The molecular mechanisms whereby hyperbaric oxygen (HBO) improves ischemic wound healing remain elusive. In this study, a rat model of wound ischemia was used to test the hypothesis that HBO enhances wound healing by modulating hypoxia-inducible factor-1alpha (HIF-1alpha) signaling. Male Sprague-Dawley rats underwent creation of a previously validated ischemic flap. Three groups underwent daily treatment: HBO (90 minutes, 2.4 atm); systemic administration of the free radical scavenger, N-acetylcysteine (NAC 150 mg kg(-1) intraperitoneal); control (neither HBO nor NAC). HBO treatment improved healing of the ischemic wounds. Analysis of ischemic wound tissue extracts demonstrated significantly reduced expression of HIF-1alpha, p53, and BNip3. Additionally, HBO increased expression of Bcl-2 while decreasing cleaved caspase-3. DNA fragmentation was abolished and the number of TUNEL-positive cells was reduced compared to the other groups. Vascular endothelial growth factor, cyclooxygenase-2, and neutrophil infiltration were reduced in ischemic wounds treated with HBO. These results indicate that HBO improves ischemic wound healing by downregulation of HIF-1alpha and subsequent target gene expression with attenuation of cell apoptosis and reduction of inflammation.

Polyphenolic compounds present in fruits, vegetables and grains are bioactive molecules which elicit a wide range of responses both in vivo and in vitro. The aim of this study is to investigate whether the soybean isoflavone, equol could induce apoptosis in ovarian cancer cells, SKOV-3. In this study, we evaluated molecular events associated with apoptosis induced by equol and paclitaxel (PTX). To assess whether growth inhibition was due to apoptosis, flow cytometry, colorimetry experiments, immunoblot analyses through measuring DNA fragmentation, the level of TRAIL, the cleavage of poly(ADP-ribose) polymerase (PARP) and the activation of caspase-3, -8 and -9 were also performed. Results showed that apoptosis was induced by extrinsic pathway triggered by TNF family members. Overall results suggested that equol induces apoptosis in SKOV-3 cells via a TRAIL and caspase 8-dependent pathway whereas paclitaxel leads to smaller apoptotic events when compared to that of equol.