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Background: The Chinese medicine, Huangqi Jianzhong Tang (HJT), is widely used to treat gastric cancer (GC). In this study, network pharmacological methods were used to analyze the potential therapeutic targets and pharmacological mechanisms of HJT in GC. Methods: Bioactive components and targets of HJT and GC-related targets were identified using public databases. The protein-protein interaction network of potential targets of HJT in GC was constructed using the Cytoscape plug-in (v3.8.0), CytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, in addition to molecular docking and animal experiments to verify the results of network pharmacology analysis. Results: A total of 538 GC-related targets were identified. The bioactive components of HJT were selected for drug-likeness evaluation and binomial statistical model screening, which revealed 63 bioactive components and 72 targets. Based on GO enrichment analysis, all targets in the protein-protein interaction network were mainly involved in the response to oxidative stress and neuronal death. Further, KEGG enrichment analysis suggested that the treatment of GC with HJT mainly involved the Wnt signaling pathway, PI3K-Akt signaling pathway, TGF-ß signaling pathway, and MAPK signaling pathway, thereby providing insights into the mechanism of the effects of HJT on GC. Conclusion: This study revealed the potential bioactive components and molecular mechanisms of HJT, which may be useful for the treatment of GC, and provided insights into the development of new drugs for GC.
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Background: Young gastric cancer (YGC) has been indicated as having a worse prognosis than in elderly gastric cancer (EGC). It has been reported that YGC and EGC patients show different genomic profiles; however, there has been no comparative study conducted to reveal their mutational characteristics. Methods: Firstly, we divided and analyzed the mutational landscape and 50 cancer-related genes characters of YGC (n=18) and EGC (n=18) patients from The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD). A total of 8 gastric cancer samples including 4 YGC and 4 EGC patients were collected to detect 50 cancer-related genes by multiplex polymerase chain reaction (PCR) next generation sequencing. The R/maftools package was used to describe the mutational characteristics. Results: Our results showed that the EGC group harbored more mutations than the YGC group. In 50 cancer-related genes in our cohort, the YGC group tended to be different from the EGC group using multiplex PCR next generation sequencing. In the YGC group, candidate mutations were identified within the following genes: IDH2, PDGFRA, KRAS, FLT3, FGFR2, and FGFR3. The YGC group showed less tumor mutational burden (TMB) level then EGC. Conclusions: The YGC group tended to be more sensitive to molecularly targeted therapy because of it having more somatic mutations in 50 cancer-related genes using targeted next-generation sequencing.
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Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn's disease (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most of the drugs for IBD used commonly in the clinic have adverse reactions, and only a few drugs present long-lasting treatment effects. Moreover, issues of drug resistance and disease recurrence are frequent and difficult to resolve. Together, these issues cause difficulties in treating patients with IBD. Therefore, the development of novel therapeutic agents for the prevention and treatment of IBD is of significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be a novel approach to developing effective therapeutic strategies for IBD. Phytochemicals such as astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, and icariin are reported to be effective in IBD treatment. In brief, natural compounds with anti-inflammatory activities are considered important candidate drugs for IBD treatment. The present review discusses the potential of certain natural compounds and their synthetic derivatives in the prevention and treatment of IBD.
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Recent studies have demonstrated that circular RNAs (circRNAs) play an important role in the development of gastric cancer (GC). The present study aimed to investigate the role of hsa_circ_0076305 (circPGC) in GC. The levels of circRNAs and mRNAs in AGS cell lines were detected via reverse transcription-quantitative PCR, and western blotting was performed to detect protein expression levels. Functional studies were explored by CCK8 assay and cell migration assay. Functional studies have indicated that circPGC orchestrates two cellular processes; it inhibits proliferation, and promotes migration and invasion in the GC AGS cell line, a phenomenon called 'migration-proliferation dichotomy', as well as epithelial-to-mesenchymal transition in AGS cells. In addition, circPGC degrades the extracellular matrix and basement membrane through matrix metallopeptidase (MMP)9 and MMP14, providing a microenvironment that facilitates cell migration. The results also demonstrated that circPGC expression is lower in clinical patients with later stages of GC, which is associated with poor prognosis. Taken together, these results suggest that circPGC exhibits migration-proliferation dichotomy during GC development, invasion and migration.
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BACKGROUND: As a multifaceted disease, atherosclerosis is often characterized by the formation and accumulation of plaque anchored to the inner wall of the arteries and causes some cardiovascular diseases and vascular embolism. Numerous studies have reported on the pathogenesis of atherosclerosis. However, fewer studies focused on both genes and immune cells, and the correlation of genes and immune cells was evaluated via comprehensive bioinformatics analyses. METHODS: 29 samples of atherosclerosis-related gene expression profiling, including 16 human advanced atherosclerosis plaque (AA) and 13 human early atherosclerosis plaque (EA) samples from the Gene Expression Omnibus (GEO) database, were analyzed to get differentially expressed genes (DEGs) and the construction of protein and protein interaction (PPI) networks. Besides, we detected the relative fraction of 22 immune cell types in atherosclerosis by using the deconvolution algorithm of "cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT)." Ultimately, based on the significantly changed types of immune cells, we executed the correlation analysis between DEGs and immune cells to discover the potential genes and pathways associated with immune cells. RESULTS: We identified 17 module genes and 6 types of significantly changed immune cells. Correlation analysis showed that the relative percentage of T cell CD8 has negative correlation with the C1QB expression (R = -0.63, p = 0.02), and the relative percentage of macrophage M2 has positive correlation with the CD86 expression (R = 0.57, p = 0.041) in EA. Meanwhile, four gene expressions (CD53, C1QC, NCF2, and ITGAM) have a high correlation with the percentages of T cell CD8 and macrophages (M0 and M2) in AA samples. CONCLUSIONS: In this study, we suggested that the progression of atherosclerosis might be related to CD86, C1QB, CD53, C1QC, NCF2, and ITGAM and that it plays a role in regulating immune-competent cells such as T cell CD8 and macrophages M0 and M2. These results will enable studies of the potential genes associated with immune cells in the progression of atherosclerosis, as well as provide insight for discovering new treatments and drugs.