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Sergio Adamo prematurely left us on January 7th 2022, just one year after his retirement, leaving his family, friends and colleagues deeply sad and grieving. Sergio was a full Professor of Histology and Embryology at the Sapienza University of Rome. Since the foundation of the Institute of Histology and Embryology more than 50 years ago, he dedicated himself to the institution, research, and teaching with integrity, generosity, and a great sense of teamwork. Sergio's main research interests have been the mechanisms of myogenesis, muscle homeostasis and regeneration under normal and pathological conditions. Most relevant results obtained by Sergio and his collaborators indicate novel functions for the neurohypophyseal hormones, vasopressin and oxytocin, upon striated muscle differentiation, trophism, and homeostasis. Here we like to give the proper tribute to a mentor, a colleague and a sincere friend. He left an indelible mark on the professional and personal lives of all of us and his absence provokes a profound sense of emptiness.

Chronic cardiac muscle inflammation and subsequent fibrotic tissue deposition are key features in Duchenne Muscular Dystrophy (DMD). The treatment of choice for delaying DMD progression both in skeletal and cardiac muscle are corticosteroids, supporting the notion that chronic inflammation in the heart plays a pivotal role in fibrosis deposition and subsequent cardiac dysfunction. Nevertheless, considering the adverse effects associated with long-term corticosteroid treatments, there is a need for novel anti-inflammatory therapies. In this study, we used our recently described exercised mdx ( ex mdx ) mouse model characterised by accelerated heart pathology, and the specific PKCθ inhibitor Compound 20 (C20), to show that inhibition of this kinase leads to a significant reduction in the number of immune cells infiltrating the heart, as well as necrosis and fibrosis. Functionally, C20 treatment also prevented the reduction in left ventricle fractional shortening, which was typically observed in the vehicle-treated ex mdx mice. Based on these findings, we propose that PKCθ pharmacological inhibition could be an attractive therapeutic approach to treating dystrophic cardiomyopathy.

Chronic cardiac muscle inflammation and fibrosis are key features of Duchenne Muscular Dystrophy (DMD). Around 90% of 18-year-old patients already show signs of DMD-related cardiomyopathy, and cardiac failure is rising as the main cause of death among DMD patients. The evaluation of novel therapies for the treatment of dystrophic heart problems depends on the availability of animal models that closely mirror the human pathology. The widely used DMD animal model, the mdx mouse, presents a milder cardiac pathology compared to humans, with a late onset, which precludes large-scale and reliable studies. In this study, we used an exercise protocol to accelerate and worsen the cardiac pathology in mdx mice. The mice were subjected to a 1 h-long running session on a treadmill, at moderate speed, twice a week for 8 weeks. We demonstrate that subjecting young mdx mice (4-week-old) to "endurance" exercise accelerates heart pathology progression, as shown by early fibrosis deposition, increases necrosis and inflammation, and reduces heart function compared to controls. We believe that our exercised mdx model represents an easily reproducible and useful tool to study the molecular and cellular networks involved in dystrophic heart alterations, as well as to evaluate novel therapeutic strategies aimed at ameliorating dystrophic heart pathology.

Satellite cells (SCs) are muscle stem cells that remain quiescent during homeostasis and are activated in response to acute muscle damage or in chronic degenerative conditions such as Duchenne Muscular Dystrophy. The activity of SCs is supported by specialized cells which either reside in the muscle or are recruited in regenerating skeletal muscles, such as for instance macrophages (MΦs). By using a dystrophic mouse model of transient MΦ depletion, we describe a shift in identity of muscle stem cells dependent on the crosstalk between MΦs and SCs. Indeed MΦ depletion determines adipogenic conversion of SCs and exhaustion of the SC pool leading to an exacerbated dystrophic phenotype. The reported data could also provide new insights into therapeutic approaches targeting inflammation in dystrophic muscles., Competing Interests: The authors have declared that no competing interests exist.

Skeletal muscle is a dynamic tissue capable of responding to a large variety of physiological stimuli by adjusting muscle fiber size, metabolism and function. However, in pathological conditions such as cancer and neural disorders, this finely regulated homeostasis is impaired leading to severe muscle wasting, reduced muscle fiber size (atrophy), and impaired function. These disease features develop due to enhanced protein breakdown, which relies on two major degradation systems: the ubiquitin-proteasome and the autophagy-lysosome. These systems are independently regulated by different signalling pathways, which in physiological conditions, determine protein and organelle turnover. However, alterations in one or both systems, as it happens in several disorders, leads to enhanced protein breakdown and muscle atrophy. Although this is a common feature in the different types of muscle atrophy, the relative contribution of each of these systems is still under debate. Here, we will briefly describe the regulation and the activity of the ubiquitin-proteasome and the autophagy-lysosome systems during muscle wasting. We will then discuss what we know regarding how these pathways are involved in cancer induced and in neurogenic muscle atrophy, highlighting common and divergent paths. It is now clear that there is no one unifying common mechanism that can be applied to all models of muscle loss. Detailed understanding of the pathways and proteolysis mechanisms involved in each model will hopefully help the development of drugs to counteract muscle wasting in specific conditions., Competing Interests: Conflict of Interest None of the authors have conflicts of interests.

