Extracellular Vesicles and Acute Kidney Injury: Potential Therapeutic Avenue for Renal Repair and Regeneration.

Acute kidney injury (AKI) is a sudden decline of renal function and represents a global clinical problem due to an elevated morbidity and mortality. Despite many efforts, currently there are no treatments to halt this devastating condition. Extracellular vesicles (EVs) are nanoparticles secreted by various cell types in both physiological and pathological conditions. EVs can arise from distinct parts of the kidney and can mediate intercellular communication between various cell types along the nephron. Besides their potential as diagnostic tools, EVs have been proposed as powerful new tools for regenerative medicine and have been broadly studied as therapeutic mediators in different models of experimental AKI. In this review, we present an overview of the basic features and biological relevance of EVs, with an emphasis on their functional role in cell-to-cell communication in the kidney. We explore versatile roles of EVs in crucial pathophysiological mechanisms contributing to AKI and give a detailed description of the renoprotective effects of EVs from different origins in AKI. Finally, we explain known mechanisms of action of EVs in AKI and provide an outlook on the potential clinical translation of EVs in the setting of AKI.

Metformin turns 62 in pharmacotherapy: Emergence of non-glycaemic effects and potential novel therapeutic applications.

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.