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关键词： necrotizing enterocolitis   adipose-derived stem cells   inflammation mediators  

摘要： Research in the field of stem cells in necrotizing enterocolitis has primarily focused on the curative role of specific cells-mostly bone marrow and amniotic fluid stem cells. The impact of stem cells on reducing inflammatory cytokine levels in the necrotizing enterocolitis (NEC) model has been studied in accordance with the effects they pose on histopathology. Taking into consideration the possible paracrine mechanism of action of stem cells, our group hypothesized that lowering the initial levels of proinflammatory cytokines may be one of the mechanisms affecting the clinical outcome. A self-modified rat NEC model was used to show the effect of intraperitoneal administration of adipose derived stem cells on the initial levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alfa) in comparison with the interleukin levels in NEC animals and control animals without adipose-derived stem cells (ADSCs) injection. We showed a statistically significant difference in the levels of interleukins when comparing an ADSC injected group and an NEC group. This suggests that one of the mechanisms in which stem cells impact the clinical outcomes in NEC may be by alleviating the initial levels of proinflammatory cytokines.

关键词： 阿尔茨海默病   β-淀粉样蛋白   单克隆抗体   临床应用建议  

摘要： 近年来阿尔茨海默病免疫治疗领域迎来重要突破，中国已与国际同步批准至少2种抗Aβ单克隆抗体上市，并应用于临床。其中，仑卡奈单抗、多奈单抗分别于2024年6月、2025年4月正式应用于国内临床。基于以上背景，为促进抗Aβ单克隆抗体在国内阿尔茨海默病治疗中的规范、合理、安全应用，本文结合作者团队及国内同道对上述单抗的临床试验数据及临床应用经验，在2024年版本的基础上，继续总结更新抗Aβ单克隆抗体的临床应用建议，包括临床用药指征、用药前评估与准备、用药时医嘱及注意事项、用药后临床监测，旨在为临床医师提供翔实的用药指导和建议。

关键词： 髓源性抑制细胞(MDSC)   宫颈癌   I粒子植入联合动脉化疗栓塞治疗   疗效  

摘要： 目的 探究宫颈癌患者CD33+髓源性抑制细胞（MDSC）介导T淋巴细胞功能及分泌的T淋巴细胞亚群相关炎症因子表达水平，分析其与125I粒子植入联合动脉化疗栓塞治疗疗效的关系及对疗效的预测价值和交互关系。方法 选择2021-01-01/2024-01-01间，我院收治的152例经病理检查确认的晚期宫颈癌患者。均接受子宫动脉化疗栓塞联合125I粒子植入治疗。采用受试者工作特征曲线（ROC）评估CD33+MDSC对宫颈癌临床疗效的预测效能。多因素Logistic回归分析CD33+MDSC与T淋巴细胞对宫颈癌临床治疗无效的相乘或相加交互作用。使用Kaplan-Meier法检验分析宫颈癌CD33+MDSC高低患者的生存的差异。结果 与有效组患者相比较，无效组患者CD3+T淋巴细胞、CD4+T淋巴细胞、白细胞介素2（IL-2）、γ干扰素（IFN-γ）表达降低，CD33+M DSC、CD8+T淋巴细胞、IL-4、IL-6、肿瘤坏死因子α（TNF-α）、肿瘤最大径以及淋巴结转移占比升高。CD33+MDSC水平对宫颈癌患者疗效的预测性能良好。CD33+MDSC高表达组OS明显低于CD33+MDSC低表达组，OS分别为6.0±1.0个月和12.0±1.2个月（t=33.280）。交互作用结果显示，CD33+MDSC、CD8+T淋巴细胞高表达，同时CD3+T淋巴细胞、CD4+T淋巴细胞低表达，宫颈癌患者临床治疗无效风险更高。结论 CD33+MDSC通过抑制CD3+T淋巴细胞、CD4+T淋巴细胞，诱导CD8+T淋巴细胞表达，形成免疫抑制微环境，降低125I粒子植入联合动脉化疗栓塞的治疗应答率，有望成为预测疗效及不良预后的独立生物标志物。

关键词： Lactobacillus reuteri   nuclear factor-kappa B signaling   tumor necrosis factor-alpha   anti-inflammatory   intestinal epithelial cells  

