Cheng Q

References (17)

Title : Rs15285, a functional polymorphism located in lipoprotein lipase, predicts the risk and prognosis of gastric cancer - Shen_2023_Appl.Microbiol.Biotechnol__
Author(s) : Shen K , Zhou X , Hu L , Xiao J , Cheng Q , Wang Y , Liu K , Fan H , Xu Z , Yang L
Ref : Applied Microbiology & Biotechnology , : , 2023
Abstract : Lipoprotein lipase (LPL), a crucial gene in lipid metabolism, has a significant role in the progression of malignant tumors. The purpose of this research was to investigate the impact of rs15285 found in the LPL gene's 3'UTR region on the risk, biological behavior, and gastric cancer (GC) prognosis as well as to examine its potential function. Genotyping of rs15285 in 888 GC cases and 874 controls was conducted by SNaPshot technology. We used bioinformatics analysis and in vitro experiments to study the role of rs15285. First, this study revealed for the first time that polymorphism rs15285 increases the risk of GC (OR = 1.48, 95%CI = 1.16-1.89, P = 0.002). Although no relationship was found between rs12585 and the pathological features of GC, the prognosis of individuals with the rs12585 TT genotype was poorer than that of patients with the CC or CC+CT genotype (HR = 2.39 for TT vs. CC, P = 0.025; HR = 2.38 for TT vs. CC+CT, P = 0.025). In addition, bioinformatics analysis showed rs12585 may affect the binding of miRNAs to LPL, resulting in an increase of LPL expression to promote cancer progression. Ultimately, in vitro tests revealed that the rs15285 T allele increased LPL expression on the mRNA as well as the protein levels, promoting GC cell proliferation, invasion, and metastasis. The LPL rs12528 TT genotype increased the risk of GC and predicted a poor prognosis. Mechanistically, the rs15285 T allele could improve the expression of LPL, and thus promotes the malignant phenotype of GC. Therefore, our study may provide new biological predictors and a theoretical basis for the prognosis and customized therapy of stomach cancer patients. KEY POINTS: Rs15285 polymorphism is a risk factor for GC. Rs12585 TT genotype predicts a bad outcome in GC individuals. Rs15285 T allele enhances GC cells malignant biological behavior.
ESTHER : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedSearch : Shen_2023_Appl.Microbiol.Biotechnol__
PubMedID: 37036527
Gene_locus related to this paper: human-LPL

Title : Synergistic effects of ferulic acid esterase-producing lactic acid bacteria, cellulase and xylanase on the fermentation characteristics, fibre and nitrogen components and microbial community structure of Broussonetia papyrifera during ensiling - Yu_2023_J.Sci.Food.Agric__
Author(s) : Yu Q , Xu J , Li M , Xi Y , Sun H , Xie Y , Cheng Q , Li P , Chen C , Yang F , Zheng Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: The high fibre content of whole plants of Broussonetia papyrifera limits its efficient utilization. Ferulic acid esterase (FAE), in combination with xylanase, can effectively cleave the lignin-carbohydrate complex, promoting the function of cellulase. However, little is known about the impact of these additives on silage. To effectively utilize natural woody plant resources, FAE-producing Lactobacillus plantarum RO395, xylanase (XY) and cellulase (CE) were used to investigate the dynamic fermentation characteristics, fibre and nitrogen components and microbial community structure during B. papyrifera ensiling. RESULTS: B. papyrifera was either not treated (CK) or treated with FAE-producing lactic acid bacteria (LP), CE, XY, LP+CE, LP+XY or LP+CE+XY for 3, 7, 15, 30 or 60 days, respectively. In comparison with those in the CK treatment, the L. plantarum and enzyme treatments (LP+CE, LP+XY and LP+XY+CE), especially the LP+XY+CE treatment, significantly increased the lactic acid concentration and decreased the pH and the contents of acid detergent insoluble protein and NH(3) -N (P < 0.05). Enzyme addition improved the degradation efficiency of lignocellulose, and a synergistic effect was observed after enzyme treatment in combination with LP; in addition, the lowest acid detergent fibre, neutral detergent fibre, hemicellulose, and cellulose contents were detected after the LP+CE+XY treatment (P < 0.05). Moreover, CE, XY and LP additions significantly improved the microbial community structure, increased the relative abundance of Lactiplantibacillus and Firmicutes, and effectively inhibited undesirable bacterial (Enterobacter) growth during ensiling. CONCLUSION: FAE-producing L. plantarum and the two tested enzymes exhibited synergistic effects on improving the quality of silage, which indicates that this combination can serve as an efficient method for improved B. papyrifera silage utilization. This article is protected by copyright. All rights reserved.
ESTHER : Yu_2023_J.Sci.Food.Agric__
PubMedSearch : Yu_2023_J.Sci.Food.Agric__
PubMedID: 38146051

