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聚乙二醇化的硒纳米颗粒作为治疗药物,可抑制感染 H1N1 甲型流感病毒的细胞凋亡和炎症反应。

PEG-SeNPs as therapeutic agents inhibiting apoptosis and inflammation of cells infected with H1N1 influenza A virus.

机构信息

Central Laboratory, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 318 Renmin Middle Road, Guangzhou, China.

State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

出版信息

Sci Rep. 2024 Sep 12;14(1):21318. doi: 10.1038/s41598-024-71486-0.

Abstract

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

摘要

流感的快速变异给疫苗和治疗带来了挑战,因此开发高效低毒的新型抗流感病毒药物成为当务之急。硒是人体必需的微量元素之一,具有良好的抗病毒活性。在本研究中,我们评估了聚乙二醇(PEG)修饰的灰硒纳米颗粒(PEG-SeNPs)在体外对 Madin-Darby Canine Kidney(MDCK)细胞感染甲型流感病毒(H1N1)的抗病毒活性。CCK-8 检测结果表明,PEG-SeNPs 对 H1N1 感染的 MDCK 细胞具有保护作用。此外,PEG-SeNPs 显著降低了 H1N1 的 mRNA 水平。TUNEL-DAPI 检测表明,DNA 损伤达到高水平,但经 PEG-SeNPs 处理后可有效预防。同时,JC-1、Annexin V-FITC 和细胞周期检测表明,用 PEG-SeNPs 处理可大大减少 H1N1 诱导的细胞凋亡。此外,p-ATM、p-ATR 和 P53 蛋白下调以及 AKT 蛋白上调表明,PEG-SeNPs 可通过活性氧(ROS)介导的相关信号通路抑制 H1N1 诱导的细胞凋亡。最后,细胞因子检测表明,PEG-SeNPs 可抑制感染后促炎因子的产生,包括 IL-1β、IL-5、IL-6 和 TNF-α。综上所述,PEG-SeNPs 可能因其抗病毒和抗炎活性而成为一种新型抗 H1N1 流感病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4789/11393426/d002bfdc6189/41598_2024_71486_Fig1_HTML.jpg

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