BACKGROUND: The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. AIM: To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. METHODS: A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. RESULTS: Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. CONCLUSION: This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.
Short-term hypoxia pretreatment significantly enhances periodontal ligament stem cell (PDLSC)-based periodontal tissue regeneration by improving various cellular biological functions, but the underlying mechanisms remain unclear. In this study, based on RNA sequencing (RNA-seq), we comprehensively analyzed the possible regulatory mechanisms of the short-term hypoxic effects on the biological functions of healthy and inflammatory PDLSCs. A total of 134 and 164 differentially expressed genes (DEGs) were identified under healthy and inflammatory conditions, respectively. Functional enrichment analyses indicated that DEGs under both conditions share certain biological processes and pathways, including metabolic processes, developmental processes, reproductive processes, localization, immune system processes and the HIF-1 signaling pathway. The DEGs identified under inflammatory conditions were more significantly enriched in cell cycle-related processes and immune-related pathways, while DEGs identified under healthy condition were more significantly enriched in the TGF-ß signaling pathway. A protein-protein interaction network analysis of the 59 DEGs in both conditions was performed, and 15 hub genes were identified. These hub genes were mainly involved in glycolysis, the cellular response to hypoxia, cell differentiation, and immune system processes. In addition, we found that hypoxia induced significant differential expression of genes associated with proliferation, differentiation, migration, apoptosis and immunoregulation under both healthy and inflammatory conditions. This study provides comprehensive insights into the effects of short-term hypoxia on the biological functions of PDLSCs and suggests a potentially feasible strategy for improving the clinical effectiveness of cell-based periodontal tissue engineering.
