Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

• MeSH
• Cell Differentiation * MeSH
• Adult MeSH
• Gene Fusion MeSH
• Oncogene Proteins, Fusion genetics   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   analysis   MeSH
• Bone Neoplasms * genetics   pathology   MeSH
• Soft Tissue Neoplasms * genetics   pathology   MeSH
• Aged MeSH
• Trans-Activators genetics   MeSH
• Transcription Factors * genetics   MeSH
• Muscle Development genetics   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

The nuclear pore complex (NPC) has emerged as a hub for the transcriptional regulation of a subset of genes, and this type of regulation plays an important role during differentiation. Nucleoporin TPR forms the nuclear basket of the NPC and is crucial for the enrichment of open chromatin around NPCs. TPR has been implicated in the regulation of transcription; however, the role of TPR in gene expression and cell differentiation has not been described. Here we show that depletion of TPR results in an aberrant morphology of murine proliferating C2C12 myoblasts (MBs) and differentiated C2C12 myotubes (MTs). The ChIP-Seq data revealed that TPR binds to genes linked to muscle formation and function, such as myosin heavy chain (Myh4), myocyte enhancer factor 2C (Mef2C) and a majority of olfactory receptor (Olfr) genes. We further show that TPR, possibly via lysine-specific demethylase 1 (LSD1), promotes the expression of Myh4 and Olfr376, but not Mef2C. This provides a novel insight into the mechanism of myogenesis; however, more evidence is needed to fully elucidate the mechanism by which TPR affects specific myogenic genes.

• MeSH
• Cell Differentiation MeSH
• Cell Line MeSH
• Gene Expression MeSH
• Nuclear Pore Complex Proteins metabolism   MeSH
• Muscle Fibers, Skeletal * cytology   metabolism   MeSH
• Myoblasts, Skeletal * cytology   metabolism   MeSH
• Mice MeSH
• Proto-Oncogene Proteins metabolism   MeSH
• Gene Expression Regulation MeSH
• Myosin Heavy Chains metabolism   MeSH
• Muscle Development MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

External load influences internal load in resistance training (RT). The purpose of the present study was to compare the total volume-load, perceptual and stress responses during three different RT protocols. Twelve resistance-trained men completed three different RT protocols with the back squat and bench press exercises: (1) power (POW) (5 sets of 6 repetitions at 50%1RM, 2-min of rest), (2) hypertrophy (HYP) (5 sets-to-failure at 75%1RM, 2-min of rest), and (3) strength (STR) (5 sets-to-failure at 90%1RM, 3-min of rest). Volume-load (kg × reps.), session rating of perceived exertion (sRPE), training impulse (TRIMP; reps. × sRPE), cortisol, immunoglobulin A (IgA), lactate, and creatine kinase (CK) were assessed before and/or after the sessions. HYP was the most demanding session in terms of volume-load (p < 0.001), TRIMP (p < 0.001), cortisol (p = 0.001), lactate (p < 0.001), and CK (p = 0.001). Despite POW exhibited a greater volume-load than STR (p = 0.016), the latter exhibiting a greater sRPE (p < 0.001), and a greater post-session CK (p = 0.05). However, the TRIMP of STR and POW were not statistically different (152 vs. 260 AU; p = 0.089). These specific responses could be meditated by the presence of muscular failure. When pooling all the sessions, significant correlations were revealed among external and internal stress markers (r = 0.35-0.80; p ≤ 0.05). The use of TRIMP could be recommended as a simple and valid monitoring tool which integrates into a single parameter the internal and the external loads of RT sessions.

• MeSH
• Analysis of Variance MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• Hydrocortisone blood   MeSH
• Hypertrophy MeSH
• Immunoglobulin A blood   MeSH
• Creatine Kinase blood   MeSH
• Lactic Acid blood   MeSH
• Humans MeSH
• Young Adult MeSH
• Resistance Training methods   MeSH
• Muscle Strength physiology   MeSH
• Physical Exertion physiology   MeSH
• Muscle Development physiology   MeSH
• Weight Lifting physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

