Construction and Expression of Fc-FGF21 by Different Expression Systems and Comparison of Their Similarity and Difference with Efruxifermin by In Vitro and In Vivo Studies.

Non-alcoholic steatohepatitis (NASH) is a potential serious disease, which almost has no available medicine for effective treatment today. Efruxifermin is a bivalent Fc-FGF21 candidate drug developed by Akero Therapeutics that has shown promising results in preclinical and clinical trials for NASH and may be approved in future. However, it is produced by Escherichia coli (E.

Establishing reference ranges for circulating biomarkers of drug-induced liver injury in healthy human volunteers.

Aims: The potential of mechanistic biomarkers to improve prediction of drug-induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration, as well as to characterize their natural variability and impact of diurnal variation.

Methods: Serum samples from 227 healthy volunteers were recruited as part of a cross-sectional study; of these, 25 subjects had weekly serial sampling over 3 weeks, while 23 had intensive blood sampling over a 24h period.

Limitations of acetaminophen as a reference hepatotoxin for the evaluation of in vitro liver models.

Acetaminophen is commonly used as a reference hepatotoxin to demonstrate that in vitro human liver platforms can emulate features of clinical drug-induced liver injury. However, the induction of substantial cell death in these models typically requires acetaminophen concentrations (∼10 mM) far higher than blood concentrations of the drug associated with clinical hepatotoxicity (∼1 mM). Using the cytochrome P450 inhibitor 1-aminobenzotriazole, we show that acetaminophen toxicity in cultured human, mouse, and rat hepatocytes is not dependent on N-acetyl-p-benzoquinonimine formation, unlike the in vivo setting.

Molecular biology of cholangiocarcinoma and its implications for targeted therapy in patient management.

Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer.