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关键词： Buffalo   Cystic ovarian disease   Follicular fluid   Gene expression   Infertility   Interleukins  

摘要： Background: Cystic ovarian disease (COD) is a prevalent cause of infertility in buffalo, necessitating a deeper understanding of the underlying molecular mechanisms. This study aimed to investigate the expression levels of IL-1RII, IL-1RA and IL-4 cytokines in naturally occurring ovarian follicular cysts obtained from a slaughter house. Methods: The relative gene expression was assessed using real-time PCR (RT-PCR) while concentrations of IL-1 and IL-4 were quantified in follicular fluid via ELISA. Result: The results revealed that the IL-4 gene was expressed in both normal and cystic follicles, with slightly higher expression observed in cystic follicles, albeit without statistical significance. Interestingly, higher concentrations of IL-1 and IL-4 were found in normal follicles compared to cystic follicles, regardless of the season, with no significant variations between seasons within the same follicle type. These findings provide valuable insights into the altered cytokine expression and hormonal profiles associated with cystic ovarian disease in buffalo. Further research is warranted to elucidate the precise roles of these cytokines and hormones in the pathophysiology of COD, potentially leading to improved diagnostic and therapeutic strategies for this infertility disorder in buffalo.

关键词： HLA   HLA-C   novel allele   sequencing-based typing  

摘要： The novel allele HLA-C*07:1088 differs from HLAC*07:01:01:01 by one non-synonymous nucleotide substitution in exon 3.

摘要： Osteoarthritis (OA), a prevalent joint disorder, can lead to disability, with no effective treatment available. Interleukin-1 (IL-1) plays a crucial role in the progression of OA, and its receptor antagonist (IL-1Ra), a natural IL-1 inhibitor, represents a promising therapeutic target by obstructing the IL-1 signaling pathway. This study delivered IL-1Ra via adeno-associated virus (AAV), a gene therapy vector enabling long-term protein expression, to treat knee osteoarthritis (KOA) in animal models. scAAV-oIL-1Ra-I1/2 injected directly into the joint in both MMT/ACLT-induced KOA model rat improved abnormal gait (increasing footprint area and pressure), subchondral bone lesions, and significantly reduced cartilage wear and pathological scores. In the MMT-induced KOA rabbit model, weight-bearing asymmetry (indicating pain) improved after 8 weeks of scAAV-oIL-1Ra-I1/2 administration, and X-ray showed decreased K-L scores (severity grade), reduced cartilage loss, and lower pathology scores compared to untreated animals. Additionally, sex-determining region Y-type high mobility group box 9 (SOX9) was co-delivered with IL-1Ra via AAV in ACLT + MMT-induced KOA rats. The combined treatment significantly alleviated subchondral bone lesions, cartilage destruction, synovial inflammation, and pathological scores, demonstrating superior efficacy compared to either treatment administered alone. Co-delivering IL-1Ra and SOX9 inhibited IL-1 mediated inflammatory signaling, maintained cartilage homeostasis, and promoted its repair in KOA models, suggesting potential for clinical use.

关键词： cord blood transplantation   donor selection   HLA   transplantation-related mortality  

摘要： Cord blood transplantation (CBT) is a valuable donor source for patients without human leukocyte antigen (HLA)-matched donors. While CBT has a lower risk of graft-versus-host disease and requires less stringent histocompatibility, it is associated with a higher transplantation-related mortality (TRM) compared to other donor sources. We hypothesized that assessing the immunogenicity of mismatched HLA could reveal non-permissive mismatches contributing to increased TRM. We retrospectively analysed 1498 single-unit CBT cases from 2000 to 2018 across eight Japanese institutions, evaluating the immunogenicity of mismatched HLA using the PIRCHE algorithm to examine binding affinities of HLA-derived epitopes to donor or recipient HLA. Results indicated that Class I epitopes from mismatched recipient HLA-B were significantly associated with poor outcomes due to higher TRM and lower neutrophil engraftment, particularly when presented on matched HLA class I. Notably, epitopes from HLA-B exon 1 showed stronger prognostic significance, with HLA-B alleles carrying M-type leader peptides exhibiting higher affinity for these epitopes. Patients with a matched M-type HLA-B and Class I epitopes derived from mismatched HLA-B exon 1 had worse outcomes. These findings suggest that immunogenicity-informed donor selection could improve CBT outcomes.

关键词： Illumina MiSeq   next generation sequencing (NGS)   novel HLA-allele  

摘要： HLA-A*68:02:27 differs from HLA-A-68:02:01:01 by a single nucleotide variation in Exon 4, codon 206.

