Jia J

References (23)

Title : Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour - Chen_2022_Phytochemistry_196_113089
Author(s) : Chen SQ , Jia J , Hu JY , Wu J , Sun WT , Zheng M , Wang X , Zhu KK , Jiang CS , Yang SP , Zhang J , Wang SB , Cai YS
Ref : Phytochemistry , 196 :113089 , 2022
Abstract : Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC(50) values of 2.61, 1.19, and 1.74 microM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 microg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC(50) of 20.06 microM) and alpha-glycosidase inhibitor (IC(50) of 17.18 microM), while tabernamine, ervahanine B, and ervadivaricatine B only showed alpha-glycosidase inhibitory activities with IC(50) values in the range of 0.95-4.61 microM.
ESTHER : Chen_2022_Phytochemistry_196_113089
PubMedSearch : Chen_2022_Phytochemistry_196_113089
PubMedID: 35074605

Title : Design, synthesis, and cholinesterase inhibition assay of liquiritigenin derivatives as anti-Alzheimer's activity - Guan_2021_Bioorg.Med.Chem.Lett__128306
Author(s) : Guan L , Peng D , Zhang L , Jia J , Jiang H
Ref : Bioorganic & Medicinal Chemistry Lett , :128306 , 2021
Abstract : The marine environment is a rich resource for discovering functional materials, and seaweed is recognized for its potential use in biology and medicine. Liquiritigenin has been isolated and identified from Sargassum pallidum. To find new anti-Alzheimer's activity, we designed and synthesized thirty-two 7-prenyloxy-2,3-dihydroflavanone derivatives (3a-3p) and 5-hydroxy-7-prenyloxy-2,3-dihydro- flavanone derivatives (4a-4p) as cholinesterases inhibitors based on liquiritigenin as the lead compound. Inhibition screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) indicated that all synthesized compounds possessed potent AChE inhibitory activity and moderated to weak BuChE inhibitory activity in vitro. Kinetic studies demonstrated that compound 4o inhibited AChE via a dual binding site ability. In addition, all compounds displayed the radical scavenging effects. Finally, the molecular docking simulation of 4o in AChE active site displayed good agreement with the obtained the pharmacological results.
ESTHER : Guan_2021_Bioorg.Med.Chem.Lett__128306
PubMedSearch : Guan_2021_Bioorg.Med.Chem.Lett__128306
PubMedID: 34371131

Title : Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials - Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
Author(s) : Yu JT , Xu W , Tan CC , Andrieu S , Suckling J , Evangelou E , Pan A , Zhang C , Jia J , Feng L , Kua EH , Wang YJ , Wang HF , Tan MS , Li JQ , Hou XH , Wan Y , Tan L , Mok V , Dong Q , Touchon J , Gauthier S , Aisen PS , Vellas B
Ref : Journal of Neurology Neurosurg Psychiatry , 91 :1201 , 2020
Abstract : BACKGROUND: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. RESULTS: A total of 44676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
ESTHER : Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
PubMedSearch : Yu_2020_J.Neurol.Neurosurg.Psychiatry_91_1201
PubMedID: 32690803

Title : Sixteen-Week Interventional Study to Evaluate the Clinical Effects and Safety of Rivastigmine Capsules in Chinese Patients with Alzheimer's Disease - Jia_2019_J.Alzheimers.Dis_72_1313
Author(s) : Jia J , Ji Y , Feng T , Ye Q , Peng D , Kuang W , Ning Y , Liang Z , Fan D , Wei W , Li Y , Xiao S
Ref : J Alzheimers Dis , 72 :1313 , 2019
Abstract : BACKGROUND: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. OBJECTIVE: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer's disease (AD). METHODS: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naive AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer's Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. RESULTS: 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (>/=6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: -3.0 to -1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). CONCLUSION: This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose.
ESTHER : Jia_2019_J.Alzheimers.Dis_72_1313
PubMedSearch : Jia_2019_J.Alzheimers.Dis_72_1313
PubMedID: 31744005

