Search results for: brain cells
3541 Neural Changes Associated with Successful Antidepressant Treatment in Adolescents with Major Depressive Disorder
Authors: Dung V. H. Pham, Kathryn Cullen
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Introduction: 40% of adolescents with major depression (MDD) are unresponsive to 1st line antidepressant treatment. The neural mechanism underlying treatment-responsive and treatment-resistant depression in adolescent are unclear. Amygdala is important for emotion processing and has been implicated in mood disorders. Past research has shown abnormal amygdala connectivity in adolescents with MDD. This research study changes in amygdala resting-state functional connectivity to find neural correlates of successful antidepressant treatment. Methods: Thirteen adolescents aged 12-19 underwent rfMRI before and after 8-week antidepressant treatment and completed BDI-II at each scan. A whole-brain approach, using anatomically defined amygdala ROIs (1) identified brain regions that are highly synchronous with the amygdala, (2) correlated neural changes with changes in overall depression and specific symptom clusters within depression. Results: Some neural correlates were common across domains: (1) decreased amygdala RSFC with the default mode network (posterior cingulate, precuneus) is associated with improvement in overall depression and many symptom clusters, (2) increased amygdala RSFC with fusiform gyrus is associated with symptom improvement across many symptom clusters. We also found unique neural changes associated with symptom improvement in each symptom cluster. Conclusion: This is the first preliminary study that looks at neural correlates of antidepressant treatment response to overall depression as well as different clusters of symptoms of depression. The finding suggests both overlapping and distinct neural mechanisms underlying improvement in each symptom clusters within depression. Some brain regions found are also implicated in MDD among adults in previous literature.Keywords: depression, adolescents, fMRI, antidepressants
Procedia PDF Downloads 2533540 Optimized Brain Computer Interface System for Unspoken Speech Recognition: Role of Wernicke Area
Authors: Nassib Abdallah, Pierre Chauvet, Abd El Salam Hajjar, Bassam Daya
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In this paper, we propose an optimized brain computer interface (BCI) system for unspoken speech recognition, based on the fact that the constructions of unspoken words rely strongly on the Wernicke area, situated in the temporal lobe. Our BCI system has four modules: (i) the EEG Acquisition module based on a non-invasive headset with 14 electrodes; (ii) the Preprocessing module to remove noise and artifacts, using the Common Average Reference method; (iii) the Features Extraction module, using Wavelet Packet Transform (WPT); (iv) the Classification module based on a one-hidden layer artificial neural network. The present study consists of comparing the recognition accuracy of 5 Arabic words, when using all the headset electrodes or only the 4 electrodes situated near the Wernicke area, as well as the selection effect of the subbands produced by the WPT module. After applying the articial neural network on the produced database, we obtain, on the test dataset, an accuracy of 83.4% with all the electrodes and all the subbands of 8 levels of the WPT decomposition. However, by using only the 4 electrodes near Wernicke Area and the 6 middle subbands of the WPT, we obtain a high reduction of the dataset size, equal to approximately 19% of the total dataset, with 67.5% of accuracy rate. This reduction appears particularly important to improve the design of a low cost and simple to use BCI, trained for several words.Keywords: brain-computer interface, speech recognition, artificial neural network, electroencephalography, EEG, wernicke area
Procedia PDF Downloads 2723539 Analysis of EEG Signals Using Wavelet Entropy and Approximate Entropy: A Case Study on Depression Patients
Authors: Subha D. Puthankattil, Paul K. Joseph
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Analyzing brain signals of the patients suffering from the state of depression may lead to interesting observations in the signal parameters that is quite different from a normal control. The present study adopts two different methods: Time frequency domain and nonlinear method for the analysis of EEG signals acquired from depression patients and age and sex matched normal controls. The time frequency domain analysis is realized using wavelet entropy and approximate entropy is employed for the nonlinear method of analysis. The ability of the signal processing technique and the nonlinear method in differentiating the physiological aspects of the brain state are revealed using Wavelet entropy and Approximate entropy.Keywords: EEG, depression, wavelet entropy, approximate entropy, relative wavelet energy, multiresolution decomposition
Procedia PDF Downloads 3333538 A Paradigm for Characterization and Checking of a Human Noise Behavior
Authors: Himanshu Dehra
