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Objective To analyze the effects of miR-181a-5p overexpression on metabolites in the small intestines of mice with subcutaneous oral cancer by detecting changes in metabolites and metabolic pathways.Methods Three groups were included in study:Control group,negative control and miR-181a-5p overexpression group.To establish a subcutaneous oral cancer model in mice,variously treated cell suspensions were subcutaneously injected into the upper right of the groin in female M-NSG severely immunodeficient mice.Changes in pathology and small intestinal tissues were assessed by HE staining.Changes in mouse body weight were also assessed.Tandem orbitrap mass spectrometry and ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry,were used to examine metabolites in the small intestines.By pre-analyzing the original data and quality rating sample data,XCMS was able to assess which metabolites were different among the groups.To identify unique metabolic pathways,KEGG enrichment analysis was used.Results A total of 170 distinct metabolites were found in the small intestinal tissues of Control and NC groups.Choline metabolism,alanine,aspartate,and glutamate metabolism,GABA synaptic metabolism,glycerophospholipid metabolism,cAMP signaling route,cancer center carbon metabolism,and niacin and niacin amine metabolic pathways were important signaling pathways for metabolite enrichment.In the NC group,16 distinct metabolites with VIP values larger than 2 were found in the small intestines compared with the OE group overexpressing miR-181a-5p.Glycerin phosphorylcholine,palmitic acid,3-hydroxybutyl carnitine,and β-hydroxybutyric acid were among the metabolites that significantly varied.The primary enhanced metabolic pathway was the choline pathway.Conclusions Mouse small intestines underwent slight changes from subcutaneous oral cancer with the greatest effect on metabolites critical for energy metabolism.The choline metabolic pathway was the pathway that selected absolutely metabolites in mouse small intestines with subcutaneous grafts of oral cancer.
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Objective:To predict the mechanism of Danggui Buxue Decoction for anti-myocardial ischemia-reperfusion injury and "treating different diseases with the same method" in ischemic stroke based on network pharmacology and molecular docking.Methods:The active components and targets of Danggui Buxue Decoction were screened by retrieving the database of TCMSP and literature; the corresponding targets of myocardial ischemia-reperfusion injury and ischemic stroke were found by OMIM and GeneCards database; the intersection targets of Danggui Buxue Decoction and disease were obtained by using Venny diagram, and the common target network and protein-protein interaction network were constructed by Cytoscape 3.7.1 software and STRING database. The GO and KEGG pathways were enriched by David Database, and the Bio GPS database was used to obtain the tissue distribution information of the key targets. The molecular docking technology was used to verify the results.Results:There were 21 active components in Danggui Buxue Decoction, 181 effective targets and 93 cross targets with diseases. The key components were quercetin, Kaempferol, β-sitosterol, formononetin and isorhamnetin. The key targets were AKT1, TNF, IL6, IL-1β and VEGFA. The enrichment results showed that the main action pathways were fluid shear force and arteriosclerosis, lipid and arteriosclerosis, AGE-RAGE signal pathway in diabetic complications, and the core targets were mainly located in the medullary cells, dendritic cell, smooth muscle, prostate, thyroid and other tissues. The results of molecular docking showed that quercetin had the best binding effect to IL-1β, while isorhamnetin had the best binding effect to IL-1β.Conclusion:Danggui Buxue Decoction is against myocardial ischemia-reperfusion injury and ischemic stroke through hemodynamics, lipid metabolism, inflammatory reaction, oxidative stress, immune reaction and cell apoptosis, plays the role of "treating different diseases with the same method".
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Aim To explore the mechanisms of action (MOA) of synergistic anticancer function in the combination of berberine and evodiamine.Methods We first analyzed the action of suppression in the drug combination from the cell level and validated the dose scope as well as ratio of concentration in synergistic effects of drug combination.Then, the miRNA chip of liver cancer cell BEL-7402 under different treatment was analyzed.By building the miRNA-mRNA network, the MOA of the synergistic drug combination was illustrated.Results Berberine and evodiamine used in combination could significantly synergistically suppress the proliferative ability of liver cancer cells.The special differentially expressed miRNAs (DEmiRNAs) mainly participated in some cancer proliferation-related pathways and biological processes, such as MAPK signaling pathway, endocytosis pathway and insulin signaling pathway.The special target genes influenced by the drug combination not only covered three kinds of membrane receptors, but also took part in the regulation of downstream pathways.Conclusions From the regulation of miRNAs, it is clear that berberine may play a primary role in the synergistical suppression activity of the drug combination in cancer cells.The discovery of synergistic MOA in the combination of berberine and evodiamine from the miRNA level will provide a new guidance to explore more synergistic drug combinations in the future.
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Objective To study the prevalence and sequence homology of virulence genes exoU and exoS in 53 strains of pan-drug-resistant Pseudomonas aeruginosa .Methods The virulence genes exoU and exoS were detected by PCR.Sequence homo-logy was analyzed by BOX-PCR.Results Of the 53 clinical isolates of pandrug-resistant Pseudomonas aeruginosa ,the exoS+/exoU- genotype was identified in 40 strains,exoU+/exoS - genotype in 10 strains,exoS +/exoU+ genotype in 1 strain, and exoS-/exoU- genotype in 2 strains.BOX-PCR results showed that 41 exoS+ isolates belonged to 24 genotypes,and 11 exoU+ strains could be grouped into 7 genotypes.Conclusions The prevalence of virulence genes is high in clinical isolates of pandrug-resistant Pseudomonas aeruginosa .BOX-PCR fingerprint analysis combined with sequence homology analysis is help-ful for effective monitoring and control of hospital pandrug-resistant pseudomonas aeruginosa infection.
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Objective To observe the change of peripheral blood CD34+ cell level in patients with acute cerebral infarction, and explore its relationships with cerebrovascular risk factors,neurological function and carotid artery intima-media thickness (IMT). Methods The 45 patients with acute cerebral infarction (onset within 72 h) (infarction group) and 27 patients with cerebr ovascular risk factors but without cerebral infarction (high-risk group) were chosen for the study. The cerebrovascular disease risk factors including history of alcohol abuse, smoking, coronary heart disease, hypertension, diabetes, abnormal levels of serum triglycerides, total cholesterol,low-density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were recorded in all subjects. The peripheral blood CD34+ cell levels were measured by flow cytometry.The correlations of peripheral blood CD34+ cell level with cerebrovascular disease risk factors were analyzed. The neurological function and carotid artery IMT were recorded in infarction group, and the correlations of peripheral blood CD34+ cell level with neurological function and carotid artery IMT were analyzed. Results (1) The peripheral blood CD34+ cell level was significantly negatively correlated with coronary heart disease, hypertension, diabetes and LDL-C level (r =- 0. 749,-0. 717, - 0. 688, - 0. 764, all P＜0. 01) ; (2) Multiple linear regression analysis showed that peripheral blood CD34+ cell level was an independent relative factor of acute cerebral infarction (P＜0.05); (3) The peripheral blood CD34+ cell level was lower in infarction group than in high-risk group, and was significantly negatively correlated with neurological deficit score (r=-0. 721, P＜0.01) and carotid artery IMT (r= -0. 695, P＜0. 01). Conclusions Peripheral blood CD34+ cell level could be an independent relative factor of acute cerebral infarction; The peripheral blood CD34+ cell level is significantly negatively correlated with neurological function and carotid artery IMT in patients with acute cerebral infarction; And it can be used as cytological marker which reflect early vascular endothelial function in patients with ischemic stroke.