Molecular immunology最新文献

FNDC4 modulates macrophage responses and suppresses NF-κB in sepsis-induced lung injury FNDC4在脓毒症诱导的肺损伤中调节巨噬细胞反应并抑制NF-κB

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-11 DOI: 10.1016/j.molimm.2026.03.001

Jiameng Chen , Juan Li , Yingying Huang , Yiwen Fan , Wenjie Li , Jiawei Ye , Guoxiang Liu , Bojie Jiang , Shuming Pan , Chengjin Gao

Regulation of pulmonary macrophages and their related functions is crucial for preventing further deterioration in many diseases. Fibronectin III domain-containing 4 (FNDC4) is a secreted factor with high homology to the exercise-related myokine irisin (FNDC5) and has been reported to be significantly upregulated in multiple mouse models of inflammation and under human inflammatory conditions. Here, we investigated the role and mechanisms of FNDC4 in regulating pulmonary macrophage function and the NF-κB pathway in sepsis. Plasma samples and clinical data from sepsis patients and healthy volunteers were collected to quantify FNDC4 levels and analyze their association with sepsis severity. In vivo, septic rat models with different disease severities were established to evaluate the effects of FNDC4 on lung injury. In vitro, LPS-stimulated mouse macrophages (RAW264.7) were preincubated with varying concentrations of FNDC4 to explore its functional effects and underlying mechanisms. Clinically, plasma FNDC4 levels were lower in sepsis patients than in healthy controls and were positively correlated with sepsis severity. In animal experiments, FNDC4 administration effectively alleviated sepsis-induced lung injury. In cell-based assays, FNDC4 preserved the proliferation and migration of LPS-stimulated RAW264.7 cells and reduced their apoptosis rate, while also inhibiting phosphorylation-dependent activation within the NF-κB pathway. Collectively, these findings suggest that FNDC4 may reflect sepsis severity and that exogenous FNDC4 can mitigate sepsis-related lung damage in vivo, potentially through modulation of the NF-κB signaling pathway, indicating its potential therapeutic value in sepsis.

肺巨噬细胞及其相关功能的调节对于预防许多疾病的进一步恶化至关重要。纤维连接蛋白III结构域4 （FNDC4）是一种与运动相关肌因子鸢尾素（FNDC5）高度同源的分泌因子，据报道在多种小鼠炎症模型和人类炎症条件下显著上调。本研究探讨了FNDC4在脓毒症中调节肺巨噬细胞功能和NF-κB通路中的作用及机制。收集脓毒症患者和健康志愿者的血浆样本和临床数据，量化FNDC4水平并分析其与脓毒症严重程度的关系。在体内建立不同疾病严重程度的脓毒症大鼠模型，评价FNDC4对肺损伤的影响。在体外，将lps刺激的小鼠巨噬细胞（RAW264.7）与不同浓度的FNDC4预孵育，探讨其功能作用及其机制。临床上，败血症患者血浆FNDC4水平低于健康对照组，且与败血症严重程度呈正相关。动物实验中，FNDC4可有效减轻败血症引起的肺损伤。在基于细胞的实验中，FNDC4保留了lps刺激的RAW264.7细胞的增殖和迁移，降低了它们的凋亡率，同时也抑制了NF-κB通路中磷酸化依赖的激活。综上所述，这些发现表明FNDC4可能反映脓毒症的严重程度，外源性FNDC4可能通过调节NF-κB信号通路，在体内减轻脓毒症相关的肺损伤，表明其在脓毒症中的潜在治疗价值。

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引用次数: 0

vtRNA1-1/p62 regulates macrophages autophagy in ankylosing spondylitis vtrna -1/p62调控强直性脊柱炎巨噬细胞自噬。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-06 DOI: 10.1016/j.molimm.2026.02.014

Minxin Jiang , Jianping Ni , Xueying Yu , Hui Zhao , Xiaofeng Lu , Lerong Cheng , Ziqi Li , Hanqing Wu , Zelong Pan , Lianchi Qu , Mengyao Gao , Guoqi Cai , Mengmeng Wang , Faming Pan

