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关键词： Biological DMARD   Observational studies/ registry   Real-world evidence  

关键词： biological DMARD   Cardiovascular system   Diagnostic test   Enthesitis  

关键词： Follicular T cells   Low-dose IL-2   Rheumatoid arthritis  

摘要： ObjectiveThis study is aimed at investigating the characteristics of RA patients at different stages and at evaluating the potential application of low-dose interleukin-2 (ld-IL-2) during the preclinical *** with undifferentiated arthritis (UA), early RA (Ea-RA), new-onset RA (New-RA), and recurrent RA (Re-RA) were included. Clinical data and laboratory parameters were collected from all participants. A comparative analysis of arthritis-related clinical features and serum levels of IL-2 and soluble IL-2 receptor (sIL-2R) was conducted. Collagen-induced arthritis (CIA) mice received ld-IL-2 on days 0, 7, 14, and 28 after primary immunisation for 4 weeks. The percentages of Treg, Tfr, Tfh, and PD-1+Tfh cells were analysed. Additionally, naive CD4+ T cells were cultured in vitro to assess the effects of IL-2 on Tfh and Tfr *** patients primarily exhibited early involvement of large joints. The sIL-2R level in UA patients was significantly lower than in those with Ea-RA, New-RA, and Re-RA and was comparable to levels in healthy controls. ld-IL-2 administration at different time points in the CIA model exerted varying effects on arthritis severity. Prophylactic ld-IL-2 administration reduced arthritis severity and incidence in CIA;it decreased the percentage of PD-1+Tfh cells while increasing Tfr cells, thereby restoring immune balance. All IL-2 intervention groups effectively reduced the Tfh/Tfr ratio and altered the distribution of B cell subsets. Mechanistically, ld-IL-2 primarily suppressed the differentiation of PD-1+Tfh cells and promoted Treg cell differentiation via STAT3 and STAT5 signalling, contributing to the restoration of immune *** findings indicate that elevated sIL-2R levels in UA patients may predict progression to Ea-RA. Furthermore, ld-IL-2 restores immune tolerance by rebalancing Tfh/Tfr populations, highlighting its potential as a novel immunoregulatory strategy during the preclinical pha

关键词： Kisspeptin-10   Osteoarthritis   p53   senescence   SIRT1  

摘要： In Osteoarthritis (OA), the senescence of chondrocytes plays a pivotal role, contributing to cartilage degradation and impairing tissue repair mechanisms. (Kp-10), a peptide hormone, exerts diverse biological functions across multiple cell types and tissues via its receptor Gpr54. However, its role in chondrocytes and OA has been understudied. This study investigates the role of Kp-10 in mitigating TNF-alpha- induced senescence in primary chondrocytes, a hallmark of OA pathogenesis. Gpr54 expression was confirmed in both primary chondrocytes and the ATDC5 chondrogenic cell line, with TNF-alpha treatment leading to a dose-dependent decrease in Gpr54 expression. Kp-10 treatment at concentrations of 50 and 100 nM effectively ameliorated TNF-alpha-induced senescence, as evidenced by diminished senescence-associated beta-galactosidase staining and enhanced telomerase activity. Moreover, Kisspeptin-10 modulated the expression of key regulators involved in cellular aging, including hTERT and TERF2, and suppressed the activation of the p53/p21 pathway. Notably, Kp-10 restored SIRT1 expression, which was downregulated by TNF-alpha. Silencing SIRT1 abolished the protective effects of Kp-10, highlighting the essential role of SIRT1 in its anti-senescence action. These findings suggest that Kp-10 may be a promising therapeutic strategy for OA by mitigating chondrocyte senescence and improving cellular function by modulating the SIRT1 and p53/p21 pathways.