Title : Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer's Disease - Schelter_2019_J.Alzheimers.Dis_72_931
Author(s) : Schelter BO , Shiells H , Baddeley TC , Rubino CM , Ganesan H , Hammel J , Vuksanovic V , Staff RT , Murray AD , Bracoud L , Riedel G , Gauthier S , Jia J , Bentham P , Kook K , Storey JMD , Harrington CR , Wischik CM
Ref : J Alzheimers Dis , 72 :931 , 2019
Abstract : BACKGROUND: Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials in mild to moderate Alzheimer's disease (AD) comparing doses in the range 150-250 mg/day with 8 mg/day intended as a control. OBJECTIVE: To determine how drug exposure is related to treatment response. METHODS: A sensitive plasma assay for the drug was used in a population pharmacokinetic analysis of samples from 1,162 of the 1,686 patients who participated in either of the Phase III trials with available samples and efficacy outcome data. RESULTS: There are steep concentration-response relationships for steady state plasma levels in the range 0.3-0.8 ng/ml at the 8 mg/day dose. Using a threshold based on the lower limit of quantitation of the assay on Day 1, there are highly significant differences in cognitive decline and brain atrophy in patients with above threshold plasma levels, both for monotherapy and add-on therapy, but with effect sizes reduced by half as add-on. Plasma concentrations in the range 4-21 ng/ml produced by the high doses are not associated with any additional benefit. CONCLUSIONS: Hydromethylthionine has pharmacological activity on brain structure and function at the 8 mg/day dose as monotherapy or as add-on to symptomatic treatments. This combined with a plateau at higher doses is consistent with the lack of dose-response seen in the Phase III trials. Treatment benefit is predicted to be maximal at 16 mg/day as monotherapy. A placebo-controlled trial in mild/moderate AD is now ongoing to confirm efficacy at this dose.
ESTHER : Schelter_2019_J.Alzheimers.Dis_72_931
PubMedSearch : Schelter_2019_J.Alzheimers.Dis_72_931
PubMedID: 31658058

Title : Orlistat response to missense mutations in lipoprotein lipase - Chen_2017_Biotechnol.Appl.Biochem_64_464
Author(s) : Chen H , Jia J , Ni Z , Vastermark A , Wu B , Le Y , Jawad U
Ref : Biotechnol Appl Biochem , 64 :464 , 2017
Abstract : The human lipoprotein lipase (LPL) is a therapeutic target for obesity, and inhibition of LPL with the approved small molecule agent orlistat has been widely used in clinic to treat obesity-related health problems such as diabetes and cardiovascular diseases. However, a variety of missense mutations in LPL protein have been observed, which may cause resistance or sensitization for orlistat, largely limiting the clinical applications of orlistat in obesity therapy. Here, we integrated molecular dynamics simulations and enzyme inhibition to investigate orlistat response to 16 disorder-associated missense mutations in LPL catalytic domain. It was found that most mutations have a modest effect on orlistat binding, and only few can exert strong impact to the binding. Three unfavorable (Trp86Arg, Ile194Thr, and Glu242Lys) and two favorable (His136Arg and Gly188Glu) mutations were identified, which can alter the binding affinity and inhibitory activity of orlistat considerably. Structural and energetic analysis revealed that these potent mutations induce orlistat resistance and sensitization by directly influencing the intermolecular interaction between LPL and orlistat or by indirectly addressing allosteric effect on LPL structure.
ESTHER : Chen_2017_Biotechnol.Appl.Biochem_64_464
PubMedSearch : Chen_2017_Biotechnol.Appl.Biochem_64_464
PubMedID: 27097985

Title : The Aegilops tauschii genome reveals multiple impacts of transposons - Zhao_2017_Nat.Plants_3_946
Author(s) : Zhao G , Zou C , Li K , Wang K , Li T , Gao L , Zhang X , Wang H , Yang Z , Liu X , Jiang W , Mao L , Kong X , Jiao Y , Jia J
Ref : Nat Plants , 3 :946 , 2017
Abstract : Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time.
ESTHER : Zhao_2017_Nat.Plants_3_946
PubMedSearch : Zhao_2017_Nat.Plants_3_946
PubMedID: 29158546
Gene_locus related to this paper: horvv-m0utz9 , wheat-a0a3b6c2m6 , wheat-a0a3b5zwb6 , wheat-a0a3b6bzs8 , wheat-a0a1d5zte7 , wheat-a0a1d5uwn5

