Search results for: attachment epithelial cells
2279 'English in Tourism' in the Project 'English for Community'
Authors: Nguyen Duc An
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To the movement towards learning community, creating friendly, positive and appropriate learning environments which best suit the local features is the most salient and decisive factor of the development and success of that learning society. With the aim at building such an English language learning community for the inhabitants in Moc Chau - the national tourist zone, Tay Bac University has successfully designed and deployed the program ‘English in Tourism’ in the project ‘English for Community’. With the strong attachment to the local reality and close knit to the certain communicative situations, this program which was carefully designed and compiled with interesting and practical activities, has greatly helped the locals confidently introduce and popularize the natural beauty, unique culture and specific characteristics of Moc Chau to the foreign tourists; in addition, reinforce awareness of the native culture of the local people as well as improve the professional development in tourism and service.Keywords: English for community, learning society, learning community, English in tourism
Procedia PDF Downloads 3682278 Effect of Yeast Selenium on CD4 T Cell and WAZ of HIV1 Positive Children in Nyamasaria in Kisumu Kenya
Authors: S. B. Otieno1, F. Were, A. Afullo, K. Waza
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Background: Multi drug resistance HIV has emerged rendering the current conventional treatment of HIV ineffective. There is a need for new treatment regime which is cheap, effective and not prone to resistance development by HIV. Methods: In randomized clinical study of 68 HIV positive children 3 – 15 years to asses the efficacy of yeast selenium in HIV/AIDS patients, 50μ yeast selenium was administered to 34 children while in matched control of 34 were put on placebo. Blood samples and weight of the both groups which were taken every 3 months intervals up to 6 months, were analyzed by ELIZA for CD4T cells, the data was analyzed by SPSS version 16, WAZ scores were analyzed by Epi Info version 6. Results: No significant difference in age { χ2 (1, 62) =0.03, p =0.853}, cause of morbidity between test and controls {χ2 (1, 65) = 5.87, p= 0.015} and on condition of foster parents {χ2 ( 1,63) = 5.57, p= 0.0172} was observed. Children on selenium showed progressive improvement of WAZ and significant difference at six months {F (5,12) = =5.758, P=0.006}, and weight gain of up to 4.1 kilograms in six months, and significant CD4 T cell count increase t= -2.943, p<0.05 compared to matched controls t = -1.258 p> 0.05. CD4 T cell count increased among all age groups on test 3-5 years (+ 267.1),5-8 years (+200.3) 9-15 years (+71.2) cells/mm3 and in matched controls a decrease 3-5 years (-71), 5-8 years (-125) and 9-13 years (-10.1) cells/mm3 . No significant difference inCD4 T cell count between boys {F (2, 32) = 1.531 p= 0.232} and between boys {F (2, 49) = 1.040, p= 0.361} on test and between boys and girls {F (5, 81) = 1.379, p= 0.241} on test. Similarly no significant difference between boys and girls were observed {F (5, 86) = 1.168, p= 0.332}.In the test group there was significant positive correlation β =252.23 between weight for age (WAZ), and CD4 T Cell Count p=0.007, R2= 0.252, F< 0.05. In matched controls no significant correlation between weight gain and CD4 T cell count change was observed at six months p > 0.05. No positive correlation β =-138.23 was observed between CD4T Cell count, WAZ, p=0.934, R2 =0.0337 F >0.05. Majority (96.78%) of children on test either remained or progressed to WHO immunological stage I. Conclusion: From this study it can be concluded that yeast Selenium is effective in slowing the progress of HIV 1 in children from WHO clinical stage I by improving CD4 T cell count and hence the immunity.Keywords: selenium, HIV, AIDS, WAZ
Procedia PDF Downloads 4762277 Integrated Grey Rational Analysis-Standard Deviation Method for Handover in Heterogeneous Networks
Authors: Mohanad Alhabo, Naveed Nawaz, Mahmoud Al-Faris
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The dense deployment of small cells is a promising solution to enhance the coverage and capacity of the heterogeneous networks (HetNets). However, the unplanned deployment could bring new challenges to the network ranging from interference, unnecessary handovers and handover failures. This will cause a degradation in the quality of service (QoS) delivered to the end user. In this paper, we propose an integrated Grey Rational Analysis Standard Deviation based handover method (GRA-SD) for HetNet. The proposed method integrates the Standard Deviation (SD) technique to acquire the weight of the handover metrics and the GRA method to select the best handover base station. The performance of the GRA-SD method is evaluated and compared with the traditional Multiple Attribute Decision Making (MADM) methods including Simple Additive Weighting (SAW) and VIKOR methods. Results reveal that the proposed method has outperformed the other methods in terms of minimizing the number of frequent unnecessary handovers and handover failures, in addition to improving the energy efficiency.Keywords: energy efficiency, handover, HetNets, MADM, small cells
Procedia PDF Downloads 1162276 Shear Stress and Oxygen Concentration Manipulation in a Micropillars Microfluidic Bioreactor
Authors: Deybith Venegas-Rojas, Jens Budde, Dominik Nörz, Manfred Jücker, Hoc Khiem Trieu
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Microfluidics is a promising approach for biomedicine cell culture experiments with microfluidic bioreactors (MBR), which can provide high precision in volume and time control over mass transport and microenvironments in small-scale studies. Nevertheless, shear stress and oxygen concentration are important factors that affect the microenvironment and then the cell culture. It is presented a novel MBR design in which differences in geometry, shear stress, and oxygen concentration were studied and optimized for cell culture. The aim is to mimic the in vivo condition with biocompatible materials and continuous perfusion of nutrients, a healthy shear stress, and oxygen concentration. The design consists of a capture system of PDMS micropillars which keep cells in place, so it is not necessary any hydrogel or complicated scaffolds for cells immobilization. Besides, the design allows continuous supply with nutrients or even any other chemical