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Background and purpose: Abnormal expression and amplification of transforming growth factor beta 1 (TGF-β1) and Notch3 in ovarian carcinoma tissues are associated with metastasis and low survival rate, respectively. The crosstalk between TGF-β1 and Notch3 signaling pathway promotes invasion and metastasis in various cancers. However, the mechanism is still under debate. Therefore, this study was designed, using in vitro cytological assays, to investigate the effects of TGF-β1 and Notch3 signaling pathway on ovarian cancer cell biological behavior and the potential mechanisms in terms of the crosstalk between TGF-β1 and Notch3 signaling pathway. Methods: Hey A8 and Hey cell lines were used as models in the study. The levels of TGF-β1 in supernatants from culture media were measured by ELISA. Both cell lines were treated with 500 ng/mL TGF-β1 neutralizing antibody (control group), 10 ng/mL TGF-β1, 50 μmol/L DAPT, 10 ng/mL TGF-β1 and 50 μmol/L DAPT, 50 μmol/L tumor necrosis factor receptor-associated factor 6 (TRAF6) peptide inhibitor, 10 ng/mL TGF-β1 and 50 μmol/L TRAF6 peptide inhibitor, respectively. The protein expression levels of TGF-β1 and Notch3 signaling pathway molecules as well as TRAF6 from cell lines with different treatments were detected by Western blot. Cell proliferation, migration and invasion were tested by cell counting kit-8 (CCK-8), scratch and Transwell assays, respectively. Results: The levels of TGF-β1 were timedependently increased in supernatants of culture media from Hey A8 and Hey cell lines. Compared with control group, TGF-β1 treatment increased the expression levels of Notch3-ICD and Hes1, while no obvious change was observed in the group treated with DAPT and TGF-β1. Moreover, TGF-β1 promoted cell proliferation, migration and invasion while DAPT decreased the proliferation, migration and invasion in cell lines treated with TGF-β1. These results indicated that TGF-β1 might promote proliferation, invasion and migration of ovarian epithelial cancer cells through activating the Notch3 signaling pathway. Further study showed that TGF-β1 up-regulated TRAF6 and activated the Notch3 signaling pathway. The activation of the Notch3 signaling pathway by TGF-β1 was inhibited in cells treated with the TRAF6 specific inhibitor. Conclusions: TGF-β1 may promote the proliferation, invasion and migration of ovarian epithelial carcinoma cells through TRAF6-mediated activation of the Notch3 signaling pathway.
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Mitochondrial disease is an unusual genetic disease .The in vitro fertilization technology of “three-parent embryos” as a new assisted reproductive technology , may help women to prevent their mitochondrial diseases passing on to their children , but it′s still controversial in many aspects .The article presents some scientific and ethical analysis and reflection on this technology .In terms of its necessity , safety, efficacy, and ethical were dis-cussed , and the application of the technology may bring the risk of concern is put forward , based on the present sit-uation of and attitude toward the technology should be taken to keep .
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Objective To explore the impacts of preeclampsia and the different extent of proteinuria on maternal and perinatal outcomes.Methods The retrospective analysis was conducted according to the perinatal clinical data of preelacmpsia,pregnancy-induced hypertension in pregnant women and normal pregnant women from the Fifth People's Hospital of Shanghai,excluding twins,diabetic mellitus and patients with chronic kidney disease previously.Patients were divided into three groups on the basis of their conditions:① preeclampsia patients (A group,220 cases); ② patients with gestational hypertension (B group,189 cases); ③ normal pregnant (C group,220 cases).Patients with pre-eclampsia according to the degree of proteinuria were further divided into three subgroups:A1:patients with mild proteinuria (n =109); A2:patients with moderate proteinuria (n =72); A3:patients with severe proteinuria (n =39).Results Compared with the other two groups,the patients in A group had higher blood pressure,serum creatinine,uric acid,cesarean section rate,perinatal prematurity,stillbirth,fetal distress and neonatal asphyxia in preeclampsia group.However,the serum albumin level,eGFR,neonatal birth weight,length and Apgar scores were lower in A group compared with B and C group (P ＜ 0.05).In three subgroups,serum creatinine level,uric acid level,cesarean section rate,perinatal prematurity and fetal distress were significantly increased in A3 group compared with A1 group,while the serum albumin level,eGFR,gestational age and neonatal birth weight were obviously lower in A3 group than in A1 group (P ＜ 0.05).In patients with preeclampsia,24 h urinary protein was negatively related with the levels of serum albumin and eGFR (P ＜ 0.05),and positivly related with the blood pressure,serum creatinine and caesarean production rate (P ＜ 0.05).Large amounts of proteinuria was a risk factor of adverse outcome for pregnant patients with preeclampsia (OR =2.899,P ＜ 0.05).Conclusions Preeclampsia patients with large amount of proteinuria have poor maternal and perinatal outcomes.Massive proteinuria is a risk factor of adverse outcome for patients with pre-eclampsia.
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Objective To investigate the association of the expressions of glomerular nephrin, vascular endothelial growth factor (VEGF) and its receptor (VEGFR) with proteinuria in preeclampsia rats. Methods A rat model of preeclampsia was developed by inhibitor of nitric oxide synthase (L-NAME). The systolic blood pressure (SBP) and 24 h urine protein were compared among the normal female group (n=6), the normal pregnant group (n=8), nonpregnant control group (n=6) and preeclampsia group(n=8). The kidney biopsies of each group were observed by light and electron microscopy. The glomerular nephrin was detected by Western blotting and real-time PCR. Immunofluorescence was used to detect the expression of WT1. The level of glomerular VEGF and VEGFR (Flt-1 and Flk-1) were evaluated by Western blotting. Results The level of glomerular nephrin protein in the rats with preeclampsia (0.0726±0.0074) was significantly lower compared with normal female group (0.3795±0.0509), normal pregnant group (0.2361±0.0437) and nonpregnant control group (0.7265±0.0503) (P＜0.01, respectively), while the levels of nephrin mRNA were not significantly different among 4 groups. The expression of WT1 was not significantly different among 4 groups as well. The level of glomerular VEGF in preeclampsia group (1.5429±0.0898) was significantly higher compared with normal female group (1.1870±0.1160), normal pregnant group (1.3741 ±0.1165) and nonpregnant control group (1.0155±0.0742)(P＜0.01,respectively). VEGFR (Flt-1 and Flk-1) was also significantly higher in preeclampsia rats compared with other control groups (P＜0.05, respectively). Conclusions In preeclampsia rats, nephrin is decreased significantly and the glomerular VEGF-VEGFR is increased significantly compared with the other control groups. The abnormal expression of nephrin and VEGF-VEGFR may be involved in the preeclampsia proteinuria. The underlying mechanism of this phenomenon needs further research.