课程文献中心 更多>>

关键词： psoriasis   biomarkers   biologic therapy   TNF-alpha  

摘要： Background: Tumor necrosis factor-alpha (TNF-alpha), IL-12/23, IL-17A, and IL-17F are key proinflammatory cytokines involved in the pathogenesis of psoriasis. Biologic therapies targeting these interleukins have demonstrated clinical efficacy. However, the exact relationship between their serum levels and clinical response remains unclear. The aims of this study are to assess changes in cytokine levels (TNF-alpha, IL-12/23, IL-17A, IL-17F) after 12 weeks of biologic treatment in psoriasis to test if there is any correlation between their serum level and PASI (Psoriasis Area Severity Index) and DLQI (Dermatology Life Quality Index) scores before or after treatment and to check the influence of clinical and lifestyle factors on these levels. Methods: In this prospective study, 36 patients with moderate-to-severe plaque psoriasis receiving anti-TNF-alpha, anti-IL-17, or anti-IL-23 therapy were assessed at baseline and after 12 weeks. The serum levels of these cytokines were measured using the ELISA technique. Clinical response was evaluated using PASI and DLQI scores. Spearman correlation analysis was used to assess the relationship between interleukins' serum levels and these scores. Results: A significant decrease in TNF-alpha levels and DLQI and PASI scores was observed after 12 weeks across all treatments. A moderate positive correlation (r = 0.391, p = 0.018) was found between serum TNF-alpha levels and PASI scores at week 12. Conclusions: The serum levels of TNF-alpha are significantly correlated with PASI scores following 12 weeks of biologic therapy, supporting their potential role as a biomarker for monitoring treatment efficacy in psoriasis.

关键词： TNF-alpha   TNFR1   TNFR2   response to TNF-alpha   rheumatoid arthritis   CITE-seq   ScRNA-seq  

摘要： Introduction Tumor Necrosis Factor Alpha is a known pro-inflammatory cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Anti-cytokine therapies targeting Tumor Necrosis Factor Alpha have greatly succeeded in treating rheumatoid arthritis in many patients. Despite these developments, many of the mechanisms of Tumor Necrosis Factor Alpha action have yet to be *** In this study, we incubated PBMCs from healthy donors and rheumatoid arthritis patients with Tumor Necrosis Factor Alpha and then performed their single-cell multi-omics analysis via BD *** We have observed that Classical Monocytes have responded to the Tumor Necrosis Factor Alpha stimulation the most and that there was an activational threshold for such response that was dependent on the TNFR2 protein expression *** The profiling of TNFR2 protein expression level on immune cell populations can be a good predictive factor for the assessment of their activation by Tumor Necrosis Factor Alpha.

关键词： HGFs   IL21R-AS1   OMVs   senescence  

摘要： AimsPeriodontitis, a chronic inflammatory disease, is associated with accelerated cellular senescence. This study aims to explore how Porphyromonas gingivalis (P. gingivalis) outer membrane vesicles (OMVs) induce senescence and senescence-associated secretory phenotype (SASP) in human gingival fibroblasts (HGFs), focusing on the role of lncRNAs in promoting periodontitis *** vivo, gingival senescence was assessed via immunohistochemistry while bone loss was evaluated using micro-CT, HE and TRAP staining. In vitro, HGFs senescence was validated using CCK-8, SA-beta-gal staining, western blot and immunofluorescence assays. IL21R-AS1 was transfected with targeted siRNAs and overexpression plasmids to verify its function. Dual-luciferase reporter assays and rescue experiments were conducted to elucidate the competing endogenous RNA (ceRNA) mechanism of IL21R-AS1. Upstream transcription factors of IL21R-AS1 were validated by CUT&Tag-qPCR and western ***. gingivalis OMVs induced gingival tissue senescence and alveolar bone loss in vivo. In vitro, P. gingivalis OMVs promoted HGFs senescence and SASP via IL21R-AS1. IL21R-AS1 acted as a ceRNA by sponging miR-500a-3p, thereby enhancing the regulation of FBXW7. Moreover, P. gingivalis OMVs activated TLR4 and increased PAX5 expression, leading to elevated IL21R-AS1 ***. gingivalis OMVs promote HGFs senescence SASP by the upregulation of IL21R-AS1, which acts as a ceRNA, mediating the miR-500a-3p/FBXW7 axis and contributes to the progression of periodontitis. These findings offer novel insights into the molecular mechanisms of OMVs-induced senescence and periodontitis.

关键词： gut microbiota   immunity   immune responses   chronic liver diseases   TNF   liver cirrhos  

摘要： Introduction: The gut microbiota plays a crucial role in regulating immune responses and maintaining a balance within the gut-liver axis. In patients with chronic liver disease (CLD), alterations in gut microbiota have been linked to disease progression and impaired immune function. This study aimed to evaluate the impact of gut-modulating therapies on the immune responses of patients with CLD. Method: Two independent authors conducted a comprehensive literature search using complementary strategies to identify relevant articles published until March 2025. Review Manager Software (RevMan 5.4) was used for data analysis, and the results were presented using forest plots. Results: Of the 373 identified studies, 16 were included in the analysis. The findings revealed that gut microbiota-modulating therapies significantly reduced tumor necrosis factor-alpha (TNF-alpha) levels compared to control interventions (standardized mean difference [SMD], -0.60;95% confidence interval [CI] [-0.93, -0.23] p = 0.001), with similar results observed at the 6-month follow-up (SMD -1.3;95% CI [-2.1, -0.4] p = 0.004). Interleukin-6 (IL-6) levels showed no significant change between the groups (SMD, -0.67;95% CI [-1.5, 0.12) p = 0.09). C-reactive protein (CRP) levels were significantly reduced by gut-modulating therapies (SMD -1.057;95% CI [-1.493, -0.621] p = 0.0005), with consistent results at 1- and 6-month follow-up. Changes in interferon-gamma (IFN-gamma) and IL-18 levels and cellular immunity were also assessed. Conclusion: This study highlights the importance of gut microbiota in modulating immune responses in patients with CLD and demonstrates the effectiveness of long-term gut-modulating therapies in reducing inflammatory markers. While CRP and TNF-alpha levels decreased, changes in IL-6 levels were inconsistent, warranting further research to elucidate the impact of gut microbiota-modulating therapies on this biomarker.

关键词： RIAE   mtDNA/RNA   IFN-(3   Macrophage  

摘要： The radiation-induced abscopal effect (RIAE) can suppress distal metastatic lesions and elicit a systemic antitumor response;however, the underlying mechanisms remain to be fully elucidated. Current research has shown that autophagy promotes the production of IFN-(3 by regulating mitochondrial DNA (mtDNA), thereby contributing to the modulation of RIAE. Nevertheless, the downstream pathways through which IFN-(3 influences RIAE require further investigation. In this study, we observed accumulation of an abundance of mtDNA in the cytosol of mammary tumor cells following RT, along with the presence of mitochondrial RNA (mtRNA). These molecules activated the cGAS-STING and RIG-I-MAVS signaling pathways, respectively, thereby synergistically promoting the production of IFN-(3 and secretion into the extracellular matrix. Subsequently, IFN-(3 facilitated the polarization of macrophages in distant non-irradiated tumor microenvironment towards the M1 phenotype through activating STAT1. Furthermore, our findings indicate that high linear energy transfer (LET) carbon ions are significantly more effective in inducing the production of IFN-(3 and promoting macrophage polarization compared to low-LET X-rays. Thus, our findings provide insights into the intricate mechanisms by which mtDNA/ RNA and IFN-(3 mediate RIAE, suggesting that IFN-(3 could be a promising target for provoking RT immunogenicity in patients with breast cancer and high-LET radiation might effectively elicit RIAE.

