Optic neuropathy, characterized by the irreversible degeneration of RGCs, leads to vision loss for which treatment options remained limited. Nanoparticle-based therapeutic strategies have been developed to stimulate RGCs regeneration; however, insufficient nanoparticles delivery to RGCs and a lack of robust stimulation of RGCs intrinsic regenerative capacity, have limited their application. Here, we demonstrate that a RGC-targeting Tet1 conjugated to liposome delivery system (Lipo-T) enhances therapeutic agent delivery to RGCs while minimizing off-target effect for activating glial cells. Targeted delivery of a mTOR-specific activator MHY1485 to RGCs via Lipo-T (MHY@Lipo-T) significantly enhances in vivo RGCs survival, neurite outgrowth, and axonal regeneration without retinal inflammation from unwanted glial activation. By conferring sustained MHY1485 to degenerated retina through Lipo-T injection, and with its high target ability potential, the first use of MHY@Lipo-T expands new therapeutic option for optic nerve injury.
Diabetes cardiomyopathy (DCM) refers to myocardial dysfunction and disorganization resulting from diabetes. In this study, we investigated the effects of berberine on cardiac function in male db/db mice with metformin as a positive control. After treatment for 8 weeks, significant improvements in cardiac function and a reduction in collagen deposition were observed in db/db mice. Furthermore, inflammation and pyroptosis were seen to decrease in these mice, as evidenced by decreased expressions of p-mTOR, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1β, IL-18, caspase-1, and gasdermin D (GSDMD). In vitro experiments on H9C2 cells showed that glucose exposure at 33 mmol/L induced pyroptosis, whereas berberine treatment reduced the expression of p-mTOR and NLRP3 inflammasome components. Moreover, berberine treatment was seen to inhibit the generation of mitochondrial reactive oxygen species (mtROS) and effectively improve cell damage in high glucose-induced H9C2 cells. The mTOR inhibitor, Torin-1, showed a therapeutic effect similar to that of berberine, by reducing the expression of NLRP3 inflammasome components and inhibiting mtROS generation. However, the activation of mTOR by MHY1485 partially nullified berberine's protective effects during high glucose stress. Collectively, our study reveals the mechanism that berberine regulates the mTOR/mtROS axis to inhibit pyroptosis induced by NLRP3 inflammasome activation, thereby alleviating DCM.
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