Xu M

References (63)

Title : Comparative analysis of organophosphorus versus carbamate pesticide poisoning: a case study - Xia_2024_Arh.Hig.Rada.Toksikol_75_81
Author(s) : Xia JD , Wang H , Hua LW , Xu M , Zheng X , Zhang K
Ref : Arh Hig Rada Toksikol , 75 :81 , 2024
Abstract : Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.
ESTHER : Xia_2024_Arh.Hig.Rada.Toksikol_75_81
PubMedSearch : Xia_2024_Arh.Hig.Rada.Toksikol_75_81
PubMedID: 38548379

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

Title : Dual-Mode Ratiometric Electrochemical and Turn-On Fluorescent Detection of Butyrylcholinesterase Utilizing a Single Probe for the Diagnosis of Alzheimer's Disease - Dong_2023_Anal.Chem_95_8340
Author(s) : Dong H , Zhao L , Wang T , Chen Y , Hao W , Zhang Z , Hao Y , Zhang C , Wei X , Zhang Y , Zhou Y , Xu M
Ref : Analytical Chemistry , 95 :8340 , 2023
Abstract : Biomarkers detection in blood with high accuracy is crucial for the diagnosis and treatment of many diseases. In this study, the proof-of-concept fabrication of a dual-mode sensor based on a single probe (Re-BChE) using a dual-signaling electrochemical ratiometric strategy and a "turn-on" fluorescent method is presented. The probe Re-BChE was synthesized in a single step and demonstrated dual mode response toward butyrylcholinesterase (BChE), a promising biomarker of Alzheimer's disease (AD). Due to the specific hydrolysis reaction, the probe Re-BChE demonstrated a turn-on current response for BChE at -0.28 V, followed by a turn-off current response at -0.18 V, while the fluorescence spectrum demonstrated a turn-on response with an emission wavelength of 600 nm. The developed ratiometric electrochemical sensor and fluorescence detection demonstrated high sensitivity with BChE concentrations with a low detection limit of 0.08 microg mL(-1) and 0.05 microg mL(-1), respectively. Importantly, the dual-mode sensor presents the following advantages: (1) dual-mode readout can correct the impact of systematic or background error, thereby achieving more accurate results; (2) the responses of dual-mode readout originate from two distinct mechanisms and relatively independent signal transduction, in which there is no interference between two signaling routes. Additionally, compared with the reported single-signal electrochemical assays for BChE, both redox potential signals were detected in the absence of biological interference within a negative potential window. Furthermore, it was discovered that the outcomes of direct dual-mode electrochemical and fluorescence quantifications of the level of BChE in serum were in agreement with those obtained from the use of commercially available assay kits for BChE sensing. This method has the potential to serve as a useful point-of-care tool for the early detection of AD.
ESTHER : Dong_2023_Anal.Chem_95_8340
PubMedSearch : Dong_2023_Anal.Chem_95_8340
PubMedID: 37192372

Title : CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease - Guo_2023_Biochem.Pharmacol_217_115845
Author(s) : Guo L , Chen Q , Gao Y , Jiang H , Zhou F , Zhang F , Xu M
Ref : Biochemical Pharmacology , 217 :115845 , 2023
Abstract : Inflammatory bowel diseases (IBD) represent chronic gastrointestinal inflammatory disorders characterized by a complex and underexplored pathogenic mechanism. Previous research has revealed that IBD patients often have a deficiency of choline and its metabolites, including acetylcholine (ACh) and phosphatidylcholine (PC), within the colon. However, a comprehensive study linking these three substances and their mechanistic implications in IBD remains lacking. This study aimed to investigate the efficacy and underlying mechanism of cytidine diphosphate (CDP)-choline (citicoline), an intermediate product of choline metabolism, in a mouse model of IBD induced by dextran sulfate sodium salt (DSS). The results demonstrated that CDP-choline effectively alleviated colonic inflammation and deficiencies in choline, ACh, and PC by increasing the raw material. Further detection showed that CDP-choline also increased the ACh content by altering the expression of high-affinity choline transporter (ChT1) and acetylcholinesterase (AChE) in DSS-induced mice colon. Moreover, CDP-choline increased the expression of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) and activated the cholinergic anti-inflammatory pathway (CAP), leading to reduced colon macrophage activation and proinflammatory M1 polarization in IBD mice, thus reducing the levels of TNF-alpha and IL-6. In addition, CDP-choline reduced intestinal ecological imbalance and increased the content of hexanoic acid in short-chain fatty acids (SCFAs) in mice. In conclusion, this study elucidates the ability of CDP-choline to mitigate DSS-induced colon inflammation by addressing choline and its metabolites deficiencies, activating the CAP, and regulating the composition of the intestinal microbiome and SCFAs content, providing a potential prophylactic and therapeutic approach for IBD.
ESTHER : Guo_2023_Biochem.Pharmacol_217_115845
PubMedSearch : Guo_2023_Biochem.Pharmacol_217_115845
PubMedID: 37827341

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 : Cisplatin increases carboxylesterases through increasing PXR mediated by the decrease of DEC1 - Xu_2023_J.Biomed.Res__431
Author(s) : Xu M , Zhang L , Lin L , Qiang Z , Liu W , Yang J
Ref : J Biomed Res , :431 , 2023
Abstract : cis-Diamminedichloroplatinum (CDDP) is widely used for the treatment of various solid cancers. Here we reported that CDDP increased the expression and enzymatic activities of carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2), along with the upregulation of pregnane X receptor (PXR) and the downregulation of differentiated embryonic chondrocyte-expressed gene 1 (DEC1) in human hepatoma cells, primary mouse hepatocytes, mouse liver and intestine. The overexpression or knockdown of PXR alone upregulated or downregulated the CES1 and CES2 expression, respectively. The increases in CES1 and CES2 expression levels induced by CDDP abolished or enhanced by PXR knockdown or overexpression, implying that CDDP induces carboxylesterases through the activation of PXR. Likewise, the overexpression or knockdown of DEC1 alone significantly decreased or increased PXR and its targets. Moreover, the increases of PXR and its targets induced by CDDP were abolished or alleviated by the overexpression or knockdown of DEC1. The overexpression or knockdown of DEC1 affected the response of PXR to CDDP, but not vice versa, suggesting that CDDP increases carboxylesterases by upregulating PXR mediated by the decrease of DEC1. In addition, CDDP did not increase DEC1 mRNA degradation but suppressed DEC1 promoter reporter activity, indicating that it suppresses DEC1 transcriptionally. The combined use of CDDP and irinotecan had a synergistic effect on two cell lines, especially when CDDP was used first.
ESTHER : Xu_2023_J.Biomed.Res__431
PubMedSearch : Xu_2023_J.Biomed.Res__431
PubMedID: 37990879

Title : A Phenotypic Screen Identifies Potent DPP9 Inhibitors Capable of Killing HIV-1 Infected Cells - Moore_2022_ACS.Chem.Biol_17_2595
Author(s) : Moore KP , Schwaid AG , Tudor M , Park S , Beshore DC , Converso A , Shipe WD , Anand R , Lan P , Moningka R , Rothman DM , Sun W , Chi A , Cornella-Taracido I , Adam GC , Bahnck-Teets C , Carroll SS , Fay JF , Goh SL , Lusen J , Quan S , Rodriguez S , Xu M , Andrews CL , Song C , Filzen T , Li J , Hollenstein K , Klein DJ , Lammens A , Lim UM , Fang Z , McHale C , Li Y , Lu M , Diamond TL , Howell BJ , Zuck P , Balibar CJ
Ref : ACS Chemical Biology , 17 :2595 , 2022
Abstract : Although current antiretroviral therapy can control HIV-1 replication and prevent disease progression, it is not curative. Identifying mechanisms that can lead to eradication of persistent viral reservoirs in people living with HIV-1 (PLWH) remains an outstanding challenge to achieving cure. Utilizing a phenotypic screen, we identified a novel chemical class capable of killing HIV-1 infected peripheral blood mononuclear cells. Tool compounds ICeD-1 and ICeD-2 ("inducer of cell death-1 and 2"), optimized for potency and selectivity from screening hits, were used to deconvolute the mechanism of action using a combination of chemoproteomic, biochemical, pharmacological, and genetic approaches. We determined that these compounds function by modulating dipeptidyl peptidase 9 (DPP9) and activating the caspase recruitment domain family member 8 (CARD8) inflammasome. Efficacy of ICeD-1 and ICeD-2 was dependent on HIV-1 protease activity and synergistic with efavirenz, which promotes premature activation of HIV-1 protease at high concentrations in infected cells. This in vitro synergy lowers the efficacious cell kill concentration of efavirenz to a clinically relevant dose at concentrations of ICeD-1 or ICeD-2 that do not result in complete DPP9 inhibition. These results suggest engagement of the pyroptotic pathway as a potential approach to eliminate HIV-1 infected cells.
ESTHER : Moore_2022_ACS.Chem.Biol_17_2595
PubMedSearch : Moore_2022_ACS.Chem.Biol_17_2595
PubMedID: 36044633
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression - Zhou_2022_Cancers.(Basel)_14_
Author(s) : Zhou X , Zhong F , Yan Y , Wu S , Wang H , Liu J , Li F , Cui D , Xu M
Ref : Cancers (Basel) , 14 : , 2022
Abstract : Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer.
ESTHER : Zhou_2022_Cancers.(Basel)_14_
PubMedSearch : Zhou_2022_Cancers.(Basel)_14_
PubMedID: 36230535
Gene_locus related to this paper: human-ABHD11

Title : Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative - Zeng_2022_Front.Immunol_13_1113070
Author(s) : Zeng Z , Liu R , Cao W , Yang L , Lin Y , Bi X , Jiang T , Deng W , Wang S , Lu H , Sun F , Shen G , Chang M , Lu Y , Wu S , Hao H , Xu M , Chen X , Hu L , Zhang L , Wan G , Xie Y , Li M
Ref : Front Immunol , 13 :1113070 , 2022
Abstract : AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.
ESTHER : Zeng_2022_Front.Immunol_13_1113070
PubMedSearch : Zeng_2022_Front.Immunol_13_1113070
PubMedID: 36685494

