Yin Yang 1 promotes the neuroendocrine differentiation of prostate cancer cells via the non-canonical WNT pathway (FYN/STAT3).

BACKGROUND: A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumours. The purpose of the current study was to determine the mechanism by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity. METHODS: Using the Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, we bioinformatically analyzed YY1 expression in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells via epithelial-mesenchymal transition induction and neuroendocrine differentiation. RESULTS: Androgen deprivation therapy induced a decrease in YY1 protein ubiquitination, enhanced its stability, and thus enhanced the transcriptional activity of FZD8. Castration enhanced FZD8 binding to Wnt9A and mediated cellular plasticity by activating the non-canonical Wnt (FZD8/FYN/STAT3) pathway. CONCLUSIONS: We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We believe that an in-depth investigation of the mechanism underlying YY1-mediated disease may lead to improved NEPC therapies.

New C21-steroidal aglycones from the roots of Cynanchum otophyllum and their anticancer activity.

Naturally occurring C21-steroidal aglycones from Cynanchum exhibit significant antitumor effects. To expand the chemical diversity and get large scale C21-steroidal aglycones, the extracts of the roots of Cynanchum otophyllum were treated with 5% HCl in aqueous and the resulting hydrolysate was investigated. Nine new C21-steroidal aglycones (1-9) namely cynotogenins A-I, along with seventeen known analogous (10-26), were isolated from the hydrolysate. The structures of compounds 1-9 were elucidated by spectroscopic analysis (IR, HR-ESI-MS, 1D and 2D NMR) and comparison of observed spectroscopic data with those of reported in the literature. Aglycones 2-5 with rare cis-cinnamoyl group as well as 8 and 9 with 5ß,6ß-epoxy group were found from the genus of Cynanchum for the first time. The cytotoxicities of compounds 1-26 toward human cancer HeLa, H1299, HepG2, and MCF-7 cells were evaluated and preliminary structure-activity relationship (SAR) was discussed. Moreover, compound 20 inhibits HepG2 cell apoptosis and induces of G0/G1 phase arrest in a dose dependent manner.

[Aging-related change of erectile function and the expression of SIRT1].

OBJECTIVE: To explore aging-related changes in erectile function and the expressions of SIRT1 and other relevant factors in rats. METHODS: We divided 40 male SD rats into four age groups of equal number: 2-month-old (2 mo), 8-month-old (8 mo), 14-month-old (14 mo), and 20-month-old (20 mo), measured the intracavernous pressure (ICP), mean arterial pressure (MAP), and ICP/MAP ratio by electrostimulation of the cavernous nerve, evaluated fibrosis in the corpus cavernosum by Masson's trichrome staining, detected the expressions of SIRT1, P53, and FOXO3a by Western blot, and determined the levels of NO and cGMP using the NO/cGMP kit. RESULTS: Both the ICP/MAP ratio and the cGMP level were elevated with aging, reaching the peak at 8 months and then gradually decreased. Masson staining showed an aging-related increase of collagen fibers in the corpus cavernosum.The expression of SIRT1 was reduced while those of P53 and FOXO3a increased with aging. CONCLUSIONS: Aging-related erectile dysfunction may be attributed to the reduced activity of the NO/cGMP pathway, apoptosis and oxidative stress, and SIRT1 may play a role in aging-related erectile dysfunction.

[Effects of oxymatrine injection combined with low-dose paclitaxel on mRNA and protein expressions of vascular endothelial growth factor and CXC chemokine receptor 4 in human gastric carcinoma SGC-7901 cells].

OBJECTIVE: To investigate the effects of oxymatrine injection (OI) combined with low-dose paclitaxel on expressions of mRNAs and proteins of vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4) in human gastric carcinoma SGC-7901 cells. METHODS: Methyl thiazolyl tetrazolium assay was used to examine the effects of OI combined with low-dose paclitaxel on proliferation of SGC-7901 cells. Real-time reverse transcription-polymerase chain reaction, immunofluorescence and enzyme-linked immunosorbent assay were employed to measure the expressions of VEGF and CXCR4 mRNAs and proteins in gastric carcinoma SGC-7901 cells respectively. RESULTS: Except that 20 µg/mL paclitaxel had no influence on expression of VEGF mRNA in SGC-7901 cells (P>0.05), 40 µg/mL OI or low-dose paclitaxel (20 µg/mL) inhibited the proliferation of SGC-7901 cells and reduced the expressions of VEGF and CXCR4 mRNAs and proteins in SGC-7901 cells (P<0.01). The expressions of VEGF and CXCR4 mRNAs and proteins in the OI plus low-dose paclitaxel group were markedly lower than those in the low-dose paclitaxel group (P<0.01). CONCLUSION: OI combined with low-dose paclitaxel can inhibit VEGF and CXCR4 of gastric carcinoma SGC-7901 cells markedly, which may be one of its mechanisms of anti-angiogenic ability.

[Sperm DNA damage and assisted reproductive technology].

With the introduction of assisted reproductive technology (ART), sperm assessment has developed progressively, from conventional semen routine tests to novel cellular and molecular measures. Sperm DNA damage is a new marker of male fertility, whose genetic mechanism involves abnormal package and segregation of chromatin, oxidative stress, abnormal cell apoptosis, etc. Sperm chromatin structure assay (SCSA) is one of the common techniques to measure sperm DNA damage. Sperm DNA damage might be associated with the pregnancy outcome of ART, recurrent spontaneous abortion and potential genetic risk of ICSI offspring. Some treatment strategies might reduce the percentage of sperm DNA damage and increase the success rate of ART, including oral administration of antioxygen drugs, ICSI with testis sperm, sperm freezing and preservation, removing of etiological factors, traditional Chinese medicine, and so on. This review focuses on the mechanism and detection of sperm DNA damage, its association with reproductive outcomes, and relevant treatment strategies in assisted reproductive technology.