Zhao P

References (18)

Title : Inquiry lipaseoring the mechanism of pancreatic lipase inhibition by isovitexin based on multispectral method and enzyme inhibition assay - Yu_2024_Luminescence_39_e4765
Author(s) : Yu H , Xing Z , Jia K , Li S , Xu Y , Zhao P , Zhu X
Ref : Luminescence , 39 :e4765 , 2024
Abstract : Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC(50) values of 0.26 +/- 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the alpha-helix content and increasing the beta-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.
ESTHER : Yu_2024_Luminescence_39_e4765
PubMedSearch : Yu_2024_Luminescence_39_e4765
PubMedID: 38769927

Title : Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN - Ma_2023_Int.J.Mol.Sci_24_
Author(s) : Ma Q , Liu Z , Wang T , Zhao P , Liu M , Wang Y , Zhao W , Yuan Y , Li S
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.
ESTHER : Ma_2023_Int.J.Mol.Sci_24_
PubMedSearch : Ma_2023_Int.J.Mol.Sci_24_
PubMedID: 38003694

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : The association between the D166E polymorphism of the lipoprotein associated phospholipase A2 and risk of myocardial infarction - Zhang_2019_Eur.Rev.Med.Pharmacol.Sci_23_3960
Author(s) : Zhang MM , Zhang CG , Yang CJ , Zhao P , Li YL
Ref : Eur Rev Med Pharmacol Sci , 23 :3960 , 2019
Abstract : OBJECTIVE: Although numerous studies have evaluated the association between lipoprotein associated phospholipase A2 (Lp-PLA2) gene polymorphisms and coronary heart disease, the conclusions are still inconsistency. Here we detected the correlation between D166E polymorphism of Lp-PLA2 and myocardial infarction (MI). Further, its clinical value as biomarker was assessed. PATIENTS AND METHODS: A total of 297 patients were enrolled, all diagnosed as MI at the Hebei General Hospital between May 2017 and May 2018, with 262 healthy subjects recruited as controls. Blood specimens of all participants were collected for testing serum lipid, blood glucose, Lp-PLA2, HsCRP, IL-17 and IL-35. The D166E polymorphism was genotyped. The correlation between D166E polymorphism and MI was explored using multiple logistic regression analysis. RESULTS: We detected higher levels of TC, TG, LDLC, Lp-PLA2, HsCRP and IL-17 but lower levels of HDLC and IL-35 in MI patients, compared with healthy controls (p<0.05). Also, the positive ratio of family history is higher in MI patients than that in control. Indexes were collected after one-week and one-month hospitalization, respectively, and levels of Lp-PLA2, HsCRP, IL-17 and IL-35 decreased to the normal levels (p>0.05). We also observed positive correlations between Lp-PLA2 with HsCRP and IL-17 (r=0.6517, 0.2689), and negative correlations between IL-35 with Lp-PLA2, HsCRP and IL-17 (r=-0.3142, -0.3968, -0.2516), respectively. The G allele at D166E accounted for a higher percentage in MI patients than in controls, and so as the GG and GC genotypes (p<0.05). Logistic regression analysis showed close associations between MI with Lp-PLA2 and GG genotype at D166E, with odds ratios of 1.239 (1.023-2.017) and 9.863 (4.107-21.331), which suggested they were independent risk factors for the development of coronary heart disease. CONCLUSIONS: The D166E (C/G) mutation of Lp-PLA2 was a potential risk factor of MI.
ESTHER : Zhang_2019_Eur.Rev.Med.Pharmacol.Sci_23_3960
PubMedSearch : Zhang_2019_Eur.Rev.Med.Pharmacol.Sci_23_3960
PubMedID: 31115024
Gene_locus related to this paper: human-PLA2G7