Title : Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry-based targeted proteomics - Wu_2021_J.Sep.Sci__
Author(s) : Wu T , Xi X , Chen Y , Jiang C , Zhang Q , Dai G , Bai Y , Zhang W , Ni T , Zou J , Ju W , Xu M
Ref : J Sep Sci , : , 2021
Abstract : Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics, using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C(18) column (100 mm x 4.6 mm, 1.8 microm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples. This article is protected by copyright. All rights reserved.
ESTHER : Wu_2021_J.Sep.Sci__
PubMedSearch : Wu_2021_J.Sep.Sci__
PubMedID: 34008891

Title : Immobilized lipase catalytic synthesis of phenolamides and their potential against alpha-glucosidase - Zeng_2021_J.Biotechnol__
Author(s) : Zeng F , Zhang H , Xu M , Huang K , Zhang T , Duan J
Ref : J Biotechnol , : , 2021
Abstract : Although coumaroyltyramine (CT) derivatives are one kind of phenolamides with remarkable biological activities, the low content in plants would inhibit their potential use in food and pharmaceutical industries. Therefore, it is necessary to screen an efficient method to produce CT derivatives. A green and efficient method by using lipase as catalyst to synthesize a series of CT derivatives, was thus proposed. To obtain optimum reaction conditions, the effects of various parameters on conversion rate were firstly evaluated. An in vitro alpha-glucosidase inhibitory assay of synthesized compounds was then carried out, and the structure-activity relationship of these compounds was conducted. Under the optimum conditions (MTBE, Nu/S: 2/1, E/S: 20/1, 50 degreesC and 24 h), the conversion rates of synthesized compounds were above 65%. The bioassay results indicated that N-trans-caffeoyltyramine and N-trans-feruloyltyramine had potent activities against alpha-glucosidase with IC(50) of 30.08 microM and 31.94 microM, respectively. The structure-activity relationship results showed that the presence of -OH or -OCH(3) group at C-3 position could boost the activities of CT derivatives. Meanwhile, the presence of -OH group at C-4 position and double bound on caffeoyl moiety as well as the presence of -OH group at C-4' position was essential for the activities of CT derivatives.
ESTHER : Zeng_2021_J.Biotechnol__
PubMedSearch : Zeng_2021_J.Biotechnol__
PubMedID: 33878390

Title : Essential Oils from Spices Inhibit Cholinesterase Activity and Improve Behavioral Disorder in AlCl(3) Induced Dementia - Chen_2021_Chem.Biodivers__e2100443
Author(s) : Chen SX , Xiang JY , Han JX , Yang F , Li HZ , Chen H , Xu M
Ref : Chem Biodivers , :e2100443 , 2021
Abstract : The chemical compositions of essential oils (EOs) prepared from six spices including cinnamon, amomum tsao-ko, cardamom, amomum, black pepper and white pepper were analyzed by gas chromatography-mass spectrometry (GC/MS), which led to identify almost 200 volatile compounds. All EOs of spices showed cholinesterase inhibitory activity. Among them, pepper EO showed most potent acetylcholinesterase (AChE) inhibitory activity with IC(50) values of 8.54microg/mL (black pepper EO) and 5.02microg/mL (white pepper EO). Molecular docking and invitro validation suggested that 3-carene, alpha-pinene and beta-pinene with IC(50) value of 1.73, 2.66, and 14.75microg/mL, respectively, might be active constituents of spices oil in inhibiting AChE. Furthermore, amomum tsao-ko EO and amomum EO can improve behavioral disorder in dementia zebrafish induced by aluminum trichloride (AlCl(3) ).
ESTHER : Chen_2021_Chem.Biodivers__e2100443
PubMedSearch : Chen_2021_Chem.Biodivers__e2100443
PubMedID: 34855291

Title : Near-infrared fluorescent probe for evaluating the acetylcholinesterase effect in the aging process and dietary restriction via fluorescence imaging - He_2021_J.Mater.Chem.B__
Author(s) : He N , Yu L , Xu M , Huang Y , Wang X , Chen L , Yue S
Ref : J Mater Chem B , : , 2021
Abstract : Dietary restriction (DR), as a natural intervention, not only benefits the neuroendocrine system, but also has an antiaging action. Acetylcholinesterase (AChE) is one of the most important bioactive substances and plays a major part in choline changes in the aging process. Thus, we aim to evaluate the effect of DR on AChE in the brains of aging animals. In this study, we synthesize a NIR fluorescent probe BD-AChE for the real-time and in situ monitoring of AChE level changes in living cells and living mice, notably in brains. In situ visualization with BD-AChE verified a decrease in the AchE level in the brains of mice aging models. Evidently, the prepared probe has the excellent capability of measuring AChE variation in the brains of aging mice with DR via NIR fluorescence bioimaging, indicating that long-term DR can effectively affect AChE levels in the brain. The attenuation of AChE level in the brain of aging mice after DR could be helpful in infering the advantageous impact of DR on age-related neurodegenerative disease, as a better treatment alternative in the future.
ESTHER : He_2021_J.Mater.Chem.B__
PubMedSearch : He_2021_J.Mater.Chem.B__
PubMedID: 33666613

Title : Reducing alcohol and\/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform - Kong_2021_Mol.Psychiatry__
Author(s) : Kong Q , Li Y , Yue J , Wu X , Xu M
Ref : Mol Psychiatry , : , 2021
Abstract : Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.
ESTHER : Kong_2021_Mol.Psychiatry__
PubMedSearch : Kong_2021_Mol.Psychiatry__
PubMedID: 33619338

Title : Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway - Zhang_2020_Exp.Cell.Res__111856
Author(s) : Zhang Y , Sun L , Sun Y , Chen Y , Wang X , Xu M , Chi P , Xu Z , Lu X
Ref : Experimental Cell Research , :111856 , 2020
Abstract : CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (P<0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment.
ESTHER : Zhang_2020_Exp.Cell.Res__111856
PubMedSearch : Zhang_2020_Exp.Cell.Res__111856
PubMedID: 31981591
Gene_locus related to this paper: human-CES2

Title : Stimulus Response of GQD-Sensitized Tb\/GMP ICP Nanoparticles with Dual-Responsive Ratiometric Fluorescence: Toward Point-of-Use Analysis of Acetylcholinesterase and Organophosphorus Pesticide Poisoning with Acetylcholinesterase as a Biomarker - Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
Author(s) : Ma R , Xu M , Liu C , Shi G , Deng J , Zhou T
Ref : ACS Appl Mater Interfaces , 12 :42119 , 2020
Abstract : In this study, by rationally designing the stimulus response of graphene quantum dot (GQD)-sensitized terbium/guanine monophosphate (Tb/GMP) infinite coordination polymer (ICP) nanoparticles, we have constructed a smartphone-based colorimetric assay with ratiometric fluorescence, which could be applied for the detection of acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) directly. First, GQDs with abundant functional groups were chosen as the guest, which not only could be used as one of the signal readouts but also served as the antenna ligand to further sensitize the fluorescence of the host Tb/GMP. Upon being excited at 330 nm, the green fluorescence of the Tb/GMP host is highly enhanced, while the blue fluorescence of GQDs is suppressed due to the confinement of the ICP host. With the presence of thiocholine (TCh), an enzymatic product hydrolyzed from acetylthiocholine (ATCh) by AChE, the competitive coordination of Tb(3+) between GMP and TCh results in the collapse of the ICP network and thereby the release of GQDs into the solution; thus, the fluorescence of Tb/GMP turns off and the fluorescence of GQDs turns on. The dual-responsive ratiometric fluorescent intensity change leads to the corresponding green-to-blue fluorescent color change obviously, which constitutes a novel mechanism for the colorimetric analysis of AChE. Moreover, when OPs are subsequently introduced, the activity of AChE is blocked, thus preventing the stimulus response of GQD@Tb/GMP ICP nanoparticles, leading to the fluorescent color change from greenish-blue to green, which could also be employed for OP detection. Benefitting from the high sensitivity, good reliability, and the obvious color changes, the method demonstrated here is a promising candidate to realize smartphone-based point-of-use applications, which is of great importance for timely clinical diagnosis and treatment of OPs related to health issues with AChE as an exposure biomarker in less industrialized countries, in remote settings, or even in home care services.
ESTHER : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedSearch : Ma_2020_ACS.Appl.Mater.Interfaces_12_42119
PubMedID: 32805836

Title : Study on the Regulation of Earthworm Physiological Function under Cadmium Stress Based on a Compound Mathematical Model - Zhou_2020_Environ.Toxicol.Pharmacol__103499
Author(s) : Zhou H , Zhang T , Zhuang J , Xu M , Liu X , Shi Q , Zhou D
Ref : Environ Toxicol Pharmacol , :103499 , 2020
Abstract : A cadmium (Cd) stress test was carried out on Eisenia fetida in artificial soil. Six Cd concentration gradient solutions (0, 50, 100, 125, 250 and 500 mg/kg) were prepared. Two treatment groups, short-term stress and long-term stress, were established. The former lasted for 10 days, and the latter lasted for 30 days. The Biolog ECO-microplate culture method was used to determine the utilization of the 31 carbon sources by the microbes in earthworm homogenate. The total protein content (TP), peroxidase activity (POD), catalase activity (CAT), superoxide dismutase activity (SOD), glutathione peroxidase activity (GPX), glutathione-S-transferase activity (GST), malondialdehyde content (MDA) and acetylcholinesterase activity (AChE) in earthworm were determined in order to investigate the regulation of oxidative stress and the functional diversity of microbial communities in earthworms under Cd stress. By combining the entropy weight method (EW) and the technique for order preference by similarity to an ideal solution model (TOPSIS), the physiological functional indices of earthworms were assessed objectively and scientifically, and the physiological changes under the different stress periods were evaluated. The results showed that a Cd-tolerant dominant population appeared in the microbial community under Cd stress. In the short-term test, oxidative stress were more effective in coping with Cd stress than the microbial community, and oxidative stress regulated the microbial community functional diversity. Under long-term Cd stress, the regulatory effect was weak or non-existent. In this study, a new evaluation model was established to explore the regulation process of earthworm on its oxidation stress and the functional diversity of microbial communities under Cd stress, and provide a theoretical basis for revealing the detoxification mechanism of earthworms.
ESTHER : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedSearch : Zhou_2020_Environ.Toxicol.Pharmacol__103499
PubMedID: 32956818

