AIM2 inflammasome regulated by the IFN-γ/JAK2/STAT1 pathway promotes activation and pyroptosis of monocytes in Coronary Artery Disease.

BACKGROUND: Numerous studies have demonstrated that Absent in Melanoma 2 (AIM2) is upregulated in aortic plaques, especially in Vascular Smooth Muscle Cells in Coronary Artery Disease (CAD), and is related to inflammasome-induced inflammation. However, the underlying mechanism of this phenomenon and the role of AIM2 in atherosclerosis remained unclear. METHODS: This study enrolled 133 CAD patients and 123 controls. We isolated Peripheral Blood Leukocytes (PBLs) and the mRNA expression of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18) were detected by real-time quantitative PCR (qPCR). We assessed correlations between AIM2 expressions and clinical characteristics by multiple linear regression and spearman's correlation. The THP-1 cells cultured in poly(dA:dT), A151, interferon-gamma (IFN-γ), AG490, or JC2-11. And then the mRNA and protein levels of AIM2, ASC, Caspase-1, IL-1ß, IL-18, GSDMD, and STAT1 were analyzed by qPCR and Western blot analysis, respectively. The migration and adhesive capacity of THP-1 cells was assessed using an inverted microscope and an inverted fluorescence microscope, respectively. RESULTS: In this study, we found that expressions of components of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18), were all increased in PBLs of CAD patients, which indicated the inflammasome activation. AIM2 inflammasome activation further induced pyroptosis, and stimulated migration and adhesion in monocyte cell lines, which was regulated by IFN-γ probably through JAK2/STAT1 pathway. In addition, AIM2 expressions were positively correlated with systemic inflammatory indicators as an independent risk factor for CAD. CONCLUSIONS: In conclusion, increased AIM2 expression, induced by the IFN-γ/JAK2/STAT1 signal, orientates monocytes to inflammatory status or even pyroptosis through AIM2 inflammasome activation, which is involved in the development of CAD.

Virtual Neonatal Echocardiographic Training System (VNETS): An Echocardiographic Simulator for Training Basic Transthoracic Echocardiography Skills in Neonates and Infants.

There is a great need for training in pediatric echocardiography. In addition to physicians being trained in pediatric cardiology and echocardiography technologists, neonatologist, pediatric intensivists, and other health care professionals may be interested in such training. Since, there is limited opportunity of training on live patients, echocardiographic simulators may be of help. No simulator with complete range of echocardiographic modalities is available for neonates and infants. The aim of this project was to develop a mannequin-based echocardiographic simulator capable of simulating full range of pediatric 2D, color flow Doppler, spectral Doppler, and M-mode echocardiograms. A mannequin, a laptop computer, a magnetic tracking device, and a six-degree freedom (6DOF) sensor incorporated in a dummy transducer serve as the hardware platform of the simulator. We obtained six to seven 4D echocardiographic datasets in DICOM format through five acoustic windows from each infant along with a complete set of 2D video clips of color flow, Doppler, and M-mode. The 4D datasets are sliced into 3D slices using the visualization toolkit and are displayed as 2D echocardiograms through the information obtained by the 6DOF sensor. The coordinates from specific 3D slices triggers display of video clips of color flow, M-mode, and Doppler echocardiogram. Software written in C++ programming language controls the basic function of the program. The main simulator screen displays the full range of 2D echocardiograms including color flow Doppler, spectral Doppler, and M-mode from each acoustic window, whereas the side screen display the position and motion of the cutting planes through a 3D heart model. The system includes a software module to perform hemodynamic measurements from specific video clips images. Our hybrid, mannequin-based pediatric echocardiography simulator provides full range of pediatric echocardiography training experience. This simulator may help training in pediatric echocardiography for which there is a growing demand in clinical medicine.