Wei Y

References (63)

Title : Human umbilical cord mesenchymal stem cells attenuate diet-induced obesity and NASH-related fibrosis in mice - Hu_2024_Heliyon_10_e25460
Author(s) : Hu J , Li S , Zhong X , Wei Y , Sun Q , Zhong L
Ref : Heliyon , 10 :e25460 , 2024
Abstract : Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may progress to cirrhosis and hepatocellular carcinoma but has no available treatment. Mesenchymal stem cells (MSCs) have become increasingly prominent in cell therapy. Human umbilical cord MSCs (hUC-MSCs) are considered superior to other MSCs due to their strong immunomodulatory ability, ease of collection, low immune rejection, and no tumorigenicity. Though hUC-MSCs have received increasing attention in research, they have been rarely applied in any investigations or treatments of NASH and associated fibrosis. Therefore, this study evaluated the therapeutic efficacy of hUC-MSCs in C57BL/6 mice with diet-induced NASH. At week 32, mice were randomized into two groups: phosphate-buffered saline and MSCs, which were injected into the tail vein. At week 40, glucose metabolism was evaluated using glucose and insulin tolerance tests. NASH-related indicators were examined using various biological methods. hUC-MSC administration alleviated obesity, glucose metabolism, hepatic steatosis, inflammation, and fibrosis. Liver RNA-seq showed that the expression of the acyl-CoA thioesterase (ACOT) family members Acot1, Acot2, and Acot3 involved in fatty acid metabolism were altered. The cytochrome P450 (CYP) members Cyp4a10 and Cyp4a14, which are involved in the peroxisome proliferator-activator receptor (PPAR) signaling pathway, were significantly downregulated after hUC-MSC treatment. In conclusion, hUC-MSCs effectively reduced Western diet-induced obesity, NASH, and fibrosis in mice, partly by regulating lipid metabolism and the PPAR signaling pathway.
ESTHER : Hu_2024_Heliyon_10_e25460
PubMedSearch : Hu_2024_Heliyon_10_e25460
PubMedID: 38356602

Title : A Novel Bacillus Velezensis for Efficient Degradation of Zearalenone - Li_2024_Foods_13_
Author(s) : Li Y , Chen S , Yu Z , Yao J , Jia Y , Liao C , Chen J , Wei Y , Guo R , He L , Ding K
Ref : Foods , 13 : , 2024
Abstract : Zearalenone (ZEN) is considered one of the most serious mycotoxins contaminating grains and their by-products, causing significant economic losses in the feed and food industries. Biodegradation pathways are currently considered the most efficient solution to remove ZEN contamination from foods. However, low degradation rates and vulnerability to environmental impacts limit the application of biodegradation pathways. Therefore, the main research objective of this article was to screen strains that can efficiently degrade ZEN and survive under harsh conditions. This study successfully isolated a new strain L9 which can efficiently degrade ZEN from 108 food ingredients. The results of sequence alignment showed that L9 is Bacillus velezensis. Meanwhile, we found that the L9 degradation rate reached 91.14% at 24 h and confirmed that the primary degradation mechanism of this strain is biodegradation. The strain exhibits resistance to high temperature, acid, and 0.3% bile salts. The results of whole-genome sequencing analysis showed that, it is possible that the strain encodes the key enzyme, such as chitinase, carboxylesterases, and lactone hydrolase, that work together to degrade ZEN. In addition, 227 unique genes in this strain are primarily involved in its replication, recombination, repair, and protective mechanisms. In summary, we successfully excavated a ZEN-degrading, genetically distinct strain of Bacillus velezensis that provides a solid foundation for the detoxification of feed and food contamination in the natural environment.
ESTHER : Li_2024_Foods_13_
PubMedSearch : Li_2024_Foods_13_
PubMedID: 38397507

Title : Association between serum cholinesterase and the prevalence of atrial fibrillation in Chinese hypertensive population: a cross-sectional study - Xue_2023_Eur.J.Med.Res_28_500
Author(s) : Xue W , Wei Y , Hu Y
Ref : European Journal of Medical Research , 28 :500 , 2023
Abstract : BACKGROUND: Atrial fibrillation (AF) is a very common arrhythmia with significant incidence rate and mortality. Several studies have shown a notable correlation between non-alcoholic fatty liver disease (NAFLD) and AF. It has been observed that serum cholinesterase (SChE) levels are elevated in individuals with fatty liver. However, the relationship between the SChE index and AF is still unclear. Therefore, the purpose of this study is to explore the association between the SChE index and the prevalence of AF in patients with hypertension. METHOD: We collected cross-sectional data from January 2018 to April 2021 based on a retrospective study of cardiovascular disease. A total of 748 patients with hypertension were included, of whom 165 had AF. We used logistic regression models to test the relationship between SChE and the prevalence of AF in hypertensive patients. RESULT: In hypertensive patients, the SChE index was significantly associated with AF (OR = 0.723, P < 0.001). After adjusting for potential confounding factors, this correlation was still significant (OR = 0.778, P < 0.001). The stability of the model was verified by adjusting the variable type of SChE. The data were further stratified according to whether the patient had fatty liver. In the stratified data, the correlation between SChE and atrial fibrillation was still significant (P < 0.05). CONCLUSION: Our study showed that SChE was significantly negatively correlated with the occurrence of AF in patients with hypertension. And this correlation was not affected by whether the patient had fatty liver.
ESTHER : Xue_2023_Eur.J.Med.Res_28_500
PubMedSearch : Xue_2023_Eur.J.Med.Res_28_500
PubMedID: 37941017

Title : Bioaccumulation, metabolism and toxicological effects of chiral insecticide malathion and its metabolites in zebrafish (Danio rerio) - Cui_2023_Chemosphere_318_137898
Author(s) : Cui J , Wei Y , Jiang J , Xiao S , Liu X , Zhou Z , Liu D , Wang P
Ref : Chemosphere , 318 :137898 , 2023
Abstract : The bioaccumulation, metabolism, tissue-specific distribution and toxicity of the widely used organophosphorous pesticide malathion to zebrafish were investigated on an enantiomeric level for evaluating the environmental risks. The metabolites were also monitored and evaluated. Malathion was metabolized by zebrafish very fast with the half-life of 0.12 d and showed a middle accumulation capacity in zebrafish with bioaccumulation factor (BCF) of 12.9 after a 15-d exposure. Brain could enrich higher concentration of malathion than other tissues. The metabolites malaoxon, malathion/malaoxon monocarboxylic acid (DMA), malathion/malaoxon dicarboxylic acid (DCA), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) were found, in which DMTP and DCA were in higher level, indicating the metabolism was mainly induced by carboxylesterase degradation. The accumulation of malathion and malaoxon was stereoselective in zebrafish tissues, exhibiting S-enantiomer preferentially enriched. The acute toxicity test showed rac-malathion was low toxic to zebrafish, which was 1.2 and 1.6 folds more toxic than S-malathion and R-malathion respectively. Malaoxon was highly toxic to zebrafish and approximately 32 times more toxic than malathion. The toxicity of other metabolites was lower than malathion. Malathion could cause an apparent developmental toxicity to zebrafish embryo, including bradycardia, hatchability reduction and deformity, and abnormal movement patterns in zebrafish larva. Chronic toxicity indicated that malathion and malaoxon induced oxidative damage and neurotoxicity in the liver, brain and gill of zebrafish, and malaoxon exhibited a relatively high injury to the zebrafish brain. The results can provide information for the comprehensive assessment of the potential risk of malathion to aquatic organisms and highlight the necessity of consideration of stereoselectivity and metabolites when systemically evaluating pesticides.
ESTHER : Cui_2023_Chemosphere_318_137898
PubMedSearch : Cui_2023_Chemosphere_318_137898
PubMedID: 36702415

Title : Assessment of the therapeutic potential of probiotics against carbon quantum dots-induced neurotoxicity in common carp (Cyprinus carpio) - Cao_2023_Aquat.Toxicol_258_106508
Author(s) : Cao X , Yuan R , Sun D , Ji X , Wei Y , Li L , Guo S , Li B , Chen J
Ref : Aquat Toxicol , 258 :106508 , 2023
Abstract : Carbon quantum dots (CQDs) have received increasing attention in recent years for their potential toxicity. However, little is known about their neurobehavioral toxicity. This study aimed to investigate the potential mechanisms by which probiotics reduce CQDs neurotoxicity from a brain-gut axis perspective by exposing carp to CQDs and/or probiotics for five weeks. The results showed that CQDs accumulation in the brain reduces the expression of blood-brain-barrier (BBB) related genes in carp, leading to brain damage. In addition, CQDs impaired motor behavior and inhibited acetylcholinesterase activity. These abnormalities were alleviated by probiotic supplementation. Microbiomic analysis showed that probiotics improved the imbalance of intestinal flora caused by CQDs and increased the abundance of Firmicutes. Serum metabolomic analysis showed that probiotic supplementation restored the abnormal metabolic levels associated with neurological, inflammatory, and apoptotic cell death caused by CQDs. Overall, probiotic supplementation improved the CQDs-induced changes in brain damage, gut microbiology, and systemic metabolism. These results suggests that CQDs may cause neurotoxicity via the brain-gut microbial axis.
ESTHER : Cao_2023_Aquat.Toxicol_258_106508
PubMedSearch : Cao_2023_Aquat.Toxicol_258_106508
PubMedID: 37001197

Title : Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective - Li_2023_Front.Nutr_10_1139558
Author(s) : Li Z , Zhao T , Shi M , Wei Y , Huang X , Shen J , Zhang X , Xie Z , Huang P , Yuan K , Li N , Qin D
Ref : Front Nutr , 10 :1139558 , 2023
Abstract : As natural functional bioactive ingredients found in foods and plants, polyphenols play various antioxidant and anti-inflammatory roles to prevent the development of disease and restore human health. The multi-target modulation of polyphenols provides a novel practical therapeutic strategy for neurodegenerative diseases that are difficult to treat with traditional drugs like glutathione and cholinesterase inhibitors. This review mainly focuses on the efficacy of polyphenols on ischemic stroke, Parkinson's disease and Alzheimer's disease, including in vivo and in vitro experimental studies. It is further emphasized that polyphenols exert neuroprotective effects primarily through inhibiting production of oxidative stress and inflammatory cytokines, which may be the underlying mechanism. However, polyphenols are still rarely used as medicines to treat neurodegenerative diseases. Due to the lack of clinical trials, the mechanism of polyphenols is still in the stage of insufficient exploration. Future large-scale multi-center randomized controlled trials and in-depth mechanism studies are still needed to fully assess the safety, efficacy and side effects of polyphenols.
ESTHER : Li_2023_Front.Nutr_10_1139558
PubMedSearch : Li_2023_Front.Nutr_10_1139558
PubMedID: 36925964

