Li H

References (281)

Title : Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors - Li_2024_Front.Bioeng.Biotechnol_12_1387146
Author(s) : Li H , Li XD , Yan CH , Ni ZH , Lu MH , Zou LW , Yang L
Ref : Front Bioeng Biotechnol , 12 :1387146 , 2024
Abstract : Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.
ESTHER : Li_2024_Front.Bioeng.Biotechnol_12_1387146
PubMedSearch : Li_2024_Front.Bioeng.Biotechnol_12_1387146
PubMedID: 38638318

Title : ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2\/STAT3 pathway and interacting with ESM1 - Li_2024_J.Transl.Med_22_46
Author(s) : Li YK , Gao AB , Zeng T , Liu D , Zhang QF , Ran XM , Tang ZZ , Li Y , Liu J , Zhang T , Shi GQ , Zhou WC , Zou WD , Peng J , Zhang J , Li H , Zou J
Ref : J Transl Med , 22 :46 , 2024
Abstract : BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
ESTHER : Li_2024_J.Transl.Med_22_46
PubMedSearch : Li_2024_J.Transl.Med_22_46
PubMedID: 38212795

Title : Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection - Jiang_2024_Int.J.Biol.Macromol__132350
Author(s) : Jiang H , Huang X , Li H , Ren F , Li D , Liu Y , Tong Y , Ran P
Ref : Int J Biol Macromol , :132350 , 2024
Abstract : Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by Pi - Pi stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections.
ESTHER : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedSearch : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedID: 38750839

Title : Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers - Wang_2024_Clin.Pharmacol.Drug.Dev__
Author(s) : Wang X , Liu H , Cui C , Niu X , Li H , Niu S , Yan P , Wu N , Li F , Wu Q , Chen K , Hu B , Liu D
Ref : Clin Pharmacol Drug Dev , : , 2024
Abstract : Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (deltaQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (deltadeltaQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (C(max)) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.
ESTHER : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedSearch : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedID: 38757550

Title : Tissue-, region-, and gene-specific induction of microsomal epoxide hydrolase expression and activity in the mouse intestine by arsenic in drinking water - Li_2024_Drug.Metab.Dispos__
Author(s) : Li H , Fan X , Ding X , Zhang QY
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2024
Abstract : This study aimed to characterize the effects of arsenic exposure on the expression of microsomal epoxide hydrolase (mEH or Ephx1) and soluble epoxide hydrolase (sEH or Ephx2) in the liver and small intestine. C57BL/6 mice were exposed to sodium arsenite in drinking water at various doses for up to 28 days. Intestinal, but not hepatic, mEH mRNA and protein expression was induced by arsenic at 25 ppm, in both males and females, whereas hepatic mEH expression was induced by arsenic at 50 or 100 ppm. The induction of mEH was gene specific, as the arsenic exposure did not induce sEH expression in either tissue. Within the small intestine, mEH expression was induced only in the proximal, but not the distal segments. The induction of intestinal mEH was accompanied by increases in microsomal enzymatic activities toward a model mEH substrate, cis-stilbene oxide, and an epoxide-containing drug, oprozomib, in vitro, and by increases in the levels of PR-176, the main hydrolysis metabolite of oprozomib, in the proximal small intestine of oprozomib-treated mice. These findings suggest that intestinal mEH, playing a major role in converting xenobiotic epoxides to less reactive diols, but not sEH, preferring endogenous epoxides as substrates, is relevant to the adverse effects of arsenic exposure, and that further studies of the interactions between drinking water arsenic exposure and the disposition or possible adverse effects of epoxide-containing drugs and other xenobiotic compounds in the intestine are warranted. Significance Statement Consumption of arsenic-contaminated water has been associated with increased risks of various adverse health effects, such as diabetes, in humans. The small intestinal epithelial cells are the main site of absorption of ingested arsenic, but they are not well characterized for arsenic exposure-related changes. This study identified gene expression changes in the small intestine that may be mechanistically linked to the adverse effects of arsenic exposure and possible interactions between arsenic ingestion and the pharmacokinetics of epoxide-containing drugs in vivo.
ESTHER : Li_2024_Drug.Metab.Dispos__
PubMedSearch : Li_2024_Drug.Metab.Dispos__
PubMedID: 38719743

Title : PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer - Chen_2024_J.Transl.Med_22_249
Author(s) : Chen M , Zhang C , Li H , Zheng S , Li Y , Yuan M , Chen Y , Wu J , Sun Q
Ref : J Transl Med , 22 :249 , 2024
Abstract : BACKGROUND: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. METHODS: We employed LC-MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. RESULTS: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. CONCLUSION: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness.
ESTHER : Chen_2024_J.Transl.Med_22_249
PubMedSearch : Chen_2024_J.Transl.Med_22_249
PubMedID: 38454407

Title : Rapid screening of acetylcholinesterase active contaminants in water: A solid phase microextraction-based ligand fishing approach - Huang_2024_Chemosphere_356_141976
Author(s) : Huang Z , He L , Li H , Zhao J , Chen T , Feng Z , Li Y , You J
Ref : Chemosphere , 356 :141976 , 2024
Abstract : Effect-directed analysis (EDA) has been increasingly used for screening toxic contaminants in the environment, but conventional EDA procedures are often time-consuming and labor-extensive. This challenges the use of EDA for toxicant identification in the scenarios when quick answers are demanded. Herein, a solid phase microextraction ligand fishing (SPME-LF) strategy has been proposed as a rapid EDA approach for identifying acetylcholinesterase (AChE) active compounds in water. The feasibility of ligand fishing techniques for screening AChE active chemicals from environmental mixtures was first verified by a membrane separation method. Then, SPME fibers were prepared through self-assembly of boronic acid groups with AChE via co-bonding and applied for SPME-LF. As AChE coated SPME fibers selectively enriched AChE-active compounds from water, comparing sorbing compounds by the SPME fibers with and without AChE coating can quickly distinguish AChE toxicants in mixtures. Compared with conventional EDA, SPME-LF does not require repeating sample separations and bioassays, endowing SPME-LF with the merits of low-cost, labor-saving, and user-friendly. It is believed that cost-efficient and easy-to-use SPME-LF strategy can potentially be a rapid EDA method for screening receptor-specific toxicants in aquatic environment, especially applicable in time-sensitive screening.
ESTHER : Huang_2024_Chemosphere_356_141976
PubMedSearch : Huang_2024_Chemosphere_356_141976
PubMedID: 38608773

Title : Characterization and validation of fatty acid metabolism-related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer - Li_2024_Biotechnol.Appl.Biochem__
Author(s) : Li H , Zhou T , Zhang Q , Yao Y , Hua T , Zhang J , Wang H
Ref : Biotechnol Appl Biochem , : , 2024
Abstract : Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis. The tumor immune microenvironment was analyzed using the CIBERSORT algorithm, followed by functional analysis and immunotherapy efficacy prediction by gene set variation analysis. The role of model genes in regulating endometrial cancer in vitro was verified by CCK-8, colony formation, wound healing, and transabdominal invasion assays, and verified in vivo by subcutaneous tumor transplantation in nude mice. A prognostic model containing 14 genes was constructed and validated in 3 cohorts and clinical samples. The results showed differences in the infiltration of immune cells between the high-risk and low-risk groups, and that the high-risk group may respond better to immunotherapy. Experiments in vitro confirmed that knockdown of epoxide hydrolase 2 (EPHX2) and acyl-CoA oxidase like (ACOXL) had an inhibitory effect on EC cells, as did overexpression of hematopoietic prostaglandin D synthase (HPGDS). The same results were obtained in experiments in vivo. Prognostic models related to fatty acid metabolism can be used for the risk assessment of endometrial cancer patients. Experiments in vitro and in vivo confirmed that the key genes HPGDS, EPHX2, and ACOXL in the prognostic model may affect the development of endometrial cancer.
ESTHER : Li_2024_Biotechnol.Appl.Biochem__
PubMedSearch : Li_2024_Biotechnol.Appl.Biochem__
PubMedID: 38616327

Title : Design, synthesis, and activity evaluation of novel multitargeted l-tryptophan derivatives with powerful antioxidant activity against Alzheimer's disease - Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
Author(s) : Zeng X , Cheng S , Li H , Yu H , Cui Y , Fang Y , Yang S , Feng Y
Ref : Arch Pharm (Weinheim) , :e2300603 , 2024
Abstract : Alzheimer's disease (AD) is a multifactorial neurological disease, and the multitarget directed ligand (MTDL) strategy may be an effective approach to delay its progression. Based on this strategy, 27 derivatives of l-tryptophan, 3a-1-3d-1, were designed, synthesized, and evaluated for their biological activity. Among them, IC(50) (inhibitor concentration resulting in 50% inhibitory activity) values of compounds 3a-18 and 3b-1 were 0.58 and 0.44 microM for human serum butyrylcholinesterase (hBuChE), respectively, and both of them exhibited more than 30-fold selectivity for human serum acetylcholinesterase. Enzyme kinetics studies showed that these two compounds were mixed inhibitors of hBuChE. In addition, these two derivatives possessed extraordinary antioxidant activity in OH radical scavenging and oxygen radical absorption capacity fluorescein assays. Meanwhile, these compounds could also prevent beta-amyloid (Abeta) self-aggregation and possessed low toxicity on PC12 and AML12 cells. Molecular modeling studies revealed that these two compounds could interact with the choline binding site, acetyl binding site, and peripheral anionic site to exert submicromolar BuChE inhibitory activity. In the vitro blood-brain barrier permeation assay, compounds 3a-18 and 3b-1 showed enough blood-brain barrier permeability. In drug-likeness prediction, compounds 3a-18 and 3b-1 showed good gastrointestinal absorption and a low risk of human ether-a-go-go-related gene toxicity. Therefore, compounds 3a-18 and 3b-1 are potential multitarget anti-AD lead compounds, which could work as powerful antioxidants with submicromolar selective inhibitory activity for hBuChE as well as prevent Abeta self-aggregation.
ESTHER : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedSearch : Zeng_2024_Arch.Pharm.(Weinheim)__e2300603
PubMedID: 38290060

Title : A Versatile Thioesterase Involved in Dimerizationduring Cinnamoyl Lipid Biosynthesis - Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
Author(s) : Deng Z , Liu C , Wang F , Song N , Liu J , Li H , Liu S , Li T , Liu Z , Xiao F , Li W
Ref : Angew Chem Int Ed Engl , :e202402010 , 2024
Abstract : The cinnamoyl lipid compound youssoufene A1 (1), featuring a unique dearomatic carbon-bridged dimeric skeleton, exhibits increased inhibition against multidrug resistant Enterococcus faecalis compared to monomeric youssoufenes. However, the formation process of this intriguing dearomatic dimerization remains unknown. In this work, an unusual"gene-within-gene"thioesterase (TE) gene ysfF was functionally characterized. The gene was found to naturally encodes two proteins, an entire YsfF with alpha/beta-hydrolase and 4-hydroxybenzoyl-CoA thioesterase (4-HBT)-like enzyme domains, and a nested YsfFHBT (4-HBT-like enzyme). Using intracellular tagged carrier-protein tracking (ITCT) strategy, in vitro reconstitution and in vivo experiments, we found that: i) both domains of YsfF displayed thioesterase activities; ii) YsfF/YsfFHBT could accomplish the 6Pi-electrocyclic ring closure for benzene ring formation; and iii) YsfF and cyclase YsfX together were responsible for the ACP-tethered dearomatic dimerization process, possibly via an unprecedent Michael-type addition reaction. Moreover, site-directed mutagenesis experiments demonstrated that N301, E483 and H566 of YsfF are critical residues for both the 6Pi-electrocyclization and dimerization processes. This study enhances our understanding of the multifunctionality of the TE protein family.
ESTHER : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedSearch : Deng_2024_Angew.Chem.Int.Ed.Engl__e202402010
PubMedID: 38462490
Gene_locus related to this paper: 9actn-YsfF

Title : Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3\/8 activity - Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
Author(s) : Chen YQ , Yang Y , Zhen EY , Beyer TP , Li H , Wen Y , Ehsani M , Jackson N , Xie K , Jung H , Scheithauer JL , Kumari A , Birrane G , Russell AM , Balasubramaniam D , Liao Z , Siegel RW , Qian Y , Ploug M , Young SG , Konrad RJ
Ref : Proc Natl Acad Sci U S A , 121 :e2322332121 , 2024
Abstract : Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5delta35"). We found that wild-type (WT) human APOA5, but not APOA5delta35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5delta40"). Mouse WT-APOA5, but not APOA5delta40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5delta40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5(-/-) mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5delta40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.
ESTHER : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedSearch : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedID: 38625948
Gene_locus related to this paper: human-LPL

Title : Preparation of functional oils rich in phytosterol esters and diacylglycerols by enzymatic transesterification - Shi_2024_Food.Chem_448_139100
Author(s) : Shi W , Li H , Fu Y , Tang X , Yu J , Wang X
Ref : Food Chem , 448 :139100 , 2024
Abstract : Phytosterol esters (PEs) and diacylglycerols (DAGs) have various health benefits in humans. In this study, PEs and DAGs were synthesized by lipase-catalyzed transesterification between a natural oil and phytosterols. First, commercial lipases were screened for transesterification and were further verified using multiple-ligand molecular docking. AYS "Amano" (a lipase from Candida rugosa) was found to be the optimum lipase. Subsequently, the enzymatic transesterification conditions were optimized. The optimized conditions were determined to be a 1:2 M ratio of phytosterols to oil, 100 mmol/L phytosterols, and 9 % AYS "Amano", and 50 degreesC for 24 h in 20 mL n-hexane. Under these conditions, over 70 % of phytosterols were converted to PEs. In this study, an efficient enzymatic process was developed to produce value-added functional oils rich in PEs and DAGs, with PEs content <= 31.6 %, DAGs content <= 11.2 %, acid value >= 0.91 mg KOH/g, and peroxide value >= 2.38 mmol/kg.
ESTHER : Shi_2024_Food.Chem_448_139100
PubMedSearch : Shi_2024_Food.Chem_448_139100
PubMedID: 38552457

Title : Mechanisms of biochar assisted di-2-ethylhexyl phthalate (DEHP) biodegradation in tomato rhizosphere by metabolic and metagenomic analysis - Lin_2024_Chemosphere__141520
Author(s) : Lin Z , Wu W , Yang C , Yang G , Wei T , Huang F , Li H , Ren L , Liang Y , Zhang D , Li Z , Zhen Z
Ref : Chemosphere , :141520 , 2024
Abstract : The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.
ESTHER : Lin_2024_Chemosphere__141520
PubMedSearch : Lin_2024_Chemosphere__141520
PubMedID: 38395368

Title : Naked-eye sensitive detection of nanoPET by pH-responsive colorimetric method based on dual-enzyme catalysis - Zhan_2024_Environ.Int_186_108598
Author(s) : Zhan W , Wang C , Yang X , Li H , Xiong S , Li X
Ref : Environ Int , 186 :108598 , 2024
Abstract : A pH-responsive colorimetric method based on dual-enzyme catalysis for rapid and facile detection and quantification of nanoPET at environment-dependent concentration is proposed. The nanoPET was hydrolyzed by the synergistic catalysis of cutinase and lipase to terephthalic acid which can be sensitive detected using bromocresol purple as the indicator. The color changed from purple to bright yellow as the nanoPET detection concentration increased from 0 mg/mL to 2 mg/mL which can be detected by UV-Vis. This naked-eye method has a high sensitivity for nanoPET detection with the visual detection cutoff of 31.00 microg/mL, and has a good linearity in the range of 0 - 1 mg/mL with LOD of 22.84 microg/mL. The reliability of this method is verified in the detection of nanoPET in lake water and beer samples, with an average recovery of 87.1 %. The as-developed dual-enzyme colorimetric chemosensor holds promising potential as a robust and effective platform for the sensitive detection of nanoPET.
ESTHER : Zhan_2024_Environ.Int_186_108598
PubMedSearch : Zhan_2024_Environ.Int_186_108598
PubMedID: 38531236

Title : Characterization of Recombinantly-Expressed Hydrolytic Enzymes from Chinese Hamster Ovary Cells: Identification of Host Cell Proteins that Degrade Polysorbate - Kovner_2023_J.Pharm.Sci__
Author(s) : Kovner D , Yuk IH , Shen A , Li H , Graf T , Gupta S , Liu W , Tomlinson A
Ref : J Pharm Sci , : , 2023
Abstract : Enzymatic hydrolysis of polysorbate in drug products is a major challenge for the biopharmaceutical industry. Polysorbate hydrolysis caused by host cell proteins (HCPs) co-purified during bioprocessing can reduce the protective effects of the surfactant for the active pharmaceutical ingredient and cause the accumulation of low-solubility degradation products over the long-term storage. The identities of such HCPs are elusive due to their extremely low concentrations after the efficient purification processes of most biopharmaceuticals. In this work, 20 enzymes-selected for their known or putative hydrolytic activity and potential to degrade polysorbate-were recombinantly expressed, purified, and characterized via orthogonal methods. First, these recombinant HCPs were assessed for hydrolytic activity against a fluorogenic esterase substrate in a recently-developed, high-throughput assay. Second, these HCPs were screened for hydrolytic activity against polysorbate in a representative mAb formulation. Third, HCPs that displayed hydrolytic activities in the first two assays were subjected to more detailed characterization of their enzyme kinetics against polysorbates. Finally, these HCPs were evaluated for substrate specificity towards different sub-species of polysorbates. This work provides critical new insights for targeted LC-MS/MS approaches for identification of relevant polysorbate-degrading enzymes and supports improvements to remove such HCPs, including knockouts or targeted removal during purification.
ESTHER : Kovner_2023_J.Pharm.Sci__
PubMedSearch : Kovner_2023_J.Pharm.Sci__
PubMedID: 36646283

Title : Identification, evolution, and expression of GDSL-type Esterase\/Lipase (GELP) gene family in three cotton species: a bioinformatic analysis - Duan_2023_BMC.Genomics_24_795
Author(s) : Duan L , Wang F , Shen H , Xie S , Chen X , Xie Q , Li R , Cao A , Li H
Ref : BMC Genomics , 24 :795 , 2023
Abstract : BACKGROUND: GDSL esterase/lipases (GELPs) play important roles in plant growth, development, and response to biotic and abiotic stresses. Presently, an extensive and in-depth analysis of GELP family genes in cotton is still not clear enough, which greatly limits the further understanding of cotton GELP function and regulatory mechanism. RESULTS: A total of 389 GELP family genes were identified in three cotton species of Gossypium hirsutum (193), G. arboreum (97), and G. raimondii (99). These GELPs could be classified into three groups and eight subgroups, with the GELPs in same group to have similar gene structures and conserved motifs. Evolutionary event analysis showed that the GELP family genes tend to be diversified at the spatial dimension and certain conservative at the time dimension, with a trend of potential continuous expansion in the future. The orthologous or paralogous GELPs among different genomes/subgenomes indicated the inheritance from genome-wide duplication during polyploidization, and the paralogous GELPs were derived from chromosomal segment duplication or tandem replication. GELP genes in the A/D subgenome underwent at least three large-scale replication events in the evolutionary process during the period of 0.6-3.2 MYA, with two large-scale evolutionary events between 0.6-1.8 MYA that were associated with tetraploidization, and the large-scale duplication between 2.6-9.1 MYA that occurred during diploidization. The cotton GELPs indicated diverse expression patterns in tissue development, ovule and fiber growth, and in response to biotic and abiotic stresses, combining the existing cis-elements in the promoter regions, suggesting the GELPs involvements of functions to be diversification and of the mechanisms to be a hormone-mediated manner. CONCLUSIONS: Our results provide a systematic and comprehensive understanding the function and regulatory mechanism of cotton GELP family, and offer an effective reference for in-depth genetic improvement utilization of cotton GELPs.
ESTHER : Duan_2023_BMC.Genomics_24_795
PubMedSearch : Duan_2023_BMC.Genomics_24_795
PubMedID: 38129780

Title : Enzymatic synthesis of branched chain fatty acid-enriched structured triacylglycerols via esterification with glycerol - Huang_2023_Food.Chem_429_136943
Author(s) : Huang Y , Li H , Wang Z , Fu Y , Chen Y , Wang X
Ref : Food Chem , 429 :136943 , 2023
Abstract : While branched-chain fatty acids (BCFA)-enriched triacylglycerols (TAG) has various health benefits, its preparation has not been reported. This study aimed to synthesize high-purity BCFA-enriched structured TAG. First, BCFA was enriched from lanolin through saponification, calcification, and urea complexation. Next, BCFA-enriched TAG was synthesized by enzymatic esterification of BCFA and glycerol. Then, lipases were screened by molecular docking and practical experiments, which suggested that Lipozyme 435 was the best lipase for esterification since it had the lowest binding energy. Structured TAG containing 92.23% BCFA was synthesized under conditions optimized by single-factor experiments. Furthermore, molecular distillation was adapted to remove excess fatty acids and small molecule impurities. Finally, high-purity BCFA-enriched structured lipid containing 70.26% TAG was obtained. Overall, this study successfully developed a method for synthesizing BCFA-enriched structured TAG, which holds great promise for applications in value-added foods.
ESTHER : Huang_2023_Food.Chem_429_136943
PubMedSearch : Huang_2023_Food.Chem_429_136943
PubMedID: 37517224

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : In silico identification of novel stilbenes analogs for potential multi-targeted drugs against Alzheimer's disease - Firdoos_2023_J.Mol.Model_29_209
Author(s) : Firdoos S , Dai R , Tahir RA , Khan ZY , Li H , Zhang J , Ni J , Quan Z , Qing H
Ref : J Mol Model , 29 :209 , 2023
Abstract : CONTEXT: Alzheimer's disease (AD) is a chronic progressive neurodegenerative syndrome, which adversely disturbs cognitive abilities as well as intellectual processes and frequently occurs in the elderly. Inhibition of cholinesterase is a valuable approach to upsurge acetylcholine concentrations in the brain and persuades the development of multi-targeted ligands against cholinesterases. METHODS: The current study aims to determine the binding potential accompanied by antioxidant and anti-inflammatory activities of stilbenes-designed analogs against both cholinesterases (Acetylcholinesterase and butyrylcholinesterase) and neurotrophin targets for effective AD therapeutics. Docking results have shown that the WS6 compound exhibited the least binding energy - 10.1 kcal/mol with Acetylcholinesterase and - 7.8 kcal/mol with butyrylcholinesterase. The WS6 also showed a better binding potential with neurotrophin targets that are Brain-derived Neurotrophic Factor, Neurotrophin 4, Nerve Growth Factor, and Neurotrophin 3. The tested compounds particularly WS6 revealed significant antioxidant and anti-inflammatory activities through the comparative docking analysis with Fluorouracil and Melatonin as control drugs of antioxidants while Celecoxib and Anakinra as anti-inflammatory. The bioinformatics approaches including molecular docking calculations followed by the pharmacokinetics analysis and molecular dynamic simulations were accomplished to explore the capabilities of designed stilbenes as effective and potential leads. Root mean square deviation, root mean square fluctuations, and MM-GBSA calculations were performed through molecular dynamic simulations to extract the structural and residual variations and binding free energies through the 50-ns time scale.
ESTHER : Firdoos_2023_J.Mol.Model_29_209
PubMedSearch : Firdoos_2023_J.Mol.Model_29_209
PubMedID: 37314512

Title : Discovery of a new highly pathogenic toxin involved in insect sepsis - Zhang_2023_Microbiol.Spectr__e0142223
Author(s) : Zhang Y , Li H , Wang F , Liu C , Reddy GVP , Li Z , Sun Y , Zhao Z
Ref : Microbiol Spectr , :e0142223 , 2023
Abstract : Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode Steinernema feltiae and the entomopathogenic bacteria Xenorhabdus bovienii, which operate symbiotically, against the wax moth Galleria mellonella. Maximum mortality was observed at 25 degreesC while the optimal infestation efficiency was 20 nematodes per host. After infestation, G. mellonella displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The X. bovienii, released by S. feltiae, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host G. mellonella was usually killed within 24 h due to disseminated septicemia. Additionally, X. bovienii infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall, X. bovienii induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides. IMPORTANCE As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found Steinernema feltiae and Xenorhabdus bovienii were highly virulent against the insects. After infective juvenile injection, Galleria mellonella quickly turned black and softened with increasing esterase activity. Simultaneously, X. bovienii attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of X. bovienii, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
ESTHER : Zhang_2023_Microbiol.Spectr__e0142223
PubMedSearch : Zhang_2023_Microbiol.Spectr__e0142223
PubMedID: 37787562

Title : A model-informed approach to accelerate the clinical development of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 inhibitor - Cui_2023_Diabetes.Obes.Metab__
Author(s) : Cui C , Cao F , Kong, II , Wu Q , Li F , Li H , Liu D
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To employ a model-informed drug development approach in facilitating decision making and expediting the clinical progress of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, for the treatment of type 2 diabetes (T2D) via a biweekly dosing regimen. METHODS: Firstly, a population pharmacokinetics and pharmacodynamics (PopPKPD) model was developed using PK and PD data from a single ascending dose study to simulate the PK and PD time profiles of HSK7653 after multiple doses. Secondly, model-based meta-analysis (MBMA) was performed on published clinical studies of Eastern Asian subjects for all DPP-4 inhibitors. We hypothesized a consistent relationship between PK and DPP-4 inhibition in both healthy individuals and in those with T2D, establishing a quantitative correlation between DPP-4 inhibition and HbA1c. Finally, the predicted PK/DPP-4 inhibition/HbA1c profiles were validated by T2D patients in late clinical trials. RESULTS: The PK/DPP-4 inhibition/HbA1c profiles of T2D patients treated with HSK7653 matched the modelled data. Our PopPKPD and MBMA models predict multiple ascending dosing PK and PD characteristics from single ascending dosing data, as well as the long-term efficacy in T2D patients, based on healthy subjects. CONCLUSIONS: Successful waiver approval for the phase 2b dose-finding study was achieved through model-informed recommendations, facilitating the clinical development of HSK7653 and other DPP-4 inhibitors.
ESTHER : Cui_2023_Diabetes.Obes.Metab__
PubMedSearch : Cui_2023_Diabetes.Obes.Metab__
PubMedID: 37953687

Title : Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats - Shao_2023_J.Invest.Surg_36_1
Author(s) : Shao Y , Li C , Jiang Y , Li H , Tang X , Gao Z , Zhang D
Ref : J Invest Surg , 36 :1 , 2023
Abstract : Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-alpha, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1 and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-alpha, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.
ESTHER : Shao_2023_J.Invest.Surg_36_1
PubMedSearch : Shao_2023_J.Invest.Surg_36_1
PubMedID: 36350036

Title : Substrate-enzyme interactions and catalytic mechanism in a novel family VI esterase with dibutyl phthalate-hydrolyzing activity - Cheng_2023_Environ.Int_178_108054
Author(s) : Cheng J , Du H , Zhou MS , Ji Y , Xie YQ , Huang HB , Zhang SH , Li F , Xiang L , Cai QY , Li YW , Li H , Li M , Zhao HM , Mo CH
Ref : Environ Int , 178 :108054 , 2023
Abstract : Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25-37 degreesC) and pH (6.5-9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV-visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of alpha-helix and reducing of beta-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification.
ESTHER : Cheng_2023_Environ.Int_178_108054
PubMedSearch : Cheng_2023_Environ.Int_178_108054
PubMedID: 37354883
Gene_locus related to this paper: pseae-PA3859

Title : Integration of clinical demographics and routine laboratory analysis parameters for early prediction of gestational diabetes mellitus in the Chinese population - Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
Author(s) : Zhang H , Dai J , Zhang W , Sun X , Sun Y , Wang L , Li H , Zhang J
Ref : Front Endocrinol (Lausanne) , 14 :1216832 , 2023
Abstract : Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy, impairing both maternal and fetal health in short and long term. As early interventions are considered desirable to prevent GDM, this study aims to develop a simple-to-use nomogram based on multiple common risk factors from electronic medical health records (EMHRs). A total of 924 pregnant women whose EMHRs were available at Peking University International Hospital from January 2022 to October 2022 were included. Clinical demographics and routine laboratory analysis parameters at 8-12 weeks of gestation were collected. A novel nomogram was established based on the outcomes of multivariate logistic regression. The nomogram demonstrated powerful discrimination (the area under the receiver operating characteristic curve = 0.7542), acceptable agreement (Hosmer-Lemeshow test, P = 0.3214) and favorable clinical utility. The C-statistics of 10-Fold cross validation, Leave one out cross validation and Bootstrap were 0.7411, 0.7357 and 0.7318, respectively, indicating the stability of the nomogram. A novel nomogram based on easily-accessible parameters was developed to predict GDM in early pregnancy, which may provide a paradigm for repurposing clinical data and benefit the clinical management of GDM. There is a need for prospective multi-center studies to validate the nomogram before employing the nomogram in real-world clinical practice.
ESTHER : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedSearch : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedID: 37900122

Title : Variants within the LPL gene confer susceptility to diabetic kidney disease and rapid decline in kidney function in Chinese patients with type 2 diabetes - Wu_2023_Diabetes.Obes.Metab__
Author(s) : Wu Y , Cheng S , Gu H , Yang K , Xu Z , Meng X , Wang Y , Jiang Y , Li H , Zhou Y
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To examine the association between lipoprotein lipase (LPL) polymorphisms and susceptibility to diabetic kidney disease (DKD) and early renal function decline in Chinese patients with type 2 diabetes (T2D). METHODS: The association of eight LPL single nucleotide polymorphisms (SNPs) with DKD was analysed in 2793 patients with T2D from the third China National Stroke Registry. DKD was defined as either an urine albumin-to-creatinine ratio (UACR) of 30 mg/g or higher at baseline and 3 months, or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m(2) at baseline and 3 months. Rapid decline in kidney function (RDKF) was defined as a reduction in the eGFR of 3 mL/min/1.73 m(2) or greater per year. Logistic regression models were used to evaluate the association of LPL SNP and DKD with an additive model. RESULTS: The SNPs rs285 C>T (OR = 1.40, P = .0154), rs328 C>G (OR = 2.24, P = .0104) and rs3208305 A>T (OR = 1.85, P = .0015) were identified to be significantly associated with DKD defined by eGFR. Among 1241 participants with follow-up data, 441 (35.5%) showed RDKF over a mean follow-up period of 1 year, and the rs285 C allele was associated with higher odds of RDKF (OR = 1.31, 95% CI 1.04-1.66; P = .025) after adjustment for multiple variables. CONCLUSIONS: These results suggest that LPL-related SNPs are new candidate factors for conferring susceptibility to DKD and may promote rapid loss of renal function in Chinese patients with T2D.
ESTHER : Wu_2023_Diabetes.Obes.Metab__
PubMedSearch : Wu_2023_Diabetes.Obes.Metab__
PubMedID: 37427758

Title : Self-ratiometric fluorescent platform based on upconversion nanoparticles for on-site detection of chlorpyrifos - Zhao_2023_Food.Chem_439_138100
Author(s) : Zhao X , Lu Y , Li B , Kong M , Sun Y , Li H , Liu X , Lu G
Ref : Food Chem , 439 :138100 , 2023
Abstract : Chromobacterium sp. USM2, a locally isolated bacterium was found to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate), P(3HB-co-3HV) copolymer with high 3HV monomer composition. The PHA synthase gene was cloned and expressed in Cupriavidus necator PHB4 to investigate the possibilities of incorporating other monomer. The recombinant successfully incorporated 3-hydroxyhexanoate (3HHx) monomer when fed with crude palm kernel oil (CPKO) as the sole carbon source. Approximately 63 2 wt% of P(3HB-co-3HHx) copolymer with 4 mol% of 3HHx was synthesized from 5 g/L of oil after 48 h of cultivation. In addition, P(3HB-co-3HV-co-3HHx) terpolymer with 9 mol% 3HV and 4 mol% 3HHx could be synthesized with a mixture of CPKO and sodium valerate. The presence of 3HV and 3HHx monomers in the copolymer and terpolymer was further confirmed with +H-NMR analysis. This locally isolated PHA synthase has demonstrated its ability to synthesize P(3HB-co-3HHx) copolymer from a readily available and renewable carbon source; CPKO, without the addition of 3HHx precursors.
ESTHER : Zhao_2023_Food.Chem_439_138100
PubMedSearch : Zhao_2023_Food.Chem_439_138100
PubMedID: 38041885

Title : Aptamer recognition-promoted hybridization chain reaction for amplified label-free and enzyme-free fluorescence analysis of pesticide - Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
Author(s) : Chen J , Yang C , Nie H , Li H
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 293 :122451 , 2023
Abstract : Development of high-performance fluorescence sensors for pesticide is highly urgent but remains a grand challenge. It is due to that most of known fluorescence sensors detect pesticides based on enzyme-inhibited strategy, which requires high-price cholinesterase, suffers from serious interference of reductive materials, and can't difference pesticides with each other; the known aptamer-based fluorescence ones entail tool enzymes or nanomaterials to transducer/amplify the signal and demand signalers to be tagged in nucleic acid, which are expensive and intricate. Herein, we develop a novel aptamer-based fluorescence system for label-free, enzyme-free and highly sensitive detection of pesticide (profenofos) based on target-initiated hybridization chain reaction (HCR)-assisted signal amplification and specific intercalation of N-methylmesoporphyrin IX (NMM) in G-quadruplex DNA. Hairpin probe ON1 recognizes profenofos to generate profenofos@ON1 complex, which switches the HCR to yield multiple G-quadruplex DNA, consequently making large numbers of NMM be locked. In comparison with profenofos absence, a sharply improved fluorescence signal was recorded and it was dependent on profenofos dose. Hence, label-free, enzyme-free and highly sensitive detection of profenofos is achieved with limit of detection of 0.085 nM, which compared favorably with or superior to those of known fluorescence methods. Furthermore, the present method was applied to determine the profenofos residue in rice with agreeable result, and will provide more valuable information for guaranteeing the pesticide-related food safety.
ESTHER : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
PubMedSearch : Chen_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_293_122451
PubMedID: 36801730

Title : Glimepiride, a novel soluble epoxide hydrolase inhibitor, protects against heart failure via increasing epoxyeicosatrienoic acids - Zhao_2023_J.Mol.Cell.Cardiol_185_13
Author(s) : Zhao C , Jiang X , Peng L , Zhang Y , Li H , Zhang Q , Wang Y , Yang F , Wu J , Wen Z , He Z , Shen J , Chen C , Wang DW
Ref : Journal of Molecular & Cellular Cardiology , 185 :13 , 2023
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2(-/-) mice. Moreover, Western blot, real-time PCR, luciferase reporter, ChIP assays were employed to explore the underlying mechanism. Finally, multiple sEH inhibitors were designed, synthesized, and validated in vitro and in vivo. RESULTS: The ratios of DHETs/EETs were increased in the plasma from patients with HF. Meanwhile, the expression of sEH was upregulated in the heart of patients and mice with HF, especially in cardiomyocytes. Cardiomyocyte-specific Ephx2(-/-) mice ameliorated cardiac dysfunction induced by TAC. Consistently, Ephx2 knockdown protected Angiotensin II (AngII)-treated cardiomyocytes via increasing EETs in vitro. Mechanistically, AngII could enhance the expression of transcript factor Krppel-like factor 15 (KLF15), which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor, which benefited from the elevated EETs during HF. CONCLUSIONS: Glimepiride attenuates HF in mice in part by increasing EETs. CLINICAL TRIAL IDENTIFIER: NCT03461107 (
ESTHER : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedSearch : Zhao_2023_J.Mol.Cell.Cardiol_185_13
PubMedID: 37871528