for cell experimentation. Finite element method simulations were used to study and optimize the effect of parameters such as flow rate, shear stress, oxygen concentration, micropillars shape, and dimensions. The micropillars device was fabricated with microsystem technology such as soft-lithography, deep reactive ion etching, self-assembled monolayer, replica molding, and oxygen plasma bonding. Eight different geometries were fabricated and tested, with different flow rates according to the simulations. During the experiments, it was observed the effect of micropillars size, shape, and configuration for stability and shear stress control when increasing flow rate. The device was tested with several successful HepG2 3D cell cultures. With this MBR, the aforementioned parameters can be controlled in order to keep a healthy microenvironment according to specific necessities of different cell types, with no need of hydrogels and can be used for a wide range of experiments with cells.Keywords: cell culture, micro-bioreactor, microfluidics, micropillars, oxygen concentration, shear stress
Procedia PDF Downloads 2892275 Histopathological Features of Infections Caused by Fusarium equiseti (Mart.) Sacc. in Onion Plants from Kebbi State, Northern Nigeria
Authors: Wadzani Dauda Palnam, Alao S. Emmanuel Laykay, Afiniki Bawa Zarafi, Olufunmilola Alabi, Dora N. Iortsuun
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Onion production is affected by several diseases including fusariosis. Study was conducted to investigate the histopathological features of different onion tissues infected with Fusarium equiseti by inoculation with soil drench, root dip and mycelia paste methods. This was carried out by fixation, dehydration, clearing, wax embedding, sectioning, staining and mounting of leaf and root sections for microscopical examination at 400x. Once infection occurred in the roots, the pathogen moved through the vascular system to colonize the whole plant. At first, it grew in the intercellular spaces of the root cortex but soon invaded the cells, followed by colonization of the cells by its hyphae and microconidia. At later stages of infection, the cortex tissue became completely disorganized and decomposed as the pathogen advance to the shoot system via the vessel elements; this may be responsible for the early wilting symptom of infected plants arising from the severe water stress due to blockage of the xylem tissues.Keywords: onion, histopathology, infection, fusaria, inoculation
Procedia PDF Downloads 2782274 Cancer Stem Cell-Associated Serum Proteins Obtained by Maldi TOF/TOF Mass Spectrometry in Women with Triple-Negative Breast Cancer
Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso
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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells
Procedia PDF Downloads 2152273 Wood Dust and Nanoparticle Exposure among Workers during a New Building Construction
Authors: Atin Adhikari, Aniruddha Mitra, Abbas Rashidi, Imaobong Ekpo, Jefferson Doehling, Alexis Pawlak, Shane Lewis, Jacob Schwartz
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Building constructions in the US involve numerous wooden structures. Woods are routinely used in walls, framing floors, framing stairs, and making of landings in building constructions. Cross-laminated timbers are currently being used as construction materials for tall buildings. Numerous workers are involved in these timber based constructions, and wood dust is one of the most common occupational exposures for them. Wood dust is a complex substance composed of cellulose, polyoses and other substances. According to US OSHA, exposure to wood dust is associated with a variety of adverse health effects among workers, including dermatitis, allergic respiratory effects, mucosal and nonallergic respiratory effects, and cancers. The amount and size of particles released as wood dust differ according to the operations performed on woods. For example, shattering of wood during sanding operations produces finer particles than does chipping in sawing and milling industries. To our knowledge, how shattering, cutting and sanding of woods and wood slabs during new building construction release fine particles and nanoparticles are largely unknown. General belief is that the dust generated during timber cutting and sanding tasks are mostly large particles. Consequently, little attention has been given to the generated submicron ultrafine and nanoparticles and their exposure levels. These data are, however, critically important because recent laboratory studies have demonstrated cytotoxicity of nanoparticles on lung epithelial cells. The above-described knowledge gaps were addressed in this study by a novel newly developed nanoparticle monitor and conventional particle counters. This study was conducted in a large new building construction site in southern Georgia primarily during the framing of wooden side walls, inner partition walls, and landings. Exposure levels of nanoparticles (n = 10) were measured by a newly developed nanoparticle counter (TSI NanoScan SMPS Model 3910) at four different distances (5, 10, 15, and 30 m) from the work location. Other airborne particles (number of particles/m3) including PM2.5 and PM10 were monitored using a 6-channel (0.3, 0.5, 1.0, 2.5, 5.0 and 10 µm) particle counter at 15 m, 30 m, and 75 m distances at both upwind and downwind directions. Mass concentration of PM2.5 and PM10 (µg/m³) were measured by using a DustTrak Aerosol Monitor. Temperature and relative humidity levels were recorded. Wind velocity was measured by a hot wire anemometer. Concentration ranges of nanoparticles of 13 particle sizes were: 11.5 nm: 221 – 816/cm³; 15.4 nm: 696 – 1735/cm³; 20.5 nm: 879 – 1957/cm³; 27.4 nm: 1164 – 2903/cm³; 36.5 nm: 1138 – 2640/cm³; 48.7 nm: 938 – 1650/cm³; 64.9 nm: 759 – 1284/cm³; 86.6 nm: 705 – 1019/cm³; 115.5 nm: 494 – 1031/cm³; 154 nm: 417 – 806/cm³; 205.4 nm: 240 – 471/cm³; 273.8 nm: 45 – 92/cm³; and 365.2 nm:2272 Experimental Investigation Of Membrane Performance
Authors: Ali Serhat Ersoyoğlu, Kevser Dincer, Salih Yayla, Derya Saygılı
