Molecular mechanisms of cell death in bronchopulmonary dysplasia.

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.

miR-296-5p Inhibits the Secretion of Pulmonary Surfactants in Pulmonary Epithelial Cells via the Downregulation of Wnt7b/ß-Catenin Signaling.

Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and ß-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/ß-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/ß-catenin signaling.

Fructo-oligosaccharides lower serum lipid levels and suppress high-fat/high-sugar diet-induced inflammation by elevating serum and gut levels of short-chain fatty acids.

OBJECTIVE: This study aimed to investigate the effects of fructo-oligosaccharides (FOS) on serum lipid levels and to determine the mechanisms underlying these effects and the potential role of inflammation. METHODS: Male C57BL/6 mice received a normal diet, a high-fat/high-sugar (HFS) diet, or an HFS diet supplemented with 10% FOS for 10 weeks. In vivo intestinal and serum short-chain fatty acid (SCFA) levels were measured by gas chromatography. In vivo serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonaldehyde (MDA) were also measured. Lipid accumulation was visualized. Reactive oxygen species (ROS) generation was evaluated and apoptosis was quantified. RESULTS: FOS reversed in vivo HFS-induced lipid accumulation in the liver. An HFS diet increased ALT, AST, TC, TG, and LDL serum levels, decreased HDL serum levels, and increased IL-6, TNF-α, 8-OHdG, and MDA levels. These changes were reduced by FOS. FOS also increased intestinal and serum levels of short chain fatty acids (SCFAs). In vitro, SCFAs ameliorated palmitic acid-induced ROS production and apoptosis of HepG2 cells. CONCLUSION: FOS supplementation lowers serum lipid levels and ameliorates HFS-induced inflammation by upregulating SCFAs.

Combination of 16S rRNA and procalcitonin in diagnosis of neonatal clinically suspected sepsis.

OBJECTIVE: To investigate the application of 16S rRNA in diagnosing patients with neonatal sepsis. METHODS: We studied 60 consecutive neonatal patients with clinically suspected sepsis and 20 non-infective cases as controls. All patients were diagnosed with sepsis by clinical and experimental criteria. Clinical characteristics were recorded and 16S rRNA sequencing was conducted for all patients. The sensitivity, specificity, and accuracy of the detection methods were analyzed. RESULTS: The detection limit of 16S rRNA sequencing was 1 × 102 CFU/mL. For suspected sepsis, the positive rate of 16S rRNA detection was 93.3%, which was similar to that of procalcitonin detection (85%), and was significantly higher than that of bacterial culture (51.7%). The specificity of procalcitonin detection (74.1%) was significantly lower than that of 16S rRNA detection (100%). Moreover, the combination of 16S rRNA and procalcitonin detection showed a sensitivity of 100%, specificity of 74.1%, and accuracy of 92.0%. For proven sepsis, the sensitivity and specificity of 16S rRNA detection were both 100.0%, and those for procalcitonin were 87.1% and 87.0%, respectively. CONCLUSION: Detection of 16S rRNA has high sensitivity and specificity in diagnosing sepsis. The combination of 16S rRNA and procalcitonin has even better sensitivity with acceptable specificity.

[Association between serum 25(OH)D levels at birth and bronchopulmonary dysplasia in preterm infants].

OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were classified into two groups: BPD and control. The association between serum 25(OH)D levels at birth and BPD was analyzed. RESULTS: Serum 25(OH)D levels in the BPD group was significantly lower than those in the control group [(37±17 nmol/L vs 47±20 nmol/L; P<0.05), and the rate of vitamin D deficiency was significantly higher than those in the control group (90.2% vs 74.0%; P<0.05). The level of serum 25(OH)D was negatively correlated with the incidence of BPD (r=-0.201, P=0.001). CONCLUSIONS: Vitamin D deficiency at birth may be associated with BPD in preterm infants, but need to be further studied by multivariate analysis.