Expression and clinical significance of dendritic cell and transforming growth factor-beta 1 in cervical cancer

Cervical cancer and precancerous cervical lesionsare major problems in women's health.Clinical,molecu-lar and epidemiological investigations have identifiedhuman papillomavirus(HPV)as a major cause of cer-vical cancer[1].Although HPV infection is very com…     

VEGF,PIGF and HIF-1α in placentas of early- and late-onset pre-eclamptic patients

Abstract

Purpose: The aim of this study was to compare the VEGF, PIGF, and HIF-1α levels in the placentas of early- and late-onset pre-eclamptic patients, which are thought to be important in pathophysiology of pre-eclampsia.

Material and method: Pre-eclamptic early-onset (n?=?22) and late-onset (n?=?24) pregnant women and a control group of healthy pregnant women (n?=?22) were recruited for this case–control study. A semi-quantitative immunohistochemical analysis of VEGF, PIGF and HIF-1α was performed in cross-sections of the placentas of the subjects, after which results were compared.

Results: Levels of VEGF and PIGF in the placentas of pre-eclamptic patients were found to be lower than the levels in the placentas of healthy pregnant women (p?<?0.001 and p?=?0.025, respectively), whereas the levels of HIF-1α were found significantly higher (p?<?0.001). No difference was observed in terms of VEGF, PIGF and HIF-1α in a comparison of the early- and late-onset pre-eclampsia groups (p?>?0.05).

Conclusion: The results of the study indicated that there is no relationship between the time of onset of pre-eclampsia and the placental changes that occur in these factors.     

The role and significance of endomorphin-1 and μ-opioid receptor in rats with endometriosis

Endomorphin-1 (EM-1) was reported to have very high affinity and selectivity for μ-opioid receptor (MOR). However, it remained unclear whether EM-1 and MOR were involved in the pathologies of endometriosis resulting in reduced fertility. In this study, RT-PCR, radioimmunoassay, immunohistochemistry, and Western blot were used, respectively. The results showed that the immune positive cells of EM-1 in hypothalamus, pituitary, and ovaries were significantly increased in endometriosis model rats, accompanied by the increase of plasma level of EM-1 and the decrease of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). Interestingly, EM-1 was negatively correlated with FSH and LH (p?相似文献   

Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia

Objective: To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE).

Methods: This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit.

Results: Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p?p?<.001) levels. There were no significant differences in the serum HIF-1 α levels between these groups (p=?.069). When PE patients were evaluated by considering subgroups; statistical analysis revealed significant inter-group differences in all biomarkers. Serum progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p?=?.000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p?p=?.000).

Conclusions: Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.     

Interleukin-1β regulates vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 secretion by human oviductal epithelial cells and stromal fibroblasts

The aim of the present study was to evaluate the effects of interleukin (IL)-1β on the production of vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in the human fallopian tube. Human oviductal epithelial cells (OECs) and oviductal stromal fibroblasts (OSFs) were isolated from ten premenopausal patients. The secretion of VEGF and sFlt-1 by cultured OECs and OSFs in response to IL-1β and IL-1 receptor antagonist (IL-1RA) was measured using an enzyme-linked immunosorbent assay. The secretion of VEGF and sFlt-1 was detected in cultured OECs and OSFs under untreated conditions; secretion of these angiogenic modulators was significantly stimulated with IL-1β administration in these cells. IL-1β-induced production of VEGF and sFlt-1 by these cells was significantly inhibited by the addition of IL-1RA. The present findings suggest that IL-1β in the local environment may stimulate oviductal vascular permeability by inducing the production of VEGF by oviductal cells via both autocrine and paracrine mechanisms. Simultaneous upregulation of sFlt-1 secretion by these cells after IL-1β stimulation may prevent an excessive upregulation of vascular permeability. The modulation of the ratio of VEGF and sFlt-1 in the fallopian tube may contribute to the normal and pathological processes of oviductal fluid secretion by regulating oviductal vascular permeability during the menstrual cycle and during the peri-implantation period.     

