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关键词： 牛蒡解肌汤   氧化锌软膏   面部过敏性皮炎   T淋巴细胞亚群  

摘要： 目的 探讨牛蒡解肌汤联合氧化锌软膏对面部过敏性皮炎患者T淋巴细胞亚群水平的影响。方法选取88例行面部过敏性皮炎治疗的患者,按随机数字表法分为对照组与联合组各44例。对照组给予氧化锌软膏进行治疗,联合组给予牛蒡解肌汤联合氧化锌软膏治疗。观察治疗前后患者中医证候积分、皮肤症状缓解所需时间及γ-干扰素(γ-IFN)、白细胞介素-18(IL-18)、C反应蛋白(CRP)、CD3^(+)、CD4^(+)、CD8^(+)水平变化情况;比较2组患者临床疗效。结果 治疗后,相较对照组,联合组皮损色红、自觉瘙痒、灼热、肿胀疼痛积分水平显著降低(P<0.001);瘙痒、皮肤红肿、脱屑症状缓解所需时间显著缩短(P<0.001);γ-IFN、IL-18、CD3^(+)、CD4^(+)水平显著升高,CRP、CD8^(+)水平显著降低(P<0.05);治疗总有效率高于对照组(P<0.05)。结论 对面部过敏性皮炎患者,采用牛蒡解肌汤联合氧化锌软膏进行治疗,能降低中医证候积分水平,缩短皮肤症状缓解所需时间,减轻炎症反应,提高免疫功能,改善角质层屏障功能,临床治疗效果显著。

关键词： Ethnic differences   Genetic variations   IL-16 polymorphisms   Knee osteoarthritis   meta-analysis   Protective effect  

摘要： Background: Knee osteoarthritis (KOA) is a multifactorial condition affected by genetic and environmental factors. Studies have explored the relationship between IL-16 genetic polymorphisms and KOA risk, but findings have been inconclusive. This meta-analysis seeks to assess the association between IL-16 polymorphisms and KOA risk. Methods: A systematic literature search was conducted in several databases, including PubMed, Web of Science, EMBASE, SciELO, and CNKI, for studies published until June 1, 2024. Two independent researchers identified peer-reviewed articles in English, Portuguese, and Chinese using keywords related to “Knee Osteoarthritis” and “Interleukin 16.” Relevant references were also manually reviewed for additional studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the association strength. Additionally, minor allele frequencies (MAFs), Hardy-Weinberg equilibrium (HWE) data, heterogeneity, publication bias, and Newcastle-Ottawa scores (NOS) were evaluated. Results: This analysis included 15 case-control studies, encompassing 1747 individuals with KOA and 1627 healthy controls. Within these studies, five investigated the genetic variations rs11556218 (584 cases, 542 controls), rs4778889 (583 cases, 543 controls), and rs4072111 (580 cases, 542 controls). The findings suggest that the IL-16 variants rs11556218 and rs4072111 may offer protection against KOA development, while no link exists between the rs4778889 variant and KOA susceptibility. The variability in IL-16 polymorphisms, particularly in Asian and Chinese populations, indicates different genetic associations with KOA risk. Strong results, supported by sensitivity analyses and the absence of significant publication bias, emphasize the influence of study methods on the relationship between these polymorphisms and KOA risk. Conclusions: The analysis of three polymorphisms—rs11556218, rs4778889, and rs4072111—shows varying associations with KOA. Rs115

