Open Life Sciences
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2024
·Vol. 19
·期 1
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IF 1.7
Xiaokeya Yasen,Renaguli Aikebaier,Atiguli Maimaiti,Munire Mushajiang
Radiotherapy for treating breast cancer is associated with cardiac damage. This study aimed to investigate the role of the interleukin (IL)-33/soluble receptor ST2 (sST2) axis in radiation-induced cardiac injury. Expressions of IL-33 and sST2 were detected in breast cancer patients following radiotherapy, radiation-induced cardiac damaged mice model, and cardiomyocytes using quantitative real-time PCR (qRT-PCR) and immunohistochemical assay. Cardiac injury was evaluated through an ultrasound imaging system and hematoxylin & eosin staining. The transcriptional factor was assessed using dual-luciferase reporter assay and chromatin immunoprecipitation. The results indicated that IL-33 and sST2 were highly expressed in breast cancer patients, which further elevated post-6 months but reduced after 12 months of radiotherapy. Radiation induces cardiac dysfunction and elevated IL-33 and sST2 levels in a time-dependent manner. However, silencing of IL-33 decreased sST2 expression to alleviate radiation-induced cardiac dysfunction. The IL-33 could be transcriptional activated by TCF7L2 by binding to IL33 promoter sites, which mutation alleviated cardiomyocyte injury caused by radiation. Additionally, radiation treatment resulted in higher levels of TCF7L2, IL-33, and sST2 in cardiomyocytes, and TCF7L2 knockdown reduced IL-33 and sST2 expression. In conclusion, TCF7L2 transcriptional-activated IL-33 mediated sST2 to regulate radiation-induced cardiac damage, providing novel insights into radiotherapy-induced cardiac damage.
Graphical abstract
研究领域:
肿瘤学
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心脏病学
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分子生物学
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PubMed
高影响因子
TALANTA
·
2025
·
IF 6.1
Mingjiang Huang,Binbin Luo,Shengxi Wu,Miwan Shi,Yan Liu,Shenghui Shi
A D-Shaped, excessively tilted fiber grating (ExTFG) immunosensor modified with molybdenum disulfide (MoS 2 ) was developed for label-free and specific detection of growth-stimulated expressed gene 2 protein (ST2), a critical biomarker for heart failure. The D-Shaped ExTFG sensor was fabricated by side-polishing an ExTFG along its slow axis to enhance refractive index (RI) sensitivity. It was subsequently biofunctionalized with MoS 2 and anti-ST2 monoclonal antibodies (anti-ST2 MAbs) for ST2 immunoassays. The RI sensitivities of the sensor after side-polishing and MoS 2 coating were thoroughly investigated. Additionally, the immunodetection properties of the sensor were evaluated across varying concentrations of ST2 antigen solutions, as well as its specificity and clinical performance in serum samples from healthy individuals and patients. Experimental results revealed that the sensitivity of the MoS 2 -modified D-Shaped ExTFG immunosensor for ST2 reached 0.335 nm/[log(mg/mL)] over a wide linear testing range of 1 ng/mL to 1000 ng/mL, with a detection limit of 0.472 ng/mL. This represents an improvement of approximately 86 % compared to the ExTFG without D-Shaped modification and demonstrates excellent specificity for ST2 biomarkers even in complex clinical sera. The MoS 2 -modified D-Shaped ExTFG immunosensor exhibits notable advantages, including stability, practical usability, and high clinical specificity, making it a promising candidate for biomedical and other analytical applications.
研究领域:
生物医学工程
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临床检验
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PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2025
·Vol. 97
·期 6
·e70432
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IF 4.6
Qing Miao,Rui Yu,Fanyu Shi,Kaixin Li,Xinqian Du,Yinuo Gao,Yan Li,Ye Cui,Yan Chen,Jie Liu,Zhe Lv,Jing Yuan,Chris J. Corrigan,Sun Ying,Wei Wang
Respiratory syncytial virus (RSV) infection has been associated with disruption of the airway epithelial barrier, potentially increasing the risk of asthma development. However, whether and how RSV and RSV-induced IL-33 contribute to this process are still unclear. In vivo, 7-day-old C57BL/6 mice were infected perinasally with RSV, then viral replication, lung inflammation and barrier integrity were evaluated at various time points postinfection. In vitro, human epithelial cells were infected with RSV in the presence or absence of IL-33, and the expression and localization of apical junction complex proteins (AJC) were assessed by western blot analysis and immunofluorescence staining. The involvement of components of the IL-33/ST2/MyD88 axis was further verified through blockade of endogenous IL-33 signaling and pharmacological inhibition of MyD88. Exposure to RSV infection resulted in impairment of the airway epithelial barrier, as indicated by reduced expression of tight junction proteins (ZO-1, Occludin) and adherents junction protein (E-cadherin) in the lung tissues. These effects on epithelial barrier disruption were significantly attenuated in St2 -/- mice compared with wild-type controls. In vitro, the RSV-induced epithelial barrier disruption was exacerbated by topical application of exogenous IL-33, partially through activation of MyD88-mediated NF-κB signaling. Notably, knockdown of St2 by siRNA transfection or pharmacological inhibition of MyD88 partially restored the expression of E-cadherin, ZO-1 and Occludin in RSV-infected epithelial cells. RSV infection triggers robust IL-33 release from airway epithelial cells, leading to disrupted expression of AJC protein via activation of the MyD88-dependent NF-κB signaling pathway. These findings highlight the IL-33/ST2/MyD88 axis as a critical mediator of epithelial barrier dysfunction, which may represent a potential target for therapeutic intervention in RSV-mediated lung diseases.
