This review provides an updated overview of the pathogenesis, classification, current management, and emerging therapies for diabetic retinopathy (DR). DR development involves dysregulation of the polyol pathway, formation of advanced glycation end products, activation of protein kinase C, and upregulation of vascular endothelial growth factor (VEGF). Disruption of the retinal neurovascular unit, including neurons, glial cells, and vascular elements, also plays a pivotal role, leading to microvascular damage, neurodegeneration, and inflammation. DR progresses from non-proliferative (NPDR) to proliferative stages (PDR) characterized by retinal neovascularization. Management emphasizes glycemic and blood pressure control, with advanced stages treated using laser photocoagulation, vitrectomy, and intravitreal anti-VEGF injections. Novel imaging technologies like optical coherence tomography angiography (OCTA) and electroretinography (ERG) enable early diagnosis and disease monitoring. Genetic factors, including VEGF polymorphisms and genes linked to oxidative stress and angiogenesis, significantly influence DR susceptibility. Innovative treatments under investigation include nanotechnology-based drug delivery, microRNA-targeted therapies, and AAV-mediated gene therapies aimed at anti-angiogenic pathways. Stem cell-based strategies utilizing adipose, bone marrow, amniotic, and umbilical cord-derived. It shows promise for retinal repair and neuroprotection. Future directions encompass CRISPR-Cas9 gene editing for precise genomic interventions, personalized medicine approaches, and integrated screening programs powered by artificial intelligence. A multifaceted approach involving risk factor modification, lifestyle interventions, advanced therapeutics, and cost-effectiveness analysis is essential to reduce the public health burden of diabetic retinopathy.

This study developed and optimized an innovative oral pH-dependent drug delivery system utilizing rosuvastatin-loaded chitosan nanoparticles (RSV-CSNPs) coated with sodium alginate (ALG). The goal was to protect RSV-CSNPs from degradation in the acidic gastric environment and facilitate targeted sustained release in the colon to address inflammatory bowel disease. Nanoparticles were initially prepared by ionic gelation. A subsequent ALG coating process was optimized using a 2³ factorial design. The optimal ALG-coated formulation demonstrated minimal drug loss (0.88% ± 0.09%), desirable particle size (407.2 ± 1.95 nm), and suitable zeta potential (−27.13 ± 1.36 mV). In vitro release tests highlighted the superiority of ALG-coated RSV-CSNPs, with significantly reduced RSV release in simulated gastric fluid (6.8% ± 1.06% after 2 h) compared to uncoated nanoparticles (38.45% ± 1.79%), affirming the protective effectiveness of the ALG coating. Extended-release studies at colonic pH (6.8) demonstrated sustained RSV release suitable for colon-specific targeting. In vivo assessments in a dextran sodium sulfate (DSS)-induced rat model of colitis revealed that ALG-RSV-CSNPs significantly outperformed both plain RSV and RSV-CSNPs. Treatment notably decreased colonic inflammation, disease severity scores, macroscopic damage, and oxidative stress indicators. Additionally, histopathological analyses showed remarkable restoration of colon tissue integrity, crypt preservation, and mucosal protection in animals treated with ALG-RSV-CSNPs. Mechanistically, ALG-RSV-CSNPs effectively attenuated colitis by significantly inhibiting the HMGB1-triggered RAGE/TLR4-NFκB inflammatory signaling pathway. Treatment resulted in substantial reductions in key inflammatory markers, including HMGB1, RAGE, TLR4 expression, NFκB activity, pro-inflammatory cytokines (TNF-α and IL-6), and apoptosis marker caspase-3. The anti-inflammatory actions were further supported by reduced neutrophil infiltration, lipid peroxidation, and enhanced antioxidant enzyme activities (SOD and GSH levels). The study identified HMGB1, RAGE, TLR4, and NFκB as critical biomarkers predicting disease activity. Correlation analysis highlighted strong positive associations among these markers, underscoring their collective involvement in colitis pathogenesis and emphasizing the multitarget therapeutic efficacy of ALG-RSV-CSNPs. Overall, this study demonstrates that the optimized pH-responsive ALG-coated RSV-CSNPs significantly enhance the therapeutic outcomes of RSV in colonic inflammation through targeted delivery and sustained release. These nanoparticles represent a promising strategy for effectively managing ulcerative colitis and related inflammatory bowel diseases. Future clinical studies are warranted to validate these findings and facilitate translation into human therapeutic applications.

Metabolic syndrome (MetS) is a cluster of several disorders where many challenges hinder effective treatment. The downregulation of SIRT1 or inhibition of its activity is implicated in its pathophysiology. We hypothesized that the combined SIRT1 direct activator E1231 and the SIRT1 stabilizer nicotinamide mononucleotide (NMN) could offer a novel approach to mitigate the pathophysiological features of MetS. Our results revealed that E1231 alone or combined with NMN increased SIRT1 level and activity. This SIRT1 activation was accompanied by upregulation in the IRS-1 and activation of AKT. In parallel, the Nrf2 level and activity were increased while the NFκB activity and subsequent inflammatory cytokines were decreased. Additionally, SIRT1 activation was associated with improved insulin resistance, blood pressure, lipid profile, fasting blood glucose, glucose tolerance, and kidney and liver functions. Moreover, improved liver histology, decreased hepatic fibrosis markers, and increased survival rates were observed. These protective functions were counteracted when EX527, a SIRT1 inhibitor, was dually administered with E1231. Furthermore, correlation analysis revealed that SIRT1 was negatively correlated with NFκB, insulin resistance, and oxidative stress, while positive correlations were observed between SIRT1, p-AKT, and Nrf2 activity. Random Forest regression algorithm and partial dependence plots highlighted the significant roles of SIRT1, IRS-1, p-AKT, and NFκB in predicting MetS severity. These analyses underscore the strong interconnections between these signals. This reinforces the central role of SIRT1 in coordinating a multifaceted protective response against MetS. To conclude, SIRT1 alleviates MetS by modulating AKT/Nrf2/NFκB signaling and their interactions. Further research is necessary to validate these findings.