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BST-1 作为一种参与精神分裂症中性粒细胞浸润的血清蛋白生物标志物。

BST-1 as a serum protein biomarker involved in neutrophil infiltration in schizophrenia.

机构信息

Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

出版信息

World J Biol Psychiatry. 2022 Sep;23(7):537-547. doi: 10.1080/15622975.2021.2014151. Epub 2021 Dec 16.

Abstract

OBJECTIVES

Schizophrenia is a serious mental illness. The serum protein biomarkers of schizophrenia were explored using isobaric tags for relative and absolute quantitation (iTRAQ) technology. The underlying function of the identified protein biomarker was also investigated.

METHODS

We first collected serum samples from 12 schizophrenia patients and 12 healthy control (HC) subjects, followed by global screening with iTRAQ and tandem mass spectrometry (LC-MS/MS). In total, 691 serum proteins were detected and eight proteins, including ZYX, OSCAR, TPM4, SDPR, BST1, ARGHDB, ITIH5 and SH3BGRL3, were selected for further specific validation with enzyme-linked immunosorbent assay (ELISA) on the serum samples from 52 schizophrenia patients and 50 HC subjects.

RESULTS

Schizophrenia patients had significantly lower serum level of BST1 and higher ITIH5 level than the HC subjects did. Using the levels of BST1, ITIH5 and OSCAR combined with machine learning algorithm, we developed a prediction model of schizophrenia with an auROC value 0.78. Moreover, cell assay confirmed that BST1 significantly repressed neutrophil infiltration through endothelial layer, highlighted the anti-inflammation nature of BST1.

CONCLUSIONS

Four novel protein markers (BST1, ITIH5, SDPR, and OSCAR) of schizophrenia were identified, and BST-1 could serve as a serum protein biomarker involved in neutrophil infiltration in schizophrenia.

摘要

目的

精神分裂症是一种严重的精神疾病。本研究采用同位素相对和绝对定量技术(iTRAQ)探索精神分裂症的血清蛋白生物标志物,并对鉴定出的蛋白生物标志物的潜在功能进行研究。

方法

首先收集 12 例精神分裂症患者和 12 例健康对照(HC)的血清样本,然后用 iTRAQ 和串联质谱(LC-MS/MS)进行全局筛选。共检测到 691 种血清蛋白,其中 8 种蛋白(ZYX、OSCAR、TPM4、SDPR、BST1、ARGHDB、ITIH5 和 SH3BGRL3)被进一步用酶联免疫吸附试验(ELISA)在 52 例精神分裂症患者和 50 例 HC 患者的血清样本中进行特异性验证。

结果

与 HC 组相比,精神分裂症患者的血清 BST1 水平显著降低,ITIH5 水平显著升高。使用 BST1、ITIH5 和 OSCAR 水平以及机器学习算法,我们开发了一个精神分裂症的预测模型,其 auROC 值为 0.78。此外,细胞实验证实 BST1 可显著抑制中性粒细胞穿过血管内皮层的浸润,突出了 BST1 的抗炎特性。

结论

本研究鉴定了 4 种精神分裂症的新型蛋白标志物(BST1、ITIH5、SDPR 和 OSCAR),BST-1 可作为参与精神分裂症中性粒细胞浸润的血清蛋白生物标志物。

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