cu/Pb increased significantly with soil levels. Bioaccumulation occurred in the order Cd > Pb > Cu in LM soil, and in the order Cd > Cu = Pb in HM soil, which was attributed to differences in available fractions between LM and HM soils. Physiological levels of biomarkers in A. hupeiensis were determined, including total protein (TP), glutathione (GSH), glutathione peroxidase (GPx), acetylcholinesterase (AChE), and malondialdehyde (MDA). Deviations in GSH, GPx, and AChE were considered to denote sensitive biomarkers using the IBRv2 index. Metabolomics data ((1)H nuclear magnetic resonance-based) revealed changes in metabolites following 28-days exposure to LM and HM soils. Differences in metabolism in A. hupeiensis following exposure to LM and HM were related to energy metabolism, amino acid biosynthesis, glycerophospholipid metabolism, inositol phosphate metabolism, and glutathione metabolism. Metal stress from LM and HM soils disturbed osmoregulation, resulting in oxidative stress, destruction of cell membranes and inflammation, and altered levels of amino acids required for energy by A. hupeiensis. These findings provide biochemical insights into the physiological and metabolic mechanisms underlying the ability of A. hupeiensis to resist metal stress, and for assessing the environmental risks of metal-contaminated soils in farmland in North China.
ESTHER : Liu_2023_Environ.Pollut__121584
PubMedSearch : Liu_2023_Environ.Pollut__121584
PubMedID: 37037277

Title : Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases - Chen_2023_J.Med.Chem__
Author(s) : Chen Y , Chen L , Xu H , Cao R , Morisseau C , Zhang M , Shi Y , Hammock BD , Wang J , Zhuang J , Liu Z , Chen G
Ref : Journal of Medicinal Chemistry , : , 2023
Abstract : Soluble epoxide hydrolase (sEH) has been identified as an attractive target for anti-inflammatory drug design in recent years. Picomolar level compound G1 against sEH was obtained by introducing the hydrophilic group homopiperazine and hydrophobic fragment propionyl onto the structure of lead compound A. G1 showed good microsomal stability, a moderate plasma protein binding rate, and good oral bioavailability and was well tolerated in rats. G1 has significant analgesic effects on CFA-induced AIA mice, ameliorated the pancreatic injury in acute pancreatitis induced by l-arginine, reversed pancreatic injury, edema, and neutrophil infiltration, and increased the survival time of C57BL/6 mice in a lipopolysaccharide (LPS)-induced sepsis model. Moreover the expression levels of sEH, COX-2, NOS-2, vascular cell adhesion molecule (VCAM), IL-6, MCP-5, and tumor necrosis factor alpha (TNF-alpha) were measured by Western blot or enzyme-linked immunosorbent assay (ELISA), with varying degrees of decrease. These results suggested that G1 is a drug candidate worthy of further evaluation for the treatment of inflammation-induced diseases such as arthritis, acute pancreatitis, and sepsis.
ESTHER : Chen_2023_J.Med.Chem__
PubMedSearch : Chen_2023_J.Med.Chem__
PubMedID: 36689364

Title : A novel skeleton alkaloid from Portulaca oleracea L. and its bioactivities - Lan_2023_Fitoterapia__105608
Author(s) : Lan X , Guo S , Zhao Y , Zhang M , Zhang D , Leng A , Ying X
Ref : Fitoterapia , :105608 , 2023
Abstract : A novel skeleton alkaloid was obtained from Portulaca oleracea L., which was identified as 10,11-dihydroxybenzo[5',6'] pentaleno[1',2':3,4]pyrrolo[2,1-b]oxazol-7(11bH)-one, named oleracone M, and its structure was determined using UHPLC-ESI-QTOF/MS, 1D NMR and 2D NMR spectroscopy, and circular dichroism. Then the bioactivities of the compound were investigated including the anti-inflammatory, anti-acetylcholinesterase and antioxidant activities. The results showed that the novel skeleton alkaloid exhibited the potent effect on inhibiting the secretion of IL-1beta at 10 microM, anticholinesterase activity with IC(50) value of 49.58 microM, and antioxidant activity with IC(50) value of 66.43 microM.
ESTHER : Lan_2023_Fitoterapia__105608
PubMedSearch : Lan_2023_Fitoterapia__105608
PubMedID: 37453700

Title : Visual evaluation of acetylcholinesterase inhibition by an easy-to-operate assay based on N-doped carbon nanozyme with high stability and oxidase-like activity - Zhang_2023_J.Mater.Chem.B__
Author(s) : Zhang M , Wang C , Wang Y , Li F , Zhu D
Ref : J Mater Chem B , : , 2023
Abstract : Acetylcholinesterase (AChE) is the key enzyme associated with neurotransmission, and thus many drugs have been explored for their inhibitory effect on AChE, such as donepezil for Alzheimer's disease and organophosphorus pesticides (OPs). Compared with clinical trials, in vitro screening bioassays for AChE inhibitors are preferable in terms of operability and cost. Herein, we developed an easy-to-operate nanozyme-based colorimetric assay for the evaluation of AChE inhibitory strength with excellent anti-interference ability and low dependence on professional equipment. The metal-free carbon nanozyme NC900 played an important role in the signal output due to its features of efficient oxidase-like activity, excellent water dispersibility, high stability and low color interference. Employing various AChE-targeted or non-targeted pesticides as examples, the as-proposed assay exhibited excellent distinguishing ability for different chemicals. The higher absorption intensity at 652 nm represents a stronger inhibitory effect, as well as blue color. In addition, this method was used to study the influence of pH on the degradation of prodrugs, and the efficiency of mixed pesticides. This work provides a simple and reliable assay to screen AChE inhibitors, which is promising for the preliminary evaluation of a large number of potential candidates.
ESTHER : Zhang_2023_J.Mater.Chem.B__
PubMedSearch : Zhang_2023_J.Mater.Chem.B__
PubMedID: 37067450

Title : Construction and Manipulation of Serial Gradient Dilution Array on a Microfluidic Slipchip for Screening and Characterizing Inhibitors against Human Pancreatic Lipase - Yang_2023_Biosensors.(Basel)_13_
Author(s) : Yang J , Deng Y , Zhang M , Feng S , Peng S , Yang S , Liu P , Cai G , Ge G
Ref : Biosensors (Basel) , 13 : , 2023
Abstract : Obesity is one of the foremost public health concerns. Human pancreatic lipase (hPL), a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, has been validated as an important therapeutic target for preventing and treating obesity. The serial dilution technique is commonly used to generate solutions with different concentrations and can be easily modified for drug screening. Conventional serial gradient dilution is often performed with tedious multiple manual pipetting steps, where it is difficult to precisely control fluidic volumes at low microliter levels. Herein, we presented a microfluidic SlipChip that enabled formation and manipulation of serial dilution array in an instrument-free manner. With simple slipping steps, the compound solution could be diluted to seven gradients with the dilution ratio of 1:1 and co-incubated with the enzyme (hPL)-substrate system for screening the anti-hPL potentials. To ensure complete mixing of solution and diluent during continuous dilution, we established a numerical simulation model and conducted an ink mixing experiment to determine the mixing time. Furthermore, we also demonstrated the serial dilution ability of the proposed SlipChip using standard fluorescent dye. As a proof of concept, we tested this microfluidic SlipChip using one marketed anti-obesity drug (Orlistat) and two natural products (1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (PGG) and sciadopitysin) with anti-hPL potentials. The IC(50) values of these agents were calculated as 11.69 nM, 8.22 nM and 0.80 microM, for Orlistat, PGG and sciadopitysin, respectively, which were consistent with the results obtained by conventional biochemical assay.
ESTHER : Yang_2023_Biosensors.(Basel)_13_
PubMedSearch : Yang_2023_Biosensors.(Basel)_13_
PubMedID: 36832040

Title : OsGELP77, a QTL for broad-spectrum disease resistance and yield in rice, encodes a GDSL-type lipase - Zhang_2023_Plant.Biotechnol.J__
Author(s) : Zhang M , Chen D , Tian J , Cao J , Xie K , He Y , Yuan M
Ref : Plant Biotechnol J , : , 2023
Abstract : Lipids and lipid metabolites have essential roles in plant-pathogen interactions. GDSL-type lipases are involved in lipid metabolism modulating lipid homeostasis. Some plant GDSLs modulate lipid metabolism altering hormone signal transduction to regulate host-defence immunity. Here, we functionally characterized a rice lipase, OsGELP77, promoting both immunity and yield. OsGELP77 expression was induced by pathogen infection and jasmonic acid (JA) treatment. Overexpression of OsGELP77 enhanced rice resistance to both bacterial and fungal pathogens, while loss-of-function of osgelp77 showed susceptibility. OsGELP77 localizes to endoplasmic reticulum and is a functional lipase hydrolysing universal lipid substrates. Lipidomics analyses demonstrate that OsGELP77 is crucial for lipid metabolism and lipid-derived JA homeostasis. Genetic analyses confirm that OsGELP77-modulated resistance depends on JA signal transduction. Moreover, population genetic analyses indicate that OsGELP77 expression level is positively correlated with rice resistance against pathogens. Three haplotypes were classified based on nucleotide polymorphisms in the OsGELP77 promoter where OsGELP77(Hap3) is an elite haplotype. Three OsGELP77 haplotypes are differentially distributed in wild and cultivated rice, while OsGELP77(Hap3) has been broadly pyramided for hybrid rice development. Furthermore, quantitative trait locus (QTL) mapping and resistance evaluation of the constructed near-isogenic line validated OsGELP77, a QTL for broad-spectrum disease resistance. In addition, OsGELP77-modulated lipid metabolism promotes JA accumulation facilitating grain yield. Notably, the hub defence regulator OsWRKY45 acts upstream of OsGELP77 by initiating the JA-dependent signalling to trigger immunity. Together, OsGELP77, a QTL contributing to immunity and yield, is a candidate for breeding broad-spectrum resistant and high-yielding rice.
ESTHER : Zhang_2023_Plant.Biotechnol.J__
PubMedSearch : Zhang_2023_Plant.Biotechnol.J__
PubMedID: 38100249

Title : Sex differences in FASN protein concentrations in urinary exosomes related to serum triglycerides levels in healthy adults - Li_2023_Lipids.Health.Dis_22_176
Author(s) : Li T , Meng W , Liu TC , Wang YZ , Zhang M
Ref : Lipids Health Dis , 22 :176 , 2023
Abstract : BACKGROUND: Dysregulation of lipid metabolism is the most prominent metabolic alteration observed in obesity, cancer, and cardiovascular diseases. The present study aimed to explore the sex differences associated with lipid metabolism in urinary exosome proteins, and evaluate the correlation of urinary exosome proteins with serum lipid biomarkers. METHODS: The key enzymes regulating lipid metabolism in healthy adults were screened using urinary exosome data. Urinary exosomes were isolated from 120 healthy subjects and the expression of urinary proteins was assessed by Western blotting and ELISA. The correlation between urinary protein concentrations and the levels of serum lipid biomarkers was analyzed using correlation analysis. RESULTS: Three urinary exosome proteins, namely fatty acid synthase (FASN), phosphoenolpyruvate carboxykinase (PCK1), and ATP-citrate synthase (ACLY) were identified, and only FASN showed sex differences. Sex differences were also observed in the serum triglyceride (TG) levels. Healthy males had higher FASN levels than females, and a moderate positive correlation was found between FASN concentrations and serum TG levels in healthy males (r = 0.479, P < 0.05). FASN concentrations in different age groups were positively correlated with the level of serum TG (18 ~ 30 years, r = 0.502; 31 ~ 44 years, r = 0.587; 45 ~ 59 years, r = 0.654; all P < 0.05). In addition, FASN concentrations was positively related to the increase in serum TG levels (range:1.0 ~ 1.7 mmol/L; r = 0.574, P < 0.05). CONCLUSIONS: Sex differences were observed in urinary exosome FASN protein levels in healthy adults. FASN protein levels positively correlated with increased serum TG levels. FASN may serve as a novel biomarker to evaluate fatty acid synthesis in the human body.
ESTHER : Li_2023_Lipids.Health.Dis_22_176
PubMedSearch : Li_2023_Lipids.Health.Dis_22_176
PubMedID: 37858194

Title : Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids - Zhou_2023_J.Agric.Food.Chem_71_18359
Author(s) : Zhou H , Jian Y , Shao Q , Guo F , Zhang M , Wan F , Yang L , Liu Y , Li Y , Yang P , Li Z , Li S , Ding W
Ref : Journal of Agricultural and Food Chemistry , 71 :18359 , 2023
Abstract : Plants employ abundant toxic secondary metabolites to withstand insect attack, while pollinators can tolerate some natural defensive compounds. Coumarins, as promising green alternatives to chemical insecticides, possess wide application prospects in the crop protection field. Herein, the bioactivities of 30 natural coumarin derivatives against Aphis gossypii were assessed and revealed that 6-methylcoumarin exhibited potent aphicidal activity against aphids but displayed no toxicity to honeybees. Additionally, using biochemical, bioinformatic, and molecular assays, we confirmed that the action mode of 6-methylcoumarin against aphids was by inhibiting acetylcholinesterase (AChE). Meanwhile, functional assays revealed that the difference in action site, which located in Lys585 in aphid AChE (equivalent to Val548 in honeybee AChE), was the principal reason for 6-methylcoumarin being toxic to aphids but safe to pollinators. This action site was further validated by mutagenesis data, which uncovered how 6-methylcoumarin was unique selective to the aphid over honeybee or mammalian AChE. Furthermore, a 2D-QSAR model was established, revealing that the central structural feature was H3m, which offers guidance for the future design of more potent coumarin compounds. This work provides a sustainable strategy to take advantage of coumarin analogues for pest management while protecting nontarget pollinators.
ESTHER : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedSearch : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedID: 37965968

Title : Resistance risk assessment of six pyrethroids and acephate toward the resistant adult tarnished plant bug, Lygus lineolaris - Du_2023_Insect.Sci__
Author(s) : Du Y , Scheibener S , Zhu Y , Portilla M , Zhang M
Ref : Insect Sci , : , 2023
Abstract : Due to rapidly developed resistance, pest management relies less on pyrethroids to control economically damaging infestations of the tarnished plant bug (TPB), Lygus lineolaris (Palisot de Beauvois) in cotton fields of Mississippi. Yet, pyrethroid resistance remains prevalent in TPB populations. This study assessed the resistance levels in adult TPB to six common pyrethroids and acephate. Resistant TBPs were collected from wild host plants in late October after harvest in the Mississippi Delta region of the United States. Based on LC(50) values, the field-resistant TPBs displayed higher resistance to permethrin, esfenvalerate, and bifenthrin (approximately 30 fold) and moderate resistance to lambda-cyhalothrin, beta-cyfluthrin, -cypermethrin, and acephate (approximately 15 fold). Further investigations showed that the inhibitors of three detoxification enzyme, triphenyl phosphate (TPP), diethyl maleate (DEM), and piperonyl butoxide (PBO) had synergistic effects on permethrin, lambda-cyhalothrin, and bifenthrin in resistant TPBs. Furthermore, elevated esterase, GST, and P450 activities were significantly expressed in field-resistant TPBs. Additionally, GST and esterase were reduced after 48 h exposure to certain pyrethroids at LC(50) dose. The synergistic and biochemical assays consistently indicated that P450 and esterase were involved in pyrethroid detoxification in TPBs. This study provides valuable information for the continued use of pyrethroids and acephate in controlling TPBs in cotton fields in the Mississippi Delta region of the United States.
ESTHER : Du_2023_Insect.Sci__
PubMedSearch : Du_2023_Insect.Sci__
PubMedID: 37850504

Title : Hollow Prussian blue with ultrafine silver nanoparticle agents (Ag-HPB) integrated sensitive and flexible biosensing platform with highly enzyme loading capability - Li_2023_Talanta_266_125036
Author(s) : Li R , Zhang W , Meng F , Li X , Li Z , Fang Y , Zhang M
Ref : Talanta , 266 :125036 , 2023
Abstract : Herein, the hollow Prussian blue with ultra-small silver nanoparticle agents (Ag-HPB) was prepared by the coating-etching method by applying Prussian blue (PB) coating on Ag nanoparticles (Ag NPs) and diffusing Ag NPs into the PB framework. The flexible biosensing platform based on Ag-HPB nanocomposites incorporated the excellent electrical conductivity of Ag NPs and the superior enzyme loading capacity of the hollow structure, which significantly enhanced its sensing performance. Subsequently, take glucose oxidase (GOx) and acetylcholinesterase (AChE) as examples. The sensing platform displayed a good sensitive response to glucose (Glu) (24.37 microA mM(-1) cm(-2)) and a considerable limit of detection (LOD) for trichlorfon (TCF) as 2.28 pg/mL while exhibiting high stability and good reproducibility. Moreover, it can be applied to monitor trichlorfon in apple samples. Promisingly, the Ag-HPB prepared by the coating-etching strategy provides a reliable strategy for further development of sensitive and flexible biosensing platforms with excellent electrical conductivity and high enzyme loading.
ESTHER : Li_2023_Talanta_266_125036
PubMedSearch : Li_2023_Talanta_266_125036
PubMedID: 37556951

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

Title : Hyperglycemia disrupted the integrity of the blood-brain barrier following diffuse axonal injury through the sEH\/NF-B pathway - Wei_2023_Immun.Inflamm.Dis_11_e1105
Author(s) : Wei X , Xing Z , Huang T , Zhang M , Song J , Zhao Y
Ref : Immun Inflamm Dis , 11 :e1105 , 2023
Abstract : OBJECTIVES: We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced-disruption of blood-brain barrier (BBB) integrity after diffuse axonal injury (DAI). METHODS: Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium-binding adapter molecule-1, beta-amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. The permeability of blood-brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the nuclear transcription factor kappa B (NF-kappaB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol-12-myristate-13-acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF-kappaB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF-kappaB pathway abrogated the protective effects of TPPU on BBB integrity in vitro. CONCLUSIONS: sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF-kappaB pathway.
ESTHER : Wei_2023_Immun.Inflamm.Dis_11_e1105
PubMedSearch : Wei_2023_Immun.Inflamm.Dis_11_e1105
PubMedID: 38156378

Title : Lipase-catalyzed ring-opening polymerization of natural compound-based cyclic monomers - Wang_2023_Chem.Commun.(Camb)__
Author(s) : Wang K , Li C , Man L , Zhang M , Jia YG , Zhu XX
Ref : Chem Commun (Camb) , : , 2023
Abstract : The need for sustainable and environment-friendly materials has led to growing interest in the development of biodegradable polymers based on natural compounds. However, metal-based catalysts used in the polymerization process may cause concerns about the toxicity of the resultant polymers. Therefore, polymers derived from natural compounds and synthesized through the use of green catalysts are highly desirable. Lipase-catalyzed ring-opening polymerization (ROP) of biocompound-based cyclic monomers has emerged as a promising and green strategy for the design and synthesis of such polymers. In this review, we summarize reports on the use of ROP catalyzed by lipase for cyclic monomers derived from natural compounds, including bile acid- and porphyrin-based macrocycles, carbonate-based macrocycles, lactones, and cyclic anhydrides, with an emphasis on ring-closure reactions for the synthesis of cyclic monomers, the types of lipases for the ROP and the choice of reaction conditions (temperature, solvent, reaction time, etc.). Moreover, the current challenges and perspectives for the choice and reusability of lipases, ring-closure versus ring-opening reactions, monomer design, and potential applications are discussed.
ESTHER : Wang_2023_Chem.Commun.(Camb)__
PubMedSearch : Wang_2023_Chem.Commun.(Camb)__
PubMedID: 37431654

Title : Single-Particle Tracking of Thermomyces lanuginosus Lipase Reveals How Mutations in the Lid Region Remodel Its Diffusion - Iversen_2023_Biomolecules_13_631
Author(s) : Iversen JF , Bohr SS , Pinholt HD , Moses ME , Iversen L , Christensen SM , Hatzakis NS , Zhang M
Ref : Biomolecules , 13 :631 , 2023
Abstract : The function of most lipases is controlled by the lid, which undergoes conformational changes at a water-lipid interface to expose the active site, thus activating catalysis. Understanding how lid mutations affect lipases' function is important for designing improved variants. Lipases' function has been found to correlate with their diffusion on the substrate surface. Here, we used single-particle tracking (SPT), a powerful tool for deciphering enzymes' diffusional behavior, to study Thermomyces lanuginosus lipase (TLL) variants with different lid structures in a laundry-like application condition. Thousands of parallelized recorded trajectories and hidden Markov modeling (HMM) analysis allowed us to extract three interconverting diffusional states and quantify their abundance, microscopic transition rates, and the energy barriers for sampling them. Combining those findings with ensemble measurements, we determined that the overall activity variation in the application condition is dependent on surface binding and lipase mobility when bound. Specifically, the L4 variant with a TLL-like lid and wild-type (WT) TLL displayed similar ensemble activity, but WT bound stronger to the surface than L4, while L4 had a higher diffusion coefficient and thus activity when bound to the surface. These mechanistic elements can only be de-convoluted by our combined assays. Our findings offer fresh perspectives on the development of the next iteration of enzyme-based detergent.
ESTHER : Iversen_2023_Biomolecules_13_631
PubMedSearch : Iversen_2023_Biomolecules_13_631
PubMedID: 37189378
Gene_locus related to this paper: humla-1lipa

Title : Hydrolysis enabled specific colorimetric assay of carbosulfan with sensitivity manipulation via metal-doped or metal-free carbon nanozyme - Zhu_2023_Biosens.Bioelectron_243_115786
Author(s) : Zhu D , Li N , Zhang M , Wang Y , Li F , Hou T
Ref : Biosensors & Bioelectronics , 243 :115786 , 2023
Abstract : Precise determination of the carbamate pesticide carbosulfan is crucial for assessing the associated risks in food and environment. Due to the strong interaction between carbosulfan and target enzyme, current methods primarily depend on the acetylcholinesterase (AChE) inhibition strategy, which generally lacks selectivity. In this study, we propose a nanozyme colorimetric sensor for the specific carbosulfan detection, based on its distinctive hydrolysis property. In contrast to other pesticides, carbosulfan can be hydrolyzed to produce the reductive sulfide compound by the cleavage of N-S bond under acidic condition, thereby significantly hindering the nanozyme-mediated chromogenic reaction. Consequently, the absorbance is significantly correlated with carbosulfan concentration. Furthermore, the influence of nanozyme type is disclosed, and two oxidase-like carbon nanozymes were formulated, namely metal-free NC and metal-based CeO(2)@NC. However, the distinct active sites significantly impact the proposed sensor. For CeO(2)@NC-based sensor, the produced sulfide compounds not only poison Ce active site, but also consume the reactive oxygen species, thereby, exhibiting high sensitivity with low detection limit of 3.3 nM. By contrast, the metal-free nature of NC allows the assay to remain unaffected by coordination effects, exhibiting superior anti-interference capability. This work not only offers an efficient alternative to the conventional method for detecting carbosulfan specifically, but also shed light on the role of metal-based or metal-free nanozyme among analytical applications.
ESTHER : Zhu_2023_Biosens.Bioelectron_243_115786
PubMedSearch : Zhu_2023_Biosens.Bioelectron_243_115786
PubMedID: 37883845

Title : A Space-Dependent 'Enzyme-Substrate' Type Probe based on 'Carboxylesterase-Amide Group' for Ultrafast Fluorescent Imaging Orthotopic Hepatocellular Carcinoma - Wen_2023_Adv.Sci.(Weinh)__e2206681
Author(s) : Wen Y , Jing N , Zhang M , Huo F , Li Z , Yin C
Ref : Adv Sci (Weinh) , :e2206681 , 2023
Abstract : Fast and selective fluorescence imaging for a biomarker to related-disease diagnosis remains a significant challenge due to complex physical environment. Human carboxylesterase (CE) is expected to be a potential biomarker of hepatocellular carcinoma (HCC) to improve the accuracy of diagnosis. However, existing probes for CE has slow response rate and low selectivity. Herein, the amide group is selected as CE-responsive sites based on the 'substrate-hydrolysis enzymatic reaction' approach. From a series of off-on probes with leave groups in the amide unit, probe J(Fast) is screened with the optimal combination of rapid response rate and high selectivity toward CE. J(Fast) requires only 150ss to reach the maximum fluorescence at 676snm in the presence of CE and free from the interference of other esterase. Computational docking simulations indicate the shortest distance between the CE and active site of J(Fast) . Cell and in vivo imaging present that the probe can turn on the liver cancer cells and tumor region precisely. Importantly, J(Fast) is allowed to specifically image orthotopic liver tumor rather than metastatic tumor and distinguish human primary liver cancer tissue from adjacent ones. This study provides a new tool for CE detection and promotes advancements in accurate HCC diagnosis.
ESTHER : Wen_2023_Adv.Sci.(Weinh)__e2206681
PubMedSearch : Wen_2023_Adv.Sci.(Weinh)__e2206681
PubMedID: 36651112

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

Title : Prognostic Value of Serum Cholinesterase Levels for In-Hospital Mortality among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease - Chen_2023_Copd_20_178
Author(s) : Chen Z , Zha L , Feng G , An Q , Shi F , Xu J , Xu Q , Xia H , Zhang M , Li L
Ref : Copd , 20 :178 , 2023
Abstract : Cholinesterase (ChE) is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD), including chronic airway inflammation and oxidation/antioxidant imbalance. However, the relationship between serum ChE levels and survival outcomes of patients hospitalized with acute exacerbations of COPD (AECOPD) is unknown. In this retrospective single-center study, we investigated the ability of the serum ChE level to predict in-hospital death in patients hospitalized with AECOPD. The clinicopathological data, including serum ChE levels as well as clinical and biochemical indicators were extracted for 477 patients from the hospital records and analyzed. Our results demonstrated that AECOPD patients with lower serum ChE levels were associated with increased mortality, frequent hospitalization due to acute exacerbations (AE) in the past year, and longer hospital stay. The optimal cutoff value for the serum ChE level was 4323 U/L. The area under the ROC curve (AUC) values for predicting in-hospital mortality based on the serum ChE level was 0.79 (95% confidence interval (CI), 0.72-0.85). Multivariate logistic regression analysis demonstrated that serum ChE level >= 4323 U/L (odds ratio (OR) 9.09, 95% CI 3.43-28.3, p < 0.001), age-adjusted Charlson comorbidity index (aCCI), and the number of hospitalizations due to AE in the past year were independent risk factors for predicting the in-hospital mortality of AECOPD patients. In conclusion, our study demonstrated that low serum ChE levels were associated with significantly higher in-hospital mortality rates of patients hospitalized with AECOPD. Therefore, serum ChE level is a promising prognostic predictor of hospitalized AECOPD patients.
ESTHER : Chen_2023_Copd_20_178
PubMedSearch : Chen_2023_Copd_20_178
PubMedID: 38178805

