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(1)H-NMR 分析为多发性硬化症患者提供了代谢组学图谱。

(1)H-NMR analysis provides a metabolomic profile of patients with multiple sclerosis.

机构信息

Department of Public Health (E.C., L.L., L.B., S.P., J.F., G.F., G.C., M.R.M., R.M.), Clinical and Molecular Medicine, Department of Biomedical Sciences (F.M., F.D.C., L.A.), and Department of Medical Science (M.G.M.), University of Cagliari, Cagliari, Italy.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2015 Dec 24;3(1):e185. doi: 10.1212/NXI.0000000000000185. eCollection 2016 Feb.

Abstract

OBJECTIVE

To investigate the metabolomic profiles of patients with multiple sclerosis (MS) and to define the metabolic pathways potentially related to MS pathogenesis.

METHODS

Plasma samples from 73 patients with MS (therapy-free for at least 90 days) and 88 healthy controls (HC) were analyzed by (1)H-NMR spectroscopy. Data analysis was conducted with principal components analysis followed by a supervised analysis (orthogonal partial least squares discriminant analysis [OPLS-DA]). The metabolites were identified and quantified using Chenomx software, and the receiver operating characteristic (ROC) curves were calculated.

RESULTS

The model obtained with the OPLS-DA identified predictive metabolic differences between the patients with MS and HC (R2X = 0.615, R2Y = 0.619, Q2 = 0.476; p < 0.001). The differential metabolites included glucose, 5-OH-tryptophan, and tryptophan, which were lower in the MS group, and 3-OH-butyrate, acetoacetate, acetone, alanine, and choline, which were higher in the MS group. The suitability of the model was evaluated using an external set of samples. The values returned by the model were used to build the corresponding ROC curve (area under the curve of 0.98).

CONCLUSION

NMR metabolomic analysis was able to discriminate different metabolic profiles in patients with MS compared with HC. With the exception of choline, the main metabolic changes could be connected to 2 different metabolic pathways: tryptophan metabolism and energy metabolism. Metabolomics appears to represent a promising noninvasive approach for the study of MS.

摘要

目的

研究多发性硬化症(MS)患者的代谢组学特征,并确定与 MS 发病机制相关的潜在代谢途径。

方法

对 73 名 MS 患者(至少 90 天未接受治疗)和 88 名健康对照者(HC)的血浆样本进行了(1)H-NMR 波谱分析。采用主成分分析(PCA)后进行有监督分析(正交偏最小二乘判别分析[OPLS-DA])进行数据分析。使用 Chenomx 软件对代谢物进行鉴定和定量,并计算接收器操作特征(ROC)曲线。

结果

OPLS-DA 模型确定了 MS 患者与 HC 之间具有预测性的代谢差异(R2X = 0.615,R2Y = 0.619,Q2 = 0.476;p < 0.001)。差异代谢物包括 MS 组中较低的葡萄糖、5-OH-色氨酸和色氨酸,以及 MS 组中较高的 3-OH-丁酸、乙酰乙酸、丙酮、丙氨酸和胆碱。使用外部样本集评估模型的适用性。模型返回的值用于构建相应的 ROC 曲线(曲线下面积为 0.98)。

结论

NMR 代谢组学分析能够区分 MS 患者与 HC 之间的不同代谢谱。除胆碱外,主要代谢变化可能与 2 种不同的代谢途径有关:色氨酸代谢和能量代谢。代谢组学似乎代表了一种有前途的用于研究 MS 的非侵入性方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37bd/4694073/2a43a45bc751/NEURIMMINFL2015004408FF1.jpg

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