Title : Impact of orientation and flexibility of peptide linkers on T. maritima lipase Tm1350 displayed on Bacillus subtilis spores surface using CotB as fusion partner - Ullah_2017_World.J.Microbiol.Biotechnol_33_166
Author(s) : Ullah J , Chen H , Vastermark A , Jia J , Wu B , Ni Z , Le Y , Wang H
Ref : World J Microbiol Biotechnol , 33 :166 , 2017
Abstract : Fusion protein construction often requires peptide linkers for prolonged conformation, extended stability and enzyme activity. In this study a series of fusion between Thermotoga maritima lipase Tm1350 and Bacillus subtillis coat protein CotB, comprising of several peptide linkers, with different length, flexibility and orientations were constructed. Effects of temperature, pH and chemicals were examined, on the activity of displayed enzyme. The fusion protein with longer flexible linkers L9 [(GGGGS)4] and L7 (GGGGS-GGGGS-EAAAK-EAAAK-GGGGS-GGGGS) possess 1.29 and 1.16-fold higher activity than the original, under optimum temperature and pH respectively. Moreover, spore surface displaying Tm1350 with L3 (EAAAK-GGGGS) and L9 ((GGGGS)4) showed extended thermostably, maintaining 1.40 and 1.35-fold higher activity than the original respectively, at 80 degrees C after 5 h of incubation. The enzyme activity of linkers with different orientation, including L5, L6 and L7 was determined, where L7 maintained 1.05 and 1.27-fold higher activity than L5 and L6. Effect of 0.1% proteinase K, bromelain, 20% ethanol and 30% methanol was investigated. Linkers with appropriate Glycine residues (flexible) showed higher activity than Alanine residues (rigid). The activity of the displayed enzyme can be improved by maintaining orientation and flexibility of peptide linkers, to evaluate high activity and stability in industrial processes.
ESTHER : Ullah_2017_World.J.Microbiol.Biotechnol_33_166
PubMedSearch : Ullah_2017_World.J.Microbiol.Biotechnol_33_166
PubMedID: 28822027

Title : Effect of Linker Length and Flexibility on the Clostridium thermocellum Esterase Displayed on Bacillus subtilis Spores - Chen_2017_Appl.Biochem.Biotechnol_182_168
Author(s) : Chen H , Wu B , Zhang T , Jia J , Lu J , Chen Z , Ni Z , Tan T
Ref : Appl Biochem Biotechnol , 182 :168 , 2017
Abstract : In fusion protein design strategies, the flexibility and length of linkers are important parameters affecting the bioactivity of multifunctional proteins. A series of fusion proteins with different linkers were constructed. The effect of temperature, pH, and organic solvents was investigated on the enzymatic activity. Fusion proteins with P1(PTPTPT) and P2((PTPTPT)2) linkers remained highly active with wide temperature range. At pH 9.6, the relative activity of fusion proteins with (PTPTPT)2 and S2(EGKSSGSGSESKST) linkers was 70 and 62 % (1.75 and 1.5 times of that of non-linker ones). Fusion proteins with S3((GGGGS)4) linker retained 55 % activity after 5 h of incubation at 80 degrees C (1.2-fold of that of non-linker fusion proteins and 1.9-fold of GGGGS-linker fusion proteins). Finally, the relative activity of fusion proteins having different linkers was increased with 20 % dimethyl sulfoxide (DMSO) and methanol; relative activity of fusion proteins with EGKSSGSGSESKST linkers was enhanced 1.5- and 2.2-fold, respectively. These results suggest that longer flexible linker can enhance the activity and stability of displayed esterase than shorter flexible linker. Optimizing peptide linkers with length, flexibility, and amino acid composition could improve the thermostability and activity of the displayed enzyme.
ESTHER : Chen_2017_Appl.Biochem.Biotechnol_182_168
PubMedSearch : Chen_2017_Appl.Biochem.Biotechnol_182_168
PubMedID: 27933482

Title : A Biotin Biosynthesis Gene Restricted to Helicobacter - Bi_2016_Sci.Rep_6_21162
Author(s) : Bi H , Zhu L , Jia J , Cronan JE
Ref : Sci Rep , 6 :21162 , 2016
Abstract : In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections.
ESTHER : Bi_2016_Sci.Rep_6_21162
PubMedSearch : Bi_2016_Sci.Rep_6_21162
PubMedID: 26868423
Gene_locus related to this paper: 9gamm-BioJ , helpy-o25061

