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维甲酸X受体拮抗剂可降低体外培养的鼠鞭虫的活力。

An antagonist of the retinoid X receptor reduces the viability of Trichuris muris in vitro.

作者信息

Hurst Rebecca J M, Hopwood Thomas, Gallagher Amanda L, Partridge Frederick A, Burgis Timothy, Sattelle David B, Else Kathryn J

机构信息

Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.

出版信息

BMC Infect Dis. 2014 Sep 27;14:520. doi: 10.1186/1471-2334-14-520.

Abstract

BACKGROUND

Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment relies mainly on general anthelmintics such as mebendazole but resistance to these drugs is increasingly problematic. Therefore, new treatments are urgently required.

METHODS

The prospect of using the retinoid X receptor (RXR) antagonist HX531 as a novel anthelmintic was investigated by carrying out multiple viability assays with the mouse whipworm Trichuris muris.

RESULTS

HX531 reduced both the motility and viability of T. muris at its L3, L4 and adult stages. Further, bioinformatic analyses show that the T. muris genome possesses an RXR-like receptor, a possible target for HX531.

CONCLUSIONS

The study suggested that Trichuris-specific RXR antagonists may be a source of much-needed novel anthelmintic candidates for the treatment of trichuriasis. The identification of an RXR-like sequence in the T. muris genome also paves the way for further research based on this new anthelmintic lead compound.

摘要

背景

鞭虫病是由人体鞭虫(毛首鞭形线虫)引起的一种寄生虫病。它影响着全球数百万人,尤其是在热带地区。这种线虫寄生虫会钻入结肠上皮,导致炎症和发病,在儿童中尤为明显。目前的治疗主要依赖于如甲苯达唑等常规驱虫药,但对这些药物的耐药性问题日益严重。因此,迫切需要新的治疗方法。

方法

通过对小鼠鞭虫(鼠鞭虫)进行多种活力测定,研究了视黄酸X受体(RXR)拮抗剂HX531作为新型驱虫药的前景。

结果

HX531降低了鼠鞭虫L3、L4和成虫阶段的活力和生存能力。此外,生物信息学分析表明,鼠鞭虫基因组拥有一种类似RXR的受体,这可能是HX531的一个靶点。

结论

该研究表明,针对鞭虫的RXR拮抗剂可能是治疗鞭虫病急需的新型驱虫候选药物的来源。在鼠鞭虫基因组中鉴定出类似RXR的序列也为基于这种新的驱虫先导化合物的进一步研究铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4d4/4261559/3fbdbe86ac32/12879_2014_Article_3841_Fig1_HTML.jpg

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