Search results for: counter-rotating cells

Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: A. Alhusban, M. Alqawasmeh, F. Alfawares

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Introduction: Despite improvements in stroke management, it remains the leading cause of disability worldwide. It has been suggested that enhancing brain angiogenesis after stroke will improve stroke outcome. Promoting post stroke angiogenesis requires the upregulation of angiogenic factors with a simultaneous reduction of anti-angiogenic factors. Thrombospondin-1 is the main anti-angiogenic protein in the living cells. Counterintuitively, it has been shown that animals with Thrombospondin-1 knockdown will have better stroke outcome. Data about the clinical significance of Thrombspondin-1 levels at the time of admission is still lacking. The objective of this work is to assess the association between serum Thrombospondin-1 levels measured at the time of admission and baseline neurologic severity after stroke. Patients and Methods: Blood samples were collected from patients admitted to the King Abdullah University Hospital (KAUH) with ischemic stroke at the time of admission and serum Thrombopsondin-1 levels were measured using ELISA. Patients neurologic severity was evaluated using the National Institute of Health Stroke Scale (NIHSS). Results: Samples from 50 patients admitted between January 2016 and December 2016 were collected. The median age of participants was 68 years and the median NIHSS was 3. Multinomial regression identified serum Thrombospondin-1 as an independent predictor of stroke outcome (p=0.003). Baseline serum Thrombsopondin-1 was negatively associated with NIHSS at the time of admission (spearman rho correlation coefficient=0.272, p=0.032). Conclusion: Serum Thrombospondin-1 at the time of admission may be a useful marker of stroke severity that predicts more severe neurologic severity.

Keywords: thrombospondin, stroke, neuroprotection, biomarkers

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Authors: Regina R. Gunawan, Indwiani Astuti, H. Raden Danarto

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Cancer is the leading cause of death worldwide. Cancer is caused by mutations that alter the function of normal human genes and give rise to cancer genes. MicroRNA (miRNA) is a small non-coding RNA that regulates the gen through complementary bond towards mRNA target and cause mRNA degradation. miRNA works by either promoting or suppressing cell proliferation. miRNA level expression in cancer may offer another value of miRNA as a biomarker in cancer diagnostic. miRNA-21 is believed to have a role in carcinogenesis by enhancing proliferation, anti-apoptosis, cell cycle progression and invasion of tumor cells. Hsa-miR-21-5p marker has been identified in Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patient’s urine. This research planned to explore the diagnostic performance of miR-21 to differentiate PCa and BPH patients. In this study, urine samples were collected from 20 PCa patients and 20 BPH patients. miR-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity with the contingency table. miR-21 relative expression against miR-16 in PCa patient and in BPH patient has 12,98 differences in fold change. From a contingency table of Cq expression of miR-21 in identifying PCa patients from BPH patient, Cq miR-21 has 100% sensitivity and 75% specificity. miR-21 relative expression can be used in discriminating PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity compared to PSA (Prostate specific antigen), therefore miR-21 has a high potential to be analyzed and developed more.

Keywords: benign prostate hyperplasia, biomarker, miRNA-21, prostate cancer

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Authors: Daniel Adjei, Mesfin Getachew Ayele, Przemyslaw Wachulak, Andrzej Bartnik, Luděk Vyšín, Henryk Fiedorowicz, Inam Ul Ahad, Lukasz Wegrzynski, Anna Wiechecka, Janusz Lekki, Wojciech M. Kwiatek

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Laser produced plasma light sources, emitting high intensity pulses of X-rays, delivering high doses are useful to understand the mechanisms of high dose effects on biological samples. In this study, a desk-top laser plasma soft X-ray source, developed for radio biology research, is presented. The source is based on a double-stream gas puff target, irradiated with a commercial Nd:YAG laser (EKSPLA), which generates laser pulses of 4 ns time duration and energy up to 800 mJ at 10 Hz repetition rate. The source has been optimized for maximum emission in the “water window” wavelength range from 2.3 nm to 4.4 nm by using pure gas (argon, nitrogen and krypton) and spectral filtering. Results of the source characterization measurements and dosimetry of the produced soft X-ray radiation are shown and discussed. The high brightness of the laser produced plasma soft X-ray source and the low penetration depth of the produced X-ray radiation in biological specimen allows a high dose rate to be delivered to the specimen of over 28 Gy/shot; and 280 Gy/s at the maximum repetition rate of the laser system. The source has a unique capability for irradiation of cells with high pulse dose both in vacuum and He-environment. Demonstration of the source to induce DNA double- and single strand breaks will be discussed.

