Search results for: transitional cell carcinoma
3265 The Antitumor Activity of Eu (III) and Er (III) Complexes of 3 - (1H-Benzimidazol-2-Yl) - 6 - Methyl - 2 (1H) - Quinolinone
Authors: Xing Lu, Yi-ming Wu, Yan-hong Zhu, Zhen-feng Chen, Hong Liang, Yan Peng
Abstract:
[Eu(BMQ)2(NO3)3(CH3OH)(H2O)] (1),and [Er(BMQ)2(NO3)3(CH3OH)(H2O)] (2),were synthesized. Compounds 1 and 2 exhibit a certain extent cytotoxicity against Hep G2, Hela 229, MGC80-3 and BEL-7404 cell lines invitro, with IC50 values in the14.51±1.41μM to 52.49±4.01μM range. Compound 1 exhibited significantly enhanced cytotoxicity against MGC80-3 cell line, comparing with free 3-(1H-benzimidazol-2-yl)-6-methyl-2(1H)- quinolinone. The binding abilities of 1 to DNA were stronger than that of 2. Intercalation is the most probable binding mode for both the complexes.Keywords: quinolinone, Eu(II) complex, Er(III) complex, cytotoxicity.
Procedia PDF Downloads 5983264 Design and Identification of Mycobacterium tuberculosis Glutamate Racemase (MurI) Inhibitors
Authors: Prasanthi Malapati, R. Reshma, Vijay Soni, Perumal Yogeeswari, Dharmarajan Sriram
Abstract:
In the present study, we attempted to develop Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria. For this purpose, glutamate racemase (coded by MurI gene) was selected. This enzyme racemize L-glutamate to D-glutamate required for the construction of peptidoglycan in the bacterial cell wall synthesis process. Furthermore this enzyme is neither expressed nor its product, D-glutamate is normally found in mammals, and hence designing inhibitors against this enzyme will not affect the host system as well act as potential antitubercular drugs. A library of BITS in house compounds were screened against Mtb MurI enzyme. Based on docking score, interactions and synthetic feasibility one hit lead was identified. Further optimization of lead was attempted and its derivatives were synthesized. Forty eight derivatives of 2-phenylbenzo[d]oxazole and 2-phenylbenzo[d]thiazole were synthesized and evaluated for Mtb MurI inhibition study, in vitro activities against Mtb, cytotoxicity against RAW 264.7 cell line. Chemical derivatization of the lead resulted in compounds NR-1213 AND NR-1124 as the potent M. tuberculosis glutamate racemase inhibitors with IC50 of 4-5µM which are remarkable and were found to be non-cytotoxic. Molecular dynamics, dormant models and cardiotoxicity studies of the most active molecules are in process.Keywords: cell wall biosynthesis, dormancy, glutamate racemase, tuberculosis
Procedia PDF Downloads 2693263 Developing a Thermo-Sensitive Conductive Stretchable Film to Allow Cell Sheet Harvest after Mechanical and Electrical Treatments
Authors: Wei-Wen Hu, Yong-Zhi Zhong
Abstract:
Depositing conductive polypyrrole (PPy) onto elastic polydimethylsiloxane (PDMS) substrate can obtain a highly stretchable conductive film, which can be used to construct a bioreactor to cyclically stretch and electrically stimulate surface cells. However, how to completely harvest these stimulated muscle tissue to repair damaged muscle is a challenge. To address this concern, N-isopropylacrylamide (NIPAAm), a monomer of temperature-sensitive polymer, was added during the polymerization of pyrrole on PDMS so that the resulting P(Py-co-NIPAAm)/PDMS should own both conductivity and thermo-sensitivity. Therefore, cells after stimulation can be completely harvested as cell sheets by reducing temperature. Mouse skeletal myoblast, C2C12 cells, were applied to examine our hypothesis. In electrical stimulation, C2C12 cells on P(Py-co-NIPAAm)/PDMS demonstrated the best myo-differentiation under the electric field of 1 V/cm. Regarding cyclic stretching, the strain equal to or higher than 9% can highly align C2C12 perpendicular to the stretching direction. The Western blotting experiments demonstrated that the cell sheets harvested by cooling reserved more extracellular matrix (ECM) than cells collected by the traditional trypsin digestion method. Immunostaining of myosin heavy chain protein (MHC) indicated that both mechanical and electrical stimuli effectively increased the number of myotubes and the differentiation ratio, and the myotubes can be aligned by cyclic stretching. Stimulated cell sheets can be harvested by cooling, and the alignment of myotubes was still maintained. These results suggested that the deposition of P(Py-co-NIPAAm) on PDMS can be applied to harvest intact cell sheets after cyclic stretching and electrical stimulation, which increased the feasibility of bioreactor for the application of tissue engineering and regenerative medicine.Keywords: bioreactor, cell sheet, conductive polymer, cyclic stretching, electrical stimulation, muscle tissue engineering, myogenesis, thermosensitive hydrophobicity
Procedia PDF Downloads 963262 The Activity of Polish Propolis and Cannabidiol Oil Extracts on Glioblastoma Cell Lines
Authors: Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Justyna Moskwa, Krystyna Gromkowska-Kepka, Konrad Mielcarek, Patryk Nowakowski, Katarzyna Socha, Anna Puscion-Jakubik, Maria H. Borawska
Abstract:
Glioblastoma (grade IV WHO) is a rapidly progressive brain tumor with very high morbidity and mortality. The vast malignant gliomas are not curable despite the therapy (surgical, radiotherapy, chemotherapy) and patients seek alternative or complementary treatments. Patients often use cannabidiol (CBD) oil as an alternative therapy of glioblastoma. CBD is one of the cannabinoids, an active component of Cannabis sativa. THC (Δ9-tetrahydrocannabinol) can be addictive, and in many countries CBD oil without THC ( < 0,2%) is available. Propolis produced by bees from the resin collected from trees has antiglioma properties in vitro and can be used as a supplement in complementary therapy of gliomas. The aim of this study was to examine the influence of extract from CBD oil in combination with propolis extract on two glioblastoma cell lines. The MTT (Thiazolyl Blue Tetrazolium Bromide) test was used to determine the influence of CBD oil extract and polish propolis extract (PPE) on the viability of glioblastoma cell lines – U87MG and LN18. The cells were incubated (24, 48 and 72 h) with CBD oil extract and PPE. CBD extract was used in concentration 1, 1.5 and 3 µM and PPE in 30 µg/mL. The data were presented compared to the control. The statistical analysis was performed using Statistica v. 13.0 software. CBD oil extract in concentrations 1, 1.5 and 3 µM did not inhibit the viability of U87MG and LN18 cells (viability more than 90% cells compared to the control). There was no dose-response viability, and IC50 value was not recognized. PPE in the concentration of 30 µg/mL time-dependently inhibited the viability of U87MG and LN18 cell line (after 48 h the viability as a percent of the control was 59,7±6% and 57,8±7%, respectively). In a combination of CBD with PPE, the viability of the treated cells was similar to PPE used alone (58,2±7% and 56,5±9%, respectively). CBD oil extract did not show anti-glioma activity and in combination with PPE did not change the activity of PPE.Keywords: anticancer, cannabidiol, cell line, glioblastoma
Procedia PDF Downloads 2463261 Therapeutic Efficacy and Safety Profile of Tolvaptan Administered in Hyponatremia Patients
Authors: Sree Vennela P., V. Samyuktha Bhardwaj
Abstract:
Hyponatremia is an electrolyte disturbance in which the sodium ion concentration in the serum is lower than normal. Sodium is the dominant extracellular cation (positive ion) and cannot freely cross from the interstitial space through the cell membrane, into the cell. Its homeostasis (stability of concentration) inside the cell is vital to the normal function of any cell. Normal serum sodium levels are between 135 and 145 mEq/L. Hyponatremia is defined as a serum level of less than 135 mEq/L and is considered severe when the serum level is below 125 mEq/L. In the vast majority of cases, Hyponatremia occurs as a result of excess body water diluting the serum sodium (salt level in the blood). Hyponatremia is often a complication of other medical illnesses in which excess water accumulates in the body at a higher rate than can be excreted (for example in congestive heart failure, syndrome of inappropriate antidiuretic hormone, SIADH, or polydipsia). Sometimes it may be a result of over-hydration (drinking too much water).Lack of sodium (salt) is very rarely the cause of Hyponatremia, although it can promote Hyponatremia indirectly. In particular, sodium loss can lead to a state of volume depletion (loss of blood volume in the body), with volume depletion serving as a signal for the release of ADH (anti-diuretic hormone). As a result of ADH-stimulated water retention (too much water in the body), blood sodium becomes diluted and Hyponatremia results.Keywords: Tolvaptan, hyponatremia, syndrome of insufficient anti diuretic hormone (SIADH), euvolemic hyponatremia
Procedia PDF Downloads 2603260 Cloning, Expression and N-Terminal Pegylation of Human Interferon Alpha-2b Analogs and Their Cytotoxic Evaluation against Cancer Cell Lines
Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir
Abstract:
In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression
Procedia PDF Downloads 1773259 Brain Derived Neurotrophic Factor (BDNF) Down Regulation in Peritoneal Carcinomatosis Patients
Authors: Awan A. Zaima, Tanvieer Ayesha, Mirshahi Shahsoltan, Pocard Marc, Mirshahi Massoud
Abstract:
Brain-derived neurotrophic factor (BDNF) is described as a factor helping to support the survival of existing neurons by involving the growth and differentiation of new neurons and synapses. Cancer diagnosis impacts the mental health, and in consequences, depression arise eventually hinders recovery and disrupts the quality of life and surviving chances of patients. The focus of this study is to hint upon a prospective biomarker as a promising diagnostic tool for an early indicator/predictor of depression prevalence in cancer patients for better care and treatment options. The study aims to analyze peripheral biomarkers from neuro immune axis (BDNF, IL21 as a NK cell activator) using co-relation approach. Samples were obtained from random non cancer candidates and advanced peritoneum carcinomatosis patients with 25% pseudomyxoma, 21% Colon cancer,19% stomach cancer, 10% ovarian cancer, 8% appendices cancer, and 10% other area of peritoneum cancer patients. Both groups of the study were categorized by gender and age, with a range of 18 to 86 years old. Biomarkers were analyzed in collected plasma by performing multiplex sandwich ELISA system. Data were subjected to statistical analysis for the assessment of the correlation. Our results demonstrate that BNDF and IL 21 down regulated significantly in patient groupas compared to non-cancer candidates (ratio of patients/normalis 2.57 for BNDF and 1.32 for IL21). This preliminary investigation suggested that the neuro immune biomarkers are down regulated in carcinomatosis patients and can be associated with cancer expansion and cancer genesis. Further studies on larger cohort are necessary to validate this hypothesis.Keywords: biomarkers, depression, peritoneum carcinoma, BNDF, IL21
Procedia PDF Downloads 1163258 Fermentation of Xylose and Glucose Mixture in Intensified Reactors by Scheffersomyces stipitis to Produce Ethanol
