Role Of Genetic Variants In Regulating Pnpla3 Expression

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that affects approximately 25 percent of people worldwide. One variant that has been strongly linked to NAFLD is the PNPLA3-I148M variant. Another variant, the PNPLA3-S453I variant, has been linked to reduced hepatic fat content and a lower incidence of NAFLD in African Americans. The aim of this research was to explore the molecular mechanism underlying how the combinations of these mutations may affect the PNPLA3 mRNA and protein expression. We hypothesized that the PNPLA3-I148M and PNPLA3-S453I variants may alter the mRNA stability of PNPLA3 in hepatocytes. Four stable cell lines were created containing various combinations of these mutations. Lipid droplet formation, mRNA and protein expression, as well as mRNA stability were analyzed. Our data showed that the PNPLA3 isoforms possessed variable protein expression, with the PNPLA3-I148M variant associated with the highest protein accumulation in the cells. This was, at least in part, due to prolonged mRNA degradation. Relative to PNPLA3-I148M, the PNPLA3-S453I variant in general lead to a reduced protein level and a shorter mRNA half-life. This variability in PNPLA3 mRNA and protein expression is correlated with the neutral lipid accumulation and lipid droplet formation as well. However, the reason why the wildtype isoform of PNPLA3 possessed a higher mRNA and protein level, but a similar mRNA stability to the PNPLA3-S453I isoforms remains unclear. We concluded that the PNPLA3 variants are associated with NAFLD, at least in part, by regulating mRNA stability. More research is needed to fully address their impacts on the function of PNPLA3

The Effect of COVID-19 on Gut Microbiota: Exploring the Complex Interplay and Implications for Human Health

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although the respiratory manifestations of COVID-19 are widely recognized, emerging evidence suggests that the disease may also significantly affect the gut microbiota, the intricate community of bacteria that lives within the gastrointestinal system. This extensive article intends to investigate the impact of COVID-19 on the gut microbiota, examining the underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding the complex interactions between COVID-19 and the gut microbiota will help us to gain valuable insights into the broader consequences of this viral infection on human health

Health Literacy Among Non-Communicable Disease Service Seekers: A Nationwide Finding from Primary Health Care Settings of Bangladesh

Background: Considering the health literacy status of service seekers is crucial while developing programs and policies to improve service delivery in primary health care settings. Objective: Our aim was to assess health literacy among adults seeking non-communicable disease (NCD)-related services in primary health care centers (PHC) of Bangladesh and identify its contributing factors and its preventive effect on risky behaviors. Methods: In this cross-sectional study, 2,793 NCD service seekers were interviewed face-to-face from eight rural and three urban PHCs selected by a multi-stage random sampling method. We used the European Health Literacy Survey Questionnaire to collect data on health literacy. We applied logistic regression analysis to identify the contributing factors related to adequate health literacy. Odds ratios were used to calculate the preventive fraction of health literacy for NCD risk behaviors. Key Results: Limited health literacy was found among 43% of the respondents. Adequate health literacy was associated with younger age, male sex, having a formal education, living in an extended family, hailing from a high socioeconomic group, and attending urban PHC. After adjusting the sociodemographic factors, the prevalence of smoking, smokeless tobacco usage, and inadequate fruits and vegetables consumption among participants were found to be 25%, 51%, and 18% lower for people with sufficient health literacy. Conclusions: NCD service seekers have a high rate of inadequate health literacy. Adequate health literacy has the potential to lower the behavioral risk factors of NCDs. [HLRP: Health Literacy Research and Practice. 2024;8(1):e12–e20.

Substrate Stiffness Modulates the Maturation of Human Pluripotent Stem-Cell-Derived Hepatocytes

Obtaining functional hepatocytes from human pluripotent stem cells (hPSCs) holds great potential for applications in drug safety testing, as well in the field of regenerative medicine. However, developing functionally mature hPSC-derived hepatocytes (hPSC-Heps) remains a challenge. We hypothesized that the cellular microenvironment plays a vital role in the maturation of immature hepatocytes. In this study, we examined the role of mechanical stiffness, a key component of the cellular microenvironment, in the maturation of hPSC-Heps. We cultured hPSC-Heps on collagen-coated polyacrylamide hydrogels with varying elastic moduli. On softer substrates the hPSC-Heps formed compact colonies while on stiffer substrates they formed a diffuse monolayer. We observed an inverse correlation between albumin production and substrate stiffness. The expression of key cytochrome enzymes, which are expressed at higher levels in the adult liver compared to the fetal liver, also correlated inversely with substrate stiffness, whereas fetal markers such as Cyp3A7 and AFP showed no correlation with stiffness. Culture of hPSC-Heps on soft substrates for 12 days led to 10–30 fold increases in the expression of drug-metabolizing enzymes. These results demonstrate that substrate stiffness similar to that of the liver enables aspects of the maturation of hPSC-Heps