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光动力效应对外瓶霉孢子和 RAW264.7 细胞的体外影响。

Photodynamic effects on Fonsecaea monophora conidia and RAW264.7 in vitro.

机构信息

Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 West Yanjiang Road, Guangzhou 510120, China.

Department of Dermatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 West Yanjiang Road, Guangzhou 510120, China.

出版信息

J Photochem Photobiol B. 2017 Nov;176:112-117. doi: 10.1016/j.jphotobiol.2017.09.001. Epub 2017 Sep 18.

Abstract

Chromoblastomycosis (CBM), one of the neglected tropical diseases, is hard to cure and easy to be recurrent. Many studies suggest that macrophage is involved in the pathogenesis of chromoblastomycosis and the fungicidal effect of 5-Aminolaevulinic Acid-Based Photodynamic Therapy (ALA-PDT) against F. monophora (one of the main causative agent of chromoblastomycosis) has shown great promise. However, the fungicidal ability of ALA-PDT to F. monophora is still controversial and the molecular mechanism and immune mechanism of ALA-PDT against F. monophora remains poorly documented. In the present work, ALA (5-Aminolaevulinic Acid) was employed as photosensitizer and a LED device was served as light source to investigate photodynamic effect on F. monophora conidia under different ALA-PDT conditions in a direct way. RAW264.7 was stimulated by conidia treated with ALA-PDT to study the photodynamic effect on F. monophora conidia in an indirect way. It was observed that ALA-PDT can inactivate F. monophora conidia directly in a concentration-dependent and dose-dependent manner. RAW264.7 was activated indirectly by photodynamically treated conidia. ALA-PDT can enhance the fungicidal ability of RAW264.7 and protect it from Infection-induced apoptosis in an indirect way. ROS generated by photodynamic treated conidia is associated with mitochondrial-related apoptosis in RAW264.7.The results of this investigation demonstrated that ALA-PDT inactivate F. monophora through two way: directly killing F. monophora conidia through ROS-dependent Oxidative damage; activating RAW264.7 in an indirect way.

摘要

着色芽生菌病(CBM)是一种被忽视的热带病,难以治愈且易于复发。许多研究表明,巨噬细胞参与着色芽生菌病的发病机制,5-氨基酮戊酸基光动力疗法(ALA-PDT)对 F. monophora(引起着色芽生菌病的主要病原体之一)的杀菌作用显示出巨大的潜力。然而,ALA-PDT 对 F. monophora 的杀菌能力仍存在争议,ALA-PDT 对 F. monophora 的分子机制和免疫机制仍知之甚少。在本工作中,以 5-氨基酮戊酸(ALA)为光敏剂,以 LED 装置为光源,在不同的 ALA-PDT 条件下直接研究对 F. monophora 分生孢子的光动力效应。用 ALA-PDT 处理的分生孢子刺激 RAW264.7 细胞,间接研究对 F. monophora 分生孢子的光动力效应。结果表明,ALA-PDT 可以直接、浓度和剂量依赖性地使 F. monophora 分生孢子失活。经光动力处理的分生孢子间接激活 RAW264.7。ALA-PDT 可以增强 RAW264.7 的杀菌能力,并间接保护其免受感染诱导的细胞凋亡。光动力处理的分生孢子产生的活性氧与 RAW264.7 中线粒体相关的凋亡有关。本研究结果表明,ALA-PDT 通过两种方式使 F. monophora 失活:通过 ROS 依赖性氧化损伤直接杀死 F. monophora 分生孢子;以间接方式激活 RAW264.7。

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