Title : Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase - Wang_2023_Foods_12_
Author(s) : Wang Y , Sun J , Zhang M , Pan K , Liu T , Zhang T , Luo X , Zhao J , Li Z
Ref : Foods , 12 : , 2023
Abstract : Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.
ESTHER : Wang_2023_Foods_12_
PubMedSearch : Wang_2023_Foods_12_
PubMedID: 36673508

Title : Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection - Pang_2022_Cell.Rep_39_110698
Author(s) : Pang Y , Cheng Z , Zhang S , Li S , Li X , Zhang X , Feng Y , Cui H , Chen Z , Liu L , Li Q , Huang J , Zhang M , Zhu S , Wang L , Feng L
Ref : Cell Rep , 39 :110698 , 2022
Abstract : Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection.
ESTHER : Pang_2022_Cell.Rep_39_110698
PubMedSearch : Pang_2022_Cell.Rep_39_110698
PubMedID: 35443182

Title : Natural products as sources of acetylcholinesterase inhibitors: Synthesis, biological activities, and molecular docking studies of osthole-based ester derivatives - Yu_2022_Front.Plant.Sci_13_1054650
Author(s) : Yu X , Zhang Y , Zhang M , Chen Y , Yang W
Ref : Front Plant Sci , 13 :1054650 , 2022
Abstract : Osthole is a natural coumarin compound which isolated from Cnidium monnieri (L.) Cusson, has extensive pharmacological activities and could be used as a leading compound for drug research and development. In a continuous effort to develop new acetylcholinesterase inhibitors from natural products, eighteen osthole esters were designed, synthesized, and confirmed by (1)H NMR, (13)C NMR and HRMS. The anti-AChE activity of These derivatives was measured at a concentration of 1.0 mol/mL in vitro by Ellman's method, and the result showed that 4m and 4o had moderate inhibitory activities with 68.8% and 62.6%, respectively. Molecular docking study results further revealed AChE interacted optimally with docking poses 4m and 4o. Network pharmacology also predicted that compound 4m could be involved in Ras signaling pathway, which made it a potential therapeutic target of AD.
ESTHER : Yu_2022_Front.Plant.Sci_13_1054650
PubMedSearch : Yu_2022_Front.Plant.Sci_13_1054650
PubMedID: 36466282

Title : Role of Bmal1 in mediating the cholinergic system to regulate the behavioral rhythm of nocturnal marine molluscs - Gao_2022_Comput.Struct.Biotechnol.J_20_2815
Author(s) : Gao X , Zhang M , Lyu M , Lin S , Luo X , You W , Ke C
Ref : Comput Struct Biotechnol J , 20 :2815 , 2022
Abstract : The circadian rhythm is one of the most general and important rhythms in biological organisms. In this study, continuous 24-h video recordings showed that the cumulative movement distance and duration of the abalone, Haliotis discus hannai, reached their maximum values between 20:00-00:00, but both were significantly lower between 08:00-12:00 than at any other time of day or night (P < 0.05). To investigate the causes of these diel differences in abalone movement behavior, their cerebral ganglia were harvested at 00:00 (group D) and 12:00 (group L) to screen for differentially expressed proteins using tandem mass tagging (TMT) quantitative proteomics. Seventy-five significantly different proteins were identified in group D vs. group L. The differences in acetylcholinesterase (AchE) expression levels between day- and nighttime and the key role in the cholinergic nervous system received particular attention during the investigation. A cosine rhythm analysis found that the concentration of acetylcholine (Ach) and the expression levels of AchE tended to be low during the day and high at night, and high during the day and low at night, respectively. However, the rhythmicity of the diel expression levels of acetylcholine receptor (nAchR) appeared to be insignificant (P > 0.05). Following the injection of three different concentrations of neostigmine methylsulfate, as an AchE inhibitor, the concentration of Ach in the hemolymph, and the expression levels of nAchR in the cerebral ganglia increased significantly (P < 0.05). Four hours after drug injection, the cumulative movement distance and duration of abalones were significantly higher than those in the uninjected control group, and the group injected with saline (P < 0.05). The expression levels of the core diurnal clock Bmal1 over a 24-h period also tended to be high during the day and low at night. First, a co-immunoprecipitation assay demonstrated the binding between Bmal1 and AchE or nAchR. A dual-luciferase gene test and electrophoretic mobility shift assay showed that Bmal1 bound to the promoter regions of AchE and nAchR. Twenty-four hours after silencing the Bmal1 gene, the expression levels of AchE and nAchR decreased significantly compared to those of the dsEGFP and PBS control groups, further showing that Bmal1 mediates the cholinergic system to regulate the behavioral rhythm of abalone. These findings shed light on the endocrine mechanism regulating the rhythmic behavior of abalone, and provide a reference for understanding the life history adaptation strategies of nocturnal organisms and the proliferation and protection of bottom dwelling economically important organisms.
ESTHER : Gao_2022_Comput.Struct.Biotechnol.J_20_2815
PubMedSearch : Gao_2022_Comput.Struct.Biotechnol.J_20_2815
PubMedID: 35765646

Title : PLA2G2A Phospholipase Promotes Fatty Acid Synthesis and Energy Metabolism in Pancreatic Cancer Cells with K-ras Mutation - Zhang_2022_Int.J.Mol.Sci_23_11721
Author(s) : Zhang M , Xiang R , Glorieux C , Huang P
Ref : Int J Mol Sci , 23 :11721 , 2022
Abstract : Oncogenic K-ras is often activated in pancreatic ductal adenocarcinoma (PDAC) due to frequent mutation (>90%), which drives multiple cellular processes, including alterations in lipid metabolism associated with a malignant phenotype. However, the role and mechanism of the altered lipid metabolism in K-ras-driven cancer remains poorly understood. In this study, using human pancreatic epithelial cells harboring inducible K-ras(G12D) (HPNE/K-ras(G12D)) and pancreatic cancer cell lines, we found that the expression of phospholipase A2 group IIA (PLA2G2A) was upregulated by oncogenic K-ras. The elevated expression of PLA2G2A was also observed in pancreatic cancer tissues and was correlated with poor survival of PDAC patients. Abrogation of PLA2G2A by siRNA or by pharmacological inhibition using tanshinone I significantly increased lipid peroxidation, reduced fatty acid synthase (FASN) expression, and impaired mitochondrial function manifested by a decrease in mitochondrial transmembrane potential and a reduction in ATP production, leading to the inhibition of cancer cell proliferation. Our study suggests that high expression of PLA2G2A induced by oncogenic K-ras promotes cancer cell survival, likely by reducing lipid peroxidation through its ability to facilitate the removal of polyunsaturated fatty acids from lipid membranes by enhancing the de novo fatty acid synthesis and energy metabolism to support cancer cell proliferation. As such, PLA2G2A might function as a downstream mediator of K-ras and could be a potential therapeutic target.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_11721
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_11721
PubMedID: 36233022

Title : Simultaneous CSM-TACE with CalliSpheres() and partial splenic embolization using 8spheres() for hepatocellular carcinoma with hypersplenism: Early prospective multicenter clinical outcome - Zhou_2022_Front.Oncol_12_998500
Author(s) : Zhou J , Feng Z , Liu S , Li X , Liu Y , Gao F , Shen J , Zhang YW , Zhao GS , Zhang M
Ref : Front Oncol , 12 :998500 , 2022
Abstract : BACKGROUND: Primary hepatocellular carcinoma is often complicated with hepatitis and liver cirrhosis. Some patients develop different degrees of splenomegaly, hypersplenism and hypohepatia due to the aggravation of liver cirrhosis, which to some extent interfere with the treatment of tumors and even affect the prognosis of patients. In this study, we prospectively evaluate the efficacy and safety of simultaneous CalliSpheres((a)) microspheres transcatheter arterial chemoembolization (CSM-TACE) and partial splenic embolization (PSE) using 8spheres((a)) for hepatocellular carcinoma (HCC) with hypersplenism. METHODS: Ninety consecutive HCC patients with hypersplenism who underwent CSM-TACE were selected: 32 patients in CSM-TACE+PSE group, and 58 patients in CSM-TACE group. The peripheral blood cell counts (leukocyte, platelet (PLT), liver function and red blood cell (RBC)), CSM-TACE and/or PSE related complications, and the tumor control rate at 1 month after CSM-TACE were compared. The survival time and prognostic factors were also observed. RESULTS: Before CSM-TACE, there were no significant differences in sex, age, Child-Pugh grade, tumor size, and alpha-fetoprotein (AFP) between the two groups. After CSM-TACE, the PLT and white blood cell (WBC) counts in CSM-TACE+PSE group were significantly higher than those in the CSM-TACE group (P<0.05). There were no significant differences in RBC before and after treatment (P > 0.05). In the CSM-TACE group, there were no significant differences in WBC, PLT, and RBC before and after treatment (P > 0.05). There was no significant difference in liver function at 1 month after treatment between the two groups. The cholinesterase (CHE) level in the CSM-TACE+PSE group after CSM-TACE+PSE was obviously higher than that before CSM-TACE+PSE and higher than that in the CSM-TACE group (P<0.05). However, the level of CHE returned to the preoperative level 1 month after CSM-TACE in the CSM-TACE group. The objective response rate (ORR) and median overall survival (OS) in the CSM-TACE+PSE group were higher than those in the CSM-TACE group (P<0.05). The adverse reactions of the two groups were fever, abdominal pain, stomach discomfort, nausea, and vomiting, and no serious complications occurred. The degree of abdominal pain and fever in the experimental group was lower than that in the control group (P > 0.05). CONCLUSIONS: Simultaneous CSM-TACE and PSE using domestic embolization particles for HCC with hypersplenism have good safety and efficacy and has a low incidence of PSE-related adverse events, it is conducive to improving liver function reserve, and can further improve the median OS.
ESTHER : Zhou_2022_Front.Oncol_12_998500
PubMedSearch : Zhou_2022_Front.Oncol_12_998500
PubMedID: 36530976

Title : Bioactivity of hamamelitannin, flavokawain A, and triacetyl resveratrol as natural compounds: Molecular docking study, anti-colon cancer and anti-Alzheimer potentials - Zhang_2022_Biotechnol.Appl.Biochem__
Author(s) : Zhang M , Xue J , Chen X , Elsaid FG , Salem ET , Ghanem RA , El-Kott AF , Xu Z
Ref : Biotechnol Appl Biochem , : , 2022
Abstract : In this study, we worked on anti-colon cancer effects and anti-Alzheimer's disease with molecular docking studies. Hamamelitannin, Flavokawain A, Triacetyl resveratrol compounds showed good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. For obtaining the inhibition effects of flavokawain A, hamamelitannin, and triacetyl resveratrol on AChE and BuChE enzymes were determined spectrophotometrically conforming to Ellman. IC(50) values of these enzymes were ranging between 0.95+/-0.12 to 93.27+/-8.14 nM for AChE and 5.71+/-0.77 to 52.10+/-8.41 nM for BuChE. The inhibitory activities of some chemical compounds such as flavokawain A, hamamelitannin, and triacetyl resveratrol were assessed by performing the molecular docking study in the presence of AChE and BChE. Also, about the features of the ligand-enzyme complex that had value of -7.722 kcal/mol for flavokawain A against AChE and -5.530 kcal/mol against BuChE. The molecular docking calculations indicated the probable interactions and their characteristics at an atomic level. Due to the outcomes gained from docking, the affinity of the chemical compounds to the enzymes was considerable. In vitro cell viabilities of Flavokawain A, Hamamelitannin, Triacetyl resveratrol with various concentrations on SW620, DLD-1, HT29, HCT8, and HCT116 were investigated by MTT assay with Dox (Doxorubicin) as the control compound. This article is protected by copyright. All rights reserved.
ESTHER : Zhang_2022_Biotechnol.Appl.Biochem__
PubMedSearch : Zhang_2022_Biotechnol.Appl.Biochem__
PubMedID: 35933706

Title : In vitro absorption and lipid-lowering activity of baicalin esters synthesized by whole-cell catalyzed esterification - Zhang_2022_Bioorg.Chem_120_105628
Author(s) : Zhang M , Xin X , Zhao G , Zou Y , Li XF
Ref : Bioorg Chem , 120 :105628 , 2022
Abstract : Baicalin, a phenolic glycoside with good lipid-lowering activity, has poor intestinal absorption due to low lipophilicity. In this study, six ester derivatives of baicalin, named BECn (n = 2, 3, 4, 6, 8, and 10) based on their fatty chain lengths, were synthesized by whole-cell catalyzed esterification to improve lipophilicity, and the intestinal absorption and lipid-lowering activity of the synthesized esters were investigated using cell models in vitro. BEC2, BEC3, and BEC4 exhibited higher P(app) values than baicalin in Caco-2 cell monolayers. The lipid-lowering activity of the three esters was stronger than baicalin in the cell models of hepatic steatosis, adipocytes and foam macrophages, and was attributed to their higher intracellular accumulation and stronger direct activation of the carnitine palmitoyltransferase 1A. Moreover, these esters were easily hydrolyzed by carboxylesterase and were unstable at pH 7.4, which significantly weakened their absorption and lipid-lowering activity. This study laid the foundation for industrial production and practical application of BAI esters.
ESTHER : Zhang_2022_Bioorg.Chem_120_105628
PubMedSearch : Zhang_2022_Bioorg.Chem_120_105628
PubMedID: 35066316

Title : Strigolactone signaling complex formation in yeast: A paradigm for studying hormone-induced receptor interaction with multiple downstream proteins - Yu_2022_Methods.Enzymol_674_519
Author(s) : Yu H , Yang L , Long H , Su X , Wang Y , Xing Q , Yao R , Zhang M , Chen L
Ref : Methods Enzymol , 674 :519 , 2022
Abstract : Strigolactones (SLs) are bioactive carotenoid derivatives which function as signaling molecules to regulate plant architecture, nutrient absorption and communication with other organisms. The alpha/beta-fold hydrolase, D14, hydrolyzes SLs, and the hydrolysis product activates D14 to bind to downstream signaling partners, including an E3 ubiquitin ligase MAX2 and SMXL6/7/8 proteins. What was not known was whether binding with one downstream partner would alter the affinity of D14 for other binding partners. Here, we developed an efficient yeast four-hybrid (Y4H) detection system and demonstrate that SL induces the interaction of D14 with both SMXL7 and MAX2 in a dose-dependent manner. Moreover, using our newly established yeast four-hybrid system, we found that the SL-induced D14 interaction with SMXL7 was strengthened by MAX2 while SMXL7 weakened the SL-induced D14 interaction with MAX2. Our findings provide novel insights into the regulatory effects of these signaling components and shed light on the molecular mechanism controlling the core SL signaling pathway. Furthermore, the heterologous yeast platform used for investigating SL complex formation has great potential to explore dynamic interactions in other signaling pathways or elucidate the unknown complex formation for biosynthesis of the parent carotenoids of SLs.
ESTHER : Yu_2022_Methods.Enzymol_674_519
PubMedSearch : Yu_2022_Methods.Enzymol_674_519
PubMedID: 36008019

Title : Chain-locked precursor ion scanning based HPLC-MS\/MS for in-depth molecular analysis of lipase-catalyzed transesterification of structured phospholipids containing w-3 fatty acyl chains - Zhang_2022_Food.Chem_399_133982
Author(s) : Zhang M , Wang P , Jin D , Jian S , Wu J , Huang M , Xie H , Zhao Q , Yang H , Luo P , Yuan H , Xue J , Shen Q
Ref : Food Chem , 399 :133982 , 2022
Abstract : Lipase-catalyzed transesterification of structured phospholipids (sPLs) is a hot topic, but the structural variation of the fatty acyl chains in intact phospholipids at the molecular level remains unclear to date. The present study explored the detailed characteristics of synthesized phospholipids through high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in precursor ion scan mode. The optimal conditions were in-depth inspected and determined for the reaction system, including phospholipase A1 as catalyst, 15% lipase loading, and 1% water content. The sPLs enriched with EPA/DHA were structurally and quantitatively characterized by focusing on the fragments of m/z 301.6 (eicosapentaenoic acid, EPA) and m/z 327.6 (docosahexaenoic acid, DHA), and the results were statistically analyzed using partial least squares discriminant analysis and clustered heatmap hierarchical clustering analysis. PC 38:6 (18:1/20:5), PC 38:7 (18:2/20:5), PC o-40:6 (o-18:0/22:6), and PE 40:8 (18:2/22:6) etc. were revealed as the main variables that were active in the reaction.
ESTHER : Zhang_2022_Food.Chem_399_133982
PubMedSearch : Zhang_2022_Food.Chem_399_133982
PubMedID: 36027811

Title : Hemoperfusion in combination with hemofiltration for acute severe organophosphorus pesticide poisoning: A systematic review and meta-analysis - Zhang_2022_J.Res.Med.Sci_27_33
Author(s) : Zhang M , Zhang W , Zhao S , Tian X , Fu G , Wang B
Ref : J Res Med Sci , 27 :33 , 2022
Abstract : BACKGROUND: Acute severe organophosphorus pesticide poisoning (ASOPP) is one of the major diseases that endanger human life and health. However, the effects of conventional therapy including gastric lavages, mechanical ventilation, muscarinic antagonist drugs, and cholinesterase reactivators were uncertain. This meta-analysis aims to investigate the safety and efficacy of hemoperfusion combined with hemofiltration besides routine therapy for ASOPP. MATERIALS AND METHODS: A comprehensive search for candidate publications was performed through PubMed, Medline, Cochrane Library, WanFang, Chinese Biomedical Literature, and China National Knowledge Infrastructure from database inception to May 12, 2020. The retrieved studies were screened by the predefined inclusion and exclusion criteria. The data of important end points were extracted. The risk ratio (RR) and weighted mean difference (WMD) were pooled for categorical variables and continuous variables, respectively. Meta-analyses and publication bias were conducted by using STATA software version 15.1. RESULTS: A total of 11 randomized controlled trials with 811 patients were included. Compared to conventional therapy group, patients in the hemoperfusion plus hemofiltration group were significantly superior with regard to mortality (RR 0.38, 95% confidence interval [CI] [0.25, 0.57], P < 0.001), total atropine dosing (WMD -147.34 mg, 95% CI [-199.49, -95.18], P < 0.001), duration of mechanical ventilation (WMD -2.34 days, 95% CI [-3.77, -0.92], P < 0.001), cholinesterase recovery time (WMD -2.49 days, 95% CI [-3.14, -1.83], P < 0.001), and length of stay (WMD -4.52 days, 95% CI [-5.31, -3.73], P < 0.001). CONCLUSION: Combined hemoperfusion and hemofiltration was a very safe and effective treatment protocol for ASOPP, not only resulting in significantly decreased mortality but also resulting in reduced total atropine dosing, duration of mechanical ventilation, cholinesterase recovery time, and length of stay.
ESTHER : Zhang_2022_J.Res.Med.Sci_27_33
PubMedSearch : Zhang_2022_J.Res.Med.Sci_27_33
PubMedID: 35548179

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

Title : A New Berberine Preparation Protects Pancreatic Islet Cells from Apoptosis Mediated by Inhibition of Phospholipase A(2)\/p38 MAPK Pathway - Bi_2022_Bull.Exp.Biol.Med_173_346
Author(s) : Bi XJ , Lv YQ , Yang XH , Ge Y , Han H , Feng JS , Zhang M , Chen L , Xu MZ , Guan FY
Ref : Bulletin of Experimental Biology & Medicine , 173 :346 , 2022
Abstract : We studied an amorphous solid dispersion of berberine with absorption enhancer sodium caprate (Huang-Gui solid dispersion preparations, HGSD). A therapeutic effect of HGSD was revealed in mice with type 2 diabetes mellitus and palmitate-induced injury to MIN6 beta-cells. HGSD treatment (150 mg/kg) improved glucose metabolism and decreased beta-cell apoptosis in diabetic mice. Furthermore, the effective component of HGSD berberine significantly attenuated the palmitate-induced decrease in MIN6 beta-cells viability and insulin secretion. Moreover, molecular docking analysis and Western blotting showed that berberine decreased cell apoptosis and expression of group VIA phospholipase A(2) (iPLA(2)), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3. These data suggest that HGSD treatment protected beta-cells via inhibiting the iPLA(2)/p38 MAPK pathway.
ESTHER : Bi_2022_Bull.Exp.Biol.Med_173_346
PubMedSearch : Bi_2022_Bull.Exp.Biol.Med_173_346
PubMedID: 35852692

Title : Comparative Genomic Analysis of Carbofuran-Degrading Sphingomonads Reveals the Carbofuran Catabolism Mechanism in Sphingobium sp. Strain CFD-1 - Jiang_2022_Appl.Environ.Microbiol__e0102422
Author(s) : Jiang W , Zhang M , Gao S , Zhu Q , Qiu J , Yan X , Xin F , Jiang M , Hong Q
Ref : Applied Environmental Microbiology , :e0102422 , 2022
Abstract : The worldwide use of the carbamate insecticide carbofuran has caused considerable concern about its environmental fate. Degradation of carbofuran by Sphingobium sp. strain CFD-1 is initiated via the hydrolysis of its ester bond by carbamate hydrolase CehA to form carbofuran phenol. In this study, another carbofuran-degrading strain, Sphingobium sp. CFD-2, was isolated. Subsequently, a cfd gene cluster responsible for the catabolism of carbofuran phenol was predicted by comparing the genomes of strains CFD-1, CFD-2, and Novosphingobium sp. strain KN65.2. The key genes verified to be involved in the catabolism of carbofuran phenol within the cfd cluster include the hydroxylase gene cfdC, epoxide hydrolase gene cfdF, and ring cleavage dioxygenase gene cfdE and are responsible for the successive conversion of carbofuran phenol, resulting in complete ring cleavage. These carbofuran-catabolic genes (cehA and the cfd cluster) are distributed on two plasmids in strain CFD-1 and are highly conserved among the carbofuran-degrading sphingomonad strains. The mobile genetic element IS6100 flanks cehA and the cfd gene cluster, indicating the importance of horizontal gene transfer in the formation of carbofuran degradation gene clusters. The elucidation of the molecular mechanism of carbofuran catabolism provides insights into the evolutionary scenario of the conserved carbofuran catabolic pathway. IMPORTANCE Owing to the extensive use of carbofuran over the past 50 years, bacteria have evolved catabolic pathways to mineralize this insecticide, which plays an important role in eliminating carbofuran residue in the environment. In this study, the cfd gene cluster, responsible for the catabolism of carbofuran phenol, was predicted by comparing sphingomonad genomes. The function of key enzymatic genes in this gene cluster was identified. Furthermore, the carbamate hydrolase gene cehA and the cfd gene cluster are highly conserved in different carbofuran-degrading strains. Additionally, the horizontal gene transfer elements flanking the cfd gene cluster were investigated. These findings help elucidate the molecular mechanism of microbial carbofuran degradation and enhance our understanding of the evolutionary mechanism of the carbofuran catabolic pathway.
ESTHER : Jiang_2022_Appl.Environ.Microbiol__e0102422
PubMedSearch : Jiang_2022_Appl.Environ.Microbiol__e0102422
PubMedID: 36314801

Title : Pseudo toxicity abatement effect of norfloxacin and copper combined exposure on Caenorhabditis elegans - Liu_2022_Chemosphere_287_132019
Author(s) : Liu L , He S , Tang M , Zhang M , Wang C , Wang Z , Sun F , Yan Y , Li H , Lin K
Ref : Chemosphere , 287 :132019 , 2022
Abstract : The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 microM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 microM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 microM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 microM and 1.25 microM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 microM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.
ESTHER : Liu_2022_Chemosphere_287_132019
PubMedSearch : Liu_2022_Chemosphere_287_132019
PubMedID: 34450372

Title : Genes, Structural, and Biochemical Characterization of Four Chlorophyllases from Solanum lycopersicum - Liu_2022_Int.J.Mol.Sci_23_11716
Author(s) : Liu G , Meng X , Ren Y , Zhang M , Chen Z , Zhang Z , Pang X , Zhang X
Ref : Int J Mol Sci , 23 :11716 , 2022
Abstract : Recent studies have confirmed that chlorophyllase (CLH), a long-found chlorophyll (Chl) dephytylation enzyme for initiating Chl catabolism, has no function in leaf senescence-related Chl breakdown. Yet, CLH is considered to be involved in fruit degreening and responds to external and hormonal stimuli. The purpose of this work was to elucidate in detail the biochemical, structural properties, and gene expression of four CLHs from the Solanum lycopersicum genome so as to understand the roles of Solanum lycopersicum chlorophyllases (SlCLHs). SlCLH1/4 were the predominantly expressed CLH genes during leaf and fruit development/ripening stages, and SlCLH1 in mature green fruit was modulated by light. SlCLH1/2/3/4 contained a highly conserved GHSXG lipase motif and a Ser-Asp-His catalytic triad. We identified Ser159, Asp226, and His258 as the essential catalytic triad by site-directed mutagenesis in recombinant SlCLH1. Kinetic analysis of the recombinant enzymes revealed that SlCLH1 had high hydrolysis activities against Chl a, Chl b, and pheophytin a (Phein a), but preferred Chl a and Chl b over Phein a; SlCLH2/3 only showed very low activity to Chl a and Chl b, while SlCLH4 showed no Chl dephytylation activity. The recombinant SlCLH1/2/3 had different pH stability and temperature optimum. Removal of the predicted N-terminal processing peptide caused a partial loss of activity in recombinant SlCLH1/2 but did not compromise SlCLH3 activity. These different characteristics among SlCLHs imply that they may have different physiological functions in tomato.
ESTHER : Liu_2022_Int.J.Mol.Sci_23_11716
PubMedSearch : Liu_2022_Int.J.Mol.Sci_23_11716
PubMedID: 36233017

