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  1. Book ; Online ; E-Book: Biologics and biosimilars

    Feng, Xiaodong / Xie, Hong-Guang / Malhotra, Ashim / Yang, Catherine F.

    drug discovery and clinical applications

    2022  

    Author's details edited by Xiaodong Feng, Hong-Guang Xie, Ashim Malhotra and Catherine F. Yang
    Keywords Electronic books
    Language English
    Size 1 Online-Ressource (745 Seiten), Illustrationen
    Publisher CRC Press
    Publishing place Boca Raton
    Publishing country United States
    Document type Book ; Online ; E-Book
    Note Description based on publisher supplied metadata and other sources
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT021463879
    ISBN 978-0-429-93928-0 ; 9781138594227 ; 0-429-93928-0 ; 1138594229
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Book ; Online ; E-Book: Applying pharmacogenomics in therapeutics

    Xie, Hong-Guang / Feng, Xiaodong

    2016  

    Author's details ed. by Xiaodong Feng and Hong-Guang Xie
    Keywords Pharmacogenomics
    Subject code 615.7
    Language English
    Size XIV, 292 S.
    Publisher CRC Press
    Publishing place Boca Raton u.a.
    Publishing country United States
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT018911001
    ISBN 978-1-4665-8268-2 ; 9781466582675 ; 1-4665-8268-5 ; 1466582677
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  3. Article ; Online: The Complement System and C4b-Binding Protein: A Focus on the Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.

    Xie, Hong-Guang / Jiang, Li-Ping / Tai, Ting / Ji, Jin-Zi / Mi, Qiong-Yu

    Molecular diagnosis & therapy

    2024  Volume 28, Issue 2, Page(s) 189–199

    Abstract: The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b- ... ...

    Abstract The complement system plays a dual role in the body, either as a first-line defense barrier when balanced between activation and inhibition or as a potential driver of complement-associated injury or diseases when unbalanced or over-activated. C4b-binding protein (C4BP) was the first circulating complement regulatory protein identified and it functions as an important complement inhibitor. C4BP can suppress the over-activation of complement components and prevent the complement system from attacking the host cells through the binding of complement cleavage products C4b and C3b, working in concert as a cofactor for factor I in the degradation of C4b and C3b, and consequently preventing or reducing the assembly of C3 convertase and C5 convertase, respectively. C4BP, particularly C4BP α-chain (C4BPα), exerts its unique inhibitory effects on complement activation and opsonization, systemic inflammation, and platelet activation and aggregation. It has long been acknowledged that crosstalk or interplay exists between the complement system and platelets. Our unpublished preliminary data suggest that circulating C4BPα exerts its antiplatelet effects through inhibition of both complement activity levels and complement-induced platelet reactivity. Plasma C4BPα levels appear to be significantly higher in patients sensitive to, rather than resistant to, clopidogrel, and we suggest that a plasma C4BPα measurement could be used to predict clopidogrel resistance in the clinical settings.
    MeSH term(s) Humans ; Biomarkers ; Clopidogrel ; Complement C3-C5 Convertases/metabolism ; Complement C4b-Binding Protein/metabolism ; Complement System Proteins
    Chemical Substances Biomarkers ; Clopidogrel (A74586SNO7) ; Complement C3-C5 Convertases (EC 3.4.21.-) ; Complement C4b-Binding Protein ; Complement System Proteins (9007-36-7) ; C4BPA protein, human
    Language English
    Publishing date 2024-01-23
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2232796-4
    ISSN 1179-2000 ; 1177-1062
    ISSN (online) 1179-2000
    ISSN 1177-1062
    DOI 10.1007/s40291-023-00691-w
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  4. Book: Applying pharmacogenomics in therapeutics

    Feng, Xiaodong / Xie, Hong-Guang

    2016  

    Author's details edited by Xiaodong Feng and Hong-Guang Xie
    MeSH term(s) Pharmacogenetics/methods ; Genomics/methods ; Precision Medicine/methods ; Drug Therapy ; Drug Discovery
    Language English
    Size xiv, 304 pages, 4 unnumber plates :, illustrations, portraits ;, 24 cm
    Document type Book
    ISBN 9781466582675 ; 1466582677 ; 9781466582682 ; 1466582685
    Database Catalogue of the US National Library of Medicine (NLM)

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  5. Article ; Online: Personalized immunosuppressive therapy in pediatric heart transplantation: Progress, pitfalls and promises.