关键词： cirrhosis   IL-6   renal impairment   spontaneous bacterial peritonitis   TNF-alpha   VCAM-1  

摘要： Background Multiple mechanisms may contribute to the occurrence of renal impairment (RI) in patients with spontaneous bacterial peritonitis (SBP). One such mechanism is systemic inflammatory response syndrome, which involves the release of pro-inflammatory cytokines (tumour necrosis factor [TNF]-alpha, interleukin [IL]-6 and vascular cell adhesion molecule [VCAM]-1). The goal of this research was to evaluate the role of IL-6, TNF-alpha and VCAM-1 as potential predictors of RI and mortality in cirrhotic patients with *** This study included 90 cirrhotic patients with SBP, divided into two equal groups: group A was patients without RI and group B was patients with RI. Based on mortality outcomes, the patients were further categorized into group 1 (recovery, n=70) and group 2 (death, n=20). TNF-alpha, IL-6 and VCAM-1 serum levels were measured using enzyme-linked immunosorbent *** RI occurred in 50% (45/90) of the study population. Among the 90 patients, 10 (11.1%) had elevated IL-6 levels, 8 (8.9%) had elevated TNF-alpha levels and 6 (6.7%) had elevated VCAM-1 levels. There were no significant variations in cytokine levels between groups A and B. With an area under the curve of 0.5, the three cytokines showed comparable sensitivity and specificity as predictors of *** The use of TNF-alpha, IL-6 and VCAM-1 as predictive markers for RI and mortality in SBP patients is not recommended, as these biomarkers demonstrated limited diagnostic value.

关键词： Respiratory Physiology  

摘要： Influenza A virus (IAV) a negative-sense, single-stranded RNA virus, which belongs in the Orthomyxoviridae family. Influenza A is a common cause of acute respiratory illnesses worldwide and associated with considerable morbidity and mortality. Ubiquitin-specific protease 13 (USP13) belongs to the deubiquitinating enzyme (DUB) superfamily. The role of USP13 in the pathogenesis of IAV-induced lung injury has not been revealed. In this study, we investigated the role of USP13 in IAV-induced lung injury. Influenza A/Puerto Rico/8/34 (H1N1) virus was used to infect human lung epithelial cells and mice. IAV infection decreased USP13 protein levels in the mouse lung tissues at 7 days post-infection (dpi). Both USP13 mRNA and protein levels were significantly decreased in IAV-infected A549 cells in dose- and time-dependent manners. Next, we investigated the role of USP13 in IAV-triggered signaling in A549 cells by silencing and overexpressing USP13. Knockdown of USP13 impaired IAV-induced IFN-β mRNA and protein expression, whereas USP13 overexpression enhanced IAV-induced IFN-β mRNA and protein expression. Moreover, knockdown of USP13 significantly increased virus titers at 48 hours post-infection (hpi) in IAV-infected A549 cells. On the other hand, overexpression of USP13 resulted in a significantly decrease in virus titers at 48 hpi. To further investigate the role of USP13 in IAV infection, we infected wild type mice (USP13+/+) and USP13 knockout mice (USP13-/-) with intranasal administration of PR8 virus. USP13-/- mice showed significant more weight loss compared to USP13+/+ mice after PR8 infection. USP13 knockout mice were more susceptible to influenza virus pathology and USP13 deficiency decreases IAV-induced IFN-β production. Mechanistically, Knockdown of USP13 impaired IAV-triggered IRF3 nuclear translocation. Moreover, we found that IAV infection promoted association between USP13 and p-IRF3. Future studies will shed light on the role of USP13 in modulating the ub

关键词： Autoimmunity   Bullous pemphigoid   IL-5   Mouse model   T cell line  

摘要： Bullous pemphigoid is an autoimmune subepidermal blistering disease caused by anti-type XVII collagen (COL17) antibodies. Bullous pemphigoid has some immunological features such as eosinophilic infiltration and the deposition of IgE autoantibodies in the skin;however, the mechanism behind such features remains largely unclear. We focused on the autoantigen-specific CD4+ T cells, which are considered to regulate immune response. We established COL17-specific CD4+ T cell lines in vitro. Wild-type mice were immunized with synthesized peptides that include a pathogenic epitope of COL17, and lymphocytes were subjected to a limiting dilution assay. We established 5 T cell lines and examined the pathogenicity by transferring them with COL17-primed B cells into Rag-2-/-/COL17-humanized mice that express human COL17 but not mouse COL17 in the skin. Notably, 3 lines induced bullous pemphigoid-like skin changes associated with subepidermal separation and eosinophilic infiltration histologically and the production of anti-COL17 antibodies. The other 2 lines did not induce such phenotypes. RNA-sequencing analysis revealed that T helper 2 cytokines, particularly IL-5, were highly expressed in the pathogenic T-cell lines. Anti-IL-5 antibody administration significantly reduced the skin changes and attenuated the production of autoantibodies. Thus, the production of IL-5 is critical for COL17-specific CD4+ T cells to induce bullous pemphigoid phenotypes in vivo.