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This paper presents a paradigm for characterization and checking of human noise behavior. The definitions of ‘Noise’ and ‘Noise Behavior’ are devised. The concept of characterization and examining of Noise Behavior is obtained from the proposed paradigm of Psychoacoustics. The measurement of human noise behavior is discussed through definitions of noise sources and noise measurements. The noise sources, noise measurement equations and noise filters are further illustrated through examples. The theory and significance of solar energy acoustics is presented for life and its activities. Human comfort and health are correlated with human brain through physiological responses and noise protection. Examples of heat stress, intense heat, sweating and evaporation are also enumerated.Keywords: human brain, noise behavior, noise characterization, noise filters, physiological responses, psychoacoustics
Procedia PDF Downloads 5103537 The Development of Solar Cells to Maximize the Utilization of Solar Energy in Al-Baha Area
Authors: Mohammed Ahmed Alghamdi, Hazem Mahmoud Ali Darwish, Mostafa Mohamed Abdelraheem
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Transparent conducting oxides (TCOs) possess low resistivity, exhibit good adherence to many substrates, and have good transmission characteristics from the visible to near-infrared wavelengths, which make it useful for various applications. Thin films of transparent conducting oxide (TCO’s) have received much attention because of their wide applications in the field of optoelectronic devices. Advancement of transparent conducting oxides TCO’s may not only lie within the improvement of existing materials in use, but also the development of novel materials. Solar cells are devices, which convert solar energy into electricity, either directly via the photovoltaic effect, or indirectly by first converting the solar energy to heat or chemical energy. Solar power has attracted attention of late as the most advanced of the alternative energy resources. The project aims to access the solar energy in Al-Baha region by search for materials (transparent-conductive oxides (TCO's)) to use in solar cells with highly transparent to the solar spectrum, have low electrical resistivity, be stable under H-plasma, and have a suitable structure in particular for a-Si solar cells. As the PV surface is exposed to the sunlight, the module temperature increases. High ambient temperatures along with long sunlight exposure time increases the temperature impact on PV cells efficiency. Since Al-Baha area is characterized by an atmosphere and pressure different from their counterparts in Saudi Arabia due to the height above sea level, hence it is appropriate to do studies to improve the efficiency of solar cells under these conditions. In this work, some ion change materials will be deposited using either sputtering/ or electron beam evaporation techniques. The optical properties of the synthesized materials will be studied in details for solar cell application. As we will study the effect of some dyes on the optical properties of the prepared films. The efficiency and other parameters of solar cell will be determined.Keywords: thin films, solar cell, optical properties, electrical properties
Procedia PDF Downloads 4703536 Neuroplasticity in Language Acquisition in English as Foreign Language Classrooms
Authors: Sabitha Rahim
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In the context of teaching vocabulary of English as Foreign Language (EFL), the confluence of memory and retention is one of the most significant factors in students' language acquisition. The progress of students engaged in foreign language acquisition is often stymied by vocabulary attrition, which leads to learners' lack of confidence and motivation. However, among other factors, little research has investigated the importance of neuroplasticity in Foreign Language acquisition and how underused neural pathways lead to the loss of plasticity, thereby affecting the learners’ vocabulary retention and motivation. This research explored the effect of enhancing vocabulary acquisition of EFL students in the Foundation Year at King Abdulaziz University through various methods and neuroplasticity exercises that reinforced their attention, motivation, and engagement. It analyzed the results to determine if stimulating the brain of EFL learners by various physical and mental activities led to the improvement in short and long term memory in vocabulary retention. The main data collection methods were student surveys, assessment records of teachers, student achievement test results, and students' follow-up interviews. A key implication of this research is for the institutions to consider having multiple varieties of student activities promoting brain plasticity within the classrooms as an effective tool for foreign language acquisition. Building awareness among the faculty and adapting the curriculum to include activities that promote brain plasticity ensures an enhanced learning environment and effective language acquisition in EFL classrooms.Keywords: language acquisition, neural paths, neuroplasticity, vocabulary attrition