    Xie, Hong-Guang

    Pharmacology & therapeutics

    2010  Volume 126, Issue 2, Page(s) 146–158

    Abstract: The use of the immunosuppressants has revolutionized organ transplantation, including pediatric heart transplantation (PHTx). Recent evidence has shown that pharmacogenomics holds the promise to maximize the likelihood of drug safety and efficacy after ... ...

    Abstract The use of the immunosuppressants has revolutionized organ transplantation, including pediatric heart transplantation (PHTx). Recent evidence has shown that pharmacogenomics holds the promise to maximize the likelihood of drug safety and efficacy after the drug and dose are tailored individually based on the translation of pharmacogenomics to patient care. In this review, the immunosuppressants used for the PHTx are introduced, including their similarities and differences in immunosuppressive mechanisms of action, and their unique clinical efficacy and safety issues in relation to genetic polymorphisms in the genes that encode drug-metabolizing enzymes, drug transporters and drug targets. In addition, genetic susceptibility to severe drug-associated complications and strategies for their prevention and treatment are discussed. Moreover, clinically important drug-drug, drug-herb, or drug-food interactions and the effects of demographic and clinical covariates of recipients and donors on clinical endpoints of the PHTx are summarized, respectively. All relevant data are focused mainly on the PHTx. Information provided in this review would be useful for pediatric patient care, in particular for personalized medication, because each and every valuable piece could be fitted to the big picture of how organ rejection would be delayed and even avoided after personalized immunosuppressive therapy.
    MeSH term(s) Child ; Drug Interactions ; Heart Transplantation ; Humans ; Immunosuppression/methods ; Immunosuppression/trends ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/pharmacokinetics ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use ; Pharmacogenetics ; Precision Medicine/methods ; Precision Medicine/trends ; Transplantation Immunology
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2010-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194735-7
    ISSN 1879-016X ; 0163-7258
    ISSN (online) 1879-016X
    ISSN 0163-7258
    DOI 10.1016/j.pharmthera.2010.01.007
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  6. Article ; Online: Choline and trimethylamine N-oxide impair metabolic activation of and platelet response to clopidogrel through activation of the NOX/ROS/Nrf2/CES1 pathway.

    Ge, Peng-Xin / Tai, Ting / Jiang, Li-Ping / Ji, Jin-Zi / Mi, Qiong-Yu / Zhu, Ting / Li, Yi-Fei / Xie, Hong-Guang

    Journal of thrombosis and haemostasis : JTH

    2022  Volume 21, Issue 1, Page(s) 117–132

    Abstract: Background: Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel.: ... ...

    Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbe-generated metabolite, elicits thrombotic events by enhancing platelet reactivity; however, no studies have reported the effects of TMAO on the metabolism of and response to clopidogrel.
    Objectives: To determine whether choline and TMAO could significantly impair metabolic activation of and platelet response to clopidogrel in choline- or TMAO-fed mice and the mechanisms involved.
    Methods: Male mice were fed with vehicle control (Ctrl), TMAO, choline alone or in combination with 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 for 14 days and then treated with Ctrl or a single oral dose of clopidogrel. Plasma TMAO, protein levels of clopidogrel-metabolizing enzymes in the liver, plasma concentrations of clopidogrel and its metabolites, and adenosine diphosphate-induced platelet aggregation and activation were measured. In addition, HepG2 cells were treated with Ctrl or TMAO alone or in combination with N-acetyl-L-cysteine, ML385, or apocynin, and CES1, reactive oxygen species (ROS), and Nrf2 protein levels were measured, respectively.
    Results: TMAO significantly increased Ces1 protein expression and activity and clopidogrel hydrolysis in the liver as well as intracellular ROS and CES1 levels and Nrf2 nucleus translocation in HepG2 cells but decreased the formation of clopidogrel active metabolite and impaired platelet response to clopidogrel. Furthermore, concomitant use of 3,3-dimethyl-1-butanol, N-acetyl-L-cysteine, or ML385 effectively reversed choline- or TMAO-induced impairment of inhibition of platelet aggregation by clopidogrel in mice, respectively.
    Conclusions: Choline and TMAO impair the metabolic activation of and platelet response to clopidogrel through the activation of the NOX-dependent ROS/Nrf2/CES1 pathway, suggesting novel strategies for overcoming clopidogrel resistance from bench to bedside.
    MeSH term(s) Male ; Animals ; Mice ; Choline/metabolism ; Clopidogrel ; NF-E2-Related Factor 2/metabolism ; Reactive Oxygen Species ; Activation, Metabolic ; Acetylcysteine/pharmacology ; Acetylcysteine/metabolism
    Chemical Substances Choline (N91BDP6H0X) ; Clopidogrel (A74586SNO7) ; trimethyloxamine (FLD0K1SJ1A) ; NF-E2-Related Factor 2 ; Reactive Oxygen Species ; 3,3-dimethylbutan-1-ol (624-95-3) ; Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2022-12-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2022.10.010
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  7. Article ; Online: Multidrug Resistance-Associated Protein 3 Is Responsible for the Efflux Transport of Curcumin Glucuronide from Hepatocytes to the Blood.

    Jia, Yu-Meng / Zhu, Ting / Zhou, Huan / Ji, Jin-Zi / Tai, Ting / Xie, Hong-Guang

    Drug metabolism and disposition: the biological fate of chemicals

    2020  Volume 48, Issue 10, Page(s) 966–971

    Abstract: Curcumin, a major polyphenol present in turmeric, is predominantly converted to curcumin- ...

    Abstract Curcumin, a major polyphenol present in turmeric, is predominantly converted to curcumin-
    MeSH term(s) Administration, Oral ; Animals ; Curcumin/administration & dosage ; Curcumin/analogs & derivatives ; Curcumin/pharmacokinetics ; Drug Evaluation, Preclinical ; Estradiol/administration & dosage ; Estradiol/analogs & derivatives ; Estradiol/pharmacokinetics ; Glucuronides/administration & dosage ; Glucuronides/pharmacokinetics ; Hepatocytes/metabolism ; Male ; Mice ; Mice, Knockout ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/metabolism
    Chemical Substances Glucuronides ; Multidrug Resistance-Associated Proteins ; estradiol-17 beta-glucuronide (1806-98-0) ; multidrug resistance-associated protein 3 (1YV0492L5Z) ; Estradiol (4TI98Z838E) ; curcumin glucuronide (BE1PK7RL4M) ; Curcumin (IT942ZTH98)
    Language English
    Publishing date 2020-01-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.119.089193
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  8. Article ; Online: Enhanced metabolic activation of and platelet response to clopidogrel in T cell-deficient mice through induction of Cyp2c and Cyp3a and inhibition of Ces1.

    Jiang, Li-Ping / Zhu, Ting / Tang, Ke / Wu, Yu / Fu, Min / Ji, Jin-Zi / Mi, Qiong-Yu / Ge, Peng-Xin / Zhao, Xiang-Hong / Tai, Ting / Xie, Hong-Guang

    Journal of thrombosis and haemostasis : JTH

    2023  Volume 21, Issue 5, Page(s) 1322–1335

    Abstract: Background: T cells and platelets reciprocally coordinate mutual functions through crosstalk or interaction. However, it is not known whether metabolic activation of and platelet response to clopidogrel could be changed if T cells were deficient or ... ...

