diabetic nephropathy (dN) is a primary cause of end-stage renal disease. Despite the beneficial effects of astragaloside IV (AS)-IV on renal disease, the underlying mechanism of its protective effects against dN has not been fully determined. The aims of the present study were to assess the effects of AS-IV against dN in db/db mice and to explore the mechanism of AS-IV involving the NLR family pyrin domain containing 3 (NLRP3), caspase-1 and interleukin (IL)-1β pathways. The 8-week-old db/db mice received 40 mg/kg AS-IV once a day for 12 weeks via intragastric administration. cultured mouse podocytes were used to further confirm the underlying mechanism in vitro. AS-IV effectively reduced weight gain, hyperglycemia and the serum triacylglycerol concentration in db/db mice. AS-IV also reduced urinary albumin excretion, urinary albumin-to-creatinine ratio and creatinine clearance rate, as well as improved renal structural changes, accompanied by the upregulation of the podocyte markers podocin and synaptopodin. AS-IV significantly inhibited the expression levels of NLRP3, caspase-1 and IL-1β in the renal cortex, and reduced the serum levels of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1. In high glucose-induced podocytes, AS-IV significantly improved the expression levels of NLRP3, pro-caspase-1 and caspase-1, and inhibited the cell viability decrease in a dose-dependent manner, while NLRP3 overexpression eliminated the effect of AS-IV on podocyte injury and the inhibition of the NLRP3 and caspase-1 pathways. The data obtained from in vivo and in vitro experiments demonstrated that AS-IV ameliorated renal functions and podocyte injury and delayed the development of dN in db/db mice via anti-NLRP3 inflammasome-mediated inflammation.

Background: To explore the impact of polydatin on mice with triple-negative breast cancer (TNBC) receiving a high-fat diet, as well as the underlying processes.Methods: A total of 40 female Balb/c mice were randomly separated into 4 groups (4T1+polydatin+fat diet group, 4T1+high-fat diet group, 4T1+polydatin group, and 4T1 group). To establish the obese TNBC mouse model, TNBC was xenografted 1×10 5 4T1 cells/50 μL per mouse at the right fourth mammary fat pad under anesthesia and the mice were fed a high fat diet. When the experiment was completed, total plasma cholesterol (TC) and cancer antigen (CA)15-3 were measured. The enzyme-linked immunosorbent assay (ELISA) method was used detect CA15-3. Oil red O staining was used to observe the morphological changes. Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the corresponding protein expression and the messenger RNA (mRNA) level.Results: Polydatin decreased the degree of fatty liver, as determined by oil red O staining. The TC level in the 4T1+fat diet group was significantly higher, and it was decreased in the 4T1+polydatin group. The results of ELISA showed that compared with the 4T1 group, CA15-3 was significantly increased in the 4T1+fat diet group, and polydatin was shown to significantly reduce the expression of CA15-3. Polydatin inhibited p-JAK2 and p-STAT3 mRNA and protein levels. Polydatin increased pyroptosis-related gene mRNA and protein level. Conclusions:We believe that polydatin can effectively reduce blood lipid levels in TNBC mice with a high-fat diet, and play an anticancer role in TNBC. The underlying mechanism may be related to the JAK2/ STAT3 signaling pathway and pyroptosis in TNBC. Our results contribute to validating the traditional use of polydatin in the treatment of TNBC with hyperlipidemia.

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.