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In this study, performance of membrane was experimentally investigated. A solution having 1,5 gr Yttria-Stabilized Zirconia (YSZ)+ 10 mL methanol was prepared. This solution was taken out and filled into a spinning syringe. 6 grill-shaped wires having the sizes of 2x2 cm2’were cladded with YSZ + methanol solution by using the spinning method. After coating, the grill-shaped wires were left to dry. The dry wires were then weighed on a precision scale to determine the amount of coating imposed. The grill-shaped wires were mounted on the anode side of the PEM fuel cell membrane. Effects of the coating on the wires on current, power and resistance performances in the PEM fuel cells were determined experimentally and compared for every case. The highest current occurred at the 1st second on current #1, while the lowest current occurred at the 1171th second on current #6. The highest resistance was recorded at the 1171th second on resistance # 6, the lowest occurred at the 1st second on resistance # 1, whereas the highest power took place at the 1st second on power #1, the lowest power appeared at the 1171th second on power #5.Keywords: membrane, electro-spinning method, Yttria-Stabilized Zirconia, fuel cells
Procedia PDF Downloads 3702271 Psychogeographic Analysis of Campus Design: Spatial Appropriation via Walking Practice in the Cases of Van Yüzüncü Yıl University and Ankara Middle East Technical University in Turkey
Authors: Yasemin İlkay
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Street is not only a crucial spatial unit in urban design and planning discipline but also the context of walking practice in urban space. Moreover, psychogeography concentrates on both ‘walking’ and, therefore, the differentiated forms of (urban) streets to examine the influence of the built environment on the feelings and attitudes of human beings. This paper focuses on ‘walking practice’ in university campuses with reference to spatial appropriation forms via a psychogeographic lens on the phenomenon of alle in two different cities of Turkey, Ankara, the capital city, and Van, in the eastern part of the country. Alle, as an extension of ‘street’ in university campuses, is the constructive spatial structure in university campuses, and as a result, it should be the (both physical and mental) spine of design policy while conceiving and constructing a university campus. The main question of the paper is: How does the interrelation of ‘campus design’ and ‘walking practice’ on alle penetrate reciprocally on the spatial representations of citizens within their urban daily lives. The body contacts with and at urban space (with other objects and subjects) via its movements and stops; this interaction occurs through the spatial pattern of occupancy and vacancy. Walking practice leads to a set of cognitive mental representations in relation to the repertoire of place attachment and spatial appropriation. University campuses are autonomous and fruitful urban spaces to investigate such an interaction. There are both physical/real and psychogeographic representations of the same urban spaces and urban spatial practices. This separation would indicate the invisible dimensions of the difference between ‘what is conceived’ and ‘what is perceived.’ This study aims to compare and contrast the role of alle in both campus design and spatial appropriation via walking at two differentiated university campuses by collecting the mental representations, doing in-depth interviews, and attending walks with the interviewees by psychogeographic techniques. Campus design and spatial appropriation will be compared [with reference to the conception and perception of alle] in three scales: (1) the historical spatial development stories and design approaches of university campuses, (2) the spatial pattern of campuses on the basis of alle, and (3) sub-behavioral regions of the alle in campuses in relation with mental representations and psychogeographic attentive walks. The sub-questions of the research are: [1] How and why do the design approaches differentiate in two university campuses in Turkey, [2] How the interrelation among alle design and spatial appropriation differs in these two cases, and [3] What do the differentiated gaps among real and psychographic maps indicate about the design and spatial appropriation interrelation. METU, as a well-designed, readable campus with its alle, promise a rich walking practice with in-depth and fruitful spatial appropriation regions; however, Van YYÜ limits both the practice and place attachment with its partial design with an alle which is later added to the campus. This research both displays the role of alle in the campus design, walking practice and spatial appropriation and opens a new methodological path to discover hidden knowledge within urban spaces.Keywords: alle, campus design, cognitive geography, psychogeography, spatial appropriation, Turkey
Procedia PDF Downloads 1052270 Application of Computational Fluid Dynamics in the Analysis of Water Flow in Rice Leaves
Authors: Marcio Mesquita, Diogo Henrique Morato de Moraes, Henrique Fonseca Elias de Oliveira, Rilner Alves Flores, Mateus Rodrigues Ferreira, Dalva Graciano Ribeiro
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This study aimed to analyze the movement of water in irrigated and non-irrigated rice (Oryza sativa L.) leaves, from the xylem to the stomata, through numerical simulations. Through three-dimensional modeling, it was possible to determine how the spacing of parenchyma cells and the permeability of these cells influence the apoplastic flow and the opening of the stomata. The thickness of the cuticle and the number of vascular bundles are greater in plants subjected to water stress, indicating an adaptive response of plants to environments with water deficit. In addition, numerical simulations revealed that the opening of the stomata, the permeability of the parenchyma cells and the cell spacing have significant impacts on the energy loss and the speed of water movement. It was observed that a more open stoma facilitates water flow, decreasing the resistance and energy required for transport, while higher levels of permeability reduce energy loss, indicating that a more permeable tissue allows for more efficient water transport. Furthermore, it was possible to note that stomatal aperture, parenchyma permeability and cell spacing are crucial factors in the efficient water management of plants, especially under water stress conditions. These insights are essential for the development of more effective agricultural management strategies and for the breeding of plant varieties that are more resistant to adverse growing conditions. Computed fluid dynamics has allowed us to overcome the limitations of conventional techniques by providing a means to visualize and understand the complex hydrodynamic processes within the vascular system of plants.Keywords: numerical modeling, vascular anatomy, vascular hydrodynamics, xylem, Oryza sativa L.