Keywords: laser produced plasma, soft X-rays, radio biology experiments, dosimetry

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Authors: Ali Golestani, Vahid Naseri, Hossein Taheri

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Recently, some of studies examined the effect of exercise on neurotrophic factors influencing the growth, protection, plasticity and function in central and peripheral nerve cells. The aim of this study was to investigate the effects of continuous and interval aerobic exercises with moderate intensity on serum levels of glial cell line-derived neurotrophic factor (GDNF) and aerobic capacity in obese children. 21 obese students with an average age of 13.6 ± 0.5 height 171 ± 5 and BMI 32 ± 1.2 were divided randomly to control, continuous aerobic and interval aerobic groups. Training protocol included continuous or interval aerobic exercises with moderate intensity 50-65%MHR, three times per week for 10 weeks. 48 hours before and after executing of protocol, blood samples were taken from the participants and their GDNF serum levels were measured by ELISA. Aerobic power was estimated using Shuttle-run test. T-test results indicated a small increase in their GDNF serum levels, which was not statistically significant (p =0.11). In addition, the results of ANOVA did not show any significant difference between continuous and interval aerobic training on the serum levels of their GDNF but their aerobic capacity significantly increased (p =0.012). Although continuous and interval aerobic exercise improves aerobic power in obese children, they had no significant effect on their serum levels of GDNF.

Keywords: aerobic power, continuous aerobic training, glial cell line-derived neurotrophic factor (GDNF), interval aerobic training, obese children

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Authors: N. Prabavathy, R. Balasundaraprabhu, S. Shalini, Dhayalan Velauthapillai, S. Prasanna, N. Muthukumarasamy

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Dye sensitized solar cell (DSSC) has become a significant research area due to their fundamental and scientific importance in the area of energy conversion. Synthetic dyes as sensitizer in DSSC are efficient and durable but they are costlier, toxic and have the tendency to degrade. Natural sensitizers contain plant pigments such as anthocyanin, carotenoid, flavonoid, and chlorophyll which promote light absorption as well as injection of charges to the conduction band of TiO2 through the sensitizer. But, the efficiency of natural dyes is not up to the mark mainly due to instability of the pigment such as anthocyanin. The stability issues in vitro are mainly due to the effect of solvents on extraction of anthocyanins and their respective pH. Taking this factor into consideration, in the present work, the anthocyanins were extracted from the flower Caesalpinia pulcherrima (C. pulcherrimma) with various solvents and their respective stability and pH values are discussed. The usage of citric acid as solvent to extract anthocyanin has shown good stability than other solvents. It also helps in enhancing the sensitization properties of anthocyanins with Titanium dioxide (TiO2) nanorods. The IPCE spectra show higher photovoltaic performance for dye sensitized TiO2nanorods using citric acid as solvent. The natural DSSC using citric acid as solvent shows a higher efficiency compared to other solvents. Hence citric acid performs to be a safe solvent for natural DSSC in boosting the photovoltaic performance and maintaining the stability of anthocyanins.

Keywords: Caesalpinia pulcherrima, citric acid, dye sensitized solar cells, TiO₂ nanorods

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Authors: Erfan Niazi, Marianne Fenech

