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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pietrangelo, Demontis, Santangelo, Pini, Bonelli, Rosato, Roberti, Locatelli, Tartaglia, Marramiero, Verratti, Bondi, Fulle, D’Aloja and D’Ovidio.)

Altitude hypoxia exposure results in increased sympathetic activity and heart rate due to several mechanisms. Recent studies have contested the validity of heart rate variability (HRV) analysis on sympathetic activity measurement. But the plethora of HRV metrics may provide meaningful insights, particularly if linked with cardiovascular and autonomic nervous system parameters. However, the population-specific nature of HRV and cardiorespiratory response to altitude hypoxia are still missing. Six Italian trekkers and six Nepalese porters completed 300 km of a Himalayan trek. The ECG analysis was conducted at baseline, and before ( bBC ) and after ( aBC ) the high-altitude (HA) circuit. Urine was collected before and after the expedition in Italians, for assessing catecholamines. Heart rate increased with altitude significantly ( p < 0.001) in the Italian group; systolic ( p = 0.030) and diastolic ( p = 0.012) blood pressure, and mean arterial pressure ( p = 0.004) increased with altitude. Instead, pulse pressure did not change, although the Nepalese group showed lower baseline values than the Italians. As expected, peripheral oxygen saturation decreased with altitude ( p < 0.001), independently of the ethnic groups. Nepalese had a higher respiratory rate ( p = 0.007), independent of altitude. The cardiac vagal index increased at altitude, from baseline to bBC ( p = 0.008). Higuchi fractal dimension (HFD) showed higher basal values in the Nepalese group ( p = 0.041), and a tendency for the highest values at bBC . Regarding the urinary catecholamine response, exposure to HA increased urinary levels, particularly of norepinephrine ( p = 0.005, d = 1.623). Our findings suggest a better cardiovascular resilience of the Nepalese group when compared with Italians, which might be due to an intrinsic adaptation to HA, resulting from their job., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Verratti, Tonacci, Bondi, Chiavaroli, Ferrante, Brunetti, Crisafulli and Cerretelli.)

Altitude ascending represents an intriguing experimental model reproducing physiological and pathophysiological conditions sharing hypoxemia as the denominator. The aim of the present study was to investigate fractional oxygen extraction and blood dynamics in response to hypobaric hypoxia and to acute resistance exercises, taking into account several factors including different ethnic origin and muscle groups. As part of the "Kanchenjunga Exploration & Physiology" project, six Italian trekkers and six Nepalese porters took part in a high altitude trek in the Himalayas. The measurements were carried out at low (1,450 m) and high altitude (HA; 4,780 m). Near-infrared spectroscopy (NIRS)-derived parameters, i.e., Tot-Hb and tissue saturation index (TSI), were gathered at rest and after bouts of 3-min resistive exercise, both in the quadriceps and in the forearm muscles. TSI decreased with altitude, particularly in forearm muscles (from 66.9 to 57.3%), whereas the decrement was less in the quadriceps (from 62.5 to 57.2%); Nepalese porters were characterized by greater values in thigh TSI than Italian trekkers. Tot-Hb was increased after exercise. At altitude, such increase appeared to be higher in the quadriceps. This effect might be a consequence of the long-term adaptive memory due to the frequent exposures to altitude. Although speculative, we suggest a long-term adaptation of the Nepalese porters due to improved oxygenation of muscles frequently undergoing hypoxic exercise. Muscle structure, individual factors, and altitude exposure time should be taken into account to move on the knowledge of oxygen delivery and utilization at altitude., (Copyright © 2020 Verratti, Bondi, Mulliri, Ghiani, Crisafulli, Pietrangelo, Marinozzi and Cerretelli.)

Skeletal muscle aging is a multifactorial process strictly related to progressive weakness. One of the results that were focused on was the fiber phenotype modification and their loss. The physiological muscle recruitment to contraction, basically prosecuted under volitional control, can also be engaged by means of Neuromuscular Electrical Stimulation (NMES). Knowing that the NMES is effective in improving muscle strength in active healthy elderly, the aim was to investigate which physiological modifications were able to produce in the Vastus lateralis muscle and the pathways involved. It was found that NMES increased the cross sectional area and the isometric strength of type II myofibers together with the activated myogenic pathway in order to shift glycolytic toward the oxidative phenotype II myofibers, at a molecular level and with an increase of maximal voluntary contraction (MVC) at a functional level. Using the TaqMan low density array on 48 different genes, we found that NMES specific gene regulation highlighted: (i) increased protein synthesis with respect to protein degradation; (ii) the activation of an apoptotic pathway involved in the differentiation process; (iii) increased regeneration signals; (iv) oxidative enzyme regulation. These pathways were validated via confirmatory RT-PCR for genes involved in the regeneration process as well as Myosin isoforms. We also investigated the oxidative stress status analyzing superoxide anion levels, the protein expression of two different superoxide dismutase and the activity of both catalase and superoxide anion dismutase, being two main antioxidant enzymes. In conclusion, data demonstrates that NMES is effective in producing physiological adaptation on Vastus Lateralis of active healthy elderly as well as providing new insights for further research on elderly who experienced muscle detriment for periodic or permanent immobility., (Copyright © 2019 Mancinelli, Toniolo, Di Filippo, Doria, Marrone, Maroni, Verratti, Bondi, Maccatrozzo, Pietrangelo and Fulle.)

The phenomenon of strength gain is highly relevant for sarcopenia and clinical aspect linked to aging. Recent advancements drive the interest toward the exercise-related cross-talk between distant tissues. We demonstrated the cross-talk between lower and upper limbs, we named the Bottom-Up Rise Strength Transfer (BURST), mainly linked to endurance training. In our opinion, this effect can be mainly related to systemic factors, likely circulating myokines and extracellular vesicles (recently defined in terms of "exerkines" and "exersomes") whit an eventual concomitant reduction of a sub-clinical chronic inflammation. The neuronal mechanisms, even if to our sight less likely involved in this adaptation, need to be deeply investigated. Further studies are needed to better characterize the exercise-related BURST, concerning the specificity of different protocols and the underlying physiological mechanisms.

Aim: The aim of this study was to determine whether a 14-day trekking expeditions, in high altitude hypoxic environment, triggers redox disturbance at the level of satellite cells (adult stem cells) in young women., Methods: We collected muscle biopsies from Vastus Lateralis muscle for both single fiber analysis and satellite cells isolation. The samples collected before (PRE-Hypoxia) and after (POST-Hypoxia) the trekking in the Himalayas were compared. Satellite cells were investigated for oxidative stress (oxidant production, antioxidant enzyme activity, and lipid damage), mitochondrial potential variation, gene profile of HIF, and myogenic transcription factors (Pax7, MyoD, myogenin), and miRNA expression (miR-1, miR-133, miR-206)., Results: The nuclear domain analysis showed a significant fusion and consequent reduction of the Pax7(+) satellite cells in the single mature fibers. The POST-Hypoxia myoblasts obtained by two out of six volunteers showed high superoxide anion production and lipid peroxidation along with impaired dismutase and catalase and mitochondrial potential. The transcription profile and miRNA expression were different for oxidized and non-oxidized cells., Conclusions: The present study supports the phenomenon of hypobaric-hypoxia-induced oxidative stress and its role in the impairment of the regenerative capacity of satellite cells derived from the V. Lateralis muscle of young adult female subjects.