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高影响因子
Nature Communications
·
2026
·Vol. 17
·期 1
·3635
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IF 18.1
Ping Yan,Qin Zhewen,Huang Xingxiao,Sun Qiuli,Yao Tao,Li Siqi,Tian Xin,Xia Xintong,Diao Bowen,Zhao Lin,Zhang Xinyuan,Wei Danni,Wang Long,Shao Mengle,Wu Ying,Huang Jinyu,Shan Bo
Tissue-resident mesenchymal stromal cells (MSC) instruct immune cell activation at injury sites, a key event in tissue repair. However, the full array of immunomodulatory mechanisms driving injury-responsive immune-stromal cell interactions is underexplored. Here, using an endovascular injury mouse model, we demonstrate that perivascular MSCs enhance arterial immune response by facilitating recruitment of ST2-expressing reparative macrophages in male mice. Time-resolved single-cell sequencing reveals an MSC-mediated, macrophage phenotypic switch, essential for vascular regeneration. Mechanistically, injury activates NFκB-dependent IL-33 production in MSCs, which acts as a paracrine signal that drives Osteopontin (OPN/SPP1) production in ST2+ macrophages and stimulates vascular smooth muscle cell (VSMC) proliferation and neointima formation. Local hydrogel-mediated delivery of siRNAs targeting Il33 or Spp1 effectively alleviates injury-induced neointimal hyperplasia, suggesting a potential therapeutic strategy to prevent restenosis and other vascular diseases. Our findings define an IL33-ST2-OPN axis that mediates functional crosstalk between perivascular MSCs and reparative macrophages, orchestrating immune-mediated reparative responses.
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高影响因子
BMC Pharmacology & Toxicology
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2024
·Vol. 25
·期 1
·1-12
·
IF 2.8
Tian Chunyan,Liu Qi,Zhang Xiaoyu,Li Zhuying
Background Calycosin, a flavonoid compound extracted from Astragalus membranaceus , has shown anti-asthma benefits in house dust mite-induced asthma. Recent studies have suggested that innate-type cells, including group 2 innate lymphoid cells (ILC2s) and macrophages, serve as incentives for type 2 immunity and targets for drug development in asthma. This work focuses on the effects of calycosin on the dysregulated ILC2s and macrophages in allergic asthma. Methods In vivo, the asthmatic mouse model was established with ovalbumin (OVA) sensitization and challenge, and calycosin was intraperitoneally administered at doses of 20 and 40 mg/kg. In vivo, mouse primary ILC2s were stimulated with interleukin (IL)-33 and mouse RAW264.7 macrophages were stimulated with IL-4 and IL-13 to establish the cell models. Cells were treated with calycosin at doses of 5 and 10 µM. Results In vivo, we observed significantly reduced numbers of eosinophils, neutrophils, monocyte macrophages and lymphocytes in the bronchoalveolar lavage fluid (BALF) of OVA-exposed mice with 40 mg/kg calycosin. Histopathological assessment showed that calycosin inhibited the airway inflammation and remodeling caused by OVA. Calycosin markedly decreased the up-regulated IL-4, IL-5, IL-13, IL-33, and suppression tumorigenicity 2 (ST2) induced by OVA in BALF and/or lung tissues of asthmatic mice. Calycosin repressed the augment of arginase 1 (ARG1), IL-10, chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1) levels in the lung tissues of asthmatic mice. In vivo, calycosin inhibited the IL-33-induced activation as well as the increase of IL-4, IL-5, IL-13 and ST2 in ILC2s. Calycosin also repressed the increase of ARG1, IL-10, YM1 and MRC1 induced by IL-4 and IL-13 in RAW264.7 macrophages. In addition, we found that these changes were more significant in 40 mg/kg calycosin treatment than 20 mg/kg calycosin. Conclusions Collectively, this study showed that calycosin might attenuate OVA-induced airway inflammation and remodeling in asthmatic mice via preventing ILC2 activation and macrophage M2 polarization. Our study might contribute to further study of asthmatic therapy.
研究领域:
免疫学
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药理学
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呼吸病学
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PubMed
高影响因子
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