Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma primarily affecting children and young adults. This disease is more prevalent in children under 15, with two main types: embryonal Rhabdomyosarcoma (eRMS), which has a better prognosis, and alveolar Rhabdomyosarcoma (aRMS), which is more aggressive and associated with specific genetic alterations. The PI3K-Akt-mTOR pathway is often hyperactivated in RMS, contributing to cell proliferation, survival, and resistance to therapies. The presence of phosphorylated components of this pathway correlates with poor survival outcomes. Here, we discuss various therapeutic approaches targeting the PI3K-Akt-mTOR pathway. These include the use of specific inhibitors (e.g., PI3K inhibitors, Akt inhibitors) and combination therapies that may enhance treatment efficacy. Dietary supplements like curcumin and repurposed drugs such as chloroquine are also mentioned for their potential to induce apoptosis in RMS cells. We also emphasize the need for innovative strategies to improve survival rates, which have remained stagnant over the years. Targeting super-enhancers and transcription factors associated with RMS may provide new therapeutic avenues. Overall, this review underscores the critical role of the PI3K-Akt-mTOR pathway in RMS and the potential for targeted therapies to improve patient outcomes.

Prolonged exposure to high dosages of dexamethasone, which is a synthetic glucocorticoid and a well-known anti-inflammatory drug, may lead to an increase in reactive oxygen species production, contributing to muscle wasting. The prevention of muscle atrophy by ingestion of functional foods is an attractive issue. In the last decade, natural antioxidant compounds have been increasingly investigated as promising molecules able to counteract oxidative-stress-induced muscle atrophy. Recently, we have demonstrated the antioxidant properties of two main olive oil polyphenols also known for their anticancer and anti-inflammatory activities in different cell models. Here, the preventive effect of tyrosol on dexamethasone-induced muscle atrophy has been investigated by means of morpho-functional approaches in C2C12 myotubes. Dexamethasone-treated cells showed a reduced fiber size when compared to control ones. While long and confluent myotubes could be observed in control samples, those exposed to dexamethasone appeared as immature syncytia. Dysfunctional mitochondria and the accumulation of autophagic vacuoles contributed to myotube degeneration and death. Tyrosol administration before glucocorticoid treatment prevented muscle wasting and rescued mitochondrial and lysosomal functionality. These findings demonstrate that tyrosol attenuates dexamethasone-induced myotube damage, and encourage the use of this natural molecule in preclinical and clinical studies and in synergy with other functional foods or physical activity with the aim to prevent muscle atrophy.

Rhabdomyosarcoma (RMS), the most common form of sarcoma typical of pediatric age, arises from the malignant transformation of the mesenchymal precursors that fail to differentiate into skeletal muscle cells. Here, we investigated whether the protein phospholipase C δ4 (PLCδ4), a member of the PLC family involved in proliferation and senescence mechanisms of mesenchymal stromal stem cells, may play a role in RMS. Our molecular and morpho-functional data reveal that PLCδ4 is highly expressed in the fusion-negative, p53-positive, SMARCB1 heterozygous mutated embryonal RMS (ERMS) cell line A204, while it is poorly expressed in the ERMS cell lines RD (fusion-negative, MYC amplification, N-RAS (Q61H), homozygous mutated p53) and Hs729 (homozygous mutated p53) and the alveolar rhabdosarcoma (ARMS) cell line SJCRH30 (RH30; fusion positive, heterozygous mutated RARA, polyheterozygous mutated p53). To characterize the role of PLCδ4, the RD cell line was stably transfected with wild-type PLCδ4 (RD/PLCδ4). Overexpressed PLCδ4 mainly localized to the nucleus in RD cells and contributed to the phosphorylation of PRAS40 (T246), Chk2(T68), WNK1(T60), and Akt 1/273 (S473), as revealed by proteome profiler array analysis. Overexpression of PLCδ4 in RD cells enhanced cyclin B1 expression and resulted in G2/M-phase cell cycle arrest. In contrast, siRNA-mediated knockdown of PLCδ4 in A204 cells resulted in reduced cyclin B1 expression. Our study identifies a novel role for nuclear PLCδ4 as a regulator of cyclin B1 via Akt-dependent phosphorylation. The modulation of PLCδ4 expression and its downstream targets could represent a crucial signaling pathway to block embryonal RMS cell proliferation.

