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Mechanism of astragaloside IV enhancing the sensitivity of non-small cell lung cancer to bevacizumab via the lncRNA-PVT1/miR-361-3p/HMGB1 axis 黄芪甲苷通过lncRNA-PVT1/miR-361-3p/HMGB1轴增强非小细胞肺癌对贝伐单抗敏感性的机制
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-08 DOI: 10.1016/j.imbio.2025.153115
Mingfang Huang, Dewei Wang, Fengxia Chen, Liang Li

Objective

This study investigated how astragaloside IV (AST-IV) enhances the responsiveness of non-small cell lung cancer (NSCLC) to bevacizumab (BV) via the lncRNA-PVT1/miR-361-3p/HMBG1 axis.

Methods

Human NSCLC A549 cells were cultured in vitro. oe-NC, A549 cells were transfected with oe-PVT1, oe-HMGB1, mimics NC, and mimics miR for 24 h using transfection reagents and then treated with 50 ng/mL AST-IV and 25 μmol/L BV for 24 h. Expression levels of PVT1, miR-361-3p, and HMGB1 were quantified by RT-qPCR, while protein levels of HMGB1, Ki67, Bax, and Cleaved-caspase-3 were examined through western blot analysis. Proliferation was measured using the CCK-8 assay, and apoptosis was assessed via flow cytometry. The targeting interactions between PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1 were predicted by the BiBiServ2 database and verified by the luciferase reporter assay.

Results

AST-IV and BV-treated A549 cells exhibited significantly inhibited cell proliferation and Ki67/lncRNA-PVT1 expression levels while enhancing apoptosis and upregulating miR-361-3p and Bax and Cleaved-caspase-3. Co-treatment of AST-IV and BV enhanced the sensitivity of A549 cells to BV, further promoted apoptosis, and inhibited cell proliferation. Overexpression of lncRNA-PVT1 down-regulated miR-361-3p levels and partially reversed the promotional effect of AST-IV and BV on the sensitivity of A549 cells to BV. On the basis of overexpression of lncRNA-PVT1, upregulation of miR-361-3p expression significantly increased the sensitivity of A549 cells to BV. Binding interactions between lncRNA-PVT1 and miR-361-3p, as well as miR-361-3p and HMGB1, were confirmed through luciferase assays. Additionally, HMGB1 overexpression counteracted the suppressive effects of AST-IV and BV on A549 cell proliferation and resistance.

