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    Functional Role of Extracellular Vesicles in Skeletal Muscle Physiology and Sarcopenia: The Importance of Physical Exercise and Nutrition
    (Mdpi, 2024) Lombardo, Mauro; Aiello, Gilda; Fratantonio, Deborah; Karav, Sercan; Baldelli, Sara
    Background/Objectives: Extracellular vesicles (EVs) play a key role in intercellular communication by transferring miRNAs and other macromolecules between cells. Understanding how diet and exercise modulate the release and content of skeletal muscle (SM)-derived EVs could lead to novel therapeutic strategies to prevent age-related muscle decline and other chronic diseases, such as sarcopenia. This review aims to provide an overview of the role of EVs in muscle function and to explore how nutritional and physical interventions can optimise their release and function. Methods: A literature review of studies examining the impact of exercise and nutritional interventions on MS-derived EVs was conducted. Major scientific databases, including PubMed, Scopus and Web of Science, were searched using keywords such as 'extracellular vesicles', 'muscle', 'exercise', 'nutrition' and 'sarcopenia'. The selected studies included randomised controlled trials (RCTs), clinical trials and cohort studies. Data from these studies were synthesised to identify key findings related to the release of EVs, their composition and their potential role as therapeutic targets. Results: Dietary patterns, specific foods and supplements were found to significantly modulate EV release and composition, affecting muscle health and metabolism. Exercise-induced changes in EV content were observed after both acute and chronic interventions, with a marked impact on miRNAs and proteins related to muscle growth and inflammation. Nutritional interventions, such as the Mediterranean diet and omega-3 fatty acids, have also shown the ability to alter EV profiles, suggesting their potential to improve cardiovascular health and reduce inflammation. Conclusions: EVs are emerging as critical mediators of the beneficial effects of diet and exercise on muscle health. Both exercise and nutritional interventions can modulate the release and content of MS-derived EVs, offering promising avenues for the development of novel therapeutic strategies targeting sarcopenia and other muscle diseases. Future research should focus on large-scale RCT studies with standardised methodologies to better understand the role of EVs as biomarkers and therapeutic targets.
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    Glucosinolates in Human Health: Metabolic Pathways, Bioavailability, and Potential in Chronic Disease Prevention
    (MDPI, 2025) Baldelli, Sara; Lombardo, Mauro; D'Amato, Alfonsina; Karav, Sercan; Tripodi, Gianluca; Aiello, Gilda
    Glucosinolates (GSLs) are sulfur-containing compounds predominantly found in cruciferous vegetables such as broccoli, kale, and Brussels sprouts, and are recognized for their health-promoting properties. Upon consumption, GSLs undergo hydrolysis by the enzyme myrosinase, resulting in bioactive compounds like isothiocyanates and specific indole glucosinolate degradation products, such as indole-3-carbinol (I3C) and 3,3 '-diindolylmethane (DIM), which contribute to a range of health benefits, including anti-cancer, anti-inflammatory, and cardioprotective effects. This review explores the structure, metabolism, and bioavailability of GSLs. Recent evidence supports the protective role of GSLs in chronic diseases, with mechanisms including the modulation of oxidative stress, inflammation, and detoxification pathways. Furthermore, the innovative strategies to enhance GSL bioactivity, such as biofortification, genetic introgression, and optimized food processing methods, have been examined. These approaches seek to increase GSL content in edible plants, thereby maximizing their health benefits. This comprehensive review provides insights into dietary recommendations, the impact of food preparation, and recent advances in GSL bioavailability enhancement, highlighting the significant potential of these bioactive compounds in promoting human health and preventing chronic diseases.
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    Nitric Oxide in Parkinson's Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate-Nitrite-Nitric Oxide Pathway
    (MDPI, 2025) Tripodi, Gianluca; Lombardo, Mauro; Kerav, Sercan; Aiello, Gilda; Baldelli, Sara
    Background/Objectives: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremor, rigidity, and bradykinesia. The pathological hallmarks of PD include Lewy bodies and mechanisms like oxidative/nitrosative stress, chronic inflammation, and mitochondrial dysfunction. Nitric oxide (NO), produced by nitric oxide synthase (NOS) isoforms, plays a dual role in neuroprotection and neurodegeneration. Excessive NO production exacerbates neuroinflammation and oxidative/nitrosative damage, contributing to dopaminergic cell death. This review explores NO's role in PD pathogenesis and investigates dietary nitrate as a therapeutic strategy to regulate NO levels. Methods: A literature review of studies addressing the role of NO in PD was conducted using major scientific databases, including PubMed, Scopus, and Web of Science, using keywords such as nitric oxide, NOSs, Parkinson's disease, and nitrate neuroprotection in PD. Studies on nitrate metabolism via the nitrate-nitrite-NO pathway and its effects on PD hallmarks were analyzed. Studies regarding the role of nitrosamine formation in PD, which are mainly formed during the nitrification process of amines (nitrogen-containing compounds), often due to chemical reactions in the presence of nitrite or nitrate, were also examined. In particular, nitrate has been shown to induce oxidative stress, affect the mitochondrial function, and contribute to inflammatory phenomena in the brain, another factor closely related to the pathogenesis of PD. Results: Excessive NO production, particularly from iNOS and nNOS, was strongly associated with neuroinflammation and oxidative/nitrosative stress, amplifying neuronal damage in PD. Dietary nitrate was shown to enhance NO bioavailability through the nitrate-nitrite-NO pathway, mitigating inflammation and oxidative/nitrosative damage. Conclusions: Dysregulated NO production contributes significantly to PD progression via inflammatory and oxidative/nitrosative pathways. Dietary nitrate, by modulating NO levels, offers a promising therapeutic strategy to counteract these pathological mechanisms. Further clinical trials are warranted to establish its efficacy and optimize its use in PD management.