1. Targeting skeletal muscle melatonin-MT2 signaling to attenuate the obesity-cancer axis : a metabolic perspectiveMihaela Jurdana, Lovro Žiberna, 2026, review article Abstract: Obesity and metabolic syndrome promote malignancies through chronic inflammation and sustained activation of insulin and insulin-like growth factor-1 (IGF-1) signaling. Skeletal muscle is central to this tumor-promoting milieu because it governs insulin-stimulated glucose disposal, lipid oxidation, and endocrine crosstalk. This narrative review explores whether melatonin signaling in skeletal muscle, particularly via melatonin receptor 2 (MT2), represents a modifiable node within the obesity–cancer axis. Experimental evidence indicates that melatonin activates MT2-linked Gi/o and calcium-sensitive pathways converging on phosphoinositide 3-kinase–protein kinase B (PI3K–Akt), extracellular signal-regulated kinases (ERK), and calcium/calmodulin-dependent protein kinase II–adenosine monophosphate-activated protein kinase–peroxisome proliferator-activated receptor gamma coactivator 1-alpha (CaMKII–AMPK–PGC-1α) signaling. These pathways enhance insulin sensitivity, mitochondrial function, and lipid partitioning while reducing myosteatosis and cellular stress. By improving muscle quality, melatonin may lower systemic insulin and IGF-1 drive and inflammatory adipokine tone that fuel tumor-promoting PI3K–Akt–mammalian target of rapamycin (mTOR) signaling. However, human evidence remains limited and timing-dependent. Melatonin exposure in the fed state or near carbohydrate intake may worsen glycemia, particularly in carriers of melatonin receptor 1B (MTNR1B) risk alleles. Chronobiology-informed, genotype-guided trials with detailed muscle phenotyping and cancer-relevant endpoints are warranted.
Keywords: melatonin, melatonin receptor 1, melatonin receptor 2, melatonin receptor 1A gene, melatonin receptor 1B gene, skeletal muscle, insulin resistance, myosteatosis, sarcopenic obesity, myokines, obesity-related cancer
Published in RUP: 26.03.2026; Views: 402; Downloads: 25
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2. Circular RNAs and their emerging roles in muscular immune-related diseasesFelicita Urzi, Anja Srpčič, Katja Lakota, 2025, review article Abstract: Circular RNAs (circRNAs) have recently emerged as a highly stable and versatile class of non-coding RNAs that play critical roles in gene regulation, yet their involvement in immune-mediated muscle disorders remains largely underexplored. This review synthesizes how circRNAs influence key processes in both skeletal muscle and immune cells, from myogenesis, regeneration, and muscle stem cell function to inflammatory signaling and muscle wasting. Our aim was to identify circRNA insights across muscle immune-mediated diseases. However, we found no idiopathic inflammatory myopathy-focused circRNA studies, only a limited body of work in Duchenne muscular dystrophy, and predominantly peripheral blood mononuclear cell-based evidence in myasthenia gravis. These gaps highlight clear priorities: subtype-resolved circRNA atlases for idiopathic inflammatory myopathy; paired muscle–biofluid and cell-type–resolved profiling (including infiltrating immune populations); rigorous in vivo functional validation beyond correlative expression; fuller mechanistic delineation beyond miRNA competition (e.g., RNA binding protein interactions, translation, epigenetic regulation); and longitudinal cohorts linking circRNA dynamics to disease activity and treatment response. We particularly noted lack of in-depth studies addressing the interplay between muscle and immune cells in these conditions. Furthermore, we examine pioneering efforts to engineer circRNAs as therapeutic agents, capable of either neutralizing pathogenic pathways that drive muscle atrophy or restoring dystrophin expression in genetic disease models. Finally, we outline future directions for circRNA profiling in patient tissues and biofluids, rigorous functional validation in vivo, and the development of circRNA-based diagnostics. This positions circRNAs at the forefront of next-generation strategies for understanding and combating immune-related muscular disorders.