Title : Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro -
Author(s) : Wang M , Cao R , Zhang L , Yang X , Liu J , Xu M , Shi Z , Hu Z , Zhong W , Xiao G
Ref : Cell Res , 30 :269 , 2020
PubMedID: 32020029

Title : A novel esterase LanE from Edaphocola flava HME-24 and the enantioselective degradation mechanism of herbicide lactofen - Hu_2020_Ecotoxicol.Environ.Saf_205_111141
Author(s) : Hu T , Xiang Y , Chen Q , Shang N , Xu M , Huang X
Ref : Ecotoxicology & Environmental Safety , 205 :111141 , 2020
Abstract : Lactofen is a chiral herbicide and widely used against broadleaf weeds in agriculture. As a pesticide, it is directly released to the environment, and easily caused contamination in soil and aquatic ecosystem. The enantioselective degradation of lactofen in the environment has been reported, but the molecular biological mechanism of this phenomenon is still unclear. In this study, strain Edaphocola flava HME-24 could degrade 96.7% of 50 mg L(-1) lactofen within 72 h. Lactofen was initially hydrolyzed to desethyl lactofen and subsequently acifluorfen by strain HME-24. A novel gene lanE, involved in lactofen transformation, was obtained from Edaphocola flava HME-24. Gene lanE encoded a protein of 471 amino acids that contained the conserved GXSXG esterase motif and clustered into esterase subfamily V. LanE shared the highest identity with esterase EstD (Q9WYH1) from Thermotoga maritima MSB8 (29.14%). This esterase was also able to transform p-nitrophenyl esters (C4-C8), and the activity decreased when the carbon chain length increased. LanE showed enantioselectivity during the degradation of lactofen, diclofop-methyl, and quizalofop-ethyl, with a higher degradation efficiency of (S)-enantiomers than (R)-enantiomers. The three-dimensional structure of LanE was simulated, and molecular docking revealed that when the (S)-enantiomers of lactofen occupied the active sites, the distance between the ligand molecule and the coordination atom was shorter than that when the (R)-enantiomers occupied the active sites, which facilitated the formation of the transition state complex. The results in this study enhanced our understanding of the preferential catabolism of the (S)-enantiomers of lactofen on the molecular level and could illustrate the reported enantioselective degradation of lactofen in the environment.
ESTHER : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedSearch : Hu_2020_Ecotoxicol.Environ.Saf_205_111141
PubMedID: 32846294
Gene_locus related to this paper: 9bact-a0a7g9u6e3

Title : An optimized acetylcholine sensor for monitoring in vivo cholinergic activity - Jing_2020_Nat.Methods_17_1139
Author(s) : Jing M , Li Y , Zeng J , Huang P , Skirzewski M , Kljakic O , Peng W , Qian T , Tan K , Zou J , Trinh S , Wu R , Zhang S , Pan S , Hires SA , Xu M , Li H , Saksida LM , Prado VF , Bussey TJ , Prado MAM , Chen L , Cheng H
Ref : Nat Methods , 17 :1139 , 2020
Abstract : The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRAB(ACh) (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors.
ESTHER : Jing_2020_Nat.Methods_17_1139
PubMedSearch : Jing_2020_Nat.Methods_17_1139
PubMedID: 32989318

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 : Triazole derivatives as inhibitors of Alzheimer's disease: Current developments and structure-activity relationships - Xu_2019_Eur.J.Med.Chem_180_656
Author(s) : Xu M , Peng Y , Zhu L , Wang S , Ji J , Rakesh KP
Ref : Eur Journal of Medicinal Chemistry , 180 :656 , 2019
Abstract : Alzheimer's disease (AD) is a well known neurodegenerative disorder alarming millions of people worldwide and the subsequent epidemiological statistics highlights the implication of the disease. AD is a multi-factorial disease, a variety of single-target directed drugs that have reached clinical trials have unsuccessful. Hence, various factors associated without set of AD have been considered in targeted drug discovery and development. Triazoles are five-membered heterocyclic scaffold due to their broad range of biological activities. The present review focuses on the recent developments in the area of medicinal chemistry to explore the diverse chemical structures of potential inhibitors of Alzheimer's disease and also look at its structure-activity relationships (SAR) studies of bioactive compounds for future discovery of suitable drug candidates. The prominence has been given on the major advancements in the medicinal brochure of this pharmacophore for the period during 2012-2019.
ESTHER : Xu_2019_Eur.J.Med.Chem_180_656
PubMedSearch : Xu_2019_Eur.J.Med.Chem_180_656
PubMedID: 31352246

Title : Pyridostigmine alleviates cardiac dysfunction via improving mitochondrial cristae shape in a mouse model of metabolic syndrome - Xue_2019_Free.Radic.Biol.Med_134_119
Author(s) : Xue RQ , Yu XJ , Zhao M , Xu M , Wu Q , Cui YL , Yang S , Li DL , Zang WJ
Ref : Free Radic Biol Med , 134 :119 , 2019
Abstract : Insulin resistance and autonomic imbalance are important pathological processes in metabolic syndrome-induced cardiac remodeling. Recent studies determined that disruption of mitochondrial cristae shape is associated with myocardial ischemia; however, the change in cristae shape in metabolic syndrome-induced cardiac remodeling remains unclear. This study determined the effect of pyridostigmine (PYR), which reversibly inhibits cholinesterase to improve autonomic imbalance, on high-fat diet (HFD)-induced cardiac insulin resistance and explored the potential effect on the shape of mitochondrial cristae. Feeding of a HFD for 22 weeks led to an irregular and even lysed cristae structure in cardiac mitochondria, which contributed to decreased mitochondrial content and ATP production and increased oxygen species production, ultimately impairing insulin signaling and lipid metabolism. Interestingly, PYR enhanced vagal activity by increasing acetylcholine production and exerted mito-protective effects by activating the LKB1/AMPK/ACC signal pathway. Specifically, PYR upregulated OPA1 and Mfn1/2 expression, promoted the formation of the mitofilin/CHCHD3/Sam50 complex, and decreased p-Drp1 and Fis1 expression, resulting in tight and parallel cristae and increasing cardiac mitochondrial complex subunit expression and ATP generation as well as decreasing release of cytochrome C from mitochondria and oxidative damage. Furthermore, PYR improved glucose and insulin tolerance and insulin-stimulated Akt phosphorylation, decreased lipid toxicity, and ultimately ameliorated HFD-induced cardiac remodeling and dysfunction. In conclusion, PYR prevented cardiac and insulin insensitivity and remodeling by stimulating vagal activity to regulate mitochondrial cristae shape and function in HFD-induced metabolic syndrome in mice. These results provide novel insights for the development of a therapeutic strategy for obesity-induced cardiac dysfunction that targets mitochondrial cristae.
ESTHER : Xue_2019_Free.Radic.Biol.Med_134_119
PubMedSearch : Xue_2019_Free.Radic.Biol.Med_134_119
PubMedID: 30633969

Title : Designing of a Cofactor Self-Sufficient Whole-Cell Biocatalyst System for Production of 1,2-Amino Alcohols from Epoxides - Liu_2019_ACS.Synth.Biol_8_734
Author(s) : Liu S , Zhang X , Liu F , Xu M , Yang T , Long M , Zhou J , Osire T , Yang S , Rao Z
Ref : ACS Synth Biol , 8 :734 , 2019
Abstract : Optically pure 1,2-amino alcohols are highly valuable products as intermediates for chiral pharmaceutical products. Here we designed an environmentally friendly non-natural biocatalytic cascade for efficient synthesis of 1,2-amino alcohols from cheaper epoxides. A redesignated omega-transaminase PAKomega-TA was tested and showed good bioactivity at a lower pH than other reported transaminases. The cascade was efficiently constructed as a single one-pot E. coli recombinant, by coupling SpEH (epoxide hydrolase), MnADH (alcohol dehydrogenase), and PAKomega-TA. Furthermore, RBS regulation strategy was used to overcome the rate limiting step by increasing expression of MnADH. For cofactor regeneration and amino donor source, an interesting point was involved as that a cofactor self-sufficient system was designed by expression of GluDH. It established a "bridge" between the cofactor and the cosubstrate, such that the cofactor self-sufficient system could release cofactor (NADP(+)) and cosubstrate (l-Glutamine) regenerated simultaneously. The recombinant E. coli BL21 (SGMP) with cofactor self-sufficient whole-cell cascade biocatalysis showed high ee value (>99%) and high yield, with 99.6% conversion of epoxide ( S)-1a to 1,2-amino alcohol ( S)-1d in 10 h. It further converted ( S)-2a-5a to ( S)-2d-5d with varying conversion rates ranging between 65-96.4%. This study first provides one-step synthesis of optically pure 1,2-amino alcohols from ( S)-epoxides employing a synthetic redox-self-sufficient cascade.
ESTHER : Liu_2019_ACS.Synth.Biol_8_734
PubMedSearch : Liu_2019_ACS.Synth.Biol_8_734
PubMedID: 30840437

Title : Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose - Li_2019_Nat.Biomed.Eng_3_105
Author(s) : Li Y , Kong Q , Yue J , Gou X , Xu M , Wu X
Ref : Nat Biomed Eng , 3 :105 , 2019
Abstract : Cocaine addiction is associated with compulsive drug-seeking, and exposure to the drug or to drug-associated cues leads to relapse, even after long periods of abstention. A variety of pharmacological targets and behavioral interventions have been explored to counteract cocaine addiction, but to date no market-approved medications for treating cocaine addiction or relapse exist, and effective interventions for acute emergencies resulting from cocaine overdose are lacking. We recently demonstrated that skin epidermal stem cells can be readily edited by using CRISPR (clustered regularly interspaced short palindromic repeats) and then transplanted back into the donor mice. Here, we show that the transplantation, into mice, of skin cells modified to express an enhanced form of butyrylcholinesterase, an enzyme that hydrolyzes cocaine, enables the long-term release of the enzyme and efficiently protects the mice from cocaine-seeking behavior and cocaine overdose. Cutaneous gene therapy through skin transplants that elicit drug elimination may offer a therapeutic option to address drug abuse.
ESTHER : Li_2019_Nat.Biomed.Eng_3_105
PubMedSearch : Li_2019_Nat.Biomed.Eng_3_105
PubMedID: 30899600

