In HUVECs subjected to normal (1 mM) and low (0.1 mM) Mg 2+ concentrations for 24 h, in a custom-made Mg 2+ -free medium supplemented with magnesium sulfate (MgSO 4 ), Mg 2+ deficiency upregulated the pro-oxidant protein thioredoxin-interacting protein (TXNIP), a contributor to ROS generation, increased endothelial permeability (altering inter-endothelial junctions by disrupting VE-cadherin distribution), and promoted the accumulation of triglycerides in lipid droplets [202]
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However, the poor bioavailability of curcumin limits its therapeutic application in brain diseases
Translational success will require (i) rigorous preclinical-to-clinical pipelines that include long-term toxicity and biodistribution studies, (ii) GMP- compliant manufacturing to ensure reproducibility and scalability, (iii) adaptive trial designs capable of evaluating patient-specific nanotherapies, and (iv) clearer regulatory alignment across FDA/EMA to classify and approve multifunctional nanoplatforms