Title : Tracing and attribution of V-type nerve agents in human exposure by strategy of assessing the phosphonylated and disulfide adducts on ceruloplasmin - Fu_2019_Toxicology_430_152346
Author(s) : Fu F , Chen J , Zhao P , Lu X , Gao R , Chen D , Liu H , Wang H , Pei C
Ref : Toxicology , 430 :152346 , 2019
Abstract : V-type agents are highly toxic organophosphorus nerve agents that inhibit acetylcholinesterase in the nervous system, causing a series of poison symptoms. Trace analytical methods are essential for the specific verification of exposure to these agents, especially for human exposure. This paper investigates the phosphonylated and disulfide adducts between human ceruloplasmin and O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX), O-isobutyl S-(2-(diethylamino)ethyl) methylphosphonothioate (VR), and O-butyl S-(2-(diethylamino)ethyl) methylphosphonothioate (Vs). After being digested by trypsin, the mixture of peptides was separated by a nano-liquid chromatography (nano-LC) and analyzed using quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS). The sensitive LC-MS/MS-assisted proteomics approach was developed to achieve the identification of human exposure to V-type agents based on these modified sites; results revealed that potential biomarkers could be derived from adducts based on the sulfur- and phosphorus-containing groups of V-type agents. This work offered a novel insight into the mechanism of disulfide-containing adducts resulting from the replacement of disulfide bridges by the thiolate groups from the V-type agents. Moreover, four disulfide adducts on human ceruloplasmin were also discovered during this research, specifically confirming exposure to the V-type agents. Furthermore, molecular simulation testified to the reactivity of the modified sites. Collectively, our findings suggest that the eleven binding sites on human ceruloplasmin have the potential use as a selective marker for prediction the V-type agent exposure in humans.
ESTHER : Fu_2019_Toxicology_430_152346
PubMedSearch : Fu_2019_Toxicology_430_152346
PubMedID: 31857189

Title : A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines - Donahue_2014_Vaccine_32_3223
Author(s) : Donahue RN , Duncan BB , Fry TJ , Jones B , Bachovchin WW , Kiritsy CP , Lai JH , Wu W , Zhao P , Liu Y , Tsang KY , Hodge JW
Ref : Vaccine , :3223 , 2014
Abstract : Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA+ in CEA-transgenic C57BL-6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model). Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral vector based). These findings provide the rationale for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as ARI-4175.
ESTHER : Donahue_2014_Vaccine_32_3223
PubMedSearch : Donahue_2014_Vaccine_32_3223
PubMedID: 24731809

Title : Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats - Wang_2014_Toxicol.Appl.Pharmacol_280_169
Author(s) : Wang T , Zhao L , Liu M , Xie F , Ma X , Zhao P , Liu Y , Li J , Wang M , Yang Z , Zhang Y
Ref : Toxicol Appl Pharmacol , 280 :169 , 2014
Abstract : Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity.
ESTHER : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedSearch : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedID: 24967689

Title : A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity - Bachovchin_2014_Nat.Chem.Biol_10_656
Author(s) : Bachovchin DA , Koblan LW , Wu W , Liu Y , Li Y , Zhao P , Woznica I , Shu Y , Lai JH , Poplawski SE , Kiritsy CP , Healey SE , DiMare M , Sanford DG , Munford RS , Bachovchin WW , Golub TR
Ref : Nat Chemical Biology , 10 :656 , 2014
Abstract : The selectivity of an enzyme inhibitor is a key determinant of its usefulness as a tool compound or its safety as a drug. Yet selectivity is never assessed comprehensively in the early stages of the drug discovery process, and only rarely in the later stages, because technical limitations prohibit doing otherwise. Here, we report EnPlex, an efficient, high-throughput method for simultaneously assessing inhibitor potency and specificity, and pilot its application to 96 serine hydrolases. EnPlex analysis of widely used serine hydrolase inhibitors revealed numerous previously unrecognized off-target interactions, some of which may help to explain previously confounding adverse effects. In addition, EnPlex screening of a hydrolase-directed library of boronic acid- and nitrile-containing compounds provided structure-activity relationships in both potency and selectivity dimensions from which lead candidates could be more effectively prioritized. Follow-up of a series of dipeptidyl peptidase 4 inhibitors showed that EnPlex indeed predicted efficacy and safety in animal models. These results demonstrate the feasibility and value of high-throughput, superfamily-wide selectivity profiling and suggest that such profiling can be incorporated into the earliest stages of drug discovery.
ESTHER : Bachovchin_2014_Nat.Chem.Biol_10_656
PubMedSearch : Bachovchin_2014_Nat.Chem.Biol_10_656
PubMedID: 24997602
Gene_locus related to this paper: human-PPME1

