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Epigenetics of exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Daniel C. Turner, Robert A. Seaborne, Adam P. Sharples
When examining further, authors also reported a significant increase in tri-methylation of H3K27 in absolute terms, and relative to levels of H3. They also reported an increase in acetylation of H3 and mono methylation of H3K4, when relativised to levels of total H3 (95), where previous in vitro work reported H3K27me3 and H3K4me1 to be negatively and positively correlated with gene transcription, respectively, in a wider range of cell types (24). In a muscle-specific context, both these marks seem to be highly conserved to the myogenic basic helix loop helix (bHLH) transcription factor, MyoD, in both myoblasts and myotubes, leading to muscle-specific gene transcription (97) (MyoD and its role in myogenesis/satellite cells with exercise are covered in Chapter 13). Despite these interesting results, very few other studies have characterised the regulation of histone modifications following RE training; thus, it remains an under-developed area of molecular exercise physiology research. It is, however, a tantalising avenue of research and is surely poised to see a flurry of exciting, explorative, and illuminating work in the near future.
Oncology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Gill A. Levitt, Penelope Brock, Tanzina Chowdhury, Mark Gaze, Darren Hargrave, Judith Kingston, Antony Michalski, Olga Slater
The histology of RMS varies, with two main subtypes alveolar and embryonal found in children, while the third pleomorphic subtype is mainly diagnosed in adults (Table 12.5). The primary tumour is usually best imaged by MRI, including draining lymph nodes (seeFig. 12.25). CT of the chest, isotope bone scan and bone marrow aspirate and trephine biopsy are routine part of the staging. Biopsy, with molecular pathology studies, can be performed percutaneously or endoscopically. Immunohistochemistry for actin, myogenin and desmin are particularly useful. The alveolar subtype of RMS has pathognomonic translocation between chromosomes 1 or 2 and 13 resulting in PAX3 or PAX7/FOXO1 fusion gene, which enhance transcription and contribute to higher aggressiveness of this subtype. The biopsy position should be clearly marked and included in the final surgical resection. Draining lymph nodes should be biopsied if the tumour arises in the limbs, or in any location if the lymph nodes are abnormal on imaging. CSF examination is indicated if the tumour is parameningeal. The use of FDG PET/CT in paediatric sarcoma is still under scrutiny but it appears useful in evaluating nodal and metastatic disease (Fig. 12.24). On the both side of the Atlantic, RMS are stratified for treatment purposes according to the recognised risk factors: postsurgical stage, pathology, size, age, nodal involvement and localisation.
Molecular Mechanisms of Training Effects
Published in Atko Viru, Adaptation in Sports Training, 2017
The protein Id has been shown to interact with myogenic transcription factors (MyoD, myogenin, MRF4, and Myf-5) by forming complexes that will not bind to DNA. Id is a negative regulator of transcription.123 Experiments on the rat and mouse muscle showed that Id is increased under conditions that lead to atrophy, such as denervation or nerve impulse block. When Id is overexpressed in a fiber type-specific fashion, the fibers with the highest levels of Id-expression show atrophy. Therefore, the Id might play a role in regulation of muscle fiber size at the transcriptional level.124
Muscle regeneration after high-dose radiation exposure: therapeutic potential of Hedgehog pathway modulation?
Published in International Journal of Radiation Biology, 2022
E. Rota Graziosi, S. François, J. Pateux, M. Gauthier, X. Butigieg, M. Oger, M. Drouet, D. Riccobono, N. Jullien
Muscle repair is a complex process that involves the regeneration of damaged fibers by new ones formed from particular stem cells identified in 1961 by Mauro and known as satellite cells (SC) (Mauro 1961; Zammit et al. 2006). These progenitors, interspersed between the plasma membrane and the basal layer of fibers, can be activated from their quiescent state following a traumatic event to proliferate and differentiate into mature myoblasts, which fuze to reconstitute myotubes. These newly-formed structures merge into myofibers and regenerate a functional muscle. The different stages of differentiation, fusion and maturation are orchestrated by a cascade of myogenic regulatory factors (MRF). SC markers Pax3 and Pax7 disappear after the early stages of activation. Then, in the intermediate stages, Myf5 and MyoD are necessary for myoblast commitment toward muscle cell differentiation. Myogenin (MyoG gene) plays a role in the late phases of fusion and in the synthesis of Myosin, essential for muscle functionality (Hawke and Garry 2001). Other mature proteins are also synthesized at the end of the process, such as beta-enolase (ENO3 gene) which is involved especially in the storage of glycogen.
Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3β pathway in C2C12 myoblasts
Published in International Journal of Neuroscience, 2020
Xiao-Bo Fang, Zu-Biao Song, Meng-Shu Xie, Yan-Mei Liu, Wei-Xi Zhang
To investigate the effect of glucocorticoids on myogenic differentiation at the myoblast stage, established C2C12 myoblasts were employed as a myogenic differentiation model in vitro. The cells were incubated for 24 h in GM that contained different concentrations of DEX (10−8 to 10−4 M). Then, the medium was replaced with DM containing the same concentration of DEX for 48 h or 4 d. We used Western blot analysis to evaluate myogenic differentiation based on the expression levels of myogenin and MyoD (early myogenic marker) and the differentiated myotube marker myosin heavy chain (MyHC). As shown in Figure 1A, the expression of myogenin increased with treatment concentrations of 10−8 to 10−5 M, but the increased expression did not continue with 10−4 M, and DEX increased the expression of MyoD in a dose-dependent manner (Figure 1A). DEX also increased the expression of MyHC in a dose-dependent manner, but MyHC expression decreased with the 10−4 M concentration (Figure 1B). These results indicate that DEX can promote C2C12 myogenic differentiation at the myoblast stage. Therefore, the treatment concentration of 10−5 M was selected for subsequent experiments; this concentration has not only been widely used to analyze the effect of glucocorticoids on C2C12 myoblast differentiation [6–8,22] but was also proven to exert no significant toxic effects on differentiating myoblasts in our previous report [7].
Encapsulation of bone marrow-MSCs in PRP-derived fibrin microbeads and preliminary evaluation in a volumetric muscle loss injury rat model: modular muscle tissue engineering
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Özge Lalegül-Ülker, Şükran Şeker, Ayşe Eser Elçin, Yaşar Murat Elçin
Among the transplantation groups, the MSC-encapsulated FM-R group showed a faster regeneration at the injury site; however, the MSC-devoid FM-R group almost reached the regeneration level of the MSC-containing group after 180 days. Thus, it is established that PRP promotes muscle regeneration and reduces scar tissue formation due to the abundance of growth factors, which are important for regulating the healing processes [58,59]. In addition, the anti-myogenin and anti-MyoD1 stainings of the tissue specimens are given in the Supplemental section (Figures S1 and S2). These myogenic markers were also observed at the vicinity of the VML site at different levels. In all of the analysed tissue specimens, a clear correlation between anti-Desmin, anti-myogenin and anti-MyoD1 stainings was detected.