Title : Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology - Jia_2015_Biomed.Res.Int_2015_497462
Author(s) : Jia J , Yang X , Wu Z , Zhang Q , Lin Z , Guo H , Lin CS , Wang J , Wang Y
Ref : Biomed Res Int , 2015 :497462 , 2015
Abstract : Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production.
ESTHER : Jia_2015_Biomed.Res.Int_2015_497462
PubMedSearch : Jia_2015_Biomed.Res.Int_2015_497462
PubMedID: 26366414

Title : Expression and Characterization of a New Thermostable Esterase from Clostridium thermocellum - Zhang_2015_Appl.Biochem.Biotechnol_177_1437
Author(s) : Zhang T , Chen H , Ni Z , Tian R , Jia J , Chen Z , Yang S
Ref : Appl Biochem Biotechnol , 177 :1437 , 2015
Abstract : The thermostable esterase from the thermophilic bacterium Clostridium thermocellum DSM 1313 was expressed in Escherichia coli and purified by Ni(2+) affinity chromatography. Its molecular weight was approximately 35 kDa according to 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The enzyme exhibited the highest specific activity with p-nitrophenyl butyrate (285 s(-1) mM(-1)). The activity of the esterase was greatest at 65 degrees C, and the esterase maintained residual activity levels of 70 and 50 % after 3 h incubation at 65 and 70 degrees C, respectively. Its activity was optimal at pH 7.0, was enhanced in the presence of Ca(2+) and Mg(2+), and was inhibited by Ni(2+) and Cu(2+). The addition of surfactants, such as Tween-20, Tween-80, Triton X-100, and SDS, at concentrations of 5 % (v/v) significantly inhibited the lipolytic action of the esterase. Enzyme activity was relatively stable in 10 % methanol, and 50 % residual activity was seen in 10 % DMSO, demonstrating its potential in biodiesel production and industrial applications.
ESTHER : Zhang_2015_Appl.Biochem.Biotechnol_177_1437
PubMedSearch : Zhang_2015_Appl.Biochem.Biotechnol_177_1437
PubMedID: 26373940
Gene_locus related to this paper: clotm-q4cf59

Title : Expression and display of a novel thermostable esterase from Clostridium thermocellum on the surface of Bacillus subtilis using the CotB anchor protein - Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
Author(s) : Chen H , Zhang T , Jia J , Vastermark A , Tian R , Ni Z , Chen Z , Chen K , Yang S
Ref : J Ind Microbiol Biotechnol , 42 :1439 , 2015
Abstract : Esterases expressed in microbial hosts are commercially valuable, but their applications are limited due to high costs of production and harsh industrial processes involved. In this study, the esterase-DSM (from Clostridium thermocellum) was expressed and successfully displayed on the spore surface, and the spore-associated esterase was confirmed by western blot analysis and activity measurements. The optimal temperature and pH of spore surface-displayed DSM was 60 and 8.5 degrees C, respectively. It also demonstrates a broad temperature and pH optimum in the range of 50-70, 7-9.5 degrees C. The spore surface-displayed esterase-DSM retained 78, 68 % of its original activity after 5 h incubation at 60 and 70 degrees C, respectively, which was twofold greater activity than that of the purified DSM. The recombinant spores has high activity and stability in DMSO, which was 49 % higher than the retained activity of the purified DSM in DMSO (20 % v/v), and retained 65.2 % of activity after 7 h of incubation in DMSO (20 % v/v). However, the recombinant spores could retain 77 % activity after 3 rounds of recycling. These results suggest that enzyme displayed on the surface of the Bacillus subtilis spore could serve as an effective approach for enzyme immobilization.
ESTHER : Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
PubMedSearch : Chen_2015_J.Ind.Microbiol.Biotechnol_42_1439
PubMedID: 26318029

