Dysregulated placental microRNAs in Early and Late onset Preeclampsia

Copyright © 2017. Published by Elsevier Ltd.INTRODUCTION: To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. METHODS: Sixteen placentas from women with PE, [11 with early onset PE (EOPE) and 5 with late onset PE (LOPE)], as well as 8 placentas from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction. RESULTS: Forty four miRNAs were found dysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls, whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE-growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR. DISCUSSION: Since specific miRNAs can differentiate EOPE and LOPE from uncomplicated placentas, they may be considered as putative PE-specific biomarkers. MiR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for PE-FGR complicated placentas, indicating a potential link to the severity of the disease.Peer reviewe

Pastoral ministry and the phenomenon of secularization

The aim of this doctoral thesis is to examine the phenomenon of secularization in relation to pastoral ministry. The need for a proper understanding of the challenges and the effects that occur in relation to the phenomenon of secularization is underlined, which is approached from a sociological and from a theological perspective. We explore the effects of secularization of society in relation to church life, at the level of the parish and at the level of individual religiosity, with special reference to the case of “nominal” Orthodox Christians. Furthermore, it is argued that in the context of secularization, pastoral ministry should be grounded on eucharistic ecclesiology. A framework for pastoral work, aiming for the renewal of the church life, is also elaborated. The priest as a person and his ministry is further explored in relation to the challenges that arise as a result of the phenomenon of secularization, both as a social and as an ecclesiastical phenomenon. It is argued that the secularization of the priest as a person at the individual level constitutes the most critical challenge in relation to pastoral ministry. Τherefore, an emphasis on the selection, education, and evaluation of the priests is of primary importance for an effective pastoral ministry in the context of secularization.Σκοπός της παρούσας διδακτορικής διατριβής είναι η μελέτη του φαινομένου της εκκοσμίκευσης σε σχέση με την ποιμαντική διακονία. Επισημαίνεται η ανάγκη μιας ορθής κατανόησης των προκλήσεων και των επιπτώσεων που προκύπτουν από την εξέλιξη του φαινομένου της εκκοσμίκευσης, το οποίο εξετάζεται ως κοινωνικό φαινόμενο, μέσα από μια κοινωνιολογική προσέγγιση, και ως εκκλησιαστικό φαινόμενο, μέσα από μια θεολογική προσέγγιση. Αναλύονται οι επιπτώσεις του φαινομένου της εκκοσμίκευσης στην εκκλησιαστική ζωή, τόσο στο επίπεδο της οργάνωσης της ενορίας όσο και στο επίπεδο της ατομικής θρησκευτικότητας, όπου εξετάζεται ειδικότερα η ύπαρξη της κατηγορίας των «κατ’ όνομα» χριστιανών. Υποστηρίζεται η απαραίτητη θεολογική θεμελίωση της ποιμαντικής με άξονα την ευχαριστιακή εκκλησιολογία ως προς την αντιμετώπιση των επιπτώσεων στο πλαίσιο της εκκοσμίκευσης. Επίσης εξετάζονται πτυχές και καταγράφονται προτάσεις για ένα πλαίσιο ποιμαντικής με στόχο την ανανέωση της εκκλησιαστικής ζωής. Στη συνέχεια προσεγγίζεται το πρόσωπο του ποιμένα και η διακονία του, όπου εξετάζονται οι προκλήσεις που υπάρχουν λόγω της εκκοσμίκευσης, τόσο ως κοινωνικό όσο και ως εκκλησιαστικό φαινόμενο. Η εκκοσμίκευση του ποιμένα σε ατομικό επίπεδο επισημαίνεται ως η βασικότερη πρόκληση σε σχέση με την ποιμαντική διακονία. Τονίζεται έτσι η καίρια σημασία της επιλογής, εκπαίδευσης και αξιολόγησης των ποιμένων για μια αποτελεσματική ποιμαντική διακονία στο πλαίσιο της εκκοσμίκευσης

Urine proteomic studies in preeclampsia

Preeclampsia (PE) is a multisystem disorder of pregnancy that develops after 20 wk of gestation in previously normotensive women and complicates 5-8% of pregnancies. This rapidly progressive syndrome is usually diagnosed when the mother develops hypertension and proteinuria. The only effective treatment is delivery of the baby although early low-dose aspirin has been shown to significantly reduce the risk for PE. Recent advances in proteomic methods of protein separation, identification, and quantitation may allow for the identification of proteins and peptides that could facilitate early detection of disease, improve assessment of prognosis, and allow closer monitoring of women at risk for PE. This review summarizes all currently available markers for prediction and diagnosis of PE and presents urine proteomic studies performed for the identification of novel biomarkers

