Volodymyr P. Tryndyak

Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease, is a leading cause of cirrhosis and lacks effective therapies. Understanding the molecular mediators of disease progression remains a critical gap. This study aimed to investigate the roles of molecular phenotypes as mediators of MASH disease features in a diet-induced mouse model. Data used for these analyses were from a previous study where male and female CC042 mice were fed either a control or high-fat, high-sucrose (HF/HS) diet for 20, 40, or 60 weeks. Associations and mediated relationships between molecular and metabolic phenotypes and histopathologic markers of liver injury, inflammation, and lipid accumulation were assessed using regression modeling and causal mediation analyses. We observed strong associations between the HF/HS diet and duration of treatment and liver pathology, with a limited effect of sex. Mediation analysis revealed that liver lipid phenotypes, particularly monounsaturated and polyunsaturated fatty acids, consistently mediated the effects of diet on liver disease scores. Tumor necrosis factor alpha and C-X-C motif chemokine ligand 10, despite being treatment-induced, showed modest evidence of mediation on MASH or specific liver disease outcomes. Serum insulin showed modest mediation of inflammation and osmium staining, while serum glucose and triglycerides were not significant mediators. These findings highlight evidence that liver lipid metabolism may act as a primary mediator of MASH progression in this mouse model. The study underscores the value of mediation analysis for improved characterization of metabolic pathways in disease pathogenesis and supports the use of serum lipids as accessible biomarkers for clinical risk stratification and therapeutic targeting in MASH.

The ability of coronaviruses to adapt to new hosts and cause widespread disease outbreaks poses a significant threat to global public health systems and economies. The severity of the COVID-19 pandemic has emphasized the importance of studying coronaviruses and monitoring them in communities. We investigated SARS-CoV-2 and its genomic changes in wastewater influent sampled from two metropolitan areas in Arkansas, USA, between April 2020 and March 2024. The data presented here are a follow up report to our previous publication on the findings from the period of April 2020 to January 2022 and show the SARS-CoV-2 variants circulating between February 2022 and March 2024. The levels of viral RNA were measured by reverse-transcription quantitative polymerase chain reaction and targeted three SARS-CoV-2 genes (encoding ORF1ab polyprotein, ORF1ab; surface glycoprotein, S-protein; and nucleocapsid phosphoprotein, N-protein). The identity and genetic diversity of the virus were investigated using amplicon-based RNA sequencing. These data provide important information on SARS-CoV-2 evolution and help to understand the occurrence of COVID-19 outbreaks in the community.

Our previous study showed that sodium arsenite (200 mg/L) affected the nervous system and induced motor neuron development via the Sonic hedgehog pathway in zebrafish larvae. To gain more insight into the effects of arsenite on other signaling pathways, including apoptosis, we have performed quantitative polymerase chain reaction array‐based gene expression analyses. The 96‐well array plates contained primers for 84 genes representing 10 signaling pathways that regulate several biological functions, including apoptosis. We exposed eggs at 5 h postfertilization until the 72 h postfertilization larval stage to 200 mg/L sodium arsenite. In the Janus kinase/signal transducers and activators of transcription, nuclear factor κ‐light‐chain‐enhancer of activated B cells, and Wingless/Int‐1 signaling pathways, the expression of only one gene in each pathway was significantly altered. The expression of multiple genes was altered in the p53 and oxidative stress pathways. Sodium arsenite induced excessive apoptosis in the larvae. This compelled us to analyze specific genes in the p53 pathway, including cdkn1a, gadd45aa, and gadd45ba. Our data suggest that the p53 pathway is likely responsible for sodium arsenite‐induced apoptosis. In addition, sodium arsenite significantly reduced global DNA methylation in the zebrafish larvae, which may indicate that epigenetic factors could be dysregulated after arsenic exposure. Together, these data elucidate potential mechanisms of arsenic toxicity that could improve understanding of arsenic's effects on human health.

Gene expression and gene-specific histone H4 lysine 16 acetylation of cell death-related genes in the livers of STAM mice at NASH stage.

Expression of cleaved caspase 3 and cleaved caspase 8 in the livers of control mice and STAM mice.