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关键词： allergic airway inflammation and asthma   Cyba   IL-17   pyroptosis   Saccharomyces boulardii  

摘要： Saccharomyces boulardii (S. boulardii), a beneficial yeast probiotic, is effective in treating asthma in children. This study aimed to examine the effects of S. boulardii on Ovalbumin (OVA)-induced pyroptosis in human bronchial epithelial cells. An OVA-induced asthma mouse model was used with S. boulardii as an intervention. S. boulardii alleviated OVA-induced lung tissue pyroptosis and intestinal tissue damage in asthmatic mice. The mRNA sequencing analysis revealed differentially expressed genes, including elevated Cyba levels in the intestinal tissues of the OVA group. However, S. boulardii reduced Cyba levels. Gene Set Enrichment analysis showed the involvement of IL-17 signaling pathway. In vivo experiments showed that S. boulardii inhibited IL-17 signaling pathway in the intestinal and lung tissues. In vitro experiments revealed that IL-17 regulation of ROS production, promoting BEAS-2B cell pyroptosis, required the involvement of Cyba. Moreover, Cyba knockdown inhibited activation of NLRC4 and NLRP3 inflammasomes induced by IL-17 in vivo. This study revealed for the first time the important role of Cyba and IL-17 pathways in asthma pathology and demonstrated that S. boulardii exerted its therapeutic effects by modulating these pathways. These findings provided a basis for developing nutrition interventions targeting gut microbiota and immune health.

关键词： hypertensive heart disease   TNF receptor 1   exercise capacity  

摘要： Background: TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate the association between TNF-R1, exercise capacity, and cardiac function in asymptomatic patients with hypertensive heart disease (HHD). Methods: We enrolled 80 patients (mean age 55 +/- 12 years) with HHD and no clinical symptoms of HF (stages A and B). Echocardiography, including tissue Doppler and left atrial and left ventricular (LV) strain assessment, was performed at rest. Peripheral venous blood samples were collected to measure serum TNF-R1 concentration. Results: The study population was divided into two subsets based on the median exercise capacity (peak VO2) value. Patients with higher VO2 had lower serum TNF-R1 concentration and higher early peak mitral annular velocity (e') and peak atrial longitudinal strain (PALS). After adjusting for other covariates, multivariable regression analysis identified TNF-R1 as an independent determinant of peak VO2. Mediation analysis revealed that the relationship between TNF-R1 and peak VO2 was mediated by LV diastolic function (PALS or e'), with a decrease in the beta coefficient after including mediator variables from 0.37 (p < 0.001) to 0.30 (p < 0.006) and 0.31 (p = 0.004), respectively. Conclusions: In patients with HHD, higher TNF-R1 levels are associated with lower exercise capacity, which may be mediated by impaired LV diastolic function. These findings might suggest a role of TNF signalling in early HF development, justifying further studies to evaluate TNF-R1 as a biomarker for risk of HF progression.

关键词： Dyslipidemia   Genetic association   Single nucleotide polymorphisms   TNF-α  

摘要： Tumor necrosis factor-α (TNF-α) polymorphisms may influence dyslipidemia, but their role remains unclear. This case-control study investigated associations between TNF-α gene polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A) and dyslipidemia in 595 participants (162 cases, 433 controls) from the Chaoshan region of China. Anthropometric, biochemical, and genetic data were analyzed using Chi-squared tests and logistic regression, with the false discovery rate (FDR) method applied to correct for multiple comparisons. Results revealed that only the -1031T/C and -863C/A polymorphisms were significantly associated with dyslipidemia. Carriers of the TC+CC genotype for -1031T/C (odds ratio [OR]=0.48, 95% CI: 0.30-0.78, =0.006) and the CA+AA genotype for -863C/A (OR=0.41, 95% CI: 0.24-0.70, =0.004) had lower odds of dyslipidemia. Protective effects were observed for the C allele at -1031T/C (OR=0.58, =0.012) and the A allele at -863C/A (OR=0.47, =0.004). Stratified analyses showed that these associations were significant in males but not females. Functional annotation linked these TNF-α gene polymorphisms to transcription factors (e.g., HNF-1A, STAT1β) in the adipogenesis pathway. This study reveals genetic associations between TNF-α polymorphisms and dyslipidemia, particularly in males, and provides mechanistic insights into their role in transcriptional regulation.