Title : Simple and novel icariin-loaded pro-glycymicelles as a functional food: physicochemical characteristics, in vitro biological activities, and in vivo experimental hyperlipidemia prevention evaluations - Cui_2023_Food.Funct__
Author(s) : Cui Q , Wang C , Zhou L , Wei Y , Liu Z , Wu X
Ref : Food Funct , : , 2023
Abstract : A novel functional food for hyperlipidemia named icariin (ICA) pro-glycymicelles (ICA-PGs) using glycyrrhizin as a phytonanomaterial was easily prepared with improved storage, pH, and salt stabilities. ICA-PGs can easily dissolve in water to self-assemble into a clear glycymicelle solution with high ICA encapsulation efficiency. The ICA in ICA-PGs exhibits significantly increased aqueous solubility, faster in vitro release, and higher bioaccessibility than bare ICA. The ICA-PGs exhibited improved in vitro activities including antioxidant, anti-alpha-glucosidase, anti-lipase, and anti-cholesterol esterase activities. The ICA-PG also demonstrated improved antioxidant activity in cells. In vivo evaluation confirmed that the ICA-PG demonstrated a significant protective effect against experimental hyperlipidemia in mice, exhibiting decreasing levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the serum, and restoring the hepatic morphology to the normal state. These results indicated that the ICA-PG could improve in vitro/in vivo profiles of ICA, providing a new concept and a promising functional food for hyperlipidemia.
ESTHER : Cui_2023_Food.Funct__
PubMedSearch : Cui_2023_Food.Funct__
PubMedID: 37853783

Title : Research Progress on Effects of Ginsenoside Rg2 and Rh1 on Nervous System and Related Mechanisms - Liu_2023_Molecules_28_
Author(s) : Liu C , Zheng P , Wang H , Wei Y , Wang C , Hao S , Liu S , Chen W , Zhao Y , Zong Y , Li J , He Z
Ref : Molecules , 28 : , 2023
Abstract : Neurological-related disorders are diseases that affect the body's neurons or peripheral nerve tissue, such as Parkinson's disease (PD) and Alzheimer's disease (AD). The development of neurological disorders can cause serious harm to the quality of life and functioning of the patient. The use of traditional therapeutic agents such as dopamine-promoting drugs, anticholinergic drugs, cholinesterase inhibitors, and NMDA receptor antagonists is often accompanied by a series of side effects such as drug resistance, cardiac arrhythmia, liver function abnormalities, and blurred vision. Therefore, there is an urgent need to find a therapeutic drug with a high safety profile and few side effects. Herbal medicines are rich in active ingredients that are natural macromolecules. Ginsenoside is the main active ingredient of ginseng, which has a variety of pharmacological effects and is considered to have potential value in the treatment of human diseases. Modern pharmacological studies have shown that ginsenosides Rg2 and Rh1 have strong pharmacological activities in the nervous system, with protective effects on nerve cells, improved resistance to neuronal injury, modulation of neural activity, resistance to cerebral ischemia/reperfusion injury, improvement of brain damage after eclampsia hemorrhage, improvement of memory and cognitive deficits, treatment of AD and vascular dementia, alleviation of anxiety, pain, and inhibition of ionic-like behavior. In this article, we searched the pharmacological research literature of Rg2 and Rh1 in the field of neurological diseases, summarized the latest research progress of the two ginsenosides, and reviewed the pharmacological effects and mechanisms of Rg2 and Rh1, which provided a new way of thinking for the research of the active ingredients in ginseng anti-neurological diseases and the development of new drugs.
ESTHER : Liu_2023_Molecules_28_
PubMedSearch : Liu_2023_Molecules_28_
PubMedID: 36677589 || 38067664

Title : Ultrathin C(3)N(4) nanosheets-based oxidase-like 2D fluorescence nanozyme for dual-mode detection of organophosphorus pesticides - Shen_2023_J.Hazard.Mater_451_131171
Author(s) : Shen Y , Gao X , Chen H , Wei Y , Yang H , Gu Y
Ref : J Hazard Mater , 451 :131171 , 2023
Abstract : Engineering efficient dual-mode portable sensor with built-in cross reference correction is of great significance for onsite reliable and precise detection of organophosphorus pesticides (OPs) and evading the false-positive outputs, especially in emergency case. Currently, most nanozyme-based sensors for OPs monitoring primarily replied on the peroxidase-like activity, which involved unstable and toxic H(2)O(2). In this scenario, a hybrid oxidase-like 2D fluorescence nanozyme (PtPdNPs@g-C(3)N(4)) was yielded by in situ growing PtPdNPs in the ultrathin two-dimensional (2D) graphitic carbon nitride (g-C(3)N(4)) nanosheet. When acetylcholinesterase (AChE) hydrolyzed acetylthiocholine (ATCh) to thiocholine (TCh), it ablated O(2)(-) from the dissolved O(2) catalyzed by PtPdNPs@g-C(3)N(4)'s oxidase-like activity, hampering the oxidation of o-phenylenediamine (OPD) into 2,3-diaminophenothiazine (DAP). Consequently, with the increasing concentration of OPs which inhibited the blocking effect by inactivating AChE, the produced DAP caused an apparent color change and a dual-color ratiometric fluorescence change in the response system. Through integrating into a smartphone, a H(2)O(2)-free 2D nanozyme-based onsite colorimetric and fluorescence dual-mode visual imaging sensor for OPs was proposed with acceptable results in real samples, which holds vast promise for further development of commercial point-of-care testing platform in early warning and controlling of OPs pollution for safeguarding environmental health and food safety.
ESTHER : Shen_2023_J.Hazard.Mater_451_131171
PubMedSearch : Shen_2023_J.Hazard.Mater_451_131171
PubMedID: 36913745

Title : Exploring the interaction between T-cell antigen receptor-related genes and MAPT or ACHE using integrated bioinformatics analysis - Guo_2023_Front.Neurol_14_1129470
Author(s) : Guo W , Gou X , Yu L , Zhang Q , Yang P , Pang M , Pang X , Pang C , Wei Y , Zhang X
Ref : Front Neurol , 14 :1129470 , 2023
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease that primarily occurs in elderly individuals with cognitive impairment. Although extracellular beta-amyloid (Abeta) accumulation and tau protein hyperphosphorylation are considered to be leading causes of AD, the molecular mechanism of AD remains unknown. Therefore, in this study, we aimed to explore potential biomarkers of AD. Next-generation sequencing (NGS) datasets, GSE173955 and GSE203206, were collected from the Gene Expression Omnibus (GEO) database. Analysis of differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein networks were performed to identify genes that are potentially associated with AD. Analysis of the DEG based protein-protein interaction (PPI) network using Cytoscape indicated that neuroinflammation and T-cell antigen receptor (TCR)-associated genes (LCK, ZAP70, and CD44) were the top three hub genes. Next, we validated these three hub genes in the AD database and utilized two machine learning models from different AD datasets (GSE15222) to observe their general relationship with AD. Analysis using the random forest classifier indicated that accuracy (78%) observed using the top three genes as inputs differed only slightly from that (84%) observed using all genes as inputs. Furthermore, another data set, GSE97760, which was analyzed using our novel eigenvalue decomposition method, indicated that the top three hub genes may be involved in tauopathies associated with AD, rather than Abeta pathology. In addition, protein-protein docking simulation revealed that the top hub genes could form stable binding sites with acetylcholinesterase (ACHE). This suggests a potential interaction between hub genes and ACHE, which plays an essential role in the development of anti-AD drug design. Overall, the findings of this study, which systematically analyzed several AD datasets, illustrated that LCK, ZAP70, and CD44 may be used as AD biomarkers. We also established a robust prediction model for classifying patients with AD.
ESTHER : Guo_2023_Front.Neurol_14_1129470
PubMedSearch : Guo_2023_Front.Neurol_14_1129470
PubMedID: 37056359

Title : Genome-wide identification and expression analysis of the cotton patatin-related phospholipase A genes and response to stress tolerance - Wei_2023_Planta_257_49
Author(s) : Wei Y , Chong Z , Lu C , Li K , Liang C , Meng Z , Wang Y , Guo S , He L , Zhang R
Ref : Planta , 257 :49 , 2023
Abstract : Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance.
ESTHER : Wei_2023_Planta_257_49
PubMedSearch : Wei_2023_Planta_257_49
PubMedID: 36752875

Title : Toxicological effects of trace amounts of pyriproxyfen on the midgut of non-target insect silkworm - Xu_2022_Pestic.Biochem.Physiol_188_105266
Author(s) : Xu K , Lan H , He C , Wei Y , Lu Q , Cai K , Yu D , Yin X , Li Y , Lv J
Ref : Pestic Biochem Physiol , 188 :105266 , 2022
Abstract : Pyriproxyfen is an insect growth regulator that is widely used in public health and pest control in agriculture. Our previous studies have shown that trace amounts of pyriproxyfen in the environment can cause serious toxic effects in the non-target insect silkworm, including failing to pupate, metamorphose and spin cocoons. However, it is unknown why pyriproxyfen not only has no lethal effects on fifth instar larvae but also tend to increase their body weight. The midgut is the main digestive organs of the silkworm, our results showed that the residual of pyriproxyfen in the silkworm at 24sh after 1sxs10(-4)smg/L pyriproxyfen treatment caused severe damage to the midgut microvilli, goblet cells, and nuclei of the silkworm, but body weight and digestibility of the larval were both increased. In addition, pyriproxyfen significantly (ps
ESTHER : Xu_2022_Pestic.Biochem.Physiol_188_105266
PubMedSearch : Xu_2022_Pestic.Biochem.Physiol_188_105266
PubMedID: 36464371

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : Structural Elucidation and Total Synthesis for the Pair of Unprecedented Polypyridines with Anti-AChE and HIV-1 Protease Activities from Alangium chinense - Hu_2022_J.Org.Chem__
Author(s) : Hu XY , Zhu SJ , Meng XH , Yu HF , Liu X , Zhang LY , Wei Y , Lei CW , Wei X , Zhou Y
Ref : J Org Chem , : , 2022
Abstract : Unlike reported pyridine hybrids, 2S (1a) and 2R-alanginenmine A (1b) from Alangium chinense featuring an unprecedented piperidine-bridged polypyridine skeleton represented a pair of alkaloid subtypes with a unique multiple pyridine scaffold. Enlightened by the rare structural characteristics and possible biosynthetic pathway, (+/-)-alanginenmine A (1) have been achieved in ideal yield by gram-class total synthesis with four steps. In addition, both compounds 1a and 1b exhibited anti-acetylcholinesterase (AChE) and HIV-1 protease activities in the biological activity evaluation. Further, molecular docking was investigated for the mechanism of action between the isolated compounds and HIV-1 protease. The stronger Coulomb interactions and van der Waals interaction, as well as the hydrogen bond interactions of 1a, might be the main cause for its better anti-HIV-1 protease activity than 1b. This work provided a comprehensive research including natural product discovery, bioactivity evaluation, and total synthesis for the new type of leading anti-HIV-1 protease.
ESTHER : Hu_2022_J.Org.Chem__
PubMedSearch : Hu_2022_J.Org.Chem__
PubMedID: 36354352

Title : Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure - Kang_2021_Environ.Sci.Pollut.Res.Int__
Author(s) : Kang L , Chen J , Wang J , Zhao T , Wei Y , Wu Y , Han L , Zheng X , Shen L , Long C , Wei G , Wu S
Ref : Environ Sci Pollut Res Int , : , 2021
Abstract : The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.
ESTHER : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedID: 34595713

Title : Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection - Yu_2021_Fish.Shellfish.Immunol__
Author(s) : Yu C , Xu W , Li X , Jin J , Zhao X , Wang S , Zhang Z , Wei Y , Chen Q , Li Y
Ref : Fish Shellfish Immunol , : , 2021
Abstract : Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Dierential gene expression analysis revealed 896 signicantly dierently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
ESTHER : Yu_2021_Fish.Shellfish.Immunol__
PubMedSearch : Yu_2021_Fish.Shellfish.Immunol__
PubMedID: 34303835