This research aims to investigate the role and mechanisms of the vtRNA1–1/p62 molecular axis in the regulation of autophagy in AS, with the goal of identifying novel diagnostic and therapeutic targets for AS. Clinical sample analysis revealed that the transcription levels of vtRNA1–1 and p62 decreased in the peripheral blood mononuclear cells (PBMCs) of the AS group; conversely, the levels of canonical autophagy-related genes (ATG3, ATG5) and inflammatory factors (TNF-α) significantly increased. Correlation analysis revealed that vtRNA1–1 levels were positively associated with p62 but were inversely associated with ATG3, ATG5, and TNF-α. In vitro cell experiments demonstrated that vtRNA1–1 depletion reduced p62 expression while increasing ATG3, ATG5, and LC3B levels. Computational modeling further confirmed significant interactions between vtRNA1–1 and p62. Notably, vtRNA1–1 and p62 demonstrated unique diagnostic value for AS, with their combination showing even greater diagnostic significance. This study innovatively links noncoding RNA regulatory networks with autophagy homeostasis imbalance, revealing that vtRNA1–1 may regulate macrophage autophagy through p62, thereby participating in the molecular pathogenesis of AS.

本研究旨在探讨vtRNA1-1/p62分子轴在AS自噬调控中的作用及机制，以期发现新的AS诊断和治疗靶点。临床样本分析显示，AS组外周血单个核细胞（PBMCs）中vtrna -1和p62的转录水平下降；相反，典型自噬相关基因（ATG3、ATG5）和炎症因子（TNF-α）水平显著升高。相关分析显示，vtrna -1水平与p62呈正相关，与ATG3、ATG5、TNF-α呈负相关。体外细胞实验表明，vtrna -1缺失降低了p62的表达，同时增加了ATG3、ATG5和LC3B的水平。计算模型进一步证实了vtrna -1与p62之间的显著相互作用。值得注意的是，vtRNA1-1和p62对AS的诊断具有独特的价值，它们的联合诊断意义更大。本研究创新性地将非编码RNA调控网络与自噬稳态失衡联系起来，揭示了vtrna -1可能通过p62调控巨噬细胞自噬，从而参与AS的分子发病机制。

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引用次数: 0

Mechanistic study of swertiamarin in treating ulcerative colitis by regulating YAP-mediated Wnt and Notch pathways for intestinal stem cell repair 獐牙菜黄素通过调控yap介导的Wnt和Notch通路参与肠道干细胞修复治疗溃疡性结肠炎的机制研究

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-09 DOI: 10.1016/j.molimm.2026.02.012

Jiawen Chen , Hui Peng , Jun Chen , Yi Liu , Lei Chen

Background

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease. In 2024, the American Gastroenterological Association updated its guidelines for UC patients, shifting the treatment goal from "clinical remission" to "mucosal healing" and "histological healing." This highlights the vital role of the interaction between intestinal stem cells (ISCs) and immune cells in maintaining and repairing intestinal tissue homeostasis. However, effective regulatory approaches targeting ISC-immune crosstalk are lacking in current clinical practice. The traditional Chinese medicine Qinjiao, which is widely used in clinical prescriptions for treating UC, contains many iridoid compounds, but whether they can promote tissue healing by regulating the ISC immune microenvironment remains to be clarified.

Methods

UHPLC-MS and an ISC injury organoid model were applied to identify and screen the four major iridoid compounds in Qinjiao. Then, the pharmacodynamic effects of swertiamarin (SW) on UC mice, the proliferation and differentiation of colonic ISCs, and the related status of Wnt, Notch, and Hippo-YAP signaling pathways were analyzed using RT-qPCR and other methods. Finally, the mechanism in organoids was verified using the YAP inhibitor Verteporfin.

Results

This study found that SW, a bioactive iridoid compound from Qinjiao, alleviated weight loss, mitigated colon atrophy, and reduced DAI scores in UC mice. SW also restored the proliferation and differentiation of ISCs. It mitigated immune-inflammatory responses and repaired the mucosal barrier by modulating YAP nuclear translocation to activate Wnt/β-catenin signaling and downregulate Notch signaling, enhancing ISC proliferation and differentiation.

Conclusion

This study revealed that iridoid compounds, represented by SW, are the primary active components in Qinjiao for treating UC by restoring mucosal barrier integrity through enhanced ISC proliferation and differentiation.