Title : Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes - Xie_2022_Biochem.Biophys.Res.Commun_641_93
Author(s) : Xie H , Liu S , Fu Y , Cheng Q , Wang P , Bi CL , Wang R , Chen MM , Fang M
Ref : Biochemical & Biophysical Research Communications , 641 :93 , 2022
Abstract : Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.
ESTHER : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedSearch : Xie_2022_Biochem.Biophys.Res.Commun_641_93
PubMedID: 36525929

Title : Assessing Dietary Pesticide Intake and Potential Health Effects: The Application of Global Metabolomics Analysis - Cheng_2022_J.Agric.Food.Chem__
Author(s) : Cheng Q , Liu QQ , Li K , Chang CH , Lu CA
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : Scientific information is not yet available to provide insight into how individual metabolome might be affected by the presence of pesticides in regular diets. This study aimed to evaluate the perturbation of metabolomic pathways in children who switched their diets from conventional foods to mostly organic foods for five consecutive days. We selected 46 child-matched spot urine samples with distinct differences of urinary pesticide metabolite levels between the conventional and organic eating days and then analyzed those urine samples on three analytical platforms to perform global metabolomics analysis. We found statistically significant perturbations of metabolic pathways relevant to inflammation, oxidative stress, and the demands of xenobiotic detoxification when children switched their conventional diets to mostly organic foods. The outcomes of this study allow us to extend the current understanding beyond organophosphate pesticides' acute toxicity of cholinesterase inhibition to the perturbation of metabolic pathways at dietary intake levels.
ESTHER : Cheng_2022_J.Agric.Food.Chem__
PubMedSearch : Cheng_2022_J.Agric.Food.Chem__
PubMedID: 35320672

Title : Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay - Juban_2021_Haematologica_106_1106
Author(s) : Juban G , Sakakini N , Chagraoui H , Cruz Hernandez D , Cheng Q , Soady K , Stoilova B , Garnett C , Waithe D , Otto G , Doondeea J , Usukhbayar B , Karkoulia E , Alexiou M , Strouboulis J , Morrissey E , Roberts I , Porcher C , Vyas P
Ref : Haematologica , 106 :1106 , 2021
Abstract : The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Here, through a detailed examination of hemopoiesis from murine GATA1s ES cells and GATA1s embryos we define defects in erythroid and megakaryocytic differentiation that occur relatively late in hemopoiesis. GATA1s causes an arrest late in erythroid differentiation in vivo, and even more profoundly in ES-cell derived cultures, with a marked reduction of Ter-119 cells and reduced erythroid gene expression. In megakaryopoiesis, GATA1s causes a differentiation delay at a specific stage, with accumulation of immature, kit-expressing CD41hi megakaryocytic cells. In this specific megakaryocytic compartment, there are increased numbers of GATA1s cells in S-phase of cell cycle and reduced number of apoptotic cells compared to GATA1 cells in the same cell compartment. There is also a delay in maturation of these immature GATA1s megakaryocytic lineage cells compared to GATA1 cells at the same stage of differentiation. Finally, even when GATA1s megakaryocytic cells mature, they mature aberrantly with altered megakaryocyte-specific gene expression and activity of the mature megakaryocyte enzyme, acetylcholinesterase. These studies pinpoint the hemopoietic compartment where GATA1s megakaryocyte myeloproliferation occurs, defining where molecular studies should now be focussed to understand the oncogenic action of GATA1s.
ESTHER : Juban_2021_Haematologica_106_1106
PubMedSearch : Juban_2021_Haematologica_106_1106
PubMedID: 32527952

