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Nutrients Jan 2024Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several... (Review)
Review
Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several studies present contradictory results of treatment protocols and therapeutic effects. Therefore, the objective of this systematic review was to investigate the current literature showing the molecular mechanism and clinical protocol of epicatechin in muscle atrophy in humans, animals, and myoblast cell-line. The search was conducted in Embase, PubMed/MEDLINE, Cochrane Library, and Web of Science. The qualitative analysis demonstrated that there is a commonness of epicatechin inhibitory action in myostatin expression and atrogenes MAFbx, FOXO, and MuRF1. Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin). Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise. Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.
Topics: Animals; Humans; Catechin; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; MyoD Protein; TOR Serine-Threonine Kinases
PubMed: 38276564
DOI: 10.3390/nu16020326 -
Nutrients Oct 2023Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle... (Review)
Review
Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D's positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery. The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population. Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery. However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D. In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery.
Topics: Aged; Humans; Animals; Mice; Vitamin D; Muscle, Skeletal; Vitamins; Vitamin D Deficiency; Muscular Diseases; Models, Animal; Regeneration
PubMed: 37892452
DOI: 10.3390/nu15204377 -
Nutrients Oct 2022The non-classical role of vitamin D has been investigated in recent decades. One of which is related to its role in skeletal muscle. Satellite cells are skeletal muscle... (Review)
Review
The non-classical role of vitamin D has been investigated in recent decades. One of which is related to its role in skeletal muscle. Satellite cells are skeletal muscle stem cells that play a pivotal role in skeletal muscle growth and regeneration. This systematic review aims to investigate the effect of vitamin D on satellite cells. A systematic search was performed in Scopus, MEDLINE, and Google Scholar. In vivo studies assessing the effect of vitamin D on satellite cells, published in English in the last ten years were included. Thirteen in vivo studies were analyzed in this review. Vitamin D increases the proliferation of satellite cells in the early life period. In acute muscle injury, vitamin D deficiency reduces satellite cells differentiation. However, administering high doses of vitamin D impairs skeletal muscle regeneration. Vitamin D may maintain satellite cell quiescence and prevent spontaneous differentiation in aging. Supplementation of vitamin D ameliorates decreased satellite cells' function in chronic disease. Overall, evidence suggests that vitamin D affects satellite cells' function in maintaining skeletal muscle homeostasis. Further research is needed to determine the most appropriate dose of vitamin D supplementation in a specific condition for the optimum satellite cells' function.
Topics: Satellite Cells, Skeletal Muscle; Vitamin D; Regeneration; Muscle Development; Muscle Fibers, Skeletal; Cell Differentiation; Muscle, Skeletal; Vitamins
PubMed: 36364820
DOI: 10.3390/nu14214558 -
Pax7 Satellite Cells in Human Skeletal Muscle After Exercise: A Systematic Review and Meta-analysis.Sports Medicine (Auckland, N.Z.) Feb 2023Skeletal muscle has extraordinary regenerative capabilities against challenge, mainly owing to its resident muscle stem cells, commonly identified by Pax7, which... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Skeletal muscle has extraordinary regenerative capabilities against challenge, mainly owing to its resident muscle stem cells, commonly identified by Pax7, which expediently donate nuclei to the regenerating multinucleated myofibers. This local reserve of stem cells in damaged muscle tissues is replenished by undifferentiated bone marrow stem cells (CD34) permeating into the surrounding vascular system.
OBJECTIVE
The purpose of the study was to provide a quantitative estimate for the changes in Pax7 muscle stem cells (satellite cells) in humans following an acute bout of exercise until 96 h, in temporal relation to circulating CD34 bone marrow stem cells. A subgroup analysis of age was also performed.
METHODS
Four databases (Web of Science, PubMed, Scopus, and BASE) were used for the literature search until February 2022. Pax7 cells in human skeletal muscle were the primary outcome. Circulating CD34 cells were the secondary outcome. The standardized mean difference (SMD) was calculated using a random-effects meta-analysis. Subgroup analyses were conducted to examine the influence of age, training status, type of exercise, and follow-up time after exercise.