Title : Development and validation of an ultrasensitive LC-MS\/MS method for the quantification of cetagliptin in human plasma and its application in a microdose clinical trial - Bai_2021_Biomed.Chromatogr_35_e4994
Author(s) : Bai H , Lu J , Cheng X , Liu L , Zhang W , Wei Y , Wang Y , Liu J , Ding J , Yu Q , Zhang Y , Chen G , Fan Y , Wang X
Ref : Biomedical Chromatography , 35 :e4994 , 2021
Abstract : This study established and validated an LC-MS/MS method for the ultrasensitive determination of cetagliptin in human plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and chromatographic separation was performed on an XB-C(18) analytical column (50x2.1mm, 5microm) with gradient elution (0.1% formic acid in acetonitrile and 0.1% formic acid) at a flow rate of 1.0mL/min. For mass spectrometric detection, multiple reaction monitoring was used, and the ion transitions monitored were m/z 421.2-86.0 for cetagliptin and m/z 424.2-88.0 for cetagliptin-d3. Method validation was performed according to the U.S. Food and Drug Administration Bioanalytical Method Validation Guidance, for which the calibration curve was linear in the range of 50.0-2000pg/mL. All of the other results, such as selectivity, lower limit of quantitation, precision, accuracy, matrix effect, recovery, and stability, met the acceptance criteria. The validated method was successfully applied in a microdose clinical trial to systematically investigate the pharmacokinetic profile of cetagliptin in healthy subjects. Both rapid absorption and prolonged duration demonstrate the potential value of cetagliptin for diabetes treatment.
ESTHER : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedSearch : Bai_2021_Biomed.Chromatogr_35_e4994
PubMedID: 32986878

Title : Cellular resolution anatomical and molecular atlases for prenatal human brains - Ding_2021_J.Comp.Neurol__
Author(s) : Ding SL , Royall JJ , Lesnar P , Facer BAC , Smith KA , Wei Y , Brouner K , Dalley RA , Dee N , Dolbeare TA , Ebbert A , Glass IA , Keller NH , Lee F , Lemon TA , Nyhus J , Pendergraft J , Reid R , Sarreal M , Shapovalova NV , Szafer A , Phillips JW , Sunkin SM , Hohmann JG , Jones AR , Hawrylycz MJ , Hof PR , Ng L , Bernard A , Lein ES
Ref : Journal of Comparative Neurology , : , 2021
Abstract : Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at post-conceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains respectively at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, segmentation, targeting, imaging and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies. This article is protected by copyright. All rights reserved.
ESTHER : Ding_2021_J.Comp.Neurol__
PubMedSearch : Ding_2021_J.Comp.Neurol__
PubMedID: 34525221

Title : Rivastigmine Transdermal Patch Treatment for Moderate to Severe Cognitive Impairment in Veterans with Traumatic Brain Injury (RiVET Study): A Randomized Clinical Trial - Brawman-Mintzer_2021_J.Neurotrauma__
Author(s) : Brawman-Mintzer O , Tang XC , Bizien M , Harvey PD , Horner MD , Arciniegas DB , Raskind M , Johnson-Greene L , Martineau RJ , Hamner M , Rodriguez-Suarez M , Jorge RE , McGarity S , Wortzel HS , Wei Y , Sindowski T , Mintzer J , Kindy AZ , Donovan K , Reda D
Ref : Journal of Neurotrauma , : , 2021
Abstract : Cognitive impairment is common in veterans with histories of traumatic brain injury (TBI). Cholinergic deficits have been hypothesized as contributors to this impairment. We report the effects of cholinesterase inhibitor rivastigmine transdermal patch treatment in veterans with TBI and post-traumatic memory impairment. Our objective was to evaluate the efficacy and safety of 9.5 mg/24 hours (10cm2) rivastigmine patch in veterans of military conflicts with persistent moderate to severe memory impairment at least 12 weeks following TBI. This randomized, outpatient, double-blind, placebo-controlled 12-week trial with exploratory double-blind phase of additional 14 weeks was conducted at 5 VA Medical Centers, among veterans with closed, non-penetrating TBI who met or exceeded modified ACRM criteria for mild TBI with verbal memory deficits, as assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R). Patients were randomized 1:1 to rivastigmine or matching placebo patches following 1-week single-blind, placebo run-in phase. At randomization, patients received 4.6 mg/24hr rivastigmine patches or matching placebo increased to 9.5 mg/24 hours patch after 4 weeks. The primary efficacy outcome measure was the proportion of participants who had at least 5-word improvement on HVLT-R Total Recall Index (Trials 1-3). A total 3671 participants were pre-screened, of whom 257 (7.0%) were screened; 96 (37%) randomized and 94 included in study analyses. The responder rates were 40.8% (20/49) and 51.1% (23/45) in rivastigmine and placebo groups respectively (p=0.41). A mixed-effect model including treatment, time, and treatment by time interaction indicated no significant difference in treatment effect over time between the groups (p=0.24). Overall, there were no significant differences in changes for all secondary outcomes between the rivastigmine and placebo groups. The most commonly observed AEs were application site reactions. This trial provides the largest sample to date of veterans with TBI and posttraumatic memory deficits enrolled in a pharmacological trial.
ESTHER : Brawman-Mintzer_2021_J.Neurotrauma__
PubMedSearch : Brawman-Mintzer_2021_J.Neurotrauma__
PubMedID: 33514274

Title : Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve - Wang_2021_J.Affect.Disord_292_565
Author(s) : Wang S , Ishima T , Qu Y , Shan J , Chang L , Wei Y , Zhang J , Pu Y , Fujita Y , Tan Y , Wang X , Ma L , Wan X , Hammock BD , Hashimoto K
Ref : J Affect Disord , 292 :565 , 2021
Abstract : BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice. METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed. RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium. LIMITATIONS: Detailed mechanisms are unclear. CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.
ESTHER : Wang_2021_J.Affect.Disord_292_565
PubMedSearch : Wang_2021_J.Affect.Disord_292_565
PubMedID: 34147969

Title : Secondary metabolites of endophytic fungi isolated from Huperzia serrata - Cao_2021_Fitoterapia__104970
Author(s) : Cao D , Sun P , Bhowmick S , Wei Y , Guo B , Mur LAJ , Sun Z
Ref : Fitoterapia , :104970 , 2021
Abstract : The natural product Huperzine A isolated from Huperzia serrata is a targeted inhibitor of acetylcholinesterase that has been approved for clinical use in the treatment of Alzheimer's disease. Given the large demand for natural sources of Huperzine A, efforts have been made to explore whether Huperzine A (Hup. A) is also produced by endophytic fungi from H. serrata and, if so, identify its biosynthetic pathway. These studies have indicated that endophytic fungi from H. serrata represent a huge and largely untapped resource for natural products (including Hup. A) with chemical structures that have been optimized by evolution for biological and ecological relevance. To date, more than three hundred endophytic fungi have been isolated from H. serrata, of which 9 strains can produce Hup. A, whilst more than 20 strains produce other important metabolites, such as polyketones, xanthones, alkaloids, steroids, triterpenoids, furanone derivatives, tremulane sesquitepenes and diterpenoids. In total, 200 secondary metabolites have been characterized in endophytic fungi from H. serrata to date. Functionally, some have cholinesterase-inhibitory or antibacterial activity. This review also considers the different classes of secondary metabolites produced by endophytic fungi, along with their possible applications. We systematically describe the taxonomy, biology, and chemistry of these secondary metabolites. It also summarizes the biosynthetic synthesis of metabolites, including that of Hup. A. The review will aid researchers in obtaining a clearer understanding of this plant-endophyte relationship to better exploit the excellent resources it offers that may be utilized by pharmaceutical industries.
ESTHER : Cao_2021_Fitoterapia__104970
PubMedSearch : Cao_2021_Fitoterapia__104970
PubMedID: 34419561

Title : Lack of rewarding effects of a soluble epoxide hydrolase inhibitor TPPU in mice: Comparison with morphine - Wan_2020_Neuropsychopharmacol.Rep_40_412
Author(s) : Wan X , Fujita Y , Chang L , Wei Y , Ma L , Wuyun G , Pu Y , Hammock BD , Hashimoto K
Ref : Neuropsychopharmacol Rep , 40 :412 , 2020
Abstract : AIM: Although opioids have been used as treatment of neuropathic pain, opioids have abuse potential in humans. Since soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids plays a key role in the pain, sEH inhibitors would be promising new therapeutic drugs for neuropathic pain. In this study, we examined the effect of the sEH inhibitor TPPU on rewarding effects in mice using the conditioned place preference (CPP) paradigm. METHODS: The rewarding effects of morphine (10 mg/kg) and TPPU (3, 10, or 30 mg/kg) in mice were examined using CPP paradigm. Furthermore, the effect of TPPU (30 mg/kg) on morphine-induced rewarding effects was examined. RESULTS: TPPU (3, 10, or 30 mg/kg) did not increase CPP scores in the mice whereas morphine significantly increased CPP scores in the mice. Furthermore, pretreatment with TPPU did not block the rewarding effects of morphine in the mice, suggesting that sEH does not play a role in the rewarding effect of morphine. CONCLUSION: This study suggests that TPPU did not have rewarding effects in rodents. This would make sEH inhibitors potential therapeutic drugs without abuse potential for neuropathic pain.
ESTHER : Wan_2020_Neuropsychopharmacol.Rep_40_412
PubMedSearch : Wan_2020_Neuropsychopharmacol.Rep_40_412
PubMedID: 32896112

Title : Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review - Wang_2020_Curr.Vasc.Pharmacol_18_358
Author(s) : Wang Z , Yang Y , Liu M , Wei Y , Liu J , Pei H , Li H
Ref : Curr Vasc Pharmacol , 18 :358 , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.
ESTHER : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedSearch : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedID: 31291876

Title : Effect and Safety of Huannao Yicong Formula () in Patients with Mild-to-Moderate Alzheimer's Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial - Yang_2019_Chin.J.Integr.Med_25_574
Author(s) : Yang Y , Liu JP , Fang JY , Wang HC , Wei Y , Cao Y , Liu JG , Liu LT , Li H
Ref : Chin J Integr Med , 25 :574 , 2019
Abstract : OBJECTIVE: To assess the effect and safety of Huannao Yicong Formula (, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-beta protein 42 (Abeta42) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. RESULTS: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Abeta42 (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups. CONCLUSION: HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].
ESTHER : Yang_2019_Chin.J.Integr.Med_25_574
PubMedSearch : Yang_2019_Chin.J.Integr.Med_25_574
PubMedID: 30109588

Title : Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy - Deng_2019_Cancer.Cell.Int_19_273
Author(s) : Deng W , Fan C , Fang Y , Zhao Y , Wei Y , Li M , Teng J
Ref : Cancer Cell Int , 19 :273 , 2019
Abstract : Background: This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP). Methods: Rat's BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays. Results: Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats. Conclusion: Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats.
ESTHER : Deng_2019_Cancer.Cell.Int_19_273
PubMedSearch : Deng_2019_Cancer.Cell.Int_19_273
PubMedID: 31660045

Title : Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats - Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
Author(s) : Wu Q , Cao Y , Liu M , Liu F , Brantner AH , Yang Y , Wei Y , Zhou Y , Wang Z , Ma L , Wang F , Pei H , Li H
Ref : Neuropsychiatr Dis Treat , 15 :3167 , 2019
Abstract : Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.
ESTHER : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedSearch : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedID: 31814724