Title : Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta - Li_2023_Front.Plant.Sci_14_1074184
Author(s) : Li J , Li F , Wu G , Gui F , Li H , Xu L , Hao X , Zhao Y , Ding X , Qin X
Ref : Front Plant Sci , 14 :1074184 , 2023
Abstract : Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3-8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 +/- 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.
ESTHER : Li_2023_Front.Plant.Sci_14_1074184
PubMedSearch : Li_2023_Front.Plant.Sci_14_1074184
PubMedID: 36844064

Title : Decapentaplegic retards lipolysis during metamorphosis in Bombyx mori and Drosophila melanogaster - Qian_2023_Insect.Biochem.Mol.Biol__103928
Author(s) : Qian W , Guo M , Peng J , Zhao T , Li Z , Yang Y , Li H , Zhang X , King-Jones K , Cheng D
Ref : Insect Biochemistry & Molecular Biology , :103928 , 2023
Abstract : Insect morphogen decapentaplegic (Dpp) functions as one of the key extracellular ligands of the Bone Morphogenetic Protein (BMP) signaling pathway. Previous studies in insects mainly focused on the roles of Dpp during embryonic development and the formation of adult wings. In this study, we demonstrate a new role for Dpp in retarding lipolysis during metamorphosis in both Bombyx mori and Drosophila melanogaster. CRISPR/Cas9-mediated mutation of Bombyx dpp causes pupal lethality, induces an excessive and premature breakdown of lipids in the fat body, and upregulates the expressions of several lipolytic enzyme genes, including brummer (bmm), lipase 3 (lip3), and hormone-sensitive lipase (hsl), and lipid storage droplet 1 (lsd1), a lipid droplets (LD)-associated protein gene. Further investigation in Drosophila reveals that salivary gland-specific knockdown of the dpp gene and fat body-specific knockdown of Mad involved in Dpp signaling phenocopy the effects of Bombyx dpp mutation on pupal development and lipolysis. Taken together, our data indicate that the Dpp-mediated BMP signaling in the fat body maintains lipid homeostasis by retarding lipolysis, which is necessary for pupa-adult transition during insect metamorphosis.
ESTHER : Qian_2023_Insect.Biochem.Mol.Biol__103928
PubMedSearch : Qian_2023_Insect.Biochem.Mol.Biol__103928
PubMedID: 36870515

Title : The roles of serine hydrolases and serum albumin in alisol B 23-acetate hydrolysis in humans - Zhang_2023_Front.Pharmacol_14_1160665
Author(s) : Zhang T , Zhang F , Zhang Y , Li H , Zhu G , Weng T , Huang C , Wang P , He Y , Hu J , Ge G
Ref : Front Pharmacol , 14 :1160665 , 2023
Abstract : Introduction: Alisol B 23-acetate (AB23A), a major bioactive constituent in the Chinese herb Zexie (Rhizoma Alismatis), has been found with multiple pharmacological activities. AB23A can be readily hydrolyzed to alisol B in mammals, but the hydrolytic pathways of AB23A in humans and the key enzymes responsible for AB23A hydrolysis are still unrevealed. This study aims to reveal the metabolic organs and the crucial enzymes responsible for AB23A hydrolysis in human biological systems, as well as to decipher the impact of AB23A hydrolysis on its biological effects. Methods: The hydrolytic pathways of AB23A in human plasma and tissue preparations were carefully investigated by using Q-Exactive quadrupole-Orbitrap mass spectrometer and LC-UV, while the key enzymes responsible for AB23A hydrolysis were studied via performing a set of assays including reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses. Finally, the agonist effects of both AB23A and its hydrolytic metabolite(s) on FXR were tested at the cellular level. Results: AB23A could be readily hydrolyzed to form alisol B in human plasma, intestinal and hepatic preparations, while human butyrylcholinesterase (hBchE) and human carboxylesterases played key roles in AB23A hydrolysis in human plasma and tissue preparations, respectively. It was also found that human serum albumin (hSA) could catalyze AB23A hydrolysis, while multiple lysine residues of hSA were covalently modified by AB23A, suggesting that hSA catalyzed AB23A hydrolysis via its pseudo-esterase activity. Biological tests revealed that both AB23A and alisol B exhibited similar FXR agonist effects, indicating AB23A hydrolysis did not affect its FXR agonist effect. Discussion: This study deciphers the hydrolytic pathways of AB23A in human biological systems, which is very helpful for deep understanding of the metabolic rates of AB23A in humans, and useful for developing novel prodrugs of alisol B with desirable pharmacokinetic behaviors.
ESTHER : Zhang_2023_Front.Pharmacol_14_1160665
PubMedSearch : Zhang_2023_Front.Pharmacol_14_1160665
PubMedID: 37089921

Title : lpla (lipoprotein lipase a) is a marker of early adipogenesis rather than late adipogenesis in grass carp (Ctenopharyngodon idellus) - Tian_2023_Fish.Physiol.Biochem__
Author(s) : Tian Z , Wei M , Xue R , Song L , Li H , Ji H , Sun J
Ref : Fish Physiol Biochem , : , 2023
Abstract : Lipoprotein lipase (LPL) functions as a marker of adipocyte differentiation in mammals, but little is known about its role in fish adipogenesis. The aim of this research is to investigate the function of Lpl in adipocyte differentiation in fish. In this paper, we isolated and characterized lipoprotein lipase a (lpla) and lipoprotein lipase b (lplb) from grass carp (Ctenopharyngodon idellus). The complete coding sequence of lpla and lplb was 1587 bp and 1437 bp in length, coding for 507 amino acids and 500 amino acids, respectively. Both lpla and lplb mRNA were expressed in a great number of tissues. During adipogenesis, the level of lpla mRNA reached its maximum at day 2 and then dropped gradually, while the level of lplb mRNA had no significant changes, indicating that lpla and lplb may have different function in the differentiation of grass carp adipocyte. Furthermore, inhibition of lpla by inhibitor of LPL(GSK264220A) at early time points most clearly reduced adipogenesis, whereas these effects were less pronounced at later stages, suggesting that lpla predominantly affects early adipogenesis rather than late adipogenesis. Based on these findings, it can be inferred that lpla and lplb in grass carp may have distinct roles in the differentiation of grass carp adipocyte, and lpla may play an important role in the early adipogenesis rather than late adipogenesis in grass carp.
ESTHER : Tian_2023_Fish.Physiol.Biochem__
PubMedSearch : Tian_2023_Fish.Physiol.Biochem__
PubMedID: 37843716

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study - Zhang_2023_Food.Chem_431_137164
Author(s) : Zhang T , Wang J , Zhao Y , Wang Z , Hu D , Liu Y , Zhang X , Li H , Zhao B , Li B
Ref : Food Chem , 431 :137164 , 2023
Abstract : Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
ESTHER : Zhang_2023_Food.Chem_431_137164
PubMedSearch : Zhang_2023_Food.Chem_431_137164
PubMedID: 37607420

Title : Time-resolved fluorescence nanoprobe of acetylcholinesterase based on ZnGeO:Mn luminescence nanorod modified with metal ions - Gao_2023_Anal.Bioanal.Chem__
Author(s) : Gao L , Chen R , Li H , Xu D , Zheng D
Ref : Anal Bioanal Chem , : , 2023
Abstract : A novel time-resolved fluorescence nanoprobe (PBMO, PLNR-BSA-Mn(2+)-OPD) is fabricated for the label-free determination of acetylcholinesterase (AChE). The ZnGeO:Mn persistent luminescence nanorod (PLNR) and Mn(II) are, respectively, exploited as the signal molecule and quencher to construct the PBMO nanopobe using bovine serum albumin (BSA) as the surface-modified shell and o-phenylenediamine (OPD) as the reducing agent. In the presence of H(2)O(2), the persistent luminescence of PBMO at 530 nm is enhanced remarkably within 30 s due to the oxidation of Mn(II). H(2)O(2) can react with thiocholine (TCh), which is produced through the enzymatic degradation of acetylcholine (ATCh) by AChE. The PBMO nanoprobe is successfully applied to the determination of AChE in the linear range of 0.08-10 U L(-1), with a detection limit of 0.03 U L(-1) (3sigma/s). The practicability of this PBMO nanoprobe is confirmed by accurately monitoring AChE contents in human serum samples, giving rise to satisfactory spiking recoveries of 96.2-103.6%.
ESTHER : Gao_2023_Anal.Bioanal.Chem__
PubMedSearch : Gao_2023_Anal.Bioanal.Chem__
PubMedID: 37889311

Title : The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma - Li_2023_BMC.Cancer_23_161
Author(s) : Li H , Ren B , Yu S , Gao H , Sun PL
Ref : BMC Cancer , 23 :161 , 2023
Abstract : BACKGROUND: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit beta5t (beta5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4. METHODS: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis. RESULTS: Our results found that for cortical epithelial markers the expression of beta5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of beta5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and beta5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival. CONCLUSION: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including beta5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.
ESTHER : Li_2023_BMC.Cancer_23_161
PubMedSearch : Li_2023_BMC.Cancer_23_161
PubMedID: 36797681

Title : Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C - Kuang_2023_Gen.Physiol.Biophys_42_361
Author(s) : Kuang Y , Wang J , Dong Y , Cheng Y , Li H , Ji Y , Gao H , Cao X
Ref : Gen Physiol Biophys , 42 :361 , 2023
Abstract : Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients were extracted from the Gene Expression Omnibus (GEO) database (GSE130036) and analyzed by weighted gene coexpression network analysis (WGCNA). A total of 31 coexpression modules were identified. The coexpression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packages in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. We further verified the expression of CES1 and CTSC was downregulated in HCM clinical blood and negatively correlated with Maxi LVWT. Finally, we demonstrated that overexpression of CTSC and CES1 could alleviate HCM in an HCM cell model. In summary, the study suggests that CES1 and CTSC negatively regulate the development of HCM and have potential as therapeutic and diagnostic targets for HCM.
ESTHER : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedSearch : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedID: 37449320

Title : Network pharmacology-based analysis of Jin-Si-Wei on the treatment of Alzheimer's disease - Zhi_2023_J.Ethnopharmacol__117291
Author(s) : Zhi J , Yin L , Zhang Z , Lv Y , Wu F , Yang Y , Zhang E , Li H , Lu N , Zhou M , Hu Q
Ref : J Ethnopharmacol , :117291 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Si-Wei (JSW), a traditional Chinese medicine (TCM) formula, have cognitive enhancing effect and delay the memory decline in an animal model of AD which has been reported. However, the therapeutic mechanism of JSW in the treatment of AD remains unclear. AIM OF THE STUDY: This study aimed to verify the pharmacodynamics of JSW in the treatment of AD, and to explore its potential mechanism based on network pharmacology, molecular docking and experimental validation both in vitro and in vivo. MATERIALS AND METHODS: In this study, the underlying mechanism of JSW against AD was investigated by the integration of network pharmacology. Then, the core pathways and biological process of JSW were verified by experiment, including behavioral test and pathological and biochemical assays with 6-month-old APP(swe)/PS1(deltaE9) transgenic (APP/PS1) mice in vivo and verified with Abeta(1-42)-stimulated SH-SY5Y cells in vitro. At last, molecular docking was used to show the binding activity of each active ingredient to the core genes of JSW treatment in AD. RESULTS: A Drug-Ingredient-Target network was established, which included 363 ingredients and 116 targets related to the JSW treatment of AD. The main metabolic pathway of JSW treatment for AD is neuroactive ligand-receptor interaction pathway, and biological processes are mainly involved in Abeta metabolic process. In vivo experiments, compared with APP/PS1 mice, the cognitive and memory ability of mice was significantly improved after JSW administration. In brain tissue of APP/PS1 mice, JSW could increase the contents of low-density lipoprotein receptor-related protein 1 (LRP-1), enkephalinase (NEP) and Acetyl choline (ACh), and decrease the contents of Abeta(1-42), amyloid precursor protein (APP) and receptor for advanced glycation end products (RAGE), decrease the vitality of cholinesterase (AChE) and choline acetyltransferase (ChAT). Besides, JSW could increase alpha-secretase expression and decrease beta/gamma-secretase expression, and improve the number and morphology of synapses in CA1 region of the hippocampus of APP/PS1 mice. In vitro experiments, Drug-Containing Serum (JSW-serum) has a neuroprotective effect by reducing the apoptosis on Abeta(1-42)-stimulated SH-SY5Y cells. Molecular docking results showed that 2-Isopropyl-8-methylphenanthrene-3,4-dione had strong binding activity with PTGS2, which maybe a potential ingredient for the treatment of AD. CONCLUSIONS: JSW improves AD in APP/PS1 mice, and this therapeutic effect may be achieved in part by altering the neuroactive ligand-receptor interaction pathway.
ESTHER : Zhi_2023_J.Ethnopharmacol__117291
PubMedSearch : Zhi_2023_J.Ethnopharmacol__117291
PubMedID: 37925002

Title : Bioactive secondary metabolites isolated from the soft coral derived Penicillium sp. SCSIO 41038 - Li_2023_Nat.Prod.Res__1
Author(s) : Li H , Long J , Wang X , She J , Liu Y , Li Y , Yang B
Ref : Nat Prod Res , :1 , 2023
Abstract : Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I (1), and one new phloroglucinol derivative, speradine J (8), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro.
ESTHER : Li_2023_Nat.Prod.Res__1
PubMedSearch : Li_2023_Nat.Prod.Res__1
PubMedID: 37129009

Title : Efficacy of donepezil plus hydrogen-oxygen mixture inhalation for treatment of patients with Alzheimer disease: A retrospective study - Dan_2023_Medicine.(Baltimore)_102_e34382
Author(s) : Dan Z , Li H , Xie J
Ref : Medicine (Baltimore) , 102 :e34382 , 2023
Abstract : To investigate the clinical effect of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of patients with Alzheimer disease (AD), a total of 273 AD patients admitted to our hospital from March 2018 to March 2022 were retrospectively analyzed and assigned into an observation group (n = 138) and a control group (n = 135) according to the different treatment that they received. The control group was treated with donepezil tablets, while the observation group was treated with donepezil tablets combined with hydrogen-oxygen mixture inhalation. The scores of mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognition, activity of daily living scale (ADL) and the P300 event-related potential were compared between the 2 groups. After treatment, MMSE score, MoCA score, and ADL score in both groups increased after treatment (P < .01), while the improvement in the observation group was more significant than that in the control group (P < .001 for MMSE, P = .003 for MoCA, and P = .013 for ADL). The scores of Alzheimer's Disease Assessment Scale-Cognition in the observation group decreased after treatment (P < .05), while the improvement in the observation group was more significant than that in the control group (P = .005). After treatment, the latency of P300 in both groups was shortened (P < .01), and the improvement in the observation group was more significant than that in the control group (P < .001). The amplitude of the observation group increased after treatment (P < .01), and the improvement of the observation group was significant than that of the control group (P = .007). The clinical efficacy of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of AD is better than that of donepezil alone, which is worthy of further study.
ESTHER : Dan_2023_Medicine.(Baltimore)_102_e34382
PubMedSearch : Dan_2023_Medicine.(Baltimore)_102_e34382
PubMedID: 37505148

Title : Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis - Li_2022_Cell.Metab__
Author(s) : Li H , Perino A , Huang Q , Von Alvensleben GVG , Banaei-Esfahani A , Velazquez-Villegas LA , Gariani K , Korbelius M , Bou Sleiman M , Imbach J , Sun Y , Li X , Bachmann A , Goeminne LJE , Gallart-Ayala H , Williams EG , Ivanisevic J , Auwerx J , Schoonjans K
Ref : Cell Metab , : , 2022
Abstract : Bile acids (BAs) are complex and incompletely understood enterohepatic-derived hormones that control whole-body metabolism. Here, we profiled postprandial BAs in the liver, feces, and plasma of 360 chow- or high-fat-diet-fed BXD male mice and demonstrated that both genetics and diet strongly influence BA abundance, composition, and correlation with metabolic traits. Through an integrated systems approach, we mapped hundreds of quantitative trait loci that modulate BAs and identified both known and unknown regulators of BA homeostasis. In particular, we discovered carboxylesterase 1c (Ces1c) as a genetic determinant of plasma tauroursodeoxycholic acid (TUDCA), a BA species with established disease-preventing actions. The association between Ces1c and plasma TUDCA was validated using data from independent mouse cohorts and a Ces1c knockout mouse model. Collectively, our data are a unique resource to dissect the physiological importance of BAs as determinants of metabolic traits, as underscored by the identification of CES1C as a master regulator of plasma TUDCA levels.
ESTHER : Li_2022_Cell.Metab__
PubMedSearch : Li_2022_Cell.Metab__
PubMedID: 36099916
Gene_locus related to this paper: mouse-Ces1c

Title : Recent Advances in the Enzymatic Synthesis of Polyester - Wang_2022_Polymers.(Basel)_14_
Author(s) : Wang H , Li H , Lee CK , Mat Nanyan NS , Tay GS
Ref : Polymers (Basel) , 14 : , 2022
Abstract : Polyester is a kind of polymer composed of ester bond-linked polybasic acids and polyol. This type of polymer has a wide range of applications in various industries, such as automotive, furniture, coatings, packaging, and biomedical. The traditional process of synthesizing polyester mainly uses metal catalyst polymerization under high-temperature. This condition may have problems with metal residue and undesired side reactions. As an alternative, enzyme-catalyzed polymerization is evolving rapidly due to the metal-free residue, satisfactory biocompatibility, and mild reaction conditions. This article presented the reaction modes of enzyme-catalyzed ring-opening polymerization and enzyme-catalyzed polycondensation and their combinations, respectively. In addition, the article also summarized how lipase-catalyzed the polymerization of polyester, which includes (i) the distinctive features of lipase, (ii) the lipase-catalyzed polymerization and its mechanism, and (iii) the lipase stability under organic solvent and high-temperature conditions. In addition, this article also focused on the advantages and disadvantages of enzyme-catalyzed polyester synthesis under different solvent systems, including organic solvent systems, solvent-free systems, and green solvent systems. The challenges of enzyme optimization and process equipment innovation for further industrialization of enzyme-catalyzed polyester synthesis were also discussed in this article.
ESTHER : Wang_2022_Polymers.(Basel)_14_
PubMedSearch : Wang_2022_Polymers.(Basel)_14_
PubMedID: 36501454

Title : The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos - Yu_2022_Chemosphere_307_135751
Author(s) : Yu H , Zhang J , Chen Y , Chen J , Qiu Y , Zhao Y , Li H , Xia S , Chen S , Zhu J
Ref : Chemosphere , 307 :135751 , 2022
Abstract : Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.
ESTHER : Yu_2022_Chemosphere_307_135751
PubMedSearch : Yu_2022_Chemosphere_307_135751
PubMedID: 35863420

Title : Pseudo toxicity abatement effect of norfloxacin and copper combined exposure on Caenorhabditis elegans - Liu_2022_Chemosphere_287_132019
Author(s) : Liu L , He S , Tang M , Zhang M , Wang C , Wang Z , Sun F , Yan Y , Li H , Lin K
Ref : Chemosphere , 287 :132019 , 2022
Abstract : The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 microM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 microM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 microM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 microM and 1.25 microM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 microM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.
ESTHER : Liu_2022_Chemosphere_287_132019
PubMedSearch : Liu_2022_Chemosphere_287_132019
PubMedID: 34450372

Title : Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease - Wu_2022_Bioorg.Chem_122_105760
Author(s) : Wu D , Chen J , Luo K , Li H , Liu T , Li L , Dai Z , Li Y , Zhao Y , Fu X
Ref : Bioorg Chem , 122 :105760 , 2022
Abstract : In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD.
ESTHER : Wu_2022_Bioorg.Chem_122_105760
PubMedSearch : Wu_2022_Bioorg.Chem_122_105760
PubMedID: 35349945

Title : Construction, Pesticidal Activities, Control Effects, and Detoxification Enzyme Activities of Osthole Ester\/Amide Derivatives - Hao_2022_J.Agric.Food.Chem_70_9337
Author(s) : Hao M , Lv M , Zhou L , Li H , Xu J , Xu H
Ref : Journal of Agricultural and Food Chemistry , 70 :9337 , 2022
Abstract : Pesticide research and development has entered an era of safety, efficiency, and environmental friendliness. Discovery of effective active products directly or indirectly from plant secondary metabolites as pesticide candidates has been one of the current research focuses. Herein, two series of new ester and amide derivatives were prepared by structural modifications of a natural coumarin-type product osthole at its C-4' position. Their structures were characterized by IR, mp, (1)H NMR, and HRMS. Confirmation of steric configuration of seven compounds was based on single-crystal analysis. Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), (2'E)-3'-ethoxycarbonylosthole (4b) and (2'E)-3'-(n)hexyloxycarbonylosthole (4e) exhibited 3.2 and 3.1 times acaricidal activity of osthole, and particularly, they also showed 2.4 and 2.2 times control efficiency on the 5th day of osthole. Against Aphis citricola Van der Goot (Homoptera: Aphididae), (2'E)-3'-(p-CF(3))benzyloxycarbonylosthole (4w), (2'E)-3'-benzylaminocarbonylosthole (5f), and (2'E)-3'-phenylethylaminocarbonylosthole (5g) showed 1.9-2.1-fold aphicidal activity of osthole. Furthermore, the changes in two detoxification enzyme [carboxylesterase (CarE) and glutathione S-transferase (GST)] activities over time in treated T. cinnabarinus were investigated. These results can pave the foundation for future design and preparation of osthole derivatives as botanical agrochemicals.
ESTHER : Hao_2022_J.Agric.Food.Chem_70_9337
PubMedSearch : Hao_2022_J.Agric.Food.Chem_70_9337
PubMedID: 35857419

Title : Moringa Oleifera Alleviates Abeta Burden and Improves Synaptic Plasticity and Cognitive Impairments in APP\/PS1 Mice - Mahaman_2022_Nutrients_14_
Author(s) : Mahaman YAR , Feng J , Huang F , Salissou MTM , Wang J , Liu R , Zhang B , Li H , Zhu F , Wang X
Ref : Nutrients , 14 : , 2022
Abstract : Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Abeta and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Abeta burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.
ESTHER : Mahaman_2022_Nutrients_14_
PubMedSearch : Mahaman_2022_Nutrients_14_
PubMedID: 36296969

Title : Biodegradation Pathway and Detoxification of beta-cyfluthrin by the Bacterial Consortium and Its Bacterial Community Structure - Li_2022_J.Agric.Food.Chem_70_7626
Author(s) : Li H , Ma Y , Yao T , Ma L , Zhang J , Li C
Ref : Journal of Agricultural and Food Chemistry , 70 :7626 , 2022
Abstract : In the process of microbial degradation of pyrethroid pesticides, the synergistic effect of the microbial community is more conducive to the complete degradation of toxic compounds than a single strain. At present, the degradation pathway of pyrethroids in a single strain has been well revealed, but the synergistic metabolism at the community level has not been well explained. This study elucidated the bacterial community succession, metabolic pathway, and phytotoxicity assessment during beta-cyfluthrin biodegradation by a novel bacterial consortium enriched from contaminated soil. The results showed that the half-life of beta-cyfluthrin at different initial concentrations of 0.25, 0.5, 0.75, and 1.0 mg mL(-1) were 4.16, 7.34, 12.81, and 22.73 days, respectively. Enterobacter was involved in beta-cyfluthrin degradation metabolism in the initial stage, and other bacterial genera (Microbacterium, Ochrobactrum, Pseudomonas, Hyphomicrobiaceae, Achromobacter, etc.) significantly contribute to the degradation of intermediate metabolites in the later stages. Functional gene prediction and metabolite analysis showed that xenobiotic biodegradation and metabolism, especially benzoate degradation and metabolism by cytochrome P450 were the major means of beta-cyfluthrin degradation. Further, two degradation pathways of beta-cyfluthrin were proposed, which were mainly ester hydrolysis and oxidation to degrade beta-cyfluthrin through the production of carboxylesterase and oxidoreductase. In addition, the inoculated bacterial consortium could degrade beta-cyfluthrin residues in water and soil and reduce its phytotoxicity in Medicago sativa. Hence, this novel bacterial consortium has important application in the remediation environments polluted by beta-cyfluthrin.
ESTHER : Li_2022_J.Agric.Food.Chem_70_7626
PubMedSearch : Li_2022_J.Agric.Food.Chem_70_7626
PubMedID: 35698868

Title : The Comparative Analysis of Genomic Diversity and Genes Involved in Carbohydrate Metabolism of Eighty-Eight Bifidobacterium pseudocatenulatum Isolates from Different Niches of China - Lin_2022_Nutrients_14_
Author(s) : Lin G , Liu Q , Wang L , Li H , Zhao J , Zhang H , Wang G , Chen W
Ref : Nutrients , 14 : , 2022
Abstract : Eighty-eight Bifidobacterium pseudocatenulatum strains, which were isolated from human, chicken and cow fecal samples from different niches of China, were compared genomically in this study to evaluate their diversity. It was found that B. pseudocatenulatum displayed a closed pan-genome, including abundant glycoside hydrolase families of the carbohydrate active enzyme (CAZy). A total of 30 kinds of glycoside hydrolases (GHs), 14 kinds of glycosyl transferases (GTs), 13 kinds of carbohydrate-binding modules (CBMs), 6 kinds of carbohydrate-esterases (CEs), and 2 kinds of auxiliary activities (AAs) gene families were identified across the genomes of the 88 B. pseudocatenulatum strains. Specifically, this showed that significant differences were also present in the number of 10 carbohydrate-active enzyme gene families (GT51, GH13_32, GH26, GH42, GH121, GH3, AA3, CBM46, CE2, and CE6) among the strains derived from the hosts of different age groups, particularly between strains from infants and those from other human age groups. Twelve different individuals of B. pseudocatenulatum from four main clusters were selected for further study to reveal the genetic diversity of carbohydrate metabolism-related genes within the same phylogenetics. The animal experiment showed that 3 weeks of oral administration and 1 week after cessation of administration of these strains did not markedly alter the serum routine inflammatory indicators in mice. Furthermore, the administration of these strains did not significantly cause adverse changes in the gut microbiota, as indicated by the alpha- and beta-diversity indexes, relative to the control group (normal diet). Beyond that, FAHBZ9L5 significantly increased the abundance of B. pseudocatenulatum after 3 weeks and significantly increased the abundance of acetic acid and butyric acid in the host's intestinal tract 3 and 4 weeks after the first administration, respectively, compared with the control group. Corresponding to this, comparative genomic analyses of 12 B. pseudocatenulatum suggest that FAHBZ9L5-specific genes were rich in ABC transporters and carbohydrate esterase. Combining the results of comparative genomics analyses and animal experiment, it is suggested that the strains containing certain gene clusters contribute to another competitive growth advantage of B. pseudocatenulatum, which facilitates its intestinal carbohydrate metabolism in a host.
ESTHER : Lin_2022_Nutrients_14_
PubMedSearch : Lin_2022_Nutrients_14_
PubMedID: 35684146

Title : Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation - Li_2022_Mol.Metab__101597
Author(s) : Li H , Chen R , Zhou Y , Wang H , Sun L , Yang Z , Bai L , Zhang J
Ref : Mol Metab , :101597 , 2022
Abstract : OBJECTIVE: Contextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. METHODS: We applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA-CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. RESULTS: In the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. CONCLUSIONS: Together, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention.
ESTHER : Li_2022_Mol.Metab__101597
PubMedSearch : Li_2022_Mol.Metab__101597
PubMedID: 36096452

Title : Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L - Li_2022_Molecules_27_6336
Author(s) : Li C , Tang W , Chen S , He J , Li X , Zhu X , Li H , Peng Y
Ref : Molecules , 27 :6336 , 2022
Abstract : Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS(+), and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, alpha-amylase, and alpha-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.
ESTHER : Li_2022_Molecules_27_6336
PubMedSearch : Li_2022_Molecules_27_6336
PubMedID: 36234873

Title : PRDX6 knockout restrains the malignant progression of intrahepatic cholangiocarcinoma - Li_2022_Med.Oncol_39_250
Author(s) : Li H , Wu Z , Zhong R , Zhang Q , Chen Q , Shen Y
Ref : Med Oncol , 39 :250 , 2022
Abstract : Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The bifunctional protein peroxiredoxin 6 (PRDX6), which has both calcium-independent phospholipase A2 (iPLA2) and glutathione peroxidase (GPx) activity, participates in the development of multiple tumors. However, the function and clinical significance of PRDX6 in ICC remain unclear. In this study, we characterized PRDX6 in both human ICC and thioacetamide (TAA)-induced rat ICC. We found PRDX6 was significantly increased in ICC tissues, compared with the peritumoral tissues, and PRDX6 expression level was positively correlated with the malignant phenotype in ICC patients. Furthermore, PRDX6 genetic knockout significantly inhibited the tumor progression in rats. By using RNA sequencing analysis, we found 127 upregulated genes and 321 downregulated genes after PRDX6 knockout. In addition, we noticed a significant repression in the Wnt7a/b cascade, which has been shown to play an important role in the occurrence of ICC. We confirmed that gene expressions in the Wnt7a/b cascade were inhibited in ICC tissues after PRDX6 knockout by using qRT-PCR and immunohistochemistry analysis. Collectively, our findings suggest that PRDX6 may promote ICC by regulating the Wnt7a/b pathway, which could be a novel therapeutic target for ICC.
ESTHER : Li_2022_Med.Oncol_39_250
PubMedSearch : Li_2022_Med.Oncol_39_250
PubMedID: 36209344

Title : Microplastics exposure as an emerging threat to ancient lineage: A contaminant of concern for abnormal bending of amphioxus via neurotoxicity - Xiang_2022_J.Hazard.Mater_438_129454
Author(s) : Xiang K , He Z , Fu J , Wang G , Li H , Zhang Y , Zhang S , Chen L
Ref : J Hazard Mater , 438 :129454 , 2022
Abstract : Growing inputs of microplastics into marine sediment have increased significantly the needs for assessment of their potential risks to the marine benthos. A knowledge gap remains with regard to the effect of microplastics on benthos, such as cephalochordates. By employing amphioxus as a model benthic chordate, here we show that exposure to microplastics for 96 h at doses of 1 mg/L and 100 mg/L results in evident accumulation of the polyethylene microplastics. The accumulated microplastics are as much as 0.027% of body weight upon high-dose exposure, causing an abnormal body-bending phenotype that limits the locomotion capability of amphioxus. Mechanistic insight reveals that microplastics can bring about histological damages in gill, intestine and hepatic cecum; In-depth assay of relevant biomarkers including superoxide dismutase, catalase, glutathione, pyruvic acid and total cholesterol indicates the occurrence of oxidative damage and metabolic disorder; Further, microplastics exposure depresses the activity of acetylcholinesterase while allowing the level of acetylcholine to rise in muscle, suggesting the emergence of neurotoxicity. These consequences eventually contribute to the muscle dysfunction of amphioxus. This study rationalizes the abnormal response of the vulnerable notochord to microplastics, signifying the dilemma suffered by the ancient lineage under the emerging threat. Given the enrichment of microplastics through marine food chains, this study also raises significant concerns on the impact of microplastics to other marine organisms, and eventually human beings.
ESTHER : Xiang_2022_J.Hazard.Mater_438_129454
PubMedSearch : Xiang_2022_J.Hazard.Mater_438_129454
PubMedID: 35803186

Title : Data collection from crystals grown in microfluidic droplets - Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
Author(s) : Babnigg G , Sherrell D , Kim Y , Johnson JL , Nocek B , Tan K , Axford D , Li H , Bigelow L , Welk L , Endres M , Owen RL , Joachimiak A
Ref : Acta Crystallographica D Struct Biol , 78 :997 , 2022
Abstract : Protein crystals grown in microfluidic droplets have been shown to be an effective and robust platform for storage, transport and serial crystallography data collection with a minimal impact on diffraction quality. Single macromolecular microcrystals grown in nanolitre-sized droplets allow the very efficient use of protein samples and can produce large quantities of high-quality samples for data collection. However, there are challenges not only in growing crystals in microfluidic droplets, but also in delivering the droplets into X-ray beams, including the physical arrangement, beamline and timing constraints and ease of use. Here, the crystallization of two human gut microbial hydrolases in microfluidic droplets is described: a sample-transport and data-collection approach that is inexpensive, is convenient, requires small amounts of protein and is forgiving. It is shown that crystals can be grown in 50-500pl droplets when the crystallization conditions are compatible with the droplet environment. Local and remote data-collection methods are described and it is shown that crystals grown in microfluidics droplets and housed as an emulsion in an Eppendorf tube can be shipped from the US to the UK using a FedEx envelope, and data can be collected successfully. Details of how crystals were delivered to the X-ray beam by depositing an emulsion of droplets onto a silicon fixed-target serial device are provided. After three months of storage at 4 degreesC, the crystals endured and diffracted well, showing only a slight decrease in diffracting power, demonstrating a suitable way to grow crystals, and to store and collect the droplets with crystals for data collection. This sample-delivery and data-collection strategy allows crystal droplets to be shipped and set aside until beamtime is available.
ESTHER : Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
PubMedSearch : Babnigg_2022_Acta.Crystallogr.D.Struct.Biol_78_997
PubMedID: 35916224

Title : Associations of PNPLA3 rs738409 Polymorphism with Plasma Lipid Levels: A Systematic Review and Meta-Analysis - Luo_2022_Horm.Metab.Res_54_686
Author(s) : Luo Z , Liu Y , Li H , Zhou Y , Peng Y , Lin X , Fang Y , Wan J , Wei B
Ref : Hormone & Metabolic Research , 54 :686 , 2022
Abstract : Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=-0.04, 95% CI=-0.07 to -0.01, p=0.02) and total cholesterol (TC) (SMD=-0.03, 95% CI=-0.05 to -0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.
ESTHER : Luo_2022_Horm.Metab.Res_54_686
PubMedSearch : Luo_2022_Horm.Metab.Res_54_686
PubMedID: 36206762

Title : Nematicidal activity of tirotundin and parthenolide isolated from Tithonia diversifolia and Chrysanthemum parthenium - Lan_2022_J.Environ.Sci.Health.B__1
Author(s) : Lan M , Gao X , Duan X , Li H , Yu H , Li J , Zhao Y , Hao X , Ding X , Wu G
Ref : J Environ Sci Health B , :1 , 2022
Abstract : Acetylcholinesterase (AChE) is an enzyme that catalyzes acetylcholine into choline and acetic acid. Conventional pesticides, including organophosphates and carbamates target and inhibit the activity of AChE. To obtain more pesticide precursors that meet the safety requirements, more than 200 compounds were screened. Tirotundin and parthenolide identified as potential neurotoxins to nematodes were isolated from Tithonia diversifolia and Chrysanthemum parthenium, respectively. Their IC(50) values were 6.89 +/- 0.30 and 5.51 +/- 0.23 microg/mL, respectively against the AChE isolated from Caenorhabditis elegans. AChE was inhibited in a dose-dependent manner using the two compounds. And the Lineweaver-Burk and Dixon plots indicated that tirotundin and parthenolide were reversible inhibitors against AChE, both inhibiting AChE in a mixed-type competitive manner and demonstrating these compounds may possess dual binding site AChE inhibitors. LC(50) values of tirotundin and parthenolide against C. elegans were 9.16 +/- 0.21 and 7.23 +/- 0.48 microg/mL, respectively. These results provide a certain theoretical basis for the development and utilization of novel pesticides.
ESTHER : Lan_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Lan_2022_J.Environ.Sci.Health.B__1
PubMedID: 34983315