Procedia PDF Downloads 1763535 Preparation of Polymer-Stabilized Magnetic Iron Oxide as Selective Drug Nanocarriers to Human Acute Myeloid Leukemia
Authors: Kheireddine El-Boubbou
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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC50 values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy
Procedia PDF Downloads 2303534 Optimal Feedback Linearization Control of PEM Fuel Cell
Authors: E. Shahsavari, R. Ghasemi, A. Akramizadeh
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This paper presents a new method to design nonlinear feedback linearization controller for polymer electrolyte membrane fuel cells (PEMFCs). A nonlinear controller is designed based on nonlinear model to prolong the stack life of PEM fuel cells. Since it is known that large deviations between hydrogen and oxygen partial pressures can cause severe membrane damage in the fuel cell, feedback linearization is applied to the PEM fuel cell system so that the deviation can be kept as small as possible during disturbances or load variations. To obtain an accurate feedback linearization controller, tuning the linear parameters are always important. So in proposed study NSGA_II method was used to tune the designed controller in aim to decrease the controller tracking error. The simulation result showed that the proposed method tuned the controller efficiently.Keywords: nonlinear dynamic model, polymer electrolyte membrane fuel cells, feedback linearization, optimal control, NSGA_II
Procedia PDF Downloads 5183533 An Experimental Investigation of the Cognitive Noise Influence on the Bistable Visual Perception
Authors: Alexander E. Hramov, Vadim V. Grubov, Alexey A. Koronovskii, Maria K. Kurovskaуa, Anastasija E. Runnova
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The perception of visual signals in the brain was among the first issues discussed in terms of multistability which has been introduced to provide mechanisms for information processing in biological neural systems. In this work the influence of the cognitive noise on the visual perception of multistable pictures has been investigated. The study includes an experiment with the bistable Necker cube illusion and the theoretical background explaining the obtained experimental results. In our experiments Necker cubes with different wireframe contrast were demonstrated repeatedly to different people and the probability of the choice of one of the cubes projection was calculated for each picture. The Necker cube was placed at the middle of a computer screen as black lines on a white background. The contrast of the three middle lines centered in the left middle corner was used as one of the control parameter. Between two successive demonstrations of Necker cubes another picture was shown to distract attention and to make a perception of next Necker cube more independent from the previous one. Eleven subjects, male and female, of the ages 20 through 45 were studied. The choice of the Necker cube projection was detected with the Electroencephalograph-recorder Encephalan-EEGR-19/26, Medicom MTD. To treat the experimental results we carried out theoretical consideration using the simplest double-well potential model with the presence of noise that led to the Fokker-Planck equation for the probability density of the stochastic process. At the first time an analytical solution for the probability of the selection of one of the Necker cube projection for different values of wireframe contrast have been obtained. Furthermore, having used the results of the experimental measurements with the help of the method of least squares we have calculated the value of the parameter corresponding to the cognitive noise of the person being studied. The range of cognitive noise parameter values for studied subjects turned to be [0.08; 0.55]. It should be noted, that experimental results have a good reproducibility, the same person being studied repeatedly another day produces very similar data with very close levels of cognitive noise. We found an excellent agreement between analytically deduced probability and the results obtained in the experiment. A good qualitative agreement between theoretical and experimental results indicates that even such a simple model allows simulating brain cognitive dynamics and estimating important cognitive characteristic of the brain, such as brain noise.Keywords: bistability, brain, noise, perception, stochastic processes
Procedia PDF Downloads 4453532 In Vitro and in Vivo Evaluation of Nano Collagen Molecules to Enhance Mesenchymal Stem Cells Differentiate into Insulin Producing Cells
Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo
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The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p < 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p < 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p < 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes
Procedia PDF Downloads 4103531 Quality Assurance Comparison of Map Check 2, Epid, and Gafchromic® EBT3 Film for IMRT Treatment Planning
Authors: Khalid Iqbal, Saima Altaf, M. Akram, Muhammad Abdur Rafaye, Saeed Ahmad Buzdar
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Objective: Verification of patient-specific intensity modulated radiation therapy (IMRT) plans using different 2-D detectors has become increasingly popular due to their ease of use and immediate readout of the results. The purpose of this study was to test and compare various 2-D detectors for dosimetric quality assurance (QA) of intensity-modulated radiotherapy (IMRT) with the vision to find alternative QA methods. Material and Methods: Twenty IMRT patients (12 of brain and 8 of the prostate) were planned on Eclipse treatment planning system using Varian Clinac DHX on both energies 6MV and 15MV. Verification plans of all such patients were also made and delivered to Map check2, EPID (Electronic portal imaging device) and Gafchromic EBT3. Gamma index analyses were performed using different criteria to evaluate and compare the dosimetric results. Results: Statistical analysis shows the passing rate of 99.55%, 97.23% and 92.9% for 6MV and 99.53%, 98.3% and 94.85% for 15 MV energy using a criteria of ±5% of 3mm, ±3% of 3mm and ±3% of 2mm respectively for brain, whereas using ±5% of 3mm and ±3% of 3mm gamma evaluation criteria, the passing rate is 94.55% and 90.45% for 6MV and 95.25%9 and 95% for 15 MV energy for the case of prostate using EBT3 film. Map check 2 results shows the passing rates of 98.17%, 97.68% and 86.78% for 6MV energy and 94.87%,97.46% and 88.31% for 15 MV energy respectively for brain using a criteria of ±5% of 3mm, ±3% of 3mm and ±3% of 2mm, whereas using ±5% of 3mm and ±3% of 3mm gamma evaluation criteria gives the passing rate of 97.7% and 96.4% for 6MV and 98.75%9 and 98.05% for 15 MV energy for the case of prostate. EPID 6 MV and gamma analysis shows the passing rate of 99.56%, 98.63% and 98.4% for the brain, 100% and 99.9% for prostate using the same criteria as for map check 2 and EBT 3 film. Conclusion: The results demonstrate excellent passing rates were obtained for all dosimeter when compared with the planar dose distributions for 6 MV IMRT fields as well as for 15 MV. EPID results are better than EBT3 films and map check 2 because it is likely that part of this difference is real, and part is due to manhandling and different treatment set up verification which contributes dose distribution difference. Overall all three dosimeter exhibits results within limits according to AAPM report.120.Keywords: gafchromic EBT3, radiochromic film dosimetry, IMRT verification, EPID
Procedia PDF Downloads 4213530 The Characteristics of Porcine Immune Synapse via Flow Cytometry and Transmission Electron Microscope
Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung
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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor
Procedia PDF Downloads 1273529 Acoustic Blood Plasmapheresis in Polymeric Resonators
Authors: Itziar Gonzalez, Pilar Carreras, Alberto Pinto, Roque Ruben Andres
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Acoustophoretic separation of plasma from blood is based on a collection process of the blood cells, driven by an acoustic radiation force. The number of cells, their concentration, and the sample hydrodynamics are involved in these processes. However, their influence on the acoustic blood response has not yet been reported in the literature. Addressing it, this paper presents an experimental study of blood samples exposed to ultrasonic standing waves at different hematocrit levels and hydrodynamic conditions. The experiments were performed in a glass capillary (700µm-square cross section) actuated by a piezoelectric ceramic at 1MHz, hosting 2D orthogonal half-wavelength resonances transverse to the channel length, with a single-pressure-node along its central axis where cells collected driven by the acoustic radiation force. Four blood dilutions in PBS of 1:20, 1:10, 1:5, and 1:2 were tested at eight flow rate conditions Q=0:120µL/min. The 1:5 dilution (H=9%) demonstrated to be optimal for the plasmapheresis at any of the flow rates analyzed, requiring the shortest times to achieve plasma free of cells. The study opens new possibilities to optimize processes of plasmapheresis processes by ultrasounds at different hematocrit conditions in future personalized diagnoses/treatments involving blood samples.Keywords: ultrasounds, microfluidics, flow rate, acoustophoresis, polymeric resonators
Procedia PDF Downloads 1363528 Surface Adjustments for Endothelialization of Decellularized Porcine Pericardium
Authors: M. Markova, E. Filova, O. Kaplan, R. Matejka, L. Bacakova
