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关键词： Arthritis   Biomarkers   Chalcone   Cytokines   Inflammation   Oxidative stress  

摘要： Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and chronic pain due to the degradation of subchondral bone and the loss of cartilage function. The present study was designed to evaluate the activity of 1N,N-dimethyl chalcone (DGCHAL) against RA. A primary 28-day investigation was conducted on adjuvant-induced arthritic rats with DGCHAL (10 mg/kg, 20 mg/kg, and 30 mg/kg) and methotrexate (STDMTX). The therapeutic effect was estimated on the basis of measurements of paw diameter, fluctuations in body weight, oxidative stress biomarkers, and hematological parameters. In addition, the study sought to quantify the expression of key cytokines, including TNF alpha, IL-6, IL-10, IL-1 beta, and NF kappa beta, using qRT-PCR and ELISA techniques. Treatment with DGCHAL significantly restored the paw volume, body weight, arthritis-induced anemia, and leukocyte count. The tested compound remarkably downregulated the expression of COX-2, TNF alpha, IL-6, IL-1 beta, and NF kappa B and upregulated the expression of IL-10. The treatment groups increased the activities of SOD, CAT, and GSH, whereas they reduced the formation of MDA and NO as compared to the arthritic group. These findings provide an evident basis for the anti-arthritic potential of DGCHAL in a chronic arthritis rat model and should be further studied for dosage form design.

关键词： Hemophagocytic lymphohistiocytosis   HLA-haploidentical transplantation   Cord blood transplantation   Post-transplant cyclophosphamide   Graft failure  

摘要： We describe a case of immunological rejection occurring twice after cord blood transplantation (CBT) for mixed phenotype blast phase chronic myeloid leukemia that was successfully salvaged by haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PT-Cy). Preengraftment immune reaction (PIR) and subsequent hemophagocytic lymphohistiocytosis (HLH), likely due to HLA mismatch in the graft-versus-host (GVH) direction, lead to poor graft function (PGF) and graft failure (GF). This case highlights the pathophysiology of PIR, HLH, PGF, and GF, collectively termed "posttransplant cytokine syndrome." PT-Cy haplo-PBSCT, with wide donor availability and reduced infection risk leading to HLH via rapid engraftment, may be a suitable salvage option for post-CBT cytokine syndromerelated GF.

关键词： 产气荚膜梭菌   β   重组蛋白   单克隆抗体   竞争ELISA   抗体检测  

摘要： 为检测产气荚膜梭菌（Cp）β2毒素抗体，合成产气荚膜梭菌β2毒素基因并插入pET-32a载体，诱导表达后得到Cp β2毒素重组蛋白，以纯化的Cp β2毒素重组蛋白为包被抗原，Cp β2毒素单抗2A4为竞争性抗体与绵羊血清竞争性反应，HRP-山羊抗鼠IgG为二抗，建立并优化Cp β2毒素抗体的竞争ELISA检测方法。结果显示，蛋白包被浓度为1.5 μg/mL，待检血清不稀释，二抗1∶20 000稀释，避光显色15 min为最优反应条件。所建方法的阴性临界值为31.44%，阳性临界值为37.65%，检测阳性血清敏感度为1∶64，批间、批内试验变异系数均小于10%。与Cp的α、β1、ε毒素，腐败梭菌以及大肠杆菌阳性血清均无非特异性反应。检测200份临床绵羊血清样品，该竞争ELISA方法与间接ELISA方法的阳性符合率为85.7%，阴性符合率为95.9%，总符合率为92%。检测100份牛血清，符合率为100%。结果表明，本试验所建方法具有良好的重复性、特异性和敏感性，可以用于检测动物体内是否存在针对Cp β2毒素的抗体，为评估动物是否感染Cp提供了有效手段，并在Cp的流行病学调查及疫苗免疫效果评价中具有广阔的应用前景。