Title : Heat shock transcription factor 3 regulates plant immune response through modulation of salicylic acid accumulation and signalling in cassava - Wei_2018_Mol.Plant.Pathol_19_2209
Author(s) : Wei Y , Liu G , Chang Y , He C , Shi H
Ref : Mol Plant Pathol , 19 :2209 , 2018
Abstract : As the terminal components of signal transduction, heat stress transcription factors (Hsfs) mediate the activation of multiple genes responsive to various stresses. However, the information and functional analysis are very limited in non-model plants, especially in cassava (Manihot esculenta), one of the most important crops in tropical areas. In this study, 32 MeHsfs were identified from the cassava genome; the evolutionary tree, gene structures and motifs were also analysed. Gene expression analysis found that MeHsfs were commonly regulated by Xanthomonas axonopodis pv. manihotis (Xam). Amongst these MeHsfs, MeHsf3 was specifically located in the cell nucleus and showed transcriptionally activated activity on heat stress elements (HSEs). Through transient expression in Nicotiana benthamiana leaves and virus-induced gene silencing (VIGS) in cassava, we identified the essential role of MeHsf3 in plant disease resistance, by regulating the transcripts of Enhanced Disease Susceptibility 1 (EDS1) and pathogen-related gene 4 (PR4). Notably, as regulators of defence susceptibility, MeEDS1 and MePR4 were identified as direct targets of MeHsf3. Moreover, the disease sensitivity of MeHsf3- and MeEDS1-silenced plants could be restored by exogenous salicylic acid (SA) treatment. Taken together, this study highlights the involvement of MeHsf3 in defence resistance through the transcriptional activation of MeEDS1 and MePR4.
ESTHER : Wei_2018_Mol.Plant.Pathol_19_2209
PubMedSearch : Wei_2018_Mol.Plant.Pathol_19_2209
PubMedID: 29660238

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : Protective effects of kinetin against aluminum chloride and D-galactose induced cognitive impairment and oxidative damage in mouse - Wei_2017_Brain.Res.Bull_134_262
Author(s) : Wei Y , Liu D , Zheng Y , Li H , Hao C , Ouyang W
Ref : Brain Research Bulletin , 134 :262 , 2017
Abstract : Increasing evidence indicates that aluminum exposure and oxidative stress play crucial roles in the initiation and development of Alzheimer's disease (AD). Aluminum chloride (AlCl3) and d-galactose (d-gal) combined treatment of mice is considered as an easy and cheap way to obtain an animal model of AD. Kinetin is a plant cytokinin, which is also reported to exert neuro-protective effects in vivo and in vitro. Thus, in this study, neuro-protective effects of kinetin were investigated in an AD model of mice induced by AlCl3 and d-gal. The Morris water maze (MWM) test was performed to directly evaluate neuro-protective effects of kinetin on the memory and spatial learning abilities, while the histopathological changes were examined by hematoxylin and eosin (H & E) staining method. To further investigate mechanisms involved, Al content in cortex and hippocampus was determined. In addition, related detection kits were used to determine acetylcholine (ACh) content and activity of acetylcholinesterase (AChE). Activities of anti-oxidative enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the content of heme oxygenase-1 (HO-1) were also measured. Besides, the content of oxidative damage bio-markers including 8-iso-prostaglandin F (8-iso-PGF), advanced glycation end products (AGEs) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were determined by ELISA kits. Finally, the distribution of beta-amyloid protein 1-42 (Abeta1-42) was detected by immunohistochemistry (IHC), while the expression levels of amyloidogenic proteins including beta-amyloid precursor protein (APP), beta-secretase, gamma-secretase and Abeta1-42 were detected by western blotting (WB) method. Results showed that kinetin improved performance in MWM test, attenuated histopathological changes, reduced Al level in cortex and hippocampus, increased ACh content and decreased AChE activity. In addition, kinetin elevated activities of anti-oxidative enzymes and reduced the levels of oxidative damage biomarkers in AD model of mice. Furthermore, kinetin also increased the content of HO-1, and inhibited the distribution of Abeta1-42 and the expressions of amyloidogenic proteins (APP, beta-secretase, gamma-secretase and Abeta1-42) in brain tissue of AD mice. Our results indicate that kinetin has neuro-protective effects on the AD model of mice induced by AlCl3 and d-gal, suggesting that kinetin may be a candidate drug for treatment of AD.
ESTHER : Wei_2017_Brain.Res.Bull_134_262
PubMedSearch : Wei_2017_Brain.Res.Bull_134_262
PubMedID: 28867383

Title : Integrated metabonomic-proteomic studies on blood enrichment effects of Angelica sinensis on a blood deficiency mice model - Hua_2017_Pharm.Biol_55_853
Author(s) : Hua Y , Yao W , Ji P , Wei Y
Ref : Pharm Biol , 55 :853 , 2017
Abstract : CONTEXT: Angelica sinensis (Oliv.) Diels (Umbelliferae) (AS) is a well-known Traditional Chinese Medicine (TCM) that enriches and regulates the blood. OBJECTIVE: An integrated metabonomic and proteomic method was developed and applied to study the blood enrichment effects and mechanisms of AS on blood deficiency (BD) mouse model. MATERIALS AND
METHODS: Forty mice were randomly divided into the control, BD, High-dose of AS (ASH), Middle-dose of AS (ASM), and Low-dose of AS (ASL) groups. BD model mice were established by injecting N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX) (ip). The aqueous extract of AS was administered at three dose of 20, 10, or 5 g/kg b. wt. orally for 7 consecutive days before/after APH and CTX administration. Gas chromatography-mass spectrometry (GC-MS) combined with pattern recognition method and 2D gel electrophoresis (2-DE) proteomics were performed in this study to discover the underlying hematopoietic regulation mechanisms of AS on BD mouse model.
RESULTS: Unlike in the control group, the HSP90 and arginase levels increased significantly (p < 0.05) in the BD group, but the levels of carbonic anhydrase, GAPDH, catalase, fibrinogen, GSTP, carboxylesterase and hem binding protein in the BD group decreased significantly (p < 0.05). Unlike the levels in the BD group, the levels of these biomarkers were regulated to a normal state near the control group in the ASM group. Unlike in the control group, l-alanine, arachidonic acid, l-valine, octadecanoic acid, glycine, hexadecanoic acid, l-threonine, butanoic acid, malic acid, l-proline and propanoic acid levels increased significantly (p < 0.05) in the BD group, the levels of d-fructose in the BD group decreased significantly (p < 0.05). The relative concentrations of 12 endogenous metabolites were also significantly affected by the ASL, ASM, and ASH treatments. Notably, most of the altered BD-related metabolites were restored to normal state after ASM administration. CONCLUSION: AS can promote hematopoietic activities, inhibit production of reactive oxygen species, regulate energy metabolism, increase antiapoptosis, and potentially contribute to the blood enrichment effects of AS against APH- and CTX-induced BD mice.
ESTHER : Hua_2017_Pharm.Biol_55_853
PubMedSearch : Hua_2017_Pharm.Biol_55_853
PubMedID: 28140733

Title : Targeting of cancerassociated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment - Li_2016_Mol.Med.Rep_13_2476
Author(s) : Li M , Yin T , Shi H , Wen Y , Zhang B , Chen M , Xu G , Ren K , Wei Y
Ref : Mol Med Rep , 13 :2476 , 2016
Abstract : Cancerassociated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the smallmolecule dipeptidyl peptidase inhibitor PT100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT100 contained lower numbers of tumorassociated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumorpromoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance.
ESTHER : Li_2016_Mol.Med.Rep_13_2476
PubMedSearch : Li_2016_Mol.Med.Rep_13_2476
PubMedID: 26846566

Title : Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator - Wittenborn_2016_J.Biol.Chem_291_25264
Author(s) : Wittenborn EC , Jost M , Wei Y , Stubbe J , Drennan CL
Ref : Journal of Biological Chemistry , 291 :25264 , 2016
Abstract : Polyhydroxybutyrate synthase (PhaC) catalyzes the polymerization of 3-(R)-hydroxybutyryl-coenzyme A as a means of carbon storage in many bacteria. The resulting polymers can be used to make biodegradable materials with properties similar to those of thermoplastics and are an environmentally friendly alternative to traditional petroleum-based plastics. A full biochemical and mechanistic understanding of this process has been hindered in part by a lack of structural information on PhaC. Here we present the first structure of the catalytic domain (residues 201-589) of the class I PhaC from Cupriavidus necator (formerly Ralstonia eutropha) to 1.80 A resolution. We observe a symmetrical dimeric architecture in which the active site of each monomer is separated from the other by approximately 33 A across an extensive dimer interface, suggesting a mechanism in which polyhydroxybutyrate biosynthesis occurs at a single active site. The structure additionally highlights key side chain interactions within the active site that play likely roles in facilitating catalysis, leading to the proposal of a modified mechanistic scheme involving two distinct roles for the active site histidine. We also identify putative substrate entrance and product egress routes within the enzyme, which are discussed in the context of previously reported biochemical observations. Our structure lays a foundation for further biochemical and structural characterization of PhaC, which could assist in engineering efforts for the production of eco-friendly materials.
ESTHER : Wittenborn_2016_J.Biol.Chem_291_25264
PubMedSearch : Wittenborn_2016_J.Biol.Chem_291_25264
PubMedID: 27742839
Gene_locus related to this paper: alceu-phbc

Title : Enrichment of omega-3 fatty acids in cod liver oil via alternate solvent winterization and enzymatic interesterification - Lei_2016_Food.Chem_199_364
Author(s) : Lei Q , Ba S , Zhang H , Wei Y , Lee JY , Li T
Ref : Food Chem , 199 :364 , 2016
Abstract : Enrichment of omega-3 fatty acids in cod liver oil via alternate operation of solvent winterization and enzymatic interesterification was attempted. Variables including separation method, solvent, oil concentration, time and temperature were optimized for the winterization. Meanwhile, Novozyme 435, Lipozyme RM IM and Lipozyme TL IM were screened for interesterification efficiency under different system air condition, time and temperature. In optimized method, alternate winterization (0.1g/mL oil/acetone, 24h, -80 degC, precooled Buchner filtration) and interesterification (Lipozyme TL IM, N2 flow, 2.5h, 40 degC) successfully doubled the omega-3 fatty acid content to 43.20 mol%. (1)H NMR was used to determine omega-3 fatty acid content, and GC-MS to characterize oil product, which mainly contained DHA (15.81 mol%) and EPA (20.23 mol%). The proposed method offers considerable efficiency and reduce production cost drastically. Oil produced thereof is with high quality and of particular importance for the development of omega-3 based active pharmaceutical ingredients.
ESTHER : Lei_2016_Food.Chem_199_364
PubMedSearch : Lei_2016_Food.Chem_199_364
PubMedID: 26775983