关键词： anti-citrullinated peptide antibody (ACPA)   italic>HLA-DRB1/DQB1   rheumatoid arthritis   treatment response  

摘要： The present study aimed to determine the association of HLA-DRB1/-DQB1 alleles with response to treatment and anti-citrullinated peptide antibody (ACPA) status in Iranian rheumatoid arthritis (RA) patients. A total of 167 RA patients, including 114 good responders (GRs) and 53 poor responders (PRs) as well as 330 ethnic-matched healthy controls, participated in this study. Disease activity and treatment response were assessed using the Disease Activity Score 28-joint (DAS28) scores during the 9-month post-treatment. HLA-DRB1/-DQB1 alleles were identified using polymerase chain reaction with a sequence-specific primers (PCR-SSP) method and compared between the study groups. Of the patients, 106 (63.5%) were ACPA-positive, 88 (52.7%) human leucocyte antigen (HLA)-shared epitope (SE)-positive, 64 (38.3%) ACPA+SE+ and 37 (22.2%) ACPA-SE-. HLA-SE alleles were significantly more frequent in patients (p = 3.2e - 05), in PR versus GR patients (p = 0.01) and in ACPA+ versus ACPA- patients (p = 0.009). PR patients had a higher prevalence of ACPA+SE+ compared to GR patients (p = 0.02). Higher frequencies of DRB1*04:02 (pc = 0.03), *04:04 (pc = 0.007), *04:05 (pc = 5.0e - 05), *10:01 (pc = 1.0e - 04), DQB1*03:02 (pc = 0.002) and *05:01 (pc = 0.002) alleles, and lower frequencies of DRB1*04:01 (pc = 0.007), *11:01 (pc = 0.03), *13:01 (pc = 0.03) and DQB1*06:03 (pc = 0.03) alleles were observed in patients compared to healthy controls. These findings suggest a relationship between HLA-SE alleles and ACPA development and a potential link between HLA-SE/non-SE alleles and therapeutic responses in RA patients.

关键词： apoptosis   cerebrovascular   endothelium   inflammation   proliferation  

摘要： The mechanism by which chronic systemic inflammation contributes to cerebral endothelial dysfunction and neurological disorders is unclear, although endothelial inflammatory signalling is considered a cornerstone of this process. Here, we have performed transcriptomic analysis of published RNASeq datasets and identified consistent upregulation of the Tumour Necrosis Factor-C-X-C Motif Chemokine Ligand 10 (TNF-CXCL10) signalling pathway in mouse cerebral endothelial cells following a single inflammatory challenge. We subsequently investigated the effects of repeated low-level inflammation on the modulation of this pathway in a mouse cerebral endothelial cell line, analysing the effect on markers of endothelial cell activation and changes in cellular function, as a potential mechanism underlying the cerebrovascular response to low-level systemic inflammation. Mouse cerebral endothelial cells (bEnd.3) were exposed to hour-long treatments with phosphate buffered saline (PBS), a single low concentration of TNF (0.5 ng/mL), repeated low-concentration TNF (0.5 ng/mL, 1 h x 4 days) or a single cumulative concentration of TNF (2.0 ng/mL). RNA and protein were extracted 4 and 24 h after the final treatment for analysis of gene/protein expression using qRT-PCR and western blotting. Repeated inflammatory challenge significantly upregulated both Intercellular Adhesion Molecule 1 (ICAM1) and CXCL10 at the mRNA and protein levels. Signal transducer and activator of transcription 1 (STAT1) and phosphorylated-STAT1 (pSTAT1) protein levels were also increased at 4 and 24 h. Differentially, tumor necrosis factor receptor-associated factor 2 (TRAF2) and Interferon gamma (IFN gamma) gene expression were decreased at 4 h, returning to control levels at 24 h. Functional analysis revealed significant increases in endothelial cell proliferation and apoptosis in the presence of repeated TNF exposure. CXCL10 knockdown with small interfering RNA (siRNA) reduced mean caspase 3/7 activity induce

关键词： Axial spondyloarthritis   Early treatment   Early diagnosis   Giant cell arteritis   IL-17A   IL-17A inhibition   Polymyalgia rheumatica   Psoriasis   Psoriatic arthritis   Rheumatic and musculoskeletal diseases  

摘要： Interleukin-17A (IL-17A) plays a pivotal role in many rheumatic immune-mediated inflammatory diseases. Targeting the IL-17 pathway has transformed the way psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are managed, with a number of IL-17A inhibitors now available for treating rheumatic and musculoskeletal diseases. This narrative review will describe the opportunities presented by novel imaging techniques in understanding the metabolic and mechanical changes that characterize the pathogenesis of PsA and axSpA. It will look at the current consensus definitions of early disease in PsA and axSpA, present evidence for the benefit of early treatment, and highlight the gaps in current knowledge. Finally, it will describe novel treatment targets to address the unmet needs in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) and discuss the potential role of IL-17A inhibition in treating GCA and PMR.

