Author Report for: Wang TNo contact information in database for Wang T
Dong H, Zhao L, Wang T, Chen Y, Hao W, Zhang Z, Hao Y, Zhang C, Wei X and Xu M <2 more 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 (- 2) Ref: Analytical Chemistry, :, 2023 : PubMed ESTHER: Dong_2023_Anal.Chem__ PubMedSearch: Dong 2023 Anal.Chem PubMedID: 37192372 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. Title: Plasminogen decreases Abeta42 and Tau deposition, and shows multi-beneficial effects on Alzheimer's disease in mice and humans Guo C, Wang T, Zhang D, Ge X, Li J Ref: Biochemical & Biophysical Research Communications, 654:102, 2023 : PubMed ESTHER: Guo_2023_Biochem.Biophys.Res.Commun_654_102 PubMedSearch: Guo 2023 Biochem.Biophys.Res.Commun 654 102 PubMedID: 36905760 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 bloodbrain 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. Title: Hyperoside inhibits pancreatic lipase activity in vitro and reduces fat accumulation in vivo Zhang X, Li D, Wang K, Xie J, Liu Y, Wang T, Liu S, Huang Q, Guo Q, Wang H Ref: Food Funct, :, 2023 : PubMed ESTHER: Zhang_2023_Food.Funct__ PubMedSearch: Zhang 2023 Food.Funct PubMedID: 37128768 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. Title: Sertoli cell survival and barrier function are regulated by miR-181c/d-Pafah1b1 axis during mammalian spermatogenesis 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 : PubMed ESTHER: Feng_2022_Cell.Mol.Life.Sci_79_498 PubMedSearch: Feng 2022 Cell.Mol.Life.Sci 79 498 PubMedID: 36008729 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. Title: Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry Hu C, Zhuang X, Zhang J, Wang T, Du S, Wang J, Peng X, Cao Q, Zhang M, Jiang Y Ref: Lab Med, :, 2022 : PubMed ESTHER: Hu_2022_Lab.Med__ PubMedSearch: Hu 2022 Lab.Med PubMedID: 35075477 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. Title: Deficiency in endocannabinoid synthase DAGLB contributes to early onset Parkinsonism and murine nigral dopaminergic neuron dysfunction Liu Z, Yang N, Dong J, Tian W, Chang L, Ma J, Guo J, Tan J, Dong A and Tang B <27 more 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 (- 27) Ref: Nat Commun, 13:3490, 2022 : PubMed 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 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. Title: Saxagliptin alleviates erectile dysfunction through increasing SDF-1 in diabetes mellitus Sun T, Xu W, Wang J, Wang T, Wang S, Liu K, Liu J Ref: Andrology, :, 2022 : PubMed ESTHER: Sun_2022_Andrology__ PubMedSearch: Sun 2022 Andrology PubMedID: 36113503 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. Title: Threaded 3D microfluidic paper analytical device-based ratiometric fluorescent sensor for background-free and visual detection of organophosphorus pesticides Tong X, Cai G, Xie L, Wang T, Zhu Y, Peng Y, Tong C, Shi S, Guo Y Ref: Biosensors & Bioelectronics, 222:114981, 2022 : PubMed ESTHER: Tong_2022_Biosens.Bioelectron_222_114981 PubMedSearch: Tong 2022 Biosens.Bioelectron 222 114981 PubMedID: 36473422 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. Title: A Portable Fluorescent Hydrogel-Based Device for On-Site Quantitation of Organophosphorus Pesticides as Low as the Sub-ppb Level Wang T, Zhang L, Xin H Ref: Front Chem, 10:855281, 2022 : PubMed ESTHER: Wang_2022_Front.Chem_10_855281 PubMedSearch: Wang 2022 Front.Chem 10 855281 PubMedID: 35572106 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. Title: Genome-Wide Identification and Analysis of Lipases in Fig Wasps (Chalcidoidea, Hymenoptera) Wei X, Li J, Wang T, Xiao J, Huang D Ref: Insects, 13:, 2022 : PubMed ESTHER: Wei_2022_Insects_13_ PubMedSearch: Wei 2022 Insects 13 PubMedID: 35621743 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. Title: Gram-Scale Synthesis of (R)-P-Chlorophenyl-1,2-Ethanediol at High Concentration by a Pair of Epoxide Hydrolases Zhang D, Lei Y, Wang T, Lin W, Chen X, Wu M Ref: Front Bioeng Biotechnol, 10:824300, 2022 : PubMed ESTHER: Zhang_2022_Front.Bioeng.Biotechnol_10_824300 PubMedSearch: Zhang 2022 Front.Bioeng.Biotechnol 10 824300 PubMedID: 35295651 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. Title: Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via alpha7nAChR-dependent JAK2/STAT3 signaling pathway Zhang C, Li M, Xie W, You C, Wang T, Fu F Ref: European Journal of Pharmacology, 940:175478, 2022 : PubMed ESTHER: Zhang_2022_Eur.J.Pharmacol_940_175478 PubMedSearch: Zhang 2022 Eur.J.Pharmacol 940 175478 PubMedID: 36563953 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. 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 Y, Wang T, Jiang Z Ref: J Sep Sci, :, 2021 : PubMed ESTHER: Huang_2021_J.Sep.Sci__ PubMedSearch: Huang 2021 J.Sep.Sci PubMedID: 33650266 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. 