BackgroundMesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidate agents for treating critical-sized bone defects; they promote angiogenesis and may be an alternative to cell therapy. In this study, we evaluated whether exosomes derived from bone marrow-derived MSCs (BMSCs) preconditioned with a low dose of dimethyloxaloylglycine (DMOG), DMOG-MSC-Exos, exert superior proangiogenic activity in bone regeneration and the underlying mechanisms involved.MethodsTo investigate the effects of these exosomes, scratch wound healing, cell proliferation, and tube formation assays were performed in human umbilical vein endothelial cells (HUVECs). To test the effects in vivo, a critical-sized calvarial defect rat model was established. Eight weeks after the procedure, histological/histomorphometrical analysis was performed to measure bone regeneration, and micro-computerized tomography was used to measure bone regeneration and neovascularization.ResultsDMOG-MSC-Exos activated the AKT/mTOR pathway to stimulate angiogenesis in HUVECs. This contributed to bone regeneration and angiogenesis in the critical-sized calvarial defect rat model in vivo.ConclusionsLow doses of DMOG trigger exosomes to exert enhanced proangiogenic activity in cell-free therapeutic applications.

341Ketamine is a relatively new recreational drug used by youngsters in recent decades. Its toxic effects on the genitourinary system were first reported in 2007, and now attract extensive attention from urologists, pharmacologists, and toxicologists all over the world. As many front-line health professionals and medical social workers are still unaware of this new clinical entity and an increasing number of the drug users seek help for urological symptoms, this mini-review aimed to summarise the clinical features and possible mechanisms of ketamine-induced genitourinary toxicity. By raising public awareness of these toxic effects, the authors hope that the contents of this review will be widely disseminated not only to medical professionals, but also to relevant government departments and the general public. Genitourinary toxicity of ketamine

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