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关键词： IgM   IgA   黏膜免疫   结构生物学   受体识别   病原体效应分子  

摘要： 免疫球蛋白(immunoglobulin, Ig)是机体防御机制的关键组成部分,包括5种主要类别:IgM、IgD、IgG、IgE和IgA. IgM是感染初期产生的首类抗体,同时具有强效的补体激活能力;而IgA则是黏膜免疫的主要抗体. IgM和IgA均以多聚体的形式在免疫防御中发挥功能.得益于冷冻电子显微镜技术的进步,近期研究揭示了IgM和IgA核心区的高分辨率结构,为理解其分子组装机制、受体结合模式以及与病原体蛋白的相互作用提供了新的视角.本综述旨在总结这些最新研究进展,以期加深对IgM和IgA分子机制的理解.

关键词： Chondrocyte   Circ_0075048   miR-663b   Osteoarthritis  

摘要： BACKGROUND: Osteoarthritis (OA) is a common type of degenerative arthropathy. Previous studies have demonstrated that circular RNAs (circRNAs) are involved in the progression of OA. This study aimed to investigate the role and associated mechanism of circ_0075048 in OA. METHODS: The expression of circ_0075048 was analyzed based on the Gene Expression Omnibus dataset GSE178724. Human chondrocytes were stimulated with IL-1β to establish an in vitro OA model. Bioinformatic analysis was performed to identify target genes of circ_0075048. The expression of circ_0075048, miR-663b, and LCP1 was detected by quantitative reverse transcription-polymerase chain reaction. The cell viability and apoptosis of C28/I2 cells were determined using Cell Counting Kit-8 assay and flow cytometry. Protein expression was detected using western blotting. RESULTS: The expression of circ_0075048 was up-regulated in IL-1β-induced chondrocytes. circ_0075048 silencing promoted the viability of and inhibited the apoptosis of and extracellular matrix (ECM) production of chondrocytes. circ_0075048 was found to be a sponge of miR-663b and LCP1 was found to be a target of miR-663b. circ_0075048 silencing increased miR-663b expression but decreased LCP1 expression levels in chondrocytes. An miR-663b inhibitor eliminated the protective effect of a circ_0075048 small interfering RNA (siRNA) on chondrocytes. However, an LCP1 siRNA abolished the effect of the miR-663b inhibitor on chondrocytes. CONCLUSION: circ_0075048 silencing inhibited the apoptosis of and ECM degradation in IL-1β-induced chondrocytes by regulating miR-663b/LCP1 axis. © 2025. The Author(s).

关键词： 动静脉内瘘   狭窄   中性粒细胞-淋巴细胞比率   血小板-淋巴细胞比率   血液透析  

摘要： 目的：探讨中性粒细胞-淋巴细胞比值（neutrophil-lymphocyte ratio,NLR）和血小板-淋巴细胞比值（plateletlymphocyte ratio,PLR）与血液透析（hemodialysis,HD）患者动静脉内瘘（arteriovenous fistula,AVF）狭窄的关系。方法：收集2021年1月至2022年6月在川北医学院附属医院肾内科就诊的625例使用动静脉内瘘透析的患者资料，其中资料完善且符合纳入标准的患者395例，有AVF狭窄的患者245例被分为1组，无AVF狭窄的患者150例为2组。记录患者的常规生化值和全血细胞计数值。结果：(1)1组患者NLR5.07(4.00,6.66) vs. 3.46(2.63,4.15),PLR(169.52(127.56,227.11)vs. 125.66(89.31,165.31)及超敏C-反应蛋白（C-reactive protein,Hs-CRP）(1.90(0.80,2.99) vs. 0.82(0.42,1.27)，水平均高于2组患者，差异具有统计学意义（均P<0.001）。(2)多因素logistic回归分析，校正年龄、性别、体重质量指数（body mass lndex,BMI）、AVF吻合方式、穿刺方式、是否合并糖尿病等因素，结果显示NLR(OR=2.195,95%CI=1.674～2.878,P<0.001),PLR(OR=1.008,95%CI=1.002～1.012,P=0.007),Hs-CRP(OR=2.170,95%CI=1.607～2.751,P<0.001)三者均是HD患者AVF狭窄的独立危险因素。(3)接受者操作特性曲线（Receiver Operating Characteristic Curve,ROC）析显示，NLR曲线下面积（Area Under Curve,AUC）0.799(95%CI=0.756～0.838,P<0.001),PLR 0.694(95%CI=0.646～0.740,P<0.001),Hs-CRP 0.717(95%CI=0.670～0.761,P<0.001)，三者均可预测AVF狭窄，预测最佳临界值分别为NLR 4.08,PLR 122.49,Hs-CRP 1.62，并且3个指标联合预测效果更佳（AUC 0.870,95%CI=0.833～0.901,P<0.001），灵敏度79.18%，特异度81.33%。结论：NLR、PLR和Hs-CRP均是AVF狭窄的独立危险因素和预测因子，且三者联合检测预测价值更高。