Title : A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 \% Ho(3+)@NaYF(4) upconversion nano-probe - Zhao_2021_Talanta_235_122784
Author(s) : Zhao X , Zhang L , Yan X , Lu Y , Pan J , Zhang M , Wang C , Suo H , Jia X , Liu X , Lu G
Ref : Talanta , 235 :122784 , 2021
Abstract : Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.
ESTHER : Zhao_2021_Talanta_235_122784
PubMedSearch : Zhao_2021_Talanta_235_122784
PubMedID: 34517642

Title : Heterologous expression and exploration of the enzymatic properties of the carbaryl hydrolase CarH from a newly isolated carbaryl-degrading strain - Ke_2021_Ecotoxicol.Environ.Saf_224_112666
Author(s) : Ke Z , Zhu Q , Jiang W , Zhou Y , Zhang M , Jiang M , Hong Q
Ref : Ecotoxicology & Environmental Safety , 224 :112666 , 2021
Abstract : Carbaryl is the representative of carbamate insecticide. As an acetylcholinesterase inhibitor, it poses potential threat to humans and other non-target organisms. Agrobacterium sp. XWY-2, which could grow with carbaryl as the sole carbon source, was isolated and characterized. The carH gene, encoding a carbaryl hydrolase, was cloned from strain XWY-2 and expressed in Escherichia coli BL21 (DE3). CarH was able to hydrolyze carbamate pesticides including carbaryl, carbofuran, isoprocarb, propoxur and fenobucarb efficiently, while it hydrolyzed oxamyl and aldicarb poorly. The optimal pH of CarH was 8.0 and the optimal temperature was 30 degC. The apparent K(m) and k(cat) values of CarH for carbaryl were 38.01 +/- 2.81 microM and 0.33 +/- 0.01 s(-1), respectively. The point mutation experiment demonstrated that His341, His343, His346, His416 and D437 are the key sites for CarH to hydrolyze carbaryl.
ESTHER : Ke_2021_Ecotoxicol.Environ.Saf_224_112666
PubMedSearch : Ke_2021_Ecotoxicol.Environ.Saf_224_112666
PubMedID: 34416635

Title : Liamocins biosynthesis, its regulation in Aureobasidium spp., and their bioactivities - Kang_2021_Crit.Rev.Biotechnol__1
Author(s) : Kang XX , Jia SL , Wei X , Zhang M , Liu GL , Hu Z , Chi Z , Chi ZM
Ref : Critical Reviews in Biotechnology , :1 , 2021
Abstract : Liamocins synthesized by Aureobasidium spp. are glycolipids composed of a single mannitol or arabitol headgroup linked to either three, four or even six 3,5-dihydroxydecanoic ester tail-groups. The highest titer of liamocin achieved was over 40.0 g/L. The substrates for liamocins synthesis include glucose, sucrose, xylose, mannitol, and others. The Pks1 is responsible for the biosynthesis of the tail-group 3,5-dihydroxydecanoic acid, both mannitol dehydrogenase (MDH) and mannitol 1-phosphate 5-dehydrogenase (MPDH) catalyze the mannitol biosynthesis and the arabitol biosynthesis is controlled by arabitol dehydrogenase (ArDH). The ester bond formation between 3,5-dihydroxydecanoic acid and mannitol or arabitol is catalyzed by the esterase (Est1). Liamocin biosynthesis is regulated by the specific transcriptional activator (Gal1), global transcriptional activator (Msn2), various signaling pathways, acetyl-CoA flux while Pks1 activity is controlled by PPTase activity. The synthesized liamocins have high bioactivity against the pathogenic bacteria Streptococcus spp. and some kinds of cancer cells while Massoia lactone released liamocins which exhibited obvious antifungal and anticancer activities. Therefore, liamocins and Massoia lactone have many applications in various sectors of biotechnology.
ESTHER : Kang_2021_Crit.Rev.Biotechnol__1
PubMedSearch : Kang_2021_Crit.Rev.Biotechnol__1
PubMedID: 34154468

Title : Identification of Conserved and Divergent Strigolactone Receptors in Sugarcane Reveals a Key Residue Crucial for Plant Branching Control - Hu_2021_Front.Plant.Sci_12_747160
Author(s) : Hu A , Zhao Q , Chen L , Zhao J , Wang Y , Feng K , Wu L , Xie M , Zhou X , Xiao L , Ming Z , Zhang M , Yao R
Ref : Front Plant Sci , 12 :747160 , 2021
Abstract : Strigolactones (SLs) are a class of important plant hormones mainly regulating plant architecture such as branching, which is crucial for crop yield. It is valuable to study SL signaling pathway and its physiological function in sugarcane, the most important sugar crop, for further molecular breeding. Here, two putative SL receptors SsD14a/b and the interacting F-box protein SsMAX2 were identified in Saccharum spontaneum. SL induced both SsD14a and SsD14b to interact with SsMAX2 in yeast. SsD14a, but not SsD14b, could bind with AtMAX2 and AtSMXL7/SsSMXL7. Overexpression of SsD14a or SsMAX2 rescued the increased branching phenotypes of Arabidopsis thaliana d14-1 or max2-3 mutants, respectively. Moreover, the crystal structure of N-terminal truncated SsD14a was solved, with an overall structure identical to AtD14 and OsD14 in the open state, consistent with its conserved branching suppression capacity in Arabidopsis. In line with the biochemical observations, SsD14b could not completely complement in d14-1 although these two SsD14 proteins have almost identical primary sequences except for very few residues. Complement with the combination of SsD14b and SsMAX2 still failed to rescue the d14-1 max2-3 double mutant multi-branching phenotype, indicating SsD14b-AtSMXL7 complex formation is required for regulating branching. Mutagenesis analyses revealed that residue R310 at alpha10 helix of SsD14a was crucial for the binding with SsSMXL7/AtSMXL7 but not SsMAX2. The site-equivalent single-residue P304R substitution enabled SsD14b to bind with AtMAX2 and AtSMXL7/SsSMXL7 and to rescue the phenotype of d14-1 max2-3 together with SsMAX2. Moreover, this conserved Arg residue across species including rice and Arabidopsis determined the activity of SL receptors through maintaining their interaction with SMXL repressors. Taken together, our work identified conserved and divergent strigolactone receptors in sugarcane core SL signaling pathway and revealed a key residue crucial for plant branching control.
ESTHER : Hu_2021_Front.Plant.Sci_12_747160
PubMedSearch : Hu_2021_Front.Plant.Sci_12_747160
PubMedID: 34858455
Gene_locus related to this paper: 9poal-a0a0d5nt23

Title : Residual behaviors and metabolic pathway of ethylparaben in Drosophila melanogaster - Wang_2021_Ecotoxicol.Environ.Saf_230_113124
Author(s) : Wang Y , Qin M , Wang X , Han J , Chen R , Zhang M , Gu W
Ref : Ecotoxicology & Environmental Safety , 230 :113124 , 2021
Abstract : OBJECTIVE: Parabens are commonly used as preservatives in foodstuffs, cosmetics, and pharmaceutical products. The widespread use of parabens has led to their leaking into the environment. Concerns about the safety of parabens have recently increased due to their potential endocrine-disrupting effects as an emerging contaminant. Thus, it is necessary to study the metabolism of parabens in vivo. METHODS: In this study, Drosophila melanogaster in males and females were exposed to ethylparaben (EP) concentration group (300 mg/L, 700 mg/L, and 1000 mg/L), and control group (0 mg/L) by the capillary feeding assay (CAFE). We quantified the activity of the detoxification-related carboxylesterase (CarE). The contents of EP metabolites in D. melanogaster, including p-hydroxybenzoic acid (PHBA), methylparaben (MP), and intact EP were carried out by high-performance liquid chromatography (HPLC). The regression model between EP metabolites (PHBA and MP) and CarE was developed using the Fourier series fitting method. RESULTS: The general level of EP metabolites (PHBA, MP, and intact EP) accumulation was accounted for 5.6-11.5% in D. melanogaster. As EP accumulated, the activity of CarE increased, and the activity of CarE in females was higher than males, which is inconsistent with the result of EP intake dose. Additionally, there were significant differences in the proportion of EP metabolites between female and male flies, and the results of sex comparison were different depending on the EP treated groups and EP metabolites. In general, PHBA of EP hydrolytic product and MP of EP transesterification product in D. melanogaster were 41.4-63.9% and 10.4-24.6%, respectively. In terms of the rest of the EP existed in intact form and ranged from 22.4% to 34.0%. Moreover, the EP metabolites in the conjugated form were higher than those in the free form. The regression model between EP metabolites and CarE was established, showing that the CarE activity can be used to estimate the content of PHBA and MP. CONCLUSION: The result indicates that the EP can accumulate in the body through food. Hydrolysis is the main metabolic pathway of EP in D. melanogaster, and transesterification is another metabolic pathway of EP. Additionally, the EP metabolites in flies mainly exist in conjugated form. Furthermore, the Fourier series fitting method model between EP metabolites and CarE, providing theoretical support to study the dose-effect relationship between metabolites of parabens and CarE. This study not only provides a mathematical basis for the safety evaluation of parabens, but also provides support for the further study of the toxicological effects of parabens.
ESTHER : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedSearch : Wang_2021_Ecotoxicol.Environ.Saf_230_113124
PubMedID: 34968799

Title : Identification of Detoxification Esterase StrH Initiating Strobilurin Fungicides Degradation in Hyphomicrobium sp. DY-1 - Jiang_2021_Appl.Environ.Microbiol__
Author(s) : Jiang W , Gao Q , Zhang L , Liu Y , Zhang M , Ke Z , Zhou Y , Hong Q
Ref : Applied Environmental Microbiology , : , 2021
Abstract : Strobilurin fungicides are widely used in agricultural production due to their broad-spectrum and fungal mitochondrial inhibitory activities. However, their massive application has detained the growth of eukaryotic algae and increased the collateral damage in freshwater systems, notably the harmful cyanobacterial blooms (HCBs). In this study, a strobilurin fungicide-degrading strain Hyphomicrobium sp. DY-1 was isolated and characterized successfully. Moreover, a novel esterase gene strH responsible for the de-esterification of strobilurin fungicides was cloned, and the enzymatic properties of StrH were studied. For trifloxystrobin, StrH displayed the maximum activity at 50 degreesC and pH 7.0. The catalytic efficiency (k (cat)/K (m)) of StrH for different strobilurin fungicides were 196.32+/-2.30 microM(-1).s(-1) (trifloxystrobin), 4.64+/-0.05 microM(-1).s(-1) (picoxystrobin), 2.94+/-0.02 microM(-1).s(-1) (pyraclostrobin), and (2.41+/-0.19)x10(-2) microM(-1).s(-1) (azoxystrobin). StrH catalyzed the de-esterification of a variety of strobilurin fungicides generating the corresponding parent acid to achieve the detoxification of strobilurin fungicides and relieve strobilurin fungicides growth inhibition on Chlorella This research will provide insight into the microbial remediation of strobilurin fungicides-contaminated environments.IMPORTANCEStrobilurin fungicides have been widely acknowledged as an essential group of pesticides worldwide. So far, their residues and toxic effects on aquatic organisms have been reported in different parts of the world. Microbial degradation could eliminate xenobiotics from the environment. Therefore, the degradation of strobilurin fungicides by microorganisms has also been reported. However, little is known about the involvement of enzyme or gene in strobilurin fungicides degradation. In this study, a novel esterase gene strH responsible for the detoxification of strobilurin fungicides was cloned in the newly isolated strain Hyphomicrobium sp. DY-1. This degradation process detoxifies the strobilurin fungicides and relieves their growth inhibition on Chlorella.
ESTHER : Jiang_2021_Appl.Environ.Microbiol__
PubMedSearch : Jiang_2021_Appl.Environ.Microbiol__
PubMedID: 33741617
Gene_locus related to this paper: hypsm-strH

Title : NLGN3 Upregulates Expression of ADAM10 to Promote the Cleavage of NLGN3 via Activating the LYN Pathway in Human Gliomas - Dang_2021_Front.Cell.Dev.Biol_9_662763
Author(s) : Dang NN , Li XB , Zhang M , Han C , Fan XY , Huang SH
Ref : Front Cell Developmental Biology , 9 :662763 , 2021
Abstract : The neuron derived synaptic adhesion molecular neuroligin-3 (NLGN3) plays an important role in glioma growth. While the role of autocrine NLGN3 in glioma has not been well-studied. The expression of NLGN3 in glioma was detected using immunohistochemistry. We further explored its function and regulatory mechanism in U251 and U87 cells with high expression of NLGN3. Knockdown of endogenous NLGN3 significantly reduced the proliferation, migration, and invasion of glioma cells and down-regulated the activity of the PI3K-AKT, ERK1/2, and LYN signaling pathways. In comparison, overexpression of NLGN3 yielded opposite results. Our results further demonstrate that LYN functions as a feedback mechanism to promote NLGN3 cleavage. This feedback regulation was achieved by upregulating the ADAM10 sheddase responsible for NLGN3 cleavage. Inhibition of ADAM10 suppressed the proliferation, migration, and invasion of glioma cells; oppositely, the expression of ADAM10 was correlated with a higher likelihood of lower grade glioma (LGG) in the brain. Our study demonstrates that glioma-derived NLGN3 promotes glioma progression by upregulating activity of LYN and ADAM10, which in turn promote NLGN3 cleavage to form a positive feedback loop. This pathway may open a potential therapeutic window for the treatment of human glioma.
ESTHER : Dang_2021_Front.Cell.Dev.Biol_9_662763
PubMedSearch : Dang_2021_Front.Cell.Dev.Biol_9_662763
PubMedID: 34485271
Gene_locus related to this paper: human-NLGN3

Title : Cholinesterase homozygous genotype as susceptible biomarker of hypertriglyceridemia for pesticide-exposed agricultural workers - Zhou_2021_Biomarkers__1
Author(s) : Zhou X , Zhang M , Wang Y , Xia H , Zhu L , Li G , Rong L , Dong H , Chen R , Tang S , Yu M
Ref : Biomarkers , :1 , 2021
Abstract : PURPOSE: Dyslipidemia is an emerging metabolic disorder among pesticide-exposed agricultural workers, and this study was aimed to explore biomarkers of hypertriglyceridemia susceptibility. METHODS: This cross-sectional study recruited 72 pesticide-exposed subjects and 78 non-exposed controls. Lipid profile, cholinesterase activity, and thyroid hormones were analyzed with routine assays. Six loci, including rs11206244 and rs2235544 for deiodinase 1, rs12885300 and rs225014 for deiodinase 2, rs1803274 for butyrylcholinesterase, and rs3757869 for acetylcholinesterase were genotyped using an improved multiplex ligation detection reaction technique. RESULTS: Pesticide-exposed subjects showed higher levels of triglyceride than controls (p = 0.009), although there were comparable cholinesterase activity and genotype frequencies of all six loci between pesticide-exposed subjects and controls. Pesticide-exposed subjects with homozygous genotype of cholinesterasehad increased triglyceride levels than controls (p < 0.05). The percentage of hypertriglyceridemia was 28.6% and 8.8% for pesticide-exposed subjects and controls with homozygous butyrylcholinesterase genotype (p = 0.007) and 20.8% and 14.3% with homozygous acetylcholinesterase genotype (p = 0.792), respectively. Multivariate logistic regression analyses found that odds ratio of hypertriglyceridemia is 21.92 and 4.56 for pesticide-exposed subjects with homozygous genotype of butyrylcholinesterase (p = 0.001) and acetylcholinesterase (p = 0.036), respectively. CONCLUSIONS: Cholinesterase homozygous genotype might be a potential susceptible biomarker in screening pesticide-exposed agricultural workers vulnerable to hypertriglyceridemia.
ESTHER : Zhou_2021_Biomarkers__1
PubMedSearch : Zhou_2021_Biomarkers__1
PubMedID: 33617373

Title : CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation - Hosokawa_2021_Nat.Neurosci__
Author(s) : Hosokawa T , Liu PW , Cai Q , Ferreira JS , Levet F , Butler C , Sibarita JB , Choquet D , Groc L , Hosy E , Zhang M , Hayashi Y
Ref : Nat Neurosci , : , 2021
Abstract : Transient information input to the brain leads to persistent changes in synaptic circuits, contributing to the formation of memory engrams. Pre- and postsynaptic structures undergo coordinated functional and structural changes during this process, but how such changes are achieved by their component molecules remains largely unknown. We found that activated CaMKII, a central player of synaptic plasticity, undergoes liquid-liquid phase separation with the NMDA-type glutamate receptor subunit GluN2B. Due to CaMKII autophosphorylation, the condensate stably persists even after Ca(2+) is removed. The selective binding of activated CaMKII with GluN2B cosegregates AMPA receptors and the synaptic adhesion molecule neuroligin into a phase-in-phase assembly. In this way, Ca(2+)-induced liquid-liquid phase separation of CaMKII has the potential to act as an activity-dependent mechanism to crosslink postsynaptic proteins, which may serve as a platform for synaptic reorganization associated with synaptic plasticity.
ESTHER : Hosokawa_2021_Nat.Neurosci__
PubMedSearch : Hosokawa_2021_Nat.Neurosci__
PubMedID: 33927400

Title : Thirteen cyathane diterpenoids with acetylcholinesterase inhibitory effects from the fungus Cyathus africanus - Yu_2021_Phytochemistry_193_112982
Author(s) : Yu M , Kang X , Li Q , Liang Y , Zhang M , Gong Y , Chen C , Zhu H , Zhang Y
Ref : Phytochemistry , 193 :112982 , 2021
Abstract : Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC(50) value of 4.60 +/- 0.85 microM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.
ESTHER : Yu_2021_Phytochemistry_193_112982
PubMedSearch : Yu_2021_Phytochemistry_193_112982
PubMedID: 34700067

Title : Natural soluble epoxide hydrolase inhibitors from Inula britanica and their potential interactions with soluble epoxide hydrolase: Insight from inhibition kinetics and molecular dynamics - Zhao_2021_Chem.Biol.Interact__109571
Author(s) : Zhao WY , Yan JJ , Zhang M , Wang C , Feng L , Lv X , Huo XK , Sun CP , Chen LX , Ma XC
Ref : Chemico-Biological Interactions , :109571 , 2021
Abstract : Soluble epoxide hydrolase (sEH) is a potential drug target to treat inammation and neurodegenerative diseases. In this study, we found that the extract of Inula britanica exhibited significantly inhibitory effects against sEH, therefore, we investigated its phytochemical constituents to obtain seven new compounds together with sixteen known ones (1-20), including two pairs of novel enantiomers, (2S,3S)-britanicafanin A (1a), (2R,3R)-britanicafanin A (1b), (2R,3S)-britanicafanin B (2a), and (2S,3R)-britanicafanin B (2b), and three new lignans britanicafanins C-E (3-5). Their structures were determined by HRESIMS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectra as well as quantum chemical computations. All the isolates were evaluated for their inhibitory effects against sEH, compounds 1-3, 5-7, 9, 10, 13, 14, and 17-20 showed significant inhibitory effects against sEH with IC(50) values from 3.56 microM to 26.93 microM. The inhibition kinetics results indicated that compounds 9, 10, 13, and 19 were all uncompetitive inhibitors, and their inhibition constants (K(i)) values were 7.11, 1.99, 4.06, and 8.78 microM, respectively. Their potential interactions were analyzed by molecular docking and molecular dynamics (MD), which suggested that amino acid residues Asp335 and Asn359, especially Gln384, played an important role in the inhibition of compounds 10 and 13 on sEH, and compounds 10 and 13 could be considered as the potential candidates for the development of sEH inhibitors.
ESTHER : Zhao_2021_Chem.Biol.Interact__109571
PubMedSearch : Zhao_2021_Chem.Biol.Interact__109571
PubMedID: 34217688

Title : A novel lipase from Aspergillus oryzae WZ007 catalyzed synthesis of brivaracetam intermediate and its enzymatic characterization - Li_2021_Chirality_33_62
Author(s) : Li Q , Zhang M , Li X , Zhang Y , Wang Z , Zheng J
Ref : Chirality , 33 :62 , 2021
Abstract : Brivaracetam is a structural derivative of the chiral drug levetiracetam and has been approved for the adjuvant treatment of partial epilepsy. As a new antiepileptic drug, it is widely used in a variety of epilepsy models. In this study, a novel lipase M16 derived from Aspergillus oryzae WZ007 was cloned, expressed, and used for chiral resolution. Lipase M16 has a high enantioselectivity to the racemic substrate (R,S)-methyl 2-propylsuccinate 4-tert-butyl ester, and the intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester of brivaracetam was obtained efficiently. Under optimal conditions, the enantiomeric excess of substrate was up to 99.26%, and the e.e.(p) was 96.23%. The conversion and apparent E value were 50.63% and 342.48, respectively. This study suggests a new biocatalytic resolution via lipase M16 for preparing the brivaracetam chiral intermediate and its potential application in the pharmaceutical industry.
ESTHER : Li_2021_Chirality_33_62
PubMedSearch : Li_2021_Chirality_33_62
PubMedID: 33274501

Title : Protective effects of chondroitin sulphate nano-selenium on a mouse model of Alzheimer's disease - Ji_2020_Int.J.Biol.Macromol__
Author(s) : Ji D , Wu X , Li D , Liu P , Zhang S , Gao D , Gao F , Zhang M , Xiao Y
Ref : Int J Biol Macromol , : , 2020
Abstract : In this study, the effect of chondroitin sulphate nano-selenium (CS@Se) on Alzheimer's disease (AD) in mice was investigated. CS@Se alleviated anxiety and improved the spatial learning and memory impairment in AD mice. CS@Se significantly reduced cell oedema and pyknosis, protected the mitochondria, and improved abnormal changes in the ultrastructure of hippocampal neuron synapses of AD mice. Moreover, CS@Se significantly increased the levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-Px), Na(+)/K(+)-ATPase assay (Na(+)/K(+)-ATPase) and acetyltransferase (ChAT), and decreased the levels of malondialdehyde (MDA) and acetylcholinesterase (ChAE) in AD mice. Western blot results showed that CS@Se can attenuate excessive phosphorylation of tau (Ser396/Ser404) by regulating the expression of glycogen synthase kinase-3 beta (GSK-3beta). In addition, CS@Se can activate the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) signalling pathways to inhibit nuclear transcription factor kappa B (NF-kappaB) nuclear translocation, thereby regulating the expression of pro-inflammatory cytokines. In summary, CS@Se can reduce oxidative stress damage, inhibit excessive tau phosphorylation, reduce inflammation to delay AD development, and increase the learning and memory capacities of AD mice.
ESTHER : Ji_2020_Int.J.Biol.Macromol__
PubMedSearch : Ji_2020_Int.J.Biol.Macromol__
PubMedID: 32171837

Title : GALNT2 regulates ANGPTL3 cleavage in cells and in vivo of mice - Li_2020_Sci.Rep_10_16168
Author(s) : Li X , Zhang Y , Zhang M , Wang Y
Ref : Sci Rep , 10 :16168 , 2020
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is an important inhibitor of lipoprotein lipase and endothelial lipase that plays critical roles in lipoprotein metabolism. It specifically expresses in the liver and undergoes proprotein convertase-mediated cleavage during secretion, which generates an N-terminal coiled-coil domain and C-terminal fibrinogen-like domain that has been considered as the activation step for its function. Previous studies have reported that the polypeptide GalNAc-transferase GALNT2 mediates the O-glycosylation of the ANGPTL3 near the cleavage site, which inhibits the proprotein convertase (PC)-mediated cleavage in vitro and in cultured cells. However, loss-of-function mutation for GALNT2 has no effect on ANGPTL3 cleavage in human. Thus whether GALNT2 regulates the cleavage of ANGPTL3 in vivo is unclear. In present study, we systematically characterized the cleavage of Angptl3 in cultured cells and in vivo of mice. We found that endogenous Angptl3 is cleaved in primary hepatocytes and in vivo of mice, and this cleavage can be blocked by Galnt2 overexpression or PC inhibition. Moreover, suppressing galnt2 expression increases the cleavage of Angptl3 in mice dramatically. Thus, our results support the conclusion that Galnt2 is a key endogenous regulator for Angptl3 cleavage both in vitro and in vivo.
ESTHER : Li_2020_Sci.Rep_10_16168
PubMedSearch : Li_2020_Sci.Rep_10_16168
PubMedID: 32999434

Title : Cognitive-enhancing effects of fibrauretine on Abeta1-42-induced Alzheimer's disease by compatibilization with ginsenosides - Zhang_2020_Neuropeptides__102020
Author(s) : Zhang M , Chen W , Zong Y , Shi K , Li J , Zeng F , He Z , Du R
Ref : Neuropeptides , :102020 , 2020
Abstract : Fibrauretine is the main active ingredient in rattan stems of Fibraurea recisa Pierre. The aim of this study was to evaluate the cognitive-enhancing effects and underlying molecular mechanisms of fibrauretine compatibilized with ginsenosides on Alzheimer's disease (AD) induced in mice with amyloid beta-protein (Abeta1-42). The results showed that the spatial learning and memory abilities of AD mice were significantly enhanced after combined treatment with fibrauretine and ginsenosides using the Morris water maze test. The levels of acetylcholinesterase (AChE) and phosphorylated Tau protein (p-Tau) in brain tissue and the levels of nitric oxide (NO), malondialdehyde (MDA), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were significantly increased in Abeta1-42-induced AD mice, and these effects were reversed after combined treatment with fibrauretine and ginsenosides. By contrast, a significant increase in the levels of catalase (CAT), superoxide dismutase (SOD), choline acetyltransferase (ChAT) and glutathione peroxidase (GSH-Px) was observed in the combined treatment group. The results of haematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) analysis, immunohistochemistry (IHC) and Western blot analysis showed that the apoptosis rate, Bax, nuclear factor kappa-B p65 (NF-kappaBp65), cleaved caspase-3 and cleaved caspase-9 expression levels were obviously decreased and that the Bcl-2 expression levels were significantly increased in the hippocampi of mice treated with fibrauretine and ginsenosides. The results of this study show that the ameliorative effect of fibrauretine against AD can be significantly enhanced by compatibilization with ginsenosides. The underlying molecular mechanisms of fibrauretine may be related to antioxidation and anti-apoptosis.
ESTHER : Zhang_2020_Neuropeptides__102020
PubMedSearch : Zhang_2020_Neuropeptides__102020
PubMedID: 31982159

