Resveratrol protects mesangial cells under high glucose by regulating the miR-1231/IGF1/ERK pathway.

Diabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end-stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines. In this study, we evaluated the protective effect of resveratrol (RES), an active ingredient known as a natural antioxidant, on HMCs under high glucose and explored its possible mechanism of action. We found that RES inhibited the proliferation of human mesangial cell (HMC) under high glucose and blocked cell cycle progression. In the high glucose environment, RES upregulated miR-1231, reduced IGF1 expression, inhibited the activity of the extracellular signal-regulated kinase (ERK) signaling pathway and reduced levels of the inflammatory factors TNF-α and IL-6. In addition, we found that miR-1231 mimics were synergistically inhibited with RES, whereas miR-1231 inhibitor attenuated the protective effect of RES on HMCs. Thus, our results suggest that the protective effect of RES on HMCs under high glucose is achieved, at least in part, through modulation of the miR-1231/IGF1/ERK pathway. The discovery of this potential mechanism may provide a new molecular therapeutic target for the prevention and treatment of DN, and may also bring new ideas for the clinical research in DN.

Preparation and evaluation in vitro and in vivo of pristinamycin enteric-coated granules based on albumin nanoparticles.

CONTEXT: The purpose of this study was to prepare enteric-coated particles based on albumin nanoparticles (NPs) using a mixture of PIA albumin NPs freeze-dried powder (PA-PIA) and PIIA albumin NPs freeze-dried powder (PA-PIIA) to improve the bioavailability effect of pristinamycin. OBJECTIVE: This is the first study on the preparation of pristinamycin into enteric-coated granules based on albumin NPs, and our study has effectively improved the bioavailability of pristinamycin and ensured its safety. METHODS: Pristinamycin albumin enteric-coated granules (PAEGs) were prepared by hybrid wet granulation. The characterizations of albumin NPs were performed by in vitro and in vivo studies of PAEGs. The assays were analyzed using zeta-sizer, transmission electron microscopy, high-performance liquid chromatography, and a fully automated biochemical index analyzer. RESULTS: The morphology of NPs was close to spherical. PIA-NPs and PIIA-NPs respectively had a zeta potential of (-24.33 ± 0.75) mV and (+7.30 ± 0.27) mV and mean size of (251.91 ± 19.64) nm and (232.83 ± 22.61) nm. The release of PIA and PIIA from PAEGs in the artificial gastrointestinal fluid was as high as 58.46% and 87.79%. In the experimental group of oral PAEGs, PIA and PIIA were AUC(0-t) (3.68 ± 0.58) mg·L-1·h-1 and (2.81 ± 1.06) mg·L-1·h-1. The results of aspartate aminotransferase and alanine aminotransferase biochemical indices showed that there was no significant difference between the experimental and normal groups of oral PAEGs. CONCLUSION: The PAEGs significantly increased the release of PIA and PIIA in simulated intestinal fluid and improved the bioavailability. The oral administration of PAEGs may not damage the liver of rats. We hope that our study will promote its industrial development or clinical application.