背景溃疡性结肠炎（UC）是一种慢性免疫介导的炎症性疾病。2024年，美国胃肠病学协会更新了UC患者的指南，将治疗目标从“临床缓解”转变为“粘膜愈合”和“组织学愈合”。这突出了肠道干细胞（ISCs）和免疫细胞之间的相互作用在维持和修复肠道组织稳态中的重要作用。然而，在目前的临床实践中，缺乏针对isc免疫串扰的有效调控方法。临床上广泛应用于UC治疗的中药沁娇含有多种环烯醚萜化合物，但其是否能通过调节ISC免疫微环境促进组织愈合尚不清楚。方法采用高效液相色谱-质谱法和ISC损伤类器官模型对秦角中4种主要环烯醚萜类化合物进行鉴定和筛选。然后，采用RT-qPCR等方法分析獐牙菜黄苷（SW）对UC小鼠的药理学作用、结肠ISCs的增殖和分化以及Wnt、Notch、hipo - yap信号通路的相关状态。最后，在类器官中使用YAP抑制剂维替波芬验证了其机制。结果本研究发现，来自秦角的生物活性环烯醚萜类化合物SW可减轻UC小鼠的体重减轻，减轻结肠萎缩，降低DAI评分。SW还能恢复ISCs的增殖和分化。它通过调节YAP核易位激活Wnt/β-catenin信号通路，下调Notch信号通路，促进ISC增殖分化，减轻免疫炎症反应，修复粘膜屏障。结论以SW为代表的环烯醚萜类化合物是秦角治疗UC的主要活性成分，其作用是通过增强ISC的增殖和分化来恢复粘膜屏障的完整性。

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引用次数: 0

Emerging molecular mechanisms of cGAS-STING activation and regulation cGAS-STING激活和调控的新分子机制

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-09 DOI: 10.1016/j.molimm.2026.02.008

Yilin Liu , Kanglong Ma , Zhengfan Jiang

The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a crucial component of the innate immune system, responsible for detecting cytosolic double-stranded DNA (dsDNA) from both pathogen invasion and host damage, thereby initiating a robust type I-interferons (IFNs) response. In this review, we summarize the complex and stringent mechanisms governing the activation and regulation of the cGAS–STING pathway. We describe the structural basis of cGAS activation by dsDNA and its catalytic synthesis of 2’3’-cGAMP, and highlight the DNA-independent activation of cGAS by manganese (Mn^2 +), which exhibits a distinct catalytic mechanism. We also discuss recent advances in the regulatory mechanisms of cGAS. The binding of 2’3’-cGAMP triggers STING translocation from the ER to the Golgi apparatus, where sulfated glycosaminoglycans (sGAGs) act as an essential second ligand to promote STING polymerization. Following this, a second translocation from the trans-Golgi network (TGN) to endosomes is required for its full activation. Conversely, supranormal concentrations of 2′3'-cGAMP induce the formation of ER-localized STING biocondensates, which restrict activation and thus prevent an excessive immune response. Dysregulation of the cGAS–STING pathway has been implicated in diverse human health conditions, including infection, autoimmune disorders, neurodegeneration, ageing, and cancer. Understanding these activation and regulatory mechanisms will inform the development of novel therapeutic strategies.

环GMP-AMP合成酶(cGAS) -干扰素基因（STING）信号通路刺激因子是先天免疫系统的重要组成部分，负责检测病原体入侵和宿主损伤的细胞质双链DNA (dsDNA)，从而启动强大的i型干扰素（ifn）应答。在这篇综述中，我们总结了控制cGAS-STING通路激活和调控的复杂而严格的机制。我们描述了dsDNA激活cGAS及其催化合成2 ' 3 ' -cGAMP的结构基础，并强调了锰（Mn2 +）对cGAS的dna非依赖性激活，其表现出独特的催化机制。我们还讨论了cGAS调控机制的最新进展。2 ' 3 ' -cGAMP的结合触发STING从内质网转移到高尔基体，在高尔基体中，硫代糖胺聚糖（sGAGs）作为促进STING聚合的重要第二配体。随后，从反式高尔基网络（TGN）到核内体的第二次易位是其完全激活所必需的。相反，2 ' 3'-cGAMP的异常浓度会诱导er定位的STING生物凝聚物的形成，从而限制激活，从而防止过度的免疫反应。cGAS-STING通路的失调与多种人类健康状况有关，包括感染、自身免疫性疾病、神经退行性疾病、衰老和癌症。了解这些激活和调节机制将为开发新的治疗策略提供信息。

