Gut microbial dysbiosis is associated with metabolism and immune factors in liver fibrosis mice.

Gut microbial dysbiosis has always served as a potential factor in the occurrence and development of liver fibrosis. Liver and gut microflora can regulate each other through the gut-liver axis. In this study, the 16S rRNA and RNA-seq were chosen to sequence gut microbiota alteration and liver differentially expressed genes (DEGs) in carbon tetrachloride (CCl4) included-liver fibrosis mice, and analyze the correlations between gut microbiota constituents and DEGs. Results indicated that, CCl4 significantly increased the abundance of Desulfobactera in the phylum level, destroyed gut microbiota balance in the genus levels, especially Enterorhabdus and Desulfovibrio. Through analysis, 1416 genes were found differentially expressed in mice liver tissue in the CCl4 Group, compared with the Control Group; and the DEGs were mainly involved in the lipid metabolic process and immune system process. The correlation analysis revealed that the relative abundance of microbiota phylum (Desulfobactera) and genus (Enterorhabdus and Desulfovibrio) was negatively correlated with the metabolism related genes, while positively correlated with immune-related genes and the genes enriched in PI3K-Akt signaling pathway. To sum up, CCl4 can partially regulate gene expression in metabolism, immune response and the PI3K/Akt pathway, and further maintain the stability of the gut environment in liver fibrosis mice.

Abnormal variation and prognostic significance of circulating immune cells in patients with nasopharyngeal carcinoma treated with chemoradiotherapy: a prospective cohort study.

Background: Circulating immune cells are associated with tumor development and poor prognosis in multiple solid tumors. However, the circulating immune-cell profile of nasopharyngeal carcinoma (NPC) remains largely unknown. Therefore, we aimed to determine the changes in immune status and the prognostic significance of circulating immune cells before and after chemoradiotherapy (CRT) in patients, which can provide clinicians with valuable insights to optimize treatment strategies, monitor immune function, and personalize interventions, ultimately improving patient outcomes. Methods: Circulating immune cells before and after CRT in 77 patients with NPC and in 30 healthy controls were measured with flow cytometry. A thorough follow-up was conducted to assess prognosis outcomes, including local failure-free rate (LFFR), distant failure-free rate (DFFR), disease-free survival (DFS), and overall survival (OS). The differences of the subpopulation distribution in the two groups were determined by t-tests or Mann-Whitney tests. The paired t-test or Wilcoxon matched-pairs signed rank test was used to compare differences in lymphocyte subsets before and after CRT. The prognostic significance of lymphocyte subsets was evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Results: Compared with the control group, the NPC group showed significant decreases in the proportions of CD3+ cells, CD4+ T cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio (P<0.05) but a significant increase in the proportion of natural killer (NK) cells (P<0.05). After CRT, the proportions of CD4+ cells, CD8+CD28+ T cells, and CD19+ B cells as well as the CD4+:CD8+ ratio were markedly decreased (P<0.05), while the proportions of CD8+ T cells and NK cells were significantly increased (P<0.05). Multivariate analysis showed that a lower percentage of CD19+ B cells [hazard ratio (HR) 6.550, 95% CI: 1.661-25.831; P=0.007] and a positive test for Epstein-Barr virus (EBV) DNA (HR 0.261, 95% CI: 0.074-0.926; P=0.038) before treatment independently predicted worse 5-year OS (P<0.05). Conclusions: The disproportion of circulating immune cells was observed in patients with NPC before treatment. CRT further aggravated immune dysfunction. Notably, a lower percentage of CD19+ B cells and EBV DNA-positive status before treatment were independent predictors of a worse prognosis. Thus, the measurement of circulating immune cells may help elucidate immune function status and predict the outcomes of patients with NPC.