MiR-155-chitosan polyplex as a novel therapeutic modality against Leishmania major: A feasibility study

IF 2.1 3区医学 Q2 PARASITOLOGY

Acta tropica Pub Date : 2025-05-25 DOI:10.1016/j.actatropica.2025.107674

Yasamin Rahmani , Samira Mohammadi-Yeganeh , Farshid Yeganeh , Azam Pourabbasi Ardekan , Ameneh Koochaki , Milad Taghizadeh-Anvar , Mostafa Haji Molla Hoseini

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引用次数: 0

Abstract

Background

Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Macrophages play a crucial role in the life cycle of Leishmania and host-parasite interactions. Leishmania parasites have evolved mechanisms to modulate macrophage miRNA, including miR-155, in order to evade immune responses. Modulation of miR-155 levels could potentially restore balanced immune responses while enhancing the host's ability to clear parasites.

Objective

This study aims to evaluate the antileishmanial effects of the miR-155 chitosan polyplex (miR-155 CP) in vitro.

Methods

The antileishmanial activity of miR-155 CP synthesized by the coacervation method was assessed against Leishmania major by analyzing the IL-12 and IL-10 secretion, nitric oxide (NO) and urea production, as well as cell death rate on infected RAW 264.7 cells in vitro.

Results

The polyplexes were produced with high transfection efficiency. MiR-155 was up-regulated over 20-fold in healthy macrophages and 6-fold among infected macrophages. The mean cell death index among treated infected cells (65.5 ± 4.5) increased significantly compared to the infected control group (25±5). Treatment with miR-155 CP triggered the production of IL-12 and NO among uninfected and infected macrophages.

Conclusion

Collectively, our findings suggest that induction of miR-155 expression via miR-155 CP may influence cellular mechanisms in two ways: eliminating infected macrophages and enabling uninfected ones to manage the parasite.

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mir -155-壳聚糖复合物作为一种治疗利什曼原虫的新方法：可行性研究

背景：利什曼病是一种被忽视的热带病，影响着全世界数百万人。巨噬细胞在利什曼原虫和宿主-寄生虫相互作用的生命周期中起着至关重要的作用。利什曼原虫已经进化出调节巨噬细胞miRNA的机制，包括miR-155，以逃避免疫反应。调节miR-155水平可能潜在地恢复平衡的免疫反应，同时增强宿主清除寄生虫的能力。目的：本研究旨在评价miR-155壳聚糖复合物（miR-155 CP）的体外抗利什曼原虫作用。方法：通过分析体外感染RAW 264.7细胞的IL-12和IL-10分泌、一氧化氮（NO）和尿素分泌以及细胞死亡率，评价凝聚法合成的miR-155 CP对利什曼原虫的抗利什曼原虫活性。结果：获得了转染效率高的复合物。MiR-155在健康巨噬细胞中上调20倍以上，在感染巨噬细胞中上调6倍。感染细胞的平均死亡指数（65.5±4.5）明显高于感染对照组（25±5）。miR-155 CP处理可触发未感染和感染巨噬细胞中IL-12和NO的产生。结论：总的来说，我们的研究结果表明，通过miR-155 CP诱导miR-155表达可能通过两种方式影响细胞机制：消除感染的巨噬细胞和使未感染的巨噬细胞能够控制寄生虫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta tropica 医学-寄生虫学

CiteScore

5.40

自引率

11.10%

发文量

383

审稿时长

37 days

期刊介绍： Acta Tropica, is an international journal on infectious diseases that covers public health sciences and biomedical research with particular emphasis on topics relevant to human and animal health in the tropics and the subtropics.