Title : Biochemical properties, expression profiles, and tissue localization of orthologous acetylcholinesterase-2 in the mosquito, Anopheles gambiae - Zhao_2013_Insect.Biochem.Mol.Biol_43_260
Author(s) : Zhao P , Wang Y , Jiang H
Ref : Insect Biochemistry & Molecular Biology , 43 :260 , 2013
Abstract : Acetylcholinesterases (AChEs) catalyze the hydrolysis of acetylcholine, a neurotransmitter for cholinergic neurotransmission in animals. Most insects studied so far possess two AChE genes: ace-1 paralogous and ace-2 orthologous to Drosophila melanogaster ace. We characterized the catalytic domain of Anopheles gambiae AChE1 in a previous study (Jiang et al., 2009) and report here biochemical properties of A. gambiae AChE2 expressed in Sf9 cells. An unknown protease in the expression system cleaved the recombinant AChE2 next to Arg(110), yielding two non-covalently associated polypeptides. A mixture of the intact and cleaved AChE2 had a specific activity of 72.3 U/mg, much lower than that of A. gambiae AChE1 (523 U/mg). The order of V(max)/K(M) values for the model substrates was acetylthiocholine > propionylthiocholine approximately acetyl-(beta-methyl)thiocholine > butyrylthiocholine. The IC(50)'s for eserine, carbaryl, BW284C51, paraoxon and malaoxon were 1.32, 13.6, 26.8, 192 and 294 nM, respectively. A. gambiae AChE2 bound eserine and carbaryl stronger than paraoxon and malaoxon, whereas eserine and malaoxon modified the active site Ser(232) faster than carbaryl or paraoxon did. Consequently, the k(i)'s were 1.173, 0.245, 0.029 and 0.018 muM(-1)min(-1) for eserine, carbaryl, paraoxon and malaoxon, respectively. Quantitative polymerase chain reactions showed a similar pattern of ace-1 and ace-2 expression. Their mRNAs were abundant in early embryos, greatly decreased in late embryos, larvae, pupae, and pharate adult, and became abundant again in adults. Both transcripts were higher in head and abdomen than thorax of adults and higher in male than female mosquitoes. Transcript levels of ace-1 were 1.9- to 361.8-fold higher than those of ace-2, depending on developmental stages and body parts. Cross-reacting polyclonal antibodies detected AChEs in adult brains, thoracic ganglia, and genital/rectal area. Activity assays, immunoblotting, and tandem mass spectrometric analysis indicated that A. gambiae AChE1 is responsible for most of acetylthiocholine hydrolysis in the head extracts. Taken together, these data indicate that A. gambiae AChE2 may play a less significant role than AChE1 does in the mosquito nervous system.
ESTHER : Zhao_2013_Insect.Biochem.Mol.Biol_43_260
PubMedSearch : Zhao_2013_Insect.Biochem.Mol.Biol_43_260
PubMedID: 23267863
Gene_locus related to this paper: anoga-ACHE2

Title : 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities - Wu_2012_Bioorg.Med.Chem.Lett_22_5536
Author(s) : Wu W , Liu Y , Milo LJ, Jr. , Shu Y , Zhao P , Li Y , Woznica I , Yu G , Sanford DG , Zhou Y , Poplawski SE , Connolly BA , Sudmeier JL , Bachovchin WW , Lai JH
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :5536 , 2012
Abstract : The boroProline-based dipeptidyl boronic acids were among the first DPP-IV inhibitors identified, and remain the most potent known. We introduced various substitutions at the 4-position of the boroProline ring regioselectively and stereoselectively, and incorporated these aminoboronic acids into a series of 4-substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg-(4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8 and DPP9.
ESTHER : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedSearch : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedID: 22853995

