Wang T

References (122)

Title : Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation - Zhou_2024_J.Mol.Model_30_68
Author(s) : Zhou C , Yan L , Xu J , Hamezah HS , Wang T , Du F , Tong X , Han R
Ref : J Mol Model , 30 :68 , 2024
Abstract : CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrodinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.
ESTHER : Zhou_2024_J.Mol.Model_30_68
PubMedSearch : Zhou_2024_J.Mol.Model_30_68
PubMedID: 38347278

Title : Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits - Li_2024_Food.Chem_443_138459
Author(s) : Li D , Li J , Wu C , Liu H , Zhao M , Shi H , Zhang Y , Wang T
Ref : Food Chem , 443 :138459 , 2024
Abstract : Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu(3) alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.
ESTHER : Li_2024_Food.Chem_443_138459
PubMedSearch : Li_2024_Food.Chem_443_138459
PubMedID: 38306911

Title : Cytochrome P450 inhibitor\/inducer treatment patterns among patients in the United States with advanced ovarian cancer who were prescribed or were eligible for poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors in the first-line maintenance setting - Rimel_2024_Gynecol.Oncol.Rep_51_101332
Author(s) : Rimel BJ , Chase DM , Perhanidis J , Ghazarian AA , Du EX , Wang T , Song J , Golembesky AK , Hurteau JA , Kalilani L , Salani R , Monk BJ
Ref : Gynecologic Oncology Rep , 51 :101332 , 2024
Abstract : Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) are metabolized either via carboxylesterase (niraparib) or cytochrome P450 (CYP) enzymes (olaparib and rucaparib). Patients with advanced epithelial ovarian cancer (aOC) who receive concomitant medication metabolized by the CYP system may be at risk of drug-drug interactions impacting PARPi efficacy and tolerability. This study investigated CYP inhibitor/inducer treatment patterns in the first-line maintenance (1Lm) setting for patients with aOC. This retrospective cohort study used de-identified databases of US patients with aOC. Eligible patients were aged <=18 years, diagnosed with aOC between January 2015-March 2021, and received CYP inhibitors/inducers during 1Lm PARPi initiation or the eligibility window (90 days before to 120 days after first-line platinum-based therapy ended [index]). Patients were either prescribed 1Lm PARPi monotherapy (PARPi cohort) or were not prescribed any 1Lm therapy within 120 days post-index (PARPi-eligible cohort). Strong/moderate CYP inhibitors/inducers were defined as area under the plasma concentration-time curve ratio (AUCR) <=2 or clearance ratio (CL) >=0.5 (inhibitors), and AUCR >=0.5 or CL ratio <=2 (inducers). Of 1411 patients (median age 63), 158 were prescribed PARPis and 1253 were PARPi-eligible. Among the PARPi cohort, 46.2%, 48.7%, and 5.1% were prescribed niraparib, olaparib, and rucaparib, respectively. For patients prescribed olaparib or rucaparib, 42.4% also received strong and/or moderate CYP inhibitors/inducers. This real-world study indicated a considerable proportion of patients received strong and/or moderate CYP inhibitors/inducers and were prescribed PARPis metabolized by the CYP system. Understanding potential impacts of concomitant CYP inhibitors/inducers on PARPi efficacy and safety is warranted.
ESTHER : Rimel_2024_Gynecol.Oncol.Rep_51_101332
PubMedSearch : Rimel_2024_Gynecol.Oncol.Rep_51_101332
PubMedID: 38362364

Title : Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea - Wang_2024_J.Agric.Food.Chem__
Author(s) : Wang Q , Wang X , Cai D , Yu J , Chen X , Niu W , Wang S , Liu X , Zhou D , Yin F , Wang T , Shi X , Wu Z , Zhang J , Hao J , Liu P
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.
ESTHER : Wang_2024_J.Agric.Food.Chem__
PubMedSearch : Wang_2024_J.Agric.Food.Chem__
PubMedID: 38226868 || 38634420

Title : Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL - Ding_2024_Nat.Cell.Biol__
Author(s) : Ding L , Huwyler F , Long F , Yang W , Binz J , Wernle K , Pfister M , Klug M , Balaz M , Ukropcova B , Ukropec J , Wu C , Wang T , Gao M , Clavien PA , Dutkowski P , Tibbitt MW , Wolfrum C
Ref : Nat Cell Biol , : , 2024
Abstract : Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7(FBXW8) in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7(FBXW8)-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.
ESTHER : Ding_2024_Nat.Cell.Biol__
PubMedSearch : Ding_2024_Nat.Cell.Biol__
PubMedID: 38561547

Title : Durable protective efficiency provide by mRNA vaccines require robust immune memory to antigens and weak immune memory to lipid nanoparticles - Tang_2024_Mater.Today.Bio_25_100988
Author(s) : Tang X , Zhang J , Sui D , Xu Z , Yang Q , Wang T , Li X , Liu X , Deng Y , Song Y
Ref : Mater Today Bio , 25 :100988 , 2024
Abstract : The Pegylated lipids in lipid nanoparticle (LNPs) vaccines have been found to cause acute hypersensitivity reactions in recipients, and generate anti-LNPs immunity after repeated administration, thereby reducing vaccine effectiveness. To overcome these challenges, we developed a new type of LNPs vaccine (SAPC-LNPs) which was co-modified with sialic acid (SA) - lipid derivative and cleavable PEG - lipid derivative. This kind of mRNA vaccine can target dendritic cells (DCs) and rapidly escape from early endosomes (EE) and lysosomes with a total endosomal escape rate up to 98 %. Additionally, the PEG component in SAPC-LNPs was designed to detach from the LNPs under the catalysis of carboxylesterase in vivo, which reduced the probability of PEG being attached to LNPs entering antigen-presenting cells. Compared with commercially formulated vaccines (1.5PD-LNPs), mice treated with SAPC-LNPs generated a more robust immune memory to tumor antigens and a weaker immune memory response to LNPs, and showed lower side effects and long-lasting protective efficiency. We also discovered that the anti-tumor immune memory formed by SAPC-LNPs mRNA vaccine was directly involved in the immune cycle to rattack tumor. This immune memory continued to strengthen with multiple cycles, supporting that the immune memory should be incorporated into the theory of tumor immune cycle.
ESTHER : Tang_2024_Mater.Today.Bio_25_100988
PubMedSearch : Tang_2024_Mater.Today.Bio_25_100988
PubMedID: 38379935

Title : Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR - Xu_2024_Xenobiotica__1
Author(s) : Xu X , Taha R , Chu C , Xiao L , Wang T , Wang X , Huang X , Jiang Z , Sun L
Ref : Xenobiotica , :1 , 2024
Abstract : Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerative colitis, and indirubin is used for the treatment of chronic myelogenous leukaemia. However, IN and indirubin have adverse reactions, such as abdominal pain, diarrhoea, and intussusception, and their specific mechanism is unclear.The purpose of our research was to determine the specific mechanism underlying the adverse effects of IN and indirubin. By tracking the modifications in guinea pigs after the intragastric administration of indirubin for 28 days.The results demonstrate that indirubin could accelerate bowel movements and decrease intestinal acetylcholinesterase (AchE) expression. Experiments with NCM460 cells revealed that indirubin significantly reduced the expression of AchE, and the AchE levels were increased after the silencing of AhR and re-exposure to indirubin.This study showed that the inhibition of AchE expression by indirubin plays a key role in the occurrence of adverse reactions to indirubin and that the underlying mechanism is related to AhR-mediated AchE downregulation.
ESTHER : Xu_2024_Xenobiotica__1
PubMedSearch : Xu_2024_Xenobiotica__1
PubMedID: 38164702

Title : Recent advances in the biodegradation of polyethylene terephthalate with cutinase-like enzymes - Sui_2023_Front.Microbiol_14_1265139
Author(s) : Sui B , Wang T , Fang J , Hou Z , Shu T , Lu Z , Liu F , Zhu Y
Ref : Front Microbiol , 14 :1265139 , 2023
Abstract : Polyethylene terephthalate (PET) is a synthetic polymer in the polyester family. It is widely found in objects used daily, including packaging materials (such as bottles and containers), textiles (such as fibers), and even in the automotive and electronics industries. PET is known for its excellent mechanical properties, chemical resistance, and transparency. However, these features (e.g., high hydrophobicity and high molecular weight) also make PET highly resistant to degradation by wild-type microorganisms or physicochemical methods in nature, contributing to the accumulation of plastic waste in the environment. Therefore, accelerated PET recycling is becoming increasingly urgent to address the global environmental problem caused by plastic wastes and prevent plastic pollution. In addition to traditional physical cycling (e.g., pyrolysis, gasification) and chemical cycling (e.g., chemical depolymerization), biodegradation can be used, which involves breaking down organic materials into simpler compounds by microorganisms or PET-degrading enzymes. Lipases and cutinases are the two classes of enzymes that have been studied extensively for this purpose. Biodegradation of PET is an attractive approach for managing PET waste, as it can help reduce environmental pollution and promote a circular economy. During the past few years, great advances have been accomplished in PET biodegradation. In this review, current knowledge on cutinase-like PET hydrolases (such as TfCut2, Cut190, HiC, and LCC) was described in detail, including the structures, ligand-protein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts were highlighted, such as improving the PET hydrolytic activity by constructing fusion proteins. The review is expected to provide novel insights for the biodegradation of complex polymers.
ESTHER : Sui_2023_Front.Microbiol_14_1265139
PubMedSearch : Sui_2023_Front.Microbiol_14_1265139
PubMedID: 37849919

Title : Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN - Ma_2023_Int.J.Mol.Sci_24_
Author(s) : Ma Q , Liu Z , Wang T , Zhao P , Liu M , Wang Y , Zhao W , Yuan Y , Li S
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.
ESTHER : Ma_2023_Int.J.Mol.Sci_24_
PubMedSearch : Ma_2023_Int.J.Mol.Sci_24_
PubMedID: 38003694

Title : Efficacy and safety of cetagliptin as monotherapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 3 trial - Ji_2023_Diabetes.Obes.Metab_25_3671
Author(s) : Ji L , Lu J , Gao L , Ying C , Sun J , Han J , Zhao W , Gao Y , Wang K , Zheng X , Xie D , Ding J , Zhao J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3671 , 2023
Abstract : AIM: To assess the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D) and inadequate glycaemic control. MATERIALS AND METHODS: In total, 504 eligible patients with T2D were enrolled and randomized to cetagliptin 50 mg once daily, cetagliptin 100 mg once daily or placebo at a ratio of 2:2:1 for 24 weeks of double-blind treatment, then all patients received cetagliptin 100 mg once daily for 28 weeks of open-label treatment. The primary efficacy endpoint was the change in HbA1c level from baseline at week 24. RESULTS: After 24 weeks, HbA1c from baseline was significantly reduced with cetagliptin 50 mg (-1.08%) and cetagliptin 100 mg (-1.07%) compared with placebo (-0.35%). The placebo-subtracted HbA1c reduction was -0.72% with cetagliptin 50 mg and 100 mg. Patients with a baseline HbA1c of 8.5% or higher had a greater HbA1c reduction with cetagliptin than those patients with a baseline HbA1c of less than 8.5%. Both doses studied led to a significantly higher proportion of patients (42.3% with 100 mg and 45.0% with 50 mg) achieving an HbA1c of less than 7.0% compared with placebo (12.9%). Cetagliptin also significantly lowered fasting plasma glucose and 2-hour postmeal plasma glucose relative to placebo. The incidence of adverse experiences was similar between cetagliptin and placebo. No drug-related hypoglycaemia was reported. CONCLUSIONS: Cetagliptin monotherapy was effective and well tolerated in Chinese patients with T2D who had inadequate glycaemic control on exercise and diet.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3671
PubMedID: 37661308

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : Molecular Machinery of Lipid Droplet Degradation and Turnover in Plants - Qin_2023_Int.J.Mol.Sci_24_
Author(s) : Qin Z , Wang T , Zhao Y , Ma C , Shao Q
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Lipid droplets (LDs) are important organelles conserved across eukaryotes with a fascinating biogenesis and consumption cycle. Recent intensive research has focused on uncovering the cellular biology of LDs, with emphasis on their degradation. Briefly, two major pathways for LD degradation have been recognized: (1) lipolysis, in which lipid degradation is catalyzed by lipases on the LD surface, and (2) lipophagy, in which LDs are degraded by autophagy. Both of these pathways require the collective actions of several lipolytic and proteolytic enzymes, some of which have been purified and analyzed for their in vitro activities. Furthermore, several genes encoding these proteins have been cloned and characterized. In seed plants, seed germination is initiated by the hydrolysis of stored lipids in LDs to provide energy and carbon equivalents for the germinating seedling. However, little is known about the mechanism regulating the LD mobilization. In this review, we focus on recent progress toward understanding how lipids are degraded and the specific pathways that coordinate LD mobilization in plants, aiming to provide an accurate and detailed outline of the process. This will set the stage for future studies of LD dynamics and help to utilize LDs to their full potential.
ESTHER : Qin_2023_Int.J.Mol.Sci_24_
PubMedSearch : Qin_2023_Int.J.Mol.Sci_24_
PubMedID: 38003229

Title : Plasminogen decreases Abeta42 and Tau deposition, and shows multi-beneficial effects on Alzheimer's disease in mice and humans - Guo_2023_Biochem.Biophys.Res.Commun_654_102
Author(s) : Guo C , Wang T , Zhang D , Ge X , Li J
Ref : Biochemical & Biophysical Research Communications , 654 :102 , 2023
Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Abeta) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. Using ex vivo, in vivo and clinical approaches, we investigated the functional effects of plasminogen on the widely used FAD, Abeta42 oligomer or Tau intracranial injection-induced AD mouse model and explored its therapeutic effects on patients with AD. The results show that intravenously injected plasminogen rapidly crosses the blood-brain barrier (BBB); increases plasmin activity in the brain; colocalizes with and effectively promotes the clearance of Abeta42 peptide and Tau protein deposits ex vivo and in vivo; increases the choline acetyltransferase (ChAT) level and decreases the acetylcholinesterase (AChE) activity; and improves the memory functions. Clinically, when GMP-level plasminogen was administered to 6 AD patients for 1-2 weeks, their average scores on the Minimum Mental State Examination (MMSE), which is a standard scoring system used to measure the memory loss and cognitive deficits, were extremely significantly improved by 4.2 +/- 2.23 points, e.g., an average increase from 15.5 +/- 8.22 before treatment to 19.7 +/- 7.09 after treatment. The preclinical study and pilot clinical study suggest that plasminogen is effective in treating AD and may be a promising drug candidate.
ESTHER : Guo_2023_Biochem.Biophys.Res.Commun_654_102
PubMedSearch : Guo_2023_Biochem.Biophys.Res.Commun_654_102
PubMedID: 36905760

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : Water in liquid crystal emulsion-based sensing platform for colorimetric detection of organophosphorus pesticide - Li_2023_Food.Chem_436_137732
Author(s) : Li B , Wu W , Lin JM , Wang T , Hu Conceptuation Q , Yu L
Ref : Food Chem , 436 :137732 , 2023
Abstract : Development of a simple and convenient method for the rapid detection of organophosphorus pesticides (OPs) is particular important for the safety of environmental water and agriculture products. In this work, the water/liquid crystal (W/LC) emulsion is obtained via dispersing an aqueous solution of sodium dodecyl sulfate (SDS) and peroxidase from horseradish (HRP) into a water-immiscible nematic LC and employed as a sensing platform for the detection of dichlorvos (2, 2-dichlorovinyl dimethyl phosphate, DDVP) that is a typical OP with acute toxicity. Remarkably, the stepwise release of the encapsulated cargo HRP from the W/LC emulsion can be triggered upon the addition of the cationic surfactant myristoylcholine chloride (Myr) due to the strong interfacial charge interactions with the anionic surfactant SDS. The released HRP induces an obvious color change of the overlaying bulk aqueous solution via the H(2)O(2)-HRP-TMB reaction system. As Myr can be enzymatically cleaved by AChE, the detection of AChE is fulfilled successfully. This approach is also employed to detect DDVP that can irreversibly inhibit the activity of AChE. This assay shows a linear response between the absorbance of the oxidized TMB solution and the DDVP concentration in the range of 0.001-10 microg/mL (R(2) = 0.99). The limit of detection (LOD) and the limit of quantity (LOQ) of DDVP are determined to be 1.9 ng/mL and 6.3 ng/mL, respectively. In addition, this strategy also demonstrates excellent performance for the DDVP detection in real samples, the detection recovery rate of DDVP in water samples (lake water and tap water) and vegetables (tomatoes and cole) by this method is 88.0 % -112.6 %, the relative standard deviation (RSD) >= 7.5 %. These results suggest the W/LC emulsion-based sensing platform shows great potential for visual detection of DDVP in real samples. In conclusion, the proposed approach is scalable for practical application in food safety as well as environmental monitoring fields, and will provide promising solutions for the assay of pesticide residues.
ESTHER : Li_2023_Food.Chem_436_137732
PubMedSearch : Li_2023_Food.Chem_436_137732
PubMedID: 37857198

Title : Current advances in the structural biology and molecular engineering of PETase - Liu_2023_Front.Bioeng.Biotechnol_11_1263996
Author(s) : Liu F , Wang T , Yang W , Zhang Y , Gong Y , Fan X , Wang G , Lu Z , Wang J
Ref : Front Bioeng Biotechnol , 11 :1263996 , 2023
Abstract : Poly(ethylene terephthalate) (PET) is a highly useful synthetic polyester plastic that is widely used in daily life. However, the increase in postconsumer PET as plastic waste that is recalcitrant to biodegradation in landfills and the natural environment has raised worldwide concern. Currently, traditional PET recycling processes with thermomechanical or chemical methods also result in the deterioration of the mechanical properties of PET. Therefore, it is urgent to develop more efficient and green strategies to address this problem. Recently, a novel mesophilic PET-degrading enzyme (IsPETase) from Ideonella sakaiensis was found to streamline PET biodegradation at 30 degreesC, albeit with a lower PET-degrading activity than chitinase or chitinase-like PET-degrading enzymes. Consequently, the molecular engineering of more efficient PETases is still required for further industrial applications. This review details current knowledge on IsPETase, MHETase, and IsPETase-like hydrolases, including the structures, ligandprotein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts are highlighted, including metabolic engineering of the cell factories, enzyme immobilization or cell surface display. The information is expected to provide novel insights for the biodegradation of complex polymers.
ESTHER : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedSearch : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedID: 37795175

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 : Hyperoside inhibits pancreatic lipase activity in vitro and reduces fat accumulation in vivo - Zhang_2023_Food.Funct_14_4763
Author(s) : Zhang X , Li D , Wang K , Xie J , Liu Y , Wang T , Liu S , Huang Q , Guo Q , Wang H
Ref : Food Funct , 14 :4763 , 2023
Abstract : Hyperoside, the main component of many anti-obesity plants, might exhibit a lipase inhibition effect to reduce fat accumulation. The anti-obesity effect of hyperoside was investigated by studying its inhibitory effect and mechanism on pancreatic lipase in vitro and evaluating its ability to reduce lipid accumulation in vivo. Hyperoside is a mixed-type inhibitor of lipase with an IC(50) of 0.67 +/- 0.02 mmol L(-)in vitro. Hyperoside changed the secondary conformation of lipase, increased the alpha-helix content, and changed the microenvironment of lipase through static quenching. The interaction between hyperoside and lipase results from a strong binding spontaneous exothermic reaction, mainly through hydrogen bonding, van der Waals force and electrostatic force. Hyperoside protected hepatic lipid accumulation and adipose tissue hypertrophy and reduced the expression of inflammatory factors in high-fat diet-induced rats. Moreover, hyperoside had a good inhibitory effect on lipase activity in serum and increased fecal fat excretion, thereby reducing lipid absorption in vivo. This study provides theoretical support for the research and development of hyperoside in fat-reducing functional foods.
ESTHER : Zhang_2023_Food.Funct_14_4763
PubMedSearch : Zhang_2023_Food.Funct_14_4763
PubMedID: 37128768