Procedia PDF Downloads 172269 The Extent of Proliferation, Apoptosis and Angiogenesis at the Site of Injury Determine the Course of Healing Either as Scar Free or as Scarred One in the Appendages of Lizard
Authors: Isha Ranadive, Sonam Patel, Suresh Balakrishnan
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It has been observed that in lizards wound can be healed by either a scar free mechanism or by scarring. The animal model used to study both these healing processes was Northern House Gecko. In lizard, the tail when amputated heals by scar free mechanism which allows it to regenerate, the same is not seen when the limb is amputated. Proliferation, apoptosis, and angiogenesis are the main events which succeed an injury. We observed that proliferation of the cells beneath the wound epidermis was much higher in case of wound healing in tail. This could be because after the wound gets covered by the epithelium, it enters in to a cross-talk with the underlying mesenchyme to recruit a pool of blastemal cells which proliferate and later differentiate to form the lost part through epimorphic regeneration. This was substantiated by mRNA expression levels of various FGFs which facilitate the cross-talk and also by PCNA which is a marker for proliferation. Western blot result reaffirms the same notion. However, in case of the limb, the rate of apoptosis was more than proliferation as there are a lot of debris that needs to be removed. We came to this conclusion as we observed that p53 the apoptotic gene was highly upregulated in case of the scarred tissue. Further, we confirmed this result by checking the anti-apoptotic gene bcl2 and found it to be significantly down-regulated. As we noticed heightened proliferation in the case of scar-free wound healing in tail, angiogenesis was targeted for the study. This is because, when the cells are proliferating they require constant supply of blood and hence neo-vascularization is inevitable. It was observed that the marker of angiogenesis, VEGF, was expressed more during wound healing as compared to the resting stage of tail. Moreover, a high up-regulation was seen in KDR, a receptor of VEGF. Thus, this study reveals how proliferation, apoptosis, and angiogenesis play a key role in the scar-free as well as scarred wound healing.Keywords: epimorphic regeneration, injury, northern house gecko, wound healing
Procedia PDF Downloads 2452268 Emotion Regulation Mediates the Relationship between Affective Disposition and Depression
Authors: Valentina Colonnello, Paolo Maria Russo
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Studies indicate a link between individual differences in affective disposition and depression, as well as between emotion dysregulation and depression. However, the specific role of emotion dysregulation domains in mediating the relationship between affective disposition and depression remains largely unexplored. In three cross-sectional quantitative studies (total n = 1350), we explored the extent to which specific emotion regulation difficulties mediate the relationship between personal distress disposition (Study 1), separation distress as a primary emotional trait (Study 2), and an insecure, anxious attachment style (Study 3) and depression. Across all studies, we found that the relationship between affective disposition and depression was mediated by difficulties in accessing adaptive emotion regulation strategies. These findings underscore the potential for modifiable abilities that could be targeted through preventive interventions.Keywords: emotions, mental health, individual traits, personality
Procedia PDF Downloads 662267 Hexahydropyrimidine-2,4-Diones: Synthesis and Cytotoxic Activity
Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan
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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay
Procedia PDF Downloads 1522266 Study of the Combinatorial Impact of Substrate Properties on Mesenchymal Stem Cell Migration Using Microfluidics
Authors: Nishanth Venugopal Menon, Chuah Yon Jin, Samantha Phey, Wu Yingnan, Zhang Ying, Vincent Chan, Kang Yuejun
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Cell Migration is a vital phenomenon that the cells undergo in various physiological processes like wound healing, disease progression, embryogenesis, etc. Cell migration depends primarily on the chemical and physical cues available in the cellular environment. The chemical cue involves the chemokines secreted and gradients generated in the environment while physical cues indicate the impact of matrix properties like nanotopography and stiffness on the cells. Mesenchymal Stem Cells (MSCs) have been shown to have a role wound healing in vivo and its migration to the site of the wound has been shown to have a therapeutic effect. In the field of stem cell based tissue regeneration of bones and cartilage, one approach has been to introduce scaffold laden with MSCs into the site of injury to enable tissue regeneration. In this work, we have studied the combinatorial impact of the substrate physical properties on MSC migration. A microfluidic in vitro model was created to perform the migration studies. The microfluidic model used is a three compartment device consisting of two cell seeding compartments and one migration compartment. Four different PDMS substrates with varying substrate roughness, stiffness and hydrophobicity were created. Its surface roughness and stiffness was measured using Atomic Force Microscopy (AFM) while its hydrphobicity was measured from the water contact angle using an optical tensiometer. These PDMS substrates are sealed to the microfluidic chip following which the MSCs are seeded and the cell migration is studied over the period of a week. Cell migration was quantified using fluorescence imaging of the cytoskeleton (F-actin) to find out the area covered by the cells inside the migration compartment. The impact of adhesion proteins on cell migration was also quantified using a real-time polymerase chain reaction (qRT PCR). These results suggested that the optimal substrate for cell migration would be one with an intermediate level of roughness, stiffness and hydrophobicity. A higher or lower value of these properties affected cell migration negatively. These observations have helped us in understanding that different substrate properties need to be considered in tandem, especially while designing scaffolds for tissue regeneration as cell migration is normally impacted by the combinatorial impact of the matrix. These observations may lead us to scaffold optimization in future tissue regeneration applications.Keywords: cell migration, microfluidics, in vitro model, stem cell migration, scaffold, substrate properties