Bigorexie byla poprvé zmíněna na počátku 20. století ve Spojených státech amerických. Jedná se o zatím neukotvenou nemoc s prvky obsedantně kompulzivní poruchy, která se vyznačuje posedlostí vzhledem svého těla, obavou nad dostatkem svalů a nutkající potřebou nadměrného fyzického cvičení. Porucha může být příčinou dalších závažných onemocnění a je také často spojená se závislostí na anabolických steroidech či jiných návykových látkách. Cílem předkládaného článku je poskytnutí základních informací o problému bigorexie, včetně diagnostiky, léčby tohoto onemocnění a zabývá se také možnými zdravotními/sociálními riziky u osob trpících bigorexií. Předkládaný text je souborem výsledků stávající literatury v oblasti svalové dysmorfie, čerpané z vědeckých databází Web of Science, PubMed, Scopus a dalších příbuzných databází. Prohledané odborné články nebyly limitovány datem vydání, neboť původní práce poskytují vhled do prvopočátečního zkoumání bigorexie a zmapování tohoto onemocnění. Vyhledávání proběhlo pomocí klíčových slov vázajících se k dané problematice, vědecké články byly doplněny diagnostickými a statistickými manuály a monografií. Výzkumem bylo zjištěno, že problematikou bigorexie se převážně zabývají zahraniční země, v České republice prozatím chybí relevantní data týkající se tohoto onemocnění. Stávající výzkumy v zahraničí jsou aplikované zejména na mužskou populaci, chybějící data jsou převážně u ženské populace.

Bigorexia was first mentioned in the early 20th century in the USA. It is an unanchored disease with elements of obsessive-compulsive disorder. It is characterized by an obsession with the appearance of one's body, fear of not having enough muscles, and the urgent need for excessive physical exercise. The disorder can cause other serious illnesses and is also often associated with dependence on anabolic steroids or other addictive substances. The aim of this article is to provide basic information about the problem of bigorexia, including the diagnosis and treatment. It also deals with the possible health and social risks in people suffering from bigorexia. This article presents a set of results of the existing literature in the field of muscle dysmorphia from Web of Science, PubMed, Scopus and other related scientific databases. The studied professional articles were not limited by the date of publication, as the original works provide insight into the initial investigation of bigorexia and the mapping of this disease. The search was performed using keywords related to the issue. The scientific articles were supplemented by diagnostic and statistical manuals and monographs. The research revealed that the issue of bigorexia is mainly dealt with in foreign countries. In the Czech Republic, relevant data regarding this disease is currently lacking. The existing foreign research has mainly been applied to the male population. The data in the female population is mostly missing.

• Keywords
• bigorexie,
• MeSH
• Humans MeSH
• Body Dysmorphic Disorders * MeSH
• Muscle Development MeSH
• Check Tag
• Humans MeSH

Gene silencing with virally delivered shRNA represents a promising approach for treatment of inherited neurodegenerative disorders. In the present study we develop a subpial technique, which we show in adult animals successfully delivers adeno-associated virus (AAV) throughout the cervical, thoracic and lumbar spinal cord, as well as brain motor centers. One-time injection at cervical and lumbar levels just before disease onset in mice expressing a familial amyotrophic lateral sclerosis (ALS)-causing mutant SOD1 produces long-term suppression of motoneuron disease, including near-complete preservation of spinal α-motoneurons and muscle innervation. Treatment after disease onset potently blocks progression of disease and further α-motoneuron degeneration. A single subpial AAV9 injection in adult pigs or non-human primates using a newly designed device produces homogeneous delivery throughout the cervical spinal cord white and gray matter and brain motor centers. Thus, spinal subpial delivery in adult animals is highly effective for AAV-mediated gene delivery throughout the spinal cord and supraspinal motor centers.

