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  1. Artikel ; Online: Analytical and Omics-Based Advances in the Study of Drug-Induced Liver Injury.

    Kralj, Thomas / Brouwer, Kim L R / Creek, Darren J

    Toxicological sciences : an official journal of the Society of Toxicology

    2021  Band 183, Heft 1, Seite(n) 1–13

    Abstract: Drug-induced liver injury (DILI) is a significant clinical issue, affecting 1-1.5 million patients annually, and remains a major challenge during drug development-toxicity and safety concerns are the second-highest reason for drug candidate failure. The ... ...

    Abstract Drug-induced liver injury (DILI) is a significant clinical issue, affecting 1-1.5 million patients annually, and remains a major challenge during drug development-toxicity and safety concerns are the second-highest reason for drug candidate failure. The future prevalence of DILI can be minimized by developing a greater understanding of the biological mechanisms behind DILI. Both qualitative and quantitative analytical techniques are vital to characterizing and investigating DILI. In vitro assays are capable of characterizing specific aspects of a drug's hepatotoxic nature and multiplexed assays are capable of characterizing and scoring a drug's association with DILI. However, an even deeper insight into the perturbations to biological pathways involved in the mechanisms of DILI can be gained through the use of omics-based analytical techniques: genomics, transcriptomics, proteomics, and metabolomics. These omics analytical techniques can offer qualitative and quantitative insight into genetic susceptibilities to DILI, the impact of drug treatment on gene expression, and the effect on protein and metabolite abundance. This review will discuss the analytical techniques that can be applied to characterize and investigate the biological mechanisms of DILI and potential predictive biomarkers.
    Mesh-Begriff(e) Biomarkers ; Chemical and Drug Induced Liver Injury/genetics ; Genomics ; Humans ; Liver ; Metabolomics ; Proteomics
    Chemische Substanzen Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2021-06-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfab069
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1709: Hefte anzeigen Standort:
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  2. Artikel: Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from in vitro‐induced steatotic hepatocytes

    Kralj, Thomas / Khatri, Raju / Brouwer, Kenneth R. / Brouwer, Kim L. R. / Creek, Darren J.

    FEBS letters. 2022 June, v. 596, no. 11

    2022  

    Abstract: Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in ... ...

    Abstract Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid‐enriched media. This study compared the lipidome of PHH cultured in fatty acid‐enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acid‐enriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid‐enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients.
    Schlagwörter fatty liver ; hepatocytes ; humans ; lipidomics ; liver ; mortality ; phospholipids
    Sprache Englisch
    Erscheinungsverlauf 2022-06
    Umfang p. 1445-1452.
    Erscheinungsort John Wiley & Sons, Ltd
    Dokumenttyp Artikel
    Anmerkung JOURNAL ARTICLE
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14318
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: Lipidomics profiles in hepatocytes from nonalcoholic steatohepatitis patients differ markedly from in vitro-induced steatotic hepatocytes.

    Kralj, Thomas / Khatri, Raju / Brouwer, Kenneth R / Brouwer, Kim L R / Creek, Darren J

    FEBS letters

    2022  Band 596, Heft 11, Seite(n) 1445–1452

    Abstract: Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in ... ...

    Abstract Nonalcoholic steatohepatitis (NASH) is a severe form of liver injury that can be caused by a variety of stimuli and has a significant mortality rate. A common technique to induce in vitro steatosis involves culturing primary human hepatocytes (PHH) in fatty acid-enriched media. This study compared the lipidome of PHH cultured in fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls. Hepatocytes from NASH patients displayed increased total cellular abundance of glycerolipids and phospholipids compared to healthy control hepatocytes. PHH cultured in fatty acid-enriched media demonstrated increased glycerolipids. However, these culture conditions did not induce elevated phospholipid levels. Thus, culturing PHH in fatty acid-enriched media has limited capacity to emulate the environment of hepatocytes in NASH patients.
    Mesh-Begriff(e) Fatty Acids ; Hepatocytes ; Humans ; Lipidomics ; Liver ; Non-alcoholic Fatty Liver Disease ; Phospholipids
    Chemische Substanzen Fatty Acids ; Phospholipids
    Sprache Englisch
    Erscheinungsdatum 2022-02-28
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14318
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.B 282: Hefte anzeigen Standort:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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  4. Artikel: Multi-Omic Analysis to Characterize Metabolic Adaptation of the

    Kralj, Thomas / Nuske, Madison / Hofferek, Vinzenz / Sani, Marc-Antoine / Lee, Tzong-Hsien / Separovic, Frances / Aguilar, Marie-Isabel / Reid, Gavin E

    Metabolites

    2022  Band 12, Heft 2

    Abstract: As an adaptive survival response to exogenous stress, bacteria undergo dynamic remodelling of their lipid metabolism pathways to alter the composition of their cellular membranes. Here, ... ...

    Abstract As an adaptive survival response to exogenous stress, bacteria undergo dynamic remodelling of their lipid metabolism pathways to alter the composition of their cellular membranes. Here, using
    Sprache Englisch
    Erscheinungsdatum 2022-02-11
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12020171
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

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