Immunobiology最新文献_第4页

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

Immunobiology

Pub Date : 2025-11-01 Epub 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

CD1-MR1 2024 unconventional immune surveillance: Uniting a rapidly growing field CD1-MR1 2024非常规免疫监测：联合一个快速增长的领域。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-01 DOI: 10.1016/j.imbio.2025.153110

Hui-Fern Koay

引用次数: 0

Higher levels of urinary extracellular vesicles and immune mediators are related to acute infection severity during the post-COVID period 尿细胞外囊泡和免疫介质水平升高与新冠肺炎后急性感染严重程度有关

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-11-17 DOI: 10.1016/j.imbio.2025.153142

Evelyn Maciel de Oliveira , Camila Carvalho , Natalia Fonseca do Rosário , Carla Rodrigues , Iris Braga da Silva , Alice Ramos , Fabiana Rabe Carvalho , Pedro Barbosa , Fernanda G. De Felice , Mauro Jorge Cabral-Castro , Jocemir Ronaldo Lugon , Thalia Medeiros , Andrea Alice Silva

Introduction: We investigated circulating and urinary inflammatory mediators and extracellular vesicles (EVs) in association with clinical and laboratory findings during the post-COVID-19 (coronavirus disease 2019) period. Methods: A cross-sectional study was conducted with individuals with history of COVID-19 stratified according to the presence of post-COVID condition (PCC) and hospitalization during the acute phase. Circulating and urinary levels of 27 inflammatory mediators were quantified by multiplex assays. EVs were isolated by differential centrifugation and assessed by nanoscale flow cytometry, nanoparticle tracking analysis, and transmission electron microscopy. Results: We included 78 participants (55 ± 14.6 years-old, 79.5 % females), of whom 56 (71.8 %) had PCC. Of these, 18 (32 %) required hospitalization during COVID-19. No differences between groups were observed regarding plasma EVs, but hospitalized PCC patients presented lower levels of circulant interleukin (IL)-9 (p = 0.03), higher monocyte-to-lymphocyte ratio (p = 0.03), prothrombin time (p = 0.02), and lactate dehydrogenase (p = 0.01). In addition, higher levels of total urinary EVs (uEVs, p = 0.006) and uIL-4 (p = 0.01), chemokine (CC motif) ligand (CCL)-2 (p = 0.02), CCL-11 (p = 0.002), and granulocyte-macrophage colony-stimulating factor (p = 0.04) were observed in the same group. Likewise, individuals infected before vaccination presented higher total uEVs (p = 0.003) and urinary CCL-11 (p = 0.01), and multiple episodes of COVID-19 were associated with higher urinary interferon-γ (p = 0.04) and IL-1Ra (p = 0.03). Conclusion: Our results may suggest a possible remnant renal inflammatory process in PCC patients who had moderate-to-severe acute COVID-19.

前言：我们研究了循环和尿路炎症介质和细胞外囊泡（ev）与covid -19（2019冠状病毒病）后时期临床和实验室结果的相关性。方法：采用横断面研究方法，对有COVID-19病史的个体进行分层，按是否存在COVID-19后症状（PCC）和急性期住院情况进行分层。通过多重测定法定量27种炎症介质的循环和尿液水平。通过差速离心分离ev，并通过纳米级流式细胞术、纳米颗粒跟踪分析和透射电镜进行评估。结果：我们纳入78名参与者（55±14.6岁，79.5%为女性），其中56名（71.8%）患有PCC。其中18人（32%）在COVID-19期间需要住院治疗。各组间血浆EVs无差异，但住院PCC患者循环白细胞介素(IL)-9水平较低（p = 0.03），单核细胞与淋巴细胞比值较高（p = 0.03），凝血酶原时间（p = 0.02），乳酸脱氢酶（p = 0.01）。此外，尿总ev （uEVs, p = 0.006）和il -4 （p = 0.01）、趋化因子（CC motif）配体(CCL)-2 （p = 0.02）、CCL-11 （p = 0.002）和粒细胞-巨噬细胞集落刺激因子（p = 0.04）水平均高于对照组。同样，接种疫苗前感染的个体总uEVs （p = 0.003）和尿CCL-11 （p = 0.01）较高，多次发作的COVID-19与尿干扰素-γ (p = 0.04)和IL-1Ra （p = 0.03）较高相关。结论：我们的研究结果可能提示中重度急性COVID-19的PCC患者可能存在残留的肾脏炎症过程。

