Morpho-Functional Analyses Demonstrate That Tyrosol Rescues Dexamethasone-Induced Muscle Atrophy.

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.

Efficient and highly reproducible production of red blood cell-derived extracellular vesicle mimetics for the loading and delivery of RNA molecules.

Extracellular vesicles (EVs) are promising natural nanocarriers for the delivery of therapeutic agents. As with any other kind of cell, red blood cells (RBCs) produce a limited number of EVs under physiological and pathological conditions. Thus, RBC-derived extracellular vesicles (RBCEVs) have been recently suggested as next-generation delivery systems for therapeutic purposes. In this paper, we show that thanks to their unique biological and physicochemical features, RBCs can be efficiently pre-loaded with several kinds of molecules and further used to generate RBCEVs. A physical vesiculation method, based on "soft extrusion", was developed, producing an extremely high yield of cargo-loaded RBCEV mimetics. The RBCEVs population has been deeply characterized according to the new guidelines MISEV2023, showing great homogeneity in terms of size, biological features, membrane architecture and cargo. In vitro preliminary results demonstrated that RBCEVs are abundantly internalized by cells and exert peculiar biological effects. Indeed, efficient loading and delivery of miR-210 by RBCEVs to HUVEC has been proven, as well as the inhibition of a known mRNA target. Of note, the bench-scale process can be scaled-up and translated into clinics. In conclusion, this investigation could open the way to a new biomimetic platform for RNA-based therapies and/or other therapeutic cargoes useful in several diseases.

The discoid lateral meniscus in children: a narrative review of pathology, diagnosis and treatment.

Background and Objective: The discoid lateral meniscus (DLM) is a congenital abnormality of the meniscal shape, characterized by a typical central hypertrophy and a diameter larger than a regular meniscus, potentially leading to knee pain and symptoms, especially in children. The present study provides an update and a general review of this uncommon meniscal pathology. The incidence of discoid meniscus is about 0.4-17% for the lateral and 0.1-0.3% for the medial, although, being often asymptomatic, the true prevalence is unknown. We aim to enhance awareness on this subject to medical care provider. Methods: A literature search was performed on PubMed, including articles written in English until October 2021. Key Content and Findings: The articles regarding etiology, diagnosis and management of DLM in children or in patients younger than 18 years were reviewed using the narrative approach. Conclusions: Recent literature has shown that DLM is one of the most frequent congenital anomalies of the knee encountered during childhood. While asymptomatic children with incidental finding can be managed nonoperatively, symptomatic painful DLM should be addressed surgically, restoring typical anatomy using saucerization, tear repair, and stable fixation of the meniscus. The risk of osteoarthritis progression seems to be higher in children with operated DLM, imposing prolonged follow-up and cartilage preserving strategies for these patients.