Background：Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants that involves pulmonary vascular development disorder as the main pathological feature; hyperoxia is its main etiology. Twist1 strictly controls the development of blood vessels via the Tie2-Angs signaling axis. However, previous research on Twist1 mainly focuses on various tumors; its effect on BPD has yet to be reported. The present study represents the first investigation of the role and related mechanisms of the Twist1-Tie2-Angs signaling pathway in hyperoxia-induced endothelial cell injury. Methods: Primary human umbilical vein endothelial cells were used as an in vitro model. A Twist1 inhibitor (harmine) was applied to normal and hyperoxia-exposed endothelial cells. Then, we observed the permeability and tubule formation ability of endothelial cells after reducing Twist1 protein. Results: Hyperoxia increased the permeability of endothelial cells and decreased tubule formation ability. Under physiological conditions dominated by angiogenin 1 (Ang1), reducing the expression of Twist1 increases the permeability of endothelial cells and reduces tubule formation ability. In contrast, under hyperoxia conditions dominated by angiogenin 2 (Ang2), reducing the expression of Twist1 reduced the permeability of endothelial cells and increased tubule formation ability. Conclusion: Twist1 depends on the balance of Ang1 and Ang2 to control the permeability and tubule formation of endothelial cells. Reducing the levels of Twist1 may be a protective mechanism for BPD.

Objective: To observe the changes of depression-like behavior in SD rats induced by maternal separation (MS) stress and to explore the effects of probiotics on antidepressant-like behavior and cAMP/CREB signaling pathway. Methods: Newborn SD rats were selected as experimental subjects and divided into MS+NS group, CON+NS group, MS+P group and CON+P group using random number table method, 12 rats in each group. At PND 22-49, the MS+P and CON+P groups were given 1×109 CFU (0.1 ml) of probiotic colonies by gavage daily and the corresponding dose (1 ml/100g) according to the change of body weight, and the MS+NS and CON+NS groups were given the corresponding saline dose (1 ml/100g). Behavioral tests were performed at PND50-56, and rats were executed at PND57 for laboratory tests. Results: FST increased, OPT increased and SPT decreased after probiotic intervention. It was suggested that the MS-induced depression-like behavior was improved to some extent. Compared with the model group, probiotic intervention increased the number of neurons in the CA1 region of the hippocampus, decreased serum-associated inflammatory factors, increased serum 5-HT concentration, and decreased CORT concentration in rats. In addition, the intervention increased the expression levels of cAMP, CREB and BDNF in the hippocampus of MS rats. Conclusion: Probiotics can alleviate anxiety/depression-like behavior in SD rats, which may be related to the activation of cAMP/CREB signaling pathway. The protective effect of probiotics as therapeutic food care in preventing or alleviating MS-induced depression-like behaviors provides an experimental basis for the application of probiotics to alleviate or improve anxiety/depression.

Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease caused by a combination of prenatal and postnatal factors that leads to the disruption of lung development and abnormal repair, this is a condition that is commonly seen in premature infants. With the improvement of treatment technology, the survival rate of very early preterm infants has increased significantly compared with before, and the incidence of severe BPD has decreased, however, the prevalence of BPD has not decreased. The overall prevalence of BPD is 45%.The prevention of prematurity, the systematic use of non-aggressive ventilator measures, the avoidance of supra-physiological oxygen exposure, and the administration of diuretics, caffeine and vitamin A have all been shown to lead to a significant reduction in the risk of BPD development. A growing number of clinical studies have shown that caffeine not only prevents apnea, but also reduces the incidence of BPD. We review the clinical value of caffeine in the treatment of BPD and its potential mechanisms of action, include anti-inflammatory, antioxidant, anti-fibrotic, anti-apoptotic pathways, and the regulation of angiogenesis. Our aim was to provide a new theoretical basis for the clinical treatment of BPD.