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Red Blood Cells (RBCs) or erythrocytes tend to form chain-like aggregates under low shear rate called rouleaux. This is a reversible process and rouleaux disaggregate in high shear rates. Therefore, RBCs aggregation occurs in the microcirculation where low shear rates are present but does not occur under normal physiological conditions in large arteries. Numerical modeling of RBCs interactions is fundamental in analytical models of a blood flow in microcirculation. Population Balance Modeling (PBM) is particularly useful for studying problems where particles agglomerate and break in a two phase flow systems to find flow characteristics. In this method, the elementary particles lose their individual identity due to continuous destructions and recreations by break-up and agglomeration. The aim of this study is to find RBCs aggregation in a dynamic situation. Simplified PBM was used previously to find the aggregation rate on a static observation of the RBCs aggregation in a drop of blood under the microscope. To find aggregation rate in a dynamic situation we propose an experimental set up testing RBCs sedimentation. In this test, RBCs interact and aggregate to form rouleaux. In this configuration, disaggregation can be neglected due to low shear stress. A high-speed camera is used to acquire video-microscopic pictures of the process. The sizes of the aggregates and velocity of sedimentation are extracted using an image processing techniques. Based on the data collection from 5 healthy human blood samples, the aggregation rate was estimated as 2.7x10³(±0.3 x10³) 1/s.

Keywords: red blood cell, rouleaux, microfluidics, image processing, population balance modeling

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Authors: Elhamalsadat Ghaffari, Moghan Amirhosseinian, Amir Khaleghipour

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Multifunctional bioactive glasses (BGs) are designed with a focus on the provision of bactericidal and biological properties desired for angiogenesis, osteogenesis, and ultimately potential applications in bone tissue engineering. To achieve these, six sol-gel copper/magnesium substituted derivatives of 58S-BG, i.e. a mol% series of 60SiO₂-4P₂O₅-5CuO-(31-x) CaO/xMgO (where x=0, 1, 3, 5, 8, and 10), were synthesized. Afterwards, the effect of MgO/CaO substitution on the in vitro formation of nano-hydroxyapatite (HA), osteoblast-like cell responses and BGs antibacterial performance were studied. During the BGs synthesis, the elimination of nitrates was achieved at 700 °C that prevented the BGs crystallization and stabilized the obtained dried gels. The structural and morphological evaluations were performed with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). These characterizations revealed that Cu-substituted 58S-BG consisting of 5 mol% MgO (BG-5/5) slightly had retarded the formation of HA. In addition, Cu-substituted 58S-BGs consisting 8 mol% and 10 mol% MgO (BG-5/8 and BG-5/10) displayed lower bioactivity probably due to the lower ion release rate of Ca–Si into the simulated body fluid (SBF). The determination of 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and alkaline phosphate (ALP) activities proved that the highest values of both differentiation and proliferation of MC3T3-E1 cells can be obtained from a 5 mol% MgO substituted BG, while the over addition of MgO (8 mol% and 10 mol%) decreased the bioactivity. Furthermore, these novel Cu/Mg-substituted 58S-BGs displayed antibacterial effect against methicillin-resistant Staphylococcus aureus bacteria. Taken together, the results suggest the equally-substituted BG-5/5 (i.e. the one consists of 5 mol% of both CuO and MgO) as a promising candidate for bone tissue engineering, among all newly designed BGs in this work, owing to its desirable cell proliferation, ALP activity and antibacterial properties.

Keywords: apatite, bioactivity, biomedical applications, sol-gel processes

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Authors: A. Elsayed, M. H. Dewaidar, M. Ghali

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We report on deposition of smooth, pinhole-free, low-surface roughness ( < 4nm) and high optical quality cadmium sulfide (CdS) thin films on glass substrates using our new method based on chemical surface deposition principle. In this method, cadmium acetate and thiourea are used as reactants under special growth conditions for deposition of CdS films. X-ray diffraction (XRD) measurements were used to examine the crystal structure properties of the deposited CdS films. In addition, UV-vis transmittance and low-temperature (4K) photoluminescence (PL) measurements were performed for quantifying optical properties of the deposited films. Interestingly, we found that XRD pattern of the deposited films has dramatically changed when the growth temperature was raised during the reaction. Namely, the XRD measurements reveal a structural change of CdS film from Cubic to Hexagonal phase upon increase in the growth temperature from 75 °C to 200 °C. Furthermore, the deposited films show high optical quality as confirmed from observation of both sharp edge in the transmittance spectra and strong PL intensity at room temperature. Also, we found a strong effect of the growth conditions on the optical band gap of the deposited films; where remarkable red-shift in the absorption edge with temperature is clearly seen in both transmission and PL spectra. Such tuning of both optical band gap and crystal structure of the deposited CdS films; can be utilized for tuning the electronic bands alignments between CdS and other light harvesting materials, like CuInGaSe or CdTe, for potential improvement in the efficiency of all-solution processed solar cells devices based on these heterostructures.