Title : Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus - Sun_2022_Andrology__
Author(s) : Sun T , Xu W , Wang J , Wang T , Wang S , Liu K , Liu J
Ref : Andrology , : , 2022
Abstract : BACKGROUND: Diabetes mellitus-induced erectile dysfunction (DMED) is one of the complications of diabetes and has a poor response to phosphodiesterase type 5 inhibitor, the first-line treatment for ED. Saxagliptin (Sax), a dipeptidyl peptidase-4 inhibitor (DPP-4i), has been officially used in the treatment of type 2 diabetes. Stromal cell-derived factor-1 (SDF-1) is one of the important substrates of DPP-4, and has been proven to be beneficial for several DM complications. However, it is unknown whether Sax contributes to the management of DMED. OBJECTIVES: To explore the effect and possible underlying mechanisms of Sax in the treatment of DMED. METHODS: The model of DM was established by intraperitoneal injection of streptozotocin. All rats were divided into 3 groups (n = 8 per group): control group, DMED group and DMED+Sax group. In cellular experiments, the corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG), and treated with Sax and AMD3100 (SDF-1 receptor inhibitor). The penile tissue and CCSMCs were harvested for detection. RESULTS: We found erectile function was impaired in DMED rats compared with the control group, which was partially relieved by Sax. Decreased expression of DPP-4 and increased level of SDF-1 were also observed in DMED+Sax group, together with elevation of PI3K/AKT pathway and inhibition of endothelial dysfunction, oxidative stress and apoptosis in corpus cavernosum. Moreover, Sax could also regulate oxidative stress and apoptosis in CCSMCs under HG condition, which was blocked in part by AMD3100. CONCLUSION: Sax could alleviate DMED through increasing SDF-1 and PI3K/AKT pathway, in company with moderation of endothelial dysfunction, oxidative stress and apoptosis. Our findings indicated that DPP-4is may be beneficial to the management of DMED. This article is protected by copyright. All rights reserved.
ESTHER : Sun_2022_Andrology__
PubMedSearch : Sun_2022_Andrology__
PubMedID: 36113503

Title : The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [(14)C] cetagliptin in healthy volunteers - Lu_2022_Xenobiotica_52_38
Author(s) : Lu J , Bian Y , Zhang H , Tang D , Tian X , Zhou X , Xu Z , Xiong Y , Gu Z , Yu Z , Wang T , Ding J , Yu Q
Ref : Xenobiotica , 52 :38 , 2022
Abstract : The metabolism and excretion of cetagliptin were investigated in healthy male subjects after a single oral dose of 100mg/50microCi [(14)C] cetagliptin.The mean concentration-time profile of cetagliptin was similar to that of total radioactivity in plasma after oral administration of [(14)C] cetagliptin in healthy male subjects. Cetagliptin was rapidly absorbed after oral administration. Unchanged cetagliptin was the most abundant radioactive component in all matrices investigated. Approximately 53.13% of plasma AUC of total radioactivity was accounted for by cetagliptin. Each metabolite plasma AUC was not higher than 2.93% of plasma AUC of total radioactivity. By 336h after administration, 91.68% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 72.88% and 18.81%, respectively. The primary route of excretion of radioactivity was via the kidneys.Four metabolites were detected at trace levels, and it involved hydroxylated (M436-1 and M436-3), N- sulphate (M500), and N-carbamoyl glucuronic acid conjugates (M640B) of cetagliptin. These metabolites were detected also in plasma, urine, and faeces at low levels, except that metabolite M640B was not detected in faeces. All metabolites were observed with <10% of parent compound systemic exposure after oral administration.
ESTHER : Lu_2022_Xenobiotica_52_38
PubMedSearch : Lu_2022_Xenobiotica_52_38
PubMedID: 34743655

Title : Disposition study of the novel dipeptidyl peptidase 4 inhibitor cetagliptin in rats - Lu_2022_Xenobiotica_52_468
Author(s) : Lu J , Hao Y , Zhang F , Pan H , Ding J , Yu Q , Wang T
Ref : Xenobiotica , 52 :468 , 2022
Abstract : Dipeptidyl peptidase-4 (DPP-4) inhibitor is a class of oral antihyperglycemic agents and therapeutic approach for type 2 diabetes. Cetagliptin is a novel oral and selective DPP-4 inhibitor and developed as a promising candidate for treatment of type 2 diabetes mellitus.This study aimed to evaluate the metabolism and excretion of cetagliptin in Sprague-Dawley (SD) rats, and to detect and identify metabolites of cetagliptin.The SD rats were administered with a single oral dose of 6mg/kg with approximately 100microCi of [(14)C] cetagliptin. The mean total recovery of radioactivity was 90.20% within 168h in SD rats excreta. Cetagliptin was the major radioactive component in SD rats plasma, urine and eliminated primarily by faecal excretion. The recovery of cetagliptin in urine and feces was 25.15% and 13.85% of the dose, respectively. Cetagliptin was well absorbed after oral administration in SD rats based on the total recovery of radioactivity in BDC SD rats bile and urine.Six major metabolites were observed and identified in SD rats, comprising 0.20 to 4.53% of total plasma AUC. These major metabolites were the hydroxylated, N-sulphate and N-carbamoyl glucuronic acid conjugates of the cetagliptin, two metabolites formed by glucuronide of a hydroxylated metabolite.
ESTHER : Lu_2022_Xenobiotica_52_468
PubMedSearch : Lu_2022_Xenobiotica_52_468
PubMedID: 35708192

Title : Gram-Scale Synthesis of (R)-P-Chlorophenyl-1,2-Ethanediol at High Concentration by a Pair of Epoxide Hydrolases - Zhang_2022_Front.Bioeng.Biotechnol_10_824300
Author(s) : Zhang D , Lei Y , Wang T , Lin W , Chen X , Wu M
Ref : Front Bioeng Biotechnol , 10 :824300 , 2022
Abstract : (R)-p-chlorophenyl-1,2-ethanediol (pCPED) is an important intermediate for the synthesis of (R)-eliprodil that is widely applied in the treatment of ischemic stroke. To prepare (R)-pCPED with high enantiomeric excess (ee (p)) and yield via the enantioconvergent hydrolysis of racemic styrene oxide (rac-pCSO) at high concentration, the bi-enzymatic catalysis was designed and investigated by a pair of epoxide hydrolases, a mutant (PvEH1(Z4X4-59)) of Phaseolus vulgaris EH1 and a mutant (RpEH(F361V)) of Rhodotorula paludigena RpEH. Firstly, the maximum allowable concentration of rac-pCSO was confirmed. Subsequently, the addition mode and the weight ratio of two Escherichia coli cells were optimized. Finally, under the optimized reaction conditions-the cell weight ratio 20:1 of E. coli/pveh1(z4x4-59) to E. coli/rpeh (F361V), a simultaneous addition mode, and reaction temperature at 25 degreesC-300 mM rac-pCSO in the 100 ml 4% (v/v) Tween-20/phosphate buffer system (100 mM, pH 7.0) was completely hydrolyzed within 5 h, affording (R)-pCPED with 87.8% ee (p), 93.4% yield, and 8.63 g/L/h space-time yield (STY). This work would be an efficient technical strategy for the preparation of chiral vicinal diols at industrial scale.
ESTHER : Zhang_2022_Front.Bioeng.Biotechnol_10_824300
PubMedSearch : Zhang_2022_Front.Bioeng.Biotechnol_10_824300
PubMedID: 35295651

Title : A double-blind, randomized, placebo and positive-controlled study in healthy volunteers to evaluate pharmacokinetic and pharmacodynamic properties of multiple oral doses of cetagliptin - Lu_2022_Br.J.Clin.Pharmacol_88_2946
Author(s) : Lu J , Wang L , Zhou S , Zhou C , Xie L , Chen J , Tang D , Tian X , Xie D , Ding J , Wang T , Yu Q , Shao F
Ref : British Journal of Clinical Pharmacology , 88 :2946 , 2022
Abstract : AIMS: This study investigated the pharmacokinetics and pharmacodynamics properties, safety and tolerability of cetagliptin. METHODS: Forty-eight healthy subjects were enrolled in this study. Three cohorts were investigated in sequential order: 50, 100 and 200mg cetagliptin. Positive control (sitagliptin 100mg) was designed as open label. Blood samples were collected and analysed for pharmacokinetic and pharmacodynamic properties. Safety and tolerability were assessed throughout the study. RESULTS: Following multiple oral doses, cetagliptin was rapidly absorbed and reached peak plasma concentrations after approximately 1.0-1.5 hours. Plasma cetagliptin concentrations increased at a rate greater than dose. Accumulation of cetagliptin was modest, and steady state was generally achieved at day 5. Doses <=50mg of cetagliptin administered once daily will result in sustained dipeptidyl peptidase-4 (DPP-4) inhibition (<=80%). The plasma concentration giving 50% of maximum drug effect of DPP-4 inhibition for cetagliptin (5.29ng/mL) was lower than that of sitagliptin (7.03ng/mL). Active glucagon-like-1 peptide (GLP-1) concentrations were significantly increased in the cetagliptin groups by 2.3- to 3.1-fold at day 1 and 3.1- to 3.6-fold at steady state compared with that of placebo, and active GLP-1 concentrations were increased with increasing dose. Compared with sitagliptin, doses <=100mg once daily of cetagliptin produced postprandial increases in active GLP-1 level and induced to long-lasting glucose-lowering efficacy. Cetagliptin was well tolerated across all doses studied. CONCLUSION: Cetagliptin demonstrates the great potential for treatment with type 2 diabetes patients based on the inhibition of DPP-4, the increase in GLP-1 and insulin, the decrease in glucose, and might be more effective in DPP-4 inhibition than sitagliptin.
ESTHER : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedSearch : Lu_2022_Br.J.Clin.Pharmacol_88_2946
PubMedID: 34965609

Title : A Portable Fluorescent Hydrogel-Based Device for On-Site Quantitation of Organophosphorus Pesticides as Low as the Sub-ppb Level - Wang_2022_Front.Chem_10_855281
Author(s) : Wang T , Zhang L , Xin H
Ref : Front Chem , 10 :855281 , 2022
Abstract : Portable devices possess powerful application prospects in on-site sensing without the limitation of bulky instruments. Given the relevance of pesticides to food safety, we herein fabricated a robust gold nanocluster (AuNC)-based hydrogel test kit for precisely quantified chlorpyrifos by using a three-dimensional (3D) printed subsidiary device. In this work, the fluorescence of AuNC-based hydrogel could be efficiently quenched by cobalt oxyhydroxide nanoflakes (CoOOH NFs) through the Forster resonance energy transfer effect. Chlorpyrifos as an acetylcholinesterase inhibitor controls the enzymatic hydrolysis reaction and further regulates the production of thiocholine that could decompose CoOOH nanoflakes into Co(2+), resulting in the fluorescence response of AuNC-based hydrogel. By using a homemade subsidiary device and smartphone, the fluorescence color was transformed into digital information, achieving the on-site quantitative detection of chlorpyrifos with the limit of detection of 0.59 ng ml(-1). Owing to specific AuNC signatures and hydrogel encapsulation, the proposed fluorescence hydrogel test kit displayed high sensitivity, good selectivity, and anti-interference capability in a real sample analysis, providing great potential in on-site applications.
ESTHER : Wang_2022_Front.Chem_10_855281
PubMedSearch : Wang_2022_Front.Chem_10_855281
PubMedID: 35572106

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

Title : Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction - Liu_2022_Nat.Commun_13_3490
Author(s) : Liu Z , Yang N , Dong J , Tian W , Chang L , Ma J , Guo J , Tan J , Dong A , He K , Zhou J , Cinar R , Wu J , Salinas AG , Sun L , Kumar M , Sullivan BT , Oldham BB , Pitz V , Makarious MB , Ding J , Kung J , Xie C , Hawes SL , Wang L , Wang T , Chan P , Zhang Z , Le W , Chen S , Lovinger DM , Blauwendraat C , Singleton AB , Cui G , Li Y , Cai H , Tang B
Ref : Nat Commun , 13 :3490 , 2022
Abstract : Endocannabinoid (eCB), 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain, regulates diverse neural functions. Here we linked multiple homozygous loss-of-function mutations in 2-AG synthase diacylglycerol lipase beta (DAGLB) to an early onset autosomal recessive Parkinsonism. DAGLB is the main 2-AG synthase in human and mouse substantia nigra (SN) dopaminergic neurons (DANs). In mice, the SN 2-AG levels were markedly correlated with motor performance during locomotor skill acquisition. Genetic knockdown of Daglb in nigral DANs substantially reduced SN 2-AG levels and impaired locomotor skill learning, particularly the across-session learning. Conversely, pharmacological inhibition of 2-AG degradation increased nigral 2-AG levels, DAN activity and dopamine release and rescued the locomotor skill learning deficits. Together, we demonstrate that DAGLB-deficiency contributes to the pathogenesis of Parkinsonism, reveal the importance of DAGLB-mediated 2-AG biosynthesis in nigral DANs in regulating neuronal activity and dopamine release, and suggest potential benefits of 2-AG augmentation in alleviating Parkinsonism.
ESTHER : Liu_2022_Nat.Commun_13_3490
PubMedSearch : Liu_2022_Nat.Commun_13_3490
PubMedID: 35715418
Gene_locus related to this paper: human-DAGLB , mouse-DGLB

Title : Sertoli cell survival and barrier function are regulated by miR-181c\/d-Pafah1b1 axis during mammalian spermatogenesis - Feng_2022_Cell.Mol.Life.Sci_79_498
Author(s) : Feng Y , Chen D , Wang T , Zhou J , Xu W , Xiong H , Bai R , Wu S , Li J , Li F
Ref : Cell Mol Life Sciences , 79 :498 , 2022
Abstract : Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
ESTHER : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedSearch : Feng_2022_Cell.Mol.Life.Sci_79_498
PubMedID: 36008729

Title : Genome-Wide Identification and Analysis of Lipases in Fig Wasps (Chalcidoidea, Hymenoptera) - Wei_2022_Insects_13_
Author(s) : Wei X , Li J , Wang T , Xiao J , Huang D
Ref : Insects , 13 : , 2022
Abstract : Lipases are the main enzymes involved in lipid metabolism. However, the characteristics of lipases in insects were scarcely investigated. Here, we screened the recently sequenced genomes of 12 fig wasp species consisting of seven pollinator fig wasps (PFWs) and five non-pollinating fig wasps (NPFWs) for the six major lipase gene families. In total, 481 lipase genes were identified, and the two most numerous families were the neutral and acid lipases. Tandem duplication accounted for the expansion of the gene family. NPFWs had significantly more lipases than PFWs. A significant gene family contraction occurred in the clade of PFWs. The difference of lipases between NPFWs and PFWs might contribute to their distinction in life histories and feeding regimes. Phylogenetic analysis showed that the lipase genes of each fig wasp species was almost equally distributed in each clade, indicating that the lipase genes were conserved. The gene structures were similar within each clade, while they were different among clades. Most of the neutral and acid lipases were signal peptides and located extracellularly. The pathways of lipases involved were predicted. This genome-wide study provides a systematic analysis of lipase gene families in 12 hymenopteran insects and further insights towards understanding the potential functions of lipases.
ESTHER : Wei_2022_Insects_13_
PubMedSearch : Wei_2022_Insects_13_
PubMedID: 35621743

Title : Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via alpha7nAChR-dependent JAK2\/STAT3 signaling pathway - Zhang_2022_Eur.J.Pharmacol_940_175478
Author(s) : Zhang C , Li M , Xie W , You C , Wang T , Fu F
Ref : European Journal of Pharmacology , 940 :175478 , 2022
Abstract : Acetylcholinesterase (AChE) inhibitor (AChEI) is well established as rst-line agents for relieving the symptoms of Alzheimer's disease (AD). Injectable sustained-release formulation of AChEI may be suitable for treating AD patients. However, it needs to know whether continuous inhibition of AChE could deteriorate or attenuate myocardial damage if myocardial ischemia (MI) occurs. Huperzine A microspheres (HAM) are a sustained-release formulation releasing sustainably huperzine A (an AChEI) for more than 7 days after a single dose of HAM. This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during HAM treatment. The heart injury was evaluated by assaying serum CK-MB, Tn-I and observing histopathological changes. The levels of proinflammatory cytokines in serum were detected. The level of p-P65 and the expression of proteins in the JAK2/STAT3 signaling pathway were assayed with Western blot. Administration with a single dose of HAM resulted in inhibiting the MI-induced increases of CK-MB and Tn-I, alleviating the damage of heart tissue, and decreasing the levels of TNF-alpha and IL-6. In addition, HAM decreased the levels of p-P65, p-JAK2, and p-STAT3 in heart tissue. The effects of HAM could be weakened or abolished by the specific alpha7nAChR antagonist. These findings suggest that continuous AChE inhibition could protect the heart from ischemic damage during administration of sustained-release formulation of AChEI, which is associated with the anti-inflammatory effect of HAM by regulating alpha7nAChR-dependent JAK2/STAT3 signaling pathway.
ESTHER : Zhang_2022_Eur.J.Pharmacol_940_175478
PubMedSearch : Zhang_2022_Eur.J.Pharmacol_940_175478
PubMedID: 36563953

Title : Threaded 3D microfluidic paper analytical device-based ratiometric fluorescent sensor for background-free and visual detection of organophosphorus pesticides - Tong_2022_Biosens.Bioelectron_222_114981
Author(s) : Tong X , Cai G , Xie L , Wang T , Zhu Y , Peng Y , Tong C , Shi S , Guo Y
Ref : Biosensors & Bioelectronics , 222 :114981 , 2022
Abstract : With the increasing concerns of food safety and environmental protection, it is desirable to develop reliable, effective, and portable sensors for detection of organophosphorus pesticides (OPs). Here, a cascade reaction system integrated with threaded 3D microfluidic paper analytical device (3D microPAD) was firstly developed for background-free and visual detection of OPs in agricultural samples. Butyrylcholinesterase (BChE) hydrolyzed acetylcholine into thiocholine (TCh), which reduced MnO(2) nanosheets into Mn(2+). With addition of OPs, BChE activity was irreversibly inhibited, and the generation of TCh and the reduction of MnO(2) nanosheets were prevented. Then the remaining MnO(2) nanosheets oxidized o-phenylenediamine into 2,3-diaminophenazine with yellow-emission fluorescence, which quenched the fluorescence intensity of red-emission carbon dots (RCDs) via inner-filter effect. Based on above mechanism, a ratiometric fluorescent system was established for OPs detection. Threaded 3D microPAD consisted of 4 layers, which allowed to load and/or add reagents to trigger the cascade reaction system for OPs detection. The fluorescent images presented distinguishable color variations from red to yellow with dichlorvos concentrations ranging from 2.5 to 120 microgsL(-1), and the limit of detection was 1.0 microgsL(-1). In the practical samples testing, threaded 3D microPAD can eliminate background influence on fluorescent signal for OPs detection. Threaded 3D microPAD integrated with ratiometric sensing platform has merits of accuracy response, facile operation, and background-free detection, which supplies a new alternative approach for on-site pesticide detection.
ESTHER : Tong_2022_Biosens.Bioelectron_222_114981
PubMedSearch : Tong_2022_Biosens.Bioelectron_222_114981
PubMedID: 36473422

Title : Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy - Zou_2021_J.Proteomics__104124
Author(s) : Zou S , Dong R , Wang J , Liang B , Zhu T , Zhao S , Zhang Y , Wang T , Zou P , Li N , Wang Y , Chen M , Zhou C , Zhang T , Luo L
Ref : J Proteomics , :104124 , 2021
Abstract : We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SIGNIFICANCE: This preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.
ESTHER : Zou_2021_J.Proteomics__104124
PubMedSearch : Zou_2021_J.Proteomics__104124
PubMedID: 33545297