Title : Two-Dimensional Cobalt-Doped Ti(3)C(2) MXene Nanozyme-Mediated Homogeneous Electrochemical Strategy for Pesticides Assay Based on In Situ Generation of Electroactive Substances - Yu_2022_Anal.Chem__
Author(s) : Yu L , Chang J , Zhuang X , Li H , Hou T , Li F
Ref : Analytical Chemistry , : , 2022
Abstract : Common homogeneous electrochemical (HEC) sensors usually suffer from the drawbacks of high background signal, low signal-to-noise ratio, and even false positive results due to the preaddition of electroactive substances. Thus, it is necessary to develop novel HEC sensors based on in situ generation of electroactive substances to overcome these shortcomings, which, however, is underexplored. In this work, two-dimensional (2D) nanozymes, i.e., cobalt-doped 2D Ti(3)C(2) MXene nanosheets (CMNSs), with excellent peroxidase-like properties were utilized to develop HEC sensors based on the in situ generation of electroactive substances for organophosphate pesticides (OPs) detection. The 2D CMNSs were synthesized via a template-directed wet chemical approach and displayed outstanding features of hydrophilia and water dispersibility, which could catalyze the oxidation of o-phenylenediamine (OPD) to generate significantly increased reduction current. Interestingly, the 2D CMNSs with peroxidase-like properties exhibited a unique response to thiol compounds and were thus employed as highly efficient catalysts to develop HEC sensors for OPs based on the hydrolysis of acetylthiocholine (ATCh) to form thiocholine catalyzed by acetylcholinesterase (AChE) and the inhibition of AChE activity by OPs. The recovery for OPs analysis of pakchoi extract solutions ranged from 97.4% to 103.3%. The as-proposed HEC sensor based on in situ generation of electroactive substances will provide a new way for the development of high-performance electrochemical sensors and demonstrate potential applicability for the determination of pesticide residues in real samples.
ESTHER : Yu_2022_Anal.Chem__
PubMedSearch : Yu_2022_Anal.Chem__
PubMedID: 35166114

Title : Association between CES1 rs2244613 and the pharmacokinetics and safety of dabigatran: Meta-analysis and quantitative trait loci analysis - Li_2022_Front.Cardiovasc.Med_9_959916
Author(s) : Li H , Zhang Z , Weng H , Qiu Y , Zubiaur P , Zhang Y , Fan G , Yang P , Vuorinen AL , Zuo X , Zhai Z , Wang C
Ref : Front Cardiovasc Med , 9 :959916 , 2022
Abstract : OBJECTIVE: To date, the influence of the carboxylesterase 1 (CES1) rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran remains controversial. Hence, a systematic review was performed to study the association between CES1 rs2244613 genotype and the PKs and safety of dabigatran and CES1 relative expression. METHODS: In addition to the three English databases (Web of Science, PubMed, and Embase), two Chinese databases (CNKI and Wanfang) were thoroughly revised. The mean differences (MD) and corresponding 95% confidence intervals (CI) were applied to evaluate the differences in PKs between the CES1 rs2244613 genotype. Odds ratio (OR) was used to study the risk for bleeding events between the CES1 rs2244613 genotypes. Subsequent expression quantitative trait loci (eQTL) analyses were performed to evaluate genotype-specific expressions in human tissues. RESULTS: Ten studies (n = 2,777) were included. CES1 rs2244613 G allele carriers exhibited significantly lower dabigatran trough concentrations compared to T allele carriers (MD: -8.00 ng/mL; 95% CI: -15.08 to -0.92; p = 0.03). The risk for bleeding events was significantly lower in carriers of the G allele compared to T allele carriers (OR: 0.65; 95% CI: 0.44-0.96; p = 0.03). Subsequent eQTL analysis showed significant genome-wide expressions in two human tissues, whole blood (p = 5.1 x 10(-10)) and liver (p = 6.2 x 10(-43)). CONCLUSION: Our meta-analysis indicated a definite relation between the CES1 rs2244613 genotype and tolerability variations or pharmacokinetic fluctuations. The carriers of T allele showed higher dabigatran concentrations; therefore, they would benefit from a dose reduction. SYSTEMATIC REVIEW REGISTRATION: [], identifier [NPLASY202260027].
ESTHER : Li_2022_Front.Cardiovasc.Med_9_959916
PubMedSearch : Li_2022_Front.Cardiovasc.Med_9_959916
PubMedID: 35990949

Title : Acidic pH and thiol-driven homogeneous cathodic electrochemiluminescence strategy for determining the residue of organophosphorus pesticide in Chinese cabbage - Yang_2022_Food.Chem_393_133349
Author(s) : Yang Q , Zhao S , Li H , Li F
Ref : Food Chem , 393 :133349 , 2022
Abstract : Electrochemiluminescent (ECL) sensors for organophosphorus pesticides (OPs) have received considerable attention, whereas complicated electrode's immobilization, response to single hydrolysate and anodic emission correlated with ECL assays restrict their potential utilization. Herein, we developed a homogeneous dual-response cathodic ECL system for highly sensitive and reliable analysis of OP using CdTe QDs as emitters. CdTe QDs, emitting red light, were fabricated through a hydrothermal reaction and generated anodic and cathodic ECL emission upon stimulation of tripropyl amine and K(2)S(2)O(8), respectively. Notably, CdTe QDs-K(2)S(2)O(8) showed a simultaneous response to thiol and acidic pH, and were regarded as a ECL sensor for methidathion with limit of detection of 0.016 ng/mL based on hydrolysis of acetylthiocholine into thiocholine and CH(3)COOH by acetylcholinesterase (AChE) and OPs' inhibition on AChE activity. This sensor also exhibited good practicability to detect methidathion in Chinese cabbage. Overall, the sensor will supply more useful information for ensuring OPs-related food safety.
ESTHER : Yang_2022_Food.Chem_393_133349
PubMedSearch : Yang_2022_Food.Chem_393_133349
PubMedID: 35691064

Title : Expression, characterization, and immobilization of a novel SGNH esterase Est882 and its potential for pyrethroid degradation - Zong_2022_Front.Microbiol_13_1069754
Author(s) : Zong W , Su W , Xie Q , Gu Q , Deng X , Ren Y , Li H
Ref : Front Microbiol , 13 :1069754 , 2022
Abstract : The widely-used pyrethroid pesticides have attracted public attention because of their potentials to cause environmental pollution and toxic effects on non-target organisms. Esterase is a kind of hydrolytic enzyme that can catalyze the cleavage or formation of ester bonds. it plays a pivotal role in the decomposition of pyrethroids and esters containing industrial pollutants through the hydrolysis of ester bonds. Here, a new esterase gene est882 was successfully screened, which encodes Est882, a SGNH family esterase composed of 294 amino acids. It was heterogeneously expressed, identified and immobilized. Multiple sequence alignment showed that Est882 had a typical GDS(X) conserved motif and a catalytic triad composed of Ser79, Asp269 and His275. Phylogenetic analysis showed that Est882 shall belong to a new esterase family. Biochemical characterization demonstrated that the optimum condition was 40 degreesC and pH 9.0. Est882 immobilization was studied with mesoporous silica SBA-15 as the carrier and found to significantly improve the tolerance and stability of Est882. Its optimum pH increased to 10.0 and stabilized within pH 8.0-11.0. Free Est882 can effectively degrade various pyrethroids within 30 min, with a degradation rate above 80%. The immobilized Est882 yet degraded more than 70% of pyrethroids within 30 min. The present study indicated that Est882 has outstanding potential in bioremediation of a pyrethroid-polluted environment. These characteristics endow Est882 with potential values in various industrial applications and hydrolysis of pyrethroid residues.
ESTHER : Zong_2022_Front.Microbiol_13_1069754
PubMedSearch : Zong_2022_Front.Microbiol_13_1069754
PubMedID: 36620037

Title : Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster - Zhu_2022_Theor.Appl.Genet__
Author(s) : Zhu K , Li M , Wu H , Zhang D , Dong L , Wu Q , Chen Y , Xie J , Lu P , Guo G , Zhang H , Zhang P , Li B , Li W , Wang Q , Zhu J , Hu W , Guo L , Wang R , Yuan C , Li H , Liu Z , Hua W
Ref : Theor Appl Genet , : , 2022
Abstract : Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.
ESTHER : Zhu_2022_Theor.Appl.Genet__
PubMedSearch : Zhu_2022_Theor.Appl.Genet__
PubMedID: 35006335

Title : Tuning the Properties of Ester-Based Degradable Polymers by Inserting Epoxides into Poly(E-caprolactone) - Hu_2022_Chem.Asian.J__e202201097
Author(s) : Hu S , Liu L , Li H , Pahovnik D , Hadjichristidis N , Zhou X , Zhao J
Ref : Chem Asian J , :e202201097 , 2022
Abstract : A series of ester-ether copolymers were obtained via the reaction between alpha,omega-dihydroxyl poly(E-caprolactone) (PCL) and ethylene oxide (EO) or monosubstituted epoxides catalyzed by strong phosphazene bases. The two types of monomeric units were distributed in highly random manners due to the concurrence of epoxide ring-opening and fast transesterification reactions. The substituent of epoxide showed an interesting bidirectional effect on the enzymatic degradability of the copolymer. Compared with PCL, copolymers derived from EO exhibited enhanced hydrophilicity and decreased crystallinity which then resulted in higher degradability. For the copolymers derived from propylene oxide and 1,2-butylene oxide, the hydrophobic alkyl pendant groups also allowed lower crystallinity of the copolymers thus higher degradation rates. However, further enlarging the pendant groups by using styrene oxide or 2-ethylhexyl glycidyl ether caused a decrease in the degradation rate, which might be ascribed to the higher bulkiness hindering the contact of ester groups with lipase.
ESTHER : Hu_2022_Chem.Asian.J__e202201097
PubMedSearch : Hu_2022_Chem.Asian.J__e202201097
PubMedID: 36424185

Title : Modulation of Trans-Synaptic Neurexin-Neuroligin Interaction in Pathological Pain - Li_2022_Cells_11_
Author(s) : Li H , Guo R , Guan Y , Li J , Wang Y
Ref : Cells , 11 : , 2022
Abstract : Synapses serve as the interface for the transmission of information between neurons in the central nervous system. The structural and functional characteristics of synapses are highly dynamic, exhibiting extensive plasticity that is shaped by neural activity and regulated primarily by trans-synaptic cell-adhesion molecules (CAMs). Prototypical trans-synaptic CAMs, such as neurexins (Nrxs) and neuroligins (Nlgs), directly regulate the assembly of presynaptic and postsynaptic molecules, including synaptic vesicles, active zone proteins, and receptors. Therefore, the trans-synaptic adhesion mechanisms mediated by Nrx-Nlg interaction can contribute to a range of synaptopathies in the context of pathological pain and other neurological disorders. The present review provides an overview of the current understanding of the roles of Nrx-Nlg interaction in the regulation of trans-synaptic connections, with a specific focus on Nrx and Nlg structures, the dynamic shaping of synaptic function, and the dysregulation of Nrx-Nlg in pathological pain. Additionally, we discuss a range of proteins capable of modulating Nrx-Nlg interactions at the synaptic cleft, with the objective of providing a foundation to guide the future development of novel therapeutic agents for managing pathological pain.
ESTHER : Li_2022_Cells_11_
PubMedSearch : Li_2022_Cells_11_
PubMedID: 35741069

Title : Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study - Li_2022_J.Neuroinflammation_19_131
Author(s) : Li J , Lin J , Pan Y , Wang M , Meng X , Li H , Wang Y , Zhao X , Qin H , Liu L
Ref : J Neuroinflammation , 19 :131 , 2022
Abstract : OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.
ESTHER : Li_2022_J.Neuroinflammation_19_131
PubMedSearch : Li_2022_J.Neuroinflammation_19_131
PubMedID: 35761288

Title : Carbon Dot-Anchored Cobalt Oxyhydroxide Composite-Based Hydrogel Sensor for On-Site Monitoring of Organophosphorus Pesticides - Li_2022_ACS.Appl.Mater.Interfaces__
Author(s) : Li H , Su C , Liu N , Lv T , Yang C , Lu Q , Sun C , Yan X
Ref : ACS Appl Mater Interfaces , : , 2022
Abstract : The development of a portable, quantitative, and user-friendly sensor for on-site monitoring of organophosphorus pesticides (OPs) is significantly urgent to guarantee food safety. Herein, a carbon dot/cobalt oxyhydroxide composite (CD/CoOOH)-based fluorescent hydrogel sensor is constructed for precisely quantifying OPs using a homemade portable auxiliary device. As a fluorescence signal indicator, the orange-emissive CD/CoOOH composite is encapsulated into an agarose hydrogel kit for amplifying the detection signals, shielding background interference, and enhancing stability. Acetylcholinesterase (AChE) catalyzes the hydrolysis of the substrate to produce thiocholine, which induces the decomposition of CoOOH and makes the fluorescence enhancement of the hydrogel platform possible. OPs can specifically block the AChE activity to limit thiocholine production, resulting in a decrease in platform fluorescence. The image color of the fluorescent hydrogel kit is transformed into digital information using a homemade auxiliary device, achieving on-site quantitative detection of paraoxon (model target) with a detection limit of 10 ng mL(-1). Harnessing CD/CoOOH composite signatures, hydrogel encapsulation, and portable optical devices, the proposed fluorescence hydrogel platform demonstrated high sensitivity and good anti-interference performance in agricultural sample analysis, indicating considerable potential in the on-site application.
ESTHER : Li_2022_ACS.Appl.Mater.Interfaces__
PubMedSearch : Li_2022_ACS.Appl.Mater.Interfaces__
PubMedID: 36380517

Title : Novel Pathogenic Mutation of PNPLA1 Identified in Autosomal Recessive Congenital Ichthyosis: A Case Report - Han_2022_Chin.Med.Sci.J_37_349
Author(s) : Han L , Lijuan Q , Nan X , Li H , Li-Xing Q
Ref : Chin Med Sci J , 37 :349 , 2022
Abstract : Autosomal recessive congenital ichthyosis (ARCI) is characterized by being born as collodion babies, hyperkeratosis, and skin scaling. We described a collodion baby at birth with mild ectropion, eclabium, and syndactyly. Whole exome sequencing showed a compound heterozygous variant c.[56C>A], p.(Ser19X) and c.[100G>A], p.(Ala34Thr) in the PNPLA1 gene [NM_001145717; exon 1]. The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride to omega-hydroxy fatty acid in ceramide, thus giving rise to omega-O-acylceramide, a particular class of sphingolipids that is essential for skin barrier function. The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein. This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.
ESTHER : Han_2022_Chin.Med.Sci.J_37_349
PubMedSearch : Han_2022_Chin.Med.Sci.J_37_349
PubMedID: 36647593

Title : The Effect of Guilingji Capsules on Vascular Mild Cognitive Impairment: A Randomized, Double-Blind, Controlled Trial - Zhang_2022_Evid.Based.Complement.Alternat.Med_2022_4778163
Author(s) : Zhang H , Chen H , Pei H , Wang H , Ma L , Li H
Ref : Evid Based Complement Alternat Med , 2022 :4778163 , 2022
Abstract : Guilingji capsules (GLJC) have been shown to have antiaging effects and improve cognitive function. The aim of this study was to evaluate the clinical efficacy and safety of GLJC for the treatment of vascular mild cognitive impairment (VaMCI). A total of 96 patients with VaMCI (aged 60-85 years) were enrolled in this 24-week, randomized, double-blind, controlled clinical trial. The patients were randomly assigned to a GLJC group (n = 48) or a Ginkgo group (n = 48). Patients in the GLJC group were treated using GLJC, whereas those in the Ginkgo group received Ginkgo extract tablets. We evaluated the participants at baseline and after a 12- and 24-week treatment period using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Chinese Medicine Symptom Scale (CM-SS). The serum acetylcholine (Ach), acetylcholinesterase (AchE), homocysteine (Hcy), and high-sensitivity C-reactive protein (hs-CRP) serum levels of the patients were measured before and after 24-week treatment. Analysis of the results of both groups showed that both interventions significantly increased the MoCA and MMSE scores of the patients and decreased their ADAS-Cog and CM-SS scores (P < 0.05). The GLJC group showed greater improvement in MoCA, MMSE, and CM-SS scores than the Ginkgo group (P < 0.05). However, both groups showed a significant increase in serum Ach and a decrease in serum AchE, Hcy, and hs-CRP levels (P < 0.05). Furthermore, serum Ach increased and Hcy decreased more significantly in the GLJC group than in the Ginkgo group (P < 0.05). These findings indicate that GLJC can improve the cognitive function, cholinergic system, and inflammatory cytokine levels of patients with VaMCI. Furthermore, this treatment can improve symptoms of syndromes diagnosed according to traditional Chinese medicine practice in patients with VaMCI.
ESTHER : Zhang_2022_Evid.Based.Complement.Alternat.Med_2022_4778163
PubMedSearch : Zhang_2022_Evid.Based.Complement.Alternat.Med_2022_4778163
PubMedID: 35116067

Title : Ratiometric fluorescent hydrogel for point-of-care monitoring of organophosphorus pesticide degradation - Li_2022_J.Hazard.Mater_432_128660
Author(s) : Li H , Zou R , Su C , Zhang N , Wang Q , Zhang Y , Zhang T , Sun C , Yan X
Ref : J Hazard Mater , 432 :128660 , 2022
Abstract : The residues of organophosphorus pesticides have caused the potential risk in environment and human health, arousing worldwidely great concern. Herein, we fabricated a robust gold nanoclusters/MnO(2) composites-based hydrogel portable kit for accurate monitoring of paraoxon residues and degradation in Chinese cabbages. With the immobilization of gold nanoclusters/MnO(2) composites into a hydrogel, a ratiometric fluorescent signal is generated by catalyzing the oxidation of o-phenylenediamine, which possesses a built-in correction with low background interference. Coupling with acetylcholinesterase catalytic reactions and pesticide inhibition effect, the portable kit can sensitively detect paraoxon residues with a detection limit of 5.0 ng mL(-1). For on-site quantification, the fluorescent color variations of portable kit are converted into digital information that exhibits applicative linear range toward pesticide. Notably, the hydrogel portable kit was successfully applied for precisely monitoring the residue and degradation of paraoxon in Chinese cabbage, providing a potential pathway toward practical point-of-care testing in food safety monitoring.
ESTHER : Li_2022_J.Hazard.Mater_432_128660
PubMedSearch : Li_2022_J.Hazard.Mater_432_128660
PubMedID: 35334266

Title : Ultrasensitive detection of butyrylcholinesterase activity based on self-polymerization modulated fluorescence of sulfur quantum dots - Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
Author(s) : Chen M , Zhang J , Chang J , Li H , Zhai Y , Wang Z
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 269 :120756 , 2021
Abstract : Butyrylcholinesterase (BChE) is an important clinical diagnosing index for liver dysfunction and organophosphate toxicity. However, the current assays for BChE activity are suffering from the relative poor detection sensitivity. In this work, an ultrasensitive fluorescence assay for BChE activity was developed based on the self-polymerization modulated fluorescence of sulfur quantum dots (S-dots). The luminescence of S-dots can be quenched by the self-polymerized dopamine. The hydrolysate of substrates, thiocholine, under the catalysis of BChE can reduce dopamine, which results in the inhibition of self-polymerization and the fluorescence recovery of S-dots. BChE can be quantitatively detected by recording the recovered fluorescence of S-dots, and a linear relationship is observed between the ratio of fluorescence and the concentration of BChE in the range from 0.01 to 10 U/L. A limit of detection as low as 0.0069 U/L calculated, which is the lowest number so far. The assay also shows excellent selectivity towards various interference species and acetylcholinesterase. These features allowed the direct detection of BChE activity in human serum, demonstrating the great practical applications of our assay.
ESTHER : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedSearch : Chen_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120756
PubMedID: 34952437

Title : Single-Nucleotide Polymorphisms Promote Dysregulation Activation by Essential Gene Mediated Bio-Molecular Interaction in Breast Cancer - Wang_2021_Front.Oncol_11_791943
Author(s) : Wang X , Zhao Z , Han X , Zhang Y , Li F , Li H
Ref : Front Oncol , 11 :791943 , 2021
Abstract : BACKGROUND: Breast cancer (BRCA) is a malignant tumor with a high mortality rate and poor prognosis in patients. However, understanding the molecular mechanism of breast cancer is still a challenge. MATERIALS AND METHODS: In this study, we constructed co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene-expression profiles and clinical data were integrated to detect breast cancer survival modules and the leading genes related to prognostic risk. Finally, we introduced machine learning algorithms to build a predictive model aiming to discover potential key biomarkers. RESULTS: A total of 42 prognostic modules for breast cancer were identified. The nomogram analysis showed that 42 modules had good risk assessment performance. Compared to clinical characteristics, the risk values carried by genes in these modules could be used to classify the high-risk and low-risk groups of patients. Further, we found that 16 genes with significant differential expressions and obvious bridging effects might be considered biological markers related to breast cancer. Single-nucleotide polymorphisms on the CYP24A1 transcript induced RNA structural heterogeneity, which affects the molecular regulation of BRCA. In addition, we found for the first time that ABHD11-AS1 was significantly highly expressed in breast cancer. CONCLUSION: We integrated clinical prognosis information, RNA sequencing data, and drug targets to construct a breast cancer-related risk module. Through bridging effect measurement and machine learning modeling, we evaluated the risk values of the genes in the modules and identified potential biomarkers for breast cancer. The protocol provides new insight into deciphering the molecular mechanism and theoretical basis of BRCA.
ESTHER : Wang_2021_Front.Oncol_11_791943
PubMedSearch : Wang_2021_Front.Oncol_11_791943
PubMedID: 34926308
Gene_locus related to this paper: human-ABHD11

Title : pH and Redox Dual-Response Disulfide Bond-Functionalized Red-Emitting Gold Nanoclusters for Monitoring the Contamination of Organophosphorus Pesticides in Foods - Li_2021_Anal.Chem_93_7362
Author(s) : Li Q , Wu J , Yang Q , Li H , Li F
Ref : Analytical Chemistry , 93 :7362 , 2021
Abstract : Most of the fluorescence sensors require choline oxidase or quenchers to detect organophosphorus pesticides (OPs) based on a single hydrolysate and suffer from high cost, complex procedures, weak stability, and low sensitivity. Here, we proposed a brand-new fluorescence strategy for highly sensitive detection of OPs based on both hydrolysate-response disulfide bond-functionalized gold nanoclusters (S-S-AuNCs) without additional substances. S-S-AuNCs were synthesized via a facile one-step redox reaction and emitted bright red light with ultrasmall size and high water dispersion. Interestingly, S-S-AuNCs displayed a unique response to thiol compounds and low pH values and were thus pioneered as a high-efficiency sensor for OPs based on acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine into thiocholine and CH(3)COOH and OP inhibition of AChE activity. Further, S-S-AuNCs were employed to monitor the residue, distribution, and metabolization of methidathion in pakchoi with acceptable results. We believe that this work supplies a simpler and more highly sensitive approach for OP assay than the known ones and opens a new avenue to development of multistimulus-responsive and high-performance fluorescence substances.
ESTHER : Li_2021_Anal.Chem_93_7362
PubMedSearch : Li_2021_Anal.Chem_93_7362
PubMedID: 33961403

Title : Cloning, characterization of a novel acetyl xylan esterase, and its potential application on wheat straw utilization - Xu_2021_All.Life_14_622
Author(s) : Xu J , Zhao X , Yao Q , Zong W , Dai S , Deng Z , Liu S , Yun J , Yang X , Li H
Ref : All life , 14 :622 , 2021
Abstract : Acetyl xylan esterases are among the key enzymes in the xylan degradation enzyme system. However, acetyl xylan esterases from natural microorganisms have low expression and low enzyme activity and are impure. In this study, a new xylanase gene, est1051, from the metagenomic library, was expressed in the prokaryotic system. Its enzymatic properties were explored, including optimum temperature and pH, thermal and pH stability, and tolerance against organic solvents, metal ions and salt solutions. Then the fermentation conditions of EST1051 were optimized by the response surface method, and the maximum enzyme yield reached 1909.32 U/L. Finally, the synergism with cellulase on straw degradation was evaluated. EST1051 displays high homology with acetylxylan esterases in terms of amino acid sequences and conserved active sites. EST1051 shows high stability across a broad temperature range, and retains more than 60% of its enzymatic activity between 4 and 60C after 24 h of incubation. Single-factor analysis and orthogonal design were conducted to determine the optimal conditions for the maximizing the saccharification rate of wheat straws. Interestingly, the synergism of EST1051 with cellulase contributes to the efficient transformation of wheat straws. These findings may open the door to significant industrial applications of this novel acetylxylan esterase.
ESTHER : Xu_2021_All.Life_14_622
PubMedSearch : Xu_2021_All.Life_14_622
Gene_locus related to this paper: 9bact-est1051

Title : pH-Response Quantum Dots with Orange-Red Emission for Monitoring the Residue, Distribution, and Variation of an Organophosphorus Pesticide in an Agricultural Crop - Yang_2021_J.Agric.Food.Chem__
Author(s) : Yang Q , Li Q , Li H , Li F
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : Development of simple, sensitive, and reliable fluorescence sensors for monitoring the residue, distribution, and variation of organophosphorus pesticides (OPs) in agricultural crops is highly urgent but remains challenging, which is ascribed to deprivation of an ideal fluorophore and ingenious detection strategy. Herein, we report the fabrication of cadmium telluride quantum dots (CdTe QDs) with bright emission, good water dispersion, and long emission wavelength for OP screening based on the unique response of CdTe QDs to pH and the inhibition of OPs on acetylcholinesterase (AChE) activity. AChE catalyzed hydrolysis of acetylcholine (ACh) into CH(3)COOH, which protonated CdTe QDs to decline the fluorescence, whereas target OP impeded AChE from catalyzing hydrolysis of ACh into CH(3)COOH, making little influence in fluorescence of CdTe QDs. On the basis of the change in fluorescence, sensitive detection of OP was acquired, with the limit of detection at 0.027 ng/mL, which was comparable or lower than that of most known OP sensors. Furthermore, the CdTe-QD-based sensor was successfully applied for precisely monitoring the residue, distribution, and variation of methidathion in Chinese cabbage and cultivated soil. Therefore, the proposed sensor was anticipated to supply a promising alternative for food safety guarantee and was an valuable application for OP screening.
ESTHER : Yang_2021_J.Agric.Food.Chem__
PubMedSearch : Yang_2021_J.Agric.Food.Chem__
PubMedID: 33635638

Title : A novel method to produce synthetic murine CXCL10 for efficient screening of functional variants - Decalf_2021_Bioorg.Chem_116_105376
Author(s) : Decalf J , Tom J , Mai E , Hernandez-Barry H , Noland CL , Vollmar BS , Li A , Li H , Xie D , Zhu L , Payandeh J , Wu C , Comps-Agrar L , Moussion C , Albert ML , Song A
Ref : Bioorg Chem , 116 :105376 , 2021
Abstract : Antitumor immune responses depend on the infiltration of solid tumors by effector T cells, a process guided by chemokines. In particular, the chemokine CXCL10 has been shown to play a critical role in mediating recruitment of CXCR3 + cytolytic T and NK cells in tumors, though its use as a therapeutic agent has not been widely explored. One of the limitations is due to the rapid inactivation of CXCL10 by dipeptidyl peptidase 4 (DPP4), a broadly expressed enzyme that is active in plasma and other bodily fluids. In the present study, we describe a novel method to produce synthetic CXCL10 that is resistant to DPP4 N-terminal truncation. Using a Fmoc solid-phase peptide synthesis approach, synthetic murine WT CXCL10 was produced, showing similar biochemical and biological properties to the recombinant protein. This synthesis method supported production of natural (amino acid substitution, insertion or deletion) and non-natural (chemical modifications) variants of CXCL10. In association with a functional screening cascade that assessed DPP4-mediated cleavage, CXCR3 signaling potency and chemotactic activity, we successfully generated 20 murine CXCL10 variants. Among those, two non-natural variants with N-methylated Leu3 (MeLeu3) and a reduced amide bond between Pro2 and Leu3 (rLeu3), respectively, showed resistance to DPP4 truncation but decreased CXCR3 signaling and chemotactic activity. Interestingly, MeLeu3 and rLeu3 CXCL10 behaved as DPP4 inhibitors, preventing the truncation of WT CXCL10. This study highlights the potential of using Fmoc solid-phase chemistry in association with biochemical and biological characterization to rapidly identify CXCL10 variants with desired properties. These novel methods unlock the opportunity to develop DPP4 resistant CXCL10 variants, as well as other chemokine substrates, while maintaining chemotactic properties.
ESTHER : Decalf_2021_Bioorg.Chem_116_105376
PubMedSearch : Decalf_2021_Bioorg.Chem_116_105376
PubMedID: 34560560

Title : Identification and Characterization of Polysorbate-Degrading Enzymes in a Monoclonal Antibody Formulation - Graf_2021_J.Pharm.Sci__
Author(s) : Graf T , Tomlinson A , Yuk IH , Kufer R , Spensberger B , Falkenstein R , Shen A , Li H , Duan D , Liu W , Wohlrab S , Edelmann F , Leiss M
Ref : J Pharm Sci , : , 2021
Abstract : Degradation of polysorbate (PS) by hydrolytically active host cell proteins (HCPs) in drug products may impair the protein-stabilizing properties of PS and lead to the formation of particles due to the accumulation of poorly soluble free fatty acids upon long-term storage. The identification of the causative enzymes is challenging due to their low-abundance even when using state-of-the-art instrumentation and workflows. To overcome these challenges, we developed a rigorous enrichment strategy for HCPs, utilizing both Protein A and anti-HCP affinity chromatography, which facilitated the in-depth characterization of the HCP population in a monoclonal antibody formulation prone to PS hydrolysis. Based on the HCPs identified by liquid chromatography coupled to tandem mass spectrometry, a number of enzymes annotated as hydrolases were recombinantly expressed and characterized in terms of polysorbate degradation. Among the selected candidates, Lipoprotein Lipase, Lysosomal Acid Lipase (LIPA) and Palmitoyl-Protein Thioesterase 1 (PPT1) exhibited notable activity towards PS. To our knowledge, this is the first report to identify LIPA and PPT1 as residual HCPs that can contribute to PS degradation in a biological product.
ESTHER : Graf_2021_J.Pharm.Sci__
PubMedSearch : Graf_2021_J.Pharm.Sci__
PubMedID: 34224732

Title : Two-Dimensional MnO(2) Nanozyme-Mediated Homogeneous Electrochemical Detection of Organophosphate Pesticides without the Interference of H(2)O(2) and Color - Wu_2021_Anal.Chem__
Author(s) : Wu J , Yang Q , Li Q , Li H , Li F
Ref : Analytical Chemistry , : , 2021
Abstract : Traditional peroxidase-like nanozyme-based sensors suffer from self-decomposition and high toxicity of H(2)O(2), as well as the interference of color from nanozymes themselves and testing samples. In this work, we adopt nanozymes (two-dimension (2D) MnO(2) sheets, manganese dioxide nanosheets (MnNS)) with oxidase-like and peroxidase-like properties as advanced catalysts to develop a novel homogeneous electrochemical sensor for organophosphate pesticides (OPs) using dissolved O(2) as a coreactant without the interference of H(2)O(2) and color. Owing to the large surface area and unique catalytic activity of MnNS, a large amount of tetramethylbenzidine (TMB) is catalyzed oxidation, leading to a significantly declined differential pulse voltammetry (DPV) current. Obviously, MnNS display an excellent response to thiocholine, deriving from the catalyzing hydrolysis of acetylthiocholine (ATCh) by acetylcholinesterase (AChE), which switches a homogeneous electrochemical OP detection process based on the depressing AChE activity with a limit of detection (LOD) of 0.025 ng mL(-1). The as-proposed strategy on using nanozymes with oxidase-like and peroxidase-like properties to develop a homogeneous electrochemical sensor will provide a new pathway for improving the performance of nanozyme-based sensors, and the established MnNS-based homogeneous electrochemical sensor will find more applications for OP residue determination in food samples.
ESTHER : Wu_2021_Anal.Chem__
PubMedSearch : Wu_2021_Anal.Chem__
PubMedID: 33588528

Title : Resistance of Bemisia tabaci Mediterranean (Q-biotype) to pymetrozine: resistance risk assessment, cross-resistance to six other insecticides and detoxification enzyme assay - Wang_2021_Pest.Manag.Sci_77_2114
Author(s) : Wang F , Liu J , Shuai S , Miao C , Chi B , Chen P , Wang K , Li H , Liu Y
Ref : Pest Manag Sci , 77 :2114 , 2021
Abstract : BACKGROUND: The whitefly Bemisia tabaci (Gennadius) is a severe pest that affects many field and glasshouse crops worldwide and has developed resistance to insecticides in most chemical classes. Pymetrozine, a neuroactive pyridine azomethine, is selective towards piercing-sucking pests in Hemiptera. The aim of this study was to assess the resistance of B. tabaci Mediterranean (MED) to pymetrozine in the laboratory. RESULTS: After successive selection of 18 generations of MED in the presence of using pymetrozine, there was an 11.28-fold increase in the median lethal concentration (LC(50) ). When the realized heritability (h(2) ) of B. tabaci to pymetrozine in the field was assumed to be the value estimated in the laboratory (h(2) = 0.1360) and the mortality was 70-90%, only 7.2-15.9 generations were estimated to be needed to obtain a ten-fold increase in resistance to pymetrozine. Compared with the susceptible populations (G(0) ), the Pyme-SEL strain (G(18) ) showed a low level of cross-resistance to neonicotinoids (nitenpyram, imidacloprid, acetamiprid, and thiamethoxam) and no cross-resistance to chlorpyrifos or abamectin. With the G(0) and the Pyme-SEL strains (G(11) and G(18) ) as test strains, the activity of multifunctional oxidase exhibited the greatest increase during selection, while the activities of carboxylesterase and glutathione-S-transferase did not change significantly. CONCLUSION: This study show that a potential risk of development of resistance to pymetrozine exists in B. tabaci after continuous application. During the application of pymetrozine to control B. tabaci in the field, the frequency of its use in combination with neonicotinoids should be used with caution. 2020 Society of Chemical Industry.
ESTHER : Wang_2021_Pest.Manag.Sci_77_2114
PubMedSearch : Wang_2021_Pest.Manag.Sci_77_2114
PubMedID: 33332688

Title : Inorganic Recognizer-Assisted Homogeneous Electrochemiluminescence Determination of Organophosphorus Pesticides via Target-Controlled Emitter Release - Li_2021_J.Agric.Food.Chem_69_6087
Author(s) : Li H , Lv W , Yang Q , Li Q , Li F
Ref : Journal of Agricultural and Food Chemistry , 69 :6087 , 2021
Abstract : Given the relevance of organophosphorus pesticides (OPs) with food safety, it is highly urgent to develop sensitive and reliable sensors for OPs. However, most of the OP sensors are developed based on colorimetric and fluorescent techniques, which are limited to severe interference of color and fluorescence from pigments and organic acids in agricultural crops. Herein, we develop an inorganic recognizer-based homogeneous electrochemiluminescence (ECL) sensor for the highly sensitive and credible determination of OPs based on manganese dioxide and tris(2,2'-bipyridine)ruthenium [Ru(bpy)(3)](2+). Through electrostatic interaction, manganese dioxide nanoflakes-[Ru(bpy)(3)](2+) nanocomposites (MnNFs-Ru) are formed and exhibit a weak ECL signal due to the confinement of [Ru(bpy)(3)](2+) in MnNFs-Ru. Interestingly, MnNFs-Ru are capable of recognizing thiols due to the analyte-initiated reduction of MnNFs into Mn(2+) and release of [Ru(bpy)(3)](2+) from MnNFs-Ru into solution. Further, MnNFs-Ru are employed for the homogeneous ECL determination of OPs, where acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylthiocholine (ATCh) into thiocholine, which in turn decomposes MnNFs of MnNFs-Ru into Mn(2+), and OPs inhibit AChE activity. This study widens the application of inorganic recognizers from colorimetry/fluorescence to homogeneous ECL and effectively avoids the interference of color and fluorescence, opening up a new path to the development of high-performance OP sensors and supplying a promising tool for guaranteed OP-related food safety.
ESTHER : Li_2021_J.Agric.Food.Chem_69_6087
PubMedSearch : Li_2021_J.Agric.Food.Chem_69_6087
PubMedID: 34018740