关键词： Head and neck squamous cell carcinoma (HNSCC)   lymph node metastasis (LNM)   Fusobacteria nucleatum (F. nucleatum)   interleukin-32 (IL-32)   preoperative  

摘要： Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high rate of lymph node metastasis (LNM), which significantly impacts prognosis. This study aims to evaluate the potential utility of Fusobacterium nucleatum (F. nucleatum) and interleukin-32 (IL-32) as co-predictors for cervical LNM in HNSCC, enhancing preoperative assessment of metastatic status in patients. Methods: Clinical information, tissue, and plasma samples were collected from a cohort of 254 HNSCC patients. IL-3 2 expression was assessed using immunohistochemistry (IHC), while fluorescence in situ hybridization (FISH) was used to evaluate F. nucleatum enrichment in both tumor and paracancer tissue. Univariate and multivariate analyses identified significant risk factors. Results: IL-32 levels were higher in tumor tissue compared to paracancer tissue (P<0.001). Patients with high F. nucleatum enrichment had higher IL-32 expression (P=0.04). Through univariate and multivariate analyses, alcohol, Ki-67 (antigen Kiel-67) expression, F. nucleatum enrichment and IL-32 expression were identified as significant risk factors of LNM. The comparison of receiver operating characteristic (ROC) curves for these factors showed that the combined use of all chosen indicators resulted in the highest diagnostic accuracy. Conclusions: The enrichment of F. nucleatum in cancer tissue is positively correlated with high expression of IL-32, suggesting that these two novel indicators, F. nucleatum and IL-32, along with Ki-67 and alcohol, may serve as preoperative predictors for LNM in HNSCC. This discovery holds great potential to facilitate the development of more precise and personalized surgical strategies for patients.

关键词： amnion epithelial cells   c-MYC   fetal membrane cells   KLF4   p38MAPK   senescence   stem cell genes   TNF-alpha inflammation  

摘要： Background It is crucial to understand the relationship between inflammation and adverse pregnancy outcomes such as preterm birth and premature membrane rupture. Inflammation alters stem cell factors and cell transitions, disrupting immune balance and leading to adverse outcomes. Objective This study explored the effects of the pro-inflammatory cytokine TNF-alpha on Amnion epithelial cells (AECs), focusing on stem cell transcription factors (TFs), senescence, and the epithelial-mesenchymal transition (EMT). Methods Transcriptomic data were generated to compare the stem cell TFs expression (KLF4, c-MYC, OCT-4, SOX2, NANOG) between the placenta and fetal membrane (FM);AEC were treated with 50 ng/mL TNF-alpha for 48 h. Gene expression of stem cell TFs was assessed using qPCR;p38 MAPK activation and differential expression of KLF4, c-MYC were subsequently verified by Western blotting. Cellular senescence was evaluated using SA-beta-Gal staining, and the pro-inflammatory cytokines IL-6 and IL-8 were measured using ELISA. The EMT was determined by measuring cell shape index and vimentin/CK-18 immunofluorescence. Results The placenta and the FM expressed higher mRNA levels of KLF4 than c-MYC, SOX2, OCT-4, and NANOG. AEC exhibited significantly higher KLF4 and c-MYC (p < 0.05). KLF4 downregulation (p < 0.05) and an increase in c-MYC (p < 0.01) in mRNA and protein levels were observed. The p38 MAPK activation (p < 0.01) increased cellular senescence (p < 0.05) and increased IL-6, IL-8 production (p < 0.01) with no change in cellular transition. Conclusion This study shows how TNF-alpha affects stem cell TFs and impacts cellular integrity, senescence, and inflammatory responses, thus influencing adverse pregnancy outcomes.