关键词： GRAVIT-D   IL-1β   Inflammation   Obesity   Pregnancy   Vitamin D3  

摘要： Background: Maternal and placental inflammatory activity is carefully regulated during pregnancy and changes in inflammatory status are associated with pregnancy complications and health deficits in the offspring including adverse effects on neurodevelopment. Overweight/obesity is associated with chronic inflammation, thereby contributing to adverse effects. Disturbingly, overweight and obesity are highly prevalent among pregnant women worldwide. Vitamin D (vitD) possess immunomodulatory effects and is believed to support healthy pregnancy. Endocrinological societies recommend empiric vitD supplementation in pregnancy but there is no consensus on the minimal supplementation dose Methods: An adjacent study to GRAVIT-D (no. NCT04291313, ***), a double-blinded randomized trial investigating the clinical benefits of increasing vitD supplementation in pregnancy from 400IU to 3600IU/day from gestational week 11–16 onwards. In a subgroup, (n = 156), multiplex ELISA targeting third-semester serum levels of IL-1β, IL-6, IL-10, TNFα, MCP-1, and IL-17A was performed. Inflammation signals were correlated with the vitD dose given, subsequently analysing the effect of vitD in relation to the pre-pregnancy body mass index (BMI) within each treatment arm comparing the inflammatory response in WHO-defined BMI groups, < 25, 25–30 and > 30 kg/m². Main Results: High pre-pregnancy BMI was associated with increased IL6 and MCP1 in both the 400IU and the 3600 IU exposed group. IL1β levels increased with BMI if using a 400IU/day supplement. High dose vitD supplementation ameliorated BMI effects on IL1β. Conclusion and Perspectives: Increased vitD supplementation during pregnancy may ameliorate some overweight/obesity-induced inflammatory activity. Further studies are needed to determine the vitD need in pregnancies complicated by obesity and overweight. © 2025 The Authors

关键词： Syringomyelia   TNF-alpha   Necroptosis   Reactive astrocytes   Infliximab   Sensory dysfunction  

摘要： Syringomyelia is a severe and progressive disease characterized by fluid-filled cavities that form within the spinal cord, leading to progressive neurological deterioration. However, the molecular mechanisms that cause neuronal death and subsequent dysfunction remain incompletely understood. This study demonstrates that tumor necrosis factor-alpha (TNF-alpha)-mediated necroptosis plays a crucial role in neuronal death during syringomyelia progression. RNA-seq analysis revealed significantly elevated necroptosis scores at both 14 and 28 days after syrinx formation, with identified disease-related differentially expressed necroptosis genes primarily enriched in TNF-alpha-related signaling pathways. Through establishing a rat model of syringomyelia with central canal dilation, significant activation of necroptosis markers, phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) and phosphorylated mixed lineage kinase domain-like protein (p-MLKL), was observed in the area surrounding the syrinx, with their expression predominantly localized to neurons. Concurrently, we found markedly elevated TNF-alpha levels around the syrinx, and primarily originating from reactive astrocytes (70.29 %). Upregulation of TNF receptor 1 (TNFR1) in perilesional neurons suggested enhanced sensitivity to TNF-alpha-mediated death signals. Subsequently, administration of the TNF-alpha inhibitor infliximab at day 14 post-modeling significantly alleviated the expression of necroptosis markers and attenuated the progression of sensory dysfunction at day 28, even in the presence of persistent syrinx. This study is the first to reveal TNF-alpha-mediated neuronal necroptosis as a crucial mechanism in neurological deterioration in syringomyelia, providing novel molecular targets for treatment. These findings suggest that targeting this pathway, particularly in combination with conventional surgical approaches, may offer therapeutic benefits for patients with syringomyelia.

关键词： TNF   Metabolic disorders   Liver diseases   Inflammatory response   Therapeutic implication  

摘要： Tumor necrosis factor (TNF) is identified as a pro-inflammatory cytokine critical to the pathology of liver disease. In the carbohydrate metabolism, TNF has been demonstrated to impede the insulin signaling pathway, thereby precipitating glucose intolerance and insulin resistance. In lipid metabolism, TNF upregulates genes implicated in fatty acid synthesis, resulting in increased lipid accumulation within the liver. In amino acid metabolism, TNF has shown to promote the gene expression for amino acid catabolism, leading to decreased protein synthesis. Additionally, TNF stimulates the production of other chemokines and inflammatory cytokines that can further exacerbate liver injury. Overall, TNF is crucial in developing liver diseases by disrupting various metabolic pathways in the liver, causing insulin resistance, lipid accumulation, and decreased protein synthesis. This review summarizes the present understanding of TNF's role in the regulation of carbohydrate, lipid and amino acid metabolism in liver disease together with its potential therapeutic implications.

