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具有强细胞侵袭性的临床菌株以及广藿香醇通过改善miR-30b/C介导的异种吞噬作用的保护效果。

Clinical Strains of With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy.

作者信息

Xu Yifei, Deng Qiuhua, Zhong Yuanzun, Jing Li, Li Haiwen, Li Jingwei, Yu Huimin, Pan Huafeng, Guo Shaoju, Cao Hongying, Huang Ping, Huang Bin

机构信息

Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Front Pharmacol. 2021 Apr 30;12:666903. doi: 10.3389/fphar.2021.666903. eCollection 2021.

DOI:10.3389/fphar.2021.666903
PMID:33995095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8120110/
Abstract

was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular and promotes its drug resistance. This study revealed that some clinical drug-resistant strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from (Blanco) Benth (Labiatae), showed reliable activity against intracellular . The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by , thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular has great implications for clinical treatment, and PA can act against invasive based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant .

摘要

被世界卫生组织列为1类致癌物。这种病原体耐药菌株的出现对全球人类健康构成严重威胁。该病原体的细胞侵袭通过介导miR-30b/c激活胃上皮细胞中的异噬作用,自噬体的出现提供了一个小生境,使细胞内的该病原体得以存活并促进其耐药性。本研究表明,一些临床耐药菌株的侵袭能力比标准菌株强得多。广藿香醇(PA)是一种从唇形科植物广藿香(Blanco)Benth中提取的三环倍半萜,对细胞内的该病原体显示出可靠的活性。其机制似乎涉及miR-30c-3p/5p和miR-30b-5p的下调,从而上调异噬相关基因表达(ULK1、ATG5、ATG12和ATG14)并增强异噬作用。PA还抑制该病原体诱导的miR-30b-5p的核转染,从而增强转录因子EB功能并增加溶酶体活性。细胞内强侵袭性该病原体的发现对临床治疗具有重要意义,PA可以基于改善miR-30b/c介导的异噬作用来对抗侵袭性该病原体。综上所述,结果表明PA有潜力作为细胞内耐药该病原体的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/8120110/9bb4f928e031/fphar-12-666903-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84c0/8120110/90099c30b1a6/fphar-12-666903-g001.jpg
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