Tspan5 promotes the EMT process to regulate the syncytialization of trophoblast cells by activating Notch signalling.

Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. ß-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.

Activation of mucosal mast cells promotes inflammation-related colon cancer development through recruiting and modulating inflammatory CD11b(+)Gr1(+) cells.

Mast cells (MCs) have been reported to be one of the important immunoregulatory cells in promoting the development of colitis-related colon cancer (CRC). It is not clear which MC subtypes play critical roles in CRC progression from colitis to cancer because mucosal mast cells (MMCs) are distinct from connective tissue mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic and inflammatory conditions. In the current study, we found that MMC numbers and the gene expressions of MMC-specific proteases increased significantly in an induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after MMC activation not only resulted in the accumulation of CD11b(+)Gr1(+) inflammatory cells in the colon tissues but also modulated the activities of CD11b(+)Gr1(+) cells to support tumor cell growth and to inhibit T cell activation. Blocking the MMC activity in mice that had developed colitis-related epithelium dysplasia, CD11b(+)Gr1(+) infiltration was reduced and CRC development was inhibited. Our results suggest that MMC activation recruited and modulated the CD11b(+)Gr1(+) cells to promote CRC and that MMCs can be potential therapeutic targets for the prevention of CRC development.

Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women.

BACKGROUND: The generation of antibodies (anti-HBe) against hepatitis B virus (HBV) e antigen (HBeAg) often coincides with clinical remission in chronic HBV patients. We aimed to examine the effect of maternal anti-HBe in protection against HBV mother-to-child transmission (MTCT). METHODS: A total of 140 chronic HBV-infected pregnant women participated in this study. Before delivery, maternal HBV serological markers and HBV viral load were determined and anti-HBe titers were semi-quantified. Neonatal hepatitis B surface antigen (HBsAg) and HBV-DNA status were determined from cord blood. The children were followed to age 1-3 years. RESULTS: The HBV-DNA positive rate in cord blood was 75.61% (31/41) in those who were born to mothers with serum HBV-DNA >10(6) IU/ml, which was significantly higher than in those who were born to mothers with HBV-DNA <10(6) IU/ml (3/99, 3.03%; p<0.0001). However, 10 newborns from mothers with serum HBV-DNA >10(6) IU/ml had no detectable HBV-DNA in cord blood; anti-HBe was positive with a median titer of 10 (interquartile range 10-55). A total of 84 children who received hepatitis B immune globulin (HBIG) within 12h after birth and who completed three doses of recombinant HBV vaccination were followed to age 1-3 years (up to May 2014). All 56 children who were born to mothers with serum HBV-DNA levels <10(6) IU/ml were HBsAg-negative. Five of the 22 children born to anti-HBe-negative mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. However, none of the six children who were born to anti-HBe-positive/weak-positive mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. CONCLUSIONS: The presence of maternal anti-HBe is protective against HBV MTCT, independent of the maternal serum HBV viral load.