Biology subjects

Made, A.

Publications and source records attributed to Made, A..

3 recordsLinked to original sources

bioRxiv2024

LEF1-AS1 deregulation in the peripheral blood of patients with persistent post-COVID symptoms

Long COVID denotes the persistence of symptoms after acute SARS-CoV-2 infection lasting for at least two months without another identifiable cause. Affecting an estimated 15% of COVID-19 patients, long COVID manifests in a wide range of symptoms. Despite extensive research on its one-year effects, limited data exist beyond 12 months. Due to the different manifestations of long COVID, its diagnosis can be challenging. Identifying potential mechanistic contributors and biomarkers would be highly valuable. Recent studies have highlighted the potential of noncoding RNAs (ncRNAs) as biomarkers for disease stratification in COVID-19. Specifically, we have recently identified miR-144-3p and a subset of lncRNAs as candidates for assessing disease severity and outcomes in COVID-19. This study extends such investigations to 98 long COVID patients recruited 18 months after hospitalization, exploring the relationship between circulating ncRNA expression and persistent symptoms. While miR-144-3p, HCG18, and lncCEACAM21 expression did not differ between symptomatic and asymptomatic patients, LEF1-AS1 was downregulated in peripheral blood mononuclear cells (PBMCs) of symptomatic patients. Of note, multiple LEF1-AS1 isoforms and LEF1 sense transcript levels were reduced and negatively correlated with relevant clinical markers. While further studies are needed, our discoveries offer new perspectives for the diagnosis and management of persistent long COVID.

molecular biology↗

bioRxiv2021

Identification of Cell-Free DNA Methylation Patterns Unique to the Human Left Ventricle as a Potential Indicator of Acute Cellular Rejection

Increased levels of donor-derived cell-free DNA (dd-cfDNA) in recipient plasma have been associated with rejection after transplantation. DNA sequence differences have been used to distinguish between donor and recipient but epigenetic differences could also potentially identify dd-cfDNA. This pilot study aimed to identify ventricle-specific differentially methylated regions of DNA (DMRs) that could be detected in cfDNA. We identified 24 ventricle-specific DMRs and chose two for further study, one on chromosome 9 and one on chromosome 12. The specificity of both DMRs for the left ventricle was confirmed using genomic DNA from multiple human tissues. Serial matched samples of myocardium (n=33) and plasma (n=24) were collected from stable adult heart transplant recipients undergoing routine endomyocardial biopsy for rejection surveillance. Plasma DMR levels increased with biopsy-proven rejection grade for individual patients. Mean cellular apoptosis in biopsy samples increased significantly with rejection severity (2.4%, 4.4% and 10.0% for ACR 0R, 1R and 2R, respectively) but did not show a consistent relationship with DMR levels. We identified multiple DNA methylation patterns unique to the human ventricle and conclude that epigenetic differences in cfDNA populations represent a promising alternative strategy for the non-invasive detection of rejection.

genetics↗

bioRxiv2020

Identification of Aorta-Specific DNA Methylation Patterns in Cell-Free DNA from Patients with Bicuspid Aortic Valve-Associated Aortopathy and Correlation with Aortic Wall Cell Death

ObjectiveIn a proof-of-concept study we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients with bicuspid aortic valve (BAV)-associated aortopathy. MethodsWe used bioinformatics and publicly-available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death. ResultsAortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 showed acceptable specificity for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter. ConclusionsElevated WSS created by abnormal flow hemodynamics is associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk. Date and Number of Institutional Review Board ApprovalREB17-0207

molecular biology↗