Title : Characterizing the potentially neuronal acetylcholinesterase reactivity toward chiral pyraclofos: Enantioselective insights from spectroscopy, in silico docking, molecular dynamics simulation and per-residue energy decomposition studies - Peng_2021_J.Mol.Graph.Model_110_108069
Author(s) : Peng W , Wang T , Liang XR , Yang YS , Wang QZ , Cheng HF , Peng YK , Ding F
Ref : J Mol Graph Model , 110 :108069 , 2021
Abstract : Chiral organophosphorus agents are distributed ubiquitously in the environment, but the neuroactivity of these asymmetric chemicals to humans remains uncertain. This scenario was to explore the stereoselective neurobiological response of human acetylcholinesterase (AChE) to chiral pyraclofos at the enantiomeric scale, and then decipher the microscopic basis of enantioselective neurotoxicity of pyraclofos enantiomers. The results indicated that (R)-/(S)-pyraclofos can form the bioconjugates with AChE with a stoichiometric ratio of 1:1, but the neuronal affinity of (R)-pyraclofos (K = 6.31 x 10(4) M(-1)) with AChE was larger than that of (S)-pyraclofos (K = 1.86 x 10(4) M(-1)), and significant enantioselectivity was existed in the biochemical reaction. The modes of neurobiological action revealed that pyraclofos enantiomers were situated at the substrate binding domain, and the strength of the overall noncovalent bonds between (S)-pyraclofos and the residues was weaker than that of (R)-pyraclofos, resulting in the high inhibitory effect of (R)-pyraclofos toward the activity of AChE. Dynamic enantioselective biointeractions illustrated that the intervention of inherent conformational flexibility in the AChE-(R)-pyraclofos was greater than that of the AChE-(S)-pyraclofos, which arises from the big spatial displacement and the conformational flip of the binding domain composed of the residues Thr-64~Asn-89, Gly-122~Asp-134, and Thr-436~Tyr-449. Energy decomposition exhibited that the Gibbs free energies of the AChE-(R)-/(S)-pyraclofos were deltaG degrees = -37.4/-30.2 kJ mol(-1), respectively, and the disparity comes from the electrostatic energy during the stereoselective neurochemical reactions. Quantitative conformational analysis further confirmed the atomic-scale computational chemistry conclusions, and the perturbation of (S)-pyraclofos on the AChE's ordered conformation was lower than that of (R)-pyraclofos, which is germane to the interaction energies of the crucial residues, e.g. Tyr-124, Tyr-337, Asp-74, Trp-86, and Tyr-119. Evidently, this attempt will contribute mechanistic information to uncovering the neurobiological effects of chiral organophosphates on the body.
ESTHER : Peng_2021_J.Mol.Graph.Model_110_108069
PubMedSearch : Peng_2021_J.Mol.Graph.Model_110_108069
PubMedID: 34773872

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

Title : In vitro study of the drug-drug interaction potential of cetagliptin and clinical study of pharmacokinetic interaction of cetagliptin and metformin in healthy volunteers - Lu_2021_Xenobiotica_51_1122
Author(s) : Lu J , Tian X , Tang D , Zhou X , Xu Z , Ding J , Wang T , Yu Q
Ref : Xenobiotica , 51 :1122 , 2021
Abstract : Cetagliptin is an oral, potent, and newly developed selective inhibitor of dipeptidyl peptidase-4 (DPP-4). We evaluated the in vitro drug-drug interaction (DDI) potential of cetagliptin, as well as the pharmacokinetics of cetagliptin and metformin and the interaction between cetagliptin and metformin.Cetagliptin did not inhibit CYP1A2, CYP2C8, CYP2B6, CYP2C9, CYP2C19, and CYP3A4, only has a moderate inhibitory effect on CYP2D6, and did not induce CYP1A2, CYP2B6, and CYP3A4. Plasma protein binding of cetagliptin didn't have species differences or concentration dependence. Cetagliptin was a substrate for P-glycoprotein (P-gp).The 34 healthy subjects enrolled were randomly divided into two sequences (A and B) with 17 subjects in each sequence. Coadministration with metformin had no effect on cetagliptin AUC(0-120) (GMR, 99.25%; 90% CI, 95.96%-102.65%). There was a slightly increase in cetagliptin C(max) (GMR, 117.33%; 90% CI, 102.54%-134.25%). Coadministration with cetagliptin did not affect the metformin's AUC(0-24) (GMR, 108.54%; 90% CI, 101.41%-116.17%) or C(max) (GMR, 97.67%; 90% CI, 90.96%-104.89%).Based on in vitro study results, cetagliptin is unlikely to cause CYP-mediated, clinically relevant DDI. Although the possibility of transporter-mediated, clinically relevant DDI cannot be ruled out, there is little or no risk of side effects. Coadministration of cetagliptin and metformin had no clinically meaningful effect on the pharmacokinetics of each drug. There was no drug-drug interaction between cetagliptin and metformin. Both monotherapies and combination therapy were well tolerated. No serious AEs and hypoglycaemia was reported.
ESTHER : Lu_2021_Xenobiotica_51_1122
PubMedSearch : Lu_2021_Xenobiotica_51_1122
PubMedID: 34329567

Title : Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds - Zhang_2021_J.Control.Release_329_1117
Author(s) : Zhang Y , He J , Shen L , Wang T , Yang J , Li Y , Wang Y , Quan D
Ref : J Control Release , 329 :1117 , 2021
Abstract : Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.
ESTHER : Zhang_2021_J.Control.Release_329_1117
PubMedSearch : Zhang_2021_J.Control.Release_329_1117
PubMedID: 33096123

Title : The N-terminus of Lactobacillus amylovorus feruloyl esterase plays an important role in its secretion by Lactobacillus plantarum and Escherichia coli - Xu_2021_Microb.Cell.Fact_20_152
Author(s) : Xu Z , Zhang R , Wang T , Kong J
Ref : Microb Cell Fact , 20 :152 , 2021
Abstract : BACKGROUND: Feruloyl esterase is a multifunctional esterase with potential industrial applications. In the present study, we found the Lactobacillus amylovorus feruloyl esterase (FaeLam) could be secreted by L. plantarum and Escherichia coli. However, no signal peptide was detected in this protein as predicted by SignalP-5.0. Therefore, experiments were carried out to propose an explanation for the extracellular release of FaeLam. RESULTS: Here, we identified that the FaeLam could be secreted to the culture medium of L. plantarum CGMCC6888 and E. coli DH5alpha, respectively. To exclude the possibility that FaeLam secretion was caused by its hydrolytic activity on the cell membrane, the inactive FaeLam(S106A) was constructed and it could still be secreted out of L. plantarum and E. coli cells. Furthermore, the truncated version of the FaeLam without the N-terminal residues was constructed and demonstrated the importance of the 20 amino acids of N-terminus (N20) on FaeLam secretion. In addition, fusion of heterologous proteins with N20 or FaeLam could carry the target protein out of the cells. These results indicated the N-terminus of FaeLam played the key role in the export process. CONCLUSIONS: We proved the N-terminus of L. amylovorus FaeLam plays an important role in its secretion by L. plantarum and E. coli. To our best knowledge, this is the first reported protein which can be secreted out of the cells of both Gram-positive and Gram-negative bacteria. Furthermore, the results of this study may provide a new method for protein secretion in L. plantarum and E. coli through fusion the target protein to N20 of FaeLam.
ESTHER : Xu_2021_Microb.Cell.Fact_20_152
PubMedSearch : Xu_2021_Microb.Cell.Fact_20_152
PubMedID: 34344368
Gene_locus related to this paper: lacam-a0a1c9u7k7

Title : Fast analysis of alkaloids from different parts of Mahonia bealei (Fort.) Carr studied for their anti-Alzheimer's activity using supercritical fluid chromatography - Huang_2021_J.Sep.Sci__
Author(s) : Huang Y , Wang T , Jiang Z
Ref : J Sep Sci , : , 2021
Abstract : In this study, a rapid and highly efficient method was developed for the separation of eight isoquinoline alkaloids using supercritical fluid chromatography. The separation conditions were carefully optimized including stationary phases, additives, backpressure and temperature. Compared to HPLC, the use of supercritical fluid chromatography could provide a 13 times faster separation. Subsequently, the method was validated and applied for the determination of eight alkaloids from different parts of Mahonia bealei (Fort.) Carr. (stem, root, leaf and seed). The results indicated a good repeatability with relative standard deviations for overall precisions lower than 3.2%. The limit of detection were between 0.4 microg/mL and 2.3 microg/mL while limit of quantitation ranged from 1.5 microg/mL to 7.5 microg/mL. Recovery ranged from 95.7 % to 102.5% indicating a validity of recovery. The content of total eight alkaloids was the highest in stem (66.0 microg/g) and root (65.1 microg/g) compared to leaf or seed. Moreover, anti-acetylcholinesterase activity for those extracts was evaluated by Ellman's colorimetric assay. As a result, the acetylcholinesterase inhibitory activity of the extracted samples was in the following decreasing order: stem> root > leaf or seed. In conclusion, the results indicated that supercritical fluid chromatography could be a useful tool for quality control of Mahonia bealei (Fort.) Carr. containing alkaloids as active compounds. This article is protected by copyright. All rights reserved.
ESTHER : Huang_2021_J.Sep.Sci__
PubMedSearch : Huang_2021_J.Sep.Sci__
PubMedID: 33650266

Title : High-quality reference genome for Clonorchis sinensis - Young_2021_Genomics_113_1605
Author(s) : Young ND , Stroehlein AJ , Kinkar L , Wang T , Sohn WM , Chang BCH , Kaur P , Weisz D , Dudchenko O , Aiden EL , Korhonen PK , Gasser RB
Ref : Genomics , 113 :1605 , 2021
Abstract : The Chinese liver fluke, Clonorchis sinensis, causes the disease clonorchiasis, affecting ~35 million people in regions of China, Vietnam, Korea and the Russian Far East. Chronic clonorchiasis causes cholangitis and can induce a malignant cancer, called cholangiocarcinoma, in the biliary system. Control in endemic regions is challenging, and often relies largely on chemotherapy with one anthelmintic, called praziquantel. Routine treatment carries a significant risk of inducing resistance to this anthelmintic in the fluke, such that the discovery of new interventions is considered important. It is hoped that the use of molecular technologies will assist this endeavour by enabling the identification of drug or vaccine targets involved in crucial biological processes and/or pathways in the parasite. Although draft genomes of C. sinensis have been published, their assemblies are fragmented. In the present study, we tackle this genome fragmentation issue by utilising, in an integrated way, advanced (second- and third-generation) DNA sequencing and informatic approaches to build a high-quality reference genome for C. sinensis, with chromosome-level contiguity and curated gene models. This substantially-enhanced genome provides a resource that could accelerate fundamental and applied molecular investigations of C. sinensis, clonorchiasis and/or cholangiocarcinoma, and assist in the discovery of new interventions against what is a highly significant, but neglected disease-complex.
ESTHER : Young_2021_Genomics_113_1605
PubMedSearch : Young_2021_Genomics_113_1605
PubMedID: 33677057
Gene_locus related to this paper: closi-h2krw6

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

Title : Expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelium to esophageal cancer: Their differences and clinical significance - Wang_2020_Oncol.Lett_19_1727
Author(s) : Wang T , Lv X , Jiang S , Han S , Wang Y
Ref : Oncol Lett , 19 :1727 , 2020
Abstract : A Disintegrin And Metalloprotease Domain 29 (ADAM29) and Family with sequence similarity 135 member B (FAM135B) genes have been reported to be associated with a carcinogenic risk of esophageal squamous cell carcinoma (ESCC). However, to the best of our knowledge, the expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelial cells to ESCC has not yet been investigated. The present study aimed to investigate the expression of ADAM29 and FAM135B in normal esophageal mucosal epithelium, low-grade and high-grade esophageal intraepithelial neoplasia, and ESCC. Furthermore, the present study aimed to investigate the role of ADAM29 and FAM135B in the development of esophageal lesions. Immunohistochemistry was performed in order to detect the expression levels of ADAM29 and FAM135B proteins in normal esophageal mucosa samples (40 cases), low-grade intraepithelial neoplasia samples (20 cases), high-grade intraepithelial neoplasia samples (20 cases) and ESCC samples (40 cases). The results of the present study demonstrated that the positive rates of ADAM29 and FAM135B proteins increased gradually from normal esophageal mucosal epithelium and esophageal intraepithelial neoplasia, to ESCC (P<0.05). Furthermore, the expression levels of ADAM29 and FAM135B proteins in ESCC were not associated with age and the tumor size (P>0.05); however, the protein levels were associated with the pathological stage, clinical stage and lymph node metastasis of ESCC (P<0.05). In addition, there was a significant association between the expression levels of ADAM29 protein and FAM135B protein ((2)=60.071; P<0.001). The results of the present study demonstrated that the expression levels of ADAM29 and FAM135B were associated with the tumor behavior characteristics and the progression of esophageal cancer, the expression of which could be used for the diagnosis of early esophageal cancer, and provide the basis for guiding individualized treatment.
ESTHER : Wang_2020_Oncol.Lett_19_1727
PubMedSearch : Wang_2020_Oncol.Lett_19_1727
PubMedID: 32194665
Gene_locus related to this paper: human-FAM135B

Title : Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis - Wang_2020_J.Agric.Food.Chem_68_12358
Author(s) : Wang X , Zhao X , Yang Z , Wang T
Ref : Journal of Agricultural and Food Chemistry , 68 :12358 , 2020
Abstract : Acyl migration occurs in many reactions and is the main obstacle for structured lipid synthesis. In this study, 2-monoacylglycerol (2-MAG) was prepared by enzymatic ethanolysis in three different media to evaluate the effect of environment on product composition. The contents of 2-MAG obtained in ethanol, hexane + ethanol, and t-butanol + ethanol systems were 30.6, 15.7, and 32.4%, respectively, after 3 h reaction. Afterward, the acyl migration kinetics of 2-MAG were studied in solvent and solventless systems without the use of lipase. Results indicate that 2-MAG in the solventless system had the highest acyl migration rate. The isomerization was efficiently prevented by the use of polar solvents, especially t-butanol. The rate constants were shown to be the highest and activation energy values were the lowest in solventless systems. The novel finding in this study was that solvent had inhibitory effect on 2-MAG isomerization, but the nonpolar hexane had the lowest inhibition of acyl migration compared to other solvents.
ESTHER : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedSearch : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedID: 33084305

Title : Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points - Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_5129562
Author(s) : Zhang Y , Du NY , Chen C , Wang T , Wang LJ , Shi XL , Li SM , Guo CQ
Ref : Evid Based Complement Alternat Med , 2020 :5129562 , 2020
Abstract : The aim of this study was to determine the effects of acupotomy on energy crises in rat trigger points (TrPs) by measuring mechanical pain thresholds (MPTs) and levels of acetylcholinesterase (AChE), free sarcoplasmic calcium (Ca(2+)), adenosine 5'-triphosphate (ATP), adenosine 5'-monophosphate (AMP), substance P (SP), and calcitonin gene-related peptide (CGRP) in rat muscle TrP tissue. Male Sprague Dawley rats (n = 32) were randomly divided into four groups: control, TrP, acupotomy, and lidocaine injection. Enzyme-linked immunosorbent assays were used to measure AChE, and free sarcoplasmic Ca(2+) concentrations were determined by fluorescent staining with Fura-2 AM; high-performance liquid chromatography was used to measure ATP and AMP, and SP and CGRP were evaluated by immunohistochemistry. Compared with the control group, free sarcoplasmic Ca(2+), AMP, SP, and CGRP were higher in the model group, while MPT, AChE, and ATP were lower. Treatment with acupotomy or lidocaine injection reduced free sarcoplasmic Ca(2+), SP, and CGRP and increased MPTs and AChE levels compared with the model group. However, only acupotomy also led to decreased AMP and increased ATP levels relative to the model group. We conclude that acupotomy can alleviate energy crises at TrPs.
ESTHER : Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_5129562
PubMedSearch : Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_5129562
PubMedID: 32190087

Title : Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea - Wang_2020_Environ.Pollut_267_115397
Author(s) : Wang X , Hu M , Gu H , Zhang L , Shang Y , Wang T , Zeng J , Ma L , Huang W , Wang Y
Ref : Environ Pollut , 267 :115397 , 2020
Abstract : In recent years, antibiotics have been widely detected in coastal waters of China, which raising concerns for coastal biodiversity and aquaculture. This study evaluated the effects of short-term exposure of norfloxacin (NOR) on oxidative stress and intestinal health of the large yellow croaker Pseudosciaena crocea. Juvenile fish were exposed to four concentrations of NOR (0.1, 10, 100 and 1000 g/L) for 14 days. The results showed that NOR inhibited growth and threatened the survival of juveniles. According to the changes of intestinal microbiota, we found that NOR led to a significant decrease in intestinal microbiota diversity, with the decreased relative abundance of Proteobacteria, but the increased Tenericutes. From the perspective of microbial function, NOR inhibited metabolism, cellular defence mechanism and information transduction process. In terms of biochemical indicators, NOR caused an increase in malondialdehyde (MDA) level and inhibited superoxide dismutase (SOD) and acetyl cholinesterase (AChE) activities. Catalase (CAT) activity was activated at low concentration but significantly inhibited at high concentration of NOR. Moreover, there was a high correlation between change in biochemical indicators and change in the microbial community. Overall, environmentally relevant concentrations (0.1 g/L) and high concentrations (10, 100 and 1000 g/L) of NOR have negative effects on the defence function and intestinal health of large yellow croaker juveniles.
ESTHER : Wang_2020_Environ.Pollut_267_115397
PubMedSearch : Wang_2020_Environ.Pollut_267_115397
PubMedID: 33254654

Title : Comparison of Enzyme Secretion and Ferulic Acid Production by Escherichia coli Expressing Different Lactobacillus Feruloyl Esterases - Xu_2020_Front.Microbiol_11_568716
Author(s) : Xu Z , Kong J , Zhang S , Wang T , Liu X
Ref : Front Microbiol , 11 :568716 , 2020
Abstract : Construction of recombinant Escherichia coli strains carrying feruloyl esterase genes for secretory expression offers an attractive way to facilitate enzyme purification and one-step production of ferulic acid from agricultural waste. A total of 10 feruloyl esterases derived from nine Lactobacillus species were expressed in E. coli BL21 (DE3) to investigate their secretion and ferulic acid production. Extracellular activity determination showed all these Lactobacillus feruloyl esterases could be secreted out of E. coli cells. However, protein analysis indicated that they could be classified as three types. The first type presented a low secretion level, including feruloyl esterases derived from Lactobacillus acidophilus and Lactobacillus johnsonii. The second type showed a high secretion level, including feruloyl esterases derived from Lactobacillus amylovorus, Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus helveticus. The third type also behaved a high secretion level but easy degradation, including feruloyl esterases derived from Lactobacillus farciminis, Lactobacillus fermentum, and Lactobacillus reuteri. Moreover, these recombinant E. coli strains could directly release ferulic acid from agricultural waste. The highest yield was 140 g on the basis of 0.1 g de-starched wheat bran by using E. coli expressed L. amylovorus feruloyl esterase. These results provided a solid basis for the production of feruloyl esterase and ferulic acid.
ESTHER : Xu_2020_Front.Microbiol_11_568716
PubMedSearch : Xu_2020_Front.Microbiol_11_568716
PubMedID: 33329424
Gene_locus related to this paper: lacam-a0a1c9u7k7

Title : OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis - Wang_2020_iScience_23_101252
Author(s) : Wang T , Wei Q , Liang L , Tang X , Yao J , Lu Y , Qu Y , Chen Z , Xing G , Cao X
Ref : iScience , 23 :101252 , 2020
Abstract : The accumulation of giant lipid droplets (LDs) increases the risk of metabolic disorders including obesity and insulin resistance. The lipolysis process involves the activation and transfer of lipase, but the molecular mechanism is not completely understood. The translocation of ATGL, a critical lipolysis lipase, from the ER to the LD surface is mediated by an energy catabolism complex. Oxysterol-binding protein-like 2 (OSBPL2/ORP2) is one of the lipid transfer proteins that regulates intracellular cholesterol homeostasis. A recent study has proven that Osbpl2(-/-) pigs exhibit hypercholesterolemia and obesity phenotypes with an increase in adipocytes. In this study, we identified that OSBPL2 links the endoplasmic reticulum (ER) with LDs, binds to COPB1, and mediates ATGL transport. We provide important insights into the function of OSBPL2, indicating that it is required for the regulation of lipid droplet lipolysis.
ESTHER : Wang_2020_iScience_23_101252
PubMedSearch : Wang_2020_iScience_23_101252
PubMedID: 32650117

Title : Chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species - Zhang_2020_Nat.Prod.Res_34_3531
Author(s) : Zhang Y , Wu D , Kuang S , Qing M , Ma Y , Yang T , Wang T , Li D
Ref : Nat Prod Res , 34 :3531 , 2020
Abstract : The chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species were studied. The contents of total phenolic and 10 phenolic compounds were highest in Juniperus rigida Zucc., of which catechin and cumaric acid were the predominant phenolic compounds, but were lowest in Juniperus sibirica Burgsd. GC-MS analysis showed the highest contents of essential oils were in J. rigida (92.61%), followed by Juniperus formosana Hayata (87.30%) and J. sibirica (84.89%). The a-pinene was the most dominant compound in J. rigida (23.99%) and J. formosana (9.71%), however, it has not been detected in J. sibirica. Ethanol extracts showed the higher radical scavenging capacity in ABTS, FRAP and DPPH assays than essential oils. The essential oils and ethanol extracts of J.sibirica showed the strong antibacterial activity against Salmonella typhimurium and Escherichia coli. Three Juniperus species showed certain acetylcholinesterase and butyrylcholinesterase inhibitions and J. formosana showed better cholinesterase inhibitory.
ESTHER : Zhang_2020_Nat.Prod.Res_34_3531
PubMedSearch : Zhang_2020_Nat.Prod.Res_34_3531
PubMedID: 30822132