Procedia PDF Downloads 5572265 Guided Information Campaigns for Counter-Terrorism: Behavioral Approach to Interventions Regarding Polarized Societal Network
Authors: Joshua Midha
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The basis for information campaigns and behavioral interventions has long reigned as a tactic. From the Soviet-era propaganda machines to the opinion hijacks in Iran, these measures are now commonplace and are used for dissemination and disassembly. However, the use of these tools for strategic diffusion, specifically in a counter-terrorism setting, has only been explored on the surface. This paper aims to introduce a larger conceptual portion of guided information campaigns into preexisting terror cells and situations. It provides an alternative, low-risk intervention platform for future military strategy. This paper highlights a theoretical framework to lay out the foundationary details and explanations for behavioral interventions and moves into using a case study to highlight the possibility of implementation. It details strategies, resources, circumstances, and risk factors for intervention. It also sets an expanding foundation for offensive PsyOps and argues for tactical diffusion of information to battle extremist sentiment. The two larger frameworks touch on the internal spread of information within terror cells and external political sway, thus charting a larger holistic purpose of strategic operations.Keywords: terrorism, behavioral intervention, propaganda, SNA, extremism
Procedia PDF Downloads 952264 DNA Fragmentation and Apoptosis in Human Colorectal Cancer Cell Lines by Sesamum indicum Dried Seeds
Authors: Mohd Farooq Naqshbandi
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The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer
Procedia PDF Downloads 882263 Oxidative Stress Related Alteration of Mitochondrial Dynamics in Cellular Models
Authors: Orsolya Horvath, Laszlo Deres, Krisztian Eros, Katalin Ordog, Tamas Habon, Balazs Sumegi, Kalman Toth, Robert Halmosi
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Introduction: Oxidative stress induces an imbalance in mitochondrial fusion and fission processes, finally leading to cell death. The two antioxidant molecules, BGP-15 and L2286 have beneficial effects on mitochondrial functions and on cellular oxidative stress response. In this work, we studied the effects of these compounds on the processes of mitochondrial quality control. Methods: We used H9c2 cardiomyoblast and isolated neonatal rat cardiomyocytes (NRCM) for the experiments. The concentration of stressors and antioxidants was beforehand determined with MTT test. We applied 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) in 125 µM, 400 µM and 800 µM concentrations for 4 and 8 hours on H9c2 cells. H₂O₂ was applied in 150 µM and 300 µM concentration for 0.5 and 4 hours on both models. L2286 was administered in 10 µM, while BGP-15 in 50 µM doses. Cellular levels of the key proteins playing role in mitochondrial dynamics were measured in Western blot samples. For the analysis of mitochondrial network dynamics, we applied electron microscopy and immunocytochemistry. Results: Due to MNNG treatment the level of fusion proteins (OPA1, MFN2) decreased, while the level of fission protein DRP1 elevated markedly. The levels of fusion proteins OPA1 and MNF2 increased in the L2286 and BGP-15 treated groups. During the 8 hour treatment period, the level of DRP1 also increased in the treated cells (p < 0.05). In the H₂O₂ stressed cells, administration of L2286 increased the level of OPA1 in both H9c2 and NRCM models. MFN2 levels in isolated neonatal rat cardiomyocytes raised considerably due to BGP-15 treatment (p < 0.05). L2286 administration decreased the DRP1 level in H9c2 cells (p < 0.05). We observed that the H₂O₂-induced mitochondrial fragmentation could be decreased by L2286 treatment. Conclusion: Our results indicated that the PARP-inhibitor L2286 has beneficial effect on mitochondrial dynamics during oxidative stress scenario, and also in the case of directly induced DNA damage. We could make the similar conclusions in case of BGP-15 administration, which, via reducing ROS accumulation, propagates fusion processes, this way aids preserving cellular viability. Funding: GINOP-2.3.2-15-2016-00049; GINOP-2.3.2-15-2016-00048; GINOP-2.3.3-15-2016-00025; EFOP-3.6.1-16-2016-00004; ÚNKP-17-4-I-PTE-209Keywords: H9c2, mitochondrial dynamics, neonatal rat cardiomyocytes, oxidative stress
Procedia PDF Downloads 1522262 Inactivation of Semicarbazide-Sensitive Amine Oxidase Induces the Phenotypic Switch of Smooth Muscle Cells and Aggravates the Development of Atherosclerotic Lesions
Authors: Miao Zhang, Limin Liu, Feng Zhi, Panpan Niu, Mengya Yang, Xuemei Zhu, Ying Diao, Jun Wang, Ying Zhao
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Background and Aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p=0.0043) and advanced (1.8-fold, p=0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ~0.74-fold, p=0.0002(early)/0.0016(advanced); SMC: ~1.55-fold, p=0.0003(early) /0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p=0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.Keywords: atherosclerosis, phenotype switch of smooth muscle cells, SSAO/VAP-1, semicarbazide
Procedia PDF Downloads 3292261 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity
Authors: Nigatu Tadesse, Li Juan, Liuhong Ming
