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关键词： HLA-DRB1*12:113   next-generation sequencing   novel allele  

摘要： HLA-DRB1*12:113 differs from HLA-DRB1*12:01:01:14 at codon 95 (GTC>ATC) and codon 191 (CGG>TGG).

关键词： Intervertebral disc degeneration   BQU57   Inflammation   Apoptosis   NF-kappa B signaling pathways  

摘要： Background: Intervertebral disc degeneration (IVDD) is a significant contributor to lower back pain (LBP), affecting approximately 80 % of the global population. The RalA inhibitor BQU57 plays a role in various cellular functions;however, its impact on nucleus pulposus cell (NPC) degeneration remains unclear. Methods: This study employed a combination of bioinformatics analysis and experimental validation to investigate the role of RalA in IVDD and its inhibitor BQU57 in its therapeutic potential. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and clinical intervertebral disc samples were collected to validate the upregulation of RalA in degenerated discs. In vivo and in vitro assessments were conducted to evaluate the effects of BQU57 on the extracellular matrix (ECM) metabolism and apoptosis of nucleus pulposus (NP) cells. Results: Elevated expression of RalA was observed in degenerated intervertebral discs from IVDD patients, and its expression was correlated with disease severity. Further mechanistic studies revealed that the RalA inhibitor BQU57 could balance ECM metabolism and apoptosis, potentially through the activation of the NF-kappa B signaling pathway. Conclusion: RalA plays a significant role in the pathogenesis of IVDD, and it may serve as a novel therapeutic target for IVDD. BQU57 demonstrates potential as an effective small molecule drug for the prevention and treatment of IVDD.

关键词： Achilles tendon regeneration   Piezoelectric PCL/BTO nanofilm   Macrophage and T cells   Immunomodulation   IL-17A/NF-kappa B signaling pathway  

摘要： Tendon injuries are often exacerbated by persistent inflammation, which hampers tissue regeneration. In this study, we developed a noninvasive, wirelessly controlled, and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone (PCL) and tetragonal barium titanate nanoparticles (BTO), and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model. In vitro study and in vivo study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors. Moreover, when bridging an Achilles tendon defect, the nanofilms could promote tenogenic gene expression including collagen deposition, and collagen remodeling, facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization. Moreover, the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis, reducing lipid deposition, and decreasing ectopic ossification. Mechanistically, the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor (NF)-kappa B signaling pathway that is mediated by interleukin (IL)-17A secreted from CD3+ T cells, and thus to reduce proinflammatory factors, such as IL-1 beta and IL-6, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha. These findings indicate the potential of piezoelectric stimulation in immunomodulation, and in promoting tendon regeneration via IL-17A/NF-kappa B-mediated pathway.

关键词： genomic full length   HLA-DQB1*06:47   PacBio sequencing  

摘要： The complete genomic sequence of HLA-DQB1*06:47 was determined using a PacBio sequencing approach conducted in China.

关键词： Cytokines   Disease activity   Interleukin 2 (IL-2)   Systemic lupus erythematosus  

