Project description:Extreme preterm infants are a growing population in the neonatal intensive care unit. Multiple factors play a role in preterm birth, resulting in complications including severe bronchopulmonary dysplasia (sBPD) without or with and pulmonary hypertension (BPD-PH). The goal of this study was to identify biomarker signatures associated with sBPD and BPD-PH. We analyzed profiles in tracheal aspirates (TAs) from 46 extremely preterm infants receiving invasive mechanical ventilation (25 sBPD, 21 BPD-PH) . We found specific miRNA signatures in TAs that may serve as biomarkers for the two disease phenotypes.
Project description:Tracheal aspirate (TAs) samples were collected from intubated preterm infants with hemodynamically significant intracardiac shunt (ICS), and a diagnosis of ICS-BPD/ICS-BPD-PH. 36 TA samples were analyzed. Small RNAs were extracted and the expression miRNAs was detected with PCR arrays.
Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with BPD severity. We analyzed profiles in tracheal aspirates (TAs) from 25 extremely preterm infants receiving invasive mechanical ventilation. Eight infants were diagnosed with mild/moderate BPD, and 17 were diagnosed with severe BPD, according to the NHLBI consensus conference classification . We found specific miRNA signatures in TAs that may serve as biomarkers for BPD severity.
Project description:Extreme preterm infants are a growing population in neonatal intensive care units who carry a high mortality and morbidity. Multiple factors play a role in preterm birth, resulting in major impact on organogenesis leading to complications including bronchopulmonary dysplasia (BPD). The goal of this study was to identify biomarker signatures associated with prematurity and BPD. We analyzed miRNA and mRNA profiles in tracheal aspirates (TAs) from 51 infants receiving invasive mechanical ventilation. 25 infants were extremely preterm and diagnosed with BPD, and 26 were term babies receiving invasive mechanical ventilation for elective procedures. We found specific mRNA-miRNA signatures in TAs that may serve as biomarkers for BPD pathogenesis, a consequence of extreme prematurity.
Project description:We analyzed mRNA profiles in tracheal aspirates from 53 newborns receiving invasive mechanical ventilation. Twenty-six infants were extremely preterm diagnosed with BPD and twenty-seven were term babies receiving invasive mechanical ventilation for elective procedure. Specific mRNA signatures in TAs may serve as potential biomarkers for extreme prematurity and BPD pathogenesis.
Project description:Integrated multi-omics analysis identified 820 differentially expressed genes, 558 differentially expressed proteins, and 1,377 differential metabolites/lipids, which were mainly enriched in pathways related to inflammation and immunity, cellular signal transduction, ferroptosis, and HIF-1 signaling. TRIM21 emerged as a central molecule exhibiting significant dynamic upregulation in the early (hyperoxic) stage and downregulation in the late (hypoxic) stage of BPD-PH. Further validation in animal models, cellular experiments and clinical samples confirmed a marked elevation of TRIM21, IL-6 and IL-8 expressions in early-stage BPD-PH infants. Mechanistic study revealed that hyperoxia induced TRIM21 upregulation, enhanced NF-κB signaling activation, and promoted PASMC proliferation and migration, while TRIM21 and NF-κB activity was decreased during later disease stages. All these data demonstrate that TRIM21 orchestrated BPD-PH inflammation and vascular remodeling in a dynamic manner of early activation and late inhibition, suggesting TRIM21 as a promising molecular target and providing mechanistic insights for the precise diagnosis and treatment of BPD-PH.