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人类相互作用的潜在抑制剂:一种基于体外细胞外基质的模型。

Potential Inhibitors of Human- Interactions: An In Vitro Extracellular Matrix-Based Model.

作者信息

Chao-Pellicer Javier, Arberas-Jiménez Iñigo, Sifaoui Ines, Díaz-Marrero Ana R, Fernández José J, Jamerson Melissa, Piñero José E, Lorenzo-Morales Jacob

机构信息

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain.

Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, 38200 La laguna, Tenerife, Islas Canarias, Spain.

出版信息

Mar Drugs. 2025 Jul 30;23(8):306. doi: 10.3390/md23080306.

DOI:10.3390/md23080306
PMID:40863624
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12387403/
Abstract

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba . The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti- activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host-pathogen interactions critical to PAM pathogenesis.

摘要

原发性阿米巴脑膜脑炎(PAM)是一种由自由生活的变形虫引起的、影响中枢神经系统的快速进展性暴发性疾病。对细胞外基质(ECM)蛋白的黏附被认为是感染成功的关键步骤之一,可能是该疾病预防和治疗中一个值得探索的有趣靶点。在这项研究中,使用基于体外ECM的模型,评估了两种具有已证实抗活性的倍半萜对寄生虫黏附的影响,并与参考药物两性霉素B和星形孢菌素进行了比较。当以不同浓度和暴露时间处理时,月桂萜醇和(+)-扁枝杉醇均能抑制滋养体对ECM主要蛋白的黏附。这项研究不仅强化了月桂萜醇和(+)-扁枝杉醇抗感染的治疗潜力,还引入了基于ECM的黏附试验作为一种新型且有价值的工具,用于筛选破坏对PAM发病机制至关重要的宿主-病原体相互作用的候选化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/9d9119c5822f/marinedrugs-23-00306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/6ce711c8b5bd/marinedrugs-23-00306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/ad2c15749c99/marinedrugs-23-00306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/f532c38f9e8a/marinedrugs-23-00306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/9d9119c5822f/marinedrugs-23-00306-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/6ce711c8b5bd/marinedrugs-23-00306-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/ad2c15749c99/marinedrugs-23-00306-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/f532c38f9e8a/marinedrugs-23-00306-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ded7/12387403/9d9119c5822f/marinedrugs-23-00306-g004.jpg

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本文引用的文献

1
Chamigrane-Type Sesquiterpenes from as Lead Compounds against .作为针对 的先导化合物的 型倍半萜
Mar Drugs. 2023 Mar 31;21(4):224. doi: 10.3390/md21040224.
2
genus pangenome reveals new structural and functional insights into the versatility of these free-living amoebae.泛基因组揭示了这些自由生活变形虫多功能性的新结构和功能见解。
Front Microbiol. 2023 Feb 1;13:1056418. doi: 10.3389/fmicb.2022.1056418. eCollection 2022.
3
Characterization of Extracellular Vesicles Secreted by a Clinical Isolate of and Identification of Immunogenic Components within Their Protein Cargo.
一株临床分离株分泌的细胞外囊泡的表征及其蛋白质货物中免疫原性成分的鉴定。
Biology (Basel). 2022 Jun 29;11(7):983. doi: 10.3390/biology11070983.
4
Laurinterol from Laurencia johnstonii eliminates Naegleria fowleri triggering PCD by inhibition of ATPases.从柳珊瑚中提取的劳瑞醇通过抑制 ATP 酶来消除福氏耐格里阿米巴原虫引发的细胞程序性死亡。
Sci Rep. 2020 Oct 20;10(1):17731. doi: 10.1038/s41598-020-74729-y.
5
Evaluation of Indolocarbazoles from as a Novel Source of Therapeutic Agents against the Brain-Eating Amoeba .源自[具体来源未给出]的吲哚咔唑作为抗食脑变形虫治疗剂新来源的评估。
Microorganisms. 2020 May 25;8(5):789. doi: 10.3390/microorganisms8050789.
6
Fibronectin and Its Role in Human Infective Diseases.纤连蛋白及其在人类感染性疾病中的作用。
Cells. 2019 Nov 26;8(12):1516. doi: 10.3390/cells8121516.
7
Invadosome-Mediated Human Extracellular Matrix Degradation by Entamoeba histolytica.溶组织内阿米巴介导的人类细胞外基质降解。
Infect Immun. 2018 Aug 22;86(9). doi: 10.1128/IAI.00287-18. Print 2018 Sep.
8
Identification and molecular typing of Naegleria fowleri from a patient with primary amebic meningoencephalitis in China.从中国原发性阿米巴脑膜脑炎患者中鉴定和分子分型福氏耐格里阿米巴。
Int J Infect Dis. 2018 Jul;72:28-33. doi: 10.1016/j.ijid.2018.05.001. Epub 2018 May 8.
9
Expression of matrix metalloproteinases in Naegleria fowleri and their role in invasion of the central nervous system.福氏耐格里阿米巴中基质金属蛋白酶的表达及其在侵袭中枢神经系统中的作用。
Microbiology (Reading). 2017 Oct;163(10):1436-1444. doi: 10.1099/mic.0.000537. Epub 2017 Sep 28.
10
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Microbiology (Reading). 2017 Jul;163(7):940-949. doi: 10.1099/mic.0.000500. Epub 2017 Jul 21.