Title : New Flavoalkaloids with Potent alpha-Glucosidase and Acetylcholinesterase Inhibitory Activities from Yunnan Black Tea 'Jin-Ya' - Li_2020_J.Agric.Food.Chem_68_7955
Author(s) : Li N , Zhu HT , Wang D , Zhang M , Yang CR , Zhang YJ
Ref : Journal of Agricultural and Food Chemistry , 68 :7955 , 2020
Abstract : As the subgroup of flavoalkaloids, N-ethyl-2-pyrrolidinone substituted flavan-3-ols are reported to possess various biological activities that may play important roles in the beneficial healthcare functions of tea. The HPLC and LC-MS analyses showed the existence of N-ethyl-2-pyrrolidinone substituted flavan-3-ols in 'Jin-Ya', which is a Yunnan black tea produced only from buds of tea plant, Camellia sinensis var. assamica. Further phytochemical study on this precious black tea led to the identification of eight flavoalkaloids, 1-8, along with 11 known flavan-3-ols (9-14) and flavonol glycosides (15-19). The new compounds, (-)-6-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin (1), (-)-8-(5''R)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2a) and (-)-8-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2b), were identified based on extensive spectroscopic analysis. Flavoalkaloids 2-6 showed inhibitory activity on alpha-glucosidase with IC50 values ranging from 2.09 to 8.47 muM, comparing to those of quercetin and acarbose (IC50 = 6.87 and 228.9 muM, resp.). Moreover, compounds 2, 3 and 6 displayed inhibitory effect on acetyl-cholinesterase with IC50 values of 14.23, 33.79 and 34.82 muM, respectively, comparing to tacrine (IC50 = 0.223 muM).
ESTHER : Li_2020_J.Agric.Food.Chem_68_7955
PubMedSearch : Li_2020_J.Agric.Food.Chem_68_7955
PubMedID: 32628847

Title : Characterization of a novel halotolerant esterase from Chromohalobacter canadensis isolated from salt well mine - Wang_2020_3.Biotech_10_430
Author(s) : Wang M , Ai L , Zhang M , Wang F , Wang C
Ref : 3 Biotech , 10 :430 , 2020
Abstract : A esterase gene was characterized from a halophilic bacterium Chromohalobacter canadensis which was originally isolated from a salt well mine. Sequence analysis showed that the esterase, named as EstSHJ2, contained active site serine encompassed by a conserved pentapeptide motif (GSSMG). The EstSHJ2 was classified into a new lipase/esterase family by phylogenetic association analysis. Molecular weight of EstSHJ2 was 26 kDa and the preferred substrate was p-NP butyrate. The EstSHJ2 exhibited a maximum activity at 2.5 M NaCl concentration. Intriguingly, the optimum temperature, pH and stability of EstSHJ2 were related to NaCl concentration. At 2.5 M NaCl concentration, the optimum temperature and pH of EstSHJ2 were 65 C and pH 9.0, and enzyme remained 81% active after 80 C treatment for 2 h. Additionally, the EstSHJ2 showed strong tolerance to metal ions and organic solvents. Among these, 10 mM K(+), Ca(2+) , Mg(2+) and 30% hexane, benzene, toluene has significantly improved activity of EstSHJ2. The EstSHJ2 was the first reported esterase from Chromohalobacter canadensis, and may carry considerable potential for industrial applications under extreme conditions.
ESTHER : Wang_2020_3.Biotech_10_430
PubMedSearch : Wang_2020_3.Biotech_10_430
PubMedID: 32983823
Gene_locus related to this paper: 9gamm-EstSHJ2

Title : Effect of salt promote the muscle triglyceride hydrolysis during dry-salting by inducing the phosphorylation of adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and lipid droplets splitting - Zhao_2020_Food.Chem_327_127061
Author(s) : Zhao S , He L , Zhang M , Liu X , Jin G
Ref : Food Chem , 327 :127061 , 2020
Abstract : This study mainly investigated the effect of different salt concentrations (1, 3, or 5%) on triglycerides (TG) hydrolysis in muscle during salting by analyzing moisture distribution, TG hydrolysis, TG hydrolase activity, native and phosphorylated adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content, lipid droplets morphology, and muscle microstructure. The results showed that increasing salt concentration could significantly decrease T21 moisture proportion and relaxation time (p < 0.05), which was more beneficial to the lipase activity. The TG hydrolase activity increased first and then decreased with the salt concentration increasing during dry-salting process, and 3% salt concentration was the point of inflection. Western blot (WB) analysis detected both ATGL, HSL and their phosphorylated proteins, which were increased with the salt content increase. The microstructure analysis showed that the lipid droplets were split into small lipid droplets with the increase of salt content, which was more conducive to the triglycerides hydrolysis.
ESTHER : Zhao_2020_Food.Chem_327_127061
PubMedSearch : Zhao_2020_Food.Chem_327_127061
PubMedID: 32454271

Title : Limonoids with diverse structures of rings-A,B from the Thai mangrove, Xylocarpus moluccensis - Shen_2020_Fitoterapia__104737
Author(s) : Shen L , Liao Q , Zhang M , Wu J
Ref : Fitoterapia , :104737 , 2020
Abstract : Nine new limonoids, named thaixylomolins S-Z (1-8) and 2-O-acetylthaixylomolin Z (9), were isolated from seeds of the mangrove, Xylocarpus moluccensis, collected in the mangrove swamp of Trang Province, Thailand. Thaixylomolin S (1) is the fourth member of the khayalactone class of limonoids containing a hexahydro-2H-2,5- propanocyclopenta[b]furan motif. Thaixylomolins T-Y (2-7) are structurally diverse mexicanolides; whereas thaixylomolin Z (8) and 2-O-acetylthaixylomolin Z (9) are phragmalin 8,9,30-orthoesters. The structures of these compounds were established by HRESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of thaixylomolins S (1), U (3), and Z (8) were unambiguously established by single-crystal X-ray diffraction analyses, conducted with Cu Kalpha radiation; whereas that of 2-O-acetylthaixylomolin Z (9) was determined to be the same as that of thaixylomolin Z (8) by the accurate fit of their experimental electronic circular dichroism spectra. Thaixylomolin S (1), featuring the presence of a 30-(2'-methyl)butyryloxy group, is the first limonoid of the khayalactone class, whose constitution and absolute configuration are unequivocally determined by X-ray crystallography. The inhibitory activities of all the compounds, except for the epimers 4, were assayed against human carboxylesterase 2. All the tested compounds exhibited inhibition rates in the range of 16-65% at the concentration of 100.0muM.
ESTHER : Shen_2020_Fitoterapia__104737
PubMedSearch : Shen_2020_Fitoterapia__104737
PubMedID: 33022332

Title : Directed evolution of Aspergillus oryzae lipase for the efficient resolution of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate - Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
Author(s) : Zhang M , Li Q , Lan X , Li X , Zhang Y , Wang Z , Zheng J
Ref : Bioprocess Biosyst Eng , 43 :2131 , 2020
Abstract : Aspergillus oryzae lipase (AOL) is a potential biocatalyst for industrial application. In this study, a mutant lipase AOL-3(F38N/V230R) was screened through two rounds of directed evolution, resulting in a fourfold increase in lipase activity, and threefold in catalytic efficiency (k(cat)/K(m)), while maintaining its excellent stereoselectivity. AOL-3(F38N/V230R) enzyme activity was maximum at pH 7.5 and also at 40 degreesC. And compared with wild-type AOL-3, AOL-3(F38N/V230R) preferentially hydrolyzed the fatty acid ethyl ester carbon chain length from C4 to C6-C10. In the same catalytic reaction conditions, the conversion of (R,S)-ethyl-2-(4-hydroxyphenoxy) propanoate ((R,S)-EHPP) by AOL-3(F38N/V230R) can be increased 169.7% compared to the original enzyme. The e.e.(s) of (R,S)-EHPP achieved 99.4% and conversion about 50.2% with E value being 829.0. Therefore, AOL-3(F38N/V230R) was a potential biocatalyst for obtaining key chiral compounds for aryloxyphenoxy propionate (APP) herbicides.
ESTHER : Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
PubMedSearch : Zhang_2020_Bioprocess.Biosyst.Eng_43_2131
PubMedID: 32959146
Gene_locus related to this paper: aspor-TGLA

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

Title : Anti-dipeptidyl-peptidase-like protein 6 encephalitis, a rare cause of reversible rapid progressive dementia and insomnia - Zhou_2020_J.Neuroimmunol_339_577114
Author(s) : Zhou Q , Zhu X , Meng H , Zhang M , Chen S
Ref : Journal of Neuroimmunology , 339 :577114 , 2020
Abstract : Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare type of autoimmune encephalitis. We present a case of a 72-year-old male with anti-DPPX encephalitis who developed rapidly progressive cognitive decline, psychiatric and sleep problems, severe abdominal pain and diarrhea. Antibodies against DPPX were positive both in serum and cerebrospinal fluid. (18)F-FDG PET-MR imaging indicated hypometabolism in the bilateral temporal lobes and thalamus. No related tumors were found, and the patient responded to immunotherapy without relapse at the 3-year follow-up. The present case enriches the understanding of the clinical, imaging manifestations and prognosis of anti-DPPX encephalitis.
ESTHER : Zhou_2020_J.Neuroimmunol_339_577114
PubMedSearch : Zhou_2020_J.Neuroimmunol_339_577114
PubMedID: 31775073
Gene_locus related to this paper: human-DPP6

Title : Degradation of dibutyl phthalate (DBP) by a bacterial consortium and characterization of two novel esterases capable of hydrolyzing PAEs sequentially - Lu_2020_Ecotoxicol.Environ.Saf_195_110517
Author(s) : Lu M , Jiang W , Gao Q , Zhang M , Hong Q
Ref : Ecotoxicology & Environmental Safety , 195 :110517 , 2020
Abstract : Phthalate esters (PAEs), a class of toxic anthropogenic compounds, have been predominantly used as additives or plasticizers, and great concern and interests have been raised regarding its environmental behavior and degradation mechanism. In the present study, a bacterial consortium consisting of Microbacterium sp. PAE-1 and Pandoraea sp. PAE-2 was isolated by the enrichment method, which could degrade dibutyl phthalate (DBP) completely by biochemical cooperation. DBP was converted to phthalic acid (PA) via monobutyl phthalate (MBP) by two sequential hydrolysis steps in strain PAE-1, and then PA was further degraded by strain PAE-2. Strain PAE-1 could hydrolyze many dialkyl Phthalate esters (PAEs) including dimethyl, diethyl, dibutyl, dipentyl, benzyl butyl, dihexyl, di-(2-ethyhexyl) and their corresponding monoalkyl PAEs. Two esterase genes named dpeH and mpeH, located in the same transcription unit, were cloned from strain PAE-1 by the shotgun method and heterologously expressed in Escherichia. coli (DE3). The Km and kcat values of DpeH for DBP were 9.60 +/- 0.97 muM and (2.72 +/- 0.06) x 10(6) s(-1), while those of MpeH for MBP were 18.61 +/- 2.00 muM and (5.83 +/- 1.00) x 10(5) s(-1), respectively. DpeH could only hydrolyze dialkyl PAEs to the corresponding monoalkyl PAEs, which were then hydrolyzed to PA by MpeH. DpeH shares the highest similarity (53%) with an alpha/beta hydrolase from Microbacterium sp. MED-G48 and MpeH shows only 25% identity with a secreted lipase from Trichophyton benhamiae CBS 112371, indicating that DpeH and MpeH are two novel hydrolases against PAEs.
ESTHER : Lu_2020_Ecotoxicol.Environ.Saf_195_110517
PubMedSearch : Lu_2020_Ecotoxicol.Environ.Saf_195_110517
PubMedID: 32220793
Gene_locus related to this paper: 9mico-DpeH , 9mico-MpeH

Title : A novel lipase from Aspergillus oryzae catalyzed resolution of (R,S)-ethyl 2-bromoisovalerate - Wu_2020_Chirality_32_231
Author(s) : Wu P , Zhang M , Zhang Y , Wang Z , Zheng J
Ref : Chirality , 32 :231 , 2020
Abstract : In this study, a novel lipase M5 derived from Aspergillus oryzae WZ007 was prone to exhibit high hydrolytic activity and stereoselectivity towards racemic substrate (R,S)-ethyl 2-bromoisovalerate. (R)-ethyl 2-bromoisovalerate was obtained by enzymatic resolution, which is the key chiral intermediate for highly efficient enantiomerically fluvalinate. The results showed that the enzymatic reaction was carried out in 120mM racemic substrate for 3 hours, the enantiomeric excess reached 98.6%, the conversion was 51.7%, and E value above 120. Therefore, the novel lipase M5 has the ability to efficiently produce (R)-ethyl 2-bromoisovalerate, which greatly reduces the industrial production cost of the highly efficient counterpart of fluvalinate.
ESTHER : Wu_2020_Chirality_32_231
PubMedSearch : Wu_2020_Chirality_32_231
PubMedID: 31856428
Gene_locus related to this paper: aspor-q2ue03

Title : Neuroprotective potential of ketamine prevents developing brain structure impairment and alteration of neurocognitive function induced via isoflurane through the PI3K\/AKT\/GSK-3beta pathway - Wang_2019_Drug.Des.Devel.Ther_13_501
Author(s) : Wang R , Zhang Z , Kumar M , Xu G , Zhang M
Ref : Drug Des Devel Ther , 13 :501 , 2019
Abstract : Background: The aim of the current experimental study was to scrutinize the neuroprotective effect of ketamine on the isoflurane (iso)-induced cognitive dysfunction in rats via phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3beta (GSK-3beta) pathway. Materials and methods: Sprague-Dawley rats were used for the current experimental study. The rats were divided into six groups and rats were treated with ketamine and memantine. For the estimation of cognitive function study, we used the Morris water test. Pro-inflammatory cytokines such as IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and caspase-6; the antioxidant parameters malondialdehyde, glutathione, superoxide dismutase, catalase, and protein carbonyl; acetylcholinesterase, amyloid beta, and brain-derived neurotrophic factor were estimated, respectively. The protein expression of AKT, GSK-3beta, p21WAF1/CIP1, and p53 was also estimated, respectively. Results: Ketamine significantly enhanced cognitive function and showed anti-inflammatory and antioxidant effects, and exhibited the neuroprotective effect of ketamine against the isoflurane-induced cognitive impairment. Additionally, ketamine significantly (P<0.005) suppressed IL-1beta, TNF-alpha, IL-6, caspase-6 and p21WAF1/CIP1, p53 expression and up-regulated the PI3K/AKT/GSK-3beta expression in the group of iso-induced rats. Conclusion: We can conclude that ketamine prevented the cognitive impairment induced by isoflurane anesthesia through anti-apoptotic, anti-inflammatory, and antioxidant effects via the PI3K/AKT/GSK-3beta pathway.
ESTHER : Wang_2019_Drug.Des.Devel.Ther_13_501
PubMedSearch : Wang_2019_Drug.Des.Devel.Ther_13_501
PubMedID: 30787593

Title : Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis - Liu_2019_J.Cancer_10_3746
Author(s) : Liu Y , Feng W , Liu W , Kong X , Li L , He J , Wang D , Zhang M , Zhou G , Xu W , Chen W , Gong A , Xu M
Ref : J Cancer , 10 :3746 , 2019
Abstract : Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.
ESTHER : Liu_2019_J.Cancer_10_3746
PubMedSearch : Liu_2019_J.Cancer_10_3746
PubMedID: 31333792
Gene_locus related to this paper: human-ABHD11

Title : Insecticide Resistance Status and Mechanisms of Anopheles sinensis (Diptera: Culicidae) in Wenzhou, an Important Coastal Port City in China - Chen_2019_J.Med.Entomol_56_803
Author(s) : Chen S , Qin Q , Zhong D , Fang X , He H , Wang L , Dong L , Lin H , Zhang M , Cui L , Yan G
Ref : Journal of Medical Entomology , 56 :803 , 2019
Abstract : Although scaled-up interventions and effective control efforts have drastically reduced malaria morbidity and mortality, malaria remains a serious threat to public health worldwide. Anopheles sinensis Wiedemann 1828 is a historically important vector of Plasmodium vivax (Haemosporida: Plasmodiidae) malaria in China. Insecticide resistance has become a major obstacle to vector-borne disease control. However, little is known about the insecticide resistance of An. sinensis in Wenzhou, an important coastal port city in Zhejiang province, China. The aim of this study was to examine insecticide resistance and mechanisms in An. sinensis field mosquito populations. Evidence of multiple insecticide resistance was found in An. sinensis adult female populations. Medium to high frequencies of target site kdr together with fixed ace-1 mutations was detected in both the Ruian and Yongjia populations. Both populations showed an association between kdr L1014 mutation and resistance phenotype when tested against deltamethrin and DDT. Significantly different metabolic enzyme activities were found between the susceptible laboratory strain and field-collected mosquitoes from both Ruian and Yongjia. Both field collected An. sinensis populations exhibited significantly higher P450 enzyme activity compared with the laboratory strain, while the field-collected resistant mosquitoes exhibited various GST and COE enzyme activities. These results indicate multiple resistance mechanisms in An. sinensis field populations. Effective implementation of insecticide resistance management strategies is urgently needed. The data collected in this study will be valuable for modeling insecticide resistance spread and vector-control interventions.
ESTHER : Chen_2019_J.Med.Entomol_56_803
PubMedSearch : Chen_2019_J.Med.Entomol_56_803
PubMedID: 30715428

Title : Effects of cadmium on fecundity and defence ability of Drosophila melanogaster - Hu_2019_Ecotoxicol.Environ.Saf_171_871
Author(s) : Hu X , Fu W , Yang X , Mu Y , Gu W , Zhang M
Ref : Ecotoxicology & Environmental Safety , 171 :871 , 2019
Abstract : Cadmium (chemical symbol, Cd) is an extremely common pollutant that poses a toxicity threat to organisms. Therefore, we tested Drosophila melanogaster fecundity, Cd accumulation, and activity of two enzymes following Cd stress and used quantitative real-time polymerase chain reaction (qPCR) to quantify the mRNA expression levels of several genes involved in fecundity and defence. D. melanogaster was placed in a medium containing different concentrations of Cd (13, 26, and 52mgL(-1)), following which, inductively coupled plasma atomic emission spectroscopy showed that Cd accumulation in Drosophila increased with the increase in its dietary intake. We also observed that Cd at these concentrations significantly prolonged the mating latency in females and reduced the number of eggs laid. However, the same Cd concentrations did not affect male fecundity. Acetylcholinesterase activity was only detected at 52mgL(-1) Cd in both sexes, whereas glutathione S-transferase activity was inhibited at 26 and 52mgL(-1) Cd in females. The results of qPCR indicated that exposure to 13-52mgL(-1) Cd affected the expression of reproduction-related genes, including downregulation of enok and upregulation of dally and dpp. The same level of exposure also induced transcriptional responses from three defence-related genes (hsp70, gstd2, and gstd6). Taken together, the results revealed that Cd exposure might negatively affect the expression of genes associated with D. melanogaster reproduction and trigger the transcription of defence-related genes. We suggest that further analyses of fecundity and defence responses may help develop indicators of Cd toxicity and improve our understanding of antitoxin defences.
ESTHER : Hu_2019_Ecotoxicol.Environ.Saf_171_871
PubMedSearch : Hu_2019_Ecotoxicol.Environ.Saf_171_871
PubMedID: 30665104

Title : The genome of broomcorn millet - Zou_2019_Nat.Commun_10_436
Author(s) : Zou C , Li L , Miki D , Li D , Tang Q , Xiao L , Rajput S , Deng P , Peng L , Jia W , Huang R , Zhang M , Sun Y , Hu J , Fu X , Schnable PS , Chang Y , Li F , Zhang H , Feng B , Zhu X , Liu R , Schnable JC , Zhu JK
Ref : Nat Commun , 10 :436 , 2019
Abstract : Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
ESTHER : Zou_2019_Nat.Commun_10_436
PubMedSearch : Zou_2019_Nat.Commun_10_436
PubMedID: 30683860
Gene_locus related to this paper: panmi-a0a3l6qvl9 , 9poal-a0a2s3hbt0 , panmi-a0a3l6sxg5 , 9poal-a0a2t7cdl4 , panmi-a0a3l6ta96 , panmi-a0a3l6qv47 , panmi-a0a3l6s688 , panmi-a0a3l6tph0

Title : Bioactive phenazines from an earwig-associated Streptomyces sp - Han_2019_Chin.J.Nat.Med_17_475
Author(s) : Han H , Guo ZK , Zhang B , Zhang M , Shi J , Li W , Jiao RH , Tan RX , Ge HM
Ref : Chin J Nat Med , 17 :475 , 2019
Abstract : Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.
ESTHER : Han_2019_Chin.J.Nat.Med_17_475
PubMedSearch : Han_2019_Chin.J.Nat.Med_17_475
PubMedID: 31262460

Title : Epigenetic mechanisms underlying the effects of triptolide and tripchlorolide on the expression of neuroligin-1 in the hippocampus of APP\/PS1 transgenic mice - Lu_2019_Pharm.Biol_57_453
Author(s) : Lu X , Yang B , Yu H , Hu X , Nie J , Wan B , Zhang M , Lu C
Ref : Pharm Biol , 57 :453 , 2019
Abstract : Context: Neuroligin-1 (NLGN1) is a cell adhesion protein located on the excitatory postsynaptic membrane. beta-Amyloid (Abeta)-induced neuroinflammation decreases NLGN1 expression through epigenetic mechanisms. Triptolide (T10) and tripchlorolide (T4) exert protective effects on synapses in Alzheimer's disease (AD) mice, but the mechanisms remain unclear. Objective: The effects of T10 and T4 on hippocampal NLGN1 expression in AD mice and the epigenetic mechanisms were assessed using chromatin immunoprecipitation and methylated DNA immunoprecipitation. Materials and methods: Sixty APP/PS1 transgenic mice were randomly divided into an AD model group, a T10-treated group and a T4-treated group (n = 20); 20 wild-type littermates served as the control group. APP/PS1 transgenic mice were intraperitoneally injected with T10 (0.1 mg/kg) and T4 (25 mug/kg) once per day for 60 days. NLGN1 expression was examined using western blotting and quantitative PCR. Results: T10 and T4 increased the levels of the NLGN1 protein and mRNA in hippocampus of AD mice. T10 and T4 inhibited the binding of HDAC2 (p< 0.01) and MeCP2 (p< 0.01 and p< 0.05, respectively) to the NLGN1 promoter, and cytosine methylation (1.2305 +/- 0.1482/1.2554 +/- 0.3570 vs. 1.6578 +/- 0.1818, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. T10 and T4 increased the level of acetylated histone H3 (0.7733 +/- 0.1611/0.8241 +/- 0.0964 vs. 0.5587 +/- 0.0925, p< 0.01) at the NLGN1 promoter in the hippocampus of AD mice. Conclusions: T10 and T4 may increase hippocampal NLGN1 expression in AD mice through epigenetic mechanisms, providing a new explanation for the mechanism underlying the protective effects of T10 and T4 on synapses.
ESTHER : Lu_2019_Pharm.Biol_57_453
PubMedSearch : Lu_2019_Pharm.Biol_57_453
PubMedID: 31311385

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

Title : Structural Basis by Which the N-Terminal Polypeptide Segment of Rhizopus chinensis Lipase Regulates Its Substrate Binding Affinity - Zhang_2019_Biochemistry_58_3943
Author(s) : Zhang M , Yu XW , Xu Y , Guo RT , Swapna GVT , Szyperski T , Hunt JF , Montelione GT
Ref : Biochemistry , 58 :3943 , 2019
Abstract : Members of an important group of industrial enzymes, Rhizopus lipases, exhibit valuable hydrolytic features that underlie their biological functions. Particularly important is their N-terminal polypeptide segment (NTPS), which is required for secretion and proper folding but is removed in the process of enzyme maturation. A second common feature of this class of lipases is the alpha-helical "lid", which regulates the accessibility of the substrate to the enzyme active site. Some Rhizopus lipases also exhibit "interfacial activation" by micelle and/or aggregate surfaces. While it has long been recognized that the NTPS is critical for function, its dynamic features have frustrated efforts to characterize its structure by X-ray crystallography. Here, we combine nuclear magnetic resonance spectroscopy and X-ray crystallography to determine the structure and dynamics of Rhizopus chinensis lipase (RCL) with its 27-residue NTPS prosequence (r27RCL). Both r27RCL and the truncated mature form of RCL (mRCL) exhibit biphasic interfacial activation kinetics with p-nitrophenyl butyrate (pNPB). r27RCL exhibits a substrate binding affinity significantly lower than that of mRCL due to stabilization of the closed lid conformation by the NTPS. In contrast to previous predictions, the NTPS does not enhance lipase activity by increasing surface hydrophobicity but rather inhibits activity by forming conserved interactions with both the closed lid and the core protein structure. Single-site mutations and kinetic studies were used to confirm that the NTPS serves as internal competitive inhibitor and to develop a model of the associated process of interfacial activation. These structure-function studies provide the basis for engineering RCL lipases with enhanced catalytic activities.
ESTHER : Zhang_2019_Biochemistry_58_3943
PubMedSearch : Zhang_2019_Biochemistry_58_3943
PubMedID: 31436959
Gene_locus related to this paper: rhich-a3fm73