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引用次数: 0

sgp130Fc alleviates cartilage degeneration and knee osteoarthritis by inhibiting IL-6 trans-signaling pathway sgp130Fc通过抑制IL-6反式信号通路缓解软骨退变和膝关节骨关节炎。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-22 DOI: 10.1016/j.imbio.2025.153122

Chunrong He , Lingjie Tan , Chi Liang , Jiewen Luo , Ke Xiao , Song Wu , Jinshen He

Background

Interleukin-6 (IL-6) trans-signaling plays a pivotal role in the pathogenesis and progression of osteoarthritis (OA), contributing to chronic intra-articular inflammation and cartilage degradation. Soluble gp130-Fc (sgp130Fc) is a selective inhibitor of IL-6 trans-signaling that spares classical signaling. This study aimed to elucidate the role of IL-6 trans-signaling in knee OA and evaluate the therapeutic potential of sgp130Fc.

Methods

Synovial fluid from OA patients at different disease stages was analyzed for IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 levels by ELISA. Primary rat chondrocytes were treated with Hyper-IL-6 to activate IL-6 trans-signaling and co-treated with sgp130Fc to assess cell viability, gene expression, and lipid metabolism alterations. A rat OA model was established via the Hulth method, followed by intra-articular administration of sgp130Fc. Histological, immunohistochemical, and lipidomic analyses were performed to evaluate cartilage integrity and inflammatory responses.

Results

Levels of IL-6, sIL-6R, and sgp130 in synovial fluid increased with OA progression. Hyper-IL-6 impaired chondrocyte viability, activated JAK1-STAT3 signaling, promoted inflammatory and catabolic gene expression, and disrupted lipid metabolism, all of which were reversed by sgp130Fc treatment. In vivo, sgp130Fc injections alleviated cartilage degradation, reduced synovitis, suppressed inflammatory mediators, and restored lipid homeostasis.

Conclusions

Targeted inhibition of IL-6 trans-signaling with sgp130Fc effectively mitigates cartilage degeneration and inflammation in OA, highlighting its potential as a novel disease-modifying therapeutic strategy for knee osteoarthritis.

背景：白细胞介素-6 （IL-6）反式信号在骨关节炎（OA）的发病和进展中起关键作用，导致慢性关节内炎症和软骨降解。可溶性gp130-Fc （sgp130Fc）是IL-6反式信号传导的选择性抑制剂，可避免经典信号传导。本研究旨在阐明IL-6反式信号在膝关节OA中的作用，并评估sgp130Fc的治疗潜力。方法：采用酶联免疫吸附法（ELISA）分析不同病程OA患者滑液中IL-6、可溶性IL-6受体（sIL-6R）和sgp130水平。用Hyper-IL-6处理原代大鼠软骨细胞以激活IL-6反式信号，并与sgp130Fc共处理以评估细胞活力、基因表达和脂质代谢改变。采用Hulth法建立大鼠骨性关节炎模型，然后关节内给药sgp130Fc。进行组织学、免疫组织化学和脂质组学分析以评估软骨完整性和炎症反应。结果：滑液中IL-6、sIL-6R和sgp130的水平随着OA的进展而升高。Hyper-IL-6损伤软骨细胞活力，激活JAK1-STAT3信号，促进炎症和分解代谢基因表达，破坏脂质代谢，所有这些都被sgp130Fc治疗逆转。在体内，注射sgp130Fc可缓解软骨退化，减轻滑膜炎，抑制炎症介质，恢复脂质稳态。结论：sgp130Fc靶向抑制IL-6反式信号传导可有效减轻OA患者的软骨退变和炎症，突显其作为膝关节骨关节炎一种新的疾病改善治疗策略的潜力。

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引用次数: 0

Pan-cancer analysis of GINS1 identifies its prognostic and immunotherapy predictive value with in vitro experimental validation in nasopharyngeal carcinoma 泛癌分析证实GINS1在鼻咽癌中的预后和免疫治疗预测价值，并进行了体外实验验证

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-11 DOI: 10.1016/j.imbio.2025.153114

Yang Xu , Qingqing Zhang , Wanting Qin , Zhiyu Yan , Shuhan Ma , Yuanyuan Chang , Kaihua Chen , Ling Li , Xiaodong Zhu

Background

GINS complex subunit 1 (GINS1) is part of the tetrameric GINS complex involved in DNA replication, playing a vital role in controlling the start and continuation of DNA replication. Its role in cancer, however, is not well understood. Still, its relevance to cancer is uncertain. This study focused on exploring the role of GINS1 in different forms of cancer.

