Biology subjects

Almeida, M. I.

Publications and source records attributed to Almeida, M. I..

3 recordsLinked to original sources

bioRxiv2024

Circulating microRNAs as biomarkers of chronic kidney disease and its association with renal and cardiovascular outcomes in non-dialysis patients

Chronic kidney disease (CKD) affects over 10% of the population worldwide and entails a significant risk for cardiovascular disease (CVD), leading to a 500-fold increase in cardiovascular mortality in advanced stages. Still, the pathophysiological mechanisms underlying kidney-heart intercommunication remain largely unknown. In recent years, microRNAs (miRNAs) emerged as important key regulators of gene expression that may serve as biomarkers for several diseases, however, their role in kidney-heart crosstalk in CKD remains underexplored. In this study, we evaluated the expression of a miRNA panel in plasma samples from non-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow-up. Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients presenting a significant power to discriminate the disease state. Importantly, only miR-30c-5p was downregulated in early glomerular filtration rate (GFR) categories, being able to discriminate these CKD patients from non-diseased individuals. Concerning cardiovascular outcomes, miR-199a-5p was found to be associated with an increased frequency of CVD. When analyzing the major disease outcomes in a 5-year time, miR-199a-5p upregulation at baseline was associated with increased mortality, while miR-324-3p was downregulated in patients who progressed to more advanced stages of the disease. These findings highlight the involvement of novel circulating miRNAs in CKD onset and progression, and identify, for the first time, the enrollment of miR-199a-5p in kidney-heart pathophysiological crosstalk, paving the way for the establishment of new biomarkers and therapeutic targets for CKD and its outcomes.

molecular biology↗

bioRxiv2023

Stage-Specific Modulation of Multinucleation, Fusion and Resorption by the Long Non-coding RNA DLEU1 and miR-16 in Human Primary Osteoclasts

Osteoclasts are multinucleated cells formed through fusion of mononucleated precursors of the myeloid lineage and are the only cells that can resorb all the constituents of the bone matrix. Our goal was to investigate the role of long non-coding RNA DLEU1 and miR-16-5p in the fusion of human primary osteoclasts and their resorptive capacity. We found DLEU1 to be markedly upregulated, whereas miR-16 was significantly suppressed, during osteoclast differentiation, suggesting a potential involvement in the multinucleation process. The knockdown of DLEU1 or the overexpression of miR-16 in human primary pre-osteoclasts from male human donors (50 years or older) impaired fusion at both early and late time-points, each in distinct ways, without affecting cell viability. Time-lapse recordings confirmed the impairment of the fusion process and showed an abrogation of the phagocytic cup fusion modality, as well as a reduction of the fusion between mononucleated precursors and multinucleated osteoclasts during DLEU1 silencing. Furthermore, mass spectrometry-based quantitative proteomics revealed that the effects of DLEU1 and miR-16 on osteoclast fusion were mediated by distinct proteins and processes. Thus, both DLEU1 inhibition and/or miR-16 overexpression hinder osteoclast fusion through modulation of different mechanisms. Moreover, decreased levels of DLEU1 specifically affected the resorption speed of pit-making osteoclasts, while increased levels of miR-16 promoted bone resorption mainly through pit-formation, impairing the resorption speed of the osteoclasts making trenches and affecting their resorbed area. Taken together, these findings identify DLEU1 and miR-16 as mediators of osteoclast fusion and activity, offering potential new therapeutic targets to ameliorate bone destruction in skeletal diseases with accentuated bone deterioration.

molecular biology↗

bioRxiv2018

S-MiRAGE: A quantitative, secreted RNA-based reporter of gene expression and cell persistence

Non-destructive measurements of cell persistence and gene expression are crucial for longitudinal research studies and for prognostic assessment of cell therapies. Here we describe S-MiRAGE, a platform that utilizes small secreted RNA molecules as sensitive and quantitatively accurate reporters of cellular processes. We demonstrate the utility of S-MiRAGE by monitoring the differentiation status of human embryonic stem cells in vitro, and tumor growth in a mouse model in vivo.

bioengineering↗