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引用次数: 0

Phillyrin attenuates TGF-β1-induced pulmonary fibrosis by modulating the Nrf2/HO-1 pathway and epithelial-mesenchymal transition philyrin通过调节Nrf2/HO-1通路和上皮-间质转化，减轻TGF-β1诱导的肺纤维化

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-10 DOI: 10.1016/j.molimm.2026.03.003

Jinjin Yu , Yang Liu , Huixin Song , Lingyi Liu , Lingli Li , Yuzhi Luo , Yajing Ma , Ruisi Zhu , Xinyao Liu , Songyuan Xia , Dezhu Zhang , Jianguo Meng , Weifeng Li , Xiaofeng Niu

Background

Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in a TGF-β1-induced model of epithelial-mesenchymal transition (EMT) in A549 human alveolar epithelial cells.

Methods

The mechanisms of Phi were initially predicted using network pharmacology and molecular docking. Subsequently, A549 cells were stimulated with TGF-β1 and treated with Phi. Key assessments included cell viability, inflammatory and oxidative stress markers, EMT-related proteins (E-cadherin, α-SMA, vimentin), and fibrosis-associated molecules (collagen I, fibronectin, MMP-2). The activation of the Nrf2/HO-1 antioxidant pathway was also examined.

Results

Phi significantly attenuated TGF-β1-induced EMT and fibrotic responses in A549 cells. It not only suppressed inflammatory cytokine production and oxidative stress but also restored epithelial marker expression and reduced mesenchymal and fibrotic protein levels. Moreover, Phi upregulated the Nrf2/HO-1 signaling pathway, enhancing cellular antioxidant capacity.

Conclusion

These findings suggest that Phi possesses potent anti-inflammatory, antioxidant, and anti-fibrotic properties, effectively inhibiting TGF-β1-driven EMT in alveolar epithelial cells. Phi may represent a promising therapeutic candidate for treating idiopathic pulmonary fibrosis and other fibrotic lung diseases.

连翘苷（phillyrin, Phi）是一种从连翘属植物中提取的天然木脂素苷，具有抗炎和抗氧化活性。在本研究中，我们在TGF-β1诱导的A549人肺泡上皮细胞上皮-间质转化（EMT）模型中研究了其治疗潜力。方法利用网络药理学和分子对接技术对Phi的作用机制进行初步预测。随后，用TGF-β1刺激A549细胞，并用Phi处理。关键评估包括细胞活力、炎症和氧化应激标志物、emt相关蛋白（E-cadherin、α-SMA、vimentin）和纤维化相关分子（胶原蛋白I、纤维连接蛋白、MMP-2）。研究了Nrf2/HO-1抗氧化途径的激活情况。结果sphi能明显减弱TGF-β1诱导的A549细胞EMT和纤维化反应。它不仅能抑制炎症细胞因子的产生和氧化应激，还能恢复上皮标志物的表达，降低间充质和纤维化蛋白的水平。此外，Phi上调Nrf2/HO-1信号通路，增强细胞抗氧化能力。结论Phi具有较强的抗炎、抗氧化和抗纤维化作用，可有效抑制TGF-β1驱动的肺泡上皮细胞EMT。Phi可能是治疗特发性肺纤维化和其他纤维化肺部疾病的有希望的治疗候选药物。

