Discovering the Secret of Diseases by Incorporated Tear Exosomes Analysis via Rapid-Isolation System: iTEARS

Discovering the Secret of Diseases by Incorporated Tear Exosomes Analysis via Rapid-Isolation System: iTEARS
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通过快速分离系统进行泪液外泌体分析来发现疾病的秘密:iTEARS

DOI:
10.1021/acsnano.2c02531
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发表时间:
2022-07-20
期刊:
影响因子:
17.1
通讯作者:
Liu, Fei
Liu, Fei
中科院分区:
材料科学1区
文献类型:
--
作者:
Hu, Liang;Zhang, Ting;Liu, Fei

文献摘要

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泪液中的纳米级小细胞外囊泡(sEV、外泌体)使我们能够研究疾病的多重特征。然而,用于生物标志物发现和临床诊断的泪液sEV的转化实际上受到低回收率、长处理时间和小样品体积的限制。在这里,我们报告了通过纳米技术通过快速分离系统(iTEARS)进行的合并泪液外泌体分析,以发现眼部疾病和全身性疾病的秘密。我们通过基于纳米多孔膜的共振器在5分钟内从几滴泪液(类似于10 μ L)中快速分离出高产率和纯度的外泌体,用于通过蛋白质组学和转录组学分析进行定量检测和生物标志物发现。我们鉴定了904个蛋白质,其中228个蛋白质被发现,426个蛋白质从干眼症的外泌体中检测到,并证明CALMLS,KRT 6A和S100 P用于干眼症的分类。我们还研究了泪液外泌体中的484种miRNA,并显示miR-145- 5 p、miR-214- 3 p、miR-218- 5 p和miR-9- 5 p在糖尿病视网膜病变发展过程中失调。我们相信iTEARS可用于通过泪液改善分子诊断,以识别眼部疾病,全身性疾病和许多其他神经退行性疾病和癌症。
Nanoscale small extracellular vesicles (sEVs, exosomes) in tears allow us to investigate the multisignatures of diseases. However, the translations of tear sEVs for biomarker discovery and clinical diagnostics are practically limited by low recovery, long processing time, and small sample volume. Here, we report an incorporated tear-exosomes analysis via rapid-isolation system (iTEARS) via nanotechnology to discover the secrets of ocular disorders and systemic diseases. We isolate exosomes rapidly with high yield and purity from a few teardrops (similar to 10 mu L) within 5 min via nanoporous membrane-based resonators for the quantitative detection and biomarker discovery through proteomic and transcriptomic analysis. We have identified 904 proteins, among which 228 proteins are discovered, 426 proteins are detected from exosomes of dry eye disease, and demonstrate CALMLS, KRT6A, and S100P for the classification of dry eye disease. We have also investigated 484 miRNAs in tear exosomes and show miR-145-5p, miR-214-3p, miR-218-5p, and miR-9-5p are dysregulated during diabetic retinopathy development. We believe iTEARS can be used for improving molecular diagnostics via tears to identify ocular disorders, systemic diseases, and numerous other neurodegenerative diseases and cancer.