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The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation.
TLDR
Evidence supporting Keap1-dependent and -independent mechanisms of Nrf2 regulation are dissected, which highlight key knowledge gaps in this important field of biology, and suggest how these may be addressed experimentally. Expand
HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin
TLDR
Findings provide new insights into the mechanism of flucloxacillin DILI and have the potential to substantially improve diagnosis of this serious disease. Expand
A Highly Conserved Enhancer in the Dlx5/Dlx6Intergenic Region is the Site of Cross-Regulatory Interactions betweenDlx Genes in the Embryonic Forebrain
TLDR
It is proposed that the Dlx genes are part of a highly conserved developmental pathway that regulates forebrain development and is supported by cotransfection and DNA-protein binding experiments. Expand
HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans.
TLDR
The presence of the HLA-A*3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. Expand
Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital
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. Expand
Circulating microRNAs as potential markers of human drug‐induced liver injury
TLDR
This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug‐induced liver injury by examining these molecules, for the first time, in humans with APAP poisoning. Expand
The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity.
TLDR
The aim of this review is to summarise the current understanding of the biochemistry that underlies the Nrf2 defence pathway, and highlight the important role of this transcription factor in the protection against drug-induced toxicity, primarily through the examination of recent investigations that have demonstrated an increased vulnerability to various toxins in animals lacking NRF2. Expand
The role of metabolic activation in drug-induced hepatotoxicity.
TLDR
This review summarizes the evidence for reactive metabolite formation from hepatotoxic drugs, such as acetaminophen, tamoxifen, diclofenac, and troglitazone, and the current hypotheses of how this leads to liver injury and indicates that the toxicity of reactive metabolites may be mediated by noncovalent binding mechanisms, which may also have profound effects on normal liver physiology. Expand
High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo.
TLDR
K18 and HMGB1 molecular forms are identified and characterized by liquid chromatography-tandem mass spectrometry differing circulating molecular forms of high-mobility group box-1 protein and keratin-18, which are linked to the mechanisms and pathological changes induced by APAP in the mouse. Expand
HLA-B locus in Caucasian patients with carbamazepine hypersensitivity.
TLDR
HLA-B*1502 does not seem to be a marker for all forms of CBZ-induced hypersensitivity in a Caucasian population, and HLA- B*0702 allele may protect against severe CBZ hypersensitivity but warrants further study. Expand
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