Insulin resistance and diabetes are associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) conditions, which are distinguished by metabolic dysfunction, oxidative stress and inflammation. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, is fundamental in regulating metabolic pathways, reducing inflammation, and improving antioxidant defenses. This is the first study to investigate the effects of SRT1720, a SIRT1 activator, in diabetic rats on a high-fat diet. SRT1720 significantly lowered fasting blood glucose and insulin levels and enhanced glucose tolerance and HOMA-IR and QUICKI scores, indicating increased insulin sensitivity. The treatment also reduced total cholesterol, triglycerides, and LDL levels, showing amelioration of dyslipidemia. Moreover, SRT1720 lowered markers of liver fibrosis, including TGF-β, TIMP-1, Col1a1, and hydroxyproline, and decreased inflammation by reducing NFκB activity and pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, SRT1720 augmented Nrf2 activity and HO-1 levels. Consequently, the SRT1720's protective role improved liver function and histology and prolonged rats' survival. These functions were suppressed by the co-administration of the SIRT1 inhibitor EX527, confirming that the beneficial effects of SRT1720 are SIRT1-dependent. Correlation analyses uncovered that increased SIRT1 activity was strongly associated with decreased oxidative stress, inflammation, insulin resistance, and fibrosis markers. To conclude, our results find that SRT1720 represents a promising therapeutic strategy for managing Type 2 diabetes in NAFLD or NASH patients possibly through the modulation of the SIRT1/Nrf2/NFκB signaling pathwa. SRT1720 could potentially halt or reverse the progression of these conditions and associated complications and merits further investigations.

Introduction: Cerebral palsy (CP) affects motor function development, requiring intensive rehabilitation. Virtual reality (VR) interventions show promise for improving motor learning through immersive, engaging experiences. This systematic review and meta-analysis evaluated VR effectiveness for motor function improvement in children with CP. Methods: Following PRISMA 2020 guidelines, we searched six electronic databases from inception to 15 June 2025. Included studies compared VR interventions versus control conditions in children with CP (ages 4–18 years), measuring motor function outcomes. Sixteen studies (n = 397 participants) met the inclusion criteria for qualitative synthesis. Random-effects models, subgroup analyses, and meta-regression were performed. Evidence certainty was evaluated using GRADE methodology. Results: Five randomized controlled trials with complete extractable data (N = 190 participants, 40 effect sizes) were included in the primary quantitative meta-analysis. The primary meta-analysis demonstrated moderate overall effects favoring VR interventions (standardized mean difference [SMD] = 0.41, 95% CI [0.16, 0.66], p = 0.001; I² = 74%); however, GRADE quality was rated LOW due to risk of bias and imprecision. Technology type critically moderated outcomes: robotic exoskeleton systems showed large effects (SMD = 1.00, p = 0.002), commercial gaming platforms showed small-to-moderate effects (SMD = 0.38, p = 0.013), while custom VR systems showed no significant benefit (SMD = 0.01, p = 0.905; Q = 29.00, p < 0.001). Age emerged as the strongest moderator: children (<6 years) demonstrated significant benefits (SMD = 0.98, p < 0.001), whereas school-age children (6–12 years) showed no effect (SMD = −0.01, p = 0.903; meta-regression slope = −0.236 per year, p < 0.001). Dose–response was non-linear, with optimal benefits at 30–40 intervention hours and diminishing returns beyond 50 h. VR proved superior to standard care (SMD = 0.83) but not to active intensive therapies (SMD = 0.09). The safety profile was favorable (1.3% adverse event rate, no serious events). No publication bias was detected. Conclusions: VR interventions demonstrated moderate, technology-dependent motor function improvements in children with CP, with benefits concentrated in young children using robotic systems. Evidence certainty is low, requiring further high-quality trials. Implementation should prioritize robotic VR for children with 30–40 h protocols.