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:Small-for-gestational-age (SGA) is a globally recognized public health concern. Infants born SGA may experience metabolic disturbances. This study elucidated the key regulatory factors and mechanisms underlying catch-up growth (CUG) and metabolic homeostasis in SGA infants. High-throughput targeted metabolomics were employed to compare the serum profiles of SGA and appropriate-for-gestational-age (AGA) neonates, identifying key metabolic pathways and associated regulatory signaling pathways enriched with differentially expressed metabolites. Animal experiments were conducted, and liver tissue samples were collected from neonatal SGA and AGA rats. Subsequently, mRNA sequencing to identify and analyze differentially expressed genes. HBEGF—a gene critically involved in metabolic processes—was significantly upregulated in SGA rat liver tissues. HBEGF silencing can suppress CUG in SGA rats and influence carbohydrate and lipid metabolism. Furthermore, metabolomic profiling was performed to investigate the role of HBEGF in metabolic regulation during CUG in individuals with SGA. Finally, the impact of HBEGF on the AKT/GSK-3β (protein kinase B/glycogen synthase kinase 3 beta) signaling pathway was explored in both in vivo and in vitro settings. This study confirms metabolic differences between SGA and AGA individuals are evident at early-life. HBEGF may be crucial in CUG progression in SGA by modulating metabolic processes via AKT/GSK-3β signaling pathway.
Project description:<p>Small-for-gestational-age (SGA) is a globally recognized public health concern. Infants born SGA may experience metabolic disturbances. This study elucidated the key regulatory factors and mechanisms underlying catch-up growth (CUG) and metabolic homeostasis in SGA infants. High-throughput targeted metabolomics were employed to compare the serum profiles of SGA and appropriate-for-gestational-age (AGA) neonates, identifying key metabolic pathways and associated regulatory signaling pathways enriched with differentially expressed metabolites. Animal experiments were conducted, and liver tissue samples were collected from neonatal SGA and AGA rats. Subsequently, mRNA sequencing to identify and analyze differentially expressed genes. HBEGF—a gene critically involved in metabolic processes—was significantly upregulated in SGA rat liver tissues. HBEGF silencing can suppress CUG in SGA rats and influence carbohydrate and lipid metabolism. Furthermore, metabolomic profiling was performed to investigate the role of HBEGF in metabolic regulation during CUG in individuals with SGA. Finally, the impact of HBEGF on the AKT/GSK-3β (protein kinase B/glycogen synthase kinase 3 beta) signaling pathway was explored in both in vivo and in vitro settings. This study confirms metabolic differences between SGA and AGA individuals are evident at early-life. HBEGF may be crucial in CUG progression in SGA by modulating metabolic processes via AKT/GSK-3β signaling pathway.</p>
Project description:<p>Small-for-gestational-age (SGA) is a globally recognized public health concern. Infants born SGA may experience metabolic disturbances. This study elucidated the key regulatory factors and mechanisms underlying catch-up growth (CUG) and metabolic homeostasis in SGA infants. High-throughput targeted metabolomics were employed to compare the serum profiles of SGA and appropriate-for-gestational-age (AGA) neonates, identifying key metabolic pathways and associated regulatory signaling pathways enriched with differentially expressed metabolites. Liver tissue samples were collected from neonatal SGA and AGA rats. Subsequently, mRNA sequencing to identify and analyze differentially expressed genes. Heparin-binding epidermal growth factor-like growth factor (HBEGF)— a gene critically involved in metabolic processes—was significantly upregulated in SGA rat liver tissues. HBEGF silencing can suppress CUG in SGA rats and influence carbohydrate and lipid metabolism. Furthermore, metabolomic profiling was performed to investigate the role of HBEGF in metabolic regulation during CUG in individuals with SGA. Finally, the impact of HBEGF on the AKT/GSK-3β (protein kinase B/glycogen synthase kinase 3 beta) signaling pathway was explored in both in vivo and in vitro settings. This study confirms metabolic differences between SGA and AGA individuals are evident at early-life. HBEGF may be crucial in CUG progression in SGA by modulating metabolic processes via AKT/GSK-3β signaling pathway.</p>
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:Neonatal health is dependent on early risk stratification, diagnosis, and timely management of many potentially devastating conditions. Preterm infants are at increased risk of prematurity-related complications, including: early-onset sepsis, chronic lung disease, intraventricular hemorrhage, necrotizing enterocolitis, and neurodevelopmental impairment.Many of these conditions are poorly predicted in real-time by clinical data, including currently available diagnostic testing. Thus, biomarkers have been sought to aid early and targeted treatment and prognosis for these conditions. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. Umbilical cord blood inflammatory markers have been studied as diagnostic indicators of early-onset sepsis. Specific cord blood cytokines have been studied as predictors or correlates of retinopathy of prematurity, atopic disease, infantile hemangioma, placental histopathology, and more. However, few of these cord blood biomarkers have been translated into diagnostic tools in clinical practice. Longitudinal profiling of postnatal proteomic changes has provided insights into the development of the immune system over the first weeks to months of life. While proteomic profiling of cord blood has demonstrated immunologic differences between preterm and term infants, prior research has lacked inclusion of preterm infants across the continuum of gestational age and consideration of key perinatal characteristics such as the route of delivery, preeclampsia, intraamniotic infection, and neonatal sepsis that are likely to affect protein expression. In this study, we have comprehensively characterized the cord blood proteome from infants born between 25 to 42 weeks using MS to provide a benchmark of normative cord blood proteomic profile and examine proteome differences across the developmental range of gestational ages.
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.