Title : Overexpression of miR-155 in the Liver of Transgenic Mice Alters the Expression Profiling of Hepatic Genes Associated with Lipid Metabolism - Lin_2015_PLoS.One_10_e0118417
Author(s) : Lin X , Jia J , Du T , Li W , Wang X , Wei J , Zeng H , Yao L , Chen X , Zhuang J , Weng J , Liu Y , Lin J , Wu Q , Wang W , Yao K , Xu K , Xiao D
Ref : PLoS ONE , 10 :e0118417 , 2015
Abstract : Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice.
ESTHER : Lin_2015_PLoS.One_10_e0118417
PubMedSearch : Lin_2015_PLoS.One_10_e0118417
PubMedID: 25799309

Title : A lifespan observation of a novel mouse model: in vivo evidence supports abeta oligomer hypothesis - Zhang_2014_PLoS.One_9_e85885
Author(s) : Zhang Y , Lu L , Jia J , Jia L , Geula C , Pei J , Xu Z , Qin W , Liu R , Li D , Pan N
Ref : PLoS ONE , 9 :e85885 , 2014
Abstract : Transgenic mouse models are powerful tools in exploring the mechanisms of AD. Most current transgenic models of AD mimic the memory impairment and the main pathologic features, among which the formation of beta-amyloid (Abeta) plaques is considered a dominant pathologic event. Recently, Abeta oligomers have been identified as more neurotoxic than Abeta plaques. However, no ideal transgenic mouse model directly support Abeta oligomers as a neurotoxic species due to the puzzling effects of amyloid plaques in the more widely-used models. Here, we constructed a single-mutant transgenic (Tg) model harboring the PS1V97L mutation and used Non-Tg littermates as a control group. Employing the Morris water maze, electrophysiology, immunohistochemistry, biochemistry, and electron microscopy, we investigated behavioral changes and pathology progression in our single-mutant transgenic model. We discovered the pathological alteration of intraneuronal accumulation of Abeta oligomers without Abeta plaques in the PS1V97L-Tg mouse model, which might be the result of PS1 gene mutation. Following Abeta oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for Abeta oligomers in the onset of AD and suggests that Abeta plaques may not be the only prerequisite. This model provides a useful tool for studying the role of Abeta oligomers in AD pathogenesis.
ESTHER : Zhang_2014_PLoS.One_9_e85885
PubMedSearch : Zhang_2014_PLoS.One_9_e85885
PubMedID: 24465766

Title : Contribution of carboxylesterase in hamster to the intestinal first-pass loss and low bioavailability of ethyl piperate, an effective lipid-lowering drug candidate - Lu_2011_Drug.Metab.Dispos_39_796
Author(s) : Lu Y , Bao N , Borjihan G , Ma Y , Hu M , Yu C , Li S , Jia J , Yang D , Wang Y
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 39 :796 , 2011
Abstract : Ethyl piperate is an effective lipid-lowering drug candidate synthesized from piperine. However, its pharmacokinetic characteristics and oral absorption process remain unclear. A liquid chromatography-tandem mass spectrometry method was applied to determine the oral bioavailability of ethyl piperate. Simulated gastrointestinal pH conditions and intestinal washings were prepared to investigate their contributions to the loss of ethyl piperate. Hydrolysis by carboxylesterase (CES) was evaluated in vitro using microsomes and S9 fractions. In situ intestinal single-pass perfusion experiments were performed to estimate the role of CES in ethyl piperate absorption. The bioavailability of ethyl piperate was extremely low (0.47%) in hamster independent of gastrointestinal environmental effects. Ethyl piperate was a typical substrate of CES with kinetic parameters K(m) and V(max) of 7.56 +/- 1.491 muM and 0.16 +/- 0.008 nmol . min(-1) . mg protein(-1), respectively. CES was responsible for 85.8% of the intestinal hydrolysis of ethyl piperate. Specific inhibition of CES with bis-p-nitrophenyl phosphate (BNPP), decreased degradation clearance to 36% of control with no significant change in absorption clearance. This contrasted with the results of Caco-2 monolayer experiments, which showed a dramatic increase in the apparent permeability coefficient after BNPP treatment. mRNA levels for the CES isozyme, CES2A3, were similar among the three regions of hamster intestine and 60% less than those in liver; CES1B1 mRNA levels were even lower in the intestine and showed a proximal-to-distal decrease. In conclusion, CES markedly contributes to intestinal first-pass hydrolysis of ethyl piperate that is sufficient, but not necessary, to cause the observed extremely low bioavailability.
ESTHER : Lu_2011_Drug.Metab.Dispos_39_796
PubMedSearch : Lu_2011_Drug.Metab.Dispos_39_796
PubMedID: 21346005

Title : A modified lipid composition in Fabry disease leads to an intracellular block of the detergent-resistant membrane-associated dipeptidyl peptidase IV - Maalouf_2010_J.Inherit.Metab.Dis_33_445
Author(s) : Maalouf K , Jia J , Rizk S , Brogden G , Keiser M , Das A , Naim HY
Ref : J Inherit Metab Dis , 33 :445 , 2010
Abstract : Fabry disease is an X-linked lysosomal storage disorder that leads to abnormal accumulation of glycosphingolipids due to a deficiency of alpha-galactosidase A (AGAL). The consequences of these alterations on the targeting of membrane proteins are poorly understood. Glycosphingolipids are enriched in Triton-X-100- resistant lipid rafts [detergent-resistant membranes (DRMs)] and play an important role in the transport of several membrane-associated proteins. Here, we show that In fibroblasts of patients suffering from Fabry disease, the colocalization of AGAL with the lysosomal marker LAMP2 is decreased compared with wild-type fibroblasts concomitant with a reduced transport of AGAL to lysosomes. Furthermore, overall composition of membrane lipids in the patients' fibroblasts as well as in DRMs reveals a substantial increase in the concentration of glycolipids and a slight reduction of phosphatidylethanolamine (PE). The altered glycolipid composition in Fabry fibroblasts is associated with an intracellular accumulation and impaired trafficking of the Triton-X-100 DRM-associated membrane glycoprotein dipeptidyl peptidase IV (DPPIV) in transfected Fabry cells, whereas no effect could be observed on the targeting of aminopeptidase N (ApN) that is not associated with this type of DRM. We propose that changes in the lipid composition of cell membranes in Fabry disease disturb the ordered Triton X-100 DRMs and have implications on the trafficking and sorting of DRM-associated proteins and the overall protein-lipid interaction at the cell membrane. Possible consequences could be altered signalling at the cell surface triggered by DRM-associated proteins, with implications on gene regulation and subsequent protein expression.
ESTHER : Maalouf_2010_J.Inherit.Metab.Dis_33_445
PubMedSearch : Maalouf_2010_J.Inherit.Metab.Dis_33_445
PubMedID: 20495958

Title : Regulated expression of pancreatic triglyceride lipase after rat traumatic brain injury - Jia_2010_Mol.Cell.Biochem_335_127
Author(s) : Jia J , Yan M , Lu Z , Sun M , He J , Xia C
Ref : Molecular & Cellular Biochemistry , 335 :127 , 2010
Abstract : Pancreatic triglyceride lipase (PTL), an enzyme of digestive system, plays very important roles in the digestion and absorption of lipids. However, its distribution and function in the central nervous system (CNS) remains unclear. In the present study, we mainly investigated the expression and cellular localization of PTL during traumatic brain injury (TBI). Western blot and RT-PCR analysis revealed that PTL was present in normal rat brain cortex. It gradually increased, reached a peak at the 3rd day after TBI, and then decreased. Double immunofluorescence staining showed that PTL was co-expressed with neuron, but had a few colocalizations in astrocytes. When TBI occurred in the rat cortex, the expression of PTL gradually increased, reached the peak at the 3rd day after TBI, and then decreased. Importantly, more PTL was colocalized with astrocytes, which is positive for proliferating cell nuclear antigen (PCNA). In addition, Western blot detection showed that the 3rd day post injury was not only the proliferation peak indicated by the elevated expression of PCNA, glial fibrillary acidic protein (GFAP) and cyclin D1, but also the apoptotic peak implied by the alteration of caspase-3 and bcl-2. These data suggested that PTL may be involved in the pathophysiology of TBI and PTL may be complicated after injury, more PTL was colocalized with astrocytes. Importantly, injury-induced expression of PTL was colabelled by proliferating cell nuclear antigen (proliferating cells marker), and the western blot for GFAP, PCNA and cyclin D1, showed that 3 days post injury was the proliferation peak, in coincidence to it, the protein level change of caspase-3 and bcl-2 revealed that the stage was peak of apoptotic too. These data suggested that PTL may be involved in the pathophysiology of TBI and that PTL may be implicated in the proliferation of astrocytes and the recovery of neurological outcomes. But the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of PTL after brain injury.
ESTHER : Jia_2010_Mol.Cell.Biochem_335_127
PubMedSearch : Jia_2010_Mol.Cell.Biochem_335_127
PubMedID: 19760487