Title : System review and metaanalysis of the relationships between five metabolic gene polymorphisms and colorectal adenoma risk - Zhao_2012_Tumour.Biol_33_523
Author(s) : Zhao ZQ , Guan QK , Yang FY , Zhao P , Zhou B , Chen ZJ
Ref : Tumour Biol , 33 :523 , 2012
Abstract : The relationships between some metabolic (including EPHX1, GSTs and NQO1) gene polymorphisms and colorectal adenoma (CRA) risk have been commonly studied, and no conclusions are available up to now. Therefore, we quantitatively studied the relationships by a metaanalysis. The databases of Medline and Embase were retrieved updated to June 15th, 2011. Crude or adjusted odds ratio (crude OR or adjusted OR) and 95% confidence interval (95%CI) were calculated to present the strength of the associations. Overall, nine case-control studies for EPHX1 Tyr113His and His139Arg, five case-control studies for GSTM1, four studies for GSTP1 Ile105Val, two studies for GSTP1 Ala114Val, six studies for GSTT1 and four studies for NQO1 Pro187Ser were included in this metaanalysis. The results of combined analyses indicated that EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1, GSTP1 Ile105Val and Ala114Val were not associated with CRA risk [crude OR (95%CI): 0.98 (0.90-1.07) and P ( z-test) = 0.65 for EPHX1 His carriers vs. Tyr/Tyr; 1.05 (0.97-1.15) and P ( z-test) = 0.21 for EPHX1 Arg carriers vs. His/His; 1.05 (0.92-1.20) and P ( z-test) = 0.47 for GSTT1 Null vs. Present; 1.01 (0.90-1.13) and P ( z-test) = 0.90 for GSTM1 Null vs. Present; 1.04 (0.92-1.17) and P ( z-test) = 0.56 for G carriers vs. AA for GSTP1 Ile105Val; 0.88 (0.70-1.11) and P ( z-test) = 0.28 for T carriers vs. CC for GSTP1 Ala114Val]. In contrast, Ser allele of NQO1 Ser187Pro might be a modest risk factor for CRA development [1.19 (1.06-1.33) and P ( z-test) = 0.003 for Ser carriers vs. Pro/Pro]. To get more precise evidences, adjusted ORs (95%CI) for EPHX1 Tyr113His, His139Arg, GSTP1 Ile105Val and NQO1 Ser187Pro were also calculated based on adjusted ORs (95%CIs) reported in primary studies. The results still indicated that EPHX1 Tyr113His, His139Arg and GSTP1 Ile105Val were not associated with CRA risk except for NQO1 Ser187Pro. When subgroup analyses were performed for population-based case-control studies or studies in HWE for EPHX1 Tyr113His and His139Arg, and NQO1 Ser187Pro polymorphisms, the results were persistent. Although with modest limitations and biases, this metaanalysis suggests that EPHX1 Tyr113His and His139Arg, GSTT1, GSTM1, GSTP1 Ile105Val and Ala114Val polymorphisms may be not risk factors for CRA development, while Ser allele of NQO1 Ser187 Pro may be a modest risk factor for CRA development, and may be used with other genetic markers for screening CRA in the future.
ESTHER : Zhao_2012_Tumour.Biol_33_523
PubMedSearch : Zhao_2012_Tumour.Biol_33_523
PubMedID: 22161138

Title : Genome sequence and transcriptome analysis of the radioresistant bacterium Deinococcus gobiensis: insights into the extreme environmental adaptations - Yuan_2012_PLoS.One_7_e34458
Author(s) : Yuan M , Chen M , Zhang W , Lu W , Wang J , Yang M , Zhao P , Tang R , Li X , Hao Y , Zhou Z , Zhan Y , Yu H , Teng C , Yan Y , Ping S , Wang Y , Lin M
Ref : PLoS ONE , 7 :e34458 , 2012
Abstract : The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential.
ESTHER : Yuan_2012_PLoS.One_7_e34458
PubMedSearch : Yuan_2012_PLoS.One_7_e34458
PubMedID: 22470573
Gene_locus related to this paper: deigi-h8gtt4 , deigi-h8h0j9