关键词： IL-23 receptor   inflammatory bowel disease   variant   gene   treatment  

摘要： Inflammatory bowel disease (IBD), which includes Crohn's Disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract. A key component of the inflammatory pathway in IBD is interleukin 23 (IL-23), which promotes the differentiation and maintenance of Th17 cells. These cells are major contributors to intestinal inflammation and the release of pro-inflammatory cytokines. A dysregulated IL-23/Th17 axis can lead to excessive gut inflammation. Notably, IL-23 affects Th17 cell responses differently in UC and CD, fostering IL-17 production in UC and interferon-gamma (IFN-gamma) production in CD. Genetic studies have pinpointed specific variants of the IL-23 receptor (IL23R) gene that confer protection against IBD. The R381Q (rs11209026) variant has been linked to a reduced risk of developing both CD and UC. Additionally, other variants, such as G149R (rs76418789) and V362I (rs41313262), inhibit IL23R function by disrupting intracellular trafficking and protein stability. This disruption results in decreased phosphorylation of downstream signal transducers, such as STAT3 and STAT4, and reduced IL23R expression on the cell surface, ultimately dampening the activation of pro-inflammatory pathways. The protective effects of these genetic variants underscore the IL-23/IL23R pathway as a significant therapeutic target in IBD management. Therapies designed to modulate this pathway have the potential to reduce pro-inflammatory cytokine production and enhance anti-inflammatory mechanisms. Ongoing research into the IL23R gene and its variants continues to provide valuable insights, paving the way for more targeted and effective treatments for IBD patients.

关键词： miR-135a-5p   STAT6   Non-small cell lung cancer   Epithelial-mesenchymal transition   Arginase 1   Tumor-associated macrophage  

摘要： Arginase 1 (Arg1), a key indicator of M2 polarization in tumor-associated macrophages (TAMs), plays a crucial role in inhibiting T-cell activation and proliferation by depleting local arginine levels, thereby facilitating tumor immune escape. The epithelial-mesenchymal transition (EMT), a fundamental biological process in cancer proliferation and progression, is intricately linked to the interactions between TAMs and cancer cells. However, the underlying mechanisms of EMT and how EMT-programmed cancer cells specifically modulate Arg1 expression in M2-like TAMs remain incompletely understood. Our comprehensive analysis confirmed that Arg1 expression was significantly upregulated in non-small cell lung cancer (NSCLC) tissues, and patients with elevated Arg1 levels exhibited a notably shorter overall survival. Furthermore, alterations in miR-135a-5p expression were found to profoundly influence the proliferation, migration, invasion, EMT, and apoptotic processes of NSCLC cells. Mechanistically, miR-135a-5p post-transcriptionally inhibited STAT6 expression by regulating its 3 '-untranslated region (3'-UTR). Subsequently, the miR-135a-5p/STAT6 axis inhibited GATA3mediated interleukin-4 (IL-4) secretion from NSCLC cells, ultimately suppressing Arg1 expression in M2-like TAMs. MiR-135a-5p may exert pivotal roles in modulating STAT6-induced EMT in tumor cells, which subsequently impacts IL-4-related Arg1 expression and M2 polarization of TAMs in NSCLC. This, in turn, reduced the capacity of M2-like TAMs to secrete tumor-promoting cytokines. Therefore, Arg1 holds potential as a diagnostic biomarker for NSCLC, and miR-135a-5p may emerge as a promising target for inhibiting NSCLC progression.

关键词： 低温暴露   细胞免疫   巨噬细胞   健康风险   低温机制   流行病学  

摘要： 低温环境对机体存在“双刃剑”效应：适度低温能够减缓机体新陈代谢，调控能量代谢模式、减少细胞损伤并降低炎症反应。同时低温能够激活生物体的棕色脂肪组织产热以及抑制过度炎症反应，增强特殊环境下的自我保护能力。长期低温暴露也对健康带来一系列风险。低温暴露下免疫功能发生改变，对机体健康产生不同程度的影响。