Mechanism of Ficus hirta-Hypericum perforatum in treatment of microvascular angina based on network pharmacology and molecular docking / 中国中药杂志

The active ingredients of Ficus hirta and Hypericum perforatum were collected from Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and related papers. The potential targets of these two medicinal herbs were searched from HERB database, and those associated with microvascular angina were screened out from GeneCards, Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), and HERB. Cytoscape was used to construct a protein-protein interaction(PPI) network of the common targets shared by the two herbs and microvascular angina based on the data of String platform. Metascape was employed to identify the involved biological processes and pathways enriched with the common targets. Cytoscape was used to draw the "active ingredient-target-pathway" network. AutoDock Vina was used to dock the core ingredients with the key targets. A total of 19 potential active ingredients and 71 potential targets were identified to be associated with microvascular angina. Bioinformatics analysis showed that phosphatidylinositol-3-kinase/protein kinase B(PI3 K-AKT), interleukin-17(IL17), hypoxia-inducible factor 1(HIF-1) and other signaling pathways were related to the treatment of microvascular angina by F. hirta and H. perforatum. Molecular docking results showed that β-sitosterol, luteolin and other ingredients had strong affinity with multiple targets including mitogen-associated protein kinase 1(MAPK1), epidermal growth factor receptor(EGFR) and so on. These findings indicated that F. hirta and H. perforatum may regulate PI3 K-AKT, IL17, HIF-1 and other signaling pathways by acting on multiple targets to alleviate oxidative stress, inhibit inflammatory response, regulate angiogenesis, and improve vascular endothelium and other functions. This study provides reference for in vitro and in vivo studies of the treatment of microvascular angina.

Effects of KLF17 on growth of xenograft tumor in nude mice and scree-ning and functional analysis of KLF17-regulated target genes in vivo / 中国病理生理杂志

AIM:To investigate the role of Krüppel-like factor 17(KLF17)in nude mouse xenograft model, and to explore the target genes regulated by KLF 17, the target gene functions and the signaling pathways involved.ME-THODS:The KLF17 was stably up-regulated in human lung adenocarcinoma A 549 cells and down-regulated in human lung adenocarcinoma H322 cells by lentiviral infection.BLAB/c nu/nu nude mice(n=11)were divided into KLF17 up-regual-tion group(n=5)and KLF17 down-regulation group(n=6).The right and left bodies of the nude mice were subcutane-ously injected with KLF17-up-/down-regulating cells and the counterpart empty vectors were used as control cells,respec-tively.The effects of KLF17 on the growth of the cell-derived xenografts in nude mice were analyzed.The mRNA and pro-tein expression levels of KLF17 in xenograft tumor tissues were analyzed by real-time PCR and immunohistochemical stai-ning,respectively.Transcriptome sequencing was used to explore the differentially expressed genes in the xenograft tumors derived from KLF17-up-regulating A549 cells,and the functions of the potential target genes were analyzed using the lung adenocarcinoma data from The Cancer Genome Atlas(TCGA)database.Gene Ontology and KEGG PATHWAY enrichment analyses were performed to analyze the functions of the differentially expressed genes and the involved signal pathways.RE-SULTS:The growth rate of KLF17-up-regulating A549 cell-derived xenograft tumors in the nude mice was significantly lower than that in empty control group(P<0.05),while the growth rate and the weight of KLF 17-down-regulating H322 cell-derived xenograft tumors in nude mice were significantly higher than those in empty control group(P<0.01 and P<0.05,respectively).In the A549 cell-derived xenograft tumor model,the KLF17 mRNA and protein were significantly in-creased in KLF17 up-regualtion group.The transcriptome sequencing showed the potential target genes regulated by KLF 17 were ras homolog family member V(RHOV)and coronin 1C(CORO1C).Ten-year cumulative survival time of the patients with lung adenocarcinoma from TCGA database was significantly different between high and low expression of RHOV and CORO1C at mRNA level.Increased expression levels of RHOV and CORO1C were correlated with short survival time in the patients with lung adnocarcinoma.The results of Gene Ontology and KEGG PATHWAY enrichment analyses indicated that the target genes(differentially expressed genes)regulated by KLF17 were related to the stimulation response,growth and adhesion of tumor cells,and participated in chemotaxis-,adhesion-and extracellular matrix receptor-related signaling path-ways.CONCLUSION:KLF17 inhibits the xenograft tumor growth in nude mice,and inhibits the oncogenes such as RHOV and CORO1C.The target genes regulated by KLF17 participate in the regulation of tumor adhesion-and growth-related sig-naling pathways.