Keywords: circular RNA, skeletal muscle, immune cells, idiopathic inflammatory myopathies, Duchenne muscular dystrophy, myasthenia gravis
Published in RUP: 18.11.2025; Views: 680; Downloads: 3
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3. Radiation-induced impairment of skeletal muscle regenerationMaja Čemažar, Mihaela Jurdana, 2025, review article Abstract: Background. Radiotherapy is a cornerstone of treatment for various cancers, but often causes collateral damage to surrounding healthy tissue, including skeletal muscle. Ionizing radiation leads to oxidative stress and inflammation, which impairs the regenerative capacity of muscle tissue. Irradiation reduces the number and functionality of satellite cells and disrupts the tightly regulated processes of myogenesis and tissue remodelling. In addition, irradiation alters the muscle microenvironment by promoting fibrosis and vascular damage, which further impedes effective regenera-tion. Cytokine signalling pathways are also dysregulated following irradiation, contributing to impaired activation and differentiation of satellite cells. Conclusions. There is evidence that factors such as melatonin and growth factors can improve muscle regenera-tion. Understanding the molecular and cellular mechanisms underlying the impairment of muscle regeneration after radiotherapy is crucial for the development of targeted strategies to mitigate side effects and improve patients’ qual-ity of life. Overall, the preservation and restoration of muscle function in irradiated tissue remains a critical challenge that requires multidisciplinary approaches
Keywords: skeletal muscle, radiotherapy, muscle regeneration, melatonine
Published in RUP: 11.09.2025; Views: 807; Downloads: 1
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4. Single muscle fibre contractile properties differ between body-builders, power athletes and control subjectsJ. P. Meijer, R. T. Jaspers, Joern Rittweger, Olivier Seynnes, S. Kamandulis, M. Brazaitis, A. Skurvydas, Rado Pišot, Boštjan Šimunič, Marco Vincenzo Narici, Hans Degens, 2015, original scientific article Keywords: skeletal muscles, muscle fibers, contractile properties, body-builders, power athletes
Published in RUP: 08.08.2016; Views: 6719; Downloads: 212
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5. Costamere remodeling with muscle loading and unloading in healthy young menRuowei Li, Marco Vincenzo Narici, Robert M. Erskine, Olivier Seynnes, Joern Rittweger, Rado Pišot, Boštjan Šimunič, M. Flück, 2013, original scientific article Keywords: costamere, atrophy, focal adhesion kinase, hypertrophy, physical inactivity, bed rest, skeletal muscle, myofibril, vinculin
Published in RUP: 15.10.2013; Views: 6148; Downloads: 163
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6. Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance trainingDesy Salvadego, R. Domenis, Stefano Lazzer, Simone Porcelli, Joern Rittweger, Giovanna Rizzo, I. Mavelli, Boštjan Šimunič, Rado Pišot, Bruno Grassi, 2013, original scientific article Abstract: Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA, body mass 102.67.3 kg, meanSD) and 11 controls (CTRL, body mass 77.86.0). Pulmonary O2 uptake (V'O2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross sectional area, volume (determined by magnetic resonance imaging) and strength were greater in RTA vs. CTRL (by ~40%, ~33% and ~20%, respectively). V'O2peak during CE was higher in RTA vs. CTRL (4.050.64 L min-1 vs. 3.560.30); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE) V'O2peak was lower (by 15-20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, both during CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.723.7 pmolO2s-1mg-1 ww) vs. CTRL (35.710.2), and a tighter coupling of oxidative phosphorylation. In RTA the greater muscle mass and maximal force, and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise, and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mass
Keywords: skeletal muscle, hypertrophy, mitochondrial respiration, oxidative metabolism, exercise
Published in RUP: 15.10.2013; Views: 7261; Downloads: 168
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7. Functional impairment of skeletal muscle oxidative metabolism during knee-extension exercise after bed restDesy Salvadego, Stefano Lazzer, Mauro Marzorati, Simone Porcelli, Enrico Rejc, Boštjan Šimunič, Rado Pišot, Pietro Enrico Di Prampero, Bruno Grassi, 2011, original scientific article Keywords: microgravity, muscle atrophy, physical deconditioning, exercise tolerance, near-infared spectroscopy, skeletal muscle, bed rest
Published in RUP: 15.10.2013; Views: 8086; Downloads: 306
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