Background: Essential hypertension (EH) is a complex disease as a consequence of interaction between environmental factors and genetic background, but the pathogenesis of EH remains elusive. The emerging tools of network medicine offer a platform to explore a complex disease at system level. In this study, we aimed to identify the key proteins and the biological regulatory pathways involving in EH and further to explore the molecular connectivities between these pathways by the topological analysis of the Protein-protein interaction (PPI) network. Result: The extended network including one giant network consisted of 535 nodes connected via 2572 edges and two separated small networks. 27 proteins with high BC and 28 proteins with large degree have been identified. NOS3 with highest BC and Closeness centrality located in the centre of the network. The backbone network derived from high BC proteins presents a clear and visual overview which shows all important regulatory pathways for blood pressure (BP) and the crosstalk between them. Finally, the robustness of NOS3 as central protein and accuracy of backbone were validated by 287 test networks. Conclusion: Our finding suggests that blood pressure variation is orchestrated by an integrated PPI network centered on NOS3.

Novel Src/Abl tyrosine kinase inhibitor bosutinib suppresses neuroblastoma growth via inhibiting Src/Abl signaling

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy of the digestive system with increasing incidence and mortality rates. The biological roles of microRNA (miR)‑378a‑3p in tumor cells remain contested, and the mechanisms underlying the functions, energy metabolism, and cell survival mechanisms in ESCC cells are yet to be fully elucidated. In the present study, miR‑378a‑3p overexpression and negative control plasmids were transfected into ECA‑109 cells using electroporation. Western blotting was used to detect the relative expression of proteins, and flow cytometry was used to detect cell apoptosis. Subsequently, ELISA assays were performed to determine enzyme activity, and an ATP detection kit was used to measure ATP content. Dual‑luciferase reporter assays were performed to identify the target genes of miR‑378a‑3p. The results of the present study demonstrated that miR‑378a‑3p inhibited the gene expression and enzyme activities of glucose transporter protein 1 (GLUT‑1), Aldolase A (ALDOA), and pyruvate kinase M2 (PKM2), all of which are involved in the glycolytic pathway of cells. Energy metabolism was suppressed by miR‑378a‑3p by reducing ATP content, and this downregulated the expression of Bcl‑2 and Survivin. Moreover, increased miR‑378a‑3p expression promoted cell apoptosis in the early stages by increasing the expression levels and the activity of Bad and Caspase‑3, while inhibiting the expression levels of Bcl‑2 and Survivin. The results of the present study also demonstrated that GLUT‑1/ALDOA/PKM2 were target genes of miR‑378a‑3p. Notably, miR‑378a‑3p blocked energy production and promoted the apoptosis of tumor cells via the downregulation of glycolytic enzyme expression and by reducing the mitochondrial membrane potential in ESCC. Bad, Caspase‑3, Survivin, and Bcl‑2 may be associated with blocking energy production and promoting apoptosis via miR‑378a‑3p in ESCC cells.

Background.KDM6A (Lysine (K)-Specific Demethylase 6A) is the driver gene related to esophageal squamous cell carcinoma (ESCC). In order to provide more biological insights into KDM6A, in this paper, we treat PPI (protein-protein interaction) network derived from KDM6A as a conceptual framework and follow it to review its biological function.Method.We constructed a PPI network with Cytoscape software and performed clustering of network with Clust&See. Then, we evaluate the pathways, which are statistically involved in the network derived from KDM6A. Lastly, gene ontology analysis of clusters of genes in the network was conducted.Result.The network includes three clusters that consist of 74 nodes connected via 453 edges. Fifty-five pathways are statistically involved in the network and most of them are functionally related to the processes of cell cycle, gene expression, and carcinogenesis. The biology themes of clusters 1, 2, and 3 are chromatin modification, regulation of gene expression by transcription factor complex, and control of cell cycle, respectively.Conclusion.The PPI network presents a panoramic view which can facilitate for us to understand the function role of KDM6A. It is a helpful way by network approach to perform system review on a certain gene.