ABSTRACT
Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.
ABSTRACT
OBJECTIVE@#To analyze the expression of microRNA-106a(miR-106a) in renal cell carcinoma (RCC) and its correlation with clinicopathological characteristics and prognosis of patients.@*METHODS@#Serum samples of 64 patients with newly diagnosed RCC were collected as the study group, and serum samples of 40 healthy individuals were used as the control group. Real-time fluorescence quantitative PCR was used to determine the expression level of miR-106a in each group. The correlation between miR-106a expression and clinicopathological characteristics of the patients was studied with single factor analysis and multiple Logistic regression model. Kaplan-Meier survival curve was used to analyze its correlation with the prognosis of patients.@*RESULTS@#Before surgery, compared with the control group (1.17± 0.58), RCC patients with high- (9.15± 0.96) and low-expression(3.45± 0.37) had increased expression of miR-106a. Postoperatively, the expression level of miR-106a in both groups of patients decreased to 1.53± 0.18 and 1.75± 0.21, respectively. The area under the curve (AUC) of the diagnostic value of serum miR-106a for RCC was 0.782 (95% CI: 0.661-0.902). With an optimal cutoff value of 0.531, the sensitivity was 78.10% and the specificity was 75.00%. Serum miR-106a level of RCC patients with TNM stage T3 or T4, clinical stage II or III, lymph node metastasis, and recurrence were significantly increased. The high expression of serum miR-106a in RCC patients has an independent relationship with the tumor TNM stage and lymph node metastasis. Of the 64 follow-up patients, 4 were lost and 30 had died. Among them, the median survival time of patients in the miR-106a high expression group was 30 months, which was significantly shorter than that of the low expression group (52 months).@*CONCLUSION@#The serum level of miR-106a is elevated in RCC patients, and may be used as a molecular marker for the diagnosis of RCC. High serum expression of miR-106a is an independent predictor for tumor TNM stage and lymph node metastasis, as well as an independent predictor for poor prognosis of RCC patients.