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源自血浆和唾液外泌体微小RNA的儿童哮喘生物标志物

Childhood Asthma Biomarkers Derived from Plasma and Saliva Exosomal miRNAs.

作者信息

Khalyfa Abdelnaby, Verma Mohit, Alexander Meghan M, Qiao Zhuanhong, Rood Tammy, Kapoor Ragini, Joshi Trupti, Gozal David, Francisco Benjamin D

机构信息

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.

Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, WV 25703, USA.

出版信息

Int J Mol Sci. 2025 Jul 22;26(15):7043. doi: 10.3390/ijms26157043.

Abstract

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9-18 years with asthma, split into two groups based on their lung function. Ten had normal lung function (NLF; FEV1/FVC > 0.84, FEF75% > 69% predicted), while ten had severe airflow obstruction (SAO; FEV1/FVC < 0.70, FEF75 < 50% predicted). Saliva and blood samples were collected. Exosomes were isolated, quantified, and analyzed via small RNA sequencing to identify differentially expressed (DE) miRNA and lncRNA profiles. Bioinformatic tools were then used to explore potential miRNA biomarkers linked to asthma severity. SAO subjects were more likely to exhibit allergen sensitization, higher IgE levels, and more eosinophils. We identified 27 DE miRNAs in plasma and 40 DE miRNAs in saliva. Additionally, five key miRNAs were identified in both saliva and plasma which underline important pathways such as neurotrophins, T-cell receptor, and B-cell receptor signaling. We further outlined key features and functions of miRNAs and long non-coding RNAS (lncRNAs) and their interactions in children with asthma. This study identified DE miRNAs and lncRNAs in children with SAO when compared to those with NLF. Exosomal miRNAs show strong potential as non-invasive biomarkers for personalized asthma diagnosis, treatment, and monitoring. These RNA markers may also aid in tracking disease progression and response to therapy, thereby supporting the need for future studies aimed at applications in precision medicine.

摘要

哮喘是儿童中最常见的慢性呼吸道疾病,涉及气道炎症、高反应性以及频繁发作,这些会使气流和炎症恶化。外泌体是携带微小RNA(miRNA)的细胞外囊泡,在细胞通讯以及其他类型的通讯中发挥关键作用,并且是哮喘严重程度的有前景的标志物。本研究比较了哮喘男孩中外泌体miRNA和长链非编码RNA(lncRNA)谱,重点关注肺功能正常者与严重气流阻塞者之间的差异。本研究纳入了20名9至18岁患有哮喘的男孩,根据他们的肺功能分为两组。10名肺功能正常(NLF;FEV1/FVC > 0.84,FEF75% > 预测值的69%),而10名有严重气流阻塞(SAO;FEV1/FVC < 0.70,FEF75 < 预测值的50%)。收集了唾液和血液样本。分离、定量外泌体,并通过小RNA测序进行分析,以鉴定差异表达(DE)的miRNA和lncRNA谱。然后使用生物信息学工具探索与哮喘严重程度相关的潜在miRNA生物标志物。SAO受试者更有可能表现出过敏原致敏、更高的IgE水平和更多的嗜酸性粒细胞。我们在血浆中鉴定出27种DE miRNA,在唾液中鉴定出40种DE miRNA。此外,在唾液和血浆中均鉴定出5种关键miRNA,它们突显了神经营养因子、T细胞受体和B细胞受体信号传导等重要途径。我们进一步概述了miRNA和长链非编码RNA(lncRNA)在哮喘儿童中的关键特征和功能及其相互作用。与NLF儿童相比,本研究在SAO儿童中鉴定出了DE miRNA和lncRNA。外泌体miRNA作为个性化哮喘诊断、治疗和监测的非侵入性生物标志物具有强大潜力。这些RNA标志物也可能有助于追踪疾病进展和对治疗的反应,从而支持未来旨在精准医学应用的研究需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f3e/12345866/5ef9e3f0a263/ijms-26-07043-g001.jpg

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