Title : Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice - Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
Author(s) : Yao L , Cao B , Cheng Q , Cai W , Ye C , Liang J , Liu W , Tan L , Yan M , Li B , He J , Hwang SH , Zhang X , Wang C , Ai D , Hammock BD , Zhu Y
Ref : American Journal of Physiology Gastrointest Liver Physiol , 316 :G527 , 2019
Abstract : Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease.
ESTHER : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedSearch : Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527
PubMedID: 30789748

Title : Muscarinic cholinergic signaling and overactive bladder-like symptoms associated with invasive bladder cancer - Wei_2018_Oncol.Lett_16_775
Author(s) : Wei W , Wang M , Li Y , Meng Q , Tang Y , Lu H , Yu W , Cheng Q , Xu L , Jian S , Wu Y , Yi X , Xie K
Ref : Oncol Lett , 16 :775 , 2018
Abstract : The objective of the present study was to explore the association between muscarinic cholinergic signaling and urothelial bladder tumors. Possible associations among overactive bladder (OAB) symptoms and bladder tumors were retrospectively investigated using a multicenter Chinese database with prospectively collected data since 2010. Firstly, it was demonstrated that OAB symptoms, such as urgency, were more severe in patients with invasive bladder cancer and were associated with a reduced prognosis. Following this, muscarinic cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R upregulation was associated with a reduced progression free survival (PFS) time. Additionally, it was also demonstrated that muscarinic cholinergic receptor 2 (M2R) was upregulated in the sub-urothelium, and this was also associated with a reduced PFS time. Furthermore, it was determined that cholinesterase and acetylcholinesterase were lower in invasive cancer than in non-invasive cancer. In conclusion, the results indicated that M3R expression was downregulated in invasive bladder cancer, which may have a role as a protective anti-oncogene, in contrast to its oncogenic role in numerous other cancer types. Therefore, muscarinic cholinergic signaling may be a novel therapeutic target for treating bladder cancer.
ESTHER : Wei_2018_Oncol.Lett_16_775
PubMedSearch : Wei_2018_Oncol.Lett_16_775
PubMedID: 29963145

Title : The effect of alpha7 nicotinic receptor activation on glutamatergic transmission in the hippocampus - Cheng_2015_Biochem.Pharmacol_97(4)_439
Author(s) : Cheng Q , Yakel JL
Ref : Biochemical Pharmacology , 97 :439 , 2015
Abstract : Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory, however the cellular mechanism of these actions remains elusive. With help from newly developed biosensors and optogenetic tools, recent studies provide new insights on signaling mechanisms involved in the activation of nAChRs. Here we will review alpha7 nAChR's action in the tri-synaptic pathway in the hippocampus. The effects of alpha7 nAChR activation via either exogenous compounds or endogenous cholinergic innervation are detailed for spontaneous and evoked glutamatergic synaptic transmission and synaptic plasticity, as well as the underlying signaling mechanisms. In summary, alpha7 nAChRs trigger intracellular calcium rise and calcium-dependent signaling pathways to enhance glutamate release and induce glutamatergic synaptic plasticity.
ESTHER : Cheng_2015_Biochem.Pharmacol_97(4)_439
PubMedSearch : Cheng_2015_Biochem.Pharmacol_97(4)_439
PubMedID: 26212541

Title : A sensitive LC-MS\/MS method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine with application to a clinical pharmacokinetic study - Zhou_2014_Biomed.Chromatogr_28_994
Author(s) : Zhou T , Zhao T , Cheng Q , Liu S , Xu L , Tan W
Ref : Biomedical Chromatography , 28 :994 , 2014
Abstract : A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R-bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 mm ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R-bambuterol and R-terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R-bambuterol involving 10 healthy volunteers. Copyright (c) 2013 John Wiley & Sons, Ltd.
ESTHER : Zhou_2014_Biomed.Chromatogr_28_994
PubMedSearch : Zhou_2014_Biomed.Chromatogr_28_994
PubMedID: 24357101