Methods

Using a range of publicly available databases, we conducted a comprehensive study on the oncogenic function of GINS1 in pan-cancer through analyses of differential expression, survival, enrichment, gene mutations and tumor immune cell infiltration. Additionally, the expression and effects of GINS1 in nasopharyngeal carcinoma (NPC) were analyzed through a series of in vitro experiments.

Results

GINS1 was found to be overexpressed in nearly all tumors, demonstrating notable diagnostic and prognostic potential. Moreover, the relationship between GINS1 and specific immune characteristics (such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability) suggests its potential role in guiding immunotherapy approaches. In vitro studies show that GINS1 notably enhances proliferation, migration, and invasion of NPC cells, with elevated expression levels correlating with a poorer prognosis.

Conclusions

GINS1 might serve as a prognostic and immunotherapy marker for different types of cancers, such as nasopharyngeal carcinoma.

GINS1复合物亚基1 （GINS1）是参与DNA复制的四聚体GINS复合物的一部分，在控制DNA复制的开始和继续方面起着至关重要的作用。然而，它在癌症中的作用尚不清楚。然而，它与癌症的关系尚不确定。本研究的重点是探索GINS1在不同形式癌症中的作用。方法利用一系列公开的数据库，通过分析GINS1在泛癌中的差异表达、存活、富集、基因突变和肿瘤免疫细胞浸润等方面，全面研究GINS1在泛癌中的致癌功能。此外，通过一系列体外实验分析GINS1在鼻咽癌（NPC）中的表达及其作用。结果gins1在几乎所有肿瘤中均过表达，显示出显著的诊断和预后潜力。此外，GINS1与特异性免疫特性（如免疫细胞浸润、免疫检查点基因、肿瘤突变负担和微卫星不稳定性）之间的关系提示其在指导免疫治疗方法方面的潜在作用。体外研究表明，GINS1显著增强鼻咽癌细胞的增殖、迁移和侵袭，表达水平升高与预后较差相关。结论sgins1可作为鼻咽癌等不同类型肿瘤的预后和免疫治疗标志物。

{"title":"Pan-cancer analysis of GINS1 identifies its prognostic and immunotherapy predictive value with in vitro experimental validation in nasopharyngeal carcinoma","authors":"Yang Xu , Qingqing Zhang , Wanting Qin , Zhiyu Yan , Shuhan Ma , Yuanyuan Chang , Kaihua Chen , Ling Li , Xiaodong Zhu","doi":"10.1016/j.imbio.2025.153114","DOIUrl":"10.1016/j.imbio.2025.153114","url":null,"abstract":"<div><h3>Background</h3><div>GINS complex subunit 1 (GINS1) is part of the tetrameric GINS complex involved in DNA replication, playing a vital role in controlling the start and continuation of DNA replication. Its role in cancer, however, is not well understood. Still, its relevance to cancer is uncertain. This study focused on exploring the role of GINS1 in different forms of cancer.</div></div><div><h3>Methods</h3><div>Using a range of publicly available databases, we conducted a comprehensive study on the oncogenic function of GINS1 in pan-cancer through analyses of differential expression, survival, enrichment, gene mutations and tumor immune cell infiltration. Additionally, the expression and effects of GINS1 in nasopharyngeal carcinoma (NPC) were analyzed through a series of in vitro experiments.</div></div><div><h3>Results</h3><div>GINS1 was found to be overexpressed in nearly all tumors, demonstrating notable diagnostic and prognostic potential. Moreover, the relationship between GINS1 and specific immune characteristics (such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability) suggests its potential role in guiding immunotherapy approaches. In vitro studies show that GINS1 notably enhances proliferation, migration, and invasion of NPC cells, with elevated expression levels correlating with a poorer prognosis.</div></div><div><h3>Conclusions</h3><div>GINS1 might serve as a prognostic and immunotherapy marker for different types of cancers, such as nasopharyngeal carcinoma.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"230 6","pages":"Article 153114"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059940","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

Attenuated S. typhimurium delivery of STAT3-siRNA and endostatin co-expression plasmids for immune and angiogenesis modulation in colorectal cancer 减毒鼠伤寒沙门氏菌递送STAT3-siRNA和内皮抑素共表达质粒用于大肠癌的免疫和血管生成调节

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-10-24 DOI: 10.1016/j.imbio.2025.153129

Ai Cui , Wenyan Fan , Tengyi Huang , Xinyi Li , Wenjing Xiong , Yongni Wang , Yu Chen

Background

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. Due to its high metastasis rate and poor prognosis, CRC is the leading cause of cancer-related deaths worldwide.

