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Translational Myology: Cellular, Genetic, Molecular Aspects

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 21262

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Special Issue Editors

Prof. Dr. Giorgio Fanò-Illic

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Guest Editor

Interuniversity Institute of Myology (IIM) 66100 Chieti (Italy), A&C M-C Foundation for Translational Myology, 35100 Padova (Italy), Free University of Alcatraz, 06024 Gubbio, Italy
Interests: human muscle senescence; skeletal muscle physiology; adaptive responses to hypoxia and microgravity; growth factors and transcription factors in excitable cells; Oxidative stress; brain physiology: cognitive aspects
Special Issues, Collections and Topics in MDPI journals

Dr. Rosa Mancinelli

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Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: muscle; skeletal
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aim of translational research is to quicken the transition of the results achieved in basic research, derived from different approaches, to possible applications aimed at improving human health.

In myology, a research field focused on the study of skeletal muscle, the translational approach concerns many aspects of its function in relation to the physiological and/or pathological conditions in the organism.

Skeletal muscle does not only produce force, with many components (growth factors, myokines, etc.) having a double function: they act both in an autocrine and paracrine way, on the tissue that produced them and on distant tissue and/or organs (bone tissue, neurons, etc.).

For this reason, it is important to define muscular metabolic patterns as they change depending on the different physiopathological conditions of the whole body.

Knowledge of the mechanisms that control protein synthesis, the removal of degradation products and fiber regeneration plays a fundamental role in the maintenance of muscle functions.

Furthermore, mechanisms that controls energy production and mitochondrial activity have a key role in the translational approach to muscular activity, as their alteration leads to the establishment of oxidative stress status.

Finally, an example of the importance of an altered state of the immune system, such as that induced by COVID-19, can be highlighted in the situation known as long COVID that, among other aspects, has a muscle component that is not yet adequately understood.

The aim of the present Special Issue is to highlight the cellular, genetic and molecular aspects of the complex machine represented by skeletal muscle, specifically, in its role as a “general regulator”, able to mediate beneficial effects throughout the body.

Prof. Dr. Giorgio Fanò-Illic
Dr. Rosa Mancinelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

myochines
regenerative potential
protein homeostasis
oxidative stress
mitochondrial homeostasis
genetic and epigenetic modifications
inflammasome
purinergic pathway
long COVID

Published Papers (7 papers)

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Research

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23 pages, 6718 KiB

Open AccessArticle

Verbascoside Elicits Its Beneficial Effects by Enhancing Mitochondrial Spare Respiratory Capacity and the Nrf2/HO-1 Mediated Antioxidant System in a Murine Skeletal Muscle Cell Line

by Francesca Sciandra, Patrizia Bottoni, Marinella De Leo, Alessandra Braca, Andrea Brancaccio and Manuela Bozzi

Int. J. Mol. Sci. 2023, 24(20), 15276; https://doi.org/10.3390/ijms242015276 - 17 Oct 2023

Cited by 2 | Viewed by 1050

Abstract

Muscle weakness and muscle loss characterize many physio-pathological conditions, including sarcopenia and many forms of muscular dystrophy, which are often also associated with mitochondrial dysfunction. Verbascoside, a phenylethanoid glycoside of plant origin, also named acteoside, has shown strong antioxidant and anti-fatigue activity in different animal models, but the molecular mechanisms underlying these effects are not completely understood. This study aimed to investigate the influence of verbascoside on mitochondrial function and its protective role against H₂O₂-induced oxidative damage in murine C2C12 myoblasts and myotubes pre-treated with verbascoside for 24 h and exposed to H₂O₂. We examined the effects of verbascoside on cell viability, intracellular reactive oxygen species (ROS) production and mitochondrial function through high-resolution respirometry. Moreover, we verified whether verbascoside was able to stimulate nuclear factor erythroid 2-related factor (Nrf2) activity through Western blotting and confocal fluorescence microscopy, and to modulate the transcription of its target genes, such as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), by Real Time PCR. We found that verbascoside (1) improved mitochondrial function by increasing mitochondrial spare respiratory capacity; (2) mitigated the decrease in cell viability induced by H₂O₂ and reduced ROS levels; (3) promoted the phosphorylation of Nrf2 and its nuclear translocation; (4) increased the transcription levels of HO-1 and, in myoblasts but not in myotubes, those of PGC-1α. These findings contribute to explaining verbascoside’s ability to relieve muscular fatigue and could have positive repercussions for the development of therapies aimed at counteracting muscle weakness and mitochondrial dysfunction. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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13 pages, 1670 KiB

Open AccessArticle

Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice

by Julián Balanta-Melo, Andrea Eyquem-Reyes, Noelia Blanco, Walter Vásquez, Kornelius Kupczik, Viviana Toro-Ibacache and Sonja Buvinic

Int. J. Mol. Sci. 2023, 24(19), 14740; https://doi.org/10.3390/ijms241914740 - 29 Sep 2023

Cited by 1 | Viewed by 796

Abstract

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d–7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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19 pages, 2231 KiB

Open AccessArticle

Modulation of the Circulating Extracellular Vesicles in Response to Different Exercise Regimens and Study of Their Inflammatory Effects

by Serena Maggio, Barbara Canonico, Paola Ceccaroli, Emanuela Polidori, Andrea Cioccoloni, Luca Giacomelli, Carlo Ferri Marini, Giosuè Annibalini, Marco Gervasi, Piero Benelli, Francesco Fabbri, Laura Del Coco, Francesco Paolo Fanizzi, Anna Maria Giudetti, Francesco Lucertini and Michele Guescini

