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制剂成分对疟原虫子孢子运动的调控。

Regulation of Plasmodium sporozoite motility by formulation components.

机构信息

Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.

Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.

出版信息

Malar J. 2019 May 2;18(1):155. doi: 10.1186/s12936-019-2794-y.

Abstract

BACKGROUND

The protective efficacy of the most promising malaria whole-parasite based vaccine candidates critically depends on the parasite's potential to migrate in the human host. Key components of the parasite motility machinery (e.g. adhesive proteins, actin/myosin-based motor, geometrical properties) have been identified, however the regulation of this machinery is an unknown process.

METHODS

In vitro microscopic live imaging of parasites in different formulations was performed and analysed, with the quantitative analysis software SMOOT, their motility; their adherence capacity, movement pattern and velocity during forward locomotion.

RESULTS

SMOOT enabled the detailed analysis of the regulation of the motility machinery of Plasmodium berghei in response to specific (macro)molecules in the formulation. Albumin acted as an essential supplement to induce parasite attachment and movement. Glucose, salts and other whole serum components further increased the attachment rate and regulated the velocity of the movement.

CONCLUSIONS

Based on the findings can be concluded that a complex interplay of albumin, glucose and certain salts and amino acids regulates parasite motility. Insights in parasite motility regulation by supplements in solution potentially provide a way to optimize the whole-parasite malaria vaccine formulation.

摘要

背景

最有前途的疟疾全寄生虫疫苗候选物的保护效果在很大程度上取决于寄生虫在人体宿主中的迁移潜力。寄生虫运动机制的关键组成部分(例如,粘附蛋白、肌动蛋白/肌球蛋白为基础的运动、几何性质)已经被确定,但是这个运动机制的调节是一个未知的过程。

方法

在不同配方中对寄生虫进行体外微观实时成像,并使用定量分析软件 SMOOT 对其运动情况、附着能力、向前运动时的运动模式和速度进行分析。

结果

SMOOT 使我们能够详细分析疟原虫伯氏疟原虫运动机制对配方中特定(大)分子的调节。白蛋白作为一种必需的补充物,可诱导寄生虫附着和运动。葡萄糖、盐和其他全血清成分进一步提高了附着率并调节了运动速度。

结论

根据研究结果可以得出结论,白蛋白、葡萄糖以及某些盐和氨基酸的复杂相互作用调节寄生虫的运动。对溶液中补充剂对寄生虫运动调节的深入了解,可能为优化全寄生虫疟疾疫苗配方提供了一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489a/6498664/dea3e100fded/12936_2019_2794_Fig1_HTML.jpg

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