Functional foods, thanks to their basic nutritional properties, can have physiological benefits and can alleviate the symptoms of many chronic diseases. They contain active components deriving either from plant or animal sources, and they show anti-inflammatory, cardiotonic, and antioxidant pharmacological activities that could be useful in preventing oxidative damage and inflammatory processes in a variety of disorders. There is evidence from in vitro, in vivo, and clinical observational studies that some compounds have significant effects in modulating the muscular dystrophy phenotype, which is characterized by fibrosis, myofiber necrotic cell death, inflammation, oxidative stress, and dysfunctional mitochondria. This review involves collecting data from the main medical databases and detailing the key features involved in muscular dystrophy progression and the relevance of fatty-acid compounds as diet supplements in the management of the disease. Omega fatty acids improve the dystrophic phenotype in terms of fibrosis and inflammation reduction, stimulating mitochondrial activity and antioxidant systems. Omega fatty acids could play a crucial role as food supplementation to delay dystrophy progression. This overview appears extremely relevant for researchers who are studying these molecules as valid alternatives to glucocorticoids, that today remain the only recognized pharmacological cure for dystrophic patients.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra and the presence of misfolded α-synuclein in the brain. Mitochondrial dysfunction and oxidative stress are factors contributing to the death of these neurons. Coenzyme Q10 (CoQ10) serve as an antioxidant and cofactor for mitochondrial enzymes, and its deficiency can exacerbate neurodegenerative processes in PD. However, the clinical efficacy of CoQ10 is limited by its low bioavailability and instability. Ubiquinol diacetate (CoQ10 Ac), an esterified form of CoQ10, shows improved pharmacokinetic properties and potential as a prodrug, converting into the reduced antioxidant form of CoQ10 by esterases in the body. This study aimed to investigate the antioxidant and neuroprotective effects of CoQ10 Ac compared to CoQ10 in SH-SY5Y cell line and Caenorhabditis elegans models of PD. CoQ10 Ac showed higher antioxidant activity than CoQ10 at both extracellular and intracellular levels, particularly in the membrane and cytosolic compartments. It exhibited superior neuroprotection against 6-hydroxydopamine toxicity, showing a greater ability to reduce the activation of caspase-3 and PARP1 compared to CoQ10. Both compounds decreased the increased ratio of mitochondrial fission protein, DRP1, to fusion protein, OPA1, induced by 6-hydroxydopamine in SH-SY5Y cells, enhancing OPA1 levels and promoting antiapoptotic death. However, CoQ10 Ac was more effective than CoQ10 in preserving mitochondrial structural integrity and mass. Additionally, both compounds significantly inhibited the aggregation of α-synuclein induced by 6-hydroxydopamine. Furthermore, CoQ10 Ac showed stronger neuroprotective effects than CoQ10 in C. elegans models of PD. It demonstrated greater anti-aggregant activity in C. elegans expressing human α-synuclein, suggesting higher bioavailability. These findings highlight CoQ10 Ac as a promising prodrug candidate and support further investigation in in vivo PD models.

Background/Objectives: Mummy studies allow to reconstruct the characteristic of a population in a specific spatiotemporal context, in terms of living conditions, pathologies and death. Radiology represents an efficient diagnostic technique able to establish the preservation state of mummified organs and to estimate the patient's pathological conditions. However, the radiological approach shows some limitations. Although bone structures are easy to differentiate, soft tissue components are much more challenging, especially when they overlap. For this reason, computed tomography, a well-established approach that achieves optimal image contrast and three-dimensional reconstruction, has been introduced. This original article focuses attention on the role of virtual dissection as a promising technology for exploring human mummy anatomy and considers the potential of environmental scanning electron microscopy and X-ray spectroscopy as complementary approaches useful to understand the state of preservation of mummified remains. Methods: Ancient mummy corps have been analyzed through Anatomage Table 10 and environmental scanning electron microscope equipped with X-ray spectrometer; Results: Anatomage Table 10 through various volumetric renderings allows us to describe spine alteration due to osteoarthritis, dental state, and other clinical-pathological characteristics of different mummies. Environmental scanning electron microscope, with the advantage of observing mummified samples without prior specimen preparation, details on the state of tissue fragments. Skin, tendon and muscle show a preserved morphology and keratinocytes, collagen fibers and tendon structures are easily recognizable. Furthermore, X-ray spectrometer reveals in our tissue remains, the presence of compounds related to soil contamination. This investigation identifies a plethora of organic and inorganic substances where the mummies were found, providing crucial information about the mummification environment. Conclusions: These morphological and analytical techniques make it possible to study mummified bodies and describe their anatomical details in real size, in a non-invasive and innovative way, demonstrating that these interdisciplinary approaches could have great potential for improving knowledge in the study of ancient corpses.