Title : Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development - Li_2021_Plant.J__
Author(s) : Li S , Li Y , Chen L , Zhang C , Wang F , Li H , Wang M , Wang Y , Nan F , Xie D , Yan J
Ref : Plant J , : , 2021
Abstract : Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.
ESTHER : Li_2021_Plant.J__
PubMedSearch : Li_2021_Plant.J__
PubMedID: 33860570

Title : Chemical composition of essential oils from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare and their acaricidal effects on Haemaphysalis longicornis (Acari: Ixodidae) - Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
Author(s) : Qiao Y , Yu Z , Bai L , Li H , Zhang S , Liu J , Gao Z , Yang X
Ref : Ecotoxicology & Environmental Safety , 224 :112672 , 2021
Abstract : Chemical acaricides are mainly used in traditional tick control, which leads to the emergence of tick resistance and concurrently results in environmental pollution. In the present study, the chemical constituents of essential oils (EOs) from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare was analyzed, and their potential application was evaluated to control the vector tick Haemaphysalis longicornis, which is widely distributed over vast areas of Eurasia, Australia, and New Zealand. Gas chromatography-mass spectrometry analysis revealed that the phenols thymol and carvacrol accounted for 34.66% and 75.72% of the EOs of T. mongolicus and O. vulgare, respectively, whereas trans-cinnamaldehyde (49.42%) was the main constituent of C. verum EO. Immersion tests showed that the EOs of C. verum and O. vulgare had significant acaricidal activity against larval H. longicornis, with the 50% lethal concentration (LC(50)) being 16.07 and 18.02 mg/mL, respectively, and the 95% lethal concentration (LC(95)) being 120.37 and 130.09 mg/mL, respectively. The EOs of O. vulgare and T. mongolicus showed significant acaricidal activity against unfed adult H. longicornis, with LC(50) being 43.50 and 44.21 mg/mL, respectively, and LC(95) being 113.66 and 137.99 mg/mL, respectively. The fumigant toxicity test showed significant acaricidal activity of the three EOs against both unfed and engorged nymphal and adult H. longicornis. Enzyme assays revealed that the EOs of both C. verum and O. vulgare significantly inhibited glutathione S-transferase activity (P < 0.05). In contrast, the activities of carboxylesterase and multifunction oxidases were significantly inhibited by EOs extracted from all three plants (P < 0.05). Taken together, these findings suggest that plant EOs may serve as an environment-friendly alternative for synthetic acaricides in future tick control.
ESTHER : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedSearch : Qiao_2021_Ecotoxicol.Environ.Saf_224_112672
PubMedID: 34416637

Title : Association of TaD14-4D, a Gene Involved in Strigolactone Signaling, with Yield Contributing Traits in Wheat - Liu_2021_Int.J.Mol.Sci_22_
Author(s) : Liu R , Hou J , Li H , Xu P , Zhang Z , Zhang X
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Tillering is a crucial agronomic trait of wheat; it determines yield and plant architecture. Strigolactones (SLs) have been reported to inhibit plant branching. D14, a receptor of SLs, has been described to affect tillering in rice, yet it has seldomly been studied in wheat. In this study, three TaD14 homoeologous genes, TaD14-4A, TaD14-4B, and TaD14-4D, were identified. TaD14-4A, TaD14-4B, and TaD14-4D were constitutively expressed, and TaD14-4D had a higher expression level in most tissues. TaD14 proteins were localized in both cytoplasm and nucleus. An SNP and a 22 bp insertion/deletion (Indel) at the exon regions of TaD14-4D were detected, forming three haplotypes, namely 4D-HapI, 4D-HapII, and 4D-HapIII. Due to the frameshift mutation in the coding region of 4D-HapII, the interaction of 4D-HapII with TaMAX2 and TaD53 was blocked, which led to the blocking of SL signal transduction. Based on the two variation sites, two molecular markers, namely dCAPS-250 and Indel-747, were developed. Association analysis suggested that haplotypes of TaD14-4D were associated with effective tillering number (ETN) and thousand kernel weight (TKW) simultaneously in four environments. The favorable haplotype 4D-HapIII underwent positive selection in global wheat breeding. This study provides insights into understanding the function of natural variations of TaD14-4D and develops two useful molecular markers for wheat breeding.
ESTHER : Liu_2021_Int.J.Mol.Sci_22_
PubMedSearch : Liu_2021_Int.J.Mol.Sci_22_
PubMedID: 33916852

Title : Structure-activity relationship, in vitro and in vivo evaluation of novel dienyl sulphonyl fluorides as selective BuChE inhibitors for the treatment of Alzheimer's disease - Wu_2021_J.Enzyme.Inhib.Med.Chem_36_1860
Author(s) : Wu C , Zhang G , Zhang ZW , Jiang X , Zhang Z , Li H , Qin HL , Tang W
Ref : J Enzyme Inhib Med Chem , 36 :1860 , 2021
Abstract : To discover novel scaffolds as leads against dementia, a series of delta-aryl-1,3-dienesulfonyl fluorides with alpha-halo, alpha-aryl and alpha-alkynyl were assayed for ChE inhibitory activity, in which compound A10 was identified as a selective BuChE inhibitor (IC(50) = 0.021 microM for eqBChE, 3.62 microM for hBuChE). SAR of BuChE inhibition showed: (i) o- > m- > p-; -OCH(3) > -CH(3) > -Cl (-Br) for delta-aryl; (ii) alpha-Br > alpha-Cl, alpha-I. Compound A10 exhibited neuroprotective, BBB penetration, mixed competitive inhibitory effect on BuChE (K(i) = 29 nM), and benign neural and hepatic safety. Treatment with A10 could almost entirely recover the Abeta(1-42)-induced cognitive dysfunction to the normal level, and the assessment of total amount of Abeta(1-42) confirmed its anti-amyloidogenic profile. Therefore, the potential BuChE inhibitor A10 is a promising effective lead for the treatment of AD.
ESTHER : Wu_2021_J.Enzyme.Inhib.Med.Chem_36_1860
PubMedSearch : Wu_2021_J.Enzyme.Inhib.Med.Chem_36_1860
PubMedID: 34425715

Title : The association between toxic pesticide environmental exposure and Alzheimer's disease: A scientometric and visualization analysis - Li_2021_Chemosphere_263_128238
Author(s) : Li Y , Fang R , Liu Z , Jiang L , Zhang J , Li H , Liu C , Li F
Ref : Chemosphere , 263 :128238 , 2021
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. The association between environmental factors (e.g., pesticide) and AD has attracted considerable attention. However, no systematic analysis has been performed and make it difficult to provide deeper insights of AD correlated with pesticide exposure. Hence, this study utilized a bibliometric and visual approach that included map collaborations, co-citations, and keywords, to identifying the knowledge structure, hot topics and the research trends based on 372 publications from the Web of Science Core Collection and PubMed databases. The results showed that 116 institutions from 52 countries published articles in this field. The United States and Israel played a leading role with numerous publications in related journals, as well as prolific institutions and authors, respectively. Three hot topics in pesticide-induced AD were recognized based on co-occurrence keywords detection, including acetylcholinesterase (AChE) inhibitor, oxidative stress, and AChE. Moreover, analysis of keywords burst suggests that some potential molecular mechanisms and therapy targets of pesticide-induced AD, especially for mitochondrial dysfunction and monoamine oxidase-B (MAO-B) that catalyzes the oxidative deamination and causes oxidative stress, are emerging trends. In addition, the study of various pesticides and the assessment method of pesticide exposure will step forward as well. To the best of our knowledge, this study is the first to specifically visualize the relationship between AD and pesticide exposure and to predict potential future research directions.
ESTHER : Li_2021_Chemosphere_263_128238
PubMedSearch : Li_2021_Chemosphere_263_128238
PubMedID: 33297185

Title : Binding mechanism and functional evaluation of quercetin 3-rhamnoside on lipase - Wu_2021_Food.Chem_359_129960
Author(s) : Wu D , Duan R , Tang L , Hu X , Geng F , Sun Q , Zhang Y , Li H
Ref : Food Chem , 359 :129960 , 2021
Abstract : The interaction between lipase and quercetin 3-rhamnoside was studied by fluorescence spectroscopy, enzyme kinetics, and molecular dynamics simulation. The results showed that quercetin 3-rhamnoside had a strong quenching effect on the intrinsic fluorescence of lipase. The binding constant decreased with increasing temperature, and the number of binding sites approached 1. Thermodynamic parameters indicated that hydrogen bonding and van der Waals forces are the dominant forces when the interaction occurs. Circular dichroism spectroscopy and infrared spectroscopy proved that the ligand perturbed the structure of lipase. Enzyme kinetics results showed that quercetin 3-rhamnoside inhibited lipase, and the inhibitory effect was dose-dependent. Molecular dynamics simulation further explained the interaction mechanism and inhibitory effect. This study confirmed the inhibitory effect of quercetin 3-rhamnoside on lipase explained their binding mechanism, which will contribute to guiding the development of fat-reducing functional foods.
ESTHER : Wu_2021_Food.Chem_359_129960
PubMedSearch : Wu_2021_Food.Chem_359_129960
PubMedID: 33945987

Title : Rational Design of Highly Selective Near-Infrared Two-Photon Fluorogenic Probe for Imaging Orthotopic Hepatocellular Carcinoma Chemotherapy - Wu_2021_Angew.Chem.Int.Ed.Engl__
Author(s) : Wu X , Wang R , Qi S , Kwon N , Han J , Kim H , Li H , Yu F , Yoon J
Ref : Angew Chem Int Ed Engl , : , 2021
Abstract : Selective fluorescence imaging of biomarker in vivo and in situ for evaluating orthotopic hepatocellular carcinoma (HCC) chemotherapy remains a great challenge due to current imaging agents suffering from the potential interferences of other hydrolases. Herein, we observed that carbamate unit showed a high selectivity toward HCC-related biomarker (carboxylesterase, CE) for evaluation of treatment. A near-infrared two-photon fluorescent probe was developed to not only specially image CE activity in vivo and in situ but also target orthotopic liver tumor after systemic administration. In vivo signals of probe correlating well with tumor apoptosis make it possible to evaluate the status of treatment. Excellent property of probe enables the first imaging of CE activity in situ with high resolution three-dimensional view. This study may promote advancements in optical imaging approach for precise imaging-guided diagnosis of HCC in situ and its evaluation of treatment.
ESTHER : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedID: 33942436

Title : Molecular Detection of Insecticide Resistance Mutations in Anopheles gambiae from Sierra Leone Using Multiplex SNaPshot and Sequencing - Yin_2021_Front.Cell.Infect.Microbiol_11_666469
Author(s) : Yin J , Yamba F , Zheng C , Zhou S , Smith SJ , Wang L , Li H , Xia Z , Xiao N
Ref : Front Cell Infect Microbiol , 11 :666469 , 2021
Abstract : Vector control interventions including long-lasting insecticidal nets and indoor residual spraying are important for malaria control and elimination. And effectiveness of these interventions depends entirely on the high level of susceptibility of malaria vectors to insecticides. However, the insecticide resistance in majority of mosquito vector species across African countries is a serious threat to the success of vector control efforts with the extensive use of insecticides, while no data on insecticide resistance was reported from Sierra Leone in the past decade. In the present study, the polymerase chain reaction was applied for the identification of species of 757 dry adult female Anopheles gambiae mosquitoes reared from larvae collected from four districts in Sierra Leone during May and June 2018. And the mutations of kdr, rdl, ace-1 genes in An. gambiae were detected using SNaPshot and sequencing. As a result, one sample from Western Area Rural district belonged to Anopheles melas, and 748 An. gambiae were identified. Furthermore, the rdl mutations, kdr west mutations and ace-1 mutation were found. The overall frequency was 35.7%, 0.3%, 97.6% and 4.5% in A296G rdl, A296S rdl, kdrW and ace-1, respectively. The frequencies of A296G rdl mutation (P < 0.001), kdrW mutation (P = 0.001) and ace-1 mutation (P < 0.001) were unevenly distributed in four districts, respectively, while no statistical significance was found in A296S rdl mutation (P = 0.868). In addition, multiple resistance patterns were also found. In conclusion, multiple mutations involved in insecticide resistance in An. gambiae populations in Sierra Leone were detected in the kdrW, A296G rdl and ace-1 alleles in the present study. It is necessary to monitor vector susceptibility levels to insecticides used in this country, and update the insecticide resistance monitoring and management strategy.
ESTHER : Yin_2021_Front.Cell.Infect.Microbiol_11_666469
PubMedSearch : Yin_2021_Front.Cell.Infect.Microbiol_11_666469
PubMedID: 34490134

Title : Light-accelerating oxidase-mimicking activity of black phosphorus quantum dots for colorimetric detection of acetylcholinesterase activity and inhibitor screening - Ren_2021_Analyst_145_8022
Author(s) : Ren L , Li H , Liu M , Du J
Ref : Analyst , 145 :8022 , 2021
Abstract : A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3',5,5'-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3',5,5'-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3',5,5'-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL-1 and a detection limit of 0.17 mU mL-1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.
ESTHER : Ren_2021_Analyst_145_8022
PubMedSearch : Ren_2021_Analyst_145_8022
PubMedID: 33057486

Title : Longitudinal Profile of Laboratory Parameters and Their Application in the Prediction for Fatal Outcome Among Patients Infected With SARS-CoV-2: A Retrospective Cohort Study - Zeng_2021_Clin.Infect.Dis_72_626
Author(s) : Zeng HL , Lu QB , Yang Q , Wang X , Yue DY , Zhang LK , Li H , Liu W , Li HJ
Ref : Clin Infect Dis , 72 :626 , 2021
Abstract : BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.
ESTHER : Zeng_2021_Clin.Infect.Dis_72_626
PubMedSearch : Zeng_2021_Clin.Infect.Dis_72_626
PubMedID: 33048116

Title : Androgen-dependent miR-125a-5p targets LYPLA1 and regulates global protein palmitoylation level in late-onset hypogonadism males - Qu_2021_J.Cell.Physiol_236_4738
Author(s) : Qu M , Zhao Y , Qing X , Zhang X , Li H
Ref : Journal of Cellular Physiology , 236 :4738 , 2021
Abstract : Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in-depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR-125a-5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR-125a-5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR-125a-5p expression by testosterone. Androgen response element in the promoter of miR-125a-5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl-protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR-125a-5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR-125a-5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR-125a-5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH.
ESTHER : Qu_2021_J.Cell.Physiol_236_4738
PubMedSearch : Qu_2021_J.Cell.Physiol_236_4738
PubMedID: 33284463

Title : Two new organic acids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities - Liu_2021_Nat.Prod.Res__1
Author(s) : Liu P , Wang L , Li H , Tan L , Ying X , Ju B
Ref : Nat Prod Res , :1 , 2021
Abstract : Two new organic acids, identified as (7E,9E,12E)-pentadecyl-7,9,12-trienoic acid, named Oleraceacid A (1), and 6,7-dihydroxy-4-(4-hydroxy-3,5-dimethoxyphenyl)-2-naphthoic acid, named Oleraceacid B (2), were isolated from Portulaca oleracea L.. The structures were verified by spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1 D and 2 D NMR. Both Oleraceacid A (1) and Oleraceacid B (2) at 20 microM inhibited the inflammatory factor, IL-1beta in the RAW 264.7 cells induced by LPS, moreover, Oleraceacid A (1) can inhibit cholinesterase activity.
ESTHER : Liu_2021_Nat.Prod.Res__1
PubMedSearch : Liu_2021_Nat.Prod.Res__1
PubMedID: 34749551

Title : sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae - Li_2021_J.Clin.Invest__
Author(s) : Li H , Bradbury JA , Edin ML , Graves JP , Gruzdev A , Cheng J , Hoopes SL , Miller-Degraff L , Fessler MB , Garantziotis S , Schurman SH , Zeldin DC
Ref : J Clinical Investigation , : , 2021
Abstract : Epoxyeicosatrienoic acids (EETs) have potent anti-inflammatory properties. Hydrolysis of EETs by soluble epoxide hydrolase (sEH/EPHX2) to less active diols attenuates their anti-inflammatory effects. Macrophage activation is critical to many inflammatory responses; however, the role of EETs and sEH in regulating macrophage function remains unknown. Lung bacterial clearance of S. pneumoniae was impaired in Ephx2-deficient (Ephx2-/-) mice and in mice treated with an sEH inhibitor. The EET receptor antagonist, EEZE, restored lung clearance of S. pneumoniae in Ephx2-/- mice. Ephx2-/- mice had normal lung Il-1beta, Il-6 and Tnfalpha expression and macrophage recruitment to lungs during S. pneumoniae infection; however, Ephx2 disruption attenuated proinflammatory cytokine induction, Tlr2 and Pgylrp1 receptor upregulation and Rac1/2 and Cdc42 activation in PGN-stimulated macrophages. Consistent with these observations, Ephx2-/-macrophages displayed reduced phagocytosis of S. pneumoniae in vivo and in vitro. Heterologous overexpression of TLR2 and PGLYRP1 in Ephx2-/- macrophages restored macrophage activation and phagocytosis. Human macrophage function was similarly regulated by EETs. Together, these results demonstrate that EETs reduce macrophage activation and phagocytosis of S. pneumoniae through down-regulation of TLR2 and PGLYRP1 expression. Defining the role of EETs and sEH in macrophage function may lead to development of new therapeutic approaches for bacterial diseases.
ESTHER : Li_2021_J.Clin.Invest__
PubMedSearch : Li_2021_J.Clin.Invest__
PubMedID: 34591792

Title : COX-2\/sEH Dual Inhibitor PTUPB Alleviates CCl (4) -Induced Liver Fibrosis and Portal Hypertension - Zhao_2021_Front.Med.(Lausanne)_8_761517
Author(s) : Zhao Z , Zhang C , Lin J , Zheng L , Li H , Qi X , Huo H , Lou X , Hammock BD , Hwang SH , Bao Y , Luo M
Ref : Front Med (Lausanne) , 8 :761517 , 2021
Abstract : Background: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl) -benzenesulfonamide (PTUPB), a dual cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) inhibitor, was found to alleviate renal, pulmonary fibrosis and liver injury. However, few is known about the effect of PTUPB on liver cirrhosis. In this study, we aimed to explore the role of PTUPB in liver cirrhosis and portal hypertension (PHT). Method: Rat liver cirrhosis model was established via subcutaneous injection of carbon tetrachloride (CCl(4)) for 16 weeks. The experimental group received oral administration of PTUPB (10 mg/kg) for 4 weeks. We subsequently analyzed portal pressure (PP), liver fibrosis, inflammation, angiogenesis, and intra- or extrahepatic vascular remodeling. Additionally, network pharmacology was used to investigate the possible mechanisms of PTUPB in live fibrosis. Results: CCl(4) exposure induced liver fibrosis, inflammation, angiogenesis, vascular remodeling and PHT, and PTUPB alleviated these changes. PTUPB decreased PP from 17.50 +/- 4.65 to 6.37 +/- 1.40 mmHg, reduced collagen deposition and profibrotic factor. PTUPB alleviated the inflammation and bile duct proliferation, as indicated by decrease in serum interleukin-6 (IL-6), liver cytokeratin 19 (CK-19), transaminase, and macrophage infiltration. PTUPB also restored vessel wall thickness of superior mesenteric arteries (SMA) and inhibited intra- or extrahepatic angiogenesis and vascular remodeling via vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), etc. Moreover, PTUPB induced sinusoidal vasodilation by upregulating endothelial nitric oxide synthase (eNOS) and GTP-cyclohydrolase 1 (GCH1). In enrichment analysis, PTUPB engaged in multiple biological functions related to cirrhosis, including blood pressure, tissue remodeling, immunological inflammation, macrophage activation, and fibroblast proliferation. Additionally, PTUPB suppressed hepatic expression of sEH, COX-2, and transforming growth factor-beta (TGF-beta). Conclusion: 4-(5-phenyl-3-{3-[3-(4-trifluoromethylphenyl)-ureido]-propyl}-pyrazol-1-yl)- benzenesulfonamide ameliorated liver fibrosis and PHT by inhibiting fibrotic deposition, inflammation, angiogenesis, sinusoidal, and SMA remodeling. The molecular mechanism may be mediated via the downregulation of the sEH/COX-2/TGF-beta.
ESTHER : Zhao_2021_Front.Med.(Lausanne)_8_761517
PubMedSearch : Zhao_2021_Front.Med.(Lausanne)_8_761517
PubMedID: 35004731

Title : A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells, mice brains and tissues - Wu_2020_Chem.Sci_11_11285
Author(s) : Wu X , An JM , Shang J , Huh E , Qi S , Lee E , Li H , Kim G , Ma H , Oh MS , Kim D , Yoon J
Ref : Chem Sci , 11 :11285 , 2020
Abstract : Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.
ESTHER : Wu_2020_Chem.Sci_11_11285
PubMedSearch : Wu_2020_Chem.Sci_11_11285
PubMedID: 34094370

Title : Mechanistic insight into esterase-catalyzed hydrolysis of phthalate esters (PAEs) based on integrated multi-spectroscopic analyses and docking simulation - Du_2020_J.Hazard.Mater_408_124901
Author(s) : Du H , Hu RW , Zhao HM , Huang HB , Xiang L , Liu BL , Feng NX , Li H , Li YW , Cai QY , Mo CH
Ref : J Hazard Mater , 408 :124901 , 2020
Abstract : A novel PAE-hydrolyzing esterase (named Hyd) gene was screened from the genomic library of Rhodococcus sp. 2G and was successfully expressed in heterologous E. coli, which was defined as a new family of esterolytic enzymes. The purified Hyd could efficiently degrade various PAEs, displaying high activity and stability with a broad range of pH (4-10) and temperature (20-60 degreesC). Interaction mechanism of Hyd with dibutyl phthalate (DBP) was investigated by integrated multi-spectroscopic and docking simulation methods. Fluorescence and UV-vis spectra revealed that DBP could quench the fluorescence of Hyd through a static quenching mechanism. The results from synchronous fluorescence and CD spectra confirmed that the DBP binding to Hyd triggered conformational and micro-environmental changes of Hyd, which were characterized by increased stretching extent and random coil, and decreased alpha-helix and beta-sheet. Molecular docking study showed that DBP could be bound to the cavity of Hyd with hydrogen bonding and hydrophobic interaction. A novel and distinctive catalytic mechanism was proposed: two key residues Thr(190) and Ser(191) might catalyze the hydrolysis of DBP, instead of the conserved catalytic triad (Ser-His-Asp) reported elsewhere, which was confirmed by site-directed mutagenesis.
ESTHER : Du_2020_J.Hazard.Mater_408_124901
PubMedSearch : Du_2020_J.Hazard.Mater_408_124901
PubMedID: 33360702
Gene_locus related to this paper: rhoso-a0a3g5hne7

Title : Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining - Tang_2020_J.Nat.Prod_83_473
Author(s) : Tang S , Zhang W , Li Z , Li H , Geng C , Huang X , Lu X
Ref : Journal of Natural Products , 83 :473 , 2020
Abstract : Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids have been characterized to produce polyketide-amino acid compounds with striking structural features and biological activities. In this study, a PKS-NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS-NRPS gene cluster was successfully activated and ten products (1-10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS-NRPS hybrid identified in A. terreus.
ESTHER : Tang_2020_J.Nat.Prod_83_473
PubMedSearch : Tang_2020_J.Nat.Prod_83_473
PubMedID: 32077283
Gene_locus related to this paper: asptn-pytb , aspte-pyti

Title : Design of Red Emissive Carbon Dots: Robust Performance for Analytical Applications in Pesticide Monitoring - Li_2020_Anal.Chem_92_3198
Author(s) : Li H , Su D , Gao H , Yan X , Kong D , Jin R , Liu X , Wang C , Lu G
Ref : Analytical Chemistry , 92 :3198 , 2020
Abstract : Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.0%) based on solvothermal treatment of citric acid and thiourea using dimethylformamide as solvent. Further investigations reveal that the conjugating sp(2)-domain controlling the incorporation of nitrogen and surface engineering are mainly responsible for the obtained red emission of CDs. Taking advantage of optical properties and abundant surface functional groups, CDs were considered to facilely construct a ratiometric fluorescent platform for quantifying trace levels of organophosphorus pesticides (OPs). Combining the acetylcholinesterase-mediated polymerization of dopamine and the inhibition of pesticide toward the enzyme, the degree of polymerization of dopamine rationally depends on the concentration of OPs. By measuring the fluorescence intensity ratio, the proposed platform exhibited highly selective and robust performance toward OPs, displaying ultrasensitive recognition in the pg L(-1) level. The multiexcitation format could efficiently shield background interference from complex samples by introducing a self-calibrated reference signal, which affords accurate and reliable quantitative information, endowing CDs as a universal candidate for a biosensing application by combining target-specific recognition elements.
ESTHER : Li_2020_Anal.Chem_92_3198
PubMedSearch : Li_2020_Anal.Chem_92_3198
PubMedID: 32008315

Title : Selective synthesis of functionalized quinazolinone derivatives via biocatalysis - Lan_2020_Mol.Catal_498_111261
Author(s) : Lan J , Le Z , Li H , Meng J , Gong B , Xie Z
Ref : Molecular Catalysis , 498 :111261 , 2020
Abstract : A novel and efficient biocatalyzed methodology for the construction of functionalized quinazolinone derivatives via tandem / hydrolysis / decarboxylation / cyclization and transesterification reactions has been developed that works with a variety of 2-aminobenzamide and beta-dicarbonyl compounds. This method requires mild conditions, and has demonstrated high catalytic activity, excellent yields, excellent chemoselectivity, and a broad substrate scope. Additionally, biocatalyzed decarboxylation does not require high temperatures or light activation, giving it a substantial advantage over alternative techniques. Most importantly, it offers a new example for the exploration of simple, convenient, and environmentally friendly synthetic routes utilizing enzymes in organic chemistry.
ESTHER : Lan_2020_Mol.Catal_498_111261
PubMedSearch : Lan_2020_Mol.Catal_498_111261

Title : Curcumin Alleviates the Side Effects of Cisplatin on Gastric Emptying of Mice by Inhibiting the Signal Changes of Acetylcholine and Interstitial Cells of Cajal - Li_2020_J.Med.Food_23_920
Author(s) : Li H , Xu W , Liu X , Ye J , Li P , Shang F , Yu X
Ref : J Med Food , 23 :920 , 2020
Abstract : Cisplatin is a widely used anticancer drug that has adverse effects on gastrointestinal function. Curcumin is a natural polyphenol extracted from the rhizome of turmeric that has a wide range of biological activities. The present study investigated the effects of cisplatin on gastric emptying in mice and examined whether these can be inhibited by curcumin. We found that pretreatment with curcumin (200mg/kg/day) for 10-30 days partly inhibited the decreases in gastric emptying rate and body weight induced by cisplatin. Furthermore, cisplatin reduced acetylcholine (ACh) concentration and the messenger RNA (mRNA) level of ACh receptor (AChR) as well as acetylcholinesterase activity in the stomach of mice; caused ultrastructural damage to interstitial cells of Cajal (ICC); and altered the expression of c-kit/stem cell factor and the gap junction protein connexin 43 in ICC. Curcumin pretreatment inhibited the effects of cisplatin on ACh indicators and ICC. These results demonstrate that curcumin can protect against cisplatin-induced gastric emptying disorder and thus has therapeutic potential for alleviating this condition in cancer patients receiving cisplatin chemotherapy.
ESTHER : Li_2020_J.Med.Food_23_920
PubMedSearch : Li_2020_J.Med.Food_23_920
PubMedID: 32833554

Title : Total flavonoids of Selaginella pulvinata alleviates cognitive impairment in mice - Zhang_2020_Biomed.Rep_13_8
Author(s) : Zhang L , Zhang Y , Hou Y , Li H , Li C , Xin J , Zhou N , Li Q , Song Y , Zhang Z
Ref : Biomed Rep , 13 :8 , 2020
Abstract : Cognitive impairment (CI) refers to dysfunctional cognition, which encompasses a spectrum of disorders, ranging from mild cognitive impairment to dementia. Any factor that results in cortical damage may cause CI. Total flavonoids of Selaginella pulvinata (TFSP), have shown promising antioxidant and protective effects in animal models. In the present study, mice were intraperitoneally treated with scopolamine, sodium nitrite or 45% ethanol to induce memory impairment, and the effects were assessed using a step-down test. After performing the behavioural test, hippocampal sections were collected for anatomical analysis, and the brain and serum levels of memory-related molecules were evaluated. The results showed that TFSP improved memory in a mouse model of CI significantly. Serum data were consistent with the behavioural results: TFSP increased blood acetylcholine levels through modulation of the acetylcholinesterase and choline acetyltransferase levels. It also ameliorated oxidative stress in neurons, increasing superoxide dismutase, glutathione peroxidase and inhibiting nitric oxide synthase levels in the brain. These results suggest that TFSP may exhibit potential as a clinical treatment for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and senile dementia.
ESTHER : Zhang_2020_Biomed.Rep_13_8
PubMedSearch : Zhang_2020_Biomed.Rep_13_8
PubMedID: 32607237

Title : Ultrasensitive detection of butyrylcholinesterase activity based on the inner filter effect of MnO(2) nanosheets on sulfur nanodots - Li_2020_Analyst_145_5206
Author(s) : Li T , Gao Y , Li H , Zhang C , Xing Y , Jiao M , Shi YE , Li W , Zhai Y , Wang Z
Ref : Analyst , 145 :5206 , 2020
Abstract : Butyrylcholinesterase (BChE) activity is an important index for a variety of diseases. In this work, a "turn-on" assay is proposed based on controlling the inner filter effect (IFE) of MnO(2) nanosheets (NSs) on sulfur nanodots (S-dots). The fluorescence of S-dots is effectively quenched by the MnO(2) NSs, due to the wide overlap of the emission spectrum of S-dots and absorption spectrum of MnO(2) NSs, together with the superior light absorption capability of MnO(2) NSs. BChE can catalyze acetylthiocholine and produce thiocholine, which effectively decomposes the MnO(2) NSs into Mn(2+), resulting in the disappearance of the IFE and recovery of fluorescence of S-dots. Two-stage linear relationships between the ratio of fluorescence intensity and concentration of BChE are observed from 0.05 to 10 and from 10 to 500 U L(-1). A limit of detection of 0.035 U L(-1) is achieved, which is the best performance so far. The as-proposed assay is robust enough for practical detection in human serum, and it can avoid interference from its sister enzyme (acetylcholinesterase) and glutathione at the micromolar level. The presented results provide a clue for the functionalization of S-dots, and offer a powerful tool as an analytic technique for nanomedicine and environmental science.
ESTHER : Li_2020_Analyst_145_5206
PubMedSearch : Li_2020_Analyst_145_5206
PubMedID: 32578586

Title : Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial - Liu_2020_Chin.J.Integr.Med_26_577
Author(s) : Liu NY , Pei H , Liu MX , Liu LT , Fu CG , Li H , Chen KJ
Ref : Chin J Integr Med , 26 :577 , 2020
Abstract : BACKGROUND: The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC, ) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome. METHODS: This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded. DISCUSSION: The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical ID: NCT03647384. Registered on 23 August 2018).
ESTHER : Liu_2020_Chin.J.Integr.Med_26_577
PubMedSearch : Liu_2020_Chin.J.Integr.Med_26_577
PubMedID: 32761337

Title : Enzymatic Synthesis of beta-Sitosterol Laurate by Candida rugosa Lipase AY30 in the Water\/AOT\/Isooctane Reverse Micelle - Chen_2020_Appl.Biochem.Biotechnol__
Author(s) : Chen S , Li J , Fu Z , Wei G , Li H , Zhang B , Zheng L , Deng Z
Ref : Appl Biochem Biotechnol , : , 2020
Abstract : Phytosterols are regarded as compounds able to reduce total and low-density lipoprotein cholesterol in the blood, and their esterified derivatives could help to improve the effectiveness of this function. In the present study, the water/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/isooctane reverse micelle (RM) system was set up as a reaction medium for Candida rugosa lipase AY30 (CRL AY30) to synthesize beta-sitosterol laurate (beta-SLE). The product was identified by TLC, FT-IR, and HPLC-APCI-QqQ-MS/MS and quantified by HPLC. Through stepwise optimization, it was found that CRL AY30 had the highest activity in the water/AOT/isooctane RM system where 50 mM PBS with a pH of 7.5 was adopted as water core to carry CRL AY30, and the proportion of [CRL AY30] (mg/mL), [water] (mM), and [AOT] (mM) was set in 3:375:25, respectively, in isooctane. After screened with single-factor experiments, the esterification reaction conditions in the CRL AY30-water/AOT/isooctane RM system were further optimized by the response surface method as follows: the mole ratio of beta-sitosterol to lauric acid of 1:3.5 (25 mM beta-sitosterol), the enzyme load of 18% (w/w total reactants), the reaction temperature of 47 degrees C, and the reaction time of 48 h. As a result, the maximum esterification rate was up to 88.12 +/- 0.79%.
ESTHER : Chen_2020_Appl.Biochem.Biotechnol__
PubMedSearch : Chen_2020_Appl.Biochem.Biotechnol__
PubMedID: 32388606

Title : Scocycamides, a Pair of Macrocyclic Dicaffeoylspermidines with Butyrylcholinesterase Inhibition and Antioxidation Activity from the Roots of Scopolia tangutica - Wang_2020_Org.Lett_22_8240
Author(s) : Wang JX , Zhao YP , Du NN , Han Y , Li H , Wang R , Xu Y , Liu YF , Liang XM
Ref : Org Lett , 22 :8240 , 2020
Abstract : A pair of new macrocyclic spermidine alkaloids, (+)-(S)-scocycamide and (-)-(R)-scocycamide, were isolated from the roots of Scopolia tangutica. Their structures were established by extensive spectroscopic data, electronic circular dichroism analyses, and chemical synthesis. They featured a unique 6/18 fused bicyclic framework with spermidine and catechol units, representing a new subtype of natural spermidine alkaloids. A plausible biosynthetic pathway was also proposed. They inhibited butyrylcholinesterase and exhibited antioxidant capacity, suggesting beneficial constituents against Alzheimer's disease and oxidation.
ESTHER : Wang_2020_Org.Lett_22_8240
PubMedSearch : Wang_2020_Org.Lett_22_8240
PubMedID: 33021797

Title : Colonization of Beauveria bassiana 08F04 in root-zone soil and its biocontrol of cereal cyst nematode (Heterodera filipjevi) - Zhang_2020_PLoS.One_15_e0232770
Author(s) : Zhang J , Fu B , Lin Q , Riley IT , Ding S , Chen L , Cui J , Yang L , Li H
Ref : PLoS ONE , 15 :e0232770 , 2020
Abstract : Cereal cyst nematodes cause serious yield losses of wheat in Hunaghuai winter wheat growing region in China. Beauveria bassiana 08F04 isolated from the surface of cysts is a promising biological control agent for cereal cyst nematodes. As the colonization capacity is a crucial criteria to assess biocontrol effectiveness for a microbial agent candidate, we aimed to label B. bassiana 08F04 for efficient monitoring of colonization in the soil. The binary pCAM-gfp plasmid containing sgfp and hph was integrated into B. bassiana 08F04 using the Agrobacterium tumefaciens-mediated transformation. The transformation caused a significant change in mycelial and conidial yields, and in extracellular chitinase activity in some transformants. The cultural filtrates of some transformants also decreased acetylcholinesterase activity and the survival of Heterodera filipjevi second-stage juveniles relative to the wild-type strain. One transformant (G10) had a growth rate and biocontrol efficacy similar to the wild-type strain, so it was used for a pilot study of B. bassiana colonization conducted over 13 weeks. Real-time PCR results and CFU counts revealed that the population of G10 increased quickly over the first 3 weeks, then decreased slowly over the following 4 weeks before stabilizing. In addition, the application of wild-type B. bassiana 08F04 and transformant G10 significantly reduced the number of H. filipjevi females in roots by 64.4% and 60.2%, respectively. The results of this study have practical applications for ecological, biological and functional studies of B. bassiana 08F04 and for bionematicide registration.
ESTHER : Zhang_2020_PLoS.One_15_e0232770
PubMedSearch : Zhang_2020_PLoS.One_15_e0232770
PubMedID: 32369513

