Search

BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used to stimulate closure of a patent ductus arteriosus (PDA) in very premature infants and may lead to aberrant neonatal lung development and bronchopulmonary dysplasia (BPD). METHODS: We investigated the effect of ibuprofen on angiogenesis in human umbilical cord vein endothelial cells (HUVECs) and the therapeutic potential of daily treatment with 50 mg/kg of ibuprofen injected subcutaneously in neonatal Wistar rat pups with severe hyperoxia-induced experimental BPD. Parameters investigated included growth, survival, lung histopathology and mRNA expression. RESULTS: Ibuprofen inhibited angiogenesis in HUVECs, as shown by reduced tube formation, migration and cell proliferation via inhibition of the cell cycle S-phase and promotion of apoptosis. Treatment of newborn rat pups with ibuprofen reduced pulmonary vessel density in the developing lung, but also attenuated experimental BPD by reducing lung inflammation, alveolar enlargement, alveolar septum thickness and small arteriolar wall thickening. CONCLUSIONS: In conclusion, ibuprofen has dual effects on lung development: adverse effects on angiogenesis and beneficial effects on alveolarization and inflammation. Therefore, extrapolation of the beneficial effects of ibuprofen to premature infants with BPD should be done with extreme caution.

Background: Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. Methods: We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. Results: Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. Conclusion: Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD. [ABSTRACT FROM AUTHOR]

Background: Extremely preterm infants (EPIs) frequently encounter challenges in feeding due to their underdeveloped digestive systems. Attaining full enteral feeding at the earliest possible stage can facilitate the removal of vascular catheters and decrease catheter-related complications. Methods: We performed a retrospective cohort study comprising 145 extremely preterm infants with a gestational age < 28 weeks who underwent non-invasive mechanical ventilation at Shenzhen Maternity & Child Healthcare Hospital between January 2019 and June 2020. The KMC group received standard nursing care along with KMC, while the control group received standard nursing care without KMC. KMC initiation took place three weeks after admission and continued for a period of two weeks or more while maintaining stable vital signs. We evaluated the rate of exclusive breastmilk feeding within 24 h prior to discharge and the time to full enteral feeding throughout hospitalization. Additionally, we conducted a multiple linear regression analysis to identify the independent factors associated with exclusive breastmilk feeding rates and the time to full enteral feeding. Results: The KMC group exhibited a significantly higher rate of exclusive breastmilk feeding in the 24 h before discharge in comparison to the Non-KMC group (52.8% vs. 31.5%, OR 2.43; 95% CI 1.24, 4.78). Moreover, the KMC group achieved full enteral feeding in a shorter duration than the Non-KMC group (43.1 ± 9.6 days vs. 48.7 ± 6.9 days, p < 0.001). Multiple linear regression analysis revealed that KMC was an independent protective factor associated with improved exclusive breastmilk feeding rates (OR 2.43; 95% CI 1.24, 4.78) and a reduction in the time to full enteral feeding (β -5.35, p < 0.001) in extremely preterm infants. Conclusion: Kangaroo Mother Care (KMC) can expedite the achievement of full enteral feeding and enhance exclusive breastmilk feeding rates in extremely preterm infants receiving non-invasive assisted ventilation. These findings highlight the beneficial effects of KMC on the feeding outcomes of this vulnerable population, underscoring the importance of implementing KMC as a part of comprehensive care for extremely preterm infants. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are implicated in heart failure (HF). Thereby, we aim to uncover the role of miR‐144‐3p in HF. Doxorubicin (Dox)‐induced HF model was constructed in rats and cardiomyocytes H9C2, and the cardiac function was determined using ultrasound cardiogram. Morphology of cardiac tissue was observed using hematoxylin–eosin (H&E) staining. The viability and apoptosis of Dox‐treated and transfected cardiomyocytes were determined using Cell Counting Kit‐8 (CCK‐8) assay and flow cytometry. Relative expressions of the HF‐associated miRs (including miR‐144‐3p), suppressor of cytokine signaling 2 (SOCS2), apoptosis‐ and phosphoinositide 3‐kinase (PI3K)/AKT pathway‐related factors (B‐cell lymphoma 2, Bcl‐2; Bcl‐2 associated X protein, Bax; cleaved [C] capsase‐3; phosphoinositide 3‐kinase, PI3K; phosphorylated‐PI3K, p‐PI3K; p‐AKT; AKT) were measured with quantitative real‐time polymerase chain reaction or Western blot. Target gene of miR‐144‐3p was predicted by Starbase and TargetScan and confirmed with dual‐luciferase reporter assay. Dox caused rat cardiac dysfunction, aggravated cardiac injury, decreased cardiomyocytes viability, and the expression of miR‐144‐3p, Bcl‐2, and phosphorylation of both PI3K and AKT yet the upregulated those of Bax and C caspase‐3, which was reversed by upregulating miR‐144‐3p, whereas downregulating miR‐144‐3p did oppositely. SOCS2 was the target gene of miR‐144‐3p, Dox promoted SOCS2 expression, which was reversed by upregulating miR‐144‐3p, while downregulating miR‐144‐3p did conversely. In addition, silencing SOCS2 reversed the effects of miR‐144‐3p downregulation in Dox‐treated cardiomyocytes. Upregulating miR‐144‐3p alleviated Dox‐induced cardiac dysfunction and cell apoptosis via targeting SOCS2, providing a novel evidence of miR‐144‐3p in HF. [ABSTRACT FROM AUTHOR]