Title : Hydroxy-alpha-sanshool isolated from Zanthoxylum bungeanum attenuates learning and memory impairments in scopolamine-treated mice - Zhang_2019_Food.Funct_10_7315
Author(s) : Zhang M , Xie M , Wei D , Wang L , Hu M , Zhang Q , He Z , Peng W , Wu C
Ref : Food Funct , 10 :7315 , 2019
Abstract : Learning and memory impairments are common symptoms of dementia in neurodegenerative disorders. Occasionally, we found that Zanthoxylum bungeanum pericarps (ZBP) significantly activated the spontaneous activity of the hippocampus (HIPP) and paraHIPP (P < 0.001, uncorrected), implying the potential ability of ZBP to improve cognitive impairments. Thus, this study aimed to investigate the improving effect of hydroxy-alpha-sanshool (HAS), a characteristic ingredient of ZBP, against scopolamine (1 mg kg(-1), i.p.)-induced learning and memory deficits. HAS (5 mg kg(-1), p.o.) markedly reversed scopolamine-induced cognitive impairments, as indicated by its performance in the passive avoidance test and Morris water maze test (P < 0.01). Furthermore, HAS (2.5 and 5.0 mg kg(-1), p.o.) also dose-dependently prevented changes in hippocampal neuronal morphology and apoptosis, inhibited acetylcholinesterase (AChE) activity, increased the acetylcholine (ACh) content, and increased the protein and mRNA expression of brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding (p-CREB) compared with those in the model group (P < 0.05 & P < 0.01). These findings demonstrated that HAS attenuated scopolamine-induced cognitive impairments mainly by enhancing the activity of the cholinergic system and increasing the CREB/BDNF signalling pathway.
ESTHER : Zhang_2019_Food.Funct_10_7315
PubMedSearch : Zhang_2019_Food.Funct_10_7315
PubMedID: 31637395

Title : Effect of organic solvent on enzymatic degradation of cyclic PBS-based polymers by lipase N435 - Li_2019_Int.J.Biol.Macromol_137_215
Author(s) : Li CT , Zhang M , Weng YX , Zhao D
Ref : Int J Biol Macromol , 137 :215 , 2019
Abstract : Poly(butylene succinate-co-cyclohexane dimethanol succinate) (P(BS-co-CHDMS)) and poly(butylene succinate-co-butanediol cyclohexanedicarboxylic acid) (P(BS-co-BCHDA)) were catalytically degraded by Candida antarctica lipase Novozyme 435 (N435) in CHCl3 and THF. The results indicated that the degradation rate was P(BS-co-CHDMS)>P(BS-co-BCHDA)>poly(butylene succinate) (PBS). The degradation rate of copolyesters was higher in CHCl3 than in THF, the highest degradation rate of 67% being obtained for P(BS-co-CHDMS). Hence, the CHCl3 solvent is more suitable for the enzyme-catalytic degradation of copolyesters, since the lipase can easier recognize the butylene succinate (BS-), (butanediol cyclohexanedicarboxylic acid) (BCA-), and (cyclohexane dimethanol succinate-type) (CMS-type) ester bonds in this solvent. Moreover, it can recognize the CMS-type ester bonds with a higher specificity than the (butanediol cyclohexanedicarboxylic acid type) (BCA-type) ester bonds. Molecular simulation results indicated that the structure of the lipase was stable in CHCl3 and THF. However, CHCl3 proved to be more suitable for a stable activity of the enzyme. The active pocket contains acyl-binding hydrophilic residues which are recognized by the substrate. The increase in the content of saturated cycles can increase the hydrophobicity of the substrate and thus, the amount of substrate bond to enzyme active site is increased, which facilitates the enzymatic degradation of copolyesters.
ESTHER : Li_2019_Int.J.Biol.Macromol_137_215
PubMedSearch : Li_2019_Int.J.Biol.Macromol_137_215
PubMedID: 31255620
Gene_locus related to this paper: canar-LipB

Title : Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes - Sun_2018_Nat.Genet_50_1289
Author(s) : Sun S , Zhou Y , Chen J , Shi J , Zhao H , Song W , Zhang M , Cui Y , Dong X , Liu H , Ma X , Jiao Y , Wang B , Wei X , Stein JC , Glaubitz JC , Lu F , Yu G , Liang C , Fengler K , Li B , Rafalski A , Schnable PS , Ware DH , Buckler ES , Lai J
Ref : Nat Genet , 50 :1289 , 2018
Abstract : Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.
ESTHER : Sun_2018_Nat.Genet_50_1289
PubMedSearch : Sun_2018_Nat.Genet_50_1289
PubMedID: 30061735
Gene_locus related to this paper: maize-a0a1d6kqc9 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a3l6d913

Title : Tissue Metabolism, Hematotoxicity, and Hepatotoxicity of Trichlorfon in Carassius auratus gibelio After a Single Oral Administration - Lu_2018_Front.Physiol_9_551
Author(s) : Lu J , Zhang M , Lu L
Ref : Front Physiol , 9 :551 , 2018
Abstract : Trichlorfon is a most widely used organophosphate insecticide in aquaculture, many successful results have been reported for bath treatments of trichlorfon to control parasites. However, immersion treatments of large stocks with trichlorfon has caused serious environmental pollution. In contrast, oral administration treatment has advantages on reducing environmental pollution and having little effect in non-targeted species. The aim of this study was to investigate the effect of trichlorfon on Carassius auratus gibelio physiology after a single oral administration. In this study, Carassius auratus gibelio was subjected to oral gavage with various concentrations of trichlorfon (0.5 g/kg, 1 g/kg, and 2 g/kg). The trichlorfon concentration in the plasma and liver tissue was quantified using liquid chromatography-tandem mass spectrometry at different time points. At the beginning of oral exposure, the uptake of trichlorfon in the plasma and liver tissue was fast, and trichlorfon was rapidly eliminated to a low level within 24 h. In addition, acetylcholinesterase, superoxide dismutase, catalase, and glutathione-S-transferase activities in the plasma and liver tissue changed significantly after trichlorfon exposure. Additionally, vacuolar degeneration, necrosis, and congestion of the central vein were observed in the liver after trichlorfon exposure, as assessed by hematoxylin and eosin staining. Our results suggested that trichlorfon could accumulate and induce hematotoxicity and hepatotoxicity in the plasma and liver tissue, the toxicity induced by trichlorfon might result in physiological disturbances in fish.
ESTHER : Lu_2018_Front.Physiol_9_551
PubMedSearch : Lu_2018_Front.Physiol_9_551
PubMedID: 29875675

Title : Backbone and Ile-delta1, Leu, Val methyl (1)H, (15)N, and (13)C, chemical shift assignments for Rhizopus chinensis lipase - Zhang_2018_Biomol.NMR.Assign_12_63
Author(s) : Zhang M , Yu XW , Swapna GVT , Liu G , Xiao R , Xu Y , Montelione GT
Ref : Biomol NMR Assign , 12 :63 , 2018
Abstract : Lipase r27RCL is a 296-residue, 33 kDa monomeric enzyme with high ester hydrolysis activity, which has significant applications in the baking, paper and leather industries. The lipase gene proRCL from Rhizopus microsporus var. chinensis (also Rhizopus chinensis) CCTCC M201021 was cloned as a fusion construct C-terminal to a maltose-binding protein (MBP) tag, and expressed as MBP-proRCL in an Escherichia coli BL21 trxB (DE3) expression system with uniform (2)H,(13)C,(15)N-enrichment and Ile-delta1, Leu, and Val (13)CH3 methyl labeling. The fusion protein was hydrolyzed by Kex2 protease at the recognition site Lys-Arg between residues -29 and -28 of the prosequence, producing the enzyme form called r27RCL. Here we report extensive backbone (1)H, (15)N, and (13)C, as well as Ile-delta1, Leu, and Val side chain methyl, NMR resonance assignments for r27RCL.
ESTHER : Zhang_2018_Biomol.NMR.Assign_12_63
PubMedSearch : Zhang_2018_Biomol.NMR.Assign_12_63
PubMedID: 28929427
Gene_locus related to this paper: rhich-a3fm73

Title : Three-dimensional reconstructed eccrine sweat glands with vascularization and cholinergic and adrenergic innervation - Zhang_2018_J.Mol.Histol_49_339
Author(s) : Zhang M , Li H , Chen L , Fang S , Xie S , Lin C
Ref : J Mol Histol , 49 :339 , 2018
Abstract : Functional integrity of the regenerated tissues requires not only structural integrity but also vascularization and innervation. We previously demonstrated that the three-dimensional (3D) reconstructed eccrine sweat glands had similar structures as those of the native ones did, but whether the 3D reconstructed glands possessing vascularization and innervation was still unknown. In the study, Matrigel-embedded eccrine sweat gland cells were implanted under the inguinal skin. Ten weeks post-implantation, the vascularization, and innervation in the 10-week reconstructed eccrine sweat glands and native human eccrine sweat glands were detected by immunofluorescence staining. The results showed that the fluorescent signals of general neuronal marker protein gene product 9.5, adrenergic nerve fiber marker tyrosine hydroxylase, and cholinergic nerve fiber markers acetylcholinesterase and vasoactive intestinal peptide embraced the 3D reconstructed glands in circular patterns, as the signals appeared in native eccrine sweat glands. There were many CD31- and von Willebrand factor-positive vessels growing into the plugs. We demonstrated that the 3D reconstructed eccrine sweat glands were nourished by blood vessels, and we for the first time demonstrated that the engineering sweat glands were innervated by both cholinergic and adrenergic fibers. In conclusion, the 3D reconstructed eccrine sweat glands may have functions as the native ones do.
ESTHER : Zhang_2018_J.Mol.Histol_49_339
PubMedSearch : Zhang_2018_J.Mol.Histol_49_339
PubMedID: 29667149

Title : Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Abeta(1-42) aggregation inhibitors and metal-chelating agents for Alzheimer's disease - Xu_2017_Eur.J.Med.Chem_127_174
Author(s) : Xu P , Zhang M , Sheng R , Ma Y
Ref : Eur Journal of Medicinal Chemistry , 127 :174 , 2017
Abstract : A series of deferiprone-resveratrol hybrids have been designed and synthesized as multitarget-directed ligands (MTDLs) through merging the chelating moiety 3-hydroxypyridin-4-one into the structure of resveratrol, a natural antioxidant agent and beta-amyloid peptide (Abeta) aggregation inhibitor. The in vitro biological evaluation revealed that most of these newly synthesized compounds exhibited good inhibitory activity against self-induced Abeta(1-42) aggregation, excellent antioxidant activity and potent metal chelating capability. Compounds 3i and 4f were identified as the most promising MTDLs with triple functions, possessing micromolar IC(50) values for Abeta(1-42) aggregation inhibition, greater 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(*+)) scavenging activity than Trolox and similar pFe(III) values to that of deferiprone.
ESTHER : Xu_2017_Eur.J.Med.Chem_127_174
PubMedSearch : Xu_2017_Eur.J.Med.Chem_127_174
PubMedID: 28061347

Title : Small molecular floribundiquinone B derived from medicinal plants inhibits acetylcholinesterase activity - Niu_2017_Oncotarget_8_57149
Author(s) : Niu B , Zhang M , Du P , Jiang L , Qin R , Su Q , Chen F , Du D , Shu Y , Chou KC
Ref : Oncotarget , 8 :57149 , 2017
Abstract : Being a neurodegenerative disorder, Alzheimer's disease (AD) is the one of the most terrible diseases. And acetylcholinesterase (AChE) is considered as an important target for treating AD. Acetylcholinesterase inhibitors (AChEI) are considered to be one of the effective drugs for the treatment of AD. The aim of this study is to find a novel potential AChEI as a drug for the treatment of AD. In this study, instead of using the synthetic compounds, we used those extracted from plants to investigate the interaction between floribundiquinone B (FB) and AChE by means of both the experimental approach such as fluorescence spectra, ultraviolet-visible (UV-vis) absorption spectrometry, circular dichroism (CD) and the theoretical approaches such as molecular docking. The findings reported here have provided many useful clues and hints for designing more effective and less toxic drugs against Alzheimer's disease.
ESTHER : Niu_2017_Oncotarget_8_57149
PubMedSearch : Niu_2017_Oncotarget_8_57149
PubMedID: 28915661

Title : MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice - Cheng_2017_Circ.J_82_28
Author(s) : Cheng HP , Gong D , Zhao ZW , He PP , Yu XH , Ye Q , Huang C , Zhang X , Chen LY , Xie W , Zhang M , Li L , Xia XD , Ouyang XP , Tan YL , Wang ZB , Tian GP , Zheng XL , Yin WD , Tang CK
Ref : Circ J , 82 :28 , 2017
Abstract : BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.
ESTHER : Cheng_2017_Circ.J_82_28
PubMedSearch : Cheng_2017_Circ.J_82_28
PubMedID: 28855441

Title : 2D-SAR and 3D-QSAR analyses for acetylcholinesterase inhibitors - Niu_2017_Mol.Divers_21_413
Author(s) : Niu B , Zhao M , Su Q , Zhang M , Lv W , Chen Q , Chen F , Chu D , Du D , Zhang Y
Ref : Mol Divers , 21 :413 , 2017
Abstract : Alzheimer's disease (AD) accounts for almost three quarters of dementia patients and interferes people's normal life. Great progress has been made recently in the study of Acetylcholinesterase (AChE), known as one of AD's biomarkers. In this study, acetylcholinesterase inhibitors (AChEI) were collected to build a two-dimensional structure-activity relationship (2D-SAR) model and three-dimensional quantitative structure-activity relationship (3D-QSAR) model based on feature selection method combined with random forest. After calculation, the prediction accuracy of the 2D-SAR model was 89.63% by using the tenfold cross-validation test and 87.27% for the independent test set. Three cutting ways were employed to build 3D-QSAR models. A model with the highest [Formula: see text] (cross-validated correlation coefficient) and [Formula: see text](non-cross-validated correlation coefficient) was obtained to predict AChEI activity. The mean absolute error (MAE) of the training set and the test set was 0.0689 and 0.5273, respectively. In addition, molecular docking was also employed to reveal that the ionization state of the compounds had an impact upon their interaction with AChE. Molecular docking results indicate that Ser124 might be one of the active site residues.
ESTHER : Niu_2017_Mol.Divers_21_413
PubMedSearch : Niu_2017_Mol.Divers_21_413
PubMedID: 28275924

Title : Cellular Transport of Esculin and Its Acylated Derivatives in Caco-2 Cell Monolayers and Their Antioxidant Properties in Vitro - Zhang_2017_J.Agric.Food.Chem_65_7424
Author(s) : Zhang M , Xin X , Lai F , Zhang X , Li X , Wu H
Ref : Journal of Agricultural and Food Chemistry , 65 :7424 , 2017
Abstract : Esculin has many pharmacological effects, but these are difficult to observe after oral administration owing to poor lipid solubility. In our previous study, five acylated derivatives with different acyl chain lengths (EA, EP, EO, EL, and EM) were synthesized to improve the lipophilicity of esculin. In this study, the bioavailability and antioxidant activity of the five derivatives were investigated. The logP of esculin, EA, EP, EO, EL, and EM were -1.1 +/- 0.1, -0.3 +/- 0.14, 0.1 +/- 0.17, 1.6 +/- 0.09, 2.4 +/- 0.11, and 2.8 +/- 0.18, and their Papp were 0.71 +/- 0.02, 1.24 +/- 0.18, 1.74 +/- 0.11, 11.6 +/- 3.6, 4.11 +/- 1.03, and 2.64 +/- 0.97 x 10(-6) cm/s, respectively. Besides, the bioavailability of EO, EL, and EM were seriously affected by carboxylesterase. The results of ABTS, ORAC, and DPPH assays indicated that the antiradical ability of the five derivatives did not exceed that of esculin. However, EA, EP, and EO showed more effective inhibition of AAPH-induced oxidative hemolysis than esculin did (p < 0.05), and EL and EM were less effective than esculin (p < 0.05). The mechanism was related to the distribution and localization of the derivatives in "oil-water interface" between the cytomembrane and the aqueous phase.
ESTHER : Zhang_2017_J.Agric.Food.Chem_65_7424
PubMedSearch : Zhang_2017_J.Agric.Food.Chem_65_7424
PubMedID: 28805379

Title : Application and comparison in biosynthesis and biodegradation by Fusarium solani and Aspergillus fumigatus cutinases - Ping_2017_Int.J.Biol.Macromol_104_1238
Author(s) : Ping LF , Chen XY , Yuan XL , Zhang M , Chai YJ , Shan SD
Ref : Int J Biol Macromol , 104 :1238 , 2017
Abstract : In this study, two synthesized cutinase genes from Fusarium solani and Aspergillus fumigatus were expressed in Pichia pastoris X33. The characteristics of these two cutinases were investigated and compared. The results indicated that F. solani and A. fumigatus cutinases hydrolyzed p-nitrophenyl substrates with different carbon chain lengths. A. fumigatus cutinase predominately hydrolyzed p-nitrophenyl butyrate, but F. solani cutinase preferred p-nitrophenyl decanoate. The abilities of polymer synthesis and bioplastic degradation were tested and compared between F. solani and A. fumigatus cutinases. The results showed that F. solani cutinase had degradation ability on poly(epsilon-caprolactone) (PCL) and synthesized polymer with a molecular weight (MW) of 2300 in organic solvent. However, A. fumigatus cutinase completely degraded PCL and synthesized molecules with a MW of 25,000, suggesting that A. fumigatus cutinase has more promising applications.
ESTHER : Ping_2017_Int.J.Biol.Macromol_104_1238
PubMedSearch : Ping_2017_Int.J.Biol.Macromol_104_1238
PubMedID: 28673841

Title : Polyacrylic acid-coated cerium oxide nanoparticles: An oxidase mimic applied for colorimetric assay to organophosphorus pesticides - Zhang_2016_Biosens.Bioelectron_85_457
Author(s) : Zhang SX , Xue SF , Deng J , Zhang M , Shi G , Zhou T
Ref : Biosensors & Bioelectronics , 85 :457 , 2016
Abstract : It is important and urgent to develop reliable and highly sensitive methods that can provide on-site and rapid detection of extensively used organophosphorus pesticides (OPs) for their neurotoxicity. In this study, we developed a novel colorimetric assay for the detection of OPs based on polyacrylic acid-coated cerium oxide nanoparticles (PAA-CeO2) as an oxidase mimic and OPs as inhibitors to suppress the activity of acetylcholinesterase (AChE). Firstly, highly dispersed PAA-CeO2 was prepared in aqueous solution, which could catalyze the oxidation of TMB to produce a color reaction from colorless to blue. And the enzyme of AChE was used to catalyze the substrate of acetylthiocholine (ATCh) to produce thiocholine (TCh). As a thiol-containing compound with reducibility, TCh can decrease the oxidation of TMB catalyzed by PAA-CeO2. Upon incubated with OPs, the enzymatic activity of AChE was inhibited to produce less TCh, resulting in more TMB catalytically oxidized by PAA-CeO2 to show an increasing blue color. The two representative OPs, dichlorvos and methyl-paraoxon, were tested using our proposed assay. The novel assay showed notable color change in a concentration-dependent manner, and as low as 8.62 ppb dichlorvos and 26.73 ppb methyl-paraoxon can be readily detected. Therefore, taking advantage of such oxidase-like activity of PAA-CeO2, our proposed colorimetric assay can potentially be a screening tool for the precise and rapid evaluation of the neurotoxicity of a wealth of OPs.
ESTHER : Zhang_2016_Biosens.Bioelectron_85_457
PubMedSearch : Zhang_2016_Biosens.Bioelectron_85_457
PubMedID: 27208478

Title : Efficient production of (2)H, (13)C, (15)N-enriched industrial enzyme Rhizopus chinensis lipase with native disulfide bonds - Zhang_2016_Microb.Cell.Fact_15_123
Author(s) : Zhang M , Yu XW , Swapna GV , Xiao R , Zheng H , Sha C , Xu Y , Montelione GT
Ref : Microb Cell Fact , 15 :123 , 2016
Abstract : BACKGROUND: In order to use most modern methods of NMR spectroscopy to study protein structure and dynamics, isotope-enriched protein samples are essential. Especially for larger proteins (>20 kDa), perdeuterated and Ile (delta1), Leu, and Val methyl-protonated protein samples are required for suppressing nuclear relaxation to provide improved spectral quality, allowing key backbone and side chain resonance assignments needed for protein structure and dynamics studies. Escherichia coli and Pichia pastoris are two of the most popular expression systems for producing isotope-enriched, recombinant protein samples for NMR investigations. The P. pastoris system can be used to produce (13)C, (15)N-enriched and even (2)H,(13)C, (15)N-enriched protein samples, but efficient methods for producing perdeuterated proteins with Ile (delta1), Leu and Val methyl-protonated groups in P. pastoris are still unavailable. Glycosylation heterogeneity also provides challenges to NMR studies. E. coli expression systems are efficient for overexpressing perdeuterated and Ile (delta1), Leu, Val methyl-protonated protein samples, but are generally not successful for producing secreted eukaryotic proteins with native disulfide bonds.
RESULTS: The 33 kDa protein-Rhizopus chinensis lipase (RCL), an important industrial enzyme, was produced using both P. pastoris and E. coli BL21 trxB (DE3) systems. Samples produced from both systems exhibit identical native disulfide bond formation and similar 2D NMR spectra, indicating similar native protein folding. The yield of (13)C, (15)N-enriched r27RCL produced using P. pastoris was 1.7 times higher that obtained using E. coli, while the isotope-labeling efficiency was ~15 % lower. Protein samples produced in P. pastoris exhibit O-glycosylation, while the protein samples produced in E. coli were not glycosylated. The specific activity of r27RCL from P. pastoris was ~1.4 times higher than that produced in E. coli.
CONCLUSIONS: These data demonstrate efficient production of (2)H, (13)C, (15)N-enriched, Ile (delta1), Leu, Val methyl-protonated eukaryotic protein r27RCL with native disulfides using the E. coli BL21 trxB (DE3) system. For certain NMR studies, particularly efforts for resonance assignments, structural studies, and dynamic studies, E. coli provides a cost-effective system for producing isotope-enriched RCL. It should also be potential for producing other (2)H, (13)C, (15)N-enriched, Ile (delta1), Leu, Val methyl-protonated eukaryotic proteins with native disulfide bonds.
ESTHER : Zhang_2016_Microb.Cell.Fact_15_123
PubMedSearch : Zhang_2016_Microb.Cell.Fact_15_123
PubMedID: 27411547

Title : NPY(+)-, but not PV(+)-GABAergic neurons mediated long-range inhibition from infra- to prelimbic cortex - Saffari_2016_Transl.Psychiatry_6_e736
Author(s) : Saffari R , Teng Z , Zhang M , Kravchenko M , Hohoff C , Ambree O , Zhang W
Ref : Transl Psychiatry , 6 :e736 , 2016
Abstract : Anxiety disorders are thought to reflect deficits in the regulation of fear memories. While the amygdala has long been considered a site of storage of fear memories, newer findings suggest that the prefrontal cortex (PFC) is essential in the regulation of amygdala-dependent memories and fear expression. Here, activation of the prelimbic cortex (PrL) enhances the expression of fear, while an elevated activity in the infralimbic cortex (IL) enhances fear extinction. Despite the presence of these facts, we still know very little about the synaptic interconnectivity within the PFC. The aim of the present study was to investigate the inhibitory circuits between prelimbic and IL using morphological and electrophysiological methods. Our immunohistochemical analysis revealed that the distribution of PV(+)- and NPY(+)-GABAergic neurons was strikingly different within the PFC. In addition, we provided the first experimental evidence that the pyramidal neurons in the PrL received a direct inhibitory input mediated by bipolar NPY(+)-GABAergic projection neurons in the IL. Deletion of the anxiety-related neuroligin 2 gene caused a decrease of this direct synaptic inhibition that originated from the IL. Thus, our data suggested that activation of the IL might not only directly activate the corresponding downstream anxiolytic pathway, but also suppress the PrL-related anxiogenic pathway and thus could differentially bias the regulation of fear expression and extinction.
ESTHER : Saffari_2016_Transl.Psychiatry_6_e736
PubMedSearch : Saffari_2016_Transl.Psychiatry_6_e736
PubMedID: 26882036

Title : Association between L55M polymorphism in Paraoxonase 1 and cancer risk: a meta-analysis based on 21 studies - Chen_2016_Onco.Targets.Ther_9_1151
Author(s) : Chen L , Lu W , Fang L , Xiong H , Wu X , Zhang M , Wu S , Yu D
Ref : Onco Targets Ther , 9 :1151 , 2016
Abstract : L55M polymorphism in Paraoxonase 1 (PON1) has been regarded as a risk factor for many cancer types. Nevertheless, the results remain controversial and inconclusive. We therefore performed a meta-analysis of all eligible case-control studies to evaluate the association between L55M polymorphism and cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, a total of 5,627 cases and 6,390 controls, arising from 21 case-control studies, were enrolled in our study. Significant associations between PON1-L55M polymorphism and overall cancer risk were identified in all genetic models. In the stratified analyses by cancer type, PON1-L55M polymorphism was a risk factor for breast cancer in all genetic models, prostate cancer in the heterozygote model (ML vs LL: OR =1.304, 95% CI =1.049-1.620, P heterogeneity=0.067), and ovarian cancer in the recessive model (MM vs ML/LL: OR =1.526, 95% CI =1.110-2.097, P heterogeneity=0.464). Similarly, an increased risk was also identified for the Caucasian population in the heterozygote comparison and homozygote models, and hospital-based controls in all genetic models. To sum up, our study suggests that the PON1-L55M allele increased the risk of cancer. Future well-designed studies with larger sample sizes are warranted to further verify these findings.
ESTHER : Chen_2016_Onco.Targets.Ther_9_1151
PubMedSearch : Chen_2016_Onco.Targets.Ther_9_1151
PubMedID: 27019599