Title : A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y - Nguyen_2020_Neuron_106_759
Author(s) : Nguyen TA , Wu K , Pandey S , Lehr AW , Li Y , Bemben MA , Badger JD, 2nd , Lauzon JL , Wang T , Zaghloul KA , Thurm A , Jain M , Lu W , Roche KW
Ref : Neuron , 106 :759 , 2020
Abstract : Autism spectrum disorder (ASD) is more prevalent in males; however, the etiology for this sex bias is not well understood. Many mutations on X-linked cell adhesion molecule NLGN4X result in ASD or intellectual disability. NLGN4X is part of an X-Y pair, with NLGN4Y sharing approximately 97% sequence homology. Using biochemistry, electrophysiology, and imaging, we show that NLGN4Y displays severe deficits in maturation, surface expression, and synaptogenesis regulated by one amino acid difference with NLGN4X. Furthermore, we identify a cluster of ASD-associated mutations surrounding the critical amino acid in NLGN4X, and these mutations phenocopy NLGN4Y. We show that NLGN4Y cannot compensate for the functional deficits observed in ASD-associated NLGN4X mutations. Altogether, our data reveal a potential pathogenic mechanism for male bias in NLGN4X-associated ASD.
ESTHER : Nguyen_2020_Neuron_106_759
PubMedSearch : Nguyen_2020_Neuron_106_759
PubMedID: 32243781
Gene_locus related to this paper: human-NLGN4X

Title : In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease - Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
Author(s) : Song X , Wang T , Guo L , Jin Y , Wang J , Yin G , Jiang K , Wang L , Huang H , Zeng L
Ref : Evid Based Complement Alternat Med , 2020 :2804849 , 2020
Abstract : Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.
ESTHER : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedSearch : Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849
PubMedID: 32148536

Title : Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents - Luo_2019_Bioorg.Med.Chem__115190
Author(s) : Luo W , Lv JW , Wang T , Zhang ZY , Guo HY , Song ZY , Wang CJ , Ma J , Chen YP
Ref : Bioorganic & Medicinal Chemistry , :115190 , 2019
Abstract : A novel series of graveolinine derivatives were synthesized and evaluated as potential anti-Alzheimer agents. Compound 5f exhibited the best inhibitory activity for acetylcholinesterase (AChE) and had surprisingly potent inhibitory activity for butyrylcholinesterase (BuChE), with IC50 values of 0.72muM and 0.16muM, respectively. The results from Lineweaver-Burk plot and molecular modeling study indicated non-competitive inhibition of AChE by compound 5f. In addition, these derivatives showed potent self-induced beta-amyloid (Abeta) aggregation inhibition. Moreover, 5f didn't show obvious toxicity against PC12 and HepG2 cells at 50muM. Finally, in vivo studies confirmed that 5f significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, these graveolinine derivatives should be thoroughly and systematically studied for the treatment of Alzheimer's disease.
ESTHER : Luo_2019_Bioorg.Med.Chem__115190
PubMedSearch : Luo_2019_Bioorg.Med.Chem__115190
PubMedID: 31744779

Title : Fabrication and Properties of a Bio-Based Biodegradable Thermoplastic Polyurethane Elastomer - Wang_2019_Polymers.(Basel)_11_
Author(s) : Wang Z , Yan J , Wang T , Zai Y , Qiu L , Wang Q
Ref : Polymers (Basel) , 11 : , 2019
Abstract : Using the melt polycondensation of five bio-based aliphatic monomers (succinic acid, sebacic acid, fumaric acid, 1,3-propanediol, and 1,4-butanediol), we first synthesized the more flexible and biodegradable polyester diols (BPD) with an average molecular weight of 3825. Then, the BPD was polymerized with excessive 4,4'-diphenylmethane diisocyanate (MDI). Finally, the molecular chain extender of 1,4-butanediol (BDO) was used to fabricate the biodegradable thermoplastic polyurethane elastomer (BTPU), comprising the soft segment of BPD and the hard segment polymerized by MDI and BDO. Atomic force microscope (AFM) images showed the two-phase structure of the BTPU. The tensile strength of the BTPU containing 60% BPD was about 30 MPa and elongation at break of the BTPU was over 800%. Notably, the BTPU had superior biodegradability in lipase solution and the biodegradation weight loss ratio of the BTPU containing 80% BPD reached 36.7% within 14 days in the lipase solution.
ESTHER : Wang_2019_Polymers.(Basel)_11_
PubMedSearch : Wang_2019_Polymers.(Basel)_11_
PubMedID: 31269638

Title : Isoform-specific cleavage of neuroligin-3 reduces synapse strength - Bemben_2019_Mol.Psychiatry_24_145
Author(s) : Bemben MA , Nguyen TA , Li Y , Wang T , Nicoll RA , Roche KW
Ref : Mol Psychiatry , 24 :145 , 2019
Abstract : The assembly and maintenance of synapses are dynamic processes that require bidirectional contacts between the pre- and postsynaptic structures. A network of adhesion molecules mediate this physical interaction between neurons. How synapses are disassembled and if there are distinct mechanisms that govern the removal of specific adhesion molecules remain unclear. Here, we report isoform-specific proteolytic cleavage of neuroligin-3 in response to synaptic activity and protein kinase C signaling resulting in reduced synapse strength. Although neuroligin-1 and neuroligin-2 are not directly cleaved by this pathway, when heterodimerized with neuroligin-3, they too undergo proteolytic cleavage. Thus protein kinase C-dependent cleavage is mediated through neuroligin-3. Recent studies on glioma implicate the neuroligin-3 ectodomain as a mitogen. Here we demonstrate: (1) there are mechanisms governing specific adhesion molecule remodeling; (2) neuroligin-3 is a key regulator of neuroligin cleavage events; and (3) there are two cleavage pathways; basal and activity-dependent that produce the mitogenic form of neuroligin-3.
ESTHER : Bemben_2019_Mol.Psychiatry_24_145
PubMedSearch : Bemben_2019_Mol.Psychiatry_24_145
PubMedID: 30242227

Title : Galantamine reversed early postoperative cognitive deficit via alleviating inflammation and enhancing synaptic transmission in mouse hippocampus - Wang_2019_Eur.J.Pharmacol_846_63
Author(s) : Wang T , Zhu H , Hou Y , Gu W , Wu H , Luan Y , Xiao C , Zhou C
Ref : European Journal of Pharmacology , 846 :63 , 2019
Abstract : Postoperative cognitive dysfunction (POCD) is commonly seen in patients undergoing major surgeries and may persist. Although neuroinflammation is one of the important contributors to the development of POCD, the mechanisms underlying POCD remain unclear. We performed stabilized tibial fracture operation in male mice. In comparison with sham mice (anesthesia only), the surgery mice exhibited cognitive deficits in a fear conditioning paradigm at postsurgery day 3-7, and increased numbers of microglia and elevated levels of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) without change of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Electrophysiological recordings from CA1 hippocampal neurons revealed that POCD mice exhibited impairment in AMPA receptor-mediated evoked excitatory postsynaptic currents (eEPSCs) without alteration in the rectification property of AMPA receptors. Interestingly, daily intraperitoneal administration of galantamine, an inhibitor of acetylcholinesterase, reversed cognitive dysfunction in surgery mice and attenuated accumulation of microglia and protein levels of IL-1beta, IL-6 and TNF-alpha in the hippocampus. Additionally, galantamine potentiated AMPA receptor-mediated eEPSCs in the hippocampus more prominent in surgery mice than in sham mice. Therefore, enhancement of cholinergic tone in the hippocampus might be a therapeutic strategy for early POCD in terms of suppression of inflammation and normalization of excitatory synaptic transmission.
ESTHER : Wang_2019_Eur.J.Pharmacol_846_63
PubMedSearch : Wang_2019_Eur.J.Pharmacol_846_63
PubMedID: 30586550

Title : Potential Pharmacokinetic Herb-Drug Interactions: Have we Overlooked the Importance of Human Carboxylesterases 1 and 2? - Xu_2019_Curr.Drug.Metab_20_130
Author(s) : Xu J , Qiu JC , Ji X , Guo HL , Wang X , Zhang B , Wang T , Chen F
Ref : Curr Drug Metab , 20 :130 , 2019
Abstract : BACKGROUND: Herbal products have grown steadily across the globe and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic Herb-drug Interactions (HDIs) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human Carboxylesterases 1 (CES1) and 2 (CES2) metabolize endogenous and exogenous chemicals including many important therapeutic medications. The growing number of CES substrate drugs also underscores the importance of the enzymes. Herein, we summarized those potential inhibitors and inducers coming from herbal constituents toward CES1 and CES2. We also reviewed the reported HDI studies focusing on herbal products and therapeutic agents metabolized by CES1 or CES2. METHODS: We searched in PubMed for manuscript published in English after Jan 1, 2000 combining terms "carboxylesterase 1", "carboxylesterase 2", "inhibitor", "inducer", "herb-drug interaction", "inhibitory", and "herbal supplement". We also searched specific websites including FDA and EMA. The data of screened papers were analyzed and summarized. RESULTS: The results showed that more than 50 natural inhibitors of CES1 or CES2, including phenolic chemicals, triterpenoids, and tanshinones were found from herbs, whereas only few inducers of CES1 and CES2 were reported. Systemic exposure to some commonly used drugs including oseltamivir, irinotecan, and clopidogrel were changed when they were co-administered with herb products such as goldenseal, black cohosh, ginger, St. John's Wort, curcumin, and some Chinese compound formula in animals. CONCLUSION: Nonclinical and clinical studies on HDIs are warranted in the future to provide safety information toward better clinical outcomes for the combination of herbal products and conventional drugs.
ESTHER : Xu_2019_Curr.Drug.Metab_20_130
PubMedSearch : Xu_2019_Curr.Drug.Metab_20_130
PubMedID: 29600756

Title : Metabolites from the endophytic fungus colletotrichum sp. F168 - Lei_2019_Nat.Prod.Res__1
Author(s) : Lei HM , Ma N , Wang T , Zhao PJ
Ref : Nat Prod Res , :1 , 2019
Abstract : An endophytic fungus, Colletotrichum sp. F168, was isolated from plant Huperzia serrata (Thunb. ex Murray) Trev. and was subjected to phytochemical investigation. Nine compounds including two new structures were obtained from SDA solid fermentation products of strain F168, which were elucidated by extensive spectroscopic analyses, including 1 D- and 2 D-NMR, and HR-MS experiments. The acetylcholinesterase inhibitory activity of two new compounds 1-2 was tested in vitro. Two new compounds didn't show evident acetylcholinesterase inhibitory activity.
ESTHER : Lei_2019_Nat.Prod.Res__1
PubMedSearch : Lei_2019_Nat.Prod.Res__1
PubMedID: 31304793

Title : The blood parameters and liver function changed inconsistently among children between burns and traumatic injuries - Nie_2019_PeerJ_7_e6415
Author(s) : Nie C , Wang T , Yu H , Wang X , Zeng X , Wei Z , Shi X
Ref : PeerJ , 7 :e6415 , 2019
Abstract : Objective: Burn and traumatic injury are two kinds of injury by modality. They cause acute phase response and lead to a series of pathological and physiological changes. In this study, we explored whether there are differences in routine blood parameters and liver enzyme levels between burned and traumatically injured children. Methods: Patients under 18 years old with injuries were recruited. Their demographic and clinical data were recorded. Collected clinical data included routine blood parameters (white blood cell count (WBC), red blood cell count (RBC), platelets (PLT), hemoglobin (HB)), serological enzyme levels (alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyltransferase (GGT), alkaline phosphatase (ALP), cholinesterase (CHE)), and total protein (TP) levels (albumin (ALB), globulin (GLB)). A generalized linear model and multivariate analysis of variance were used to conduct comparisons. Results: A total of 162 children (109 with burns and 53 with traumatic injuries) with a mean age of 4.36 +/- 4.29 years were enrolled in the study. Burned children had higher levels of RBC, HB, WBC, AST and lower levels of TP, CHE, ALB than traumatically injured children (P < 0.05). Moreover, the concentration of WBC and HB was higher in males compared to females (P < 0.001). Conversely, the level of AST and TP in males was lower, AST levels were significantly lower in males (P = 0.005). Age positively correlated with the levels of HB, AST and TP (P < 0.001), and negatively correlated with WBC (P < 0.001). With decreasing body mass index (BMI), the levels of WBC, HB, AST and TP significantly increased in both groups of injured children (P < 0.001). In addition, ISS was positively correlated with WBC and HB levels (P < 0.001), but negatively correlated with AST and TP levels (P < 0.001). Conclusions: Children with burn injuries suffered a greater acute response and liver damage than traumatically injured children. This may in part underlie clinical observations of differences in children morbidity and mortality in response to different injury types.
ESTHER : Nie_2019_PeerJ_7_e6415
PubMedSearch : Nie_2019_PeerJ_7_e6415
PubMedID: 30775182

Title : Chemical characterization of main bioactive constituents in Paeonia ostii seed meal and GC-MS analysis of seed oil - Tian_2019_J.Food.Biochem__e13088
Author(s) : Tian X , Guo S , Zhang S , Li P , Wang T , Ho CT , Pan MH , Bai N
Ref : J Food Biochem , :e13088 , 2019
Abstract : The seeds of tree peony (Paeonia ostii) are promulgated as emerging edible oil crops. However, biological properties of principal constituents of peony seeds were not well studied. Fifteen main constituents including suffruticosols A and B, trans-epsilon-viniferin, ampelopsin E, resveratrol, trans-resveratrol-4'-O-beta-d-glucopyranoside, paeoniflorin, luteolin, luteolin-4'-O-beta-d-glucopyranoside, apigenin, kaempferol, oleanic acid, betulinic acid, hederagenin, and caffeic acid were isolated and identified. Their cytotoxicity against human tumor cell lines (COLO205, HT-29, HepG2, AGS, and HL-60) were evaluated. Among them, trans-epsilon-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 muM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 muM) and HT-29 (IC50 4.2 muM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 muM) and AGS (IC50 5.4 muM) cells. Three enzymes (tyronsinase, alpha-glucosidase, and acetylcholinesterase) inhibitory activities of 12 compounds were also screened. Stilbene compounds, especially suffruticosols A and B, showed a significant inhibitory activity on all three enzymes. PRACTICAL APPLICATIONS: The cytotoxicity of 15 main constituents from peony seeds against COLO205, HT-29, HepG2, AGS, and HL-60 cells were evaluated. Among them, trans-epsilon-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 muM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 muM) and HT-29 (IC50 4.2 muM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 muM) and AGS (IC50 5.4 muM) cells. Collectively, these results suggested that Paeonia ostii seed (POS) extracts are potential candidates for anticancer agents.
ESTHER : Tian_2019_J.Food.Biochem__e13088
PubMedSearch : Tian_2019_J.Food.Biochem__e13088
PubMedID: 31646682

Title : A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3 - Zhang_2018_Biomed.Res.Int_2018_3109251
Author(s) : Zhang Q , Xiao X , Zheng J , Li M , Yu M , Ping F , Wang T , Wang X
Ref : Biomed Res Int , 2018 :3109251 , 2018
Abstract : The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S-methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo.
ESTHER : Zhang_2018_Biomed.Res.Int_2018_3109251
PubMedSearch : Zhang_2018_Biomed.Res.Int_2018_3109251
PubMedID: 29951533

Title : A pH responsive AIE probe for enzyme assays - Shi_2018_Analyst_143_741
Author(s) : Shi L , Liu Y , Wang Q , Wang T , Ding Y , Cao Y , Li Z , Wei H
Ref : Analyst , 143 :741 , 2018
Abstract : By combining leucine (Leu) and tetraphenylethene (TPE), a pH-sensitive aggregation induced emission (AIE) probe TPE-Leu was developed. The aliphatic amine in TPE-Leu was more easily protonated under acidic conditions, which made TPE-Leu more water soluble. Therefore, the protonated AIE probe showed weak fluorescence under acidic conditions. When the pH was changed to basic conditions, it showed strong fluorescence due to the hydrophobic nature of TPE-Leu. We demonstrated that the probe showed high selectivity toward pH changes with the coexistence of other potential species such as metal ions, redox agents, and biomolecules. In contrast, TPE-NH2 did not exhibit obvious pH-sensitive properties. Moreover, TPE-Leu was further utilized to develop a sensitive and selective sensing platform for urease and acetylcholinesterase (AChE) detection. The current study not only provides a new strategy for designing pH-sensitive fluorescent probes for bioassays but also broadens the applications of AIE probes.
ESTHER : Shi_2018_Analyst_143_741
PubMedSearch : Shi_2018_Analyst_143_741
PubMedID: 29323362

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

Title : Neurotrophins and cholinergic enzyme regulated by calpain-2: New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153 - Zhang_2018_Toxicol.Lett_291_29
Author(s) : Zhang H , Yang X , Li X , Zhang Z , Hou L , Wang Z , Niu Q , Wang T
Ref : Toxicol Lett , 291 :29 , 2018
Abstract : Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment.
ESTHER : Zhang_2018_Toxicol.Lett_291_29
PubMedSearch : Zhang_2018_Toxicol.Lett_291_29
PubMedID: 29621559

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

Title : Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System - Jin_2017_Neurochem.Res_42_1299
Author(s) : Jin Y , Peng J , Wang X , Zhang D , Wang T
Ref : Neurochem Res , 42 :1299 , 2017
Abstract : Bacterial endotoxin lipopolysaccharide (LPS) can induce systemic inflammation, and therefore disrupt learning and memory processes. Ginsenoside Rg1, a major bioactive component of ginseng, is shown to greatly improve cognitive function. The present study was designed to further investigate whether administration of ginsenoside Rg1 can ameliorate LPS-induced cognitive impairment in the Y-maze and Morris water maze (MWM) task, and to explore the underlying mechanisms. Results showed that exposure to LPS (500 mug/kg) significantly impaired working and spatial memory and that repeated treatment with ginsenoside Rg1 (200 mg/kg/day, for 30 days) could effectively alleviate the LPS-induced cognitive decline as indicated by increased working and spatial memory in the Y-maze and MWM tests. Furthermore, ginsenoside Rg1 treatment prevented LPS-induced decrease of acetylcholine (ACh) levels and increase of acetylcholinesterase (AChE) activity. Ginsenoside Rg1 treatment also reverted the decrease of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) protein expression in the prefrontal cortex (PFC) and hippocampus of LPS-treated rats. These findings suggest that ginsenoside Rg1 has protective effect against LPS-induced cognitive deficit and that prevention of LPS-induced changes in cholinergic system is crucial to this ameliorating effect.
ESTHER : Jin_2017_Neurochem.Res_42_1299
PubMedSearch : Jin_2017_Neurochem.Res_42_1299
PubMedID: 28078612