{"title":"Phillyrin attenuates TGF-β1-induced pulmonary fibrosis by modulating the Nrf2/HO-1 pathway and epithelial-mesenchymal transition","authors":"Jinjin Yu , Yang Liu , Huixin Song , Lingyi Liu , Lingli Li , Yuzhi Luo , Yajing Ma , Ruisi Zhu , Xinyao Liu , Songyuan Xia , Dezhu Zhang , Jianguo Meng , Weifeng Li , Xiaofeng Niu","doi":"10.1016/j.molimm.2026.03.003","DOIUrl":"10.1016/j.molimm.2026.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Phillyrin (Phi), a natural lignan glycoside derived from Fructus Forsythiae, has been reported to exhibit anti-inflammatory and antioxidant activities. In this study, we investigated its therapeutic potential in a TGF-β1-induced model of epithelial-mesenchymal transition (EMT) in A549 human alveolar epithelial cells.</div></div><div><h3>Methods</h3><div>The mechanisms of Phi were initially predicted using network pharmacology and molecular docking. Subsequently, A549 cells were stimulated with TGF-β1 and treated with Phi. Key assessments included cell viability, inflammatory and oxidative stress markers, EMT-related proteins (E-cadherin, α-SMA, vimentin), and fibrosis-associated molecules (collagen I, fibronectin, MMP-2). The activation of the Nrf2/HO-1 antioxidant pathway was also examined.</div></div><div><h3>Results</h3><div>Phi significantly attenuated TGF-β1-induced EMT and fibrotic responses in A549 cells. It not only suppressed inflammatory cytokine production and oxidative stress but also restored epithelial marker expression and reduced mesenchymal and fibrotic protein levels. Moreover, Phi upregulated the Nrf2/HO-1 signaling pathway, enhancing cellular antioxidant capacity.</div></div><div><h3>Conclusion</h3><div>These findings suggest that Phi possesses potent anti-inflammatory, antioxidant, and anti-fibrotic properties, effectively inhibiting TGF-β1-driven EMT in alveolar epithelial cells. Phi may represent a promising therapeutic candidate for treating idiopathic pulmonary fibrosis and other fibrotic lung diseases.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"193 ","pages":"Pages 39-49"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

m⁶A-modified circMELK regulates nasopharyngeal carcinoma progression via a YTHDF1/circMELK-miR-4775-HMGA2 feedback loop a修饰的circMELK通过YTHDF1/circMELK- mir -4775- hmga2反馈回路调控鼻咽癌进展

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-05-01 Epub Date: 2026-03-10 DOI: 10.1016/j.molimm.2026.03.002

Qiang Yi , Kui Zhong , Zheng Chen , Xinting Ouyang , Weijian Zhu , Leifeng Liang , Jinghua Zhong

Background

Circular RNAs (circRNAs) are emerging regulators in tumor biology. However, their roles in nasopharyngeal carcinoma (NPC) remain poorly defined.

Methods

By analyzing GSE190271, we identified hsa_circ_0138742 (circMELK) as significantly upregulated in NPC. Functional assays in vitro and in vivo were performed to explore its biological role. Mechanistic studies included RIP, ChIP, RNA pull-down, dual-luciferase assays, and rescue experiments.

Results

circMELK was markedly elevated in NPC tissues and cells. Silencing circMELK inhibited NPC cell proliferation, migration, and invasion, while overexpression enhanced these malignant traits. Mechanistically, YTHDF1-mediated m6A modification serves as a key determinant for the cytoplasmic export of circMELK. There, circMELK acts as a ceRNA for miR-4775, relieving suppression of HMGA2. Elevated HMGA2 upregulates YTHDF1 by transcriptional activation, forming a YTHDF1/circMELK-miR-4775-HMGA2 positive feedback loop that drives epithelial–mesenchymal transition (EMT) and promotes metastasis.

Conclusion

circMELK promotes NPC progression via a novel m6A-dependent ceRNA regulatory loop. Targeting this axis may offer new therapeutic opportunities.

环状rna （circRNAs）是肿瘤生物学中新兴的调控因子。然而，它们在鼻咽癌（NPC）中的作用仍然不明确。方法通过分析GSE190271，我们发现hsa_circ_0138742 （circMELK）在NPC中显著上调。体外和体内功能试验探讨其生物学作用。机制研究包括RIP、ChIP、RNA下拉、双荧光素酶测定和救援实验。结果circmelk在鼻咽癌组织和细胞中显著升高。沉默circMELK抑制鼻咽癌细胞的增殖、迁移和侵袭，而过表达则增强了这些恶性性状。从机制上讲，ythdf1介导的m6A修饰是circMELK胞质输出的关键决定因素。在那里，circMELK作为miR-4775的ceRNA，缓解HMGA2的抑制。HMGA2升高通过转录激活上调YTHDF1，形成YTHDF1/circMELK-miR-4775-HMGA2正反馈回路，驱动上皮-间质转化（EMT）并促进转移。circmelk通过一个新的依赖m6a的ceRNA调控环促进NPC进展。靶向这一轴可能提供新的治疗机会。