Keywords: thin film, CdS, new method, optical properties

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Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet

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Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.

Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation

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Authors: Fabrice Houngnandan, Celia Fery, Thomas Bockel, Julie Deter

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Getting water cleaner and stopping global biodiversity loss requires indices to measure changes and evaluate the achievement of objectives. The endemic and protected seagrass species Posidonia oceanica is a biological indicator used to monitor the ecological quality of marine Mediterranean waters. One ecosystem index (EBQI), two biotic indices (PREI, Bipo), and several landscape indices, which measure the composition and configuration of the P. oceanica seagrass at the population scale have been developed. While the formers are measured at monitoring sites, the landscape indices can be calculated for the entire seabed covered by this ecosystem. This present work aims to search on the link between these indices and the best scale to be used in order to maximize this link. We used data collected between 2014 to 2019 along the French Mediterranean coastline to calculate EBQI, PREI, and Bipo at 100 sites. From the P. oceanica seagrass distribution map, configuration and composition indices around these different sites in 6 different grid sizes (100 m x 100 to 1000 m x 1000 m) were determined. Correlation analyses were first used to find out the grid size presenting the strongest and most significant link between the different types of indices. Finally, several models were compared basis on various metrics to identify the one that best explains the nature of the link between these indices. Our results showed a strong and significant link between biotic indices and the best correlations between biotic and landscape indices within the 600 m x 600 m grid cells. These results showed that the use of landscape indices is possible to monitor the health of seagrass beds at a large scale.

Keywords: ecological indicators, decline, conservation, submerged aquatic vegetation

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Authors: Emil F. Khisamutdinov

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Development of functional materials undergoing structural transformations in response to an external stimulus such as environmental changes (pH, temperature, etc.), the presence of particular proteins, or short oligonucleotides are of great interest for a variety of applications ranging from medicine to electronics. The dynamic operations of most nucleic acid (NA) devices, including circuits, nano-machines, and biosensors, rely on networks of NA strand displacement processes in which an external or stimulus strand displaces a target strand from a DNA or RNA duplex. The rate of strand displacement can be greatly increased by the use of “toeholds,” single-stranded regions of the target complex to which the invading strand can bind to initiate the reaction, forming additional base pairs that provide a thermodynamic driving force for transformation. Herein, we developed a highly robust nanoparticle shape transition, sequentially transforming DNA polygons from one shape to another using the toehold-mediated DNA strand displacement technique. The shape transformation was confirmed by agarose gel electrophoresis and atomic force microscopy. Furthermore, we demonstrate that our approach is applicable for RNA shape transformation from triangle to square, which can be detected by fluorescence emission from malachite green binding RNA aptamer. Using gel-shift and fluorescence assays, we demonstrated efficient transformation occurs at isothermal conditions (37°C) that can be implemented within living cells as reporter molecules. This work is intended to provide a simple, cost-effective, and straightforward model for the development of biosensors and regulatory devices in nucleic acid nanotechnology.

Keywords: RNA nanotechnology, bionanotechnology, toehold mediated DNA switch, RNA split fluorogenic aptamers

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Authors: Dhruv J. Limaye, Hanga Galfalvy, Cheick A. Sissoko, Yung-yu Huang, Chunanning Tang, Ying Liu, Shu-Chi Hsiung, Andrew J. Dwork, Gorazd B. Rosoklija, Victoria Arango, Lewis Brown, J. John Mann, Maura Boldrini

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Memory and emotion require hippocampal cell viability and connectivity and are disrupted in major depressive disorder (MDD). Applying shotgun proteomics and stereological quantification of neural progenitor cells (NPCs), intermediate neural progenitors (INPs), and mature granule neurons (GNs), to postmortem human hippocampus, identified differentially expressed proteins (DEPs), and fewer NPCs, INPs and GNs, in untreated MDD (uMDD) compared with non-psychiatric controls (CTRL) and antidepressant-treated MDD (MDDT). DEPs lower in uMDD vs. CTRL promote mitosis, differentiation, and prevent apoptosis. DEPs higher in uMDD vs. CTRL inhibit the cell cycle, and regulate cell adhesion, neurite outgrowth, and DNA repair. DEPs lower in MDDT vs. uMDD block cell proliferation. We observe group-specific correlations between numbers of NPCs, INPs, and GNs and an abundance of proteins regulating mitosis, differentiation, and apoptosis. Altered protein expression underlies hippocampus cellular and volume loss in uMDD, supports a trophic effect of antidepressants, and offers new treatment targets.