Title : 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) Urea, a Selective and Potent Dual Inhibitor of Soluble Epoxide Hydrolase and p38 Kinase Intervenes in Alzheimer's Signaling in Human Nerve Cells - Liang_2019_ACS.Chem.Neurosci_10_4018
Author(s) : Liang Z , Zhang B , Xu M , Morisseau C , Hwang SH , Hammock BD , Li QX
Ref : ACS Chem Neurosci , 10 :4018 , 2019
Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disorder. Neuroinflammation is a prevalent pathogenic stress leading to neuronal death in AD. Targeting neuroinflammation to keep neurons alive is an attractive strategy for AD therapy. 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) is a potent inhibitor of soluble epoxide hydrolase (sEH) and can enter into the brain. It has good efficacy on a wide range of chronic inflammatory diseases in preclinical animal models. However, the anti-neuroinflammatory effects and molecular mechanisms of TPPU for potential AD interventions remain elusive. With an aim to develop multitarget therapeutics for neurodegenerative diseases, we screened TPPU against sEH from different mammalian species and a broad panel of human kinases in vitro for potential new targets relevant to neuroinflammation in AD. TPPU inhibits both human sEH and p38beta kinase, two key regulators of inflammation, with nanomolar potencies and distinct selectivity. To further elucidate the molecular mechanisms, differentiated SH-SY5Y human neuroblastoma cells were used as an AD cell model, and we investigated the neuroprotection of TPPU against amyloid oligomers. We found that TPPU effectively prevents neuronal death by mitigating amyloid neurotoxicity, tau hyperphosphorylation, and mitochondrial dysfunction, promoting neurite outgrowth and suppressing activation and nuclear translocation of NF-kappaB for inflammatory responses in human nerve cells. The results indicate that TPPU is a potent and selective dual inhibitor of sEH and p38beta kinase, showing a synergistic action in multiple AD signaling pathways. Our study sheds light upon TPPU and other sEH/p38beta dual inhibitors for potential pharmacological interventions in AD.
ESTHER : Liang_2019_ACS.Chem.Neurosci_10_4018
PubMedSearch : Liang_2019_ACS.Chem.Neurosci_10_4018
PubMedID: 31378059

Title : Infraspecific Variation of Huperzine A and B in Icelandic Huperzia selago Complex - Xu_2019_Planta.Med_85_160
Author(s) : Xu M , Heidmarsson S , Thorsteinsdottir M , Wasowicz P , Sun H , Deng T , Omarsdottir S , Olafsdottir ES
Ref : Planta Med , 85 :160 , 2019
Abstract : The alkaloids huperzine A and huperzine B were originally isolated from the Chinese club moss Huperzia serrata. They are known inhibitors of acetylcholinesterase, and especially huperzine A shows pharmaceutical potential for the treatment of Alzheimer's disease. Its supply heavily relies on natural plant sources belonging to the genus Huperzia, which shows considerable interspecific huperzine A variations. Furthermore, taxonomic controversy remains in this genus, particularly in the Huperzia selago group. With focus on Icelandic H. selago taxa, we aimed to explore the relatedness of Huperzia species using multi-locus phylogenetic analysis, and to investigate correlations between huperzine A contents, morphotypes, and genotypes. Phylogenetic analysis was performed with five chloroplastic loci (the intergenic spacer between the photosystem II protein D1 gene and the tRNA-His gene, maturase K, ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, tRNA-Leu, and the intergenic spacer region between tRNA-Leu and tRNA-Phe). Huperzine A and huperzine B contents were determined using an HPLC-UV method. The phylogenetic analysis suggests that previously proposed Huperzia appressa and Huperzia arctica should not be considered species, but rather subspecies of H. selago. Three genotypes of Icelandic H. selago were identified and presented in a haplotype networking diagram. A significantly (p < 0.05) higher amount of huperzine A was found in H. selago genotype 3 (264 - 679 microg/g) than genotype 1 (20 - 180 microg/g), where the former shows a typical green and reflexed "selago" morphotype. The huperzine A content in genotype 3 is comparable to Chinese H. serrata and a good alternative huperzine A source. Genotype 2 contains multiple morphotypes with a broad huperzine A content (113 - 599 microg/g). The content of huperzine B in Icelandic taxa (6 - 13 microg/g) is much lower than that in Chinese H. serrata (79 - 207 microg/g).
ESTHER : Xu_2019_Planta.Med_85_160
PubMedSearch : Xu_2019_Planta.Med_85_160
PubMedID: 30290396

Title : Bidirectional interactions between beet armyworm and its host in response to different fertilization conditions - Wang_2018_PLoS.One_13_e0190502
Author(s) : Wang S , Ding T , Xu M , Zhang B
Ref : PLoS ONE , 13 :e0190502 , 2018
Abstract : Fertilizer with different ratios of nitrogen (N) to phosphorus (P) can influence crop plant performance and defense against herbivores. Spodoptera exigua is an important agricultural pest that has caused serious economic loss, especially in recent decades. In the present study, we explored effects of different intensities and durations of S. exigua herbivory on host plant biomass and on S. exigua enzyme activities in response to five fertilizer treatments with different N: P ratios of 1: 5, 1: 3, 1: 1, 3: 1 and 5: 1. The results showed that fertilizer type can significantly influence interactions between caterpillars and its hosts. Compensatory growth of leaf biomass was detected under fertilizer with N: P = 3: 1. Fertilizer with a higher proportion of N appears to maintain stem biomass in defoliated seedlings similar to controls that are not exposed to herbivory. There was no significant difference in root biomass under most conditions. High proportion of N also enhanced the activity of two antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD) in low density of beet armyworm. However, with increased herbivorous intensity, a higher proportion of P played a more important role in increasing the activities of CAT and SOD. Higher P likely enhanced acetylcholine esterase (AChE) activity at lower degrees of defoliation, but a higher N proportion resulted in higher AChE activity at higher degrees of defoliation. Higher N proportion contributed to reduced carboxylesterase (CarE) activity at high intensity, short-term defoliation. However, when defoliation intensity increased, the difference in CarE activity between fertilizer categories was little. The study explored the interaction between the damage of S. exigua and the biomass accumulation of its host plant Brassica rapa, and the influence of the N/P ratio in plant fertilizer on this interaction. Systematic analysis was provided on the biomass of B. rapa and the activity of metabolic enzymes of S. exigua under different treatments.
ESTHER : Wang_2018_PLoS.One_13_e0190502
PubMedSearch : Wang_2018_PLoS.One_13_e0190502
PubMedID: 29293621

Title : The binding interaction between cadmium-based, aqueous-phase quantum dots with Candida rugosa lipase - Zhao_2018_J.Mol.Recognit__e2712
Author(s) : Zhao L , Hu S , Meng Q , Xu M , Zhang H , Liu R
Ref : J Mol Recognit , :e2712 , 2018
Abstract : As a promising biolabeling biomaterials, quantum dots (QDs) present a great potential. However, the toxicity of QDs to organisms has attracted wide attention. In our research, we introduced an in vitro method to study the molecular mechanisms for the structure and activity alterations of Candida rugosa lipase (CRL) with the binding of 3-mercaptopropionic acid-capped CdTe QDs. Multiple spectroscopic methods, isothermal titration calorimetry, and enzyme activity measurements were used in this paper. QDs statically quenched the intrinsic fluorescence of CRL with the quenching constant decreases from 2.46 x 10(13) to 1.64 x 10(13) L mol(-1) second(-1) (298 to 310 K). It binds to CRL through hydrophobic force with 1 binding site, unfolding and loosening the skeleton and changed its secondary structure. Rather than aggregating on the surface, it enters the pocket of the CRL to interact with Ser-209 (2.43 A) and the residues surrounding Ser-209, making the catalytic triad more exposed. Furthermore, the activity of CRL was inhibited by approximately 15%. This work demonstrates that 3-mercaptopropionic acid-capped CdTe QDs may cause negative effects to CRL and obtains a molecular mechanism on QD-induced toxicity to proteins in vitro.
ESTHER : Zhao_2018_J.Mol.Recognit__e2712
PubMedSearch : Zhao_2018_J.Mol.Recognit__e2712
PubMedID: 29655217

Title : Deficiency in hormone-sensitive lipase accelerates the development of pancreatic cancer in conditional KrasG12D mice - Xu_2018_BMC.Cancer_18_797
Author(s) : Xu M , Chang HH , Jung X , Moro A , Chou CEN , King J , Hines OJ , Sinnett-Smith J , Rozengurt E , Eibl G
Ref : BMC Cancer , 18 :797 , 2018
Abstract : BACKGROUND: Hormone sensitive lipase (HSL) is a neutral lipase that preferentially catalyzes the hydrolysis of diacylglycerol contributing to triacylglycerol breakdown in the adipose tissue. HSL has been implicated to play a role in tumor cachexia, a debilitating syndrome characterized by progressive loss of adipose tissue. Consequently, pharmacological inhibitors of HSL have been proposed for the treatment of cancer-associated cachexia. In the present study we used the conditional KrasG12D (KC) mouse model of pancreatic ductal adenocarcinoma (PDAC) with a deficiency in HSL to determine the impact of HSL suppression on the development of PDAC. METHODS: KC;Hsl(+/+) and KC;Hsl(-/-) mice were fed standard rodent chow for 20 weeks. At sacrifice, the incidence of PDAC was determined and inflammation in the mesenteric adipose tissue and pancreas was assessed histologically and by immunofluorescence. To determine statistical significance, ANOVA and two-tailed Student's t-tests were performed. To compare PDAC incidence, a two-sided Fisher's exact test was used. RESULTS: Compared to KC;Hsl(+/+) mice, KC;Hsl(-/-) mice gained similar weight and displayed adipose tissue and pancreatic inflammation. In addition, KC;Hsl(-/-) mice had reduced levels of plasma insulin and leptin. Importantly, the increased adipose tissue and pancreatic inflammation was associated with a significant increase in PDAC incidence in KC;Hsl(-/-) mice. CONCLUSIONS: HSL deficiency is associated with adipose tissue and pancreatic inflammation and accelerates PDAC development in the KC mouse model.
ESTHER : Xu_2018_BMC.Cancer_18_797
PubMedSearch : Xu_2018_BMC.Cancer_18_797
PubMedID: 30086728
Gene_locus related to this paper: mouse-hslip

