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通过分析血清外泌体 miRNA 表达评价非酒精性脂肪性肝病的严重程度。

Evaluation of the severity of nonalcoholic fatty liver disease through analysis of serum exosomal miRNA expression.

机构信息

Medical Science Research Center, Korea University College of Medicine, Seoul, South Korea.

Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.

出版信息

PLoS One. 2021 Aug 6;16(8):e0255822. doi: 10.1371/journal.pone.0255822. eCollection 2021.

Abstract

Noninvasive techniques for evaluating the severity of nonalcoholic fatty liver disease (NAFLD) have shown limited diagnostic performance. MicroRNAs (miRNAs) are useful biomarkers for diagnosing and monitoring the progression and treatment response to several diseases. Here, we evaluated whether serum exosomal miRNAs could be used for the diagnosis and prognosis of NAFLD severity. Exosomal miRNAs were isolated from the sera of 41 patients with NAFLD (diagnosed using liver biopsy) for microarray profiling. The degree of NAFLD severity was determined using inflammation, steatosis, and ballooning scores and the NAFLD activity score (NAS). Correlations between miRNA expression, clinical and biochemical parameters, and mRNA expression were analyzed. Overall, 25, 11, 13, and 14 miRNAs correlated with the inflammation score, steatosis score, ballooning score, and NAS, respectively, with 33 significant correlations observed between 27 miRNAs and six clinical variables. Eight miRNAs (let-7b-5p, miR-378h, -1184, -3613-3p, -877-5p, -602, -133b, and 509-3p) showed anticorrelated patterns with the corresponding mRNA expression. In fibrosis, 52 and 30 interactions corresponding to high miRNA-low mRNA and low miRNA-high mRNA expression, respectively, were observed. The present results therefore suggest that serum exosomal miRNAs can be used to evaluate NAFLD severity and identify potential targets for NAFLD treatment.

摘要

非酒精性脂肪性肝病(NAFLD)严重程度的无创评估技术显示出有限的诊断性能。微小 RNA(miRNA)是诊断和监测多种疾病进展和治疗反应的有用生物标志物。在这里,我们评估了血清外泌体 miRNA 是否可用于诊断和预测 NAFLD 严重程度。从 41 名 NAFLD 患者(通过肝活检诊断)的血清中分离出外泌体 miRNA,进行微阵列分析。使用炎症、脂肪变性和气球样变性评分以及 NAFLD 活动评分(NAS)来确定 NAFLD 严重程度。分析 miRNA 表达与临床和生化参数以及 mRNA 表达之间的相关性。总体而言,有 25、11、13 和 14 个 miRNA 分别与炎症评分、脂肪变性评分、气球样变性评分和 NAS 相关,在 27 个 miRNA 和 6 个临床变量之间观察到 33 个显著相关性。有 8 个 miRNA(let-7b-5p、miR-378h、-1184、-3613-3p、-877-5p、-602、-133b 和 509-3p)与相应的 mRNA 表达呈反相关模式。在纤维化中,观察到分别对应高 miRNA-低 mRNA 和低 miRNA-高 mRNA 表达的 52 和 30 个相互作用。因此,本研究结果表明,血清外泌体 miRNA 可用于评估 NAFLD 严重程度,并鉴定出 NAFLD 治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf09/8345824/5f8c76c62c00/pone.0255822.g001.jpg

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