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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase
Procedia PDF Downloads 482260 Self-Assembled Nano Aggregates Based On Polyaspartamide Graft Copolymers for pH-Controlled Release of Doxorubicin
Authors: Van Tran Thi Thuy, Cheol Won Lim, Dukjoon Kim
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A series of biodegradable copolymers based on polyaspartamide (PASPAM) were synthesized by grafting hydrophilic O-(2-aminoethyl)-O'-methylpoly(ethylene glycol) (MPEG), hydrophobic cholic acid (CA), and pH-sensitive hydrazine (Hyd) segments on a PASPAM backbone. The hydrazine group was effectively cleaved to release doxorubicin (DOX) conjugated on PASPAM in an acidic environment. The chemical structure of the polymer and the degree of substitution of each graft segment were analyzed using FT-IR and 1H-NMR spectroscopy. The size of the MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates was examined by dynamic light scattering (DLS) and transmission electron microscope (TEM). The mean diameter of the self - aggregates increased from 125 to 200 nm at pH 7.4, as the degree of substitution of CA increased from 10 to 20 %. The release kinetics of DOX was strongly affected by the pH of the releasing medium. While less than 30% of the DOX-loaded was released in about 30 h at pH 7.4, more than 60% was released at pH 5.0 within the same time. The viability tests of human breast cancer cells (MCF-7) and human embryonic kidney cells (293T) show the potential application of MPEG/Hyd/CA-g-PASPAM copolymer self-aggregates in the controlled intracellular delivery for cancer treatments.Keywords: pH-sensitive, drug delivery, polyaspartamide, self-assembly, nano-aggregates
Procedia PDF Downloads 3582259 Quantum Dots Incorporated in Biomembrane Models for Cancer Marker
Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli
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Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces
Procedia PDF Downloads 1962258 Enhanced Enzymes Production through Immobilization of Filamentous Fungi
Authors: Zhanara B. Suleimenova, Zhazira K. Saduyeva
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Filamentous fungi are major producers of enzymes that have important applications in the food and beverage industries. The overall objective of this research is a strain improvement technology for efficient industrial enzymes production. The new way of filamentous fungi cultivation method has been developed. Such technology prolong producers’ cultivation period up to 60 days and create the opportunity to obtain enzymes repeatedly in every 2-3 days of fungal cultivation. This method is based on immobilizing enzymes producers with solid support in submerged conditions of growth. Immobilizing has a range of advantages: Decreasing the price of the final product, absence of foreign substances, controlled process of enzyme-genesis, ability of various enzymes simultaneous production, etc. Design of proposed technology gives the opportunity to increase the activity of immobilized cells culture filtrate comparing to free cells, growing in periodic culture conditions. Thus, proposed research focuses on new, more versatile, microorganisms capable of squeezing more end-products as well as proposed cultivation technology led to increased enzymatic productivity by several times.Keywords: filamentous fungi, immobilization, industrial enzymes production, strain improvement
Procedia PDF Downloads 3602257 Modeling the Intricate Relationship between miRNA Dysregulation and Breast Cancer Development
Authors: Sajed Sarabandi, Mostafa Rostampour Vajari
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Breast cancer is the most frequent form of cancer among women and the fifth-leading cause of cancer-related deaths. A common feature of cancer cells is their ability to survive and evade apoptosis. Understanding the mechanisms of these pathways and their regulatory factors can lead to the development of effective treatment strategies. In this study, we aim to model the effect of key miRNAs, which are significant regulatory factors in breast cancer. We designed a Petri net focusing on two crucial pathways, proliferation, and apoptosis, and identified the role of miRNAs in these pathways. Our analysis indicates that the upregulation of miRNAs 99a and 372 can effectively increase apoptosis and decrease proliferation. Moreover, we demonstrate that miRNA-600, previously reported as a potential candidate for treatment, may not be a suitable target due to its dual activity in proliferation. Therefore, further research is required to investigate the potential of this miRNA in cancer treatment. Our model shows that a combination of miRNA upregulation and knockdown can efficiently influence key genes such as MDM2 and PTEN, leading to the activation of apoptosis in cancer cells. Ultimately, our model successfully simulates the connection between regulatory miRNAs and key genes in breast cancer.Keywords: breast cancer, microRNAs, bio-modeling, Petri net
Procedia PDF Downloads 292256 Cytotoxicity of a Short Chain Fatty Acid Histone Deactylase Inhibitor on HCT116 Human Colorectal Carcinoma Cell Line
Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar
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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT
Procedia PDF Downloads 3612255 Effect of Long-Term Boron Exposure on Liver Structure of Adult Male Albino Rats and a Possible Role of Vitamin C
Authors: Ola Abdel-Tawab Hussein