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The porcine pericardium is used as a material for cardiac and aortic valves substitutes. Current biological aortic heart valve prosthesis have a limited lifetime period because they undergo degeneration. In order to make them more biocompatible and prolong their lifetime it is necessary to reseed the decellularized prostheses with endothelial cells and with valve interstitial cells. The endothelialization of the prosthesis-surface may be supported by suitable chemical surface modification of the prosthesis. The aim of this study is to prepare bioactive fibrin layers which would both support endothelialization of porcine pericardium and enhance differentiation and maturation of the endothelial cells seeded. As a material for surface adjustments we used layers of fibrin with/without heparin and some of them with adsorbed or chemically bound FGF2, VEGF or their combination. Fibrin assemblies were prepared in 24-well cell culture plate and were seeded with HSVEC (Human Saphenous Vein Endothelial Cells) at a density of 20,000 cells per well in EGM-2 medium with 0.5% FS and without heparin, without FGF2 and without VEGF; medium was supplemented with aprotinin (200 U/mL). As a control, surface polystyrene (PS) was used. Fibrin was also used as homogeneous impregnation of the decellularized porcine pericardium throughout the scaffolds. Morphology, density, and viability of the seeded endothelial cells were observed from micrographs after staining the samples by LIVE/DEAD cytotoxicity/viability assay kit on the days 1, 3, and 7. Endothelial cells were immunocytochemically stained for proteins involved in cell adhesion, i.e. alphaV integrin, vinculin, and VE-cadherin, markers of endothelial cells differentiation and maturation, i.e. von Willebrand factor and CD31, and for extracellular matrix proteins typically produced by endothelial cells, i.e. type IV collagen and laminin. The staining intensities were subsequently quantified using a software. HSVEC cells grew on each of the prepared surfaces better than on control surface. They reached confluency. The highest cell densities were obtained on the surface of fibrin with heparin and both grow factors used together. Intensity of alphaV integrins staining was highest on samples with remained fibrin layer, i.e. on layers with lower cell densities, i.e. on fibrin without heparin. Vinculin staining was apparent, but was rather diffuse, on fibrin with both FGF2 and VEGF and on control PS. Endothelial cells on all samples were positively stained for von Willebrand factor and CD31. VE-cadherin receptors clusters were best developed on fibrin with heparin and growth factors. Significantly stronger staining of type IV collagen was observed on fibrin with heparin and both growth factors. Endothelial cells on all samples produced laminin-1. Decellularized pericardium was homogeneously filled with fibrin structures. These fibrin-modified pericardium samples will be further seeded with cells and cultured in a bioreactor. Fibrin layers with/without heparin and with adsorbed or chemically bound FGF2, VEGF or their combination are good surfaces for endothelialization of cardiovascular prostheses or porcine pericardium based heart valves. Supported by the Ministry of Health, grants No15-29153A and 15-32497A, and the Grant Agency of the Czech Republic, project No. P108/12/G108.Keywords: aortic valves prosthesis, FGF2, heparin, HSVEC cells, VEGF
Procedia PDF Downloads 2663527 Angiogenesis and Blood Flow: The Role of Blood Flow in Proliferation and Migration of Endothelial Cells
Authors: Hossein Bazmara, Kaamran Raahemifar, Mostafa Sefidgar, Madjid Soltani
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Angiogenesis is formation of new blood vessels from existing vessels. Due to flow of blood in vessels, during angiogenesis, blood flow plays an important role in regulating the angiogenesis process. Multiple mathematical models of angiogenesis have been proposed to simulate the formation of the complicated network of capillaries around a tumor. In this work, a multi-scale model of angiogenesis is developed to show the effect of blood flow on capillaries and network formation. This model spans multiple temporal and spatial scales, i.e. intracellular (molecular), cellular, and extracellular (tissue) scales. In intracellular or molecular scale, the signaling cascade of endothelial cells is obtained. Two main stages in development of a vessel are considered. In the first stage, single sprouts are extended toward the tumor. In this stage, the main regulator of endothelial cells behavior is the signals from extracellular matrix. After anastomosis and formation of closed loops, blood flow starts in the capillaries. In this stage, blood flow induced signals regulate endothelial cells behaviors. In cellular scale, growth and migration of endothelial cells is modeled with a discrete lattice Monte Carlo method called cellular Pott's model (CPM). In extracellular (tissue) scale, diffusion of tumor angiogenic factors in the extracellular matrix, formation of closed loops (anastomosis), and shear stress induced by blood flow is considered. The model is able to simulate the formation of a closed loop and its extension. The results are validated against experimental data. The results show that, without blood flow, the capillaries are not able to maintain their integrity.Keywords: angiogenesis, endothelial cells, multi-scale model, cellular Pott's model, signaling cascade
