PurposeExosomes are small nanoscale vesicles secreted from cells. Exosome-based therapeutic approaches have been evaluated in treating ischemic diseases. In the present study, we explored the effect of exosomes on streptozotozin (STZ)-induced diabetic mouse and its underlying mechanisms.MethodsExosomes were isolated from MIN6 cells. Transmission electron microscopy, dynamic light scattering and Western blot were used to identify the exosomes. STZ was used to establish diabetic or abnormal glucose tolerance mouse model. Histology study and flow cytometry were applied to detect the changes in immune responses.ResultsTransplantation of the exosomes into diabetic mice resulted in a longer median survival time compared with the untreated diabetic mice (P<0.01). Transplantation of the exosomes improved glucose tolerance, increased insulin content and preserved the architectures of islets in mice with abnormal glucose tolerance. Moreover, exosome treatment enhanced the expression of CD31, a marker of endothelial cells, and tended to reduce macrophage infiltration in islets of STZ-treated mice.ConclusionExosomes derived from β-cells play a role in preserving pancreatic islet architecture and its function, and in inducing islet angiogenesis, which implicates that exosome treatment could be a novel therapeutic strategy for diabetes.

Acute lung injury (ALI) is a significant contributor to the morbidity and mortality of sepsis. Characterized by uncontrolled inflammation and excessive inflammatory cells infiltration in lung, ALI has been exacerbated by impaired efferocytosis (clearance of apoptotic cells by macrophages). Through specific receptor recognition and activation of downstream signaling, efferocytic macrophages promote resolution of inflammation by efficiently engulfing dying cells, avoiding the consequent release of cellular inflammatory contents. Here, inspired by the intrinsic recovery mechanism of efferocytosis, an apoptotic cell membrane (ACM) coated antioxidant nanozyme (AOzyme) is engineered, thus obtaining an inhalable pro‐efferocytic nanozyme (AOzyme@ACM). Notably, AOzyme@ACM can efficiently increase apoptotic cell removal by combing enhanced macrophages recognition of “eat me” signals through apoptotic body mimicking and scavenge of intracellular excessive reactive oxygen species (ROS), a significant barrier for efferocytosis. AOzyme@ACM can significantly inhibit inflammatory response, promote pro‐resolving (M2) phenotype transition of macrophage, and alleviate ALI in endotoxemia mice compared with AOzyme group. By addressing the critical factor in the pathogenesis of sepsis‐related ALI through restoring efferocytosis activity, the ACM‐based antioxidant nanozyme in this study is envisioned to provide a promising strategy to treat this complex and challenging disease.

The soluble dietary fiber polydextrose (PDX) is a randomly linked glucose oligomer containing small amounts of sorbitol and citric acid and is widely used in the food industry. However, whether PDX can prevent and treat obesity in high-fat diet (HFD)-fed mice has not been directly investigated, and further studies are needed to better understand the complex interactions among PDX, adipose tissue inflammation and the gut microbiota. In the present study, PDX reduced body weight, fasting blood glucose (FBG), adipose tissue accumulation, adipocyte hypertrophy, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels in HFD-fed mice. Moreover, PDX alleviated serum lipopolysaccharide (LPS) levels and macrophage infiltration in epididymal adipose tissue and resulted in macrophage polarization toward the M2 phenotype. Gut microbiota analysis revealed that PDX promoted the growth of beneficial microbes such as Bacteroides, Parabacteroides, Alloprevotella, Muribaculum, Akkermansia, Ruminococcaceae_UCG-014 and UBA1819 in obese mice, which were negatively correlated with subcutaneous fat, epididymal fat, body weight, FBG, serum TC, HDL-C, LDL-C and LPS levels. Our results indicates that PDX can prevent and treat obesity in HFD-fed mice, specifically in alleviating glucolipid metabolism disorders and adipose tissue inflammation, which may be mediated by modulating the structure of the gut microbiota. Therefore, PDX may become a promising nondrug therapy for obesity.

Pancreatic β cell apoptosis is important in the pathogenesis of type 2 diabetes mellitus (T2DM). Generally, apoptotic β cells are phagocytosed by macrophages in a process known as “efferocytosis.” Efferocytosis is critical to the resolution of inflammation and is impaired in T2DM. Advanced glycation end products (AGEs), which are increased in T2DM, are known to suppress phagocytosis function in macrophages. In this study, we found that AGEs inhibited efferocytosis of apoptotic β cells by primary peritoneal macrophages in C57BL/6J mice or mouse macrophage cell line Raw264.7. Mechanistically, AGEs inhibit efferocytosis by blocking Ras-related C3 botulinum toxin substrate 1 activity and cytoskeletal rearrangement through receptor for advanced glycation end products/ras homolog family member A/Rho kinase signaling in macrophages. Furthermore, it was observed that AGEs decreased the secretion of anti-inflammatory factors and promoted the proinflammatory ones to modulate the inflammation function of efferocytosis. Taken together, our results indicate that AGEs inhibit efferocytosis through binding to receptor for advanced glycation end products and activating ras homolog family member A/Rho kinase signaling, thereby inhibiting the anti-inflammatory function of efferocytosis.