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无标记定量蛋白质组学分析揭示皮肤利什曼病早期愈合的潜在生物标志物。

Label-free quantitative proteomic analysis reveals potential biomarkers for early healing in cutaneous leishmaniasis.

作者信息

Montoya Andrés, López Manuel Carlos, Vélez Ivan D, Robledo Sara M

机构信息

PECET, Facultad de Medicina, Universidad de Antioquia, Medellin, Antioquia, Colombia.

Molecular Biology Department Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina "López Neyra", Granade, Spain.

出版信息

PeerJ. 2019 Jan 11;6:e6228. doi: 10.7717/peerj.6228. eCollection 2019.

Abstract

BACKGROUND

Leishmaniasis is a parasitic disease caused by more than 20 species of the genus. The disease is globally distributed and is endemic in 97 countries and three territories in the tropical and subtropical regions. The efficacy of the current treatments is becoming increasingly low either due to incomplete treatment or resistant parasites. Failure of treatment is frequent, and therefore, the search for early biomarkers of therapeutic response in cutaneous leishmaniasis (CL) is urgently needed.

OBJECTIVE

The aim of this study was to compare the proteomic profiles in patients with CL before and after 7 days of treatment and identify early biomarkers of curative response.

METHODS

Four patients with a parasitological diagnosis of leishmaniasis with confirmation of species by PCR-RFLP were recruited. All patients had a single lesion, and a protein from the middle of the ulcer was quantified by liquid chromatography and mass spectrometry.

RESULTS

A total of 12 proteins showed differential expression in the comparative LC-electrospray ionization MS/MS (LC-ESI-MS/MS) triplicate analysis. Seven of them were up-regulated and five of them were down-regulated. Calcium binding proteins A2, A8, and A9 and hemoglobin subunits alpha-2 and delta showed high correlation with epidermis development and immune response.

CONCLUSION

We identified changes in the profiles of proteins that had a positive therapeutic response to the treatment. The proteins identified with differential expression are related to the reduction of inflammation and increased tissue repair. These proteins can be useful as biomarkers for early monitoring of therapeutic response in CL.

摘要

背景

利什曼病是由该属20多种寄生虫引起的一种寄生虫病。该病在全球范围内分布,在热带和亚热带地区的97个国家和三个领地呈地方性流行。由于治疗不彻底或寄生虫产生耐药性,目前治疗方法的疗效正变得越来越低。治疗失败很常见,因此,迫切需要寻找皮肤利什曼病(CL)治疗反应的早期生物标志物。

目的

本研究的目的是比较CL患者治疗7天前后的蛋白质组学图谱,并确定治愈反应的早期生物标志物。

方法

招募了4例经寄生虫学诊断为利什曼病且通过PCR-RFLP确认虫种的患者。所有患者均有单个病灶,通过液相色谱和质谱对溃疡中部的一种蛋白质进行定量分析。

结果

在液相色谱-电喷雾电离串联质谱(LC-ESI-MS/MS)一式三份分析中,共有12种蛋白质表现出差异表达。其中7种上调,5种下调。钙结合蛋白A2、A8和A9以及血红蛋白亚基α-2和δ与表皮发育和免疫反应高度相关。

结论

我们确定了对治疗有积极治疗反应的蛋白质图谱的变化。鉴定出的差异表达蛋白质与炎症减轻和组织修复增加有关。这些蛋白质可作为CL治疗反应早期监测的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b84/6330957/7de88be65b92/peerj-07-6228-g001.jpg

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