Objective:To investigate the expression of CXCR4/CXCL12 and effect on the expression of CXCR4 by hypoxia in trophoblasts of human first trimester gestation.Methods:To detect the expression of CXCR4 and CXCL12 in placental tissue and primary cytotrophoblasts by immunohistochemistry and to assess the level of CXCR4mRNA under the condition of hypoxia in the trophoblasts of first trimester gestation by reas-time PCR.Results:The expression of CXCR4/CXCL12 were detected in the villous column,blood vessels and trophoblasts in the early pregnancy;CXCR4 mRNA was significantly higher through 12,24,48 and 72 h incubation periods in the hypoxic condition than that under normal oxygen condition respectively.Conclusion:Human first trimester trophoblasts produced CXCR4/CXCL12,which may play important biological role on the normal human pregnancy;Hypoxia could regulate the expression of CXCR4,which may contribute to the physiological pregnancy process.

Anti-Bacterial Agents ; poisoning ; Education, Veterinary ; Ethers ; poisoning ; Veterinary Drugs ; poisoning

Objective To investigate the expression of netrin-1 in placenta from patients with pre- eclampsia and the relation to placental angiogenesis.Methods Twenty patients with pre-eclampsia(12 mild cases and 8 severe cases)and 20 normal late pregnant women were investigated.The expression of netrin-1 mRNA and protein was determined with RT-PCR and Western blotting respectively.The placenta vascular density was examined by immunohistochemical F8 staining.Results (1)The values of netrin-1 mRNA in normal group and pre-eclampsia groups were 0.51?0.08 and 0.41?0.06;The values of netrin- 1 protein in normal group and pre-eclampsia groups were 26.4?1.8 and 20.5?1.3(P

Cognition ; Cognition Disorders ; Humans ; Manganese ; Occupational Exposure

This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability, migration and tubular formation were studied, in order to examine the effects of netrin-1. The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro. In addition, netrin-1 enhanced the viability, migration and tube formation of HPMECs. Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.

In this study, we investigated the expression of CXCL12 (SDF-1)/CXCR4 in trophoblasts and the role they play in the gestation. Immunochemistry was used to detect the expression of CXCR4 and CXCL12 in human villi and placenta. Highly purified extra-villous trophoblasts (EVTs) ere detected for CXCR4 and CXCL12 in vitro by immunocytochemistry. The chemotaxis of CXCL12 was tested in transwell and the chemotactic activity was quantitatively examined. It was suggested that both CXCR4 and CXCL12 were expressed in trophoblasts and were decreased with the gestation time P < 0.05). In a certain coverage, CXCL12 exhibited chemotactic activity which was positively correlated with its concentration [(r) = 0.68, P < 0.01], the maximum chemotactic index (CI) was 1.62 +/- 0.12. Our results suggest that interaction between CXCR4 and CXCL12 is involved in materno-fetal immunological tolerance in all three trimesters of gestation and contributes to the invasion of EVTs during pregnancy.

Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed a statistical procedure to identify expression biomarkers for treatment subtype classification by constructing an F-statistic based on Henderson method III. Monte Carlo simulations were conducted to examine the robustness and efficiency of the proposed method. Simulation results showed that our method could provide satisfying power of identifying differentially expressed genes (DEGs) with false discovery rate (FDR) lower than the given type I error rate. In addition, we analyzed a leukemia dataset collected from 38 leukemia patients with 27 samples diagnosed as acute lymphoblastic leukemia (ALL) and 11 samples as acute myeloid leukemia (AML). We compared our results with those from the methods of significance analysis of microarray (SAM) and microarray analysis of variance (MAANOVA). Among these three methods, only expression biomarkers identified by our method can precisely identify the three human acute leukemia subtypes.
Biomarkers ; Gene Expression Profiling ; Humans ; Leukemia, Myeloid, Acute ; classification ; diagnosis ; Monte Carlo Method ; Oligonucleotide Array Sequence Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; classification ; diagnosis ; Statistics as Topic

Microarray has become increasingly popular biotechnology in biological and medical researches, and has been widely applied in classification of treatment subtypes using expression patterns of biomarkers. We developed a statistical procedure to identify expression biomarkers for treatment subtype classification by constructing an F-statistic based on Henderson method Ⅲ.Monte Carlo simulations were conducted to examine the robustness and efficiency of the proposed method. Simulation results showed that our method could provide satisfying power of identifying differentially expressed genes (DEGs) with false discovery rate (FDR) lower than the given type Ⅰ error rate. In addition, we analyzed a leukemia dataset collected from 38 leukemia patients with 27 samples diagnosed as acute lymphoblastic leukemia (ALL) and 11 samples as acute myeloid leukemia (AML). We compared our results with those from the methods of significance analysis of microarray (SAM) and microarray analysis of variance (MAANOVA). Among these three methods, only expression biomarkers identified by our method can precisely identify the three human acute leukemia subtypes.