Promoter region polymorphisms in the transforming growth factor beta-1 (TGFβ1) gene and serum TGFβ1 concentration in preeclamptic and control Iranian women

Preeclampsia (PE) is a pregnancy associated disorder characterized by hypertension and proteinuria, which causes neonatal and maternal morbidity and mortality. The Th1/Th2 cytokine paradigm of the immune adaptation in pregnancy is now expanded to include Th1/Th2/Th17 and regulatory T (Treg) cells. Among cytokines, TGFβ1 has properties that justify evaluation of its role in PE etiopathology. In this investigation the polymorphisms of the TGFβ1 gene at promoter region, positions -800G→A and -509C→T, were studied in 142 PE and 140 normal pregnant female subjects using PCR-RFLP. Additionally, serum TGFβ1 was determined by ELISA. At position -800G→A genotypes and allele frequencies showed no significant differences between PE patients (GG 73.9%; GA 21.1%; AA 4.93%) and normal control (GG 70%; GA 28.6%; AA 1.4%) women. However the AA genotype at this position was more frequent in PE patients than in the control group. At -509C→T position, genotypes and allele frequencies showed no significant differences between PE patients and control individuals. The CC genotype at -509C→T position was more prevalent in PE patients than in the control group. The mean serum TGFβ1 level was significantly higher (62.14 ng/ml) in PE patients compared with pregnant and non-pregnant control groups (and 47.01 and 40.68 ng/ml, respectively). In conclusion, the promoter region polymorphisms of TGFβ1 may not be associated with PE, but serum levels of this cytokine may contribute to the etiopathology of PE.     

Is genetic polymorphism of ER-α, CYP1A1, and CYP1B1 a risk factor for uterine leiomyoma?

Introduction  

Uterine leiomyoma is the most common benign smooth muscle tumor.     

Serum levels of interleukin-6, interleukin-1β and human chorionic gonadotropin in pre-eclamptic and normal pregnancy

Studies in placentas from the first trimester and in vitro models indicate that interleukin (IL)-1β and IL-6 induce the release of human chorionic gonadotropin (hCG). During pre-eclampsia there is an increase of pro-inflammatory cytokines; however, its relationship with hCG levels during the third trimester of pregnancy has not been determined. The aim of the present study was to evaluate the relationship between blood levels of IL-6, IL-1β and hCG in normal pregnancy and pre-eclampsia. Blood samples during the third trimester of pregnancy from women with severe pre-eclampsia (n = 20) or normal pregnancy (n = 20) were assayed for hCG by immunoassay, IL-6 and IL-1β by enzyme-linked immunosorbent assay. Serum level of IL-6 was significantly higher in pre-eclamptic than in normal women (16.5 ± 2.1 vs. 4.9 ± 1.1 pg/ml); however, IL-1β was similar in both groups. Although hCG was higher in pre-eclampsia than normal pregnancy, the difference was not statistically significant. Furthermore, IL-1β in normal pregnancy was correlated negatively with hCG (r = ?0.69, p < 0.001). In conclusion, serum levels of IL-6 were increased in pre-eclampsia but were not correlated with hCG or IL-1β; however, in normal pregnancy there was a negative correlation between IL-1β and hCG. The interaction between IL-1β and hCG at the third trimester needs to be investigated.     

IL-1β and IL-23 in amniotic fluids of ultrasound-detected aortic intima/media thickness and growth retardation

Intrauterine growth restriction (IUGR) and/or neonatal low birth weight are often associated with increased intima/media thickness of the abdominal aortic wall (aIMT). Several studies in children suggested that aIMT might be related to inflammation, probably indicating an early stage of adulthood diseases, such as atherosclerosis. Our previous study performed on the abdominal aortic wall of a stillbirth presenting with IUGR and aIMT suggested an association among IUGR, aIMT, and inflammation, also highlighting the presence of fibroblastoid cells, which are thought to represent peculiar elements of the pre-atherosclerotic lesions. These observations led us to analyze two cytokines involved in the inflammation cascade, IL-1β and IL-23, in amniotic fluid samples of IUGR fetuses and small-for-gestational-age newborns presenting with aIMT and in normal controls. Our results indicate that IL-23, but not IL-1β, concentrations differed in the groups analyzed. Therefore, IL-23, a regulatory element that bridges the innate and adaptive arms of the immune system, might be involved in the inflammatory process observed in fetal aIMT.     