First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth

Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case–control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk

Validation of Serum Biomarkers Derived from Proteomic Analysis for the Early Screening of Preeclampsia

Aim. To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE). Methods. 24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11–13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded. Results. Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 in the PE group as compared to controls were 909.1 gEq/mL versus 480.0 gEq/mL, P=.000, 832.0 gEq/mL versus 738.8 gEq/mL, P=.024, and 234.4 gEq/mL versus 74.9 gEq/mL, P=.064, respectively. Areas under the receiver-operating characteristic curves (AUC, standard error (SE)) for predicting PE were Cystatin-C: 0.90 (SE 0.04), VCAM-1: 0.66 (SE 0.074), and Pappalysin-1: 0.63 (SE 0.083). To discriminate between cases at risk for PE and normal controls, cut-off values of 546.8 gEq/mL for Cystatin-C, 1059.5 gEq/mL for sVCAM-1, and 220.8 gEq/mL for Pappalysin-1 were chosen, providing sensitivity of 91%, 41%, and 54% and specificity of 85%, 100%, and 95%, respectively. Conclusions. sVCAM-1 and Pappalysin-1 do not improve early screening for PE. Cystatin-C, however, seems to be associated with subsequent PE development, but larger studies are necessary to validate these findings

RASSF1A in maternal plasma as a molecular marker of preeclampsia

Objectives This study aimed to quantitate cell free (cf) and cell free fetal (cff) DNA in maternal plasma by determining RASSF1A levels before and after enzyme digestion in women who subsequently developed preeclampsia (PE) and compare them with uncomplicated pregnancies. Methods Twenty-four samples from pregnant women who developed PE and 48 samples from women with uncomplicated pregnancies were analysed. Blood samples were obtained at 11-13 weeks. cfDNA was determined by quantifying RASSF1A using qRT-PCR. A second qRT-PCR was performed following methylation-sensitive enzyme digestion by BstUI, to quantitate hypermethylated RASSF1A sequences of fetal origin. ACTB gene was used as control to confirm complete enzyme digestion. Results cfDNA and cffDNA levels were significantly increased in women who developed PE as compared with uncomplicated pregnancies (median cfDNA: 9402 vs 2698, median cffDNA: 934.5 vs 62, respectively). Following operating characteristic curve analysis, cut-off values of 7486.q/mL for cfDNA and 512.q/mL for cffDNA were chosen, which provided a sensitivity of 75% and 100% and specificity of 98% and 100%, respectively, to identify women at risk for PE. Conclusions The study demonstrates potential use of cfDNA and cffDNA in maternal plasma as markers for the early prediction of women at risk for PE. (C) 2013 John Wiley & Sons, Ltd

Plasma biomarkers for the identification of women at risk for early-onset preeclampsia

Background: To identify potential biomarkers in the 1st trimester of pregnancy for the identification of women destined to develop early onset preeclampsia (EOPE).Methods: Blood samples were obtained from pregnant women at 11-13weeks of gestation. Women were followed up until delivery. Five samples from EOPE complicated pregnancies and 5 from unaffected ones were analysed using 2-DE and MALDI-TOF-TOF MS/MS. The altered expression of selected proteins was verified by ELISA in an extended sample cohort.Results: Twelve proteins were differentially expressed in the plasma of women who subsequently developed EOPE as compared to controls. Alpha-1-antitrypsin (A1AT), CD5 antigen-like molecule (CD5L) Keratin, type I cytoskeletal 9 (K1C9), Myeloid cell nuclear differentiation antigen (MNDA), Transferrin (TRFE) and Vitamin D-binding protein (VTDB) were up-regulated with fold changes 3.14, 2.18, 1.53, 1.53, 4.26 3.38 respectively, whereas Alpha-2-HS-glycoprotein (FETUA), Beta-2-glycoprotein 1 (APOH), Complement factor B (CFAB), Haptoglobin (HPT), Vitronectin (VTNC) and Zinc-alpha-2-glycoprotein (ZA2G) were down-regulated with fold changes -0.38, -0.76, -0.24, -0.47, -0.23, and -0.50 respectively. The down-regulation of APOH, VTNC and HPT was verified using ELISA.Conclusions: The differentially expressed proteins represent potential biomarkers for the early screening for EOPE. Follow-up experiments however are necessary for evaluation