Title : Baicalein alters PI3K\/Akt\/GSK3beta signaling pathway in rats with diabetes-associated cognitive deficits - Qi_2015_Int.J.Clin.Exp.Med_8_1993
Author(s) : Qi Z , Xu Y , Liang Z , Li S , Wang J , Wei Y , Dong B
Ref : Int J Clin Exp Med , 8 :1993 , 2015
Abstract : Our present investigation focused on assessing the neuroprotective potential of baicalein (BAC) against diabetes-associated cognitive deficit (DACD) using a diabetic model and further figure out the potential molecular mechanisms. Diabetic rat model was established by streptozotocin (STZ). Vehicle or BAC by the doses of 2 and 4 mg/kg was intraperitoneally injected once a day for seven consecutive weeks. Memory function was evaluated by Morris water maze test and avoidance passive test. The activities of acetylcholinesterase (AChE), choline acetylase (ChAT), caspase-9 and caspase-3 in STZ-induced diabetic rats' hippocampus were detected via responsive commercial kits. Western blot assay were used to determine the protein levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-Akt (p-Akt), and phospho-glycogen synthase kinase-3beta (p-GSK3beta). Our results showed that BAC remarkably increased body weight and ChAT activity, decreased blood glucose level and AChE activity as well as improved cognitive deficits in diabetic rats. Additionally, it was also found that treatment with BAC to diabetes obviously stimulated the p-PI3K and p-Akt and inhibited the level of p-GSK3beta. Furthermore, the neuronal apoptosis was also prevented after BAC treatment by decreasing caspase-9 and caspase-3 activities in diabetic rats' hippocampus. It is concluded that BAC exerted beneficial effects against DACD in rats and its neuroprotection might be linked with activating PI3K and Akt phosphorylation accompanied with suppressing the phosphorylated level of GSK3beta. These results hint that BAC is likely to be served as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as DACD.
ESTHER : Qi_2015_Int.J.Clin.Exp.Med_8_1993
PubMedSearch : Qi_2015_Int.J.Clin.Exp.Med_8_1993
PubMedID: 25932128

Title : Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP\/PS1 transgenic mice and scopolamine-induced memory impairment mice - He_2015_Eur.J.Pharmacol_768_96
Author(s) : He D , Wu H , Wei Y , Liu W , Huang F , Shi H , Zhang B , Wu X , Wang C
Ref : European Journal of Pharmacology , 768 :96 , 2015
Abstract : Harmine, a beta-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.
ESTHER : He_2015_Eur.J.Pharmacol_768_96
PubMedSearch : He_2015_Eur.J.Pharmacol_768_96
PubMedID: 26526348

Title : Expression, purification and characterization of a functional, recombinant, cold-active lipase (LipA) from psychrotrophic Yersinia enterocolitica - Ji_2015_Protein.Expr.Purif_115_125
Author(s) : Ji X , Li S , Wang B , Zhang Q , Lin L , Dong Z , Wei Y
Ref : Protein Expr Purif , 115 :125 , 2015
Abstract : A novel cold-active lipase gene encoding 294 amino acid residues was obtained from the Yersinia enterocolitica strain KM1. Sequence alignment and phylogenetic analysis revealed that this novel lipase is a new member of the bacterial lipase family I.1. The lipase shares the conserved GXSXG motif and catalytic triad Ser85-Asp239-His261. The recombinant protein LipA was solubly and heterogeneously expressed in Escherichia coli, purified by Ni-affinity chromatography, and then characterized. LipA was active over a broad range spanning 15-60 degrees C with an optimum activity at 25 degrees C and across a wide pH range from 5.0 to 11.0 with an optimum activity at pH 7.5. The molecular weight was estimated to be 34.2KDa. The lipase could be activated by Mg(2+) and a low concentration (10%) of ethanol, dimethyl sulfoxide, methanol and acetonitrile, whereas it was strongly inhibited by Zn(2+), Cu(2+) and Mn(2+). This cold-active lipase may be a good candidate for detergents and biocatalysts at low temperature.
ESTHER : Ji_2015_Protein.Expr.Purif_115_125
PubMedSearch : Ji_2015_Protein.Expr.Purif_115_125
PubMedID: 26256062

Title : Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits - Xu_2015_Gene_557_146
Author(s) : Xu H , Tao X , Wei Y , Chen J , Xing S , Cen W , Wen A , Zhu L , Tang G , Li M , Jiang A , Jiang Y , Li X
Ref : Gene , 557 :146 , 2015
Abstract : Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits.
ESTHER : Xu_2015_Gene_557_146
PubMedSearch : Xu_2015_Gene_557_146
PubMedID: 25498336

Title : Covalent immobilization of porcine pancreatic lipase on carboxyl-activated magnetic nanoparticles: Characterization and application for enzymatic inhibition assays - Zhu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_38_278
Author(s) : Zhu YT , Ren XY , Liu YM , Wei Y , Qing LS , Liao X
Ref : Mater Sci Eng C Mater Biol Appl , 38 :278 , 2014
Abstract : Using carboxyl functionalized silica-coated magnetic nanoparticles (MNPs) as carrier, a novel immobilized porcine pancreatic lipase (PPL) was prepared through the 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling reaction. Transmission electron microscopic images showed that the synthesized nanoparticles (Fe3O4-SiO2) possessed three dimensional core-shell structures with an average diameter of ~20nm. The effective enzyme immobilization onto the nanocomposite was confirmed by atomic force microscopic (AFM) analysis. Results from Fourier-transform infrared spectroscopy (FT-IR), Bradford protein assay, and thermo-gravimetric analysis (TGA) indicated that PPL was covalently attached to the surface of magnetic nanoparticles with a PPL immobilization yield of 50mg enzyme/g MNPs. Vibrating sample magnetometer (VSM) analysis revealed that the MNPs-PPL nanocomposite had a high saturation magnetization of 42.25emu.g(-1). The properties of the immobilized PPL were investigated in comparison with the free enzyme counterpart. Enzymatic activity, reusability, thermo-stability, and storage stability of the immobilized PPL were found significantly superior to those of the free one. The Km and the Vmax values (0.02mM, 6.40U.mg(-1) enzyme) indicated the enhanced activity of the immobilized PPL compared to those of the free enzyme (0.29mM, 3.16U.mg(-1) enzyme). Furthermore, at an elevated temperature of 70 degrees C, immobilized PPL retained 60% of its initial activity. The PPL-MNPs nanocomposite was applied in the enzyme inhibition assays using orlistat, and two natural products isolated from oolong tea (i.e., EGCG and EGC) as the test compounds.
ESTHER : Zhu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_38_278
PubMedSearch : Zhu_2014_Mater.Sci.Eng.C.Mater.Biol.Appl_38_278
PubMedID: 24656379

Title : Modulation of cholinergic pathways and inflammatory mediators in blast-induced traumatic brain injury - Valiyaveettil_2013_Chem.Biol.Interact_203_371
Author(s) : Valiyaveettil M , Alamneh YA , Miller SA , Hammamieh R , Arun P , Wang Y , Wei Y , Oguntayo S , Long JB , Nambiar MP
Ref : Chemico-Biological Interactions , 203 :371 , 2013
Abstract : Cholinergic activity has been recognized as a major regulatory component of stress responses after traumatic brain injury (TBI). Centrally acting acetylcholinesterase (AChE) inhibitors are also being considered as potential therapeutic candidates against TBI mediated cognitive impairments. We have evaluated the expression of molecules involved in cholinergic and inflammatory pathways in various regions of brain after repeated blast exposures in mice. Isoflurane anesthetized C57BL/6J mice were restrained and placed in a prone position transverse to the direction of the shockwaves and exposed to three 20.6psi blast overpressures with 1-30min intervals. Brains were collected at the 6h time point after the last blast exposure and subjected to cDNA microarray and microRNA analysis. cDNA microarray analysis showed significant changes in the expression of cholinergic (muscarinic and nicotinic) and gammaaminobutyric acid and glutamate receptors in the midbrain region along with significant changes in multiple genes involved in inflammatory pathways in various regions of the brain. MicroRNA analysis of cerebellum revealed differential expression of miR-132 and 183, which are linked to cholinergic anti-inflammatory signaling, after blast exposure. Changes in the expression of myeloperoxidase in the cerebellum were confirmed by Western blotting. These results indicate that early pathologic progression of blast TBI involves dysregulation of cholinergic and inflammatory pathways related genes. Acute changes in molecules involved in the modulation of cholinergic and inflammatory pathways after blast TBI can cause long-term central and peripheral pathophysiological changes.
ESTHER : Valiyaveettil_2013_Chem.Biol.Interact_203_371
PubMedSearch : Valiyaveettil_2013_Chem.Biol.Interact_203_371
PubMedID: 23159883

Title : Inhibition of porcine liver carboxylesterase by phosphorylated flavonoids - Wei_2013_Chem.Biol.Interact_204_75
Author(s) : Wei Y , Peng AY , Huang J
Ref : Chemico-Biological Interactions , 204 :75 , 2013
Abstract : We have recently synthesized a series of phosphorylated flavonoids and identified some of them as potent inhibitors of pancreatic cholesterol esterase (CEase) with excellent selectivity for CEase over acetylcholinesterase (AChE). In the present paper, we investigated the inhibitory activities of these compounds against porcine liver carboxylesterase (CE) since carboxylesterases (CEs) are another family of serine esterases responsible for the metabolism and detoxification of many ester-containing xenobiotics and clinical esterified drugs, and there exists much structural similarity between CEase and CEs. The results indicated that phosphorylated flavonoids exhibited significantly improved inhibition potency toward CE than their parent compounds, and six of them had IC50 values less than 5.0nM. Among all compounds tested, compounds 3d and 3e are the two most potent inhibitors of CE, giving IC50 values of 1.79nM and 1.58nM, respectively. Interestingly, these compounds inhibited CEase and CE with similar structure activity correlations, and those with high inhibitory activities toward CEase could also inhibit CE efficiently. The presences of a free hydroxyl group at position 5 and a phosphate group at position 7 of the phosphorylated flavonoids are favorable to the inhibition of CE. The inhibition mechanism and kinetic characterization studies of the most potent inhibitors revealed that they are irreversible competitive inhibitors.
ESTHER : Wei_2013_Chem.Biol.Interact_204_75
PubMedSearch : Wei_2013_Chem.Biol.Interact_204_75
PubMedID: 23643881
Gene_locus related to this paper: pig-EST1

Title : A combination of [+] and [-]-Huperzine A improves protection against soman toxicity compared to [+]-Huperzine A in guinea pigs - Wang_2013_Chem.Biol.Interact_203_120
Author(s) : Wang Y , Wei Y , Oguntayo S , Doctor BP , Nambiar MP
Ref : Chemico-Biological Interactions , 203 :120 , 2013
Abstract : The neuropathologic mechanisms after exposure to lethal doses of nerve agent are complex and involve multiple biochemical pathways. Effective treatment requires drugs that can simultaneously protect by reversible binding to the acetylcholinesterase (AChE) and blocking cascades of seizure related brain damage, inflammation, neuronal degeneration as well as promoting induction of neuroregeneration. [-]-Huperzine A ([-]-Hup A), is a naturally occurring potent reversible AChE inhibitor that penetrates the blood-brain barrier. It also has several neuroprotective effects including modification of beta-amyloid peptide, reduction of oxidative stress, anti-inflammatory, anti-apoptotic and induction and regulation of nerve growth factor. Toxicities at higher doses restrict the neuroporotective ability of [-]-Hup A for treatment. The synthetic stereoisomer, [+]-Hup A, is less toxic due to poor AChE inhibition and is suitable for both pre-/post-exposure treatments of nerve agent toxicity. [+]-Hup A block the N-methyl-d-aspartate (NMDA)-induced seizure in rats, reduce excitatory amino acid induced neurotoxicity and also prevent soman induced toxicity with minimum performance decrement. Unique combinations of two stereo-isomers of Hup A may provide an excellent pre/post-treatment drug for the nerve agent induced seizure/status epilepticus. We investigated a combination of [+]-Hup A with a small dose of [-]-Hup A ([+] and [-]-Hup A) against soman toxicity. Our data showed that pretreatment with a combination [+] and [-]-Hup A significantly increased the survival rate and reduced behavioral abnormalities after exposure to 1.2xLD50 soman compared to [+]-Hup A in guinea pigs. In addition, [+] and [-]-Hup A pretreatment inhibited the development of high power of EEG better than [+]-Hup A pretreatment alone. These data suggest that a combination of [+] and [-]-Hup A offers better protection than [+]-Hup A and serves as a potent medical countermeasure against lethal dose nerve agent toxicity in guinea pigs.
ESTHER : Wang_2013_Chem.Biol.Interact_203_120
PubMedSearch : Wang_2013_Chem.Biol.Interact_203_120
PubMedID: 23123250