    Abstract Background: T cells and platelets reciprocally coordinate mutual functions through crosstalk or interaction. However, it is not known whether metabolic activation of and platelet response to clopidogrel could be changed if T cells were deficient or impaired in some cases and, if any, how it would work.
    Objectives: The objective of this study was to dissect the potential changes in platelet responses to and metabolic activation of clopidogrel in the case of T cell deficiency and to elucidate their mechanisms involved.
    Methods: BALB/c athymic nude mice or euthymic mice (controls) pretreated with cyclosporine A (CsA), thymosin α1 (Tα1), or their combination were used to investigate the changes in ADP-induced platelet activation and aggregation, systemic exposure of clopidogrel and its metabolites, and mRNA/protein expression and activity levels of clopidogrel-metabolizing enzymes in the liver, respectively.
    Results: Nude mice exhibited significantly enhanced antiplatelet effects of clopidogrel due to increased formation of clopidogrel active metabolite in the liver, where the enzyme activity levels of Cyp2c and Cyp3a were significantly elevated compared with control mice. Furthermore, the effects of CsA pretreatment on the metabolism of clopidogrel in euthymic mice were identical to those seen in athymic mice. As expected, concomitant use of Tα1 reversed all the observed effects of CsA on clopidogrel metabolism and relevant metabolic enzymes.
    Conclusions: T cell deficiency or suppression enhances the antiplatelet effects of clopidogrel due to the boosted metabolic activation of clopidogrel in the liver through a dramatic induction of Cyp2c and Cyp3a in mice, suggesting that the metabolism of substrate drugs of Cyp2c and Cyp3a may be enhanced by T cell impairment.
    MeSH term(s) Animals ; Mice ; Activation, Metabolic ; Blood Platelets/metabolism ; Clopidogrel/pharmacology ; Cytochrome P-450 CYP3A/metabolism ; Mice, Nude ; Platelet Aggregation ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; T-Lymphocytes/metabolism ; Ticlopidine/pharmacology
    Chemical Substances Clopidogrel (A74586SNO7) ; cytochrome P-450 CYP2C subfamily ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Platelet Aggregation Inhibitors ; Ticlopidine (OM90ZUW7M1) ; carboxylesterase 1, mouse (EC 3.1.1.-)
    Language English
    Publishing date 2023-02-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2023.01.028
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  9. Article ; Online: Short-term standard alcohol consumption enhances platelet response to clopidogrel through inhibition of Nrf2/Ces1 pathway and induction of Cyp2c in mice.

    Ge, Peng-Xin / Jiang, Li-Ping / Tai, Ting / Zhu, Ting / Ji, Jin-Zi / Li, Yi-Fei / Mi, Qiong-Yu / Xie, Hong-Guang

    Life sciences

    2021  Volume 279, Page(s) 119268

    Abstract: Aims: Drinking alcohol is prevalent worldwide; however, it is unknown whether alcohol could affect the antiplatelet effects of clopidogrel in patients when taking both concomitantly. This study was designed to investigate the influence of short-term ... ...

