Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body’s antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

Among the deadliest human cancers is glioblastoma (GBM) for which new treatment approaches are urgently needed. Here, the effects of the cyclic decapeptide, uPAcyclin, are investigated using the U87-MG, U251-MG, and U138-MG human GBM and C6 rat cell models. All GBM cells express the αV-integrin subunit, the target of uPAcyclin, and bind specifically to nanomolar concentrations of the decapeptide. Although peptide exposure affects neither viability nor cell proliferation rate, nanomolar concentrations of uPAcyclin markedly inhibit the directional migration and matrix invasion of all GBM cells, in a concentration- and αV-dependent manner. Moreover, wound healing rate closure of U87-MG and C6 rat glioma cells is reduced by 50% and time-lapse videomicroscopy studies show that the formation of vascular-like structures by U87-MG in three-dimensional matrix cultures is markedly inhibited by uPAcyclin. A strong reduction in the branching point numbers of the U87-MG, C6, and U251-MG cell lines undergoing vasculogenic mimicry, in the presence of nanomolar peptide concentrations, was observed. Lysates from matrix-recovered uPAcyclin-exposed cells exhibit a reduced expression of VE-cadherin, a prominent factor in the acquisition of vascular-like structures. In conclusion, these results indicate that uPAcyclin is a promising candidate to counteract the formation of new vessels in novel targeted anti-GBM therapies.