Title : Resistance to age-related, normal body weight gain in RGS2 deficient mice - Nunn_2011_Cell.Signal_23_1375
Author(s) : Nunn C , Zhao P , Zou MX , Summers K , Guglielmo CG , Chidiac P
Ref : Cell Signal , 23 :1375 , 2011
Abstract : RGS2 (regulator of G protein signaling 2) is known to limit signals mediated via Gq- and Gs-coupled GPCRs (G protein coupled receptors), and it has been implicated in the differentiation of several cells types. The physiology of RGS2 knockout mice (rgs2(-/-)) has been studied in some detail, however, a metabolic phenotype has not previously been reported. We observed that old (21-24month) rgs2(-/-) mice weigh much less than wild-type C57BL/6 controls, and exhibit greatly reduced fat deposits, decreased serum lipids, and low leptin levels. Lower weight was evident as early as four weeks and continued throughout life. Younger adult male rgs2(-/-) mice (4-8months) were found to show similar strain-related differences as the aged animals, as well improved glucose clearance and insulin sensitivity, and enhanced beta-adrenergic and glucagon signaling in isolated hepatocytes. In addition, rgs2(-/-) pre-adipocytes had reduced levels of differentiation markers (Peroxisome proliferator-activated receptor gamma (PPARgamma); lipoprotein lipase (Lpl); CCAAT/enhancer binding protein alpha (CEBPalpha)) and also rgs2(-/-) white adipocytes were small relative to controls, suggesting altered adipogenesis. In wild-type animals, RGS2 mRNA was decreased in brown adipose tissue after cold exposure (7 h at 4 degrees C) but increased in white adipose tissue in response to a high fat diet, also suggesting a role in lipid storage. No differences between strains were detected with respect to food intake, energy expenditure, GPCR-stimulated lipolysis, or adaptive thermogenesis. In conclusion this study points to RGS2 as being an important regulatory factor in controlling body weight and adipose function.
ESTHER : Nunn_2011_Cell.Signal_23_1375
PubMedSearch : Nunn_2011_Cell.Signal_23_1375
PubMedID: 21447383

Title : Heterologous expression, purification, and biochemical characterization of a greenbug (Schizaphis graminum) acetylcholinesterase encoded by a paralogous gene (ace-1) - Zhao_2010_J.Biochem.Mol.Toxicol_24_51
Author(s) : Zhao P , Zhu KY , Jiang H
Ref : J Biochem Mol Toxicol , 24 :51 , 2010
Abstract : Acetylcholinesterase is a critical enzyme in the regulation of cholinergic neurotransmission in insects. To produce Schizaphis graminum acetylcholinesterase-1 for structure-function analysis, we constructed a recombinant baculovirus to infect Sf9 cells, which secreted the soluble protein at a final concentration of 4.0 mg/L. The purified enzyme had an apparent M(r) of 70 and 130 kDa in the reducing and nonreducing SDS-polyacrylamide gels, respectively, indicating that it formed a dimer via an intermolecular disulfide bond. The fresh enzyme had a specific activity of 245 U/mg, which stabilized at a lower level (115 U/mg) in storage. The Michaelis constant and maximum velocity were 88.3 +/- 9.6 microM and 133.2 +/- 1.6 U/mg for acetylthiocholine iodide, 113.9 +/- 12.5 muM and 106.4 +/- 3.0 U/mg for acetyl(beta-methyl)thiocholine iodide, 68.9 +/- 7.8 microM and 76.7 +/- 1.0 U/mg for propionylthiocholine iodide, and 201.1 +/- 21.0 microM and 4.4 +/- 0.1 U/mg for S-butyrylthiocholine iodide, respectively. The IC(50) values (5 min, room temperature) of ethopropazine, BW284C51, carbaryl, eserine, malaoxon, and paraoxon were 102, 1.66, 0.94, 0.20, 0.061, 0.016 microM, respectively. The bimolecular reaction constants (k(i)) were (6.50 +/- 0.40) x 10(4) for carbaryl, (1.00 +/- 0.16) x 10(5) for eserine, (4.70 +/- 0.13) x 10(5) for malaoxon, and (9.06 +/- 0.23) x 10(5) M(-1) min(-1) for paraoxon. The enzyme was also inhibited by one of its products, choline, at concentrations higher than 20 mM, suggesting that choline bound to an anionic site and regulated the enzymatic activity.
ESTHER : Zhao_2010_J.Biochem.Mol.Toxicol_24_51
PubMedSearch : Zhao_2010_J.Biochem.Mol.Toxicol_24_51
PubMedID: 20146377

