Synergic Integration of the miRNome, Machine Learning and Bioinformatics for the Identification of Potential Disease-Modifying Agents in Obstructive Sleep Apnea.

Introduction: Understanding the diverse pathogenetic pathways in obstructive sleep apnea (OSA) is crucial for improving outcomes. microRNA (miRNA) profiling is a promising strategy for elucidating these mechanisms.

Objective: To characterize the pathogenetic pathways linked to OSA through the integration of miRNA profiles, machine learning (ML) and bioinformatics.

Guidelines for mitochondrial RNA analysis.

Mitochondria are the energy-producing organelles of mammalian cells with critical involvement in metabolism and signaling. Studying their regulation in pathological conditions may lead to the discovery of novel drugs to treat, for instance, cardiovascular or neurological diseases, which affect high-energy-consuming cells such as cardiomyocytes, hepatocytes, or neurons. Mitochondria possess both protein-coding and noncoding RNAs, such as microRNAs, long noncoding RNAs, circular RNAs, and piwi-interacting RNAs, encoded by the mitochondria or the nuclear genome.

Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of non-ST-segment elevation myocardial infarction.

Background: Long noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers. Here, we investigated the cardiac-expressed and plasma-detectable lncRNA PDE4DIPP6 as a biomarker for non-ST-segment elevation myocardial infarction (NSTEMI), specifically assessing its potential to enhance the diagnostic efficacy of high-sensitivity cardiac troponin (hs-cTnT).

Methods And Results: The study enrolled individuals presenting with suspected acute coronary syndrome (ACS).

Association between Reactogenicity and Immunogenicity in a Vaccinated Cohort with Two mRNA SARS-CoV-2 Vaccines at a High-Complexity Reference Hospital: A Analysis on Immunology Aspects of a Prospective Cohort Study.

Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question.

Exploring the translational landscape of the long noncoding RNA transcriptome in acute respiratory distress syndrome: it is a long way to the top.

Acute respiratory distress syndrome (ARDS) poses a significant and widespread public health challenge. Extensive research conducted in recent decades has considerably improved our understanding of the disease pathophysiology. Nevertheless, ARDS continues to rank among the leading causes of mortality in intensive care units and its management remains a formidable task, primarily due to its remarkable heterogeneity.

Decoding viral and host microRNA signatures in airway-derived biosamples: Insights for biomarker discovery in viral respiratory infections.

The global public health crisis caused by the COVID-19 pandemic has intensified the global concern regarding viral respiratory tract infections. Despite their considerable impact on health, society and the economy, effective management of these conditions remains a significant challenge. Integrating high-throughput analyses is pivotal for early detection, prognostication of adverse outcomes, elucidating pathogenetic pathways and developing therapeutic approaches.

Circular RNA regulatory role in pathological cardiac remodelling.

Cardiac remodelling involves structural, cellular and molecular alterations in the heart after injury, resulting in progressive loss of heart function and ultimately leading to heart failure. Circular RNAs (circRNAs) are a recently rediscovered class of non-coding RNAs that play regulatory roles in the pathogenesis of cardiovascular diseases, including heart failure. Thus, a more comprehensive understanding of the role of circRNAs in the processes governing cardiac remodelling may set the ground for the development of circRNA-based diagnostic and therapeutic strategies.

Navigating the path of reproducibility in microRNA-based biomarker research with ring trials.

The development of microRNA (miRNA)-based biomarkers has gained significant attention due to their potential diagnostic, prognostic and therapeutic applications. However, the reproducibility of miRNA biomarker research faces unique challenges, primarily due to the influence of pre-analytical and analytical factors. The absence of standardized procedures contributes to inconsistencies across studies, alongside challenges in reference gene selection, data analysis methods and miRNA profiling platforms.

Addressing the unsolved challenges in microRNA-based biomarker development: Suitable endogenous reference microRNAs for SARS-CoV-2 infection severity.

Circulating cell-free microRNAs (miRNAs) are promising biomarkers for medical decision-making. Suitable endogenous controls are essential to ensure reproducibility. We aimed to identify and validate endogenous reference miRNAs for qPCR data normalization in samples from SARS-CoV-2-infected hospitalized patients.

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort.

Background: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.

microRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice.

Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney injury and dysfunction in obesity-associated nephropathy remain unclear. The present study aimed to unveil the kidney microRNA (miRNA) expression profile in a model of obesity-induced kidney disease in C57BL/6J mice using next-generation sequencing (NGS) analysis. High-fat diet (HFD)-induced obesity led to notable structural alterations in tubular and glomerular regions of the kidney, increased renal expression of proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism.

MicroRNA-guided drug discovery for mitigating persistent pulmonary complications in critical COVID-19 survivors: A longitudinal pilot study.

Background And Purpose: The post-acute sequelae of SARS-CoV-2 infection pose a significant global challenge, with nearly 50% of critical COVID-19 survivors manifesting persistent lung abnormalities. The lack of understanding about the molecular mechanisms and effective treatments hampers their management. Here, we employed microRNA (miRNA) profiling to decipher the systemic molecular underpinnings of the persistent pulmonary complications.

MicroRNA-centered theranostics for pulmoprotection in critical COVID-19.

Elucidating the pathobiological mechanisms underlying post-acute pulmonary sequelae following SARS-CoV-2 infection is essential for early interventions and patient stratification. Here, we investigated the potential of microRNAs (miRNAs) as theranostic agents for pulmoprotection in critical illness survivors. Multicenter study including 172 ICU survivors.

Academic challenges on advanced therapy medicinal products' development: a regulatory perspective.

Advanced therapy medicinal products (ATMPs) are becoming the new kid on the block for the treatment of a variety of indications with promising results. Despite the academic contribution to the basic and clinical research of ATMPs, undertaking a full product development process is extraordinarily challenging and demanding for academic institutions. Meeting regulatory requirements is probably the most challenging aspect of academic development, considering the limited experience and resources compared with pharmaceutical companies.

Recommendations for detection, validation, and evaluation of RNA editing events in cardiovascular and neurological/neurodegenerative diseases.

RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling.

Circulating miR-133a-3p defines a low-risk subphenotype in patients with heart failure and central sleep apnea: a decision tree machine learning approach.

Background: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes.

Objective: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA.

Methods: The study included patients with HFrEF and CSA from the SERVE-HF trial.