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急性缺血性脑卒中进展的代谢物生物标志物的发现

Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression.

作者信息

Liu Peifang, Li Ruiting, Antonov Anton A, Wang Lihua, Li Wei, Hua Yunfei, Guo Huimin, Wang Lijuan, Liu Peijia, Chen Lixia, Tian Yuan, Xu Fengguo, Zhang Zunjian, Zhu Yulan, Huang Yin

机构信息

Department of Neurology, The Second Affiliated Hospital, Harbin Medical University , Xuefu Road No. 246, Harbin 150001, China.

Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education , Xuefu Road No. 246, Harbin 150001, China.

出版信息

J Proteome Res. 2017 Feb 3;16(2):773-779. doi: 10.1021/acs.jproteome.6b00779. Epub 2017 Jan 25.

Abstract

Stroke remains a major public health problem worldwide; it causes severe disability and is associated with high mortality rates. However, early diagnosis of stroke is difficult, and no reliable biomarkers are currently established. In this study, mass-spectrometry-based metabolomics was utilized to characterize the metabolic features of the serum of patients with acute ischemic stroke (AIS) to identify novel sensitive biomarkers for diagnosis and progression. First, global metabolic profiling was performed on a training set of 80 human serum samples (40 cases and 40 controls). The metabolic profiling identified significant alterations in a series of 26 metabolites with related metabolic pathways involving amino acid, fatty acid, phospholipid, and choline metabolism. Subsequently, multiple algorithms were run on a test set consisting of 49 serum samples (26 cases and 23 controls) to develop different classifiers for verifying and evaluating potential biomarkers. Finally, a panel of five differential metabolites, including serine, isoleucine, betaine, PC(5:0/5:0), and LysoPE(18:2), exhibited potential to differentiate AIS samples from healthy control samples, with area under the receiver operating characteristic curve values of 0.988 and 0.971 in the training and test sets, respectively. These findings provided insights for the development of new diagnostic tests and therapeutic approaches for AIS.

摘要

中风仍是全球主要的公共卫生问题;它会导致严重残疾,并与高死亡率相关。然而,中风的早期诊断很困难,目前尚未建立可靠的生物标志物。在本研究中,基于质谱的代谢组学被用于表征急性缺血性中风(AIS)患者血清的代谢特征,以识别用于诊断和病情进展的新型敏感生物标志物。首先,对80份人类血清样本(40例病例和40例对照)的训练集进行了全局代谢谱分析。代谢谱分析确定了一系列26种代谢物的显著变化,其相关代谢途径涉及氨基酸、脂肪酸、磷脂和胆碱代谢。随后,在由49份血清样本(26例病例和23例对照)组成的测试集上运行多种算法,以开发不同的分类器来验证和评估潜在的生物标志物。最后,一组五种差异代谢物,包括丝氨酸、异亮氨酸、甜菜碱、PC(5:0/5:0)和LysoPE(18:2),具有区分AIS样本与健康对照样本的潜力,在训练集和测试集中的受试者工作特征曲线下面积值分别为0.988和0.971。这些发现为AIS新诊断测试和治疗方法的开发提供了思路。

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