Title : A ratiometric fluorescence probe based on graphene quantum dots and o-phenylenediamine for highly sensitive detection of acetylcholinesterase activity - Ye_2020_Mikrochim.Acta_187_511
Author(s) : Ye M , Lin B , Yu Y , Li H , Wang Y , Zhang L , Cao Y , Guo M
Ref : Mikrochim Acta , 187 :511 , 2020
Abstract : By using graphene quantum dots (GQDs) and o-phenylenediamine (OPD), a ratiometric fluorescence probe was designed for the highly sensitive and selective detection of AChE. GQDs with strong fluorescence were synthesized by the one-step hydrothermal method. The optimal emission wavelength of GQDs was 450 nm at the excitation wavelength of 375 nm. MnO(2) nanosheets with a wide absorption band of 300-600 nm were prepared at room temperature. Because of the extensive overlap between the absorption spectrum of MnO(2) nanosheets and the excitation and emission spectra of GQDs, the fluorescence of GQDs at 450 nm was efficiently quenched by the inner-filter effect. Meanwhile, due to the peroxidase-like activity of MnO(2) nanosheets, OPD was catalytically oxidized to 2,3-diaminophenazine (oxOPD), a yellow fluorescent substance with a new emission peak at 572 nm. When AChE was present, the substrate acetylthiocholine (ATCh) was hydrolyzed to thiocholine (TCh) that is capable of decomposing MnO(2) nanosheets. Therefore, the quench of GQDs and the oxidation of OPD by MnO(2) nanosheets were suppressed, resulting in the fluorescence recovery of GQDs at 450 nm, while the fluorescence decrease of oxOPD at 572 nm. Utilizing the fluorescence intensity ratio F(450)/F(572) as the signal readout, the ratiometric fluorescence method was established to detect AChE activity. The ratio F(450)/F(572) against the AChE concentration demonstrated two linear relationships in the range 0.1-2.0 and 2.0-4.5 mU mL(-1) with a detection limit of 0.09 mU mL(-1). The method was applied to the detection of positive human serum samples and the analysis of the inhibitor neostigmine. Due to the advantages of high sensitivity, favorable selectivity, and strong anti-interference, the method possesses an application prospect in clinical diagnosis of AChE and the screening of inhibitors. Graphical abstract Schematic presentation of a ratiometric fluorescence method for the detection of acetylcholinesterase (AChE). The fluorescence of graphene quantum dots (GQDs) is quenched and o-phenylenediamine (OPD) is oxidized to generate fluorescent product 2,3-diaminophenazine (oxOPD) by MnO(2) nanosheets. When AChE is present, acetylthiocholine iodide (ATCh) is hydrolyzed to thiocholine (TCh) with reducibility for decomposing MnO(2) nanosheets. Due to the decomposition of MnO(2) nanosheets, the quenching of GQDs and oxidation of OPD are suppressed. The fluorescence of GQDs at 450 nm is enhanced, while the fluorescence of oxOPD at 572 nm is reduced. The fluorescence intensity ratio F(450)/F(572) is used to establish the ratiometric fluorescence method for AChE activity.
ESTHER : Ye_2020_Mikrochim.Acta_187_511
PubMedSearch : Ye_2020_Mikrochim.Acta_187_511
PubMedID: 32833082

Title : Simple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase - Zhou_2020_Eur.J.Med.Chem_200_112415
Author(s) : Zhou B , Li H , Cui Z , Li D , Geng H , Gao J , Zhou L
Ref : Eur Journal of Medicinal Chemistry , 200 :112415 , 2020
Abstract : As simple analogues of the natural compound chelerythrine, a novel anti-cholinesterase 2-phenylisoquinolin-2-ium scaffold was designed by structure imitation. The activity evaluation led to the discovery of seven compounds with potent anti-acetylcholinesterase activity with IC50 values of
ESTHER : Zhou_2020_Eur.J.Med.Chem_200_112415
PubMedSearch : Zhou_2020_Eur.J.Med.Chem_200_112415
PubMedID: 32454229

Title : The basal transcription factor II H subunit Tfb5 is required for stress response and pathogenicity in the tangerine pathotype of Alternaria alternata - Fu_2020_Mol.Plant.Pathol_21_1337
Author(s) : Fu H , Chung KR , Gai Y , Mao L , Li H
Ref : Mol Plant Pathol , 21 :1337 , 2020
Abstract : The basal transcription factor II H (TFIIH) is a multicomponent complex. In the present study, we characterized a TFIIH subunit Tfb5 by analysing loss- and gain-of-function mutants to gain a better understanding of the molecular mechanisms underlying stress resistance and pathogenicity in the citrus fungal pathogen Alternaria alternata. Tfb5 deficiency mutants (deltaAatfb5) decreased sporulation and pigmentation, and were impaired in the maintenance of colony surface hydrophobicity and cell wall integrity. deltaAatfb5 increased sensitivity to ultraviolet light, DNA-damaging agents, and oxidants. The expression of Aatfb5 was up-regulated in the wild type upon infection in citrus leaves, implicating the requirement of Aatfb5 in fungal pathogenesis. Biochemical and virulence assays revealed that deltaAatfb5 was defective in toxin production and cellwall-degrading enzymes, and failed to induce necrotic lesions on detached citrus leaves. Aatfb5 fused with green fluorescent protein (GFP) was localized in the cytoplasm and nucleus and physically interacted with another subunit, Tfb2, based on yeast two-hybrid and co-immunoprecipitation analyses. Transcriptome and Antibiotics & Secondary Metabolite Analysis Shell (antiSMASH) analyses revealed the positive and negative roles of Aatfb5 in the production of various secondary metabolites and in the regulation of many metabolic and biosynthetic processes in A. alternata. Aatfb5 may play a negative role in oxidative phosphorylation and a positive role in peroxisome biosynthesis. Two cutinase-coding genes (AaCut2 and AaCut15) required for full virulence were down-regulated in deltaAatfb5. Overall, this study expands our understanding of how A. alternata uses the basal transcription factor to deal with stress and achieve successful infection in the plant host.
ESTHER : Fu_2020_Mol.Plant.Pathol_21_1337
PubMedSearch : Fu_2020_Mol.Plant.Pathol_21_1337
PubMedID: 32776683

Title : Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial - Wang_2020_Curr.Med.Res.Opin_36_1107
Author(s) : Wang W , Yao J , Guo X , Guo Y , Yan C , Liu K , Zhang Y , Wang X , Li H , Wen Z , Li S , Xiao X , Liu W , Li Z , Zhang L , Shao S , Ye S , Qin G , Li Y , Li F , Zhang X , Li X , Peng Y , Deng H , Xu X , Zhou L , Huang Y , Cao M , Xia X , Shi M , Dou J , Yuan J
Ref : Curr Med Res Opin , 36 :1107 , 2020
Abstract : Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
ESTHER : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedSearch : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedID: 32338063

Title : Genomics-Driven Discovery of Phytotoxic Cytochalasans Involved in the Virulence of the Wheat Pathogen Parastagonospora nodorum - Li_2020_ACS.Chem.Biol_15_226
Author(s) : Li H , Wei H , Hu J , Lacey E , Sobolev AN , Stubbs KA , Solomon PS , Chooi YH
Ref : ACS Chemical Biology , 15 :226 , 2020
Abstract : The etiology of fungal pathogenesis of grains is critical to global food security. The large number of orphan biosynthetic gene clusters uncovered in fungal plant pathogen genome sequencing projects suggests that we have a significant knowledge gap about the secondary metabolite repertoires of these pathogens and their roles in plant pathogenesis. Cytochalasans are a family of natural products of significant interest due to their ability to bind to actin and interfere with cellular processes that involved actin polymerization; however, our understanding of their biosynthesis and biological roles remains incomplete. Here, we identified a putative polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) gene cluster (phm) that was upregulated in the pathogen Parastagonospora nodorum during its infection on wheat. Overexpression of the transcription factor gene phmR encoded in the phm gene cluster resulted in the production of two leucine-derived cytochalasans, phomacins D and E (1 and 2, respectively), and an acetonyl adduct phomacin F. Heterologous expression of the PKS-NRPS gene phmA and the trans-enoyl reductase (ER) gene phmE in Aspergillus nidulans resulted in the production of a novel 2-pyrrolidone precursor prephomacin. Reverse genetics and wheat seedling infection assays showed that deltaphmA mutants exhibited significantly reduced virulence compared to the wild type. We further demonstrated that both 1 and 2 showed potent actin polymerization-inhibitory activities and exhibited potentially monocot-specific antigerminative activities. The findings from this study have advanced our knowledge based on the biosynthesis and biological roles of cytochalasans, the latter of which could have significant implications for our understanding of the molecular mechanisms of fungus-plant interactions.
ESTHER : Li_2020_ACS.Chem.Biol_15_226
PubMedSearch : Li_2020_ACS.Chem.Biol_15_226
PubMedID: 31815421
Gene_locus related to this paper: phano-phmG

Title : Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease - Nguyen_2020_Cell.Rep_33_108316
Author(s) : Nguyen HD , Ticer T , Bastian D , Kuril S , Li H , Du H , Yan C , Yu XZ
Ref : Cell Rep , 33 :108316 , 2020
Abstract : Graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic cell transplantation (allo-HCT). Lysosomal acid lipase (LAL) mediates the intrinsic lipolysis of cells to generate free fatty acids (FFAs), which play an essential role in the development, proliferation, and function of T cells. Here, we find that LAL is essential for donor T cells to induce GVHD in murine models of allo-HCT. Specifically, LAL is required for donor T cell survival, differentiation, and alloreactivity in GVHD target organs, but not in lymphoid organs. LAL induces the differentiation of donor T cells toward GVHD pathogenic Th1/Tc1 and Th17 while suppressing regulatory T cell generation. LAL(-/-) T cells succumb to oxidative stress and become anergic in target organs. Pharmacologically targeting LAL effectively prevents GVHD development while preserving the GVL activity. Thus, the present study reveals the role of LAL in T cell alloresponse and pathogenicity and validates LAL as a target for controlling GVHD and tumor relapse after allo-HCT.
ESTHER : Nguyen_2020_Cell.Rep_33_108316
PubMedSearch : Nguyen_2020_Cell.Rep_33_108316
PubMedID: 33113360

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 : Genetic Manipulation of an Aminotransferase Family Gene dtlA Activates Youssoufenes in Marine-Derived Streptomyces youssoufiensis - Li_2020_Org.Lett_22_729
Author(s) : Li H , Liu J , Deng Z , Li T , Liu Z , Che Q , Li W
Ref : Org Lett , 22 :729 , 2020
Abstract : Disruption of an aminotransferase family gene dtlA activated the production of a novel dimeric benzoic polyene acids (BPAs), named youssoufene A1 (1), along with four new (2-5, youssoufenes B1-B4) and a known (6) monomeric BPA in the marine-derived Streptomyces youssoufiensis OUC6819. The structures of 1-5 were elucidated by extensive spectroscopic and computational approaches. Youssoufene A1 (1) exhibited notably increased growth inhibition (MIC = 12.5 microg/mL) against multidrug resistant Enterococcus faecalis compared to monomeric structures (2-6).
ESTHER : Li_2020_Org.Lett_22_729
PubMedSearch : Li_2020_Org.Lett_22_729
PubMedID: 31891272
Gene_locus related to this paper: 9actn-YsfF

Title : Identification of a Bacillus amyloliquefaciens H6 Thioesterase Involved in Zearalenone Detoxification by Transcriptomic Analysis - Xu_2020_J.Agric.Food.Chem_68_10071
Author(s) : Xu L , Sun X , Wan X , Li H , Yan F , Han R , Li Z , Tian Y , Liu X , Kang X , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 68 :10071 , 2020
Abstract : Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin produced by Fusarium graminearum, induces hyperestrogenic responses in mammals and can cause reproductive disorders in farm animals. In this study, a transcriptome analysis of Bacillus amyloliquefaciens H6, which was previously identified as a ZEA-degrading bacterium, was conducted with high-throughput sequencing technology, and the differentially expressed genes were subjected to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Among the 16 upregulated genes, BAMF_RS30125 was predicted to be the key gene responsible for ZEA degradation. The protein encoded by BAMF_RS30125 was then expressed in Escherichia coli, and this recombinant protein (named ZTE138) significantly reduced the ZEA content, as determined by the enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), and decreased the proliferating activity of ZEA in MCF-7 cells. What is more, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results showed that the relative molecular mass and the structure of ZEA also changed. Sequence alignment of the ZTE138 protein showed that it is a protease that belongs to the YBGC/FADM family of coenzyme A thioesterases, and thus, the protein can presumably cleave the ZEA lactone bond and break down its macrolide ring.
ESTHER : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedSearch : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedID: 32815728

Title : A novel 15-spiro diterpenoid dimer from Andrographis paniculata with inhibitory potential against human carboxylesterase 2 - Sun_2020_Bioorg.Chem_97_103680
Author(s) : Sun CP , Yang ZJ , Zhao WY , Zhang RY , Li H , Chen LX
Ref : Bioorg Chem , 97 :103680 , 2020
Abstract : The phytochemical investigation of Andrographis paniculata resulted in the isolation of a novel 15-spiro diterpenoid dimer bisandrographolide G (1). Its structure was determined by 1D and 2D NMR, HRESIMS, electronic circular dichroism (ECD), and TD DFT calculations of ECD spectra. It showed potent inhibitory activity against human carboxylesterase 2 (CES 2) with an IC50 value of 4.61 +/- 0.23 muM, and it was defined as a mixed-competitive type inhibitor with a Ki value of 8.88 muM based on the inhibition kinetics result. This finding gave us a hit to develop new generation of human CES 2 inhibitors.
ESTHER : Sun_2020_Bioorg.Chem_97_103680
PubMedSearch : Sun_2020_Bioorg.Chem_97_103680
PubMedID: 32120078

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

Title : Evaluation of toxicological responses and promising biomarkers of topmouth gudgeon (Pseudorasbora parva) exposed to fipronil at environmentally relevant levels - Li_2020_Environ.Sci.Pollut.Res.Int__
Author(s) : Li H , Zhang R , Sun F , Zhang Y
Ref : Environ Sci Pollut Res Int , : , 2020
Abstract : Fipronil is an insecticide commonly used in agriculture. We report here on the sublethal and sub-chronic effects of fipronil on non-target topmouth gudgeon (Pseudorasbora parva) at environmentally relevant levels. The results showed that fipronil did not cause significant changes in brain acetylcholinesterase activities, glutathione S-transferase (GST) activities in the intestine, and GST, glutamic pyruvic transaminase (GPT), and glutamic oxaloacetic transaminase (GOT) activities in the liver tissues at environmentally relevant levels for 96-h exposure. In the further test for a 12-day exposure, dose-dependent responses of the serum GPT and GOT activities were observed in all treated groups with sublethal concentrations of fipronil. Furthermore, fipronil could reduce the liver mitochondrial membrane fluidity of P. parva, especially with high concentration of fipronil at high temperature. The results suggest that serum GPT and GOT in P. parva might be useful biomarkers for effects of fipronil exposure at environmentally relevant level, and reducing fluidity of liver mitochondrial membrane may be one toxic mechanism of fipronil.
ESTHER : Li_2020_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Li_2020_Environ.Sci.Pollut.Res.Int__
PubMedID: 32304060

Title : Biodegradation of phthalate esters by Paracoccus kondratievae BJQ0001 isolated from Jiuqu (Baijiu fermentation starter) and identification of the ester bond hydrolysis enzyme - Xu_2020_Environ.Pollut_263_114506
Author(s) : Xu Y , Minhazul K , Wang X , Liu X , Li X , Meng Q , Li H , Zhang C , Sun X , Sun B
Ref : Environ Pollut , 263 :114506 , 2020
Abstract : Phthalate ester (PAE) pollution is an increasing problem globally. Paracoccus kondratievae BJQ0001 was isolated from the fermentation starter of Baijiu and showed an efficient degradation capability toward PAEs. To our poor knowledge, this is the first report of a P. kondratievae strain capable of degrading PAEs. The first complete genome sequence of P. kondratievae was presented without gaps, and composed of two circular chromosomes and one plasmid. The species simultaneously degraded di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP) and di-(2-ethylhexyl) phthalate (DEHP), with DMP and DEP as the preferred substrates. The half-life (t(1/2)) of DMP was only 6.34 h with an initial concentration of 200 mg/L. Combined with gene annotation and metabolic intermediate analysis, a metabolic pathway was proposed for the species. Benzoic acid, the intermediate of anaerobic PAE metabolism, was identified in the aerobic degradation process. Two key enzymes for alkyl ester bond hydrolysis were obtained, and belonged to families IV and VI of hydrolases, respectively. These results will promote the investigation of PAE degradation by P. kondratievae, and provide useful information for improving the quality control of food and environmental PAE treatment.
ESTHER : Xu_2020_Environ.Pollut_263_114506
PubMedSearch : Xu_2020_Environ.Pollut_263_114506
PubMedID: 32268225
Gene_locus related to this paper: 9rhob-a0a5p8jcg2 , 9rhob-a0a5p8jaa4

Title : Ultrasonic-pretreated lipase-catalyzed synthesis of medium-long-medium lipids using different fatty acids as sn-2 acyl-site donors - Wang_2019_Food.Sci.Nutr_7_2361
Author(s) : Wang Q , Xie Y , Johnson DR , Li Y , He Z , Li H
Ref : Food Sci Nutr , 7 :2361 , 2019
Abstract : The current work aimed to evaluate the effect of ultrasonic treatment on the enzymatic transesterification of medium-long-medium (MLM) lipids using 2-monoacylglycerol, bearing distinct fatty acids at the sn-2 position with palmitic acid, octadecanoic acid, oleic acid, eicosapentaenoic acid, and docosahexaenoic acids as sn-2 acyl donors. The effects of ultrasonic treatment conditions, including substrate concentration, reaction temperature and time, and enzyme loading, on the insertion of fatty acids into the sn-2 acyl position of MLM lipids were investigated. The data showed that low-frequency ultrasonic treatment could remarkably improve the insertion rate of polyunsaturated fatty acid (PUFA) into the sn-2 position of MLM lipids, compared with the conventional treatment method. By increasing the ultrasonic frequency from 20 to 30 KHz, while maintaining power at 150 W, the rate of synthesis of monounsaturated fatty acid and PUFA increased from 23.7% and 26.8% to 26.6% and 32.4% (p < 0.05), respectively. Moreover, ultrasonic treatment reduced the optimum reaction temperature from 45 to 35 degC. However, the activity of Lipozyme RM-IM treated with ultrasound considerably declined from 31.10% to 26.90% (p < 0.05) after its fourth cycle, which was lower than that without ultrasonic treatment. This work provokes new routes for the utilization of ultrasonic technology in the synthesis of MLM lipids using different fatty acids as sn-2 acyl donors.
ESTHER : Wang_2019_Food.Sci.Nutr_7_2361
PubMedSearch : Wang_2019_Food.Sci.Nutr_7_2361
PubMedID: 31367365

Title : Bioaugmentation of Exogenous Strain Rhodococcus sp. 2G Can Efficiently Mitigate Di(2-ethylhexyl) Phthalate Contamination to Vegetable Cultivation - Zhao_2019_J.Agric.Food.Chem_67_6940
Author(s) : Zhao HM , Du H , Huang CQ , Li S , Zeng XH , Huang XJ , Xiang L , Li H , Li YW , Cai QY , Mo CH , He Z
Ref : Journal of Agricultural and Food Chemistry , 67 :6940 , 2019
Abstract : This work developed a bioaugmentation strategy that simultaneously reduced soil di(2-ethylhexyl) phthalate (DEHP) pollution and its bioaccumulation in Brassica parachinensis by inoculating the isolated strain Rhodococcus sp. 2G. This strain could efficiently degrade DEHP at a wide concentration range from 50 to 1600 mg/L and transformed DEHP through a unique biochemical degradation pathway that distinguished it from other Rhodococcus species. Besides, strain 2G colonized well in the rhizosphere soil of the inoculated vegetable without competition with indigenous microbes, resulting in increased removal of DEHP from soil (95%) and reduced DEHP bioaccumulation in vegetables (75% in the edible part) synchronously. Improved enzyme activities and DOC content in the rhizosphere of the planting vegetable and inoculating strain 2G were responsible for the high efficiency in mitigating DEHP contamination to vegetable cultivation. This work demonstrated a great potential application to grow vegetables in contaminated soil for safe food production.
ESTHER : Zhao_2019_J.Agric.Food.Chem_67_6940
PubMedSearch : Zhao_2019_J.Agric.Food.Chem_67_6940
PubMedID: 31021627
Gene_locus related to this paper: rhoso-a0a3g5hne7

Title : Heterologous biosynthesis of elsinochrome A sheds light on the formation of the photosensitive perylenequinone system - Hu_2019_Chem.Sci_10_1457
Author(s) : Hu J , Sarrami F , Li H , Zhang G , Stubbs KA , Lacey E , Stewart SG , Karton A , Piggott AM , Chooi YH
Ref : Chem Sci , 10 :1457 , 2019
Abstract : Perylenequinones are a class of aromatic polyketides characterised by a highly conjugated pentacyclic core, which confers them with potent light-induced bioactivities and unique photophysical properties. Despite the biosynthetic gene clusters for the perylenequinones elsinochrome A (1), cercosporin (4) and hypocrellin A (6) being recently identified, key biosynthetic aspects remain elusive. Here, we first expressed the intact elc gene cluster encoding 1 from the wheat pathogen Parastagonospora nodorum heterologously in Aspergillus nidulans on a yeast-fungal artificial chromosome (YFAC). This led to the identification of a novel flavin-dependent monooxygenase, ElcH, responsible for oxidative enolate coupling of a perylenequinone intermediate to the hexacyclic dihydrobenzo(ghi)perylenequinone in 1. In the absence of ElcH, the perylenequione intermediate formed a hexacyclic cyclohepta(ghi)perylenequinone system via an intramolecular aldol reaction resulting in 6 and a novel hypocrellin 12 with opposite helicity to 1. Theoretical calculations supported that 6 and 12 resulted from atropisomerisation upon formation of the 7-membered ring. Using a bottom-up pathway reconstruction approach on a tripartite YFAC system developed in this study, we uncovered that both a berberine bridge enzyme-like oxidase ElcE and a laccase-like multicopper oxidase ElcG are involved in the double coupling of two naphthol intermediates to form the perylenequinone core. Gene swapping with the homologs from the biosynthetic pathway of 4 showed that cognate pairing of the two classes of oxidases is required for the formation of the perylenequinone core, suggesting the involvement of protein-protein interactions.
ESTHER : Hu_2019_Chem.Sci_10_1457
PubMedSearch : Hu_2019_Chem.Sci_10_1457
PubMedID: 30809363
Gene_locus related to this paper: phano-elca

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 : Artificial Nanometalloenzymes for Cooperative Tandem Catalysis - Li_2019_ACS.Appl.Mater.Interfaces_11_15718
Author(s) : Li H , Qiu C , Cao X , Lu Y , Li G , He X , Lu Q , Chen K , Ouyang P , Tan W
Ref : ACS Appl Mater Interfaces , 11 :15718 , 2019
Abstract : Artificial metalloenzymes that combine the advantages of natural enzymes and metal catalysts have been getting more attention in research. As a proof of concept, an artificial nanometalloenzyme (CALB-Shvo@MiMBN) was prepared by co-encapsulation of metallo-organic catalyst and enzyme in a soft nanocomposite consisting of 2-methylimidazole, metal ions, and biosurfactant in mild reaction conditions using a one-pot self-assembly method. The artificial nanometalloenzyme with lipase acted as the core, and the metallo-organic catalyst embedded in micropore exhibited a spherical structure of 30-50 nm in diameter. The artificial nanometalloenzyme showed high catalytic efficiency in the dynamic kinetic resolution of racemic primary amines or secondary alcohols compared to the one-pot catalytic reaction of immobilized lipase and free metallo-organic catalyst. This artificial nanometalloenzyme holds great promise for integrated enzymatic and heterogeneous catalysis.
ESTHER : Li_2019_ACS.Appl.Mater.Interfaces_11_15718
PubMedSearch : Li_2019_ACS.Appl.Mater.Interfaces_11_15718
PubMedID: 30986032

Title : A laser-induced TiO2-decorated graphene photoelectrode for sensitive photoelectrochemical biosensing - Ge_2019_Chem.Commun.(Camb)_55_4945
Author(s) : Ge L , Hong Q , Li H , Li F
Ref : Chem Commun (Camb) , 55 :4945 , 2019
Abstract : Herein, direct-laser-writing of TiO2-decorated graphene on indium-tin oxide glass was demonstrated to fabricate a unique photoelectrode with a rapid and stable photoelectrochemical response under visible light; this photoelectrode was then applied in a photoelectrochemical enzymatic biosensor for the sensitive detection of an acetylcholinesterase inhibitor.
ESTHER : Ge_2019_Chem.Commun.(Camb)_55_4945
PubMedSearch : Ge_2019_Chem.Commun.(Camb)_55_4945
PubMedID: 30957826

Title : Different durations of cognitive stimulation therapy for Alzheimer's disease: a systematic review and meta-analysis - Chen_2019_Clin.Interv.Aging_14_1243
Author(s) : Chen J , Duan Y , Li H , Lu L , Liu J , Tang C
Ref : Clin Interv Aging , 14 :1243 , 2019
Abstract : Objective: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of cognitive stimulation therapy (CST) of different durations for Alzheimer's disease (AD). Methods: A comprehensive search was carried out in three databases. The primary outcome was Mini-Mental State Examination (MMSE) score. We conducted a meta-analysis with Review Manager, version 5.3 and assessed the methodological quality of the included studies using the Cochrane Collaboration Recommendations assessment tool. Results: Treatment effects from the meta-analysis showed that CST plus acetylcholinesterase inhibitors (ChEIs) was better than the control assessed by MMSE. In addition, the meta-analysis indicated that long-term CST was better than short-term or maintenance CST. Conclusion: Our study confirmed that the combination of CST and drug treatment for AD is effective in AD, regardless of whether short-term CST, maintenance CST, or long-term CST is used. The long-term CST appears to be more effective.
ESTHER : Chen_2019_Clin.Interv.Aging_14_1243
PubMedSearch : Chen_2019_Clin.Interv.Aging_14_1243
PubMedID: 31371930

Title : Candida sp. 99-125 lipase-catalyzed synthesis of ergosterol linolenate and its characterization - He_2019_Food.Chem_280_286
Author(s) : He WS , Li L , Zhao J , Xu H , Rui J , Cui D , Li H , Zhang H , Liu X
Ref : Food Chem , 280 :286 , 2019
Abstract : As a major sterol in edible mushroom, ergosterol has gained much attention owing to its potential bioactivities. However, ergosterol has a high melting point, poor oil solubility and stability, which restrict its scope of application. In this study, an ergosterol ester of alpha-linolenic acid was successfully and efficiently prepared using Candida sp. 99-125 lipase as a biocatalyst. The desired product was confirmed to be ergosterol linolenate using MS, FT-IR, and NMR analyses. Using Candida sp. 99-125 lipase, the product conversion exceeded 92% in 12h under the following optimized parameters: 75mmol/L ergosterol, 40g/L lipase, 1:1.25 ergosterol-to-alpha-linolenic acid molar ratio, and 45 degrees C. The results confirmed that Candida sp. 99-125 lipase has good reusability and stability and is also relatively low cost, suggesting its great potential for large-scale production of ergosterol ester. Most importantly, the physiochemical properties (oil solubility and melting point) of ergosterol significantly improved after esterification with alpha-linolenic acid, thus facilitating its application in oil-based systems.
ESTHER : He_2019_Food.Chem_280_286
PubMedSearch : He_2019_Food.Chem_280_286
PubMedID: 30642499

Title : Fabricating an Acetylcholinesterase Modulated UCNPs-Cu(2+) Fluorescence Biosensor for Ultrasensitive Detection of Organophosphorus Pesticides-Diazinon in Food - Wang_2019_J.Agric.Food.Chem_67_4071
Author(s) : Wang P , Li H , Hassan MM , Guo Z , Zhang ZZ , Chen Q
Ref : Journal of Agricultural and Food Chemistry , 67 :4071 , 2019
Abstract : In this study, a highly sensitive upconversion fluorescence (FL) biosensor was developed for the detection of organophosphorus pesticides (OPs) based on an acetylcholinesterase (AChE) modulated FL "off-on-off" strategy. The luminescence of synthesized UCNPs could be quenched strongly by Cu(2+) due to an energy transfer effect. Upon addition of AChE and acetylthiocholine (ATCh), the enzymatic hydrolysate (thiocholine) could seize Cu(2+) from UCNPs-Cu(2+) mixture, resulting in the quenched FL triggered on. OPs could irreversibly impede the activity of AChE, which caused the formation of thiocholine to decrease, thus, reduced the recovery of FL. Under the optimum conditions, a linear detection range from 0.1 to 50 ng/mL was achieved for the representative OPs (diazinon) with LOD of 0.05 ng/mL. Furthermore, the ability of the biosensor to detect OPs was also confirmed in adulterated environmental and agricultural samples. In validation analysis, the proposed sensor showed satisfactory results ( p > 0.05) with GC-MS.
ESTHER : Wang_2019_J.Agric.Food.Chem_67_4071
PubMedSearch : Wang_2019_J.Agric.Food.Chem_67_4071
PubMedID: 30888170

Title : Inhibition of Pancreatic Carcinoma Growth Through Enhancing omega-3 Epoxy Polyunsaturated Fatty Acid Profile by Inhibition of Soluble Epoxide Hydrolase - Xia_2019_Anticancer.Res_39_3651
Author(s) : Xia R , Sun L , Liao J , Li H , You X , Xu D , Yang J , Hwang SH , Jones RD , Hammock B , Yang GY
Ref : Anticancer Research , 39 :3651 , 2019
Abstract : BACKGROUND/AIM: Cytochrome P450 epoxygenase is a major enzyme involved in the metabolism of omega-3 polyunsaturated fatty acids (PUFAs) to produce biologically active omega-3 epoxy fatty acids (omega-3 epoxides). In general, all epoxy PUFAs including omega-3 epoxides are quickly metabolized/inactivated by soluble epoxide hydrolase (sEH) to form diol products. The aims of this study were to determine the effect and mechanism of fat-1 transgene, and omega-3 PUFA combined with sEH gene knockout or inhibitor on inhibiting pancreatic cancer and the related mechanisms involved. MATERIALS AND METHODS: PK03-mutant Kras(G12D) murine pancreatic carcinoma cells were inoculated into mouse models including fat-1, sEH(-/-) and C57BL/6J mice. The mice were fed with AIN-76A diet with or without omega-3 PUFA supplementation or treated with sEH inhibitor. In addition to tumor growth (tumor size and weight), cell proliferation, mutant Kras-mediated signaling, inflammatory reaction and angiogenesis were analyzed immunohisto-chemically and by western blot assay. omega-3 PUFA metabolism, particularly focusing on omega-3 epoxy fatty acids (omega-3 epoxides), was measured using a liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach. RESULTS: Significant decreases of weight and size of the PK03 pancreatic carcinoma were observed in the fat-1 transgenic mice treated with sEH inhibitor compared to those of C57BL/6J control mice fed with AIN-76A diet (weight: 0.28+/-0.04 g vs. 0.58+/-0.06 g; size: 187.0+/-17.5 mm(3) vs. 519.3+/-60.6 mm(3)). In a separate experiment, sEH(-/-) mice fed omega-3 PUFA supplement and C57BL/6J mice treated with sEH inhibitor and fed omega-3 PUFA supplement exhibited a significant reduction in the weight and size of the pancreatic carcinoma compared to C57BL/6J control mice (weight: 0.26+/-.26 g and 0.39+/-.39 g vs. 0.69+/-0.11 g, respectively; size: 274.2+/-36.2 mm(3) and 296.4+/-99.8 mm(3) vs. 612.6+/-117.8 mm(3), respectively). Moreover, compared to the pancreatic tumors in C57BL/6J control mice, the tumors in fat-1 transgenic mice treated with sEH inhibitor showed a significant less inflammatory cell infiltrate (62.6+/-9.2/HPF (high power field) vs. 8.0+/-1.2/HPF), tumor cell proliferation (48.5+/-1.7% vs. 16.5+/-1.6%), and angiogenesis (micro-vessel density (MVD): 35.0+/-1.0 vs. 11.1+/-0.5) immunohistochemically, as well as significantly increased caspase-3 labeled apoptosis (0.44+/-0.06% vs. 0.69+/-0.06%, respectively). Using western blot approach, significant inhibition of mutant Kras-activated signals including phosphorylated Serine/threonine kinases (cRAF), Mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK) were identified in pancreatic carcinoma of fat-1 transgenic mice treated with sEH inhibitor. Eicosanoic acid metabolic profiling of the serum specimens detected a significant increase of the ratios of epoxides to dihydroxy fatty acid (DiHDPE) for docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and epoxides/dihydroxy octadecenoic acid (DiHOME) for arachidonic acid (ARA) and linoleic acid (LA), as well as a significant increase of epoxy metabolites of DHA, EPA, ARA and LA in fat-1 transgenic mice treated with a sEH inhibitor. CONCLUSION: omega-3 epoxy products from omega-3 PUFA metabolism play a crucial role in inhibiting pancreatic cancer growth, and use of omega-3 PUFAs combined with sEH inhibition is a strategy with high potential for pancreatic cancer treatment and prevention.
ESTHER : Xia_2019_Anticancer.Res_39_3651
PubMedSearch : Xia_2019_Anticancer.Res_39_3651
PubMedID: 31262891

Title : Fungal Dirigent Protein Controls the Stereoselectivity of Multicopper Oxidase-Catalyzed Phenol Coupling in Viriditoxin Biosynthesis - Hu_2019_J.Am.Chem.Soc_141_8068
Author(s) : Hu J , Li H , Chooi YH
Ref : Journal of the American Chemical Society , 141 :8068 , 2019
Abstract : Paecilomyces variotii produces the antibacterial and cytotoxic ( M)-viriditoxin (1) together with a trace amount of its atropisomer ( P)-viriditoxin 1'. Elucidation of the biosynthesis by heterologous pathway reconstruction in Aspergillus nidulans identified the multicopper oxidase (MCO) VdtB responsible for the regioselective 6,6'-coupling of semiviriditoxin (10), which yielded 1 and 1' at a ratio of 1:2. We further uncovered that VdtD, an alpha/beta hydrolase-like protein lacking the catalytic serine, directs the axial chirality of the products. Using recombinant VdtB and VdtD as cell-free extracts from A. nidulans, we demonstrated that VdtD acts like a dirigent protein to control the stereoselectivity of the coupling catalyzed by VdtB to yield 1 and 1' at a ratio of 20:1. Furthermore, we uncovered a unique Baeyer-Villiger monooxygenase (BVMO) VdtE that could transform the alkyl methylketone side chain to methyl ester against the migratory aptitude.
ESTHER : Hu_2019_J.Am.Chem.Soc_141_8068
PubMedSearch : Hu_2019_J.Am.Chem.Soc_141_8068
PubMedID: 31045362
Gene_locus related to this paper: byssn-VdtD , byssp-vdta1