Title : Susceptibility and potential biochemical mechanism of Oedaleus asiaticus to beta-cypermethrin and deltamethrin in the Inner Mongolia, China - Dong_2016_Pestic.Biochem.Physiol_132_47
Author(s) : Dong W , Zhang X , Wu H , Zhang M , Ma E , Zhang J
Ref : Pestic Biochem Physiol , 132 :47 , 2016
Abstract : Oedaleus asiaticus is a highly destructive grass pest in Inner Mongolia, China, and likely developed resistance to pyrethroid insecticides due to their frequent application for control of this locust. In this study, the susceptibility of five field populations of O. asiaticus to two pyrethroid insecticides was investigated. The Wulate Middle Banner (WB) population was the least susceptible, whereas the Ewenki Banner (EB) population appeared to be the most sensitive. The WB population was 3.16 and 5.15-fold less sensitive to beta-cypermethrin and deltamethrin than EB population, respectively. Further, the enzyme activities and mRNA expression levels of carboxylesterase (CarE) and glutathione-S-transferase (GST) were determined and we found that their activities in the WB population were 5.15 and 2.8-fold higher than those in the EB population, respectively. Quantitative real-time PCR (qRT-PCR) analysis demonstrated that the mRNA expression levels of CarE and GST genes were positively correlated with the LD50 in the WB, Siziwang Banner (SB) and EB populations. Our findings suggest that differences in susceptibility to pyrethroids in O. asiaticus might be attributed to the elevated activities and mRNA expression levels of CarE and GST genes.
ESTHER : Dong_2016_Pestic.Biochem.Physiol_132_47
PubMedSearch : Dong_2016_Pestic.Biochem.Physiol_132_47
PubMedID: 27521912

Title : Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro - Bai_2016_Int.J.Biol.Macromol_96_214
Author(s) : Bai Y , Liu L , Zhang R , Huang F , Deng Y , Zhang M
Ref : Int J Biol Macromol , 96 :214 , 2016
Abstract : An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by beta-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function.
ESTHER : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedSearch : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedID: 27908719

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Molecular evaluation of herbal compounds as potent inhibitors of acetylcholinesterase for the treatment of Alzheimer's disease - Chen_2016_Mol.Med.Rep_14_446
Author(s) : Chen YX , Li GZ , Zhang B , Xia ZY , Zhang M
Ref : Mol Med Rep , 14 :446 , 2016
Abstract : Alzheimer's disease (AD) is a progressive disease and the predominant cause of dementia. Common symptoms include short-term memory loss, and confusion with time and place. Individuals with AD depend on their caregivers for assistance, and may pose a burden to them. The acetylcholinesterase (AChE) enzyme is a key target in AD and inhibition of this enzyme may be a promising strategy in the drug discovery process. In the present study, an inhibitory assay was carried out against AChE using total alkaloidal plants and herbal extracts commonly available in vegetable markets. Subsequently, molecular docking simulation analyses of the bioactive compounds present in the plants were conducted, as well as a proteinligand interaction analysis. The stability of the docked proteinligand complex was assessed by 20 ns molecular dynamics simulation. The inhibitory assay demonstrated that Uncaria rhynchophylla and Portulaca oleracea were able to inhibit AChE. In addition, molecular docking simulation analyses indicated that catechin present in Uncaria rhynchophylla, and dopamine and norepinephrine present in Portulaca oleracea, had the best docking scores and interaction energy. In conclusion, catechin in Uncaria rhynchophylla, and dopamine and norepinephrine in Portulaca oleracea may be used to treat AD.
ESTHER : Chen_2016_Mol.Med.Rep_14_446
PubMedSearch : Chen_2016_Mol.Med.Rep_14_446
PubMedID: 27176468

Title : Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning - Tang_2016_Respir.Care_61_965
Author(s) : Tang W , Ruan F , Chen Q , Chen S , Shao X , Gao J , Zhang M
Ref : Respir Care , 61 :965 , 2016
Abstract : BACKGROUND: Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis.
METHODS: The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors.
RESULTS: Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value.
CONCLUSIONS: High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis.
ESTHER : Tang_2016_Respir.Care_61_965
PubMedSearch : Tang_2016_Respir.Care_61_965
PubMedID: 27048625

Title : Drug Repositioning for Alzheimer's Disease Based on Systematic 'omics' Data Mining - Zhang_2016_PLoS.One_11_e0168812
Author(s) : Zhang M , Schmitt-Ulms G , Sato C , Xi Z , Zhang Y , Zhou Y , St George-Hyslop P , Rogaeva E
Ref : PLoS ONE , 11 :e0168812 , 2016
Abstract : Traditional drug development for Alzheimer's disease (AD) is costly, time consuming and burdened by a very low success rate. An alternative strategy is drug repositioning, redirecting existing drugs for another disease. The large amount of biological data accumulated to date warrants a comprehensive investigation to better understand AD pathogenesis and facilitate the process of anti-AD drug repositioning. Hence, we generated a list of anti-AD protein targets by analyzing the most recent publically available 'omics' data, including genomics, epigenomics, proteomics and metabolomics data. The information related to AD pathogenesis was obtained from the OMIM and PubMed databases. Drug-target data was extracted from the DrugBank and Therapeutic Target Database. We generated a list of 524 AD-related proteins, 18 of which are targets for 75 existing drugs-novel candidates for repurposing as anti-AD treatments. We developed a ranking algorithm to prioritize the anti-AD targets, which revealed CD33 and MIF as the strongest candidates with seven existing drugs. We also found 7 drugs inhibiting a known anti-AD target (acetylcholinesterase) that may be repurposed for treating the cognitive symptoms of AD. The CAD protein and 8 proteins implicated by two 'omics' approaches (ABCA7, APOE, BIN1, PICALM, CELF1, INPP5D, SPON1, and SOD3) might also be promising targets for anti-AD drug development. Our systematic 'omics' mining suggested drugs with novel anti-AD indications, including drugs modulating the immune system or reducing neuroinflammation that are particularly promising for AD intervention. Furthermore, the list of 524 AD-related proteins could be useful not only as potential anti-AD targets but also considered for AD biomarker development.
ESTHER : Zhang_2016_PLoS.One_11_e0168812
PubMedSearch : Zhang_2016_PLoS.One_11_e0168812
PubMedID: 28005991

Title : An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF\/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch - Zhao_2015_J.Pharm.Biomed.Anal_120_235
Author(s) : Zhao H , Zhou S , Zhang M , Feng J , Wang S , Wang D , Geng Y , Wang X
Ref : J Pharm Biomed Anal , 120 :235 , 2015
Abstract : In this study, an in vitro acetylcholinesterase (AChE) inhibition assay based on microplate reader combined with ultrafiltration high performance liquid chromatography-electrospray quadrupole time of flight mass (UF-HPLC-ESI-Q-TOF/MS) was developed for the rapid screening and identification of acetylcholinesterase inhibitors (AChEI) from roots of Coptis chinensis Franch. Incubation conditions such as enzyme concentration, incubation time, incubation temperature and co-solvent was optimized so as to get better screening results. Five alkaloids including columbamine, jatrorrhizine, coptisine, palmatine and berberine were found with AChE inhibition activity in the 80% ethanol extract of C. chinensis Franch. The screened compounds were identified by HPLC-DAD-ESI-Q-TOF/MS compared with the reference stands and literatures. The screened results were verified by in vitro AChE inhibition assays, palmatine showed the best AChE inhibitory activities with IC50 values of 36.6muM among the five compounds. Results of the present study indicated that the combinative method using in vitro AChE inhibition assay and UF-HPLC-ESI-Q-TOF/MS could be widely applied for rapid screening and identification of AChEI from complex TCM extract.
ESTHER : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedSearch : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedID: 26760241

Title : Activator of G protein signaling 3 forms a complex with resistance to inhibitors of cholinesterase-8A without promoting nucleotide exchange on Galphai3 - Tse_2015_Mol.Cell.Biochem_401_27
Author(s) : Tse MK , Morris CJ , Zhang M , Wong YH
Ref : Molecular & Cellular Biochemistry , 401 :27 , 2015
Abstract : Activator of G protein signaling 3 (AGS3) is a guanine nucleotide dissociation inhibitor (GDI) which stabilizes the Galphai/o subunits as an AGS3/Galphai/o-GDP complex. It has recently been demonstrated in reconstitution experiments that the AGS3/Galphai/o-GDP complex may act as a substrate of resistance to inhibitors of cholinesterase 8A (Ric-8A), a guanine exchange factor (GEF) for heterotrimeric Galpha proteins. Since the ability of Ric-8A to activate Galphai/o subunits that are bound to AGS3 in a cellular environment has not been confirmed, we thus examined the effect of Ric-8A on cAMP accumulation in HEK293 cells expressing different forms of AGS3 and Galphai3. Co-immunoprecipitation assays indicate that full-length AGS3 and its N- and C-terminal truncated mutants can interact with Ric-8A in HEK293 cells. Yeast two-hybrid assay further confirmed that Ric-8A can directly bind to AGS3S, a short form of AGS3 which is endogenously expressed in heart. However, Ric-8A failed to facilitate Galphai-induced suppression of adenylyl cyclase, suggesting that it may not serve as a GEF for AGS3/Galphai/o-GDP complex in a cellular environment.
ESTHER : Tse_2015_Mol.Cell.Biochem_401_27
PubMedSearch : Tse_2015_Mol.Cell.Biochem_401_27
PubMedID: 25480567

Title : Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population - Hong_2015_Mamm.Genome_26_191
Author(s) : Hong M , Zhang M , Lu X
Ref : Mamm Genome , 26 :191 , 2015
Abstract : Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy-Weinberg equilibrium). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 x 10(-3) and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.
ESTHER : Hong_2015_Mamm.Genome_26_191
PubMedSearch : Hong_2015_Mamm.Genome_26_191
PubMedID: 25690150
Gene_locus related to this paper: human-PLA2G7

Title : Dynamic changes of serum cholinesterase activity after severe trauma - Ba_2014_J.Zhejiang.Univ.Sci.B_15_1023
Author(s) : Ba L , Wu DQ , Qian AY , Zhang M , Xiong B
Ref : J Zhejiang Univ Sci B , 15 :1023 , 2014
Abstract : OBJECTIVE: The aim of the present study was to examine dynamic changes in serum cholinesterase (ChE) activity during early-stage severe trauma and the clinical significance of these changes.
METHODS: This prospective, observational study included 81 patients with severe trauma who were treated between October 2011 and April 2013 in the emergency intensive care unit (EICU) of a university-affiliated, tertiary-care, grade A general hospital in China. Serum ChE activity was measured on Days 1, 3, and 7 post-injury. The correlation of dynamic changes in serum ChE activity with trauma severity and prognosis was assessed. Correlations between changes in serum ChE activity after injury and albumin (ALB), prealbumin (PAB), transferrin (TRF), and C-reactive protein (CRP) levels were also analyzed.
RESULTS: Serum ChE activity in trauma patients was 42.3%-50.2% lower on Days 1, 3, and 7 compared with the control (P<0.001 for all time points), and it continued to decrease after Day 7 in both the survival and death subgroups. In the subgroup with an injury severity score (ISS) of </=25, serum ChE activity initially decreased, but eventually increased. However, activity decreased continuously in the ISS>25 subgroup. ChE activity was significantly lower in both the death and the ISS>25 subgroups than in the survival and ISS</=25 subgroups on Days 1, 3, and 7 after injury. Activity was negatively correlated with ISS and acute physiology and chronic health evaluation III (APACHE III) at all time points. When comparing the receiver operating characteristic (ROC) curves for predicting prognosis, the area under the curve (AUC) in the plot of serum ChE was similar to the AUCs in plots of ISS and APACHE III, but significantly smaller than the AUC in the plot of the trauma and injury severity score (TRISS). Serum ChE activity was positively correlated with ALB, PAB, and TRF at all time points post-injury. Activity was not significantly correlated with CRP on Day 1, but was significantly and negatively correlated with CRP on Days 3 and 7.
CONCLUSIONS: There is a significant decrease in serum ChE activity after severe trauma. Serum ChE may be regarded as a negative acute phase protein (APP) and the dynamic changes in serum ChE may be useful as an auxiliary indicator for evaluating trauma severity and predicting prognosis.
ESTHER : Ba_2014_J.Zhejiang.Univ.Sci.B_15_1023
PubMedSearch : Ba_2014_J.Zhejiang.Univ.Sci.B_15_1023
PubMedID: 25471831

Title : Lactobacillus casei-01 Facilitates the Ameliorative Effects of Proanthocyanidins Extracted from Lotus Seedpod on Learning and Memory Impairment in Scopolamine-Induced Amnesia Mice - Xiao_2014_PLoS.One_9_e112773
Author(s) : Xiao J , Li S , Sui Y , Wu Q , Li X , Xie B , Zhang M , Sun Z
Ref : PLoS ONE , 9 :e112773 , 2014
Abstract : Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (109 cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.
ESTHER : Xiao_2014_PLoS.One_9_e112773
PubMedSearch : Xiao_2014_PLoS.One_9_e112773
PubMedID: 25396737

Title : Highly sensitive assay for acetylcholinesterase activity and inhibition based on a specifically reactive photonic nanostructure - Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
Author(s) : Tian T , Li X , Cui J , Li J , Lan Y , Wang C , Zhang M , Wang H , Li G
Ref : ACS Appl Mater Interfaces , 6 :15456 , 2014
Abstract : Assays for acetylcholinesterase (AChE) with high sensitivity and high selectivity as well as facile manipulation have been urgently required in various fields. In this work, a reaction-based photonic strategy was developed for the efficient assay of AChE activity and inhibition based on the synergetic combination of the specific thiol-maleimide addition reaction with photonic porous structure. It was found that various applications including detection of AChE activity, measurement of the related enzymatic kinetics, and screening of inhibitors could be efficiently implemented using such strategy. Remarkably, the unique photonic nanostructure endows the constructed sensing platform with high sensitivity with a limit of detection (LOD) of 5 mU/mL for AChE activity, high selectivity, and self-reporting signaling. Moreover, the label-free solid film-based sensing approach described here has advantages of facile manipulation and bare-eye readout, compared with conventional liquid-phase methods, exhibiting promising potential in practical application for the AChE assay.
ESTHER : Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
PubMedSearch : Tian_2014_ACS.Appl.Mater.Interfaces_6_15456
PubMedID: 25130420

Title : Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics - Zhang_2014_Nat.Commun_5_3849
Author(s) : Zhang Y , Zhang K , Fang A , Han Y , Yang J , Xue M , Bao J , Hu D , Zhou B , Sun X , Li S , Wen M , Yao N , Ma LJ , Liu Y , Zhang M , Huang F , Luo C , Zhou L , Li J , Chen Z , Miao J , Wang S , Lai J , Xu JR , Hsiang T , Peng YL , Sun W
Ref : Nat Commun , 5 :3849 , 2014
Abstract : Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U. virens that encodes 8,426 predicted genes. The genome has ~25% repetitive sequences that have been affected by repeat-induced point mutations. Evolutionarily, U. virens is close to the entomopathogenic Metarhizium spp., suggesting potential host jumping across kingdoms. U. virens possesses reduced gene inventories for polysaccharide degradation, nutrient uptake and secondary metabolism, which may result from adaptations to the specific floret infection and biotrophic lifestyles. Consistent with their potential roles in pathogenicity, genes for secreted proteins and secondary metabolism and the pathogen-host interaction database genes are highly enriched in the transcriptome during early infection. We further show that 18 candidate effectors can suppress plant hypersensitive responses. Together, our analyses offer new insights into molecular mechanisms of evolution, biotrophy and pathogenesis of U. virens.
ESTHER : Zhang_2014_Nat.Commun_5_3849
PubMedSearch : Zhang_2014_Nat.Commun_5_3849
PubMedID: 24846013
Gene_locus related to this paper: ustvr-a0a063bxn3

Title : Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses - Chu_2014_Int.Immunopharmacol_19_317
Author(s) : Chu S , Gu J , Feng L , Liu J , Zhang M , Jia X , Liu M , Yao D
Ref : Int Immunopharmacol , 19 :317 , 2014
Abstract : Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-alpha and IL-1beta (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Abeta deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Abeta deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.
ESTHER : Chu_2014_Int.Immunopharmacol_19_317
PubMedSearch : Chu_2014_Int.Immunopharmacol_19_317
PubMedID: 24503167

Title : Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes - Zhang_2014_Proc.Natl.Acad.Sci.U.S.A_111_E3708
Author(s) : Zhang M , Chekan JR , Dodd D , Hong PY , Radlinski L , Revindran V , Nair SK , Mackie RI , Cann I
Ref : Proc Natl Acad Sci U S A , 111 :E3708 , 2014
Abstract : Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose-configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 A), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 A), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 A) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health.
ESTHER : Zhang_2014_Proc.Natl.Acad.Sci.U.S.A_111_E3708
PubMedSearch : Zhang_2014_Proc.Natl.Acad.Sci.U.S.A_111_E3708
PubMedID: 25136124

Title : A reference genome for common bean and genome-wide analysis of dual domestications - Schmutz_2014_Nat.Genet_46_707
Author(s) : Schmutz J , McClean PE , Mamidi S , Wu GA , Cannon SB , Grimwood J , Jenkins J , Shu S , Song Q , Chavarro C , Torres-Torres M , Geffroy V , Moghaddam SM , Gao D , Abernathy B , Barry K , Blair M , Brick MA , Chovatia M , Gepts P , Goodstein DM , Gonzales M , Hellsten U , Hyten DL , Jia G , Kelly JD , Kudrna D , Lee R , Richard MM , Miklas PN , Osorno JM , Rodrigues J , Thareau V , Urrea CA , Wang M , Yu Y , Zhang M , Wing RA , Cregan PB , Rokhsar DS , Jackson SA
Ref : Nat Genet , 46 :707 , 2014
Abstract : Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.
ESTHER : Schmutz_2014_Nat.Genet_46_707
PubMedSearch : Schmutz_2014_Nat.Genet_46_707
PubMedID: 24908249
Gene_locus related to this paper: phavu-v7azs2 , phavu-v7awu7 , phavu-v7bpt6 , phavu-v7b6k3 , phavu-v7cry4

Title : Genome sequence of the date palm Phoenix dactylifera L - Al-Mssallem_2013_Nat.Commun_4_2274
Author(s) : Al-Mssallem IS , Hu S , Zhang X , Lin Q , Liu W , Tan J , Yu X , Liu J , Pan L , Zhang T , Yin Y , Xin C , Wu H , Zhang G , Ba Abdullah MM , Huang D , Fang Y , Alnakhli YO , Jia S , Yin A , Alhuzimi EM , Alsaihati BA , Al-Owayyed SA , Zhao D , Zhang S , Al-Otaibi NA , Sun G , Majrashi MA , Li F , Tala , Wang J , Yun Q , Alnassar NA , Wang L , Yang M , Al-Jelaify RF , Liu K , Gao S , Chen K , Alkhaldi SR , Liu G , Zhang M , Guo H , Yu J
Ref : Nat Commun , 4 :2274 , 2013
Abstract : Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants.
ESTHER : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedSearch : Al-Mssallem_2013_Nat.Commun_4_2274
PubMedID: 23917264
Gene_locus related to this paper: phodc-a0a2h3y3d5 , phodc-a0a2h3z529 , phodc-a0a2h3y147 , phodc-a0a2h3xrz4 , phodc-a0a3q0ic37 , phodc-a0a2h3yxf0 , phodc-a0a2h3zh01 , phodc-a0a3q0hs32

Title : Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers - Zhang_2013_J.Occup.Environ.Med_55_1001
Author(s) : Zhang M , Wang Y , Wang Q , Yang D , Zhang J , Wang F , Gu Q
Ref : J Occup Environ Med , 55 :1001 , 2013
Abstract : OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers.
METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined.
RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase.
CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.
ESTHER : Zhang_2013_J.Occup.Environ.Med_55_1001
PubMedSearch : Zhang_2013_J.Occup.Environ.Med_55_1001
PubMedID: 23969497

Title : Investigation Binding Patterns of Human Carboxylesterase I (hCES I) with Broad Substrates by MD Simulations - Chu_2013_Curr.Top.Med.Chem_13_1222
Author(s) : Chu H , Min H , Zhang M , Shen H , Li G
Ref : Curr Top Med Chem , 13 :1222 , 2013
Abstract : Human carboxylesterase I (hCES 1) plays an important role in the metabolism and activation of prodrugs, such as, the hydrolysis of a variety of drugs of prodrugs featuring an ester, amide or carbamate function. The bindings of the substrates of different lengths and cocaine to hCES1 at two different binding sites, catalytic site and Z-site, were studies through MD simulations. For each case, the correlation analysis has been performed to explore the binding patterns of a broad range of substrates binding to the hCES1.
ESTHER : Chu_2013_Curr.Top.Med.Chem_13_1222
PubMedSearch : Chu_2013_Curr.Top.Med.Chem_13_1222
PubMedID: 23647544

Title : A randomized, 4-week double-blind placebo control study on the efficacy of donepezil augmentation of lithium for treatment of acute mania - Chen_2013_Neuropsychiatr.Dis.Treat_9_839
Author(s) : Chen J , Lu Z , Zhang M , Zhang J , Ni X , Jiang X , Xu H , Heeramun-Aubeeluck A , Hu Q , Jin H , Davis JM
Ref : Neuropsychiatr Dis Treat , 9 :839 , 2013
Abstract : INTRODUCTION: A significant number of mania patients fail to respond to current pharmacotherapy, thereby there is need for novel augmentation strategies. The results of some early studies showed the effectiveness of cholinomimetics in the treatment of mania. One open case series suggested the efficacy of donepezil in the treatment of bipolar disorder. Our aim was to explore whether an oral cholinesterase inhibitor, donepezil, administered during a 4-week treatment period, would benefit patients with acute mania.
METHODS: We conducted a 4-week double-blind, placebo-controlled trial of donepezil as an adjunctive treatment to lithium in patients with acute mania. Eligible subjects were randomly assigned to receive donepezil or placebo in addition to lithium. Donepezil was started at 5 mg/day, and increased to 10 mg/day in the first week. Patients were rated with the Young Mania Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS) at baseline, day 1, week 1, week 2, and week 4.
RESULTS: Out of the 30 patients who were enrolled, 15 were on donepezil and 15 were on placebo. All patients completed the 4-week trial. On the first day, there was a difference of 1.97 units on the psychomotor symptoms scale of the YMRS in the donepezil group as compared to the placebo group (t = 2.39, P = 0.02). There was a difference of 0.57 units (t = 2.09, P = 0.04) in the speech item and a difference of 0.29 units in the sexual interest item (t = 2.11, P = 0.04) in the donepezil group as compared to the placebo group. The total YMRS difference on the first day approached the conventional significance level (1.97 units, t = 1.84, P = 0.07). Over the course of 4 weeks, we failed to find that donepezil produced any significant difference in the YMRS (6.71 units difference, t = -1.44, P = 0.16) or the BPRS scale (1.29 units difference, t = -0.33, P = 0.75) as compared to placebo. Ten subjects (66.67%) in both groups met the criteria for clinical response (Fisher's exact P = 1.00). Five subjects (33.33%) in the donepezil group met the criteria for clinical remission while nine subjects (60.00%) in the placebo group met the remission criteria (Fisher's exact P = 0.27). CONCLUSION: Use of the oral anticholinergic donepezil had some benefit in the augmentation of lithium treatment on the first day, but did not provide any significant benefits in the long-term.
ESTHER : Chen_2013_Neuropsychiatr.Dis.Treat_9_839
PubMedSearch : Chen_2013_Neuropsychiatr.Dis.Treat_9_839
PubMedID: 23807849

Title : Optimal dose of zinc supplementation for preventing aluminum-induced neurotoxicity in rats - Lu_2013_Neural.Regen.Res_8_2754
Author(s) : Lu H , Hu J , Li J , Pang W , Hu Y , Yang H , Li W , Huang C , Zhang M , Jiang Y
Ref : Neural Regen Res , 8 :2754 , 2013
Abstract : Zinc supplementation can help maintain learning and memory function in rodents. In this study, we hypothesized that zinc supplementation could antagonize the neurotoxicity induced by aluminum in rats. Animals were fed a diet containing different doses of zinc (50, 100, 200 mg/kg) for 9 weeks, and orally administered aluminum chloride (300 mg/kg daily) from the third week for 7 consecutive weeks. Open-field behavioral test results showed that the number of rearings in the group given the 100 mg/kg zinc supplement was significantly increased compared with the group given the 50 mg/kg zinc supplement. Malondialdehyde content in the cerebrum was significantly decreased, while dopamine and 5-hydroxytryptamine levels were increased in the groups given the diet supplemented with 100 and 200 mg/kg zinc, compared with the group given the diet supplemented with 50 mg/kg zinc. The acetylcholinesterase activity in the cerebrum was significantly decreased in the group given the 100 mg/kg zinc supplement. Hematoxylin-eosin staining revealed evident pathological damage in the hippocampus of rats in the group given the diet supplemented with 50 mg/kg zinc, but the damage was attenuated in the groups given the diet supplemented with 100 and 200 mg/kg zinc. Our findings suggest that zinc is a potential neuroprotective agent against aluminum-induced neurotoxicity in rats, and the optimal dosages are 100 and 200 mg/kg.
ESTHER : Lu_2013_Neural.Regen.Res_8_2754
PubMedSearch : Lu_2013_Neural.Regen.Res_8_2754
PubMedID: 25206586

Title : Enhancement of lipase r27RCL production in Pichia pastoris by regulating gene dosage and co-expression with chaperone protein disulfide isomerase - Sha_2013_Enzyme.Microb.Technol_53_438
Author(s) : Sha C , Yu XW , Lin NX , Zhang M , Xu Y
Ref : Enzyme Microb Technol , 53 :438 , 2013
Abstract : Pichia pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, but there is still a large room of improvement for this expression system. Two factors drastically influence the lipase r27RCL production from Rhizopus chinensis CCTCC M201021, which are gene dosage and protein folding in the endoplasmic reticulum (ER). Regarding the effect of gene dosage, the enzyme activity for recombinant strain with three copies lipase gene was 1.95-fold higher than that for recombinant strain with only one copy lipase gene. In addition, the lipase production was further improved by co-expression with chaperone PDI involved in the disulfide bond formation in the ER. Overall, the maximum enzyme activity reached 355U/mL by the recombinant strain with one copy chaperone gene PDI plus five copies lipase gene proRCL in shaking flasks, which was 2.74-fold higher than that for the control strain with only one copy lipase gene. Overall, co-expression with PDI vastly increased the capacity for processing proteins of ER in P. pastoris.
ESTHER : Sha_2013_Enzyme.Microb.Technol_53_438
PubMedSearch : Sha_2013_Enzyme.Microb.Technol_53_438
PubMedID: 24315648
Gene_locus related to this paper: rhich-a3fm73