The association of urinary cytokine concentration with the incidence of urinary tract infection in patients with diabetes mellitus was explored. Urinary interleakin-6 (IL-6) level in 156 female type 2 diabetes mellitus patients was tested and followed up for 6 months. The incidence of urinary tract infection between the top quartile of baseline urinary cytokine concentration with the bottom quartile was compared. The incidence of top quartile of urinary IL-6 concentration at baseline was significantly lower than that of bottom quartile ( 13.5% vs 37.8%, P＜0.05 ). Abnormality of urinary IL-6 concentration may be involved in the mechanism leading to higher prevalence of urinary tract infection in patients with diabetes mellitus.

Objective To investigate mechanism of netrin-1 regulating invasion of extra villous trophoblasts. Methods RT-PCR was used to detect six receptors expression including UNC5A, UNC5B, UNC5C, UNC5D, DCC and neogenin in extra villous trophoblast cell line TEV-1. The TEV-1 cells were cultured and devided into seven groups according to the concentration of netrin-1 adding into the medium, which include 10 μg/L, 50 μg/L, 100 μg/L, 500 μg/L, 1000 μg/L, 5000 μg/L and the control(the concentration of netrin-1 was 0 μg/L) groups. The proliferation and invasion of TEV-1 induced by netrin-1 were determined by CCK-8 assay and transwell invasion assay respectively. Results (1) Only neogenin and UNC5B were found to be expressed on TEV-1 by RT-PCR method. (2) In CCK-8 proliferation assay, after 72 hours culture, the proliferation of TEV-1 were 1.55 ±0.29 in 10 μg/L, 1.72±0. 31 in 50 μg/L, 2.15 ±0.35 in 100 μg/L, 1.42 ±0. 25 in 500 μg/L, 1.50±0. 27 in 1000 μg/L, and 1.38±0.23 in 5000 μg/L group, which were all higher than 1.00 ± 0.16 in control group significantly ( P<0.05 ). (3) In matfigel invasion assay, after 6 hours culture, the number of the trans-membrane cells in various netrin-1 group, including 41 ±4 in 10 μg/L, 47 ±5 in 50 μg/L, 55±6 in 100 μg/L, 44 3=5 in 500 μg/L, 43±5 in 1000 μg/L and 42 ±5 in 5000 μg/L group, were all higher than 30 ±4 in control group with statistical significance( P<0.05 ). (4) The fold changes of neogenin were 1.50 ± 0.16 in 10 μg/L, 1.83 ± 0.19 in 50 μg/L, 2.24 ± 0.25 in 100 μg/L, 2.12 ±0.24 in 500 μg/L, 2.12±0.23 in 1000 μg/L and 2.13 ± O. 23 in 5000 μg/L group, which were all higher than 1.00 ±0.11 in control group significantly( P <0.05 ). There were significant difference between group 10 μg/L and 50 μg/L, group 50 μg/L and 100 μg/L (P < 0.05). There were no significant difference between group 100 μg/L and 500 μg/L, group 1000 μg/L and 5000 μg/L (P>0.05). (5) The fold changes of UNC5 B 1.09 ± 0.11 in 10 μg/L, 1.47±0.14 in 50 μg/ L, 1.61 ±0.16 in 100 μg/L, 1.85±0.19 in 500 μg/L, 2.21±0.21 in 1000 μg/L and 2.42±0.23 in 5000 μg/L group, were all higher significantly when compared with 1.00 ± 0.07 in control group (P<0.05 ). There were significant difference between all groups ( P<0.05). Conclusion Netfin-1 can promote the potential of proliferation and invasion of extravillous trophohlasts in vitro through its receptors including neogenin and UNC5 B.