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

Title : Downregulated lncRNA-MIAT confers protection against erectile dysfunction by downregulating lipoprotein lipase via activation of miR-328a-5p in diabetic rats - Huo_2019_Biochim.Biophys.Acta.Mol.Basis.Dis_1865_1226
Author(s) : Huo W , Hou Y , Li Y , Li H
Ref : Biochimica & Biophysica Acta Mol Basis Dis , 1865 :1226 , 2019
Abstract : Erectile dysfunction (ED) is a common comorbidity in males with diabetes. In this study, we aimed to investigate how lncRNA-MIAT affects ED in diabetes and the involved mechanism. Microarray analysis was performed to screen ED-related differentially expressed genes, regulatory microRNA (miR) and long noncoding RNA (lncRNA). Highly expressed lipoprotein lipase (LPL) was identified, and subsequently miR-328a-5p and lncRNA-MIAT were determined. Diabetes was induced by streptozotocin in rats, and diabetic rats with ED were selected. Vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were cocultured. The siRNA against lncRNA-MIAT, miR-328a-5p mimic and overexpression vector of LPL were transfected to investigate the specific effects of miR-328a-5p, lncRNA-MIAT and LPL on ED in diabetes. The expression of LPL, lncRNA-MIAT and miR-328a-5p in the serum of diabetic patients was measured. Increased LPL and lncRNA-MIAT and reduced miR-328a-5p were observed in diabetic patients. In addition, ED led to upregulated LPL and lncRNA-MIAT and downregulated miR-328a-5p in serum of diabetic patients and VSMCs of diabetic rats, especially in those with ED. LncRNA-MIAT directly regulated miR-328a-5p, which directly targeted LPL. LncRNA-MIAT upregulated LPL by acting as a ceRNA of miR-328a-5p. Silencing of lncRNA-MIAT and LPL or miR-328a-5p overexpression reduced VEC apoptosis and increased cell proliferation. In addition, an increased intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was noted in the corpus cavernosum of rats and inhibited VEC injury. Taken together, our data demonstrated that depleted lncRNA-MIAT suppressed LPL by increasing miR-328a-5p, thereby inhibiting VEC injury to attenuate ED in diabetic rats.
ESTHER : Huo_2019_Biochim.Biophys.Acta.Mol.Basis.Dis_1865_1226
PubMedSearch : Huo_2019_Biochim.Biophys.Acta.Mol.Basis.Dis_1865_1226
PubMedID: 30660685

Title : Developmental Toxicity of a Neonicotinoid Insecticide, Acetamiprid to Zebrafish Embryos - Ma_2019_J.Agric.Food.Chem_67_2429
Author(s) : Ma X , Li H , Xiong J , Mehler WT , You J
Ref : Journal of Agricultural and Food Chemistry , 67 :2429 , 2019
Abstract : Agricultural use of neonicotinoid insecticides is increasing worldwide, posing a risk to nontarget organisms. The present study investigated developmental toxicity of a widely used neonicotinoid, acetamiprid, to zebrafish embryos. Sublethal (malformations, hatchability, heart rate, body length, alteration of spontaneous movement and touch responses) and lethal effects were monitored during exposure period from 6 h post fertilization (hpf) to 120 hpf. Zebrafish embryos exhibited significant mortality and teratogenic effects at acetamiprid concentration greater than 263 mg/L, with bent spine being the main malformation. Toxicity spectra were constructed to rank the sensitivity of individual end points to acetamiprid exposure and impaired spontaneous movement was the most sensitive end point of those tested. The present study provides the basis for understanding developmental toxicity of acetamiprid exposure to zebrafish embryos. This information is critical for future studies evaluating aquatic risk from neonicotinoids as little is known regarding adverse effects of neonicotinoids to aquatic vertebrate species.
ESTHER : Ma_2019_J.Agric.Food.Chem_67_2429
PubMedSearch : Ma_2019_J.Agric.Food.Chem_67_2429
PubMedID: 30735371

Title : Assessment of phthalate ester residues and distribution patterns in Baijiu raw materials and Baijiu - Dong_2019_Food.Chem_283_508
Author(s) : Dong W , Guo R , Sun X , Li H , Zhao M , Zheng F , Sun J , Huang M , Wu J
Ref : Food Chem , 283 :508 , 2019
Abstract : Phthalate esters (PAEs) are harmful to human health and have been repeatedly identified in Baijiu samples. In our study, the distribution and degradation characteristics of 14 PAEs in Baijiu raw materials (BRMs) and Baijiu during distillation were detected using QuEChERS or vortex-assisted surfactant-enhanced-emulsification liquid-liquid micro-extraction (VSLLME) methods coupled with gas chromatography-mass spectrometry. The same five PAEs were detected in all tested samples, values ranged from 0.003 to 0.292 mg/kg; however, higher concentrations existed in BRMs compared to Baijiu samples. Using multivariate statistical analysis, detailed distinctions between different varieties of Baijiu and BRMs and separation-related PAE markers were revealed. PAEs concentration during Baijiu distillation showed a decreasing trend. The highest concentrations detected in distillate heads, were 1.6-, 2.3-, and 8.1-fold higher than those in heart1, heart2, and tail distillates, respectively. These findings revealed that PAEs may migrate from BRMs; moreover, that PAEs content can be regulated by distillation.
ESTHER : Dong_2019_Food.Chem_283_508
PubMedSearch : Dong_2019_Food.Chem_283_508
PubMedID: 30722905

Title : Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis - Sun_2019_Ann.Gen.Psychiatry_18_6
Author(s) : Sun H , Yang Y , Zhang L , Wu H , Zhang H , Li H
Ref : Ann Gen Psychiatry , 18 :6 , 2019
Abstract : Background: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD.
ESTHER : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedSearch : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedID: 31139237
Gene_locus related to this paper: human-NLGN4X

Title : Biochemical Characteristics of Microbial Enzymes and Their Significance from Industrial Perspectives - Thapa_2019_Mol.Biotechnol_61_579
Author(s) : Thapa S , Li H , J OH , Bhatti S , Chen FC , Nasr KA , Johnson T , Zhou S
Ref : Mol Biotechnol , 61 :579 , 2019
Abstract : Microbes are ubiquitously distributed in nature and are a critical part of the holobiont fitness. They are perceived as the most potential biochemical reservoir of inordinately diverse and multi-functional enzymes. The robust nature of the microbial enzymes with thermostability, pH stability and multi-functionality make them potential candidates for the efficient biotechnological processes under diverse physio-chemical conditions. The need for sustainable solutions to various environmental challenges has further surged the demand for industrial enzymes. Fueled by the recent advent of recombinant DNA technology, genetic engineering, and high-throughput sequencing and omics techniques, numerous microbial enzymes have been developed and further exploited for various industrial and therapeutic applications. Most of the hydrolytic enzymes (protease being the dominant hydrolytic enzyme) have broad range of industrial uses such as food and feed processing, polymer synthesis, production of pharmaceuticals, manufactures of detergents, paper and textiles, and bio-fuel refinery. In this review article, after a short overview of microbial enzymes, an approach has been made to highlight and discuss their potential relevance in biotechnological applications and industrial bio-processes, significant biochemical characteristics of the microbial enzymes, and various tools that are revitalizing the novel enzymes discovery.
ESTHER : Thapa_2019_Mol.Biotechnol_61_579
PubMedSearch : Thapa_2019_Mol.Biotechnol_61_579
PubMedID: 31168761

Title : Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest - Hai_2019_Crit.Care.Med_47_e144
Author(s) : Hai K , Chen G , Gou X , Jang H , Gong D , Cheng Y , Gong C , Li X , Liu Y , Li H , Zhang G , Yang L , Ke B , Liu J
Ref : Critical Care Medicine , 47 :e144 , 2019
Abstract : OBJECTIVES: Monoacylglycerol lipase participates in organ protection by regulating the hydrolysis of the endocannabinoid 2-arachidonoylglycerol. This study investigated whether blocking monoacylglycerol lipase protects against postresuscitation myocardial injury and improves survival in a rat model of cardiac arrest and cardiopulmonary resuscitation. DESIGN: Prospective randomized laboratory study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rat (n = 96). INTERVENTIONS: Rats underwent 8-minute asphyxia-based cardiac arrest and resuscitation. Surviving rats were randomly divided into cardiopulmonary resuscitation + URB602 group, cardiopulmonary resuscitation group, and sham group. One minute after successful resuscitation, rats in the cardiopulmonary resuscitation + URB602 group received a single dose of URB602 (5 mg/kg), a small-molecule monoacylglycerol lipase inhibitor, whereas rats in the cardiopulmonary resuscitation group received an equivalent volume of vehicle solution. The sham rats underwent all of the procedures performed on rats in the cardiopulmonary resuscitation and cardiopulmonary resuscitation + URB602 groups minus cardiac arrest and asphyxia. MEASUREMENTS AND MAIN RESULTS: Survival was recorded 168 hours after the return of spontaneous circulation (n = 22 in each group). Compared with vehicle treatment (31.8%), URB602 treatment markedly improved survival (63.6%) 168 hours after cardiopulmonary resuscitation. Next, we used additional surviving rats to evaluate myocardial and mitochondrial injury 6 hours after return of spontaneous circulation, and we found that URB602 significantly reduced myocardial injury and prevented myocardial mitochondrial damage. In addition, URB602 attenuated the dysregulation of endocannabinoid and eicosanoid metabolism 6 hours after return of spontaneous circulation and prevented the acceleration of mitochondrial permeability transition 15 minutes after return of spontaneous circulation. CONCLUSIONS: Monoacylglycerol lipase blockade may reduce myocardial and mitochondrial injury and significantly improve the resuscitation effect after cardiac arrest and cardiopulmonary resuscitation.
ESTHER : Hai_2019_Crit.Care.Med_47_e144
PubMedSearch : Hai_2019_Crit.Care.Med_47_e144
PubMedID: 30431495

Title : Integrating Target-Responsive Hydrogels with Smartphone for On-Site ppb-Level Quantitation of Organophosphate Pesticides - Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
Author(s) : Jin R , Kong D , Yan X , Zhao X , Li H , Liu F , Sun P , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :27605 , 2019
Abstract : Precise on-site profiling of organophosphate pesticides (OPs) is of significant importance for monitoring pollution and estimating poisoning. Herein, we designed a simple and convenient portable kit based on Ag(+)-responsive hydrogels for accurate detection of OPs. The newly developed hydrogels employed o-phenylenediamine (OPD) and silicon quantum dots (SiQDs) as indicator, which possessed ratiometric response. In this sensor, OPs as inhibitor of acetylcholinesterase prevented the generation of thiocholine, which blocked the formation of metal-polymer with Ag(+), further triggered the oxidation of OPD to yield yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 557 nm. The fluorescence intensity of SiQDs (444 nm) was quenched by DAP through inner filter effect (IFE) process, emerging a typical ratiometric response. Interestingly, the ratiometric signal of kit, which was recorded by smartphone's camera, can be transduced by ImageJ software into the hue parameter that was linearly proportional to the concentration of OPs. The simplicity of portable kit combined with smartphone operation, which possessed high sensitivity (detection limit <10 ng mL(-1)) and rapid sample-to-answer detection time (45 min) in agricultural sample, indicating that the methodology offered a new sight for portable monitoring of food safety and human health.
ESTHER : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedSearch : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedID: 31291083

Title : Epoxy-Oxylipins and Soluble Epoxide Hydrolase Metabolic Pathway as Targets for NSAID-Induced Gastroenteropathy and Inflammation-Associated Carcinogenesis - Jones_2019_Front.Pharmacol_10_731
Author(s) : Jones RD , Liao J , Tong X , Xu D , Sun L , Li H , Yang GY
Ref : Front Pharmacol , 10 :731 , 2019
Abstract : Polyunsaturated fatty acids (PUFAs) including epoxide-modified omega-3 and omega-6 fatty acids are made via oxidation to create highly polarized carbon-oxygen bonds crucial to their function as signaling molecules. A critical PUFA, arachidonic acid (ARA), is metabolized to a diverse set of lipids signaling molecules through cyclooxygenase (COX), lipoxygenase (LOX), cytochrome P450 epoxygenase, or cytochrome P450 hydroxylase; however, the majority of ARA is metabolized into anti-inflammatory epoxides via cytochrome P450 enzymes. These short-lived epoxide lipids are rapidly metabolized or inactivated by the soluble epoxide hydrolase (sEH) into diol-containing products. sEH inhibition or knockout has been a practical approach to study the biology of the epoxide lipids, and has been shown to effectively treat inflammatory conditions in the preclinical models including gastrointestinal ulcers and colitis by shifting oxylipins to epoxide profiles, inhibiting inflammatory cell infiltration and activation, and enhancing epithelial cell defense via increased mucin production, thus providing further evidence for the role of sEH as a pro-inflammatory protein. Non-steroidal anti-inflammatory drugs (NSAIDs) with COX-inhibitor activity are among the most commonly used analgesics and have demonstrated applications in the management of cardiovascular disease and intriguingly cancer. Major side effects of NSAIDs however are gastrointestinal ulcers which frequently precludes their long-term application. In this review, we hope to bridge the gap between NSAID toxicity and sEH-mediated metabolic pathways to focus on the role of epoxy fatty acid metabolic pathway of PUFAs in NSAIDS-ulcer formation and healing as well as inflammation-related carcinogenesis. Specifically we address the potential application of sEH inhibition to enhance ulcer healing at the site of inflammation via their activity on altered lipid signaling, mitochondrial function, and diminished reactive oxygen species, and further discuss the significance of dual COX and sEH inhibitor in anti-inflammation and carcinogenesis.
ESTHER : Jones_2019_Front.Pharmacol_10_731
PubMedSearch : Jones_2019_Front.Pharmacol_10_731
PubMedID: 31293429

Title : Protective effects of phenformin on zebrafish embryonic neurodevelopmental toxicity induced by X-ray radiation - Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
Author(s) : Gan L , Guo M , Si J , Zhang J , Liu Z , Zhao J , Wang F , Yan J , Li H , Zhang H
Ref : Artif Cells Nanomed Biotechnol , 47 :4202 , 2019
Abstract : Radiotherapy (RT) is a common treatment for head and neck cancers, but central nervous system function can be impaired by clinical radiation doses. This experimental study evaluated the protective efficacy of the anti-hyperglycaemic/anti-neoplastic agent phenformin against radiation-induced developmental toxicity in zebrafish embryos. Zebrafish embryos pre-treated with 25 muM phenformin 1 h before x-ray irradiation were compared to irradiation-only embryos for mortality, hatching rate, morphology, spontaneous movement, heart beat, larval swimming, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), malondialdehyde content (MDA, a by-product of membrane lipid oxidation), and acetylcholinesterase (AChE) activity. In addition, expression levels of multiple genes related to neural development and apoptosis (sod2, bdnf, ache, p53, bax, and bcl-2) were compared by RT-PCR and associated protein expression levels by western blotting. Pre-treatment with phenformin increased hatching rate, spontaneous movement, heart beat, and larval motor activity, decreased mortality and malformation rate, increased SOD, CAT, and AChE activities, and reduced MDA compared to irradiation-only embryos. The mRNA expression levels of anti-apoptotic sod2, bdnf, ache, and bcl-2 were enhanced while mRNA expression of p53 and pro-apoptotic bax were reduced in the phenformin pre-treatment group. Further, p53, Bax, and gamma-H2AX (a biomarker of DNA damage) were downregulated while Bcl-2 and BDNF were upregulated by phenformin pre-treatment. Taken together, this study supports the protective efficacy of phenformin against radiation toxicity in zebrafish embryos by suppressing oxidative stress and ensuing apoptosis.
ESTHER : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedSearch : Gan_2019_Artif.Cells.Nanomed.Biotechnol_47_4202
PubMedID: 31713449

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 : Electropolymerization-Induced Positively Charged Phenothiazine Polymer Photoelectrode for Highly Sensitive Photoelectrochemical Biosensing - Wang_2019_Anal.Chem_91_13831
Author(s) : Wang J , Lv W , Wu J , Li H , Li F
Ref : Analytical Chemistry , 91 :13831 , 2019
Abstract : Exploring the fabrication of an electrode with high photoelectric conversion efficiency and abundant functional groups for ideal photoelectrochemical (PEC) sensor development is highly urgent but faces a significant challenge. Herein we report an electropolymerization strategy for the preparation of phenothiazine polymeric film on an indium tin oxide (ITO) surface (PPT/ITO), within only a few seconds, and monomers. The fabricated PPT/ITO electrode possessed excellent stability and abundant quaternary ammonium salt groups for developing a highly sensitive PEC sensor through electrostatic binding with negatively charged materials. In this context, a CdS QDs-functionalized PPT/ITO electrode (CdS/PPT/ITO) was proposed and applied to the analysis of chlorpyrifos, used as a model target organophosphorous pesticide (OP). The thiocholine generated from acetylcholinesterase (AChE)-induced catalyzed hydrolysis of acetylthiocholine (ATCh) efficiently directed CdS QDs away from PPT/ITO via electrostatic repulsion, subsequently decreasing PEC current, whereas chlorpyrifos prohibited the generation of thiocholine through inhibiting AChE activity. As compared to the case where chlorpyrifos is absent, significantly enhanced PEC current is determined and is proportional to chlorpyrifos amounts. Thus, the developed CdS/PPT/ITO-based PEC sensor achieved excellent chlorpyrifos biosensing with improved sensitivity down to approximately ng/mL level with good specificity. We envision the proposed strategy will provide a new path to conveniently fabricate photoelectrodes possessing high performance, which will have more useful applications in PEC sensing.
ESTHER : Wang_2019_Anal.Chem_91_13831
PubMedSearch : Wang_2019_Anal.Chem_91_13831
PubMedID: 31560517

Title : Colletotryptins A-F, new dimeric tryptophol derivatives from the endophytic fungus Colletotrichum sp. SC1355 - Shao_2019_Fitoterapia__104465
Author(s) : Shao L , Wu P , Xu L , Xue J , Li H , Wei X
Ref : Fitoterapia , :104465 , 2019
Abstract : Seven new dimeric tryptophol-related alkaloids (1-4, 5a, 5b, and 6) were isolated from solid cultures of the endophytic fungus Colletotrichum sp. SC1355. The structures and absolute configurations of these compounds were determined by NMR spectroscopic analyses in combination with quantum chemical calculations of NMR (GIAO) shifts and ECD spectra. This is the first report of fungus-derived tryptophol dimers. In addition, the isolated compounds were evaluated for acetylcholinesterase (AchE) inhibitory activity.
ESTHER : Shao_2019_Fitoterapia__104465
PubMedSearch : Shao_2019_Fitoterapia__104465
PubMedID: 31870947

Title : Protein-Inorganic Hybrid Nanoflower-Rooted Agarose Hydrogel Platform for Point-of-Care Detection of Acetylcholine - Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
Author(s) : Kong D , Jin R , Zhao X , Li H , Yan X , Liu F , Sun P , Gao Y , Liang X , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :11857 , 2019
Abstract : Rapid and precise profiling of acetylcholine (ACh) has become important for diagnosing diseases and safeguarding health care because of its pivotal role in the central nervous system. Herein, we developed a new colorimetric sensor based on protein-inorganic hybrid nanoflowers as artificial peroxidase, comprising a test kit and a smartphone reader, which sensitively quantifies ACh in human serum. In this sensor, ACh indirectly triggered the substrate reaction with the help of a multienzyme system including acetylcholinesterase, choline oxidase, and mimic peroxidase (nanoflowers), accompanying the enhancement of absorbance intensity at 652 nm. Therefore, the multienzyme platform can be used to detect ACh via monitoring the change of the absorbance in a range from 0.0005 to 6.0 mmol L(-1). It is worth mentioning that the platform was used to prepare a portable agarose gel-based kit for rapid qualitative monitoring of ACh. Coupling with ImageJ program, the image information of test kits can be transduced into the hue parameter, which provides a directly quantitative tool to identify ACh. Based on the advantages of simple operation, good selectivity, and low cost, the availability of a portable kit for point-of-care testing will achieve the needs of frequent screening and diagnostic tracking.
ESTHER : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedSearch : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedID: 30830739

Title : Asperversins A and B, Two Novel Meroterpenoids with an Unusual 5\/6\/6\/6 Ring from the Marine-Derived Fungus Aspergillus versicolor - Li_2018_Mar.Drugs_16_
Author(s) : Li H , Sun W , Deng M , Qi C , Chen C , Zhu H , Luo Z , Wang J , Xue Y , Zhang Y
Ref : Mar Drugs , 16 : , 2018
Abstract : Asperversins A (1) and B (2), two novel meroterpenoids featuring an uncommon 5/6/6/6 ring system, along with five new analogues (3(-)7) and a known compound asperdemin (8), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures and absolute configurations were confirmed by extensive spectroscopic analyses, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculation. All new compounds were tested for their acetylcholinesterase enzyme (AChE) inhibitory activities and cytotoxic activities, of which compound 7 displayed moderate inhibitory activity against the AChE with an IC50 value of 13.6 μM.
ESTHER : Li_2018_Mar.Drugs_16_
PubMedSearch : Li_2018_Mar.Drugs_16_
PubMedID: 29882867

Title : NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma - Jing_2018_Biosci.Rep_38_
Author(s) : Jing JS , Li H , Wang SC , Ma JM , Yu LQ , Zhou H
Ref : Bioscience Reports , 38 : , 2018
Abstract : N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan-Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan-Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.
ESTHER : Jing_2018_Biosci.Rep_38_
PubMedSearch : Jing_2018_Biosci.Rep_38_
PubMedID: 30413609
Gene_locus related to this paper: human-NDRG3

Title : Left Atrial Appendage Thrombus Formation in a Patient on Dabigatran Therapy Associated With ABCB1 and CES-1 Genetic Defect - Gu_2018_Front.Pharmacol_9_491
Author(s) : Gu ZC , Ma XW , Zheng XY , Shen L , Shi FH , Li H
Ref : Front Pharmacol , 9 :491 , 2018
Abstract : Dabigatran, directly targeting thrombin, is widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF). We reported a rare case of left atrial appendage thrombus formation in a persistent NVAF patient despite the 31 months uninterrupted treatment with dabigatran 110 mg twice daily. The patient is a carrier of ABCB1 variant alleles with 7 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167) as well as CES-1 variant alleles with 2 homozygote SNPs (rs2244613 and rs4122238) and 2 heterozygote SNPs (rs8192935 and rs4580160), which may contribute to the changes of dabigatran plasma concentration. In addition, Drug-drug interaction with atorvastatin may also play a role to decrease dabigatran plasma concentration. There are only four such cases till date, of which had thrombus in the left atrium, reported in the literature. We firstly reported the documented case in a Chinese patient carrying multiple alleles of ABCB1 and CES-1, who suffered from thrombus in the left atrial appendage despite long-term anticoagulation with dabigatran. More clinical data are required to elucidate the impact of CES-1 and ABCB1 polymorphism on dabigatran pharmacokinetics, especially for Asian.
ESTHER : Gu_2018_Front.Pharmacol_9_491
PubMedSearch : Gu_2018_Front.Pharmacol_9_491
PubMedID: 29867495

Title : Omega-6 fatty acids down-regulate matrix metalloproteinase expression in a coronary heart disease-induced rat model - Lu_2018_Int.J.Exp.Pathol_99_210
Author(s) : Lu N , Du Y , Li H , Luo Y , Ouyang B , Chen Y , Yang Y , Yang L
Ref : International Journal of Experimental Pathology , 99 :210 , 2018
Abstract : The present study investigated the therapeutic potential of omega-6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease-induced rats. Rats were grouped into group I (sham control), group II (control), group III (0.5 g/kg bwt of omega-6 fatty acids) and group IV (1 g/kg bwt of omega-6 fatty acids). Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, glutathione peroxidase (Gpx) and acetylcholinesterase (AChE) enzyme activities were determined. ROS and MDA were substantially reduced, whereas SOD, catalase, Gpx and AChE were significantly increased, following supplementation with omega-6 fatty acids. MMP-2 mRNA expression was drastically increased by 95% in group II. Treatment significantly reduced MMP-2 mRNA expression by 12.3% and 26.7% in groups III and IV respectively. MMP-9 mRNA expression drastically increased, by 121%, in group II. Treatment significantly reduced MMP-9 mRNA expression by 22.6% and 29.4% in groups III and IV respectively. MMP-2 protein expression was drastically increased, by 81%, in group II. Treatment significantly reduced MMP-2 protein expression by 9.4% and 26% in groups III and IV respectively. MMP-9 protein expression was drastically increased, by 100%, in group II. Treatment significantly reduced MMP-9 protein expression by 18.9% and 26.9% in groups III and IV respectively. In summary, the consumption of omega-6 fatty acids significantly decreased MDA and ROS, while SOD, catalase, GHS, Gpx and AChE were increased. Furthermore, omega-6 fatty acids significantly downregulated MMP-2 and MMP-9 expression in our coronary heart disease-induced rat model.
ESTHER : Lu_2018_Int.J.Exp.Pathol_99_210
PubMedSearch : Lu_2018_Int.J.Exp.Pathol_99_210
PubMedID: 30443948

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : Biodegradation pathway of di-(2-ethylhexyl) phthalate by a novel Rhodococcus pyridinivorans XB and its bioaugmentation for remediation of DEHP contaminated soil - Zhao_2018_Sci.Total.Environ_640-641_1121
Author(s) : Zhao HM , Hu RW , Chen XX , Chen XB , Lu H , Li YW , Li H , Mo CH , Cai QY , Wong MH
Ref : Sci Total Environ , 640-641 :1121 , 2018
Abstract : A novel bacterial strain designated as Rhodococcus pyridinivorans XB, capable of utilizing various endocrine disruptor phthalates or phthalic acid (PA) as sole source of carbon and energy, was isolated from activated sludge. Under the optimal culture conditions (pH7.08, 30.4 degrees C, inoculum size (OD600 nm) of 0.6) obtained by response surface methodology, di-(2-ethylhexyl) phthalate (DEHP, 200mg/L) could be degraded by strain XB with a removal rate of 98% within 48h. Under the observation of an atomic force microscope, it was confirmed that DEHP did not inhibit the growth of strain XB which might produce some extracellular polymeric substances as a response to DEHP stress, resulting in rapid degradation of DEHP. At initial concentrations of 50-800mg/L DEHP, its degradation curves were well fitted with the first-order kinetic model, and the half-life of DEHP degradation varied from 5.44 to 23.5h. The degradation intermediates of DEHP were identified by both GC-MS and high performance liquid chromatography-time of flight-mass spectrometry (HPLC-TOF-MS). Significant up-regulation was observed for the relative expression levels of genes (i.e., phthalate hydrolase, PA 3,4-dioxygenase, protocatechuate 3,4-alpha and 3,4-beta dioxygenase) involved in DEHP degradation determined by real-time quantitative PCR (RT-qPCR). A DEHP biodegradation pathway by strain XB was proposed based on the identified intermediates and the degrading genes. Bioaugmentation of DEHP-contaminated soils with strain XB could efficiently promote DEHP removal, offering great potential in bioremediation of DEHP-contaminated environment.
ESTHER : Zhao_2018_Sci.Total.Environ_640-641_1121
PubMedSearch : Zhao_2018_Sci.Total.Environ_640-641_1121
PubMedID: 30021277

Title : Three-dimensional reconstructed eccrine sweat glands with vascularization and cholinergic and adrenergic innervation - Zhang_2018_J.Mol.Histol_49_339
Author(s) : Zhang M , Li H , Chen L , Fang S , Xie S , Lin C
Ref : J Mol Histol , 49 :339 , 2018
Abstract : Functional integrity of the regenerated tissues requires not only structural integrity but also vascularization and innervation. We previously demonstrated that the three-dimensional (3D) reconstructed eccrine sweat glands had similar structures as those of the native ones did, but whether the 3D reconstructed glands possessing vascularization and innervation was still unknown. In the study, Matrigel-embedded eccrine sweat gland cells were implanted under the inguinal skin. Ten weeks post-implantation, the vascularization, and innervation in the 10-week reconstructed eccrine sweat glands and native human eccrine sweat glands were detected by immunofluorescence staining. The results showed that the fluorescent signals of general neuronal marker protein gene product 9.5, adrenergic nerve fiber marker tyrosine hydroxylase, and cholinergic nerve fiber markers acetylcholinesterase and vasoactive intestinal peptide embraced the 3D reconstructed glands in circular patterns, as the signals appeared in native eccrine sweat glands. There were many CD31- and von Willebrand factor-positive vessels growing into the plugs. We demonstrated that the 3D reconstructed eccrine sweat glands were nourished by blood vessels, and we for the first time demonstrated that the engineering sweat glands were innervated by both cholinergic and adrenergic fibers. In conclusion, the 3D reconstructed eccrine sweat glands may have functions as the native ones do.
ESTHER : Zhang_2018_J.Mol.Histol_49_339
PubMedSearch : Zhang_2018_J.Mol.Histol_49_339
PubMedID: 29667149

Title : Purification and characterization of a hydroxynitrile lyase from Amygdalus pedunculata Pall - Yao_2018_Int.J.Biol.Macromol_118_189
Author(s) : Yao L , Li H , Yang J , Li C , Shen Y
Ref : Int J Biol Macromol , 118 :189 , 2018
Abstract : Hydroxynitrile lyases (HNLs) are widely used in the asymmetric synthesis of cyanohydrins which are organic compounds used in the production of fine chemicals and pharmaceuticals, because these enzymes exhibit high catalytic efficiency and are very economical. In the present study, seeds of A. pedunculata Pall were identified as new potential source of HNLs. The HNL from A. pedunculata Pall (APHNL) was purified 138 fold and 4.20% yield with a specific activity of 661U/mg. SDS-PAGE result showed the enzyme to be present as a monomer and the relative molecular mass determined by MALDI-TOF MS was 61kDa. APHNL owned highest activity at pH6.0 and at 60 degrees C temperature, showing activity up to 80 degrees C and stable up to 60 degrees C. APHNL has a Km of 0.5mM, Vmax of 665.9mumolmg(-1)min(-1), Kcat of 676.5s(-1) and Kcat/Km of 1353s(-1)mM(-1) using mandelonitrile as substrate. Syntheses of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were carried out using APHNL and molar conversion of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were 90% and 98% with 94% and 93% ee, respectively. These results indicated that APHNL was an excellent biocatalyst and has very high potential for synthesis of enantiopure cyanohydrins.
ESTHER : Yao_2018_Int.J.Biol.Macromol_118_189
PubMedSearch : Yao_2018_Int.J.Biol.Macromol_118_189
PubMedID: 29890248

Title : Benzo(a)pyrene inhibits the accumulation and toxicity of cadmium in subcellular fractions of Eisenia fetida - Zhang_2018_Chemosphere_219_740
Author(s) : Zhang L , Zhou L , Han L , Zhao C , Norton JM , Li H , Hu F , Xu L
Ref : Chemosphere , 219 :740 , 2018
Abstract : Cadmium (Cd) and benzo [a]pyrene (BaP) often co-occur in the environment, and the critical body residue of organisms is used as an indicator of the toxic effects of contaminants. However, little is known about their distributions and toxicities when pollution of Cd and BaP are combined. Semi-static solution culture experiment was used to study the impacts of BaP on the subcellular distribution of the toxic metal Cd in the earthworm Eisenia fetida. We explored the mechanisms by which this organism responds to combined exposure to these pollutants by measuring the protein content of each of three subcellular fractions, as well as acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities. The subcellular partitioning of Cd was heterogeneous and Cd mainly accumulated in the cytosolic fraction (Fraction C), which was previously reported to be involved in metal immobilization. In Fraction C, Cd accumulation was correlated with the external concentration to which the earthworm had been exposed; however, in the presence of BaP, Cd accumulation was inhibited and plateaued at high external Cd concentrations. A principal component analysis revealed that this decreased Cd accumulation might be caused by increases in GST activity, which likely increased the excretion of Cd. BaP was also found to stimulate protein biosynthesis and upregulate AChE and GST activities in the debris fraction (Fraction E), indicating other potential detoxification mechanisms in this fraction. Granule fraction (Fraction D) had a lower protein content, AChE and GST activities than the other subcellular fractions, supporting previous findings that Fraction D is largely inert.
ESTHER : Zhang_2018_Chemosphere_219_740
PubMedSearch : Zhang_2018_Chemosphere_219_740
PubMedID: 30557731

Title : New 2-Aryl-9-methyl-beta-carbolinium salts as Potential Acetylcholinesterase Inhibitor agents: Synthesis, Bioactivity and Structure-Activity Relationship - Zhou_2018_Sci.Rep_8_1559
Author(s) : Zhou B , Zhang B , Li X , Liu X , Li H , Li D , Cui Z , Geng H , Zhou L
Ref : Sci Rep , 8 :1559 , 2018
Abstract : A series of 2-aryl-9-methyl-beta-carbolinium bromides (B) were synthesized and explored for anti-acetylcholinesterase (AChE) activities in vitro, action mechanism and structure-activity relationship. All the compounds B along with their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10 muM. Thirteen compounds B showed the excellent activity with IC50 values of 0.11-0.76 muM and high selectivity toward AChE relative to butyrylcholinesterase (BChE), superior to galantamine (IC50 = 0.79 muM), a selective AChE inhibitor drug. Kinetic analysis showed that the action mechanisms of both compounds B and A are a competitive inhibition model. Structure-activity relationship analyses showed that the C = N(+) moiety is a determinant for the activity. Substituents at 6, 7 or 4' site, the indole-N-alkyl and the aromatization of the C-ring can significantly improve the activity. Molecular docking studies showed that the compounds could combine with the active site of AChE by the pi-pi or cation-pi action between the carboline ring and the phenyl rings of the residues, and the beta-carboline moiety is embedded in a cavity surrounded by four aromatic residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, 2-aryl-9-methyl-beta-carboliniums emerged as novel and promising tool compounds for the development of new AChE inhibitor agents.
ESTHER : Zhou_2018_Sci.Rep_8_1559
PubMedSearch : Zhou_2018_Sci.Rep_8_1559
PubMedID: 29367595

Title : Yellow-Emissive Carbon Dot-Based Optical Sensing Platforms: Cell Imaging and Analytical Applications for Biocatalytic Reactions - Li_2018_ACS.Appl.Mater.Interfaces_10_7737
Author(s) : Li H , Yan X , Qiao S , Lu G , Su X
Ref : ACS Appl Mater Interfaces , 10 :7737 , 2018
Abstract : Carbon dots (CDs) have attracted increasing interest in bioimaging and sensing recently. Herein, we present a simple synthetic strategy to prepare yellow-emissive CDs (lambdaem = 535 nm) by one-pot hydrothermal treatment of p-phenylenediamine and aspartic acid. The as-prepared CDs possess outstanding optical features, excellent biocompatibility, and low cytotoxicity, especially for fluorescence (FL) cellular imaging. Interestingly, by combining the quenching and recognition ability of silver nanoparticles (AgNPs) with the optical capacity of CDs, a label-free strategy for specifically monitoring H2O2-generated biocatalytic processes was proposed, such as glucose oxidase-induced conversion of glucose, cholesterol oxidase-catalyzed oxidization of cholesterol, and bienzyme of acetylcholinesterase and choline oxidase-mediated reaction of acetylcholine. In this process, AgNPs act as a "nanoquencher" to decrease the FL intensity of CDs via surface plasmon-enhanced energy-transfer mechanism. The enzymatic oxidation product (H2O2) subsequently etches the AgNPs to silver ions, thus recovering the FL of CDs, which enabled this proposed nanosensor to sensitively detect H2O2-generated biocatalytic processes. The above results pave the way to implement CDs as FL labels for biosensors and biological imaging.
ESTHER : Li_2018_ACS.Appl.Mater.Interfaces_10_7737
PubMedSearch : Li_2018_ACS.Appl.Mater.Interfaces_10_7737
PubMedID: 29441784

