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Placentation, which is critical for maternal-fetal exchange of nutrients and gases, is a complicated process comprising stepwise vasculogenesis and angiogenesis. Hypoxia caused by impaired trophoblast invasion may cause various angiogenic abnormalities in human placenta. The Notch1 signaling pathway plays an important role in the regulation of angiogenesis. The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notch1/Dell4/Jagged1 were investigated in this study. The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay, so as to discover the possible role of notch1 signaling pathway in the angiogenesis of human placenta. The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions. The mRNA and protein levels of Notch1/Dell4/Jagged1 were decreased in the hypoxic group compared to the control one. In addition, the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition, but promoted when treated with JAG-1. The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway. [ABSTRACT FROM AUTHOR]

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas ( P<0.05) and healthy fertile non-pregnant controls ( P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas ( P<0.05) and healthy fertile non-pregnant controls ( P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer. [ABSTRACT FROM AUTHOR]

This study aimed to identify biochemical predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP). A total of 106 ICP cases were analyzed retrospectively by the combination of receiver operating characteristic curve and binary logistic regression analysis. 'Adverse perinatal outcomes' included spontaneous preterm labor, meconium-staining of amniotic fluid, stillbirth and Apgar score ≤7 at 1 or 5 min. Total bile acid (TBA) [AUC=0.658, 95%CI (0.536, 0.781), P=0.031] was a valuable predictor for adverse perinatal outcomes. The critical value of TBA above which adverse perinatal outcomes were observed was 40.15 μmol/L (Youden's index=0.3). Binary multivariate logistic regression analysis revealed that the risk of adverse perinatal outcomes increased when TBA ≥40.15 μmol/L [OR=3.792, 95%CI (1.226, 11.727), P=0.021]. It is concluded that the risk of adverse perinatal outcomes in ICP increases when maternal TBA ≥40.15 μmol/L. [ABSTRACT FROM AUTHOR]