Oxidative stress destabilizes microRNA homeostasis in the retinal pigment epithelium (RPE), driving apoptosis and the epithelial-to-mesenchymal transition, which contribute to age-related macular degeneration. We investigated whether Quantum Molecular Resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. The deep sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated > 50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40% of these miRNAs and upregulated additional cytoprotective species such as miR-590-3p, a known regulator of the NF-κB and NLRP3 pathways according to validated target databases. While these observations suggest the potential involvement of inflammatory and stress-related cascades, functional assays will be required to directly confirm such effects. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest miRNA response, normalizing over two-thirds of stress-altered miRNAs. These changes are predicted to influence antioxidant, anti-apoptotic, and anti-fibrotic pathways, although they did not translate into additional short-term cytoprotection compared with QMR^® alone. These data indicate that QMR^® and PBD secretome modulate complementary miRNA programs that converge on stress response networks. This broader molecular reprogramming may reflect regulatory complementarity, but functional validation is needed to determine whether it provides benefits beyond those observed with QMR^® alone. These findings offer molecular insights into potential non-invasive, cell-free strategies for retinal degeneration, although in vivo validation will be required before any clinical translation to Age-Related Macular Degeneration (AMD) therapy.

Alzheimer’s disease (AD) is increasingly recognized as a disorder that extends beyond amyloid-β (Aβ) and tau pathology. To this end, growing evidence suggests that aberrant neuronal cell cycle re-entry (CCR) may contribute to neurodegeneration. To investigate this mechanism, we profiled the expression of 84 cell cycle-related genes in the brains of aged APP/PS1 mice, a widely used transgenic model of AD, and compared them with age-matched non-transgenic littermates. Our analysis revealed 32 differentially expressed genes (DEGs), 8 of which exhibited significant changes (fold change > 2, p < 0.05). Several of these DEGs, including CDC7 and CCNC, displayed consistent dysregulation in human AD brains as assessed using the AMP-AD knowledge portal, supporting their translational relevance. Furthermore, integration with miRNA prediction analyses identified candidate post-transcriptional regulators of these DEGs, highlighting novel layers of regulation. Collectively, our results provide the first systematic overview of cell cycle gene dysregulation in aged APP/PS1 mice, establish cross-species concordance with human AD, and propose miRNA–gene interactions as potential contributors to neuronal vulnerability. These findings underscore the importance of cell cycle pathways in AD pathogenesis and point to new avenues for therapeutic exploration.

Oxidative stress destabilizes microRNA homeostasis in retinal pigment epithelium (RPE), driving apoptosis and epithelial-to-mesenchymal transition that contribute to age-related macular degeneration. We investigated whether quantum molecular resonance (QMR^®) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR^®, PBD secretome, or their combination. Deep-sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated >50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR^® restored roughly 40 % of these miRNAs and up-regulated additional cytoprotective species such as miR-590-3p, collectively dampening NF-κB and NLRP3 axes. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR^® + secretome triggered the broadest response, normalizing over two-thirds of stress-altered miRNAs and synergistically reinforcing antioxidant, anti-apoptotic, and anti-fibrotic gene networks. These data indicate that QMR^® and PBD secretome act through complementary miRNA programs that converge to preserve RPE viability under oxidative insult; their combination offers additive modulation of key survival pathways, supporting development of a non-invasive, cell-free therapeutic strategy for retinal degenerative disorders.