Clinical and Experimental Medicine最新文献

Hepatitis B virus (HBV) infection is an important worldwide health issue and attribute to hepatocellular carcinoma (HCC) via direct oncogenic and indirect mechanisms. HBV reprograms the tumor microenvironment (TME) through immunosuppression, metabolic adaptation, and stromal remodel, allowing tumor promotion and immune evasion. This review examines HBV-induced TME changes, including epigenetic dysregulation, immune cell dysfunction, and fibrosis, as well as new therapeutic options including immune checkpoint blockade, adoptive cell therapy, and metabolic targeting to improve outcomes in HBV-related HCC.

Autoimmune gastritis (AIG) is a chronic disease characterized by specific immune damage to the gastric mucosa. Previous studies have mostly focused on the single immune pathway mainly mediated by T cells, but the synergistic role of humoral immunity in disease progression cannot be ignored. This article systematically reviews the immunological mechanism of AIG, and analyzes the inflammatory cascade immune mechanism centered on the self-attack of gastric parietal cells mediated by CD4⁺ T, with the pro-inflammatory roles of Th1/Th17 cells and defective suppressive function of Tregs as a supplement. This article emphasizes the imbalance between humoral and cellular immunity, including the pathogenic potential of autoantibodies and the synergistic role of T-B cells in promoting inflammation. Furthermore, while existing animal models (including genetic modification, lymphopenic, and non-lymphopenic models) can replicate features of human AIG such as gastric gland atrophy, they exhibit significant limitations regarding the mechanism of T-B cell collaboration, differences in cancer risk, and species specificity. This article systematically clarifies that AIG results from an imbalance between cellular and humoral immunity, providing a theoretical basis for targeted immunotherapy strategies.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, with unknown pathogenesis and no effective treatment. Identifying the key molecular of IPF in underlying mechanisms is critical for developing targeted therapies. Differentially expressed genes (DEGs) were identified based on GSE53845 data from the Gene Expression Omnibus (GEO) database and the Limma R package, followed by gene set enrichment analysis (GSEA). The key module genes selected by Weighted Gene Co-expression Network Analysis (WGCNA) were integrated with the DEGs. The hub genes were screened using three machine-learning algorithms, with further performance validated through Receiver Operating Characteristic (ROC) curves and nomogram models. In addition, validation was performed using external validation sets, in vitro experiments and human lung tissues. Enrichment analyses were conducted using GeneMANIA and GSEA. Branched chain amino acid transferase 2 (BCAT2) was identified as a central hub gene in IPF by intersecting key module genes with DEGs through WGCNA and machine learning methods. Experimental validation confirmed the significantly downregulation of BCAT2 in the lung tissues of IPF patients and in TGF-β1-treated alveolar epithelial cells (AECs). Moreover, upregulation of BCAT2 attenuated the expression of fibrosis markers in AECs exposed to TGF-β1. Ultimately, Co-expression analysis and GSEA indicated that BCAT2 is closely involved in several key signaling pathways. Collectively, our findings suggest that BCAT2 is a critical protective molecule in the pathogenesis of IPF and represents a potential therapeutic target for modulating the progression of pulmonary fibrosis.

The REBECCA project taps into the potential of using real-world data (RWD) for supporting groundbreaking clinical research on complex chronic conditions as a complement to Randomised Controlled Trials. REBECCA moves beyond the analysis of clinical data from Electronic health records, by combining it with detailed monitoring data from multiple wearables, online behaviour and self-reported data to monitor patients's quality of life in terms of their functional and emotional status. The project focuses on the detection of cancer-related fatigue, developed during breast cancer recovery, using digital biomarker profiles for early detection of the disease and assessing the value of detailed and longitudinal patient monitoring as a means of improving patient care. The project also demonstrates the extensibility of REBECCA monitoring to other forms of cancer, such as prostate cancer. We describe the three clinical trials being conducted in Norway and the use of the REBECCA platform, capable of detailed monitoring and privacy preserving federated cross-country data analysis. The RWD will be analyzed in the context of data from questionnaires (Patient Reported Outcome Measures) and results from analysis of biological samples. Through this approach we expect that the REBECCA project will produce new knowledge on clinical management of cancer patients and contribute to new biological knowledge on cancer-related fatigue. Status and perspectives: The REBECCA project is ongoing, and patient follow-up will be completed during February 2026. The initial analyses of RWD, PROMs and biological samples have started together with the partners in the REBECCA consortium. The REBECCA trials are approved by the Regional Ethics Committee of the Western Health Authority (REK Vest) under the IDs 225,855 (REBECCA-1), 242,088 (REBECCA-2) and 619,903 (REBECCA-3). All trials have also been registered at clinicaltrials.gov (NCT05587777, NCT06120595 and NCT06435091). Trial registration: NCT05587777, Retrospectively registered 19th of October 2022, https://clinicaltrials.gov/study/ NCT05587777; NCT05587777, Retrospectively registered 6th of November 2023, https://clinicaltrials.gov/study/ NCT06120595; NCT05587777, Retrospectively registered 23rd of May 2024, https://clinicaltrials.gov/study/ NCT06435091.

Cytokines are pivotal regulators of immune responses and inflammation, and their dysregulation is implicated in cancer initiation and progression. A deeper understanding of cytokine-mediated modulation of tumor cell behavior may uncover novel therapeutic targets for cancer treatment.A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases using keywords such as "cytokines," "tumor sensitization," "immune regulation," and "cancer therapy." Peer-reviewed articles published between 2002 and 2025 were evaluated and synthesized to provide an updated overview of cytokine-related therapeutic strategies.This review highlights the complex roles of key cytokines-including interleukins (IL-1, IL-6, IL-8, IL-10, IL-17), interferons (types I and II), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β)-in modulating tumor cell susceptibility to therapeutic interventions. While cytokines exhibit both tumor-promoting and tumor-suppressive properties, recent advances in cytokine engineering, targeted delivery systems, and combination immunotherapies have enhanced their clinical potential.Integrating cytokine modulation into oncology may improve personalized immunotherapy outcomes.

Female-related cancers, including breast, ovarian, endometrial, and cervical malignancies, are among the most prevalent and clinically significant health challenges worldwide. Their development involves a complex interplay of genetic mutations, environmental factors, lifestyle influences, and therapeutic interventions. Long non-coding RNAs (lncRNAs) have emerged as critical regulators in these cancers, modulating epigenetic mechanisms, transcriptional programs, and post-transcriptional processes. Aberrant lncRNA expression promotes tumor initiation, drives progression and metastasis, and facilitates epithelial-mesenchymal transition (EMT) and angiogenesis. Among these, colon cancer-associated transcript 2 (CCAT2) has been identified as an oncogenic lncRNA across multiple tumor types. CCAT2 primarily activates the Wnt/β-catenin signaling pathway, enhancing β-catenin transcriptional activity and upregulating downstream targets such as MYC and cyclin D1, which are essential for cancer cell proliferation and survival. Despite growing evidence of its oncogenic role, the specific contribution of CCAT2 to female-related cancers remains incompletely understood. This study systematically reviews recent findings on CCAT2's role in the development and progression of breast, ovarian, endometrial, and cervical cancers, elucidates the underlying molecular mechanisms, and evaluates its potential as a diagnostic and prognostic biomarker. Furthermore, the translational potential of CCAT2 as a therapeutic target is discussed, highlighting opportunities for improving clinical outcomes in these malignancies.