Conclusions

AST-IV increased miR-361-3p expression while suppressing HMGB1 via downregulation of lncRNA-PVT1, thereby enhancing BV sensitivity in NSCLC.
目的:本研究探讨黄芪甲苷(AST-IV)如何通过lncRNA-PVT1/miR-361-3p/HMBG1轴增强非小细胞肺癌(NSCLC)对贝伐单抗(BV)的反应性。方法:体外培养人NSCLC A549细胞。用转染试剂转染e-PVT1、e-HMGB1、mimic NC和mimic miR 24 h,然后用50 ng/mL AST-IV和25 μmol/L BV处理24 h, RT-qPCR检测PVT1、miR-361-3p和HMGB1的表达水平,western blot检测HMGB1、Ki67、Bax和aved-caspase-3的蛋白表达水平。CCK-8法检测细胞增殖,流式细胞术检测细胞凋亡。通过BiBiServ2数据库预测PVT1与miR-361-3p、miR-361-3p与HMGB1之间的靶向相互作用,并通过荧光素酶报告基因检测进行验证。结果:AST-IV和bv处理的A549细胞明显抑制细胞增殖和Ki67/lncRNA-PVT1表达水平,增强细胞凋亡,上调miR-361-3p、Bax和Cleaved-caspase-3。AST-IV与BV共处理可增强A549细胞对BV的敏感性,进一步促进细胞凋亡,抑制细胞增殖。lncRNA-PVT1过表达可下调miR-361-3p水平,部分逆转AST-IV和BV对A549细胞对BV敏感性的促进作用。在lncRNA-PVT1过表达的基础上,上调miR-361-3p表达可显著提高A549细胞对BV的敏感性。lncRNA-PVT1与miR-361-3p以及miR-361-3p与HMGB1之间的结合相互作用通过荧光素酶测定得到证实。HMGB1过表达可抵消AST-IV和BV对A549细胞增殖和耐药的抑制作用。结论:AST-IV上调miR-361-3p表达,同时通过下调lncRNA-PVT1抑制HMGB1,从而增强了BV在NSCLC中的敏感性。
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引用次数: 0
Complement at the crossroads of inflammation and metabolism: implications for diabetes and metabolic functions 炎症和代谢十字路口的补体:对糖尿病和代谢功能的影响。
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-05 DOI: 10.1016/j.imbio.2025.153113
Vaishnavi Dandavate, Anna M. Blom, Ben C. King
Diabetes is a growing global problem, with hundreds of millions of people living with the disease worldwide. Diabetes can be divided into two major subtypes, autoimmune type 1 diabetes (T1D), and type 2 diabetes (T2D), which has stronger causal links in obesity, lifestyle, and age. Although immunity and inflammation are clearly defined in T1D, it is also understood that inflammation has a role in metabolic dysregulation in T2D, inducing insulin resistance as well as affecting β-cell function, survival, and therefore insulin secretion. Cytokines and other inflammatory mediators can affect function of cells important for metabolism, most studied in adipose tissue, muscle, and pancreatic islets. Similarly, evidence shows that complement can also have positive roles in metabolic homeostasis in adipose tissue and pancreatic islets. This review will give an introduction to this field, with focus on established and emerging roles of the complement system, an arm of humoral innate immunity that has been found to have roles in metabolic homeostasis.
糖尿病是一个日益严重的全球性问题,全世界有数亿人患有这种疾病。糖尿病可分为两大亚型,自身免疫性1型糖尿病(T1D)和2型糖尿病(T2D),其与肥胖、生活方式和年龄有更强的因果关系。虽然免疫和炎症在T1D中有明确的定义,但我们也知道炎症在T2D的代谢失调中起作用,诱导胰岛素抵抗,影响β细胞功能、存活,从而影响胰岛素分泌。细胞因子和其他炎症介质可影响代谢重要细胞的功能,在脂肪组织、肌肉和胰岛中研究最多。同样,有证据表明补体也可以在脂肪组织和胰岛的代谢稳态中发挥积极作用。本文将介绍这一领域,重点介绍补体系统已建立的和新出现的作用,补体系统是体液先天免疫的一个分支,已被发现在代谢稳态中起作用。
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引用次数: 0
Research progress of animal models of antigen-induced autoimmune diseases 抗原性自身免疫性疾病动物模型的研究进展
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-09-01 DOI: 10.1016/j.imbio.2025.153111
Haixiang Zhang , Jingying Sun , Chunyan Guo , Cuixiang Xu , Jun Hu
Autoimmune diseases (AID) are chronic debilitating diseases characterized by excessive or prolonged autoimmune responses, which lead to the destruction of normal tissue structures and consequent clinical symptoms. AID poses a significant threat to human health, and its pathogenic mechanism remains poorly understood. Etiological studies suggest that the onset of AID primarily caused by the combined influence of environmental and genetic factors. The development of stable and effective animal models is a crucial approach and method for studying the pathogenesis of AID and for accurate prevention and treatment. This paper presents a review of the classification of immune antigens, heterophilic antigen epitopes, and the role of autoantigens in the construction of AID animal models, focusing particularly on the establishment of antigen-induced AID animal models, aiming to provide theoretical references for subsequent research on AID.
自身免疫性疾病(AID)是一种慢性衰弱性疾病,其特征是过度或长期的自身免疫反应,导致正常组织结构的破坏和随之而来的临床症状。艾滋病对人类健康构成重大威胁,其致病机制仍知之甚少。病因学研究表明,艾滋病的发病主要是由环境和遗传因素共同影响所致。建立稳定有效的动物模型是研究艾滋病发病机制、准确防治艾滋病的重要途径和方法。本文综述了免疫抗原的分类、嗜异性抗原表位以及自身抗原在AID动物模型构建中的作用,重点介绍了抗原诱导AID动物模型的建立,旨在为后续的AID研究提供理论参考。
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引用次数: 0
Stability testing of HPCs and MNCs from apheresis products 血浆中HPCs和MNCs的稳定性试验
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-29 DOI: 10.1016/j.imbio.2025.153112
Jinxia Ma, Lipei Shao, Tatyana Fuksenko, Hui Liu, Chunjie Jiang, Yihua Cai, Yong Soo Kim, Kathryn Martin, Larry Moses, Nan Zhang, Anh Dinh, Robert P. Somerville, David F. Stroncek, Ping Jin

Background

Hematopoietic progenitor cells (HPCs) and mononuclear cells (MNCs) are critical components of cell-based therapies, including bone marrow transplantation and regenerative treatments. Evaluation of the characteristics of these products during collection, storage, and transport is essential for maintaining cell viability and functionality. In this study, we evaluated the functional and molecular stability of samples collected for the evaluation of fresh HPC and MNC products. The samples stored at 4 °C for up to 4 days and were evaluated using white blood cell (WBC) counts, flow cytometry, and bulk RNA sequencing (RNA-seq) across five time points.

