Sorafenib inhibits transforming growth factor ß1-mediated epithelial-mesenchymal transition and apoptosis in mouse hepatocytes.

Epithelial-mesenchymal transition (EMT) is a physiological process that has been recognized to occur during the progression of an increasingly large number of human diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. The activation of transforming growth factor ß (TGF-ß) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-ß signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-ß signaling. When applied to AML12 cells and primary hepatocytes, sorafenib strikingly suppressed TGF-ß1-induced EMT and apoptosis. Additionally, sorafenib inhibited TGF-ß1-induced signal transducer and activator of transcription 3 phosphorylation. We further present in vitro evidence that sorafenib ameliorates the proapoptotic and profibrotic effects of TGF-ß1 in mouse primary hepatocytes, suggesting that this drug exerts a protective effect on hepatocytes and has therapeutic potential for the treatment of liver fibrosis.

Successful pregnancy following the transfer of vitrified blastocyst which developed from poor quality embryos on day 3.

BACKGROUND: The selection of pre-embryos for transferred is based on morphological appearance. But some poor quality cleaved embryos also can be cultured to the blastocyst stage and implanted. OBJECTIVE: To assess the clinical pregnancy outcomes of blastocyst transfer which developed from poor quality embryos. MATERIALS AND METHODS: A total of 109 cleaved embryos with poor quality were cultured to day 5/day 6 and 27 (24.8%) blastocysts were collected from the 15 cycles/patients undergoing conventional IVF. All the blastocysts were cooling with fast-freezing. Then the blastocysts were warmed for transfer. RESULTS: All of 25 vitrified blastocysts (92.6%) survived after warming and were transferred to 15 patients. Five of the women became pregnant. CONCLUSION: Our results suggest that vitrified human day 5/day 6 blastocyst transfer which develop from poor quality embryo at day 3 can contribute to increasing cumulative pregnancy rates in assisted reproduction.

Effect of the size of zona pellucida thinning by laser assisted hatching on clinical outcome of human frozen-thawed embryo transfers.

Of 122 consecutive procedures, 31 were not assisted hatching (AH), which served as the control group, 34 were AH with 40 microm thinning of the zona, and 57 were AH with 80 microns of the zona thinning. The pregnancy and implantation rates were significantly higher in 80 microns thinning group compared to control group (40.3 vs. 16.1 percent, P=0.03; 21.5 vs. 7.5 percent, P=0.007, respectively). In addition, the implantation rate was signigicantly higher in 80 microns group than in 40 microns group (21.5 percent vs.9.4 percent, P=0.024). The results indicated that the size of the zona pellucida thinning by laser may influence the pregnancy and implantation rates following frozen-thawed cleaved embryo transfer.