Title : De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor canadensis) - Lok_2017_G3.(Bethesda)_7_755
Author(s) : Lok S , Paton TA , Wang Z , Kaur G , Walker S , Yuen RK , Sung WW , Whitney J , Buchanan JA , Trost B , Singh N , Apresto B , Chen N , Coole M , Dawson TJ , Ho K , Hu Z , Pullenayegum S , Samler K , Shipstone A , Tsoi F , Wang T , Pereira SL , Rostami P , Ryan CA , Tong AH , Ng K , Sundaravadanam Y , Simpson JT , Lim BK , Engstrom MD , Dutton CJ , Kerr KC , Franke M , Rapley W , Wintle RF , Scherer SW
Ref : G3 (Bethesda) , 7 :755 , 2017
Abstract : The Canadian beaver (Castor canadensis) is the largest indigenous rodent in North America. We report a draft annotated assembly of the beaver genome, the first for a large rodent and the first mammalian genome assembled directly from uncorrected and moderate coverage (< 30 x) long reads generated by single-molecule sequencing. The genome size is 2.7 Gb estimated by k-mer analysis. We assembled the beaver genome using the new Canu assembler optimized for noisy reads. The resulting assembly was refined using Pilon supported by short reads (80 x) and checked for accuracy by congruency against an independent short read assembly. We scaffolded the assembly using the exon-gene models derived from 9805 full-length open reading frames (FL-ORFs) constructed from the beaver leukocyte and muscle transcriptomes. The final assembly comprised 22,515 contigs with an N50 of 278,680 bp and an N50-scaffold of 317,558 bp. Maximum contig and scaffold lengths were 3.3 and 4.2 Mb, respectively, with a combined scaffold length representing 92% of the estimated genome size. The completeness and accuracy of the scaffold assembly was demonstrated by the precise exon placement for 91.1% of the 9805 assembled FL-ORFs and 83.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set used to assess the quality of genome assemblies. Well-represented were genes involved in dentition and enamel deposition, defining characteristics of rodents with which the beaver is well-endowed. The study provides insights for genome assembly and an important genomics resource for Castoridae and rodent evolutionary biology.
ESTHER : Lok_2017_G3.(Bethesda)_7_755
PubMedSearch : Lok_2017_G3.(Bethesda)_7_755
PubMedID: 28087693
Gene_locus related to this paper: cascn-a0a250y2s0 , cascn-a0a250y135 , cascn-a0a250y1i6 , cascn-a0a250y2u8 , cascn-a0a250xy53 , ursma-a0a384cw87 , cascn-a0a250y6h8

Title : Further brominated polyacetylenes with pancreatic lipase inhibitory activity from Chinese marine sponge Xestospongia testudinaria - Yang_2017_J.Asian.Nat.Prod.Res_19_732
Author(s) : Yang M , Liang LF , Wang T , Wang HY , Liu HL , Guo YW
Ref : J Asian Nat Prod Res , 19 :732 , 2017
Abstract : A new brominated polyacetylene, xestonariene I (1), along with three known related analogues (2-4), was obtained from Chinese marine sponge Xestospongia testudinaria. Its structure was determined on the basis of detailed spectroscopic analysis and by comparison with literature data. Compound 4 exhibited significant inhibitory activity against pancreatic lipase, which plays a key role in preventing obesity, with an IC50 value of 0.61 muM, being comparable to that of the positive control orlistat (IC50 = 0.78 muM).
ESTHER : Yang_2017_J.Asian.Nat.Prod.Res_19_732
PubMedSearch : Yang_2017_J.Asian.Nat.Prod.Res_19_732
PubMedID: 28152617

Title : New Drug Research and Development for Alzheimer's Pathology: Present and Prospect - Wang_2017_Shanghai.Arch.Psychiatry_29_237
Author(s) : Wang T
Ref : Shanghai Arch Psychiatry , 29 :237 , 2017
Abstract : Cholinesterase inhibitors and N-methyl-D-aspartic receptor antagonists are currently the main treatments for Alzheimer's disease (AD), targeting the clinical symptoms of AD. beta-amyloid (Abeta) deposition and the highly-phosphorylated Tau protein-induced neurofibrillary tangles are some of the common pathological features of AD. In the past 20 years, many new drugs that focus on the pathogenesis of Alzheimer's disease have been assessed in clinical trials. Drugs such as beta-amyloid monoclonal antibody and gamma-secretase inhibitor target the Abeta pathological pathway. New drugs targeting the Tau pathological pathway inhibit the generation of neurofibrillary tangles and the Tau protein antibodies. But until now, none of these drugs has brought a fundamental breakthrough. This initial breakthrough may come out of China as there are several groups here which already have disease-modifying drugs in phase II and phase III of clinical trials.
ESTHER : Wang_2017_Shanghai.Arch.Psychiatry_29_237
PubMedSearch : Wang_2017_Shanghai.Arch.Psychiatry_29_237
PubMedID: 28955143

Title : Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity - Cen_2017_Eur.J.Med.Chem_144_128
Author(s) : Cen J , Guo H , Hong C , Lv J , Yang Y , Wang T , Fang D , Luo W , Wang C
Ref : Eur Journal of Medicinal Chemistry , 144 :128 , 2017
Abstract : A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced beta-amyloid (Abeta) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation.
ESTHER : Cen_2017_Eur.J.Med.Chem_144_128
PubMedSearch : Cen_2017_Eur.J.Med.Chem_144_128
PubMedID: 29268129

Title : Efficacy and safety of a novel acetylcholinesterase inhibitor octohydroaminoacridine in mild-to-moderate Alzheimer's disease: a Phase II multicenter randomised controlled trial - Xiao_2017_Age.Ageing__1
Author(s) : Xiao S , Wang T , Ma X , Qin Y , Li X , Zhao Z , Liu X , Wang X , Xie H , Jiang Q , Sun L , Luo B , Shang L , Chen W , Bai Y , Tang M , He M , Wu L , Ma Q , Hou D , He J
Ref : Age Ageing , :1 , 2017
Abstract : Background: inhibition of acetylcholinesterase (AChE) has been a effective treatment for Alzheimer's disease (AD). Octohydroaminoacridine, a new AChE inhibitor, is a potential treatment for AD. Method: we conducted a multicenter, randomised, double blind, placebo-controlled, parallel-group Phase II clinical trial to investigate the effects of octohydroaminoacridine in patients with mild-to-moderate AD. Patients were randomised to receive placebo thrice daily, octohydroaminoacridine 1 mg/thrice daily (TID) (low-dose group), 2 mg/TID (middle-dose group) or 4 mg/TID (high-dose group). Doses in the middle-dose and high-dose group were titrated over 2-4 weeks. Changes from baseline to Week 16 were assessed with the AD Assessment Scale-Cognitive Subscale (ADAS-cog), Clinician's Interview-Based Impression of Change Plus (CIBIC+), activities of daily living (ADL) and the neuropsychiatric inventory (NPI). ADAS-cog was the primary end point of the study. A two-way analysis of covariance and least squares mean t-test were used. Results: at Week 16, the changes from baseline in ADAS-cog were 1.4, -2.1, -2.2 and -4.2 for placebo, low-, middle- and high-dose groups, respectively. Patients in the high-dose group had better performance in CIBIC+ and ADL scores at the end of the study. There was no significant difference in the change in NPI score among the groups. The effects of octohydroaminoacridine were dose dependent, and were effective within 16 weeks of treatment. No evidence was found for more adverse events that occurred in different drug groups than placebo group. Conclusions: octohydroaminoacridine significantly improved cognitive function and behaviour in patients with mild-to-moderate AD and this effect was dose dependent.
ESTHER : Xiao_2017_Age.Ageing__1
PubMedSearch : Xiao_2017_Age.Ageing__1
PubMedID: 28419192

Title : Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease - Sang_2017_Eur.J.Med.Chem_135_307
Author(s) : Sang Z , Qiang X , Li Y , Xu R , Cao Z , Song Q , Wang T , Zhang X , Liu H , Tan Z , Deng Y
Ref : Eur Journal of Medicinal Chemistry , 135 :307 , 2017
Abstract : A series of scutellarein-O-acetamidoalkylbenzylamines derivatives were designed based on a multitarget-directed ligands strategy for the treatment of Alzheimer's disease. Among these compounds, compound T-22 demonstrated excellent acetylcholinesterase inhibitory, moderate inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils, and also acted as potential antioxidant and biometals chelator. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that T-22 interacted with both the catalytic active site and peripheral anionic site of AChE. Moreover, compound T-22 showed a good neuroprotective effect against H2O2-induced PC12 cell injury and low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated T-22 significantly reversed scopolamine-induced memory deficit in mice. Taken together, the data showed that T-22 was an interesting multifunctional lead compound worthy of further study for AD.
ESTHER : Sang_2017_Eur.J.Med.Chem_135_307
PubMedSearch : Sang_2017_Eur.J.Med.Chem_135_307
PubMedID: 28458136

Title : End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration - Yu_2017_Neural.Regen.Res_12_1703
Author(s) : Yu Q , Zhang SH , Wang T , Peng F , Han D , Gu YD
Ref : Neural Regen Res , 12 :1703 , 2017
Abstract : End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% +/- 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% +/- 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.
ESTHER : Yu_2017_Neural.Regen.Res_12_1703
PubMedSearch : Yu_2017_Neural.Regen.Res_12_1703
PubMedID: 29171436

Title : Wolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency - Pericleous_2017_Lancet.Gastroenterol.Hepatol_2_670
Author(s) : Pericleous M , Kelly C , Wang T , Livingstone C , Ala A
Ref : Lancet Gastroenterol Hepatol , 2 :670 , 2017
Abstract : Lysosomal acid lipase deficiency is a rare, autosomal recessive condition caused by mutations in the gene encoding lysosomal acid lipase (LIPA) that result in reduced or absent activity of this essential enzyme. The severity of the resulting disease depends on the nature of the underlying mutation and magnitude of its effect on enzymatic function. Wolman's disease is a severe disorder that presents during infancy, resulting in failure to thrive, hepatomegaly, and hepatic failure, and an average life expectancy of less than 4 months. Cholesteryl ester storage disorder arises later in life and is less severe, although the two diseases share many common features, including dyslipidaemia and transaminitis. The prevalence of these diseases has been estimated at one in 40 000 to 300 000, but many cases are undiagnosed and unreported, and awareness among clinicians is low. Lysosomal acid lipase deficiency-which can be diagnosed using dry blood spot testing-is often misdiagnosed as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hereditary dyslipidaemia, or cryptogenic cirrhosis. There are no formal guidelines for treatment of these patients, and treatment options are limited. In this Review we appraise the existing literature on Wolman's disease and cholesteryl ester storage disease, and discuss available treatments, including enzyme replacement therapy, oral lipid-lowering therapy, stem-cell transplantation, and liver transplantation.
ESTHER : Pericleous_2017_Lancet.Gastroenterol.Hepatol_2_670
PubMedSearch : Pericleous_2017_Lancet.Gastroenterol.Hepatol_2_670
PubMedID: 28786388

Title : Clinicians' prescription preferences for treating patients with Alzheimer's disease in Shanghai - Ban_2016_Transl.Neurodegener_5_8
Author(s) : Ban CX , Xiao SF , Lin X , Wang T , Qiu Q , Zhu MJ , Li X
Ref : Transl Neurodegener , 5 :8 , 2016
Abstract : BACKGROUND: China has more cases of Alzheimer's disease (AD) than any other country in the world. As training to recognize and manage dementia is in its early stage, it is important to study clinicians' current prescription preferences for treating patients with AD.
METHODS: This study surveyed neurologists, psychiatrists, and general physicians (GPs) in Shanghai who had outpatients with AD, using a questionnaire asking about their prescription preferences for these patients.
RESULTS: Among the 148 clinicians in the study, 26.4 % were psychiatrists, 44.6 % were neurologists, and 29.1 % were GPs. The groups did not differ significantly in age, gender, or their monthly cases of new patients with mild or moderate AD (P > 0.05). Most clinicians prescribed Cholinesterase inhibitors (ChEIs), including Huperzine A, but there were significant group-differences in prescribing specific ChEIs (P < 0.05). The daily dosages of ChEI and Memantine prescribed by all three groups were small (P > 0.05), and all three groups prescribed piracetam, ergot, and ginkgo biloba drugs. All three groups also tended to treat AD patients with a combination of antidepressants and anxiolytics, although psychiatrists were significantly more likely than neurologists to combine antipsychotics with other drugs (P < 0.05). CONCLUSION: Clinicians in Shanghai prescribed low doses of ChEIs and Memantine for patients with AD. A relatively high proportion also prescribed cognitive enhancers, which lack evidence-based support of their use, and antipsychotics. There is a need for more training about treating patients with AD and for clinicians to standardize their clinical practice.
ESTHER : Ban_2016_Transl.Neurodegener_5_8
PubMedSearch : Ban_2016_Transl.Neurodegener_5_8
PubMedID: 27114822

Title : Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities - Luo_2016_Bioorg.Med.Chem_24_672
Author(s) : Luo W , Chen Y , Wang T , Hong C , Chang LP , Chang CC , Yang YC , Xie SQ , Wang CJ
Ref : Bioorganic & Medicinal Chemistry , 24 :672 , 2016
Abstract : A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64muM for AChE and 0.42muM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10muM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease.
ESTHER : Luo_2016_Bioorg.Med.Chem_24_672
PubMedSearch : Luo_2016_Bioorg.Med.Chem_24_672
PubMedID: 26752094

Title : Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents - Luo_2016_Eur.J.Med.Chem_122_17
Author(s) : Luo W , Wang T , Hong C , Yang YC , Chen Y , Cen J , Xie SQ , Wang CJ
Ref : Eur Journal of Medicinal Chemistry , 122 :17 , 2016
Abstract : A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced beta-amyloid (Abeta) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Abeta aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD.
ESTHER : Luo_2016_Eur.J.Med.Chem_122_17
PubMedSearch : Luo_2016_Eur.J.Med.Chem_122_17
PubMedID: 27343850

Title : Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation - Zhang_2016_J.Pharmacol.Exp.Ther_359_374
Author(s) : Zhang J , Zhang L , Sun X , Yang Y , Kong L , Lu C , Lv G , Wang T , Wang H , Fu F
Ref : Journal of Pharmacology & Experimental Therapeutics , 359 :374 , 2016
Abstract : Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.
ESTHER : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedSearch : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedID: 27535978

Title : Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population - Wang_2016_Sci.Rep_6_20691
Author(s) : Wang T , Ma X , Peng D , Zhang R , Sun X , Chen M , Yan J , Wang S , Yan D , He Z , Jiang F , Bao Y , Hu C , Jia W
Ref : Sci Rep , 6 :20691 , 2016
Abstract : Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 x 10(-5) and 6.54 x 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 x 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 x 10(-8) and 4.43 x 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 x 10(-4) and 4.65 x 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.
ESTHER : Wang_2016_Sci.Rep_6_20691
PubMedSearch : Wang_2016_Sci.Rep_6_20691
PubMedID: 26848030

Title : Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy - Murakami_2015_Antimicrob.Agents.Chemother_59_3563
Author(s) : Murakami E , Wang T , Park Y , Hao J , Lepist EI , Babusis D , Ray AS
Ref : Antimicrobial Agents & Chemotherapy , 59 :3563 , 2015
Abstract : Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) currently in clinical evaluation for treatment for HIV and hepatitis B virus (HBV) infections. Since the target tissue for HBV is the liver, the hepatic delivery and metabolism of TAF in primary human hepatocytes in vitro and in dogs in vivo were evaluated here. Incubation of primary human hepatocytes with TAF resulted in high levels of the pharmacologically active metabolite tenofovir diphosphate (TFV-DP), which persisted in the cell with a half-life of >24 h. In addition to passive permeability, studies of transfected cell lines suggest that the hepatic uptake of TAF is also facilitated by the organic anion-transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3, respectively). In order to inhibit HBV reverse transcriptase, TAF must be converted to the pharmacologically active form, TFV-DP. While cathepsin A is known to be the major enzyme hydrolyzing TAF in cells targeted by HIV, including lymphocytes and macrophages, TAF was primarily hydrolyzed by carboxylesterase 1 (CES1) in primary human hepatocytes, with cathepsin A making a small contribution. Following oral administration of TAF to dogs for 7 days, TAF was rapidly absorbed. The appearance of the major metabolite TFV in plasma was accompanied by a rapid decline in circulating TAF. Consistent with the in vitro data, high and persistent levels of TFV-DP were observed in dog livers. Notably, higher liver TFV-DP levels were observed after administration of TAF than those given TDF. These results support the clinical testing of once-daily low-dose TAF for the treatment of HBV infection.
ESTHER : Murakami_2015_Antimicrob.Agents.Chemother_59_3563
PubMedSearch : Murakami_2015_Antimicrob.Agents.Chemother_59_3563
PubMedID: 25870059
Gene_locus related to this paper: human-CTSA

Title : Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis - Carey_2015_J.Abnorm.Psychol_124_860
Author(s) : Carey CE , Agrawal A , Zhang B , Conley ED , Degenhardt L , Heath AC , Li D , Lynskey MT , Martin NG , Montgomery GW , Wang T , Bierut LJ , Hariri AR , Nelson EC , Bogdan R
Ref : J Abnorm Psychol , 124 :860 , 2015
Abstract : Despite evidence for heritable variation in cannabis involvement and the discovery of cannabinoid receptors and their endogenous ligands, no consistent patterns have emerged from candidate endocannabinoid (eCB) genetic association studies of cannabis involvement. Given interactions between eCB and stress systems and associations between childhood stress and cannabis involvement, it may be important to consider childhood adversity in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Comorbidity and Trauma Study (N = 1,558) to examine whether genetic variation in six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism: MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual abuse (CSA) predict cannabis dependence symptoms. Significant interactions with CSA emerged for MGLL at the gene level (p = .009), and for rs604300 within MGLL (DeltaR2 = .007, p < .001), the latter of which survived SNP-level Bonferroni correction and was significant in an additional sample with similar directional effects (N = 859; DeltaR2 = .005, p = .026). Furthermore, in a third sample (N = 312), there was evidence that rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the eCB system and addiction (DeltaR2 = .013, p = .047). Rs604300 may be related to epigenetic modulation of MGLL expression. These results are consistent with rodent models implicating 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid metabolized by the enzyme encoded by MGLL, in the etiology of stress adaptation related to cannabis dependence, but require further replication.
ESTHER : Carey_2015_J.Abnorm.Psychol_124_860
PubMedSearch : Carey_2015_J.Abnorm.Psychol_124_860
PubMedID: 26595473

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 : Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses - Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551
Author(s) : Bemben MA , Nguyen QA , Wang T , Li Y , Nicoll RA , Roche KW
Ref : Proc Natl Acad Sci U S A , 112 :2551 , 2015
Abstract : Autism spectrum disorders (ASDs) comprise a highly heritable, multifarious group of neurodevelopmental disorders, which are characterized by repetitive behaviors and impairments in social interactions. Point mutations have been identified in X-linked Neuroligin (NLGN) 3 and 4X genes in patients with ASDs and all of these reside in their extracellular domains except for a single point mutation in the cytoplasmic domain of NLGN4X in which an arginine is mutated to a cysteine (R704C). Here we show that endogenous NLGN4X is robustly phosphorylated by protein kinase C (PKC) at T707, and R704C completely eliminates T707 phosphorylation. Endogenous NLGN4X is intensely phosphorylated on T707 upon PKC stimulation in human neurons. Furthermore, a phospho-mimetic mutation at T707 has a profound effect on NLGN4X-mediated excitatory potentiation. Our results now establish an important interplay between a genetic mutation, a key posttranslational modification, and robust synaptic changes, which can provide insights into the synaptic dysfunction of ASDs.
ESTHER : Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551
PubMedSearch : Bemben_2015_Proc.Natl.Acad.Sci.U.S.A_112_2551
PubMedID: 25675530

Title : Comparative genomic analysis of N2-fixing and non-N2-fixing Paenibacillus spp.: organization, evolution and expression of the nitrogen fixation genes - Xie_2014_PLoS.Genet_10_e1004231
Author(s) : Xie JB , Du Z , Bai L , Tian C , Zhang Y , Xie JY , Wang T , Liu X , Chen X , Cheng Q , Chen S , Li J
Ref : PLoS Genet , 10 :e1004231 , 2014
Abstract : We provide here a comparative genome analysis of 31 strains within the genus Paenibacillus including 11 new genomic sequences of N2-fixing strains. The heterogeneity of the 31 genomes (15 N2-fixing and 16 non-N2-fixing Paenibacillus strains) was reflected in the large size of the shell genome, which makes up approximately 65.2% of the genes in pan genome. Large numbers of transposable elements might be related to the heterogeneity. We discovered that a minimal and compact nif cluster comprising nine genes nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV encoding Mo-nitrogenase is conserved in the 15 N2-fixing strains. The nif cluster is under control of a sigma(70)-depedent promoter and possesses a GlnR/TnrA-binding site in the promoter. Suf system encoding [Fe-S] cluster is highly conserved in N2-fixing and non-N2-fixing strains. Furthermore, we demonstrate that the nif cluster enabled Escherichia coli JM109 to fix nitrogen. Phylogeny of the concatenated NifHDK sequences indicates that Paenibacillus and Frankia are sister groups. Phylogeny of the concatenated 275 single-copy core genes suggests that the ancestral Paenibacillus did not fix nitrogen. The N2-fixing Paenibacillus strains were generated by acquiring the nif cluster via horizontal gene transfer (HGT) from a source related to Frankia. During the history of evolution, the nif cluster was lost, producing some non-N2-fixing strains, and vnf encoding V-nitrogenase or anf encoding Fe-nitrogenase was acquired, causing further diversification of some strains. In addition, some N2-fixing strains have additional nif and nif-like genes which may result from gene duplications. The evolution of nitrogen fixation in Paenibacillus involves a mix of gain, loss, HGT and duplication of nif/anf/vnf genes. This study not only reveals the organization and distribution of nitrogen fixation genes in Paenibacillus, but also provides insight into the complex evolutionary history of nitrogen fixation.
ESTHER : Xie_2014_PLoS.Genet_10_e1004231
PubMedSearch : Xie_2014_PLoS.Genet_10_e1004231
PubMedID: 24651173
Gene_locus related to this paper: 9bacl-x4zf35 , 9bacl-x4zxj9 , 9bacl-x5a3k6 , 9bacl-x4zet8

