An Open Medical Platform to Share Source Code and Various Pre-Trained Weights for Models to Use in Deep Learning Research

Deep learning-based applications have great potential to enhance the quality of medical services. The power of deep learning depends on open databases and innovation. Radiologists can act as important mediators between deep learning and medicine by simultaneously playing pioneering and gatekeeping roles. The application of deep learning technology in medicine is sometimes restricted by ethical or legal issues, including patient privacy and confidentiality, data ownership, and limitations in patient agreement. In this paper, we present an open platform, MI2RLNet, for sharing source code and various pre-trained weights for models to use in downstream tasks, including education, application, and transfer learning, to encourage deep learning research in radiology. In addition, we describe how to use this open platform in the GitHub environment. Our source code and models may contribute to further deep learning research in radiology, which may facilitate applications in medicine and healthcare, especially in medical imaging, in the near future. All code is available at https://github.com/mi2rl/MI2RLNet.

Effects of Mycophenolic Acid and Rapamycin on PDGF-induced Mesangial Cell Proliferation and Extracellular Matrix Production / 대한이식학회지

BACKGROUND: Excess proliferation and extracellular matrix (ECM) accumulation of mesenchymal cells such as vascular smooth muscle cells (VSMC) and glomerular mesangial cells cause chronic allograft nephropathy showing transplant vascular sclerosis and glomerulosclerosis. Mycophenolic acid (MPA) and rapamycin (RPM) are well known as strong inhibitors of VSMC proliferation, but their effects on the glomerular mesangial cells are not yet clearly understood. This study examined the effects of MPA or RPM on PDGF-induced proliferation and ECM accumulation in rat glomerular mesangial cells. METHODS: Mesangial cells isolated from the glomeruli of Sprague-Dawley rats were cultured with DMEM containing 20% fetal bovine serum. Growth arrested and synchronized cells were administered with test drugs (MPA10 nM~10micrometer, RPM 0.1 nM~1micrometer) before the addition of PDGF 10 ng/mL. Cell proliferation was assessed by [3H]thymidine incorporation, collagen by [3H]proline incorporation, and fibronectin, ERK, and p38 MAPK by Western blot analysis. RESULTS: PDGF increased mesangial cell proliferation by 4.64-fold. Compared to stimulated control, MPA above 500 nM and RPM above 10 nM showed a significant inhibitory effect in a dose- dependent manner. The IC50 of MPA and RPM against PDGF-induced mesangial cell proliferation were around 500 nM and 100 nM, respectively. The collagen synthesis was also inhibited by MPA and RPM, but the fibronectin secretion was inhibited by MPA alone. The proliferation of mesangial cell correlated with activation of ERK and p38 MAPK. MPA, but not RPM, inhibited ERK and p38 MAPK activation. CONCLUSIONS: This study demonstrated that MPA and RPM significantly inhibited PDGF-induced proliferation and ECM production in rat glomerular mesangial cells. The inhibitory effects of MPA, but not RPM, are correlated with ERK and p38 MAPK.

Effect of Mycophenolic Acid and Rapamycin on the Proliferation and Collagen Synthesis of the Vascular Smooth Muscle Cell of Rat / 대한이식학회지

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix protein accumulation play important roles in chronic allograft vasculopathy. Mycophenolic acid (MPA) or rapamycin (RPM) was reported to inhibit VSMC proliferation in vitro and in vivo. However, effects of MPA or RPM on collagen synthesis of VSMCs, and the combined effects of MPA and RPM treatment on VSMC proliferation are not yet reported. METHODS: VSMCs isolated from the aorta of Sprague-Dawley rats were cultured with EMEM supplemented with 10% fetal bovine serum and insulin/ transferrin. Growth arrested and synchronized cells were pretreated with test drugs (alone or combination of various concentrations of MPA and RPM) 1 hour before the addition of 10 ng/ml PDGF. Cell proliferation was assessed by [H3]- thymidine incorporation, and collagen synthesis by [H3]- proline incorporation. RESULTS: PDGF increased cell proliferation and collagen synthesis by 3.4- and 2.1-fold, respectively, compared to control. MPA at above 100 nM or RPM at above 1 nM effectively inhibited PDGF-induced cell proliferation and collagen synthesis. The IC50 of MPA or RPM against PDGF-stimulated cell proliferation was between 100 nM and 1 micrometer or between 1 nM and 10 nM, respectively. The combination of MPA and RPM showed additive effects on PDGF-induced VSMC proliferation in a multiple regression analysis (R2=0.508, P<0.05). CONCLUSION: The present study demonstrated that MPA or RPM significantly inhibited PDGF-induced VSMC proliferation. These independent phenomena were well maintained as suggested by additive effects after combination treatment. PDGF-induced collagen synthesis was also effectively suppressed by the treatment of MPA or RPM.

