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Skeletal muscle tissue can regenerate after damage through the action of satellite cells, which proliferate as myoblasts when activated. Oxidative stress, marked by high rates of reactive oxygen species (e.g., hydrogen peroxide, H 2 O 2 ), impairs this process by increasing myoblast cell death. Moringa oleifera leaf extract (MOLE), known for its antioxidant properties, was tested for its protective effects on C2C12 myoblasts under oxidative stress. We assessed MOLE's impact on total antioxidant capacity (TAC), glutathione homeostasis (GSH/GSSG), cell viability, and wound recovery. The metabolomic analysis of MOLE using an LC-MSMS ZenoTOF 7600 mass spectrometry system identified key compounds, including peculiar glucosinolates (42.1%) and flavonoids (18.8%), as well as phenolic acids (4.5%) and other significant metabolites (34.6%; among them, amino acids, vitamins, and fatty acids). H 2 O 2 disrupted myoblast redox balance and caused cell death, but MOLE treatment restored the GSH/GSSG ratio, improved TAC, and increased cell viability. Additionally, MOLE promoted faster wound closure in myoblasts exposed to H 2 O 2 . These findings suggest that MOLE can protect C2C12 myoblasts by restoring redox balance and enhancing recovery under oxidative stress.

Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disturbance, and no therapy has been developed to alleviate its symptoms or delay disease onset. SMS occurs due to haploinsufficiency of the retinoic acid-induced-1 (RAI1) gene caused by either chromosomal deletion (SMS-del) or RAI1 missense/nonsense mutation. The molecular mechanisms underlying SMS are unknown. Here, we generated and characterized primary cells derived from four SMS patients (two with SMS-del and two carrying RAI1 point mutations) and four control subjects to investigate the pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we found altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and blocked autophagic flux. We also found that SMS cells exhibited increased cell death associated with the mitochondrial pathology and the production of reactive oxygen species. Treatment with N-acetylcysteine reduced cell death and lipid accumulation, which suggests a causative link between metabolic dyshomeostasis and cell viability. Our results highlight the pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment., (© 2022. The Author(s).)

Homotaurine is a potential therapeutic compound for treatment of Alzheimer's disease (AD), but its efficacy is still under investigation. Emerging data have shown that other than neuroprotective, homotaurine is endowed with anti-inflammatory activities, though with still unclear underlying mechanisms. Inflammation plays a critical role in the pathogenesis of AD and we previously suggested that homotaurine supplementation in patients with amnestic mild cognitive impairment (MCI) plays beneficial effects associated to a decrease in the circulating levels of the pro-inflammatory cytokine IL-18. Here we report that MCI patients supplemented with homotaurine for 12 months show elevated serum levels of IL-10 and IL-33, as compared to baseline, in addition to the described IL-18 decrease. Furthermore, we observed a significant positive correlation between IL-10 and IL-33 levels after treatment but not at the baseline, underlining the effectiveness of the compound in modulating both cytokines in an inter-related fashion and in regulating the pro/anti-inflammation balance. Furthermore, the elevation of both IL-10 and IL-33 is significantly associated with an improvement of episodic memory of treated patients, as measured by the Delayed Verbal Ray Test. In conclusion, our results confirm that homotaurine treatment exerts an overall anti-inflammatory action in MCI patients, based not only on the down-regulation of pro-inflammatory IL-18, but also on up-regulation of the anti-inflammatory IL-33 and IL-10 cytokines, which in turn are associated with an amelioration of patient's cognitive functions. Future studies should be addressed to investigate the molecular mechanisms of homotaurine anti-inflammatory activity and its therapeutic exploitation in early AD., Competing Interests: The author GS consulted for Neuraxpharm in 2019, on the role of nutraceuticals in neurodegenerative dementias. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer VC declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Toppi, Sireno, Lembo, Banaj, Messina, Golesorkhtafti, Spalletta and Bossù.)