Authors: S. C. Santos, S. R. Dionísio, A. L. D. De Andrade, L. R. Roque, A. C. Da Costa, J. L. Ienczak
Abstract:
In this work, two fermentations at different temperatures (25 and 30 ºC), with cell recycling, were accomplished to produce ethanol, using a mix of commercial substrates, xylose (70%) and glucose (30%), as organic source for Scheffersomyces stipitis. Five consecutive fermentations of 80 g L-1 (1º, 2º and 3º recycles), 96 g L-1 (4º recycle) and 120 g L-1 (5º recycle)reduced sugars led to a final maximum ethanol concentration of 17.2 and 34.5 g L-1, at 25 and 30 ºC, respectively. Glucose was the preferred substrate; moreover xylose startup degradation was initiated after a remaining glucose presence in the medium. Results showed that yeast acid treatment, performed before each cycle, provided improvements on cell viability, accompanied by ethanol productivity of 2.16 g L-1 h-1 at 30 ºC. A maximum 36% of xylose was retained in the fermentation medium and after five-cycle fermentation an ethanol yield of 0.43 g ethanol/g sugars was observed. S. stipitis fermentation capacity and tolerance showed better results at 30 ºC with 83.4% of theoretical yield referenced on initial biomass.Keywords: 5-carbon sugar, cell recycling fermenter, mixed sugars, xylose-fermenting yeast
Procedia PDF Downloads 4193257 Retrospective Assessment of the Safety and Efficacy of Percutaneous Microwave Ablation in the Management of Hepatic Lesions
Authors: Suang K. Lau, Ismail Goolam, Rafid Al-Asady
Abstract:
Background: The majority of patients with hepatocellular carcinoma (HCC) are not suitable for curative treatment, in the form of surgical resection or transplantation, due to tumour extent and underlying liver dysfunction. In these non-resectable cases, a variety of non-surgical therapies are available, including microwave ablation (MWA), which has shown increasing popularity due to its low morbidity, low reported complication rate, and the ability to perform multiple ablations simultaneously. Objective: The aim of this study was to evaluate the validity of MWA as a viable treatment option in the management of HCC and hepatic metastatic disease, by assessing its efficacy and complication rate at a tertiary hospital situated in Westmead (Australia). Methods: A retrospective observational study was performed evaluating patients that underwent MWA between 1/1/2017–31/12/2018 at Westmead Hospital, NSW, Australia. Outcome measures, including residual disease, recurrence rates, as well as major and minor complication rates, were retrospectively analysed over a 12-months period following MWA treatment. Excluded patients included those whose lesions were treated on the basis of residual or recurrent disease from previous treatment, which occurred prior to the study window (11 patients) and those who were lost to follow up (2 patients). Results: Following treatment of 106 new hepatic lesions, the complete response rate (CR) was 86% (91/106) at 12 months follow up. 10 patients had the residual disease at post-treatment follow up imaging, corresponding to an incomplete response (ICR) rate of 9.4% (10/106). The local recurrence rate (LRR) was 4.6% (5/106) with follow-up period up to 12 months. The minor complication rate was 9.4% (10/106) including asymptomatic pneumothorax (n=2), asymptomatic pleural effusions (n=2), right lower lobe pneumonia (n=3), pain requiring admission (n=1), hypotension (n=1), cellulitis (n=1) and intraparenchymal hematoma (n=1). There was 1 major complication reported, with pleuro-peritoneal fistula causing recurrent large pleural effusion necessitating repeated thoracocentesis (n=1). There was no statistically significant association between tumour size, location or ablation factors, and risk of recurrence or residual disease. A subset analysis identified 6 segment VIII lesions, which were treated via a trans-pleural approach. This cohort demonstrated an overall complication rate of 33% (2/6), including 1 minor complication of asymptomatic pneumothorax and 1 major complication of pleuro-peritoneal fistula. Conclusions: Microwave ablation therapy is an effective and safe treatment option in cases of non-resectable hepatocellular carcinoma and liver metastases, with good local tumour control and low complication rates. A trans-pleural approach for high segment VIII lesions is associated with a higher complication rate and warrants greater caution.Keywords: hepatocellular carcinoma, liver metastases, microwave ablation, trans-pleural approach
Procedia PDF Downloads 1373256 Policy Initiatives That Increase Mass-Market Participation of Fuel Cell Electric Vehicles
Authors: Usman Asif, Klaus Schmidt
Abstract:
In recent years, the development of alternate fuel vehicles has helped to reduce carbon emissions worldwide. As the number of vehicles will continue to increase in the future, the energy demand will also increase. Therefore, we must consider automotive technologies that are efficient and less harmful to the environment in the long run. Battery Electric Vehicles (BEVs) have gained popularity in recent years because of their lower maintenance, lower fuel costs, and lower carbon emissions. Nevertheless, BEVs show several disadvantages, such as slow charging times and lower range than traditional combustion-powered vehicles. These factors keep many people from switching to BEVs. The authors of this research believe that these limitations can be overcome by using fuel cell technology. Fuel cell technology converts chemical energy into electrical energy from hydrogen power and therefore serves as fuel to power the motor and thus replacing heavy lithium batteries that are expensive and