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关键词： HLA   Novel HLA alleles   NGS  

摘要： HLA compatibility between patients and donors is a determining factor for the success of stem cell and solid organ transplantations. However, finding suitable donors remains challenging due to the highly polymorphic nature of HLA genes. Here we are describing 16 novel HLA-A,-B,-C and-DRB1 alleles identified over the period of 2 years. Fourteen differed from their closest reference allele sequence by single nucleotide substitutions detected in the coding regions and 13 contained polymorphism outside antigen recognition domains (exons 2 and 3 in class I and exon 2 in HLA class II). Two novel alleles, a non-sense substitution and a deletion of 2 bp resulted in two null alleles, while a substitution in a splice site resulted in an allele with questionable expression status. In HLA matching procedures, particularly in donor selection, it is important to determine alternatively expressed HLA alleles. Thirteen additional HLA-A,-B,-C and-DRB1 alleles detected as novel at the time of testing were already reported by other laboratories by the time of submission.

关键词： MSC   Chemokine   TSG-6  

关键词： Interleukin 6   Lung function   Mycoplasma pneumoniae pneumonia   Procalcitonin   severity   Prognostic predictions  

摘要： Objective: To explore the correlation of interleukin 6 (IL-6) and procalcitonin (PCT) with severity of Mycoplasma pneumoniae pneumonia (MPP) in children and their prognostic value. Methods: One hundred twenty children with MPP and 100 healthy children who underwent physical examination at the Clinical Laboratory Department of Nantong University Maternal and Child Health Hospital from November 2023 to December 2023 were selected as the study subjects, and were divided into the experimental group and the control group. The experimental group was divided into mild MPP group (n=70 ) and severe MPP group (n=50 ) according to the severity of the disease. According to the condition after one course of treatment, separated MPP children into good prognosis group (n=96) and poor prognosis group (n=24). The IL-6 and PCT levels of the experimental/control group before treatment and the good/bad prognosis group after treatment were compared, respectively. The lung function of children with MPP before and after treatment was also examined, and the changes of respiratory rate (RR), tidal volume (VT), expiratory time (Te), peak time (TPTEF), and peak volume (VPTEF) were observed. The correlation between pulmonary function and IL-6, PCT in MPP children was analyzed by Pearson analysis. Receiver operation curve was adopted to analyze the predictive value of IL-6, PCT for poor prognosis. Results: IL-6 and PCT were increased in the severe MPP group compared to the mild MPP group (P<0.001) and tended to decrease in the good prognosis group compared to the poor prognosis group (P<0.001). Fifty-nine of the 70 cases in the good prognosis group were patients with mild MPP, suggesting that patients with mild MPP have a better prognosis. The results of respiratory function showed an increase in RR (P<0.001) and a decrease in VT (P=0.007), TPTEF/Te (P<0.001), VPTEF/VT (P<0.001) in the severe MPP group compared to the mild MPP group. The results of correlation analysis revealed that IL-6, PCT w

关键词： Rosacea   STAT3   Skin inflammation   IL-36G   Pogostone  

摘要： Background: Rosacea is an inflammatory skin disorder characterized by the release of inflammatory mediators from keratinocytes, which are thought to play a crucial role in its pathogenesis. Despite an incidence of approximately 5.5%, rosacea is associated with a poor quality of life. However, as the pathogenesis of rosacea remains enigmatic, treatment options are limited. Objectives: To investigate the pathogenesis of rosacea and explore new therapeutic strategies. Methods: Transcriptome data from rosacea patients combined with immunohistochemical staining were used to investigate the activation of STAT3 in rosacea. The role of STAT3 activation in rosacea was subsequently explored by inhibiting STAT3 activation both in vivo and in vitro. The key molecules downstream of STAT3 activation were identified through data analysis and experiments. Dual-luciferase assay and ChIP-qPCR analysis were used to validate the direct binding of STAT3 to the IL-36G promoter. DARTS, in combination with experimental screening, was employed to identify effective drugs targeting STAT3 for rosacea treatment. Results: STAT3 signaling was hyperactivated in rosacea and served as a promoter of the keratinocytedriven inflammatory response. Mechanistically, activated STAT3 directly bind to the IL-36G promoter region to amplify downstream inflammatory signals by promoting IL-36G transcription, and treatment with a neutralizing antibody (a-IL36c) could mitigate rosacea-like inflammation. Notably, a natural plant extract (pogostone), which can interact with STAT3 directly to inhibit its activation and affect the STAT3/ IL36G signaling pathway, was screened as a promising topical medication for rosacea treatment. Conclusions: Our study revealed a pivotal role for STAT3/IL36G signaling in the development of rosacea, suggesting that targeting this pathway might be a potential strategy for rosacea treatment. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open

摘要： Interleukin-10 (IL-10) is pivotal in suppressing innate immune activation, in large part by suppressing induction of inflammatory genes. Despite decades of research, the molecular mechanisms underlying this inhibition have not been resolved. Here we utilized an integrated epigenomic analysis to investigate IL-10-mediated suppression of LPS and TNF responses in primary human monocytes. Instead of inhibiting core TLR4-activated pathways such as NF-kappa B, MAPK-AP-1 and TBK1-IRF3 signaling, IL-10 targeted IRF transcription factor activity and DNA binding, particularly IRF5 and an IRF1-mediated amplification loop. This resulted in suppression of inflammatory NF-kappa B target genes and near-complete suppression of interferon-stimulated genes. Mechanisms of gene inhibition included downregulation of chromatin accessibility, de novo enhancer formation and IRF1-associated H3K27ac activating histone marks. These results provide a mechanism by which IL-10 suppresses inflammatory NF-kappa B target genes, highlight the role of IRF1 in inflammatory gene expression and describe the suppression of IFN responses by epigenetic mechanisms.

