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循环游离 DNA 种类在非酒精性脂肪性肝病中的意义。

Significance of Circulating Cell-Free DNA Species in Non-Alcoholic Fatty Liver Disease.

机构信息

Department of Physiology, Medical School of National and Kapodistrian University of Athens, 11527 Athens, Greece.

Department of Clinical Therapeutics, "Alexandra" General Hospital of Athens, Medical School of National and Kapodistrian University of Athens, 11528 Athens, Greece.

出版信息

Int J Mol Sci. 2021 Aug 17;22(16):8849. doi: 10.3390/ijms22168849.

Abstract

The pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) have not been completely elucidated, while the significance of circulating cell-free DNA (cf-DNA) species has been rarely evaluated in NAFLD. Herein, we assessed the serum levels of cf-DNA species in NAFLD patients and investigated their potential associations with patients' characteristics and severity of liver disease. Forty-nine adult patients with NAFLD of any stage were included in this cohort study. Cf-DNA was isolated from patients' sera and the levels of several distinct cf-DNA species including total cf-DNA, gene-coding cf-DNA, Alu repeat sequences, mitochondrial DNA copies and 5-methyl-2'-deoxycytidine were determined. Cirrhotic compared to non-cirrhotic patients had significantly lower serum levels of cf-DNA and RNAse P coding DNA as well as higher expression of 5-methyl-2'-deoxycytidine. After adjustment for the significant clinico-epidemiological factors, lower serum levels of cf-DNA or RNAse P were independently associated with the presence of cirrhosis. Serum levels of total and gene-coding DNA are associated with the presence of cirrhosis in NAFLD patients regardless of clinical or epidemiological parameters and may therefore be used as a screening tool for NAFLD progression.

摘要

非酒精性脂肪性肝病(NAFLD)进展中涉及的发病机制尚未完全阐明,而循环无细胞 DNA(cf-DNA)种类的意义在 NAFLD 中很少被评估。在此,我们评估了 NAFLD 患者的血清 cf-DNA 水平,并研究了它们与患者特征和肝病严重程度的潜在关联。在这项队列研究中,纳入了 49 名任何阶段的成人 NAFLD 患者。从患者的血清中分离 cf-DNA,并测定几种不同的 cf-DNA 种类的水平,包括总 cf-DNA、基因编码 cf-DNA、Alu 重复序列、线粒体 DNA 拷贝和 5-甲基-2'-脱氧胞苷。与非肝硬化患者相比,肝硬化患者的血清 cf-DNA 和 RNAse P 编码 DNA 水平显著降低,5-甲基-2'-脱氧胞苷的表达水平更高。在校正了重要的临床流行病学因素后,较低的 cf-DNA 或 RNAse P 血清水平与肝硬化的存在独立相关。无论临床或流行病学参数如何,总 DNA 和基因编码 DNA 的血清水平与 NAFLD 患者的肝硬化存在相关,因此可作为 NAFLD 进展的筛查工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b979/8396264/196b0380ab9c/ijms-22-08849-g001.jpg

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