Single myofiber isolation protocols allow to obtain an in vitro system in which the physical association between the myofiber and its stem cells, the satellite cells, is adequately preserved. This technique is an indispensable tool by which the muscle regeneration process can be recapitulated and studied in each specific phase, from satellite cell activation to proliferation, from differentiation to fusion. This study aims to clarify the effect of different culture conditions on single myofibers, their associated satellite cells, and the physiological behavior of the satellite cells upon long term culture. By direct observations of the cultures, we compared different experimental conditions and their effect on both satellite cell behavior and myofiber viability., Competing Interests: Conflict of Interest: The authors declare that there is no conflict of interest regarding the publication of this article.

Aim: Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear., Results: Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration., Innovation: The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity., Conclusions: Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

In skeletal muscle, the resting chloride conductance (gCl), due to the ClC-1 chloride channel, controls the sarcolemma electrical stability. Indeed, loss-of-function mutations in ClC-1 gene are responsible of myotonia congenita. The ClC-1 channel can be phosphorylated and inactivated by protein kinases C (PKC), but the relative contribution of each PKC isoforms is unknown. Here, we investigated on the role of PKCθ in the regulation of ClC-1 channel expression and activity in fast- and slow-twitch muscles of mouse models lacking PKCθ. Electrophysiological studies showed an increase of gCl in the PKCθ-null mice with respect to wild type. Muscle excitability was reduced accordingly. However, the expression of the ClC-1 channel, evaluated by qRT-PCR, was not modified in PKCθ-null muscles suggesting that PKCθ affects the ClC-1 activity. Pharmacological studies demonstrated that although PKCθ appreciably modulates gCl, other isoforms are still active and concur to this role. The modification of gCl in PKCθ-null muscles has caused adaptation of the expression of phenotype-specific genes, such as calcineurin and myocyte enhancer factor-2, supporting the role of PKCθ also in the settings of muscle phenotype. Importantly, the lack of PKCθ has prevented the aging-related reduction of gCl, suggesting that its modulation may represent a new strategy to contrast the aging process.

This study intended to demonstrate that the thyroid hormone T3 counteracts the onset of a Streptozotocin (STZ) induced diabetes in wild type mice. To test our hypothesis diabetes has been induced in Balb/c male mice by multiple low dose Streptozotocin injection; and a group of mice was contemporaneously injected with T3. After 48 h mice were tested for glucose tolerance test, insulin serum levels and then sacrificed. Whole pancreata were utilized for morphological and biochemical analyses, while protein extracts and RNA were utilized for expression analyses of specific molecules. The results showed that islets from T3 treated mice were comparable to age- and sex-matched control, untreated mice in number, shape, dimension, consistency, ultrastructure, insulin and glucagon levels, Tunel positivity and caspases activation, while all the cited parameters and molecules were altered by STZ alone. The T3-induced pro survival effect was associated with a strong increase in phosphorylated Akt. Moreover, T3 administration prevented the STZ-dependent alterations in glucose blood level, both during fasting and after glucose challenge, as well as in insulin serum level. In conclusion we demonstrated that T3 could act as a protective factor against STZ induced diabetes.

After a brief consideration of the recent therapeutic approaches to endometriosis, the Authors suggest their laparoscopic method which includes drainage by aspiration of the endometrioma using a wide biopsy, followed by careful lavage of the cystic cavity and abdomen and partial thermocoagulation of the same capsule and any visible residual implants. The patients were admitted for infertility in 47% of cases, chorionic pelvic pain in 16% of cases and pelvic mass in 10%. By using this procedure symptomatic relief was seen in 72% of cases and a pregnancy rate of 81% obtained with encouraging results even in moderate and severe endometriosis.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces, in cultured chick embryo fibroblasts, a generalised increase of the incorporation of labelled inorganic phosphate, and stimulates the phosphorylation of at least two polypeptide bands, 26 K and 65 K. Stimulation of the phosphorylation of 26 K and 65 K occurs within minutes of the addition of TPA to the culture medium of chick embryo fibroblasts, but it can also be evidenced at later times. Removal of TPA from the culture medium causes reversion of this effect. Stimulation of the phosphorylation of 26 K is also induced by the Ca2+-ionophore A23187, but the calmodulin inhibitor trifluoperazine does not inhibit the TPA induced stimulation of polypeptide phosphorylation. Agents increasing the intracellular cAMP concentration do not stimulate the phosphorylation of 26 K and 65 K. The results obtained suggest that the phosphorylation of specific polypeptides, probably induced by TPA through a Ca2+-phospholipid dependent mechanism, may represent an early regulative event which may be relevant for the pleiotropic effect of TPA in cultured normal cells.