An update on the therapeutic role of RNAi in NAFLD/NASH.

Unhealthy lifestyles have given rise to a growing epidemic of metabolic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD often occurs as a consequence of obesity, and currently, there is no FDA-approved drug for its treatment. However, therapeutic oligonucleotides, such as RNA interference (RNAi), represent a promising class of pharmacotherapy that can target previously untreatable conditions. The potential significance of RNAi in maintaining physiological homeostasis, understanding pathogenesis, and improving metabolic liver diseases, including NAFLD, is discussed in this article. We explore why NAFLD/NASH is an ideal target for therapeutic oligonucleotides and provide insights into the delivery platforms of RNAi and its therapeutic role in addressing NAFLD/NASH.

IL-18 and CD14 variants in chronic HBV predisposition: a case-control study with in silico analyses focused on transcription and splicing.

Hepatitis B virus (HBV), a vaccine-avoidable infection, is a health concern worldwide, leading to liver disorders such as acute self-constraint and chronic hepatitis, liver failure, hepatic cirrhosis, and even hepatocellular carcinoma if untreated. 'Immunogeneticprofiling', genetic variations of the pro- and anti-inflammatory cytokines responsible for regulating the immune responses, cause person-to-person differences and impact the clinical manifestation of the disease. The current experimental-bioinformatics research was conducted to examine whether promoteric IL-18-rs187238 C > G and -rs1946518 T > G and intronic CD14-rs2569190 A > G variations are associated with chronic HBV. A total of 400 individuals (200 in each case and control group) participated in the study and were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The data was also assessed bioinformatics-wise for conservation, genomic transcription and splicing, and protein interactions. Findings proposed that unlike the IL-18-rs1946518 T > G and CD14-rs2569190 A > G, the IL-18-rs187238 C > G is a protector against chronic HBV (odds ratio [OR] = 0.62, 95% confidence intervals [CI]: 0.46-0.83, and p = 0.002). The TG/CC/AA, TG/CC/AG, TT/CC/AG, and GG/CC/AA combined genotypes significantly increased chronic HBV risk (p < 0.05), while the IL-18 G/T and G/G haplotypes lessened it (p < 0.05). Moreover, IL-18-rs1946518 T > G is in the protected genomic regions across mammalian species. In contrast to the IL-18-rs1946518 T > G, IL-18-rs187238 C > G is likely to create novel binding sites for transcription factors, and the CD14-rs2569190 A > G presumably changed the ribonucleic acid splicing pattern. More research on larger populations and other ethnicities is required to authenticate these results.