关键词： Cell Signalling   Breast cancer   IL6   cFLIP   Autophagy   EMT  

摘要： c-FLIP (cellular FLICE-Like Inhibitor of Apoptotic protein) alias CFLAR (Cellular FADD-like apoptosis regulator) is an inhibitor of Caspase 8 and thus plays a key role in the regulation of extrinsic apoptotic pathway. However, the mechanisms of cFLIP regulation during the course of progression of cancer and it's involvement in tumour cell migration and invasion is yet to be known. Our TCGA data analysis has shown that cFLIP is downregulated in many cancers, including breast cancer, especially at the later stages. Next, we have analysed the role of cFLIP in breast cancer progression in In-vitro study. In doing so, we have used luminal breast cancer cell line MCF7 as non-aggressive and non-invasive breast cancer model and triple negative breast cancer cell lines MDA-MB-231, MDA-MB-468 and MDA-MB-453 as highly aggressive and invasive breast cancer cell model. When, we analysed and compared MCF7 and triple negative cell lines, we found a negative correlation between cFLIP expression pattern and metastasis which supported our In-silico study. Moreover, we found that Il6, one of the most prominent cytokines inside tumour microenvironment, helped in cFLIP downregulation via activation of p38 in MDA-MB-231 cell line. Not only that we have shown that cFLIP negatively regulated autophagy and this autophagy down-regulation resulted in decrease in metastasis. Thus, we have shown in an In-vitro model, for the first time, a complete interconnecting pathway in which IL6 mediated p38 activation directly influences metastasis by regulating autophagy via cFLIP downregulation.

摘要： Objectives: Transmembrane serine protease 2 (TMPRSS2) plays a key role in the entry of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and influenza A into host cells, and its elevated expression is a risk factor for the spread of viral infection. However, TMPRSS2 expression and the factors related to its induction in oral keratinocytes and fibroblasts remain largely unknown. Here, we examined TMPRSS2 expression and factors related to its induction in oral mucosal cells. Methods: TMPRSS2 expression was examined in oral keratinocytes (RT7) and fibroblasts (GT1). Subsequently, TMPRSS2 induction in was analyzed in both cell types following transfection of nucleic acid and inflammatory cytokines, such as interleukin (IL)-1 beta. Finally, the effects of IL-1 beta on STAT1 activation related to double- stranded RNA (dsRNA)-induced TMPRSS2 expression were examined. Results: RT7 and GT1 cells exhibited constitutive TMPRSS2 mRNA and protein expression. Transfection with Poly(I:C) (as a dsRNA) and poly (dA:dT) (as a double- stranded DNA [dsDNA]) increased TMPRSS2 expression. TMPRSS2 expression was also increased by IL-1 beta, but not IFN-gamma or TNF-alpha, while the combination of IL-1 beta and transfected Poly(I:C) caused a dramatic increase in TMPRSS2 expression as compared to each alone in both cell types. IL-1 beta also enhanced transfected Poly(I:C)activated STAT1 related to TMPRSS2 expression. Conclusions: TMPRSS2-expressing oral keratinocytes and fibroblasts are targets of SARS-CoV-2 and influenza A virus. TMPRSS2 expression, in cooperation with IL-1 beta, plays an important role in promoting infection during virus invasion in oral mucosal cells.

关键词： IL‑17A   heat shock protein 70   keratinocytes   psoriasis  

摘要： Psoriasis, which is characterized by keratinocyte hyperproliferation, presents complex management challenges. The heat shock protein 70 (HSP 70) family, which is essential in protein folding and stress responses, also modulates inflammation, suggesting its therapeutic potential in inflammation‑driven diseases. The present study aimed to explore the effects of brevilin A, a natural compound known to alleviate imiquimod‑induced psoriasis, on HSP 70 expression and proinflammatory cytokine production in HaCaT cells stimulated with IL‑17A. An HSP 70 inhibitor was used to determine its role in cytokine regulation, and the effect of brevilin A on skin pathology in mice was examined via immunohistochemistry and hematoxylin and eosin staining. The results revealed that brevilin A markedly decreased IL‑6 and IL‑8 levels after IL‑17A stimulation at both 9 and 24 h in HaCaT cells, and increased HSP 70 and HSP 90 expression levels. Notably, the brevilin A‑induced suppression of cytokine levels was reversed when cells were co‑treated with the HSP 70 inhibitor. In vivo, brevilin A enhanced HSP 70 expression and reduced skin hyperproliferation. These findings suggested that brevilin A may modulate HSP 70 expression and dampen the inflammatory response induced by IL‑17A, indicating its potential as an innovative treatment for psoriasis.