Title : DWARF3 participates in an SCF complex and associates with DWARF14 to suppress rice shoot branching - Zhao_2014_Plant.Cell.Physiol_55_1096
Author(s) : Zhao J , Wang T , Wang M , Liu Y , Yuan S , Gao Y , Yin L , Sun W , Peng L , Zhang W , Wan J , Li X
Ref : Plant Cell Physiol , 55 :1096 , 2014
Abstract : Strigolactones (SLs) are a novel class of plant hormones that inhibit shoot branching. Currently, two proteins in rice are thought to play crucial roles in SL signal transduction. DWARF14 (D14), an alpha/beta hydrolase, is responsible for SL perception, while DWARF3 (D3), an F-box protein with leucine-rich repeats, is essential for SL signal transduction. However, how these two proteins transmit SL signals to downstream factors remains unclear. Here, we characterized a high-tillering dwarf rice mutant, gsor300097, which is insensitive to GR24, a synthetic analog of SL. Mapping and sequencing analysis showed that gsor300097 is a novel allelic mutant of D3, in which a nonsense mutation truncates the protein from 720 to 527 amino acids. The D3 gene was strongly expressed in root, leaf, shoot base and panicle. Nuclear-localized F-box protein D3 played a role in the SCF complex by interacting with OSK1, OSK5 or OSK20 and OsCullin1. In addition, D3 associated with D14 in a GR24-dependent manner in vivo. Taken together, our findings suggested that D3 assembled into an SCF(D3) complex and associated with D14 to suppress rice shoot branching.
ESTHER : Zhao_2014_Plant.Cell.Physiol_55_1096
PubMedSearch : Zhao_2014_Plant.Cell.Physiol_55_1096
PubMedID: 24616269

Title : Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors - Liang_2014_Eur.J.Med.Chem_79C_290
Author(s) : Liang LF , Wang T , Cai YS , He WF , Sun P , Li YF , Huang Q , Taglialatela-Scafati O , Wang HY , Guo YW
Ref : Eur Journal of Medicinal Chemistry , 79C :290 , 2014
Abstract : Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A-H (3-10) and thirteen known analogues (11-23). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14, exhibited a marked inhibitory activity (IC50 = 3.11 muM), similar to that of the positive control Orlistat (IC50 = 0.78 muM). The preliminary structure-activity relationships on the series of compounds clearly evidenced that a terminal (E)-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity.
ESTHER : Liang_2014_Eur.J.Med.Chem_79C_290
PubMedSearch : Liang_2014_Eur.J.Med.Chem_79C_290
PubMedID: 24747066

Title : Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 - Zhang_2014_Crit.Care.Med_42_e345
Author(s) : Zhang H , Wang T , Zhang K , Liu Y , Huang F , Zhu X , Wang MH , Tang W , Wang J , Huang H
Ref : Critical Care Medicine , 42 :e345 , 2014
Abstract : OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN
RESULTS: Four weeks after transverse aorta constriction, Ephx2 (-/-) mice did not develop significant cardiac hypertrophy as that of wild-type mice, indicated by no changes in the ratio of heart weight/body weight and ventricular wall thickness after transverse aorta constriction. Cardiac fibroblast growth factor-2 increased in wild-type-transverse aorta constriction group but this did not change in Ephx2 (-/-)-transverse aorta constriction group, and the serum level of fibroblast growth factor-2 did not change in both groups. In vitro, cardiac fibroblasts were stimulated by angiotensin II to analyze the expression of fibroblast growth factor-2. The effect of increased fibroblast growth factor-2 from cardiac fibroblasts induced by angiotensin II was attenuated by soluble epoxide hydrolase deletion. ERK1/2, p38, and AKT kinase were involved in fibroblast growth factor-2 expression regulated by angiotensin II, and soluble epoxide hydrolase deletion lowered the phosphorylation of ERK1/2 not p38 or AKT to mediate fibroblast growth factor-2 expression. In addition, soluble epoxide hydrolase deletion did not attenuate cardiomyocytes hypertrophy induced by exogenous fibroblast growth factor-2.
CONCLUSIONS: Our present data demonstrated that deletion of soluble epoxide hydrolase prevented cardiac hypertrophy not only directly to cardiomyocytes but also to cardiac fibroblasts by reducing expression of fibroblast growth factor-2.
ESTHER : Zhang_2014_Crit.Care.Med_42_e345
PubMedSearch : Zhang_2014_Crit.Care.Med_42_e345
PubMedID: 24448199

Title : Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats - Wang_2014_Toxicol.Appl.Pharmacol_280_169
Author(s) : Wang T , Zhao L , Liu M , Xie F , Ma X , Zhao P , Liu Y , Li J , Wang M , Yang Z , Zhang Y
Ref : Toxicol Appl Pharmacol , 280 :169 , 2014
Abstract : Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity.
ESTHER : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedSearch : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedID: 24967689

Title : The impact of surgery and anesthesia on post-operative cognitive decline and Alzheimer's disease development: biomarkers and preventive strategies - Kapila_2014_J.Alzheimers.Dis_41_1
Author(s) : Kapila AK , Watts HR , Wang T , Ma D
Ref : J Alzheimers Dis , 41 :1 , 2014
Abstract : Alzheimer's disease (AD) is a major social and clinical burden in the elderly, affecting 5% of people aged over 65 and 20% aged over 80. Despite improved management, a cure has not been found and hence analysis of predisposing factors to identify preventive strategies has become increasingly important. Surgery and anesthesia have been proposed to increase the incidence of post-operative cognitive decline (POCD) and AD. This is hypothesized to be the result of a malignant neuroinflammatory response and subsequent synaptic impairment in the elderly and susceptible individuals. As a result, strategies are being explored to prevent surgery and anesthesia induced cognitive impairment. Whereas previously the diagnosis of AD was primarily dependent on clinical examination, biomarkers such as inflammatory cytokines, amyloid-beta, and tau deposition in the cerebrospinal fluid have received increased attention. Nonetheless, AD is currently still treated symptomatically with acetylcholinesterase inhibitors and NMDA antagonists to improve cholinergic transmission and prevent glutamatergic excitotoxicity. Therapeutic success is, however, often not achieved, since these treatment methods do not address the ongoing neuroinflammatory processes and hence novel therapeutic and protective strategies are urgently needed. This review provides an insight into the current understanding of age-related cognitive impairment post-surgery and reflects on novel markers of AD pathogeneses exploring their use as targets for treatment. It gives a summary of recent efforts in preventing and treating POCD or AD with regards to the choice and depth of anesthesia, surgical strategy, and peri-operative medication, and discusses the mechanism of action and therapeutic prospects of novel agents.
ESTHER : Kapila_2014_J.Alzheimers.Dis_41_1
PubMedSearch : Kapila_2014_J.Alzheimers.Dis_41_1
PubMedID: 24577482

Title : Associations of platelet-activating factor acetylhydrolase (PAF-AH) gene polymorphisms with circulating PAF-AH levels and risk of coronary heart disease or blood stasis syndrome in the Chinese Han population - Zheng_2014_Mol.Biol.Rep_41_7141
Author(s) : Zheng GH , Xiong SQ , Chen HY , Mei LJ , Wang T
Ref : Mol Biol Rep , 41 :7141 , 2014
Abstract : The circulating level of platelet-activating factor acetylhydrolase (PAF-AH) is a novel biomarker to predict the presence of coronary heart disease. PAF-AH gene polymorphisms may be responsible for the variance of circulating PAF-AH levels in individuals. However, the association of PAF-AH gene polymorphisms with circulating PAF-AH levels and the susceptibility to coronary heart disease (CHD) remains unsolved. Blood stasis syndrome (BSS) of CHD is the most common type of TCM syndromes, and a previous study discovered its relationship with the elevated circulating PAF-AH levels. However, the association of gene polymorphisms and CHD with BSS is unclear at present. In this study, four polymorphisms (R92H, I198T, A379V, V279F) of the PAF-AH gene were genotyped in 570 CHD patients, of which 299 had BSS. In addition, 317 unaffected individuals from the same hospitals served as controls. Plasma PAF-AH levels were measured in 155 controls and 271 CHD patients selected randomly, including 139 CHD patients with BSS. In the Chinese Han population, plasma PAF-AH levels in CHD patients with BSS or without BSS were significantly higher (12.9 +/- 6.5 and 11.1 +/- 5.0 microM, respectively) than in controls (9.3 +/- 5.2 microM); this difference still remained significant after adjustment for traditional risk factors or the inflammatory factors. The R92H polymorphism was highly related to the plasma PAF-AH levels and the risk of CHD, especially among patients with BSS, even with the adjustment for the effects of traditional factors. The I198T polymorphism was highly associated with risk of CHD with BSS, but was associated with neither the risk of CHD with no BSS nor with elevated plasma PAF-AH levels.
ESTHER : Zheng_2014_Mol.Biol.Rep_41_7141
PubMedSearch : Zheng_2014_Mol.Biol.Rep_41_7141
PubMedID: 25034894
Gene_locus related to this paper: human-PLA2G7

Title : Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice - Morgan_2013_J.Cardiovasc.Pharmacol_61_291
Author(s) : Morgan LA , Olzinski AR , Upson JJ , Zhao S , Wang T , Eisennagel SH , Hoang B , Tunstead JR , Marino JP, Jr. , Willette RN , Jucker BM , Behm DJ
Ref : J Cardiovasc Pharmacol , 61 :291 , 2013
Abstract : Epoxyeicosatrienoic acids, substrates for soluble epoxide hydrolase (sEH), exhibit vasodilatory and antihypertrophic activities. Inhibitors of sEH might therefore hold promise as heart failure therapeutics. We examined the ability of sEH inhibitors GSK2188931 and GSK2256294 to modulate cardiac hypertrophy, fibrosis, and function after transverse aortic constriction (TAC) in rats and mice. GSK2188931 administration was initiated in rats 1 day before TAC, whereas GSK2256294 treatment was initiated in mice 2 weeks after TAC. Four weeks later, cardiovascular function was assessed, plasma was collected for drug and sEH biomarker concentrations, and left ventricle was isolated for messenger RNA and histological analyses. In rats, although GSK2188931 prevented TAC-mediated increases in certain genes associated with hypertrophy and fibrosis (alpha-skeletal actin and connective tissue growth factor), the compound failed to attenuate TAC-induced increases in left ventricle mass, posterior wall thickness, end-diastolic volume and pressure, and perivascular fibrosis. Similarly, in mice, GSK2256294 did not reverse cardiac remodeling or systolic dysfunction induced by TAC. Both compounds increased the sEH substrate/product (leukotoxin/leukotoxin diol) ratio, indicating sEH inhibition. In summary, sEH inhibition does not prevent cardiac remodeling or dysfunction after TAC. Thus, targeting sEH seems to be insufficient for reducing pressure overload hypertrophy.
ESTHER : Morgan_2013_J.Cardiovasc.Pharmacol_61_291
PubMedSearch : Morgan_2013_J.Cardiovasc.Pharmacol_61_291
PubMedID: 23232840

Title : A novel approach to medical countermeasures against organophosphorus compound toxicity - Wang_2013_Biomed.Rep_1_901
Author(s) : Wang T , Wang Y , Zhang L , Han B , Wang H , Li Y , Fu F
Ref : Biomed Rep , 1 :901 , 2013
Abstract : The toxicity of organophosphorus compounds (OPs) results primarily from the irreversible inhibition of acetylcholinesterase (AChE). Huperzine A (HupA) is a reversible inhibitor of AChE and HupA sustained-release microspheres (HSMs) steadily release HupA, resulting in the continual inhibition of AChE activity for 14 days in mice. The present study aimed to investigate the preventive effects of HSMs on the toxicity of methyl parathion (MP). The mice were pretreated with HSMs followed by MP exposure. Subsequently, the median lethal dose (LD50) and survival of the mice were determined. A histopathological examination of the brain, liver, lungs, heart, kidneys and intercostal muscles was also performed. The results revealed that the LD50 was 51.4 mg/kg in the control group and 70.0, 67.5, 63.4 and 53.5 mg/kg at 2 h, 5, 10 and 15 days after pretreatment with HSMs, respectively. Pretreatment with HSMs at 2 h, 5 days and 10 days prior to an acute challenge with 1.2 x LD50 MP was sufficient to counteract the lethality and acute toxicity of MP. HSM pretreatment also attenuated the pulmonary edema induced by MP. The results demonstrated that pretreatment with HSMs may be an effective method to counteract MP poisoning. To the best of our knowledge, the present study was the first to demonstrate that pretreatment with an AChE reversible inhibitor sustained-release agent may be a novel approach to effective protection against OP toxicity.
ESTHER : Wang_2013_Biomed.Rep_1_901
PubMedSearch : Wang_2013_Biomed.Rep_1_901
PubMedID: 24649050

Title : The effects of huperzine A on gastrointestinal acetylcholinesterase activity and motility after single and multiple dosing in mice - Zhang_2013_Exp.Ther.Med_5_793
Author(s) : Zhang L , Song Y , Lu C , Zhang J , Yuan J , Wang T , Fu F
Ref : Exp Ther Med , 5 :793 , 2013
Abstract : The acetylcholinesterase inhibitor (AChEI), huperzine A has been used in the treatment of the cognitive deterioration associated with Alzheimer's disease (AD). However, the side-effects of huperzine A associated with increased cholinergic activity, particularly in the gastrointestinal system, are evident. It is not yet known how quickly these side-effects become tolerated; this information would provide guidance to doctors on how to use huperzine A so as to attenuate the adverse events. The present study aimed to observe the effects of huperzine A on gastrointestinal motility and acetylcholinesterase (AChE) activity in mice. After oral administration of huperzine A with single and multiple dosing, the gastrointestinal motility and AChE activity of the mice were examined. The results revealed that, following a single dose of huperzine A, the AChE activity in the stomach and duodenum were significantly inhibited and the gastrointestinal motility was significantly increased. However, following multiple doses (7 or 28 doses, one dose per day), no significant changes in the AChE activity and gastrointestinal motility were identified. These findings indicate that the gastrointestinal adverse effects of huperzine A may be well-tolerated relatively quickly and do not recur. Additionally, it suggests that patients with AD are likely to have minimal gastrointestinal side-effects after taking multiple doses of huperzine A.
ESTHER : Zhang_2013_Exp.Ther.Med_5_793
PubMedSearch : Zhang_2013_Exp.Ther.Med_5_793
PubMedID: 23403922

Title : Polyphenolic acetylcholinesterase inhibitors from Hopea chinensis - Yan_2012_Planta.Med_78_1015
Author(s) : Yan T , Wang T , Wei W , Jiang N , Qin YH , Tan RX , Ge HM
Ref : Planta Med , 78 :1015 , 2012
Abstract : Bioassay-guided investigation of the stem bark of Hopea chinensis led to the isolation of two new polyphenols, hopeachinols C(1) and D(2), together with ten known compounds (3-12). Compounds 1 and 2 were determined by extensive analysis of spectroscopic data and computational methods. All of these phytochemicals were tested for acetylcholinesterase inhibitory activity, and five resveratrol-derived compounds (1 and 7-10) exhibited significant activity with their IC(5)(0) values ranging from 4.81 to 11.71 microM.
ESTHER : Yan_2012_Planta.Med_78_1015
PubMedSearch : Yan_2012_Planta.Med_78_1015
PubMedID: 22628156

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

Title : Steady and fluctuant methods of inhibition of acetylcholinesterase differentially regulate neurotrophic factors in the hippocampus of juvenile mice - Li_2012_Exp.Ther.Med_3_269
Author(s) : Li C , Wang T , Jiang N , Yu P , Du Y , Ren R , Fu F
Ref : Exp Ther Med , 3 :269 , 2012
Abstract : The present study was designed to evaluate the effects of steady and fluctuant inhibition of acetylcholinesterase (AChE) activity on neurotrophic factors in the hippocampus of juvenile mice. Steady inhibition of AChE activity was induced by an intramuscular injection of huperizine A (HupA) sustained-release microspheres. Fluctuant inhibition of AChE activity was induced by an intragastric administration of HupA tablets. Six days after cessation of steady AChE inhibition, there was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In contrast, fluctuant AChE inhibition had no effect on BDNF and NGF levels. Additionally, neither steady nor fluctuant inhibition of AChE activity altered the choline acetyltransferase activity or spatial learning in juvenile mice. These findings indicate that steady and fluctuant methods of inhibition of AChE have different effects on the levels of BDNF and NGF in the hippocampus. In addition, the effects of AChE inhibitors may not improve learning in normal juvenile animals.
ESTHER : Li_2012_Exp.Ther.Med_3_269
PubMedSearch : Li_2012_Exp.Ther.Med_3_269
PubMedID: 22969880

Title : Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress - Wang_2012_J.Ethnopharmacol_139_214
Author(s) : Wang T , Choi RC , Li J , Bi CWC , Ran W , Chen X , Dong TTX , Bi K , Tsim KWK
Ref : J Ethnopharmacol , 139 :214 , 2012
Abstract : ETHNOPHARMACOLOGICAL EVIDENCE: Numerous efforts have been conducted in searching for effective agents against cardiovascular diseases, in particular from herbal medicines. The rhizome of Dioscorea nipponica (Dioscoreae Nipponicae Rhizoma) is a traditional Chinese herb being prescribed to improve the blood circulation. Here, we identified a steroidal saponin trillin from Dioscorea nipponica, which showed robust anti-hyperlipidemic effects. MATERIALS AND
METHODS: Rats were induced for hyperlipidemia and subjected to the drug treatment. The anti-hyperlipidemic effects of trillin were evaluated by different biochemical assays.
RESULTS: In hyperlipidemic rat model, fed with high-fat diet, the blood levels of cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) were increased. The intra-peritoneal administration of trillin into those rats significantly improved the bleeding and blood coagulation time, and in parallel the treatment restored the levels of cholesterol, glyceride, LDL and HDL back to the normal condition. In addition, the administration of trillin in rats exerted beneficial effects in improving the levels of lipid peroxidation and superoxide dismutase activity. CONCLUSION: This was the first time to reveal the anti-hyperlipidemic and anti-oxidative effects of trillin. These results would be important in developing food supplements for health improvements and therapeutic drugs against hyperlipidemia and cardiovascular diseases in future.
ESTHER : Wang_2012_J.Ethnopharmacol_139_214
PubMedSearch : Wang_2012_J.Ethnopharmacol_139_214
PubMedID: 22100563

Title : Sodium aescinate ameliorates liver injury induced by methyl parathion in rats - Du_2012_Exp.Ther.Med_3_818
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Li C , Li CK , Fu FH
Ref : Exp Ther Med , 3 :818 , 2012
Abstract : Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural pest control for several years. The present study investigated the protective effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg) poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and antioxidative parameters were measured. Histopathological examination of the liver was also performed. The results revealed that SA had no effect on AChE. Treatment with SA decreased the activities of ALT and AST, and the levels of malondialdehyde and NO. Treatment with SA also increased the level of glutathione and the activities of superoxide dismutase and glutathione peroxidase. SA administration also ameliorated liver injury induced by methyl parathion poisoning. The findings indicate that SA protects against liver injury induced by methyl parathion and that the mechanism of action is related to the antioxidative and anti-inflammatory effects of SA.
ESTHER : Du_2012_Exp.Ther.Med_3_818
PubMedSearch : Du_2012_Exp.Ther.Med_3_818
PubMedID: 22969975