Methods

HPC samples from seven products (June–December 2022) and MNC samples from six products (October 2022–August 2023) were analyzed on days 0 through 4 after collection. WBC counts were measured, and viability was assessed using 7-AAD staining and flow cytometry. HPC samples were stained with antibodies against CD34, CD3, CD19, CD56, CD14, CD16, CD15, and CD45, while MNC samples were stained with antibodies directed to CD3, CD4, CD8, CD19, CD56, CD14, CD16, CD15, and CD45. Total RNA was isolated from each sample and subjected to bulk RNA-seq to assess transcriptomic changes during storage.

Results

While WBC counts varied between products, no significant differences were observed across time points within individual products. Flow cytometry markers remained relatively stable over time in both HPC and MNC samples, although greater variability was observed in HPCs. A modest decrease in lymphocyte percentages was noted at later time points, primarily driven by a reduction in CD3+ cells; however, these changes were not statistically significant. Cell viability declined significantly over time within individual products and showed inter-product variability. RNA-seq analysis revealed stable gene expression profiles in MNC samples across all time points. In contrast, HPC samples exhibited notable transcriptomic changes as early as day 1 of storage at 4 °C, indicating greater molecular instability.

Conclusion

WBC counts and flow cytometry markers remain stable for up to 3 days in samples collected from fresh HPC and MNC products when stored at 4 °C, although cell viability progressively declines. However, RNA-seq data reveal early transcriptomic changes in HPC samples, suggesting that immediate evaluation of these samples is critical to preserve their molecular integrity and functionality. These findings support the feasibility of delayed phenotypic analysis but emphasize the need for prompt molecular assays in HPC-based applications.
造血祖细胞(HPCs)和单核细胞(MNCs)是细胞治疗的重要组成部分,包括骨髓移植和再生治疗。在收集、储存和运输过程中评估这些产品的特性对于维持细胞活力和功能至关重要。在这项研究中,我们评估了收集的样品的功能和分子稳定性,以评估新鲜HPC和MNC产品。样品在4°C下保存4天,并在五个时间点使用白细胞计数、流式细胞术和大量RNA测序(RNA-seq)进行评估。方法7种产品(2022年6月- 12月)的shpc样品和6种产品(2022年10月- 2023年8月)的MNC样品在采集后第0 ~ 4天进行分析。测定白细胞计数,并用7-AAD染色和流式细胞术评估细胞活力。HPC样品用针对CD34、CD3、CD19、CD56、CD14、CD16、CD15和CD45的抗体染色,而MNC样品用针对CD3、CD4、CD8、CD19、CD56、CD14、CD16、CD15和CD45的抗体染色。从每个样品中分离总RNA,并进行大量RNA测序以评估储存期间转录组学的变化。结果白细胞计数在不同产品之间存在差异,但在单个产品的不同时间点上没有观察到显著差异。随着时间的推移,流式细胞术标记在HPC和MNC样品中保持相对稳定,尽管在HPC中观察到更大的变异性。淋巴细胞百分比在较晚的时间点略有下降,主要是由于CD3+细胞的减少;然而,这些变化在统计学上并不显著。随着时间的推移,单个产品内的细胞活力显著下降,并表现出产品间的可变性。RNA-seq分析显示,MNC样品在所有时间点上的基因表达谱都是稳定的。相比之下,HPC样品早在4°C储存的第1天就表现出显著的转录组变化,表明更大的分子不稳定性。结论从新鲜HPC和MNC产品中采集的样品在4°C下保存时,白细胞计数和流式细胞术标记在3天内保持稳定,但细胞活力逐渐下降。然而,RNA-seq数据揭示了HPC样品的早期转录组变化,这表明立即评估这些样品对于保持其分子完整性和功能至关重要。这些发现支持延迟表型分析的可行性,但强调在基于hpc的应用中需要及时的分子分析。
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引用次数: 0
Increase CD24+CD27+ B cells within pleural effusions derived from lung adenocarcinoma presents enhanced potential for clinical utility 肺腺癌胸膜积液中CD24+CD27+ B细胞增多,临床应用潜力增强
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-21 DOI: 10.1016/j.imbio.2025.153109
Yueming Liang , Danqi Sun , Qizhi Xu , Xiaofan Mao , Minjing Li , XingLin Gao , Sifei Yu

Background

The increasing interest in the roles of B cells, particularly regulatory B cells, within the tumor microenvironment has become prominent, though their immunological characteristics in malignant pleural effusions (PE) remain poorly elucidated.

