Idiopathic pulmonary fibrosis (IPF) is an idiopathic interstitial lung disease. At present, the pathogenesis of IPF has not been fully elucidated, which has affected the development of effective treatment methods. Here, we explored the function and potential mechanism of long noncoding RNA (lncRNA) CDKN2B antisense RNA 1 (CDKN2B-AS1) in IPF.Transforming growth factor-β (TGF-β) and bleomycin (BLM) were used to induce IPF in cells and animal models. Real Time quantitative Polymerase Chain Reaction (RT-qPCR) showed the expression of CDKN2B-AS1, miR-199a-5p and Sestrin-2 (SESN2) in cells and tissues. The double luciferase reporter gene assay confirmed the targeting relationship among CDKN2B-AS1, miR-199a-5p, and SESN2. Related protein levels were detected by Western blot combined with Cell Counting Kit-8 (CCK-8), wound healing, and flow cytometry to analyze cell proliferation, migration, and apoptosis. The pathological characteristics of mouse lung tissue were determined by Hematoxylin-eosin (HE) and Masson staining. We found that the expression of CDKN2B-AS1 was decreased in TGF-β-treated cells and BLM-treated mice. Overexpression of CDKN2B-AS1 inhibited cell proliferation and migration, promoted apoptosis, decreased the expression of fibrosis-related proteins and promoted autophagy. In addition, overexpression of CDKN2B-AS1 alleviated pulmonary fibrosis in BLM-treated mice. Mechanistically, CDKN2B-AS1 acts as a miR-199a-5p sponge to regulate SESN2 expression. Our results indicate the importance of the CDKN2B-AS1/miR-199a-5p/SESN2 axis. Graphical abstract

Primary biliary cholangitis (PBC) is a chronic autoimmune disease of biliary stasis in which immune factors cause the gradual destruction of small bile ducts, biliary stasis, and eventually the development of liver fibrosis, cirrhosis, and even liver failure. One of the main characteristics of PBC is that it primarily affects middle-aged women, but the precise cause is still unknown. This article analyzes the unique causes and mechanisms of the female predominance of PBC and summarizes the potential causes.The female domination of PBC is reported to be primarily caused by sex hormones, environmental circumstances, and epigenetic changes, each of which has a different subtle impact on patients' gender disparities.

Background: Primary biliary cholangitis (PBC) patients in the decompensated stage face poor prognoses, with recompensation being crucial for improving long‐term outcomes.Aim: This study aims to evaluate the predictive value of the lymphocyte‐to‐monocyte ratio (LMR) for recompensation in decompensated PBC patients.Methods: We retrospectively analysed 410 patients with PBC‐related decompensated cirrhosis receiving ursodeoxycholic acid (UDCA) treatment. The association between the LMR and recompensation was examined using Cox regression analysis, with additional trend analysis performed based on LMR quartiles. The predictive accuracy of the LMR, neutrophil‐to‐lymphocyte ratio (NLR), systemic immune‐inflammation index (SII) and platelet‐to‐lymphocyte ratio (PLR) was evaluated using receiver operating characteristic (ROC) curve analysis. Sensitivity analyses were conducted to confirm the robustness of the findings.Results: During follow‐up, among 401 patients with decompensated cirrhosis (age: 60.0 [IQR: 53.0–69.0] years; 88.3% female), 105 patients (26.18%) achieved recompensation. Multivariate Cox regression analysis showed that higher LMR was an independent promoting factor for recompensation after adjusting for all confounding factors in the model (HR = 1.415, 95% CI: 1.264–1.585, p < 0.001), with a linear positive correlation trend. ROC curve analysis demonstrated that LMR had superior predictive performance compared to other inflammatory markers (SII, PLR, NLR), with an area under the curve (AUC) of 0.787 (95% CI: 0.736–0.838, p < 0.001).Conclusion: LMR serves as a robust independent predictor for recompensation in decompensated PBC patients.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts. This review synthesizes current knowledge on the critical role of innate immunity, specifically involving cholangiocytes, bile components, and associated immune cells. Cholangiocytes function not only as passive targets but also as active immunomodulators through mechanisms including Toll-like receptor (TLR) signaling, antigen presentation, and immune cell recruitment. Dysregulated bile acid signaling via receptors like TGR5 disrupts immune homeostasis, while apoptosis of biliary epithelial cells releases antigens (e.g., PDC-E2), triggering aberrant innate and adaptive immune responses. Innate lymphoid cells (ILCs), natural killer (NK) cells, and macrophages exhibit altered frequencies and functions in PBC, driving chronic inflammation and fibrosis through cytokine cascades (e.g., IL-17, IFNγ) and interactions within the gut-liver axis. Furthermore, biliary microbiota dysbiosis exacerbates disease by promoting bacterial translocation, modifying bile acid metabolism, and activating innate immune pathways. Current clinical management with ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) primarily addresses cholestasis. However, the immunomodulatory effects of these agents remain constrained. Targeted therapeutic strategies addressing innate immune pathways—exemplified by RIPK2 (Receptor Interacting Serine/Threonine Kinase 2) inhibition, IL-1 blockade(Canakinumab), and T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) modulation—alongside cell-based interventions such as mesenchymal stem cell therapy, demonstrate considerable therapeutic potential. Advancing these modalities necessitates multidisciplinary integration to facilitate clinical translation. Additionally, Prognostic indices like the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) reflect systemic inflammation and correlate with disease progression. Achieving therapeutic precision requires deeper elucidation of the gut-biliary-immune axis, trained immunity mechanisms, and cholangiocyte senescence, paving the way for targeted interventions in PBC. Establishing a comprehensive treatment burden assessment system is imperative to facilitate the transition from investigational platforms to clinical care.

Background: Liver cirrhosis is one of the leading causes of decreased life expectancy worldwide. However, the molecular mechanisms underlying liver cirrhosis remain unclear. In this study, we performed a comprehensive analysis using transcriptome and metabolome sequencing to explore the genes, pathways, and interactions associated with liver cirrhosis. Methods: We performed transcriptome and metabolome sequencing of blood samples from patients with cirrhosis and healthy controls (1:1 matched for sex and age). We validated the differentially expressed microRNA (miRNA) and mRNAs using real-time quantitative polymerase chain reaction. Results: For transcriptome analysis, we screened for differentially expressed miRNAs and mRNAs, analyzed mRNAs to identify possible core genes and pathways, and performed coanalysis of miRNA and mRNA sequencing results. In terms of the metabolome, we screened five pathways that were substantially enriched in the differential metabolites. Next, we identified the metabolites with the most pronounced differences among these five metabolic pathways. We performed receiver operating characteristic (ROC) curve analysis of these five metabolites to determine their diagnostic efficacy for cirrhosis. Finally, we explored possible links between the transcriptome and metabolome. Conclusion: Based on sequencing and bioinformatics, we identified miRNAs and genes that were differentially expressed in the blood of patients with liver cirrhosis. By exploring pathways and disease-specific networks, we identified unique biological mechanisms. In terms of metabolomes, we identified novel biomarkers and explored their diagnostic efficacy. We identified possible common pathways in the transcriptome and metabolome that could serve as candidates for further studies.