关键词： Adaptive immunity   Breast cancer   Cytokines   Immunology   Oncology  

摘要： CD4⁺ T cells contribute to antitumor immunity and are implicated in the efficacy of cancer immunotherapies. In particular, CD4⁺ T helper 2 (Th2) cells were recently found to block spontaneous breast carcinogenesis. However, the antitumor potential of Th2 cells in targeting established breast cancer remains uncertain. Herein, we demonstrate that Th2 cells induced by the topical calcipotriol/thymic stromal lymphopoietin cytokine axis suppressed the growth of established mammary tumors in mice. Interleukin-24 (IL-24), an anticancer cytokine, was highly upregulated in macrophages infiltrating calcipotriol-treated mammary tumors. Macrophages expressed IL-24 in response to IL-4 signaling in combination with Toll-like receptor 4 (TLR4) agonists (e.g., HMGB1) in vitro. Calcipotriol treatment significantly increased HMGB1 release by tumor cells in vivo. CD4⁺ T cell depletion reduced HMGB1 and IL-24 expression, reversing calcipotriol’s therapeutic efficacy. Macrophage depletion and TLR4 inhibition also reduced the therapeutic efficacy of calcipotriol. Importantly, calcipotriol treatment failed to control mammary tumors lacking the IL-24 receptor on tumor cells. Collectively, our findings reveal that Th2 cell–macrophage crosstalk leads to IL-24–mediated tumor cell death, highlighting a promising therapeutic strategy to tackle breast cancer. © 2025, Wang et al.

摘要： Morinda officinalis polysaccharide (MOP) is a major active component of Morinda officinalis, known for its roles in supporting bone health and reducing oxidation and inflammation. However, no studies to date have specifically examined the effects of MOP on interleukin-1β (IL-1β)-stimulated chondrocyte inflammation or the progression of osteoarthritis (OA). To investigate, cell counting kit-8 assays were performed to evaluate MOP's impact on the viability of human chondrocytes (C28/I2 c...

关键词： ASIA   adalimumab   anti‐TNF   granuloma   silicone  

关键词： Cancer   Cytokines   Immunology   Immunotherapy   Oncology  

摘要： The cytokine IL-18 has immunostimulatory effects but is negatively regulated by a secreted binding protein, IL-18BP, that limits IL-18’s anticancer efficacy. A decoy-resistant form of IL-18 (DR-18) that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential has recently been developed. Here, we investigated the therapeutic potential of DR-18 in renal cell carcinoma (RCC). Using pantumor transcriptomic data, we found that clear cell RCC had among the highest expression of IL-18 receptor subunits and IL18BP of tumor types in the database. In samples from patients with RCC treated with immune checkpoint inhibitors, IL-18BP protein expression increased in the tumor microenvironment and in circulation within plasma in nonresponding patients, and it decreased in the majority of responding patients. We used immunocompetent RCC murine models to assess the efficacy of DR-18 in combination with single- and dual-agent anti–PD-1 and anti–CTLA-4. In contrast to preclinical models of other tumor types, in RCC models, DR-18 enhanced the activity of anti–CTLA-4 but not anti–PD-1 treatment. This activity correlated with intratumoral enrichment and clonal expansion of effector CD8⁺ T cells, decreased Treg levels, and enrichment of proinflammatory antitumor myeloid cell populations. Our findings support further clinical investigation of the combination of DR-18 and anti–CTLA-4 in RCC. Copyright: © 2024, Schoenfeld et al.

关键词： Gene expression   Periodontal health   Periodontitis   Psoriasis  

摘要： The purpose of this study was to determine the levels of IL-17, Bcl-3 and IκBζ gene expression in the gingival crevicular fluid (GCF) of psoriatic and healthy individuals and to compare the clinical periodontal parameters in the patient and control groups. A total of 10 psoriasis patients and 2 healthy patients in the control group were included in the analysis for IL-17, Bcl-3, and IκBζ gene expression in the GCF. Periodontal health, gingival index, plaque index, and mobility (using a periotest device) levels were compared between the groups. While considering the down-expressed patients, the expression level of the Bcl-3 gene showed the most variability among the genes studied in psoriasis disease. IL-17 gene expression levels were significantly higher and up-regulated in all patients compared to the control group. In addition, when comparing IL-17 with Bcl-3, IL-17 gene expression was notably high in all patients except patients 4, 9 and 10. The highest expression levels of the IκBζ gene were observed in the patient sample, except for patients 7 and 8. While plaque index, gingival index, and pocket depth parameters were higher in the psoriasis group, there was no significant difference between the two groups (p = 0.257, p = 0.390, p = 0.240, respectively). In the periotest (mobility) parameter, while the mean value was higher in the psoriasis group significantly (p = 0.030), clinically mean values of two groups were in the same grade according to Miller mobility index. The IκBζ gene showed notable high expression levels in psoriasis patients. It was concluded that psoriasis may be associated with periodontitis. CLINICAL TRIAL REGISTRATION NUMBER: NCT06408454-05/06/2024. NAME OF THE TRIAL REGISTER: Interleukin- 17 (IL-17), Bcl-3, and NF-kappa-B Inhibitor Zeta (IκBζ) Expression Levels in the Psoriasis Patients.

关键词： IFN   SARS-CoV-2   COVID-19   固有免疫   疾病预后  

摘要： 自2019年12月至今，严重急性呼吸系统综合征冠状病毒2(Severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)感染所致的新型冠状病毒肺炎（Coronavirus disease 2019, COVID-19）疫情蔓延全球，对人类健康和社会经济产生了严重影响。病毒感染后机体可启动以干扰素（Interferon,IFN）为核心的固有免疫应答，而IFN作为一种重要的固有免疫分子，具有抗病毒和调节免疫反应的双重作用。近期研究表明，SARS-CoV-2可通过多种机制逃逸IFN反应，且在IFN应答缺陷或机体产生IFN自身抗体的条件下，COVID-19患者重症率增加、预后差，提示IFN对COVID-19病情转归具有重要调控作用。本综述将重点讨论IFN在SARS-CoV-2感染中的作用及其对疾病预后的影响，为COVID-19的防控和治疗提供理论支持。