摘要： ObjectiveLow-dose interleukin 2 (IL-2) administration has been shown to selectively modulate regulatory T (Treg) cell abundance and alleviate the progression of systemic lupus erythematosus (SLE). IL-2 level could be indicator of low-dose IL-2 usage in SLE patients. However, current methods for IL-2 detection are generally not sensitive to be used in clinic. This study aims to establish flow cytometry-based IL-2 detection as a feasible approach in determining IL-2 in peripheral blood of SLE *** cytometry was used to quantify the relative mean fluorescence intensity (MFI) of IL-2 in CD3+T cells and other lymphocyte subsets in peripheral blood mononuclear cell (PBMCs) from a cohort of 134 SLE patients and 112 healthy controls (HC). Correlations between IL-2 MFI and clinical or laboratory parameters in SLE patients were also *** of IL-2 represented IL-2 expression in CD3+T cells. IL-2 MFI was significantly lower in SLE patients compared to the HC group and negatively associated with anti-ribosomal protein antibodies, erythrocyte sedimentation rate (ESR), and blood urea. Conversely, it was positively correlated with IgA and hemoglobin. These associations with IgA, hemoglobin, ESR, and blood urea remained significant after adjusting for age and disease duration. IL-2 level was also positively correlated with the relative abundance of Th1, Th2, and Th17 cells. Furthermore, MFI of IL-2 recovered with effective treatment in SLE *** of IL-2 serves as a feasible marker of IL-2, which is significantly decreased in SLE patients and recovered with treatment, suggesting its potential for assessing short-term disease status and treatment response in SLE patients. Key Points center dot IL-2 MFI can be used to estimate IL-2 expression level in SLE patients. center dot IL-2 MFI is significantly reduced in SLE *** dot IL-2 MFI can serve as a marker for monitoring SLE activity and short-term status.

关键词： Psoriasis   Interleukin 17   IL17RA genetic variant   PASI   Psoriatic arthritis  

摘要： Background: Genetic variants that can play an important role in psoriasis (PsO) ethiology and pathophysiology. Objective: To evaluate the association between the IL17RA genetic variants with the susceptibility and severity of PsO. Methods: This study included 154 patients with PsO and 154 healthy controls. The severity of PsO was determined using Psoriatic Activity and Severity Index (PASI). The IL17RA single nucleotide variants T > C rs2241043, A > G rs2241049, and G > A rs6518661 were genotyped. Results: The IL17RA A > G (rs2241049) GG genotype was associated with protection against PsO [odds ratio (OR): 0.391, 95 % confidence interval (CI):0.199-0.768, p = 0.006)] while the IL17RA T > C (rs2241043) CC genotype and the IL17RA G > A (rs6518661) AA genotype were associated with the PsO severity (OR = 0.30, 95 % CI 0.10-0.093, p = 0.020 and OR = 0.22, 95 % CI 0.05-0.99, p = 0.020, respectively). Conclusion: The results demonstrated that the IL17RA A > G (rs2241049) GG genotype may be a protective factor against the development of PsO and the CC genotype of the IL17RA T > C (rs2241043) and the AA genotype of the IL17RA G > A (rs6518661) variants were associated with protection against the severity of PsO. Considering that these variants are located in intronic regions of the IL17RA, other genetic and epigenetic mechanisms involved in these associations should be investigated.

关键词： AMR   antibody-mediated rejection   BPAR   biopsy-proven rejection   DSA   donor-specific antibodies   HLA   human leukocyte antigen   MFI   mean fluorescence intensity   TCMR   t-cell mediated rejection   pDSA   pre-formed DSA   XM   crossmatch  

摘要： Evidence is mixed regarding the effect of positive crossmatch (XM) and preformed donor-specific antibodies (DSA) on rejection in liver transplant recipients. We categorized liver transplant recipients by XM and DSA status (XM negative, XM positive with resolved DSA, and XM positive with persistent DSA or any de novo DSA) and examined biopsy-proven rejection incidence within 6 months post-transplant, DSA trends, and immunosuppression management. Of 273 liver transplant recipients, 237 (86.8 %) were XM negative and 36 (13.2 %) were XM-positive, of whom 13 (36.1 %) had persistent or de novo DSA and 23 (63.8 %) had resolved DSA. Recipients in the persistent DSA group experienced earlier rejection at a higher rate (69.2 % at median of 25 days post-transplant) compared to the other two groups (21.7 % at median of 31 days in the resolved DSA group and 19.4 % at median of 46 days in the XM negative group;p < 0.001). Recipients in the persistent DSA group were also more likely to experience multiple rejection events (p < 0.001). XM positive recipients with persistent DSA or de novo DSA are at higher risk for early allograft rejection, while those who can clear their DSA early have a rejection risk profile similar to recipients with a negative crossmatch.