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引用次数: 0

CYR61 promotes obesity-induced kidney injury by activating endoplasmic reticulum stress. CYR61通过激活内质网应激促进肥胖引起的肾损伤。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-03-18 DOI: 10.1016/j.molimm.2026.03.005

Bing Li, Hailin Lv, Kunjing Gong, Yanxia Gao, Junhui Zhen, Zhao Hu

The objective was to assess the influence of cellular communication network factor 1 (CYR61) in obesity-induced kidney damage, as well as its potential mechanisms. An obesity-induced kidney damage was established in rats using a high-fat diet (HFD), and human proximal tubule epithelial (HK-2) cells were treated with palmitic acid (PA) for an in vitro model. Biochemical analysis was performed using test kits. The influence of CYR61 on kidney damage were evaluated by HE staining, periodic acid-Schiff staining, Masson's trichrome staining and western blot. The effect of CYR61 on cell apoptosis in vitro was assessed employing flow cytometry. The influence of CYR61 on lipid accumulation in vitro was assessed by Oil red O staining. Besides, the protein and mRNA expression levels were determined via western blot, immunohistochemistry, immunofluorescence and qRT-PCR. CYR61 was upregulated in rats with HFD-induced kidney injury and PA-treated HK-2 cells. CYR61 knockdown ameliorated metabolic parameters, kidney injury, oxidative stress, apoptosis, and inflammation, while suppressing endoplasmic reticulum (ER) stress in rats with HFD-induced kidney damage. CYR61 knockdown inhibited apoptosis, inflammation, oxidative stress, lipid accumulation and ER stress in the PA-treated HK-2 cells; however, tunicamycin reversed these inhibitory effects. These findings confirmed that CYR61 knockdown could ameliorated oxidative stress and inflammation in PA-treated HK-2 cells and HFD-induced renal damage in rats by suppressing ER stress.

目的是评估细胞通信网络因子1 （CYR61）在肥胖引起的肾损伤中的影响及其潜在机制。采用高脂饮食（HFD）建立了肥胖诱导的大鼠肾损伤模型，并用棕榈酸（PA）处理人近端小管上皮（HK-2）细胞建立了体外模型。使用检测试剂盒进行生化分析。采用HE染色、周期性酸-希夫染色、Masson三色染色和western blot评价CYR61对大鼠肾损伤的影响。采用流式细胞术观察CYR61对体外细胞凋亡的影响。油红O染色评价CYR61对体外脂质积累的影响。western blot、免疫组织化学、免疫荧光和qRT-PCR检测各组蛋白和mRNA的表达水平。在hfd诱导的肾损伤大鼠和pa处理的HK-2细胞中，CYR61表达上调。CYR61敲低可改善hfd诱导的肾损伤大鼠的代谢参数、肾损伤、氧化应激、细胞凋亡和炎症，同时抑制内质网（ER）应激。CYR61敲低可抑制pa处理的HK-2细胞的凋亡、炎症、氧化应激、脂质积累和内质网应激；然而，tunicamycin逆转了这些抑制作用。这些研究结果证实，CYR61敲低可以通过抑制内质网应激来改善pa处理的HK-2细胞的氧化应激和炎症以及hfd诱导的大鼠肾损伤。

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引用次数: 0

Mechanistic understanding of the protective effects of baicalein against the inflammatory response induced by Toxoplasma gondii in Ana-1 macrophages 黄芩素对刚地弓形虫诱导的Ana-1巨噬细胞炎症反应保护作用的机制研究。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-03-01 Epub Date: 2026-02-09 DOI: 10.1016/j.molimm.2026.01.012

XiaoJuan Wang, ZhengQing Yu, WeiYu Qi, YuChen Jiang, PingLong Yang, JiuSu Tu, YunNan Fang, Pan Zhou, Li Zhang

Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. However, the precise mechanisms underlying the anti-inflammatory effects of baicalein in Toxoplasma gondii infection-induced inflammation remain unclear. This study aims to systematically investigate the regulatory effects of baicalein on inflammation associated with T. gondii infection and its molecular mechanisms. The results indicate that baicalein significantly inhibits T. gondii proliferation, the production of inflammatory mediators and reduces the expression levels of pro-inflammatory cytokines. Further experiments revealed that baicalein effectively blocks the excessive activation of the cGAS-STING and NOD-like receptor signaling pathways in T. gondii-stimulated Ana-1 cells, thereby inhibiting the amplification of inflammatory signals. Additionally, baicalein enhances the expression of autophagy-related proteins, promoting autophagy and alleviating oxidative stress-induced cellular damage and inflammation. In conclusion, this study demonstrates that baicalein exerts its anti-inflammatory effects by activating autophagy and inhibiting the excessive activation of cGAS-STING and NOD-like receptor signaling pathways, effectively suppressing T. gondii infection-induced macrophage inflammation. These findings provide new theoretical insights into the potential therapeutic application of baicalein in infectious diseases.

黄芩素是一种从黄芩科植物黄芩中提取的活性类黄酮化合物，具有抗氧化、抗炎和抗菌作用。然而，黄芩素在刚地弓形虫感染诱导炎症中的抗炎作用的确切机制尚不清楚。本研究旨在系统探讨黄芩苷对弓形虫感染相关炎症的调控作用及其分子机制。结果表明，黄芩苷能显著抑制弓形虫的增殖、炎症介质的产生，降低促炎细胞因子的表达水平。进一步实验发现，黄芩素可有效阻断弓形虫刺激的Ana-1细胞中cGAS-STING和nod样受体信号通路的过度激活，从而抑制炎症信号的放大。此外，黄芩素增强自噬相关蛋白的表达，促进自噬，减轻氧化应激诱导的细胞损伤和炎症。综上所述，本研究表明黄芩苷通过激活自噬，抑制cGAS-STING和nod样受体信号通路的过度激活来发挥其抗炎作用，有效抑制弓形虫感染诱导的巨噬细胞炎症。这些发现为黄芩苷在感染性疾病的潜在治疗应用提供了新的理论见解。

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引用次数: 0

Skin sensitisation to gluten in the absence and presence of atopic dermatitis drives changes in skin and systemic T cell phenotype composition in a rat model of food allergy 在食物过敏大鼠模型中，在不存在特应性皮炎的情况下，皮肤对麸质的致敏驱动皮肤和全身T细胞表型组成的变化。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-03-01 Epub Date: 2026-02-09 DOI: 10.1016/j.molimm.2026.02.001

Jeppe Madura Larsen , Sara Benazzouz , Viktor Karl Wilhelm Törnblom , Martin Iain Bahl , Katrine Lindholm Bøgh

Atopic dermatitis is associated with higher risk for developing immune-related comorbidities, including other atopic diseases like food allergy as well as certain infections, autoimmune diseases, and cancers. It remains largely unknown whether this increased risk of comorbidities is attributable to underlying AD-induced changes in non-skin immune composition and function beyond the exacerbation of allergic immune responses. Here Brown Norway rats were sensitised to hydrolysed gluten though the skin in the absence or presence of AD-like skin inflammation induced by topical application of MC903. T cell phenotype composition was analysed in skin, blood, and gut tissues by flow cytometry. M1/M2 differentiation and cytokine production by intraperitoneal-derived macrophages stimulated with bacteria, inflammatory cytokines, or food allergens were analysed using flow cytometry and ELISA. Gut microbiota composition was analysed by partial 16S rRNA gene sequencing. Sensitisation in both the absence and presence of induced AD-like skin inflammation was found to predominantly affect T cell phenotype composition in skin and blood immune compartments. This systemic effect of AD had a minor effect on M1/M2 differentiation but did not affect cytokine production by intraperitoneal-derived macrophages. These findings highlight some systemic effects of skin sensitisation and AD that potentially could affect non-skin immune responses.