关键词： ANXA1   differential gene expression   immunotherapy   Mendelian randomization   MHC-II   PD-1/PD-L1 resistance   single-cell sequencing   triple-negative breast cancer  

摘要： BackgroundTriple-negative breast cancer (TNBC) presents significant treatment challenges and poor prognosis. While immune checkpoint blockade (ICB) therapy shows promise, patient responses vary widely, highlighting the urgent need for reliable biomarkers to predict efficacy and guide treatment *** study aims to investigate the role of Major Histocompatibility Complex class II (MHC-II) expression in breast cancer, specifically focusing on its impact on immune evasion, tumor metastasis, and immunotherapy efficacy. The objective is to emphasize the necessity of targeted research in order to enhance therapeutic strategies for *** employed Limma for conducting differential expression analysis, clusterProfiler for performing GO and KEGG pathway enrichment analyses, and Mendelian randomization analyses utilizing data from the UK Biobank and GEO data sets. Single-cell sequencing data were analyzed using Scanpy and CellTypist, where UMAP, PCA, and the Leiden algorithm were applied to explore cellular heterogeneity as well as gene expression *** observed significant differential gene expression between MHC-II-high and MHC-II-low hematopoietic stem cells, which has an impact on immune responses and cancer pathways, particularly in TNBC. Mendelian randomization analysis identified key genes associated with breast cancer risk and PD-L1 status. Additionally, ANXA1 was significantly decreased in expression in breast cancer tissues compared to normal tissues and demonstrated increased expression in nonresponders to PD-1/PD-L1 therapies in TNBC patients, suggesting its potential involvement in immunotherapy resistance despite lacking a direct correlation with overall survival *** findings of this study highlight the potential role of ANXA1 in mediating resistance to PD-1/PD-L1 therapy in breast cancer, which is associated with MHC-II expression. ANXA1 could serve as both a predictive marker for treatment resistance and a thera

关键词： 急性冠脉综合征   中性粒细胞   淋巴细胞   不稳定心绞痛   急性心肌梗死   Acute Coronary Syndrome   Neutrophils   Lymphocytes   Unstable Angina Pectoris   Acute Myocardial Infarction  

摘要： 目的：探究中性粒细胞与淋巴细胞比值与老年急性冠脉综合征患者的冠脉狭窄程度的相关性及对严重冠脉狭窄的诊断效能。方法：回顾性收集2022年8月至2024年8月于邯郸市中心医院行冠状动脉造影术的老年急性冠脉综合征患者共154例，其UA组79例(男性41例，女性38例)，AMI组75例(男性57例，女性18例)，选取Gensini评分对冠脉造影结果进行评估，分为中低分组(GS < 68)，高分组(GS ≥ 68)。结果：(1) UA组和AMI组在高脂血症、收缩压、WBC、NEUT、HDL-C、TC、NLR评分的比较，差异存在统计学意义(P < 0.05)；(2) WBC、NEUT、LDL-C、TG、NLR均与Gensini评分呈正相关(P < 0.05)，LYM、HDL-C与Gensini评分呈负相关(P < 0.05)；(3) 不同Gensini评分分组在WBC、NEUT、LYM、LDL-C、HDL-C、TG、NLR的差异具有统计学意义(P < 0.05)；(4) 多因素logistic回归分析结果进一步显示NLR、LDL-C、TG是Gensini评分的独立危险因素。(5) ROC曲线显示NLR诊断老年急性冠脉综合征患者的严重冠脉狭窄的截断值为2.978，灵敏度90.0%，特异度54.4%，曲线下面积0.773 (95% CI: 0.699~0.846)。结论：NLR与老年急性冠脉综合征患者的冠脉狭窄程度呈正相关，是冠脉严重狭窄的独立危险因素。

关键词： Rheumatoid Arthritis   IL17   Single-nucleotide polymorphism   Anti-CCP  

摘要： Background Rheumatoid arthritis (RA) is a long-term autoimmune disease causing chronic progressive inflammatory disease. In this study, we aimed to evaluate a new strategy for gene polymorphism of IL17A which may be related to the risk of rheumatoid arthritis in Iranian patients. Methods We examined the genes IL17A and IL17F in relation to RA. They compared the DNA of 100 RA patients and 92 healthy individuals for the IL17A gene, and 116 RA patients and 107 healthy individuals for the IL17F gene. A technique called PCR-RFLP was used to analyze their genetic makeup. SPSS software was used for statistical analyses. Results There was a significant association between the patients and control group in rs2275913 (OR = 2.97, 95%CI = 1.38-6.46, P = < 0.001). However, there was no significant relationship between the patient and control group at rs763780 (OR = 1.49, 95%CI = 0.806-2.76, P = 0.201). Also, in this study, the association between genotypes mentioned above and Anti-ccp was investigated. There was no significant correlation between any genotype and positive Anti-ccp. (P = 0.142 for rs2275913 and P = 0.330 for rs763780). Conclusion Based on this study, rs2275913 polymorphism of gene IL17A could contribute to the risk of rheumatoid arthritis in Iranian patients.

