Project description:We conducted a prospective cohort study with independent Discovery and Validation cohorts, to formulate predictive biomarkers for Bronchopulmonary Dysplasia in extremely preterm infants. Tracheal aspirate samples were collected at birth from extremely preterm infants. Exosomes were extracted from tracheal aspirates and total RNA was extracted from these exosomes from individual samples. miRNA profiling for all ~ 800 miRNAs was conducted on each sample by nanostring platform. This study found that a distinct airway exosomal miRNA sigrature at birth (decreased miR 876-3p) predicts future development of severe Bronchopulmonary Dysplasia in extremely preterm infants.
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina 450K methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD.
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Peripheral blood DNA (at days 14 and 28) from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina EPIC methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD at different time points.
Project description:Bronchopulmonary dysplasia (BPD) is a major complication of preterm birth, with lasting effects on respiratory outcomes in extremely low birth weight (ELBW) and very low birth weight (VLBW) infants. This pilot study aimed to identify non-invasive salivary microRNA biomarkers for early BPD risk stratification in preterm neonates. Saliva samples were collected from 20 preterm infants (BPD+: n=10; BPD-: n=10) at days 10-14 of life. Total RNA including the miRNA fraction was isolated from saliva using the MagMAX mirVana Total RNA Isolation Kit. RNA was profiled using the Affymetrix GeneChip miRNA 4.1 Array (GeneTitan MC instrument, 96-well plate format). RMA normalization and limma differential expression identified three candidate salivary miRNA biomarkers (hsa-let-7b-5p, hsa-miR-4454, hsa-let-7c-5p), all significantly upregulated in BPD infants.
Project description:We procured PBMCs whole blood from five HC preterm infants and five preterm infants with BPD. PBMCs were extracted using a density gradient centrifugation method. Initially, 10ml of peripheral blood was mixed with an equal volume of physiological saline, then carefully layered onto Ficoll solution (T10124, from Shangbao Biotech Co., Ltd., Shanghai). After centrifugation at 2,000 rpm for 20 minutes, the cells stratified due to differences in density, with PBMCs positioned between the red blood cells and plasma. Subsequently, the intermediate layer containing PBMCs was gently collected, washed several times with physiological saline to remove residual medium and red blood cells, and finally, PBMCs were isolated and collected through centrifugation.
Project description:Preterm infants exhibit marked heterogeneity in the developmental stages of their immune systems at birth, which vary significantly across gestational ages. The molecular basis of immune incompetence in preterm infants and its association with immunosuppressive mechanisms have not been fully elucidated. To gain a comprehensive understanding of immune heterogeneity pertaining to the early neonatal immune system, we collected peripheral blood samples from preterm infants and full-term infants within 12 h after birth alongside peripheral blood samples from four adults for comparative single-cell transcription analysis. Using single-cell RNA sequencing, we found that myeloid-derived cells from the peripheral blood of preterm infants, especially extremely preterm infants (< 28 weeks), highly expressed IL1R2. IL1R2+ myeloid-derived cells with S100P high expression and IL1R2+ regulatory T cells with LEF1 high expression may play an important role in immunosuppression during early immune development. High expression of IL1R2 in preterm infants may lead to immune suppression, and IL1R2 may affect both myeloid-derived cells and regulatory T cells, promoting immunosuppression with high S100P and LEF1 expression and playing an important role in immune suppression during early immune development in preterm infants.
Project description:Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. The underlying mechanisms are still poorly understood. The hypothesis of this study is that dysregulated macrophage activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants.
Cord blood samples of preterm infants (n=14) and term infants (n=19) as well as peripheral blood from healthy adults (n=17) were collected. Age-dependent differences in immune responses of monocyte-derived Mä from preterm infants were characterized and compared to term infants and adults after lipopolysaccharide (LPS) exposure.
Project description:91 preterm infant gut metaproteomes measured in technical duplicate using an eleven salt pulse 2D-LC-MS/MS method. Samples represent 17 preterm infants over the first several weeks of life, of which 6 preterm infants eventually developed necrotizing enterocolitis.