Human trophoblast progenitor cells differentiate via two distinct pathways, to become the highly invasive extravillous cytotrophoblast (CTB) cells (EVT) or fuse to form syncytiotrophoblast. Inadequate trophoblast differentiation results in poor placenta perfusion, or even complications such as pre-eclampsia (PE). Cullin1 (CUL1), a scaffold protein in cullin-based ubiquitin ligases, plays an important role in early embryonic development. However, the role of CUL1 in trophoblast differentiation during placenta development has not been examined. Here we show that CUL1 was expressed in CTB cells and EVT in the first trimester human placentas by immunohistochemistry. CUL1 siRNA significantly inhibited outgrowth of extravillous explants in vitro, as well as invasion and migration of HTR8/SVneo cells of EVT origin. This inhibition was accompanied by decreased gelatinolytic activities of matrix metalloproteinase (MMP)-9 and increased expression of tissue inhibitors of MMPs (TIMP-1 and -2). Consistently, exogenous CUL1 promoted invasion and migration of HTR8/SVneo cells. Notably, CUL1 was gradually decreased during trophoblast syncytialization and CUL1 siRNA significantly enhanced forskolin-induced fusion of choriocarcinoma BeWo cells. CUL1 protein levels in human pre-eclamptic placental villi were significantly lower as compared to their matched control placentas. Taken together, our results suggest that CUL1 promotes human trophoblast cell invasion and dysregulation of CUL1 expression may be associated with PE.

Aim To evaluate the effects of phacoemulsification on intraocular pressure (IOP) and ultrasound biomicroscope (UBM) images of filtering bleb in eyes with cataract and a previous functioning filtering bleb. Methods The IOPs and UBM images of filtering bleb of 24 patients (27 eyes) who underwent phacoemulsification after successful trabeculectomy were recorded at each follow-up examination and at the 12 months after phacoemulsification, respectively. Preoperative IOP and two parameters of the UBM images, including visibility of a route under the scleral flap and reflectivity inside the bleb were evaluated for an association with postoperative success rate using Kaplan-Meier survival analysis.

and aggregation responses to agonists. This enhanced basal Ca 2+ was largely dependent on intracellular Ca 2+ and insensitive to inositol 1,4,5-trisphosphate receptor (IP 3 R) antagonism. Additionally, the expression of the skeletal CSQ isotype (CSQ-1) was detected in both rat and human platelets, but its levels were significantly lowered in diabetic platelets as compared with normal platelets. Impairment of CSQ by trifluoperazine caused concentration-dependent Ca 2+ release in normal platelets and HEK293 cells. Knocking down CSQ-1 in HEK293 cells resulted in increased leakage of Ca 2+ , which was also insensitive to IP 3 R inhibition, and exaggerated Ca 2+ release following carbachol treatment. Conclusions: Downregulation of CSQ-1 in diabetic platelets and impairment of CSQ-1 in normal cells leads to disturbed Ca 2+ release, demonstrating a potential role for CSQ-1 in the regulation of the platelet Ca 2+ release process and a possible causal contribution to diabetic platelet hyperactivity.