RESUMEN
Bronchopulmonary dysplasia (BPD) in neonates is the most common pulmonary disease that causes neonatal mortality, has complex pathogenesis, and lacks effective treatment. It is associated with chronic obstructive pulmonary disease, pulmonary hypertension, and right ventricular hypertrophy. The occurrence and development of BPD involve various factors, of which premature birth is the most crucial reason for BPD. Under the premise of abnormal lung structure and functional product, newborns are susceptible to damage to oxides, free radicals, hypoxia, infections and so on. The most influential is oxidative stress, which induces cell death in different ways when the oxidative stress balance in the body is disrupted. Increasing evidence has shown that programmed cell death (PCD), including apoptosis, necrosis, autophagy, and ferroptosis, plays a significant role in the molecular and biological mechanisms of BPD and the further development of the disease. Understanding the mode of PCD and its signaling pathways can provide new therapeutic approaches and targets for the clinical treatment of BPD. This review elucidates the mechanism of BPD, focusing on the multiple types of PCD in BPD and their molecular mechanisms, which are mainly based on experimental results obtained in rodents.
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Displasia Broncopulmonar , Hipertensión Pulmonar , Humanos , Embarazo , Femenino , Recién Nacido , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/patología , Apoptosis , Pulmón/metabolismo , Estrés OxidativoRESUMEN
OBJECTIVES: To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure. METHODS: A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups. RESULTS: After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05). CONCLUSIONS: Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.
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Infecciones por Citomegalovirus , Ventilación de Alta Frecuencia , Síndrome de Dificultad Respiratoria del Recién Nacido , Insuficiencia Respiratoria , Lactante , Niño , Recién Nacido , Humanos , Recien Nacido Prematuro , Estudios Prospectivos , Edad Gestacional , Dióxido de Carbono , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Ventilación de Alta Frecuencia/métodos , Respiración Artificial , Insuficiencia Respiratoria/terapia , OxígenoRESUMEN
OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
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Cafeína , Respiración Artificial , Cafeína/uso terapéutico , Citratos , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Estudios RetrospectivosRESUMEN
With advances in neonatology, a greater percentage of premature infants now survive and consequently, diseases of lung development, including bronchopulmonary dysplasia and neonatal respiratory distress syndrome, have become more common. However, few studies have addressed the association between fetal lung development and long non-coding RNA (lncRNA). In the present study, right lung tissue samples of fetuses at different gestational ages were collected within 2 h of the induction of labor in order to observe morphological discrepancies. An Affymetrix Human GeneChip was used to identify differentially expressed lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. A total of 687 lncRNAs were identified to be differentially expressed among three groups of fetal lung tissue samples corresponding to the three embryonic periods. A total of 34 significantly upregulated and 12 significantly downregulated lncRNAs (fold-change, ≥1.5; P<0.05) were detected at different time points (embryonic weeks 7-16, 16-25 and 25-28) of fetal lung development and compared with healthy tissues Expression changes in lncRNAs n340848, n387037, n336823 and ENST00000445168 were validated by reverse transcription-quantitative PCR and the results were consistent with the GeneChip results. These novel identified lncRNAs may have roles in fetal lung development and the results of the present study may lay the foundation for subsequent in-depth studies into lncRNAs in fetal lung development and subsequent clarification of the pathogenesis of neonatal pulmonary diseases.
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The synthesis and secretion of surfactant proteins (SPs) is an important sign of lung maturation. Furthermore, the morbidity of lung developmental diseases, including respiratory distress syndrome and bronchopulmonary dysplasia which are mainly caused by immature lung development and lack of SPs, is increasing. As is well known, multiple microRNAs (miRs/miRNAs) are able to influence lung development via numerous different signaling pathways. However, few studies examine the association between the miRNAs and lung developmental diseases. A previous study has demonstrated that miR431 was significantly (F=33.49; P<0.001) downregulated in the lung tissues of SpragueDawley rats at 3 time points, embryonic day 19, embryonic day 21 and postnatal day 3. The present study reported that the regulation of miR431 may influence the expression of SPs. Thus, the further potential mechanisms of miR431 in negatively regulating lung development were examined in the present study. Stable A549 cell lines overexpressing or knocking down SMAD family member 4 (SMAD4) transfected with miR431 overexpressed or knocked down, and their control groups were established. Subsequently, the expression of bone morphogenetic protein 4 (BMP4), SMAD4 and SPs (SPA, SPB and SPC) at the RNA and protein levels were validated respectively by reverse transcription quantitative PCR and western blotting. miR431 exhibited a decreased expression, while BMP4 and SPs exhibited increased expression at the mRNA and protein levels in the SMAD4 knockdown group. Meanwhile, the expression of SPs were reduced in the SMAD4knockdown group via overexpressing miR431 and increased in the SMAD4overexpression group via inhibiting miR431. The present results indicate that SMAD4 negatively regulates the expression of SPs, and that miR431 negatively regulates the expression of SPs through inhibiting the BMP4/activin/transforming growth factorß signaling pathway by targeting SMAD4.
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Activinas/genética , Proteína Morfogenética Ósea 4/genética , MicroARNs/genética , Proteínas Asociadas a Surfactante Pulmonar/genética , Transducción de Señal/genética , Proteína Smad4/genética , Factor de Crecimiento Transformador beta/genética , Células A549 , Línea Celular Tumoral , Regulación hacia Abajo/genética , Regulación de la Expresión Génica/genética , Humanos , Pulmón/metabolismo , ARN Mensajero/genéticaRESUMEN
Deficiency of surfactant proteins (SPs) is the main cause of respiratory distress syndrome (RDS) and chronic lung diseases. Our previous study demonstrated that miR431 was differentially expressed between infants with RDS and infants without RDS using microarray analysis. However, the potential role of miR431 in the development of lung function is still unknown. In the present study, the morphological characteristics of lung tissues and the expression levels of miR431 were examined at three time points of rat lung development [gestational days 19 and 21 (E19, and E21) and postnatal day (P3)]. The protein and mRNA levels of SMAD4 and SPs (SPA, SPB, SPC and SPD) were also validated by reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blot analysis, respectively. The expression levels of miR431 were gradually decreased over time periods of E19, E21 and P3, as determine using RTqPCR and fluorescence in situ hybridization. Dual luciferasereporter assays revealed that SMAD4 is a direct target of miR431. The mRNA and protein expression levels of SMAD4 and SPs increased gradually in rat lung tissues from E19 to P3. The order of magnitude was as follows: E19, E21 and P3. The present study demonstrated that the expression level of miR431 decreased in the order of E19, E21 and P3 during rat lung development. The target gene of miR431, SMAD4, was negatively regulated by miR431, and its expression levels in the rat lung tissue increased from E19 to the P3. Surfactant synthesis was further increased over the E19 to P3 time period. Further studies are required to determine how miR431 regulates pulmonary surfactant synthesis by targeting SMAD4.