关键词： Plasmablast   Il-21   Cytokine   B cell   iGB  

摘要： Antibodies of the IgE and IgG1 isotypes are relevant for type 2 immunity. In vivo, the production of both is elevated by IL-4, but differentially affected by IL-21, with IgE suppressed and IgG1 production enhanced by IL- 21. However, whether the cytokines drive these outcomes primarily by impacting antibody-secreting, proliferating plasmablasts (PB), or their germinal center B cell precursors, is challenging to unravel. In vitro analyses using Nojima cultures, wherein na & iuml;ve B cells are activated on fibroblasts co-expressing CD40L and BAFF, allows for evaluation of this problem. Here, we explore how IL-4 and IL-21 alone and in combination affect Nojimacultured B cell proliferation and fate, asking what is unique or redundant about exposure to each. In secondary culture, as expected, IL-21 amplified replicative expansion. IL-21 also selectively promoted the differentiation of IgG1+ B cells into PB. The effect was countermanded by synchronous exposure to IL-4, suggesting competing signaling pathways are triggered by the two cytokines independently. Secondary culture with IL-4 alone promoted IgE+ B cell genesis without increasing replicative expansion. Combined exposure to IL-21 and IL-4 led to increased IgE class-switching and proliferative expansion, suggesting that once B cells are switched to IgE, IL-21 can promote IgE+ B cell proliferation. Thus, in culture IL-21 operates to promote proliferation and also drives differentiation of IgG1+ B cells into PB whereas IL-4 has an ongoing role in IgE B cell genesis. The balance of IL-4 and IL-21 thus impacts the fate of in vitro-generated germinal center B cells and highlights how the notable IgE-suppressing effects of IL-21 in vivo likely precede the class-switch step, after which IL-21 may amplify IgE production by virtue of its pro-proliferative effects.

关键词： IL4   clinical relevance   inflammation   prognostic model   pulmonary hypertension  

摘要： BACKGROUND:The anti-inflammatory cytokine interleukin-4 (IL4) has been recognised as a protective factor in various cardiovascular events, yet its prognostic value in patients with pulmonary hypertension (PH) remains unclear. The study aimed to measure the levels of plasma IL4 in patients with PH and to explore their potential association with disease risk and outcomes. METHODS:In this observational study, we analysed the levels of plasma IL4 in 766 PH patients and 191 healthy controls in Shanghai Pulmonary Hospital from October 2009 to January 2024. To establish the correlations between plasma IL4 levels and the risk and outcomes of PH, all patients were followed up from June 2013 to June 2024. The Spearman correlation test was employed to evaluate the relationships between IL4 and right heart catheterisation parameters among patients with PH. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of IL4 for PH. The Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the prognostic value of IL4 levels. Logistic regression analysis was performed to predict PH incidence. A nomogram was constructed to predict mortality, and its clinical utility was validated using decision curve analysis (DCA). RESULTS:Plasma IL4 levels were significantly decreased in patients with PH compared with controls (p < 0.001), as well as in different PH groups (p < 0.05 for all). The logistic regression analyses indicated that the lower IL4 levels were associated with the high risk of PH (OR = 0.79, 95% CI: 0.716-0.872; p < 0.001). IL4 levels correlated inversely with NT-proBNP (r = -0.10, p < 0.05) and mPAP (r = -0.01, p < 0.05), and positively with CI (r = 0.12, p < 0.05) and PaSaO2 (r = 0.11, p < 0.05), indicating an association with disease severity. Kaplan-Meier analysis revealed that patients with IL4 ≥ 2.8774 pg/mL had a 3-year cumulative survival rate of 91.28%, compared with 82.83% for those with IL4 < 2.