Zebrafish facilitates drug screening: potential of 3-deoxy-andrographoside from Chuanxinlian ) as an anti-inflammatory agent.

OBJECTIVE: To systematically evaluate the anti-inflammatory potential of diterpene lactones from Chuanxinlian () (AP). METHODS: We firstly adopted zebrafish, a novel and ideal animal model for high-throughput drug screening, to investigate the anti-inflammatory activities of 17 diterpene lactones isolated from AP. RESULTS: The results showed that most of diterpene lactones displayed significant anti-inflammatory effects in lipopolysaccharide microinjection-, copper sulfate exposure- or tail transection-induced zebrafish inflammation models. Moreover, diterpene lactone 3-deoxy-andrographoside (AP-5) was firstly found to attenuate inflammatory responses, which was closely associated with the myeloid differentiation primary response 88/nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways. CONCLUSION: Our research sheds light on the inestimable roles of zebrafish in high-throughput drug screening, elucidates the potent inhibitory effects of diterpene lactones against inflammation and indicates that AP-5 may serve as a potential alternative agent for the treatment of inflammatory diseases.

Anti-inflammatory Effect and Mechanism of Lianggesan and Its Component Glycyrrhiza Radix et Rhizoma Based on Zebrafish Inflammation Model / 中国实验方剂学杂志

ObjectiveLipopolysaccharide （LPS）-induced zebrafish inflammation model was used to evaluate the anti-inflammatory activity of different extracts from Lianggesan （LGS） and its component Glycyrrhiza Radix et Rhizoma. MethodDifferent polar fractions of LGS and Glycyrrhiza Radix et Rhizoma were obtained by the principle of similar miscibility. For toxicity observation， the zebrafish （3 day-post-fertilization） was exposed to different concentrations of extracts for 24， 48 and 72 h. The yolk sac of the zebrafish was microinjected with 0.5 g·L-1 LPS to establish the inflammation model， and then the embryos were soaked with different concentrations of extracts to observe their survival status at 72 h and the aggregation of neutrophils in yolk sac at 12 h after treatment. Hematoxylin-eosin staining was used to analyze the yolk sac of the zebrafish microinjected with LPS. Quantitative Real-time polymerase chain reaction （Real-time PCR） was performed to further investigate the anti-inflammatory effects and mechanisms of LGS and Glycyrrhiza Radix et Rhizoma. ResultThe toxicity of LGS and Glycyrrhiza Radix et Rhizoma was decreased with the increase of polarity， and the descending order was petroleum ether>ethyl acetate>n-butanol>water. Compared with model group， the extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma prolonged the survival time of the zebrafish， and inhibited the recruitment and aggregation of neutrophils and decreased the infiltration of inflammatory cells in the yolk sac， among which the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma had the most significant effect （P<0.01）. In addition， compared with model group， the water fraction of LGS and the ethyl acetate fraction of Glycyrrhiza Radix et Rhizoma down-regulated the mRNA expression of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， and suppressed the expression of toll like receptor 4 （TLR4） and nuclear factor kappa-B （NF-κB） in LPS-stimulated zebrafish （P<0.01）. ConclusionThe extracts from different fractions of LGS and Glycyrrhiza Radix et Rhizoma exerted protective effects in LPS-induced zebrafish by inhibiting the TLR4 and NF-κB signaling pathways. Moreover， in zebrafish model， the method of administration by soaking was applicable to the high-throughput screening of anti-inflammatory Chinese medicine， which was suitable for the evaluation of anti-LPS activity of Chinese medicine and the different extracts.

Application of PBL combined with mind mapping and the situational teaching in cardiology teaching of rural doctors / 中华医学教育探索杂志

Objective:To explore the application effect of problem-based learning (PBL) combined with mind mapping and situational teaching in cardiology teaching of rural doctors.Methods:Twenty rural doctors of Batch 2017 and 24 rural doctors of Batch 2018 were selected as study subjects, and they were divided into the experimental group (Batch 2018) taught by PBL combined with mind mapping and situational teaching and the control group (Batch 2017) taught by traditional teaching. Classroom tests and questionnaires were used to compare the students' mastery of the teaching content, and the teaching effect and student feedback were evaluated. SPSS 18.0 was performed for t test, rank-sum test and χ2 test. Results:The theoretical results of the experimental group were significantly higher than those of the control group ( P<0.05). The scores of learning interest and initiative ( Z=-3.606, P<0.001), classroom attraction ( Z=-3.455, P=0.001), understanding ( Z=-3.757, P<0.001) and mastering ( Z=-4.259, P<0.001) in the study effect evaluation of the experimental group were significantly higher than those of the control group. The satisfaction to teachers about active classroom atmosphere ( χ2=4.556, P<0.05), flexible methods ( χ2=12.813, P<0.05), satisfaction ( P<0.05), theory with practice ( P<0.05), and thinking inspiration ( χ2=21.042, P<0.05) of the experimental group were significantly greater than those of the control group. Conclusion:PBL combined with mind mapping and situational teaching has a good effect on the teaching of cardiology of rural doctors, and it is worthy of promotion in the grassroots.

Research progress of exosomes in epithelial-mesenchymal transition / 南方医科大学学报

Exosome, a membranous vesicle with biological activity, not only transmits active substances between cells but also transfers information between cells to participate in cell communication. Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells acquire migratory and invasive properties to become mesenchymal stem cells. EMT is essential for the development of a spectrum of diseases. Studies have shown that exosomes have dual effects on EMT to, on the one hand, promote EMT and tumor cell invasion and metastasis and accelerate angiogenesis and tumor growth; on the other hand, exosomes can suppress tumor cell invasion, inhibit fibrosis of the heart, liver and kidney, and improve myocardial infarction by inhibiting EMT. Exosomes modulate EMT-related signaling pathways by carrying EMT-related proteins or miRNA to exert their bi-directional regulatory effects.