Procedia PDF Downloads 4253526 Cratoxy Formosum (Jack) Dyer Leaf Extract-Induced Human Breast and Liver Cancer Cells Death
Authors: Benjaporn Buranrat, Nootchanat Mairuae
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Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death
Procedia PDF Downloads 2113525 Correlation of Leptin with Clinico-Pathological Features of Breast Cancer
Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan
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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.Keywords: breast cancer, expression, leptin, leptin receptors
Procedia PDF Downloads 1403524 An in silico Approach for Exploring the Intercellular Communication in Cancer Cells
Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez
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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation
Procedia PDF Downloads 2513523 miR-200c as a Biomarker for 5-FU Chemosensitivity in Colorectal Cancer
Authors: Rezvan Najafi, Korosh Heydari, Massoud Saidijam
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5-FU is a chemotherapeutic agent that has been used in colorectal cancer (CRC) treatment. However, it is usually associated with the acquired resistance, which decreases the therapeutic effects of 5-FU. miR-200c is involved in chemotherapeutic drug resistance, but its mechanism is not fully understood. In this study, the effect of inhibition of miR-200c in sensitivity of HCT-116 CRC cells to 5-FU was evaluated. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was evaluated using quantitative real- time PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were analyzed by western blotting. Annexin V and propidium iodide staining assay were applied for apoptosis detection. The caspase-3 activation was evaluated by an enzymatic assay. The results showed LNA-anti-miR-200c inhibited the expression of PTEN and E-cadherin protein, apoptosis and activation of caspase 3 compared with control cells. In conclusion, these results suggest that miR-200c as a prognostic marker can overcome to 5-FU chemoresistance in CRC.Keywords: colorectal cancer, miR-200c, 5-FU resistance, E-cadherin, PTEN
Procedia PDF Downloads 1663522 Brain-Computer Interface Based Real-Time Control of Fixed Wing and Multi-Rotor Unmanned Aerial Vehicles
Authors: Ravi Vishwanath, Saumya Kumaar, S. N. Omkar
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Brain-computer interfacing (BCI) is a technology that is almost four decades old, and it was developed solely for the purpose of developing and enhancing the impact of neuroprosthetics. However, in the recent times, with the commercialization of non-invasive electroencephalogram (EEG) headsets, the technology has seen a wide variety of applications like home automation, wheelchair control, vehicle steering, etc. One of the latest developed applications is the mind-controlled quadrotor unmanned aerial vehicle. These applications, however, do not require a very high-speed response and give satisfactory results when standard classification methods like Support Vector Machine (SVM) and Multi-Layer Perceptron (MLPC). Issues are faced when there is a requirement for high-speed control in the case of fixed-wing unmanned aerial vehicles where such methods are rendered unreliable due to the low speed of classification. Such an application requires the system to classify data at high speeds in order to retain the controllability of the vehicle. This paper proposes a novel method of classification which uses a combination of Common Spatial Paradigm and Linear Discriminant Analysis that provides an improved classification accuracy in real time. A non-linear SVM based classification technique has also been discussed. Further, this paper discusses the implementation of the proposed method on a fixed-wing and VTOL unmanned aerial vehicles.Keywords: brain-computer interface, classification, machine learning, unmanned aerial vehicles
Procedia PDF Downloads 2843521 Production of Hydroxy Marilone C as a Bioactive Compound from Streptomyces badius
Authors: Osama H. Elsayed, Mohsen M. S. Asker, Mahmoud A. Swelim, Ibrahim H. Abbas, Aziza I. Attwa, Mohamed E. El Awady
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Hydroxy marilone C is a bioactive metabolite was produced from the culture broth of Streptomyces badius isolated from Egyptian soil. hydroxy marilone C was purified and fractionated by silica gel column with a gradient mobile phase dicloromethane (DCM) : Methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many instruments as Infrared (IR), nuclear magnetic resonance (NMR), Mass spectroscopy (MS) and UV spectroscopy to the elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549) and human breast adenocarcinoma cell line (MCF-7) and antiviral activities; showed that the maximum antioxidant activity was 78.8 % at 3000 µg/ml after 90 min. and the IC50 value against DPPH radical found about 1500 µg/ml after 60 min. By Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells were 443 µg/ml and 147.9 µg/ml, respectively. While for detection of antiviral activity using Madin-Darby canine kidney (MDCK) cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1µg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50) was 33.25% for 80 µg/ml. This results indicated that the hydroxy marilone C has a potential antitumor and antiviral activities.Keywords: hydroxy marilone C, production, bioactive compound, Streptomyces badius
