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关键词： CCL11   CCL26   Ciliated epithelial cell   Goblet cell   IL-4R   IL-5   IL-5R  

关键词： PHB1   PHB2   IFN-beta   Ducks   Innate immunity  

摘要： PHB1 and PHB2, two subunits of the mitochondrial prohibitin complex, are critical regulators of antiviral innate immunity. Ducks, as natural reservoirs for RNA viruses, exhibit unique antiviral mechanisms. RIG-I is a key receptor for recognizing RNA viruses in ducks. However, the roles of PHB1 and PHB2 in the RIG-I-MAVS-IFN-beta signaling pathway remain unclear. Here, we characterized the duPHB1 and PHB2 structure and functional domains, which contains similar N-terminal transmembrane domain, PHB domain and coil-coiled C-terminal domain, revealing high conservation with avian and mammalian orthologs. Both genes were ubiquitously expressed in duck tissues, with elevated levels in immune-related organs (e.g., pancreas, thymus) and tissues with high metabolic activity and tissue regeneration ability (e.g., heart, liver and muscle) post-NDV infection. We next sought to investigate the functional roles by which duPHB1 and duPHB2 triggered antiviral innate immune response. Overexpression of duPHB1/2 in DEFs enhanced MAVS activation and IFN-beta production upon 5 ' ppp dsRNA stimulation, while siRNA-mediated knockdown suppressed these effects. Co-transfection of duPHB1 and duPHB2 synergistically amplified MAVS-dependent IFN-beta induction. Crucially, MAVS depletion abolished PHB1/ 2-mediated IFN-beta upregulation, demonstrating their dependence on MAVS signaling. Our findings establish duPHB1/2 as key regulators of mitochondrial-mediated antiviral responses in ducks, providing insights into avian innate immunity.

关键词： Saposhnikovia divaricata (Turcz.) Schisch   TNF-alpha   RAGE   Rheumatoid arthritis   UPLC-Q-TOF-MS  

摘要： Saposhnikovia divaricata (Turcz.) Schisch (SADS) is classified as a special-grade traditional Chinese medicine in Shennong's Materia Medical due to its immune-protective effects, including dispelling cold, relieving edema and pain, and its potential in treating rheumatoid arthritis (RA). Over 130 traditional Chinese medicine formulations containing SADS are used for RA treatment. However, the active ingredients and serum metabolites of SADS remain underexplored, and its precise mechanism of action in RA is not fully understood. Therefore, the study aims to explore the active ingredients and serum metabolites of SADS by UPLC-Q-TOF-MS and investigate its therapeutic mechanisms in the context of RA. A total of 5536 compounds were identified in SADS, and 19 active components were finally selected. In serum metabolites following SADS administration, 4945 compounds were identified, of which 17 showed anti-inflammatory activity. Network pharmacology analysis showed that SADS may play a role in the treatment of RA through the TNF and Receptor for Advanced Glycation End-products (RAGE) signaling pathway. SADS alleviated RA symptoms in IL-1RA deficient RA mice. In cellular models, SADS inhibited the abnormal proliferation of fibroblast-like synoviocytes through regulating the TNF-alpha and RAGE pathways. In addition, SADS promoted the polarization of M2 macrophages but inhibited the polarization of M1 macrophages. SADS alleviated the progression of experimental arthritis in a RA mouse model by modulating the TNF-alpha and RAGE signaling pathways, supporting its potential as a therapeutic agent for RA.

关键词： Esophageal cancer   IL-38   Sirt1/HIF-1 alpha   Treg/Th17  

摘要： Objective: This study aimed to identify biomarkers of esophageal cancer and elucidate their mechanisms of action in esophageal cancer. Methods: Differential protein expression between esophageal tumor tissue and adjacent normal tissue was analyzed using proteomics in a mouse model of esophageal cancer. Differential proteins were identified through bioinformatics analysis. The mechanisms of action of differential proteins in esophageal cancer were validated using techniques such as western blotting and immunohistochemistry. Results: Proteomic analysis revealed that IL-38 exhibited the greatest differential expression. Molecular biology techniques including western blotting and immunohistochemistry demonstrated that IL-38 modulates Regulatory T cell (Treg)/ T helper 17 cell (Th17) balance through the Sirtuin 1 (SIRT1)/ hypoxia-inducible factor 1-alpha (HIF-1 alpha) signaling pathway in esophageal cancer. Conclusion: IL-38 is a novel biomarker for esophageal cancer and regulates Treg/Th17 balance through the Sirt1/ HIF-1 alpha signaling pathway, providing new insights for the treatment of esophageal cancer.