Keywords: proteomics, hippocampus, depression, mitosis, migration, differentiation, mitochondria, apoptosis, antidepressants, human brain

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Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

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Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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Authors: Sharda Nara, Bansi Dhar Malhotra

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Investigation of the vitamins as an electron transfer mediator could significantly assist in merging the area of tissue engineering and electronics required for the implantable therapeutic devices. The present study report that the molecules of folic acid released by Providencia rettgeri via fermentation route under the anoxic condition of the microbial fuel cell (MFC) exhibit characteristic electrochemical and optical properties, as indicated by absorption spectroscopy, photoluminescence (PL), and cyclic voltammetry studies. The absorption spectroscopy has depicted an absorption peak at 263 nm with a small bulge around 293 nm on day two of bacterial culture, whereas an additional peak was observed at 365 nm on the twentieth day. Furthermore, the PL spectra has indicated that the maximum emission occurred at various wavelengths 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm. The change of emission spectra with varying excitation wavelength might be indicating the presence of tunable optical bands in the folic acid molecules co-related with the redox activity of the molecules. The results of cyclic voltammetry studies revealed that the oxidation and reduction occurred at 0.25V and 0.12V, respectively, indicating the electrochemical behavior of the folic acid. This could be inferred that the released folic acid molecules in a MFC might undergo inter as well as intra molecular electron transfer forming different intermediate states while transferring electrons to the electrode surface. Synchronization of electrochemical and optical properties of folic acid molecules could be potentially promising for the designing of electroactive scaffold and biocompatible conductive surface for the applications of tissue engineering and biofuel cells, respectively.

Keywords: biofuel cell, electroactivity, folic acid, tissue engineering

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Authors: Alieh Farshbaf, Tayyeb Bahrami

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Introduction: Cc-chemokine receptor-5 (CCR5) is known as a main co-receptor in human immunodeficiency virus type-1 (HIV-1) infection. Many studies showed 32bp deletion (Δ32) in CCR5 gene, provide natural resistance to HIV-1 infection in homozygous individuals. Inducing the resistance mechanism by CCR5 in HIV-1 infected patients eliminated many problems of highly-active-anti retroviral therapy (HAART) drugs like as low safety, side-effects and virus rebounding from latent reservoirs. New treatments solved some restrictions that are based on gene modification and cell therapy. Literature review: The stories of the “Berlin and Boston patients” showed autologous hematopoietic stem cells transplantation (HSCT) could provide effective cure of HIV-1 infected patients. Furthermore, gene modification by zinc finger nuclease (ZFN) demonstrated another successful result again. Despite the other studies for gene therapy by ∆32 genotype, there is another mutation -CCR5 ∆32/m303- that provides HIV-1 resistant. It is a heterozygote genotype for ∆32 and T→A point mutation at nucleotide 303. These results approved the key role of CCR5 gene. Conclusion: Recent studies showed immune gene therapy and cell therapy could provide effective cure for refractory disease like as HIV. Eradication of HIV-1 from immune system was not observed by HAART, because of reloading virus genome from latent reservoirs after stopping them. It is showed that CCR5 could induce natural resistant to HIV-1 infection by the new approaches based on stem cell transplantation and gene modifying.

