Respiratory exposure to graphene oxide induces pulmonary fibrosis and organ damages in rats involving caspase-1/p38MAPK/TGF-ß1 signaling pathways.

Numerous studies have shown that graphene oxide (GO) respiratory exposure led to severe lung injury, but whether pulmonary fibrosis caused by GO respiratory exposure is related to the activation of the caspase-1/p38MAPK/TGF-ß1 remains unclear. In this study, rats were administrated GO by intratracheal instillation and fed for three months, and the molecular mechanisms of GO on the pulmonary fibrosis and other organ damage caused by GO respiratory exposure were examined. The results showed that the expression of caspase-1/p38MAPK/TGF-ß1 pathway-related factors were significantly elevated with the increase of exposure concentrations of GO. Those data proved that the caspase-1/p38MAPK/TGF-ß1 signaling pathway was involved in the pulmonary fibrosis caused by GO respiratory exposure. The trends of related factors also proved that the caspase-1/p38MAPK/TGF-ß1 pathway was likely to play a dominant role in the sub-acute and sub-chronic stages. The other organ damage examination found that the liver and spleen were damaged initially by the GO respiratory exposure. Meanwhile for the testicle, although the acute injury was severe, signs of recovery were found during the three-month trial period.

17Beta-estradiol mediates the sex difference in capsaicin-induced nociception in rats.

We have previously shown that the male sex steroid testosterone inhibits slightly, but the female sex steroid 17beta-estradiol (E(2)) potentiates dramatically, the capsaicin receptor-mediated current in rat dorsal root ganglion (DRG) neurons. Here, we used pharmacological methods and the nociceptive behavioral test to determine whether there is a sex difference in capsaicin-induced acute pain in rats in vivo and what mechanism underlies this sex difference. Results revealed that intradermal injection of capsaicin induced a dose-dependent nocifensive response in males and females, with the dose required to produce a comparable level of nociception being approximately 3- to 4-fold higher in males than in females. In addition, females during the proestrus stage exhibited significantly greater capsaicin-induced nocifensive responses compared with the estrus stage. Moreover, the female's enhanced sensitivity to the capsaicin-induced nocifensive response was completely reversed by ovariectomy 6 weeks before capsaicin injection. It is noteworthy that intradermal coinjection of E(2) but not progesterone with capsaicin potentiated the capsaicin-induced nocifensive response in ovariectomized rats. Likewise, intradermal E(2) injection dose-dependently potentiated the capsaicin-induced nocifensive response in male rats. Furthermore, potentiation by E(2) of the capsaicin-induced nocifensive response in male rats was not significantly reduced by a selective protein kinase C (PKC) inhibitor or by a selective protein kinase A (PKA) inhibitor, indicating that neither PKC nor PKA was involved in the effect of E(2). These data demonstrate that E(2) mediates the female's enhanced sensitivity to capsaicin-induced acute pain, consistent with potentiation by E(2) of the capsaicin receptor-mediated current in rat DRG neurons.

[Study on differentiation of human mesenchymal stem cells into epidermal cells].

OBJECTIVE: To investigate the possibility of differentiation of human mesenchymal stem cells (hMSC) into epidemic cells in vitro. METHODS: hMSCs were segregated from normal adult human bone marrow by Percoll solution (1.073 g/ml) , and were cultured, purified, and amplified to 3th passage in vitro. Then the hMSCs were randomly divided into control group ( with treatment of normal L-DMEM medium) and experimental group (with treatment of L-DMEM medium containing epidermal growth factor,insulin,tretinoin, calcium chloride). After 7 days of culture, the morphologic changes of hMSCs in the 2 groups were observed with inverted phase contrast microscope. The expressions of P63 and PCK of hMSCs were assessed with immunohistochemical methods. RESULTS: The shape of hMSCs in experimental group became irregular or oblong in shape, while that in control group were still in spindle shape. Immunohistochemical results showed that hMSCs were P63 and PCK positive in the experimental group, while those in control group were negative. CONCLUSION: Human mesenchymal stem cells can differentiate into epidemic cell in vitro.