Methods

Flow cytometry was performed in 143 pleural effusion and peripheral blood samples from patients in order to analyze the proportions of PB-derived B and T cells, and to assess surface markers and cytokines, such as IFN-γ and IL-10. Moreover, we compared clinical role of CD24+CD27+ B cell populations.

Results

B cell populations were significantly higher in PE from lung adenocarcinoma (LUAD) than tuberculosis (TB). Compared to PB from patients, the proportion of CD24+CD27+ B cells was markedly elevated in LUAD-PE and exhibited reduced levels of CD38, CD5, CD71, PD-1, and PD-L1, as well as an upregulation of IL-10 and CD39. PD-1 and PD-L1 were largely found to be upregulated within the CD27+CD38+ B cell subset despite declining proportions overall. Re-interpretations illustrated significant relationships between CD24+CD27+ B cells and clinical measurements.

Conclusions

This study highlights the heterogenic phenotypes and functions of various B cell subsets in LUAD-PE, with specific attention to CD24+CD27+ B cells as potential diagnostic markers and the need for further studies investigating their immunoregulatory functions to unveil new immunotherapeutic strategies in lung cancer.
背景:B细胞,特别是调节性B细胞在肿瘤微环境中的作用越来越受到关注,尽管它们在恶性胸腔积液(PE)中的免疫学特性仍不清楚。方法采用流式细胞术对143例患者的胸腔积液和外周血进行检测,分析pb来源的B细胞和T细胞的比例,并评估表面标志物和细胞因子,如IFN-γ和IL-10。此外,我们比较了CD24+CD27+ B细胞群的临床作用。结果肺腺癌(LUAD)肺组织中b细胞群明显高于结核(TB)肺组织。与患者的PB相比,LUAD-PE中CD24+CD27+ B细胞的比例显著升高,CD38、CD5、CD71、PD-1和PD-L1水平降低,IL-10和CD39水平上调。PD-1和PD-L1在CD27+CD38+ B细胞亚群中大部分被发现上调,尽管总体比例下降。重新解释表明CD24+CD27+ B细胞与临床测量之间存在显著关系。结论本研究强调了LUAD-PE中各种B细胞亚群的异质性表型和功能,特别关注CD24+CD27+ B细胞作为潜在的诊断标记,需要进一步研究其免疫调节功能,以揭示新的肺癌免疫治疗策略。
{"title":"Increase CD24+CD27+ B cells within pleural effusions derived from lung adenocarcinoma presents enhanced potential for clinical utility","authors":"Yueming Liang ,&nbsp;Danqi Sun ,&nbsp;Qizhi Xu ,&nbsp;Xiaofan Mao ,&nbsp;Minjing Li ,&nbsp;XingLin Gao ,&nbsp;Sifei Yu","doi":"10.1016/j.imbio.2025.153109","DOIUrl":"10.1016/j.imbio.2025.153109","url":null,"abstract":"<div><h3>Background</h3><div>The increasing interest in the roles of B cells, particularly regulatory B cells, within the tumor microenvironment has become prominent, though their immunological characteristics in malignant pleural effusions (PE) remain poorly elucidated.</div></div><div><h3>Methods</h3><div>Flow cytometry was performed in 143 pleural effusion and peripheral blood samples from patients in order to analyze the proportions of<!--> <!-->PB-derived B and T cells, and to assess surface markers and cytokines, such as IFN-γ and IL-10. Moreover, we compared clinical role of CD24<sup>+</sup>CD27<sup>+</sup> <!-->B cell populations.</div></div><div><h3>Results</h3><div>B cell populations were significantly higher in PE from lung adenocarcinoma (LUAD)<!--> <!-->than tuberculosis (TB). Compared to PB from patients, the proportion of CD24<sup>+</sup>CD27<sup>+</sup> B cells was markedly elevated in LUAD-PE and exhibited reduced levels of CD38, CD5, CD71,<!--> <!-->PD-1, and PD-L1, as well as an upregulation of IL-10 and CD39. PD-1 and PD-L1 were<!--> <!-->largely found to be upregulated within the CD27<sup>+</sup>CD38<sup>+</sup> B cell subset despite declining proportions overall. <em>Re</em>-interpretations illustrated significant relationships<!--> <!-->between CD24<sup>+</sup>CD27<sup>+</sup> B cells and clinical measurements.</div></div><div><h3>Conclusions</h3><div>This study highlights the heterogenic<!--> <!-->phenotypes and functions of various B cell subsets in LUAD-PE, with specific attention to CD24<sup>+</sup>CD27<sup>+</sup> B cells as potential diagnostic markers and the need for further studies investigating their immunoregulatory functions to unveil new immunotherapeutic strategies in lung cancer.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 5","pages":"Article 153109"},"PeriodicalIF":2.3,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice uni -77靶向MCL-1激活线粒体自噬,改善小鼠牙周炎
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-16 DOI: 10.1016/j.imbio.2025.153108
Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin
<div><h3>Objective</h3><div>To investigate the therapeutic and ameliorative effects of the Myeloid Cell Leukemia 1 protein (MCL-1) inhibitor UMI-77 on experimental murine periodontitis via mitophagy activation, with a focus on comparing administration routes (local/intraperitoneal) and doses (high/low/combined).</div></div><div><h3>Methods</h3><div>A ligature-induced periodontitis model was established in 54 male C57BL/6 J mice, randomized into 9 groups (<em>n</em> = 6 per group): normal control (Group Aa), periodontitis model (Group Ab), positive control (Group Ac, local minocycline), local PBS control (Group Ad), intraperitoneal PBS control (Group Ae), local high-dose UMI-77 (Group Ba, 2 mg/kg), local low-dose UMI-77 (Group Bb, 1 mg/kg), intraperitoneal UMI-77 (Group Ca, 2 mg/kg), and combined intraperitoneal UMI-77 + local minocycline (Group Cb, 2 mg/kg + standard minocycline regimen). Outcomes included periodontal bleeding on probing (BOP), alveolar bone resorption via micro-CT, histopathological analysis (HE/methylene blue staining), MCL-1 expression (Western blot), autolysosome detection (transmission electron microscopy, TEM), and systemic organ safety (HE staining).</div></div><div><h3>Results</h3><div>All UMI-77 treatment groups exhibited significant amelioration of periodontal inflammation and bone resorption compared to the model group (Ab, <em>p</em> < 0.0001). Local high-dose UMI-77 (Group Ba) demonstrated the most potent efficacy, reducing BOP by 76 % (0.67 ± 0.5 vs. Ab: 2.8 ± 0.4, <em>p</em> < 0.001) and cementoenamel junction–alveolar bone crest distance by 48.7 % (0.20 ± 0.04 mm vs. Ab: 0.41 ± 0.05 mm, <em>p</em> < 0.0001), outperforming the positive control (Group Ac, BOP: 2.17 ± 0.4, <em>p</em> < 0.001). Histological analysis showed reduced inflammatory cell infiltration and organized periodontal fibers in Group Ba. Western blot confirmed downregulation of MCL-1 expression to near-normal levels in Group Ba, while TEM detected autolysosomes in both Group Ba and Group Ca, indicating mitophagy activation. Systemic safety assessments revealed only mild grade 1 cardiac septal thickening in Group Ba and transient splenic lymphocyte elevation in Group Ca, with no severe organ toxicity.</div></div><div><h3>Conclusion</h3><div>UMI-77 exerts significant therapeutic and ameliorative effects against periodontitis in mice, with local high-dose administration (Group Ba) demonstrating optimal efficacy. Intraperitoneal UMI-77 combined with local minocycline (Group Cb) achieved comparable outcomes to high-dose local UMI-77, highlighting potential combinatorial strategies. These findings establish UMI-77 as a promising agent for periodontitis treatment via MCL-1-targeted mitophagy activation.</div></div><div><h3>Clinical significance</h3><div>UMI-77, especially with local high-dose administration, offers a new, potentially effective and safe approach for periodontitis treatment, holding great promise for clinical translation.</div></
目的探讨骨髓细胞白血病1蛋白(Myeloid Cell Leukemia 1 protein, MCL-1)抑制剂UMI-77通过线粒体自噬激活对实验性小鼠牙周炎的治疗和改善作用,重点比较给药途径(局部/腹腔)和剂量(高/低/联合)。方法将54只雄性C57BL/ 6j小鼠建立结扎性牙周炎模型,随机分为9组(每组6只):正常对照组(Aa组)、牙周炎模型组(Ab组)、阳性对照组(Ac组,局部米诺环素)、局部PBS对照组(Ad组)、腹腔PBS对照组(Ae组)、局部高剂量UMI-77 (Ba组,2mg /kg)、局部低剂量UMI-77 (Bb组,1mg /kg)、腹腔注射UMI-77 (Ca组,2mg /kg)、腹腔注射UMI-77 +局部米诺环素(Cb组,2mg /kg +米诺环素标准方案)。结果包括牙周探诊出血(BOP)、显微ct观察的牙槽骨吸收、组织病理学分析(HE/亚甲基蓝染色)、MCL-1表达(Western blot)、自溶酶体检测(透射电镜,TEM)和全身器官安全性(HE染色)。结果与模型组相比,所有uni -77治疗组的牙周炎症和骨吸收均有显著改善(p < 0.0001)。局部高剂量uni -77 (Ba组)效果最显著,BOP降低76%(0.67±0.5比Ab: 2.8±0.4,p < 0.001),牙骨质牙釉质连接-牙槽骨嵴距离降低48.7%(0.20±0.04 mm比Ab: 0.41±0.05 mm, p < 0.0001),优于阳性对照组(Ac组,BOP: 2.17±0.4,p < 0.001)。组织学分析显示,Ba组炎症细胞浸润减少,牙周纤维组织整齐。Western blot证实Ba组MCL-1表达下调至接近正常水平,TEM检测到Ba组和Ca组均有自溶酶体,表明自噬激活。系统安全性评估显示,Ba组只有轻微的1级心间隔增厚,Ca组只有短暂的脾淋巴细胞升高,没有严重的器官毒性。结论umi -77对小鼠牙周炎具有明显的治疗和改善作用,局部大剂量给药(Ba组)效果最佳。腹腔注射UMI-77联合局部米诺环素(Cb组)取得了与高剂量局部UMI-77相当的结果,突出了潜在的联合策略。这些发现表明uni -77是一种通过mcl -1靶向线粒体自噬激活治疗牙周炎的有希望的药物。临床意义umi -77,特别是局部大剂量给药,为牙周炎治疗提供了一种新的、潜在的有效和安全的方法,具有很大的临床应用前景。
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引用次数: 0
Proportional and functional anomalies of CD38+ NK Cells:A new mechanism for impaired anti-tumour immunity in multiple myeloma? CD38+ NK细胞比例和功能异常:多发性骨髓瘤抗肿瘤免疫功能受损的新机制?
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-12 DOI: 10.1016/j.imbio.2025.153107
Huixian Chen , Kehua Fang , Jinbao Zong , Xiaotian Chang