Title : Xenobiotic metabolism of plant secondary compounds in the English grain aphid, Sitobion avenae (F.) (Hemiptera: Aphididae) - Zhang_2013_Pestic.Biochem.Physiol_107_44
Author(s) : Zhang M , Fang T , Pu G , Sun X , Zhou X , Cai Q
Ref : Pestic Biochem Physiol , 107 :44 , 2013
Abstract : Plant secondary compounds have been documented to be deleterious to insects and other herbivores in diverse ways. In this study, the effect of catechol (phenolics), gramine (alkaloid) and L-ornithine-HCI (non-protein amino acid) on the activities of xenobiotic metabolizing enzymes in English grain aphid, Sitobion avenae, was evaluated. Phase I enzymes investigated in this study included carboxylesterase (CarE), and oxidoreductase, whereas Phase II enzymes were represented by glutathione S-transferase (GST). In general, CarE and GST activities in S. avenae were positively correlated with the concentration of plant secondary compounds in artificial diets. Oxidoreductase activity, however, displayed a different profile. Specifically, peroxidase (POD) and polyphenol oxidase (PPO) activities in S. avenae were positively correlated with concentrations of dietary catechol and gramine, respectively, whereas catalase (CAT) activity was significantly suppressed by the higher concentration of catechol, gramine and L-ornithine-HCl. These combined results suggest that CarE and GST in S. avenae are key enzymes to breakdown a broad spectrum of plant secondary compounds, whereas oxidoreductase, including PPO and POD, degrades specific groups of plant secondary compounds.
ESTHER : Zhang_2013_Pestic.Biochem.Physiol_107_44
PubMedSearch : Zhang_2013_Pestic.Biochem.Physiol_107_44
PubMedID: 25149234

Title : Genome Sequence of Streptomyces violaceusniger Strain SPC6, a Halotolerant Streptomycete That Exhibits Rapid Growth and Development - Chen_2013_Genome.Announc_1_e00494
Author(s) : Chen X , Zhang B , Zhang W , Wu X , Zhang M , Chen T , Liu G , Dyson P
Ref : Genome Announc , 1 : , 2013
Abstract : Streptomyces violaceusniger strain SPC6 is a halotolerant streptomycete isolated from the Linze desert in China. The strain has a very high growth rate and a short life cycle for a streptomycete. For surface-grown cultures, the period from spore germination to formation of colonies with mature spore chains is only 2 days at 37 degrees C. Additionally, the strain is remarkably resistant to osmotic, heat, and UV stress compared with other streptomycetes. Analysis of the draft genome sequence indicates that the strain has the smallest reported genome (6.4 Mb) of any streptomycete. The availability of this genome sequence allows us to investigate the genetic basis of adaptation for growth in an extremely arid environment.
ESTHER : Chen_2013_Genome.Announc_1_e00494
PubMedSearch : Chen_2013_Genome.Announc_1_e00494
PubMedID: 23868127
Gene_locus related to this paper: 9actn-a0a1d3dv58

Title : The presence of hepatitis B core antibody is associated with more advanced liver disease in alcoholic patients with cirrhosis - Zhang_2013_Alcohol_47_553
Author(s) : Zhang M , Wu R , Jiang J , Minuk GY , Niu J
Ref : Alcohol , 47 :553 , 2013
Abstract : BACKGROUND: Liver disease is more severe in patients with chronic hepatitis B virus (HBV) infections and alcohol-induced liver injury. Whether the same is true for alcoholic patients with cirrhosis who have recovered from previous HBV infections remains to be determined. OBJECTIVES: To document the extent of liver disease in alcoholic patients with cirrhosis who test negative for hepatitis B surface antigen (HBsAg) and test positive for antibody to hepatitis B core antigen (anti-HBc).
METHODS: Two hundred fifty-four alcoholic patients with cirrhosis were divided into anti-HBc-positive (N = 171) and anti-HBc-negative (N = 83) cohorts. Demographic, clinical, and biochemical features were retrospectively analyzed. Prognostic scores and the prevalence of patients at high risk for short-term mortality were calculated. Logistic regression was used to identify factors associated with an increased risk for short-term mortality.
RESULTS: Jaundice was more common in the anti-HBc-positive cohort (32.2% vs. 18.1%, p = 0.02). This cohort also had higher serum bilirubin (70.9 vs. 50.4 mum/L, p = 0.03), prothrombin times (15.6 vs. 14.4 s, p = 0.01), MELD scores (8.5 vs. 4.6, p = 0.01), i-MELD scores (28.6 vs. 24.7, p = 0.03), MDF scores (14.2 vs. 6.8, p = 0.02) and ABIC scores (7.2 vs. 6.6, p = 0.01). In addition, anti-HBC-positive patients were more often at high risk for short-term mortality (40.4% vs. 26.5%, p = 0.03). Multivariate analysis identified anti-HBc-positive status (OR: 1.84; 95% CI: 1.10-3.36) and alcohol intake >/=150 g/day (OR: 2.01; 95% CI: 1.10-3.66) as independent risk factors for high risk of mortality. CONCLUSION: The anti-HBc-positive state is associated with more advanced liver disease in alcoholic patients with cirrhosis. A prospective study including HBV-DNA testing and liver biopsies should be considered to validate and further elucidate these findings.
ESTHER : Zhang_2013_Alcohol_47_553
PubMedSearch : Zhang_2013_Alcohol_47_553
PubMedID: 24041840

Title : Efficient secretion of lipase r27RCL in Pichia pastoris by enhancing the disulfide bond formation pathway in the endoplasmic reticulum - Sha_2013_J.Ind.Microbiol.Biotechnol_40_1241
Author(s) : Sha C , Yu XW , Zhang M , Xu Y
Ref : J Ind Microbiol Biotechnol , 40 :1241 , 2013
Abstract : The lipase r27RCL from Rhizopus chinensis CCTCC M201021 was heterologously expressed in Pichia pastoris GS115 by simultaneous co-expression with two secretion factors ERO1p and PDI involved in the endoplasmic reticulum (ER). Compared to the expression of the lipase alone (12,500 U/ml), co-expression with these two proteins resulted in the production of larger total quantities of enzymes. The largest increase was seen when the combined ERO1p/PDI system was co-expressed, resulting in approximately 30 % higher enzyme yields (16,200 U/ml) than in the absence of co-expressed secretion factors. The extracellular protein concentration of the recombinant strain Co XY RCL-5 reached 9.39 g/l in the 7-l fermentor. Simultaneously, the fermentation time was also shortened by about 8 h compared to that of the control. The substrate-specific consumption rate (Qs) and the product-specific production rate (Qp) were both investigated in this research. In conclusion, the space-time yield was improved by co-expression with ERO1p and PDI. This is a potential strategy for high level expression of other heterologous proteins in P. pastoris.
ESTHER : Sha_2013_J.Ind.Microbiol.Biotechnol_40_1241
PubMedSearch : Sha_2013_J.Ind.Microbiol.Biotechnol_40_1241
PubMedID: 23990169
Gene_locus related to this paper: rhich-a3fm73

Title : Study on the enzymatic degradation of PBS and its alcohol acid modified copolymer - Ding_2012_Biodegradation_23_127
Author(s) : Ding M , Zhang M , Yang J , Qiu JH
Ref : Biodegradation , 23 :127 , 2012
Abstract : Enzymatic hydrolytic degradation of polybutylene succinate (PBS), poly(polybutylenesuccinate-co-1,4-cyclohexane dimethanol) (PBS/CHDM) and poly(polybutylene succinate-co-diglycolic acid) (PBS/DGA) in mixed solvent of tetrahydrofuran (THF) and toluene was examined. Lipase was used as catalyst to degrade polymers with molecular weight of more than 100,000, and the molecular weight of products ranged from hundreds to thousands. Thermal decomposition temperatures of all products were below 250 degrees C. The degradation products of both PBS/CHDM and PBS/DGA showed two melting points at about 85 and 99 degrees C. Mass spectrometry (MS) was employed to obtain the molecular weight of oligomers extracted from the products, which proved to be low-polyesters with the molecular weight of less 1,000. The butanediol (BDO) monomer was found in PBS/CHDM degradation product for the first time.
ESTHER : Ding_2012_Biodegradation_23_127
PubMedSearch : Ding_2012_Biodegradation_23_127
PubMedID: 21732135

Title : Genome sequences of wild and domestic bactrian camels - Jirimutu_2012_Nat.Commun_3_1202
Author(s) : Jirimutu , Wang Z , Ding G , Chen G , Sun Y , Sun Z , Zhang H , Wang L , Hasi S , Zhang Y , Li J , Shi Y , Xu Z , He C , Yu S , Li S , Zhang W , Batmunkh M , Ts B , Narenbatu , Unierhu , Bat-Ireedui S , Gao H , Baysgalan B , Li Q , Jia Z , Turigenbayila , Subudenggerile , Narenmanduhu , Wang J , Pan L , Chen Y , Ganerdene Y , Dabxilt , Erdemt , Altansha , Altansukh , Liu T , Cao M , Aruuntsever , Bayart , Hosblig , He F , Zha-ti A , Zheng G , Qiu F , Zhao L , Zhao W , Liu B , Li C , Tang X , Guo C , Liu W , Ming L , Temuulen , Cui A , Li Y , Gao J , Wurentaodi , Niu S , Sun T , Zhai Z , Zhang M , Chen C , Baldan T , Bayaer T , Meng H
Ref : Nat Commun , 3 :1202 , 2012
Abstract : Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
ESTHER : Jirimutu_2012_Nat.Commun_3_1202
PubMedSearch : Jirimutu_2012_Nat.Commun_3_1202
PubMedID: 23149746
Gene_locus related to this paper: 9ceta-s9yik4 , 9ceta-s9yb99 , 9ceta-s9x0n3 , 9ceta-s9xqa3 , 9ceta-s9xi02 , camfr-s9wiw9 , camfr-s9x3r3 , camfr-s9xce1 , camfr-s9xcr2 , camfr-s9yuz0 , camfr-s9xlc8 , camfr-s9w5f6 , camfr-s9xmm4

Title : The association of HLA-DQA1*0401 and DQB1*0604 with thymomatous myasthenia gravis in northern Chinese patients - Yang_2012_J.Neurol.Sci_312_57
Author(s) : Yang H , Hao J , Peng X , Simard AR , Zhang M , Xie Y , Wang S
Ref : Journal of Neurology Sci , 312 :57 , 2012
Abstract : Genetic analyses indicate that HLA complex genes can be involved in susceptibility to autoimmune myasthenia gravis (MG). Various HLA alleles serve as genetic elements that either predispose to or protect against MG. This study investigates the probable relationship between HLA-DQ allele polymorphisms and MG cases in northern China. The HLA-DQA1 and DQB1 alleles were determined by polymerase chain reaction/sequence-specific primers (PCR-SSP) in 84 MG patients, and the results were compared to 293 healthy controls. Our findings indicate that DQ A1*0401(P=0.008, OR: 2.5, 95%CI: 1.24-3.07) and B1*0301(P=0.000, OR: 2.29, 95%CI: 1.48-3.54) were the most frequent allele; the frequencies of DQA1*0103(P=0.000, OR:0.24, 95%CI 0.13-0.49) and DQB1*0601(P=0.001, OR:0.40, 95%CI 0.22-0.50) were significantly decreased in MG patients compared with healthy controls. Patients with thymomatous MG were positively associated with DQA1 *0401(P=0.011, OR:4.57, 95% CI 1.40-14.90) and DQB1 *0604 (P=0.001, OR:4.01, 95% CI 1.65-9.73) as compared to MG patients without thymoma. Different genetic mechanisms may exist between MG patients with thymoma and those without thymoma. The HLA-DQ associations in MG subgroups suggest that disease heterogeneity may be influenced by different genes or alleles.
ESTHER : Yang_2012_J.Neurol.Sci_312_57
PubMedSearch : Yang_2012_J.Neurol.Sci_312_57
PubMedID: 21917268

Title : Enhanced thermostability of a Rhizopus chinensis lipase by in vivo recombination in Pichia pastoris - Yu_2012_Microb.Cell.Fact_11_102
Author(s) : Yu XW , Wang R , Zhang M , Xu Y , Xiao R
Ref : Microb Cell Fact , 11 :102 , 2012
Abstract : BACKGROUND: Lipase from Rhizopus chinensis is a versatile biocatalyst for various bioconversions and has been expressed at high-level in Pichia pastoris. However, the use of R. chinensis lipase in industrial applications is restricted by its low thermostability. Directed evolution has been proven to be a powerful and efficient protein engineering tool for improvement of biocatalysts. The present work describes improvement of the thermostability of R. chinensis lipase by directed evolution using P. pastoris as the host. RESULTS: An efficient, fast and highly simplified method was developed to create a mutant gene library in P. pastoris based on in vivo recombination, whose recombination efficiency could reach 2.3 x 10/microg DNA. The thermostability of r27RCL was improved significantly by two rounds of error-prone PCR and two rounds of DNA shuffling in P. pastoris. The S4-3 variant was found to be the most thermostable lipase, under the conditions tested. Compared with the parent, the optimum temperature of S4-3 was two degrees higher, Tm was 22 degrees higher and half-lives at 60 degreesC and 65 degreesC were 46- and 23- times longer. Moreover, the catalytic efficiency kcat/Km of S4-3 was comparable to the parent. Stabilizing mutations probably increased thermostability by increasing the hydrophilicity and polarity of the protein surface and creating hydrophobic contacts inside the protein. CONCLUSIONS: P. pastoris was shown to be a valuable cell factory to improve thermostability of enzymes by directed evolution and it also could be used for improving other properties of enzymes. In this study, by using P. pastoris as a host to build mutant pool, we succeeded in obtaining a thermostable variant S4-3 without compromising enzyme activity and making it a highly promising candidate for future applications at high temperatures.
ESTHER : Yu_2012_Microb.Cell.Fact_11_102
PubMedSearch : Yu_2012_Microb.Cell.Fact_11_102
PubMedID: 22866667
Gene_locus related to this paper: rhich-a3fm73

Title : [The changes of blood neurotransmitter levels in workers occupationally exposed to ethylbenzene] - Wang_2011_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_29_125
Author(s) : Wang YR , Yang DY , Zhang M , Wang Q , Liu J , Li JG
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 29 :125 , 2011
Abstract : OBJECTIVE: To explore the effects of occupational ethylbenzene exposure on blood neurotransmitter levels in population. METHODS: The exposure group consisted of 246 workers occupationally exposed to ethylbenzene and the control group was composed of 122 staffs from the offices. The basic information on ethylbenzene exposure was collected by the questionnaire. The mandelic acid (MA) and phenylglyoxylic acid (PGA) in the post-working urine were measured using the high performance liquid chromatography. The levels of gamma-aminobutyric acid (GABA), dopamine (DA) and acetylcholinesterase (AchE) activity were detected by reversed phase high performance liquid chromatography, spectrofluorometry and DTNB method, respectively. The blood biochemical indexes: alanine transaminase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), alkaline phosphatase (ALP), total bilirubin (TBIL) were examined. Also the hematologic indexes: red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB) and platelet (PLT) were determined. RESULTS: The levels of MA, PGA and MA+PGA of urine in the exposed group were significantly higher than those in the control group (P < 0.05). There were no significant differences of the biochemical indexes (AST, ALT, TP, ALB, BUN, Cr, ALP and TBIL), hematologic indexes (WBC, RBC, Hb and PLT) and serum GABA between the exposure group and the control group (P > 0.05). But the serum DA [(0.21 +/- 0.011) mg/L] and AChE levels [(0.321 +/- 0.066) U/L] in the exposure group were significantly lower than those in the control group [(0.25 +/- 0.015) mg/L, (0.583 +/- 0.125) U/L], respectively (P < 0.05). CONCLUSION: MA and PGA in urine can serve as the biomarkers of internal exposure dose. Before the obvious changes of biochemical indexes and hematologic indexes appear, the exposure to ethylbenzene can influence the blood neurotransmitter levels in workers exposed to ethylbenzene.
ESTHER : Wang_2011_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_29_125
PubMedSearch : Wang_2011_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_29_125
PubMedID: 21619842

Title : Visual detection of organophosphorus pesticides represented by mathamidophos using Au nanoparticles as colorimetric probe - Li_2011_Talanta_87_93
Author(s) : Li H , Guo J , Ping H , Liu L , Zhang M , Guan F , Sun C , Zhang Q
Ref : Talanta , 87 :93 , 2011
Abstract : With citrate-coated Au nanoparticles as colorimetric probe, a novel visual method for rapid assay of organophosphorus pesticides has been developed. The assay principle is based on catalytic hydrolysis of acetylthiocholine into thiocholine by acetylcholinesterase, which induces the aggregation of Au nanoparticles and the color change from claret-red to purple or even grey. The original plasmon absorption of Au nanoparticles at 522 nm decreases, and simultaneously, a new absorption band appears at 675 nm. The irreversible inhibition of organophosphorus pesticides on acetylcholinesterase prevents aggregation of Au nanoparticles. Under optimum conditions, the absorbance at 522 nm of Au nanoparticles is related linearly to the concentration of mathamidophos in the range of 0.02-1.42 mug/mL with a detection limit of 1.40 ng/mL. This colorimetric method has been successfully utilized to detect mathamidophos in vegetables with satisfactory results. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for the analysis of organophosphorus pesticides.
ESTHER : Li_2011_Talanta_87_93
PubMedSearch : Li_2011_Talanta_87_93
PubMedID: 22099654

Title : Phenolic compounds from the whole plants of Gentiana rhodantha (Gentianaceae) - Xu_2011_Chem.Biodivers_8_1891
Author(s) : Xu M , Zhang M , Wang D , Yang CR , Zhang YJ
Ref : Chem Biodivers , 8 :1891 , 2011
Abstract : Gentiana rhodantha Franch. ex Hemsl. (Gentianaceae), an annual herb widely distributed in the southwest of China, has been medicinally used for the treatment of inflammation, cholecystitis, and tuberculosis by the local people of its growing areas. Chemical investigation on the whole plants led to the identification of eight new phenolic compounds, rhodanthenones A-D (1-4, resp.), apigenin 7-O-glucopyranosyl-(1-->3)-glucopyranosyl-(1-->3)-glucopyranoside (5), 1,2-dihydroxy-4-methoxybenzene 1-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (6), 1,2-dihydroxy-4,6-dimethoxybenzene 1-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (7), and methyl 2-O-beta-D-glucopyranosyl-2,4,6-trihydroxybenzoate (8), together with eleven known compounds, 9-19. Their structures were determined on the basis of detailed spectroscopic analyses and chemical methods. Acetylcholinesterase (AChE) inhibition and cytotoxicity tests against five human cancer cell lines showed that only rhodanthenone D (4) and mangiferin (12) exhibited 18.4 and 13.4% of AChE inhibitory effects at a concentration of 10(-4) M, respectively, while compounds 1-5 and the known xanthones lancerin (11), mangiferin (12), and neomangiferin (13) displayed no cytotoxicity at a concentration of 40 muM.
ESTHER : Xu_2011_Chem.Biodivers_8_1891
PubMedSearch : Xu_2011_Chem.Biodivers_8_1891
PubMedID: 22006717

Title : Poster: The use of the scopolamine-induced cognitive impairment model to translate on-target activity for ABT-894 from rodents\/monkeys to humans: Preclinical evidences -
Author(s) : Rueter LE , Relo AL , van Gaalen MM , Ballard ME , Terry AV, Jr. , Buccafusco JJ , Zhang M
Ref : Biochemical Pharmacology , 82 :1043 , 2011

Title : The evolution of host specialization in the vertebrate gut symbiont Lactobacillus reuteri - Frese_2011_PLoS.Genet_7_e1001314
Author(s) : Frese SA , Benson AK , Tannock GW , Loach DM , Kim J , Zhang M , Oh PL , Heng NC , Patil PB , Juge N , Mackenzie DA , Pearson BM , Lapidus A , Dalin E , Tice H , Goltsman E , Land M , Hauser L , Ivanova N , Kyrpides NC , Walter J
Ref : PLoS Genet , 7 :e1001314 , 2011
Abstract : Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In order to differentiate true host-specific genome content from strain-level differences, comparative genome hybridizations were performed to query 57 L. reuteri strains originating from six different vertebrate hosts in combination with genome sequence comparisons of nine strains encompassing five phylogenetic lineages of the species. This approach revealed that rodent strains, although showing a high degree of genomic plasticity, possessed a specific genome inventory that was rare or absent in strains from other vertebrate hosts. The distinct genome content of L. reuteri lineages reflected the niche characteristics in the gastrointestinal tracts of their respective hosts, and inactivation of seven out of eight representative rodent-specific genes in L. reuteri 100-23 resulted in impaired ecological performance in the gut of mice. The comparative genomic analyses suggested fundamentally different trends of genome evolution in rodent and human L. reuteri populations, with the former possessing a large and adaptable pan-genome while the latter being subjected to a process of reductive evolution. In conclusion, this study provided experimental evidence and a molecular basis for the evolution of host specificity in a vertebrate gut symbiont, and it identified genomic events that have shaped this process.
ESTHER : Frese_2011_PLoS.Genet_7_e1001314
PubMedSearch : Frese_2011_PLoS.Genet_7_e1001314
PubMedID: 21379339
Gene_locus related to this paper: lacre-b3xl60 , lacrj-b2g622 , lacre-a0a0s4nmr3

Title : Comparative genome sequence analysis underscores mycoparasitism as the ancestral life style of Trichoderma - Kubicek_2011_Genome.Biol_12_R40
Author(s) : Kubicek CP , Herrera-Estrella A , Seidl-Seiboth V , Martinez DA , Druzhinina IS , Thon M , Zeilinger S , Casas-Flores S , Horwitz BA , Mukherjee PK , Mukherjee M , Kredics L , Alcaraz LD , Aerts A , Antal Z , Atanasova L , Cervantes-Badillo MG , Challacombe J , Chertkov O , McCluskey K , Coulpier F , Deshpande N , von Dohren H , Ebbole DJ , Esquivel-Naranjo EU , Fekete E , Flipphi M , Glaser F , Gomez-Rodriguez EY , Gruber S , Han C , Henrissat B , Hermosa R , Hernandez-Onate M , Karaffa L , Kosti I , Le Crom S , Lindquist E , Lucas S , Lubeck M , Lubeck PS , Margeot A , Metz B , Misra M , Nevalainen H , Omann M , Packer N , Perrone G , Uresti-Rivera EE , Salamov A , Schmoll M , Seiboth B , Shapiro H , Sukno S , Tamayo-Ramos JA , Tisch D , Wiest A , Wilkinson HH , Zhang M , Coutinho PM , Kenerley CM , Monte E , Baker SE , Grigoriev IV
Ref : Genome Biol , 12 :R40 , 2011
Abstract : BACKGROUND: Mycoparasitism, a lifestyle where one fungus is parasitic on another fungus, has special relevance when the prey is a plant pathogen, providing a strategy for biological control of pests for plant protection. Probably, the most studied biocontrol agents are species of the genus Hypocrea/Trichoderma.
RESULTS: Here we report an analysis of the genome sequences of the two biocontrol species Trichoderma atroviride (teleomorph Hypocrea atroviridis) and Trichoderma virens (formerly Gliocladium virens, teleomorph Hypocrea virens), and a comparison with Trichoderma reesei (teleomorph Hypocrea jecorina). These three Trichoderma species display a remarkable conservation of gene order (78 to 96%), and a lack of active mobile elements probably due to repeat-induced point mutation. Several gene families are expanded in the two mycoparasitic species relative to T. reesei or other ascomycetes, and are overrepresented in non-syntenic genome regions. A phylogenetic analysis shows that T. reesei and T. virens are derived relative to T. atroviride. The mycoparasitism-specific genes thus arose in a common Trichoderma ancestor but were subsequently lost in T. reesei.
CONCLUSIONS: The data offer a better understanding of mycoparasitism, and thus enforce the development of improved biocontrol strains for efficient and environmentally friendly protection of plants.
ESTHER : Kubicek_2011_Genome.Biol_12_R40
PubMedSearch : Kubicek_2011_Genome.Biol_12_R40
PubMedID: 21501500
Gene_locus related to this paper: hypai-g9nem6 , hypai-g9ng36 , hypai-g9ngu2 , hypai-g9nks5 , hypai-g9nks6 , hypai-g9nqe5 , hypai-g9nqk5 , hypai-g9nrx6 , hypai-g9nsx1 , hypai-g9ntn3 , hypai-g9nzc9 , hypai-g9nzd7 , hypai-g9p1t1 , hypai-g9p1v2 , hypai-g9p2n8 , hypai-g9p4z2 , hypai-g9p878 , hypai-g9pa17 , hypai-g9pbz9 , hypvg-g9mem8 , hypvg-g9mg52 , hypvg-g9mga2 , hypvg-g9mhi3 , hypvg-g9mjc7 , hypvg-g9mk44 , hypvg-g9mms1 , hypvg-g9mnf0 , hypvg-g9mng3 , hypvg-g9mpt0 , hypvg-g9mrp9 , hypvg-g9ms16 , hypvg-g9ms32 , hypvg-g9msv5 , hypvg-g9muh6 , hypvg-g9muk0 , hypvg-g9mwe2 , hypvg-g9my79 , hypvg-g9n0p7 , hypvg-g9n2g3 , hypvg-g9n2g4 , hypvg-g9n4k5 , hypvg-g9n9n0 , hypvg-g9n561 , hypvg-g9n988 , hypvg-g9nb12 , hypvg-g9nb54 , hypvg-g9nbh8 , hypai-g9npz7 , hypai-g9njw6 , hypvg-g9mx08 , hypvg-g9mlt2 , hypai-g9p4j3 , hypvg-g9nbd3 , hypai-g9nxf6 , hypvg-g9n3y9 , hypvg-g9mgs4 , hypai-g9p6m2 , hypvg-g9my62 , hypvg-g9nbv2 , hypvg-g9my22 , hypai-g9p2e2 , hypai-g9p596 , hypai-g9nf87 , hypvg-g9me87 , hypvg-g9ndn9 , hypai-g9niy5 , hypai-g9ntx6 , hypvg-g9n3e7 , hypai-g9nu29 , hypvg-g9n2z0 , hypvg-g9ndf4 , 9hypo-a0a2p4zt82 , hypvg-g9n0g0 , hypvg-g9muj2 , hypvg-g9mud0 , hypai-g9nkx5

