Multiple large clinical trials have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors reduce the risk of renal events. However, the mechanism responsible for this outcome remains unknown. Here we investigated the effects of the SGLT2 inhibitor luseogliflozin on the development of renal fibrosis after renal ischemia/reperfusion injury in non-diabetic mice. Luseogliflozin significantly suppressed development of renal fibrosis, prevented peritubular capillary congestion/hemorrhage, attenuated CD31-positive cell loss, suppressed hypoxia, and increased vascular endothelial growth factor (VEGF)-A expression in the kidney after ischemia/reperfusion injury. Luseogliflozin failed to induce the above-mentioned protection in animals co-treated with sunitinib, a VEGF receptor inhibitor. Additionally, luseogliflozin reduced glucose uptake and increased VEGF-A expression in the kidneys of glucose transporter 2 (GLUT2)-downregulated mice following ischemia/reperfusion and in GLUT2-knock-down cells compared with those in normal controls. Withdrawal of glucose from cultured medium, to halt glucose uptake, remarkably increased VEGF-A expression and reversed the luseogliflozin-induced increase in VEGF-A expression in the proximal tubular cells. Thus, luseogliflozin prevented endothelial rarefaction and subsequent renal fibrosis after renal ischemia/reperfusion injury through a VEGF-dependent pathway induced by the dysfunction of proximal tubular glucose uptake in tubules with injury-induced GLUT2 downregulation.

The gut microbiota is characterized as a complex ecosystem that has effects on health and diseases of host with the interactions of many other factors together. Sika deer is the national level for the protection of wild animals in China. The available sequencing data of gut microbiota from feces of wild sika deer, especially for Cervus nippon hortulorum in Northeast China, are limited. Here, we characterized the gastrointestinal bacterial communities of wild (7 samples) and captive (12 samples) sika deer from feces, and compared their gut microbiota by analyzing the V3–V4 region of 16S rRNA gene using high-throughput sequencing technology on the Illumina Hiseq platform. Firmicutes (77.624%), Bacteroidetes (18.288%) and Tenericutes (1.342%) were the most predominant phyla in wild sika deer. While in captive sika deer, Firmicutes (50.710%) was the dominant phylum, followed by Bacteroidetes (31.996%) and Proteobacteria (4.806%). A total of 9 major phyla, 22 families and 30 genera among gastrointestinal bacterial communities showed significant differences between wild and captive sika deer. The specific function and mechanism of Tenericutes in wild sika deer need further study. Our results indicated that captive sika deer in farm had higher fecal bacterial diversity than the wild. Abundance and quantity of diet source for sika deer played crucial role in shaping the composition and structure of gut microbiota.Electronic supplementary materialThe online version of this article (10.1186/s13568-017-0517-8) contains supplementary material, which is available to authorized users.

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Hepatic ischemia‐reperfusion injury (IRI), in which an insufficient oxygen supply followed by reperfusion leads to an inflammatory network and oxidative stress in disease tissue to cause cell death, always occurs after liver transplantations and sections. Although pharmacological treatments favorably prevent or protect the liver against experimental IRI, there have been few successes in clinical applications for patient benefits because of the incomprehension of complicated IRI‐induced signaling events as well as short blood circulation time, poor solubility, and severe side reactions of most antioxidants and anti‐inflammatory drugs. Nanomaterials can achieve targeted delivery and controllable release of contrast agents and therapeutic drugs in desired hepatic IRI regions for enhanced imaging sensitivity and improved therapeutic effects, emerging as novel alternative approaches for hepatic IRI diagnosis and therapy. In this review, the application of nanotechnology is summarized in the management of hepatic IRI, including nanomaterial‐assisted hepatic IRI diagnosis, nanoparticulate systems‐mediated remission of reactive oxygen species‐induced tissue injury, and nanoparticle‐based targeted drug delivery systems for the alleviation of IRI‐related inflammation. The current challenges and future perspectives of these nanoenabled strategies for hepatic IRI treatment are also discussed.