Title : Biodegradation of phenanthrene by endophytic fungus Phomopsis liquidambari in vitro and in vivo - Fu_2018_Chemosphere_203_160
Author(s) : Fu W , Xu M , Sun K , Hu L , Cao W , Dai C , Jia Y
Ref : Chemosphere , 203 :160 , 2018
Abstract : Phenanthrene, as a widespread polycyclic aromatic hydrocarbons (PAHs) contaminant in vitro and in vivo of plant, has the characteristics of carcinogenicity, teratogenicity and mutagenicity. This work aimed to explore the phenanthrene metabolic mechanism by Phomopsis liquidambari in vitro, as well as the bioremediation ability through P. liquidambari-rice combination. This strain was able to use phenanthrene as source of carbon and energy to grow, more than 77% of added 50mgL(-1) phenanthrene was removed after 10d in MSM. We identified the metabolic products via HPLC-MS and proposed two possible degradation pathways. Phenanthrene was firstly combined with oxygen to become phenanthrene 9,10-oxide, and then degraded to 9-phenanthrol, followed by oxidization to 9,10-dihydroxyphenanthrene. In addition, that epoxide (phenanthrene 9,10-oxide) was also hydrolyzed to phenanthrene trans-9,10-dihydrodiol, and then dehydrogenized to 9,10-dihydroxyphenanthrene, which was further degraded to 9,10-phenanthrenequinone; during this metabolic pathway, the changes of P450 monooxygenase, epoxide hydrolase, dehydrogenase and catechol 2,3-dioxygenase activities and their corresponding gene transcription levels were closely related. What's more, P. liquidambari could combine with rice to eliminate phenanthrene accumulated in vivo of rice seedlings, and the removal rate in inoculation treatment represented a significant difference (increased 25.68%) compared with uninoculation treatment after cultivation 30d. Therefore, we concluded that P. liquidambari could not only respond to phenanthrene pollution stress in vitro but also exert a mitigation effect on plants accumulated phenanthrene. This work provides a foundation for applying endophytic fungi to PAHs bioremediation in vitro and in vivo.
ESTHER : Fu_2018_Chemosphere_203_160
PubMedSearch : Fu_2018_Chemosphere_203_160
PubMedID: 29614409

Title : Interaction of a digestive protease, Candida rugosa lipase, with three surfactants investigated by spectroscopy, molecular docking and enzyme activity assay - Zhang_2017_Sci.Total.Environ_622-623_306
Author(s) : Zhang R , Liu Y , Huang X , Xu M , Liu R , Zong W
Ref : Sci Total Environ , 622-623 :306 , 2017
Abstract : The extensive use of surfactants in food, laundry products and agriculture has caused concern about their biosafety. However, few studies have been done on their potential effect on the lipase which has always been used with surfactants in food and laundry industry. Herein, we investigated the interaction of three surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), sodium lauryl sulfonate (SLS)) with Candida rugosa lipase (CRL), which is a popular biocatalyst used regularly with surfactants. The effect of the three surfactants on the conformation and activity of CRL was evaluated by using multiple spectral methods, enzyme activity assay and molecular docking modeling. The results demonstrated that CRL interacted with SDS, SDBS and SLS primarily through hydrophobic forces, H-bonding and electrostatic forces, respectively. The binding constants (KA) of SDBS with CRL varied with temperature: 1.99x10(3)mol/L at 298K and 4.13x10(3)mol/L at 318K. SDS and SDBS affected the secondary structure and skeleton of CRL, which changed the polarity of CRL and enhanced its activity. SLS also changed the secondary structure and activity of CRL moderately, but had little effect on its polarity and chromophore microenvironment. Accordingly, all three surfactants exhibited effect to CRL on the molecular level calling for more attention to pay on their biosafety. The work demonstrates that SDS, SDBS and SLS could cause negative effects to CRL from different angles and therefore are not bio-friendly detergents.
ESTHER : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedSearch : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedID: 29220758

Title : Chemical Composition and Acetylcholinesterase Inhibitory Activity of Essential Oils from Piper Species - Xiang_2017_J.Agric.Food.Chem_65_3702
Author(s) : Xiang CP , Han JX , Li XC , Li YH , Zhang Y , Chen L , Qu Y , Hao CY , Li HZ , Yang CR , Zhao SJ , Xu M
Ref : Journal of Agricultural and Food Chemistry , 65 :3702 , 2017
Abstract : The essential oils (EOs) derived from aromatic plants such as Piper species are considered to play a role in alleviating neuronal ailments that are associated with inhibition of acetylcholinesterase (AChE). The chemical compositions of 23 EOs prepared from 16 Piper spp. were analyzed by both gas chromatography with a flame ionization detector (GC-FID) and gas chromatography-mass spectrometry (GC-MS). A total of 76 compounds were identified in the EOs from the leaves and stems of 19 samples, while 30 compounds were detected in the EOs from the fruits of four samples. Sesquiterpenes and phenylpropanoids were found to be rich in these EOs, of which asaricin, caryophyllene, caryophyllene oxide, isospathulenol, (+)-spathulenol, and beta-bisabolene are the major constituents. The EOs from the leaves and stems of Piper austrosinense, P. puberulum, P. flaviflorum, P. betle, and P. hispidimervium showed strong AChE inhibitory activity with IC50 values in the range of 1.51 to 13.9 mg/mL. A thin-layer chromatography (TLC) bioautography assay was employed to identify active compound(s) in the most active EO from P. hispidimervium. The active compound was isolated and identified as asaricin, which gave an IC50 value of 0.44 +/- 0.02 mg/mL against AChE, comparable to galantamine with an IC50 0.15 +/- 0.01 mg/mL.
ESTHER : Xiang_2017_J.Agric.Food.Chem_65_3702
PubMedSearch : Xiang_2017_J.Agric.Food.Chem_65_3702
PubMedID: 28436658

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 : Donepezil delays photoreceptor apoptosis induced by N-methyl-N-nitrosourea in mice - Wu_2016_Exp.Ther.Med_11_2446
Author(s) : Wu L , Xu M , Liu S , Chen G , Zhang F , Zhao Y , Yi J
Ref : Exp Ther Med , 11 :2446 , 2016
Abstract : Retinitis pigmentosa (RP) is a group of inherited retinal degeneration diseases characterized by photoreceptor cell death that causes visual disturbances and eventual blindness. Intraperitoneal injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor loss, and is used to create an animal model for investigating the mechanisms that cause retinal degeneration diseases. Donepezil is an acetylcholinesterase inhibitor that has a protective effect on retinal ganglion cells in vitro and in vivo, and it is understood that donepezil increases the expression of a heat shock protein 70 (Hsp70), which serves to protect neurons. Hsp70 functions as a chaperone molecule that protects cells from protein aggregation and assists in the refolding of denatured proteins. In the present study, the effects of donepezil on photoreceptor survival in mice was investigated. It was observed that donepezil upregulates the expression of Hsp70, to increase resistance to MNU-induced photoreceptor cell apoptosis by using its anti-apoptotic properties. In addition, the present study observed that Hsp70 promotes photoreceptor cell survival by upregulating the expression levels of B-cell lymphoma 2 (Bcl-2). In conclusion, the results of the present study indicate that donepezil has the potential to be used as a treatment for retinal degenerative diseases.
ESTHER : Wu_2016_Exp.Ther.Med_11_2446
PubMedSearch : Wu_2016_Exp.Ther.Med_11_2446
PubMedID: 27284332

Title : The protective role of tacrine and donepezil in the retina of acetylcholinesterase knockout mice - Yi_2015_Int.J.Ophthalmol_8_884
Author(s) : Yi YM , Cai L , Shao Y , Xu M , Yi JL
Ref : Int J Ophthalmol , 8 :884 , 2015
Abstract : AIM: To determine the effect of different concentrations of the acetylcholinesterase (AChE) inhibitors tacrine and donepezil on retinal protection in AChE(+/-) mice (AChE knockout mice) of various ages.
METHODS: Cultured ARPE-19 cells were treated with hydrogen peroxide (H2O2) at concentrations of 0, 250, 500, 1000 and 2000 micromol/L and protein levels were measured using Western blot. Intraperitoneal injections of tacrine and donepezil (0.1 mg/mL, 0.2 mg/mL and 0.4 mg/mL) were respectively given to AChE(+/-) mice aged 2mo and 4mo and wild-type S129 mice for 7d; phosphate buffered saline (PBS) was administered to the control group. The mice were sacrificed after 30d by in vitro cardiac perfusion and retinal samples were taken. AChE-deficient mice were identified by polymerase chain reaction (PCR) analysis using specific genotyping protocols obtained from the Jackson Laboratory website. H&E staining, immunofluorescence and Western blot were performed to observe AChE protein expression changes in the retinal pigment epithelial (RPE) cell layer.
RESULTS: Different concentrations of H2O2 induced AChE expression during RPE cell apoptosis. AChE(+/-) mice retina were thinner than those in wild-type mice (P<0.05); the retinal structure was still intact at 2mo but became thinner with increasing age (P<0.05); furthermore, AChE(+/-) mice developed more slowly than wild-type mice (P<0.05). Increased concentrations of tacrine and donepezil did not significantly improve the protection of the retina function and morphology (P>0.05). CONCLUSION: In vivo, tacrine and donepezil can inhibit the expression of AChE; the decrease of AChE expression in the retina is beneficial for the development of the retina.
ESTHER : Yi_2015_Int.J.Ophthalmol_8_884
PubMedSearch : Yi_2015_Int.J.Ophthalmol_8_884
PubMedID: 26558196

