Sciacqua, A. | bioRxiv Science

bioRxiv2025

INFLAMMATORY ACTIVATION, EPIGENETIC SIGNATURE AND MORPHO-STRUCTURAL ALTERATION IN A COHORT OF PATIENTS WITH CHRONIC HEART FAILURE AND PERMANENT ATRIAL FIBRILLATION: A CROSS-SECTIONAL STUDY.

BackgroundAtrial fibrillation (AF) is a complex disorder involving inflammatory, morpho-structural, and genetic factors. Emerging evidence suggests inflammation plays a pivotal role in AF initiation, maintenance, and outcomes. MethodsWe conducted a cross-sectional case-control study to assess whether, among patients with chronic heart failure (CHF) and permanent AF, serum inflammatory cytokines, metabolic parameters, epigenetic factors, and echocardiographic markers of structural remodeling are interrelated. Eighty-two consecutive CHF patients with permanent AF and 82 CHF patients with sinus rhythm and no AF history were enrolled from the Internal Medicine and Stroke Care Unit at "P. Giaccone" Hospital, Palermo, between January 2020 and May 2022. ResultsAF patients were older and exhibited higher left atrial volume index (LAVI), reduced left atrial (LA) strain, increased relative wall thickness (RWT), and lower ejection fraction (EF%). Renal markers, including estimated glomerular filtration rate (eGFR) and microalbuminuria, were significantly different. Inflammatory markers such as C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and NT-proBNP were elevated in the AF group. Multivariable logistic regression identified LAVI, LA strain, microalbuminuria, albumin/creatinine ratio (ACr), and protein/creatinine ratio (PCr) as independent predictors of AF. Correlation analyses demonstrated strong associations between echocardiographic, inflammatory, and renal parameters. No significant differences in circulating miRNAs were observed. ConclusionsThese findings highlight the intricate interconnection between atrial remodeling, renal dysfunction, and systemic inflammation in AF pathogenesis. A better understanding of these mechanisms may inform future risk stratification strategies and support the development of more effective, targeted therapies in patients with CHF.

scientific communication and education↗

bioRxiv2024

A post-mitotic in vitro murine as a model of muscle damage and repair

Sarcopenia is a degenerative condition characterized by the atrophy and functional decline of myofibers, resulting in disability. While the clinical risk factors are known, there is no validated in vitro model to understand the molecular mechanisms and identify therapeutics. To tackle this challenge, we generated an in vitro post-mitotic muscular system by differentiating mouse myoblast cells, namely C2C12. After 12 days of differentiation, cells were expressing physiological markers of myotubes and became self-contracting. Importantly, transcriptomic analyses demonstrated high similarity (r=0.70) when compared to primary human myotubes (HSkMC) providing evidence of resemblance to human cells. Next, we starved and incubated cells with dexamethasone and observed myotube shrinkage, oxidative stress, modification of anabolic, inflammatory, and catabolic markers recapitulating sarcopenia. Conversely, cell refeeding resulted in a recovery in the model with nutrient deprivation but not when incubated also with dexamethasone. In conclusion, we present a model of sarcopenia due to nutrient deprivation and corticosteroids. This model may allow more efficient and effective future research to identify therapeutics against sarcopenia in humans.

cell biology↗