Regulation of ROS-NF-κB axis by tuna backbone derived peptide ameliorates inflammation in necrotizing enterocolitis.

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.

Serum IL-6, IL-23 profile and Treg/Th17 peripheral cell populations in pediatric patients with inflammatory bowel disease.

IL-6 and IL-23 are both pleiotropic cytokines involved in the regulation of the immune response, inflammation, and hematopoeisis. They also could mediate effector cells and tolerance mediated by cells with regulatory function. Inflammatory bowel disease (IBD) is associated with a reduced ratio of Treg cells ato Th17 effector cells in peripheral blood and is characterised by a pro-inflammatory cytokine microenvironment which supports the continued generation of Th17 cells. It is well described in adults but little is known in a pediatric population. This study was aimed to investigate the role of IL-6, IL-23 and its association with Treg and Th17 subsets in pediatric IBD patients. Peripheral blood mononuclear cells from patients and controls were stimulated with PMA, ionomycin, and brefeldin A. The frequencies of CD4+Foxp3+ cells, and CD4+IL17a+ cells were analyzed by flow cytometry. The serum level of IL-6 and IL-23 was determined by Elisa kit. The mRNA expression of Foxp3, IL-17a, IL-6 and IL-23 was detected by real-time quantitative PCR. The ratio of Treg/Th17 decreased in pediatric IBD patients, and it strongly correlated with IL-6 and IL-23. The present study provides a quantitative analysis regarding the Th17/Treg cell balance in peripheral blood of children with IBD and its association with serum IL-6 and IL-23 level.

Treating idiopathic hypertrophic pyloric stenosis with sequential therapy: A clinical study.

AIM: The aim of this study was to explore the efficacy and safety of treating idiopathic hypertrophic pyloric stenosis with sequential therapy (ST). METHODS: From January 2010 to June 2013, 49 children with idiopathic hypertrophic pyloric stenosis were divided into two groups to accept either atropine ST (ST group, n = 26) or laparoscopic surgery (operation group, n = 23). The remission rate of vomiting, complications, hospital stay and medical expenditure were compared between the two groups. The body weight and the thickness of the pyloric muscle at 6 months after the treatments were also compared. RESULTS: The remission rate of vomiting was lower in the ST group (88.5%; 23/26) than in the operation group (100%, 23/23). The difference in the incidence rate of complications, body weight and pyloric muscle thickness was not statistically significant between the two groups. However, the hospital stay was significantly longer, while the medical expenditure was significantly lower in the ST group than in the operation group. CONCLUSIONS: Atropine ST is safe, effective and cost-effective as compared with operation; however, the efficacy of ST is lower than operation.

Aberrant frequency of IL-10-producing B cells and its association with the balance of Treg/Th17 in children with inflammatory bowel disease.

Regulatory B cells (Breg) are a distinct B cell subset, which contribute to the pathogenesis of autoimmune disorders. Interleukin-10 (IL-10) plays a pivotal function to Breg. It is well described in adults but little is known in a pediatric population. This study was to investigate the role of IL-10-producing B cell (B10) and its association with Treg and Th17 subsets in the children with inflammatory bowel diseases (IBD). Peripheral blood mononuclear cells from IBD children patients and controls were stimulated with PMA, ionomycin, and brefeldin A. The frequencies of CD19+IL-10+ B cells, CD3+CD4+IL-17+Th17 cells, and CD4+ CD25(hi)Foxp3+ Treg cells were analyzed by flow cytometry. The mRNA expression of Foxp3, IL-17a and RORγt was detected by real-time quantitative PCR. The number of B10 cells was elevated in IBD children patients. There was a positive correlation between B10 cells and Tregs in IBD. The ratio of Treg/Th17 decreased in IBD, and it strongly correlated with B10 cells. The frequency of B10 cells is elevated in IBD and it correlates with both the Tregs counts and the Treg/Th17 ratio. B10 cells to regulate functional T cell subsets might be impaired in paediatric patients with IBD.

B7-H3 Regulates Glucose Metabolism in Neuroblastom via Stat3/c-Met Pathway.

Neuroblastoma (NB), which mainly originates from the adrenal gland, is one of the most common tumors in infants and young children. Abnormal B7 homolog 3 (B7-H3) expression has been reported in human NB, although its mechanism of action and precise role in NB are still unclear. The present study was performed to explore the role of B7-H3 in glucose metabolism in NB cells. Our findings showed that B7-H3 expression was increased in NB samples, and markedly promoted the migration and invasion of NB cells. B7-H3 silencing decreased the migration and invasion of NB cells. Moreover, B7-H3 overexpression also increased tumor proliferation in the human NB cell xenograft animal model. B7-H3 silencing reduced NB cell viability and proliferation, while B7-H3 overexpression had the opposite effects. Furthermore, B7-H3 increased PFKFB3 expression, resulting in increased glucose uptake and lactate production. This study suggested that B7-H3 regulated the Stat3/c-Met pathway. Taken together, our data showed that B7-H3 regulates NB progression by increasing glucose metabolism in NB.

Neutrophil Extracellular Traps Formation and Citrullinated Histones 3 Levels in Patients with Kawasaki Disease.