• MeSH
• Amyotrophic Lateral Sclerosis genetics   physiopathology   therapy   MeSH
• Atrophy MeSH
• Nerve Degeneration genetics   physiopathology   therapy   MeSH
• Dependovirus metabolism   MeSH
• Interneurons pathology   MeSH
• Humans MeSH
• RNA, Small Interfering administration & dosage   MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Spinal Cord diagnostic imaging   pathology   physiopathology   MeSH
• Evoked Potentials, Motor MeSH
• Motor Neurons pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Pia Mater pathology   physiopathology   MeSH
• Swine MeSH
• Primates MeSH
• Disease Progression MeSH
• Gene Expression Regulation MeSH
• Protein Folding MeSH
• Superoxide Dismutase-1 genetics   metabolism   MeSH
• Gene Transfer Techniques * MeSH
• Gene Silencing * MeSH
• Muscle Development MeSH
• Inflammation pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Ammonia is very toxic to the body and has detrimental effects on many different organ systems. Using cultured myoblast cells, we examined ammonia's effect on myostatin expression, a negative regulator of skeletal muscle growth, and myotube diameters. The objective of this study was to examine how murine, avian, and fish cells respond to increasing levels of ammonia up to 50 mM. The murine myoblast cell line (C2C12), primary chick, and primary tilapia myoblast cells were cultured and then exposed to 10, 25, and 50 mM ammonium acetate, sodium acetate, and an untreated control for 24 h. High levels of ammonia were detrimental to the C2C12 cells, causing increased Myostatin (MSTN) expression and decreased myotube diameters between 10 and 25 mM (p < 0.002). Ammonia at 10 mM continued the positive myogenic response in the chick, with lower MSTN expression than the C2C12 cells and larger myotube diameters, but the myotube diameter at 50 mM ammonium acetate was significantly smaller than those at 10 and 25 mM (p < 0.001). However, chick myotubes at 50 mM were still significantly larger than the sodium acetate-treated and untreated control (p < 0.001). The tilapia cells showed no significant difference in MSTN expression or myotube diameter in response to increasing the concentrations of ammonia. Overall, these results confirm that increasing concentrations of ammonia are detrimental to mammalian skeletal muscle, while chick cells responded positively at lower levels but began to exhibit a negative response at higher levels, as the tilapia experienced no detrimental effects. The differences in ammonia metabolism strategies between fish, avian, and mammalian species could potentially contribute to the differences between species in response to high levels of ammonia. Understanding how ammonia affects skeletal muscle is important for the treatment of muscle wasting observed in liver failure patients.

• MeSH
• Ammonia pharmacology   MeSH
• Cell Differentiation * MeSH
• Muscle, Skeletal drug effects   metabolism   pathology   MeSH
• Humans MeSH
• Myostatin genetics   metabolism   MeSH
• Mice MeSH
• Birds MeSH
• Gene Expression Regulation drug effects   MeSH
• Fishes MeSH
• Muscle Development * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Typically, mammalian and avian models have been used to examine the effects of ammonia on skeletal muscle. Hyperammonemia causes sarcopenia or muscle wasting, in mammals and has been linked to sarcopenia in liver disease patients. Avian models of skeletal muscle have responded positively to hyperammonemia, differing from the mammalian response. Fish skeletal muscle has not been examined as extensively as mammalian and avian muscle. Fish skeletal muscle shares similarities with avian and mammalian muscle but has notable differences in growth, fiber distribution, and response to the environment. The wide array of body sizes and locomotion needs of fish also leads to greater diversity in muscle fiber distribution and growth between different fish species. The response of fish muscle to high levels of ammonia is important for aquaculture and quality food production but has not been extensively studied to date. Understanding the differences between fish, mammalian and avian species' myogenic response to hyperammonemia could lead to new therapies for muscle wasting due to a greater understanding of the mechanisms behind skeletal muscle regulation and how ammonia effects these mechanisms. This paper provides an overview of fish skeletal muscle and ammonia excretion and toxicity in fish, as well as a comparison to avian and mammalian species.

• MeSH
• Ammonia pharmacology   toxicity   MeSH
• Hyperammonemia etiology   MeSH
• Liver Cirrhosis etiology   MeSH
• Muscle Fibers, Skeletal drug effects   MeSH
• Muscle, Skeletal drug effects   metabolism   MeSH
• Birds MeSH
• Fishes MeSH
• Sarcopenia etiology   MeSH
• Mammals MeSH
• Muscular Atrophy metabolism   physiopathology   MeSH
• Muscle Development drug effects   physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Therefore, we aimed to develop a functionalized electrospun mesh that promotes tissue ingrowth and provides adequate mechanical strength and compliance during degradation. We describe the in vivo function of a new supramolecular bioactivated polycarbonate (PC) material based on fourfold hydrogen bonding ureidopyrimidinone (UPy) units (UPy-PC). The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Morphometric analysis of the musculofascial content during wound healing showed that cRGD functionalization promotes myogenesis with inhibition of collagen deposition at 14 days. It also prevents muscle atrophy at 90 days and exerts an immunomodulatory effect on infiltrating macrophages at 14 days and foreign body giant cell formation at 14 and 90 days. Additionally, the bioactivated material promotes neovascularization and connective tissue ingrowth. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in the rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. Our results provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP. STATEMENT OF SIGNIFICANCE: Development of biomaterials for hernia and pelvic organ prolapse (POP) repair is encouraged because of high local complication rates with current materials. Ureidopyrimidinone-polycarbonate is a elastomeric and biodegradable electrospun mesh, which could mimic physiological compliance. The UPy-PC material was functionalized with UPy-modified cyclic arginine-glycine-aspartic acid (cRGD) peptide additives. Supramolecular cRGD-bioactivation of UPy-PC-meshes promotes integration of the implant, accelerates tissue ingrowth and reduces scar formation, resulting in physiological neotissue formation when used for abdominal wall reconstruction in rat hernia model. Moreover, cRGD-bioactivation prevents muscle atrophy and modulates the inflammatory response. These data provide a promising outlook towards a new type of biomaterial for the treatment of hernia and POP.

