Elevated expression of KiSS-1 in placenta of preeclampsia and its effect on trophoblast

The expression of KiSS-1, MMP-9 and MMP-2 mRNAs and proteins was studied in placentas of women with preeclampsia (PE, n=47) and women of normal pregnancy (NP; n=30). In addition, KiSS-1 mRNA expression as well as cell growth, proliferation and invasion were examined in JAR cells (human trophoblast cell line) transfected with pcDNA3-KiSS-1vector. Expression of KiSS-1 mRNA and protein was higher (p<0.05) in women with PE compared with that of NP women. In contrast, expression of MMP-9 and MMP-2 was lower (p<0.05) in PE than in NP women. KiSS-1 mRNA was detected in JAR cells successfully transfected with pcDNA3-KiSS-1 gene (JAR-K1, JAR-K2, JAR-K3). KiSS-1 mRNA was not detected in JAR cells transfected with pcDNA3 gene (JAR-P1, JAR-P2) and non-transfected JAR cells. No difference (p>0.05) was observed in cell growth among these three cell types. Invasion ability was significantly lower (p<0.01) in JAR-K1, JAR-K2 and JAR-K3 cells compared to JAR-P cells and non-transfected JAR cells. Overexpression of KiSS-1 and insufficient expression of MMP-9 and MMP-2 in placenta were demonstrated in women with PE. The data suggests that KiSS-1 gene plays an important role in inhibiting trophoblast invasion during placental development.     

Global DNA methylation patterns in placenta and its association with maternal hypertension in pre-eclampsia

Maternal nutrition is an important determinant of one-carbon metabolism that lies at the heart of intrauterine epigenetic programming. Exchange of nutrients and other vital molecules between the mother and fetus takes place across the placenta and hence may play direct role in fetal programming. Pre-eclampsia (PE) originates in the placenta and altered maternal nutrition may influence epigenetic patterns in the placenta, thereby affecting birth outcome. In the present study, we investigated the global DNA methylation levels in placentas of pre-eclampsia women (i.e., women delivering at term and those delivering preterm) and studied their associations with maternal blood pressure and birth outcome. Increased homocysteine and global DNA methylation levels were seen in the pre-eclampsia group (term and preterm PE) when compared with the normotensive group (p?相似文献   

The association of insulin resistance with serum osteoprotegerin in obese adolescents

Some data indicate a potential relationship between insulin resistance level and the concentration of osteoprotegerin (OPG) in the body. There have been few studies concerning OPG level and its relationship with insulin resistance and body composition in young people. The aim of this study was to assess serum osteoprotegerin concentration in obese adolescents, and to evaluate its potential association with insulin resistance. Seventy-eight obese adolescents and 20 healthy volunteers aged 12–18 years were recruited in the study. Selected anthropometrical measurements and blood biochemical analyses were performed. Insulin resistance in the participants was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol. Level of OPG was assessed in serum. Obese subjects had significantly higher HOMA-IR indices and OPG levels in serum than the control group. A significant positive correlation between OPG and insulin resistance was found. It was observed that high concentrations of osteoprotegerin are associated with insulin resistance in obese adolescents.     

Expression of CAMK1 and its association with clinicopathologic characteristics in pancreatic cancer

Calcium/calmodulin-dependent protein kinase (CAMKs) can control a wide range of cancer-related functions in multiple tumour types. Herein, we explore the expressions and clinical significances of calcium/calmodulin-dependent protein kinase 1 (CAMK1) in pancreatic cancer (PC). The expression of CAMK1 in PC was analysed by Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database and the Oncomine database. For further validation, the protein level of CAMK1 in PC tissues was also detected in the Human Protein Atlas (HPA) database and the tissue microarray (TMA)-based immunohistochemistry (IHC). GEPIA 2 and Kaplan-Meier Plotter (KM Plotter) databases were used to explore the prognostic significances of CAMK1 in overall survival (OS) and disease-free survival (DFS) of PC at mRNA level. The relationship between CAMK1 expression and the clinicopathological characteristics of PC was further explored. Additionally, the Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyse protein-protein interactions (PPI). We found CAMK1 was highly expressed in PC both in bioinformatics analyses and TMA-IHC results. The prognostic analyses from the public databases also showed consistent results with follow-up data. The PPI network suggested that CALM1, CALM3, CREB1, CALM2, SYN1, NOS3, ATF1, GAPDH, PPM1F and FBXL12 were important significant genes associated with CAMK1. Our finding revealed CAMK1 has prognostic value in PC patients, suggesting that CAMK1 may has a distinct role in PC patients and can be used as a candidate marker for investigating clinical prognosis of PC.     

