The CRAC channel inhibitor BTP2 restricts Tulane virus and human norovirus replication independent of store-operated calcium entry.

Unlabelled: Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds.

Congenital erythropoietic porphyria: the overlooked inherited disorder.

Congenital erythropoietic porphyria (CEP) also known as Gunther's disease is a subtype of porphyria. It is an autosomal recessive disorder caused by a mutation in the uroporphyrinogen III gene (URO III) coding for the enzyme UROS synthase, an essential enzyme in the heme synthesis pathway. The condition may present as non-immune hydrops in foetuses, dark-red urine-stained diapers in neonates and skin blistering and mutilation in sun-exposed areas in older children.

Organic cation transporters 2: Structure, regulation, functions, and clinical implications.

The SLC22A2 gene encodes organic cation transporter 2 (OCT2), which is predominantly expressed in renal proximal tubule cells. OCT2 is critical for the active renal excretion of various cationic drugs and endogenous metabolites. OCT2 expression varies across species, with higher levels in mice and monkeys compared with humans and rats.

Is 1-Methylnicotinamide a Good Organic Cation Transporter 2 (OCT2) Biomarker?

The impact of potential precipitant drugs on plasma or urinary exposure of endogenous biomarkers is emerging as an alternative approach to evaluating drug-drug interaction (DDI) liability. 1-Methylnicotinamide (NMN) has been proposed as a potential biomarker for renal organic cation transporter 2 (OCT2). NMN is synthesized in the liver from nicotinamide by nicotinamide N-methyltransferase (NNMT) and is subsequently metabolized by aldehyde oxidase (AO).

Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver.

In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption.