Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder of the esophagus. However, the T-cell transcriptional programs distinguishing active disease from remission remain incompletely understood. In this study, we applied single-cell RNA sequencing to esophageal biopsies obtained from normal subjects and patients in remission or with active EoE, to characterize T-cell heterogeneity, state-dependent transcriptional changes, and intercellular communication networks. After stringent quality control, no substantial batch effects were observed. We identified five major T-cell subsets, with natural killer T (NKT) cells representing the most abundant population. Notably, naïve T cells and T helper 2 (Th2) cells were detected exclusively in active EoE samples, whereas regulatory T (Treg) and Th17 cells were present in all groups. The abundance of Tregs surpassed that of Th17 cells in active EoE but was similar to Th17 levels in normal and remission tissues. Functional enrichment analysis revealed a preferential association of NKT cells with receptor-binding functions. Th2 and naïve T cells shared signatures related to ribosome biology; naïve T cells additionally exhibited 5'-UTR binding and translation-regulator activity, aligning with their maturation potential. Consistent with the non-malignant nature of EoE, copy-number variation signals were minimal. Cell-type-specific differential expression analysis uncovered activated immune programs in NKT cells from active EoE, enriched for cytokine activity, along with epigenetic and transcriptional alterations in Tregs, including demethylase-linked functions, and protein-folding-related changes in Th17 cells. Cell-cell communication inference indicated a substantial rewiring of interaction networks in active EoE, suggesting activation of IL-16, IL-10, TRAIL, and PECAM1 pathways and heightened outgoing signaling from Th2 cells. Across all conditions, NKT cells served as dominant signaling senders and receivers. Collectively, these results delineate the T-cell composition and signaling circuits specific to active EoE, offering mechanistic insights into the maintenance of disease activity.
Background microRNAs play critical roles in modulating the molecular pathways involved in liver fibrosis. miR-107 has been reported to be elevated in the liver of patients with non-alcoholic fatty liver disease (NAFLD), and it is believed to regulate the PTEN gene, a negative regulator of the PI3K/PTEN/Akt signaling cascade. The PI3K/Akt pathway responds to metabolic stimuli like insulin and growth factors, influencing key functions such as lipid and glucose metabolism. In addition, hypoxia-inducible factors (HIFs), particularly HIF-2α, are also involved in liver metabolism and may contribute to lipid synthesis by activating the same signaling axis. The present study aimed to examine the gene expression patterns of miR-107, PTEN, Akt, and HIF-2α in liver tissue of patients with simple steatosis and cirrhosis. Methods This case-control study assessed the gene expression levels using quantitative real-time PCR (qRT-PCR) in liver tissues from individuals with simple steatosis (n = 6), cirrhosis (n = 32), and histologically normal controls (n = 7). Results miR-107 expression was significantly increased in cirrhotic tissues compared with controls (p < 0.05). The increase was mostly related to viral cirrhosis. PTEN expression was reduced in both disease groups; however, this decline reached statistical significance only in the NASH cirrhosis (p < 0.01). Also, HIF-2α and Akt gene expression decrease and increase in cirrhosis, respectively. No correlation was detected between miR-107 and PTEN gene expressions in liver tissues. Conclusion These findings suggest that there are complex interactions between miR-107 and PTEN gene expression. Apparently, Increased miR-107 expression in viral cirrhosis and reduced PTEN expression in NASH cirrhosis suggest potential associations with specific cirrhosis etiologies.