关键词： acute viral myocarditis   children   immune factors   interleukin  

摘要： The study examines variations of serum interleukin (IL)-6, IL-17, and transforming growth factor-beta (TGF-beta) in pediatric viral myocarditis. One hundred and twenty children diagnosed with acute viral myocarditis were divided into survival (n = 60) and death (n = 60) groups according to their prognosis. Troponin I, serum IL-6, IL-17, TGF-beta, creatine kinase isoenzyme MB, and brain natriuretic peptide levels were significantly increased on admission and gradually increased during 1 week of immune monitoring, of which TGF-beta and IL-6 peaked in the second week and IL-17 peaked in the fourth week. The above-mentioned indices were significantly lower in the survival group than those in the death group (P < .05). The survival group exhibited significantly higher left ventricular ejection fraction (LVEF) (P < .05) and significantly lower brain natriuretic peptide (BNP) level (t = -0.408, P = .72) than the death group. The serum levels of IL-6, IL-17, and TGF-beta were significantly increased in children with acute viral myocarditis, and the LVEF was the main influencing factor leading to poor prognosis.

摘要： INTRODUCTION:Psoriasis is a chronic inflammatory multisystem disease for which IL-17 and IL-23 inhibitors have transformed treatment. However, high costs and the possibility of overtreatment in patients with excellent and sustained responses have driven interest in dose reduction (DR) to lower expenses without compromising efficacy. MATERIALS & METHODS:We conducted a multicenter observational trial assessing the efficacy and safety of DRs for secukinumab, brodalumab, guselkumab, and risankizumab in adults with stable plaque psoriasis. Eligible participants were adults with low disease activity (PASI ≤ 3, DLQI ≤ 3 for at least 9 months). DR involved lengthening intervals to approximately 67% of the authorized standard dose. From the 361 enrolled (March 2023-January 2025), we analyzed data on 156 participants with ≥12 months of follow-up or early discontinuation due to DR failure. RESULTS:Seventy of these patients (44.87%) received IL-17 inhibitors, and 86 (55.13%) received IL-23 inhibitors. After 52 weeks, the overall dose-reduction survival was 0.75 (95% CI: 0.69-0.82). For IL-23 inhibitor and IL-17 inhibitor cohorts, the dose-reduction survival was 0.83 (95% CI: 0.75-0.91) and 0.66 (95% CI: 0.55-0.78), respectively. Moreover, Kaplan-Meier curves suggested significant (p-value log-rank test=0.018) higher dose reduction survival for IL-23 inhibitors compared to IL-17. DISCUSSION:Our preliminary findings suggest that extended dosing intervals for IL-17 and IL-23 inhibitors can effectively maintain disease control in stable plaque psoriasis. Larger randomized trials are needed to confirm these results, identify predictive markers of DR success, and optimize patient selection for safe and cost-effective management of psoriasis.

摘要： Investigation of crosstalk between antagonistic pro- and anti-inflammatory cytokines has focused on mechanisms and functional consequences of cross-inhibition. We investigated cross-regulation between proinflammatory TNF and anti-inflammatory IL-4 in primary human monocytes and in a skin wound-healing model. Surprisingly, TNF functioned mainly as a costimulator of IL-4-induced gene expression, whereas IL-4 selectively inhibited the TNF-induced IFN response, leaving inflammatory gene expression mostly intact. TNF and IL-4 synergistically induced gene sets important for regulating inflammation and tissue repair, which were highly induced during the phase of wound healing when these cytokines are co-expressed. Crosstalk between TNF and IL-4 was mediated by epigenetic chromatin-mediated mechanisms associated with cooperation between NF-κB and STAT6 transcription factors, erasure of negative histone mark H3K27me3, and selective inhibition of IRF1. These results identify a long-sought mechanism for expansion of the IL-4 response, and highlight the complexity of crosstalk between antagonistic cytokines that includes cooperation for select gene responses important in immune response and tissue repair.