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Open AccessCharacterisation of the NRF2 transcriptional network and its response to chemical insult in primary human hepatocytes: implications for prediction of drug-induced liver injury
The transcription factor NRF2, governed by its repressor KEAP1, protects cells against oxidative stress. There is interest in modelling the NRF2 response to improve the prediction of clinical toxicities such a...
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Article
Open AccessNRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis
Expression of the glutamine transporter SNAT3 increases in kidney during metabolic acidosis, suggesting a role during ammoniagenesis. Microarray analysis of Nrf2 knock-out (KO) mouse kidney identified Snat3 as th...
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Article
Open AccessReal-time in vivo imaging reveals localised Nrf2 stress responses associated with direct and metabolism-dependent drug toxicity
The transcription factor Nrf2 coordinates an adaptive response to chemical and oxidative stress characterised by the upregulated expression of cytoprotective target genes. In order to understand the mechanisti...
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Article
Open AccessA tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance
K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of mode...
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Article
Open AccessExamination of the Cytotoxic and Embryotoxic Potential and Underlying Mechanisms of Next-Generation Synthetic Trioxolane and Tetraoxane Antimalarials
Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the eme...
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Article
Open AccessNrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy
Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for prote...