Title : Epidemiology of Dementia in Elderly Chronic Obstructive Pulmonary Disease Patients Living in China's Northwestern High-Elevation Area - Mei_2018_Med.Sci.Monit_24_7742
Author(s) : Mei L , Wu S , Wang D , Li H , Zhang H , Wang M
Ref : Med Sci Monit , 24 :7742 , 2018
Abstract : BACKGROUND The aim of this study was to investigate the effects of oxygen and cholinesterase inhibitor (donepezil) therapy on dementia in patients with age-exacerbated chronic obstructive pulmonary disease (COPD) in China's northwestern high-altitude area. MATERIAL AND METHODS A total of 145 patients with acute exacerbation of COPD admitted to the Gerontology Department of the First People's Hospital of Xining City were initially retrospectively screened. From among these 145 patients, we selected 33 cases with dementia and 33 patients without dementia through use of the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Activities of Daily Living (ADL) Scale evaluated before, 7 days after, and at the end of the treatment after 3 months. Both patient groups received oxygen therapy for 7 days, but patients with dementia in the intervention group were medicated additionally with donepezil (5 mg/day for 1 week, followed by 10 mg/day for another 12 weeks). RESULTS Mild dementia was found in 35 of the 145 COPD patients. ADL, MMSE, and ADAS-Cog scores were all significantly lower in the intervention group before treatment, improved after the first 7 days, and continued to improve significantly until week 12 in the intervention group, but were still significantly lower than in the control group. CONCLUSIONS Dementia in elderly COPD patients was mainly manifested as decreased executive function, attention, language, and delayed recall, while oxygen and donepezil therapy had beneficial effects on the symptoms.
ESTHER : Mei_2018_Med.Sci.Monit_24_7742
PubMedSearch : Mei_2018_Med.Sci.Monit_24_7742
PubMedID: 30372705

Title : MnO2 Nanosheet-Carbon Dots Sensing Platform for Sensitive Detection of Organophosphorus Pesticides - Yan_2018_Anal.Chem_90_2618
Author(s) : Yan X , Song Y , Zhu C , Li H , Du D , Su X , Lin Y
Ref : Analytical Chemistry , 90 :2618 , 2018
Abstract : Carbon dots (CDs) combined with a nanomaterial-based quencher has created an innovative way for designing promising sensors. Herein, a novel fluorescent-sensing platform was designed for sensitive detection of organophosphorus pesticides (OPs). The preparation of CDs was based on one-step hydrothermal reaction of 3-aminobenzeneboronic acid. The fluorescence of CDs can be quenched by manganese dioxide (MnO2) nanosheets via the Forster resonance energy transfer (FRET). In the presence of butyrylcholinesterase (BChE) and acetylthiocholine, the enzymatic hydrolysate (thiocholine) can efficiently trigger the decomposition of MnO2 nanosheets, resulting in the recovery of CDs fluorescence. OPs as inhibitors for BChE activity can prevent the generation of thiocholine and decomposition of MnO2 nanosheets, accompanying the fluorescence "turn-off" of the system. So the BChE-ATCh-MnO2-CDs system can be utilized to detect OPs quantitatively based on the fluorescence turn "on-off". Under the optimum conditions, the present FRET-based approach can detect paraoxon ranging from 0.05 to 5 ng mL(-1) with a detection limit of 0.015 ng mL(-1). Meanwhile, the present strategy also showed a visual color change in a concentration-dependent manner. Thus, the proposed assay can potentially be a candidate for OPs detection.
ESTHER : Yan_2018_Anal.Chem_90_2618
PubMedSearch : Yan_2018_Anal.Chem_90_2618
PubMedID: 29237266

Title : Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice - Zhang_2018_Mol.Med.Rep_17_6873
Author(s) : Zhang Y , Sha R , Wang K , Li H , Yan B , Zhou N
Ref : Mol Med Rep , 17 :6873 , 2018
Abstract : Tetrahydropalmatine exerts numerous pharmacological activities, including analgesic and narcotic effects; anti-arrhythmic, blood pressure lowering and cardioprotective effects; protective effects against cerebral ischemia-reperfusion injury; inhibition of platelet aggregation; prevention of ulcerative diseases and inhibition of gastric acid secretion; antitumor effects; and beneficial effects on the withdrawal symptoms associated with drug addiction. The present study aimed to investigate the protective effects of tetrahydropalmatine against ketamineinduced learning and memory impairment in mice. The Morris water maze test and open field test were used to analyzed learning and memory impairment in mice. ELISA kits and western blotting were used to analyze oxidative stress, inflammation factors, caspease3 and caspase9, iNOS, glial fibrillary acidic protein (GFAP), glial cellderived neurotrophic factor (GDNF), cytochrome c and phospholipase C (PLC)gamma1 protein expression. The results demonstrated that tetrahydropalmatine treatment significantly decreased escape latency in the learning phase and increased the number of platform site crossings in ketamineinduced mice. In addition, tetrahydropalmatine significantly inhibited oxidative stress, inflammation and acetylcholinesterase activity, and decreased acetylcholine levels in ketamineinduced mice. Tetrahydropalmatine also suppressed iNOS protein expression, weakened caspase3 and caspase9 activation, inhibited nuclear factorkappaB, glial fibrillary acidic protein, cytochrome c and phospholipase Cgamma1 protein expression, and induced glial cellderived neurotrophic factor protein expression in ketamineinduced mice. Taken together, these results indicated that tetrahydropalmatine may protect against ketamineinduced learning and memory impairment in mice via antioxidative, antiinflammatory and antiapoptotic mechanisms. The present study provided an experimental basis for the clinical application of tetrahydropalmatine to reduce the severe side effects associated with ketamine therapy in future studies.
ESTHER : Zhang_2018_Mol.Med.Rep_17_6873
PubMedSearch : Zhang_2018_Mol.Med.Rep_17_6873
PubMedID: 29512789

Title : Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats - Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
Author(s) : Wang Z , Chen Z , Yang J , Yang Z , Yin J , Duan X , Shen H , Li H , Chen G
Ref : Journal of Cerebral Blood Flow & Metabolism , :271678X18762637 , 2018
Abstract : Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH.
ESTHER : Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
PubMedSearch : Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637
PubMedID: 29513122

Title : Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain - Guo_2018_Neurosci_382_14
Author(s) : Guo R , Li H , Li X , Sun Y , Miao H , Ma D , Hong F , Zhang Y , Guan Y , Li J , Tian M , Wang Y
Ref : Neuroscience , 382 :14 , 2018
Abstract : Neuroligin 2 is a synaptic cell adhesion molecule that is mainly located in inhibitory synapses and is crucial in the regulation of synapse function through protein-protein interactions. However, researchers have not clearly determined whether neuroligin 2 is involved in the development of postoperative pain. In the current study, Western blot, immunofluorescence staining and co-immunoprecipitation were used to examine the critical role of neuroligin 2 in postoperative pain hypersensitivity. A small interfering ribonucleic acid (siRNA)-targeting neuroligin 2 was used to inhibit neuroligin 2 expression. Our data found that plantar incision induced postoperative pain hypersensitivity, which was characterized by paw withdrawal threshold and cumulative pain score. The upregulation of neuroligin 2 and GluR1 expression in the postsynaptic membranes of ipsilateral spinal dorsal horn was observed at 3h and 1day after plantar incision. Additionally, at 3h after plantar incision, the amount of PSD-95 that was co-immunoprecipitated with neuroligin 2 antibody was significantly increased in the ipsilateral dorsal horn, as compared to that of the control group. Intrathecal pretreatment of siRNA-targeting neuroligin 2 to reduce the neuroligin 2 expression in the spinal cord significantly inhibited the pain hypersensitivity and reduced the synaptic targeting of GluR1 in ipsilateral dorsal horns. Our study indicates that the incision-induced interaction between neuroligin 2 and PSD-95 and subsequent synaptic targeting of GluR1 in ipsilateral dorsal horns contribute to postoperative pain hypersensitivity.
ESTHER : Guo_2018_Neurosci_382_14
PubMedSearch : Guo_2018_Neurosci_382_14
PubMedID: 29715511

Title : A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study - Zhou_2018_Eur.J.Hum.Genet_26_838
Author(s) : Zhou D , Zhang D , Sun X , Li Z , Ni Y , Shan Z , Li H , Liu C , Zhang S , Liu Y , Zheng R , Pan F , Zhu Y , Shi Y , Lai M
Ref : Eur J Hum Genet , 26 :838 , 2018
Abstract : Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (Pcombined = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.
ESTHER : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedSearch : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedID: 29476167

Title : Csn5 Is Required for the Conidiogenesis and Pathogenesis of the Alternaria alternata Tangerine Pathotype - Wang_2018_Front.Microbiol_9_508
Author(s) : Wang M , Yang X , Ruan R , Fu H , Li H
Ref : Front Microbiol , 9 :508 , 2018
Abstract : The COP9 signalosome (CSN) is a highly conserved protein complex involved in the ubiquitin-proteasome system. Its metalloisopeptidase activity resides in subunit 5 (CSN5). Functions of csn5 in phytopathogenic fungi are poorly understood. Here, we knocked out the csn5 ortholog (Aacsn5) in the tangerine pathotype of Alternaria alternata. The deltaAacsn5 mutant showed a moderately reduced growth rate compared to the wildtype strain and was unable to produce conidia. The growth of deltaAacsn5 mutant was not affected in response to oxidative and osmotic stresses. Virulence assays revealed that deltaAacsn5 induced no or significantly reduced necrotic lesions on detached citrus leaves. The defects in hyphal growth, conidial sporulation, and pathogenicity of deltaAacsn5 were restored by genetic complementation of the mutant with wildtype Aacsn5. To explore the molecular mechanisms of conidiation and pathogenesis underlying Aacsn5 regulation, we systematically examined the transcriptomes of both deltaAacsn5 and the wildtype. Generally, 881 genes were overexpressed and 777 were underexpressed in the deltaAacsn5 mutant during conidiation while 694 overexpressed and 993 underexpressed during infection. During asexual development, genes related to the transport processes and nitrogen metabolism were significantly downregulated; the expression of csn1-4 and csn7 in deltaAacsn5 was significantly elevated; secondary metabolism gene clusters were broadly affected; especially, the transcript level of the whole of cluster 28 and 30 was strongly induced. During infection, the expression of the host-specific ACT toxin gene cluster which controls the biosynthesis of the citrus specific toxin was significantly repressed; many other SM clusters with unknown products were also regulated; 86 out of 373 carbohydrate-active enzymes responsible for breaking down the plant dead tissues showed uniquely decreased expression. Taken together, our results expand our understanding of the roles of csn5 on conidiation and pathogenicity in plant pathogenic fungi and provide a foundation for future investigations.
ESTHER : Wang_2018_Front.Microbiol_9_508
PubMedSearch : Wang_2018_Front.Microbiol_9_508
PubMedID: 29616013
Gene_locus related to this paper: altal-actt2

Title : Clinical diagnostic significance of prealbumin, cholinesterase and retinol binding protein in liver cirrhosis combined with encephalopathy - Tan_2018_Br.J.Biomed.Sci__1
Author(s) : Tan L , Meng Y , Zeng T , Wang Q , Long T , Wu S , Guan X , Fu H , Zheng W , Tian Y , Chen J , Yu J , Wu Y , Li H , Cao L
Ref : Br J Biomed Sci , :1 , 2018
Abstract : OBJECTIVE: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy. METHODS: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy. RESULTS: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01). CONCLUSIONS: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy.
ESTHER : Tan_2018_Br.J.Biomed.Sci__1
PubMedSearch : Tan_2018_Br.J.Biomed.Sci__1
PubMedID: 30392460

Title : Spatial-temporal expression of NDRG2 in brain tissues in a rat model of intracerebral hemorrhage: A pilot study - Gao_2018_Neurosci.Lett_662_356
Author(s) : Gao L , Li X , Li H , Li J , Shen H , Chen G
Ref : Neuroscience Letters , 662 :356 , 2018
Abstract : N-myc downstream regulated gene 2 (NDRG2) was a member of the N-myc down regulated gene family which belongs to the alpha/beta hydrolase superfamily and played important roles in cell death. To date, the expression and effects of NDRG2 in brain after intracerebral hemorrhage (ICH) are unclear. In this study, we investigated the spatial-temporal expression of NDRG2 in brain tissues in a rat model of ICH. The expression levels of NDRG2 were tested in 3h, 6h, 12h, 24h, 48h, 72h, and 7d after ICH by western blot analysis. The results showed that the NDRG2 levels were increased and peaked at 24h after ICH, and then declined subsequently. Meanwhile, we also examined the NDRG2 cellular localization in brain tissues by immunofluorescence analysis with NeuN and GFAP (biomarker of neuron and astrocytes respectively). The results demonstrated that NDRG2 was mainly expressed in astrocytes, but not neurons, after ICH. Additionally, the results of double staining indicated that the rate of NDRG2- and TUNEL -positive cells was significantly higher in the brain tissues in rats after ICH. The roles of NDRG2 in ICH needed further investigation and inhibiting the expression of NDRG2 may have potential therapeutic effects in ICH.
ESTHER : Gao_2018_Neurosci.Lett_662_356
PubMedSearch : Gao_2018_Neurosci.Lett_662_356
PubMedID: 29037792

Title : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity - Turcot_2018_Nat.Genet_50_26
Author(s) : Turcot V , Lu Y , Highland HM , Schurmann C , Justice AE , Fine RS , Bradfield JP , Esko T , Giri A , Graff M , Guo X , Hendricks AE , Karaderi T , Lempradl A , Locke AE , Mahajan A , Marouli E , Sivapalaratnam S , Young KL , Alfred T , Feitosa MF , Masca NGD , Manning AK , Medina-Gomez C , Mudgal P , Ng MCY , Reiner AP , Vedantam S , Willems SM , Winkler TW , Abecasis G , Aben KK , Alam DS , Alharthi SE , Allison M , Amouyel P , Asselbergs FW , Auer PL , Balkau B , Bang LE , Barroso I , Bastarache L , Benn M , Bergmann S , Bielak LF , Bluher M , Boehnke M , Boeing H , Boerwinkle E , Boger CA , Bork-Jensen J , Bots ML , Bottinger EP , Bowden DW , Brandslund I , Breen G , Brilliant MH , Broer L , Brumat M , Burt AA , Butterworth AS , Campbell PT , Cappellani S , Carey DJ , Catamo E , Caulfield MJ , Chambers JC , Chasman DI , Chen YI , Chowdhury R , Christensen C , Chu AY , Cocca M , Collins FS , Cook JP , Corley J , Corominas Galbany J , Cox AJ , Crosslin DS , Cuellar-Partida G , D'Eustacchio A , Danesh J , Davies G , Bakker PIW , Groot MCH , Mutsert R , Deary IJ , Dedoussis G , Demerath EW , Heijer M , Hollander AI , Ruijter HM , Dennis JG , Denny JC , Angelantonio E , Drenos F , Du M , Dube MP , Dunning AM , Easton DF , Edwards TL , Ellinghaus D , Ellinor PT , Elliott P , Evangelou E , Farmaki AE , Farooqi IS , Faul JD , Fauser S , Feng S , Ferrannini E , Ferrieres J , Florez JC , Ford I , Fornage M , Franco OH , Franke A , Franks PW , Friedrich N , Frikke-Schmidt R , Galesloot TE , Gan W , Gandin I , Gasparini P , Gibson J , Giedraitis V , Gjesing AP , Gordon-Larsen P , Gorski M , Grabe HJ , Grant SFA , Grarup N , Griffiths HL , Grove ML , Gudnason V , Gustafsson S , Haessler J , Hakonarson H , Hammerschlag AR , Hansen T , Harris KM , Harris TB , Hattersley AT , Have CT , Hayward C , He L , Heard-Costa NL , Heath AC , Heid IM , Helgeland O , Hernesniemi J , Hewitt AW , Holmen OL , Hovingh GK , Howson JMM , Hu Y , Huang PL , Huffman JE , Ikram MA , Ingelsson E , Jackson AU , Jansson JH , Jarvik GP , Jensen GB , Jia Y , Johansson S , Jorgensen ME , Jorgensen T , Jukema JW , Kahali B , Kahn RS , Kahonen M , Kamstrup PR , Kanoni S , Kaprio J , Karaleftheri M , Kardia SLR , Karpe F , Kathiresan S , Kee F , Kiemeney LA , Kim E , Kitajima H , Komulainen P , Kooner JS , Kooperberg C , Korhonen T , Kovacs P , Kuivaniemi H , Kutalik Z , Kuulasmaa K , Kuusisto J , Laakso M , Lakka TA , Lamparter D , Lange EM , Lange LA , Langenberg C , Larson EB , Lee NR , Lehtimaki T , Lewis CE , Li H , Li J , Li-Gao R , Lin H , Lin KH , Lin LA , Lin X , Lind L , Lindstrom J , Linneberg A , Liu CT , Liu DJ , Liu Y , Lo KS , Lophatananon A , Lotery AJ , Loukola A , Luan J , Lubitz SA , Lyytikainen LP , Mannisto S , Marenne G , Mazul AL , McCarthy MI , McKean-Cowdin R , Medland SE , Meidtner K , Milani L , Mistry V , Mitchell P , Mohlke KL , Moilanen L , Moitry M , Montgomery GW , Mook-Kanamori DO , Moore C , Mori TA , Morris AD , Morris AP , Muller-Nurasyid M , Munroe PB , Nalls MA , Narisu N , Nelson CP , Neville M , Nielsen SF , Nikus K , Njolstad PR , Nordestgaard BG , Nyholt DR , O'Connel JR , O'Donoghue ML , Olde Loohuis LM , Ophoff RA , Owen KR , Packard CJ , Padmanabhan S , Palmer CNA , Palmer ND , Pasterkamp G , Patel AP , Pattie A , Pedersen O , Peissig PL , Peloso GM , Pennell CE , Perola M , Perry JA , Perry JRB , Pers TH , Person TN , Peters A , Petersen ERB , Peyser PA , Pirie A , Polasek O , Polderman TJ , Puolijoki H , Raitakari OT , Rasheed A , Rauramaa R , Reilly DF , Renstrom F , Rheinberger M , Ridker PM , Rioux JD , Rivas MA , Roberts DJ , Robertson NR , Robino A , Rolandsson O , Rudan I , Ruth KS , Saleheen D , Salomaa V , Samani NJ , Sapkota Y , Sattar N , Schoen RE , Schreiner PJ , Schulze MB , Scott RA , Segura-Lepe MP , Shah SH , Sheu WH , Sim X , Slater AJ , Small KS , Smith AV , Southam L , Spector TD , Speliotes EK , Starr JM , Stefansson K , Steinthorsdottir V , Stirrups KE , Strauch K , Stringham HM , Stumvoll M , Sun L , Surendran P , Swift AJ , Tada H , Tansey KE , Tardif JC , Taylor KD , Teumer A , Thompson DJ , Thorleifsson G , Thorsteinsdottir U , Thuesen BH , Tonjes A , Tromp G , Trompet S , Tsafantakis E , Tuomilehto J , Tybjaerg-Hansen A , Tyrer JP , Uher R , Uitterlinden AG , Uusitupa M , Laan SW , Duijn CM , Leeuwen N , van Setten J , Vanhala M , Varbo A , Varga TV , Varma R , Velez Edwards DR , Vermeulen SH , Veronesi G , Vestergaard H , Vitart V , Vogt TF , Volker U , Vuckovic D , Wagenknecht LE , Walker M , Wallentin L , Wang F , Wang CA , Wang S , Wang Y , Ware EB , Wareham NJ , Warren HR , Waterworth DM , Wessel J , White HD , Willer CJ , Wilson JG , Witte DR , Wood AR , Wu Y , Yaghootkar H , Yao J , Yao P , Yerges-Armstrong LM , Young R , Zeggini E , Zhan X , Zhang W , Zhao JH , Zhao W , Zhou W , Zondervan KT , Rotter JI , Pospisilik JA , Rivadeneira F , Borecki IB , Deloukas P , Frayling TM , Lettre G , North KE , Lindgren CM , Hirschhorn JN , Loos RJF
Ref : Nat Genet , 50 :26 , 2018
Abstract : Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
ESTHER : Turcot_2018_Nat.Genet_50_26
PubMedSearch : Turcot_2018_Nat.Genet_50_26
PubMedID: 29273807

Title : IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata - Wingfield_2018_IMA.Fungus_9_199
Author(s) : Wingfield BD , Bills GF , Dong Y , Huang W , Nel WJ , Swalarsk-Parry BS , Vaghefi N , Wilken PM , An Z , de Beer ZW , De Vos L , Chen L , Duong TA , Gao Y , Hammerbacher A , Kikkert JR , Li Y , Li H , Li K , Li Q , Liu X , Ma X , Naidoo K , Pethybridge SJ , Sun J , Steenkamp ET , van der Nest MA , van Wyk S , Wingfield MJ , Xiong C , Yue Q , Zhang X
Ref : IMA Fungus , 9 :199 , 2018
Abstract : Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi.
ESTHER : Wingfield_2018_IMA.Fungus_9_199
PubMedSearch : Wingfield_2018_IMA.Fungus_9_199
PubMedID: 30018880
Gene_locus related to this paper: 9helo-a0a370tge3 , 9helo-a0a3d8spg6 , 9euro-a0a3d8t2t6 , 9euro-a0a3d8t644 , 9helo-a0a370te58 , 9helo-a0a370tt42 , 9helo-a0a370u2s4 , 9helo-a0a3d8s0y2 , 9helo-a0a3d8stp9 , 9helo-a0a370u370 , 9euro-a0a3d8rk78 , 9helo-a0a370tat5 , 9helo-a0a3d8qpi0

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 : Graphene Oxide Dysregulates Neuroligin\/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans - Chen_2017_Sci.Rep_7_41655
Author(s) : Chen H , Li H , Wang D
Ref : Sci Rep , 7 :41655 , 2017
Abstract : Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.
ESTHER : Chen_2017_Sci.Rep_7_41655
PubMedSearch : Chen_2017_Sci.Rep_7_41655
PubMedID: 28128356

Title : Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice - Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
Author(s) : Li N , Liu C , Jing S , Wang M , Wang H , Sun J , Wang C , Chen J , Li H
Ref : Evid Based Complement Alternat Med , 2017 :8632016 , 2017
Abstract : Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement.
ESTHER : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedSearch : Li_2017_Evid.Based.Complement.Alternat.Med_2017_8632016
PubMedID: 28814961

Title : Brain explorer for connectomic analysis - Li_2017_Brain.Inform_4_253
Author(s) : Li H , Fang S , Contreras JA , West JD , Risacher SL , Wang Y , Sporns O , Saykin AJ , Goni J , Shen L
Ref : Brain Inform , 4 :253 , 2017
Abstract : Visualization plays a vital role in the analysis of multimodal neuroimaging data. A major challenge in neuroimaging visualization is how to integrate structural, functional, and connectivity data to form a comprehensive visual context for data exploration, quality control, and hypothesis discovery. We develop a new integrated visualization solution for brain imaging data by combining scientific and information visualization techniques within the context of the same anatomical structure. In this paper, new surface texture techniques are developed to map non-spatial attributes onto both 3D brain surfaces and a planar volume map which is generated by the proposed volume rendering technique, spherical volume rendering. Two types of non-spatial information are represented: (1) time series data from resting-state functional MRI measuring brain activation; (2) network properties derived from structural connectivity data for different groups of subjects, which may help guide the detection of differentiation features. Through visual exploration, this integrated solution can help identify brain regions with highly correlated functional activations as well as their activation patterns. Visual detection of differentiation features can also potentially discover image-based phenotypic biomarkers for brain diseases.
ESTHER : Li_2017_Brain.Inform_4_253
PubMedSearch : Li_2017_Brain.Inform_4_253
PubMedID: 28836134

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Screening and characterization of a novel thermostable lipase with detergent-additive potential from the metagenomic library of a mangrove soil - Tang_2017_Gene_625_64
Author(s) : Tang L , Xia Y , Wu X , Chen X , Zhang X , Li H
Ref : Gene , 625 :64 , 2017
Abstract : One clone (Lip906) exhibiting lipase activity was screened from a metagenomic library by using a medium containing tricaprylin. A novel lipase gene from the inserted fragment of Lip906 was obtained by sequencing. The phylogenetic analysis of Lip906 lipase exhibited 34% and 32% homologue to lipases from Streptomyces sp. MspMP-M5 and Rhodopirellula europaea. This gene was expressed in Escherichia coli (E. coli) BL21 (DE3), and the recombinant protein was purified and characterized. The best substrate of the recombinant Lip906 lipase was p-nitrophenyl myristate (C14). The lipase expressed maximum activity at 74 degrees C and pH7.8, and it was found to be stable at pH values and temperatures ranging from 6.0-8.0 and 4-78 degrees C, respectively. Furthermore, the lipase was found to be highly resistant to commercial detergent, DMSO, and EDTA, whereas its activity was stimulated in the presence of methanol and ethanol at low concentrations. The lipase showed enhanced activity in the presence of Hg2+, whereas the presence of the metal ions Fe2+, Ca2+, Co2+, and Mg2+ inhibited the activity. These beneficial characteristics of Lip906 lipase provide some advantages for its potential application in industry.
ESTHER : Tang_2017_Gene_625_64
PubMedSearch : Tang_2017_Gene_625_64
PubMedID: 28457984

Title : Synaptic vesicles isolated from the electric organ of Torpedo californica and from the central nervous system of Mus musculus contain small ribonucleic acids (sRNAs) - Li_2017_Genom.Data_12_52
Author(s) : Li H , Wu C , Aramayo R , Sachs MS , Harlow ML
Ref : Genom Data , 12 :52 , 2017
Abstract : Synaptic vesicles (SVs) are presynaptic organelles that load and release small molecule neurotransmitters at chemical synapses. In addition to classic neurotransmitters, we have demonstrated that SVs isolated from the Peripheral Nervous Systems (PNS) of the electric organ of Torpedo californica, a model cholinergic synapse, and SVs isolated from the Central Nervous System (CNS) of Mus musculus (mouse) contain small ribonucleic acids (sRNAs; <= 50 nucleotides) (Scientific Reports, 5:1-14(14918) Li et al. (2015) [1]). Our previous publication provided the five most abundant sequences associated with the T. californica SVs, and the ten most abundant sequences associated with the mouse SVs, representing 59% and 39% of the total sRNA reads sequenced, respectively). We provide here a full repository of the SV sRNAs sequenced from T. californica and the mouse deposited in the NCBI as biosamples. Three data studies are included: SVs isolated from the electric organ of T. californica using standard techniques, SVs isolated from the electric organ of T. californica using standard techniques with an additional affinity purification step, and finally, SVs isolated from the CNS of mouse. The three biosamples are available at SRS1523467, SRS1523466, and SRS1523472 respectively.
ESTHER : Li_2017_Genom.Data_12_52
PubMedSearch : Li_2017_Genom.Data_12_52
PubMedID: 28367405

Title : Aii810, a Novel Cold-Adapted N-Acylhomoserine Lactonase Discovered in a Metagenome, Can Strongly Attenuate Pseudomonas aeruginosa Virulence Factors and Biofilm Formation - Fan_2017_Front.Microbiol_8_1950
Author(s) : Fan X , Liang M , Wang L , Chen R , Li H , Liu X
Ref : Front Microbiol , 8 :1950 , 2017
Abstract : The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti-infection therapeutic strategy that does not rely on antibiotics. Here, a novel gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao-tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the highest activity at 20 degrees C, and it maintained 76.5% of activity at 0 degrees C and more than 50% activity at 0-40 degrees C. The optimal pH was 8.0. It was stable in both neutral and slightly alkaline conditions and at temperatures below 40 degrees C. The enzyme hydrolyzed several rho-nitrophenyl esters, but its best substrate was rho-nitrophenyl acetate. Its kcat and Km values were 347.7 S(-1) and 205.1 muM, respectively. It efficiently degraded N-butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone, exceeding hydrolysis rates of 72.3 and 100%, respectively. Moreover, Aii810 strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase reported, which makes it an attractive enzyme for use as a therapeutic agent against P. aeruginosa infection.
ESTHER : Fan_2017_Front.Microbiol_8_1950
PubMedSearch : Fan_2017_Front.Microbiol_8_1950
PubMedID: 29067011
Gene_locus related to this paper: 9bact-Aii810

Title : Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes - Sun_2017_Mol.Plant_10_1293
Author(s) : Sun H , Wu S , Zhang G , Jiao C , Guo S , Ren Y , Zhang J , Zhang H , Gong G , Jia Z , Zhang F , Tian J , Lucas WJ , Doyle JJ , Li H , Fei Z , Xu Y
Ref : Mol Plant , 10 :1293 , 2017
Abstract : The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima x C. moschata interspecific F(1) hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops.
ESTHER : Sun_2017_Mol.Plant_10_1293
PubMedSearch : Sun_2017_Mol.Plant_10_1293
PubMedID: 28917590
Gene_locus related to this paper: cucma-a0a6j1jlb1 , cucma-a0a6j1i8e2 , cucma-a0a6j1hwl6

Title : Expression of Topoisomerase 1 and carboxylesterase 2 correlates with irinotecan treatment response in metastatic colorectal cancer - Shaojun_2017_Cancer.Biol.Ther__0
Author(s) : Shaojun C , Li H , Haixin H , Guisheng L
Ref : Cancer Biol Ther , :0 , 2017
Abstract : Topoisomerase 1 (TOPO-1) and carboxylesterase 2 (CES-2) are found to play crucial roles in the pathogenesis of various cancers. The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy. A total of 98 patients with mCRC were included in this study. The expression of TOPO-1 and CES-2 in mCRC tissues was evaluated by immunohistochemistry. For TOPO-1, 46 patients showed high expression and 52 patients showed low expression. For CES-2, 53 patients showed high expression and 45 patients showed low expression. The correlation between TOPO-1 or CES-2 expression and clinicopathological characteristics of mCRC patients was analyzed. Neither TOPO-1 nor CES-2 had significant correlation with age, gender, tumor site, tumor grade and metastatic sites in mCRC patients. However, high expression of CES-2 but not TOP-1 was positively correlated with better curative effect. Kaplan-Meier and log-rank test were applied to assess the correlation between progression-free survival (PFS)/overall survival (OS) and TOPO-1 or CES-2 expression in mCRC patients. High expression of TOPO-1 and CES-2 are correlated with longer PFS and OS. In summary, our findings suggest that TOPO-1 and CES-2 may play important roles irinotecan sensitivity in mCRC patients. Evaluation of expression of TOPO-1 and CES-2 may provide preliminary clinical evidence for the management of irinotecan-based therapy in mCRC patients.
ESTHER : Shaojun_2017_Cancer.Biol.Ther__0
PubMedSearch : Shaojun_2017_Cancer.Biol.Ther__0
PubMedID: 29261002

Title : Effects and mechanism of cerebroprotein hydrolysate on learning and memory ability in mice - An_2016_Genet.Mol.Res_15_
Author(s) : An L , Han X , Li H , Ma Y , Shi L , Xu G , Yuan G , Sun J , Zhao N , Sheng Y , Wang M , Du P
Ref : Genet Mol Res , 15 : , 2016
Abstract : Cerebroprotein hydrolysate is an extract from porcine brain tissue that acts on the central nervous system in various ways to protect neurons and improve memory, attention, and vigilance. This study examined the effect and mechanism of cerebroprotein hydrolysate on learning and memory in mice with scopolamine-induced impairment. Mice were given an intraperitoneal injection of scopolamine hydrobromide to establish a murine model of learning and memory impairment. After 35 successive days of cerebroprotein hydrolysate treatment, their behaviors were observed in the Morris water maze and step-down test. Superoxide dismutase (SOD), Na+-K+-ATPase, and acetylcholinesterase (AChE) activity, and malondialdehyde (MDA), gamma-aminobutyric acid (GABA), and glutamic acid (Glu) levels in the brain tissue of the mice were determined, and pathological changes in the hippocampus were examined. The results of the water-maze test showed that cerebroprotein hydrolysate shortened the escape latency and increased the number of platform crossings. In the step-down test, cerebroprotein hydrolysate treatment prolonged the step-down latency and reduced the number of errors; cerebroprotein hydrolysate increased the activity of SOD, Na+-K+-ATPase, and AChE, reduced the levels of MDA, decreased the Glu/GABA ratio in brain tissue, and reduced pathological changes in the hippocampus. The results indicate that cerebroprotein hydrolysate can improve learning and memory in mice with scopolamine-induced impairment. This effect may be associated with its ability to reduce injury caused by free radicals, improve acetylcholine function, and modulate the Glu/GABA learning and memory regulation system, reducing excitotoxicity caused by Glu.
ESTHER : An_2016_Genet.Mol.Res_15_
PubMedSearch : An_2016_Genet.Mol.Res_15_
PubMedID: 27525868

Title : Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review - Wang_2016_Am.J.Chin.Med__1
Author(s) : Wang ZY , Liu JG , Li H , Yang HM
Ref : Am J Chin Med , :1 , 2016
Abstract : Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.
ESTHER : Wang_2016_Am.J.Chin.Med__1
PubMedSearch : Wang_2016_Am.J.Chin.Med__1
PubMedID: 27848250

Title : Glutathione regulation-based dual-functional upconversion sensing-platform for acetylcholinesterase activity and cadmium ions - Fang_2016_Biosens.Bioelectron_87_545
Author(s) : Fang A , Chen H , Li H , Liu M , Zhang Y , Yao S
Ref : Biosensors & Bioelectronics , 87 :545 , 2016
Abstract : A dual-functional platform for the sensing of acetylcholinesterase (AChE) activity and cadmium ions (Cd2+) was developed based on the fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) via glutathione regulation. The detection mechanism is based on the fact that AuNPs can quench the fluorescence of UCNPs. AChE catalyzes the hydrolysis of acetylthiocholine (ATC) into thiocholine which reacts with AuNPs by S-Au conjunction and results the aggregation of AuNPs and change in fluorescence of UCNPs. Therefore, the AChE activity can be detected through the changes of the color of solution and fluorescence recovery of UCNPs. However, the presence of glutathione (GSH) can protect AuNPs from aggregation and enlarge the inter-particle distance between AuNPs and UCNPs. When Cd2+ is added into the stable mixture of AuNPs, GSH and AChE/ATC, Cd2+ could interact with GSH to form a spherical shaped (GSH)4Cd complex, which decreases the free GSH on the surface of AuNPs to weaken the stability of AuNPs and lead to the easily aggregation of them in the system. The aggregated-AuNPs are released from the surface of UCNPs, which results in the fluorescence of UCNPs gradually recovered. Under the optimized conditions, the detection limits of AChE activity and Cd2+ are estimated to be 0.015mU/mL and 0.2microM, respectively. The small molecules regulated dual-functional platform based on UCNPs/AuNPs is a simple, label-free method and can be applied for the turn-on fluorescence detection of AChE activity in human serum and Cd2+ in real water samples. The present work demonstrates a general strategy for the design of small molecules regulated multifunctional platform and will be expanded for different areas in the future.
ESTHER : Fang_2016_Biosens.Bioelectron_87_545
PubMedSearch : Fang_2016_Biosens.Bioelectron_87_545
PubMedID: 27611473

Title : Crystal structure of methylesterase family member 16 (MES16) from Arabidopsis thaliana - Li_2016_Biochem.Biophys.Res.Commun_474_226
Author(s) : Li H , Pu H
Ref : Biochemical & Biophysical Research Communications , 474 :226 , 2016
Abstract : Methylesterase family member 16 (MES16) is an integral component of chlorophyll breakdown. It catalyzes the demethylation of fluorescent chlorophyll catabolite (FCC) and pheophorbide in vitro, and specifically demethylates FCC in vivo. Here we report the crystal structure of MES16 from Arabidopsis thaliana at 2.8 A resolution. The structure confirm that MES16 is a member of the alpha/beta-hydrolase superfamily with Ser-87, His-239, and Asp-211 as the catalytic triad. Our biochemical studies reveal that MES16 has esterase activity with methyl-indole acetic acid as the substrate, and the catalytically essential role of Ser-87 has been demonstrated.
ESTHER : Li_2016_Biochem.Biophys.Res.Commun_474_226
PubMedSearch : Li_2016_Biochem.Biophys.Res.Commun_474_226
PubMedID: 27109476
Gene_locus related to this paper: arath-AT4G16690

