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维生素A综合疗法治疗砷相关皮炎的生物学靶点及分子机制洞察

Insight Into Biological Targets and Molecular Mechanisms in the Treatment of Arsenic-Related Dermatitis With Vitamin A Integrated Approach.

作者信息

Qin Qiuhai, Qin Lixiu, Xie Ruitang, Peng Shuihua, Guo Chao, Yang Bin

机构信息

Department of Surgery, The People's Hospital of Gangbei District, Guigang, China.

College of Pharmacy, Guangxi Medical University, Nanning, China.

出版信息

Front Nutr. 2022 May 23;9:847320. doi: 10.3389/fnut.2022.847320. eCollection 2022.

Abstract

Exposure to arsenic (As), an inorganic poison, may lead to skin lesions, including dermatitis. Vitamin A (VA), a fat-soluble vitamin essential for mucous membrane integrity, plays a key role in skin protection. Although the beneficial actions of VA are known, the anti-As-related dermatitis effects of VA action remain unclear. Hence, in this study, we aimed to interpret and identify the core target genes and therapeutic mechanisms of VA action in the treatment of As-related dermatitis through integrated approaches of network pharmacology and molecular docking. We integrated the key VA-biological target-signaling pathway-As-related dermatitis networks for identifying core drug targets and interaction pathways associated with VA action. The network pharmacology data indicated that VA may possess potential activity for treating As-related dermatitis through the effective regulation of core target genes. An enrichment analysis in biological processes further revealed multiple immunoregulation-associated functions, including interferon-gamma production and negative regulation of T-cell activation and production of molecular mediator of immune response. An enrichment analysis in molecular pathways mainly uncovered multiple biological signaling, including natural killer cell mediated cytotoxicity, autophagy, apoptosis, necroptosis, platelet activation involved in cell fate, and immunity regulations. Molecular docking study was used to identify docked well core target proteins with VA, including Jun, tumor protein p53 (TP53), mitogen-activated protein kinase-3 (MAPK3), MAPK1, and MAPK14. In conclusion, the potential use of VA may suppress the inflammatory stress and enhance the immunity against As-related dermatitis. In the future, VA might be useful in the treatment of dermatitis associated with As through multi-targets and multi-pathways in clinical practice.

摘要

接触无机毒物砷(As)可能导致皮肤病变,包括皮炎。维生素A(VA)是一种对粘膜完整性至关重要的脂溶性维生素,在皮肤保护中起关键作用。尽管VA的有益作用已为人所知,但其对砷相关皮炎的作用仍不清楚。因此,在本研究中,我们旨在通过网络药理学和分子对接的综合方法,阐释并确定VA在治疗砷相关皮炎中的核心靶基因和治疗机制。我们整合了关键的VA-生物学靶标-信号通路-砷相关皮炎网络,以识别与VA作用相关的核心药物靶标和相互作用途径。网络药理学数据表明,VA可能通过有效调控核心靶基因而具有治疗砷相关皮炎的潜在活性。生物过程的富集分析进一步揭示了多种免疫调节相关功能,包括γ-干扰素产生以及T细胞活化的负调控和免疫反应分子介质的产生。分子途径的富集分析主要揭示了多种生物信号,包括自然杀伤细胞介导的细胞毒性、自噬、凋亡、坏死性凋亡、参与细胞命运的血小板活化和免疫调节。分子对接研究用于确定与VA对接良好的核心靶蛋白,包括Jun、肿瘤蛋白p53(TP53)、丝裂原活化蛋白激酶-3(MAPK3)、MAPK1和MAPK14。总之,VA的潜在用途可能是抑制炎症应激并增强对砷相关皮炎的免疫力。未来,VA在临床实践中可能通过多靶点和多途径用于治疗与砷相关的皮炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06ff/9171494/ad6c274b82c7/fnut-09-847320-g001.jpg

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