hard to recycle. Also, in contrast to battery-powered electric vehicle technology, Fuel Cell Electric Vehicles (FCEVs) offer higher ranges and lower fuel-up times and therefore are more competitive with electric vehicles. However, FCEVs have not gained the same popularity as electric vehicles due to stringent legal frameworks, underdeveloped infrastructure, high fuel transport, and storage costs plus the expense of fuel cell technology itself. This research will focus on the legal frameworks for hydrogen-powered vehicles, and how a change in these policies may affect and improve hydrogen fueling infrastructure and lower hydrogen transport and storage costs. These policies may also facilitate reductions in fuel cell technology costs. In order to attain a better framework, a number of countries have developed conceptual roadmaps. These roadmaps have set out a series of objectives to increase the access of FCEVs to their respective markets. This research will specifically focus on policies in Japan, Europe, and the USA in their attempt to shape the automotive industry of the future. The researchers also suggest additional policies that may help to accelerate the advancement of FCEVs to mass-markets. The approach was to provide a solid literature review using resources from around the globe. After a subsequent analysis and synthesis of this review, the authors concluded that in spite of existing legal challenges that have hindered the advancement of fuel-cell technology in the automobile industry in the past, new initiatives that enhance and advance the very same technology in the future are underway.Keywords: fuel cell electric vehicles, fuel cell technology, legal frameworks, policies and regulations
Procedia PDF Downloads 1173255 The Tourism in the Regional Development of South Caucasus
Authors: Giorgi Sulashvili, Vladimer Kekenadze, Olga Khutsishvili, Bela Khotenashvili, Tsiuri Phkhakadze, Besarion Tsikhelashvili
Abstract:
The article dealt with the South Caucasus is a complex economic policy, which consists of strands: The process of deepening economic integration in the South Caucasus region; deepening economic integration with the EU in the framework of "Neighbourhood policy with Europe" and in line with the Maastricht criteria; the development of bilateral trade and economic relations with many countries of the world community; the development of sufficient conditions for the integration of the South Caucasus region in the world to enter the market. According to the author, to determine the place of Georgia in the regional policy of the South Caucasus, it is necessary to consider two views about Georgia: The first is the view of Georgia, as a part of global economic and political processes and the second look at Georgia, as a country located in the geo-economic and geopolitical space of the South Caucasus. Such approaches reveal the place of Georgia in two dimensions; in the global and regional economies. In the countries of South Caucasus, the tourism has been developing fast and has a great social and economic importance. Tourism influences deeply on the social and economic growth of the regions of the country. Tourism development formulates thousand new jobs, fixes the positions of small and middle businesses, ensures the development of the education and culture of the population. In the countries of South Caucasus, the Tourist Industry can be specified as the intersectoral complex, which consists of travel transport and it’s technical service network, tourist enterprises which are specialized in various types, wide network services. Tourists have a chance to enjoy all of these services. At the transitional stage of shifting to the market economy, tourism is among the priorities in the development of the national economy of our country. It is true that the Georgian tourism faces a range of problems at present, but its recognition and the necessity for its development may be considered as a fact. Besides, we would underline that the revitalization of the Georgian tourism is not only the question of time. This area can bring a lot of benefits as to private firms, as to specific countries. It also has many negative effects were conducted fundamental research and studies to consider both, positive and negative impacts of tourism. In the future such decisions will be taken that will bring, the maximum benefit at minimum cost, in order for tourism to take its place in Georgia it is necessary to understand the role of the tourism sector in the economic structure.Keywords: transitional stage, national economy, Georgian tourism, positive and negative impacts
Procedia PDF Downloads 3983254 RACK1 Integrates Light and Brassinosteroid Signaling to Coordinate Cell Division During Root Soil Penetration
Authors: Liang Jiansheng, Zhu Wei
Abstract:
Light and brassinosteroids are essential external and internal cues for plant survival. Although the coordination of light with phytohormone signals is crucial for plant growth and development, the molecular connection between light and brassinosteroid signaling during root soil penetration remains elusive. Here, we reveal that light-stabilized RACK1 couples a brassinosteroid signaling cascade to drive cell division in root meristems. RACK1 family scaffold proteins positively regulate light-induced the promotion of root elongation during soil penetration. Under the light condition, RACK1A interacts with both phyB and SPA1, then reinforces the phyB-SPA1 association to accumulate its abundance in roots. In response to brassinosteroid signals, RACK1A competes with BKI1 to attenuate the BRI1-BKI1 interaction, thereby leading to activating BRI1 actions in root development. Furthermore, RACK1A binds to BES1 to repress its DNA binding activity toward the target gene CYCD3;1. This ultimately allows to release the inhibition of CYCD3;1 transcription, and promotes cell division during root growth. Our study illustrates a new mechanistic model of how plants engage scaffold proteins in transducing light information to facilitate brassinosteroid signaling for root growth in the soil.Keywords: root growth, cell division, light signaling, brassinosteroid signaling, soil penetration, scaffold protein, RACK1