Background

The abnormal quantity and dysfunction of immune cells in patients with multiple myeloma impede anti-tumour immunity and prompt the occurrence and development of disease. It has been reported that CD38+ NK cells are involved in immune regulation.

Methods

Peripheral blood (PB) samples were collected from healthy volunteers (HV) and newly diagnosed multiple myeloma (NDMM) patients. The proportions of CD38+ NK cells and CD38+CD16+ NK cells were measured. Moreover, CD38+ NK cells separated from PB were co-cultured with RPMI-8226 assess their impact on myeloma cell apoptosis and proliferation. Similar co-culture experiments were also initiated with naive CD4+ T cells from HV to ascertain the influence of CD38+ NK cells on regulatory T cells (Tregs) differentiation.

Results

The percentages of CD38+ NK and CD38+CD16+ NK cells in the PB of NDMM patients were markedly decrease than that in HV. The apoptosis rate of RPMI-8226 was slightly increased following co-culture with CD38+ NK cells from NDMM samples, as opposed to those from HV samples. CD38+ NK cells from NDMM or HV had similar inhibitory effect on MM cell proliferation. Furthermore, CD38+ NK cells from NDMM fostered CD4+ T cell differentiation to Tregs more than those from HV.

Conclusion

In MM, the proportion and function of CD38+ NK cells undergo changes, which may be related to the formation of the immunosuppressive microenvironment.
背景多发性骨髓瘤患者免疫细胞数量的异常和功能障碍阻碍了抗肿瘤免疫,促进了疾病的发生和发展。有报道称CD38+ NK细胞参与免疫调节。方法采集健康志愿者(HV)和新诊断的多发性骨髓瘤(NDMM)患者外周血(PB)。测定CD38+ NK细胞和CD38+CD16+ NK细胞的比例。此外,将PB分离的CD38+ NK细胞与rpm -8226共培养,评估其对骨髓瘤细胞凋亡和增殖的影响。类似的共培养实验也开始与来自HV的初始CD4+ T细胞进行,以确定CD38+ NK细胞对调节性T细胞(Tregs)分化的影响。结果NDMM患者外周血中CD38+ NK和CD38+CD16+ NK细胞的百分比明显低于HV患者。RPMI-8226与来自NDMM样品的CD38+ NK细胞共培养后,与来自HV样品的细胞共培养相比,RPMI-8226的凋亡率略有增加。来自NDMM和HV的CD38+ NK细胞对MM细胞增殖的抑制作用相似。此外,与HV相比,NDMM的CD38+ NK细胞更能促进CD4+ T细胞向treg的分化。结论MM中CD38+ NK细胞比例及功能发生改变,可能与免疫抑制微环境的形成有关。
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引用次数: 0
Prior appendectomy attenuates the immune protective efficacy of BCG vaccination against Mycobacterium tuberculosis infection 先前阑尾切除术降低了卡介苗接种对结核分枝杆菌感染的免疫保护作用
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-08 DOI: 10.1016/j.imbio.2025.153106
Huirong Huang , Wei Xu , Sidong Xiong
Cecal appendix is a unique niche for commensal bacteria, and has been considered the primary site for immunoglobulin A production. Yet its immune function in anti-infection immunity has not been fully understood. In order to elucidate whether cecal patch (CeP), the murine version of appendix, would influence the immune response induced by Mycobacterium tuberculosis (M. tb) and the vaccine effect of Bacillus Calmette-Guérin (BCG), BALB/c mice at 4 weeks