关键词： Crohn's disease   elderly   anti-TNF   ustekinumab   safety   effectiveness  

摘要： Background Biologic therapies are associated with increased infection risk among elderly patients with inflammatory bowel disease (IBD). However, there are few data on the safety and effectiveness of ustekinumab compared with anti-tumor necrosis factor (anti-TNF) agents in the *** The study sought to compare the safety and effectiveness of ustekinumab and anti-TNF agents in elderly Crohn's disease (CD) patients. Patients >= 60 years of age who commenced ustekinumab or an anti-TNF agent for CD were included in this retrospective multicenter cohort. The primary outcome was incidence of serious infections requiring hospitalization. Effectiveness was assessed by clinical remission, clinical response, and treatment persistence rates at 6 months. We adjusted for confounders using inverse probability of treatment weighting (IPTW) and performed a logistic regression analysis to assess factors associated with serious infections, clinical remission, and treatment *** Eighty-three patients commencing ustekinumab and 124 commencing anti-TNF therapy were included. There was no difference in serious infection rates between anti-TNF agents (2.8%) and ustekinumab (3.1%) (P = .924) after propensity adjustment. Clinical remission rates were comparable at 6 months for ustekinumab (55.9%) and anti-TNF agents (52.4%) (P = .762). There was a significant reduction in HBI at 6 months in both groups. Treatment persistence was comparable between ustekinumab (90.6%) and anti-TNF agents (90.0%) at 6 months. Cox regression analysis did not show differences in treatment persistence (hazard ratio, 1.23;95% confidence interval, 0.57-2.61;P = .594) and serious infection incidence (hazard ratio, 1.38;95% confidence interval, 0.25-7.57;P = .709) by 6 *** We observed comparable safety and effectiveness for ustekinumab and anti-TNF agents in treating elderly CD patients. In this retrospective multicenter cohort study, we report equal safety and effectiveness f

摘要： Highlights•There is no standard treatment in NSCLC and acquired resistance to immunotherapy. •OSE2101, a therapeutic cancer vaccine, demonstrated survival benefit in this setting. •We present the design of the phase 3 trial to confirm initial positive results.

关键词： deep learning   evolutionary scale model   human leukocyte antigen   peptide   prediction  

摘要： The recognition of endogenous peptides by HLA class I plays a crucial role in CD8+ T cell immune responses and human adaptive cell immune. Thus, the prediction of HLA class I-peptide binding affinities is always the core issue for the research of immune recognition and vaccine development. In this study, an evolutionary scale model (ESM) combined with parallel CNN blocks and a cross attention mechanism was used to construct a novel ESMpHLA model for predicting HLA class I binding peptides. Based on the 91,560 binding peptides of 41 HLA-A alleles, 56,731 of 50 HLA-B alleles and 2444 of 10 HLA-C alleles, the ESMpHLA model was successfully established and achieved satisfying prediction performances with the overall accuracy and AUC values of 0.874 and 0.938 for the test dataset. The results indicate that the ESMpHLA model performs well in dealing with different HLA class I 2-field alleles as well as the peptides with different lengths. Then, the generalisation ability of the ESMpHLA model was validated by an independent test dataset compiled from recent IEDB weekly benchmark datasets. The results showed that the ESMpHLA model achieved the highest ROC-AUC and PR-AUC values when compared with the latest BVMHC, CapsNet-MHC, STMHCpan and BVLSTM models. In addition, two ensemble models were also established by integrating the above 5 deep learning models using soft-voting and hard-voting strategies.

关键词： Viruses   Epstein-Barr virus (EBV) BSRF1   Cellular moleculars   Antiviral response   Protein-protein interaction   NF-kappa B signaling pathway  

摘要： The Epstein-Barr virus (EBV) encoded tegument protein BSRF1 plays a significant role in the processes of viral maturation and release, however, it's not clear whether BSRF1 is involved in the modulation of host innate immunity. In this study, we demonstrated that BSRF1 can inhibit interferon beta (IFN-beta) production by down- regulating nuclear factor kappa B (NF-kappa B) activity and subsequently reducing the yield of inflammatory cytokines, thereby facilitating viral replication. Dual luciferase reporter assays indicated that BSRF1 may inhibit NF kappa B signaling at the level of IKK or between IKK and p65, while co-immunoprecipitation experiments revealed its association with multiple critical host adaptor proteins. Mechanistically, BSRF1 hinders the phosphorylation of I kappa B alpha at Ser32/36 and K48-linked polyubiquitination, thereby preventing proteasome-mediated degradation of I kappa B alpha by disrupting the assembly of the regulatory subunits within the IKK complex. Although BSRF1 interacts with p65 and its N-terminal domain, it does not alter the formation of the p65/p50 heterodimer. Instead, it prevents the nuclear translocation of p65 by inhibiting the dissociation of I kappa B alpha from the NF-kappa B dimer. Collectively, these findings suggested that BSRF1 assists EBV's evasion of host innate immune system by inhibiting the antiviral response to IFN-beta through the NF-kappa B signaling pathway, potentially contributing to the virus's ability to establish persistent infection and its association with tumorigenesis.