Procedia PDF Downloads 803253 Study into the Interactions of Primary Limbal Epithelial Stem Cells and HTCEPI Using Tissue Engineered Cornea
Authors: Masoud Sakhinia, Sajjad Ahmad
Abstract:
Introduction: Though knowledge of the compositional makeup and structure of the limbal niche has progressed exponentially during the past decade, much is yet to be understood. Identifying the precise profile and role of the stromal makeup which spans the ocular surface may inform researchers of the most optimum conditions needed to effectively expand LESCs in vitro, whilst preserving their differentiation status and phenotype. Limbal fibroblasts, as opposed to corneal fibroblasts are thought to form an important component of the microenvironment where LESCs reside. Methods: The corneal stroma was tissue engineered in vitro using both limbal and corneal fibroblasts embedded within a tissue engineered 3D collagen matrix. The effect of these two different fibroblasts on LESCs and hTCEpi corneal epithelial cell line were then subsequently determined using phase contrast microscopy, histolological analysis and PCR for specific stem cell markers. The study aimed to develop an in vitro model which could be used to determine whether limbal, as opposed to corneal fibroblasts, maintained the stem cell phenotype of LESCs and hTCEpi cell line. Results: Tissue culture analysis was inconclusive and required further quantitative analysis for remarks on cell proliferation within the varying stroma. Histological analysis of the tissue-engineered cornea showed a comparable structure to that of the human cornea, though with limited epithelial stratification. PCR results for epithelial cell markers of cells cultured on limbal fibroblasts showed reduced expression of CK3, a negative marker for LESC’s, whilst also exhibiting a relatively low expression level of P63, a marker for undifferentiated LESCs. Conclusion: We have shown the potential for the construction of a tissue engineered human cornea using a 3D collagen matrix and described some preliminary results in the analysis of the effects of varying stroma consisting of limbal and corneal fibroblasts, respectively, on the proliferation of stem cell phenotype of primary LESCs and hTCEpi corneal epithelial cells. Although no definitive marker exists to conclusively illustrate the presence of LESCs, the combination of positive and negative stem cell markers in our study were inconclusive. Though it is less traslational to the human corneal model, the use of conditioned medium from that of limbal and corneal fibroblasts may provide a more simple avenue. Moreover, combinations of extracellular matrices could be used as a surrogate in these culture models.Keywords: cornea, Limbal Stem Cells, tissue engineering, PCR
Procedia PDF Downloads 2793252 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy
Authors: Caroline Mendes, Mary McNamara, Orla Howe
Abstract:
Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers
Procedia PDF Downloads 3103251 Tumor Cell Detection, Isolation and Monitoring Using Bi-Layer Magnetic Microfluidic Chip
Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari
Abstract:
The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation
Procedia PDF Downloads 1433250 Statistical Analysis of Parameters Effects on Maximum Strain and Torsion Angle of FRP Honeycomb Sandwich Panels Subjected to Torsion
Authors: Mehdi Modabberifar, Milad Roodi, Ehsan Souri
Abstract:
In recent years, honeycomb fiber reinforced plastic (FRP) sandwich panels have been increasingly used in various industries. Low weight, low price, and high mechanical strength are the benefits of these structures. However, their mechanical properties and behavior have not been fully explored. The objective of this study is to conduct a combined numerical-statistical investigation of honeycomb FRP sandwich beams subject to torsion load. In this paper, the effect of geometric parameters of the sandwich panel on the maximum shear strain in both face and core and angle of torsion in a honeycomb FRP sandwich structures in torsion is investigated. The effect of Parameters including core thickness, face skin thickness, cell shape, cell size, and cell thickness on mechanical behavior of the structure were numerically investigated. Main effects of factors were considered in this paper and regression equations were derived. Taguchi method was employed as experimental design and an optimum parameter combination for the maximum structure stiffness has been obtained. The results showed that cell size and face skin thickness have the most significant impacts on torsion angle, maximum shear strain in face and core.Keywords: finite element, honeycomb FRP sandwich panel, torsion, civil engineering
Procedia PDF Downloads 4183249 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection
Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément
Abstract:
The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars
Procedia PDF Downloads 1173248 Modeling of a Concentrating Photovoltaic Module with and without Cooling System