Does plasminogen activator inhibitor-1 (PAI-1) control trophoblast invasion? A study of fetal and maternal tissue in intrauterine, tubal and molar pregnancies

Urokinase plasminogen activator, its receptor and the inhibitor PAI-1 are believed to control proteolysis and remodelling of maternal tissue during trophoblast invasion. This system appears to be strictly regulated in normal intrauterine pregnancies whereas tubal and molar pregnancies seem to be characterized by an uncontrolled excessive placental invasion. This study evaluates subcellular PAI-1 by immunohistochemistry in the villous placenta, in the basal plate and placental bed, and in the decidual compartments of normal, tubal and molar pregnancies. PAI-1 was present in villous syncytiotrophoblasts and co-localized focally with fibrin-type fibrinoid on the surface of the chorionic villi. Basal plate and placental bed extravillous interstitial trophoblasts, as well as vascular trophoblasts, were also PAI-1 positive. In the decidua parietalis, PAI-1 was observed in the cytoplasm of the non-invaded decidual cells. In the decidua basalis comprising the basal plate, PAI-1 was seen to be membrane-associated or confined to the extracellular matrix (ECM) facing the invasive front of anchoring villi. The ECM of decidua capsularis and chorion laeve displayed the most pronounced PAI-1 expression towards the maternal interface. In contrast, the majority of placental bed decidual cells adjacent to the interstitial and vascular trophoblasts were PAI-1 negative. Only a few stromal cells distant from the implantation site were PAI-1 positive in the tubal pregnancies and decidualization was not present. Likewise, excessive decidual necrosis and fibrinoid deposition devoid of PAI-1 was a common finding in complete molar pregnancies. These results suggest that PAI-1 defines specific extravillous invasive trophoblasts within the maternal decidua. Moreover, maternal cellular lack of PAI-1 in tubal pregnancies and excessive decidual necrosis in molar pregnancies indicate an uncontrolled placental invasion. The present data indicate that trophoblast invasion is primarily regulated by signals from decidual cells.     

Investigation of the effects of α1-adrenoceptor antagonism and L-type calcium channel blockade on ejaculation and vas deferens and seminal vesicle contractility in vitro

IntroductionPremature ejaculation is one of the most common male sexual dysfunctions. Current pharmacological treatments involve reduction in penile sensitivity by local anesthetics or increase of ejaculatory threshold by selective serotonin reuptake inhibitors. α₁‐Adrenoceptors (α₁‐ARs) and L‐type calcium channels are expressed in the smooth muscles of the male reproductive tract, and their activations play an important role in the physiological events involved in the seminal emission phase of ejaculation.AimTo evaluate if the inhibition of the contractility of the vas deferens and seminal vesicle by α₁‐AR antagonism or the L‐type calcium channel blockade can delay ejaculation.MethodsThe effects of the α₁‐AR antagonist tamsulosin and of the L‐type calcium channel blockers, nifedipine and (S)‐(+)‐niguldipine, on contractions induced by norepinephrine in the rat vas deferens and seminal vesicles in vitro and on the ejaculation latency of male rats in behavioral mating tests were evaluated.Main Outcome MeasureTension development of vas deferens and seminal vesicles in response to norepinephrine in vitro and behavioral mating parameters were quantified.ResultsTension development of vas deferens and seminal vesicle to α₁‐AR activation was significantly inhibited by tamsulosin, nifedipine, and (S)‐(+)‐niguldipine. Tamsulosin displayed insurmountable antagonism of contractions induced by norepinephrine in the rat vas deferens and seminal vesicle. Ejaculation latency of male rats was not modified by tamsulosin, nifedipine, or (S)‐(+)‐niguldipine; however, both the number and weight of the seminal plugs recovered from female rats mated with male rats treated with tamsulosin were significantly reduced.ConclusionSeminal emission impairment by inhibition of vas deferens or seminal vesicle contractility by L‐type calcium channel blockade or α₁‐AR antagonism is not able to delay the ejaculation. de Almeida Kiguti LR and Pupo AS. Investigation of the effects of α₁‐adrenoceptor antagonism and L‐type calcium channel blockade on ejaculation and vas deferens and seminal vesicle contractility in vitro. J Sex Med 2012;9:159–168.     

