BACKGROUND: Heart failure is typical in the elderly. Metabolic remodeling of cardiomyocytes underlies inexorable deterioration of cardiac function with aging: glycolysis increases at the expense of oxidative phosphorylation, causing an energy deficit contributing to impaired contractility. Better understanding of the mechanisms of this metabolic switching could be critical for reversing the condition. METHODS: To investigate the role of 3 histone modifications (H3K27ac, H3K27me3, and H3K4me1) in the metabolic remodeling occurring in the aging heart, we cross-compared epigenomic, transcriptomic, and metabolomic data from mice of different ages. In addition, the role of the transcriptional coactivator p300 (E1A-associated binding protein p300)/CBP (CREB binding protein) in cardiac aging was investigated using a specific inhibitor of this histone acetyltransferase enzyme. RESULTS: We report a set of species-conserved enhancers associated with transcriptional changes underlying age-related metabolic remodeling in cardiomyocytes. Activation of the enhancer region of Hk2 —a key glycolysis pathway gene—was fostered in old age–onset mouse heart by pseudohypoxia, wherein hypoxia-related genes are expressed under normal O ₂ levels, via increased activity of P300/CBP. Pharmacological inhibition of this transcriptional coactivator before the onset of cardiac aging led to a more aerobic, less glycolytic, metabolic state, improved heart contractility, and overall blunting of cardiac decline. CONCLUSIONS: Taken together, our results suggest how epigenetic dysregulation of glycolysis pathway enhancers could potentially be targeted to treat heart failure in the elderly.

Background: Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF) has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results: We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion: The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.

Aim: After in vivo implantation of cell-loaded devices, only the cells close to the capillaries can obtain nutrients to maintain their functions. It is known that factors secreted by stem cells, rather than stem cells themselves, are fundamental to guarantee new vascularization in the area of implant. Materials & methods: To investigate this possibility, we have grafted mice with Bilayer and Flowable Integra® scaffolds, loaded or not with human adipose-derived stem cells. Results: Our results support the therapeutic potential of human adipose-derived stem cells to induce new vascular networks of engineered organs and tissues. Conclusion: This finding suggests that our approach can help to form new vascular networks that allow sufficient vascularization of engineered organs and tissues in cases of difficult wound healing due to ischemic conditions.

The ecosystem is being anthropogenically disturbed, which has serious consequences for the environment and human health, having strong social and economic impacts on the community. One of the most common methods to evaluate the effects of toxic contaminants is based on biomonitoring, e.g., placing Mytilus galloprovincialis in the polluted areas investigated. In this study, we have combined two different methods, transcriptomic and morphological analysis, with the purpose of determining whether cell morphology and the ultrastructural organization of our animal model are related to gene expression in outdoor experiments. The most pronounced changes were observed in mussel gills and digestive gland for mRNA involved in protein machinery (18S, 28S and EF1), while HSP70, MT10, CYP4Y1, SOD1, and CAT mRNAs showed scattered modifications not related to the studied area. In agreement with 18S, 28S, and EF1 mRNA evaluation, optical and electron microscopy demonstrated an initial inflammatory response of the cells that can lead to apoptosis in the caged mussels in all the polluted areas. In conclusion, the application of a multi-disciplinary approach proved to be effective for assessing the biological effects of contaminations on the health of aquatic organisms, and thus suitable to be applied in eco-toxicological studies. Although affected by several uncontrolled environmental variables, the assessment of mRNA can represent a useful endpoint for an integrated estimation of the overall threats to the sea environment within a field research approach.

The spread of antimicrobial resistance in Gram-positive pathogens represents a threat to human health. To counteract the current lack of novel antibiotics, alternative antibacterial treatments have been increasingly investigated. This review covers the last decade's developments in using nanoparticles as carriers for the two classes of frontline antibiotics active on multidrug-resistant Gram-positive pathogens, i.e., glycopeptide antibiotics and daptomycin. Most of the reviewed papers deal with vancomycin nanoformulations, being teicoplanin- and daptomycin-carrying nanosystems much less investigated. Special attention is addressed to nanoantibiotics used for contrasting biofilm-associated infections. The status of the art related to nanoantibiotic toxicity is critically reviewed.