摘要： The widespread misuse of antibiotics in livestock production has raised growing concerns about antimicrobial resistance and residue contamination. These challenges have led to global restrictions on the use of antibiotic growth promoters (AGPs). However, the ban on AGPs has made the management of intestinal inflammation significantly more difficult, highlighting the urgent need for safe and effective alternatives. Lactic acid bacteria (LAB), known for their immunomodulatory properties, have emerged as promising candidates, though their anti-inflammatory mechanisms remain poorly understood. This study investigated the anti-inflammatory effects and underlying molecular mechanisms of a porcine-derived Lactobacillus reuteri (L. reuteri) strain, SBC5-3. Using tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory models in the HT-29 cells, we employed RNA sequencing (RNA-seq) combined with Western blot analyses to systematically explore the modulation of inflammatory signaling pathways. RNA-seq demonstrated that L. reuteri SBC5-3 downregulated 9 out of 14 TNF-alpha-induced genes associated with the TNF and/or nuclear factor kappa B (NF-kappa B) signaling pathways, including BIRC3, PTGS2, CCL20, TNFAIP3, LTB, CXCL1, CXCL10, IL-8, and CSF1. Specifically, L. reuteri SBC5-3 downregulated key genes in the NF-kappa B pathway, such as TAK1, IKK alpha, and NFKB1, while upregulating NFKBIA. Concurrent transcriptional suppression occurred in mitogen-activated protein kinase (MAPK) signaling pathway components ERK and JNK. Western blot analysis further confirmed attenuation of phosphorylation involving TAK1, IKK alpha/beta, and I kappa B alpha following SBC5-3 treatment. The collective data demonstrate that immunomodulation mediated by L. reuteri SBC5-3 involves inhibiting I kappa B alpha degradation, which is known to be essential for the nuclear translocation of the p50/p65 heterodimer, thereby suggesting inhibition of TNF-alpha-induced NF-kappa B nuclear translocation. The

关键词： cell surface molecules   inflammasome   inflammation   parasitic-helminth   transcriptomics  

摘要： Ascaris lumbricoides cystatin (Al-CPI), a cysteine protease inhibitor, has shown anti-inflammatory effects in models of house dust mite-induced respiratory allergy and experimental colitis. Since monocytes are primary targets of cystatins, and helminth-derived products can induce immunoregulatory monocytes that mitigate autoimmune and inflammatory diseases in murine models, we aimed to investigate the immunoregulatory effects of Al-CPI on human monocytes and its mechanisms. Monocytes were isolated from healthy donors using CD14+ magnetic beads and treated with recombinant Al-CPI (rAl-CPI) before activation with LPS. Surface marker expression and caspase-1 activity were analysed by flow cytometry, while cytokine levels were quantified using bead-based assays. Caspase-8 inhibition was measured by fluorescence, and pro-IL-1 beta expression was evaluated by Western blot. RNA-seq and differential gene expression analyses were performed using DESeq2 and GSEA. rAl-CPI reduced cell surface expression of HLA-DR and CD14 as well as IL-1 beta levels in cell culture supernatants. Transcriptomic analysis identified 30 differentially expressed genes (12 upregulated and 18 downregulated;padj < 0.05 and fold change [FC] < |1.5|), including the downregulation of CD14 and SLAMF1, both involved in LPS-mediated signalling through the TLR4-TRIF pathway. GSEA analysis showed that rAl-CPI plus LPS induced an enrichment of the IFN signalling pathway compared with LPS (NES = 1.88;padj < 0.0001). Further analysis of IL-1 beta production and maturation showed that rAl-CPI did not alter pro-IL-1 beta levels, but reduced caspase-1 activation. In conclusion, rAl-CPI may impair IL-1 beta maturation and release by modulating the alternative inflammasome activation, potentially through downregulation of CD14 and other key regulatory molecules involved in this pathway.