Procedia PDF Downloads 2533520 Role of Nano Gelatin and Hydrogel Based Scaffolds in Odontogenic Differentiation of Human Dental Pulp Stem Cells
Authors: Husain S. Yawer, Vasim Raja Panwar, Nidhi Priya
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The objective of this study is to evaluate and compare the role of nano-gelatin and Bioengineered Scaffolds on the attachment, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSCs). Tooth decay and early fall have each been one of the most prevailing dental disorders which cause physical and emotional suffering and compromise the patient's quality of life. The design of novel scaffolding materials will be based on mimicking the architecture of natural dental extracellular matrix which may provide as in vivo environments for proper cell growth. This methodology will involve the combination of nano-fibred gelatin as well as biodegradable hydrogel based tooth scaffold. We have measured and optimized the Dental Pulp Stem Cells growth profile in cultures carried out on collagen-coated plastic surface, however, for tissue regeneration study, we aim to develop an enhanced microenvironment for stem cell growth and dental tissue regeneration. We believe biomimetic cell adhesion and scaffolds might provide a near in vivo growth environment for proper growth and differentiation of human DPSCs, which further help in dentin/pulp tissue regeneration.Keywords: nano-gelatin, stem cells, dental pulp, scaffold
Procedia PDF Downloads 3303519 Computational Cell Segmentation in Immunohistochemically Image of Meningioma Tumor Using Fuzzy C-Means and Adaptive Vector Directional Filter
Authors: Vahid Anari, Leila Shahmohammadi
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Diagnosing and interpreting manually from a large cohort dataset of immunohistochemically stained tissue of tumors using an optical microscope involves subjectivity and also is tedious for pathologist specialists. Moreover, digital pathology today represents more of an evolution than a revolution in pathology. In this paper, we develop and test an unsupervised algorithm that can automatically enhance the IHC image of a meningioma tumor and classify cells into positive (proliferative) and negative (normal) cells. A dataset including 150 images is used to test the scheme. In addition, a new adaptive color image enhancement method is proposed based on a vector directional filter (VDF) and statistical properties of filtering the window. Since the cells are distinguishable by the human eye, the accuracy and stability of the algorithm are quantitatively compared through application to a wide variety of real images.Keywords: digital pathology, cell segmentation, immunohistochemically, noise reduction
Procedia PDF Downloads 673518 Mental Wellbeing Using Music Intervention: A Case Study of Therapeutic Role of Music, From Both Psychological and Neurocognitive Perspectives
Authors: Medha Basu, Kumardeb Banerjee, Dipak Ghosh
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After the massive blow of the COVID-19 pandemic, several health hazards have been reported all over the world. Serious cases of Major Depressive Disorder (MDD) are seen to be common in about 15% of the global population, making depression one of the leading mental health diseases, as reported by the World Health Organization. Various psychological and pharmacological treatment techniques are regularly being reported. Music, a globally accepted mode of entertainment, is often used as a therapeutic measure to treat various health conditions. We have tried to understand how Indian Classical Music can affect the overall well-being of the human brain. A case study has been reported here, where a Flute-rendition has been chosen from a detailed audience response survey, and the effects of that clip on human brain conditions have been studied from both psychological and neural perspectives. Taking help from internationally-accepted depression-rating scales, two questionnaires have been designed to understand both the prolonged and immediate effect of music on various emotional states of human lives. Thereafter, from EEG experiments on 5 participants using the same clip, the parameter ‘ALAY’, alpha frontal asymmetry (alpha power difference of right and left frontal hemispheres), has been calculated. Works of Richard Davidson show that an increase in the ‘ALAY’ value indicates a decrease in depressive symptoms. Using the non-linear technique of MFDFA on EEG analysis, we have also calculated frontal asymmetry using the complexity values of alpha-waves in both hemispheres. The results show a positive correlation between both the psychological survey and the EEG findings, revealing the prominent role of music on the human brain, leading to a decrease in mental unrest and an increase in overall well-being. In this study, we plan to propose the scientific foundation of music therapy, especially from a neurocognition perspective, with appropriate neural bio-markers to understand the positive and remedial effects of music on the human brain.Keywords: music therapy, EEG, psychological survey, frontal alpha asymmetry, wellbeing
