Salivary cortisol is not associated with dexamethasone response in preterm infants with evolving bronchopulmonary dysplasia.

Objective: Short-term treatment efficacy of systemic dexamethasone (DEX) in preterm infants with bronchopulmonary dysplasia (BPD) is highly variable. Our objective was to assess if salivary cortisol may serve as a reliable biomarker of steroid response.

Study Design: Multi-site prospective observational cohort study.

Association between congenital heart disease and parenteral nutrition-associated liver disease in neonates: A retrospective cohort study.

Objective: Infants receiving parenteral nutrition (PN) are at increased risk of PN-associated liver disease (PNALD), which can lead to hepatic fibrosis. Congenital heart disease (CHD) represents a risk factor for hepatic fibrosis, so this study sought to better understand whether infants with CHD were at elevated risk of PNALD when receiving long-term PN.

Study Design: This study includes a retrospective cohort of infants at a level IV neonatal intensive care unit from 2010 to 2020 who received long-term PN during the first 8 weeks of life.

Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti-Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity.

Importance: Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified.

Objective: To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment.

Design, Setting, And Participants: This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020.

Corticosteroid response predicts bronchopulmonary dysplasia status at 36 weeks in preterm infants treated with dexamethasone: A pilot study.

Importance: A major barrier to therapeutic development in neonates is a lack of standardized drug response measures that can be used as clinical trial endpoints. The ability to quantify treatment response in a way that aligns with relevant downstream outcomes may be useful as a surrogate marker for new therapies, such as those for bronchopulmonary dysplasia (BPD).

Objective: To construct a measure of clinical response to dexamethasone that was well aligned with the incidence of severe BPD or death at 36 weeks' postmenstrual age.

Intestinal Stem Cell Development in the Neonatal Gut: Pathways Regulating Development and Relevance to Necrotizing Enterocolitis.

The intestine is extremely dynamic and the epithelial cells that line the intestine get replaced every 3-5 days by highly proliferative intestinal stem cells (ISCs). The instructions for ISCs to self-renew or to differentiate come as cues from their surrounding microenvironment or their niche. A small number of evolutionarily conserved signaling pathways act as a critical regulator of the stem cells in the adult intestine, and these pathways are well characterized.

FOSL1 is a novel mediator of endotoxin/lipopolysaccharide-induced pulmonary angiogenic signaling.

Systemic sepsis is a known risk factor for bronchopulmonary dysplasia (BPD) in premature infants, a disease characterized by dysregulated angiogenesis and impaired vascular and alveolar development. We have previoulsy reported that systemic endotoxin dysregulates pulmonary angiogenesis resulting in alveolar simplification mimicking BPD in neonatal mice, but the underlying mechanisms remain unclear. We undertook an unbiased discovery approach to identify novel signaling pathways programming sepsis-induced deviant lung angiogenesis.

Stem cell therapy for preventing neonatal diseases in the 21st century: Current understanding and challenges.

Diseases of the preterm newborn such as bronchopulmonary dysplasia, necrotizing enterocolitis, cerebral palsy, and hypoxic-ischemic encephalopathy continue to be major causes of infant mortality and long-term morbidity. Effective therapies for the prevention or treatment for these conditions are still lacking as recent clinical trials have shown modest or no benefit. Stem cell therapy is rapidly emerging as a novel therapeutic tool for several neonatal diseases with encouraging pre-clinical results that hold promise for clinical translation.

Optimization of In Vitro and Growth Assays for Therapeutic Development.

Infection with nontuberculous mycobacteria (NTM) is a complication of lung disease in immunocompromised patients, including those with human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). The most widespread, disease-causing NTM is complex (), which colonizes the lungs as a combination of , , and other mycobacterial species. While combination drug therapy exists for colonization, there is no cure.

Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages.

Rationale: The underlying pathophysiology of bronchopulmonary dysplasia includes a macrophage-mediated host response orchestrated by anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ) and anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). These have not yet been studied in combination. This study tested the hypothesis that combined inflammatory and oxidative stressors would interact and change PPARγ- and Nrf2-regulated gene expression and antioxidant capacity.

Concise Review: Mesenchymal Stem Cell Therapy for Pediatric Disease: Perspectives on Success and Potential Improvements.

Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell-based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors.

A novel retinoic acid receptor beta isoform and retinoid resistance in lung carcinogenesis.

Background: We previously reported that all-trans-retinoic acid (RA) treatment can prevent in vitro transformation of immortalized human bronchial epithelial (HBE) cells.

Methods: To determine whether methylation inhibits RARbeta expression in HBE cells, we used sodium bisulfite sequencing to compare RARbeta P2 promoter methylation patterns in RA-sensitive (BEAS-2B) and RA-resistant (BEAS-2B-R1) HBE cells. Immunoblotting was used to assess induction of the RARbeta, placental transforming growth factor beta (PTGF-beta), Fos-related antigen 1 (Fra-1), and transglutaminase II (TGase II) proteins by RA following treatment with azacitidine, a DNA demethylating agent.