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

Title : Characterization of the multiple CRISPR loci on Streptomyces linear plasmid pSHK1 - Guo_2011_Acta.Biochim.Biophys.Sin.(Shanghai)_43_630
Author(s) : Guo P , Cheng Q , Xie P , Fan Y , Jiang W , Qin Z
Ref : Acta Biochim Biophys Sin (Shanghai) , 43 :630 , 2011
Abstract : The complete nucleotide sequence including the novel telomere sequence of Streptomyces linear plasmid pSHK1 consists of 187,263-bp, 158 genes, in which 51 genes resemble those of the linear plasmid SCP1 of Streptomyces coelicolor A3(2), and 20 genes encode transposases. Strikingly, the repetitive CRISPRs (clustered regularly interspaced short palindromic repeats) and cas (CRISPR-associated) genes were found, including a cluster of eight cas genes, in the order cas2B-cas1B-cas3B-cas5-cas4-cas2A-cas1A-cas3A, bracketed by a pair of divergent CRISPRs, and five other dispersed CRISPRs. The cas2B-cas1B-cas3B-cas5 or cas4-cas2A-cas1A genes were co-transcribed. Protein-protein interactions between Cas5 and Cas1A, 2A, 2B, 3B were detected by yeast two-hybrids, indicating a critical role of Cas5 for the formation of protein complexes. By polymerase chain reaction and Southern hybridization, 12 cas4 genes including three on linear plasmids were found among 75 newly isolated Streptomyces strains. The paired-CRISPRs and bracketed cas were also conserved in several other Streptomyces or actinomycete species. However, unlike other bacteria, the CRISPRs-cas in pSHK1 could not provide immunity against introduction of phage PhiC31 and plasmid containing the particular spacers in Streptomyces.
ESTHER : Guo_2011_Acta.Biochim.Biophys.Sin.(Shanghai)_43_630
PubMedSearch : Guo_2011_Acta.Biochim.Biophys.Sin.(Shanghai)_43_630
PubMedID: 21705768
Gene_locus related to this paper: 9acto-b0lty2

Title : Comparative genomics of the neglected human malaria parasite Plasmodium vivax - Carlton_2008_Nature_455_757
Author(s) : Carlton JM , Adams JH , Silva JC , Bidwell SL , Lorenzi H , Caler E , Crabtree J , Angiuoli SV , Merino EF , Amedeo P , Cheng Q , Coulson RM , Crabb BS , Del Portillo HA , Essien K , Feldblyum TV , Fernandez-Becerra C , Gilson PR , Gueye AH , Guo X , Kang'a S , Kooij TW , Korsinczky M , Meyer EV , Nene V , Paulsen I , White O , Ralph SA , Ren Q , Sargeant TJ , Salzberg SL , Stoeckert CJ , Sullivan SA , Yamamoto MM , Hoffman SL , Wortman JR , Gardner MJ , Galinski MR , Barnwell JW , Fraser-Liggett CM
Ref : Nature , 455 :757 , 2008
Abstract : The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
ESTHER : Carlton_2008_Nature_455_757
PubMedSearch : Carlton_2008_Nature_455_757
PubMedID: 18843361
Gene_locus related to this paper: plakh-b3lb44 , plavi-a5kcq0 , plavs-a5k2k6 , plavs-a5k3z4 , plavs-a5k4s6 , plavs-a5k5e4 , plavs-a5k7t5 , plavs-a5k686 , plavs-a5kaa1 , plavs-a5kaa3 , plavs-a5kas6 , plavs-a5kcm2

