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通过细胞有丝分裂阻断微核细胞胞质测定法测量糖尿病和肥胖症中的染色体损伤 - 系统评价和荟萃分析。

Chromosomal damage measured by the cytokinesis block micronucleus cytome assay in diabetes and obesity - A systematic review and meta-analysis.

机构信息

University of Vienna, Research Platform Active Ageing, Department of Nutritional Sciences, Althanstraße 14, 1090 Vienna, Austria.

University of Freiburg, Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.

出版信息

Mutat Res Rev Mutat Res. 2020 Oct-Dec;786:108343. doi: 10.1016/j.mrrev.2020.108343. Epub 2020 Nov 2.

Abstract

The percentage of people affected by overweight, obesity and/or diabetes drastically increased within the last decades. This development is still ongoing, which puts a large part of our society at increased risk for diseases, such as cancer, cardiovascular diseases and cognitive impairment. Especially the development of type 2 diabetes and overweight/obesity could theoretically be prevented. The loss of DNA and genome stability is associated with the above-mentioned metabolic diseases. Insulin resistance, high blood glucose levels or increased body fat are linked to a chronically elevated inflammatory state. This amplifies oxidative stress, might lead to oxidative DNA damage, impairs the cellular proliferation process and results in mutations; all of which increase the possibility for the development of dysfunctional cells, tissue and organs. An established method to measure chromosomal damage is the cytokinesis block micronucleus (CBMN) cytome assay. The aim of this systematic review and meta-analysis is to collect and analyse the current literature of diabetic, obese and overweight patients and their link to cellular mutations measured by the CBMN assay. A clear trend towards increased genome damage in these metabolic diseases was observed. Significantly increased frequencies of chromosomal aberrations were seen in type 2 diabetic subjects (micronuclei frequency: SMD: 1.18, 95% CI: 0.76, 1.60; I = 84%). In both, type 1 and type 2 diabetics, disease progression as well as medical quality and quantity were linked to further elevated genome instability. In type 1 diabetic and overweight/obese subjects the number of studies is small and for valid and reliable results more data are needed. Besides the traditionally used material for this method, PBMCs, we extended our analysis to buccal cells in order to qualitatively compare the two cell types. Finally, we discuss knowledge as well as technical/methodical gaps of the CBMN cytome assay and its usability for clinical practice in these metabolic diseases.

摘要

在过去几十年中,超重、肥胖和/或糖尿病患者的比例大幅上升。这种发展仍在继续,这使我们社会的很大一部分人面临癌症、心血管疾病和认知障碍等疾病的风险增加。特别是 2 型糖尿病和超重/肥胖的发展在理论上是可以预防的。DNA 和基因组稳定性的丧失与上述代谢性疾病有关。胰岛素抵抗、高血糖水平或体脂肪增加与慢性炎症状态升高有关。这会加剧氧化应激,可能导致氧化 DNA 损伤,损害细胞增殖过程并导致突变;所有这些都会增加功能失调细胞、组织和器官发生的可能性。一种测量染色体损伤的既定方法是胞质分裂阻滞微核(CBMN)细胞遗传学检测。本系统评价和荟萃分析的目的是收集和分析糖尿病、肥胖和超重患者的当前文献及其与 CBMN 检测测量的细胞突变之间的联系。观察到这些代谢性疾病中基因组损伤明显增加的趋势。2 型糖尿病患者的染色体畸变频率显著增加(微核频率:SMD:1.18,95%CI:0.76,1.60;I = 84%)。1 型和 2 型糖尿病患者的疾病进展以及医疗质量和数量都与进一步升高的基因组不稳定性有关。1 型糖尿病和超重/肥胖患者的研究数量较少,为了获得有效和可靠的结果,需要更多的数据。除了传统上用于该方法的材料 PBMC 外,我们还将分析扩展到口腔细胞,以定性比较这两种细胞类型。最后,我们讨论了 CBMN 细胞遗传学检测的知识以及技术/方法差距及其在这些代谢性疾病中的临床实用性。

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