RESUMEN
OBJECTIVE: We investigated and compared the functionality of two 3D visualization software provided by a CT vendor and a third-party vendor, respectively. Using surgical anatomical measurement as baseline, we evaluated the accuracy of 3D visualization and verified their utility in computer-aided anatomical analysis. METHODS: The study cohort consisted of 50 adult cadavers fixed with the classical formaldehyde method. The computer-aided anatomical analysis was based on CT images (in DICOM format) acquired by helical scan with contrast enhancement, using a CT vendor provided 3D visualization workstation (Syngo) and a third-party 3D visualization software (Mimics) that was installed on a PC. Automated and semi-automated segmentations were utilized in the 3D visualization workstation and software, respectively. The functionality and efficiency of automated and semi-automated segmentation methods were compared. Using surgical anatomical measurement as a baseline, the accuracy of 3D visualization based on automated and semi-automated segmentations was quantitatively compared. RESULTS: In semi-automated segmentation, the Mimics 3D visualization software outperformed the Syngo 3D visualization workstation. No significant difference was observed in anatomical data measurement by the Syngo 3D visualization workstation and the Mimics 3D visualization software (P>0.05). CONCLUSIONS: Both the Syngo 3D visualization workstation provided by a CT vendor and the Mimics 3D visualization software by a third-party vendor possessed the needed functionality, efficiency and accuracy for computer-aided anatomical analysis.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Programas Informáticos , Adulto , Arterias/anatomía & histología , Automatización , Huesos/anatomía & histología , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Piel/anatomía & histología , Tomografía Computarizada por Rayos XRESUMEN
ATP-binding cassette transporter A1 (ABCA1) plays a critical role in maintaining cellular cholesterol homeostasis. The purpose of this study is to identify the molecular mechanism(s) underlying ABCA1 epigenetic modification and determine its potential impact on ABCA1 expression in macrophage-derived foam cell formation and atherosclerosis development. DNA methylation induced foam cell formation from macrophages and promoted atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. Bioinformatics analyses revealed a large CpG island (CGI) located in the promoter region of ABCA1. Histone methyltransferase enhancer of zeste homolog 2 (EZH2) downregulated ABCA1 mRNA and protein expression in THP-1 and RAW264.7 macrophage-derived foam cells. Pharmacological inhibition of DNA methyltransferase 1 (DNMT1) with 5-Aza-dC or knockdown of DNMT1 prevented the downregulation of macrophage ABCA1 expression, suggesting a role of DNA methylation in ABCA1 expression. Polycomb protein EZH2 induced DNMT1 expression and methyl-CpG-binding protein-2 (MeCP2) recruitment, and stimulated the binding of DNMT1 and MeCP2 to ABCA1 promoter, thereby promoting ABCA1 gene DNA methylation and atherosclerosis. Knockdown of DNMT1 inhibited EZH2-induced downregulation of ABCA1 in macrophages. Conversely, EZH2 overexpression stimulated DNMT1-induced ABCA1 gene promoter methylation and atherosclerosis. EZH2-induced downregulation of ABCA1 gene expression promotes foam cell formation and the development of atherosclerosis by DNA methylation of ABCA1 gene promoter.
Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , Aterosclerosis/genética , Aterosclerosis/patología , Metilación de ADN , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Regiones Promotoras Genéticas , Transportador 1 de Casete de Unión a ATP/metabolismo , Animales , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Línea Celular , Colesterol/análisis , Colesterol/metabolismo , Regulación hacia Abajo , Proteína Potenciadora del Homólogo Zeste 2/genética , Epigénesis Genética , Eliminación de Gen , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7RESUMEN
Akt2 is considered as a potential target for cancer therapy. In order to find novel Akt2 inhibitors which have different scaffolds, structure-based pharmacophore model and 3D-QSAR pharmacophore model were built and validated by different methods. Then, they were used for chemical databases virtual screening. The selected compounds were further analyzed and refined using drug-like filters and ADMET analysis. Finally, seven hits with different scaffolds were picked out for docking studies. These seven hits were predicted to have high inhibitory activity and good ADMET properties, they may act as novel leads for Akt2 inhibitors designing.