Title : Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]-L-valine] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes - Cheng_2008_J.Pharmacol.Exp.Ther_327_683
Author(s) : Cheng Q , Law PK , de Gasparo M , Leung PS
Ref : Journal of Pharmacology & Experimental Therapeutics , 327 :683 , 2008
Abstract : LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] is an inhibitor of dipeptidyl peptidase IV that delays the degradation of glucagon-like peptide-1 (GLP-1). Valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine] is an antagonist of the angiotensin II type 1 receptor (AT1R) that reduces the incidence of type 2 diabetes mellitus. LAF237 and valsartan act on a common target through separate pathways to improve pancreatic islet cell function. We hypothesize that the combination of these two drugs acts in a synergistic or additive manner on islet function and structure. To test this hypothesis, we performed in vitro and in vivo studies. To measure the acute effect of the treatment, pancreatic islets of db/db mice were isolated and stimulated in vitro with glucose in the presence of valsartan (1 microM) and exendin-4 (100 nM), a GLP-1 receptor agonist. Combination treatment with valsartan and exendin-4 significantly enhanced glucose-stimulated insulin secretion from isolated islets. For studies of chronic effect, db/db mice received LAF237 (1 mg/kg/day) and/or valsartan (10 mg/kg/day). Islet cell reactive oxygen species (ROS), proliferation, apoptosis, fibrosis, beta-cell area, and glucose homeostasis were evaluated after 8 weeks of treatment, which showed that combination treatment resulted in a significant increase in pancreatic islet beta-cell area compared with monotherapy. This beneficial effect correlated with an increase in beta-cell proliferation and a decrease in ROS-induced islet apoptosis and fibrosis. These in vitro and in vivo data indicate that combination treatment with LAF237 and valsartan has significant beneficial additive effects on pancreatic beta-cell structure and function compared with their respective monotherapeutic effects.
ESTHER : Cheng_2008_J.Pharmacol.Exp.Ther_327_683
PubMedSearch : Cheng_2008_J.Pharmacol.Exp.Ther_327_683
PubMedID: 18787107

Title : Synthesis of trifluoromethylaryl diazirine and benzophenone derivatives of etomidate that are potent general anesthetics and effective photolabels for probing sites on ligand-gated ion channels - Husain_2006_J.Med.Chem_49_4818
Author(s) : Husain SS , Nirthanan S , Ruesch D , Solt K , Cheng Q , Li GD , Arevalo E , Olsen RW , Raines DE , Forman SA , Cohen JB , Miller KW
Ref : Journal of Medicinal Chemistry , 49 :4818 , 2006
Abstract : To locate the binding sites of general anesthetics on ligand-gated ion channels, two derivatives of the intravenous general anesthetic etomidate (2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate), in which the 2-ethyl group has been replaced by photoactivable groups based on either aryl diazirine or benzophenone chemistry, have been synthesized and characterized pharmacologically. TDBzl-etomidate (4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate) and BzBzl-etomidate (4-benzoylbenzyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate are both potent general anesthetics with half-effective anesthetic concentrations of 700 and 220 nM, respectively. Both agents resembled etomidate in enhancing currents elicited by low concentrations of GABA on heterologously expressed GABAA receptors and in shifting the GABA concentration-response curve to lower concentrations. They also allosterically enhanced the binding of flunitrazepam to mammalian brain GABAA receptors. Both agents were also effective and selective photolabels, photoincorporating into some, but not all, subunits of the Torpedo nicotinic acetylcholine receptor to a degree that was allosterically regulated by an agonist or a noncompetitive inhibitor. Thus, they have the necessary pharmacological and photochemical properties to be useful in identifying the site of etomidate-induced anesthesia.
ESTHER : Husain_2006_J.Med.Chem_49_4818
PubMedSearch : Husain_2006_J.Med.Chem_49_4818
PubMedID: 16884293

Title : Characterization of two polyketide synthase genes in Exophiala lecanii-corni, a melanized fungus with bioremediation potential - Cheng_2004_Bioorg.Chem_32_92
Author(s) : Cheng Q , Kinney KA , Whitman CP , Szaniszlo PJ
Ref : Bioorg Chem , 32 :92 , 2004
Abstract : Exophiala lecanii-corni has significant bioremediation potential because it can degrade a wide range of volatile organic compounds. In order to identify sites for the insertion of genes that might enhance this potential, a genetic analysis of E. lecanii-corni was undertaken. Two polyketide synthase genes, ElPKS1 and ElPKS2, have now been discovered by a PCR-based strategy. ElPKS1 was isolated by a marker rescue technique. The nucleotide sequence of ElPKS1 consists of a 6576-bp open reading frame encoding a protein with 2192 amino acids, which was interrupted by a 60-bp intron near the 5' end and a 54-bp intron near the 3' end. Sequence analysis, results from disruption experiments, and physiological tests showed that ElPKS1 encoded a polyketide synthase required for melanin biosynthesis. Since ElPKS1 is non-essential, it is a desirable bioengineering target site for the insertion of native and foreign genes. The successful expression of these genes could enhance the bioremediation capability of the organism. ElPKS2 was cloned by colony hybridization screening of a partial genomic library with an ElPKS2 PCR product. ElPKS2 had a 6465-bp open reading frame that encoded 2155 amino acids and had introns of 56, 67, 54, and 71 bp. Although sequence analysis of the derived protein of ElPKS2 confirmed the polyketide synthase nature of its protein product, the function of that product remains unclear.
ESTHER : Cheng_2004_Bioorg.Chem_32_92
PubMedSearch : Cheng_2004_Bioorg.Chem_32_92
PubMedID: 14990308
Gene_locus related to this paper: 9pezi-q7z9k6 , exole-PKS2

