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能够自我信号放大用于阿尔茨海默病早期诊断的微小RNA传感水凝胶。

miRNA sensing hydrogels capable of self-signal amplification for early diagnosis of Alzheimer's disease.

作者信息

Lim Jaewoo, Kim Sujin, Oh Seung Jae, Han Song Mi, Moon So Young, Kang Byunghoon, Seo Seung Beom, Jang Soojin, Son Seong Uk, Jung Juyeon, Kang Taejoon, Park Sun Ah, Moon Minho, Lim Eun-Kyung

机构信息

Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea; Department of Nanobiotechnology, KRIBB School of Biotechnology, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34113, South Korea.

Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon, 35365, South Korea.

出版信息

Biosens Bioelectron. 2022 Aug 1;209:114279. doi: 10.1016/j.bios.2022.114279. Epub 2022 Apr 12.

Abstract

Alzheimer's disease (AD), one of the leading senile disorders in the world, causes severe memory loss and cognitive impairment. To date, there is no clear cure for AD. However, early diagnosis and monitoring can help mitigate the effects of this disease. In this study, we reported a platform for diagnosing early-stage AD using microRNAs (miRNAs) in the blood as biomarkers. First, we selected an appropriate target miRNA (miR-574-5p) using AD model mice (4-month-old 5XFAD mice) and developed a hydrogel-based sensor that enabled high-sensitivity detection of the target miRNA. This hydrogel contained catalytic hairpin assembly (CHA) reaction-based probes, leading to fluorescence signal amplification without enzymes and temperature changes, at room temperature. This sensor exhibited high sensitivity and selectivity, as evidenced by its picomolar-level detection limit (limit of detection: 1.29 pM). Additionally, this sensor was evaluated using the plasma of AD patients and non-AD control to validate its clinical applicability. Finally, to use this sensor as a point-of-care-testing (POCT) diagnostic system, a portable fluorometer was developed and verified for feasibility of application.

摘要

阿尔茨海默病(AD)是世界上主要的老年疾病之一,会导致严重的记忆丧失和认知障碍。迄今为止,尚无明确治愈AD的方法。然而,早期诊断和监测有助于减轻该疾病的影响。在本研究中,我们报告了一个利用血液中的微小RNA(miRNA)作为生物标志物来诊断早期AD的平台。首先,我们使用AD模型小鼠(4个月大的5XFAD小鼠)选择了合适的靶标miRNA(miR-574-5p),并开发了一种基于水凝胶的传感器,能够对靶标miRNA进行高灵敏度检测。这种水凝胶包含基于催化发夹组装(CHA)反应的探针,在室温下无需酶和温度变化即可实现荧光信号放大。该传感器表现出高灵敏度和选择性,其皮摩尔级的检测限(检测限:1.29 pM)证明了这一点。此外,使用AD患者和非AD对照的血浆对该传感器进行评估,以验证其临床适用性。最后,为了将该传感器用作即时检测(POCT)诊断系统,开发了一种便携式荧光计并验证了其应用的可行性。

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