Satellite cells that reside on the myofibre surface are crucial for the muscle homeostasis and regeneration. Aging goes along with a less effective regeneration of skeletal muscle tissue mainly due to the decreased myogenic capability of satellite cells. This phenomenon impedes proper maintenance and contributes to the age-associated decline in muscle mass, known as sarcopenia. The myogenic potential impairment does not depend on a reduced myogenic cell number, but mainly on their difficulty to complete a differentiation program. The unbalanced production of reactive oxygen species in elderly people could be responsible for skeletal muscle impairments. microRNAs are conserved post-transcriptional regulators implicated in numerous biological processes including adult myogenesis. Here, we measure the ROS level and analyze myomiR (miR-1, miR-133b and miR-206) expression in human myogenic precursors obtained from Vastus lateralis of elderly and young subjects to provide the molecular signature responsible for the differentiation impairment of elderly activated satellite cells.

The aim of this study was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 wk of NMES were allowed to proliferate to provide myogenic populations of adult stem cells [myogenic precursor cells (MPCs)]. These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca concentrations, and their expression of myogenic regulatory factors (, and ) and micro-RNAs (miR-1, miR-133a/b, and miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross-sectional area, and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca concentrations and gene expression of and on MPCs. Muscle-specific miR-1, miR-133a/b, and miR-206 were upregulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cell fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly subjects significantly improved. NMES may thus be further considered for clinical or ageing populations. The neuromuscular electrical stimulation (NMES) effect on skeletal muscle regeneration was assessed in healthy elderly subjects for the first time. NMES improved the regenerative capacity of skeletal muscle through increased myogenic precursor cell proliferation and fusion with mature myofibers. The increased cytoplasmic free Ca concentration along with ,, and micro-RNA upregulation could be related to reduced O production, which, in turn, favors myogenic regeneration. Accordingly, the skeletal muscle strength of NMES-stimulated lower limbs of healthy elderly subjects improved along with their mobility.

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The (R)-α-lipoyl-glycyl-L-prolyl-L-glutamyl dimethyl ester codrug (LA-GPE, 1) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA-GPE to penetrate the blood-brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA-GPE against the cytotoxicity induced by 6-hydroxydopamine (6-OHDA) and H2O2 on the human neuroblastoma cell line SH-SY5Y by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH-dependent permeability profile. Furthermore, LA-GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H2O2- and 6-OHDA-induced neurotoxicity in SH-SY5Y cells.

The surface roughness of dental implants influences the proliferation and differentiation rate of adult mesenchymal stem cells (MSCs). The aim of the present study was to evaluate whether specifically treated titanium implant surfaces influenced human dental pulp stem cells (DPSCs) differentiation in an osteogenic pattern through modulation of microRNAs expression. The degree of differentiation was evaluated after 7, 14, and 21 days, through the expression of microRNAs characterizing the osteogenesis (miR-133 and miR-135), of Runx2 and Smad5 (key factor transcriptions associated with osteoblast differentiation) and Osteocalcin, marker for the bone formation process. DPSCs were cultured on sandblasted and acid-etched titanium disks, with (Test) or without the presence of ions (Control). Early differentiation of DPSCs cultured on titanium could be detected at all the evaluated time points, respect to cells grown alone. Moreover, the Test surfaces seemed to induce a more marked cells differentiation. The obtained results demonstrated that microRNAs played a pivotal role in the differentiation of MSCs and could be used as marker of osteogenic differentiation. Furthermore, the evaluated ionized sandblasted and acid-etched surface seemed to markedly enhance the development of osteoblast cells. A faster osseointegration could be achieved in the presence of specifically treated implant surfaces, promising encouraging clinical outcomes. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 953-965, 2017.