Keywords: CCR5, HIV-1, stem cell, immune gene therapy, gene modification

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Authors: T. Scattolin, E. Cavarzerani, F. Visentin, F. Rizzolio

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Organopalladium compounds have recently attracted attention for their high stability even under physiological conditions and, above all, for their remarkable in vitro cytotoxicity towards cisplatin-resistant cell lines. Among the organopalladium derivatives, those bearing at least one N-heterocyclic carbene ligand (NHC) and the Pd(II)-η³-allyl fragment have exhibited IC₅₀ values in the micro and sub-micromolar range towards several cancer cell lines in vitro and in some cases selectivity towards cancerous vs. non-tumorigenic cells. Herein, a selection of allyl and indenyl palladates were synthesized using a solvent-free method consisting of grinding the corresponding palladium precursors with different saturated and unsaturated azolium salts. All compounds have been fully characterized by NMR, XRD and elemental analyses. The intramolecular H, Cl interaction has been elucidated and quantified using the Voronoi Deformation Density scheme. Most of the complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with I₅₀ values comparable to or even lower than cisplatin. Interestingly, the potent anticancer activity was also confirmed in a high-serous ovarian cancer (HGSOC) patient-derived tumoroid, with a clear superiority of this class of compounds over classical platinum-based agents. Finally, preliminary enzyme inhibition studies of the synthesized palladate complexes against the model TrxR show that the compounds have high activity comparable to or even higher than auranofin and classical Au(I) NHC complexes. Based on such promising data, further in vitro and in vivo experiments and in-depth mechanistic studies are ongoing in our laboratories.

Keywords: anticancer activity, palladium complexes, organoids, indenyl and allyl ligands

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Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

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Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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Authors: JaeYoon Lee, Gi-Hoon Yang, JongHan Ha, MyungGu Yeo, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

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One of the important factors in tissue engineering is to design optimal biomedical scaffolds, which can be governed by topographical surface characteristics, such as size, shape, and direction. Of these properties, we focused on the effects of nano- to micro-sized hierarchical surface. To fabricate the hierarchical surface structure on poly(ε-caprolactone) (PCL) film, we employed a micro-casting technique by pressing the mold and nano-etching technique using a modified plasma process. The micro-sized topography of PCL film was controlled by sizes of the micro structures on lotus leaf. Also, the nano-sized topography and hydrophilicity of PCL film were controlled by a modified plasma process. After the plasma treatment, the hydrophobic property of the PCL film was significantly changed into hydrophilic property, and the nano-sized structure was well developed. The surface properties of the modified PCL film were investigated in terms of initial cell morphology, attachment, and proliferation using osteoblast-like-cells (MG63). In particular, initial cell attachment, proliferation and osteogenic differentiation in the hierarchical structure were enhanced dramatically compared to those of the smooth surface. We believe that these results are because of a synergistic effect between the hierarchical structure and the reactive functional groups due to the plasma process. Based on the results presented here, we propose a new biomimetic surface model that maybe useful for effectively regenerating hard tissues.

Keywords: hierarchical surface, lotus leaf, nano-etching, plasma treatment

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Authors: Mohamed Moheyeldin Mahmoud

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Various Islamic, Coptic and Jewish archeological places are located in many Egyptian neighborhoods such as Alsayeda zainab, Aldarb Alahmar, Algammaleya and many other in which they are daily exposed to a great traffic intensity causing vibrations. Vibrations could be stated as one of the most important challenges that face the archeological buildings and threaten their survival. The impact of vibrations varies according to the nature of the soil, nature and building conditions, how far the source of vibration is and the period of exposure. Traffic vibrations could be also stated as one of the most common types of vibrations having the greatest impact on buildings and archaeological installations. These vibrations result from the way that the vehicles act with different types of roads which vary according to the shape, nature, and type of obstacles. Other elements concerning the vehicle itself such as speed, weight, and load have a direct impact on the vibrations resulting from the vehicle movement that couldn't be neglected. The research aims to determine some of the requirements that must be observed when designing the public means of transport operating in the archaeological areas, in order to preserve the archaeological nature of the place. The research concludes that light weight slow motion vehicles should be used (25-50 km/h at maximum) having a multi-leaf steel spring suspension system instead of having an air-bag one should be used in order to reduce generated vibrations that could destroy the archeological buildings. Isolation layers could be used in the engine chamber in order to reduce the resulting noise causing vibrations. Electrically operated engines that use solar photovoltaic cells as a source of electricity could be used instead of gas ones in order to reduce the resulting engine noise.

