Project description:The aim of this study was to identify umbilical cord microRNA (miRNA) associated with catch-up growth in SGA infants. miRCURY LNA™ Universal RT microRNA PCR Human Panel I+II (Exiqon) were used to study the miRNA profile in umbilical cord tissue of 5 SGA infants with catch-up (SGA-CU), 5 SGA infants without catch-up (SGA-nonCU) and 5 control infants (appropriate-for-gestational-age, AGA). Catch-up differentially expressed miRNA were studied and validated in a larger cohort.
Project description:Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis- related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.
Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born between January and May 2010 at the maternity unit of Jorvi hospital (Espoo, Finland; n=48), maternity units of Tartu and PM-CM-5lva (Estonia; n=25), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=40) according to the manufacturerM-BM-4s protocol and then stored in M-bM-^HM-^R70 M-BM-0C until analyzed. All newborn infants were full-term (>36 gestational weeks) and born vaginally. 113 cord blood RNA samples were analyzed with Affymetrix U219 gene array. Gender, pregnancy week, month of birth and HLA risk class were included as confounding factors in the analysis model.
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 470 cord blood samples from infants born to women in the Southampton Women's Survery (SWS) cohort, to examine the association between DNA methylation in the infant and aspects of health and disease in early and life and childhood.
Project description:This randomized research trial studies the Community-based Health Information Technology (HIT) Tools for Cancer Screening and Health Insurance Promotion (CATCH-UP) intervention in increasing cancer screening and prevention care in uninsured patients at community health centers. The CATCH-UP intervention may contribute to increased rates of insurance coverage, leading to improved cancer screening and prevention rates in community health care settings, and general recommended preventive care.
Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples using the Illumina Infinium MethylationEPIC array (approximately 850,000 CpGs). Samples included cord blood samples from infants born to women with (exposed) and without (control) infection with Trypanosoma cruzi parasites, to test for a potential epigenetic effect of in utero exposure to maternal infection.
Project description:Mesenchymal stem cells (MSCs) hold great therapeutic potential in morbidities associated with preterm birth. However, the molecular expressions of hMSCs in preterm birth infants have not been systematically evaluated. In this study, we presented the dual-omics analyses of umbilical cord (UC) derived hMSCs to identify the dysregulated cellular functions. Materials and methods: The UC-MSCs were collected from 10 full-term and 8 preterm birth infants for transcriptomics and proteomics analyses by using microarray and iTRAQ-based proteome profiling. The integrative analysis of dual-omics data discovered 5,615 commonly identified genes/proteins of which 29 genes/proteins showed consistent up- or down-regulation in preterm birth. The Gene Ontology analysis revealed that the biological processes of mitochondrial translation and cellular response to oxidative stress were mainly enriched in 290 differential expression proteins (DEPs) while the 421 differential expression genes (DEGs) were majorly involved in secondary alcohol metabolic process, cellular response to stress, and mitotic cell cycle in preterm birth. Besides, we identified a 13-protein module involving CUL2 and CUL3, which plays an important role in cullin-RING-based ubiquitin ligase complex, as potential mechanism for preterm birth. The dual-omics data not only provided new insights to the molecular mechanism but also to identify panel of candidate markers associated with preterm birth.
Project description:There were no studies about gene expression of umbilical cord tissue before. We performed this study to identify the gene expression of umbilical cord tissue.
Project description:To search for genes regulated by the transcription factor Forkhead box Protein P1 (FoxP1) in endothelial cells, we transfected human umbilical cord endothelial cells (HUVECs) with a combination of three siRNA oligonucleotides directed against human FoxP1 . Human umbilical vein endothelial cells (HUVECs) were isolated from donated umbilical cords, pooled from two donors and cultivated up to passage 5. For transfection with FoxP1-siRNA cells were cultured to 70% confluence and transfected with a combination of three FoxP1-targeting siRNAs or an irrelevant control oligonucleotide (all from invitrogen) using Lipofectamin RNAiMax (Invitrogen) according to the manufacturers instructions. Total RNA was isolated 48h after transfection.