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

Title : Long-term but not short-term aspirin treatment attenuates diabetes-associated learning and memory decline in mice - Wang_2011_Exp.Clin.Endocrinol.Diabetes_119_36
Author(s) : Wang T , Fu FH , Han B , Zhang LM , Zhang XM
Ref : Experimental & Clinical Endocrinology & Diabetes Diabetes , 119 :36 , 2011
Abstract : Increasing studies have shown that the patients with diabetes mellitus have an increased risk of cognitive impairment, dementia, and neurodegeneration. The present study was designed to evaluate the effect of aspirin on diabetes-associated learning and memory decline in mice. Diabetes was induced by a single intraperitoneal injection of streptozocin (150 mg/kg body weight) in C57BL/6 mice. The mice were administered with aspirin at a dose of 30 mg/kg by intragastric administration once a day for 1, 4 or 8 weeks respectively. 8 weeks after aspirin or vehicle treatment, the effect of aspirin on diabetes-associated learning and memory decline in mice was investigated by evaluating the mean escape latency and the percentage of time spent in target quadrant. The TNF-alpha, IL-1beta contents, and acetylcholinesterase activity in hippocampus were assayed as well. The results showed that administration with aspirin for 4 weeks or 8 weeks significantly reduced the mean escape latency, the acetylcholinesterase activity, the TNF-alpha, IL-1beta levels and increased the percentage of time spent in target quadrant. However, treatment with aspirin for 1 week did not ameliorate diabetes-associated learning and memory decline. The present study demonstrated that long-term aspirin treatment attenuates diabetes-associated learning and memory decline in mice, and that the effect of aspirin was related to its anti-inflammatory potency.
ESTHER : Wang_2011_Exp.Clin.Endocrinol.Diabetes_119_36
PubMedSearch : Wang_2011_Exp.Clin.Endocrinol.Diabetes_119_36
PubMedID: 20690072

Title : The MDGA1 gene confers risk to schizophrenia and bipolar disorder - Li_2011_Schizophr.Res_125_194
Author(s) : Li J , Liu J , Feng G , Li T , Zhao Q , Li Y , Hu Z , Zheng L , Zeng Z , He L , Wang T , Shi Y
Ref : Schizophr Res , 125 :194 , 2011
Abstract : OBJECTIVE: The structural, cytoarchitectural and functional brain abnormalities reported in patients with mental disorders may be due to aberrant neuronal migration influenced by cell adhesion molecules. MDGA1, like Ig-containing cell adhesion molecules, has several cell adhesion molecule-like domains. Moreover, Kahler et al. (2008) reported that the MDGA1 gene was a schizophrenia susceptibility gene in Scandinavian population. To further investigate whether the MDGA1 gene is a shared risk factor of schizophrenia, bipolar disorder and major depressive disorder in Chinese Han population, we conducted this study.
METHODS: We recruited 1135 unrelated schizophrenia patients, 1135 unrelated bipolar disorder patients, 1135 unrelated major depressive disorder patients and 1135 unrelated controls of Chinese Han origin. A total of eleven common SNPs were genotyped using TaqMan(R) technology.
RESULTS: The genotype frequency of rs11759115 differed significantly between schizophrenia patients and controls. The C-C haplotype of rs11759115-rs7769372 was also positively associated with schizophrenia (permutated p=0.046). Rs1883901 was found to be positively associated with bipolar disorder (allele: permutated p=0.0085; genotype: permutated p=0.0009; OR=1.31 [95%CI=1.12-1.52]). The A-G-G haplotype of rs1883901-rs10807187-rs9462343 was also positively associated with bipolar disorder with a global p value of 0.0391 after permutations. No individual SNP or haplotype was associated with major depressive disorder after permutations. CONCLUSION: The MDGA1 gene may confer risk to schizophrenia and bipolar disorder in Chinese Han population.
ESTHER : Li_2011_Schizophr.Res_125_194
PubMedSearch : Li_2011_Schizophr.Res_125_194
PubMedID: 21146959

Title : Protective effect of sodium aescinate on lung injury induced by methyl parathion - Du_2011_Hum.Exp.Toxicol_30_1584
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Zhao DL , Li C , Fu FH
Ref : Hum Exp Toxicol , 30 :1584 , 2011
Abstract : Methyl parathion (MP) is a high venenosus insecticide. It has been used in pest control of agriculture for several years. The present study is performed to investigate the protective effect of sodium aescinate (SA) on lung injury induced by MP. Forty male Sprague-Dawley rats are randomly divided into five groups, with 8 animals in each group: control group, MP administration group, MP plus SA at doses of 0.45 mg/kg, 0.9 mg/kg and 1.8 mg/kg groups. Acetylcholinesterase (AChE) activity and nitric oxide (NO) level in plasma, myeloperoxidase (MPO) activity, NO level, and antioxidative parameters in lung tissue are assayed. Histopathological examination of lung is also performed. The results show that SA has no effect on AChE. Treatment with SA decreases the activity of MPO in lung and the level of NO in plasma and lung. The level of malondialdehyde in lung is decreased after SA treatments. SA increases the activities of superoxide dismutase, glutathione peroxidase and the content of glutathione in lung. SA administration also ameliorates lung injury induced by MP. The findings indicate that SA could protect lung injury induced by MP and the mechanism of action is related to the anti-inflammatory and anti-oxidative effect of SA.
ESTHER : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedSearch : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedID: 21177729

Title : Huperzine A Activates Wnt\/beta-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse Model - Wang_2011_Neuropsychopharmacology_36_1073
Author(s) : Wang CY , Zheng W , Wang T , Xie JW , Wang SL , Zhao BL , Teng WP , Wang ZY
Ref : Neuropsychopharmacology , 36 :1073 , 2011
Abstract : Huperzine A (HupA) is a reversible and selective inhibitor of acetylcholinesterase (AChE), and it has multiple targets when used for Alzheimer's disease (AD) therapy. In this study, we searched for new mechanisms by which HupA could activate Wnt signaling and reduce amyloidosis in AD brain. A nasal gel containing HupA was prepared. No obvious toxicity of intranasal administration of HupA was found in mice. HupA was administered intranasally to beta-amyloid (Abeta) precursor protein and presenilin-1 double-transgenic mice for 4 months. We observed an increase in ADAM10 and a decrease in BACE1 and APP695 protein levels and, subsequently, a reduction in Abeta levels and Abeta burden were present in HupA-treated mouse brain, suggesting that HupA enhances the nonamyloidogenic APP cleavage pathway. Importantly, our results further showed that HupA inhibited GSK3alpha/beta activity, and enhanced the beta-catenin level in the transgenic mouse brain and in SH-SY5Y cells overexpressing Swedish mutation APP, suggesting that the neuroprotective effect of HupA is not related simply to its AChE inhibition and antioxidation, but also involves other mechanisms, including targeting of the Wnt/beta-catenin signaling pathway in AD brain.
ESTHER : Wang_2011_Neuropsychopharmacology_36_1073
PubMedSearch : Wang_2011_Neuropsychopharmacology_36_1073
PubMedID: 21289607

Title : Functional motor nerve regeneration without motor-sensory specificity following end-to-side neurorrhaphy: an experimental study - Yu_2011_J.Hand.Surg.Am_36_2010
Author(s) : Yu Q , Lin ZK , Ding J , Wang T , Chi YL , Gao WY
Ref : J Hand Surg Am , 36 :2010 , 2011
Abstract : PURPOSE: To evaluate the quality of regenerating myelinated axons and motor-sensory specificity in an end-to-side nerve repair model. METHODS: We divided 20 rats into 3 groups: (1) end-to-side neurorrhaphy using the ulnar nerve as donor nerve and the musculocutaneous nerve as recipient nerve; (2) normal control; and (3) transected nerve with the stumps buried. At 5 months, we monitored the grooming test, the electrophysiological response, and the histologic changes in nerve and muscle. RESULTS: Grooming recovered successfully, and electrophysiological investigations revealed that the target muscles had been reinnervated in the end-to-side group. The mean wet weight of the reinnervated biceps brachii muscle was 72% of the normal muscle, and the mean muscle fiber cross-sectional area of the reinnervated muscle was similar to the normal muscle. The implanted musculocutaneous nerve contained varying but satisfactory numbers of axons (end-to-side group: 596 +/- 348 vs normal group: 1,340 +/- 241). Acetylcholinesterase staining revealed a similar percentage of myelinated fibers in the musculocutaneous nerve (39%) and the biceps brachii branch of the musculocutaneous nerve (38%) in the end-to-side group. This was similar to the number of myelinated fibers in the donor ulnar nerve (37%). CONCLUSIONS: The present study confirms that limited but functional reinnervation can occur on the basis of collateral sprouting of intact axons from the ulnar nerve. The motor-sensory specificity is not important.
ESTHER : Yu_2011_J.Hand.Surg.Am_36_2010
PubMedSearch : Yu_2011_J.Hand.Surg.Am_36_2010
PubMedID: 22123048

Title : Cardiac abnormalities in severe acute dichlorvos poisoning - He_2011_Crit.Care.Med_39_1906
Author(s) : He X , Li C , Wei D , Wu J , Shen L , Wang T
Ref : Critical Care Medicine , 39 :1906 , 2011
Abstract : OBJECTIVE: Patients with organophosphorus poisoning sometimes die suddenly during rigorous treatment, possibly from myocardial injury. This study sought to elucidate the mechanisms underlying organophosphorus poisoning-induced cardiotoxicity. DESIGN: Prospective observational study. SETTING: Urban, tertiary teaching hospital emergency intensive care unit with 10 beds. PATIENTS: Forty-one patients with severe acute dichlorvos poisoning were consecutively enrolled (n = 92) at emergency intensive care unit and followed for 3 months. MEASUREMENTS AND MAIN RESULTS: Levels of serum creatine kinase isoenzyme myocardium, cardiac troponin I, acetylcholinesterase, acetylcholine, epinephrine, and norepinephrine were tested on hospital days 1, 3, and 5 and on discharge day. Electrocardiography was recorded on admission and then every other day. Transthoracic echocardiography was performed at admission, in the acute phase, before discharge, and during follow-up. Technetium 99m-sestamibi myocardial single photon emission computed tomography was conducted in four patients. Thirty-seven (90.2%) patients survived and four (9.8%) patients died during treatment. We observed sinus tachycardia in 37 (90.2%) patients and ST-T changes in 33 (80.4%) patients. Creatine kinase isoenzyme myocardium and cardiac troponin I levels peaked at day 3 postadmission and then decreased to normal levels. Serum acetylcholine, epinephrine, and norepinephrine peaked at day 1 after admission and then decreased. Echocardiography revealed marked decreases in wall motion of the interventricular septum and left ventricle in the acute phase but returned to normal in the recovery phase. The left ventricular ejection fraction improved significantly from 42 +/- 5% to 59 +/- 4% (p = .001). Single photon emission computed tomography showed abnormal left ventricle perfusion. CONCLUSION: Severe acute dichlorvos poisoning is associated with reversible myocardial dysfunction, possibly through an increase in catecholamine levels.
ESTHER : He_2011_Crit.Care.Med_39_1906
PubMedSearch : He_2011_Crit.Care.Med_39_1906
PubMedID: 21516037

Title : Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization - Zhao_2011_Hepatology_53_493
Author(s) : Zhao Y , Wang X , Wang T , Hu X , Hui X , Yan M , Gao Q , Chen T , Li J , Yao M , Wan D , Gu J , Fan J , He X
Ref : Hepatology , 53 :493 , 2011
Abstract : UNLABELLED: Acetylcholinesterase (ACHE) plays important roles in the cholinergic system, and its dysregulation is involved in a variety of human diseases. However, the roles and implications of ACHE in hepatocellular carcinoma (HCC) remain elusive. Here we demonstrate that ACHE was significantly down-regulated in the cancerous tissues of 69.2% of HCC patients, and the low ACHE expression in HCC was correlated with tumor aggressiveness, an elevated risk of postoperative recurrence, and a low survival rate. Both the recombinant ACHE protein and the enhanced expression of ACHE significantly inhibited HCC cell growth in vitro and tumorigenicity in vivo. Further study showed that ACHE suppressed cell proliferation via its enzymatic activity of acetylcholine catalysis and degradation. Moreover, ACHE could inactivate mitogen-activated protein kinase and phosphatidyl inositol-3'-phosphate kinase/protein kinase B pathways in HCC cells and thereby increase the activation of glycogen synthase kinase 3beta and lead to beta-catenin degradation and cyclin D1 suppression. In addition, increased ACHE expression could remarkably sensitize HCC cells to chemotherapeutic drugs (i.e., adriamycin and etoposide). CONCLUSION: For the first time, we describe the function of ACHE as a tumor growth suppressor in regulating cell proliferation, the relevant signaling pathways, and the drug sensitivity of HCC cells. ACHE is a promising independent prognostic predictor for HCC recurrence and the survival of HCC patients. These findings provide new insights into potential strategies for drug discovery and improved HCC treatment.
ESTHER : Zhao_2011_Hepatology_53_493
PubMedSearch : Zhao_2011_Hepatology_53_493
PubMedID: 21274871

Title : Reduced glutathione attenuates liver injury induced by methyl parathion in rats - Jiang_2010_Toxicol.Mech.Methods_20_69
Author(s) : Jiang N , Lu L , Wang T , Zhang L , Xin W , Fu F
Ref : Toxicol Mech Methods , 20 :69 , 2010
Abstract : The aim of this study was to investigate whether exogenous reduced glutathione (GSH) could protect liver injury induced by methyl parathion. Rats were allocated into four groups named as control, MP (methyl parathion poisoning), MP+GSH1 (methyl parathion poisoning treated with GSH 600 mg/kg), and MP+GSH2 (methyl parathion poisoning treated with GSH 1200 mg/kg). Each one of the last three groups was assigned into 6 h, 24 h, and 72 h sub-groups. The activities of acetylcholinesterase (AChE), glutamate pyruvate transaminase (GPT), and glutamic oxalacetic transaminase (GOT) in plasma, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver were assayed. The malondialdehyde (MDA) in liver was also determined. Histopathological changes in liver were observed. Results showed that AChE activity was significantly inhibited by methyl parathion and attenuated after GSH administered. GSH could relieve hepatocellular edema and fatty degeneration, and attenuate the increased activities of GPT and GOT. GSH treatment increased the SOD and GPx activities, but had no effect on the MDA level. These results indicated that GSH could attenuate liver injury induced by methyl parathion.
ESTHER : Jiang_2010_Toxicol.Mech.Methods_20_69
PubMedSearch : Jiang_2010_Toxicol.Mech.Methods_20_69
PubMedID: 20100039

Title : Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes - Zhang_2010_Neurochem.Int_57_119
Author(s) : Zhang L , Fu F , Zhang X , Zhu M , Wang T , Fan H
Ref : Neurochem Int , 57 :119 , 2010
Abstract : Considerable evidence has been accumulated demonstrating an important role for inflammation in ischemic brain injury and its contribution to greater cerebral damage after ischemia. Blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, demonstrates antiedematous and anti-inflammatory effects. Here we assessed neuroprotective effects of escin with a transient global cerebral ischemia model. Global cerebral ischemia was induced by occluding both common carotid arteries and withdrawing 0.3ml of blood from the tail vein in mice. Treatment with escin was initiated 0.5h after ischemia induction and given once a day for three consecutive days. Then animals were assessed using the Morris water-maze test and step-down passive avoidance test. Acetylcholinesterase (AChE) activity, histological pathology, and expression of inflammatory genes in the hippocampus were determined. The results showed escin significantly improved learning and memory recovery and reduced hippocampal damage in the cerebral ischemic mice. However, donepezil merely improved learning and memory recovery but did not ameliorate hippocampal damage in the cerebral ischemic mice. Furthermore, we found escin significantly downregulated certain inflammatory gene expression and upregulated expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was recently reported as a neuroprotective protein in the brain. Our results indicate that inhibition of inflammation and protection of hippocampal neurons by escin may be a potentially useful therapy for ischemic brain injury.
ESTHER : Zhang_2010_Neurochem.Int_57_119
PubMedSearch : Zhang_2010_Neurochem.Int_57_119
PubMedID: 20466027

Title : Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica - Wang_2010_Planta.Med_76_1642
Author(s) : Wang T , Choi RC , Li J , Bi CWC , Zang L , Liu Z , Dong TTX , Bi K , Tsim KWK
Ref : Planta Med , 76 :1642 , 2010
Abstract : Developing drugs against metabolic-related disorders, including obesity and hyperlipidemia, is of importance for human health. Here, a bioactive phytochemical, protodioscin, isolated from the rhizomes of Dioscorea nipponica (Rhizoma Dioscoreae Nipponicae), was identified for its anti-hyperlipidemic effect. In hyperlipidemic rats, the post-administration of protodioscin significantly reduced the time of blood coagulation. In addition, the blood levels of triglyceride, cholesterol, low-density and high-density lipoproteins were also changed accordingly. Taken together, this was the first report of an antihyperlipidemic effect of protodioscin. Its great availability in various vegetables and medicinal plants will be useful in developing health food supplement(s) and/or drug(s) against hyperlipidemia.
ESTHER : Wang_2010_Planta.Med_76_1642
PubMedSearch : Wang_2010_Planta.Med_76_1642
PubMedID: 20509104

Title : Synthesis of benzofuran derivatives via rearrangement and their inhibitory activity on acetylcholinesterase - Zhou_2010_Molecules_15_8593
Author(s) : Zhou X , Li M , Wang XB , Wang T , Kong LY
Ref : Molecules , 15 :8593 , 2010
Abstract : During a synthesis of coumarins to obtain new candidates for treating Alzheimer's Disease (AD), an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.
ESTHER : Zhou_2010_Molecules_15_8593
PubMedSearch : Zhou_2010_Molecules_15_8593
PubMedID: 21116228

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Immobilization of lipase on methyl-modified silica aerogels by physical adsorption - Gao_2009_Bioresour.Technol_100_996
Author(s) : Gao S , Wang Y , Wang T , Luo G , Dai Y
Ref : Bioresour Technol , 100 :996 , 2009
Abstract : In this work, methyl-modified silica aerogels, a new kind of macro-porous material with high porosity, were used as carriers to immobilize lipase by adsorption. SEM, TEM, nitrogen adsorption device, and thermogravimetric analysis were used to characterize the properties of modified aerogels. The surface area was 395.6 m(2)/g, and the average pore diameter was 68.72 nm. The contact angle of aerogel particles increased from 20.9 degrees to 99.2 degrees after methyl modification. Reaction characteristics of the material after enzyme loading were also discussed. The results showed that adsorption capacity could reach 67.42 mg/g; and the maximal enzyme activity was 19.87 micromol min(-1)mg(-1) (protein), and activity retention could reach 56.44%. It is worth mentioning that the amount of modified aerogels added had significant effects on the diameter of droplets and the mass transfer behavior of substrates in the reaction emulsion. Online microscope was used to visualize the droplets in the emulsion, where the aerogel particles were observed locating at the interface of oil and water. The average diameter of droplets reached the minimum when 0.06 g of modified aerogels was added into the reaction emulsion which contained 10 ml of oil and 10 ml of phosphate buffer solution. The phenomenon was resulted from the wettability of methyl-modified silica aerogels.
ESTHER : Gao_2009_Bioresour.Technol_100_996
PubMedSearch : Gao_2009_Bioresour.Technol_100_996
PubMedID: 18684619

Title : Effects of G994T in the Lp-PLA2 gene on the plasma oxidized LDL level and carotid intima-media thickness in Japanese: the Shimane study - Wang_2009_Am.J.Hypertens_22_742
Author(s) : Wang T , Karino K , Yamasaki M , Zhang Y , Masuda J , Yamaguchi S , Shiwaku K , Nabika T
Ref : Am J Hypertens , 22 :742 , 2009
Abstract : BACKGROUND: A single-nucleotide polymorphism (SNP), G994T, in the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) gene is known to have a potent influence on the activity of the enzyme. As this enzyme hydrolyzes oxidized low-density lipoprotein (oxLDL), which is an important player in atherogenesis, the present study evaluated effects of the G994T genotype on the oxLDL level as well as on intima media thickness (IMT) in vivo.
METHODS: Participants of a health examination (1,307 in total) were recruited from two rural communities in Shimane, Japan. Genotyping was performed by an allele-specific PCR and the TaqMan method. The oxLDL level was determined by an enzyme immunoassay.
RESULTS: The minor allele (994T) frequency (0.19) in the studied populations was consistent with previous reports on Japanese. The 994T allele increased the plasma oxLDL/LDL ratio in a recessive manner, whereas 994T had a codominant effect on the Lp-PLA(2) activity. A multivariate analysis revealed that age and the G994T genotype had independent effects on the oxLDL/LDL level. By contrast, the G994T genotype was not associated with IMT. All of these results were reproducible in the two independent populations studied.
CONCLUSIONS: G994T influenced plasma LDL oxidation. Further studies on the effect of this polymorphism in cardiovascular diseases are warranted.
ESTHER : Wang_2009_Am.J.Hypertens_22_742
PubMedSearch : Wang_2009_Am.J.Hypertens_22_742
PubMedID: 19373214
Gene_locus related to this paper: human-PLA2G7

