Supermolecular poly-N-acryloyl glycinamide/polyglutamic acid/Fe hydrogel incorporated with bioactive small extracellular vesicles promote diabetic wound healing by suppressing ferroptosis.

Poorly-controlled blood glucose frequently develop in diabetic wounds and hydrogel has been reported of great performance for diabetic wound healing. Consequently, we prepared poly-N-acryloyl glycinamide (PNAGA) and introduced polyglutamic acid (γ-PGA), Fe, small extracellular vesicles (sEVs) into PNAGA to form a dual physical cross-linking supramolecular hydrogel system (PFF) for diabetic wound healing. In this study, we successfully synthesized the PFF hydrogel and extracted the sEVs that were incorporated into PPF as PPF/sEVs.

A novel delivery nanobiotechnology: engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization.

Background: Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro.

Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver.

This study is to investigate the relationship between berberine (BBR) and mitochondrial complex I in lipid metabolism. BBR reversed high-fat diet-induced obesity, hepatic steatosis, hyperlipidemia and insulin resistance in mice. Fatty acid consumption, β-oxidation and lipogenesis were attenuated in liver after BBR treatment which may be through reduction in SCD1, FABP1, CD36 and CPT1A.

Development of a novel RNAi therapy: Engineered miR-31 exosomes promoted the healing of diabetic wounds.

Rationale: Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment. Exosome therapy is an extension of stem cell therapy, and RNA interference (RNAi)-based therapy is a type of advanced precision therapy. Based on the discovery of chronic wound-related genes in diabetes, we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.

Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway.

Background: Mesenchymal stem cell (MSC)-derived exosomes emerge as promising candidates for treating delayed wound healing in diabetes due to the promotion of angiogenesis. Preconditioned MSC with chemical or biological factors could possibly enhance the biological activities of MSC-derived exosomes. The purpose of this research focused on whether exosomes derived from the bone marrow MSC (BMSC) pretreated with atorvastatin (ATV), could exhibit better pro-angiogenic ability in diabetic wound healing or not and its underlying molecular mechanism.

Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway.

Background: After surgery, wound recovery in diabetic patients may be disrupted due to delayed inflammation, which can lead to undesired consequences, and there is currently a lack of effective measures to address this issue. Mesenchymal stem cell (MSC)-derived exosomes (Exo) have been proven to be appropriate candidates for diabetic wound healing through the anti-inflammatory effects. In this study, we investigated whether melatonin (MT)-pretreated MSCs-derived exosomes (MT-Exo) could exert superior effects on diabetic wound healing, and we attempted to elucidate the underlying mechanism.

Liraglutide-loaded PLGA/gelatin electrospun nanofibrous mats promote angiogenesis to accelerate diabetic wound healing via the modulation of miR-29b-3p.

Diabetic wounds remain a serious clinical challenge whereas current therapies have limited effects on reducing the high disability and morbidity. Impaired vascularization is closely associated with delayed healing of diabetic wounds and liraglutide (Lira), a GLP-1R receptor agonist, has been reported to promote the angiogenic ability of endothelial cells. However, its application is hindered owing to the unsustainable drug concentration.

Enhanced liver but not muscle OXPHOS in diabetes and reduced glucose output by complex I inhibition.

Mitochondrial function is critical in energy metabolism. To fully capture how the mitochondrial function changes in metabolic disorders, we investigated mitochondrial function in liver and muscle of animal models mimicking different types and stages of diabetes. Type 1 diabetic mice were induced by streptozotocin (STZ) injection.

miR-21-3p regulates AGE/RAGE signalling and improves diabetic atherosclerosis.

To explore the effects of miR-21-3p on diabetic atherosclerosis. Using enzyme-linked immunosorbent assay (ELISA), we also detected the levels of soluble receptor for advanced glycation endproducts RAGE (sRAGE) in the cellular supernatant of vascular endothelial cells after transfecting them with adenovirus vector having miR-21-3p mimic or inhibitor. We found decrease in the expression levels of miR-21-3p in vascular endothelial cells (VECs) induced by high-concentration glucose.