Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN. Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined. We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7. The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is characterized by increase of intraosseous pressure because of lipid metabolism disturbance such as elevation of adipogenesis and fat cell hypertrophy in the bone marrow, subsequently leading to disturbances of coagulation-fibrinolysis system in the femoral head and finally resulting in bone ischemia. Pravastatin has been demonstrated to be useful in preventing steroid-induced ONFH in animal models. However, its exact mechanisms acting on this disease have not been fully elucidated. To address this problem, steroid-induced ONFH rat model was constructed to evaluate the effects of pravastatin treatment on the osteonecrotic changes and repair processes. Then, Micro-CT-based micro-angiography was performed to assess the effects of pravastatin treatment on vascularization. In addition, serum lipid levels were detected by haematological examination. After that, the expression of peroxisome proliferator-activated receptor gamma (PPARγ), Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5), β-catenin and runt-related transcription factor 2 (RUNX2) at both mRNA and protein levels were further detected by immunohistochemistry, real-time quantitative PCR, and Western blot analyses. The results, the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were dramatically lower in the pravastatin treatment groups than in the model group (all P < 0.05). Moreover, by micro-CT quantification, pravastatin treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads of steroid-induced ONFH rats. Importantly, pravastatin treatment could prevent steroid-induced ONFH by suppressing the expression of PPARγ, and increasing the expression of Wnt3a, LRP5, β-catenin, and RUNX2, at both mRNA and protein levels, in the femoral heads of steroid-induced ONFH rats. In conclusion, Pravastatin may prevent steroid-induced ONFH by suppressing PPARγ expression and activating Wnt signaling pathway.

Background: Short internodes contribute to plant dwarfism, which is exceedingly beneficial for crop production. However, the underlying mechanisms of internode elongation are complicated and have been not fully understood.Results: Here, we report a maize dwarf mutant,dwarf2014(d2014), which displays shortened lower internodes. Map-based cloning revealed that thed2014gene is a novelbr2allele with a splicing variation, resulting in a higher expression ofBR2-T02instead of normalBR2-T01. Then, we found that the internode elongation ind2014/br2exhibited a pattern of inhibition-normality-inhibition (transient for the ear-internode), correspondingly, at the 6-leaf, 12-leaf and 14-leaf stages. Indeed,BR2encodes a P-glycoprotein1 (PGP1) protein that functions in auxin efflux, and our in situ hybridization assay showed thatBR2was mainly expressed in vascular bundles of the node and internode. Furthermore, significantly higher auxin concentration was detected in the stem apex ofd2014at the 6-leaf stage and strictly in the node region for the ear-internode at the 14-leaf stage. In such context, we propose that BR2/PGP1 transports auxin from node to internode through the vascular bundles, and excessive auxin accumulation in the node (immediately next to the intercalary meristem) region suppresses internode elongation ofd2014.Conclusions: These findings suggest that low auxin levels mediated by BR2/PGP1 in the intercalary meristem region are crucial for internode elongation.

Diabetic nephropathy is one of the most significant microvascular complications in patients with type 2 diabetics. The concise mechanism of diabetic nephropathy is unknown and there is no successful treatment. The objective of study was to investigate effects of Chinese herbs (Tangshen Formula) on diabetic nephropathy in Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. OLETF rats and LETO rats were divided into four groups: LETO control, OLETF diabetics, OLETF diabetics treated with Tangshen Formula, and OLETF diabetics treated with Monopril. Body weight, blood glucose, and 24 h urinary proteins were measured once every four weeks. Blood samples and kidney tissues were obtained for analyses of total cholesterol, triglyceride, whole blood viscosity, plasma viscosity, and pathohistological examination at 36 and 56 weeksrespectively. Untreated OLETF rats displayed diabetic nephropathy over the study period. Treatment of OLETF rats with Tangshen Formula attenuated the increases in blood glucose, body weight, 24 h urinary protein content, serum total cholesterol, whole blood viscosity and plasma viscosity at certain time. Treatment with Tangshen Formula also reduced glomerulosclerotic index and interstitial fibrotic index seen in OLETF rats. In conclusion, Tangshen Formula could attenuate the development of diabetic nephropathy in OLETF rat diabetic model.