of age received appendectomy or sham operation and recovered for 2 weeks before intranasal infection with 2 × 107 CFU Mycobacterium tuberculosis H37Ra. Appendectomy of mice led to a reduction in lung macrophage numbers 7 days post infection (p. i.), and aggravated lung immunohistopathology 4 weeks p. i.. Appendectomized mice vaccinated with 5 × 106 CFU BCG exhibited attenuated BCG-specific serum IgG, reduced lung/splenic IFN-γ+ T response, and weakened T proliferation and cytotoxicity, and eventually worsened lung pathology compared to sham operated mice. Mechanistically, we found that appendectomized mice at a young age (4 weeks) had an attenuated maturation of mesenteric lymph node (MLN) conventional dendritic cells (cDCs), which accounted for the impaired systemic IFN-γ+ T response and cytotoxicity against M. tb. Our data suggest that intact appendix maintain intestinal DC maturation and systemic Th1 induction against M. tb and has an assistant role in increasing immune efficiency of BCG vaccine.
盲肠阑尾是共生细菌的独特生态位,被认为是免疫球蛋白a产生的主要部位。但其在抗感染免疫中的免疫功能尚不完全清楚。为了阐明盲肠贴片(cecal patch, CeP)是否会影响结核分枝杆菌(M. tb)诱导的免疫应答和卡介苗(Bacillus calmette - gusamrin, BCG)疫苗的效果,BALB/c小鼠在4周龄时接受阑尾切除或假手术,并在鼻内感染2 × 107 CFU结核分枝杆菌H37Ra前恢复2周。小鼠阑尾切除术导致感染后7天肺巨噬细胞数量减少(p. i.), 4周肺免疫组织病理学加重。与假手术小鼠相比,接种5 × 106 CFU卡介苗的阑尾切除小鼠表现出BCG特异性血清IgG减弱,肺/脾IFN-γ+ T反应降低,T增殖和细胞毒性减弱,最终肺部病理恶化。在机制上,我们发现年幼(4周)阑尾切除小鼠的肠系膜淋巴结(MLN)常规树突状细胞(cDCs)成熟减弱,这是导致系统性IFN-γ+ T反应和抗结核分枝杆菌细胞毒性受损的原因。我们的数据表明,完整的阑尾维持了肠道DC成熟和对M. tb的全身Th1诱导,并在提高卡介苗免疫效率方面具有辅助作用。
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引用次数: 0
Serological assessment of rubella immunity in Iranian children post 2019 elimination: A pilot study 2019年消除后伊朗儿童风疹免疫的血清学评估:一项试点研究
IF 2.3 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-08-07 DOI: 10.1016/j.imbio.2025.153105
Tasnim Jamalvandi , Akram Sadat Ahmadi , Somayeh Shatizadeh Malekshahi , Maryam Tatari , Azadeh Shadab , Vahid Salimi , Nazanin-Zahra Shafiei-Jandaghi , Talat Mokhtari-Azad

Background and aim

The elimination of rubella in Iran, achieved in 2019, represents a significant public health success. A limited number of studies have investigated rubella IgG seropositivity levels in Iran across different populations over the last two decades. This study evaluated rubella vaccination coverage and immunity status among Iranian children born between 2016 and 2021, before and during the COVID-19 pandemic.

Methods

Using ELISA, 722 serum samples from children negative for measles and rubella IgM antibodies were analyzed for rubella-specific IgG. Samples were divided into two groups: Group A (born 2016–2018, pre-pandemic) and Group B (born 2019–2021, during the pandemic). Vaccination status was obtained from parental reports.