Effect of Mycophenolic Acid and Rapamycin on the Proliferation of Glomerular Mesangial Cell of Rat

PURPOSE: Excess proliferation of mesenchymal cells such as vascular smooth muscle cells and glomerular mesangial cells, cause transplant vascular sclerosis and glomerulosclerosis, which are typical pathological lesions of chronic allograft dysfunction. Mycophenoic acid (MPA) and rapamycin (RPM) were recently reported to have strong anti-proliferative potentials toward vascular smooth muscle cells. However, the potential effects of these drugs, either alone or in combination, on glomerular mesangial cells, remain to be reported. METHODS: Primary cultured mesangial cells, from Sprague-Dawley rats, were isolated, and stimulated with 10ng/ml of PDGF. The test drugs MPA and RPM were administered at various concentrations, either alone or in combination, 15 minutes before the addition of the PDGF. The cell proliferation was assessed by [3H]-thymidine incorporation. RESULTS: The PDGF effectively stimulated the proliferation of the mesangial cells. The MPA inhibited the proliferation in a dose-dependent manner. In comparison to the stimulated control, the MPA (above 500 nM) showed a significant inhibitory effect. The IC50 of the MPA, against PDGF-stimulated mesangial cell proliferation, was between 500 nM and 1microM. The RPM, at 10 nM, showed a significant inhibitory effect. In a linear regression analysis, the RPM was supposed to suppress the mesangial proliferation in a dose-dependent manner (P<0.05). The pattern of inhibition for the MPA and RPM combination was very similar to that of either the MPA or the RPM alone. Both the MPA and RPM were shown to independently suppress the mesangial proliferation from a multiple regression analysis (R2=0.415, P<0.001). CONCLUSION: We demonstrated that MPA and RPM significantly inhibited the proliferation of glomerular mesangial cells, and that these effects were well maintained when used in combination. Our data indicate that both MPA and RPM have unique potentials in preventing the development of transplant mesangial proliferation in renal transplant recipients.

Effects of Mycophenolic Acid, Rapamycin, and Carvedilol on the PDGF-induced Fibronectin Secretion by Rat Vascular Smooth Muscle Cells: Implication of MAP Kinase / 대한이식학회지

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and extra-cellular matrix (ECM) protein accumulation play important roles in transplant vascular sclerosis and re- stenosis after balloon vascular injury. Mycophenolic acid (MPA), rapamycin (RPM), and carvedilol (CA) were proven to inhibit the proliferation of VSMC. Fibronectin is a multifunctional ECM protein and induces tissue fibrosis. Since mitogen-activated protein kinases (MAPK) are upstream signaling molecules of VSMC proliferation and fibronectin production, this study examined the effects of MPA, RPM, and CA on the fibronectin secretion and MAPK activation in rat VSMC stimulated by platelet derived growth factor (PDGF). METHODS: VSMC was isolated from the aorta of male Sprague-Dawley rat, weighing 200-250 g and cultured with EMEM containing 10% fetal bovine serum and insulin/transferrin supplement. Near confluent VSMC were incubated with serum-free media for 48 hours to arrest and synchronize the cell growth. Test drugs were administered 15 minutes before the addition of PDGF 10 ng/mL. Cell proliferation, fibronectin secretion, and MAPK activation in VSMCs were measured by Western blot analysis. RESULTS: PDGF induced cell proliferation, fibronectin secretion, and extracellular- regulatary protein kinase 1/2 (ERK 1/2) and p38 MAPK activation by 1.7-, 1.5-, 3.3-, 3.9-fold, respectively, compared to control. MPA (>1 microM), CA (>100 nM), PD98059 (>30 microM), and p38 MAPK inhibitor (>10 nM) effectively inhibited PDGF-induced proliferation and fibronectin secretion. RPM, up to 100 nM, effectively inhibited cell proliferation, but did not inhibit fibronectin secretion. MPA and CA, but not RPM, inhibited PDGF-induced ERK 1/2 and p38 MAPK activation. CONCLUSION: The present study demonstrates that MPA and CA inhibit both cell proliferation and fibronectin secretion in rat VSMC stimulated by PDGF. Inhibition of both ERK 1/2 and p38 molecules are significantly associated with these events. Even though, it has a significant anti-proliferative effect on the rat VSMC, RPM neither affected the phosphorylation of ERK 1/2 and p38 nor secretion of fibronectin. These data suggest that ERK 1/2- and p38 MAPK-independent, more proximal pathway may exist for PDGF-induced proliferation of rat VSMC.

Effect of Carvedilol on Human Vascular Smooth Muscle Cell Proliferation and Its Signal Transduction

PURPOSE: Vascular smooth muscle cells (VSMCs) migration and proliferation play important roles in transplant vascular sclerosis and restenosis after balloon vascular injury. The anti-proliferative and anti- migratory effects of carvedilol (CA), a unique alpha- and beta-blocking anti-hypertensive drug, on the VSMCs were confirmed previously. Since reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPK) family play important roles in proliferation of VSMCs, the present study examined the effects of CA on intracellular ROS generation, activation of ERK1/2 and p38 MAPK, and proliferation of VSMCs cultured under platelet derived growth factor (PDGF). METHODS: Human VSMCs obtained from ATCC were cultured with RPMI-1640 containing 10% fetal bovine serum. Near confluent VSMCs were incubated with serum-free media for 48 hours to arrest and synchronize the cell growth. CA was administered 1 hour before the addition of PDGF. 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein (DCF)-sensitive intracellular ROS was detected by FACS. Activations of ERK1/2 and p38 MAPK were measured by Western blot analysis. Proliferation of VSMCs was assessed by [3H]-thymidine incorporation. RESULTS: PDGF at 10 ng/ml, which induced human VSMCs proliferation, rapidly increased intracellular ROS by 1.6-fold (P<0.01), ERK1/2 activation by 2.1-fold (P<0.01), and p38 MAPK activation by 1.9-fold (P<0.01), respectively, as compared to the control. CA 1 and 10muM effectively inhibited PDGF-induced human VSMCs proliferation. CA also effectively inhibited PDGF-induced intracellular ROS generation as well as ERK1/2 and P38 MAPK activation. CONCLUSION: The present study suggests that CA inhibits PDGF-induced human VSMCs proliferation, possibly by inhibiting intracellular ROS generation and activation of ERK1/2 and p38 MAPK.