Title : Genetic analysis of a gene cluster for cyclohexanol oxidation in Acinetobacter sp. Strain SE19 by in vitro transposition - Cheng_2000_J.Bacteriol_182_4744
Author(s) : Cheng Q , Thomas SM , Kostichka K , Valentine JR , Nagarajan V
Ref : Journal of Bacteriology , 182 :4744 , 2000
Abstract : Biological oxidation of cyclic alcohols normally results in formation of the corresponding dicarboxylic acids, which are further metabolized and enter the central carbon metabolism in the cell. We isolated an Acinetobacter sp. from an industrial wastewater bioreactor that utilized cyclohexanol as a sole carbon source. A cosmid library was constructed from Acinetobacter sp. strain SE19, and oxidation of cyclohexanol to adipic acid was demonstrated in recombinant Escherichia coli carrying a SE19 DNA segment. A region that was essential for cyclohexanol oxidation was localized to a 14-kb fragment on the cosmid DNA. Several putative open reading frames (ORFs) that were expected to encode enzymes catalyzing the conversion of cyclohexanol to adipic acid were identified. Whereas one ORF showed high homology to cyclohexanone monooxygenase from Acinetobacter sp. strain NCIB 9871, most of the ORFs showed only moderate homology to proteins in GenBank. In order to assign functions of the various ORFs, in vitro transposon mutagenesis was performed using the cosmid DNA as a target. A set of transposon mutants with a single insertion in each of the ORFs was screened for cyclohexanol oxidation in E. coli. Several of the transposon mutants accumulated a variety of cyclohexanol oxidation intermediates. The in vitro transposon mutagenesis technique was shown to be a powerful tool for rapidly assigning gene functions to all ORFs in the pathway.
ESTHER : Cheng_2000_J.Bacteriol_182_4744
PubMedSearch : Cheng_2000_J.Bacteriol_182_4744
PubMedID: 10940013
Gene_locus related to this paper: acisp-CHNC

Title : C-terminal domain of apolipoprotein CII as both activator and competitive inhibitor of lipoprotein lipase - Cheng_1990_Biochem.J_269_403
Author(s) : Cheng Q , Blackett P , Jackson KW , McConathy WJ , Wang CS
Ref : Biochemical Journal , 269 :403 , 1990
Abstract : In this study we have prepared peptides of the C-terminal domain of apolipoprotein CII (ApoCII) by a solid-peptide-synthesis technique and demonstrated that the C-terminal tetrapeptide, Lys-Gly-Glu-Glu, represents an inhibitor of lipoprotein lipase. The tetrapeptide not only inhibits the basal activity of lipoprotein lipase, but also blocks the activation effect of native ApoCII. The lengthening of this tetrapeptide resulted in a corresponding increase in affinity for lipoprotein lipase. This suggested that amino acids other than those of the C-terminal tetrapeptide also contribute to the binding affinity of ApoCII for lipoprotein lipase. On the basis of an essential requirement of the ApoCII terminal domain for binding to lipoprotein lipase, we suggest that the initial interaction of ApoCII, mediated via the C-terminal tetrapeptide, promotes the proper alignment of ApoCII with lipoprotein lipase, followed by the weak interaction of the ApoCII activator domain with the lipoprotein lipase activator site, enhancing the lipolysis process.
ESTHER : Cheng_1990_Biochem.J_269_403
PubMedSearch : Cheng_1990_Biochem.J_269_403
PubMedID: 2386483