Procedia PDF Downloads 433517 Effective Cooling of Photovoltaic Solar Cells by Inserting Triangular Ribs: A Numerical Study
Authors: S. Saadi, S. Benissaad, S. Poncet, Y. Kabar
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In photovoltaic (PV) cells, most of the absorbed solar radiation cannot be converted into electricity. A large amount of solar radiation is converted to heat, which should be dissipated by any cooling techniques. In the present study, the cooling is achieved by inserting triangular ribs in the duct. A comprehensive two-dimensional thermo-fluid model for the effective cooling of PV cells has been developed. It has been first carefully validated against experimental and numerical results available in the literature. A parametric analysis was then carried out about the influence of the number and size of the ribs, wind speed, solar irradiance and inlet fluid velocity on the average solar cell and outlet air temperatures as well as the thermal and electrical efficiencies of the module. Results indicated that the use of triangular ribbed channels is a very effective cooling technique, which significantly reduces the average temperature of the PV cell, especially when increasing the number of ribs.Keywords: effective cooling, numerical modeling, photovoltaic cell, triangular ribs
Procedia PDF Downloads 1783516 Nanomechanical Characterization of Healthy and Tumor Lung Tissues at Cell and Extracellular Matrix Level
Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti
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The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor
Procedia PDF Downloads 2803515 The Use of Industrial Ecology Principles in the Production of Solar Cells and Solar Modules
Authors: Julius Denafas, Irina Kliopova, Gintaras Denafas
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Three opportunities for implementation of industrial ecology principles in the real industrial production of c-Si solar cells and modules are presented in this study. It includes: material flow dematerialisation, product modification and industrial symbiosis. Firstly, it is shown how the collaboration between R&D institutes and industry helps to achieve significant reduction of material consumption by a) refuse from phosphor silicate glass cleaning process and b) shortening of SiNx coating production step. This work was performed in the frame of Eco-Solar project, where Soli Tek R&D is collaborating together with the partners from ISC-Konstanz institute. Secondly, it was shown how the modification of solar module design can reduce the CO2 footprint for this product and enhance waste prevention. It was achieved by implementing a frameless glass/glass solar module design instead of glass/backsheet with aluminium frame. Such a design change is possible without purchasing new equipment and without loss of main product properties like efficiency, rigidity and longevity. Thirdly, industrial symbiosis in the solar cell production is possible in such case when manufacturing waste (silicon wafer and solar cell breakage) are collected, sorted and supplied as raw-materials to other companies involved in the production chain of c-Si solar cells. The obtained results showed that solar cells produced from recycled silicon can have a comparable electrical parameters like produced from standard, commercial silicon wafers. The above mentioned work was performed at solar cell producer Soli Tek R&D in the frame of H2020 projects CABRISS and Eco-Solar.Keywords: solar cells and solar modules, manufacturing, waste prevention, recycling
Procedia PDF Downloads 2143514 Electrospinning of Nanofibrous Meshes and Surface-Modification for Biomedical Application
Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee
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Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.Keywords: nanofiber, tissue, mesh, drug
Procedia PDF Downloads 3403513 Evaluation of Cytotoxic Effect of Mitoxantrone Conjugated Magnetite Nanoparticles and Graphene Oxide-Magnetite Nanocomposites on Mesenchymal Stem Cells
Authors: Abbas Jafarizad, Duygu Ekinci
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In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells
Procedia PDF Downloads 2733512 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells
Authors: S. Pradhan, D. Pradhan, G. Tripathy
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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells
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