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  1. Article ; 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  Volume 183, Issue 1, Page(s) 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 term(s) Biomarkers ; Chemical and Drug Induced Liver Injury/genetics ; Genomics ; Humans ; Liver ; Metabolomics ; Proteomics
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-06-03
    Publishing country United States
    Document type 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1709: Show issues Location:
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  2. Article: 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.
    Keywords fatty liver ; hepatocytes ; humans ; lipidomics ; liver ; mortality ; phospholipids
    Language English
    Dates of publication 2022-06
    Size p. 1445-1452.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 212746-5
    ISSN 1873-3468 ; 0014-5793
    ISSN (online) 1873-3468
    ISSN 0014-5793
    DOI 10.1002/1873-3468.14318
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; 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  Volume 596, Issue 11, Page(s) 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 term(s) Fatty Acids ; Hepatocytes ; Humans ; Lipidomics ; Liver ; Non-alcoholic Fatty Liver Disease ; Phospholipids
    Chemical Substances Fatty Acids ; Phospholipids
    Language English
    Publishing date 2022-02-28
    Publishing country England
    Document type 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 282: Show issues Location:
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  4. Article: 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  Volume 12, Issue 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
    Language English
    Publishing date 2022-02-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12020171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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