Title : [Genomic analysis of serine carboxypeptidase-like protein family of Arabidopsis thaliana] - Feng_2005_Yi.Chuan.Xue.Bao_32_864
Author(s) : Feng Y , Liu QP , Jia J , Xue QZ
Ref : Yi Chuan Xue Bao , 32 :864 , 2005
Abstract : Based on hidden Markov models (HMM), the paper utilized reported SCP (Serine Carboxypeptidases) protein sequences as datasets to build HMM profile. To search Arabidopsis thaliana whole proteome,and identified 54 SCPL (Serine Carboxypeptidase-Like) proteins coding genes. The intron-exon structure, the chromosome mapping and the characteristic of coded protein sequences of those 54 putative genes were analyzed in details, revealing seven gene clusters probably resulted from recent gene duplication. This implied that a remarkable number of Arabidopsis thaliana SCPL genes are harboring alternative splice sites. Phylogenetics evolution analysis suggested 88.9% proteins encoded by Arabidopsis genes belong to two string subfamily of carboxypeptidase, I or II, while only 11.1% proteins fall into single string carboxypeptidase III subfamily. Our results indicated besides the facts that all enzymes of this family contained a central catalytic domain of unique topology and three dimensional structure designated as "alpha/beta hydrolase fold", the DNA and their encoded protein sequences also gave clues to phylogentics studies.
ESTHER : Feng_2005_Yi.Chuan.Xue.Bao_32_864
PubMedSearch : Feng_2005_Yi.Chuan.Xue.Bao_32_864
PubMedID: 16231742

Title : Single-wall carbon nanotube-based voltammetric sensor and biosensor - Xu_2004_Biosens.Bioelectron_20_579
Author(s) : Xu Z , Chen X , Qu X , Jia J , Dong S
Ref : Biosensors & Bioelectronics , 20 :579 , 2004
Abstract : The pH-sensitive property of the single-wall carbon nanotube modified electrode based on the electroactive group on the single-wall carbon nanotube was explored by differential pulse voltammetry technique. In pH range 1-13 investigated in Britton-Robinson (B-R) buffer, the anodic peak shifted negatively along with the increase of pH exhibiting a reversible Nernstian response. Experiments were carried out to investigate the response of the single-wall carbon nanotube (SWNT) modified electrode to analytes associated with pH change. The response behavior of the modified electrode to ammonia was studied as an example. The potential response could reach equilibrium within 5 min. The modified electrode had good operational stability. Voltammetric urease and acetylcholinesterase biosensors were constructed by immobilizing the enzymes with sol-gel hybrid material. The maximum potential shift could reach 0.130 and 0.220 V for urea and acetylthiocholine, respectively. The methods for preparing sensor and biosensor were simple and reproducible and the range of analytes could be extended to substrates of other hydrolyases and esterases. This broadened the biosensor application of carbon nanotube in electrochemical area.
ESTHER : Xu_2004_Biosens.Bioelectron_20_579
PubMedSearch : Xu_2004_Biosens.Bioelectron_20_579
PubMedID: 15494242

