Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells.

The efficient gene transfection, cellular uptake and targeted delivery in vivo are key issues for non-viral gene delivery vectors in cancer therapy. To solve these issues, we designed a new targeted gene delivery system based on epidermal growth factor receptor (EGFR) targeting strategy. An anti-EGFR monoclonal antibody h-R3 was introduced to dendriplexes of PAMAM and DNA via electrostatic interactions to form self-assembled h-R3-PAMAM-DNA complexes (h-R3-dendriplexes). Dendriplexes h-R3-dendriplexes represented excellent DNA encapsulation ability and formed unique nanostructures. Compared to dendriplexes, h-R3-dendriplexes presented lower cytotoxicity, higher gene transfection efficiency, excellent endosome escape ability and high nuclear accumulation in the EGFR-overexpressing HepG2 cells. Both ex vivo fluorescence imaging and confocal results of frozen section revealed that h-R3-dendriplexes showed higher targeted delivery and much better gene expression in the tumors than dendriplexes at the same N/P ratio, and h-R3-dendriplexes had accumulation primarily in the tumor and kidney. Moreover, h-R3-dendriplexes for p53 delivery indicated efficient cell growth inhibition and potentiated paclitaxel-induced cell death. These results indicate that the h-R3-dendriplexes represent a great potential to be used as efficient targeted gene delivery carriers in EGFR-overexpressing tumor cells.

Association of obestatin with blood pressure in the third trimesters of pregnancy.

Obestatin is a recently discovered 23-amino acid peptide encoded by the same gene that encodes ghrelin. It has been reported that there is a significant negative correlation between the plasma ghrelin concentration and systemic blood pressure in patients with pregnancy-induced hypertension. We investigated the plasma concentration of obestatin in 18 non-pregnant women, 18 normal pregnant women, and 15 patients with pregnancy-induced hypertension. The plasma concentrations of obestatin in these 3 groups of women were 63.4+/-9.5pg/ml, 38.1+/-6.3pg/ml, and 46.0+/-9.3pg/ml, respectively. In non-pregnant women, there was no correlation between the plasma obestatin concentration and the mean arterial pressure. However, there was a positive correlation between the plasma obestatin concentration and the mean arterial pressure in normal pregnant women and pregnant women with pregnancy-induced hypertension. These results suggest that obestatin may have some potential role in the regulation of blood pressure in normal pregnant women and women with pregnancy-induced hypertension.

[Relationship of vascular endothelial growth factor with bile acid in intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the relationship of vascular endothelial growth factor (VEGF) with bile acid in intrahepatic cholestasis of pregnancy patients (ICP). METHODS: Thirty three ICP patients and 30 normal pregnant women in late pregnancy were studied, maternal serum VEGF concentrations were examined by enzyme linked immunoadsorbent assay (ELISA). Capillaries density in placenta are detected by s-ABC immunohistochemistry, radio-immunity method is used to assay the maternal serum glycocholic acid. RESULTS: Serum VEGF in ICP (2 072 +/- 17) ng/L has negative correlation with glycocholic acid (47.9 +/- 14.2) ng/L, however, positive correlation with capillaries density in placenta (68 +/- 5)/HP; The serum VEGF in normal pregnant woman (2 256 +/- 30) ng/L does not have relationship to glycocholic acid (1.6 +/- 0.7) ng/L but it has positive correlation with capillaries density in placenta (74 +/- 7)/HP. CONCLUSION: Cytotoxicity of high concentration bile acids impairs vascular endothelial cells resulting in lower excretion of VEGF in vascular endothelial cells of ICP, which lead to placental blood capillaries dysplasia and lower permeability, it may be one of reasons of fetal distress and fetal death in uteri in ICP.