Decreased expression of MMP-9 in CD8+ cells in placenta with severe preeclampsia

We compared the number of CD4-positive (CD4⁺) and CD8-positive (CD8⁺) cells in severe and non-severe preeclampsia (PE), and in normal pregnancy. We also evaluated the expression of matrix metalloproteinase 9 (MMP-9) in CD4⁺ and CD8⁺ cells. Immunohistochemistry for CD4⁺ and CD8⁺ was performed on the decidua basalis of 15 severe and 13 non-severe PE women and compared to decidual tissue of 19 normal pregnancies (control group). Co-expression of MMP-9 with CD8⁺ and CD4⁺ cells was determined by double immunofluorescence staining. The median number of CD8⁺ cells/mm² was significantly lower for the severe PE group than for the normal pregnancy group, as was the number of CD4⁺ cells and MMP-9⁺CD8⁺ cells. No statistical difference was found between the non-severe PE group and the normal pregnancy group. The significant decrease of CD4⁺, CD8⁺ and MMP-9⁺CD8⁺ cells at the fetal-maternal interface only in the severe PE group suggests that immunological disorders play a role in the pathophysiology of severe PE.     

Coenzyme Q10 is increased in placenta and cord blood during preeclampsia

Preeclampsia is a common (approximately 7% of all pregnancies) disorder of pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the levels of coenzyme Q(10) (CoQ(10)) in placental tissue compared to maternal and umbilical cord levels both during normal pregnancy and in those complicated with preeclampsia. Pregnant women (n = 30) and women with preeclampsia (n = 30) were included. Maternal, newborn cord blood levels and placental content of coenzyme Q(10) were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q(10) levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ(10) content in placenta from women with preeclampsia (mean 0.28 SEM 0.11 nmol/mg protein) was significantly higher compared to normal pregnancy (mean 0.09 SEM 0.01 nmol/mg protein; p = 0.05). Levels of CoQ(10) in cord blood from normal pregnant women (mean 0.30 SEM 0.05 micromol/l) were significantly lower than in preeclamptic women (mean 4.03 SEM 2.38 micromol/l). In conclusion, these data indicate a possible involvement of CoQ(10) in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated.     

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta

BackgroundAdipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine.Material and methodsPref-1 was quantified in patients with PE (n = 51) and healthy pregnant controls (n = 51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2).ResultsIn study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 μg/l) as compared to healthy pregnant controls (0.7 μg/l) (p < 0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue.ConclusionMaternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.     

乳腺癌细胞肿瘤标记物表达及其与临床病理特征相关性研究

目的 探讨肿瘤标记物14-3-3σ、Akt 和p27Kip1 蛋白在乳腺癌中的表达及其与临床病理特征及Her-2 的相关性.方法 选取43 份乳腺癌石蜡标本和10 份正常乳腺组织标本,采用免疫组织化学技术(SABC)检测组织中14-3-3σ、Akt 和p27Kip1 蛋白的表达,结合临床资料和随访资料,进行回顾性研究,...     

Expression of Th17 cells in breast cancer tissue and its association with clinical parameters

Th17 cells are newly identified effector CD4⁺ T cells, which play an active role in inflammation and autoimmune diseases and may be relevant for anti-tumor defenses. In the present study, we examined expression of Th17 cells in specimens of breast cancer tissue and its association with clinical, pathology, and immunological parameters. Expression rates of Th17 and T regulatory (Treg) cells in breast cancer and normal (i.e. non-cancerous) tissue were evaluated using flow cytometry in 30 patients with breast carcinoma. Further, expression of interleukin-17 (IL-17), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in breast cancer tissue was evaluated by immunohistochemical staining. Associations between Th17 expression and other parameters were analyzed by multiple linear regression analysis. We observed that expression of Th17 cells was significantly higher in breast cancer compared to normal breast tissue. Further, expressions of IL-17, IL-1β, and IL-6 in cancer tissue positively correlated with expression of Th17 cells. In addition, there was a negative association between the numbers of Th17 cells and TNM stage, blood vessel invasion, and increased numbers of metastatic lymph nodes. Finally, expression of Th17 was not associated with expression of Treg. In conclusion, Th17 cells appear to be involved in anti-tumor immune responses and are associated with a more favorable prognosis.     

Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia.

AIM: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. METHODS: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37-38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at -20 degrees C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at -80 degrees C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at -80 degrees C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. RESULTS: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. CONCLUSIONS: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.     

The kappa-opioid receptor from human placenta: hydrodynamic characteristics and evidence for its association with a G protein

The kappa nature of opioid binding sites in a brush border membrane (BBM) fraction from human placenta has been confirmed: these sites display considerably higher apparent affinity (KI = 1.2 nM) for the kappa selective ligand U-50488 than they do for the mu and delta selective ligands [D-Ala2, MePhe4, Glyol5] enkephalin (KI = 1.5-2 microM) and [D-Thr2, Leu5] enkephalyl-Thr (KI = 10-15 microM), respectively. The BBM fraction from human placenta was incubated either with the agonist 3H-etorphine or with the antagonist 3H-diprenorphine and subsequently solubilized with digitonin. The solubilized macromolecular radioactivity was found to behave as a homogeneous entity both in molecular exclusion chromatography (app. rs = 6.1 nm) and in linear sucrose gradients (app. S20.w = 12 S). Two lines of evidence indicated that the placental kappa opioid receptor is capable of interacting with a guanine nucleotide regulatory (G) protein: (i) equilibrium binding of the agonist 3H-etorphine in the BBM fraction was clearly inhibited by 5'-guanylylimidodiphosphate (Gpp(NH)p), especially in the presence of Na+ ions while binding of the antagonist 3H-diprenorphine was significantly less so and (ii) the sedimentation velocity of the kappa opioid receptor was decreased down to about 10 S when the BBM fraction was prelabeled with radioligand in the presence of Gpp(NH)p prior to its solubilization with digitonin. The G protein that mediates the effect of Gpp(NH)p might be neither Gs nor Gi since no adenylate cyclase activity could be demonstrated in the BBM fraction from human placenta.     

Expression of Jagged1 and its association with hepatitis B virus X protein in hepatocellular carcinoma

Jagged1 is one of the ligands of Notch signaling pathway, which controls cellular proliferation and differentiation, and also plays important roles in various malignant tumors. However, the expression of Jagged1 in hepatocellular carcinoma (HCC) has not been elucidated, nor whether it is associated with hepatitis B virus X protein (HBx). In this study, we found that Jagged1 was highly expressed in 79.2% (42/53) of HCC tissues compared with adjacent nontumor liver (P <0.05), and its expression was found to be closely related with HBx (rs=0.522, P <0.001) in HCC tissues. Our in vitro study also showed that alteration of HBx expression in HCC cell lines led to a consistent change of Jagged1. Moreover, Jagged1 was found to co-localize and directly interact with HBx in HCC tissues and HBx expressed HCC cell lines. Our results reveal that Jagged1, which is regulated by HBx, may contribute to the development of HCC.     

Expression and identification of mutated osteoprotegerin in culture cells and larvae of silkworm

Osteoprotegerin (OPG, or osteoclastogenesis inhibitoryfactor, OCIF) is a soluble member of the tumor-necrosisfactor receptor family discovered in 1997 that can inhibitosteoclastogenesis and prevent bone loss from resorption.Simonet et al. [1] reported tha…     

Crystal structure of human RANKL complexed with its decoy receptor osteoprotegerin

Receptor activator of NF-κB ligand (RANKL), its signaling receptor RANK, and its decoy receptor osteoprotegerin (OPG) constitute a molecular triad that is critical in regulating bone remodeling, and also plays multiple roles in the immune system. OPG binds RANKL directly to block its interaction with RANK. In this article, we report the 2.7-? crystal structure of human RANKL trimer in complex with the N-terminal fragment of human OPG containing four cysteine-rich TNFR homologous domains (OPG-CRD). The structure shows that RANKL trimer uses three equivalent grooves between two neighboring monomers to interact with three OPG-CRD monomers symmetrically. A loop from the CRD3 domain of OPG-CRD inserts into the shallow groove of RANKL, providing the major binding determinant that is further confirmed by affinity measurement and osteoclast differentiation assay. These results, together with a previously reported mouse RANKL/RANK complex structure, reveal that OPG exerts its decoy receptor function by directly blocking the accessibilities of important interacting residues of RANKL for RANK recognition. Structural comparison with TRAIL/death receptor 5 complex also reveals structural basis for the cross-reactivity of OPG to TRAIL.