    Abstract Aims: Drinking alcohol is prevalent worldwide; however, it is unknown whether alcohol could affect the antiplatelet effects of clopidogrel in patients when taking both concomitantly. This study was designed to investigate the influence of short-term standard alcohol consumption on the metabolic activation of and platelet response to clopidogrel in mice as well as the mechanisms involved.
    Main methods: Male C57BL/6J mice were administered with normal saline (vehicle control) or alcohol at 2 g/kg/day for 7 days, and then gavaged with vehicle control or a single dose of clopidogrel at 10 mg/kg. Inhibition of ADP-induced platelet aggregation and activation by clopidogrel, plasma concentrations of clopidogrel and its active metabolite H4, and changes in mRNA and protein expression of genes related to clopidogrel metabolism and its regulation were measured in mice pretreated with or without alcohol.
    Key findings: Compared with vehicle control, alcohol pretreatment significantly reduced hydrolysis of clopidogrel as a result of significant down-regulation of Nrf2-mediated Ces1 expression (responsible for the formation of clopidogrel carboxylate), increased metabolic activation of clopidogrel due to significant up-regulation of Cyp2c (for the formation of active thiol metabolite H4), and consequently enhanced inhibition of ADP-induced platelet aggregation and activation by clopidogrel.
    Significance: Short-term standard alcohol consumption would significantly enhance suppression of ADP-induced platelet aggregation and activation by clopidogrel through significant inhibition of Nrf2/Ces1 signaling pathway and induction of Cyp2c, suggesting that alcohol may interact with drugs that are predominantly metabolized by CES1 or CYP2C in patient care, including clopidogrel.
    MeSH term(s) Alcohol Drinking/adverse effects ; Animals ; Carboxylic Ester Hydrolases/antagonists & inhibitors ; Clopidogrel/pharmacology ; Cytochrome P-450 Enzyme System/metabolism ; Drug Synergism ; Gene Expression Regulation/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/antagonists & inhibitors ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology
    Chemical Substances NF-E2-Related Factor 2 ; Nfe2l2 protein, mouse ; Platelet Aggregation Inhibitors ; cytochrome P-450 CYP2C subfamily ; Cytochrome P-450 Enzyme System (9035-51-2) ; Clopidogrel (A74586SNO7) ; Carboxylic Ester Hydrolases (EC 3.1.1.-) ; carboxylesterase 1, mouse (EC 3.1.1.-)
    Language English
    Publishing date 2021-02-21
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2021.119268
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  10. Article ; Online: Is platelet responsiveness to clopidogrel attenuated in overweight or obese patients and why? A reverse translational study in mice.

    Jiang, Li-Ping / Ji, Jin-Zi / Ge, Peng-Xin / Zhu, Ting / Mi, Qiong-Yu / Tai, Ting / Li, Yi-Fei / Xie, Hong-Guang

    British journal of pharmacology

    2021  Volume 179, Issue 1, Page(s) 46–64

    Abstract: Background and purpose: Overweight or obese patients exhibit poorer platelet responses to clopidogrel. However, the mechanisms behind this phenotype remain to be elucidated. Here, we sought to discover whether and why obesity could affect the metabolic ... ...

    Abstract Background and purpose: Overweight or obese patients exhibit poorer platelet responses to clopidogrel. However, the mechanisms behind this phenotype remain to be elucidated. Here, we sought to discover whether and why obesity could affect the metabolic activation of and/or platelet response to clopidogrel in obese patients and high-fat diet-induced obese mice.
    Experimental approach: A post hoc stratified analysis of an observational clinical study was performed to investigate changes in residual platelet reactivity with increasing body weight in patients taking clopidogrel. Furthermore, high-fat diet-induced obese mice were used to reveal alterations in systemic exposure of clopidogrel thiol active metabolite H4, ADP-induced platelet activation and aggregation, the expression of genes involved in the metabolic activation of clopidogrel, count of circulating reticulated and mature platelets, and proliferation profiles of megakaryocytes in bone marrow. The relevant genes and potential signalling pathways were predicted and enriched according to the GEO datasets available from obese patients.
    Key results: Obese patients exhibited significantly attenuated antiplatelet effects of clopidogrel. In diet-induced obese mice, systemic exposure of clopidogrel active metabolite H4 was reduced but that of its hydrolytic metabolite was increased due to down-regulation of certain P450s but up-regulation of carboxylesterase-1 in the liver. Moreover, enhanced proliferation of megakaryocytes and elevated platelet count also contributed.
    Conclusion and implications: Obesity attenuated metabolic activation of clopidogrel and increased counts of circulating reticulated and mature platelets, leading to impaired platelet responsiveness to the drug in mice, suggesting that clopidogrel dosage may need to be adjusted adequately in overweight or obese patients.
    MeSH term(s) Animals ; Blood Platelets ; Clopidogrel/metabolism ; Clopidogrel/pharmacology ; Humans ; Mice ; Obesity/drug therapy ; Obesity/metabolism ; Overweight/metabolism ; Platelet Aggregation ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Ticlopidine/pharmacology
    Chemical Substances Platelet Aggregation Inhibitors ; Clopidogrel (A74586SNO7) ; Ticlopidine (OM90ZUW7M1)
    Language English
    Publishing date 2021-10-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.15667
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