Mor, I. | bioRxiv Science

bioRxiv2025

Sex-Based Transcriptomic Differences in Psoriatic Lesions: A Comprehensive Meta-Analysis

Psoriasis, a chronic inflammatory skin disease affecting men and women equally, presents distinct gender-based differences in severity and treatment response. While molecular mechanisms underlying psoriasis are well-studied, sex-specific differences remain largely unexplored. To address this, we conducted a meta-analysis of transcriptomic data from lesional psoriasis skin and healthy controls, comparing male and female cohorts.Our findings reveal 2,760 overlapping differentially expressed genes (DEGs) between sexes, highlighting shared pathways like IL-17 signaling and Th17 differentiation. However, sex-specific pathways emerged, including male-enriched PI3K-Akt signaling and chemokine receptor activity, and female-enriched glycolysis and AHR-NRF2 pathways. Upstream regulator analysis identified sex-specific drivers, including VEGFA activation and CFTR inhibition in males, and AHR activation and FGF21 inhibition in females. Notably, Tregs and neutrophil abundance differed by sex, aligning with disease severity trends. These results highlight critical molecular and cellular disparities, emphasizing the need for personalized, sex-specific therapeutic approaches in psoriasis management. TeaserGender disparities in psoriatic lesions reveal transcriptomic differences and variations in neutrophil cell type abundance.

bioinformatics↗

bioRxiv2023

Fatty liver-mediated glycine restriction impairs glutathione synthesis and causes hypersensitization to acetaminophen

Non-alcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Understanding metabolic pathways involved can provide insights into disease progression. Untargeted metabolomics of livers from mice with early-stage steatosis indicated a decrease in methylated metabolites suggesting altered one carbon metabolism. The levels of glycine, a central component of one carbon metabolism, were lower in steatotic mice, in line with clinical evidence. Isotope tracing studies demonstrated that increased synthesis of serine from glycine is the underlying cause for glycine limitation in fatty livers. Consequently, the low glycine availability in steatotic livers impaired glutathione (GSH) synthesis under oxidative stress induced by acetaminophen (APAP), enhancing hepatic toxicity. Glycine supplementation mitigated acute liver damage and overall toxicity caused by APAP in fatty livers by supporting de novo GSH synthesis. Thus, early metabolic changes in NAFLD that lead to glycine depletion sensitize mice to xenobiotic toxicity even at a reversible stage of NAFLD.

biochemistry↗