Title : Simultaneous enantioselective determination of isocarbophos and its main metabolite isocarbophos oxon in rice, soil, and water by chiral liquid chromatography and tandem mass spectrometry - Yao_2015_J.Sep.Sci_38_1663
Author(s) : Yao Z , Lin M , Xu M , Wang T , Ping X , Wu S , Wang Q , Zhang H
Ref : J Sep Sci , 38 :1663 , 2015
Abstract : An efficient enantioselective method for the simultaneous determination of isocarbophos and its main metabolite isocarbophos oxon in rice, soil, and water was developed using liquid chromatography with tandem mass spectrometry. The enantioseparation was performed on a Chiralpak AD-3R column at 30 degrees C using gradient elution. Target compounds were extracted from soil and rice using acetonitrile with omission of a clean-up procedure, while a C18 solid-phase extraction column was used for water samples. Quantification was achieved using matrix-matched calibration. The overall mean recoveries for isocarbophos and isocarbophos oxon enantiomers from the five matrices were 89.7-103 and 90.1-98.7%, with relative standard deviations of 2.1-5.4 and 2.5-4.7%, respectively. Moreover, the absolute configurations of isocarbophos oxon enantiomers were determined by liquid chromatography with tandem mass spectrometry through incubation of each isocarbophos enantiomer in soil, the first eluting enantiomer being confirmed as (R)-(-)-isocarbophos oxon. The proposed method was applied to real soil samples and satisfactory results were obtained.
ESTHER : Yao_2015_J.Sep.Sci_38_1663
PubMedSearch : Yao_2015_J.Sep.Sci_38_1663
PubMedID: 25755196

Title : Association of and with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls - Ji_2015_Exp.Ther.Med_9_1831
Author(s) : Ji H , Dai D , Wang Y , Jiang D , Zhou X , Lin P , Ji X , Li J , Zhang Y , Yin H , Chen R , Zhang L , Xu M , Duan S , Wang Q
Ref : Exp Ther Med , 9 :1831 , 2015
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date.
ESTHER : Ji_2015_Exp.Ther.Med_9_1831
PubMedSearch : Ji_2015_Exp.Ther.Med_9_1831
PubMedID: 26136901

Title : Schisandrin C Ameliorates Learning and Memory Deficits by Abeta(1-42) -induced Oxidative Stress and Neurotoxicity in Mice - Mao_2015_Phytother.Res_29_1373
Author(s) : Mao X , Liao Z , Guo L , Xu X , Wu B , Xu M , Zhao X , Bi K , Jia Y
Ref : Phytother Res , 29 :1373 , 2015
Abstract : Schisandrin C (SCH-C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH-C on memory impairment and further research on pathological changes in Abeta(1-42) -induced Alzheimer's disease mice. Mice were administration with SCH-C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y-maze test, active avoidance test and Morris water maze test in all groups, and the level of Abeta(1-42) and neuronal injury induced by Abeta(1-42) were reversed remarkably following SCH-C treatment compared with sham group; meanwhile the impairment of short-term or working memory was dramatically improved. In addition, SCH-C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH-C offers protection against Abeta(1-42) -induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright 2015 John Wiley & Sons, Ltd.
ESTHER : Mao_2015_Phytother.Res_29_1373
PubMedSearch : Mao_2015_Phytother.Res_29_1373
PubMedID: 26074330

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

Title : Lysinibacillus varians sp. nov., an endospore-forming bacterium with a filament-to-rod cell cycle - Zhu_2014_Int.J.Syst.Evol.Microbiol_64_3644
Author(s) : Zhu C , Sun G , Chen X , Guo J , Xu M
Ref : Int J Syst Evol Microbiol , 64 :3644 , 2014
Abstract : Six Gram-stain-positive, motile, filamentous and/or rod-shaped, spherical spore-forming bacteria (strains GY32(T), L31, F01, F03, F06 and F07) showing polybrominated diphenyl ether transformation were investigated to determine their taxonomic status. After spore germination, these organisms could grow more than one hundred microns long as intact single cells and then divide into rod cells and form endospores in 33 h. The cell-wall peptidoglycan of these strains was type A4alpha, the predominant menaquinone was MK-7 and the major fatty acids were iso-C(16:0), iso-C(15:0) and C(16:1)omega7C. Diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine were detected in the polar lipid profile. Analysis of the 16S rRNA gene sequences indicated that these strains should be placed in the genus Lysinibacillus and they were most closely related to Lysinibacillus sphaericus DSM 28(T) (99% 16S rRNA gene sequence similarity). The gyrB sequence similarity and DNA-DNA relatedness between strain GY32(T) and L. sphaericus JCM 2502(T) were 81% and 52%, respectively. The G+C content of the genomic DNA of strain GY32(T) was 43.2 mol%. In addition, strain GY32(T) showed differences in nitrate reduction, starch and gelatin hydrolysis, carbon resource utilization and cell morphology. The phylogenetic distance from its closest relative measured by DNA-DNA relatedness and DNA G+C content, and its phenotypic properties demonstrated that strain GY32(T) represents a novel species of the genus Lysinibacillus, for which the name Lysinibacillus varians sp. nov. is proposed. The type strain is GY32(T) ( = NBRC 109424(T) = CGMCC 1.12212(T) = CCTCC M 2011307(T)).
ESTHER : Zhu_2014_Int.J.Syst.Evol.Microbiol_64_3644
PubMedSearch : Zhu_2014_Int.J.Syst.Evol.Microbiol_64_3644
PubMedID: 25070216
Gene_locus related to this paper: 9baci-d7ws01 , lyssh-a0a081klr2 , 9baci-x2gv08 , 9baci-x2gxj4

Title : Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma - Hu_2014_Int.J.Clin.Exp.Pathol_7_3704
Author(s) : Hu WR , Lian YF , Peng LX , Lei JJ , Deng CC , Xu M , Feng QS , Chen LZ , Bei JX , Zeng YX
Ref : Int J Clin Exp Pathol , 7 :3704 , 2014
Abstract : Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases.
ESTHER : Hu_2014_Int.J.Clin.Exp.Pathol_7_3704
PubMedSearch : Hu_2014_Int.J.Clin.Exp.Pathol_7_3704
PubMedID: 25120746

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Acetylcholinesterase function in apoptotic retina pigment epithelial cells induced by H2O2 - Cai_2013_Int.J.Ophthalmol_6_772
Author(s) : Cai L , Liao HF , Zhang XJ , Shao Y , Xu M , Yi JL
Ref : Int J Ophthalmol , 6 :772 , 2013
Abstract : AIM: To investigate the acetylcholinesterase (AChE) expression involved in retina pigment epithelial (RPE) apoptosis induced by higher concentrations H2O2.
METHODS: The human retinal pigment epithelium cell line ARPE-19 was from ATCC (Rockville, MD). Cultured ARPE-19 cells were treated with H2O2 at 0, 250, 500, 1 000, 2 000micromol/L and cell viability was measured with MTT assay. AChE expression and DNA fragments were analyzed by immunocytochemistry, TUNEL and PARP-1 Western blotting.
RESULTS: Immunofluorescence detected AChE exist in the normal human retinal tissue. When H2O2 >500micromol/L, AChE expression showed an increase after 2h, and this concentration was selected for the present study. RPE cell was induced with 1 000micromol/L H2O2 for 2h, compared to the control group, cell activity decline detected by MTT, AChE and PARP-1 protein expression was significantly increased detected by Western blotting. AChE immunofluorescence staining was positive in RPE cell after H2O2 incubate 2h. In addition, pretreatment with 100micromol/L epigallocatechin gallate (EGCG), cell viability increased from 31.20%+/-3.90% to 70.23%+/-12.96%. CONCLUSION: AChE is weakly expressed in normal human RPE cells. Stimulation with H2O2 caused the stable increase of AChE expression in RPE cells, which may indicate that AChE may be an important role in AMD.
ESTHER : Cai_2013_Int.J.Ophthalmol_6_772
PubMedSearch : Cai_2013_Int.J.Ophthalmol_6_772
PubMedID: 24392323

Title : Draft Genome Sequence of Shewanella decolorationis S12, a Dye-Degrading Bacterium Isolated from a Wastewater Treatment Plant - Xu_2013_Genome.Announc_1_e00993
Author(s) : Xu M , Fang Y , Liu J , Chen X , Sun G , Guo J , Hua Z , Tu Q , Wu L , Zhou J , Liu X
Ref : Genome Announc , 1 : , 2013
Abstract : Shewanella decolorationis is a valuable microorganism for degrading diverse synthetic textile dyes. Here, we present an annotated draft genome sequence of S. decolorationis S12, which contains 4,219 protein-coding genes and 86 structural RNAs. This information regarding the genetic basis of this bacterium can greatly advance our understanding of the physiology of this species.
ESTHER : Xu_2013_Genome.Announc_1_e00993
PubMedSearch : Xu_2013_Genome.Announc_1_e00993
PubMedID: 24309738
Gene_locus related to this paper: 9gamm-v1dg58 , 9gamm-v1daq6

Title : Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics - Tan_2013_Int.J.Nanomedicine_8_737
Author(s) : Tan Q , Jiang R , Xu M , Liu G , Li S , Zhang J
Ref : Int J Nanomedicine , 8 :737 , 2013
Abstract : BACKGROUND: Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine.
METHODS: The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium.
RESULTS: The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. CONCLUSION: PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors.
ESTHER : Tan_2013_Int.J.Nanomedicine_8_737
PubMedSearch : Tan_2013_Int.J.Nanomedicine_8_737
PubMedID: 23459707

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

Title : Sequencing the genome of Marssonina brunnea reveals fungus-poplar co-evolution - Zhu_2012_BMC.Genomics_13_382
Author(s) : Zhu S , Cao YZ , Jiang C , Tan BY , Wang Z , Feng S , Zhang L , Su XH , Brejova B , Vinar T , Xu M , Wang MX , Zhang SG , Huang MR , Wu R , Zhou Y
Ref : BMC Genomics , 13 :382 , 2012
Abstract : BACKGROUND: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf spot that devastates poplar plantations by defoliating susceptible trees before normal fall leaf drop.
RESULTS: We sequence the genome of M. brunnea with a size of 52 Mb assembled into 89 scaffolds, representing the first sequenced Dermateaceae genome. By inoculating this fungus onto a poplar hybrid clone, we investigate how M. brunnea interacts and co-evolves with its host to colonize poplar leaves. While a handful of virulence genes in M. brunnea, mostly from the LysM family, are detected to up-regulate during infection, the poplar down-regulates its resistance genes, such as nucleotide binding site domains and leucine rich repeats, in response to infection. From 10,027 predicted proteins of M. brunnea in a comparison with those from poplar, we identify four poplar transferases that stimulate the host to resist M. brunnea. These transferas-encoding genes may have driven the co-evolution of M. brunnea and Populus during the process of infection and anti-infection.
CONCLUSIONS: Our results from the draft sequence of the M. brunnea genome provide evidence for genome-genome interactions that play an important role in poplar-pathogen co-evolution. This knowledge could help to design effective strategies for controlling Marssonina leaf spot in poplar.
ESTHER : Zhu_2012_BMC.Genomics_13_382
PubMedSearch : Zhu_2012_BMC.Genomics_13_382
PubMedID: 22876864
Gene_locus related to this paper: marbu-k1wj37 , marbu-k1xt94 , marbu-k1wdc0 , marbu-k1wht2 , marbu-k1wj82 , marbu-k1wkk6 , marbu-k1wnk8 , marbu-k1wpc4 , marbu-k1wrg1 , marbu-k1wsf4 , marbu-k1wtx1 , marbu-k1x087 , marbu-k1x383 , marbu-k1x3g3 , marbu-k1x464 , marbu-k1x8c9 , marbu-k1xi08 , marbu-k1xzh8 , marbu-k1y283 , marbu-k1x918 , marbu-k1wzc0 , marbu-k1xu92 , marbu-k1xws5 , marbu-k1wxv8

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 : Characterization of Thermobifida fusca cutinase-carbohydrate-binding module fusion proteins and their potential application in bioscouring - Zhang_2010_Appl.Environ.Microbiol_76_6870
Author(s) : Zhang Y , Chen S , Xu M , Cavaco-Paulo A , Wu J , Chen J
Ref : Applied Environmental Microbiology , 76 :6870 , 2010
Abstract : Cutinase from Thermobifida fusca is thermally stable and has potential application in the bioscouring of cotton in the textile industry. In the present study, the carbohydrate-binding modules (CBMs) from T. fusca cellulase Cel6A (CBM(Cel6A)) and Cellulomonas fimi cellulase CenA (CBM(CenA)) were fused, separately, to the carboxyl terminus of T. fusca cutinase. Both fusion enzymes, cutinase-CBM(Cel6A) and cutinase-CBM(CenA), were expressed in Escherichia coli and purified to homogeneity. Enzyme characterization showed that both displayed similar catalytic properties and pH stabilities in response to T. fusca cutinase. In addition, both fusion proteins displayed an activity half-life of 53 h at their optimal temperature of 50 degrees C. Compared to T. fusca cutinase, in the absence of pectinase, the binding activity on cotton fiber was enhanced by 2% for cutinase-CBM(Cel6A) and by 28% for cutinase-CBM(CenA), whereas in the presence of pectinase, the binding activity was enhanced by 40% for the former and 45% for the latter. Notably, a dramatic increase of up to 3-fold was observed in the amount of released fatty acids from cotton fiber by both cutinase-CBM fusion proteins when acting in concert with pectinase. This is the first report of improving the scouring efficiency of cutinase by fusing it with CBM. The improvement in activity and the strong synergistic effect between the fusion proteins and pectinase suggest that they may have better applications in textile bioscouring than the native cutinase.
ESTHER : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedSearch : Zhang_2010_Appl.Environ.Microbiol_76_6870
PubMedID: 20729325

Title : Investigation of the mechanism of enhanced effect of EGCG on huperzine A's inhibition of acetylcholinesterase activity in rats by a multispectroscopic method - Xiao_2008_J.Agric.Food.Chem_56_910
Author(s) : Xiao J , Chen X , Zhang L , Talbot SG , Li GC , Xu M
Ref : Journal of Agricultural and Food Chemistry , 56 :910 , 2008
Abstract : The mechanism of enhanced effect of (-)-epigallocatechin-3-gallate (EGCG) on huperzine A's (HUP) inhibition of acetylcholinesterase (AChE) activity in rats was investigated. The inhibitory effects of HUP at 10 and 5 microg/kg on AChE activity were quite weak in the whole phase. In contrast, upon addition of EGCG (100 mg/kg) to the HUP 10 and 5 microg/kg groups, remarkably enhanced inhibitory effects with maximum inhibitory percentages of 90.94 and 88.13% were observed under the same conditions. EGCG also can greatly prolong the inhibitory time. The mechanism of the enhanced effects of EGCG on HUP's inhibition of AChE activity was investigated by steady fluorescence spectroscopy, infrared spectroscopy, and ultraviolet spectroscopy. HUP hardly interacted with the main transport protein, whereas there was a very strong binding interaction between EGCG and bovine serum albumin. The enhanced transport of HUP is a possible cause of the enhanced effect of EGCG on HUP bioactivity.
ESTHER : Xiao_2008_J.Agric.Food.Chem_56_910
PubMedSearch : Xiao_2008_J.Agric.Food.Chem_56_910
PubMedID: 18193834

Title : Mapping and expression analysis of chicken NDRG1 and NDRG3 genes - Tian_2008_Biochem.Genet_46_677
Author(s) : Tian Y , Xu M , Fu Y , Yuan A , Wang D , Li G , Liu G , Lu L
Ref : Biochemical Genetics , 46 :677 , 2008
Abstract : N-myc downstream-regulated genes 1 and 3 (NDRG1 and NDRG3) are members of the alpha/beta hydrolase superfamily. Phylogenetic analysis of the family demonstrated that human NDRG1 and 3 belong to a subfamily. The mapping and gene expression patterns of these genes represent one step toward further investigation into their possible roles in the chicken (Gallus gallus). To map these genes in the chicken chromosome, a 6000 rads chicken-hamster radiation hybrid panel (ChickRH6) was used. Primers were designed according to the published human sequences for amplification of those two genes. We compared the corresponding human mRNA sequences with the predicted coding sequences of the chicken NDRG1 and 3 genes and found that the assembled contigs shared a high percentage of similarity with the human genes. PCR of samples from ChickRH6 revealed that the locations of NDRG1 and 3 are linked to the markers MYC (58 cRs away, LOD score 4.52) and SEQ0265 (10 cRs away, LOD score 17.81), respectively. This result adds two new markers to the chicken RH map, and it reinforces that the RH technique is indeed a powerful tool for mapping genes due to its rapidity, precision, convenience, and reproducibility. In addition, we detected the gene expression and distribution of chicken NDRG1 and 3 in seven tissues, including heart, liver, spleen, lung, muscle, brain, and thymus, by RT-PCR, and found that NDRG1 is relatively ubiquitously expressed in all the tested tissues and highly expressed in heart and liver, whereas NDRG3 is high in heart, muscle, and brain.
ESTHER : Tian_2008_Biochem.Genet_46_677
PubMedSearch : Tian_2008_Biochem.Genet_46_677
PubMedID: 18751885

Title : Systematic review on the efficacy and safety of herbal medicines for Alzheimer's disease - Man_2008_J.Alzheimers.Dis_14_209
Author(s) : Man SC , Durairajan SS , Kum WF , Lu JH , Huang JD , Cheng CF , Chung V , Xu M , Li M
Ref : J Alzheimers Dis , 14 :209 , 2008
Abstract : A systematic review was conducted to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (cholinesterase inhibitors and nootropic agents, OM) for Alzheimer's disease (AD). Sixteen studies testing different HM were included. Out of the 15 HM monotherapy studies, 13 reported HM to be significantly better than OM or placebo; one reported similar efficacy between HM and OM. Only the HM adjuvant study reported significant efficacy. No major adverse events for HM were reported and HMs were found to reduce the adverse effects arising from OM. Imbalance in ethnicity among participants was observed; gender distribution was unclear. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies comparing HM with OM suggest that HM can be a safe, effective treatment for AD, either alone or in conjunction with OM. Methodological flaws in the design of the studies, however, limited the extent to which the results could be interpreted. Among various HMs, the safety and tolerability of EGb761 was best established. Further multi-center trials with large sample size, high methodological qualities and standardized HM ingredients are necessary for clinical recommendations on the use of HM in treating AD.
ESTHER : Man_2008_J.Alzheimers.Dis_14_209
PubMedSearch : Man_2008_J.Alzheimers.Dis_14_209
PubMedID: 18560132

Title : Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the binding and activity at muscarinic receptor subtypes and chimeras - Tejada_2006_J.Med.Chem_49_7518
Author(s) : Tejada FR , Nagy PI , Xu M , Wu C , Katz T , Dorsey J , Rieman M , Lawlor E , Warrier M , Messer WS, Jr.
Ref : Journal of Medicinal Chemistry , 49 :7518 , 2006
Abstract : As part of a continuing effort to design and synthesize highly selective muscarinic agonists for different muscarinic receptor subtypes, several tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (1) analogues were prepared and characterized. Different analogues were synthesized having hydrophilic spacers of di-, tri-, tetra-, penta(ethylene glycol) and tri(propylene glycol) separating the 1,2,5,6-tetrahydropyridine ring from the terminal heterocycle, which was either a 1,2,5-thiadiazole or 1,2,4-thiadiazole ring. Chimeric receptor and molecular modeling studies also were conducted to determine how the ligands interact with muscarinic receptors. The studies revealed that varying the distance of the terminal thiadiazole and the positioning of the methoxy group can increase binding affinity for certain muscarinic receptor subtypes (at M(2) for 13d and M(4) for 1) and enhance functional efficacy at M(4) receptors for 13e and 18b. Moreover, compound 1 exhibited antipsychotic activity as assessed by reversal of apomorphine-induced sensory motor gating deficits, suggesting potential utility in the treatment of schizophrenia.
ESTHER : Tejada_2006_J.Med.Chem_49_7518
PubMedSearch : Tejada_2006_J.Med.Chem_49_7518
PubMedID: 17149881

