ABSTRACT
Objective:Network pharmacology was used to investigate the mechanism of the Sargassum treating thyroid nodule. Methods:The main active ingredients of Sargassum and the targets of active ingredients were obtained by TCMSP, and thyroid nodule disease targets were obtained through GeneCards and OMIM. The STRING database and Cytoscape 3.2.1 software were used to construct the active ingredients-disease-targets network and protein interaction network (PPI). The GO enrichment and KEGG pathway analysis of the targets were analyzed by using R version 4.0.0 software. Results:Two active ingredients were screened from Sargassum and 59 targets were related to thyroid nodule. Biological function analysis showed that the targets of Sargassum included DNA-binding transcription activator activity, RNA polymerase Ⅱ-specific, ubiquitin-like protein ligase binding. Sargassum played an important role in treating thyroid nodule by the gene targets such as RELA, CASP3, IL6, CASP9, EGFR, VEGFA and other targets mediating the signaling pathways such as PI3K-Akt signaling pathway, Kaposi sarcoma-associated herpesvirus infection and other pathways. Conclusion:The potential multi-target and multi-pathway network mechanism of Sargassum in the treatment of thyroid nodule provided theoretical basis for further research.
ABSTRACT
Objective To investigate the dynamic changes of cardiomyocyte apoptosis and Caspase-12 activation after coronary microembolization (CME) in rats. Methods The CME models were produced by injection of 42 μm microspheres (3000/0.1 ml) into the left ventricle during clampinduced ascending aorta occlusion for 10 seconds in adult male Sprague-Dawley rats (CME group).The sham-operation group was injected with saline instead (S group). The survivors were randomly divided into five groups: 3 h, 6 h, 12 h, 24 h and 4 weeks (n=10, each), respectively. In addition,10 rats were designed as normal control group. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The expressions of Caspase-3, 12 and procaspase-3 and 12 were detected with Western-blot analysis. The activity of Caspase-12 was determined with fluorometric assay kit. Results (1)Compared with the shamoperation group and normal control group, the apoptosis rates of cardiomyocytes in CME group were significantly increased at each time point respectively (all P＜0.05). Apoptotic cardiomyocytes were found mainly in the border zones and infarct foci. The apoptosis rates of cardiomyocytes at 3 h, 6 h,12 h, 24 h and 4 weeks after CME were (1.76±0.68)%, (3.17±1.26)%, (1.34±0.12)%,(1.07±0.65)% and (0.30±0.13)%, respectively. The apoptosis rates of cardiomyocytes increased at 3 h after CME, peaked at 6 h after CME (all P＜0.05), and then gradually decreased with lowest value at 4 weeks (all P＜0.01). (2)Compared with sham-operation group and normal control group,the relative activation level of Caspase-3 and 12 in CME group increased remarkably (all P＜0.05).The time courses of Caspase-3 and 12 expressions corresponded well to those of cardiomyocyte apoptosis after CME. Conclusions The amount of cardiomyocytes apoptosis is significantly increased after CME. Caspase-12 may be involved in the apoptosis of cardiomyocyte after CME.