关键词： allergy   Der p 1   epitope   immunotherapy   tolerance  

摘要： Background Peptides were designed to induce immune tolerance to the major antigen associated with house dust mite (HDM) allergy, Der p 1. HDM is commonly associated with allergic responses in allergic rhinitis and asthma, with Der p 1 specific T-cells implicated in ongoing disease. Tolerogenic peptide immunotherapy can induce tolerance in pathogenic T-cells, bypass mast cell activation and hence reduce the risk of anaphylaxis. A pan-DR binding epitope of Der p 1, covering the broad population, was tested for efficacy in HLA-DR transgenic *** Potential pan-HLA-DR binding tolerogenic T-cell epitopes from Der p 1 were predicted in silico and manufactured (synthetic peptides A-E). Participants included HDM sensitised (allergic rhinitis/asthma, n=25), non-HDM sensitised (atopic controls sensitised to >= 1 other aero-allergens, n=10) and non-atopic healthy controls, n=10). Peripheral blood mononuclear cells (PBMC) were collected and screened for immune responses to Der p 1 or test peptides A-E. Mapping of minimal T-cell epitopes, apitope (antigen-processing independent epitope) validation and tolerance induction were tested in HLA-DR transgenic *** HDM-sensitised subjects have an elevated response to pan-DR binding peptide D 30mer. Peptide analogue D121B, containing the minimal epitope and optimised for solubility, was verified as a tolerogenic apitope and induced tolerance against Der p 1 antigens in HLA-DR4 transgenic mice in *** A tolerogenic peptide, apitope D121B, reduces T-cell immune responses to Der p 1 and is a promising candidate for further development as an immunotherapy for HDM-associated allergic rhinitis and asthma.

关键词： rheumatoid arthritis   anti-TNF therapy   cognitive function   inflammation   disease activity  

摘要： Objectives: To evaluate cognitive improvement in patients with rheumatoid arthritis (RA) after 6 months of treatment with tumor necrosis factor (TNF) inhibitors, analyze associated factors, and determine the percentage of patients achieving cognitive improvement. Methods: This was a single-center prospective observational study conducted over 12 months on 70 RA patients initiating their first biologic disease-modifying antirheumatic drug (bDMARD) with a TNF inhibitor. Cognitive function was assessed at baseline and after 6 months using validated neuropsychological tests, including the Montreal Cognitive Assessment (MoCA) for global cognitive function, the digit span forward and backward tests for attention and working memory, and the Stroop-W, Stroop-C, and Stroop-CW tests for executive function and processing speed. Patient-reported outcomes were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life-Rheumatoid Arthritis Scale-II (QOL-RA II). Clinical variables, disease activity measured by the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP), inflammatory markers including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and patient-reported outcomes were recorded. Associations with average CRP and Health Assessment Questionnaire (HAQ) scores were analyzed throughout the follow-up period. Cognitive improvement was defined as a >= 20% increase in MoCA test scores. Logistic regression was performed to identify factors associated with improvement. Results: A total of 70 patients (mean age, 56.2 years;81.4% female) were included. After 6 months, patients showed significant cognitive improvement in a validated questionnaire, namely, the Montreal Cognitive Assessment (MoCA test 23.1 +/- 3.6 to 24.1 +/- 3.3;p = 0.001), particularly in the executive and memory domains. Significant improvements were also observed in the digit span forward test (p = 0.003), digit span backward test (p = 0.021), Stroop

关键词： Th2 cytokines   Pulpitis   Biomarkers   Pulpal blood   Diagnostic efficacy   Inflammation markers  

摘要： ObjectiveTo evaluate the diagnostic utility of T-helper type 2 (Th2) cytokines, specifically Interleukin-4 (IL-4), IL-5, IL-10, and IL-13, in distinguishing different stages of pulpitis and their combined performance in clinical *** total of 161 participants were enrolled and categorized into normal pulp (NP, n = 45), reversible pulpitis (RP, n = 75), and symptomatic irreversible pulpitis (IP, n = 41). Th2 cytokine levels in pulpal blood samples were measured using enzyme-linked immunosorbent assays (ELISA).ResultsTh2 cytokine levels (IL-4, IL-5, IL-10, and IL-13) were significantly elevated in pulpitis cases compared to normal pulp, with the highest concentrations observed in symptomatic IP. Diagnostic analysis showed that IL-4 and IL-13 had the highest diagnostic accuracy for distinguishing pulpitis (both RP and IP) from normal pulp, with AUCs of 0.91, and perfect specificity (100%). IL-5 demonstrated the best balance between sensitivity (68%) and specificity (97%) for differentiating IP from NP (AUC = 0.84). IL-13, though less effective overall, provided moderate accuracy (AUC = 0.63) for distinguishing RP from NP. Additionally, the combined diagnostic model of all four cytokines achieved high AUCs, particularly in distinguishing irreversible pulpitis from normal pulp (AUC = 0.94) and irreversible pulpitis from reversible pulpitis (AUC = 0.90).ConclusionsTh2 cytokines, especially IL-4, IL-5, and IL-13, are effective biomarkers for identifying different stages of pulpitis. Their elevated levels, particularly in irreversible pulpitis, provide strong diagnostic accuracy. Combined cytokine analysis enhances diagnostic precision, making Th2 cytokine profiling a valuable tool for assessing pulpitis severity.

