MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells.

BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated. METHODS: The regulatory effects by MDM2 on cell motility was emulated by wound-healing and transwell assays. The effects on EMT transition and Smad pathway were studied by depicting the expression levels of epithelial marker E-cadherin as well as key components of Smad pathway. To evaluate the clinical relevance of our findings, the correlation of MDM2 expression levels with the stages of 104 ovarian cancer patients was investigated by immunohistochemistry assay. RESULTS: We demonstrate that MDM2 functions as a key factor to drive EMT and motility of ovarian SKOV3 cells, by facilitating the activation of TGF-ß-Smad pathway, which results in the increased transcription of snail/slug and the subsequent loss of E-cadherin levels. Such induction of EMT is sustained in either E3 ligase-depleted MDM2 or E3 ligase inhibitor HLI-373-treated cells, while being impaired by the N-terminal deletion of MDM2, which is also reflected by the inhibitory effects against EMT by Nutlin-3a, the N-terminal targeting agent. The expression levels of MDM2 is highly correlated with the stages of the ovarian cancer patients, and the higher expression of MDM2 together with TGFB are closely correlated with poor prognosis and predict a high risk of ovarian cancer patients. CONCLUSIONS: This study suggests that MDM2 activates Smad pathway to promote EMT in ovarian cancer metastasis, and targeting the N-terminal of MDM2 can reprogram EMT and impede the mobility of cancer cells.

Bio-inspired semi-transparent silver nanowire conductor based on a vein network with excellent electromechanical and photothermal properties.

A bio-inspired conductive binary-network of vein-silver nanowires (AgNWs) was embedded in poly(dimethylsiloxane) (PDMS) to prepare a semi-transparent stretchable conductor (vein-AgNWs-PDMS) by a simple dipping process. The special conductive structure was constructed by using veins with a porous structure as an ideal skeleton to load AgNW networks, which allowed the vein-AgNWs-PDMS composite to show a low sheet resistance of 1 Ω sq-1 with 74% transmittance. The figure of merit of vein-AgNWs-PDMS is as high as 2502 and can be adjusted easily by controlling the times of the dipping cycle. Furthermore, the vein-AgNWs-PDMS conductor can retain high conductivity after 150% mechanical elongation and exhibit excellent electromechanical stability in repeated stretch/release tests with 60% strain (500 cycles). As an example of an application, patterned light-emitting diode (LED) arrays using the vein-AgNWs-PDMS conductors have been fabricated, and worked well under deformation. Moreover, the photo-thermal properties of the vein-AgNWs-PDMS composite have been demonstrated by a position heating experiment using near-infrared (NIR) laser irradiation and the generated heat can be effectively dissipated through the vein network to avoid local overheating. Due to the high-performance and facile fabrication process, the vein-AgNWs-PDMS conductors will have multifunctional applications in stretchable electronic devices.

[A control study of a school-based life skills education on prevention of behavior problems in third-grade schoolchildren].

OBJECTIVE: To evaluate the effectiveness on the prevention of behavior problems of life skills education combining school-based and parent-involved approaches for third-grade students in China. METHODS: This research was targeted at the population of third-grade children in two elementary schools in Qinhuangdao City, Hebei Province. Nine regular school classrooms were randomly divided into three groups: the intervention group (n=208), internal control group (n=209) and external control group (n=204). The intervention included 26-hour competence promotion for students and 5-hour parent training. The Rutter Scale by parent and teacher were used to evaluate the effects at pretest, posttest and 6-month follow-up. RESULTS: Improvement was observed among children in the intervention group than those in the control groups. The statistical difference was significant (P<0.05).1.The prevalence of total behavior problems, antisocial behavior and neurotic behavior problem at home: At termination, the prevalence in intervention group(11.2%,3.6% and 6.1%)was lower (except neurotic behavior) than those in internal control group (19.4%,5.6% and 6.1%)and external control group (18.9%,8.9% and 5.3%). At 6-month follow-up, the prevalence in intervention group (10.2%,2.5% and 3.6%)was still lower than those in internal control group (17.2%,6.8% and 6.8%)and external control group (17.8%,7.8% and 6.7%).2. The prevalence of total behavior problems and antisocial behavior problem at school: At termination, the prevalence in intervention group(5.3% and 4.3%)was lower than those in internal control group(10.1% and 7.7%)and external control group(14.9% and 12.4%). At 6-month follow-up, the prevalence in intervention group(2.9% and 2.4%)was still lower than those in internal control group (10.2% and 9.7%)and external control group(11.3% and 10.3%). CONCLUSION: Life skills education could reduce the children's home and school behavior problems, especially for antisocial behavior. The effects of intervention maintained during the 6-month follow-up study.