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 W, Wang T, Liang XR, Yang YS, Wang QZ, Cheng HF, Peng YK, Ding F Ref: J Mol Graph Model, 110:108069, 2021 : PubMed ESTHER: Peng_2021_J.Mol.Graph.Model_110_108069 PubMedSearch: Peng 2021 J.Mol.Graph.Model 110 108069 PubMedID: 34773872 Inhibitor(s) related to this paper: Pyraclofos 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. Title: Plasma cholinesterase activity is influenced by interactive effect between omethoate exposure and CYP2E1 polymorphisms Wang T, Zhang H, Li L, Zhang W, Wang Q, Wang W Ref: J Environ Sci Health B, :1, 2021 : PubMed ESTHER: Wang_2021_J.Environ.Sci.Health.B__1 PubMedSearch: Wang 2021 J.Environ.Sci.Health.B 1 PubMedID: 33872129 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. Title: The N-terminus of Lactobacillus amylovorus feruloyl esterase plays an important role in its secretion by Lactobacillus plantarum and Escherichia coli Xu Z, Zhang R, Wang T, Kong J Ref: Microb Cell Fact, 20:152, 2021 : PubMed ESTHER: Xu_2021_Microb.Cell.Fact_20_152 PubMedSearch: Xu 2021 Microb.Cell.Fact 20 152 PubMedID: 34344368 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. Title: A Valuable Product of Microbial Cell Factories: Microbial Lipase Yao W, Liu K, Liu H, Jiang Y, Wang R, Wang W, Wang T Ref: Front Microbiol, 12:743377, 2021 : PubMed ESTHER: Yao_2021_Front.Microbiol_12_743377 PubMedSearch: Yao 2021 Front.Microbiol 12 743377 PubMedID: 34616387 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. Title: Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds Zhang Y, He J, Shen L, Wang T, Yang J, Li Y, Wang Y, Quan D Ref: J Control Release, 329:1117, 2021 : PubMed ESTHER: Zhang_2021_J.Control.Release_329_1117 PubMedSearch: Zhang 2021 J.Control.Release 329 1117 PubMedID: 33096123 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. Title: Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy Zou S, Dong R, Wang J, Liang B, Zhu T, Zhao S, Zhang Y, Wang T, Zou P and Luo L <5 more 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 (- 5) Ref: J Proteomics, :104124, 2021 : PubMed ESTHER: Zou_2021_J.Proteomics__104124 PubMedSearch: Zou 2021 J.Proteomics 104124 PubMedID: 33545297 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. Title: A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y Nguyen TA, Wu K, Pandey S, Lehr AW, Li Y, Bemben MA, Badger JD, 2nd, Lauzon JL, Wang T and Roche KW <4 more 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 (- 4) Ref: Neuron, 106:759, 2020 : PubMed ESTHER: Nguyen_2020_Neuron_106_759 PubMedSearch: Nguyen 2020 Neuron 106 759 PubMedID: 32243781 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. Title: In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease 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 : PubMed ESTHER: Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849 PubMedSearch: Song 2020 Evid.Based.Complement.Alternat.Med 2020 2804849 PubMedID: 32148536 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. Title: OSBPL2 Is Required for the Binding of COPB1 to ATGL and the Regulation of Lipid Droplet Lipolysis 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 : PubMed ESTHER: Wang_2020_iScience_23_101252 PubMedSearch: Wang 2020 iScience 23 101252 PubMedID: 32650117 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. Title: Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea 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 : PubMed ESTHER: Wang_2020_Environ.Pollut_267_115397 PubMedSearch: Wang 2020 Environ.Pollut 267 115397 PubMedID: 33254654 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. Title: Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis Wang X, Zhao X, Yang Z, Wang T Ref: Journal of Agricultural and Food Chemistry, 68:12358, 2020 : PubMed ESTHER: Wang_2020_J.Agric.Food.Chem_68_12358 PubMedSearch: Wang 2020 J.Agric.Food.Chem 68 12358 PubMedID: 33084305 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. Title: Expression of ADAM29 and FAM135B in the pathological evolution from normal esophageal epithelium to esophageal cancer: Their differences and clinical significance Wang T, Lv X, Jiang S, Han S, Wang Y Ref: Oncol Lett, 19:1727, 2020 : PubMed ESTHER: Wang_2020_Oncol.Lett_19_1727 PubMedSearch: Wang 2020 Oncol.Lett 19 1727 PubMedID: 32194665 Gene_locus related to this paper: human-FAM135B 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. Title: Comparison of Enzyme Secretion and Ferulic Acid Production by Escherichia coli Expressing Different Lactobacillus Feruloyl Esterases Xu Z, Kong J, Zhang S, Wang T, Liu X Ref: Front Microbiol, 11:568716, 2020 : PubMed ESTHER: Xu_2020_Front.Microbiol_11_568716 PubMedSearch: Xu 2020 Front.Microbiol 11 568716 PubMedID: 33329424 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. Title: Chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species Zhang Y, Wu D, Kuang S, Qing M, Ma Y, Yang T, Wang T, Li D Ref: Nat Prod Res, 34:3531, 2020 : PubMed ESTHER: Zhang_2020_Nat.Prod.Res_34_3531 PubMedSearch: Zhang 2020 Nat.Prod.Res 34 3531 PubMedID: 30822132 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 Sieb.et 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. Title: Acupotomy Alleviates Energy Crisis at Rat Myofascial Trigger Points 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 : PubMed ESTHER: Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_5129562 PubMedSearch: Zhang 2020 Evid.Based.Complement.Alternat.Med 2020 5129562 PubMedID: 32190087 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. Title: Isoform-specific cleavage of neuroligin-3 reduces synapse strength Bemben MA, Nguyen TA, Li Y, Wang T, Nicoll RA, Roche KW Ref: Mol Psychiatry, 24:145, 2019 : PubMed ESTHER: Bemben_2019_Mol.Psychiatry_24_145 PubMedSearch: Bemben 2019 Mol.Psychiatry 24 145 PubMedID: 30242227 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. Title: Metabolites from the endophytic fungus colletotrichum sp. F168 Lei HM, Ma N, Wang T, Zhao PJ Ref: Nat Prod Res, :1, 2019 : PubMed ESTHER: Lei_2019_Nat.Prod.Res__1 PubMedSearch: Lei 2019 Nat.Prod.Res 1 PubMedID: 31304793 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. Title: Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents Luo W, Lv JW, Wang T, Zhang ZY, Guo HY, Song ZY, Wang CJ, Ma J, Chen YP Ref: Bioorganic & Medicinal Chemistry, :115190, 2019 : PubMed ESTHER: Luo_2019_Bioorg.Med.Chem__115190 PubMedSearch: Luo 2019 Bioorg.Med.Chem 115190 PubMedID: 31744779 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. Title: The blood parameters and liver function changed inconsistently among children between burns and traumatic injuries Nie C, Wang T, Yu H, Wang X, Zeng X, Wei Z, Shi X Ref: PeerJ, 7:e6415, 2019 : PubMed ESTHER: Nie_2019_PeerJ_7_e6415 PubMedSearch: Nie 2019 PeerJ 7 e6415 PubMedID: 30775182 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. Title: Chemical characterization of main bioactive constituents in Paeonia ostii seed meal and GC-MS analysis of seed oil Tian X, Guo S, Zhang S, Li P, Wang T, Ho CT, Pan MH, Bai N Ref: J Food Biochem, :e13088, 2019 : PubMed ESTHER: Tian_2019_J.Food.Biochem__e13088 PubMedSearch: Tian 2019 J.Food.Biochem e13088 PubMedID: 31646682 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. Title: Fabrication and Properties of a Bio-Based Biodegradable Thermoplastic Polyurethane Elastomer Wang Z, Yan J, Wang T, Zai Y, Qiu L, Wang Q Ref: Polymers (Basel), 11:, 2019 : PubMed ESTHER: Wang_2019_Polymers.(Basel)_11_ PubMedSearch: Wang 2019 Polymers.(Basel) 11 PubMedID: 31269638 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. Title: Galantamine reversed early postoperative cognitive deficit via alleviating inflammation and enhancing synaptic transmission in mouse hippocampus Wang T, Zhu H, Hou Y, Gu W, Wu H, Luan Y, Xiao C, Zhou C Ref: European Journal of Pharmacology, 846:63, 2019 : PubMed ESTHER: Wang_2019_Eur.J.Pharmacol_846_63 PubMedSearch: Wang 2019 Eur.J.Pharmacol 846 63 PubMedID: 30586550 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. Title: Potential Pharmacokinetic Herb-Drug Interactions: Have we Overlooked the Importance of Human Carboxylesterases 1 and 2? Xu J, Qiu JC, Ji X, Guo HL, Wang X, Zhang B, Wang T, Chen F Ref: Curr Drug Metab, 20:130, 2019 : PubMed ESTHER: Xu_2019_Curr.Drug.Metab_20_130 PubMedSearch: Xu 2019 Curr.Drug.Metab 20 130 PubMedID: 29600756 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. Title: Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers Ding M, Yang Y, Duan X, Wang S, Feng X, Wang T, Wang P, Liu S, Li L and Wang W <7 more 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 (- 7) Ref: Ecotoxicology & Environmental Safety, 161:563, 2018 : PubMed ESTHER: Ding_2018_Ecotoxicol.Environ.Saf_161_563 PubMedSearch: Ding 2018 Ecotoxicol.Environ.Saf 161 563 PubMedID: 29929132 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. Title: Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate 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 : PubMed ESTHER: Duan_2018_R.Soc.Open.Sci_5_172357 PubMedSearch: Duan 2018 R.Soc.Open.Sci 5 172357 PubMedID: 29892419 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. Title: A pH responsive AIE probe for enzyme assays Shi L, Liu Y, Wang Q, Wang T, Ding Y, Cao Y, Li Z, Wei H Ref: Analyst, 143:741, 2018 : PubMed ESTHER: Shi_2018_Analyst_143_741 PubMedSearch: Shi 2018 Analyst 143 741 PubMedID: 29323362 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. Title: Neurotrophins and cholinergic enzyme regulated by calpain-2: New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153 Zhang H, Yang X, Li X, Zhang Z, Hou L, Wang Z, Niu Q, Wang T Ref: Toxicol Lett, 291:29, 2018 : PubMed ESTHER: Zhang_2018_Toxicol.Lett_291_29 PubMedSearch: Zhang 2018 Toxicol.Lett 291 29 PubMedID: 29621559 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. Title: A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3 Zhang Q, Xiao X, Zheng J, Li M, Yu M, Ping F, Wang T, Wang X Ref: Biomed Res Int, 2018:3109251, 2018 : PubMed ESTHER: Zhang_2018_Biomed.Res.Int_2018_3109251 PubMedSearch: Zhang 2018 Biomed.Res.Int 2018 3109251 PubMedID: 29951533 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. Title: Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity 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 : PubMed ESTHER: Cen_2017_Eur.J.Med.Chem_144_128 PubMedSearch: Cen 2017 Eur.J.Med.Chem 144 128 PubMedID: 29268129 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. Title: Ameliorative Effect of Ginsenoside Rg1 on Lipopolysaccharide-Induced Cognitive Impairment: Role of Cholinergic System Jin Y, Peng J, Wang X, Zhang D, Wang T Ref: Neurochem Res, 42:1299, 2017 : PubMed ESTHER: Jin_2017_Neurochem.Res_42_1299 PubMedSearch: Jin 2017 Neurochem.Res 42 1299 PubMedID: 28078612 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. Title: De Novo Genome and Transcriptome Assembly of the Canadian Beaver (Castor canadensis) Lok S, Paton TA, Wang Z, Kaur G, Walker S, Yuen RK, Sung WW, Whitney J, Buchanan JA and Scherer SW <27 more 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 (- 27) Ref: G3 (Bethesda), 7:755, 2017 : PubMed 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 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. Title: Wolman's disease and cholesteryl ester storage disorder: the phenotypic spectrum of lysosomal acid lipase deficiency Pericleous M, Kelly C, Wang T, Livingstone C, Ala A Ref: Lancet Gastroenterol Hepatol, 2:670, 2017 : PubMed ESTHER: Pericleous_2017_Lancet.Gastroenterol.Hepatol_2_670 PubMedSearch: Pericleous 2017 Lancet.Gastroenterol.Hepatol 2 670 PubMedID: 28786388 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. Title: Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease Sang Z, Qiang X, Li Y, Xu R, Cao Z, Song Q, Wang T, Zhang X, Liu H and Deng Y <1 more author(s)> Sang Z, Qiang X, Li Y, Xu R, Cao Z, Song Q, Wang T, Zhang X, Liu H, Tan Z, Deng Y (- 1) Ref: Eur Journal of Medicinal Chemistry, 135:307, 2017 : PubMed ESTHER: Sang_2017_Eur.J.Med.Chem_135_307 PubMedSearch: Sang 2017 Eur.J.Med.Chem 135 307 PubMedID: 28458136 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. Title: New Drug Research and Development for Alzheimer's Pathology: Present and Prospect Wang T Ref: Shanghai Arch Psychiatry, 29:237, 2017 : PubMed ESTHER: Wang_2017_Shanghai.Arch.Psychiatry_29_237 PubMedSearch: Wang 2017 Shanghai.Arch.Psychiatry 29 237 PubMedID: 28955143 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. 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 S, Wang T, Ma X, Qin Y, Li X, Zhao Z, Liu X, Wang X, Xie H and He J <11 more 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 (- 11) Ref: Age Ageing, :1, 2017 : PubMed ESTHER: Xiao_2017_Age.Ageing__1 PubMedSearch: Xiao 2017 Age.Ageing 1 PubMedID: 28419192 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. Title: Further brominated polyacetylenes with pancreatic lipase inhibitory activity from Chinese marine sponge Xestospongia testudinaria Yang M, Liang LF, Wang T, Wang HY, Liu HL, Guo YW Ref: J Asian Nat Prod Res, 19:732, 2017 : PubMed ESTHER: Yang_2017_J.Asian.Nat.Prod.Res_19_732 PubMedSearch: Yang 2017 J.Asian.Nat.Prod.Res 19 732 PubMedID: 28152617 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). Title: End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration Yu Q, Zhang SH, Wang T, Peng F, Han D, Gu YD Ref: Neural Regen Res, 12:1703, 2017 : PubMed ESTHER: Yu_2017_Neural.Regen.Res_12_1703 PubMedSearch: Yu 2017 Neural.Regen.Res 12 1703 PubMedID: 29171436 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. Title: Clinicians' prescription preferences for treating patients with Alzheimer's disease in Shanghai Ban CX, Xiao SF, Lin X, Wang T, Qiu Q, Zhu MJ, Li X Ref: Transl Neurodegener, 5:8, 2016 : PubMed ESTHER: Ban_2016_Transl.Neurodegener_5_8 PubMedSearch: Ban 2016 Transl.Neurodegener 5 8 PubMedID: 27114822 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. Title: Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities 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 : PubMed ESTHER: Luo_2016_Bioorg.Med.Chem_24_672 PubMedSearch: Luo 2016 Bioorg.Med.Chem 24 672 PubMedID: 26752094 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. Title: Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents 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 : PubMed ESTHER: Luo_2016_Eur.J.Med.Chem_122_17 PubMedSearch: Luo 2016 Eur.J.Med.Chem 122 17 PubMedID: 27343850 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. Title: Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population Wang T, Ma X, Peng D, Zhang R, Sun X, Chen M, Yan J, Wang S, Yan D and Jia W <4 more 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 (- 4) Ref: Sci Rep, 6:20691, 2016 : PubMed ESTHER: Wang_2016_Sci.Rep_6_20691 PubMedSearch: Wang 2016 Sci.Rep 6 20691 PubMedID: 26848030 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. Title: Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation 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 : PubMed ESTHER: Zhang_2016_J.Pharmacol.Exp.Ther_359_374 PubMedSearch: Zhang 2016 J.Pharmacol.Exp.Ther 359 374 PubMedID: 27535978 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. Title: Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses Bemben MA, Nguyen QA, Wang T, Li Y, Nicoll RA, Roche KW Ref: Proc Natl Acad Sci U S A, 112:2551, 2015 : PubMed 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 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. 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 CE, Agrawal A, Zhang B, Conley ED, Degenhardt L, Heath AC, Li D, Lynskey MT, Martin NG and Bogdan R <5 more 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 (- 5) Ref: J Abnorm Psychol, 124:860, 2015 : PubMed ESTHER: Carey_2015_J.Abnorm.Psychol_124_860 PubMedSearch: Carey 2015 J.Abnorm.Psychol 124 860 PubMedID: 26595473 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. Title: Implications of Efficient Hepatic Delivery by Tenofovir Alafenamide (GS-7340) for Hepatitis B Virus Therapy Murakami E, Wang T, Park Y, Hao J, Lepist EI, Babusis D, Ray AS Ref: Antimicrobial Agents & Chemotherapy, 59:3563, 2015 : PubMed 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 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. 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 Z, Lin M, Xu M, Wang T, Ping X, Wu S, Wang Q, Zhang H Ref: J Sep Sci, 38:1663, 2015 : PubMed ESTHER: Yao_2015_J.Sep.Sci_38_1663 PubMedSearch: Yao 2015 J.Sep.Sci 38 1663 PubMedID: 25755196 Inhibitor(s) related to this paper: Isocarbophos 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. Title: The impact of surgery and anesthesia on post-operative cognitive decline and Alzheimer's disease development: biomarkers and preventive strategies Kapila AK, Watts HR, Wang T, Ma D Ref: J Alzheimers Dis, 41:1, 2014 : PubMed ESTHER: Kapila_2014_J.Alzheimers.Dis_41_1 PubMedSearch: Kapila 2014 J.Alzheimers.Dis 41 1 PubMedID: 24577482 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. Title: Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors 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 : PubMed ESTHER: Liang_2014_Eur.J.Med.Chem_79C_290 PubMedSearch: Liang 2014 Eur.J.Med.Chem 79C 290 PubMedID: 24747066 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. Title: Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M and Zhang Y <1 more author(s)> Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M, Yang Z, Zhang Y (- 1) Ref: Toxicol Appl Pharmacol, 280:169, 2014 : PubMed ESTHER: Wang_2014_Toxicol.Appl.Pharmacol_280_169 PubMedSearch: Wang 2014 Toxicol.Appl.Pharmacol 280 169 PubMedID: 24967689 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. Title: Comparative genomic analysis of N2-fixing and non-N2-fixing Paenibacillus spp.: organization, evolution and expression of the nitrogen fixation genes Xie JB, Du Z, Bai L, Tian C, Zhang Y, Xie JY, Wang T, Liu X, Chen X and Li J <2 more 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 (- 2) Ref: PLoS Genet, 10:e1004231, 2014 : PubMed 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 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. Title: Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 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 : PubMed ESTHER: Zhang_2014_Crit.Care.Med_42_e345 PubMedSearch: Zhang 2014 Crit.Care.Med 42 e345 PubMedID: 24448199 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 Title: DWARF3 participates in an SCF complex and associates with DWARF14 to suppress rice shoot branching Zhao J, Wang T, Wang M, Liu Y, Yuan S, Gao Y, Yin L, Sun W, Peng L and Li X <2 more 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 (- 2) Ref: Plant Cell Physiol, 55:1096, 2014 : PubMed ESTHER: Zhao_2014_Plant.Cell.Physiol_55_1096 PubMedSearch: Zhao 2014 Plant.Cell.Physiol 55 1096 PubMedID: 24616269 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. 