Title : Recombinant expression and biochemical characterization of the catalytic domain of acetylcholinesterase-1 from the African malaria mosquito, Anopheles gambiae - Jiang_2009_Insect.Biochem.Mol.Biol_39_646
Author(s) : Jiang H , Liu S , Zhao P , Pope C
Ref : Insect Biochemistry & Molecular Biology , 39 :646 , 2009
Abstract : Acetylcholinesterases (AChEs) and their genes from susceptible and resistant insects have been extensively studied to understand the molecular basis of target site insensitivity. Due to the existence of other resistance mechanisms, however, it can be problematic to correlate directly a mutation with the resistant phenotype. An alternative approach involves recombinant expression and characterization of highly purified wild-type and mutant AChEs, which serves as a reliable platform for studying structure-function relationships. We expressed the catalytic domain of Anopheles gambiae AChE1 (r-AgAChE1) using the baculovirus system and purified it 2,500-fold from the conditioned medium to near homogeneity. While K(M)'s of r-AgAChE1 were comparable for ATC, AbetaMTC, PTC, and BTC, V(max)'s were substantially different. The IC(50)'s for eserine, carbaryl, paraoxon, BW284C51, malaoxon, and ethopropazine were 8.3, 72.5, 83.6, 199, 328, and 6.59 x 10(4) nM, respectively. We determined kinetic constants for inhibition of r-AgAChE1 by four of these compounds. The enzyme bound eserine or paraoxon stronger than carbaryl or malaoxon. Because the covalent modification of r-AgAChE1 by eserine occurred faster than that by the other compounds, eserine is more potent than paraoxon, carbaryl, and malaoxon. Furthermore, we found that choline inhibited r-AgAChE1, a phenomenon related to the enzyme activity decrease at high concentrations of acetylcholine.
ESTHER : Jiang_2009_Insect.Biochem.Mol.Biol_39_646
PubMedSearch : Jiang_2009_Insect.Biochem.Mol.Biol_39_646
PubMedID: 19607916
Gene_locus related to this paper: anoga-ACHE1

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : The genome of the model beetle and pest Tribolium castaneum - Richards_2008_Nature_452_949
Author(s) : Richards S , Gibbs RA , Weinstock GM , Brown SJ , Denell R , Beeman RW , Gibbs R , Bucher G , Friedrich M , Grimmelikhuijzen CJ , Klingler M , Lorenzen M , Roth S , Schroder R , Tautz D , Zdobnov EM , Muzny D , Attaway T , Bell S , Buhay CJ , Chandrabose MN , Chavez D , Clerk-Blankenburg KP , Cree A , Dao M , Davis C , Chacko J , Dinh H , Dugan-Rocha S , Fowler G , Garner TT , Garnes J , Gnirke A , Hawes A , Hernandez J , Hines S , Holder M , Hume J , Jhangiani SN , Joshi V , Khan ZM , Jackson L , Kovar C , Kowis A , Lee S , Lewis LR , Margolis J , Morgan M , Nazareth LV , Nguyen N , Okwuonu G , Parker D , Ruiz SJ , Santibanez J , Savard J , Scherer SE , Schneider B , Sodergren E , Vattahil S , Villasana D , White CS , Wright R , Park Y , Lord J , Oppert B , Brown S , Wang L , Weinstock G , Liu Y , Worley K , Elsik CG , Reese JT , Elhaik E , Landan G , Graur D , Arensburger P , Atkinson P , Beidler J , Demuth JP , Drury DW , Du YZ , Fujiwara H , Maselli V , Osanai M , Robertson HM , Tu Z , Wang JJ , Wang S , Song H , Zhang L , Werner D , Stanke M , Morgenstern B , Solovyev V , Kosarev P , Brown G , Chen HC , Ermolaeva O , Hlavina W , Kapustin Y , Kiryutin B , Kitts P , Maglott D , Pruitt K , Sapojnikov V , Souvorov A , Mackey AJ , Waterhouse RM , Wyder S , Kriventseva EV , Kadowaki T , Bork P , Aranda M , Bao R , Beermann A , Berns N , Bolognesi R , Bonneton F , Bopp D , Butts T , Chaumot A , Denell RE , Ferrier DE , Gordon CM , Jindra M , Lan Q , Lattorff HM , Laudet V , von Levetsow C , Liu Z , Lutz R , Lynch JA , da Fonseca RN , Posnien N , Reuter R , Schinko JB , Schmitt C , Schoppmeier M , Shippy TD , Simonnet F , Marques-Souza H , Tomoyasu Y , Trauner J , Van der Zee M , Vervoort M , Wittkopp N , Wimmer EA , Yang X , Jones AK , Sattelle DB , Ebert PR , Nelson D , Scott JG , Muthukrishnan S , Kramer KJ , Arakane Y , Zhu Q , Hogenkamp D , Dixit R , Jiang H , Zou Z , Marshall J , Elpidina E , Vinokurov K , Oppert C , Evans J , Lu Z , Zhao P , Sumathipala N , Altincicek B , Vilcinskas A , Williams M , Hultmark D , Hetru C , Hauser F , Cazzamali G , Williamson M , Li B , Tanaka Y , Predel R , Neupert S , Schachtner J , Verleyen P , Raible F , Walden KK , Angeli S , Foret S , Schuetz S , Maleszka R , Miller SC , Grossmann D
Ref : Nature , 452 :949 , 2008
Abstract : Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
ESTHER : Richards_2008_Nature_452_949
PubMedSearch : Richards_2008_Nature_452_949
PubMedID: 18362917
Gene_locus related to this paper: trica-ACHE1 , trica-ACHE2 , trica-d2a0g9 , trica-d2a0h0 , trica-d2a0w9 , trica-d2a0x0 , trica-d2a0x1 , trica-d2a0x3 , trica-d2a0x4.1 , trica-d2a0x4.2 , trica-d2a0x6 , trica-d2a2b8 , trica-d2a2h1 , trica-d2a3c3 , trica-d2a3g9 , trica-d2a5y5 , trica-d2a309 , trica-d2a514 , trica-d2a515 , trica-d2a516 , trica-d2a577 , trica-d2a578 , trica-d6w6x8 , trica-d6w7f9 , trica-d6w7h2 , trica-d6w8e7 , trica-d6w9c0 , trica-d6w855 , trica-d6wac8 , trica-d6wan4 , trica-d6wd50 , trica-d6wd73 , trica-d6wd74 , trica-A0A139WM97 , trica-d6wfu3 , trica-d6wgl2 , trica-d6wj57 , trica-d6wj59 , trica-d6wjs3 , trica-d6wl31 , trica-d6wnv1 , trica-d6wpl0 , trica-d6wqd6 , trica-d6wqr4 , trica-d6ws52 , trica-d6wsm0 , trica-d6wu38 , trica-d6wu39 , trica-d6wu40 , trica-d6wu41 , trica-d6wu44 , trica-d6wvk5 , trica-d6wvz7 , trica-d6wwu9 , trica-d6wwv0 , trica-d6wxz0 , trica-d6wyy1 , trica-d6wyy2 , trica-d6x0z2 , trica-d6x0z5 , trica-d6x0z6 , trica-d6x4b2 , trica-d6x4e8 , trica-d6x4e9 , trica-d6x197 , trica-d7eip7 , trica-d7eld3 , trica-d7us45 , trica-q5wm43 , trica-q5zex9 , trica-d6wie5 , trica-d6w7t0 , trica-d6x4h0 , trica-d6x4h1 , trica-a0a139wae8 , trica-a0a139wc96 , trica-d6x325 , trica-d2a4s2 , trica-d6wvw8