RESULTS
The final search identified 20 studies for Pax7 cells comprising a total of 370 participants between the average age of 21 and 74 years and 26 studies for circulating CD34 bone marrow stem cells comprising 494 participants between the average age of 21 and 67 years. Only one study assessed Pax7 cells immediately after aerobic exercise and showed a 32% reduction in exercising muscle followed by a fast repletion to pre-exercise level within 3 h. A large effect on increasing Pax7 cell content in skeletal muscles was observed 24 h after resistance exercise (SMD = 0.89, p < 0.001). Pax7 cells increased to ~ 50% above pre-exercise level 24-72 h after resistance exercise. For a subgroup analysis of age, a large effect (SMD = 0.81, p < 0.001) was observed on increasing Pax7 cells in exercised muscle among adults aged > 50 years, whereas adults at younger age presented a medium effect (SMD = 0.64, p < 0.001). Both resistance exercise and aerobic exercise showed a medium overall effect in increasing circulating CD34 cells (SMD = 0.53, p < 0.001), which declined quickly to the pre-exercise baseline level after exercise within 6 h.
CONCLUSIONS
An immediate depletion of Pax7 cells in exercising skeletal muscle concurrent with a transient release of CD34 cells suggest a replenishment of the local stem cell reserve from bone marrow. A protracted Pax7 cell expansion in the muscle can be observed during 24-72 h after resistance exercise. This result provides a scientific basis for exercise recommendations on weekly cycles allowing for adequate recovery time. Exercise-induced Pax7 cell expansion in muscle remains significant at higher age, despite a lower stem cell reserve after age 50 years. More studies are required to confirm whether Pax7 cell increment can occur after aerobic exercise.
CLINICAL TRIAL REGISTRATION
Registered at the International Prospective Register of Systematic Reviews (PROSPERO) [identification code CRD42021265457].
Topics: Adult; Humans; Young Adult; Middle Aged; Aged; Muscle, Skeletal; Exercise; Satellite Cells, Skeletal Muscle; PAX7 Transcription Factor
PubMed: 36266373
DOI: 10.1007/s40279-022-01767-z -
Frontiers in Physiology 2021Vitamin D (VD) deficiency is associated with muscle weakness. A reduction in the incidence of falls in the elderly following VD supplementation and identification of the...
Vitamin D (VD) deficiency is associated with muscle weakness. A reduction in the incidence of falls in the elderly following VD supplementation and identification of the VD receptor within muscle cells suggests a direct effect of VD on muscle, but little is known about the underlying mechanisms. Here we systematically searched the literature to identify effects of active VD [1,25(OH)2D3] on skeletal muscle myogenesis , with no restriction on year of publication. Eligibility was assessed by strict inclusion/exclusion criteria and agreed by two independent investigators. Twelve relevant pa-pers were identified using four different cell types (C2C12, primary mouse satellite cells, primary chick myoblasts, and primary human myoblasts) and a range of myogenic markers (myoD, myogenin, creatine kinase, myosin heavy chain, and myotube size). A clear inhibitory effect of 1,25(OH)2D3 on proliferation was reported, while the effects on the different stages of differentiation were less consistent probably due to variation in cell type, time points and doses of 1,25(OH)2D3 used. However, myotube size was consistently increased by 1,25(OH)2D3. Overall, the evidence suggests that 1,25(OH)2D3 inhibits proliferation and promotes differentiation of myoblasts, but future studies should use time courses to gain a clearer understanding.
PubMed: 34566700
DOI: 10.3389/fphys.2021.736708 -
Frontiers in Physiology 2021In skeletal muscle tissue, oxygen (O) plays a pivotal role in both metabolism and the regulation of several intercellular pathways, which can modify proliferation,...
In skeletal muscle tissue, oxygen (O) plays a pivotal role in both metabolism and the regulation of several intercellular pathways, which can modify proliferation, differentiation and survival of cells within the myogenic lineage. The concentration of oxygen in muscle tissue is reduced during embryogenesis and pathological conditions. Myogenic progenitor cells, namely satellite cells, are necessary for muscular regeneration in adults and are localized in a hypoxic microenvironment under the basal lamina, suggesting that the O level could affect their function. This review presents the effects of reduced oxygen levels (hypoxia) on satellite cell survival, myoblast regeneration and differentiation in vertebrates. Further investigations and understanding of the pathways involved in adult muscle regeneration during hypoxic conditions are maybe clinically relevant to seek for novel drug treatments for patients with severe muscle damage. We especially outlined the effect of hypoxia-inducible factor 1-alpha (HIF1A), the most studied transcriptional regulator of cellular and developmental response to hypoxia, whose investigation has recently been awarded with the Nobel price.
PubMed: 34248671
DOI: 10.3389/fphys.2021.684899 -
Cells Apr 2021Exercise training promotes muscle adaptation and remodelling by balancing the processes of anabolism and catabolism; however, the mechanisms by which exercise delays...
