Alzheimer disease (AD) is a multifactorial and age-dependent neurodegenerative disorder, whose pathogenesis, classically associated with the formation of senile plaques and neurofibrillary tangles, is also dependent on oxidative stress and neuroinflammation chronicization. Currently, the standard symptomatic therapy, based on acetylcholinesterase inhibitors, showed a limited therapeutic potential, whereas disease-modifying treatment strategies are still under extensive research. Previous studies have demonstrated that Oxotremorine-M (Oxo), a non-selective muscarinic acetylcholine receptors agonist, exerts neurotrophic functions in primary neurons, and modulates oxidative stress and neuroinflammation phenomena in rat brain. In the light of these findings, in this study, we aimed to investigate the neuroprotective effects of Oxo treatment in an in vitro model of AD, represented by differentiated SH-SY5Y neuroblastoma cells exposed to Aβ_1-42 peptide. The results demonstrated that Oxo treatment enhances cell survival, increases neurite length, and counteracts DNA fragmentation induced by Aβ_1-42 peptide. The same treatment was also able to block oxidative stress and mitochondria morphological/functional impairment associated with Aβ_1-42 cell exposure. Overall, these results suggest that Oxo, by modulating cholinergic neurotransmission, survival, oxidative stress response, and mitochondria functionality, may represent a novel multi-target drug able to achieve a therapeutic synergy in AD. Graphical Abstract Illustration of the main pathological hallmarks and mechanisms underlying AD pathogenesis, including neurodegeneration and oxidative stress, efficiently counteracted by treatment with Oxo, which may represent a promising therapeutic molecule. Created with BioRender.com under academic license.

In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin’s therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.

The differentiation of neural progenitors is a complex process that integrates different signals to drive transcriptional changes, which mediate metabolic, electrophysiological, and morphological cellular specializations. Understanding these adjustments is essential within the framework of stem cell and cancer research and therapy. Human neuroblastoma SH-SY5Y cells, widely used in neurobiology research, can be differentiated into neuronal-like cells through serum deprivation and retinoic acid (RA) supplementation. In our study, we observed that the differentiation process triggers the expression of Heat Shock Protein 70 (HSP70). Notably, inhibition of HSP70 expression by KNK437 causes a dramatic increase in cell death. While undifferentiated SH-SY5Y cells show a dose-dependent decrease in cell survival following exposure to hydrogen peroxide (H₂O₂), differentiated cells become resistant to H₂O₂-induced cell death. Interestingly, the differentiation process enhances the expression of SOD1 protein, and inhibition of HSP70 expression counteracts this effect and increases the susceptibility of differentiated cells to H₂O₂-induced cell death, suggesting that the cascade HSP70-SOD1 is involved in promoting survival against oxidative stress-dependent damage. Treatment of differentiated SH-SY5Y cells with Oxotremorine-M (Oxo), a muscarinic acetylcholine receptor agonist, enhances the expression of HSP70 and SOD1 and counteracts tert–Butyl hydroperoxide-induced cell death and reactive oxygen species (ROS) generation. It is worth noting that co-treatment with KNK437 reduces SOD1 expression and Oxo-induced protection against oxidative stress damage, suggesting the involvement of HSP70/SOD1 signaling in this beneficial effect. In conclusion, our findings demonstrate that manipulation of the HSP70 signal modulates SH-SY5Y differentiation and susceptibility to oxidative stress-dependent cell death and unravels novel mechanisms involved in Oxo neuroprotective functions. Altogether these data provide novel insights into the mechanisms underlying neuronal differentiation and preservation under stress conditions.

Background/Objectives: The increasing use of electronic devices is reshaping lifestyle by offering new avenues for health behavior change. These tools provide to monitor health, fitness, and nutrition, promoting healthier lifestyles to prevent non-communicable diseases (NCDs). This umbrella review (conducted according to PRISMA 2020 guidelines, registered on PROSPERO CRD42024511141) assesses the effectiveness of wearable devices and mobile applications in improving healthy lifestyle behaviors to mitigate the risk of NCDs. Methods: Systematic reviews and meta-analyses (n = 27) focusing on digital tools for health behavior change were analyzed, with emphasis on their integration into daily life and their impact on health outcomes, including body weight, metabolic and anthropometric parameters, and dietary quality. Results and Conclusions: Interventions leveraging gamification, social interaction, and goal-setting (6/27) have shown greater efficacy in improving body-nutrition profile. The integration of eHealth technologies holds transformative potential for preventive healthcare and positive biology. These tools can contribute to healthier lifestyles, extended life expectancy, and reduced healthcare costs, although current limitations exist, including data accuracy, privacy concerns, and sustaining user engagement over time.

Background and aim: Despite the intense research, most therapeutic strategies failed in preventing or treating neurodegenerative diseases, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation. The broad protective activity of IntegroPectin derived from industrial waste grapefruit peel via hydrodynamic cavitation has been recently characterized. In this study, we investigated the beneficial effects of grapefruit IntegroPectin treatment in microglia cells exposed to oxidative stress conditions. Experimental procedure: Human microglial HMC3 cells were challenged with tert-butyl hydroperoxide (TBH), a powerful hydroperoxide, in the presence of grapefruit IntegroPectin. The apoptotic process, the oxidative stress and the neuroinflammatory responses with the relative intracellular cascades were evaluated. Key results: Grapefruit IntegroPectin fully counteracted the apoptotic process induced by cell exposure to TBH. The protective effects of grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the PI3K/Akt cascade. Finally, IntegroPectin treatment inhibited basal microglia activation and the neuroinflammatory response by down-regulating the PI3K-NF-kB-iNOS cascade. Conclusions and implications: These findings reveal that the innovative IntegroPectin exerts a potent protective activity on microglia cells and strongly support further investigations aimed at exploring its therapeutic role in in vivo models of neurodegenerative disorders.