ABSTRACT
5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs for malignant tumors. However, intestinal mucositis caused by 5-FU is a severe dose-limiting toxic effect and even leads to treatment interruption. Isoliquiritigenin (ISL) is one of the main active compounds of licorice, which is a traditional Chinese herbal medicine commonly used in inflammation and gastrointestinal diseases. It is speculated that ISL have protective effects on intestinal mucositis. However, no such studies have been reported. Therefore, to investigate the impact of ISL on 5-Fu-induced intestinal mucositis, a strategy based on network prediction and pharmacological experimental validation was proposed in this study. Firstly, the targets and mechanism of ISL in alleviating 5-Fu-induced gastrointestinal toxicity were predicted by network analysis. And the results were further confirmed by molecular docking. Then, a mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU (384 µmol/kg) to verify the prediction of network analysis. The network analysis results suggested that PTGS2 (Prostaglandin G/H synthase 2) and NOS2 (Nitric oxide synthase, inducible) might be the critical targets of ISL for reducing the intestinal toxicity of 5-FU. In addition, KEGG and GO enrichment analysis revealed that the HIF-1, TNF, MAPK, IL-17, PI3K-Akt, Ras, NF-kappa B signaling pathway, and biological processes of the inflammatory response, apoptosis regulation, NO production and NF-kappa B transcription factor activity might be involved in the mechanism of ISL against intestinal mucositis. Subsequent animal experiments showed that ISL could reduce the weight loss, leukopenia and mucosal damage caused by 5-FU. Compared with the intestinal mucositis model, the protein expressions of PTGS2, NOS2, TNFα (Tumor necrosis factor-alpha) and NF-κB p65 (nuclear factor kappa-B P65) were decreased after ISL treatment. In conclusion, this study is the fist time to find that ISL can attenuate 5-FU-induced intestinal mucositis in mice. Its anti-mucositis effect may be through regulating TNF/NF-κB pathway and inhibiting inflammatory mediators PTGS2 and NOS2. It will provide a potential candidate for the prevention and treatment of chemotherapy-induced intestinal mucositis.
ABSTRACT
With the continuous development of information technology, new teaching resources "micro-video class" and teaching model "flipped classroom" have gradually attracted the attention of teachers. Whether and how they can be applied in pharmacology teaching has already become the focus of medical education research in recent years. This paper explores the application and evaluation of the flipped classroom based on micro-video class in pharmacology teaching in our college. Students in Class 1 and Class 2 majoring in clinical medicine of 2018 in Chengdu Medical College were randomly divided into experimental group and control group. The teaching model of flipped classroom based on micro-video class was used in the experimental group, while the traditional teaching model was used in the control group. Theory tests and questionnaires were carried out at the end of the course. The average scores of theoretical knowledge in experimental group were significantly higher than those in control group (P < 0.05). In addition, the results of the feedback questionnaire showed that the overall satisfaction of students participating in flipped classroom based on micro-video class was higher (P < 0.05), and students thought that their learning enthusiasm, learning efficiency, and abilities of autonomous learning and problem-solving were greatly improved compared with those of students taught applying the traditional teaching model. Flipped classroom based on micro-video class model successfully improved the outcome of pharmacology teaching. It is supposed to provide reference for the reform of pharmacology teaching in medical college.
