Bronchopulmonary dysplasia (BPD) manifests in premature neonates with aberrant pulmonary function. Numerous long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of BPD. This study aims to elucidate the impact of the lncRNA myocardial infarction-associated transcript (MIAT) on the initiation and progression of BPD. Initially, BPD murine models were established through hyperoxia induction in newborn mice. Subsequently, MIAT and GATA binding protein 3 (GATA3) expression levels were assessed, and intravenous administration of short hairpin RNAs (shRNAs) targeting MIAT and GATA3 was performed. Pulmonary histological alterations were examined through histological staining. Levels of inflammatory mediators were quantified using enzyme-linked immunosorbent assay (ELISA) kits. The interaction between MIAT and GATA3 was scrutinized through RNA immunoprecipitation, RNA pull-down, and fluorescence in situ hybridization. The downstream mechanisms of GATA3 were explored using bioinformatics analysis. In summary, lncRNA MIAT exhibited elevated expression in the lung tissues of BPD-afflicted mice. MIAT localized to the nucleus and interacted with GATA3, thereby activating the mitogen-activated protein kinase (MAPK) pathway. Knockdown of MIAT or silencing of GATA3 attenuated the inflammatory response, deactivated the MAPK pathway, and ameliorated BPD symptoms in mice, on the other hand, p-Cresyl sulfate potassium can activate the MAPK signaling pathway and attenuates the effects of si-MIAT or si-GAT3. These improvements were characterized by enhanced alveolar differentiation and reduced glycogen and collagen deposition. In conclusion, lncRNA MIAT plays a pivotal role in activating the MAPK pathway and exacerbating hyperoxia-induced BPD in mice through the binding to GATA3. It's an important discovery for the pathogenesis of BPD and may provide some new treatment for infants diagnosed with BPD.

miR-146b-5p has been studied to be highly expressed in bronchopulmonary dysplasia (BPD), but whether it is involved in regulating the process of BPD in premature infants remains unclear. This study was to explore miR-146b-5p in premature BPD and reveal its molecular mechanism. BPD mouse model and high-oxygen MLE-12 cell model were established. HE staining, TUNEL staining, and IF staining were conducted to evaluate the pathological injury and protein expression in mouse lung tissue. LDH assay, MMT assay, and flow cytometry were achieved to evaluate cytotoxicity, cell viability, and apoptosis. ELISA and immunoblotting were performed to evaluate inflammatory cytokines and Wnt pathway proteins in lung tissues and cells. Dual-luciferase reporter assay and RIP assay were needed to examine the targeting relationship between miR-146b-5p and KDM6B. miR-146b-5p was abundantly expressed in BPD and KDM6B was lowly expressed. miR-146b-5p knockdown improved hyperoxia-induced lung epithelial cell inflammation and apoptosis in both models. miR-146b-6p upregulation or KDM6B downregulation aggravated hyperoxia-induced inflammation and apoptosis of lung epithelial cells. This effect of overexpressing miR-146b-5p was rescued by forcing KDM6B. MiR-146b-5p activated Wnt signaling by regulating KDM6B. miR-146b-5p activates the Wnt pathway through targeted regulation of KDM6B, thereby aggravating hyperoxia-induced inflammation and apoptosis of lung epithelial cells.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants characterized by alveolar dysplasia, vascular simplification and dysmorphic vascular development. Supplemental oxygen and mechanical ventilation commonly used as life-saving measures in premature infants may cause BPD. microRNAs (miRNAs), a class of small, non-coding RNAs, regulate target gene expression mainly through post-transcriptional repression. miRNAs play important roles in modulating oxidative stress, proliferation, apoptosis, senescence, inflammatory responses, and angiogenesis. These cellular processes play pivotal roles in the pathogenesis of BPD. Accumulating evidence demonstrates that miRNAs are dysregulated in the lung of premature infants with BPD, and in animal models of this disease, suggesting contributing roles of dysregulated miRNAs in the development of BPD. Therefore, miRNAs are considered promising biomarker candidates and therapeutic agents for this disease. In this review, we discuss how dysregulated miRNAs and their modulation alter cellular processes involved in BPD. We then focus on therapeutic approaches targeting miRNAs for BPD. This review provides an overview of miRNAs as biomarkers, and highlights potential pathogenic roles, and therapeutic strategies for BPD using miRNAs.

Bronchopulmonary dysplasia (BPD) is a common morbidity affecting preterm infants and is associated with substantial long-term disabilities. The pathogenesis of BPD is multifactorial, and the clinical phenotype is variable. Extensive research has improved the current understanding of the factors contributing to BPD pathogenesis. However, effectively preventing and managing BPD remains a challenge. This review aims to provide an overview of the current evidence regarding the prevention of BPD in preterm infants, offering practical insights for clinicians.

Bronchopulmonary dysplasia (BPD) is associated with hyperoxia-induced oxidative stress-associated ferroptosis. This study examined the effect of E26 oncogene homolog 1 (ETS1) on oxidative stress-associated ferroptosis in BPD.

Hyperoxia-induced A549 cells and neonatal mice were used to establish BPD models. The effects of ETS1 on hyperoxia-induced ferroptosis-like changes in A549 cells were investigated by overexpression of ETS1 plasmid transfection and erastin treatment. Glucose consumption, lactate production, and NADPH levels were assessed by the glucose, lactate, and NADP+/NADPH assay kits, respectively. The potential regulatory relationship between ETS1 and Nrf2/HO-1 was examined by treating hyperoxia-induced A549 cells with the Nrf2 inhibitor ML385. ETS1 effect on the Nrf2 promoter was explored by dual-luciferase reporter and chromatin immunoprecipitation assay. The effect of ETS1 on the symptoms of BPD mice was examined by injecting an adenovirus overexpressing ETS1.

ETS1 overexpression increased hyperoxia-induced cell viability, glucose consumption, lactate production, and NADPH levels and reduced inflammation and apoptosis in A549 cells. In animal experiments, ETS1 overexpression prevented weight loss, airway enlargement, and reductions in radial alveolar counts in BPD mice, while reducing the mean linear intercept, mean alveolar diameter and inflammation. ETS1 overexpression suppressed PTGS2 and CHAC1 expression, reduced ROS, MDA and ferrous iron (Fe2+) production and increased GSH levels in hyperoxia-induced A549 cells and BPD mice. In addition, ETS1 can bind to the Nrf2 promoter region and thus promote Nrf2 transcription. ETS1 overexpression increased the mRNA and protein levels of Nrf2, HO-1, xCT, and GPX4 in hyperoxia-induced A549 cells and BPD mice. In hyperoxia-induced A549 cells, erastin and ML385 treatment abolished the effect of ETS1 overexpression.

ETS1 is important in oxidative stress-related ferroptosis in a hyperoxia-induced BPD model, and the effect is partially mediated by the Nrf2/HO-1 axis.

Myocardial ischemia-reperfusion injury (MIRI) is a pathological process characterized by cardiomyocyte death. Long noncoding RNAs (lncRNAs) have been shown to be dysregulated in the course of MIRI. Accordingly, the current study investigated the mechanism of lncRNA Rian in MIRI-induced cardiomyocyte pyroptosis. First, a murine model of MIRI was established by using the left anterior descending (LAD) coronary artery ligation method. Cardiac function and myocardial histopathological changes were evaluated by echocardiography and hematoxylin and eosin staining. Then, a cell model of MIRI was established by oxygen-glucose deprivation/reoxygenation (OGD/R), followed by analysis of NLRP3, cleaved caspase-1, and GSDMD-N levels by western blotting. The levels of IL-1β, IL-18, TNF-α, and IL-10 were measured using ELISA. LncRNA Rian, miR-17-5p, and CCND1 expression in myocardial tissues and OGD/R cells were examined using RT-qPCR. Finally, the binding relationships between Rian and miR-17-5p and miR-17-5p and CCND1 were validated with the help of dual-luciferase and RNA pull-down assays. Rian was poorly expressed in MIRI mice and OGD/R cells. LncRNA Rian overexpression reduced cardiomyocyte pyroptosis in vivo and in vitro, as indicated by decreased NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, IL-18, and TNF-α levels and increased IL-10 levels. Furthermore, Rian bound to miR-17-5p and promoted CCND1 transcription. Notably, miR-17-5p overexpression or CCND1 silencing reversed the inhibitory effect of Rian overexpression on cardiomyocyte pyroptosis. Collectively, our findings indicate that Rian overexpression reduces cardiomyocyte pyroptosis and alleviates MIRI through the miR-17-5p/CCND1 axis.

Bronchopulmonary Dysplasia (BPD) is a multifactorial disease affecting over 35% of extremely preterm infants born each year. Despite the advances made in understanding the pathogenesis of this disease over the last five decades, BPD remains one of the major causes of morbidity and mortality in this population, and the incidence of the disease increases with decreasing gestational age. As inflammation is one of the key drivers in the pathogenesis, it has been targeted by majority of pharmacological and non-pharmacological methods to prevent BPD. Most extremely premature infants receive a myriad of medications during their stay in the neonatal intensive care unit in an effort to prevent or manage BPD, with corticosteroids, caffeine, and diuretics being the most commonly used medications. However, there is no consensus regarding their use and benefits in this population. This review summarizes the available literature regarding these medications and aims to provide neonatologists and neonatal providers with evidence-based recommendations.

Inflammation is a multifactorial process and various biological mechanisms and pathways participate in its development. The presence of inflammation is involved in pathogenesis of different diseases such as diabetes mellitus, cardiovascular diseases and even, cancer. Non-coding RNAs (ncRNAs) comprise large part of transcribed genome and their critical function in physiological and pathological conditions has been confirmed. The present review focuses on miRNAs, lncRNAs and circRNAs as ncRNAs and their potential functions in inflammation regulation and resolution. Pro-inflammatory and anti-inflammatory factors are regulated by miRNAs via binding to 3'-UTR or indirectly via affecting other pathways such as SIRT1 and NF-κB. LncRNAs display a similar function and they can also affect miRNAs via sponging in regulating levels of cytokines. CircRNAs mainly affect miRNAs and reduce their expression in regulating cytokine levels. Notably, exosomal ncRNAs have shown capacity in inflammation resolution. In addition to pre-clinical studies, clinical trials have examined role of ncRNAs in inflammation-mediated disease pathogenesis and cytokine regulation. The therapeutic targeting of ncRNAs using drugs and nucleic acids have been analyzed to reduce inflammation in disease therapy. Therefore, ncRNAs can serve as diagnostic, prognostic and therapeutic targets in inflammation-related diseases in pre-clinical and clinical backgrounds.