Inactivation of tumor suppressor genes and cancer therapy : an evolutionary game theory approach

Inactivation of alleles in tumor suppressor genes (TSG) is one of the important issues resulting in evolution of cancerous cells. In this paper, the evolution of healthy, one and two missed allele cells is modeled using the concept of evolutionary game theory and replicator dynamics. The proposed model also takes into account the interaction rates of the cells as designing parameters of the system. Different combinations of the equilibrium points of the parameterized nonlinear system is studied and categorized into some cases. In each case, the interaction rates’ values are suggested in a way that the equilibrium points of the replicator dynamics are located on an appropriate region of the state space. Based on the suggested interaction rates, it is proved that the system doesn't have any undesirable interior equilibrium point as well. Therefore, the system will converge to the desirable region, where there is a scanty level of cancerous cells. In addition, the proposed conditions for interaction rates guarantee that, when a trajectory of the system reaches the boundaries, then it will stay there forever which is a desirable property since the equilibrium points have been already located on the boundaries, appropriately. The simulation results show the effectiveness of the suggestions in the elimination of the cancerous cells in different scenarios

Fabrication of Pd NPs on pectin-modified Fe3O4 NPs: A magnetically retrievable nanocatalyst for efficient C-C and C-N cross coupling reactions and an investigation of its cardiovascular protective effects

The present report represents the synthesis of a novel Pd NPs immobilized over a natural polysaccharide (pectin) coated Fe3O4 magnetic nanocomposite material (Fe3O4@pectin/Pd) for investigating the cardiovascular protective effects. The biomolecular functionalization not only stabilizes the ferrite nanoparticles from agglomeration but also provides an environment for the biogenic reduction of Pd2+ ions. This protocol is a promising breakthrough for the synthesis of a quasi-heterogeneous catalyst, a bridge between heterogeneous and homogeneous medium. The structure, morphology and physicochemical properties of the material were characterized utilizing various analytical techniques like FT-IR FE-SEM, TEM, VSM, EDX-elemental mapping, ICP, EDX and XPS. The catalyst showed excellent reactivity in C-C and C-N cross coupling reactions via Suzuki and Buchwald-Hartwig reactions respectively. An array of different biphenyls and aryl amines were then procured by reactions of various aryl halides with phenyl boronic acid or secondary amines over the catalyst affording good to excellent yields. The catalyst was easily recoverable using an external magnet and thereafter recycled for several trials with insignificant palladium leaching or loss in catalytic performance. To investigate the cardiovascular protective activities of catalyst, the MTT assay was done on Human Aortic Endothelial Cells (HAEC), Human Coronary Artery Endothelial Cells (HCAEC), and Human Pulmonary Artery Endothelial Cells (HPAEC) cell lines. Nanocatalyst-treated cell cutlers significantly (p <= 0.01) decreased the caspase-3 activity, and DNA fragmentation. It raised the cell viability and mitochondrial membrane potential in the high concentration of Mitoxantrone-treated HAEC, HCAEC, and HPAEC cells. According to the above findings, nanocatalyst can be administrated as a cardiovascular protective drug for the treatment of cardiovascular diseases after approving in the clinical trial studies in humans. (C) 2020 Published by Elsevier B.V

Palladium nanoparticles supported on fluorine-doped tin oxide as an efficient heterogeneous catalyst for Suzuki coupling and 4-nitrophenol reduction

Immobilization of palladium nanoparticles onto the fluorine-doped tin oxide (FTO) as support Pd/FTO, resulted in a highly active heterogeneous catalyst for Suzuki-Miyaura cross-coupling reactions and 4-nitrophenol reduction. The Pd/FTO catalyst has been synthesized by immobilization of palladium nanoparticles onto FTO via a simple impregnation method. ICP-MS analysis confirmed that there is 0.11 mmol/g of palladium was loaded successfully on FTO support. The crystallinity, morphologies, compositions and surface properties of Pd/FTO were fully characterized by various techniques. It was further examined for its catalytic activity and robustness in Suzuki coupling reaction with different aryl halides and solvents. The yields obtained from Suzuki coupling reactions were basically over 80%. The prepared catalyst was also tested on mild reaction such as reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). Pd/FTO catalyst exhibited high catalytic activity towards 4-NP reduction with a rate constant of 1.776 min(-1) and turnover frequency (TOF) value of 29.1 hr(-1). The findings revealed that Pd/FTO also maintained its high stability for five consecutive runs in Suzuki reactions and 4-NP reductions. The catalyst showed excellent catalytic activities by using a small amount of Pd/FTO for the Suzuki coupling reaction and 4-NP reduction

Modeling and analyzing stem-cell therapy toward cancer : evolutionary game theory perspective

