The nitric oxide donor drugs have the functions of anti-hyperplasia, inhibiting platelet adhesion and aggregation, regulating immune response, etc. It suggests that these drugs play important roles in therapy of cardiovascular diseases, male impotence and pregnancy-induced hypertension syndrome.

ObjectiveTo study the inhibiting effects on the invasion and metastasis of melanoma by CXCR4 gene silence in nude mice.MethodsThe CXCR4 specific recombinant plasmid vector was constructed and transfected into the cultured MV3 cell line with lipofectamine.The models of subcutaneous melanoma in nude mice were established with MV3 cells.The nude mouse model of lung metastasis was established by injection of MV3 cells into the tail vein.The animals were sacrificed at 8weeks after the melanoma cells injection.CXCR4-shRNA plasmid vectors were discontinuously injected directly into the established tumor and vein.The changes of weight and size of the tumors and the mice body weight during the therapy were calculated respectively.Histological observation was performed to evaluate the presence and number of metastatic tumors.ResultsThe subcutaneous melanoma tumors in nude mice were established successfully.The growth of tumors in the CXCR4-shRNA injected nude mice was inhibitted obviously through tumor growth curve. There were significant differences between negative shRNA control nude mice and blank control nude mice (P＜0.01).Melanoma cells with CXCR4 shRNA permanent transfection had a much lower lung and brain and liver metastatic potential in nude mice than control cells and mock control cells in vivo.ConclusionsCXCR4 gene silencing mediated by shRNA significantly suppresses the growth of MV3 cell in vitro.Silencing of CXCR4 mediated by shRNA can also effectively decrease the metastatic potential of lung and liver and brain.

During the central nervous system (CNS) development, the interactions between intrinsic genes and extrinsic environment ensure that each neuronal developmental stage (eg. neuronal proliferation, differentiation, migration, axon extension, dendritogenesis and formation of functional synapses) occurs in the proper timing and sequence. The successful coordination requires that numerous groups of genes are exquisitely regulated in a spatiotemporal manner by various regulatory mechanisms, including sequence-specific DNA-binding proteins, histone modifications, DNA methylation, chromatin remodeling, and microRNAs (miRNAs). By targeting chromatin structure, transcription and translation processes, these mechanisms form a regulatory network to accomplish the fine regulation of gene expression in response to environmental stimuli at different developmental stages. Dysregulation of the gene expression during neuronal development has been shown to be implicated in a number of neurodevelopmental disorders, such as autism spectrum disorders (ASD), Rett syndrome (RTT), Fragile-X syndrome (FXS) and other genetic diseases. The further understanding of the regulation of gene expression during neuronal development may provide new approaches for the diagnosis and treatment of these disorders.
Cell Differentiation ; Child Development Disorders, Pervasive ; genetics ; DNA Methylation ; DNA-Binding Proteins ; Gene Expression Regulation, Developmental ; Heredodegenerative Disorders, Nervous System ; genetics ; Humans ; MicroRNAs ; Neurons ; pathology ; Synapses