Authors: Intissar Benrhouma, Marta Victoria, Ignacio Anton, Bechir Chaouachi
Abstract:
Concentrating photovoltaic systems CPV use optical elements, such as Fresnel lenses, to concentrate solar intensity. The concentrated solar energy is delivered to the solar cell from 20 to 100 W/cm². Some of this energy is converted to electricity, while the rest must be disposed of as a residual heat. Solar cells cooling should be a necessary part of CPV modeling because these systems allowed increasing the power received by the cell. This high power can rise the electrons’ potential causing the heating of the cell, which reduces the global module’s efficiency. This work consists of modeling a concentrating photovoltaic module with and without a cooling system. We have established a theoretical model based on energy balances carried out on a photovoltaic module using solar radiation concentration cells. Subsequently, we developed a calculation program on Matlab which allowed us to simulate the functioning of this module. The obtained results show that the addition of a cooling system to the module improves greatly the performance of our CPV system.Keywords: solar energy, photovoltaic, concentration, cooling, performance improvement
Procedia PDF Downloads 3983247 Translingual Discrimination and Migrants
Authors: Sender Dovchin
Abstract:
Moving beyond two main frameworks of interlingual and intralingual discrimination, this paper will address the understanding of translingual discrimination. This concept refers to discrimination based on how one uses certain languages, linguistic and communicative repertoires, which are (il)legitimised by the interactants. Translingual discrimination contributes intensity to transnational migrations processes, where migrants with transitional backgrounds seem to illustrate two main characteristics of marginalizations – “name discrimination” and “accentism”. The lifelong accumulation of these characteristics of translingual discrimination may cause negative emotionality, such as translingual inferiority complexes, to its victims. As a result, these transnational migrants seem to adopt varied coping strategies such as CV-whitening and accent purifications while probing for translingual safe spaces. The presentation concludes with the socio-cultural and pedagogical implications of translingual discrimination in relation to the language usage of transnational migrants.Keywords: accentism, discrimination, migrants, translingualism
Procedia PDF Downloads 793246 Evaluation of Iron Oxide-Functionalized Multiwall Carbon Nanotube Self-Standing Electrode for Symmetric Supercapacitor Application
Authors: B. V. Bhaskara Rao, Rodrigo Espinoza
Abstract:
The rapid development of renewable energy sources has drawn great attention to energy storage devices, especially supercapacitors, because of their high power density and rate performance. This work focus on Fe₃O₄ nanoparticles synthesized by reverse co-precipitation and MWCNTs functionalized by –COOH acid functionalization. The results show that Optimized 25wt% Fe₃O₄@FMWCNT show high specific capacitance 100 mF/cm² at one mA/cm² whereas 15wt% Fe₃O₄@FMWCNT showed high stability (80% retention capacity) over 5000 cycles. The electrolyte used in the coin cell is LiPF6 and the thickness of the electrode is 30 microns. The optimized Fe₃O₄@FMWCNT bucky papers coin cell electrochemical studies suggest that 25wt% Fe₃O₄@FMWCNT could be a good candidate for high-capacity supercapacitor devices. This could be further tested for flexible and planar supercapacitor device application with gel electrolytes.Keywords: self-standing electrode, Fe₃O4@FMWCNT, supercapacitor, symmetric coin-cell
Procedia PDF Downloads 1573245 Binding Mechanism of Synthesized 5β-Dihydrocortisol and 5β-Dihydrocortisol Acetate with Human Serum Albumin to Understand Their Role in Breast Cancer
Authors: Monika Kallubai, Shreya Dubey, Rajagopal Subramanyam
Abstract:
Our study is all about the biological interactions of synthesized 5β-dihydrocortisol (Dhc) and 5β-dihydrocortisol acetate (DhcA) molecules with carrier protein Human Serum Albumin (HSA). The cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. The further experiment proved that Dhc and DhcA induced 35.6% and 37.7% early apoptotic cells and 2.5%, 2.9% late apoptotic cells respectively. Morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA–Dhc and HSA–DhcA were observed as static quenching, and the binding constants (K) was 4.7±0.03×104 M-1 and 3.9±0.05×104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4±0.05×104 M-1 replaced Dhc, and phenylbutazone 1.5±0.05×104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular sizes of the HSA–Dhc and HSA–DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported the greater stability of HSA–Dhc and HSA–DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for the further development of steroid derivatives with improved pharmacological significance as novel anti-cancer drugs.Keywords: apoptosis, dihydrocortisol, fluorescence quenching, protein conformations
Procedia PDF Downloads 1313244 An Industrial Scada System Remote Control Using Mobile Phones
Authors: Ahmidah Elgali
Abstract:
SCADA is the abbreviation for "Administrative Control And Data Acquisition." SCADA frameworks are generally utilized in industry for administrative control and information securing of modern cycles. Regular SCADA frameworks use PC, journal, slim client, and PDA as a client. In this paper, a Java-empowered cell phone has been utilized as a client in an example SCADA application to show and regulate the place of an example model crane. The paper presents a genuine execution of the online controlling of the model crane through a cell phone. The remote correspondence between the cell phone and the SCADA server is performed through a base station by means of general parcel radio assistance GPRS and remote application convention WAP. This application can be used in industrial sites in areas that are likely to be exposed to a security emergency (like terrorist attacks) which causes the sudden exit of the operators; however, no time to perform the shutdown procedures for the plant. Hence this application allows shutting down units and equipment remotely by mobile and so avoids damage and losses.Keywords: control, industrial, mobile, network, remote, SCADA
Procedia PDF Downloads 793243 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells
Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra
Abstract:
MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.Keywords: breast cancer, microRNA, metastasis, EMT
Procedia PDF Downloads 5673242 Glucose Uptake Rate of Insulin-Resistant Human Liver Carcinoma Cells (IR/HepG2) by Flavonoids from Enicostema littorale via IR/IRS1/AKT Pathway
Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita
Abstract:
Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance
Procedia PDF Downloads 3073241 The Impact of the Cell-Free Solution of Lactic Acid Bacteria on Cadaverine Production by Listeria monocytogenes and Staphylococcus aureus in Lysine-Decarboxylase Broth
Authors: Fatih Özogul, Nurten Toy, Yesim Özogul
Abstract:
The influences of cell-free solutions (CFSs) of lactic acid bacteria (LAB) on cadaverine and other biogenic amine production by Listeria monocytogenes and Staphylococcus aureus were investigated in lysine decarboxylase broth (LDB) using HPLC. Cell-free solutions were prepared from Lactococcus lactis subsp. lactis, Leuconostoc mesenteroides subsp. cremoris, Pediococcus acidophilus and Streptococcus thermophiles. Two different concentrations that were 50% and 25% CFS and the control without CFSs were prepared. Significant variations on biogenic amine production were observed in the presence of L. monocytogenes and S. aureus (P<0.05). The role of CFS on biogenic amine production by foodborne pathogens varied depending on strains and specific amine. Cadaverine formation in control by L. monocytogenes and S. aureus were 500.9 and 948.1 mg/L, respectively while the CFSs of LAB induced 4-fold lower cadaverine production by L. monocytogenes and 7-fold lower cadaverine production by S. aureus. CFSs resulted in strong decreases in cadaverine and putrescine production by L. monocytogenes and S. aureus, although remarkable increases were observed for histamine, spermidine, spermine, serotonin, dopamine, tyramine, and agmatine, in the presence of LAB in lysine decarboxylase broth.Keywords: cell-free solution, lactic acid bacteria, cadaverine, food borne-pathogen
Procedia PDF Downloads 5413240 Cytotoxicological Evaluation of a Folate Receptor Targeting Drug Delivery System Based on Cyclodextrins
Authors: Caroline Mendes, Mary McNamara, Orla Howe
Abstract:
For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers
Procedia PDF Downloads 3013239 iPSCs More Effectively Differentiate into Neurons on PLA Scaffolds with High Adhesive Properties for Primary Neuronal Cells
Authors: Azieva A. M., Yastremsky E. V., Kirillova D. A., Patsaev T. D., Sharikov R. V., Kamyshinsky R. A., Lukanina K. I., Sharikova N. A., Grigoriev T. E., Vasiliev A. L.
Abstract:
Adhesive properties of scaffolds, which predominantly depend on the chemical and structural features of their surface, play the most important role in tissue engineering. The basic requirements for such scaffolds are biocompatibility, biodegradation, high cell adhesion, which promotes cell proliferation and differentiation. In many cases, synthetic polymers scaffolds have proven advantageous because they are easy to shape, they are tough, and they have high tensile properties. The regeneration of nerve tissue still remains a big challenge for medicine, and neural stem cells provide promising therapeutic potential for cell replacement therapy. However, experiments with stem cells have their limitations, such as low level of cell viability and poor control of cell differentiation. Whereas the study of already differentiated neuronal cell culture obtained from newborn mouse brain is limited only to cell adhesion. The growth and implantation of neuronal culture requires proper scaffolds. Moreover, the polymer scaffolds implants with neuronal cells could demand specific morphology. To date, it has been proposed to use numerous synthetic polymers for these purposes, including polystyrene, polylactic acid (PLA), polyglycolic acid, and polylactide-glycolic acid. Tissue regeneration experiments demonstrated good biocompatibility of PLA scaffolds, despite the hydrophobic nature of the compound. Problem with poor wettability of the PLA scaffold surface could be overcome in several ways: the surface can be pre-treated by poly-D-lysine or polyethyleneimine peptides; roughness and hydrophilicity of PLA surface could be increased by plasma treatment, or PLA could be combined with natural fibers, such as collagen or chitosan. This work presents a study of adhesion of both induced pluripotent stem cells (iPSCs) and mouse primary neuronal cell culture on the polylactide scaffolds of various types: oriented and non-oriented fibrous nonwoven materials and sponges – with and without the effect of plasma treatment and composites with collagen and chitosan. To evaluate the effect of different types of PLA scaffolds on the neuronal differentiation of iPSCs, we assess the expression of NeuN in differentiated cells through immunostaining. iPSCs more effectively differentiate into neurons on PLA scaffolds with high adhesive properties for primary neuronal cells.Keywords: PLA scaffold, neurons, neuronal differentiation, stem cells, polylactid