Exercise training promotes muscle adaptation and remodelling by balancing the processes of anabolism and catabolism; however, the mechanisms by which exercise delays accelerated muscle wasting are not fully understood. Intramuscular extracellular matrix (ECM) proteins are essential to tissue structure and function, as they create a responsive environment for the survival and repair of the muscle fibres. However, their role in muscle adaptation is underappreciated and underinvestigated. The PubMed, COCHRANE, Scopus and CIHNAL databases were systematically searched from inception until February 2021. The inclusion criteria were on ECM adaptation after exercise training in healthy adult population. Evidence from 21 studies on 402 participants demonstrates that exercise training induces muscle remodelling, and this is accompanied by ECM adaptation. All types of exercise interventions promoted a widespread increase in collagens, glycoproteins and proteoglycans ECM transcriptomes in younger and older participants. The ECM controlling mechanisms highlighted here were concerned with myogenic and angiogenic processes during muscle adaptation and remodelling. Further research identifying the mechanisms underlying the link between ECMs and muscle adaptation will support the discovery of novel therapeutic targets and the development of personalised exercise training medicine.
Topics: Adaptation, Physiological; Animals; Collagen; Exercise; Extracellular Matrix; Extracellular Matrix Proteins; Glycoproteins; Humans; Mice; Movement; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Neovascularization, Pathologic; Proteoglycans; Regeneration; Risk; Satellite Cells, Skeletal Muscle; Transcriptome
PubMed: 33926070
DOI: 10.3390/cells10051022 -
Frontiers in Medicine 2020Sarcopenia, which is characterized by the loss of skeletal muscle, has been reported to contribute to development of physical disabilities, various illnesses, and...
Sarcopenia, which is characterized by the loss of skeletal muscle, has been reported to contribute to development of physical disabilities, various illnesses, and increasing mortality. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit translation of target messenger RNAs. Previous studies have shown that miRNAs play pivotal roles in the development of sarcopenia. Therefore, this systematic review focuses on miRNAs that regulate sarcopenia.
PubMed: 32549041
DOI: 10.3389/fmed.2020.00180 -
British Journal of Clinical Pharmacology Jun 2021Advanced therapy medicinal products (ATMPs) represent a new category of medicinal products with a potential for transformative improvements in health outcomes but at... (Review)
Review
AIMS
Advanced therapy medicinal products (ATMPs) represent a new category of medicinal products with a potential for transformative improvements in health outcomes but at exceptionally high prices. Routine adoption of ATMPs requires robust evidence of their cost-effectiveness.
METHODS
A systematic literature review of economic evaluations of ATMPs, including gene therapies, somatic cell therapies and tissue-engineered products, was conducted. Literature was searched using MedLine, Embase, PubMed, Cochrane Register, the NHS Economic Evaluation Database and the grey literature of health technology assessment organisations with search terms relating to ATMPs and economic evaluations. Titles were screened independently by 2 reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts reviewed. Study findings were appraised critically.
RESULTS
4514 articles were identified, of which 23 met the inclusion criteria. There was some evidence supporting the cost-effectiveness of: chimeric antigen receptor T-cell therapy axicabtagene-ciloleucel (Yescarta), embryonic neural stem cells, tumour infiltrating lymphocytes, in vitro expanded myoblast, autologous chondrocyte implantation, ex vivo gene therapy (Strimvelis) and voretigene neparvovec (Luxturna). However, estimates of cost-effectiveness were associated with significant uncertainty and high likelihood of bias, resulting from largely unknown long-term outcomes, a paucity of evidence on health state utilities and extensive modelling assumptions.
CONCLUSION
There are critical limitations to the economic evidence for ATMPs, most notably in relation to evidence on the durability of treatment effect, and the reliability of opinion-based assumptions necessary when evidence is absent.
Topics: Cost-Benefit Analysis; Reproducibility of Results; Technology Assessment, Biomedical
PubMed: 32154598
DOI: 10.1111/bcp.14275 -
Journal of Cardiovascular... Nov 2019The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD).
METHODS AND RESULTS
PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups.
CONCLUSION
Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.
Topics: Aged; Arrhythmias, Cardiac; Chronic Disease; Death, Sudden, Cardiac; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Randomized Controlled Trials as Topic; Recovery of Function; Risk Assessment; Risk Factors; Stem Cell Transplantation; Time Factors; Treatment Outcome; Ventricular Function; Ventricular Remodeling
PubMed: 31535744
DOI: 10.1111/jce.14185