Title : Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes - Herman_2006_J.Clin.Endocrinol.Metab_91_4612
Author(s) : Herman GA , Bergman A , Stevens C , Kotey P , Yi B , Zhao P , Dietrich B , Golor G , Schrodter A , Keymeulen B , Lasseter KC , Kipnes MS , Snyder K , Hilliard D , Tanen M , Cilissen C , De Smet M , De Lepeleire I , Van Dyck K , Wang AQ , Zeng W , Davies MJ , Tanaka W , Holst JJ , Deacon CF , Gottesdiener KM , Wagner JA
Ref : J Clinical Endocrinology Metab , 91 :4612 , 2006
Abstract : CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of sitagliptin. DESIGN: This was a randomized, double-blind, placebo-controlled, three-period, single-dose crossover study. SETTING: The study was conducted at six investigational sites. PATIENTS: The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents. INTERVENTIONS: Interventions included sitagliptin 25 mg, sitagliptin 200 mg, or placebo. MAIN OUTCOME MEASURES: Measurements included plasma DPP-4 activity; post-OGTT glucose excursion; active and total incretin GIP levels; insulin, C-peptide, and glucagon concentrations; and sitagliptin pharmacokinetics.
RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin. Sitagliptin was generally well tolerated, with no hypoglycemic events.
CONCLUSIONS: In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.
ESTHER : Herman_2006_J.Clin.Endocrinol.Metab_91_4612
PubMedSearch : Herman_2006_J.Clin.Endocrinol.Metab_91_4612
PubMedID: 16912128