当前位置: X-MOL 学术Clin. Epigenet. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).
Clinical Epigenetics ( IF 5.7 ) Pub Date : 2020-08-20 , DOI: 10.1186/s13148-020-00917-2
Diana Buzova 1 , Andrea Maugeri 2, 3 , Antonio Liguori 4 , Cecilia Napodano 4 , Oriana Lo Re 2 , Jude Oben 5 , Anna Alisi 6 , Antonio Gasbarrini 4 , Antonio Grieco 4 , Jan Cerveny 1 , Luca Miele 4 , Manlio Vinciguerra 2, 5
Affiliation  

Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0–33%), 24 patients with steatosis grade 2 (34–66%) and 9 patients with steatosis grade 3 (67–100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

中文翻译:

人类瘦肉代谢相关脂肪肝 (MAFLD) 的循环组蛋白特征。

虽然代谢相关脂肪肝 (MAFLD) 与肥胖有关,但它也可能发生在瘦人身上。与肥胖患者相比,瘦患者的 MAFLD 更具侵袭性,死亡风险更高。缺少诊断差异性瘦或超重 MAFLD 的特定生物标志物。细胞死亡后,组蛋白和核小体会释放到血液中。在这里,我们提出了一种新的、快速的、基于成像和表观遗传学的方法来研究瘦 MAFLD 患者脂肪变性的严重程度。共招募了 53 名经组织学确诊为 MAFLD 的非肥胖患者。20 名患者的脂肪变性为 1 级(0-33%),24 名患者为 2 级(34-66%),9 名患者为 3 级(67-100%)。使用酶联免疫吸附测定法测定循环核小体的水平,而单个组蛋白或组蛋白二聚体在血清样品中通过新的先进流式细胞术 ImageStream(X) 适应方法进行检测。在没有肥胖的情况下,循环核小体水平与 MAFLD 的相关性较差。我们在 ImageStream(X) 上成功实施了多通道流方法,以对单组蛋白染色(H2A、H2B、H3、H4、macroH2A1.1 和 macroH2A1.2)进行成像。我们在这里报告了瘦 MAFLD 患者血清中组蛋白变体 macroH2A1.1 和 macroH2A1.2 水平的显着消耗,无论是单独的还是与 H2B 复合的。总之,我们使用基于 ImageStream(X) 的快速非侵入性成像技术确定了一种新的循环组蛋白特征,能够区分瘦 MAFLD 患者脂肪变性的严重程度。
更新日期:2020-08-20
down
wechat
bug