Materials and methods

Combined gene therapy is a promising treatment that can be used to alter the genes involved in cancer genesis and development. This report describes the use of a eukaryotic co-expression plasmid that encodes both STAT3 siRNAs (si-STAT3) and endostatin for the treatment of CRC homografts in C57BL/6 mice, with attenuated Salmonella typhimurium (S. typhimurium) used to facilitate efficient delivery of the plasmid.

Results

In this study, single treatment with either si-STAT3 or endostatin showed antitumor effects in the CRC homograft model, and the co-expression treatment had more significant antitumor effects. Not only did the co-expressed plasmids alter the STAT3 and endostatin expression, this treatment also down-regulated MMP2 and cyclin D1 expression and up-regulated caspase 3 expression. The levels of CD4⁺ T cells, CD8⁺ T cells, NK cells, and CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg cells) were also affected by the combined treatment. In addition, the combined therapy altered cytokine expression, enhancing antitumor immunity.

Conclusion

The combined gene therapy used in this study additively inhibited colorectal homograft tumor growth.

结直肠癌（CRC）是世界范围内男性第三大常见癌症，女性第二常见癌症。由于其高转移率和预后差，结直肠癌是全球癌症相关死亡的主要原因。材料和方法联合基因治疗是一种很有前途的治疗方法，可以用来改变参与癌症发生和发展的基因。本报告描述了一种真核共表达质粒的使用，该质粒编码STAT3 sirna （si-STAT3）和内皮抑素，用于治疗C57BL/6小鼠CRC同种移植物，并使用减毒鼠伤寒沙门氏菌（S. typhimurium）促进质粒的有效递送。结果在本研究中，si-STAT3或内皮抑素单独治疗在CRC同种移植模型中均有抗肿瘤作用，且共表达治疗的抗肿瘤作用更为显著。共表达质粒不仅改变了STAT3和内皮抑素的表达，还下调了MMP2和cyclin D1的表达，上调了caspase 3的表达。CD4+ T细胞、CD8+ T细胞、NK细胞和CD4+CD25+Foxp3+调节性T细胞（Treg细胞）水平也受到联合治疗的影响。此外，联合治疗可改变细胞因子表达，增强抗肿瘤免疫。结论联合基因治疗可抑制结直肠同种移植物肿瘤的生长。

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引用次数: 0

Corrigendum to “UMI-77 targets MCL-1 to activate mitophagy and ameliorate periodontitis in mice” [Immunobiology 230(5) (2025) 153108] “uni -77靶向MCL-1激活线粒体自噬并改善小鼠牙周炎”的更正[免疫生物学230(5)(2025)153108]。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-24 DOI: 10.1016/j.imbio.2025.153120

Dalei Sun , Shu Ouyang , Xiaoxuan Xu , Jingjing Yan , Heqian Wang , Chenkai Lan , Wubin Ouyang , Liangjun Zhong , Jun Lin

引用次数: 0

Changpu Yujin Tang mitigates tourette syndrome by enhancing mitophagy and suppressing NLRP3 inflammasome-mediated pyroptosis 长骨育金汤通过增强线粒体自噬和抑制NLRP3炎症小体介导的焦亡来减轻图雷特综合征

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-22 DOI: 10.1016/j.imbio.2025.153118

Shuang Huang , Liwei Huang , Mengxue Li , Mingyang Sun , Kexin Sun , Xing Wei , Bing Jiang , Yuezhen He , Fuchun Xue , Lv Gao , Manqi Lu , Jing Shang , Zhenggang Shi

Background

Changpu Yujin Tang (CPYJT) is an effective Chinese herbal compound for treating Tourette syndrome (TS). However, its precise molecular mechanisms remain to be fully elucidated.