Title : Contamination of bananas with beauvericin and fusaric acid produced by Fusarium oxysporum f. sp. cubense - Li_2013_PLoS.One_8_e70226
Author(s) : Li C , Zuo C , Deng G , Kuang R , Yang Q , Hu C , Sheng O , Zhang S , Ma L , Wei Y , Yang J , Liu S , Biswas MK , Viljoen A , Yi G
Ref : PLoS ONE , 8 :e70226 , 2013
Abstract : BACKGROUND: Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense (Foc), is one of the most destructive diseases of banana. Toxins produced by Foc have been proposed to play an important role during the pathogenic process. The objectives of this study were to investigate the contamination of banana with toxins produced by Foc, and to elucidate their role in pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Twenty isolates of Foc representing races 1 and 4 were isolated from diseased bananas in five Chinese provinces. Two toxins were consistently associated with Foc, fusaric acid (FA) and beauvericin (BEA). Cytotoxicity of the two toxins on banana protoplast was determined using the Alamar Blue assay. The virulence of 20 Foc isolates was further tested by inoculating tissue culture banana plantlets, and the contents of toxins determined in banana roots, pseudostems and leaves. Virulence of Foc isolates correlated well with toxin deposition in the host plant. To determine the natural occurrence of the two toxins in banana plants with Fusarium wilt symptoms, samples were collected before harvest from the pseudostems, fruit and leaves from 10 Pisang Awak 'Guangfen #1' and 10 Cavendish 'Brazilian' plants. Fusaric acid and BEA were detected in all the tissues, including the fruits. CONCLUSIONS/SIGNFICANCE: The current study provides the first investigation of toxins produced by Foc in banana. The toxins produced by Foc, and their levels of contamination of banana fruits, however, were too low to be of concern to human and animal health. Rather, these toxins appear to contribute to the pathogenicity of the fungus during infection of banana plants.
ESTHER : Li_2013_PLoS.One_8_e70226
PubMedSearch : Li_2013_PLoS.One_8_e70226
PubMedID: 23922960
Gene_locus related to this paper: gibf5-fub5

Title : Regional specific alterations in brain acetylcholinesterase activity after repeated blast exposures in mice - Valiyaveettil_2012_Neurosci.Lett_506_141
Author(s) : Valiyaveettil M , Alamneh Y , Oguntayo S , Wei Y , Wang Y , Arun P , Nambiar MP
Ref : Neuroscience Letters , 506 :141 , 2012
Abstract : Acetylcholinesterase (AChE) which catalyzes the hydrolysis of the neurotransmitter acetylcholine has been recognized as one of the major regulators of stress responses after traumatic brain injury (TBI). Repeated blast exposure induces TBI (blast TBI) with a variable neuropathology at different brain regions. Since AChE inhibitors are being used as a line of treatment for TBI, we sought to determine the time course of AChE activity in the blood and different brain regions after repeated blast exposures using modified Ellman assay. Our data showed that repeated blast exposures significantly reduced AChE activity in the whole-blood and erythrocytes by 3-6h, while plasma AChE activity was significantly increased by 3h post-blast. In the brain, significant increase in AChE activity was observed at 6h in the frontal cortex, while hind cortex and hippocampus showed a significant decrease at 6h post-blast, which returned to normal levels by 7 days. AChE activity in the cerebellum and mid brain showed a decrease at 6h, followed by significant increase at 3 days and that was decreased significantly at 14 days post-blast. Medulla region showed decreased AChE activity at 24h post-blast, which was significantly increased at 14 days. These results suggest that there are brain regional and time-related changes in AChE activity after tightly coupled repeated blast exposures in mice. In summary, acute and chronic regional specific changes in the AChE activity after repeated blast exposures warrant systematic evaluation of the possibility of AChE inhibitor therapeutics against blast TBI.
ESTHER : Valiyaveettil_2012_Neurosci.Lett_506_141
PubMedSearch : Valiyaveettil_2012_Neurosci.Lett_506_141
PubMedID: 22079491

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

Title : Neuroprotective effects of imidazenil against chemical warfare nerve agent soman toxicity in guinea pigs - Wang_2012_Neurotoxicol_33_169
Author(s) : Wang Y , Oguntayo S , Wei Y , Wood E , Brown A , Jensen N , Auta J , Guiodotti A , Doctor BP , Nambiar MP
Ref : Neurotoxicology , 33 :169 , 2012
Abstract : The chemical warfare nerve agent, soman irreversibly inhibits acetylcholinesterase (AChE) leading to hypercholinergy and seizures which trigger glutamate toxicity and status epilepticus ultimately resulting in neuropathology and neurobehavioral deficits. The standard emergency treatment comprising of anticholinergic, AChE reactivator and anticonvulsant does not completely protect against soman toxicity. We have evaluated imidazenil, a new anticonvulsant imidazo benzodiazepine with high affinity and intrinsic efficacy at alpha5-, alpha2-, and alpha3- but low intrinsic efficacy at alpha1-containing GABA(A) receptors and is devoid of cardiorespiratory depression, sedative/hypnoitc and amnestic actions and does not elicit tolerance and dependence liabilities unlike diazepam, for protection against soman toxicity. Guinea pigs implanted with bipotential radiotelemetry probes for recording EEG and ECG were administered with 26 mug/kg pyridostigmine bromide 30 min prior to 2x LD(50) soman exposure and 1 min later treated with a combination of 2mg/kg atropine sulfate and 25mg/kg 2-pralidoxime and various doses of imidazenil. Intramuscular administration of imidazenil, dose-dependently protected against 2x LD(50) of soman toxicity up to 1mg/kg. Further increase in the dose of imidazenil to 2.5mg/kg was less effective than 1mg/kg probably due to non-specific actions at sites other than GABA(A) receptors. Compared to vehicle group, 1mg/kg imidazenil treatment showed optimal increase in survival rate, reduction in behavioral manifestations and high power of EEG spectrum as well as neuronal necrosis. These data suggest that imidazenil is an effective anticonvulsant for medical countermeasure against soman-induced toxicity.
ESTHER : Wang_2012_Neurotoxicol_33_169
PubMedSearch : Wang_2012_Neurotoxicol_33_169
PubMedID: 22245390

Title : [Effects of early intervention with Huannao Yicong formula effective components on behavior and cholinergic system of beta-amyloid precursor protein transgenic mice] - Cai_2011_Zhong.Xi.Yi.Jie.He.Xue.Bao_9_292
Author(s) : Cai LL , Li H , Liu JG , Liu LT , Guan J , Liu MF , Hu J , Wei Y
Ref : Zhong Xi Yi Jie He Xue Bao , 9 :292 , 2011
Abstract : OBJECTIVE: To observe the effects of early intervention with effective components from a Chinese herbal formula (Huannao Yicong formula, HNYCF) on behavior and related indicators of cholinergic system in beta-amyloid precursor protein (APP) transgenic mice. METHODS: Sixty 3-month-old APP695 V717I transgenic mice were randomly divided into model group, high-dose HNYCF group (2.80 g/(kg.d)), low-dose HNYCF group (1.40 g/(kg.d)) and donepezil group (0.65 mg/(kg.d)), with 15 mice in each group. Fifteen non-transgenic mice of the same genetic background were used as normal group. The model group and normal group were fed with equal volume of distilled water by gavage. After 6-month continuous medication, the Morris water maze and the passive avoidance test were used to detect the visual spatial learning and memory ability of each mouse. Then the mice were decapitated and their cerebral cortex and hippocampus were isolated to homogenate by sonication. Contents of acetylcholine (ACh) and acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity in the homogenate were determined by enzyme-linked immunosorbent assay, and protein contents of cerebral cortex and hippocampus were measured by Coomassie brilliant blue method. RESULTS: Compared with the model group, high- and low-dose HNYCF and donepezil hydrochloride all improved spatial learning of APP mice in the Morris water maze. The ratio of swimming distance in the central area in the high-dose HNYCF group was longer than that in the model group (P<0.05). In the passive avoidance test, high- and low-dose HNYCF and donepezil hydrochloride improved memory function of APP mice by improving the escape latency and reducing the number of errors (P<0.05, P<0.01). High- and low-dose HNYCF and donepezil hydrochloride reduced the content of AChE, increased the activity of ChAT (P<0.01, P<0.05) and improved the content of ACh in hippocampus (P<0.05); high- and low-dose HNYCF and donepezil hydrochloride increased the content of ACh in cortex (P<0.05). Donepezil hydrochloride reduced the content of AChE in cortex (P<0.05), however, high- and low-dose HNYCF had no obvious influence (P>0.05). High- and low-dose HNYCF increased the content of ChAT in cortex (P<0.05), whereas donepezil hydrochloride had no obvious influence (P>0.05). CONCLUSION: Early intervention with HNYCF effective components can improve the learning and memory ability of APP transgenic mice. The mechanism may be related to enhancing the function of cholinergic system.
ESTHER : Cai_2011_Zhong.Xi.Yi.Jie.He.Xue.Bao_9_292
PubMedSearch : Cai_2011_Zhong.Xi.Yi.Jie.He.Xue.Bao_9_292
PubMedID: 21419082

Title : Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population - Li_2011_Ann.Hum.Genet_75_605
Author(s) : Li L , Qi L , Lv N , Gao Q , Cheng Y , Wei Y , Ye J , Yan X , Dang A
Ref : Ann Hum Genet , 75 :605 , 2011
Abstract : The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.
ESTHER : Li_2011_Ann.Hum.Genet_75_605
PubMedSearch : Li_2011_Ann.Hum.Genet_75_605
PubMedID: 21834908
Gene_locus related to this paper: human-PLA2G7

Title : Analysis of the promoter region of the gene LIP1 encoding triglyceride lipase from Fusarium graminearum - Feng_2011_Microbiol.Res_166_618
Author(s) : Feng J , Bhadauria V , Liu G , Selvaraj G , Hughes GR , Wei Y
Ref : Microbiol Res , 166 :618 , 2011
Abstract : Triglyceride lipases catalyze the reversible degradation of glycerol esters with long-chain fatty acids into fatty acids and glycerol. In silico analysis of 5'-end flanking sequence of the gene LIP1 encoding a triglyceride lipase from the wheat head blight pathogen Fusarium graminearum revealed the presence of several cis-regulatory elements. To delineate the function of these regulatory elements, we constructed a series of deletion mutants in the LIP1 promoter region fused to the open reading frame of a green fluorescent protein (GFP) and assayed the promoter activity. Analysis of GFP expression levels in mutants indicated that a 563-bp promoter sequence was sufficient to drive the expression of LIP1 and regulatory elements responsible for the gene induction were located within the 563-372bp region. To further investigate the regulatory elements, putative cis-acting elements spanned within the 563-372bp region were mutated using a targeted mutagenesis approach. A CCAAT box, a CreA binding site, and a fatty acid responsive element (FARE) were identified and confirmed to be required for the basal expression of LIP1, glucose suppression and fatty acid induction, respectively.
ESTHER : Feng_2011_Microbiol.Res_166_618
PubMedSearch : Feng_2011_Microbiol.Res_166_618
PubMedID: 21295455