• MeSH
• Biocompatible Materials chemistry   pharmacology   MeSH
• Abdominal Wall surgery   MeSH
• Surgical Mesh * MeSH
• Cartilage metabolism   MeSH
• Peptides, Cyclic chemistry   pharmacology   MeSH
• Granuloma prevention & control   MeSH
• Polycarboxylate Cement chemistry   pharmacology   MeSH
• Rats, Sprague-Dawley MeSH
• Pyrimidinones chemistry   pharmacology   MeSH
• Muscular Atrophy prevention & control   MeSH
• Muscle Development drug effects   MeSH
• Inflammation prevention & control   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Rhabdomyosarcoma (RMS) is a malignant tumour of soft tissues, occurring mainly in children and young adults. RMS cells derive from muscle cells, which due to mutations and epigenetic modifications have lost their ability to differentiate. Epigenetic modifications regulate expression of genes responsible for cell proliferation, maturation, differentiation and apoptosis. HDAC inhibitors suppress histone acetylation; therefore, they are a promising tool used in cancer therapy. Trichostatin A (TsA) is a pan-inhibitor of HDAC. In our study, we investigated the effect of TsA on RMS cell biology. Our findings strongly suggest that TsA inhibits RMS cell proliferation, induces cell apoptosis, and reactivates tumour cell differentiation. TsA up-regulates miR-27b expression, which is involved in the process of myogenesis. Moreover, TsA increases susceptibility of RMS cells to routinely used chemotherapeutics. In conclusion, TsA exhibits anti-cancer properties, triggers differentiation, and thereby can complement an existing spectrum of chemotherapeutics used in RMS therapy.

• MeSH
• Acetylation drug effects   MeSH
• Apoptosis drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Epigenesis, Genetic drug effects   genetics   MeSH
• Histone Deacetylase Inhibitors pharmacology   MeSH
• Hydroxamic Acids pharmacology   MeSH
• Humans MeSH
• MicroRNAs metabolism   MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation drug effects   MeSH
• Rhabdomyosarcoma metabolism   MeSH
• Muscle Development drug effects   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The biochemical properties of muscle extracellular matrix are essential for stem cell adhesion, motility, proliferation and myogenic development. Recombinant elastin-like polypeptides are synthetic polypeptides that, besides maintaining some properties of the native protein, can be tailored by fusing bioactive sequences to their C-terminal. Our laboratory synthesized several Human Elastin-Like Polypeptides (HELP) derived from the sequence of human tropoelastin. Here, we developed a novel HELP family member by fusing the elastin-like backbone to the sequence of human Epidermal Growth Factor. We employed this synthetic protein, named HEGF, either alone or in combination with other proteins of the HELP family carrying RGD-integrin binding sites, as adhesion substrate for C2C12 myoblasts and satellite cells primary cultures. Adhesion of myoblasts to HEGF-based substrates induced scattering, decreased adhesion and cytoskeleton assembly; the concomitant presence of the RGD motifs potentiated all these effects. Recombinant substrates induced myoblasts proliferation, differentiation and the development of multinucleated myotubes, thus favoring myoblasts expansion and preserving their myogenic potential. The effects induced by adhesion substrates were inhibited by AG82 (Tyrphostin 25) and herbimycin A, indicating their dependence on the activation of both the EGF receptor and the tyrosine kinase c-src. Finally, HEGF increased the number of muscle stem cells (satellite cells) derived from isolated muscle fibers in culture, thus highlighting its potential as a novel substrate for skeletal muscle regeneration strategies.

• MeSH
• Cell Adhesion physiology   MeSH
• Cell Differentiation physiology   MeSH
• Epidermal Growth Factor metabolism   physiology   MeSH
• Extracellular Matrix MeSH
• Stem Cells cytology   MeSH
• Muscle Fibers, Skeletal cytology   MeSH
• Muscle, Skeletal cytology   MeSH
• Cells, Cultured MeSH
• Myoblasts cytology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Cell Movement physiology   MeSH
• Primary Cell Culture MeSH
• Cell Proliferation physiology   MeSH
• Satellite Cells, Skeletal Muscle metabolism   physiology   MeSH
• Signal Transduction MeSH
• Muscle Development physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH