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关键词： Brazilian population   new allele   NGS   REDOME  

摘要： Identification of the novel HLA alleles HLA-DRB1*13:358 and HLA-DQB1*05:333 in Brazilian individuals.

关键词： family   HLA-DPB1   Indian   NGS   novel allele  

摘要： HLA-DPB1*1799:01 differs from HLA-DPB1*05:01:01:01 by a single non-synonymous change in exon 3, changing codon 148 from AAT -> AAA.

关键词： APECED   IFN-γ   IL-17   antimicrobial peptides   barrier integrity   candidiasis   epithelial disruption   immunopathology   mucocutaneous surfaces  

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关键词： Quercetin   Human umbilical cord-derived mesenchymal stem cells   Inflammatory bowel disease   Interleukin 10   Janus kinase   Signal transducer and activator of transcription   Suppressor of cytokine signaling signal  

摘要： BACKGROUND Inflammatory bowel disease (IBD) is a chronic, progressive inflammatory condition of the intestine. Mesenchymal stem cell (MSC) therapy for IBD has made significant progress in recent years. To better exploit the therapeutic potential of MSCs, pretreatment strategies are employed to enhance their therapeutic capabilities. As a compound with diverse pharmacological effects, quercetin (QUR) is applied to pretreat human umbilical cord-derived MSCs (hUCMSCs) in this study, thereby augmenting their immunotherapeutic potential. AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs. METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution. Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group. Interestingly, the therapeutic effect was superior to that of untreated hUCMSCs. Mice exhibited significantly reduced weight loss, diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining, improved Disease Activity Index and Histological Activity Index scores. Furthermore, colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10 (IL-10), accompanied by a downregulation of the pro-inflammatory cytokine IL-6. Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription (STAT) phosphorylation. RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity. This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway. CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs, resulting in enhanced therapeutic efficacy for IBD treatmen

关键词： OSMRβ   STAT5 phosphorylation   crystal structure   monoclonal antibody   neutralization   pruritus  

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关键词： Rheumatoid arthritis   Macrophage   Glycolysis   HIF-1 alpha   IL-1 beta  

摘要： BackgroundRheumatoid arthritis (RA) is an aggressive, systemic autoimmune disease in which overactivated macrophages play a critical role in its pathogenesis. This study aimed to explore the potential role of glycolytic reprogramming in the production of proinflammatory cytokines by macrophages in *** Seahorse assay was conducted on RA or healthy control (HC) serum-treated human monocyte-derived macrophages (HMDMs) to evaluate glycolysis levels. RNA sequencing was performed to identify activated signaling pathways and key molecules in HMDMs stimulated by RA serum. The proinflammatory cytokines and hypoxia-inducible factor 1 alpha (HIF-1 alpha) were verified by Western blotting and quantitative polymerase chain reaction (qPCR).ResultsWe found that HMDMs stimulated with RA serum showed higher aerobic glycolysis levels than those treated with HC serum, along with higher expression of glycolysis-related genes, including hexokinase2 (HK2), pyruvate kinase L/R (PKLR), and phosphoglycerate kinase 1 (PGK1). Furthermore, RA serum-treated macrophages exhibited a higher level of interleukin-1 beta (IL-1 beta), and the expression of IL-1 beta positively correlated with HK2. Inhibition of glycolysis by 3-bromopyruvate (3BrPA) or HK2 knockdown significantly suppressed IL-1 beta production in macrophages. The HIF-1 alpha-associated signaling pathways and HIF-1 alpha protein levels were also elevated in RA serum-treated macrophages. Inhibition of glycolysis by 3BrPA or knockdown of HK2 reduced HIF-1 alpha. Inhibiting HIF-1 alpha can suppress IL-1 beta production of RA serum-treated macrophages, and vice versa. TNF-alpha and IL-1 beta enhanced HIF-1 alpha and IL-1 beta expression in macrophages, an effect attenuated by glycolysis inhibition. Blocking TNF-alpha and IL-1 beta in RA serum diminished both glycolysis and IL-1 beta *** findings demonstrate that RA serum triggers aerobic glycolysis in macrophages, which promotes HIF-1 alpha to drive IL-1 beta

关键词： Osteoarthritis   IL-33   Autophagy   Chondrocyte senescence   Nanoparticles  

摘要： Osteoarthritis (OA) imposes a substantial health and economic burden globally. Currently, there is a lack of disease-modifying osteoarthritis drugs (DMOADs). This study aimed to elucidate the relationship between chondrocyte senescence and OA progression, as well as to develop an effective siRNA nanodelivery platform for OA treatment. We engineered neutrophil membrane-coated, siIL33-loaded nanoparticles (NM-NP-siIL33) for OA management. The therapeutic efficacy of NM-NP-siIL33 was evaluated through both in vitro and in vivo experiments. Our findings revealed that IL-33 expression was significantly upregulated in damaged articular cartilage in both young and aged mice following anterior cruciate ligament transection (ACLT) surgery. In vitro experiments demonstrated that IL-33 promotes chondrocyte senescence by inhibiting cellular autophagy via activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Additional in vivo studies showed that NM-NP-siIL33 effectively delivered siIL33 to target cells within OA tissues, thereby mitigating the degradation of articular cartilage. Our results suggest that IL-33 plays a critical role in OA progression by accelerating chondrocyte senescence. Furthermore, NM-NP-siIL33 represents a promising therapeutic strategy for managing OA.

摘要： Macrophages integrate microenvironmental cues to orchestrate complex transcriptional and metabolic programs that drive functional polarization. Here, we demonstrate that STK11 links interleukin-4 (IL-4) signaling with metabolic reprogramming to restrain alternatively activated (M2) macrophage polarization. Through integrative transcriptomic and metabolomic analyses, we identified STK11 as a key transcriptional and metabolic regulator during M2 polarization. STK11 deficiency enhanced the expression of M2-associated markers and promoted glutamine metabolism in IL-4-stimulated macrophages. Mechanistically, STK11 deficiency led to increased FOXO1 activation, thereby promoting M2 polarization. Pharmacological inhibition of FOXO1 or glutamine metabolism effectively reversed the enhanced M2 polarization. In an orthotopic model of pancreatic ductal adenocarcinoma, myeloid-specific deletion of STK11 resulted in increased accumulation of M2-like tumor-associated macrophages, impaired antitumor immunity, and accelerated tumor progression. These findings uncover a previously unrecognized role for STK11 in modulating M2 macrophage polarization, offering mechanistic insights that may inform the development of immunometabolic therapies for pancreatic cancer.

关键词： Triple-negative breast cancer   Major histocompatibility complex class-I (MHC-I)   DNA methyltransferase inhibitor   PD-L1 inhibitor   DNA methylation  

摘要： Background There are few studies on the effect of DNA methyltransferase (DNMT) inhibitors and immunotherapy on major histocompatibility complex class-1 (MHC-1) gene methylation in triple negative breast cancer (TNBC).
Methods The relationship between the expression of MHC-1 and DNA methylation was analyzed using data from The Cancer Genome Atlas (TCGA). The expression of DNMTs and MHC-I, and DNA methylation status of MHC-I genes was analyzed in TNBC cell lines. TNBC cell lines were treated with DNMT inhibitors and programmed cell death-ligand 1 (PD-L1) inhibitor. Then, changes in the expression of DNMT and MHC-1, and methylation patterns of MHC-I genes were analyzed.
Results TCGA data analysis confirmed that there was an inverse correlation between DNA methylation and expression of MHC-I. After treating TNBC cell lines with DNMT inhibitors and PD-L1 inhibitor alone as well as in combination, the DNA methylation pattern of the HLA-B and HLA-C gene was suppressed, but not the HLA-A gene. After Decitabine treatment, MHC-I expression was increased in BT-20, while after Zebularine treatment, it was increased only in BT-549. MHC-I expression was increased in BT-549 after Atezolizumab treatment, and in MDA-MB231 after co-administration of Decitabine and Atezolizumab.
Conclusions The effects of DNMT inhibitors and PD-L1 inhibitor were different
depending on the TNBC cell lines and the types of drugs, suggesting that the treatment target needs to be applied differently. Further study is needed to determine specific treatment targets and appropriate drugs according to the characteristics of TNBC

关键词： 系统性红斑狼疮   单克隆抗体   文献计量学   Systemic Lupus Erythematosus   Monoclonal Antibodies  

摘要： 目的：系统性红斑狼疮(SLE)是一种多系统受累的自身免疫病，单抗类药物的应用显著改善了疾病管理。本研究旨在通过文献计量学分析，探讨国内单抗类药物治疗SLE的研究现状、热点及发展趋势。方法：检索中国学术期刊全文数据库(CNKI) 2000年1月1日至2024年8月25日的相关文献，提取期刊、作者、机构、关键词、基金等数据，采用Excel 2019进行统计分析。结果：共纳入298篇文献，年发文量呈上升趋势，2022~2023年达峰值(各36篇)。载文期刊以《中华临床免疫和变态反应杂志》(10篇)、《中国实用儿科杂志》(8篇)为主。上海交通大学(26篇)、中南大学(23篇)为高产机构。关键词分析显示研究热点集中于贝利尤单抗、利妥昔单抗及狼疮性肾炎治疗。35.57%文献获基金支持，其中国家自然科学基金占比最高(29项次)。