Int. J. Mol. Sci. 2023, 24(3), 3039; https://doi.org/10.3390/ijms24033039 - 3 Feb 2023

Cited by 6 | Viewed by 2670

Abstract

Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81⁺/SGCA⁺/CD45⁻ EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1β, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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18 pages, 2128 KiB

Open AccessArticle

Repeated and Interrupted Resistance Exercise Induces the Desensitization and Re-Sensitization of mTOR-Related Signaling in Human Skeletal Muscle Fibers

by Daniel Jacko, Kirill Schaaf, Lukas Masur, Hannes Windoffer, Thorben Aussieker, Thorsten Schiffer, Jonas Zacher, Wilhelm Bloch and Sebastian Gehlert

Int. J. Mol. Sci. 2022, 23(10), 5431; https://doi.org/10.3390/ijms23105431 - 12 May 2022

Cited by 7 | Viewed by 8856

Abstract

The acute resistance exercise (RE)-induced phosphorylation of mTOR-related signaling proteins in skeletal muscle can be blunted after repeated RE. The time frame in which the phosphorylation (_p) of mTOR^S2448, p70S6k^T421/S424, and rpS6^S235/236 will be reduced during an RE training period in humans and whether progressive (PR) loading can counteract such a decline has not been described. (1) To enclose the time frame in which _pmTOR^S2448, _prpS6^S235/236, and _pp70S6k^T421/S424 are acutely reduced after RE occurs during repeated RE. (2) To test whether PR will prevent that reduction compared to constant loading (CO) and (3) whether 10 days without RE may re-increase blunted signaling. Fourteen healthy males (24 ± 2.8 yrs.; 1.83 ± 0.1 cm; 79.3 ± 8.5 kg) were subjected to RE with either PR (n = 8) or CO (n = 6) loading. Subjects performed RE thrice per week, conducting three sets with 10–12 repetitions on a leg press and leg extension machine. Muscle biopsies were collected at rest (T0), 45 min after the first (T1), seventh (T7), 13th (T13), and 14th (X-T14) RE session. No differences were found between PR and CO for any parameter. Thus, the groups were combined, and the results show the merged values. _prpS6^S235/236 and _pp70s6k^T421/S424 were increased at T1, but were already reduced at T7 and up to T13 compared to T1. Ten days without RE re-increased _prpS6^S235/236 and _pp70S6k^T421/S424 at X-T14 to a level comparable to that of T1. _pmTOR^S2448 was increased from T1 to X-T14 and did not decline over the training period. Single-fiber immunohistochemistry revealed a reduction in _prpS6^S235/236 in type I fibers from T1 to T13 and a re-increase at X-T14, which was more augmented in type II fibers at T13 (p < 0.05). The entity of myofibers revealed a high heterogeneity in the level of _prpS6^S235/236, possibly reflecting individual contraction-induced stress during RE. The type I and II myofiber diameter increased from T0 and T1 to T13 and X-T14 (p < 0.05) _prpS6^S235/236 and _pp70s6k^T421/S424 reflect RE-induced states of desensitization and re-sensitization in dependency on frequent loading by RE, but also by its cessation. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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Review

Jump to: Research

21 pages, 1672 KiB

Open AccessReview

Frailty and the Interactions between Skeletal Muscle, Bone, and Adipose Tissue-Impact on Cardiovascular Disease and Possible Therapeutic Measures

by María Elena Soto, Israel Pérez-Torres, María Esther Rubio-Ruiz, Agustina Cano-Martínez, Linaloe Manzano-Pech and Verónica Guarner-Lans

Int. J. Mol. Sci. 2023, 24(5), 4534; https://doi.org/10.3390/ijms24054534 - 25 Feb 2023

Cited by 8 | Viewed by 2608

Abstract

Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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19 pages, 1559 KiB

Open AccessReview

The Impact of Corticosteroids on Human Airway Smooth Muscle Contractility and Airway Hyperresponsiveness: A Systematic Review

by Luigino Calzetta, Alfredo Chetta, Marina Aiello, Elena Pistocchini and Paola Rogliani

Int. J. Mol. Sci. 2022, 23(23), 15285; https://doi.org/10.3390/ijms232315285 - 4 Dec 2022

Cited by 3 | Viewed by 1726

Abstract

Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of α-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gsα–cyclic-adenosine-monophosphate–protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS/long-acting β₂-adrenoceptor agonist/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3–5 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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14 pages, 325 KiB

Open AccessReview

The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker

by Boel De Paepe

Int. J. Mol. Sci. 2022, 23(21), 13180; https://doi.org/10.3390/ijms232113180 - 29 Oct 2022

Cited by 5 | Viewed by 2324

Abstract

Growth differentiation factor 15 (GDF-15) is a stress-induced transforming growth factor-β superfamily cytokine with versatile functions in human health. Elevated GDF-15 blood levels associate with multiple pathological conditions, and are currently extensively explored for diagnosis, and as a means to monitor disease progression and evaluate therapeutic responses. This review analyzes GDF-15 in human conditions specifically focusing on its association with muscle manifestations of sarcopenia, mitochondrial myopathy, and autoimmune and viral myositis. The use of GDF-15 as a widely applicable health biomarker to monitor muscle disease is discussed, and its potential as a therapeutic target is explored. Full article

(This article belongs to the Special Issue Translational Myology: Cellular, Genetic, Molecular Aspects)

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