Title : Analysis of a Blumeria graminis-secreted lipase reveals the importance of host epicuticular wax components for fungal adhesion and development - Feng_2009_Mol.Plant.Microbe.Interact_22_1601
Author(s) : Feng J , Wang F , Liu G , Greenshields D , Shen W , Kaminskyj S , Hughes GR , Peng Y , Selvaraj G , Zou J , Wei Y
Ref : Mol Plant Microbe Interact , 22 :1601 , 2009
Abstract : The biotrophic powdery mildew fungus Blumeria graminis releases extracellular materials to the surface of fungal infection structures that facilitate anchoring them to hydrophobic plant surfaces prior to infection; however, the chemistry of fungal adhesives and the mechanism of adhesion remain largely unclear. Expressed sequence tag analysis led to identification of a secreted lipase, Lip1, from B. graminis. Expression of LIP1 is dramatically upregulated during the early stages of fungal development. Lip1, secreted to the surface of fungal cell walls, possesses lipolytic activity against a broad range of glycerides and releases alkanes and primary fatty alcohols from the epicuticular wax of wheat leaves. Of the epicuticular wax components released by Lip1 activity, long-chain alkanes are the most efficient cues for triggering appressorium formation. Pretreatment of wheat leaves with Lip1, thereby removing leaf surface wax, severely compromises components of fungal pathogenicity, including conidial adhesion, appressorium formation, and secondary hypha growth. Our data suggest that Lip1 activity releases cues from the host surface to promote pathogen development and infection.
ESTHER : Feng_2009_Mol.Plant.Microbe.Interact_22_1601
PubMedSearch : Feng_2009_Mol.Plant.Microbe.Interact_22_1601
PubMedID: 19888825
Gene_locus related to this paper: blugr-d2cql4

Title : A novel biosensor based on photoelectro-synergistic catalysis for flow-injection analysis system\/amperometric detection of organophosphorous pesticides - Wei_2009_Anal.Chim.Acta_643_13
Author(s) : Wei Y , Li Y , Qu Y , Xiao F , Shi G , Jin L
Ref : Anal Chim Acta , 643 :13 , 2009
Abstract : In this study, a highly sensitive amperometric biosensor based on photoelectro-synergistic catalysis for detecting organophosphorus pesticides (OPs) in flow-injection analysis (FIA) system has been developed. The acetylcholinesterase enzyme (AChE) was immobilized by adsorption into the nanostructured PbO2/TiO2/Ti, which also acted as the working electrode. This strategy was found to catalyze the oxidative reaction of thiocholine effectively, make the AChE/PbO2/TiO2/Ti biosensor detect the substrate at 0.30 V (vs. SCE), hundreds milli-volts lower than others reported. PbO2/TiO2/Ti and TiO2/Ti electrodes were prepared and investigated with atomic force microscope (AFM). Factors influencing the performance were optimized. The resulting flow system offered a fast, sensitive, and stable response. A value of 1.34 mM for the apparent Michaelis-Menten constant (K(M)(app)) was obtained. A wide linear inhibition response for trichlorfon was observed in the range of 0.01-20 microM with the detection limit of 0.1 nM. The results using this biosensor agreed very well with chromatographic method and we also examined the real samples successfully in this work.
ESTHER : Wei_2009_Anal.Chim.Acta_643_13
PubMedSearch : Wei_2009_Anal.Chim.Acta_643_13
PubMedID: 19446058

Title : Monitoring enzyme reaction and screening of inhibitors of acetylcholinesterase by quantitative matrix-assisted laser desorption\/ionization Fourier transform mass spectrometry - Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
Author(s) : Xu Z , Yao S , Wei Y , Zhou J , Zhang L , Wang C , Guo Y
Ref : J Am Soc Mass Spectrom , 19 :1849 , 2008
Abstract : A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)-based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (K(m)) of acetylcholinesterase (AChE) was determined to be 73.9 micromol L(-1) by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC(50)) value of galantamine obtained for AChE was 2.39 micromol L(-1). Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE.
ESTHER : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedSearch : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedID: 18789720

Title : The strength of dehalogenase-substrate hydrogen bonding correlates with the rate of Meisenheimer intermediate formation - Dong_2003_Biochemistry_42_9482
Author(s) : Dong J , Lu X , Wei Y , Luo L , Dunaway-Mariano D , Carey PR
Ref : Biochemistry , 42 :9482 , 2003
Abstract : 4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolytic dehalogenation of 4-CBA-CoA to 4-hydroxybenzoyl-CoA by using an active site aspartate as the nucleophile. Formation of the corresponding Meisenheimer complex (EMc) is followed by chloride ion expulsion which forms the arylated intermediate (EAr). This is then hydrolyzed to the product. In this paper, we explore the relationship between active site polarizing forces acting on the benzoyl carbonyl and the rate of formation of the Meisenheimer complex. The polarizing forces at the C[double bond]O group were modulated by introducing site-selected mutations (A112V, Y65D, G113A, G113S, G113N, and F64P), near the C[double bond]O binding site. Using either the substrate, 4-CBA-CoA, or the substrate analogue, 4-methylbenzoyl-CoA (4-MBA-CoA), Raman difference spectroscopy provided the position of the C[double bond]O stretching frequency (nu(C)[double bond](O)) for a total of 10 enzyme-ligand complexes. In turn, the values of the C[double bond]O frequencies could be converted to differences in effective hydrogen bonding strengths between members of the series, based on earlier model studies [Clarkson, J., Tonge, P. J., Taylor, K. L., Dunaway-Mariano, D., and Carey, P. (1997) Biochemistry 36, 10192-10199]. Catalysis in the F64P, G113A, G113S, and G113N dehalogenase mutants was very slow with k(cat) values ranging from 8 x 10(-3) to 7.6 x 10(-6) s(-1). The EAr intermediate did not accumulate to a detectable level on these enzymes during a single turnover. Catalysis in the Y65D and A112V dehalogenase mutants were almost as efficient as catalysis in wild-type dehalogenase with k(cat) values of 0.1-0.6 s(-1). In wild-type dehalogenase, 22% of the bound substrate accumulated as the EAr intermediate during a single turnover (k(obs) for EAr formation = 24 s(-(1)); in the Y65D mutant, the level of accumulation is 17% (k(obs) for EAr formation = 3 s(-1)), and in the A112V mutant, the level is 23% (k(obs) for EAr formation = 17 s(-1)). The k(obs) for EAr formation in wild-type dehalogenase and the more active dehalogenase mutants (Y65D and A112V) was taken to be an estimate of the k for EMc formation, and the k(obs) for EP formation in a single turnover was taken to be an estimate of the k for EMc formation in the severely impaired mutants (F64P, G113A, G113S, and G113N). A plot of the log k(obs) for EMc formation versus the C[double bond]O stretching frequency of bound 4-CBA-CoA (or 4-MBA-CoA) is a straight line (R(2) = 0.9584). Throughout the series, nu(C)[double bond](O) varied by 61 cm(-1), corresponding to the change in hydrogen bonding enthalpy of 67 kJ/mol. The results show that changes in polarizing forces at the benzoyl carbonyl are transmitted to the benzoyl (4) position and correlate with the rate of aromatic nucleophilic addition five chemical bonds away. Interestingly, the relationship between effective polarizing forces and reactivity seen here for dehalogenase is similar to that reported for the addition-elimination reaction involving the hydrolysis of a series of acyl serine proteases.
ESTHER : Dong_2003_Biochemistry_42_9482
PubMedSearch : Dong_2003_Biochemistry_42_9482
PubMedID: 12899635

Title : Crystal structure of brefeldin A esterase, a bacterial homolog of the mammalian hormone-sensitive lipase - Wei_1999_Nat.Struct.Biol_6_340
Author(s) : Wei Y , Contreras JA , Sheffield P , Osterlund T , Derewenda U , Kneusel RE , Matern U , Holm C , Derewenda ZS
Ref : Nat Struct Biol , 6 :340 , 1999
Abstract : Brefeldin A esterase (BFAE), a detoxifying enzyme isolated from Bacillus subtilis, hydrolyzes and inactivates BFA, a potent fungal inhibitor of intracellular vesicle-dependent secretory transport and poliovirus RNA replication. We have solved the crystal structure of BFAE and we discovered that the previously reported amino acid sequence was in serious error due to frame shifts in the cDNA sequence. The correct sequence, inferred from the experimentally phased electron density map, revealed that BFAE is a homolog of the mammalian hormone sensitive lipase (HSL). It is a canonical alpha/beta hydrolase with two insertions forming the substrate binding pocket. The enzyme contains a lipase-like catalytic triad, Ser 202, Asp 308 and His 338, consistent with mutational studies that implicate the homologous Ser 424, Asp 693 and His 723 in the catalytic triad in human HSL.
ESTHER : Wei_1999_Nat.Struct.Biol_6_340
PubMedSearch : Wei_1999_Nat.Struct.Biol_6_340
PubMedID: 10201402
Gene_locus related to this paper: bacsu-brefe

Title : Structure-Function Relationships in High Molecular Weight PAF-Acetylhydrolases from the Studies of a Microbial alpha\/beta Hydrolase -
Author(s) : Derewenda Z , Wei Y , Derewenda U
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :309 , 1998

Title : Structure of a microbial homologue of mammalian platelet-activating factor acetylhydrolases: Streptomyces exfoliatus lipase at 1.9 A resolution - Wei_1998_Structure_6_511
Author(s) : Wei Y , Swenson L , Castro C , Derewenda U , Minor W , Arai H , Aoki J , Inoue K , Servin-Gonzalez L , Derewenda ZS
Ref : Structure , 6 :511 , 1998
Abstract : Neutral lipases are ubiquitous and diverse enzymes. The molecular architecture of the structurally characterized lipases is similar, often despite a lack of detectable homology at the sequence level. Some of the microbial lipases are evolutionarily related to physiologically important mammalian enzymes. For example, limited sequence similarities were recently noted for the Streptomyces exfoliatus lipase (SeL) and two mammalian platelet-activating factor acetylhydrolases (PAF-AHs). The determination of the crystal structure of SeL allowed us to explore the structure-function relationships in this novel family of homologous hydrolases. RESULTS: The crystal structure of SeL was determined by multiple isomorphous replacement and refined using data to 1.9 A resolution. The molecule exhibits the canonical tertiary fold of an alpha/beta hydrolase. The putative nucleophilic residue, Ser131, is located within a nucleophilic elbow and is hydrogen bonded to His209, which in turn interacts with Asp177. These three residues create a triad that closely resembles the catalytic triads found in the active sites of other neutral lipases. The mainchain amides of Met132 and Phe63 are perfectly positioned to create an oxyanion hole. Unexpectedly, there are no secondary structure elements that could render the active site inaccessible to solvent, like the lids that are commonly found in neutral lipases. CONCLUSIONS: The crystal structure of SeL reinforces the notion that it is a homologue of the mammalian PAF-AHs. We have used the catalytic triad in SeL to model the active site of the PAF-AHs. Our model is consistent with the site-directed mutagenesis studies of plasma PAF-AH, which implicate Ser273, His351 and Asp296 in the active site. Our study therefore provides direct support for the hypothesis that the plasma and isoform II PAF-AHs are triad-containing alpha/beta hydrolases.
ESTHER : Wei_1998_Structure_6_511
PubMedSearch : Wei_1998_Structure_6_511
PubMedID: 9562561
Gene_locus related to this paper: strex-lipas

