ABSTRACT
Objective:To investigate the mechanism of Sinisan in treating type 2 diabetes mellitus（T2DM） based on network pharmacology. Method:Based on electronic databases， active ingredients of Sinisan and target genes of ingredients as well as type 2 diabetes were screened out. Cytoscape software was applied to construct "herb-active ingredient-target-disease" interaction network diagram，respectively. The common genes of ingredients and disease were uploaded to the STRING database， and the protein interaction network map （PPI） was constructed. CytoNCA and Cluster Marker were used to analyze PPI，respectively. Finally，ClueGO was used to analyze gene ontology （GO） enrichment and Kyoto Encyclopedia of genes and genomes （KEGG） pathway enrichment. Result:A total of 137 active components and 110 effective genes of Sinisan in the treatment of type 2 diabetes were screened out. Based on PPI analysis，these effective genes were divided into 4 different clusters， and 12 genes were considered as the most effective targets. GO enrichment analysis showed that cluster 1 mainly involved acute inflammatory response and acetylcholine receptor signaling pathway， cluster 2 mainly involved cellular response to steroid hormone stimulu and xenobiotic stimulus，and cluster 3 was mainly engaged in the metabolism process of protein，fatty and glucose and the response to hypoxia. KEGG analysis was highly correlated with advanced glycation end products-receptor for AGE （AGE-RAGE） pathway，apoptosis pathway，inflammatory pathway，cell cycles and various metabolic pathways. Conclusion:Sinisan has a regulatory effect in pathogenesis and prognosis of T2DM，such as inflammation，cell apoptosis and nutrition metabolism. Moreover，its potential mechanisms on diabetic angiopathies，diabetic cognitive impairment and cancers were reveal，so as to define a direction for the fundamental research of Sinisan.
ABSTRACT
AIM:To investigate the effects of kaempferol-3-O-rutinoside(KR)on the proliferation,migration of vascular smooth muscle cells(VSMC)and the activation of transforming growth factor βreceptor 1(TGFBR1)signaling pathway in the cells.METHODS: The viability of VSMC was detected by MTT assay.The proliferation of VSMC was measured by EdU staining.The migration ability of VSMC was examined by Transwell assay.The protein levels of the mi-gration-associated proteins matrix metalloproteinase 2(MMP2)and matrix metalloproteinase 9(MMP9)were detected by Western blot.Molecular docking study was conducted to explore the interaction between KR and TGFBR 1.The protein le-vels of the phosphorylated TGFBR1,Smad2 and Smad3 were determined by Western blot.RESULTS: KR inhibited the viability of VSMC in a dose-and time-dependent manner.KR reduced the ratio of EdU-positive cells in a dose-dependent manner.KR dose-dependently suppressed the migration ability of VSMC and decreased the protein levels of MMP 2 and MMP9(P<0.05).KR docked into TGFBR1 with the binding energy of -9.804 kcal/mol by forming hydrogen bonds with SER-280,ARG-215,ASP-290 and LYS-335 of TGBFR1.KR dose-dependently suppressed the activation of TGFBR 1 and its downstream proteins Smad2 and Smad3(P<0.05).CONCLUSION: KR inhibits the proliferation and migration of VSMC,possibly via blocking the TGFBR1 signaling pathway.
ABSTRACT
The medical CT scanner is rapidly evolving from the fan-beam mode to the cone-beam geometry mode. In this paper, a new cone-beam pseudo Lambda tomography was proposed based on the Noo's fan beam super-short scan formula and FDK framework. The proposed pseudo-LT algorithm, which avoids the computation of any PI line and any differential operation, has a significant practical implementation, thus leading to the images with quality improvement and reduced artifacts. The results in the simulation studies confirm the observation that the new algorithm can improve the image resolution over the traditional algorithms with noise projection data.