Exposome on skeletal muscle system: a mini-review.

Exposomics is an ever-expanding field which captures the cumulative exposures to chemical, biological, physical, lifestyle, and social factors associated with biological responses. Since skeletal muscle is currently considered as the largest secretory organ and shows substantial plasticity over the life course, this reviews addresses the topic of exposome and skeletal muscle by reviewing the state-of-the-art evidence and the most intriguing perspectives. Muscle stem cells react to stressors via phosphorylated eukaryotic initiation factor 2α and tuberous sclerosis 1, and are sensible to hormetic factors via sirtuin 1. Microplastics can delay muscle regeneration via p38 mitogen-activated protein kinases and induce transdifferentiation to adipocytes via nuclear factor kappa B. Acrolein can inhibit myogenic differentiation and disrupt redox system. Heavy metals have been associated with reduced muscle strength in children. The deep study of pollutants and biological features can shed new light on neuromuscular pathophysiology. The analysis of a time-varying and dynamic exposome risk score from a panel of exposure and phenotypes of interest is promising. The systematization of hormetic factors and the role of the microbiota in modulating the effects of exposure on skeletal muscle responses are also promising. The comprehensive exposure assessment and its interactions with endogenous processes and the resulting biological effects deserve more efforts in the field of muscle health across the lifespan.

Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID-19 pandemic since ME/CFS and long-COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research. This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long-standing debate on terminology.

Broadband Electrical Spectroscopy to Distinguish Single-Cell Ca2+ Changes Due to Ionomycin Treatment in a Skeletal Muscle Cell Line.

Many skeletal muscle diseases such as muscular dystrophy, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and sarcopenia share the dysregulation of calcium (Ca2+) as a key mechanism of disease at a cellular level. Cytosolic concentrations of Ca2+ can signal dysregulation in organelles including the mitochondria, nucleus, and sarcoplasmic reticulum in skeletal muscle. In this work, a treatment is applied to mimic the Ca2+ increase associated with these atrophy-related disease states, and broadband impedance measurements are taken for single cells with and without this treatment using a microfluidic device. The resulting impedance measurements are fitted using a single-shell circuit simulation to show calculated electrical dielectric property contributions based on these Ca2+ changes. From this, similar distributions were seen in the Ca2+ from fluorescence measurements and the distribution of the S-parameter at a single frequency, identifying Ca2+ as the main contributor to the electrical differences being identified. Extracted dielectric parameters also showed different distribution patterns between the untreated and ionomycin-treated groups; however, the overall electrical parameters suggest the impact of Ca2+-induced changes at a wider range of frequencies.

Endurance-dependent urinary extracellular vesicle signature: shape, metabolic miRNAs, and purine content distinguish triathletes from inactive people.

Extracellular vesicles (EVs) enriched with bioactive molecules have gained considerable attention in nanotechnology because they are critical to intercellular communication while maintaining low immunological impact. Among biological matrices, urine has emerged as a noninvasive source of extracellular-contained liquid biopsy, currently of interest as a readout for physiological adaptations. Therefore, we aimed to evaluate chronic adaptations of endurance sport practice in terms of urinary EV parameters and evaluated by food consumption assessment. Two balanced groups of 13 inactive controls vs. triathlon athletes were enrolled; their urinary EVs were obtained by differential ultracentrifugation and analyzed by dynamic light scattering and transmission electron and atomic force microscopy. The cargo was analyzed by means of purine and miRNA content through HPLC-UV and qRT-PCR. Specific urinary EV signatures differentiated inactive versus endurance-trained in terms of peculiar shape. Particularly, a spheroid shape, smaller size, and lower roughness characterize EVs from triathletes. Metabolic and regulatory miRNAs often associated with skeletal muscle (i.e., miR378a-5p, miR27a-3p, miR133a, and miR206) also accounted for a differential signature. These miRNAs and guanosine in urinary EVs can be used as a readout for metabolic status along with the shape and roughness of EVs, novel informative parameters that are rarely considered. The network models allow scholars to entangle nutritional and exercise factors related to EVs' miRNA and purine content to depict metabolic signatures. All in all, multiplex biophysical and molecular analyses of urinary EVs may serve as promising prospects for research in exercise physiology.

Redox-based Disruption of Cellular Hormesis and Promotion of Degenerative Pathways: Perspectives on Aging Processes.

The present work aims to link the redox and cell-centric theories of chronic processes in human biology, focusing on aging. A synthetic overview of cellular redox pathways will be integrated by the concept of hormesis, which disruption leads to several physiopathological processes. The onset of age-related diseases due to the restriction of homeodynamic capacity will be herein considered in a redox fashion. Up-to-date arguments on hormetic agents, such as geroprotectors, dietary interventions, and physical exercise are refining the presented theoretical framework, integrated by insights from extracellular vesicles, microbiota, pollutants, and timing mechanisms. The broad concepts of exposome encompass the redox-based alteration of cellular hormesis for providing meaningful perspectives on redox biogerontology.

New Perspectives for Postmortem Human Satellite Cells of Different Embryological Origin.

Human postmortem skeletal muscles are a unique source of satellite cells for skeletal muscle regenerative studies. Presomite and somite satellite cells obtained by postmortem muscles have been established as populations of human skeletal muscle precursor cells able to proliferate and differentiate in vitro. It is extremely interesting to have access to a large amount of postmortem human skeletal muscle precursor cells, especially from craniofacial as well as limb skeletal muscles in order to evaluate their potential application not only for the fundamental understanding of muscle physiology and diseases but also for drug testing in a challenging 3D-shaping muscles like skeletal muscle microphysiological systems.

The wonder exerkines-novel insights: a critical state-of-the-art review.

Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. "Exerkine" has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving the way for both physiological novel insights and potential medical strategies. The five exerkines identified all play a significant role in the healthy effect of exercise. Specifically: miR-1192, released by muscles and myocardium into circulation, by modulating cardioprotective effect in trained mice; miR-342-5p, located into exosomes from vascular endothelial cells, also a cardioprotective miRNA in trained young humans; apelin, released by muscles into circulation, involved in anti-inflammatory pathways and muscle regenerative capacity in rats; GDF-15, released into circulation from yet unknown source, whose effects can be observed on multiple organs in young men after a single bout of exercise; oxytocin, released by myoblasts and myotubes, with autocrine and paracrine functions in myotubes. The systemic transport by vesicles and the crosstalk between distant organs deserve a deep investigation. Sources, targets, transport mechanisms, biological roles, population samples, frequency, intensity, time and type of exercise should be considered for the characterization of existing and novel exerkines. The "exercise is medicine" framework should include exerkines in favor of novel insights for public health.