Title : Protective effect of reduced glutathione on the respiratory muscle injury induced by acute omethoate poisoning - Lu_2009_Pestic.Biochem.Physiol_95_135
Author(s) : Lu L , Fu F , Wang T , He P , Xin W , Li C
Ref : Pesticide Biochemistry and Physiology , 95 :135 , 2009
Abstract : The aim of this work was to investigate whether reduced glutathione (GSH) could protect rats from the respiratory muscle injury induced by omethoate. Three groups named as control, OM (omethoate poisoning) and OM + GSH (omethoate poisoning treated with GSH) were arranged. The cholinesterase (ChE) activity was assayed and the pathological observation of respiratory muscles was carried out. Furthermore, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and the free organophosphate (FOP) remained in the respiratory muscles were measured. The results indicated that ChE activity was significantly inhibited by omethoate and not be changed by GSH. GSH could attenuate the respiratory muscle injury after omethoate poisoning. No changes of SOD, GPx, CAT and FOP were found after GSH was given. The findings suggested that GSH could protect the respiratory muscle against injury induced by omethoate, which was not the result of GSH to reactivate ChE or regulate the antioxidant enzymes.
ESTHER : Lu_2009_Pestic.Biochem.Physiol_95_135
PubMedSearch : Lu_2009_Pestic.Biochem.Physiol_95_135

Title : From a consortium sequence to a unified sequence: the Bacillus subtilis 168 reference genome a decade later - Barbe_2009_Microbiology_155_1758
Author(s) : Barbe V , Cruveiller S , Kunst F , Lenoble P , Meurice G , Sekowska A , Vallenet D , Wang T , Moszer I , Medigue C , Danchin A
Ref : Microbiology , 155 :1758 , 2009
Abstract : Comparative genomics is the cornerstone of identification of gene functions. The immense number of living organisms precludes experimental identification of functions except in a handful of model organisms. The bacterial domain is split into large branches, among which the Firmicutes occupy a considerable space. Bacillus subtilis has been the model of Firmicutes for decades and its genome has been a reference for more than 10 years. Sequencing the genome involved more than 30 laboratories, with different expertises, in a attempt to make the most of the experimental information that could be associated with the sequence. This had the expected drawback that the sequencing expertise was quite varied among the groups involved, especially at a time when sequencing genomes was extremely hard work. The recent development of very efficient, fast and accurate sequencing techniques, in parallel with the development of high-level annotation platforms, motivated the present resequencing work. The updated sequence has been reannotated in agreement with the UniProt protein knowledge base, keeping in perspective the split between the paleome (genes necessary for sustaining and perpetuating life) and the cenome (genes required for occupation of a niche, suggesting here that B. subtilis is an epiphyte). This should permit investigators to make reliable inferences to prepare validation experiments in a variety of domains of bacterial growth and development as well as build up accurate phylogenies.
ESTHER : Barbe_2009_Microbiology_155_1758
PubMedSearch : Barbe_2009_Microbiology_155_1758
PubMedID: 19383706

Title : Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice - Chen_2008_Pharmacol.Biochem.Behav_90_441
Author(s) : Chen J , Long Y , Han M , Wang T , Chen Q , Wang R
Ref : Pharmacol Biochem Behav , 90 :441 , 2008
Abstract : The water-soluble derivative of propolis (WSDP) was prepared from fresh Chinese propolis. Its major constituents were identified by high performance liquid chromatography (HPLC) analysis. It has been reported that propolis possessed a broad spectrum of biological activities but including few studies on learning and memory by now. Thus, this study was aimed to investigate the effect of WSDP on scopolamine-induced learning and memory impairment in mice. WSDP (50 mg/kg, 100 mg/kg) was given by intragastric administration (i.g.) 40 min prior to the intraperitoneal (i.p.) injection of scopolamine (1 mg/kg). The effect on amnesia was investigated with both hidden-platform acquisition training and probe trial testing in Morris water maze test. The results from 100 mg/kg WSDP group showed significant mitigation scopolamine-induced amnesia in mice. Furthermore, WSDP's effect on the acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus was also assayed. As a result, WSDP (100 mg/kg) significantly inhibited AChE activity in the hippocampus of scopolamine-treated mice. These results indicated that WSDP may mitigate amnesia in vivo through inhibition of AChE activity in the hippocampus, which suggested propolis may have potential as a pharmaceutical of brain protection with elderly population for preventing Alzheimer's disease (AD) and other neurodegenerative diseases.
ESTHER : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedSearch : Chen_2008_Pharmacol.Biochem.Behav_90_441
PubMedID: 18485465

Title : Design, synthesis, and acetylcholinesterase inhibitory activity of novel coumarin analogues - Zhou_2008_Bioorg.Med.Chem_16_8011
Author(s) : Zhou X , Wang XB , Wang T , Kong LY
Ref : Bioorganic & Medicinal Chemistry , 16 :8011 , 2008
Abstract : Three series (series A-C) of coumarin analogues with phenylpiperazine functions as substitution were designed and synthesized for studying their potential for treating Alzheimer's (AD) disease. Their anticholinesterase activities were assayed according to Ellmann's method against freshly prepared acetylcholinesterase (AChE) from Electrophorus electricus using donepezil as the reference compound. Pharmacological study and preliminary structure-activity relationships showed that coumarins with substitution on positions 3 and/or 4 have parallel anti-AchE activities compared with the reference compound.
ESTHER : Zhou_2008_Bioorg.Med.Chem_16_8011
PubMedSearch : Zhou_2008_Bioorg.Med.Chem_16_8011
PubMedID: 18701305

Title : Immobilized capillary enzyme reactor based on layer-by-layer assembling acetylcholinesterase for inhibitor screening by CE - Tang_2007_Electrophoresis_28_2981
Author(s) : Tang Z , Wang T , Kang J
Ref : Electrophoresis , 28 :2981 , 2007
Abstract : A method for creating an immobilized capillary acetylcholinesterase (AChE) reactor based on a layer-by-layer (LBL) assembly for inhibitor screening is described. The unique capillary AChE reactor was easily prepared by the instrument in three steps: first, a 0.5 cm long plug of a solution of the cationic polyelectrolyte polydiallyldimethylammonium (PDDA) was injected into the capillary to produce a positively charged coating on the surface of the capillary; subsequently, the enzyme solution with the same plug length was injected into the capillary and incubated for 10 min to immobilize the enzyme on the capillary wall via electrostatic interaction; third, PDDA solution with the same plug length was injected again into the capillary to cover the immobilized enzyme by forming PDDA-AChE-PDDA sandwich-like structure. The enzyme reactor can be easily renewed after removing the immobilized enzyme by flushing the column with 1 M NaCl solution. Activity of the immobilized enzyme can be assayed simply by carrying out an electrophoretic separation, i.e., the substrate solution was injected and incubated for a short time, followed by applying a voltage to separate the product from the unreacted substrate. The measured peak area of the product then represented the enzyme activity. For enzyme inhibitor screening, the mixture solution of the substrate and the inhibitor was injected and assayed the reduction of the enzyme activity. The immobilized enzyme could withstand 100 consecutive assays by only losing 10% activity. The reproducibility in terms of time-to-time, day-to-day, and batch-to-batch was measured with RSD% less than 4.7%. Furthermore, the screening system was validated by a known inhibitor. Finally, screening a small compound library containing four known AChE inhibitors and 42 natural extracts was demonstrated, and species with inhibition activity can be straightforwardly identified with the system.
ESTHER : Tang_2007_Electrophoresis_28_2981
PubMedSearch : Tang_2007_Electrophoresis_28_2981
PubMedID: 17674420

Title : Immobilization of lipase on epoxy activated (1-->3)-alpha-D-glucan isolated from Penicillium chrysongenum - Wang_2006_Biosci.Biotechnol.Biochem_70_2883
Author(s) : Wang T , Li H , Nie K , Tan T
Ref : Biosci Biotechnol Biochem , 70 :2883 , 2006
Abstract : A water-insoluble linear (1-->3)-alpha-D-glucan was isolated from Penicillium mycelia. Three kinds of epoxy-activated microspheres of this glucan were prepared as supports for Candida sp. lipase (EC3.1.1.3) immobilization. The highest immobilization yield was 36.4%. The specific activity was 26.85 U/mg, and only 4.1% of activity was lost in comparison with the free enzyme used for immobilization. The higher thermal stability, storage stability, and reusability of the immobilized lipase make it a potential candidate for wide application.
ESTHER : Wang_2006_Biosci.Biotechnol.Biochem_70_2883
PubMedSearch : Wang_2006_Biosci.Biotechnol.Biochem_70_2883
PubMedID: 17151459

Title : Proteomic analyses of Oryza sativa mature pollen reveal novel proteins associated with pollen germination and tube growth - Dai_2006_Proteomics_6_2504
Author(s) : Dai S , Li L , Chen T , Chong K , Xue Y , Wang T
Ref : Proteomics , 6 :2504 , 2006
Abstract : As a highly reduced organism, pollen performs specialized functions to generate and carry sperm into the ovule by its polarily growing pollen tube. Yet the molecular genetic basis of these functions is poorly understood. Here, we identified 322 unique proteins, most of which were not reported previously to be in pollen, from mature pollen of Oryza sativa L. ssp japonica using a proteomic approach, 23% of them having more than one isoform. Functional classification reveals that an overrepresentation of the proteins was related to signal transduction (10%), wall remodeling and metabolism (11%), and protein synthesis, assembly and degradation (14%), as well as carbohydrate and energy metabolism (25%). Further, 11% of the identified proteins are functionally unknown and do not contain any conserved domain associated with known activities. These analyses also identified 5 novel proteins by de novo sequencing and revealed several important proteins, mainly involved in signal transduction (such as protein kinases, receptor kinase-interacting proteins, guanosine 5'-diphosphate dissociation inhibitors, C2 domain-containing proteins, cyclophilins), protein synthesis, assembly and degradation (such as prohibitin, mitochondrial processing peptidase, putative UFD1, AAA+ ATPase), and wall remodeling and metabolism (such as reversibly glycosylated polypeptides, cellulose synthase-like OsCsLF7). The study is the first close investigation, to our knowledge, of protein complement in mature pollen, and presents useful molecular information at the protein level to further understand the mechanisms underlying pollen germination and tube growth.
ESTHER : Dai_2006_Proteomics_6_2504
PubMedSearch : Dai_2006_Proteomics_6_2504
PubMedID: 16548068

Title : Enzymatic chlorophyll degradation in wheat near-isogenic lines elicited by cereal aphid (Homoptera: Aphididae) feeding - Wang_2004_J.Econ.Entomol_97_661
Author(s) : Wang T , Quisenberry SS , Ni X , Tolmay V
Ref : J Econ Entomol , 97 :661 , 2004
Abstract : Chlorophyll degradation enzyme (i.e., chlorophyllase, Mg-dechelatase, and chlorophyll oxidase) activities of aphid-infested and uninfested 'Tugela' and Tugela near-isogenic wheat lines (i.e., Tugela-Dn1, Tugela-Dn2, and Tugela-Dn5) were assayed. Chlorophyllase activity was higher in bird cherry-oat aphid, Rhopalosiphum padi (L.) (Homoptera: Aphididae),-infested wheat lines compared with Russian wheat aphid, Diuraphis noxia (Mordvilko) (Homoptera: Aphididae)]-infested and uninfested plants. Mg-dechelatase activity was higher in D. noxia-infested wheat lines than in R. padi-infested and uninfested plants. Also, Mg-dechelatase activity was lower in Tugela wheat infested with D. noxia than in Tugela near-isogenic lines with Dn genes. Based on the in vitro assays of chlorophyll degradation enzyme (i.e., chlorophyllase and Mg-dechelatase) activities, we proposed that the chlorotic symptoms observed on D. noxia-infested Tugela wheat were most likely to be elicited by unbalanced chlorophyll biosynthesis and degradation.
ESTHER : Wang_2004_J.Econ.Entomol_97_661
PubMedSearch : Wang_2004_J.Econ.Entomol_97_661
PubMedID: 15154496

Title : Global analysis of the Bacillus subtilis Fur regulon and the iron starvation stimulon - Baichoo_2002_Mol.Microbiol_45_1613
Author(s) : Baichoo N , Wang T , Ye R , Helmann JD
Ref : Molecular Microbiology , 45 :1613 , 2002
Abstract : The Bacillus subtilis ferric uptake repressor (Fur) protein coordinates a global transcriptional response to iron starvation. We have used DNA microarrays to define the Fur regulon and the iron starvation stimulon. We identify 20 operons (containing 39 genes) that are derepressed both by mutation of fur and by treatment of cells with the iron chelator 2,2'-dipyridyl. These operons are direct targets of Fur regulation as judged by DNase I footprinting. Analyses of lacZ reporter fusions to six Fur-regulated promoter regions reveal that repression is highly selective for iron. In addition to the Fur regulon, iron starvation induces members of the PerR regulon and leads to reduced expression of cytochromes. However, we did not find any evidence for genes that are directly activated by Fur or repressed by Fur under iron-limiting conditions. Although genome searches using the 19 bp Fur box consensus are useful in identifying candidate Fur-regulated genes, some genes associated with Fur boxes are not demonstrably regulated by Fur, whereas other genes are regulated from sites with little apparent similarity to the conventional Fur consensus.
ESTHER : Baichoo_2002_Mol.Microbiol_45_1613
PubMedSearch : Baichoo_2002_Mol.Microbiol_45_1613
PubMedID: 12354229
Gene_locus related to this paper: bacsu-YUII

Title : Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine - Wang_1998_Eur.J.Pharmacol_349_137
Author(s) : Wang T , Tang XC
Ref : European Journal of Pharmacology , 349 :137 , 1998
Abstract : The effects of (-)-huperzine A ((5R,9R,11E)-5-amino-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5, 9-methanocycloocta[b]pyridin-2(1H)-one), and of the hydrochloride salt of E2020 ((R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine) and tacrine (9-amino-1,2,3,4-tetrahydroacridine), on the scopolamine-induced memory deficits in rats were compared in a radial maze, using a 4-out-of-8 baiting procedure. Scopolamine (0.15 mg/kg, i.p.) caused significant impairment in the rats' ability to fulfil the radial maze task. (-)-Huperzine A (0.2-0.4 mg/kg, p.o.; 0.1-0.4 mg/kg, i.p.) had greater efficacy than E2020 (0.6-0.9 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) and tacrine (1.5-2.5 mg/kg, p.o.; 0.3-0.6 mg/kg, i.p.) on the improvement of scopolamine-induced working and reference memory errors, respectively. There appeared to be an inverse bell-shape dose-dependent effect for all three compounds tested. The compared data demonstrate that (-)-huperzine A is the most potent and orally active acetylcholinesterase inhibitor of the three, and fits more closely the established criterions for an ideal acetylcholinesterase inhibitor to be used in clinical studies.
ESTHER : Wang_1998_Eur.J.Pharmacol_349_137
PubMedSearch : Wang_1998_Eur.J.Pharmacol_349_137
PubMedID: 9671090

Title : [Injury effects of nicotine on isolated rat common carotid artery] - Wang_1997_Zhonghua.Yi.Xue.Za.Zhi_77_115
Author(s) : Wang T , Gu Y , Wu G
Ref : Zhonghua Yi Xue Za Zhi , 77 :115 , 1997
Abstract : OBJECTIVES: To investigate the injured effects of nicotine on isolated rat common carotid artery and to supply experimental proofs for vascular vessel and organ transplantation.
METHODS: Asins relaxing and contractile functional test of isolated vascular vessel and scanning electron microscopy techniques, we observed the influence of nicotine on the contractile and the relaxing function of isolated artery and the intact of the intima.
RESULTS: Lower concentrations of nicotine (6 x-10 mol/L-6 x 10(-6) mol/L) produced a concentration-dependent constrictor response of 18%-41% relative to those induced by norepinephrine (NE, 10(-7) mol/L), whereas removal of endothelium reduced nicotine-induced constrictions to 5%-21%. Higher concentrations of nicotine (6 x 10(-5) mol/L-6 x 10(-3) mol/L) not only injured contractile function of vascular smooth muscle but also caused severe damage to the intima. Various concentrations of nicotine all inhibited acetylcholine-induced relaxation response.
CONCLUSIONS: Nicotine not only has cytotoxicity to vascular vessel but also results in vasoconstrictor effects which depend upon endothelium intact, probably by inhibiting the release of endothelium-derived relaxing factor.
ESTHER : Wang_1997_Zhonghua.Yi.Xue.Za.Zhi_77_115
PubMedSearch : Wang_1997_Zhonghua.Yi.Xue.Za.Zhi_77_115
PubMedID: 9596942

Title : Repetitive impulse activity potentiates spontaneous acetylcholine secretion at developing neuromuscular synapses - Lo_1991_J.Physiol.Paris_85_71
Author(s) : Lo YJ , Wang T , Poo MM
Ref : Journal de Physiologie (Paris) , 85 :71 , 1991
Abstract : The effects of presynaptic impulse activity on the transmitter secretion at developing neuromuscular junctions were examined in Xenopus nerve-muscle cultures. Repetitive suprathreshold stimulation of the presynaptic neuron results in marked potentiation of spontaneous synaptic activity, as shown by whole-cell voltage-clamp recording of synaptic currents in the postsynaptic muscle cell. Our results are consistent with the notion that synaptic efficacy of the developing synapse is potentiated by the presence of electrical activity. Such activity-dependent synaptic modulation enables the early neuronal activity to play a regulatory role during the maturation of synaptic connections.
ESTHER : Lo_1991_J.Physiol.Paris_85_71
PubMedSearch : Lo_1991_J.Physiol.Paris_85_71
PubMedID: 1757892

Title : Presynaptic calcium channels in rat cortical synaptosomes: fast-kinetics of phasic calcium influx, channel inactivation, and relationship to nitrendipine receptors - Suszkiw_1986_J.Neurosci_6_1349
Author(s) : Suszkiw JB , O'Leary ME , Murawsky MM , Wang T
Ref : Journal of Neuroscience , 6 :1349 , 1986
Abstract : Fast-mixing and rapid-filtration techniques were used to analyze the kinetics of potassium-depolarization-dependent (delta K+ = 47.5 mM) influx of 45Ca into synaptosomes, in the time range from 50 msec to 5 sec. The results are consistent with the presence in synaptosomes of a homogeneous population of voltage-sensitive Ca channels. With 1 mM Cao in the medium, the delta K+-dependent Ca influx has a single-exponential time course with the half-life, t1/2 approximately 0.5-0.7 sec. Ca influx, measured between 0.1 and 10 mM Cao, shows half-saturation (KCa) at 1.5 mM Cao and has the limiting value (JCamax) of 5.9 nmol/sec/mg protein, or a current of approximately 0.06 pA/micron2 surface area. The estimated density of functional Ca channels is 0.6-6 micron-2. Voltage- and time-dependent inactivation of Ca channels was measured in synaptosomes predepolarized in 52.5 mM Ko+ with Ca omitted from the medium. Channel inactivation is a single-exponential process with a half-life of t1/2 approximately 2.3 sec. Channel recovery in 5 mM Ko+ media is likewise a single-exponential process with a half-life of t1/2 approximately 4.3 sec. The slower rate of voltage-dependent channel inactivation than of decay of Ca influx suggests that Ca entry into synaptosomes terminates by a mechanism that depends on Ca influx itself. Synaptosomes contain 200 fmol/mg protein, or approximately 6 micron-2 high-affinity (KD = 0.12 nM) 3H-nitrendipine binding sites; however, nitrendipine at concentrations greater than 10(4) X KD is without effect on the phasic influx of Ca measured at 215 msec with either 1.0 or 0.1 mM Cao. This suggests that Ca channels characterized in this study belong to a class of dihydropyridine-insensitive channels.
ESTHER : Suszkiw_1986_J.Neurosci_6_1349
PubMedSearch : Suszkiw_1986_J.Neurosci_6_1349
PubMedID: 2423658