Background: Immunotherapy is a recently developed method of cancer therapy, aiming to strengthen a patient’s immune system in different ways to fight cancer. One of these ways is to add stem cells into the patient’s body. Methods: The study was conducted in Kermanshah, western Iran, 2016-2017. We first modeled the interaction between cancerous and healthy cells using the concept of evolutionary game theory. System dynamics were analyzed employing replicator equations and control theory notions. We categorized the system into separate cases based on the value of the parameters. For cases in which the system converged to undesired equilibrium points, “stem-cell injection” was employed as a therapeutic suggestion. The effect of stem cells on the model was considered by reforming the replicator equations as well as adding some new parameters to the system. Results: By adjusting stem cell-related parameters, the system converged to desired equilibrium points, i.e., points with no or a scanty level of cancerous cells. In addition to the theoretical analysis, our simulation results suggested solutions were effective in eliminating cancerous cells. Conclusion: This model could be applicable to different types of cancer, so we did not restrict it to a specific type of cancer. In fact, we were seeking a flexible mathematical framework that could cover different types of cancer by adjusting the system parameters

An image processing approach for rigid gas-permeable lens base-curve identification

This research is aimed at accurate identification of base-curve in rigid gas-permeable (RGP) lens based on supervised image processing and classification of Pentacam four refractive maps in irregular astigmatism cases. Base-curve, is typically identified based on expert�s opinion of the corneal structure of the eye. Studies have applied time-consuming methods, focusing on manual and device-based techniques. For the identification of the base-curve of a lens, image analysis is proposed. As each map in the four refractive maps is of a singular view, multi-view learning is recommended to provide a single representation. To this end, an authentic dataset consisting of 247 labeled Pentacam four refractive maps was gathered in which labels were verified manually. We have proposed two novel feature extraction techniques in this domain: quantization-based radial�sectoral segmentation (QRSS) in image processing and deep convolutional neural networks. Feature fusion is applied and RGP base-curve is identified by the regression layer of a neural network. A combination of QRSS and multilayered perceptron delineates the best result, achieving a coefficient of determination of 0.9642 and satisfactory mean square error (0.0089) which is acceptable by the experts. The proposed multi-view model could improve base-curve detection accuracy, with less trial and error and patient visits in the lens fitting process. © 2020, Springer-Verlag London Ltd., part of Springer Nature

Multi-view deep learning for rigid gas permeable lens base curve fitting based on Pentacam images

Many studies in the rigid gas permeable (RGP) lens fitting field have focused on providing the best fit for patients with irregular astigmatism, a challenging issue. Despite the ease and accuracy of fitting in the current fitting methods, no studies have provided a high-pace solution with the final best fit to assist experts. This work presents a deep learning solution for identifying features in Pentacam four refractive maps and RGP base curve identification. An authentic dataset of 247 samples of Pentacam four refractive maps was gathered, providing a multi-view image of the corneal structure. Scratch-based convolutional neural network (CNN) architectures and well-known CNN architectures such as AlexNet, GoogLeNet, and ResNet have been used to extract features and transfer learning. Features are aggregated through a fusion technique. Based on a comparison of means square error (MSE) of normalized labels, the multi-view scratch-based CNN provided R-squared of 0.849, 0.846, 0.835, and 0.834 followed by GoogLeNet, comparable with current methods. Transfer learning outperforms various scratch-based CNN models, through which proper specifications some scratch-based models were able to increase coefficient of determinations. CNNs on multi-view Pentacam images have enabled fast detection of the RGP lens base curve, higher patient satisfaction, and reduced chair time. Figure not available: see fulltext.. © 2020, International Federation for Medical and Biological Engineering

Dual effects of atorvastatin on angiogenesis pathways in the differentiation of mesenchymal stem cells

Atorvastatin (ATO) can improve the transplantation efficacy of mesenchymal stem cells (MSCs) after acute myocardial infarction. The present study aimed at ATO effects on the angiogenesis-signaling pathways from MSCs' differentiation to tissue angiogenesis. MSCs were first prepared from BALB/c mouse bone marrow. MTT assay was then done for the biodegradability of MSCs with the extracellular matrix. After that, the differentiation of cells into the bone and fat tissues was confirmed by Alizarin and Oil Red O staining. The extracellular matrix was then combined with the cells to the implant. Animals were intraperitoneally treated with ATO (2 and 40 mg/kg, daily) three days before cell transplantation to one week after. Finally, the assays were carried out by electron microscopy, immunocytochemistry, ELISA, Western blot, and RT-qPCR techniques. A phase-contrast microscope confirmed the morphology of cells. The cell differentiation into bone and fat tissues was confirmed by Alizarin red staining and flow cytometry, and the cell proliferation was confirmed by MTT assay. Unlike ATO 40 mg/kg group, ATO 2 mg/kg was significantly increased the CD31, eNOS, podocalyxin, von Willibrand factor, and alpha-smooth muscle actin proteins levels compared to the control group in vitro experiment. The expression of CD31 and VEGF proteins, as angiogenesis markers, and Ki-67 protein, as a proliferation marker, was significantly higher in a low dose of ATO (2 mg/kg) than that of the control group in vivo experiment. Unlike ATO 40 mg/kg, the expression levels of ERK, AKT, NF-�B, Rho, STAT3, Ets-1, HIF-1α, and VEGF proteins and genes were significantly increased in ATO 2 mg/kg compared to the control. A low dose of ATO can be a beneficial tool in the function of MSCs and their differentiation to tissue angiogenesis. © 2021 Elsevier B.V