First trimester maternal plasma proteomic changes predictive of spontaneous moderate/late preterm delivery.

Objective: Identification of differentially expressed proteins (DEPs) in first trimester maternal plasma between pregnant women with a subsequent spontaneous moderate/late Preterm Delivery (sPTD) and women who delivered at term. The sPTD group consisted of women who delivered between 32° and 36weeks of gestation.

Methods: Isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS was used for the analysis of five first trimester maternal plasma samples obtained from women with a subsequent moderate/late preterm sPTD and five women with term deliveries.

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.

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence.

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes.

Deep Sequencing Identified Dysregulated Circulating MicroRNAs in Late Onset Preeclampsia.

Background/aim: To characterize global microRNA (miRNA) expression profile in the first trimester maternal plasma of women who subsequently develop late-onset preeclampsia (LOPE) compared to uncomplicated pregnancies.

Materials And Methods: Five first trimester plasma samples from women who developed LOPE and 5 controls were analyzed using next generation sequencing technology (NGS) followed by target prediction, Gene Ontology analysis and pathway identification. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for confirmation in an independent cohort of 12 LOPE cases and 12 controls.

Quantitative Comparative Proteomics Reveals Candidate Biomarkers for the Early Prediction of Gestational Diabetes Mellitus: A Preliminary Study.

Aim: To identify differentially expressed proteins (DEPs) in 1 trimester maternal plasma between pregnant women at risk for gestational diabetes mellitus (GDM) and uncomplicated controls.

Materials And Methods: First-trimester plasma from five women who developed GDM and five from non-diabetic ones were analyzed using isobaric tag for relative and absolute quantitation - labeled proteomics. Enzyme-linked immunosorbent assay was further applied in an independent cohort of 25 GDM cases and 25 controls for verification.

Two novel variants in the gene identified in cases with craniosynostosis.

Craniosynostosis (CS) is a condition where one or more of the cranial sutures fuse prematurely. It affects almost 1/2,000 newborns, and includes both syndromic and non-syndromic cases. To date, variants in over 70 different genes have been associated with the expression of CS.

Dysregulated placental microRNAs in Early and Late onset Preeclampsia.

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.

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 11-13 weeks of gestation. Women were followed up until delivery.

miRNAs in pregnancy-related complications.

MicroRNAs (miRNAs) constitute a highly conserved class of small non-coding RNAs, involved in post-transcriptional regulation processes by modifying the expression of specific mRNAs. During placental development, cell differentiation, adhesion, migration, apoptosis and angiogenesis are regulated by specific miRNAs and aberrant expression has been associated with the pathogenesis of pregnancy-related complications. Recent studies focusing on placental and maternal peripheral blood miRNA profiling showed different expression between normal and complicated pregnancies, providing valuable information about the pathophysiological role of miRNAs and identifying potential biomarkers for monitoring pregnancy complications.

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.

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.

Microrna expression signatures predict patient progression and disease outcome in pediatric embryonal central nervous system neoplasms.

Background: Although, substantial experimental evidence related to diagnosis and treatment of pediatric central nervous system (CNS) neoplasms have been demonstrated, the understanding of the etiology and pathogenesis of the disease remains scarce. Recent microRNA (miRNA)-based research reveals the involvement of miRNAs in various aspects of CNS development and proposes that they might compose key molecules underlying oncogenesis. The current study evaluated miRNA differential expression detected between pediatric embryonal brain tumors and normal controls to characterize candidate biomarkers related to diagnosis, prognosis and therapy.

In situ assessment of PI3K and PTEN alterations in mycosis fungoides: correlation with clinicopathological features.

Deregulated signalling through phosphatidylinositol 3-kinase (PI3K) pathway plays a critical role in tumour initiation and progression. We have already shown that AKT is activated in skin lesions in Mycosis Fungoides (MF) and we herein further investigate the frequency and clinical significance of PTEN and PI3K at the protein and at the DNA level as well as the presence of AKT1 mutations in skin lesions from 50 patients with MF clinical stages I-IV in relation to clinicopathological features. Increased p-AKT expression correlated with poor prognosis in plaques (P = 0.

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.

Review: advances in non-invasive prenatal diagnosis.

The invasive procedures amniocentesis and chorionic villus sampling are routinely applied in pregnancies at risk for fetal genetic disorders and the results obtained are the gold standard for prenatal diagnosis. These procedures have an approximately 0.5-1% risk for fetal loss and are mainly used in cases at risk for fetal chromosomal abnormalities and single-gene disorders.

An unusual case of Cat-Eye syndrome phenotype and extragonadal mature teratoma: review of the literature.

BACKGROUND Cat-Eye syndrome (CES) with teratoma has not been previously reported. We present the clinical and molecular findings of a 9-month-old girl with features of CES and also a palpable midline neck mass proved to be an extragonadal mature teratoma, additionally characterized by array comparative genomic hybridization (aCGH). RESULTS High resolution oligonucleotide-based aCGH confirmed that the supernumerary marker chromosome (SMC) derived from chromosome 22, as was indicated by molecular cytogenetic analysis with fluorescence in situ hybridization (FISH).

Early non-invasive detection of fetal Y chromosome sequences in maternal plasma using multiplex PCR.

Objective: Clinical indications for fetal sex determination include risk of X-linked disorders, a family history of conditions associated with ambiguous development of the external genitalia, and some fetal ultrasound findings. It is usually performed in the first trimester from fetal material obtained through CVS and is associated with an approximately 1% risk of miscarriage. Ultrasound fetal sex determination is often performed after 11 weeks of gestation.

Non-invasive prenatal diagnosis using cell-free fetal nucleic acids in maternal plasma: Progress overview beyond predictive and personalized diagnosis.

The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma allowed for the development of alternative methodologies that may facilitate safe non-invasive prenatal diagnosis (NIPD). The low concentration of cffDNA in maternal plasma, however, and the coexistence of maternal DNA limit its clinical application to the detection or exclusion of fetal targets that are not present in the mother, such as Y chromosome sequences, the RHD gene in a RhD-negative woman and genetic conditions inherited from the father. Strategies for NIPD of monogenic disorders and fetal chromosomal aneuploidies have also been achieved using next-generation sequencing and could be introduced to the clinics as soon as cost-effective and high throughput protocols are developed.

Biomarker development for non-invasive prenatal diagnosis of fetal aneuploidies: predictive reliability and potential clinical application.

Current non-invasive prenatal diagnosis for fetal aneuploidies is based on biochemical and ultrasound markers and needs to be improved in order to reduce the number of pregnant women subjected to invasive diagnostic procedures. Proteomic technologies allow for new strategies for discovering biomarkers in complex biological fluids in a high-throughput and sensitive manner. Application of advance proteomic tools to profile pathology-specific proteins in maternal plasma obtained from pregnancies with aneuploid fetuses revealed biomarker-candidates that can potentially revolutionize the diagnostic and treatment procedure in favor of better prediction and improved individual outcomes.

Application of proteomics for the identification of biomarkers in amniotic fluid: are we ready to provide a reliable prediction?

Proteomics-based identification of biomarkers for fetal abnormalities and pregnancy complications in amniotic fluid (AF) has made significant progress in the past 5 years. This is attributed mainly to advances in mass spectrometry-based proteomic technologies that enable new strategies for discovering biomarkers from complex biological fluids in a high-throughput and sensitive manner. These markers, although they still need to be verified, are diagnostic and may in the future provide targets for therapeutic intervention.