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关键词： Crohn's disease   Mesenteric fat   Fibrogenesis   Group 1 Innate lymphoid cell  

摘要： Background Creeping fat is a characteristic of Crohn's disease and impacts the disease course. We evaluated creeping fat formation, focusing on innate lymphoid cell-mediated fibrogenesis and its clinical significance. Methods Patients with inflammatory lesions in the ileum (the most commonly affected area), who underwent surgical resection at Osaka University or Hyogo Medical University (n = 34), were included. The ileum and mesentery were obtained from three sites: the control, non-creeping fat part, and creeping fat part. The distribution and properties of the innate lymphoid cells were analyzed by cell isolation. Furthermore, the correlation between macrophages and their effects on adipose tissue and clinical course were also investigated in a prospective cohort study. Results Group 1 innate lymphoid cells in creeping fat were increased, correlating with inflammatory macrophages in the mesentery and showing higher interferon-gamma expression. Co-culture experiment involving stromal vascular fraction from the control mesentery and Group 1 innate lymphoid cells from creeping fat revealed increased mRNA expression of fibrosis-related genes and inflammatory markers of macrophages, although these changes were nullified by interferon-gamma-neutralizing antibody. Next, we examined the clinical importance of Group 1 innate lymphoid cells and identified their high frequency in creeping fat as a risk factor for early recurrence (P = 0.008, odds ratio: 1.19). Furthermore, the higher Group 1 innate lymphoid cell frequency group (>= 80%) had shorter relapse-free survival (P = 0.03). Conclusions Group 1 innate lymphoid cells and inflammatory macrophages contribute to creeping fat formation via interferon-gamma secretion, affecting post-surgery intestinal outcomes.

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   italic>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： 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： 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： 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