Title : Genomic characterization of the Guillain-Barre syndrome-associated Campylobacter jejuni ICDCCJ07001 Isolate - Zhang_2010_PLoS.One_5_e15060
Author(s) : Zhang M , He L , Li Q , Sun H , Gu Y , You Y , Meng F , Zhang J
Ref : PLoS ONE , 5 :e15060 , 2010
Abstract : Campylobacter jejuni ICDCCJ07001 (HS:41, ST2993) was isolated from a Guillain-Barre syndrome (GBS) patient during a 36-case GBS outbreak triggered by C. jejuni infections in north China in 2007. Sequence analysis revealed that the ICDCCJ07001 genome consisted of 1,664,840 base pairs (bp) and one tetracycline resistance plasmid of 44,084 bp. The GC content was 59.29% and 1,579 and 37 CDSs were identified on the chromosome and plasmid, respectively. The ICDCCJ07001 genome was compared to C. jejuni subsp. jejuni strains 81-176, 81116, NCTC11168, RM1221 and C. jejuni subsp. doylei 269.97. The length and organization of ICDCCJ07001 was similar to that of NCTC11168, 81-176 and 81-116 except that CMLP1 had a reverse orientation in strain ICDCCJ07001. Comparative genomic analyses were also carried out between GBS-associated C. jejuni strains. Thirteen common genes were present in four GBS-associated strains and 9 genes mapped to the LOS cluster and the ICDCCJ07001_pTet (44 kb) plasmid was mosaic in structure. Thirty-seven predicted CDS in ICDCCJ07001_pTet were homologous to genes present in three virulence-associated plasmids in Campylobacter: 81-176_pTet, pCC31 and 81-176_pVir. Comparative analysis of virulence loci and virulence-associated genes indicated that the LOS biosynthesis loci of ICDCCJ07001 belonged to type A, previously reported to be associated with cases of GBS. The polysaccharide capsular biosynthesis (CPS) loci and the flagella modification (FM) loci of ICDCCJ07001 were similar to corresponding sequences of strain 260.94 of similar serotype as strain ICDCCJ07001. Other virulence-associated genes including cadF, peb1, jlpA, cdt and ciaB were conserved between the C. jejuni strains examined.
ESTHER : Zhang_2010_PLoS.One_5_e15060
PubMedSearch : Zhang_2010_PLoS.One_5_e15060
PubMedID: 21124772
Gene_locus related to this paper: camjr-q5ht69

Title : A structural approach to decipher the neurexin and neuroligin splice isoform code - Wei_2010_Neuron_67_1
Author(s) : Wei Z , Zhang M
Ref : Neuron , 67 :1 , 2010
Abstract : The alternative splicing of neurexins (NRXs) and neuroligins (NLs) has been implicated in specifying synaptic connections. In this issue of Neuron, Koehnke et al. took a structural approach for assessing the contribution of alternative splice isoforms for beta-NRX/NL-mediated synaptic recognition.
ESTHER : Wei_2010_Neuron_67_1
PubMedSearch : Wei_2010_Neuron_67_1
PubMedID: 20624584

Title : [Effects of ethylbenzene on oxidative damage, ultrastructure and expressions of apoptosis-related genes in rat brain tissues] - Wang_2010_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_28_810
Author(s) : Wang YR , Yang DY , Zhang M , Wang Q , Liu J , Yang XY , Jiang SQ
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 28 :810 , 2010
Abstract : OBJECTIVE: To investigate the influence of ethylbenzene on oxidative damage, ultrastructure and the expressions of apoptosis-related genes in the rat brain tissues. METHODS: Four groups of 10 males of Sprague-Dawley rats were allocated randomly, and inhaled daily with different doses of ethylbenzene: 0, 433.5 mg/m(3), 4335.0 mg/m(3), and 6500.0 mg/m(3) 6 h daily, 5 days per week for 13 weeks. The contents of glutathione (GSH) and malondialdehyde (MDA) and activity of acetylcholinesterase (AChE) were assayed, respectively. The ultrastructure of brain tissues was observed via electron microscope. The gene expression levels of Bax, Bcl-2, cytochrome C, caspase-9 and caspase-3 in brain tissues were measured by real-time polymerase chain reaction (PCR), respectively. RESULTS: The contents of MDA [(2.03 +/- 0.56), (4.17 +/- 1.31) nmol/mg pro] in the brain tissues of 4335.0 mg/m(3) and 6500.0 mg/m(3) ethylbenzene-treated groups were significantly higher than that [(1.08 +/- 0.26) nmol/mg pro] in the control group (P < 0.05), while AChE activities [(0.321 +/- 0.066), (0.276 +/- 0.031), (0.202 +/- 0.041) U/mg] and GSH contents [(35.19 +/- 15.08), (33.42 +/- 15.32), (27.99 +/- 7.53) mg/g pro] in all ethylbenzene-treated groups were remarkably depressed (P < 0.05, P < 0.05, respectively). After 6500.0 mg/m(3) ethylbenzene inhalation, the nucleolus exhibit demilune with decreased mitochondria. Electrondense of myelin occurred in the injured nerve, ascribing to lipid peroxidationed membrane. The gene expression level of Bax in brain tissue of 4335.0 mg/m(3) and 6500.0 mg/m(3) ethylbenzene-treated group was significantly higher than that in the control group (P < 0.05). Compared with the control group, the gene expression levels of cytochrome C, caspase-9 and caspase-3 in all ethylbenzene-treated groups were enhanced (P < 0.05, P < 0.05, respectively), while bcl-2 gene expression levels in all ethylbenzene-treated groups were decreased (P < 0.05). CONCLUSION: Ethylbenzene can induce oxidative damage and apoptosis in brain tissues. The apoptotic mechanism might be involved with up-regulation of Bax, cytochrome C, caspase-9 and caspase-3, as well as restraint of Bcl-2.
ESTHER : Wang_2010_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_28_810
PubMedSearch : Wang_2010_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_28_810
PubMedID: 21241565

Title : Putative innate immunity of antiatherogenic paraoxanase-2 via STAT5 signal transduction in HIV-1 infection of hematopoietic TF-1 cells and in SCID-hu mice - Yuan_2010_J.Stem.Cells_5_43
Author(s) : Yuan J , Devarajan A , Moya-Castro R , Zhang M , Evans S , Bourquard N , Dias P , Lacout C , Vainchenker W , Reddy ST , Koka PS
Ref : J Stem Cells , 5 :43 , 2010
Abstract : Paraoxanase-2 (PON2) activity was increased upon HIV-1 infection of the CD34+CD4+ hematopoietic cell line TF-1. Thymocytes derived from the human fetal conjoint thymus/liver hematopoietic organ of SCID-hu mice also exhibited an increase in PON2 activity. Additionally, a remarkable increase of PON2 mRNA expression was also observed in both TF-1 and thymocytes following HIV-1 infection. The phosphorylation of STAT5 was decreased in TF-1 cells upon HIV-1 infection. Interestingly, phosphorylation of STAT5 does not occur in GM-CSF "starved" TF-1 cells; however, PON2 protein, activity and mRNA expression are increased under these conditions, similar to HIV-1 infection. We conclude that PON2 is induced in HIV-1 infection through a mechanism that may involve STAT5 inactivation.
ESTHER : Yuan_2010_J.Stem.Cells_5_43
PubMedSearch : Yuan_2010_J.Stem.Cells_5_43
PubMedID: 20861927

Title : DGAT1 and PDAT1 acyltransferases have overlapping functions in Arabidopsis triacylglycerol biosynthesis and are essential for normal pollen and seed development - Zhang_2009_Plant.Cell_21_3885
Author(s) : Zhang M , Fan J , Taylor DC , Ohlrogge JB
Ref : Plant Cell , 21 :3885 , 2009
Abstract : Triacylglycerol (TAG) biosynthesis is a principal metabolic pathway in most organisms, and TAG is the major form of carbon storage in many plant seeds. Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is the only acyltransferase enzyme that has been confirmed to contribute to TAG biosynthesis in Arabidopsis thaliana seeds. However, dgat1 null mutants display only a 20 to 40% decrease in seed oil content. To determine whether other enzymes contribute to TAG synthesis, candidate genes were expressed in TAG-deficient yeast, candidate mutants were crossed with the dgat1-1 mutant, and target genes were suppressed by RNA interference (RNAi). An in vivo role for phospholipid:diacylglycerol acyltransferase 1 (PDAT1; At5g13640) in TAG synthesis was revealed in this study. After failing to obtain double homozygous plants from crossing dgat1-1 and pdat1-2, further investigation showed that the dgat1-1 pdat1-2 double mutation resulted in sterile pollen that lacked visible oil bodies. RNAi silencing of PDAT1 in a dgat1-1 background or DGAT1 in pdat1-1 background resulted in 70 to 80% decreases in oil content per seed and in disruptions of embryo development. These results establish in vivo involvement of PDAT1 in TAG biosynthesis, rule out major contributions by other candidate enzymes, and indicate that PDAT1 and DGAT1 have overlapping functions that are essential for normal pollen and seed development of Arabidopsis.
ESTHER : Zhang_2009_Plant.Cell_21_3885
PubMedSearch : Zhang_2009_Plant.Cell_21_3885
PubMedID: 20040537
Gene_locus related to this paper: arath-At5g13640

Title : Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin - Poulopoulos_2009_Neuron_63_628
Author(s) : Poulopoulos A , Aramuni G , Meyer G , Soykan T , Hoon M , Papadopoulos T , Zhang M , Paarmann I , Fuchs C , Harvey K , Jedlicka P , Schwarzacher SW , Betz H , Harvey RJ , Brose N , Zhang W , Varoqueaux F
Ref : Neuron , 63 :628 , 2009
Abstract : In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to presynaptic sites of transmitter release. We identified protein interactions of the synaptic adhesion molecule neuroligin 2 that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2 binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and functions as a specific activator of collybistin, thus guiding membrane tethering of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and collybistin are sufficient for cell-autonomous clustering of inhibitory neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic and glycinergic synaptic transmission and leads to a loss of postsynaptic specializations specifically at perisomatic inhibitory synapses.
ESTHER : Poulopoulos_2009_Neuron_63_628
PubMedSearch : Poulopoulos_2009_Neuron_63_628
PubMedID: 19755106

Title : Multimedia transport and risk assessment of organophosphate pesticides and a case study in the northern San Joaquin Valley of California - Luo_2009_Chemosphere_75_969
Author(s) : Luo Y , Zhang M
Ref : Chemosphere , 75 :969 , 2009
Abstract : This paper presents a framework for cumulative risk characterization of human exposure to pesticides through multiple exposure pathways. This framework is illustrated through a case study of selected organophosphate (OP) pesticides in the northern San Joaquin Valley of California. Chemical concentrations in environmental media were simulated using a multimedia environmental fate model, and converted to contamination levels in exposure media. The risk characterization in this study was based on a residential-scale exposure to residues of multiple pesticides through everyday activities. Doses from a mixture of OP pesticides that share a common mechanism of toxicity were estimated following US Environmental Protection Agency guidelines for cumulative risk analysis. Uncertainty in the human exposure parameters was included in the Monte Carlo simulation in order to perform stochastic calculations for intakes and corresponding risks of OP pesticides. Risk of brain acetylcholinesterase inhibition was reported as margins of exposure (MOEs) of the 99.9th population percentile for two age groups living in the northern San Joaquin Valley during 1992-2005. Diet was identified as the dominant exposure pathway in cumulative exposure and risk, while the temporal trend and spatial variation in total MOE levels were associated with exposures to contaminated drinking water and ambient air. Uniformly higher risks were observed for children because of their greater inhalation and ingestion rates per body weight, relative to adults. The results indicated that exposures for children were about twice of those estimated for adults. Concerns over children's exposure to OP pesticide through food and water ingestion were suggested based on the spatiotemporal variations predicted for the subchronic MOEs at the 99.9th percentile of exposure in the study area.
ESTHER : Luo_2009_Chemosphere_75_969
PubMedSearch : Luo_2009_Chemosphere_75_969
PubMedID: 19211125

Title : [3D visualization research on microstructure of human ulnar nerve] - Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
Author(s) : Liu T , Hu P , Zhang J , Zhang M , Li H , Chen Z , Chen T
Ref : Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi , 22 :1026 , 2008
Abstract : OBJECTIVE: To explore the application of 3D nerve visualization system in processing 2D image information of human ulnar nerve acquired by series freezing tissue section, staining and scanning. And to draw the 3D anatomical atlas of human ulnar nerve through 3D Nerve visualization software system. METHODS: One left ulnar nerve (from medial fasciculus of brachial plexus to transverse carpal ligament, about 50 cm) was taken from a fresh donated cadaver. After marked with human hair and embedded in OCT, series freezing tissue sections were made and stained with acetylcholinesterase histochemically. Series 2D image information was obtained through high resolution scanner. Then the microstructure of ulnar nerve was reconstructed with 3D Nerve visualization software system. RESULTS: Different cross sections of ulnar nerve have different numbers, positions and characters of the internal nerve fibers. The microstructure of ulnar nerve could be observed in magnifying visual field at any cross section after reconstructed in 3D Nerve visualization soft ware system, which made it possible to track stereo course of fascicles. CONCLUSION: Reconstructed 3D Nerve visualization software system shows the whole microstructure of ulnar nerve and the 3D stereo-structure of its internal fascicles, thus provides exact topography atlas for medical teaching and facilitates precise repair of ulnar nerve injury to improve therapeutic effect.
ESTHER : Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
PubMedSearch : Liu_2008_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_22_1026
PubMedID: 18822720

Title : Genome sequence diversity and clues to the evolution of variola (smallpox) virus - Esposito_2006_Science_313_807
Author(s) : Esposito JJ , Sammons SA , Frace AM , Osborne JD , Olsen-Rasmussen M , Zhang M , Govil D , Damon IK , Kline R , Laker M , Li Y , Smith GL , Meyer H , Leduc JW , Wohlhueter RM
Ref : Science , 313 :807 , 2006
Abstract : Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.
ESTHER : Esposito_2006_Science_313_807
PubMedSearch : Esposito_2006_Science_313_807
PubMedID: 16873609
Gene_locus related to this paper: cowvi-M5L

Title : Expression and characterization of the carboxyl esterase Rv3487c from Mycobacterium tuberculosis - Zhang_2005_Protein.Expr.Purif_42_59
Author(s) : Zhang M , Wang JD , Li ZF , Xie J , Yang YP , Zhong Y , Wang HH
Ref : Protein Expr Purif , 42 :59 , 2005
Abstract : Rv3487c (lipF), a member of the lipase family of Mycobacterium tuberculosis, is related to virulence of this pathogen. Real-time RT-PCR analysis indicated that Rv3487c was induced at low pH in M. tuberculosis cultured in vitro. The gene of Rv3487c was cloned and expressed as fusion protein in Escherichia coli. After removal of the N-terminal domain of the fusion partner by enterokinase treatment, the effect of pH, temperature, and detergents on the purified enzyme activity and stability was characterized. Rv3487c could efficiently hydrolyze short chain esters. The catalytic triad of Rv3487c consists of residues Ser90, Glu189, and His219 as demonstrated by amino acid sequence alignment, three-dimensional modeling, and site-directed mutagenesis.
ESTHER : Zhang_2005_Protein.Expr.Purif_42_59
PubMedSearch : Zhang_2005_Protein.Expr.Purif_42_59
PubMedID: 15939293
Gene_locus related to this paper: myctu-Rv3487c

Title : Identification of acyloxyacyl hydrolase, a lipopolysaccharide-detoxifying enzyme, in the murine urinary tract - Feulner_2004_Infect.Immun_72_3171
Author(s) : Feulner JA , Lu M , Shelton JM , Zhang M , Richardson JA , Munford RS
Ref : Infect Immun , 72 :3171 , 2004
Abstract : Acyloxyacyl hydrolase (AOAH) is an unusual but highly conserved lipase, previously described only in myeloid cells, that removes secondary fatty acyl chains from bacterial lipopolysaccharides (LPS) and may also act on various glycero(phospho)lipids. Deacylation by AOAH greatly reduces the ability of LPS to stimulate cells via CD14-MD-2-Toll-like receptor 4. We report here that renal cortical tubule cells produce AOAH and secrete it into urine, where it can deacylate LPS. In vitro studies revealed that proximal tubule cells secrete pro-AOAH, which can be taken up by bladder cells and processed to the heterodimeric, more enzymatically active, mature form of AOAH. AOAH can then be used by the recipient cells to deacylate LPS. The enzyme produced by proximal tubule epithelium may thus be shared with downstream cells. In addition, mature AOAH is found in the urine. We suggest that cortical tubule cells may produce and secrete AOAH to limit inflammatory responses to gram-negative bacteria throughout the urinary tract.
ESTHER : Feulner_2004_Infect.Immun_72_3171
PubMedSearch : Feulner_2004_Infect.Immun_72_3171
PubMedID: 15155618

Title : Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders - Cao_2003_J.Med.Chem_46_4273
Author(s) : Cao Y , Zhang M , Wu C , Lee S , Wroblewski ME , Whipple T , Nagy PI , Takacs-Novak K , Balazs A , Toros S , Messer WS, Jr.
Ref : Journal of Medicinal Chemistry , 46 :4273 , 2003
Abstract : Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M(1), M(2), and M(4) receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.
ESTHER : Cao_2003_J.Med.Chem_46_4273
PubMedSearch : Cao_2003_J.Med.Chem_46_4273
PubMedID: 13678406

Title : The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment - Clark_2003_Genome.Res_13_2265
Author(s) : Clark HF , Gurney AL , Abaya E , Baker K , Baldwin D , Brush J , Chen J , Chow B , Chui C , Crowley C , Currell B , Deuel B , Dowd P , Eaton D , Foster J , Grimaldi C , Gu Q , Hass PE , Heldens S , Huang A , Kim HS , Klimowski L , Jin Y , Johnson S , Lee J , Lewis L , Liao D , Mark M , Robbie E , Sanchez C , Schoenfeld J , Seshagiri S , Simmons L , Singh J , Smith V , Stinson J , Vagts A , Vandlen R , Watanabe C , Wieand D , Woods K , Xie MH , Yansura D , Yi S , Yu G , Yuan J , Zhang M , Zhang Z , Goddard A , Wood WI , Godowski P , Gray A
Ref : Genome Res , 13 :2265 , 2003
Abstract : A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.
ESTHER : Clark_2003_Genome.Res_13_2265
PubMedSearch : Clark_2003_Genome.Res_13_2265
PubMedID: 12975309
Gene_locus related to this paper: human-CES3 , human-CES4A

Title : Acetylcholine contributes to hypoxic chemotransmission in co-cultures of rat type 1 cells and petrosal neurons - Nurse_1999_Respir.Physiol_115_189
Author(s) : Nurse CA , Zhang M
Ref : Respir Physiol , 115 :189 , 1999
Abstract : The neurotransmitter mechanisms that mediate chemosensory transmission in the mammalian carotid body (CB), i.e. the primary arterial P(O2) detector, are controversial. Given the inherent difficulty of recording from afferent terminals in situ, the authors have adopted an alternative approach based on co-culture of dissociated CB receptor (type 1) cell clusters and petrosal neurons (PN) from 8-14-day-old rat pups. Electrophysiological, perforated patch recordings from petrosal somas, juxtaposed to type 1 clusters, revealed the development of a high incidence of functional 'synapses' in vitro. Recent evidence has strengthened the case for acetylcholine (ACh) as a co-released transmitter: (i) cultured type 1 cells express several cholinergic markers including the vesicular ACh transporter (VAChT), intracellular acetylcholinesterase (AChE), and occasional clear cored vesicles (approximately 50 nm diameter); (ii) the frequency of spontaneous synaptic activity, as well as the hypoxia-induced depolarization recorded in 'juxtaposed' PN in co-culture, were partially suppressed by the nicotinic ACh receptor (nAChR) blocker, mecamylamine (2 microM); (iii) consistent with the presence of extracellular AChE, ACh-mediated membrane noise in type 1 cells as well as the hypoxia-evoked PN response in co-culture were potentiated in a few cases by the AChE inhibitor, eserine (100 microM). Thus, since many PN and type 1 cells express mecamylamine-sensitive nAChR, released ACh may act presynaptically on type 1 cell autoreceptors and/or postsynaptically on petrosal terminals. Other CB transmitter candidates (e.g. 5-HT and ATP) were found to excite PN, though their potential role as co-released sensory transmitters requires further investigation.
ESTHER : Nurse_1999_Respir.Physiol_115_189
PubMedSearch : Nurse_1999_Respir.Physiol_115_189
PubMedID: 10385033

Title : A retinoblastoma-binding protein that affects cell-cycle control and confers transforming ability - Woitach_1998_Nat.Genet_19_371
Author(s) : Woitach JT , Zhang M , Niu CH , Thorgeirsson SS
Ref : Nat Genet , 19 :371 , 1998
Abstract : The retinoblastoma (RB) gene is one of the most extensively studied tumour-suppressor genes. Deletion or inactivation of both RB alleles is an essential, rate-limiting step in the formation of retinoblastoma and osteosarcoma that arise in families that carry mutant RB (ref. 2). RB inactivation is also found in other human tumours. Whereas loss of RB function is associated with the loss of cellular proliferative control, introduction of a wild-type RB can suppress cell growth and tumorigenicity. Thus, identification of factors that interfere with and/or control the function of the RB protein is critical for understanding both cell-cycle control and oncogenesis. Here we describe a new gene, Bog (for B5T over-expressed gene), which was identified and shown to be overexpressed in several transformed rat liver epithelial (RLE) cell lines resistant to the growth-inhibitory effect of TGF-beta1, as well as in primary human liver tumours. The Bog protein shares homology with other retinoblastoma-binding proteins and contains the Rb-binding motif LXCXE. Using the yeast two-hybrid system and co-immunoprecipitation, we demonstrated that Bog binds to Rb. In vivo, Bog/Rb complexes do not contain E2F-1, and Bog can displace E2F-1 from E2F-1/Rb complexes in vitro. Overexpression of Bog in normal RLE cells conferred resistance to the growth-inhibitory effect of TGF-beta1. Furthermore, normal RLE cells are rapidly transformed when Bog is continuously overexpressed and form hepatoblastoma-like tumours when transplanted into nude mice. These data suggest that Bog may be important in the transformation process, in part due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta1 through interaction with Rb and the subsequent displacement of E2F-1.
ESTHER : Woitach_1998_Nat.Genet_19_371
PubMedSearch : Woitach_1998_Nat.Genet_19_371
PubMedID: 9697699
Gene_locus related to this paper: human-RBBP9 , ratno-rbbp9

Title : Characterization of ethyl (3-quinuclidinyl) acetate (EQA) as a ligand for acetylcholine receptors - Canney_1998_Life.Sci_63_PL329
Author(s) : Canney DJ , Zhang M , Doukas PH , Massakowski C , Aronstam RS , Gattu M , Buccafusco JJ , Aronstam R
Ref : Life Sciences , 63 :PL329 , 1998
Abstract : Recent studies suggest that neuronal nicotinic acetylcholine receptors (nAChRs) may play a role in several CNS disorders and that subtype selective nicotinic ligands may be useful in the treatment of these disorders. Ethyl (3-quinuclidinyl)acetate (EQA) is a bulky, reverse-ester analog of ACh, that produces signs of cholinergic stimulation that may be nicotinic in origin The objective of the present study was to further evaluate EQA as a potential cholinergic ligand. Behavioral studies, smooth muscle assays, and radioligand binding assays were performed on this novel ligand. The effects of EQA on blood pressure and acetylcholinesterase activity were also evaluated. The results of the study suggest that EQA is an agonist at peripheral nicotinic acetylcholine receptors and may have antagonist properties at central nicotinic receptors.
ESTHER : Canney_1998_Life.Sci_63_PL329
PubMedSearch : Canney_1998_Life.Sci_63_PL329
PubMedID: 9851313

Title : Differentiation of myoblasts and CNS cells grown either separately or as co-cultures on microcarriers - Shahar_1992_Cytotech_9_107
Author(s) : Shahar A , Reuveny S , Zhang M , Espinosa de los Monteros A , de Vellis J , Shainberg A
Ref : Cytotechnology , 9 :107 , 1992
Abstract : Dispersed neuronal and muscular elements from fetal or neonatal origin, can organize and mature in culture when grown on positively charged cylindrical microcarriers (MCS), to a stage which simulate in vivo maturation. Cells arrange themselves on the MCS to form aggregates which remain floating in the nutrient medium. In such a tridimensional organization, the neuronal tissue is capable of regenerating a network of nerve fibers which establish synapse interconnections and undergo myelination. Oligodendrocytes organize on MCS in a tridimensional pattern and produce extensive myelin-like membranes. Myoblasts in MC-cultures fuse into polynucleated myotubes which become striated and contract spontaneously. Creatine kinase and acetylcholine receptor (AChR) are formed during myogenesis in similar quantities in MC-cultures and in monolayers. When both neuronal and muscle tissues are prepared from the same fetus (autologous nerve-muscle co-cultures) and are cultured on MCS, they interconnect to form neuro-muscular junctions. Cells from both tissues, exhibit better differentiation, for longer periods in MC-cultures than they do in monolayers. The floating functional entities are easy to sample and can be harvested for ultrastructural, immunocytochemical and biochemical analysis. In addition, MC-cultures can be used as a good tool for the study of acute and chronic exposures to toxicological agents, as well as for implantation into demyelinated, injured or dystrophic tissues. In this case the MCS in the implanted entities will serve as identifiable markers.
ESTHER : Shahar_1992_Cytotech_9_107
PubMedSearch : Shahar_1992_Cytotech_9_107
PubMedID: 1369162