Primary research of human bone marrow mesenchymal stem cells transfected by Smad7 / 重庆医学

Objective Human bone marrow mesenchymal stem cells were transfected by Smad7 and labeled with green fluores-cent mark.BMMSCs were implanted into rabbit glaucoma operational model and observed surviving condition.Methods Through BP and LR reaction,Smad7 with green fluorescent mark was inserted into human bone marrow mesenchymal stem cells by bacterio-phage,filtered positive colony and picked out cell line.15 New Zealand white rabbits were enforced trabeculectomy with BMMSC, then following up cell survival condition.Results Smad7 expressed stable in human bone marrow mesenchymal stem cells with sat-isfactory green fluorescent mark.BMMSC survived in rabbit trabecula with stable green fluorescent and effective ocular press.Con-clusion Smad7 with green fluorescent mark could be inserted into human bone marrow mesenchymal stem cells stably,and has ef-fective results in rabbit model.

Computerized system validation of clinical researches / 药学学报

Validation is a documented process that provides a high degree of assurance. The computer system does exactly and consistently what it is designed to do in a controlled manner throughout the life. The validation process begins with the system proposal/requirements definition, and continues application and maintenance until system retirement and retention of the e-records based on regulatory rules. The objective to do so is to clearly specify that each application of information technology fulfills its purpose. The computer system validation (CSV) is essential in clinical studies according to the GCP standard, meeting product's pre-determined attributes of the specifications, quality, safety and traceability. This paper describes how to perform the validation process and determine relevant stakeholders within an organization in the light of validation SOPs. Although a specific accountability in the implementation of the validation process might be outsourced, the ultimate responsibility of the CSV remains on the shoulder of the business process owner-sponsor. In order to show that the compliance of the system validation has been properly attained, it is essential to set up comprehensive validation procedures and maintain adequate documentations as well as training records. Quality of the system validation should be controlled using both QC and QA means.

Correlation analysis of chronic renal failure patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

?AlM: To investigate the clinical characteristics and influencing factors of chronic renal failure ( CRF) patients with dry eye, and to provide clinical reference.?METHODS:Sixty-one cases (122 eyes) of patients with CRF ( CRF group ) and 61 cases ( 122 eyes ) of healthy persons ( control group) were carried out on Schirmer ▏test ( S▏t ) , break-up time of tear film ( BUT ) , corneal fluorescein staining ( FL) , test results of two groups were compared and related factors of dry eye in CRF patients were analyzed.?RESULTS: The results of S▏t and BUT in CRF group were lower than that in the control group (P<0. 05). The proportion of tear secretion reduce in CRF group ( S▏t<10mm/5min) was 49. 2% ( 60/122 ), which was higher than that in the control group ( 10. 0%, 12/122 ), the difference was statistically significant ( X2 = 45. 39, P <0. 05). The percentage of instability of tear film in CRF group (BUT≤10s) was 75. 4% (92/122), which was significantly higher than that in the control group (27. 0%, 33/122) (X2=57. 1, P<0. 05). The positive rate of corneal FL was 37. 7% (46/122), which was higher than that of the control group (10. 7%, 13/122), there was a statistically significant difference (X2= 24. 34, P<0. 05).?CONCLUSlON:CRF patients with a decrease in tear film stability and tear secretion are susceptible population to dry eye, clinically should be paid attention to the treatment.