Procedia PDF Downloads 853238 Spatial Architecture Impact in Mediation Open Circuit Voltage Control of Quantum Solar Cell Recovery Systems
Authors: Moustafa Osman Mohammed
Abstract:
The photocurrent generations are influencing ultra-high efficiency solar cells based on self-assembled quantum dot (QD) nanostructures. Nanocrystal quantum dots (QD) provide a great enhancement toward solar cell efficiencies through the use of quantum confinement to tune absorbance across the solar spectrum enabled multi-exciton generation. Based on theoretical predictions, QDs have potential to improve systems efficiency in approximate regular electrons excitation intensity greater than 50%. In solar cell devices, an intermediate band formed by the electron levels in quantum dot systems. The spatial architecture is exploring how can solar cell integrate and produce not only high open circuit voltage (> 1.7 eV) but also large short-circuit currents due to the efficient absorption of sub-bandgap photons. In the proposed QD system, the structure allows barrier material to absorb wavelengths below 700 nm while multi-photon processes in the used quantum dots to absorb wavelengths up to 2 µm. The assembly of the electronic model is flexible to demonstrate the atoms and molecules structure and material properties to tune control energy bandgap of the barrier quantum dot to their respective optimum values. In terms of energy virtual conversion, the efficiency and cost of the electronic structure are unified outperform a pair of multi-junction solar cell that obtained in the rigorous test to quantify the errors. The milestone toward achieving the claimed high-efficiency solar cell device is controlling the edge causes of energy bandgap between the barrier material and quantum dot systems according to the media design limits. Despite this remarkable potential for high photocurrent generation, the achievable open-circuit voltage (Voc) is fundamentally limited due to non-radiative recombination processes in QD solar cells. The orientation of voltage recovery system is compared theoretically with experimental Voc variation in mediation upper–limit obtained one diode modeling form at the cells with different bandgap (Eg) as classified in the proposed spatial architecture. The opportunity for improvement Voc is valued approximately greater than 1V by using smaller QDs through QD solar cell recovery systems as confined to other micro and nano operations states.Keywords: nanotechnology, photovoltaic solar cell, quantum systems, renewable energy, environmental modeling
Procedia PDF Downloads 1573237 CoFe₂O₄ as Anode for Enhanced Energy Recovery in Microbial Fuel Cell
Authors: Mehak Munjal, Raj Kishore Sharma, Gurmeet Singh
Abstract:
Microbial Fuel Cells (MFCs) are an alternative sustainable approach that utilize bacteria present in waste water as a bio-catalyst for the production of energy. It is a promising growing technology with minimal requirement for chemical supplements. Here electrode material plays a vital role in its performance. The present study represents CoFe2O4 spinel as a novel anode material in the MFC. It not only improve the bacterial metabolics but also enhance the power output. Generally, biocompatible conductive carbon paper/cloth, graphite and stainless steel are utilised as anode in MFCs. However, these materials lack electrochemical activity for anodic microbial reaction. Therefore, we developed CoFe2O4 on graphite sheet which enhanced the anodic charge transfer process. Redox pair in CoFe2O4 helped in improvement of extracellular electron transfer, thereby enhancing the performance. The physical characterizations (FT-IR, XRD, Raman) and electrochemical measurements demonstrate the strong interaction with E.coli bacteria and thus providing an excellent power density i.e. 1850 mW/m2 .The maximum anode half -cell potential is measured to be 0.65V. Therefore, use of noble metal free anodic material further decrease the cost and the long term cell stability makes it an effective material for practical applications.Keywords: microbial fuel cell, cobalt ferrite, E. coli, bioelectricity
Procedia PDF Downloads 1433236 A Soft Switching PWM DC-DC Boost Converter with Increased Efficiency by Using ZVT-ZCT Techniques
Authors: Yakup Sahin, Naim Suleyman Ting, Ismail Aksoy
Abstract:
In this paper, an improved active snubber cell is proposed on account of soft switching (SS) family of pulse width modulation (PWM) DC-DC converters. The improved snubber cell provides zero-voltage transition (ZVT) turn on and zero-current transition (ZCT) turn off for main switch. The snubber cell decreases EMI noise and operates with SS in a wide range of line and load voltages. Besides, all of the semiconductor devices in the converter operate with SS. There is no additional voltage and current stress on the main devices. Additionally, extra voltage stress does not occur on the auxiliary switch and its current stress is acceptable value. The improved converter has a low cost and simple structure. The theoretical analysis of converter is clarified and the operating states are given in detail. The experimental results of converter are obtained by prototype of 500 W and 100 kHz. It is observed that the experimental results and theoretical analysis of converter are suitable with each other perfectly.Keywords: active snubber cells, DC-DC converters, zero-voltage transition, zero-current transition
Procedia PDF Downloads 1020