Background: Kawasaki disease (KD) is a vasculitis associated with vascular injury and autoimmune response. Inflammatory factors stimulate neutrophils to produce web-like structures called neutrophil extracellular traps (NETs). Citrullinated histone 3 (H3Cit) is one of the main protein components of neutrophil extracellular traps involved in the process of NETosis. The levels of NETs and H3Cit in the KD are not known. Objective: To determine the changes in the levels of NETs and H3Cit in KD. Methods: Children with KD were recruited and divided into the acute KD and the sub-acute KD group according to the disease phase and whether intravenous immunoglobulin (IVIG) was used or not. Peripheral venous blood was taken before and after the IVIG administration and sent for the examination of NETs by flow cytometry. The level of H3Cit was measured by enzyme-linked immunosorbent assay (ELISA). Results: The counts of NETs in the acute KD group significantly increased compared with the healthy controls (p<0.01). The level of H3Cit was significantly higher in the acute KD group than in the healthy control subjects. Of note, both the counts of NETs and the level of H3Cit decreased in the KD patients treated with IVIG compared with the acute KD group (p<0.01). Conclusion: Acute KD is characterized by an increased formation of NETs and high levels of H3Cit. IVIG significantly inhibited NETs formation and also reduced the level of plasma H3Cit in children with KD.

The Remission Effects of First Injection of Sclerotherapy for Pediatric Rectal Prolapse: A Systematic Review and Meta-Analysis.

Background: Pediatric rectal prolapse is a common issue in clinical practice. Among various managements, sclerotherapy is an important method to successfully treat pediatric rectal prolapse, especially for the first injection. The knowledge of the first injection of sclerotherapy can be revealed by a systemic review and meta-analysis of randomized clinical trials. Methods: We performed a systematic search and a meta-analysis for the retrospective clinical studies of sclerotherapy in pediatric rectal prolapse. The comparison between remission and recurrence after the first injection of sclerotherapy was performed to find if the first injection of sclerotherapy can treat rectal prolapse completely. After a restricted selection, 17 studies involving 1,091 pediatric rectal prolapse subjects with sclerotherapy were enrolled in a variety of classifications of injection agents. The focused outcome was to check whether the first injection of sclerotherapy can achieve a remission status. The meta-analysis was performed by Review Manager 5.4. Results: Among the subjects receiving sclerotherapy, the meta-analysis favors the remission status after receiving the first injection of sclerotherapy. The meta-analysis results showed significant remission tests for the overall effect and significant heterogeneities in odds ratio and the fixed-effects model. The significant therapeutic effects remained, however, even after testing in the relative risk and the random-effects model. Conclusions: Despite significant heterogeneity and relatively low quality of evidence, the first injection of sclerotherapy may conceivably demonstrate therapeutic effects to help the patients of pediatric rectal prolapse achieve a remission status.

Identification of a novel cell cycle-related risk signature predicting prognosis in patients with pancreatic adenocarcinoma.

BACKGROUND: Growing evidence have indicated that cell cycle-related genes (CRGs) play an essential role in the progression of pancreatic adenocarcinoma (PAAD). Nevertheless, the application of CRGs in estimating the prognosis of PAAD patients is still lacking. This study aimed to establish a risk signature based on CRGs that can predict patients' overall survival for PAAD. METHODS: The expression and corresponding clinical data of PAAD patients from The Cancer Genome Atlas database and 200 cell cycle-related genes from the MSigDB were used for the generation and validation of the signature. LASSO Cox regression was applied to build the prediction model. The diagnostic value of signature was evaluated by receiver operating characteristic curves. Univariate and multivariate regression was used to construct the nomogram providing the clinicians a useful tool. RESULTS: A total of 103 CRGs were identified. Seven genes (RBM14, SMAD3, CENPA, KIF23, NUSAP1, INCENP, SMC4) with non-zero coefficients in LASSO analysis were used to construct the prognostic signature. The 7-gene signature significantly stratified patients into high- and low-risk groups in terms of overall survival, and the area under the receiver operating characteristic curve of 5-year survival reached 0.749. Multivariate analysis showed that the signature is an independent prognostic factor. We then mapped a nomogram to predict 1-, 3-, and 5-year survival for PAAD patients. The calibration curves indicated that the model was reliable. Finally, we discovered that TP53 and KRAS mutated most frequently in low and high-risk groups, respectively. CONCLUSION: Our findings suggested that the seven genes identified in this study are valuable prognostic predictors for patients with PAAD. These findings provided us with a novel insight that it is useful for understanding cell cycle mechanisms and for identifying patients with PAAD with poor prognosis.

Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model.

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-ß 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.

Double simultaneous intussusception caused by Meckel's diverticulum and intestinal duplication in a child.

Intussusception is common in children. Double simultaneous intussusception is a peculiar variety of intussusception with only 14 previously reported cases. We report a unique case of a child who suffered from double simultaneous intussusception with two lead points (Meckel's diverticulum and intestinal duplication). The patient was successfully treated with manual reduction along with resection of Meckel's diverticulum and intestinal duplication. The child recovered well.

Safety and benefit of pre-operative oral carbohydrate in infants: a multi-center study in China.

BACKGROUND AND OBJECTIVES: Pre-operative oral carbohydrate administration (POCA) is an important aspect of enhanced recovery after surgery and has many advantages. The objective of this study was to explore the safety and effect of pre-operative oral carbohydrate administration in infants. METHODS AND STUDY DESIGN: This was a prospective, multi-center, randomized study that randomly assigned 1200 infants into four groups. In the control group (group A), the infants were strictly restricted to 6-h preoperative fasting before anesthesia. In the enhanced recovery after surgery (ERAS) groups (groups B, C, and D), the infants were orally administered a 10% carbohydrate solution (10% glucose water; 5, 10, and 15 mL/kg, respectively) 2 h before anesthesia. Blood glucose, gastric residual volumes, crying ratios, and the length of hospital stay were observed. RESULTS: The blood glucose was significantly higher in groups B, C, and D than group A at the time of anesthesia. The gastric residual volume revealed virtually no residue in groups A, B, and C, but 15 infants in group D had a gastric residual volume. The crying ratio was significantly higher in group A. The length of hospital stay was not significantly different between the groups. CONCLUSIONS: POCA is well-tolerated in infants at a dose of 10 mL/kg.