Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.
Daniel J. Antoine,James W. Dear,Philip J. Starkey Lewis,Vivien Platt,Judy Coyle,Moyra Masson,Ruben Thanacoody,Alasdair Gray,David J. Webb,Jonathan G. Moggs,D. Nicholas Bateman,Christopher E. Goldring,B. Kevin Park +12 more
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TLDR
Elevations in plasma miR‐122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range.About:
This article is published in Hepatology.The article was published on 2013-08-01 and is currently open access. It has received 374 citations till now. The article focuses on the topics: acetaminophen overdose & Alanine transaminase.read more
Citations
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Journal ArticleDOI
Transformative biomarkers for drug-induced liver injury: are we there yet?
Daniel J. Antoine,James W. Dear +1 more
Book ChapterDOI
MicroRNA-Dependent Gene Regulation of the Human Cytochrome P450
Dongying Li,William H. Tolleson,Dianke Yu,Si Chen,Lei Guo,Wenming Xiao,Weida Tong,Baitang Ning +7 more
TL;DR: Direct and indirect epigenetic molecular mechanisms for the regulation of CYP expression by miRNAs are described along with research strategies applied in the elucidation of these systems.
Journal ArticleDOI
Circulating MicroRNAs, Polychlorinated Biphenyls, and Environmental Liver Disease in the Anniston Community Health Survey.
Matthew Carver,Christina Pinkston,Shesh N. Rai,Banrida Wahlang,Marian Pavuk,Kimberly Z. Head,Gleta Carswell,Gail M. Nelson,Carolyn M. Klinge,Douglas A. Bell,Linda S. Birnbaum,Brian N. Chorley +11 more
TL;DR: The results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action and represents a promising new technique for environmental hepatology cohort studies.
Journal ArticleDOI
Methodological considerations for measuring biofluid-based microRNA biomarkers.
Brian N. Chorley,Elnaz Atabakhsh,Graeme Doran,Jean-Charles Gautier,Heidrun Ellinger-Ziegelbauer,David Jackson,Tatiana Sharapova,Peter S.T. Yuen,Rachel J. Church,Philippe Couttet,Roland Froetschl,James Eric McDuffie,Victor D. Martinez,Parimal Pande,Lauren Peel,Conor Rafferty,Frank J. Simutis,Alison H. Harrill +17 more
TL;DR: The microRNA Biomarkers Workgroup within the Health and Environmental Sciences Institute's (HESI) Committee on Emerging Systems Toxicology for the Assessment of Risk (eSTAR) is a consortium of private and public-sector scientists dedicated to developing miRNAs as applied biomarkers as discussed by the authors.
DissertationDOI
Development of a spheroid model to investigate drug-induced liver injury
TL;DR: C3A spheroids act as a human-relevant in vitro model with the potential to be incorporated into an initial drug safety screen, replacing 2D models with poor sensitivity and specificity.
References
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Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Tiziana Bonaldi,Fabio Talamo,Paola Scaffidi,Denise Ferrera,Annalisa Porto,Angela Bachi,Anna Rubartelli,Alessandra Agresti,Marco Bianchi +8 more
TL;DR: It is shown here that in all cells HMGB1 shuttles actively between the nucleus and cytoplasm, and secreted when monocytic cells receive an appropriate second signal.
Journal ArticleDOI
Circulating microRNAs, potential biomarkers for drug-induced liver injury
Kai Wang,Shile Zhang,Bruz Marzolf,Pamela Troisch,Amy Brightman,Zhiyuan Hu,Leroy Hood,David J. Galas +7 more
TL;DR: It is demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier.
Journal ArticleDOI
Characterization of microRNA expression profiles in normal human tissues
TL;DR: A global view of tissue distribution of miRNAs in relation to their chromosomal locations and genomic structures is presented to support their tissue-specific functional roles to regulate the physiologies of the normal tissues in which they are expressed.
Journal ArticleDOI
Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity
TL;DR: The formation of oxidants and the defense mechanisms available for cells are addressed and knowledge is applied to better understand mechanisms of drug hepatotoxicity, especially acetaminophen-induced liver injury.
Journal ArticleDOI
The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation.
Mitchell R. McGill,Matthew R. Sharpe,C. David Williams,Mohammad Taha,Steven C. Curry,Hartmut Jaeschke +5 more
TL;DR: It is suggested that mitochondrial damage and nuclear DNA fragmentation are likely to be critical events in APAP hepatotoxicity in humans, resulting in necrotic cell death.