Methods

105 SD rats were randomly divided into the Control (n = 15) and the TS (n = 90) groups. The TS group was induced by intraperitoneal injection of 3,3′-iminodipropionitrile. After successful modeling, the TS group was further divided into 6 subgroups (n = 15 in each group): the Model group, the Tiapride group, the CPYJT group, the Rapamycin (RAPA) group, the 3-methyladenine (3-MA) group, and the CPYJT +3-MA group, and were treated with the corresponding drugs for 4 weeks.

Results

Compared with the Control group, rats in the Model group showed increased stereotyped and motor behaviors, damage to striatal neuronal cells and mitochondrial ultrastructure, decreased PINK1/Parkin-mediated mitophagy, and activation of NLRP3 inflammasome. CPYJT reduced stereotyped and motor behaviors, attenuated neuronal cell damage, and repaired mitochondrial pathology in the TS rats. Furthermore, both CPYJT and RAPA enhanced PINK1/Parkin-mediated mitophagy, eliminated ROS accumulation, and inhibited NLRP3 inflammasome activation. Notably, CPYJT counteracted 3-MA's inhibitory effect on PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation and pyroptosis.

Conclusion

CPYJT inhibits NLRP3 inflammasome activation and reduces pyroptosis by enhancing PINK1/Parkin-mediated mitophagy and attenuating ROS accumulation, which in turn ameliorates TS.

长朴育金汤是治疗抽动秽语综合征（TS）的有效中药复方。然而，其精确的分子机制仍有待充分阐明。方法105只SD大鼠随机分为对照组（n = 15）和TS组（n = 90）。TS组采用3,3′-亚氨基二丙腈腹腔注射诱导。造模成功后，将TS组进一步分为模型组、噻必利组、CPYJT组、雷帕霉素（RAPA）组、3-甲基腺嘌呤（3-MA）组、CPYJT +3-MA组6个亚组（每组n = 15），分别给予相应药物治疗4周。结果与对照组相比，模型组大鼠的刻板行为和运动行为增加，纹状体神经元细胞和线粒体超微结构受损，PINK1/ parkin介导的线粒体自噬减少，NLRP3炎症小体活化。CPYJT减少了TS大鼠的刻板和运动行为，减轻了神经元细胞损伤，并修复了线粒体病理。此外，CPYJT和RAPA均能增强PINK1/ parkinson介导的有丝分裂，消除ROS积累，抑制NLRP3炎性体活化。值得注意的是，CPYJT抵消了3-MA对PINK1/ parkin介导的有丝分裂的抑制作用，从而抑制NLRP3炎性体的激活和热凋亡。结论cpyjt通过增强PINK1/ parkin介导的线粒体自噬和减少ROS积累，抑制NLRP3炎性小体活化，减少焦亡，从而改善TS。

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引用次数: 0

Absence of complement terminal pathway activity in C6-deficient mice prolongs survival in a mouse model of severe malarial infection 在严重疟疾感染小鼠模型中，缺乏补体末端通路活性的c6缺陷小鼠延长了生存期。

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-11-11 DOI: 10.1016/j.imbio.2025.153140

Tomoaki Kamiya , Yuki Miyasaka , Hangsoo Kim , Sosuke Fukui , Masatoshi Inoue , Masatoshi Ishigami , Yasuhiro Suzuki , Shoichi Maruyama , Tamio Ohno , Timothy R. Hughes , B. Paul Morgan , Masashi Mizuno

Background

Malaria is an important and serious parasite-induced disease associated with severe anemia and multiple organ failure (MOF) that can be lethal in humans. We explored the contribution of the terminal pathway of complement in a mouse model of malaria-induced lethal MOF following infection with Plasmodium (P.) bergei.

Methods

We compared organ damage and survival between C57BL/6 J mice deficient in the terminal pathway component C6 (C6def) and wild type C57BL/6 J mice (WT) after intraperitoneal injection of 10⁶ P. bergei-parasitized erythrocytes. We measured survival, relevant blood parameters, assessed severity of injury and complement activation in relevant organs.

Results

All WT mice died between 7 and 13 days after exposure to the parasite challenge; in contrast, C6def mice showed prolonged survival with 80 % alive at day 20, although all then died by day 26. Parasite load and anemia at day 7 were similar in C6def and WT mice. Liver and lung injuries, fibrosis and organ complement deposition assessed at day 7 post-infection were significantly milder in C6def mice compared to WT. Blood platelet count at day 7 post-infection was markedly reduced in WT but not in C6def mice; in contrast, white cell count was increased and hemoglobin levels decreased to similar degrees in WT and C6def mice post-infection. Albumin levels were reduced, significantly more in WT, while blood markers of liver injury were increased, significantly more in WT. Serum levels of complement activation product, C5a, and IL6 were increased in both groups, the latter significantly higher in WT versus C6def mice.