摘要： PURPOSE:Ewing sarcoma, in contrast to some adult sarcoma subtypes, generally does not respond to single agent immunotherapy targeting PD1. The features of Ewing sarcoma that preclude the effectiveness of immunotherapy remain largely unknown. To address this question, we utilized biopsies from patients with Ewing sarcoma obtained pre- and post-pembrolizumab (anti-PD1) therapy from the phase 2 clinical trial SARC028 to interrogate the Ewing tumor microenvironment and features associated with resistance to checkpoint inhibition. EXPERIMENTAL DESIGN:We utilize multiplexed immunofluorescence, spatial proteomics and spatial transcriptomics to analyze paired pre- and 8 weeks post- treatment biopsy specimens from patients with Ewing sarcoma enrolled on SARC028. RESULTS:Pembrolizumab therapy did not alter the quantity of immune cell infiltration in Ewing tumor biopsies. Analysis of tumor-associated protein markers revealed increased immunoregulatory markers after pembrolizumab. Spatial transcriptomics identified ten cellular neighborhoods (CN) across patients consisting of specific cell subsets. CN10 was consistently observed across patients with poor response. This cellular neighborhood was enriched for a tumor subpopulation with high TGF-β response, low interferon (IFN) response, and low HLA class I expression. IFN response, HLA class I expression, and overall immune infiltration were correlated. CONCLUSIONS:Analyses of paired Ewing sarcoma tumor samples from SARC028 reveals an immunosuppressive triad, the disruption of which should be pursued to improve antitumor immunity. This work highlights the unique insight that can be gained from the analysis of paired patient Ewing sarcoma tumor biopsy samples from clinical trials.

关键词： trained immunity   acute lung injury   beta-glucan  

摘要： Alveolar macrophages (AMs) reside in the lower airways and play a crucial role in lung health and response to sterile inflammation and infections. AMs possess remarkable adaptability to different environmental challenges that can persist through their memory capacity (trained immunity). beta-Glucan has been characterized as a potent inducer of central trained immunity by reprogramming haematopoietic stem cells in the bone marrow. In the present study, we show that systemic administration of beta-glucan in mice induces peripheral trained immunity by reprogramming AMs in the lungs, in a Dectin1-independent manner. We furthermore demonstrate that AM reprogramming at both the transcriptional and metabolic levels exacerbate lung injury following bacterial (lipopolysaccharide) or viral (polyI:C) challenges via a neutrophil/IFN-gamma-dependent manner. These findings identify an additional facet of beta-glucan in trained immunity involving AM reprogramming and shed light on the potential detrimental effects of trained immunity.

关键词： non-small cell lung cancer (NSCLC)   immune checkpoint inhibitors (ICIs)   IL-2   sPD-L1   IL-23   biomarkers   nivolumab  

摘要： Background This study investigates the predictive potential of circulating cytokines for response and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) *** and methods A cohort of 64 patients with advanced NSCLC receiving ICI therapy were included. Baseline serum samples were collected prior to ICI initiation and profiled using a multiplex cytokine panel. Logistic regression, Cox regression, and Kaplan-Meier survival analysis were employed to assess associations between cytokine levels, therapeutic response, progression-free survival (PFS), and overall survival (OS). Gene expression levels of key cytokines were validated in peripheral blood mononuclear cells (PBMCs) of 17 patients (Responders = 7, Non-Responders = 10) and 3 Healthy Controls using quantitative real-time *** Elevated baseline levels of IL-2, IL-23, and sPD-L1 were significantly associated with clinical response to ICI therapy. Among these, sPD-L1 emerged as an independent predictor of response (AUC = 0.87). Multivariate Cox regression showed IL-2 (HR = 0.67), sPD-L1 (HR = 0.15), and IL-23 (HR = 1.18) were significantly associated with PFS and also predictive of OS. Notably, combined profiling of IL-2 and sPD-L1 enhanced predictive power (AUC = 0.95 for both PFS and OS). RT-PCR analysis of PBMCs corroborated these findings, confirming upregulation of IL-2 in responders and elevated IL-23 expression in *** Baseline cytokine profiling particularly of IL-2, sPD-L1, and IL-23 provides important prognostic and predictive information in advanced NSCLC patients undergoing ICI therapy. These biomarkers may facilitate more personalized approaches to immunotherapy and guide clinical decision-making.

关键词： IL-36   IL-38   cardiovascular disease   biomarker   anthogenesis  

摘要： Members of the interleukin-1 (IL-1) superfamily play crucial roles in orchestrating inflammation and immune responses. Among them, IL-36 and IL-38 have emerged as cytokines with contrasting roles in cardiovascular disease (CVD). IL-36 typically promotes inflammation, contributing to endothelial dysfunction, atherogenesis, and myocardial injury. In contrast, IL-38 exerts predominantly anti-inflammatory effects, modulating immune responses and promoting tissue repair. This mini-review provides a critical synthesis of current findings on IL-36 and IL-38 in the context of atherosclerosis, myocardial ischaemia-reperfusion (I/R) injury, and post-percutaneous coronary intervention (PCI) outcomes. We discuss their molecular mechanisms, potential as biomarkers, and therapeutic implications, while identifying key gaps in knowledge that merit further investigation.