关键词： Chemokines   Breast cancer stem cells   PRAME   Anti-Tumor immunity  

摘要： Background/objective: Tumor-associated macrophages (TAMs) and chemokine CCL18 play a pivotal role in breast cancer (BC) metastasis. They also promote breast cancer stem cells (BCSCs) enrichment. The melanomaassociated antigen such as preferentially expressed antigen in Melanoma (PRAME) is abnormally expressed in many cancers and is also associated with BC metastasis, but the specific mechanism is unclear. This study explores the role of PRAME and other tumor-linked antigens in BCSCs and their potential for immunotherapy in specific human leukocytes antigen (HLA) phenotypes. Methods: We analyzed 28 BC tissues (non-metastatic: 17;metastatic: 11) via immunohistochemistry (IHC) and Western blot. Bioinformatics profiling of 1102 BC samples (TCGA/Oncomine) assessed CCL18-PRAME-BCSC correlations. In vitro, CCL18-induced BCSC self-renewal (sphere formation) and PRAME upregulation were validated in MCF-7/MDA-MB-231 cells. HLA-A*11:01 prevalence was determined by PCR/Sanger sequencing. PRAME-derived peptides were screened in silico (NetMHC/EpiJen) and validated in dendritic cell (DC)-T cell cocultures, with Granzyme B activation measured via Luminex assay. Results: CCL18 expression correlated with BCSCs markers (such as CD44+/CD24-/ALDH1A1+) and PRAME in BC tissues. PRAME was significantly upregulated in BCSCs and BC metastasis, increased in human BC under CCL18 induction, and enhanced BCSC self-renewal and metastatic potential. T cells infiltration was activated when PRAME was highly expressed in the HLA-A*1101 phenotype. In this phenotype, PRAME derived peptides (such as SMSVWTSPR, YVDSLFFLR, and ELFSYLIEK) presented by dendritic cells significantly increased the level of granzyme B and activated T cell immunity against tumor cells. Conclusion: The PRAME's interaction with the tumor microenvironment and immune system highlights its potential as a biomarker for BC prognosis and a candidate for targeted immunotherapy, offering new targets for precision medicine in BC treatmen

关键词： ABC   ATP-binding cassette   ADORA2A   adenosine A2A receptor   ccRCC   clear cell type renal cell carcinoma   CML   chronic myeloid leukemia   CNS   central nervous system   CSC   cancer stem cell   CTLA   cytotoxic T-lymphocyte associated protein   EMT   epithelial-mesenchymal transition   EPO   erythropoietin   FDA   U.S. Food and Drug Administration   GVHE   graft vs host effect   GVLE   graft vs leukemia effect   HCC   hepatocellular carcinoma   HIF   hypoxia-inducible factor   HRE   hypoxia response element   ICB   immune checkpoint blockade   LOX   lysyl oxidase   MDSC   myeloid-derived suppressor cell   MHC   major histocompatibility complex   NK   natural killer   PD   programmed cell death   PDL   programmed cell death 1 ligand   RCC   renal cell carcinoma   TAM   tumor-associated macrophage   TKI   tyrosine kinase inhibitor   TNBC   triple-negative breast cancer   Treg   regulatory T cell   VEGFA   vascular endothelial growth factor A   VHL   von Hippel-Lindau tumor suppressor protein  