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Background: Boron is a naturally occurring agent and an essential trace element of human, animals and higher plants. It is released in the form of boric acid (BA) that is water soluble and biolologically available. Its largest uses are in glass, detergents, agriculture, leather tanning industries, cosmetics, photographic materials, soaps and cleaners. Human consume daily few milligrams in the water, fruits and vegetables. High doses of boron had been recorded to be developmental and reproductive toxin in animals(Only few studies on human had investigated the health effects associated with exposure to boron. Vitamin C is a major water soluble non-enzymatic antioxidant, acts to overcome the oxidative stress. Aim of the work: However , the liver is exposed to toxic substances that are absorbed, degraded or conjugated there were little information exists about the effects of boron that it would specifically have in the liver tissue of experimental rats. So the present work aimed to study the effects of long-term boron ingestion on histological structural of the liver of adult male albino rats and to evaluate the protective role of vitamin C against induced changes. Material and Methods: 30 adult male albino rats were divided into 3 equal groups; Group I: control, Group II: recieved drinking water containing 55x10-6 gm boron/liter for 90 days and Group III: recieved vitamin C (200mg/Kg.B.W) orally concomitant with boron for the same period. liver specimens were processed for light and electron microscopic(TEM) study. Results: Examination of the liver sections of group II revealed foci of severe dilatation and congestion of central and portal veins with mononuclear cellular infiltration and hepatocellular vacuolation. Increased collagen deposition specially around the portal areas. Marked electrolucent areas in the cytoplasm, heterochromatic nuclei and destroyed organelles of the hepatocytes. Apoptotic cells were observed and decreased lipid content of ito cells. In Group III the co administration of vitamin C improved most of the structural changes of the hepatocytes, Ito cells, increased binucleated cells and decreased collagen fibers deposition. Conclusion: Thus, the long term exposure to boron, induced histological changes on the structure of liver. The co administration of vitamin C improved most of these structural changes.Keywords: boron, liver, vitamin C, rats
Procedia PDF Downloads 3462254 The Cleavage of DNA by the Anti-Tumor Drug Bleomycin at the Transcription Start Sites of Human Genes Using Genome-Wide Techniques
Authors: Vincent Murray
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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing
Procedia PDF Downloads 1202253 Red Blood Cells Deformability: A Chaotic Process
Authors: Ana M. Korol, Bibiana Riquelme, Osvaldo A. Rosso
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Since erythrocyte deformability analysis is mostly qualitative, the development of quantitative nonlinear methods is crucial for restricting subjectivity in the study of cell behaviour. An electro-optic mechanic system called erythrodeformeter has been developed and constructed in our laboratory in order to evaluate the erythrocytes' viscoelasticity. A numerical method formulated on the basis of fractal approximation for ordinary (OBM) and fractionary Brownian motion (FBM), as well as wavelet transform analysis, are proposed to distinguish chaos from noise based on the assumption that diffractometric data involves both deterministic and stochastic components, so it could be modelled as a system of bounded correlated random walk. Here we report studies on 25 donors: 4 alpha thalassaemic patients, 11 beta thalassaemic patients, and 10 healthy controls non-alcoholic and non-smoker individuals. The Correlation Coefficient, a nonlinear parameter, showed evidence of the changes in the erythrocyte deformability; the Wavelet Entropy could quantify those differences which are detected by the light diffraction patterns. Such quantifiers allow a good deal of promise and the possibility of a better understanding of the rheological erythrocytes aspects and also could help in clinical diagnosis.Keywords: red blood cells, deformability, nonlinear dynamics, chaos theory, wavelet trannsform
Procedia PDF Downloads 592252 A 4-Month Low-carb Nutrition Intervention Study Aimed to Demonstrate the Significance of Addressing Insulin Resistance in 2 Subjects with Type-2 Diabetes for Better Management
Authors: Shashikant Iyengar, Jasmeet Kaur, Anup Singh, Arun Kumar, Ira Sahay
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Insulin resistance (IR) is a condition that occurs when cells in the body become less responsive to insulin, leading to higher levels of both insulin and glucose in the blood. This condition is linked to metabolic syndromes, including diabetes. It is crucial to address IR promptly after diagnosis to prevent long-term complications associated with high insulin and high blood glucose. This four-month case study highlights the importance of treating the underlying condition to manage diabetes effectively. Insulin is essential for regulating blood sugar levels by facilitating the uptake of glucose into cells for energy or storage. In IR individuals, cells are less efficient at taking up glucose from the blood resulting in elevated blood glucose levels. As a result of IR, beta cells produce more insulin to make up for the body's inability to use insulin effectively. This leads to high insulin levels, a condition known as hyperinsulinemia, which further impairs glucose metabolism and can contribute to various chronic diseases. In addition to regulating blood glucose, insulin has anti-catabolic effects, preventing the breakdown of molecules in the body, such as inhibiting glycogen breakdown in the liver, inhibiting gluconeogenesis, and inhibiting lipolysis. If a person is insulin-sensitive or metabolically healthy, an optimal level of insulin prevents fat cells from releasing fat and promotes the storage of glucose and fat in the body. Thus optimal insulin levels are crucial for maintaining energy balance and plays a key role in metabolic processes. During the four-month study, researchers looked at the impact of a low-carb dietary (LCD) intervention on two male individuals (A & B) who had Type-2 diabetes. Althoughvneither of these individuals were obese, they were both slightly overweight and had abdominal fat deposits. Before the trial began, important markers such as fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, and Hba1c were measured. These markers are essential in defining metabolic health, their individual values