ABSTRACT
Aim To explore the mechanism of Polygonum capitatum(PC)in the treatment of Helicobacter Pylori associated gastritis(HAG). Methods The databases were used to identify the target of PC active compounds and HAG-related genes,and the intersection was taken to obtain the potential targets of PC treatment of HAG. The interaction network diagram of “drug-active compound-target-disease” and the protein-protein interaction(PPI)network of potential target protein interaction in HAG treated by PC were constructed by software Cytoscape 3.6.0. The important nodes in the network were screened by several topological indexes,and the GO and KEGG enrichment were analyzed by STRING database to obtain the potential signaling pathway of PC in the treatment of HAG. The binding ability of PC active components with key target proteins was observed by molecular docking method. On this basis,the related targets of PC in the treatment of HAG were verified in vivo and in vitro experiments. Results The PC active compounds and targets were identified through the database,and the “drug-active compound-target-disease” network diagram and the PPI network of potential target proteins were constructed. Combined with several topological indexes,the PPI network of potential target-protein interaction was analyzed,and 52 hub genes were screened. Further bioinformatics analysis and high-throughput sequencing revealed that PC exerted an effect on HAG through the Akt/NF-κB/NLRP3 pathway. Based on this,it was found that PC could reduce IL-18 and IL-1β in HAG GES-1 cells and HAG SD rats,up-regulate Akt and its phosphorylation level and reduce NF-κB expression,inhibit the activation of NLRP3 inflammatory body,so as to improve HAG inflammatory response. Conclusions PC could exert a therapeutic effect on HAG by activating Akt and its phosphorylation level,and inhibiting the expression of NF-κB and NLRP3 inflammasome related factors. This study provides a theoretical basis for explaining the mechanism of PC in the treatment of HAG.
ABSTRACT
Gastric cancer (GC) remains a threat to the health of the global population. The present study investigated the effects and mechanisms of the long non-coding RNA myocardial infarction associated transcript (MIAT) on the proliferation, apoptosis and metastasis of GC (HGC-27 and AGS) cells. The expression levels of MIAT, micoRNA (miR)-331-3p and RAB5B mRNA were analyzed using reverse transcription-quantitative PCR analysis. Cell growth, apoptosis, migration and invasion were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-331-3p targeted MIAT and RAB5B. The results indicated that MIAT levels were significantly upregulated in GC tissues and cells, correlated with RAB5B levels and inversely associated with miR-331-3p levels. MIAT overexpression promoted proliferation and metastasis, and inhibited the apoptosis of GC cells. MIAT knockdown had the opposite effect on GC cells. The rescue experiments revealed that the effects of MIAT knockdown on the biological behaviour of GC cells were attenuated by RAB5B overexpression. These data suggest that MIAT promotes GC progression via modulating miR-331-3p/RAB5B pathway.
ABSTRACT
A radical relay strategy is described to synthesize functionalized ß-amino alcohols. This strategy is enabled by photoredox-catalyzed and nitrogen-centered radical-triggered cascade reactions of styrenes (or phenylacetylenes), enol derivatives, and O-acyl hydroxylamines in DMSO. The broad synthetic application of this method is demonstrated by the reaction of structurally diverse reaction components, including complex molecular scaffolds. Multiple functional groups of the resultant highly functionalized ß-amino alcohol derivatives facilitate their further transformations.
ABSTRACT
Photoredox-catalyzed difunctionalizations of alkenes with O-acyl hydroxylamine derivatives are described. The solvent tunes the outcome of these reactions. Diamidation and oxidative amidation of alkenes can be achieved in CH3CN and DMSO, respectively. A variety of 1,2-diamidates and α-amino ketones bearing many functional groups are prepared using Ir(ppy)3 as the photocatalyst under visible light irradiation.
