It is not known whether H(2)S can promote angiogenesis with improvement of regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H(2)S donor) was administered once a day for 4 w following femoral artery ligation. Collateral vessel growth, capillary density, regional tissue blood flow, the expression of endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and Akt were examined during or at the end of the treatment period. NaHS treatment significantly increased collateral vessel growth, capillary density, and regional tissue blood flow in ischemic hind limb muscles compared with the controls. These effects were associated with an increase in VEGF expression in the skeletal muscles and VEGFR2 phosphorylation in the neighboring vascular endothelial cells, suggesting a role of VEGF in mediating the NaHS effects in a cell-cell interaction pattern. Moreover, NaHS treatment also resulted in an increase in Akt phosphorylation in ischemic hind limb muscles. In conclusion, our observations with NaHS strongly suggest that H(2)S is a proangiogenic factor in chronic ischemia. The proangiogenic effect of NaHS may be mediated by interaction between the upregulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its downstream signaling element Akt in the vascular endothelial cells.
Aims: To examine if hydrogen sulfide (H 2 S) can promote glucose uptake and provide amelioration in type 2 diabetes. Results: Treatment with sodium hydrosulfide (NaHS, an H 2 S donor) increased glucose uptake in both myotubes and adipocytes. The H 2 S gas solution showed similar effects. The NaHS effects were blocked by an siRNA-mediated knockdown of the insulin receptor (IR). NaHS also increased phosphorylation of the IR, PI3K, and Akt. In Goto-Kakizaki (GK) diabetic rats, chronic NaHS treatment (30 lmol$kg -1 $day -1 ) decreased fasting blood glucose, increased insulin sensitivity, and increased glucose tolerance with increased phosphorylation of PI3K and Akt in muscles. Similar insulin-sensitizing effects of NaHS treatment were also observed in Wistar rats. Moreover, glucose uptake was reduced in the cells with siRNA-mediated knockdown of the H 2 S-generating enzyme cystathionine c-lyase in the presence or absence of exogenous H 2 S. Moreover, chronic NaHS treatment reduced oxygen species and the number of crescentic glomeruli in the kidney of GK rats. Innovation and Conclusion: This study provides the first piece of evidence for the insulin-sensitizing effect of NaHS/H 2 S in the both in vitro and in vivo models of insulin resistance. Rebound Track: This work was rejected during a standard peer review and rescued by the Rebound Peer Review (Antoxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers:
A novel experimental approach, based on time-resolved two-dimensional (2D) ATR−FTIR spectroscopy has been used to study water diffusion behavior of novolac epoxy resins cured with novolac resin and novolac acetate resin named as EP and EPA, respectively. The diffusion coefficients calculated by a nonlinear curve fitting are quite consistent with the results of gravimetric analysis. In 2D-IR spectra, the splitting of the water OH vibration band at 2800−3700 and 1500−1800 cm-1 shows that there are two different states of water in epoxy networks, in which one could be confined into free volume (microvoids) or molecularly dispersed with less hydrogen-bonding (bulk dissolved), while the other could be attributed to bound water forming strong hydrogen-bonding with hydrophilic groups of epoxy networks. The sequential order of intensity changes of the two water bands elucidates that, in the process of water diffusion into epoxy networks, water molecules first bind with specific hydrophilic groups as bound water and then diffuse into free volume (microvoids) or molecularly dispersed with less hydrogen-bonding (bulk dissolved). The wavenumber difference of OH vibration band appearing from bound water between EP and EPA indicates that water molecules form much stronger hydrogen-bonding with EP networks than with EPA networks.
In the present work, water sorption behaviors at different temperatures ranging from 20 to 80 °C were monitored in a model Novolac cured epoxy resin (EP) and its esterfied ramifications (with CH 3 COO, CH 3 CH 2 CH 2 COO, and C 6 H 5 CH 2 COO side groups referred to as EPA, EPB, and EPP, respectively). In light of gravimetric measurements and positron annihilation lifetime spectroscopy, a sorption mechanism was established, which suggested that the equilibrium water content was thermodynamically controlled, while the diffusion process was kinetically controlled. The driving force of the diffusion resulted in energy released by the hydrogen bonds, whereas the transportation rate was essentially subject to the local-chain mobility as well as the dissociation of water molecules from the epoxy network. To verify this model, dynamic mechanical analysis and time-resolved attenuated total reflection Fourier transform infrared spectroscopy experiments were employed. With generalized two-dimensional correlation analysis, the results obtained from IR spectra were consistent with the mechanism proposed.
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