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This review is aimed at providing an overview of the key hallmarks of cardiomyocytes in physiological and pathological conditions. The main feature of cardiac tissue is the force generation through contraction. This process requires a conspicuous energy demand and therefore an active metabolism. The cardiac tissue is rich of mitochondria, the powerhouses in cells. These organelles, producing ATP, are also the main sources of ROS whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases. This review highlights the metabolic aspects of cardiomyocytes and wanders through the main systems of these cells: (a) the unique structural organization (such as different protein complexes represented by contractile, regulatory, and structural proteins); (b) the homeostasis of intracellular Ca 2+ that represents a crucial ion for cardiac functions and E-C coupling; and (c) the balance of Zn 2+ , an ion with a crucial impact on the cardiovascular system. Although each system seems to be independent and finely controlled, the contractile proteins, intracellular Ca 2+ homeostasis, and intracellular Zn 2+ signals are strongly linked to each other by the intracellular ROS management in a fascinating way to form a "functional tetrad" which ensures the proper functioning of the myocardium. Nevertheless, if ROS balance is not properly handled, one or more of these components could be altered resulting in deleterious effects leading to an unbalance of this "tetrad" and promoting cardiovascular diseases. In conclusion, this "functional tetrad" is proposed as a complex network that communicates continuously in the cardiomyocytes and can drive the switch from physiological to pathological conditions in the heart., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Michele Bevere et al.)

Microgravity affects human cardiovascular function inducing heart rhythm disturbances and even cardiac atrophy. The mechanisms triggered by microgravity and the search for protection strategies are difficult to be investigated in vivo. This study is aimed at investigating the effects induced by simulated microgravity on a cardiomyocyte-like phenotype. The Random Positioning Machine (RPM), set in a CO 2 incubator, was used to simulate microgravity, and H9C2 cell line was used as the cardiomyocyte-like model. H9C2 cells were exposed to simulated microgravity up to 96 h, showing a slower cell proliferation rate and lower metabolic activity in comparison to cell grown at earth gravity. In exposed cells, these effects were accompanied by increased levels of intracellular reactive oxygen species (ROS), cytosolic Ca 2+ , and mitochondrial superoxide anion. Protein carbonyls, markers of protein oxidation, were significantly increased after the first 48 h of exposition in the RPM. In these conditions, the presence of an antioxidant, the N-acetylcysteine (NAC), counteracted the effects induced by the simulated microgravity. In conclusion, these data suggest that simulated microgravity triggers a concomitant increase of intracellular ROS and Ca 2+ levels and affects cell metabolic activity which in turn could be responsible for the slower proliferative rate. Nevertheless, the very low number of detectable dead cells and, more interestingly, the protective effect of NA, demonstrate that simulated microgravity does not have "an irreversible toxic effect" but, affecting the oxidative balance, results in a transient slowdown of proliferation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Simone Guarnieri et al.)

Extremely low-frequency electromagnetic fields (ELF-EMFs) can interact with biological systems. Although they are successfully used as therapeutic agents in physiatrics and rehabilitative practice, they might represent environmental pollutants and pose a risk to human health. Due to the lack of evidence of their mechanism of action, the effects of ELF-EMFs on differentiation processes in skeletal muscle were investigated. C2C12 myoblasts were exposed to ELF-EMFs generated by a solenoid. The effects of ELF-EMFs on cell viability and on growth and differentiation rates were studied using colorimetric and vital dye assays, cytomorphology, and molecular analysis of MyoD and myogenin expression, respectively. The establishment of functional gap junctions was investigated analyzing connexin 43 expression levels and measuring cell permeability, using microinjection/dye-transfer assays. The ELF-EMFs did not affect C2C12 myoblast viability or proliferation rate. Conversely, at ELF-EMF intensity in the mT range, the myogenic process was accelerated, through increased expression of MyoD, myogenin, and connexin 43. The increase in gap-junction function suggests promoting cell fusion and myotube differentiation. These data provide the first evidence of the mechanism through which ELF-EMFs may provide therapeutic benefits and can resolve, at least in part, some conditions of muscle dysfunction.

We propose a human-derived neuro-/glial cell three-dimensional in vitro model to investigate the effects of microgravity on cell-cell interactions. A rotary cell-culture system (RCCS) bioreactor was used to generate a modelled microgravity environment, and morphofunctional features of glial-like GL15 and neuronal-like SH-SY5Y cells in three-dimensional individual cultures (monotypic aggregates) and cocultures (heterotypic aggregates) were analysed. Cell survival was maintained within all cell aggregates over 2 weeks of culture. Moreover, compared to cells as traditional static monolayers, cell aggregates cultured under modelled microgravity showed increased expression of specific differentiation markers (e.g., GL15 cells: GFAP, S100B; SH-SY5Y cells: GAP43) and modulation of functional cell-cell interactions (e.g., N-CAM and Cx43 expression and localisation). In conclusion, this culture model opens a wide range of specific investigations at the molecular, biochemical, and morphological levels, and it represents an important tool for in vitro studies into dynamic interactions and responses of nervous system cell components to microgravity environmental conditions.

We previously observed tht low oral doses of melatonin given at noon increase blood melatonin concentrations to those normally occurring nocturnally and facilitate sleep onset, as assessed using and involuntary muscle relaxation test. In this study we examined the induction of polysomnographically recorded sleep by similar doses given later in the evening, close to the times of endogenous melatonin release and habitual sleep onset. Volunteers received the hormone (oral doses of 0.3 or 1.0 mg) or placebo at 6, 8, or 9 PM. Latencies to sleep onset, to stage 2 sleep, and to rapid eye movement (REM) sleep were measured polysomnographically. Either dose given at any of the three time points decreased sleep onset latency and latency to stage 2 sleep. Melatonin did not suppress REM sleep or delay its onset. Most volunteers could clearly distinguish between the effects of melatonin and those of placebo when the hormone was tested at 6 or 8 PM. Neither melatonin dose induced "hangover" effects, as assessed with mood and performance tests administered on the morning after treatment. These data provide new evidence that nocturnal melatonin secretion may be involved in physiologic sleep onset and that exogenous melatonin may be useful in treating insomnia.