Title : Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula - Chang_2004_J.Nat.Prod_67_1356
Author(s) : Chang Z , Sitachitta N , Rossi JV , Roberts MA , Flatt PM , Jia J , Sherman DH , Gerwick WH
Ref : Journal of Natural Products , 67 :1356 , 2004
Abstract : Curacin A (1) is a potent cancer cell toxin obtained from strains of the tropical marine cyanobacterium Lyngbya majuscula found in Curacao. Its structure is unique in that it contains the sequential positioning of a thiazoline and cyclopropyl ring, and it exerts its potent cell toxicity through interaction with the colchicine drug binding site on microtubules. A series of stable isotope-labeled precursors were fed to cultures of curacin A-producing strains and, following NMR analysis, allowed determination of the metabolic origin of all atoms in the natural product (one cysteine, 10 acetate units, two S-adenosyl methionine-derived methyl groups) as well as several unique mechanistic insights. Moreover, these incorporation experiments facilitated an effective gene cloning strategy that allowed identification and sequencing of the approximately 64 kb putative curacin A gene cluster. The metabolic system is comprised of a nonribosomal peptide synthetase (NRPS) and multiple polyketide synthases (PKSs) and shows a very high level of collinearity between genes in the cluster and the predicted biochemical steps required for curacin biosynthesis. Unique features of the cluster include (1) all but one of the PKSs are monomodular multifunctional proteins, (2) a unique gene cassette that contains an HMG-CoA synthase likely responsible for formation of the cyclopropyl ring, and (3) a terminating motif that is predicted to function in both product release and terminal dehydrative decarboxylation.
ESTHER : Chang_2004_J.Nat.Prod_67_1356
PubMedSearch : Chang_2004_J.Nat.Prod_67_1356
PubMedID: 15332855
Gene_locus related to this paper: 9cyan-d0e8e2 , 9cyan-q6dnd9

Title : Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing - Ren_2003_Nature_422_888
Author(s) : Ren SX , Fu G , Jiang XG , Zeng R , Miao YG , Xu H , Zhang YX , Xiong H , Lu G , Lu LF , Jiang HQ , Jia J , Tu YF , Jiang JX , Gu WY , Zhang YQ , Cai Z , Sheng HH , Yin HF , Zhang Y , Zhu GF , Wan M , Huang HL , Qian Z , Wang SY , Ma W , Yao ZJ , Shen Y , Qiang BQ , Xia QC , Guo XK , Danchin A , Saint Girons I , Somerville RL , Wen YM , Shi MH , Chen Z , Xu JG , Zhao GP
Ref : Nature , 422 :888 , 2003
Abstract : Leptospirosis is a widely spread disease of global concern. Infection causes flu-like episodes with frequent severe renal and hepatic damage, such as haemorrhage and jaundice. In more severe cases, massive pulmonary haemorrhages, including fatal sudden haemoptysis, can occur. Here we report the complete genomic sequence of a representative virulent serovar type strain (Lai) of Leptospira interrogans serogroup Icterohaemorrhagiae consisting of a 4.33-megabase large chromosome and a 359-kilobase small chromosome, with a total of 4,768 predicted genes. In terms of the genetic determinants of physiological characteristics, the facultatively parasitic L. interrogans differs extensively from two other strictly parasitic pathogenic spirochaetes, Treponema pallidum and Borrelia burgdorferi, although similarities exist in the genes that govern their unique morphological features. A comprehensive analysis of the L. interrogans genes for chemotaxis/motility and lipopolysaccharide synthesis provides a basis for in-depth studies of virulence and pathogenesis. The discovery of a series of genes possibly related to adhesion, invasion and the haematological changes that characterize leptospirosis has provided clues about how an environmental organism might evolve into an important human pathogen.
ESTHER : Ren_2003_Nature_422_888
PubMedSearch : Ren_2003_Nature_422_888
PubMedID: 12712204
Gene_locus related to this paper: lepin-AXEA , lepin-ESTA , lepin-LA0357 , lepin-LA0587 , lepin-LA0823 , lepin-LA0932 , lepin-LA1069 , lepin-LA1345 , lepin-LA1541 , lepin-LA1702 , lepin-LA1861 , lepin-LA1902 , lepin-LA1936 , lepin-LA1955 , lepin-LA2034 , lepin-LA2132 , lepin-LA2501 , lepin-LA2505 , lepin-LA2526 , lepin-LA2544 , lepin-LA2857 , lepin-LA2958 , lepin-LA3100 , lepin-LA3107 , lepin-LA3147 , lepin-LA3604 , lepin-LA3661 , lepin-LA3669 , lepin-LA3672 , lepin-LA3770 , lepin-LA3788 , lepin-LA3851 , lepin-LA3897 , lepin-LA3998 , lepin-LA4247 , lepin-LB147 , lepin-LB264 , lepin-LB265 , lepin-METX , lepin-q8f7a8 , lepin-q72tt9

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1