关键词： 1，25(OH)   D   系统性红斑狼疮   cGAS/STING/IFN-Ⅰ   IFN-α   IFN-β  

摘要： 目的 探讨1，25（OH）2D3是否通过抑制cGAS/STING/IFN-Ⅰ信号通路，从而使dsDNA诱导的小鼠外周血单个核细胞（PBMC）中的炎症因子IFN-α、IFN-β分泌减少，探讨1，25（OH）2D3治疗SLE的新靶点。方法 取10只8周龄雌性C57BL/6小鼠，10%水合氯醛麻醉小鼠，腹主动脉取血，分离PBMCs，将其分为2组，第1组为dsDNA（0μg/L、20μg/L、40μg/L、80μg/L）诱导组，其中0μg/L的dsDNA为对照组，筛选dsDNA最佳作用剂量。第2组PBMCs首先使用诱导dsDNA（40μg/L）处理，然后再用1，25（OH）2D3(10-8μmol/L、10-7μmol/L、10-6μmol/L)进行治疗，其中空白组为未经1，25（OH）2D3处理的0μg/LdsDNA的小鼠外周血PBMCs，对照组为未经1，25（OH）2D3处理的40μg/LdsDNA的小鼠外周血PBMCs。48小时后，采用CCK8检测各组PBMCs的细胞活力，ELISA法分别各组PBMCs中IFN-α和IFN-β的分泌水平，Western blot检测各组小鼠外周血PBMCs中cGAS、pTBK1、pSTING、pIRF3的蛋白表达水平，观察1，25（OH）2D3对cGAS/STING/IFN-Ⅰ信号的蛋白表达及IFN-α、IFN-β分泌的影响。结果 dsDNA剂量依赖性地使PBMCs的细胞活力显著下降（P<0.01），在40μg/L的dsDNA时，细胞活力差异较显著性，且dsDNA剂量依赖性地促进炎症因子IFN-α和IFN-β的分泌（P<0.01），小鼠外周血PBMCs中cGAS、pTBK1、pSTING、pIRF3的表达水平较对照组上调（P<0.05）。在1，25（OH）2D3治疗dsDNA诱导PBMCs 的细胞组中，1，25（OH）2D3剂量依赖性地使dsDNA处理的PBMCs 细胞活力显著提升（P<0.01），降低了炎症因子IFN-α和IFN-β的分泌（P<0.01），在加入1，25（OH）2D3治疗的dsDNA处理的PBMCs中cGAS、pTBK1、pSTING、pIRF3、IFN-Ⅰ的表达水平较对照组下调（P<0.05）。结论 1，25（OH）2D3可负反馈调节dsDNA激活PBMCs中的cGAS/STING/IFN-Ⅰ信号通路且降低炎症因子的IFN-α和IFN-β的分泌。

摘要： Resistance to DNA damage is one of the primary mechanisms by which tumor cells evade the effects of standard chemotherapeutic agents and radiotherapy. Dynamic and complex interactions between the tumor microenvironment (TME) and tumor cells critically influence the DNA damage response. Interleukin-33 (IL-33) is a multifunctional cytokine secreted at high levels in response to cellular damage and stress. Recently, increasing evidence has suggested that IL-33 plays a key role in promoting the therapeutic resistance of tumors. However, the actual source of IL-33 during cancer therapy and how IL-33 contributes to a resistant TME remain incompletely understood. In this study, we found that both cancer-associated fibroblasts (CAFs) and tumor cells treated with DNA damage-inducing agents expressed and secreted high levels of IL-33, subsequently leading to enhanced DNA damage repair efficacy. Mechanistically, nuclear IL-33 primarily functions as a transcriptional co-activator of homologous recombination repair (HRR) genes, whereas the active form of IL-33 can drive the non-homologous end joining (NHEJ) pathway via the canonical IL-33/ST2 axis. Overall, we demonstrated that IL-33 plays a key role in mediating a DNA damage-resistant TME, which could represent a potential therapeutic vulnerability in chemoresistant cancer cells.