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
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HMGB1 in Health and Disease
Rui Kang,Ruochan Chen,Qiuhong Zhang,Wen Hou,Sha Wu,Lizhi Cao,Jin Huang,Yan Yu,Xue Gong Fan,Zhengwen Yan,Zhengwen Yan,Xiaofang Sun,Haichao Wang,Qingde Wang,Allan Tsung,Timothy R. Billiar,Herbert J. Zeh,Michael T. Lotze,Daolin Tang +18 more
TL;DR: High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside thecell as the prototypic damage associated molecular pattern molecule (DAMP).
Journal ArticleDOI
Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance
TL;DR: The clinical relevance of celldeath, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets are reviewed.
Journal ArticleDOI
Drug-induced liver injury: recent advances in diagnosis and risk assessment
Gerd A. Kullak-Ublick,Raúl J. Andrade,Michael Merz,Peter End,Andreas Benesic,Alexander L. Gerbes,Guruprasad P. Aithal +6 more
TL;DR: The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public–private partnerships.
Journal ArticleDOI
MD-2 is required for disulfide HMGB1-dependent TLR4 signaling
Huan Yang,Haichao Wang,Zhongliang Ju,Ahmed A. Ragab,Peter Lundbäck,Wei Long,Sergio I. Valdés-Ferrer,Mingzhu He,John P. Pribis,Jianhua Li,Ben Lu,Domokos Gero,Csaba Szabó,Daniel J. Antoine,Helena Erlandsson Harris,Doug T. Golenbock,Jianmin Meng,Jesse Roth,Sangeeta S. Chavan,Ulf Andersson,Timothy R. Billiar,Kevin J. Tracey,Yousef Al-Abed +22 more
TL;DR: An HGMB1 peptide inhibitor, P5779, which when administered in vivo can protect mice from acetaminophen-induced hepatoxicity, ischemia/reperfusion injury, and sepsis, is identified.
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The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis
Peter Huebener,Jean-Philippe Pradere,Céline Hernandez,Geum-Youn Gwak,Jorge Matias Caviglia,Xueru Mu,John D. Loike,Rosalind E. Jenkins,Daniel J. Antoine,Robert F. Schwabe +9 more
TL;DR: This study establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a neutrophil-mediated injury amplification loop in the setting of necrosis.
References
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Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity
Jeffrey Cummings,Cassandra L Hodgkinson,Rajesh Odedra,Patrizia Sini,Simon P. Heaton,Kirsten E. Mundt,Timothy H Ward,Robert W. Wilkinson,Jim Growcott,Andrew Hughes,Caroline Dive +10 more
TL;DR: It is concluded that M30 is a pharmacodynamic biomarkers of AZD1152-induced apoptosis in the SW620 xenograft model, whereas M65 is a biomarker of therapeutic response.
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Serum Apoptosis Markers in Acute Liver Failure: A Pilot Study
Anna E. Rutherford,Linda S. Hynan,Carolina B. De Sa Borges,David G. Forcione,Jason T. Blackard,Wenyu Lin,April R. Gorman,Obaid S. Shaikh,Adrian Reuben,Edwyn M Harrison,K. Rajender Reddy,William M. Le,Raymond T. Chung +12 more
TL;DR: TNF-alpha, HGF, IL-6, and M-30 antigen were significantly elevated in ALF, and high levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF.
Journal ArticleDOI
Mechanism-based bioanalysis and biomarkers for hepatic chemical stress
TL;DR: The aim of this review is to summarise the potential of novel mechanism-based biomarkers of hepatic stress which provide information to connect the intracellular events ultimately leading to tissue damage (apoptosis, necrosis and inflammation).
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Apoptosis versus necrosis rate as a predictor in acute liver failure following acetaminophen intoxication compared with acute-on-chronic liver failure.
TL;DR: The results indicate the role of M30 and M65 immunoexpression as markers for functioning liver cell mass, capacity for recovery and therefore as predictive markers in acute liver failure.
Journal ArticleDOI
Mechanistic biomarkers in acute liver injury: Are we there yet?
TL;DR: The paper by Antoine and colleagues in the present issue of the Journal is welcome as it starts to address the lack of biomarkers that may indicate progression of liver failure early as decision making regarding listing for transplantation in patients with ALF is challenging.