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关键词： cancer immunotherapy   immune responses   MHC loss   tumour microenvironment  

摘要： Loss or downregulation of major histocompatibility complex (MHC) molecules represents a key mechanism by which tumours escape immune recognition and acquire resistance to immunotherapeutic interventions. This review focuses on the central regulatory pathways. These includes transcriptional repression, lysosomal degradation, and post-translational modifications that disrupt MHC stability, trafficking, and surface expression. We highlight how these mechanisms impair antigen presentation and contribute to tumour immune evasion. In addition, we explore emerging therapeutic strategies focused on reactivating MHC expression to enhance tumour immunogenicity and improve the efficacy of immunotherapy. Finally, we discuss the translational potential of these approaches and the remaining challenges, including tumour heterogeneity, immunotoxicity and dynamic regulation within the tumour microenvironment, that must be addressed to optimize MHC-targeted interventions in cancer *** Tumour cells evade immune surveillance by downregulating MHC expression through transcriptional repression, lysosomal degradation and post-translational modifications. Pharmacological agents interventing epigenetic and metabolic can upregulate MHC expression and improve T cell activation. Combination strategies potentiate immunotherapy efficacy by reinvigorating tumour immunogenicity.

关键词： HLA   HLA-DQB1*06:03:57   novel allele   sequencing-based typing  

摘要： HLA-DQB1*06:03:57 differs from HLA-DQB1*06:03:01:01 by one nucleotide substitution in codon 21 in exon 2.

关键词： high-sensitivity C-reactive protein   inflammatory marker   interleukin-1 beta   interleukin-6   ischemic stroke   mononuclear cell tissue factor   sP-selectin   tumor necrosis factor-alpha  

摘要： Objectives Stroke is an injury occurring due to a sudden interruption of blood supply to the brain. It is the leading cause of disability worldwide and the second most prevalent cause of mortality. The objective of this study is whether momentous inflammatory and coagulation markers may have a correlation with each other in stroke patients. Material and methods Sixty stroke patients and twenty sex-age matched normal controls were sampled. Interleukin (IL)-6, IL-1 beta, sP-selectin, and high-sensitivity C-reactive protein (hsCRP), key inflammatory markers, were selected and measured by ELISA, and tissue factor gene expression level was evaluated by real-time PCR in peripheral blood mononuclear cells. Results The serum levels of sP-selectin, IL-1 beta, IL-6, and hsCRP increased significantly in patients (P-value < 0.05). In the patient group, a significant correlation was observed between these inflammatory markers and coagulant tissue factor gene expression in peripheral blood mononuclear cells (P-values < 0.05), while it was not significant in the control group. Conclusion This study proposed that the main inflammatory markers in connection with tissue factor may play a role in the occurrence of thrombosis in stroke patients. Therefore, targeting and inhibiting the key inflammatory factors along with existing anticoagulants may greatly reduce the complications associated with stroke. Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved.

关键词： IL-28A   IL-10R(3   Angiogenesis   HSP70-1  

摘要： Introduction: Angiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated. Objectives: We report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses. Methods: To know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10R(3 in IL-28Ainduced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hindlimb ischemia ***: Autocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-jB/ MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28Ainduced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL10Rb gene impeded the an

关键词： HLA-DQB1*06:04:01:11   HLA-genotyping   Illumina   next generation sequencing   novel allele  

摘要： The HLA-DQB1*06:04:01:11 allele differs from HLA-DQB1*06:04:01:01 by a single nucleotide substitution in intron 2.

关键词： ASCVD   atherosclerotic cardiovascular disease   CABG   coronary artery bypass graft   CAD   coronary artery disease   HR   hazard ratio   IL   interleukin   KIV-2   kringle IV type 2   LDL   low-density lipoprotein   LDL-C   low-density lipoprotein cholesterol   Lp(a)   lipoprotein(a)   MACE   major adverse cardiovascular events   MI   myocardial infarction   NLRP3   Nod-like receptor family pyrin domain containing 3   OR   odds ratio   PCI   percutaneous coronary intervention   PCSK9   proprotein convertase subtilisin/kexin type 9   RR   relative risk  

摘要： BACKGROUND Coronary artery bypass grafting (CABG) remains a cornerstone in the management of coronary artery disease (CAD). In nonurgent surgical revascularization cases, preoperative optimization of modifiable risk factors can improve outcomes. There is increasing interest in the relationship between lipoprotein(a) levels and the risk for ischemic cardiovascular disease, particularly how CABG outcomes are in turn affected. This review highlights the role of lipoprotein(a) in the pathogenesis of CAD and CABG outcomes and discusses future directions for its optimal management in the perioperative period. METHODS The PubMed/MEDLINE database was reviewed until March 2024 to capture publications that evaluated and/or described the relationship between lipoprotein(a) and CABG surgery or CAD outcomes. RESULTS The available literature supports lipoprotein(a) as a causal and independent risk factor for the pathogenesis of CAD. Elevated lipoprotein(a) levels are associated with an increased risk of adverse post-CABG outcomes, including graft occlusion incidence and major adverse cardiovascular events. Genetic variations influencing lipoprotein(a) levels play a role in disease progression and surgical outcomes. Several therapies aimed at reducing lipoprotein(a) levels, currently in phase III clinical trials, show promise for improving the prognosis after CABG. CONCLUSIONS Among individuals undergoing surgical revascularization for CAD, lipoprotein(a) levels may help define risk and inform best practices for perioperative management. We advocate for the routine measurement of lipoprotein(a) in all patients undergoing CABG. Emerging lipoprotein(a)-lowering agents show promise for secondary prevention of cardiac events, although dedicated analyses in cardiac surgical subcohorts will be important to evaluate their role in improving CABG outcomes. (Ann Thorac Surg 2025;120:167-76) (c) 2025 The Authors. Published by Elsevier Inc. on behalf of The Society of Thoracic Surgeons. This