摘要： The hypoxia-inducible factors (HIFs)& horbar;HIF-1 and HIF-2 & horbar;play critical roles in cancer progression by controlling the transcription of thousands of genes across the full range of human cell types. Inhibition of their activity blocks cancer growth, vascularization, and metastasis in mouse models. Small-molecule HIF inhibitors, with varying degrees of specificity and mechanism of action have been reported to have antitumor activity in mouse models. An HIF-2 inhibitor, belzutifan, has recently been approved for the treatment of renal cell carcinoma. Dual HIF-1/2 inhibitors are being developed and are likely to have utility as cancer therapeutics, particularly in combination with immune checkpoint blockade. Significance Statement: Hypoxia-inducible factor inhibitors represent a powerful new therapeutic approach that has the potential to improve patient survival in many types of cancer when administered in combination with existing therapies. (c) 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Tc   cytotoxic T   Th   helper T   TNF   tumor necrosis factor   IFN   Interferon   IL   interleukin  

摘要： Cytokine and CD49a expression by skin CD8 + T RM cells. (a) and (c) Representative indicated cytokine expressions in epidermal (a) and dermal (c) CD8 + T RM cells. (b) and (d) A summary of the percentage of indicated cytokine-positive cells in eac...

关键词： Eleusine indica   Inflammatory bowel disease   Transmural inflammation   TNBS   p38 MAPK   TNF-alpha  

摘要： Inflammatory bowel disease (IBD) is a relapsing-remitting gastrointestinal disorder characterized by chronic mucosal inflammation and dysregulated immune responses to gut microorganisms. Despite the many advancements in its management, current treatments are often limited by their adverse effects, high cost, and incomplete remission. Eleusine indica, a medicinal plant used in folkloric medicine, is known for its anti-inflammatory properties. However, its efficacy in IBD remains not known. This study evaluated the potential effect of the hydroethanolic extract of Eleusine indica (EI) in a rat model of trinitrobenzene sulphonic acid (TNBS)-induced colitis. Colitis was induced in Sprague Dawley rats via rectal administration of TNBS. Rats were subsequently treated orally with EI (200, 400, or 600 mg/kg) or sulfasalazine (500 mg/kg) for 7 days. Disease activity index (DAI), colon weight-to-length ratio, macroscopic and histopathological changes, haematological parameters, and serum levels of markers of inflammation: TNF-alpha, p38 MAPK, and of oxidative stress: glutathione (GSH) were assessed. EI significantly improved the DAI (p < 0.05) and reduced colon weight-to-length ratio (p < 0.05) and macroscopic colonic damage in TNBS-induced rats. Histopathological analysis revealed preserved mucosal architecture and reduced inflammatory infiltration in EI-treated groups. EI also significantly downregulated TNF-alpha (p < 0.0001) and p38 MAPK (p < 0.0001) while preserving GSH levels (p < 0.05), indicating suppression of inflammation and oxidative stress. Haematological parameters showed reversal of TNBS-induced leucocytosis (p < 0.05). EI demonstrated potent anti-colitic activity comparable to sulfasalazine. The findings from this study support its potential as a herbal therapeutic option for IBD.

关键词： Cervical cancer   HLA-DRB1.2   HRM   MHC   Papillomavirus  

摘要： Cervical cancer is a significant public health concern, particularly in women infected with the human papillomavirus (HPV). Recent evidence suggests that host genetic factors, specifically those related to the human leukocyte antigen (HLA) system, may also play a crucial role in determining susceptibility to cervical cancer in HPV-infected individuals. In this study, 86 patients with HPV and 27 healthy donors were selected from May 2023 to February 2024. HLA-DRB1 genotypes were determined using polymerase chain reaction followed by high-resolution melting curve analysis (HRM). Genotype frequencies in patients were compared with those in the control group from donors. Based on the HRM analysis, 10 genotypes were found in both patients and controls (profiles A-J). In the analysis of HLA-DRB1 genotypes, C, F, and I showed significant associations with HPV infection, indicating a possible protective effect against infection. Notably, genotype B was strongly linked to high-risk HPV, while genotype A was associated with low-risk HPV and is relevant to infection history. However, the remaining genotypes examined in the study did not exhibit significant associations with the analyzed parameters. This study contributes valuable evidence regarding the role of HLA-DRB1 genotypes in cervical cancer susceptibility and highlights the potential clinical implications for risk assessment and targeted immunotherapies. The use of HRM for HLA typing offers advantages that are efficient, accurate, and scalable, making it suitable for large-scale studies and clinical applications.