Association between TGF-β1-509C/T polymorphism and endometriosis: a systematic review and meta-analysis

Objective

To evaluate the association between the transforming growth factor β1 gene-509C/T (TGF-β1-509C/T) polymorphism and the risk of endometriosis.

Study design

Relevant studies published before October 2011 were identified by searching PubMed and Embase. Studies were selected using prior defined criteria. The strength of the relationship between the TGF-β1-509C/T polymorphism and endometriosis risk was assessed by Odds Ratios (ORs). Fixed- or random-effects model was calculated according to study heterogeneity. Stratification analysis and sensitivity analysis were also conducted. Possible publication bias was tested by funnel plots and Egger's test.

Results

Of 49 potentially relevant studies, six case–control studies were identified in this meta-analysis. The integrated result showed that the TGF-β1-509C/T polymorphism was not associated with the endometriosis risk for the allele contrast (T vs. C: OR = 1.57, 95%CI = 0.88–2.79), the additive genetic model (T/T vs. C/C: OR = 2.96, 95%CI = 0.97–9.10), the dominant genetic model (T/T + T/C vs. C/C: OR = 1.80, 95%CI = 0.80–4.07) and the recessive genetic model (T/T vs. C/C + T/C: OR = 1.91, 95%CI = 0.89–4.12). In the stratified analysis by ethnicity, genotyping method and source of control, no significantly association was found. Publication bias was not detected in the included studies.

Conclusions

Meta-analyses of the available data showed that the association between TGF-β1-509C/T polymorphism and susceptibility of endometriosis was not significant. More studies are needed to elucidate its role in endometriosis.     

Amniotic fluid HIF1α and exosomal HIF1α in cervical insufficiency patients with physical examination-indicated cerclage

Objective: Hypoxia inducible factor 1α (HIF1α) has been reported to activate inflammatory cascade. Recently, exosomes have been known to have pivotal roles in intercellular communication. The aim of this study was to compare the concentration of amniotic fluid (AF) HIF1α, exosomal HIF1α, and inflammatory cytokines such as interleukin 1α (IL1α), interleukin 1β (IL1β), interleukin 6 (IL6), and tumor necrosis factor α (TNFα) between physical examination-indicated cerclage (PEIC) and control group. We also investigated the associations between biomarkers and amniocentesis-to-delivery interval and the correlations of inflammatory cytokines, HIF1α, and exosomal HIF1α.

Methods: Case-control study was performed. Cases are defined as 16 patients who underwent PEIC and controls are 19 women who underwent amniocentesis for confirming chromosomal abnormalities. The concentration of IL1α, IL1β, IL6, TNFα, HIF1α, and exosomal HIF1α were measured using enzyme-linked immunosorbent assay (ELISA). Exosomes were confirmed by tumor susceptibility Gene 101 (TSG 101) and transmission electron microscopy (TEM).

Results: The mean HIF1α in PEIC group was higher than control group (PEIC, 15.03?±?9.60-pg/mL versus control, 2.96?±?1.99?pg/mL; p?p?p?p?p?p?p?p?=?.01.) Exosomal HIF1α also had correlation with IL6 (rho?=?0.52, p?=?.03).

Conclusions: This study demonstrated that amniotic fluid (AF) HIF1α and AF exosomal HIF1α were higher in physical examination-indicated cerclage (PEIC) group than control group. AF HIF1α and AF exosomal HIF1α were associated with shorter amniocentesis-to-delivery interval. More importantly, they had positive correlations with AF inflammatory cytokines such as IL1α, IL6, and TNFα. Our results may indicate that AF HIF1α and AF exosomes interact with AF inflammatory cytokines and contribute inflammatory cascade in complicated pregnancies.