Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19

IF 6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Antioxidants Pub Date : 2024-08-28 DOI:10.3390/antiox13091047

Giorgia Ammirata, Maddalena Arigoni, Danilo Licastro, Gian Paolo Caviglia, Michela Disabato, Ghania Zubair, Cristina Bezzio, Simone Saibeni, Amedeo De Nicolò, Jessica Cusato, Alice Palermiti, Alessandra Manca, Emanuela Tolosano, Stefano Cozzini, Marcello Mancini, Fiorella Altruda, Antonio D'Avolio, Davide Giuseppe Ribaldone, Ugo Ala, Sharmila Fagoonee

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引用次数: 0

Abstract

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin D (Vit.D), and positivity to SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) and COVID-19, we investigated this issue by analyzing the molecular contents of serum extracellular vesicles (EVs) from six groups of IBD patients (n = 32), classified according to anti-SARS-CoV-2 status, 25(OH)D level, and Vit.D supplementation, by small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, small nucleolar RNAs, and protein-coding RNAs in the EVs obtained from these cohorts of IBD patients. Experimental validation evidenced a statistically significant increase in miR30d-5p, miR150-5p, Let-7f-5p, and Let-7a-5p in the anti-SARS-CoV-2-positive and low 25(OH)D and Vit.D supplemented groups with respect to the non-Vit.D supplemented group, indicating their responsiveness to Vit.D treatment. Bioinformatics analysis highlighted the regulation of these validated miRNAs by oxidative stress and inflammation, hallmarks of IBD and COVID-19. Our study reports an unprecedented panel of circulating EV-enclosed inflammation- and oxidative stress-related miRNAs, the potentiality of which, as biomarkers for Vit.D responsivity in IBD patients, needs to be explored in future studies on larger cohorts in order to allow clinicians to optimize current treatment strategies upon viral infection.

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细胞外囊封闭的氧化应激和炎症相关 microRNAs 作为维生素 D 反应性的潜在生物标志物：对患有或未患有 COVID-19 的炎症性肠病患者的试点研究

血清25-羟基维生素D（25(OH)D）水平、基因组对维生素D（Vit.D）的反应和SARS-CoV-2阳性率之间的关系仍未得到充分研究。在这项试验性研究中，我们在对炎症性肠病（IBD）和 COVID-19 患者进行随访期间，通过小 RNA-seq，分析了根据抗 SARS-CoV-2 状态、25(OH)D 水平和 Vit.D 补充情况分类的六组 IBD 患者（n = 32）血清细胞外囊泡（EVs）的分子内容，从而研究了这一问题。这项分析揭示了从这些 IBD 患者队列中获得的 EV 中不同表达的 miRNA、PIWI-RNA、转移 RNA、小核 RNA 和蛋白编码 RNA。实验验证表明，抗SARS-CoV-2阳性组、低25(OH)D组和补充Vit.D组的miR30d-5p、miR150-5p、Let-7f-5p和Let-7a-5p比未补充Vit.D组明显增加，表明它们对Vit.D治疗有反应。生物信息学分析强调了氧化应激和炎症对这些有效 miRNA 的调控作用，而氧化应激和炎症是 IBD 和 COVID-19 的特征。我们的研究报告了一组前所未有的循环EV封闭的炎症和氧化应激相关的miRNAs，它们作为IBD患者Vit.D反应性的生物标志物的潜力需要在未来更大规模的队列研究中进行探索，以便让临床医生在病毒感染时优化当前的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology

CiteScore

10.60

自引率

11.40%

发文量

2123

审稿时长

16.3 days

期刊介绍： Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.