Long-term exposure to ambient particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) has been associated with optic neuropathy and retinal neurodegeneration, but experimental evidence remains limited. We assessed two certified environmental particulate reference materials in primary mouse retinal cells and after repeated ocular-surface exposure in mice. For the in vitro analyses, technical replicate wells were first averaged within each independent cell isolation, and each experimental condition was then normalized to the corresponding control from the same biological replicate. Particulate exposure produced condition-dependent changes in 2',7'-dichlorofluorescin diacetate (DCFDA) fluorescence and ATP-dependent viability, with statistically significant effects concentrated in selected retinal glial-cell conditions. After within-experiment normalization and multiplicity adjustment, direct comparisons did not demonstrate a statistically significant protective effect of α-tocopherol or N-acetylcysteine on particulate-associated responses, and retinal glial-cell coculture did not significantly improve RGC survival relative to monoculture. In postnatal mice, topical particulate administration was associated with inner retinal thinning and lower RGC-marker-positive cell counts. In adult Thy1-CFP mice, neither sample-specific nor post hoc pooled within-mouse comparisons with contralateral saline-treated eyes were statistically significant. A separate post hoc exploratory between-animal comparison showed fewer CFP-positive cells in pooled particulate-treated eyes than in independent bilateral-saline controls (mean difference, -14.4 cells; 95% CI, -28.1 to -0.7; P = 0.040). These findings support cellular and retinal susceptibility under the conditions used, but they do not establish particle transport to the retina, a causal oxidative mechanism, or quantitative risk from ambient PM2.5 exposure in humans.
Objective:To clarify the core regulatory role and molecular mechanism of farnesoid X receptor (FXR) in the progression from liver inflammation/fibrosis to hepatocellular carcinoma (HCC), and to provide a theoretical basis for targeted prevention and treatment of liver diseases. Methods:A systematic review was performed to integrate FXR's key regulatory mechanisms in bile acid homeostasis, inflammatory signaling, metabolic reprogramming, tumor pathways, and the tumor immune microenvironment. Intervention effects of natural compounds and FXR agonists/antagonists were analyzed for clinical translational potential. Results:FXR acts as a core regulator throughout the inflammation-fibrosis-HCC axis via bidirectional mechanisms. (1) In inflammation/fibrosis, FXR activation upregulates BSEP, FGF15/19, and SHP, inhibits CYP7A1 to maintain bile acid homeostasis, suppresses the TLR4/NF-κB axis and NLRP3 inflammasome, reduces IL-6/TNF-α, and directly inhibits hepatic stellate cell activation and matrix deposition. Agonists like INT-767 block progression from chronic hepatitis to fibrosis/cirrhosis (2) In HCC, FXR dysfunction (e.g., HBx C40-mediated). causes bile acid accumulation, glucose metabolic disorders, and Notch1/STAT3 activation, driving HCC progression. FXR activation inhibits STAT3 phosphorylation, glycolytic enzymes, and Wnt activity. Quercetin and obeticholic acid suppress tumor growth via FXR signaling. (3) Aberrant FXR signaling correlates with immune microenvironment dysregulation and immune escape. FXR agonists reshape the microenvironment and enhance anti-PD-1 efficacy; combined FXR and GPC3 detection improves HCC diagnostic specificity. Conclusion:FXR is a central hub regulating the liver inflammation-fibrosis-HCC axis. FXR-targeting agonists, natural compounds, and combination immunotherapy hold significant translational potential. Further studies are needed to clarify FXR's tissue-specific functions and bidirectional mechanisms, and to develop highly selective modulators for precise liver disease prevention and treatment.
metaKEGG is a comprehensive software package designed to streamline the visualization and integration of pathway enrichment results from multi-omics data, providing accessible and detailed insights into the molecular mechanisms driving health and disease. Unlike standard pipeline approaches, metaKEGG incorporates novel concepts allowing for clear, granular representation of gene-level or transcript-level expression changes. Beyond transcriptomic analysis, metaKEGG also supports epigenetic and regulatory metadata layers, such as methylation profiles and miRNA target annotations, offering users a versatile solution to depict complex regulatory interactions within a single pathway map. Its modular architecture provides nine analysis pipelines to suit various experimental designs, from comparing gene expression across multiple conditions to the integration of compound-based metabolomics data. Its implementation in Python ensures easy adoption and reproducibility, while a user-friendly web app allows researchers with limited bioinformatics expertise to harness metaKEGG's full potential.