Title : Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer - Ho_1997_Nature_385_89
Author(s) : Ho YS , Swenson L , Derewenda U , Serre L , Wei Y , Dauter Z , Hattori M , Adachi T , Aoki J , Arai H , Inoue K , Derewenda ZS
Ref : Nature , 385 :89 , 1997
Abstract : The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer.
ESTHER : Ho_1997_Nature_385_89
PubMedSearch : Ho_1997_Nature_385_89
PubMedID: 8985254

Title : A novel variant of the catalytic triad in the Streptomyces scabies esterase - Wei_1995_Nat.Struct.Biol_2_218
Author(s) : Wei Y , Schottel JL , Derewenda U , Swenson L , Patkar S , Derewenda ZS
Ref : Nat Struct Biol , 2 :218 , 1995
Abstract : The crystal structure of a novel esterase from Streptomyces scabies, a causal agent of the potato scab disease, was solved at 2.1 A resolution. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases. The active site contains a dyad of Ser 14 and His 283, closely resembling two of the three components of typical Ser-His-Asp(Glu) triads from other serine hydrolases. Proper orientation of the active site imidazol is maintained by a hydrogen bond between the N delta-H group and a main chain oxygen. Thus, the enzyme constitutes the first known natural variation of the chymotrypsin-like triad in which a carboxylic acid is replaced by a neutral hydrogen-bond acceptor.
ESTHER : Wei_1995_Nat.Struct.Biol_2_218
PubMedSearch : Wei_1995_Nat.Struct.Biol_2_218
PubMedID: 7773790

Title : Conformational lability of lipases observed in the absence of an oil-water interface: crystallographic studies of enzymes from the fungi Humicola lanuginosa and Rhizopus delemar - Derewenda_1994_J.Lipid.Res_35_524
Author(s) : Derewenda U , Swenson L , Wei Y , Green R , Kobos PM , Joerger R , Haas MJ , Derewenda ZS
Ref : J Lipid Res , 35 :524 , 1994
Abstract : Considerable controversy exists regarding the exact nature of the molecular mechanism of interfacial activation, a process by which most lipases achieve maximum catalytic activity upon adsorption to an oil water interface. X-ray crystallographic studies show that lipases contain buried active centers and that displacements of entire secondary structure elements, or "lids," take place when the enzymes assume active conformations [Derewenda, U., A. M. Brzozowski, D. M. Lawson, and Z. S. Derewenda. 1992. Biochemistry: 31: 1532-1541; van Tilbeurgh, H., M-P. Egloff, C. Martinez, N. Rugani, R. Verger, and C. Cambillau. 1993. Nature: 362: 814-820; Grochulski, P., L. Yunge, J. D. Schrag, F. Bouthillier, P. Smith, D. Harrison, B. Rubin, and M. Cygler. 1993. J. Biol. Chem. 268: 12843-12847]. A simple two-state model inferred from these results implies that the "closed" conformation is stable in an aqueous medium, rendering the active centers inaccessible to water soluble substrates. We now report that in crystals of the Humicola lanuginosa lipase the "lid" is significantly disordered irrespective of the ionic strength of the medium, while in a related enzyme from Rhizopus delemar, crystallized in the presence of a detergent, the two molecules that form the asymmetric unit show different "lid" conformations. These new results call into question the simplicity of the "enzyme theory" of interfacial activation.
ESTHER : Derewenda_1994_J.Lipid.Res_35_524
PubMedSearch : Derewenda_1994_J.Lipid.Res_35_524
PubMedID: 8014587
Gene_locus related to this paper: humla-1lipa , rhidl-lipas

Title : An unusual buried polar cluster in a family of fungal lipases - Derewenda_1994_Nat.Struct.Biol_1_36
Author(s) : Derewenda U , Swenson L , Green R , Wei Y , Dodson GG , Yamaguchi S , Haas MJ , Derewenda ZS
Ref : Nat Struct Biol , 1 :36 , 1994
Abstract : The stability of globular proteins arises largely from the burial of non-polar amino acids in their interior. These residues are efficiently packed to eliminate energetically unfavorable cavities. Contrary to these observations, high resolution X-ray crystallographic analyses of four homologous lipases from filamentous fungi reveal an alpha/beta fold which contains a buried conserved constellation of charged and polar side chains with associated cavities containing ordered water molecules. It is possible that this structural arrangement plays an important role in interfacial catalysis.
ESTHER : Derewenda_1994_Nat.Struct.Biol_1_36
PubMedSearch : Derewenda_1994_Nat.Struct.Biol_1_36
PubMedID: 7656005
Gene_locus related to this paper: humla-1lipa , penca-mdgli , rhidl-lipas

Title : Current progress in crystallographic studies of new lipases from filamentous fungi - Derewenda_1994_Protein.Eng_7_551
Author(s) : Derewenda U , Swenson L , Green R , Wei Y , Yamaguchi S , Joerger R , Haas MJ , Derewenda ZS
Ref : Protein Engineering , 7 :551 , 1994
Abstract : Lipases from filamentous fungi have been studied extensively over many years. They exhibit properties attractive for industrial applications, e.g. in laundry detergents, tanning and paper industries and stereospecific organic synthesis. Enzymes from the fungi Rhizomucor miehei and Geotrichum candidum have been among the first neutral lipases to be characterized structurally by X-ray diffraction methods. In this paper we report a preliminary account of crystallographic studies of three other fungal lipases homologous to that from R. miehei and obtained from Humicola lanuginosa, Penicillium camembertii and Rhizopus delemar. These newly characterized structures have important implications for our understanding of structure-function relationships in lipases in general and the molecular basis of interfacial activation.
ESTHER : Derewenda_1994_Protein.Eng_7_551
PubMedSearch : Derewenda_1994_Protein.Eng_7_551
PubMedID: 8029211
Gene_locus related to this paper: humla-1lipa , penca-mdgli , rhidl-lipas

Title : Crystallization and preliminary crystallographic studies of the precursor and mature forms of a neutral lipase from the fungus Rhizopus delemar - Swenson_1994_Proteins_18_301
Author(s) : Swenson L , Green R , Joerger R , Haas M , Scott K , Wei Y , Derewenda U , Lawson DM , Derewenda ZS
Ref : Proteins , 18 :301 , 1994
Abstract : A neutral lipase from the filamentous fungus Rhizopus delemar has been crystallized in both its proenzyme and mature forms. Although the latter crystallizes readily and produces a variety of crystal forms, only one was found to be suitable for X-ray studies. It is monoclinic (C2, a = 92.8 A, b = 128.9 A, c = 78.3 A, beta = 135.8) with two molecules in the asymmetric unit related by a noncrystallographic diad. The prolipase crystals are orthorhombic (P2(1)2(1)2(1), with a = 79.8 A, b = 115.2 A, c = 73.0 A) and also contain a pair of molecules in the asymmetric unit. Initial results of molecular replacement calculations using the refined coordinates of the related lipase from Rhizomucor miehei identified the correct orientations and positions of the protein molecules in the unit cells of crystals of both proenzyme and the mature form.
ESTHER : Swenson_1994_Proteins_18_301
PubMedSearch : Swenson_1994_Proteins_18_301
PubMedID: 8202471

Title : Crystal structure, at 2.6-A resolution, of the Streptomyces lividans xylanase A, a member of the F family of beta-1,4-D-glycanases - Derewenda_1994_J.Biol.Chem_269_20811
Author(s) : Derewenda U , Swenson L , Green R , Wei Y , Morosoli R , Shareck F , Kluepfel D , Derewenda ZS
Ref : Journal of Biological Chemistry , 269 :20811 , 1994
Abstract : The crystal structure of the 32-kDa catalytic domain of the Streptomyces lividans xylanase A was solved by molecular isomorphous replacement methods and subsequently refined at 2.6-A resolution to a conventional crystallographic R factor of 0.21. This is the first successful structure determination of a member of the F family of endo-beta-1,4-D-glycanases. Unlike the recently determined xylanases of the G family (Wakarchuk, W. W., Campbell, R. L., Sung, W. L., Davoodi, J., and Yaguchi, M. (1994) Protein Sci. 3, 467-475), where the catalytic domains have a unique beta-sheet structure, the 32-kDa domain of the S. lividans xylanase A is folded into a complete (alpha/beta)8 barrel, the first such fold observed among beta-1,4-D-glycanases. The active site is located at the carbonyl end of the beta barrel. The crystal structure supports the earlier assignment of Glu-128 and Glu-236 as the catalytic amino acids (Moreau, A., Roberge, M., Manin, C., Shareck, F., Kluepfel, D., and Morosoli, R. (1994) Biochem. J., in press).
ESTHER : Derewenda_1994_J.Biol.Chem_269_20811
PubMedSearch : Derewenda_1994_J.Biol.Chem_269_20811
PubMedID: 8063693

Title : Structure of a myristoyl-ACP-specific thioesterase from Vibrio harveyi - Lawson_1994_Biochemistry_33_9382
Author(s) : Lawson DM , Derewenda U , Serre L , Ferri S , Szittner R , Wei Y , Meighen EA , Derewenda ZS
Ref : Biochemistry , 33 :9382 , 1994
Abstract : The crystal structure of a myristoyl acyl carrier protein specific thioesterase (C14ACP-TE) from a bioluminescent bacterium, Vibrio harveyi, was solved by multiple isomorphous replacement methods and refined to an R factor of 22% at 2.1-A resolution. This is the first elucidation of a three-dimensional structure of a thioesterase. The overall tertiary architecture of the enzyme resembles closely the consensus fold of the rapidly expanding superfamily of alpha/beta hydrolases, although there is no detectable homology with any of its members at the amino acid sequence level. Particularly striking similarity exists between the C14ACP-TE structure and that of haloalkane dehalogenase from Xanthobacter autotrophicus. Contrary to the conclusions of earlier studies [Ferri, S. R., & Meighen, E. A. (1991) J. Biol. Chem. 266, 12852-12857] which implicated Ser77 in catalysis, the crystal structure of C14ACP-TE reveals a lipase-like catalytic triad made up of Ser114, His241, and Asp211. Surprisingly, the gamma-turn with Ser114 in a strained secondary conformation (phi = 53 degrees, psi = -127 degrees), characteristic of the so-called nucleophilic elbow, does not conform to the frequently invoked lipase/esterase consensus sequence (Gly-X-Ser-X-Gly), as the positions of both glycines are occupied by larger amino acids. Site-directed mutagenesis and radioactive labeling support the catalytic function of Ser114. Crystallographic analysis of the Ser77-->Gly mutant at 2.5-A resolution revealed no structural changes; in both cases the loop containing the residue in position 77 is disordered.
ESTHER : Lawson_1994_Biochemistry_33_9382
PubMedSearch : Lawson_1994_Biochemistry_33_9382
PubMedID: 8068614
Gene_locus related to this paper: pholu-lxd1 , phopo-luxd , vibha-1luxd