and variability are integral in deciphering metabolic health. The ratio of TG to HDL is used as a surrogate marker for IR. This ratio has a high correlation with the prevalence of metabolic syndrome and with IR itself. It is a convenient measure because it can be calculated from a standard lipid profile and does not require more complex tests. In this four-month trial, an improvement in insulin sensitivity was observed through the ratio of TG/HDL, which, in turn, improves fasting blood glucose levels and HbA1c. For subject A, HbA1c dropped from 13 to 6.28, and for subject B, it dropped from 9.4 to 5.7. During the trial, neither of the subjects were taking any diabetic medications. The significant improvements in their health markers, such as better glucose control, along with an increase in energy levels, demonstrate that incorporating LCD interventions can effectively manage diabetes.Keywords: metabolic disorder, insulin resistance, type-2 diabetes, low-carb nutrition
Procedia PDF Downloads 402251 Electrospinning in situ Synthesis of Graphene-Doped Copper Indium Disulfide Composite Nanofibers for Efficient Counter Electrode in Dye-Sensitized Solar Cells
Authors: Lidan Wang, Shuyuan Zhao, Jianxin He
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In this paper, graphene-doped copper indium disulfide (rGO+CuInS2) composite nanofibers were fabricated via electrospinning, in situ synthesis, and carbonization, using polyvinyl pyrrolidone (PVP), copper dichloride (CuCl2), indium trichloride (InCl3), thiourea (C2H5NS) and graphene oxide nanosheets (Go) as the precursor solution for electrospinning. The average diameter of rGO+CuInS2 nanofibers were about 100 nm, and graphene nanosheets anchored with chalcopyrite CuInS2 nanocrystals 8-15 nm in diameter were overlapped and embedded, aligning along the fiber axial direction. The DSSC with a rGO+CuInS2 counter electrode exhibits a power conversion efficiency of 5.93%; better than the corresponding values for a DSSC with a CuInS2 counter electrode, and comparable to that of a reference DSSC with a Pt counter electrode. The excellent photoelectric performance of the rGO+CuInS2 counter electrode was attributed to its high specific surface area, which facilitated permeation of the liquid electrolytes, promoted electron and ion transfer and provided numerous catalytically active sites for the oxidation reaction of the electrolytic (I- /I3-).Keywords: dye-sensitized solar cells, counter electrode, electrospinning, graphene
Procedia PDF Downloads 4572250 Effect of Wheat Germ Agglutinin- and Lactoferrin-Grafted Catanionic Solid Lipid Nanoparticles on Targeting Delivery of Etoposide to Glioblastoma Multiforme
Authors: Yung-Chih Kuo, I-Hsin Wang
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Catanionic solid lipid nanoparticles (CASLNs) with surface wheat germ agglutinin (WGA) and lactoferrin (Lf) were formulated for entrapping and releasing etoposide (ETP), crossing the blood–brain barrier (BBB), and inhibiting the growth of glioblastoma multiforme (GBM). Microemulsified ETP-CASLNs were modified with WGA and Lf for permeating a cultured monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and for treating malignant U87MG cells. Experimental evidence revealed that an increase in the concentration of catanionic surfactant from 5 μM to 7.5 μM reduced the particle size. When the concentration of catanionic surfactant increased from 7.5 μM to 12.5 μM, the particle size increased, yielding a minimal diameter of WGA-Lf-ETP-CASLNs at 7.5 μM of catanionic surfactant. An increase in the weight percentage of BW from 25% to 75% enlarged WGA-Lf-ETP-CASLNs. In addition, an increase in the concentration of catanionic surfactant from 5 to 15 μM increased the absolute value of zeta potential of WGA-Lf-ETP-CASLNs. It was intriguing that the increment of the charge as a function of the concentration of catanionic surfactant was approximately linear. WGA-Lf-ETP-CASLNs revealed an integral structure with smooth particle contour, displayed a lighter exterior layer of catanionic surfactant, WGA, and Lf and showed a rigid interior region of solid lipids. A variation in the concentration of catanionic surfactant between 5 μM and 15 μM yielded a maximal encapsulation efficiency of ETP ata 7.5 μM of catanionic surfactant. An increase in the concentration of Lf/WGA decreased the grafting efficiency of Lf/WGA. Also, an increase in the weight percentage of ETP decreased its encapsulation efficiency. Moreover, the release rate of ETP from WGA-Lf-ETP-CASLNs reduced with increasing concentration of catanionic surfactant, and WGA-Lf-ETP-CASLNs at 12.5 μM of catanionic surfactant exhibited a feature of sustained release. The order in the viability of HBMECs was ETP-CASLNs ≅ Lf-ETP-CASLNs ≅ WGA-Lf-ETP-CASLNs > ETP. The variation in the transendothelial electrical resistance (TEER) and permeability of propidium iodide (PI) was negligible when the concentration of Lf increased. Furthermore, an increase in the concentration of WGA from 0.2 to 0.6 mg/mL insignificantly altered the TEER and permeability of PI. When the concentration of Lf increased from 2.5 to 7.5 μg/mL and the concentration of WGA increased from 2.5 to 5 μg/mL, the enhancement in the permeability of ETP was minor. However, 10 μg/mL of Lf promoted the permeability of ETP using Lf-ETP-CASLNs, and 5 and 10 μg/mL of WGA could considerably improve the permeability of ETP using WGA-Lf-ETP-CASLNs. The order in the efficacy of inhibiting U87MG cells was WGA-Lf-ETP-CASLNs > Lf-ETP-CASLNs > ETP-CASLNs > ETP. As a result, WGA-Lf-ETP-CASLNs reduced the TEER, enhanced the permeability of PI, induced a minor cytotoxicity to HBMECs, increased the permeability of ETP across the BBB, and improved the antiproliferative efficacy of U87MG cells. The grafting of WGA and Lf is crucial to control the medicinal property of ETP-CASLNs and WGA-Lf-ETP-CASLNs can be promising colloidal carriers in GBM management.Keywords: catanionic solid lipid nanoparticle, etoposide, glioblastoma multiforme, lactoferrin, wheat germ agglutinin
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