Title : Expression of a novel dipeptidyl peptidase 8 (DPP8) transcript variant, DPP8-v3, in human testis - Zhu_2005_Asian.J.Androl_7_245
Author(s) : Zhu H , Zhou ZM , Lu L , Xu M , Wang H , Li JM , Sha JH
Ref : Asian J Androl , 7 :245 , 2005
Abstract : AIM: To investigate the role of a novel dipeptidyl peptidase 8 transcript variant (DPP8-v3) gene in testis development and/or spermatogenesis.
METHODS: A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) and Southern-blot analysis.
RESULTS: A new transcript variant of the human dipeptidyl peptidase (DPP8), exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 (DPP8-v3). The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. CONCLUSION: DPP8-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility.
ESTHER : Zhu_2005_Asian.J.Androl_7_245
PubMedSearch : Zhu_2005_Asian.J.Androl_7_245
PubMedID: 16110352

Title : Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia - Jia_2004_Chin.Med.J.(Engl)_117_1161
Author(s) : Jia JP , Jia JM , Zhou WD , Xu M , Chu CB , Yan X , Sun YX
Ref : Chinese Medical Journal (Engl) , 117 :1161 , 2004
Abstract : BACKGROUND: An important aspect of Alzheimer's disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment.
METHODS: Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status.
RESULTS: ACh concentrations in CSF of AD patients [(10.7 +/- 5.1) nmol/L] and VD patients [(16.8 +/- 7.4) nmol/L] were both significantly lower than in controls [(34.5 +/- 9.0) nmol/L, t = 10.67, P < 0.001; t = 6.91, P < 0.001]. Both results correlated positively with MMSE scores (rs = 0.88 and rs = 0.85, respectively, P < 0.01). The CSF concentration of Ch was significantly higher in VD patients [(887.4 +/- 187.4) nmol/L] compared to AD patients [(627.6 +/- 145.1) nmol/L, t = 6.4, P < 0.001] and controls [(716.0 +/- 159.4) nmol/L, t = 4.2, P = 0.002]. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups.
CONCLUSIONS: The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.
ESTHER : Jia_2004_Chin.Med.J.(Engl)_117_1161
PubMedSearch : Jia_2004_Chin.Med.J.(Engl)_117_1161
PubMedID: 15361288

Title : [The activity of blood cholinesterase in rats exposed to dimehypo] - Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_416
Author(s) : Wan W , Xu M , Zou H , Lu A , Shen X , Chen Y
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 20 :416 , 2002
Abstract : OBJECTIVE: To determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)]. METHOD: Rats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE. RESULT: 1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P < 0.01). In rats dosed with methamidophos, even 1/16 LD50 dose inhibited the activity of ChE by 42.4% compared with that of control group. When the dose of methamidophos increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of methamidophos inhibited the activity of ChE by 52.9%. The activity of ChE in the rats dosed with dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P < 0.01). CONCLUSION: Higher doses of dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.
ESTHER : Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_416
PubMedSearch : Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_416
PubMedID: 14694587

Title : [The activity of blood cholinesterase in rats exposed to dimethypo after drug intervention] - Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_419
Author(s) : Wan W , Xu M , Zou H , Lu A , Shen X , Chen Y
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 20 :419 , 2002
Abstract : OBJECTIVE: To investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol. METHOD: Rats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups. RESULT: The ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good. CONCLUSION: Pralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.
ESTHER : Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_419
PubMedSearch : Wan_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_419
PubMedID: 14694588

Title : Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog - Xu_1998_Mol.Biochem.Parasitol_91_327
Author(s) : Xu M , Molento M , Blackhall W , Ribeiro P , Beech R , Prichard R
Ref : Molecular & Biochemical Parasitology , 91 :327 , 1998
Abstract : Resistance to ivermectin and related drugs is an increasing problem for parasite control. The mechanism of ivermectin resistance in nematode parasites is currently unknown. Some P-glycoproteins and multidrug resistance proteins have been found to act as membrane transporters which pump drugs from the cell. A disruption of the mdrla gene, which encodes a P-glycoprotein in mice, results in hypersensitivity to ivermectin. Genes encoding members of the P-glycoprotein family are known to exist in nematodes but the involvement of P-glycoprotein in nematode ivermectin-resistance has not been described. Our data suggest that a P-glycoprotein may play a role in ivermectin resistance in the sheep nematode parasite Haemonchus contortus. A full length P-glycoprotein cDNA from H. contortus has been cloned and sequenced. Analysis of the sequence showed 61-65% homology to other P-glycoprotein/multidrug resistant protein sequences, such as mice, human and Caenorhabditis elegans. Expression of P-glycoprotein mRNA was higher in ivermectin-selected than unselected strains of H. contortus. An alteration in the restriction pattern was also found for the genomic locus of P-glycoprotein derived from ivermectin-selected strains of H. contortus compared with unselected strains. P-glycoprotein gene structure and/or its transcription are altered in ivermectin-selected H. contortus. The multidrug resistance reversing agent, verapamil, increased the efficacy of ivermectin and moxidectin against a moxidectin-selected strain of this nematode in jirds (Meriones unguiculatus). These data indicate that a P-glycoprotein may be involved in resistance to ivermectin and other macrocyclic lactones in H. contortus.
ESTHER : Xu_1998_Mol.Biochem.Parasitol_91_327
PubMedSearch : Xu_1998_Mol.Biochem.Parasitol_91_327
PubMedID: 9566525

Title : Structures involved in binding, gating, and conduction in nicotinic acetylcholine receptors -
Author(s) : Karlin A , Akabas MH , Czajkowski C , Kaufmann C , Stauffer D , Xu M
Ref : Ren Physiol Biochem , 17 :184 , 1994
PubMedID: 7518954

Title : Acetylcholine receptor channel structure probed in cysteine-substitution mutants - Akabas_1992_Science_258_307
Author(s) : Akabas MH , Stauffer DA , Xu M , Karlin A
Ref : Science , 258 :307 , 1992
Abstract : In order to understand the structural bases of ion conduction, ion selectivity, and gating in the nicotinic acetylcholine receptor, mutagenesis and covalent modification were combined to identify the amino acid residues that line the channel. The side chains of alternate residues--Ser248, Leu250, Ser252, and Thr254--in M2, a membrane-spanning segment of the alpha subunit, are exposed in the closed channel. Thus alpha 248-254 probably forms a beta strand, and the gate is closer to the cytoplasmic end of the channel than any of these residues. On channel opening, Leu251 is also exposed. These results lead to a revised view of the closed and open channel structures.
ESTHER : Akabas_1992_Science_258_307
PubMedSearch : Akabas_1992_Science_258_307
PubMedID: 1384130

Title : Determination of basal acetylcholine release in vivo by rat brain dialysis with a U-shaped cannula: effect of SM-10888, a putative therapeutic drug for Alzheimer's disease - Xu_1991_Neurosci.Lett_123_179
Author(s) : Xu M , Nakamura Y , Yamamoto T , Natori K , Irie T , Utsumi H , Kato T
Ref : Neuroscience Letters , 123 :179 , 1991
Abstract : A U-shaped dialysis cannula was implanted into rat frontal cortex, hippocampus and striatum, and after 1 day for surgical recovery the cannula was perfused with Ringer's solution without any acetylcholinesterase (AChE) inhibitor under freely moving conditions. With a highly sensitive assay method for acetylcholine (ACh), the basal ACh content in the dialysates were detectable in those brain regions for several hours. The basal levels in the frontal cortex, hippocampus and striatum were 82 +/- 9, 72 +/- 4, 70 +/- 8 fmol/20 microliters (mean +/- S.E.M.), respectively. When SM-10888, a novel AChE inhibitor and putative therapeutic drug for Alzheimer's disease, was injected intraperitoneally, ACh in the dialysate of the cortex increased in a dose-dependent manner. Changes in the levels of hippocampal and striatal ACh release evoked by SM-10888 were similar to, but smaller than, that in the cortex. These data suggest that since the present assay method is able to determine in vivo basal ACh release in the dialysate without any AChE inhibitor, it is possible to study the effect of a novel drug such as SM-10888 in the brain regions.
ESTHER : Xu_1991_Neurosci.Lett_123_179
PubMedSearch : Xu_1991_Neurosci.Lett_123_179
PubMedID: 2027531

Title : Differential effects of M1- and M2-muscarinic drugs on striatal dopamine release and metabolism in freely moving rats - Xu_1989_Brain.Res_495_232
Author(s) : Xu M , Mizobe F , Yamamoto T , Kato T
Ref : Brain Research , 495 :232 , 1989
Abstract : A dialysis loop cannula was implanted into rat striatum under anesthetized condition, and the area was perfused with Ringer's solution under freely moving condition after 3 days for surgical recovery. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid recovered in the dialysate were measured by high-performance liquid chromatography with electrochemical detection. The effects of M1- and M2-muscarinic receptor agents, which were perfused continuously into the striatum through the dialysis membrane, were investigated. Continuous perfusion of AF102B, an M1-selective agonist, and oxotremorine, a non-selective agonist, resulted in a dose-dependent increase in the striatal DA release. Pirenzepine (10(-5) and 10(-7) M), an M1-selective antagonist, decreased the release of DA, and the stimulatory effect of AF102B (10(-5) M) was completely inhibited by 10(-5) and 10(-7) M pirenzepine, while the stimulatory effect of oxotremorine (10(-4) M) was only partly inhibited by 10(-5) M pirenzepine. AF-DX116 (10(-5) M), an M2-selective antagonist, increased the DA release, and showed an additive effect on the DA release evoked by AF102B (10(-5) M), whereas it produced no significant effect on oxotremorine (10(-5) M)-evoked DA release. These results suggest that in vivo DA release in the rat striatum is modulated by different subtypes of muscarinic receptors; i.e., the stimulatory effect is mainly mediated by M1-sites and inhibitory effect is mainly mediated by M2-sites. The changes in the DA release induced by the various drugs were prevented by pretreatment with tetrodotoxin (TTX). Since action potential-dependent DA release (exocytosis) is blocked by the pretreatment with TTX, those drugs affect DA release by means of action potential-dependent processes.
ESTHER : Xu_1989_Brain.Res_495_232
PubMedSearch : Xu_1989_Brain.Res_495_232
PubMedID: 2765928