The significance of the Wnt/β-catenin signaling cascade in Rotavirus (RV) infection has not been elucidated. In this study, we attempt to elucidate the importance of the Wnt/β-catenin pathway in the RV pathogenesis and investigate a miRNA-mediated approach to regulate the pathway to repress the RV infection in the host. The regulation of the Wnt signaling pathway in terms of β-catenin accumulation and activation was analyzed by Western blotting and Confocal imaging analysis. The expression levels of miR-192 family members and miR-181a were enquired into using qPCR assays, whereas their targets in the Wnt pathway were confirmed using the Luciferase Reporter Assays. Members of the miR-192 family and miR-181a, which target the components of the pathway, were also found to be considerably decreased in expression during RV infection. Ectopic expression of these miRNAs could restrict the RV pathogenesis by targeting the intermediates of the Wnt signaling pathway. The miR-192 family and miR-181a were capable of suppressing the RV infection via targeting of the Wnt/β-catenin pathway. The study not only highlights the role of the Wnt signaling cascade in RV infection but also suggests that miRNAs can synergistically decrease RV replication by a significant amount. Thus, the miR-192 family and miR-181a present themselves as prospective antivirals against RV infection.

miR-122 and miR-192 were investigated as indicators of toxic liver injury caused by acetaminophen, but their role in idiosyncratic toxic liver injury remains controversial. So, this work aimed to assess and compare the expressions of miR-122 and miR-192 in two different types of toxic liver injury (intrinsic [acetaminophen] and idiosyncratic [diclofenac]). Forty male adult Wistar albino rats were divided into equal five groups, in which serum liver enzymes; microRNAs (miRNAs) expressions (miR-122 and miR-192) and histopathological findings were studied. The present study showed that (1) miR-122 and miR-192 are good serum biomarkers of toxic liver injury whatever its etiology, as their serum levels exhibited a significantly earlier increase and earlier return to normal baseline levels as compared to serum aminotransferase levels; (2) miR-122 is more specific than miR-192; and (3) both serum levels of miR-122 and miR-192 showed non-significant differences in relation to the type of toxic liver injury.

Statins are potent cholesterol-lowering drugs and are generally well tolerated. Hepatotoxicity is a rare but serious adverse effect of statins; however, its mechanisms are not clear. Coenzyme Q10 deficiency has been suggested, and supplementation of reduced coenzyme Q10 (ubiquinol) has been shown to have hepatoprotective effects. MicroRNAs (miRNAs) are small nucleotides that have been shown to be up-regulated in drug-induced liver injury. We hypothesized that circulating miRNAs may be differentially regulated after simvastatin treatment and by comparing with that of simvastatin and ubiquinol supplementation could potentially uncover signatory miRNA profile for simvastatin-induced liver injury. In this double-blind, prospective, randomized-controlled trial, miRNA profiles and liver enzymes were compared between simvastatin-treated patients, with and without ubiquinol supplementation, over 12 weeks compared to baseline. miRNA expression was further validated in HepG2 liver cell lines by real-time PCR. Changes in miR-192, miR-146a, miR-148a, miR-15a, and miR-21 were positively correlated (p<0.05) with alanine aminotransferase in simvastatin-only treated patients. In ubiquinol supplementation group, alanine aminotransferase and alkaline phosphatase were significantly down-regulated after 12 weeks and changes in miR-15a, miR-21 and miR-33a were negatively correlated with alkaline phosphatase (p < 0.05). Bioinformatics analyses predicted that miRNA regulation in simvastatin group was related to reduce proliferation and adenosine triphosphate-binding cassette transporters. Ubiquinol supplementation additionally regulated miRNAs that inhibit apoptotic and inflammatory pathways, suggesting potential hepatoprotective effects. Our results suggest that 20 mg/day of simvastatin does not have significant risk of hepatotoxicity and ubiquinol supplementation may, at the miRNA level, provide potential beneficial changes to reduce the effects of coenzyme Q10 deficiency in the liver.