Necrotizing enterocolitis (NEC) is the most common life‐threatening gastrointestinal disease encountered in the premature infant. It has been shown that the intercellular reactive oxygen species (ROS) generation activated by lipopolysaccharide involved in the nuclear factor kappa B (NF‐κB) activation and pathogenesis of NEC. Here, we report that an antioxidant peptide from tuna backbone protein (APTBP) reduces the inflammatory cytokines transcription and release. APTBP directly scavenges the free radical through 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2‐phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (PTIO) assay. In addition, APTBP reduces the intracellular ROS level, exhibiting an antioxidant activity within cells. Remarkably, gavage with APTBP attenuates the phenotype of NEC in the mice model. Mechanically, the NF‐κB activation, together with the expression of inflammatory cytokines are decreased significantly when intracellular ROS are eliminated by APTBP. Therefore, our findings demonstrated that an antioxidant peptide, APTBP, ameliorates inflammation in NEC through attenuating ROS–NF‐κB axis.

Background Bronchopulmonary dysplasia is a serious and lifelong pulmonary disease in premature neonates that influences around one-quarter of premature newborns. The wingless-related integration site /β-catenin signaling pathway, which is abnormally activated in the lungs with pulmonary fibrosis, affects cell differentiation and lung development. Methods Newborn rats were subjected to hyperoxia exposure. Histopathological changes to the lungs were evaluated through immunohistochemistry, and the activation of disheveled and Wnt /β-catenin signaling pathway components was assessed by Western blotting and real-time PCR. The abilities of proliferation, apoptosis and migration were detected by Cell Counting Kit-8, flow cytometry and scratch wound assay, respectively. Results Contrasting with normoxic lungs, hyperoxia-exposed lungs demonstrated larger alveoli, fewer alveoli and thicker alveolar septa. Superoxide dismutase activity was significantly decreased (7th day: P < 0.05; 14th day: P < 0.01) and malondialdehyde significantly increased (7th day: P < 0.05; 14th day: P < 0.01) after hyperoxia exposure. Protein and mRNA expression levels of β-catenin, Dvl-1, CTNNBL1 and cyclin D1 were significantly upregulated by hyperoxia exposure on 7th day (P < 0.01) and 14th day (P < 0.01). In hyperoxic conditions, Dvl-l downregulation and Dvl-l downregulation + MSAB treatment significantly increased the proliferation rates, decreased the apoptosis rates and improved the ability of cell migration. In hyperoxic conditions, Dvl-l downregulation could decrease the mRNA expression levels of GSK3β, β-catenin, CTNNBL1 and cyclin D1 and decrease the protein relative expression levels of GSK3β, p-GSK3β, β-catenin, CTNNBL1 and cyclin D1. Conclusions We confirmed the positive role of Dvl-1 and the Wnt/β-catenin signaling pathway in promoting BPD in hyperoxia conditions and provided a promising therapeutic target.

Necrotizing enterocolitis (NEC) is a common devastating gastrointestinal disease in premature infants, the molecular mechanisms of which have not been fully elucidated. Recently, endogenous peptides have garnered much attention owing to their role in diagnosis and treatment. However, changes in the peptide expression of NEC intestinal tissues remain poorly understood. In the present study, a comparative peptidomics profiling analysis was performed between NEC and control intestinal tissues via liquid chromatography-tandem mass spectrometry (LC-MS). In total, 103 upregulated and 73 downregulated peptides were identified in the intestinal tissues ( fold   change ≥ 1.5 , p < 0.05 ). Bioinformatics analysis revealed that these differentially expressed peptides were significantly associated with NEC pathophysiology, including apoptosis, the TGF-β signaling pathway, the Wnt signaling pathway, and the MAPK signaling pathway. Furthermore, two putative peptides could inhibit apoptosis and promote the migration of intestinal epithelial cells induced by lipopolysaccharide; these peptides were derived from the protein domains MT1 and EZRI, respectively. In conclusion, our study revealed that endogenous peptides are involved in the pathophysiologic mechanism of NEC; nevertheless, further exploration is required in this regard.