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 GH, Xiong SQ, Chen HY, Mei LJ, Wang T Ref: Mol Biol Rep, 41:7141, 2014 : PubMed 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 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. Title: Soluble epoxide hydrolase inhibition does not prevent cardiac remodeling and dysfunction after aortic constriction in rats and mice Morgan LA, Olzinski AR, Upson JJ, Zhao S, Wang T, Eisennagel SH, Hoang B, Tunstead JR, Marino JP, Jr. and Behm DJ <2 more 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 (- 2) Ref: J Cardiovasc Pharmacol, 61:291, 2013 : PubMed ESTHER: Morgan_2013_J.Cardiovasc.Pharmacol_61_291 PubMedSearch: Morgan 2013 J.Cardiovasc.Pharmacol 61 291 PubMedID: 23232840 Inhibitor(s) related to this paper: GSK2256294A 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. Title: A novel approach to medical countermeasures against organophosphorus compound toxicity Wang T, Wang Y, Zhang L, Han B, Wang H, Li Y, Fu F Ref: Biomed Rep, 1:901, 2013 : PubMed ESTHER: Wang_2013_Biomed.Rep_1_901 PubMedSearch: Wang 2013 Biomed.Rep 1 901 PubMedID: 24649050 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. Title: The effects of huperzine A on gastrointestinal acetylcholinesterase activity and motility after single and multiple dosing in mice Zhang L, Song Y, Lu C, Zhang J, Yuan J, Wang T, Fu F Ref: Exp Ther Med, 5:793, 2013 : PubMed ESTHER: Zhang_2013_Exp.Ther.Med_5_793 PubMedSearch: Zhang 2013 Exp.Ther.Med 5 793 PubMedID: 23403922 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. Title: Sodium aescinate ameliorates liver injury induced by methyl parathion in rats Du Y, Wang T, Jiang N, Ren RT, Li C, Li CK, Fu FH Ref: Exp Ther Med, 3:818, 2012 : PubMed ESTHER: Du_2012_Exp.Ther.Med_3_818 PubMedSearch: Du 2012 Exp.Ther.Med 3 818 PubMedID: 22969975 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. Title: Steady and fluctuant methods of inhibition of acetylcholinesterase differentially regulate neurotrophic factors in the hippocampus of juvenile mice Li C, Wang T, Jiang N, Yu P, Du Y, Ren R, Fu F Ref: Exp Ther Med, 3:269, 2012 : PubMed ESTHER: Li_2012_Exp.Ther.Med_3_269 PubMedSearch: Li 2012 Exp.Ther.Med 3 269 PubMedID: 22969880 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. Title: Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress Wang T, Choi RC, Li J, Bi CWC, Ran W, Chen X, Dong TTX, Bi K, Tsim KWK Ref: J Ethnopharmacol, 139:214, 2012 : PubMed ESTHER: Wang_2012_J.Ethnopharmacol_139_214 PubMedSearch: Wang 2012 J.Ethnopharmacol 139 214 PubMedID: 22100563 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 Title: Polyphenolic acetylcholinesterase inhibitors from Hopea chinensis Yan T, Wang T, Wei W, Jiang N, Qin YH, Tan RX, Ge HM Ref: Planta Med, 78:1015, 2012 : PubMed ESTHER: Yan_2012_Planta.Med_78_1015 PubMedSearch: Yan 2012 Planta.Med 78 1015 PubMedID: 22628156 Inhibitor(s) related to this paper: Hopeahainol-A 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. Title: The oyster genome reveals stress adaptation and complexity of shell formation Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X and Yin Y <66 more 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 (- 66) Ref: Nature, 490:49, 2012 : PubMed 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 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. Title: Protective effect of sodium aescinate on lung injury induced by methyl parathion Du Y, Wang T, Jiang N, Ren RT, Zhao DL, Li C, Fu FH Ref: Hum Exp Toxicol, 30:1584, 2011 : PubMed ESTHER: Du_2011_Hum.Exp.Toxicol_30_1584 PubMedSearch: Du 2011 Hum.Exp.Toxicol 30 1584 PubMedID: 21177729 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. Title: Cardiac abnormalities in severe acute dichlorvos poisoning He X, Li C, Wei D, Wu J, Shen L, Wang T Ref: Critical Care Medicine, 39:1906, 2011 : PubMed ESTHER: He_2011_Crit.Care.Med_39_1906 PubMedSearch: He 2011 Crit.Care.Med 39 1906 PubMedID: 21516037 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. Title: The MDGA1 gene confers risk to schizophrenia and bipolar disorder Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z and Shi Y <2 more 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 (- 2) Ref: Schizophr Res, 125:194, 2011 : PubMed ESTHER: Li_2011_Schizophr.Res_125_194 PubMedSearch: Li 2011 Schizophr.Res 125 194 PubMedID: 21146959 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. Title: Huperzine A Activates Wnt/beta-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse Model Wang CY, Zheng W, Wang T, Xie JW, Wang SL, Zhao BL, Teng WP, Wang ZY Ref: Neuropsychopharmacology, 36:1073, 2011 : PubMed ESTHER: Wang_2011_Neuropsychopharmacology_36_1073 PubMedSearch: Wang 2011 Neuropsychopharmacology 36 1073 PubMedID: 21289607 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. Title: Long-term but not short-term aspirin treatment attenuates diabetes-associated learning and memory decline in mice Wang T, Fu FH, Han B, Zhang LM, Zhang XM Ref: Experimental & Clinical Endocrinology & Diabetes Diabetes, 119:36, 2011 : PubMed ESTHER: Wang_2011_Exp.Clin.Endocrinol.Diabetes_119_36 PubMedSearch: Wang 2011 Exp.Clin.Endocrinol.Diabetes 119 36 PubMedID: 20690072 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. Title: Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques Yan G, Zhang G, Fang X, Zhang Y, Li C, Ling F, Cooper DN, Li Q, Li Y and Wang X <32 more 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 (- 32) Ref: Nat Biotechnol, 29:1019, 2011 : PubMed 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 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. Title: Functional motor nerve regeneration without motor-sensory specificity following end-to-side neurorrhaphy: an experimental study Yu Q, Lin ZK, Ding J, Wang T, Chi YL, Gao WY Ref: J Hand Surg Am, 36:2010, 2011 : PubMed ESTHER: Yu_2011_J.Hand.Surg.Am_36_2010 PubMedSearch: Yu 2011 J.Hand.Surg.Am 36 2010 PubMedID: 22123048 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. Title: Acetylcholinesterase, a key prognostic predictor for hepatocellular carcinoma, suppresses cell growth and induces chemosensitization Zhao Y, Wang X, Wang T, Hu X, Hui X, Yan M, Gao Q, Chen T, Li J and He X <4 more 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 (- 4) Ref: Hepatology, 53:493, 2011 : PubMed ESTHER: Zhao_2011_Hepatology_53_493 PubMedSearch: Zhao 2011 Hepatology 53 493 PubMedID: 21274871 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. Title: Reduced glutathione attenuates liver injury induced by methyl parathion in rats Jiang N, Lu L, Wang T, Zhang L, Xin W, Fu F Ref: Toxicol Mech Methods, 20:69, 2010 : PubMed ESTHER: Jiang_2010_Toxicol.Mech.Methods_20_69 PubMedSearch: Jiang 2010 Toxicol.Mech.Methods 20 69 PubMedID: 20100039 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. Title: Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica Wang T, Choi RC, Li J, Bi CWC, Zang L, Liu Z, Dong TTX, Bi K, Tsim KWK Ref: Planta Med, 76:1642, 2010 : PubMed ESTHER: Wang_2010_Planta.Med_76_1642 PubMedSearch: Wang 2010 Planta.Med 76 1642 PubMedID: 20509104 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. Title: Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes Zhang L, Fu F, Zhang X, Zhu M, Wang T, Fan H Ref: Neurochem Int, 57:119, 2010 : PubMed ESTHER: Zhang_2010_Neurochem.Int_57_119 PubMedSearch: Zhang 2010 Neurochem.Int 57 119 PubMedID: 20466027 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. Title: Synthesis of benzofuran derivatives via rearrangement and their inhibitory activity on acetylcholinesterase Zhou X, Li M, Wang XB, Wang T, Kong LY Ref: Molecules, 15:8593, 2010 : PubMed ESTHER: Zhou_2010_Molecules_15_8593 PubMedSearch: Zhou 2010 Molecules 15 8593 PubMedID: 21116228 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. Title: From a consortium sequence to a unified sequence: the Bacillus subtilis 168 reference genome a decade later Barbe V, Cruveiller S, Kunst F, Lenoble P, Meurice G, Sekowska A, Vallenet D, Wang T, Moszer I and Danchin A <1 more author(s)> Barbe V, Cruveiller S, Kunst F, Lenoble P, Meurice G, Sekowska A, Vallenet D, Wang T, Moszer I, Medigue C, Danchin A (- 1) Ref: Microbiology, 155:1758, 2009 : PubMed ESTHER: Barbe_2009_Microbiology_155_1758 PubMedSearch: Barbe 2009 Microbiology 155 1758 PubMedID: 19383706 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. Title: Immobilization of lipase on methyl-modified silica aerogels by physical adsorption Gao S, Wang Y, Wang T, Luo G, Dai Y Ref: Bioresour Technol, 100:996, 2009 : PubMed ESTHER: Gao_2009_Bioresour.Technol_100_996 PubMedSearch: Gao 2009 Bioresour.Technol 100 996 PubMedID: 18684619 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. Title: Protective effect of reduced glutathione on the respiratory muscle injury induced by acute omethoate poisoning Lu L, Fu F, Wang T, He P, Xin W, Li C Ref: Pesticide Biochemistry and Physiology, 95:135, 2009 : PubMed ESTHER: Lu_2009_Pestic.Biochem.Physiol_95_135 PubMedSearch: Lu 2009 Pestic.Biochem.Physiol 95 135 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. Title: The B73 maize genome: complexity, diversity, and dynamics Schnable PS, Ware D, Fulton RS, Stein JC, Wei F, Pasternak S, Liang C, Zhang J, Fulton L and Wilson RK <147 more 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 (- 147) Ref: Science, 326:1112, 2009 : PubMed 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 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. 