Sonic hedgehog improves delayed wound healing via enhancing cutaneous nitric oxide function in diabetes.

Sonic hedgehog (SHH) plays an important role in postnatal tissue repair. The present study tested the hypothesis that impaired SHH pathway results in delayed wound healing by suppressing cutaneous nitric oxide (NO) function in type 1 diabetes. Adult male C57/B6 mice and streptozotocin (STZ)-induced type 1 diabetic mice were used. Although cutaneous SHH and Patched-1 (Ptc-1 encoded by PTCH, PTCH 1) proteins were increased significantly on day 4 after wounding compared with day 0 in normal mice, both were decreased significantly in STZ-induced diabetic mice. Topical application of SHH restored wound healing delay in STZ-induced diabetic mice, with a concomitant augmentation of both cutaneous constitutive nitric oxide synthase (NOS) activity and nitrite level. The effects of SHH on wound healing and cutaneous NO function were markedly inhibited by SHH receptor inhibitor cyclopamine. After 24-h treatment in vitro, SHH (5-20 microg/ml) significantly increased cutaneous endothelial NOS protein expression, NOS activity and NO level in normal mice and STZ-induced diabetic mice in a concentration-dependent manner, an effect that was blunted by cyclopamine and NOS inhibitor N(omega)-nitro-L-arginine methyl ester. The phosphatidylinositol 3-kinase inhibitor LY-294002 significantly blunted the increase of NOS activity and NO level induced by SHH treatment in human umbilican vein endothelial cells. These results demonstrate that the SHH pathway is activated in a normal wound, and its reduction results in impaired NO function and wound healing in diabetes. Strategies aimed at augmenting the endogenous SHH pathway may provide an effective means in ameliorating delayed diabetic wound healing.

Phthalimide-based "D-N-A" emitters with thermally activated delayed fluorescence and isomer-dependent room-temperature phosphorescence properties.

Phthalimide-based "D-N-A" emitters o-AI-Cz, m-AI-Cz and p-AI-Cz showed TADF and RTP properties due to their small ΔEST in both film and crystalline states. In particular, o-AI-Cz exhibited an ultralong RTP with a lifetime of 602 ms in air and remarkable afterglow, which could allow it to be used as a security ink for application in anti-counterfeiting materials. Moreover, o-AI-Cz showed intense intramolecular interaction between the donor and the acceptor subunits, while p-AI-Cz could form regular hexagonal pores with a diameter of 13.171 Å in the solid state, which might result in their different RTP properties.

Simvastatin inhibits leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes.

AIM: To test the hypothesis that statins inhibit leptin-induced hypertrophy in cultured neonatal rat cardiomyocytes. METHODS: Cultured neonatal rat cardiomyocytes were used to evaluate the effects of simvastatin on leptin-induced hypertrophy. Intracellular reactive oxygen species (ROS) levels were determined by using 2',7'-dichlorofluorescein diacetate (DCF-DA) fluorescence. Total intracellular RNA and cell protein content, which serve as cell proliferative markers, were assayed by using propidium iodide (PI) fluorescence and the Bio-Rad DC protein assay, respectively. The cell surface area, an indicator of cell hypertrophy, was quantified by using Leica image analysis software. RESULTS: After 72 h treatment, leptin markedly increased RNA levels, cell surface area, and total cell protein levels in cardiomyocytes, which were significantly inhibited by simvastatin or catalase treatment. ROS levels were significantly elevated in cardiomyocytes treated with leptin for 4 h compared with those cells without leptin treatment. The increase in ROS levels in cardiomyocytes induced by leptin was reversed by treatment with simvastatin and catalase. CONCLUSION: Simvastatin inhibits leptin-induced ROS-mediated hypertrophy in cultured neonatal rat cardiac myocytes. Statin therapy may provide an effective means of improving cardiac dysfunction in obese humans.