Conclusion

We show that complement terminal pathway activation exacerbates organ injuries and thrombocytopenia associated with P. bergei infection, contributing to rapid progression to death in the model. Inhibition of terminal pathway activation in human malarial infections using available drugs might slow progression to organ failure, extending the window of opportunity for the effective use of anti-malarial medicines.

背景：疟疾是一种重要且严重的寄生虫引起的疾病，与人类严重贫血和多器官衰竭（MOF）相关，可致人死亡。我们探索了补体终末通路在感染柏氏疟原虫后疟疾诱导的致死性MOF小鼠模型中的作用。方法：腹腔注射106P后，比较末端通路组分C6 （C6def）缺失的C57BL/6 J小鼠和野生型C57BL/6 J小鼠（WT）的器官损伤和存活情况。bergei-parasitized红细胞。我们测量了存活率，相关血液参数，评估了损伤的严重程度和相关器官的补体激活。结果：所有WT小鼠在暴露于寄生虫攻击后7 ~ 13天死亡；相比之下，C6def小鼠的存活时间较长，在第20天有80%的小鼠存活，但在第26天全部死亡。C6def和WT小鼠第7天的寄生虫载量和贫血相似。感染后第7天，C6def小鼠的肝和肺损伤、纤维化和器官补体沉积明显轻于WT。感染后第7天，WT小鼠的血小板计数明显减少，而C6def小鼠则没有；相比之下，WT和C6def小鼠感染后白细胞计数增加，血红蛋白水平下降程度相似。白蛋白水平降低，WT组明显更多，而肝损伤血液标志物升高，WT组明显更多。两组血清补体活化产物、C5a和il - 6水平升高，后者在WT组明显高于C6def小鼠。结论：我们的研究表明，补体末端通路激活加剧了与伯格氏杆菌感染相关的器官损伤和血小板减少症，在模型中促进了快速进展至死亡。使用现有药物抑制人类疟疾感染的终末通路激活可能会减缓器官衰竭的进展，从而扩大有效使用抗疟疾药物的机会之窗。

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引用次数: 0

Specific human antibodies against SARS-CoV-2 and monkeypox virus generated via a rapid construction and screening system 通过快速构建和筛选系统生成针对SARS-CoV-2和猴痘病毒的特异性人抗体

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-11-01 Epub Date: 2025-10-02 DOI: 10.1016/j.imbio.2025.153124

Guanglei Gu , Jinhai Wang , Xiaoyun Hu , Xiuling Gu , Shirui Li , Hanle Li , Min Fang

Monoclonal antibodies are playing an increasingly important role in modern medicine. Human monoclonal antibodies have become a key focus in the development of monoclonal antibody therapeutics due to their safety. We developed an integrated platform that rapidly constructs and screens human antibodies by combining recombinant antigen production, fluorescent antigen tetramers, memory B-cell sorting, single-cell gene amplification, and single-chain antibody expression for rapid screening of antibody specificity. Using peripheral blood mononuclear cells from healthy donors, we successfully generated human monoclonal antibodies targeting the N and S1 proteins of SARS-CoV-2. Furthermore, we applied the platform to produce protective human antibodies against the M1R protein of the monkeypox virus (MPXV). These results demonstrate that our system enables the rapid and efficient discovery of specific monoclonal antibodies, offering broad applicability for combating emerging infectious diseases and advancing cancer immunotherapies.

单克隆抗体在现代医学中发挥着越来越重要的作用。人单克隆抗体由于其安全性已成为单克隆抗体治疗发展的一个重点。我们开发了一个综合平台，通过重组抗原生产、荧光抗原四聚体、记忆b细胞分选、单细胞基因扩增和单链抗体表达，快速构建和筛选人抗体，快速筛选抗体特异性。利用健康供者外周血单个核细胞，成功制备了针对SARS-CoV-2 N和S1蛋白的人单克隆抗体。此外，我们利用该平台制备了猴痘病毒（MPXV） M1R蛋白的保护性人抗体。这些结果表明，我们的系统能够快速有效地发现特异性单克隆抗体，为对抗新出现的传染病和推进癌症免疫治疗提供广泛的适用性。

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