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 T, Karino K, Yamasaki M, Zhang Y, Masuda J, Yamaguchi S, Shiwaku K, Nabika T Ref: Am J Hypertens, 22:742, 2009 : PubMed 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 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. Title: Water-soluble derivative of propolis mitigates scopolamine-induced learning and memory impairment in mice Chen J, Long Y, Han M, Wang T, Chen Q, Wang R Ref: Pharmacol Biochem Behav, 90:441, 2008 : PubMed ESTHER: Chen_2008_Pharmacol.Biochem.Behav_90_441 PubMedSearch: Chen 2008 Pharmacol.Biochem.Behav 90 441 PubMedID: 18485465 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. Title: Design, synthesis, and acetylcholinesterase inhibitory activity of novel coumarin analogues Zhou X, Wang XB, Wang T, Kong LY Ref: Bioorganic & Medicinal Chemistry, 16:8011, 2008 : PubMed ESTHER: Zhou_2008_Bioorg.Med.Chem_16_8011 PubMedSearch: Zhou 2008 Bioorg.Med.Chem 16 8011 PubMedID: 18701305 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. Title: Immobilized capillary enzyme reactor based on layer-by-layer assembling acetylcholinesterase for inhibitor screening by CE Tang Z, Wang T, Kang J Ref: Electrophoresis, 28:2981, 2007 : PubMed ESTHER: Tang_2007_Electrophoresis_28_2981 PubMedSearch: Tang 2007 Electrophoresis 28 2981 PubMedID: 17674420 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. Title: Proteomic analyses of Oryza sativa mature pollen reveal novel proteins associated with pollen germination and tube growth Dai S, Li L, Chen T, Chong K, Xue Y, Wang T Ref: Proteomics, 6:2504, 2006 : PubMed ESTHER: Dai_2006_Proteomics_6_2504 PubMedSearch: Dai 2006 Proteomics 6 2504 PubMedID: 16548068 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. Title: Immobilization of lipase on epoxy activated (1-->3)-alpha-D-glucan isolated from Penicillium chrysongenum Wang T, Li H, Nie K, Tan T Ref: Biosci Biotechnol Biochem, 70:2883, 2006 : PubMed ESTHER: Wang_2006_Biosci.Biotechnol.Biochem_70_2883 PubMedSearch: Wang 2006 Biosci.Biotechnol.Biochem 70 2883 PubMedID: 17151459 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. Title: Enzymatic chlorophyll degradation in wheat near-isogenic lines elicited by cereal aphid (Homoptera: Aphididae) feeding Wang T, Quisenberry SS, Ni X, Tolmay V Ref: J Econ Entomol, 97:661, 2004 : PubMed ESTHER: Wang_2004_J.Econ.Entomol_97_661 PubMedSearch: Wang 2004 J.Econ.Entomol 97 661 PubMedID: 15154496 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. Title: Global analysis of the Bacillus subtilis Fur regulon and the iron starvation stimulon Baichoo N, Wang T, Ye R, Helmann JD Ref: Molecular Microbiology, 45:1613, 2002 : PubMed ESTHER: Baichoo_2002_Mol.Microbiol_45_1613 PubMedSearch: Baichoo 2002 Mol.Microbiol 45 1613 PubMedID: 12354229 Gene_locus related to this paper: bacsu-YUII 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. Title: Reversal of scopolamine-induced deficits in radial maze performance by (-)-huperzine A: comparison with E2020 and tacrine Wang T, Tang XC Ref: European Journal of Pharmacology, 349:137, 1998 : PubMed ESTHER: Wang_1998_Eur.J.Pharmacol_349_137 PubMedSearch: Wang 1998 Eur.J.Pharmacol 349 137 PubMedID: 9671090 Inhibitor(s) related to this paper: Aricept~Donepezil~E2020, HuperzineA, Tacrine 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. Title: [Injury effects of nicotine on isolated rat common carotid artery] Wang T, Gu Y, Wu G Ref: Zhonghua Yi Xue Za Zhi, 77:115, 1997 : PubMed ESTHER: Wang_1997_Zhonghua.Yi.Xue.Za.Zhi_77_115 PubMedSearch: Wang 1997 Zhonghua.Yi.Xue.Za.Zhi 77 115 PubMedID: 9596942 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. Title: Repetitive impulse activity potentiates spontaneous acetylcholine secretion at developing neuromuscular synapses Lo YJ, Wang T, Poo MM Ref: Journal de Physiologie (Paris), 85:71, 1991 : PubMed ESTHER: Lo_1991_J.Physiol.Paris_85_71 PubMedSearch: Lo 1991 J.Physiol.Paris 85 71 PubMedID: 1757892 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. Title: Presynaptic calcium channels in rat cortical synaptosomes: fast-kinetics of phasic calcium influx, channel inactivation, and relationship to nitrendipine receptors Suszkiw JB, O'Leary ME, Murawsky MM, Wang T Ref: Journal of Neuroscience, 6:1349, 1986 : PubMed ESTHER: Suszkiw_1986_J.Neurosci_6_1349 PubMedSearch: Suszkiw 1986 J.Neurosci 6 1349 PubMedID: 2423658 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. | |||||||
|