Title : Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism - Hu_2016_Mol.Cell.Endocrinol_423_60
Author(s) : Hu X , Chen R , Fu C , Fan X , Wang J , Qian J , Yi S , Li C , Luo J , Su J , Zhang S , Xie B , Zheng H , Lai Y , Chen Y , Li H , Gu X , Chen S , Shen Y
Ref : Mol Cell Endocrinol , 423 :60 , 2016
Abstract : Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency.
ESTHER : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedSearch : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedID: 26777470
Gene_locus related to this paper: human-TG

Title : Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors - Cheng_2016_Nat.Commun_7_13396
Author(s) : Cheng H , Ang HY , C AEF , Li P , Fang HT , Liu TM , Kong SL , Chin ML , Ling WY , Lim EK , Li H , Huber T , Loh KM , Loh YH , Lim B
Ref : Nat Commun , 7 :13396 , 2016
Abstract : Recent efforts have attempted to convert non-blood cells into hematopoietic stem cells (HSCs) with the goal of generating blood lineages de novo. Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally distant lineage (fibroblasts) into 'induced hematopoietic progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase+ megakaryocytes and phagocytic myeloid cells in vitro and can also engraft immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4 months in vivo. Molecularly, iHPs transcriptionally resemble native Kit+ hematopoietic progenitors. Mechanistically, reprogramming factor Lmo2 implements a hematopoietic programme in fibroblasts by rapidly binding to and upregulating the Hhex and Gfi1 genes within days. Moreover the reprogramming transcription factors also require extracellular BMP and MEK signalling to cooperatively effectuate reprogramming. Thus, the transcription factors that orchestrate embryonic hematopoiesis can artificially reconstitute this programme in developmentally distant fibroblasts, converting them into engraftable blood progenitors.
ESTHER : Cheng_2016_Nat.Commun_7_13396
PubMedSearch : Cheng_2016_Nat.Commun_7_13396
PubMedID: 27869129

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Does cadmium affect the toxicokinetics of permethrin in Chironomus dilutus at sublethal level? Evidence of enzymatic activity and gene expression - Chen_2016_Environ.Pollut_218_1005
Author(s) : Chen X , Li H , Zhang J , Ding Y , You J
Ref : Environ Pollut , 218 :1005 , 2016
Abstract : Pyrethroids and metals were simultaneously detected in aquatic environment and showed antagonistic lethality to the benthic invertebrate, Chironomus dilutus. Accelerated biotransformation of pyrethroids in organism by the presence of metals was proposed as the likely reason for the antagonism. Mechanistic explanation for the role of toxicokinetics of pyrethroids in the antagonistic interaction would help better understanding the reasons for the joint toxicity. The goal was achieved in the current study by evaluating the impact of cadmium on toxicokinetic parameters of permethrin in C. dilutus, and by explaining the interaction through quantifying the activity and gene expression of biotransformation-related enzymes. Toxicokinetic parameters were simulated using a first-order kinetic model. Bioconcentration factors and uptake and elimination rate constants for permethrin were not significantly changed with the addition of cadmium at sublethal level, neither did the activity of enzymes, including glutathione S-transferase (GST), carboxylesterase (CarE), catalase and lipid peroxidation. Yet, the activities of metabolism-related enzymes (GST and CarE) showed an elevating tendency with adding cadmium. Furthermore, the expression of metabolism-related genes, including cytochrome P450 and glutathione S-transferase genes were significantly up-regulated in C. dilutus exposed to a mixture of permethrin and cadmium compared with permethrin only. Although co-exposure to cadmium did not induce toxicokinetic changes of permethrin in C. dilutus, it did enhance the activity of metabolic enzymes which were encoded by the metabolism-related genes, suggesting an acceleration of biotransformation of permethrin to less toxic metabolites in the midges. This possibly explained the antagonistic interaction for permethrin and cadmium.
ESTHER : Chen_2016_Environ.Pollut_218_1005
PubMedSearch : Chen_2016_Environ.Pollut_218_1005
PubMedID: 27567170

Title : Artificial hydrolase based on carbon nanotubes conjugated with peptides - Zhang_2016_Nanoscale_8_16851
Author(s) : Zhang Q , He X , Han A , Tu Q , Fang G , Liu J , Wang S , Li H
Ref : Nanoscale , 8 :16851 , 2016
Abstract : An artificial enzyme was constructed by attaching short peptides with active sites (SHELKLKLKL, WLKLKLKL) onto carbon nanotubes (CNT). It was found that the combination of SHE amino acids was essential to form a catalytic triad. W was also incorporated into this artificial enzyme and acted as a substrate binding site, thus producing an enzyme model with synergism of 67.7% catalytic groups and 32.3% binding groups, CNT-(SHE/W)2:1-LKLKLKL. When the peptide SHELKLKLKL was attached with the catalytic triad site close to the surface of CNT, the composite had higher activity than a leucine-attached system terminated with the catalytic triad site, suggesting that CNT not only served as a platform for attaching active amino acids, but also created a hydrophobic microenvironment and facilitated the proton transfer process to enhance the catalytic activity. The artificial enzyme exhibited Michaelis-Menten behaviour, indicating that it was indeed a mimic of the corresponding natural enzyme. This work showed that a well-designed combination of CNT and short peptides containing active sites can mimic a natural enzyme.
ESTHER : Zhang_2016_Nanoscale_8_16851
PubMedSearch : Zhang_2016_Nanoscale_8_16851
PubMedID: 27714071

Title : Enhanced alpha-Zearalenol Hydrolyzing Activity of a Mycoestrogen-Detoxifying Lactonase by Structure-Based Engineering - Xu_2016_ACS.Catal_6_7657
Author(s) : Xu Z , Liu W , Chen CC , Li Q , Huang JW , Ko TP , Liu G , Peng W , Cheng YS , Chen Y , Jin J , Li H , Zheng Y , Guo RT
Ref : ACS Catal , 6 :7657 , 2016
Abstract : The enzyme ZHD101 from Clonostachys rosea hydrolyzes and deactivates the mycotoxin zearalenone (ZEN) and its zearalenol (ZOL) derivatives. ZHD101 prefers ZEN to ZOL as its substrate, but ZOL, especially the -form, shows higher estrogenic toxicity than ZEN. To enhance alpha-ZOL selectivity, we solved the complex structures of ZHD101 with both ZOLs and modified several lactone-surrounding residues. Among the mutants, V153H maintained activity for ZEN but showed a 3.7-fold increase in specific activity against alpha-ZOL, with an 2.7-fold reduction in substrate affinity but a 5.2-fold higher turnover rate. We then determined two V153H/ZOL complex structures. Here, the alpha-ZOL lactone ring is hydrogen-bonded to the H153 side chain, yielding a larger space for H242 to reconstitute the catalytic triad. In conclusion, structure-based engineering was successfully employed to improve the ZHD101 activity toward the more toxic alpha-ZOL, with great potential in further industrial applications.
ESTHER : Xu_2016_ACS.Catal_6_7657
PubMedSearch : Xu_2016_ACS.Catal_6_7657
Gene_locus related to this paper: biooc-ZHD101

Title : Paper-based fluorescent sensor for rapid naked-eye detection of acetylcholinesterase activity and organophosphorus pesticides with high sensitivity and selectivity - Chang_2016_Biosens.Bioelectron_86_971
Author(s) : Chang J , Li H , Hou T , Li F
Ref : Biosensors & Bioelectronics , 86 :971 , 2016
Abstract : Various strategies have been proposed for the sensing of acetylcholinesterase (AChE) activity and organophosphorus pesticides (OPs). However, the practical application of most methods is restricted by their intrinsic drawbacks such as complexity, long analysis time, and high cost. Thus, it is highly desirable to develop simple, fast and sensitive approaches for AChE activity and OPs detection. Herein, we reported a simple paper-based fluorescent sensor (PFS) based on the aggregation induced emission (AIE) effect of tetraphenylethylene (TPE) and the addition reaction capability of maleimide, which has been used as a powerful tool for rapid naked-eye detection of AChE activity and OPs. The introduction of TPE provides the probe with unique fluorescence property in solid state and is of great importance for improving the sensitivity of PFS. The hydrolysis product of acetylthiocholine catalyzed by AChE induced the maleimide ring destruction and activated the fluorescence performance of TPE. Given that AChE activity can be specifically inhibited by OPs, the as-proposed PFS can also be utilized for sensitive detection of OPs. Meanwhile, the variation of fluorescence signal can be readily detected by naked eyes, and low detection limits of 2.5mUmL-1 and 0.5ngmL-1 for AChE activity and OPs are obtained, respectively. Moreover, it has been successfully applied for AChE activity and OPs detection in diluted human serum samples, showing its great potential to be applied in real samples. Thus, this strategy possesses considerable advantages of simplicity, rapid detection, portability, cost efficiency and visualization.
ESTHER : Chang_2016_Biosens.Bioelectron_86_971
PubMedSearch : Chang_2016_Biosens.Bioelectron_86_971
PubMedID: 27498323

Title : Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in Caenorhabditis elegans - Li_2016_Oxid.Med.Cell.Longev_2016_4856761
Author(s) : Li H , Shi R , Ding F , Wang H , Han W , Ma F , Hu M , Ma CW , Huang Z
Ref : Oxid Med Cell Longev , 2016 :4856761 , 2016
Abstract : Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson's disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.
ESTHER : Li_2016_Oxid.Med.Cell.Longev_2016_4856761
PubMedSearch : Li_2016_Oxid.Med.Cell.Longev_2016_4856761
PubMedID: 27885333

Title : Muscle-specific deletion of comparative gene identification-58 (CGI-58) causes muscle steatosis but improves insulin sensitivity in male mice - Xie_2015_Endocrinology_156_1648
Author(s) : Xie P , Kadegowda AK , Ma Y , Guo F , Han X , Wang M , Groban L , Xue B , Shi H , Li H , Yu L
Ref : Endocrinology , 156 :1648 , 2015
Abstract : Intramyocellular accumulation of lipids is often associated with insulin resistance. Deficiency of comparative gene identification-58 (CGI-58) causes cytosolic deposition of triglyceride (TG)-rich lipid droplets in most cell types, including muscle due to defective TG hydrolysis. It was unclear, however, whether CGI-58 deficiency-induced lipid accumulation in muscle influences insulin sensitivity. Here we show that muscle-specific CGI-58 knockout mice relative to their controls have increased glucose tolerance and insulin sensitivity on a Western-type high-fat diet, despite TG accumulation in both heart and oxidative skeletal muscle and cholesterol deposition in heart. Although the intracardiomyocellular lipid deposition results in cardiac ventricular fibrosis and systolic dysfunction, muscle-specific CGI-58 knockout mice show increased glucose uptake in heart and soleus muscle, improved insulin signaling in insulin-sensitive tissues, and reduced plasma concentrations of glucose, insulin, and cholesterol. Hepatic contents of TG and cholesterol are also decreased in these animals. Cardiac steatosis is attributable, at least in part, to decreases in cardiac TG hydrolase activity and peroxisome proliferator-activated receptor-alpha/peroxisome proliferator-activated receptor-gamma coactivator-1-dependent mitochondrial fatty acid oxidation. In conclusion, muscle CGI-58 deficiency causes cardiac dysfunction and fat deposition in oxidative muscles but induces a series of favorable metabolic changes in mice fed a high-fat diet.
ESTHER : Xie_2015_Endocrinology_156_1648
PubMedSearch : Xie_2015_Endocrinology_156_1648
PubMedID: 25751639

Title : Effects of supplementation of rumen-protected choline on growth performance, meat quality and gene expression in longissimus dorsi muscle of lambs - Li_2015_Arch.Anim.Nutr_69_340
Author(s) : Li H , Wang H , Yu L , Wang M , Liu S , Sun L , Chen Q
Ref : Arch Anim Nutr , 69 :340 , 2015
Abstract : This study determined the effects of rumen-protected choline (RPC) on growth performance, blood lipids, meat quality and expression of genes involved in fatty-acid metabolism in young lambs. A total of 24 Dorper x Hu lambs (about 20 kg body weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and 0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of lambs, whereas treatments had no significant effect on feed intake. The pH values of meat were increased at 0.25% RPC and both, dripping loss and shear force of meat, were significantly decreased in RPC-supplemented lambs. No significant changes were observed for dressing percentage and intramuscular fat. RPC supplementations had no significant effect on the concentrations of triglycerides and cholesterols in serum, but the concentration of high-density lipoprotein was decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75% RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and had no effect on CD36 gene. The results of this study showed that supplementation of 0.25% RPC could promote growth performance of lambs and improve meat quality. This may be mediated by effects on blood lipid profiles and the metabolism of fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC supplementation need to be validated with a larger number of animals. Higher doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC expression.
ESTHER : Li_2015_Arch.Anim.Nutr_69_340
PubMedSearch : Li_2015_Arch.Anim.Nutr_69_340
PubMedID: 26305383

Title : Molecular cloning and characterization of a thermostable lipase from deep-sea thermophile Geobacillus sp. EPT9 - Zhu_2015_World.J.Microbiol.Biotechnol_31_295
Author(s) : Zhu Y , Li H , Ni H , Xiao A , Li L , Cai H
Ref : World J Microbiol Biotechnol , 31 :295 , 2015
Abstract : A gene (1,254 bp) encoding a lipase was identified from a deep-sea hydrothermal field thermophile Geobacillus sp. EPT9. The open reading frame of this gene encoded 417 amino acid residues. The gene was cloned, overexpressed in Escherichia coli, and the target protein was purified to homogeneity. The purified recombinant enzyme presented a molecular mass of 44.8 kDa. When p-nitrophenyl palmitate was used as a substrate, the recombinant lipase was optimally active at 55 degrees C and pH 8.5. The recombinant enzyme retained 44 % residual activity after incubation at 80 degrees C for 1 h, which indicated that Geobacillus sp. EPT9 lipase was thermostable. Homology modeling of strain EPT9 lipase was developed with the lipase from Bacillus sp. L2 as a template. The core structure exhibits an alpha/beta-hydrolase fold and the typical catalytic triad might consist of Ser142, Asp346, and His387. The enzymatic activity of EPT9 lipase was inhibited by addition of phenylmethylsulfonyl fluoride, indicating that it contains serine residue, which plays an important role in the catalytic mechanism.
ESTHER : Zhu_2015_World.J.Microbiol.Biotechnol_31_295
PubMedSearch : Zhu_2015_World.J.Microbiol.Biotechnol_31_295
PubMedID: 25388475

Title : Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke - Lin_2015_Neurology_85_1585
Author(s) : Lin J , Zheng H , Cucchiara BL , Li J , Zhao X , Liang X , Wang C , Li H , Mullen MT , Johnston SC , Wang Y
Ref : Neurology , 85 :1585 , 2015
Abstract : OBJECTIVE: To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke.
METHODS: We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days.
RESULTS: The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 +/- 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase).
CONCLUSIONS: Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events.
ESTHER : Lin_2015_Neurology_85_1585
PubMedSearch : Lin_2015_Neurology_85_1585
PubMedID: 26311748

Title : Identification and Characterization of Lipase Activity and Immunogenicity of LipL from Mycobacterium tuberculosis - Cao_2015_PLoS.One_10_e0138151
Author(s) : Cao J , Dang G , Li H , Li T , Yue Z , Li N , Liu Y , Liu S , Chen L
Ref : PLoS ONE , 10 :e0138151 , 2015
Abstract : Lipids and lipid-metabolizing esterases/lipases are highly important for the mycobacterial life cycle and, possibly, for mycobacterial virulence. In this study, we expressed 10 members of the Lip family of Mycobacterium tuberculosis. Among the 10 proteins, LipL displayed a significantly high enzymatic activity for the hydrolysis of long-chain lipids. The optimal temperature for the lipase activity of LipL was demonstrated to be 37 degrees C, and the optimal pH was 8.0. The lipase active center was not the conserved motif G-x-S-x-G, but rather the S-x-x-K and GGG motifs, and the key catalytic amino acid residues were identified as G50, S88, and K91, as demonstrated through site-directed mutagenesis experiments. A three-dimensional modeling structure of LipL was constructed, which showed that the GGG motif was located in the surface of a pocket structure. Furthermore, the subcellular localization of LipL was demonstrated to be on the mycobacterial surface by Western blot analysis. Our results revealed that the LipL protein could induce a strong humoral immune response in humans and activate a CD8+ T cell-mediated response in mice. Overall, our study identified and characterized a novel lipase denoted LipL from M. tuberculosis, and demonstrated that LipL functions as an immunogen that activates both humoral and cell-mediated responses.
ESTHER : Cao_2015_PLoS.One_10_e0138151
PubMedSearch : Cao_2015_PLoS.One_10_e0138151
PubMedID: 26398213
Gene_locus related to this paper: myctu-Rv1076 , myctu-Rv2485c , myctu-Rv3097c

Title : Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats - Shen_2015_Stroke_46_2607
Author(s) : Shen H , Chen Z , Wang Y , Gao A , Li H , Cui Y , Zhang L , Xu X , Wang Z , Chen G
Ref : Stroke , 46 :2607 , 2015
Abstract : BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction.
METHODS: In vivo, 228 Sprague-Dawley rats were used. An experimental SAH model was induced by single blood injection to prechiasmatic cistern. Primary cultured hippocampal neurons were exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation, neurological scoring, and Morris water maze were performed to evaluate the mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the expressions of neurexin-1beta and neuroligin-1 and the interaction between neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by their overexpression. The formation of excitatory synapses was inhibited by oxyhemoglobin treatment, which was significantly ameliorated by overexpression of neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1 overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin-1beta and neuroligin-1 knockdown induced an opposite effect.
CONCLUSIONS: Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the interaction between them and the formation of excitatory synapses, which is helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin-1 might be good targets for improving cognitive function after SAH.
ESTHER : Shen_2015_Stroke_46_2607
PubMedSearch : Shen_2015_Stroke_46_2607
PubMedID: 26219651

Title : Identification of novel esterase-active enzymes from hot environments by use of the host bacterium Thermus thermophilus - Leis_2015_Front.Microbiol_6_275
Author(s) : Leis B , Angelov A , Mientus M , Li H , Pham VT , Lauinger B , Bongen P , Pietruszka J , Goncalves LG , Santos H , Liebl W
Ref : Front Microbiol , 6 :275 , 2015
Abstract : Functional metagenomic screening strategies, which are independent of known sequence information, can lead to the identification of truly novel genes and enzymes. Since E. coli has been used exhaustively for this purpose as a host, it is important to establish alternative expression hosts and to use them for functional metagenomic screening for new enzymes. In this study we show that Thermus thermophilus HB27 is an excellent screening host and can be used as an alternative provider of truly novel biocatalysts. In a previous study we constructed mutant strain BL03 with multiple markerless deletions in genes for major extra- and intracellular lipolytic activities. This esterase-diminished strain was no longer able to grow on defined minimal medium supplemented with tributyrin as the sole carbon source and could be used as a host to screen for metagenomic DNA fragments that could complement growth on tributyrin. Several thousand single fosmid clones from thermophilic metagenomic libraries from heated compost and hot spring water samples were subjected to a comparative screening for esterase activity in both T. thermophilus strain BL03 and E. coli EPI300. We scored a greater number of active esterase clones in the thermophilic bacterium than in the mesophilic E. coli. From several thousand functionally screened clones only two thermostable alpha/beta-fold hydrolase enzymes with high amino acid sequence similarity to already characterized enzymes were identifiable in E. coli. In contrast, five further fosmids were found that conferred lipolytic activities in T. thermophilus only. Four open reading frames (ORFs) were found which did not share significant similarity to known esterase enzymes but contained the conserved GXSXG motif regularly found in lipolytic enzymes. Two of the genes were expressed in both hosts and the novel thermophilic esterases, which based on their primary structures could not be assigned to known esterase or lipase families, were purified and preliminarily characterized. Our work underscores the benefit of using additional screening hosts other than E. coli for the identification of novel biocatalysts with industrial relevance.
ESTHER : Leis_2015_Front.Microbiol_6_275
PubMedSearch : Leis_2015_Front.Microbiol_6_275
PubMedID: 25904908

Title : The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis - Fujita-Jimbo_2015_Mol.Autism_6_17
Author(s) : Fujita-Jimbo E , Tanabe Y , Yu Z , Kojima K , Mori M , Li H , Iwamoto S , Yamagata T , Momoi MY , Momoi T
Ref : Mol Autism , 6 :17 , 2015
Abstract : BACKGROUND: Autism spectrum disorder (ASD) has a complex genetic etiology. Some symptoms and mutated genes, including neuroligin (NLGN), neurexin (NRXN), and SH3 and multiple ankyrin repeat domains protein (SHANK), are shared by schizophrenia and ASD. Little is known about the molecular pathogenesis of ASD. One of the possible molecular pathogenesis is an imbalance of excitatory and inhibitory receptors linked with the NLGN-PSD-95-SHANK complex via postsynaptic density protein/Drosophila disc large tumor suppressor/zonula occludens-1 protein (PDZ) binding. In the present study, we focused on GPR85 as a candidate gene for ASD because the C-terminal amino acid sequence of GPR85 [Thr-Cys-Val-Ile (YCVI)] is classified as a type II PDZ-binding motif, and GPR85 is a risk factor for schizophrenia. GPR85 is an orphan receptor that regulates neural and synaptic plasticity and modulates diverse behaviors, including learning and memory. While searching for molecules that associate with GPR85, we found that GPR85 was associated with postsynaptic density protein (PSD)-95 linked with NLGN in the brain.
METHODS: We examined the proteins that associate with the C-terminal sequence of GPR85 by pull-down assay and immunoblot analysis and searched for a mutation of the GPR85 gene in patients with ASD. We used immunostaining to examine the intracellular localization of mutated GPR85 and its influence on the morphology of cells and neurons.
RESULTS: The C-terminal sequence of GPR85 interacted with PSD-95 at PDZ1, while NLGN interacted with PSD-95 at PDZ3. Two male patients with ASD from independent Japanese families possessed inherited missense mutations at conserved sites in GPR85: one had T1033C (M152T) and the other had G1239T (V221L). These mutations were located in a domain related to G protein interaction and signal transduction. In contrast to wild-type GPR85, mutated GPR85 was more preferentially accumulated, causing endoplasmic reticulum stress, and disturbed the dendrite formation of hippocampal neurons.
CONCLUSIONS: GPR85 associated with the PSD-95 linked with NLGN, which is related to ASD. GPR85 carrying the mutations detected in ASD patients disturbed dendrite formation that could be the candidate for molecular pathogenesis of ASD through the associated NLGN-PSD-95 receptor complex.
ESTHER : Fujita-Jimbo_2015_Mol.Autism_6_17
PubMedSearch : Fujita-Jimbo_2015_Mol.Autism_6_17
PubMedID: 25780553

Title : Joint toxicity of sediment-associated permethrin and cadmium to Chironomus dilutus: The role of bioavailability and enzymatic activities - Chen_2015_Environ.Pollut_207_138
Author(s) : Chen X , Li H , You J
Ref : Environ Pollut , 207 :138 , 2015
Abstract : Pyrethroid insecticides and metals commonly co-occurred in sediment and caused toxicity to benthic organisms jointly. To improve accuracy in assessing risk of the sediments contaminated by insecticides and metals, it is of great importance to understand interaction between the contaminants and reasons for the interaction. In the current study, permethrin and cadmium were chosen as representative contaminants to study joint toxicity of pyrethroids and metals to a benthic invertebrate Chironomus dilutus. A median effect/combination index-isobologram was applied to evaluate the interaction between sediment-bound permethrin and cadmium at three dose ratios. Antagonistic interaction was observed in the midges for all treatments. Comparatively, cadmium-dominated group (the ratio of toxicity contribution from permethrin and cadmium was 1:3) showed stronger antagonism than equitoxicity (1:1) and permethrin-dominated groups (3:1). The reasons for the observed antagonism were elucidated from two aspects, including bioavailability and enzymatic activity. The bioavailability of permethrin, expressed as the freely dissolved concentrations in sediment porewater and measured by solid phase microextraction, was not altered by the addition of cadmium, suggesting the change in permethrin bioavailability was not the reason for the antagonism. On the other hand, the activities of metabolic enzymes, glutathione S-transferase and carboxylesterase in the midges which were exposed to mixtures of permethrin and cadmium were significantly higher than those in the midges exposed to permethrin solely. Cadmium considerably enhanced the detoxifying processes of permethrin in the midges, which largely explained the observed antagonistic interaction between permethrin and cadmium.
ESTHER : Chen_2015_Environ.Pollut_207_138
PubMedSearch : Chen_2015_Environ.Pollut_207_138
PubMedID: 26367707

Title : Contribution of carboxylesterase and cytochrome p450 to the bioactivation and detoxification of isocarbophos and its enantiomers in human liver microsomes - Zhuang_2014_Toxicol.Sci_140_40
Author(s) : Zhuang XM , Wei X , Tan Y , Xiao WB , Yang HY , Xie JW , Lu C , Li H
Ref : Toxicol Sci , 140 :40 , 2014
Abstract : Organophosphorus pesticides are the most widely used pesticides in modern agricultural systems to ensure good harvests. Isocarbophos (ICP), with a potent acetylcholinesterase inhibitory effect is widely utilized to control a variety of leaf-eating and soil insects. However, the characteristics of the bioactivation and detoxification of ICP in humans remain unclear. In this study, the oxidative metabolism, esterase hydrolysis, and chiral inversion of ICP in human liver microsomes (HLMs) were investigated with the aid of a stereoselective LC/MS/MS method. The depletion of ICP in HLMs was faster in the absence of carboxylesterase inhibitor (BNPP) than in the presence of NADPH and BNPP, with t1/2 of 5.2 and 90 min, respectively. Carboxylesterase was found to be responsible for the hydrolysis of ICP, the major metabolic pathway. CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19 were all involved in the secondary metabolism pathway of desulfuration of ICP. Flavin-containing monooxygenase (FMO) did not contribute to the clearance of ICP. The hydrolysis and desulfuration of (+/-)ICP, (+)ICP, and (-)ICP in HLMs follow Michaelis-Menten kinetics. Individual enantiomers of ICP and its oxidative desulfuration metabolite isocarbophos oxon (ICPO) were found to be inhibitors of acetylcholinesterases at different extents. For example, (+/-)ICPO is more potent than ICP (IC50 0.031muM vs. 192muM), whereas (+)ICPO is more potent than (-)ICPO (IC50 0.017muM vs. 1.55muM). Given the finding of rapid hydrolysis of ICP and low abundance of oxidative metabolites presence in human liver, the current study highlights that human liver has a greater capacity for detoxification of ICP.
ESTHER : Zhuang_2014_Toxicol.Sci_140_40
PubMedSearch : Zhuang_2014_Toxicol.Sci_140_40
PubMedID: 24752505

Title : Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe - Liu_2014_Anal.Biochem_465C_172
Author(s) : Liu C , Shen Y , Yin P , Li L , Liu M , Zhang Y , Li H , Yao S
Ref : Analytical Biochemistry , 465C :172 , 2014
Abstract : A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl-1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity.
ESTHER : Liu_2014_Anal.Biochem_465C_172
PubMedSearch : Liu_2014_Anal.Biochem_465C_172
PubMedID: 25132563

Title : Genetic analysis of lipolytic activities in Thermus thermophilus HB27 - Leis_2014_J.Biotechnol_191_150
Author(s) : Leis B , Angelov A , Li H , Liebl W
Ref : J Biotechnol , 191 :150 , 2014
Abstract : The extremely thermophilic bacterium Thermus thermophilus HB27 displays lipolytic activity for the hydrolysis of triglycerides. In this study we performed a mutational in vivo analysis of esterases and lipases that confer growth on tributyrin. We interrupted 10 ORFs suspected to encode lipolytic enzymes. Two chromosomal loci were identified that resulted in reduced hydrolysis capabilities against tributyrin and various para-nitrophenyl acyl esters. By implementation of a convenient new one-step method which abstains from the use of selectable markers, a mutant strain with multiple scar-less deletions was constructed by sequentially deleting ORFs TT_C1787, TT_C0340, TT_C0341 and TT_C0904. The quadruple deletion mutant of T. thermophilus exhibited significantly lower lipolytic activity (approximately 25% residual activity compared to wild type strain) over a broad range of fatty acyl esters and had lost the ability to grow on agar plates containing tributyrin as the sole carbon source. Furthermore, we were able to determine the impact of each gene disruption on the lipolytic activity profile in this model organism and show that the esterase activity in T. thermophilus HB27 is due to a concerted action of several hydrolases having different substrate preferences and activities. The esterase-less T. thermophilus multi-deletion mutant from this study can be used as a screening and expression host for esterase genes from thermophiles or metagenomes.
ESTHER : Leis_2014_J.Biotechnol_191_150
PubMedSearch : Leis_2014_J.Biotechnol_191_150
PubMedID: 25102235

Title : Tanshinol protects hippocampus and attenuates vascular dementia development - Shi_2014_J.Asian.Nat.Prod.Res_16_667
Author(s) : Shi CG , Yang YS , Li H , Zhang Y , Wang N , Wang SM , Wang JD , Zhang SC
Ref : J Asian Nat Prod Res , 16 :667 , 2014
Abstract : Tanshinol (3-(3',4'-dihydroxyphenyl)-(2R)-lactic acid, TSL) is widely used in traditional Chinese medicine for the treatment of cardiovascular and cerebrovascular diseases. Here, we assessed whether TSL protected hippocampus and attenuated vascular dementia (VD) development in rats. The behavioral analysis showed that TSL could decrease the distance and latency time, and increase the swim speed in water maze in rats subjected to VD. TSL remarkably increased acetylcholine level and decreased acetylcholinesterase activity in rats subjected to VD. Likewise, TSL remarkably decreased malondialdehyde and increased superoxide dismutase levels in rats subjected to VD. Furthermore, treatment with TSL reduced the level of dead neurons in dentate gyrus. In addition, TSL upregulated growth-associated protein 43 (GAP43) and vascular endothelial growth factor (VEGF) expression and downregulated phosphorylated Akt (p-AKt) and phosphorylated glycogen synthase kinase (p-GSK3beta) expression in hippocampus in rats subjected to VD. These results suggest that TSL may be a potential compound in VD model.
ESTHER : Shi_2014_J.Asian.Nat.Prod.Res_16_667
PubMedSearch : Shi_2014_J.Asian.Nat.Prod.Res_16_667
PubMedID: 24957473

Title : The Effects of Sesquiterpenes-Rich Extract of Miq. on Amyloid- -Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice - Shi_2014_Oxid.Med.Cell.Longev_2014_451802
Author(s) : Shi SH , Zhao X , Liu B , Li H , Liu AJ , Wu B , Bi KS , Jia Y
Ref : Oxid Med Cell Longev , 2014 :451802 , 2014
Abstract : As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Abeta 1-42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-beta (Abeta), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions.
ESTHER : Shi_2014_Oxid.Med.Cell.Longev_2014_451802
PubMedSearch : Shi_2014_Oxid.Med.Cell.Longev_2014_451802
PubMedID: 25180067

Title : Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Abeta - Liu_2014_Eur.J.Pharmacol_738C_206
Author(s) : Liu Z , Zhao X , Liu B , Liu AJ , Li H , Mao X , Wu B , Bi KS , Jia Y
Ref : European Journal of Pharmacology , 738C :206 , 2014
Abstract : Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS. In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Abeta1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Abeta1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Abeta1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Abeta1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Abeta1-42, however, JuA noticeably improved the histopathological damage. Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimers disease.
ESTHER : Liu_2014_Eur.J.Pharmacol_738C_206
PubMedSearch : Liu_2014_Eur.J.Pharmacol_738C_206
PubMedID: 24886882

Title : Genome characteristics reveal the impact of lichenization on lichen-forming fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota) - Wang_2014_BMC.Genomics_15_34
Author(s) : Wang YY , Liu B , Zhang XY , Zhou QM , Zhang T , Li H , Yu YF , Zhang XL , Hao XY , Wang M , Wang L , Wei JC
Ref : BMC Genomics , 15 :34 , 2014
Abstract : BACKGROUND: Lichen is a classic mutualistic organism and the lichenization is one of the fungal symbioses. The lichen-forming fungus Endocarpon pusillum is living in symbiosis with the green alga Diplosphaera chodatii Bialsuknia as a lichen in the arid regions.
RESULTS: 454 and Illumina technologies were used to sequence the genome of E. pusillum. A total of 9,285 genes were annotated in the 37.5 Mb genome of E. pusillum. Analyses of the genes provided direct molecular evidence for certain natural characteristics, such as homothallic reproduction and drought-tolerance. Comparative genomics analysis indicated that the expansion and contraction of some protein families in the E. pusillum genome reflect the specific relationship with its photosynthetic partner (D. chodatii). Co-culture experiments using the lichen-forming fungus E. pusillum and its algal partner allowed the functional identification of genes involved in the nitrogen and carbon transfer between both symbionts, and three lectins without signal peptide domains were found to be essential for the symbiotic recognition in the lichen; interestingly, the ratio of the biomass of both lichen-forming fungus and its photosynthetic partner and their contact time were found to be important for the interaction between these two symbionts.
CONCLUSIONS: The present study lays a genomic analysis of the lichen-forming fungus E. pusillum for demonstrating its general biological features and the traits of the interaction between this fungus and its photosynthetic partner D. chodatii, and will provide research basis for investigating the nature of its drought resistance and symbiosis.
ESTHER : Wang_2014_BMC.Genomics_15_34
PubMedSearch : Wang_2014_BMC.Genomics_15_34
PubMedID: 24438332
Gene_locus related to this paper: endpu-u1ggx3 , endpu-u1hiw6 , endpu-u1gx33 , endpu-u1hli9 , endpu-u1hmu1 , endpu-u1htc7 , endpu-u1gu60

Title : Selective and sensitive detection of acetylcholinesterase activity using denatured protein-protected gold nanoclusters as a label-free probe - Li_2014_Analyst_139_285
Author(s) : Li H , Guo Y , Xiao L , Chen B
Ref : Analyst , 139 :285 , 2014
Abstract : Based on the fluorescence quenching of novel denatured protein-protected gold nanoclusters, a label-free detection method of acetylcholinesterase (AChE) activity has been developed. Using denatured bovine serum albumin (dBSA), in which 35 cysteine residues can interact polyvalently with Au nanoclusters (AuNCs) as a stabilizing agent, water-soluble and stable fluorescent gold nanoclusters were synthesized. The fluorescence of the AuNCs was quenched by thiocholine that was produced from the AChE hydrolysis of S-acetylthiocholine iodide (ACTI) to detect the AChE activity. The linear range of the method was 0.005-0.15 U mL(-1). The limit of detection (LOD) was 0.02 mU mL(-1). Other enzymes and metal ions, i.e., GPT, gamma-GT, GOx, K(+), Ca(2+) and Na(+), showed minimal interference. Using the fluorescence probe, satisfactory results for the detection of the AChE activity in human serum were obtained.
ESTHER : Li_2014_Analyst_139_285
PubMedSearch : Li_2014_Analyst_139_285
PubMedID: 24251311

Title : Upconversion nanoparticle-based fluorescence resonance energy transfer assay for organophosphorus pesticides - Long_2014_Biosens.Bioelectron_68C_168
Author(s) : Long Q , Li H , Zhang Y , Yao S