关键词： Mucus hyperproduction   Tobacco   IL-13R   Air-liquid-interface culture   Airway chronic inflammation  

摘要： Chronic airway inflammation, such as that occurring in chronic obstructive pulmonary disease, induces goblet cell metaplasia and hyperplasia (GCMH) and leads to hyperproduction of mucus and thickening of airway walls, restricting airflow. Cigarette smoke causes chronic inflammation and GCMH in the airways through a complex mechanism involving various factors, including immune cells. Previous studies reported direct effects of cigarette smoke on epithelial cells. Replicating the physiological condition of immune cells, we assessed the interaction between cigarette smoke extract (CSE) and interleukin (IL)-13, a GCMH inducer, on air-liquid interface-cultured normal human bronchial epithelial cells (NHBEs) from a single non-smoking subject. While single exposure to IL13 or CSE induced mucus production, as previously reported, co-exposure to IL-13 and CSE synergistically enhanced this effect. We also investigated IL-13 receptor expression, which revealed that CSE exposure significantly induced the expression of the functional IL-13 receptor subunit, IL-13R alpha 1. To analyze the signaling pathway involved, we exposed NHBE cultures to benzo(a)pyrene, an aryl hydrocarbon receptor (AhR) ligand and constituent of CSE, which increased IL-13R alpha 1 expression in a concentration-dependent manner. Furthermore, treatment with the AhR inhibitor resveratrol erased the effects of CSE on mucus production and IL-13R alpha 1 expression. Here, we present a novel pathway to GCMH by which cigarette smoke induces IL-13R alpha 1 expression through AhR stimulation, making epithelial cells sensitive to IL-13. This discovery not only contributes to our understanding of chronic airway inflammation, but also supports the use of in vitro models to reproduce chronic inflammation without co-culture of epithelial cells and immune cells.

摘要： Objectives: Interleukin (IL)-17A is a key driver of spondyloarthritis (SpA) joint pathology. We aimed to identify its cellular source in synovial tissue from patients with 2 forms of SpA, namely axial SpA (AxSpA) and psoriatic arthritis (PsA). Methods: Synovial tissue from patients with SpA was profiled using single-cell RNA sequencing (scRNA-seq;AxSpA, n = 5;PsA, n = 6) or spatial RNA profiling (PsA, n = 4). CellPhoneDB was used to infer cell-cell communication. Tissue-resident memory Th17 (TRM17)-like cells were generated in vitro using blood memory CD4+ T cells from SpA patients. An epigenetic inhibitor library, siRNA, and clustered regularly interspaced short palindromic repeats (CRISPR) were used to identify epigenetic regulator(s) for TRM17. Results: scRNA-seq showed that CD4+CXCR6+ TRM17 cells are the predominant spontaneous IL17A producers in SpA synovium. Cell-cell communication and single-cell spatial analysis support the interaction between TRM17 and CLEC10A+ dendritic cells, which were activated in SpA. Both sublining and lining fibroblasts in SpA synovium showed evidence of interleukin (IL)-17A activation. In vitro-generated CD4+ TRM17-like cells phenocopied joint tissue TRM17, producing IL-17A/F upon T cell-receptor (TCR) stimulation, which was further enhanced by cytokines. Perturbation of BRD1 inhibited the generation of TRM17-like cells. Conclusions: CD4+ TRM17 cells are the predominant source of IL-17A in SpA synovial tissue. TCR stimulation is essential for the secretion of IL-17A by CD4+TRM17-like cells. The epigenetic regulator bromodomain-containing protein 1 (BRD1) contributes to the generation of CD4 +TRM17. Depleting CD4+TRM17 cells in SpA is thus a therapeutic strategy with potential to induce long-term remission.

关键词： Chlamydia infection   NK cells   Organoids   Macrophages   Secretion   Inflammation   Immune cells   Cytokines  

摘要： Interferon-gamma (IFN-gamma) is an immunoregulatory cytokine essential for cellular immunity against intracellular pathogens, including Chlamydia. Interferon-stimulated gene (ISG) 15, a member of the ubiquitin family, contributes to host resistance to viral and bacterial infections. ISG15 can exist either in and unconjugated form or covalently attached to host proteins through a process known as ISGylation. Here, we show that infection with Chlamydia trachomatis (Ct) induces the expression and secretion of ISG15 in human primary cells and mouse female genital tract (FGT) organoids. ISG15 secretion by genital tract epithelial cells resulted in increased IFN-gamma release from natural killer (NK) cells. The production of IFN-gamma by NK cells in response to ISG15 was completely abolished in NK cells lacking the interleukin-18 receptor alpha (IL-18Ra), demonstrating a co-stimulatory effect of ISG15 with IL-18 in enhancing IFN-gamma release. ISG15 was secreted into the FGT and was involved in controlling bacterial load in a murine infection model. Furthermore, ISG15 reduced macrophage responsiveness to IFN-gamma as an M1-polarizing signal for pro-inflammatory responses, potentially "shielding" macrophages from excessive IFN-gamma. Evidence of uterine horn pathology and reduced IL-10 levels in the FGT of infected ISG15-/- mice further supports a critical dual function of ISG15 in controlling chlamydial infection and modulating the resulting inflammatory responses.