Abstract. Astragaloside IV (AS-IV) is a flavonoid from the plant Astragalus membranaceus (Fisch) Bge that has a wide range of therapeutic effects. The aim of the present study was to examine the effect of AS-IV on rats with necrotizing enterocolitis (NEC) under oxidative stress and inflammation. Newborn Sprague-Dawley rats were induced with NEC by asphyxia and hypothermia applied on 3 consecutive days. The rats were orally administered AS-IV at 25, 50 and 75 mg/kg for 4 days. The results revealed that AS-IV administration prevented NEC-induced decrease in the concentration of malondialdehyde and myeloperoxidase, and increase in the activity of glutathione (GSH) and superoxide dismutase in murine models. AS-IV also inhibited NEC-induced elevation in the levels of interleukin (IL) -6, IL-1β, tumor necrosis factor-α and nuclear factor (NF)-κB. The effects of AS-IV were achieved under inflammation and oxidative stress. Western blotting demonstrated that AS-IV substantially inhibited the phosphorylated (p)-IκBα, NF-κBp65, p-NF-κBp65 protein levels and increased vitamin D3 upregulated protein 1 (VDUP1) and IκBα protein levels. These data indicate that AS-IV may be effective in the protection of NEC-induced ileum degeneration by inhibiting the levels of inflammatory markers and oxidative stress via the regulation of the VDUP1/NF-κB signaling pathway.

Objective The objective of this study was to investigate the efficacy and safety profile of levetiracetam as add-on therapy in patients with refractory epilepsy. Methods Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar were systematically searched to identify potential eligible randomized controlled trials by two reviewers independently. Pooled estimates of risk ratios (RRs) for 50%, 75%, and 100% reduction from baseline were calculated using the fixed-effect model or random-effect model. Quality of included studies was assessed with the Cochrane Collaboration’s Risk of Bias tool. Serious adverse events and withdrawals induced by interventions and the most common side effects were analyzed. Results Seventeen trials with a total of 3,205 participants were included in this meta-analysis, including 14 trials for adulthood and three trials for children. Pooled estimates suggested that levetiracetam was an effective anti-epileptic drug at 1,000–3,000 mg/day (RR =2.00 for 1,000 mg/day, RR =2.68 for 2,000 mg/day, RR =2.18 for 3,000 mg/day) for adults and 60 mg/kg/day (RR =2.00) for children compared to placebo in terms of 50% reduction from baseline. Likewise, as for seizure freedom rate, levetiracetam had an advantage over placebo at 1,000–3,000 mg/day (RR =5.84 for 1,000 mg/day, RR =4.55 for 2,000 mg/day, RR =4.57 for 3,000 mg/day, respectively) for adults and 60 mg/kg/day (RR =4.52) for children. Regarding safety profile, patients treated with levetiracetam had significantly higher occurrence than placebo for somnolence, asthenia, dizziness, infection, nasopharyngitis, anxiety, and irritability; however, most studies reported that these adverse events were mild and transient. Conclusion Levetiracetam is an effective anti-epileptic drug for both adults and children with generalized or partial-onset refractory seizures at 1,000–3,000 or 60 mg/kg/day, with a favorable adverse event profile.

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.

This study aimed to explore novel long non-coding RNAs (lncRNAs) and the underlying mechanisms involved in childhood acute lymphoblastic leukemia (cALL). The GSE67684 dataset was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and lncRNAs (DELs) between Days 0, 8, 15 and 33 were isolated using random variance model corrective analysis of variance. Overlapping DEGs and DELs were clustered using Cluster 3.0. Bio-functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Interactions between lncRNAs and mRNAs were calculated using dynamic simulations, and interactions among mRNAs were predicted using the STRING database. lncRNA-mRNA and protein-protein interaction (PPI) networks were visualized using Cytoscape. Subsequently, the expression levels of lncRNAs in biological samples from children with or without cALL were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 593 overlapping DEGs and 21 DELs were identified. After clustering, Profile 26 exhibited a continuously increasing temporal trend, whereas Profile 1 exhibited a continuous decreasing trend. Upregulated DEGs were significantly enriched in 1,825 GO terms and 166 KEGG pathways, whereas downregulated DEGs were significantly enriched in 196 GO terms and 90 KEGG pathways. The lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were the top two regulators in the lncRNA-mRNA network. Toll-like receptor 4, cathepsin G, nucleotide-binding oligomerization domain containing 2 and cathepsin S may be considered the hub genes of the PPI network. RT-qPCR results indicated that the expression levels of the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were significantly elevated in the blood and bone marrow of patients with cALL compared with the controls. In conclusion, the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 may serve important roles in the pathogenesis of cALL via regulating immune response-associated pathways.

No abstract