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关键词： C*04:NEW   HLA   IPD-IMGT/HLA  

摘要： HLA-C*04:533 differs from C*04:01:01:14 by a single non-synonymous nucleotide change in codon 216 (ACC>AAC).

关键词： chondrocytes   ferroptosis   Nrf2   osteoarthritis   Relaxin-2  

摘要： Excessive inflammatory responses and ferroptosis-associated dysfunction of chondrocytes are significant pathological features of osteoarthritis (OA). Relaxin-2, a well-known hormone involved in metabolic regulation across various tissues and cells, has not been extensively studied in the context of chondrocyte dysfunction and OA. T/C-28a2 cells were stimulated with tumor necrosis factor alpha (TNF-alpha) (10 ng/mL) with or without recombinant human relaxin-2 (rh relaxin-2) (25, 50 nM) for 48 h. Various techniques, including 2 ',7 '-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, real-time PCR, western blot analysis, enzyme-linked immunosorbent assay (ELISA), and luciferase activity assays, were employed. We discovered that exposure to TNF-alpha decreased the expression of Relaxin-2 at both the mRNA and protein levels. Further investigation revealed that treatment with rh relaxin-2 mitigated lipid peroxidation by reducing levels of reactive oxygen species (ROS), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (4-HNE), while increasing superoxide dismutase (SOD) activity and glutathione (GSH) content. Notably, rh relaxin-2 restored iron metabolism balance disrupted by TNF-alpha in human T/C-28a2 chondrocytes by decreasing Fe2+ levels, downregulating transferrin receptor 1 (TFR1) gene expression, and upregulating ferritin gene expression. Additionally, rh relaxin-2 alleviated ferroptosis induced by TNF-alpha in these cells by increasing glutathione peroxidase 4 (GPX4) expression, decreasing acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, and reducing lactate dehydrogenase (LDH) release. Rh relaxin-2 also inhibited the TNF-alpha-induced expression of pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Interestingly, rh relaxin-2 attenuated TNF-alpha-induced chondrocyte degeneration by suppressing matrix metalloproteinase-13 (MMP-13) expression and preventing degradation of collagen type II alpha1 chain (Col2 al

关键词： Single nucleotide polymorphisms (SNPs)   Tuberculosis(TB)   Susceptibility   Interleukin-32 (IL-32)  

摘要： Objective: Interleukin (IL)-32, encoded by the IL-32 gene, is a crucial constituent of the autophagy pathway and is involved in the regulation of Mycobacterium tuberculosis (***) infection, a major global health challenge. This study aimed to examine the potential association between IL-32 polymorphisms and susceptibility to Tuberculosis(TB), highlighting the significance of genetic factors in TB risk. Design: Sequence analysis of IL-32 was conducted in 570 individuals diagnosed with pulmonary tuberculosis (PTB), 363 individuals diagnosed with extrapulmonary tuberculosis (EPTB), and 604 healthy controls from the Chinese Han population, representing a broad spectrum of TB manifestations. Five single nucleotide polymorphisms(SNPs) were selected for analysis based on their potential impact on IL-32 function and TB susceptibility. Results: The study revealed that the polymorphism rs12934561C allele exhibits a positive correlation with elevated susceptibility to PTB (P = 0.003, OR (95%CI) = 1.28 (1.09-1.51)), highlighting its potential role as a biomarker for PTB risk. A noteworthy relationship was observed between the rs12934561 TT genotype and the decreased likelihood of PTB, further underscoring the complexity of IL-32's role in PTB susceptibility. Moreover, it was found that protective haplotypes for PTB are TCAAC (P = 0.001, OR (95%CI) = 0.75 (0.62-0.90)) and TCGTT (P = 0.002, OR (95%CI) = 0.47 (0.29-0.77)) may be present in IL-32;Conversely, the potential risk haplotypes for PTB are CCGAA (P = 0.007, OR (95%CI) = 1.29 (1.07-1.55)) and TCATT (P = 0.033, OR (95%CI) = 1.30 (1.02-1.66)), indicating genetic variations that increase PTB susceptibility. In contrast, neither allelic nor genotypic associations were statistically significant among EPTB cases, highlighting the distinct genetic influences on the different forms of TB. Conclusion: In this study, we discovered that polymorphisms in IL-32 are significantly associated with increased susceptibility to pulmonary TB

关键词： A*02:1173   A*03:01:128   A*03:489   A*23:141   new HLA allele   NGS  

摘要： Four novel HLA-A alleles HLA-A*02:1173, -A*03:01:128, -A*03:489, and -A*23:141 alleles were detected during routine next generation sequencing.

摘要： Whereas acute inflammation plays an important role in both tissue damage and repair, chronic inflammation favors tissue injury. Monocytes contribute to this deleterious effect by secreting proinflammatory cytokines. Amini et al. propose a novel mechanism involving adenosine triphosphate-induced purinergic P2X purinoceptor 7 receptor activation, which leads to calcium ion-dependent mitochondrial reactive oxygen species production, triggering interleukin-1 alpha release by monocytes. This stimulates kidney immune cell infiltration and fibrosis in chronic kidney disease and promotes adverse cardiac remodeling following myocardial infarction.

关键词： ACR   Acute Cellular Rejection   AMR   Antibody-mediated Rejection   CMV   Cytomegalovirus   DSA   Donor-specific antibody   HLA   Human leukocyte antigen   IT   Intestinal Transplant   IVIG   Intravenous Immunoglobulin   MFI   Mean fluorescence intensity   mTOR inhibitors   Mammalian target of rapamycin inhibitors   PRA   Panel-reactive antibodies  

摘要： Background. Intestinal transplantation (IT) is a complex procedure that requires nuanced variability remains in immunosuppressive protocols across transplant centers due to a lack of consensus on the optimal approaches for induction, maintenance, and clinical testing. This variability complicates standardization and identification of best practices for IT recipients. Methods. A descriptive survey study was conducted to characterize immunosuppressive and testing strategies in IT at major transplant centers in the United States. Ten centers known to have performed over 10 ITs since 2015 were selected from the Scientific Registry of Transplant Recipients database. A 22-question survey was distributed to surgical directors, collecting data on pre-, peri-, and post-transplant immunological testing, desensitization strategies, immunosuppressive regimens, and management of antibody-mediated rejection (AMR) and acute cellular antigen (HLA) and donor-specific antibody (DSA) testing, with varying frequencies and methodologies. Desensitization was reported by 44% of centers for isolated IT and by 22% for multilevel targets across centers. Post-transplant DSA testing was performed by all centers, and protocol-driven endoscopic bowel biopsies were routine at 67% of centers. AMR was diagnosed at 89% of centers, with plasmapheresis and IVIG being the most common treatments. Variability was noted in desensitization practices and AMR management. Conclusion. This survey highlights considerable consistency in pre- and post-transplant test- ing and immunosuppressive regimens for IT recipients, while significant variability exists in desensitization strategies and AMR management. Further research is needed to standardize these practices to improve patient outcomes across transplant centers