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Although surgery with or without (neo)adjuvant chemo/radiotherapy, as the standard treatments, can be suitable therapeutic strategies for gastric cancer, side effects and drug resistance are two main treatment obstacles. It has been discovered that pomegranate and its natural derivatives, especially ellagic acid (EA), offer significant anti-cancer effects while causing trivial side effects. In this study, we aimed to explore the anti-cancer effects of EA on a human gastric adenocarcinoma cell line (AGS) as well as in immunocompromised mice bearing human gastric tumors, for the first time. HPLC was used for determining EA in samples. MTT assay, apoptosis and scratch assay, gelatin zymography, and quantitative RT-PCR were used to determine the anti-cancer properties of different concentrations of pomegranate fruit juice, pomegranate peel extract, and EA. Furthermore, the effects of these compounds were investigated on immunosuppressed C57BL/6 mice carrying human gastric cancer tumors. EA could inhibit the proliferation and migration of gastric cancer cells. It also had significant effects on reducing both expression and activity of MMP-2 and MMP-9. Further, it was demonstrated that with alterations in the expression of genes involved in apoptosis and inflammation including P53, BAX, APAF1, BCL2, iNOS, NF-κB, IL-8, and TNF-α, EA treatment led to increased cancer cell death and reduced inflammation. Furthermore, its use in mice bearing gastric tumors resulted in a significant reduction in tumor volume without any obvious side effects. Ellagic acid exhibited anti-cancer effects on gastric adenocarcinoma, and can be considered as a safe anti-cancer agent for further preclinical studies on this cancer.

Context: Asthma, characterized by airway inflammation, is a common chronic disease of childhood. Cytokines and chemokines could be used in the diagnosis, treatment, and management of asthma severity in children. In this review, we have explained the application of cytokines and chemokines as biomarkers in pediatric asthma. Evidence Acquisition: All related articles were separately searched by two researchers using the following keywords in PubMed, Scopus, and Embase databases: Cytokine biomarkers, chemokines biomarkers, and children asthma. Articles published from 2000 to 2017 were investigated in the research, and 28 articles were included in the final analysis for this review. Results: About cytokines, serum Interleukin 4 (IL-4) level is a marker of the presence of asthma, and IL-13 is a key cytokine involved in the manifestation of asthma symptoms. High IL-13 concentration and number of IL-13+ cells in the bronchial submucosa specimens are characteristic of severe asthma. Serum IL-5 concentration 3.1 times in children with severe asthma. IL-17 is involved in airway obstruction. IFN-γ gene polymorphism (+874A/T) in children elevates susceptibility to asthma. TGFB1 polymorphisms are considered as indicators of asthma severity. IL-26 plays an important role in asthma severity. IP-10 may be a useful inflammatory marker of asthma severity. High periostin level has been identified in pediatric asthma. PDGF level, which is high in asthma patients, plays an important role in bronchial fibrosis. About chemokines, plasma TARC concentration may be a useful biomarker of airway inflammation and asthma severity in children. Studies have supported the association between high serum RANTES levels and severe airway obstruction in children. CXCR4 levels are high in pediatric asthma and are associated with disease severity. Conclusions: A wide range of cytokines and chemokines may play important roles in asthma severity in pediatric patients. Therefore, several studies have recommended the use of multiple molecular biomarkers, such as cytokines, for determining asthma severity in children.

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Background: Pediatric observational studies have indicated that most critically ill children have low serum selenium level, which is associated with the increased incidence of multiple organ failure and deteriorated clinical outcomes. Selenium plays a key role in the endogenous antioxidant defense mechanism and inflammatory pathways. Objectives: The present study aimed to assess the effects of high-dose selenium supplementation on the improvement of inflammatory and oxidative stress indices, as well as clinical outcomes, in pediatric patients with severe oxidative stress and inflammation following major gastrointestinal surgeries. Methods: This prospective, single-blind, randomized, parallel group superiority trial was conducted at the pediatric intensive care unit (PICU) of Akbar Pediatric Hospital in Mashhad, Iran in 2019. Patients were assigned to the supplementation (high-dose selenium: 20 µg/kg/d) and control groups (placebo with the recommended dietary allowance doses of selenium) using stratified blocks. Among 72 eligible critically ill children after gastrointestinal surgery, 66 patients completed the study. Inflammatory markers were measured and compared between the groups, including high-sensitivity C-reactive protein (hsCRP), interleukin 1 beta (IL-1β), prooxidant-antioxidant balance (PAB) assay, and clinical outcomes. Data analysis was performed in SPSS version 20 using the intention-to-treat approach. Results: Only 14 patients had optimal serum selenium concentrations before the surgery and PICU admission. At the end of the study, 90.6% of the patients (n = 29) in the intervention group and 100% (n = 34) of those in the placebo group had suboptimal serum selenium levels (< 50 ng/mL). Although supplementation with high-dose selenium decreased the inflammatory markers in the post-surgical critically ill children (-18 mg/mL and -37.5 pg/mL for hsCRP and IL-1β, respectively), the administered dose could not improve the serum glutathione peroxidase (GPx) concentrations as the selenium functional marker, as well as the PAB assay as the single test to assess the balance/imbalance of the oxidants and antioxidants simultaneously. Additionally, clinical outcomes such as infections, length of ICU stay, and 28-day mortality did not improve after the intervention. Conclusions: According to the results, high-dose selenium supplementation (20 µg/kg/d) in the post-surgical critically ill children could improve the serum inflammatory markers. However, the changes were suboptimal with no significant effects of the serum GPx concentrations, antioxidant defense system, and clinical outcomes.

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Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that affected significantly spinal cord, nevertheless, the pathogenesis pathway. This study aimed to employ high throughput metaanalysis to find major genes involved in the pathogenesis of HAM/TSP. High-throughput statistical analyses identified 385, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. STRING and further network analyses highlighted 32, 29, and 13 hub genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. Biological network analyses indicated the involvement of hub genes in the HAM/TSP group in many vital pathways like apoptosis and immune pathways. Moreover, the meta-analysis results disclosed three major genes including STAT1, TAP1, and PSMB8 which have function role in HAM/TSP progression. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P=0.01 and P=0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P=0. 04 and P=0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P=0.008 and P=0.02, respectively). No significant difference was found among three groups in terms of percentage of T helper and cytotoxic T lymphocytes (P= 0.55 and P=0.12). Our results confirm that STAT1, TAP1, and PSMB8 are three important genes which their expressions levels were changed in three different groups. These proteins in association with other proteins can involve in the immune and apoptosis pathways.