特应性皮炎与发生免疫相关合并症的风险较高有关，包括其他特应性疾病，如食物过敏，以及某些感染，自身免疫性疾病和癌症。目前尚不清楚这种合并症风险的增加是否归因于潜在的ad诱导的非皮肤免疫成分和功能的变化，而不是过敏性免疫反应的加剧。褐挪威大鼠在局部应用MC903引起ad样皮肤炎症的情况下，通过皮肤对水解谷蛋白敏感。用流式细胞术分析皮肤、血液和肠道组织中的T细胞表型组成。采用流式细胞术和ELISA分析腹腔源性巨噬细胞受细菌、炎症细胞因子或食物过敏原刺激后M1/M2分化和细胞因子产生情况。采用部分16S rRNA基因测序法分析肠道菌群组成。在没有和存在诱导ad样皮肤炎症的情况下，发现致敏主要影响皮肤和血液免疫室中的T细胞表型组成。AD的这种全身效应对M1/M2分化有轻微影响，但不影响腹腔源性巨噬细胞产生的细胞因子。这些发现强调了皮肤致敏和AD的一些全身效应，这些效应可能会影响非皮肤免疫反应。

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引用次数: 0

Luteolin alleviates ox-LDL-induced endothelial cell inflammation, apoptosis and ferroptosis by inhibiting the NAT10/ALOX12 pathway 木犀草素通过抑制NAT10/ALOX12通路减轻ox- ldl诱导的内皮细胞炎症、凋亡和铁下垂

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2026-03-01 Epub Date: 2026-02-02 DOI: 10.1016/j.molimm.2026.01.011

Biao Yang , Hui Zhang , Shi-jie Fang , Yuan-zhi Liu , Shuang-yue Zhang

Background

Luteolin has been shown to have inhibitory effects on many human diseases, including atherosclerosis (AS). However, the specific role and underlying molecular mechanisms of luteolin in the progression of AS need to be further elucidated.

Methods

Oxidized-low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) was used to construct AS models in vitro. Cell proliferation, inflammation, apoptosis and angiogenesis were examined by CCK8 assay, EdU assay, ELISA, flow cytometry, and tube formation assay. The mRNA and protein levels of arachidonate 12-lipoxygenase (ALOX12) and N-acetyltransferase 10 (NAT10) were tested by qRT-PCR and western blot. The regulation of NAT10 on ALOX12 was confirmed by ac4C-RIP assay, RIP assay and dual-luciferase reporter assay.

Results

Luteolin promoted cell proliferation and angiogenesis, while inhibited ox-LDL-induced HUVECs inflammation, apoptosis and ferroptosis. Luteolin targeted ALOX12 to reduce its expression. ALOX12 overexpression reversed the inhibitory effect of luteolin on ox-LDL-induced HUVECs injury. NAT10 promoted the ac4C modification of ALOX12 to increase its expression. NAT10 knockdown alleviated ox-LDL-induced HUVECs injury by downregulating ALOX12, and the protective effect of luteolin against ox-LDL-induced HUVECs injury could also be reversed by NAT10 overexpression.

Conclusion

Luteolin may inhibit ox-LDL-induced endothelial cell injury by suppressing NAT10-mediated the ac4C modification of ALOX12, thereby alleviating the progression of AS.

木犀草素已被证明对许多人类疾病有抑制作用，包括动脉粥样硬化（AS）。然而，木犀草素在AS进展中的具体作用及其分子机制有待进一步阐明。方法采用氧化低密度脂蛋白（ox-LDL）诱导的人脐静脉内皮细胞（HUVECs）体外构建AS模型。CCK8法、EdU法、ELISA法、流式细胞术、成管法检测细胞增殖、炎症、凋亡和血管生成。采用qRT-PCR和western blot检测花生四烯酸12-脂氧合酶（ALOX12）和n -乙酰转移酶10 (NAT10) mRNA和蛋白水平。ac4C-RIP实验、RIP实验和双荧光素酶报告基因实验证实了NAT10对ALOX12的调控作用。结果芦竹素促进HUVECs细胞增殖和血管生成，抑制ox- ldl诱导的HUVECs炎症、凋亡和铁下垂。木犀草素靶向ALOX12降低其表达。ALOX12过表达逆转了木犀草素对ox- ldl诱导的HUVECs损伤的抑制作用。NAT10促进ALOX12的ac4C修饰，使其表达增加。NAT10敲低可通过下调ALOX12减轻ox- ldl诱导的HUVECs损伤，木犀草素对ox- ldl诱导的HUVECs损伤的保护作用也可被NAT10过表达逆转。结论木犀草素可能通过抑制nat10介导的ALOX12的ac4C修饰来抑制ox- ldl诱导的内皮细胞损伤，从而缓解AS的进展。

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