Results

Overall rubella IgG seropositivity was 75.3 %, with Group B showing significantly higher immunity (82.4 %) than Group A (68.6 %) (p < 0.001). Parental reports indicated MMR vaccination coverage of 95.7 % overall, with Group B coverage (98.9 %) significantly exceeding Group A (92.7 %) (p < 0.001). No significant gender differences were observed. Regional vaccination coverage varied, but rubella IgG positivity was consistent across provinces.

Conclusions

Despite maintaining high MMR vaccination coverage, the overall rubella immunity level in Iranian children in this pilot study remained below the WHO's recommended herd immunity threshold, posing a potential risk for rubella re-emergence. This finding underscored the ongoing surveillance and targeted immunization efforts to sustain rubella elimination in Iran.
背景和目的2019年在伊朗消除了风疹,这是一项重大的公共卫生成功。在过去二十年中,有限数量的研究调查了伊朗不同人群中风疹IgG血清阳性水平。本研究评估了2016年至2021年之间、COVID-19大流行之前和期间出生的伊朗儿童的风疹疫苗接种覆盖率和免疫状况。方法采用ELISA法对麻疹和风疹IgM抗体阴性儿童血清722份进行风疹特异性IgG检测。样本分为两组:A组(出生于2016-2018年,大流行前)和B组(出生于2019-2021年,大流行期间)。疫苗接种情况从家长报告中获得。结果风疹IgG血清总阳性率为75.3%,其中B组免疫阳性率为82.4%,显著高于A组(68.6%)(p <;0.001)。家长报告显示MMR疫苗接种率为95.7%,B组接种率(98.9%)显著超过A组(92.7%)(p <;0.001)。没有观察到显著的性别差异。区域疫苗接种覆盖率各不相同,但风疹IgG阳性在各省是一致的。结论:尽管MMR疫苗接种率保持在较高水平,但在本试点研究中,伊朗儿童的风疹总体免疫水平仍低于世卫组织建议的群体免疫阈值,存在风疹再次出现的潜在风险。这一发现强调了正在进行的监测和有针对性的免疫工作,以维持在伊朗消除风疹。
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引用次数: 0
Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia Kasumi-1外泌体在tp53型急性白血病中起主要的t细胞免疫逃避作用
IF 2.5 4区 医学 Q3 IMMUNOLOGY Pub Date : 2025-07-01 DOI: 10.1016/j.imbio.2025.153102
Yunyun Du , Zhenfeng Fan , Lijiao Li , Yong Xue , Shixiang Zhao

Background

The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.

Methods

Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.

Results

In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8+ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.

Conclusion

Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8+ T cell expression and increased Treg expression.
背景:tp53突变型急性白血病(AL)的治疗和预后非常不利。肿瘤源性外泌体参与肿瘤发生和免疫调节。我们的目的是表征外泌体介导的TP53突变体的免疫景观。方法选择4个TP53 AL细胞系进行研究。采用RT-qPCR和western blot检测PD-L1和TP53。AL外泌体与PBMC共培养。流式细胞术检测免疫细胞和PD-1的表达。透射电镜和western blot检测MOLM-13和Kasumi-1外泌体表面标记物HSP70、CD9、CD63和CD81。随后,进行miRNA测序。结果在TP53 AL细胞系中,MOLM-13、Kasumi-1、Molt-4和KG-1细胞中PD-L1蛋白和mRNA的表达量依次升高。值得注意的是,MOLM-13和Kasumi-1的TP53表达量最高。流式细胞术结果表明,kasumi -1外泌体对免疫细胞有更明显的作用,导致CD8+ T细胞群显著减少,Tregs显著增加。值得注意的是,PD-1表达明显升高。miRNA分析显示,deg主要富集于信号转导和内吞途径。结论kasumi -1-exos通过网格蛋白介导的质膜融合促进DNA损伤和PD-L1富集,最终导致AL免疫逃逸,主要表现为CD8+ T细胞表达降低和Treg表达增加。
{"title":"Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia","authors":"Yunyun Du ,&nbsp;Zhenfeng Fan ,&nbsp;Lijiao Li ,&nbsp;Yong Xue ,&nbsp;Shixiang Zhao","doi":"10.1016/j.imbio.2025.153102","DOIUrl":"10.1016/j.imbio.2025.153102","url":null,"abstract":"<div><h3>Background</h3><div>The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.</div></div><div><h3>Methods</h3><div>Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.</div></div><div><h3>Results</h3><div>In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8<sup>+</sup> T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.</div></div><div><h3>Conclusion</h3><div>Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8<sup>+</sup> T cell expression and increased Treg expression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 4","pages":"Article 153102"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Immunobiology
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