Keywords: archeological, design, isolation layers, suspension, vibrations

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Authors: Sepideh Jabbari Behnam, Shadabeh Gashtasbi Iraei, Elnaz Mohsenin, MohammadAli Aghajani

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Urban neighborhoods, as important urban forming cells, play a key role in creating urban texture and integrated form. Nowadays, most of neighborhood divisions are based on urban management systems but without considering social issues and the other aspects of urban life. This can cause problems such as providing inappropriate services for city dwellers, the loss of local identity and etc. In this regard for regenerating of such neighborhoods, it is essential to locate neighborhood centers with appropriate access and services for all residents. The main objective of this article is reaching to the location of neighborhood centers in a way that, most of issues relating to the physical features (such as the form of access network and texture permeability and etc.) and other qualities such as land uses, densities and social and economic features can be done simultaneously. This paper attempts to use methods of spatial analysis in order to surveying spatial structure and space syntax of urban textures and Urban Network Analysis Systems. This can be done by one of GIS toolbars which is named UNA (Urban Network Analysis) with the use of its five functions (include: Reach, Betweenness, Gravity, Closeness, Straightness).These functions were written according to space syntax theory and offer its relating output. This paper tries to locate and evaluate the optimal location of neighborhood centers in order to create local centers. This is done through weighing of each of these functions and taking into account of spatial features.

Keywords: evaluate optimal location, Local centers, location of neighborhood centers, Spatial analysis, Urban network

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Authors: Mahsa Taghavi

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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

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Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

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Authors: Farideh Tabatabei-Yazdi, Fereshteh Falah, Alireza Vasiee

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Nowadays, production of functional foods has become very essential. Inulin is one of the most functional hydrocolloid compounds used in such products. In the present study, the production of a synbiotic yogurt containing 1, 2.5, and 5% (w/v) inulin has been investigated. The yogurt was fermented with Lactobacillus brevis PML1 derived from Tarkhineh, an Iranian cereal-dairy fermented food. Furthermore, the physicochemical properties, antioxidant activity, sensory attributes, and microbial viability properties were investigated on the 0th, 7th, and 14th days of storage after fermentation. The viable cells of L. brevis PML1 reached 108 CFU/g, and the product resisted to simulated digestive juices. Moreover, the synbiotic yogurt impressively increased the production of antimicrobial compounds and had the most profound antimicrobial effect on S. typhimurium. The physiochemical properties were in the normal range, and the fat content of the synbiotic yogurt was reduced remarkably. The antioxidant capacity of the fermented yogurt was significantly increased (p<0:05), which was equal to those of DPPH (69:18±1:00%) and BHA (89:16±2:00%). The viability of L. brevis PML1 was increased during storage. Sensory analysis showed that there were significant differences in terms of the impressive parameters between the samples and the control (p<0:05). Addition of 2.5% inulin not only improved the physical properties but also retained the viability of the probiotic after 14 days of storage, in addition to the viability of L. brevis with a viability count above 6 log CFU/g in the yogurt. Therefore, a novel synbiotic product containing L. brevis PML1, which can exert the desired properties, can be used as a suitable carrier for the delivery of the probiotic strain, exerting its beneficial health effects.

Keywords: functional food, lactobacillus brevis, symbiotic yogurt, physiochemical properties

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Authors: Moussa Majed, Omar Yaser

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The main objective of this experiment was to study the impact of Probiotic compound on the specific immunity as the case study of infectious bursal disease. Total of 8000 one-day old Ross 108 broiler were randomly divided into two experimental groups; control group (4500 birds) and experimental group (3500 birds). Birds in two groups were reared under similar environmental conditions. Birds in control group received basal diets without probiotic whereas the birds in experimental one were fed basal diets supplemented with a commercial probiotic mixture) probiotic lacting k, which contains bacteria cells beyond to lactobacillus, Streptococcus and bifidobacterium genus that are isolated from gut microflora in healthy chickens(. The commercial probiotic were used according to the manufacturer instruction. 400 blood samples for each group were collected from wing vein every 5-7 days as interval period till 42 days old. Indirect Enzyme-Linked Immunosorbent Assay (ELISA) test was performed to detect the level of infectious bursal disease virus (IBDV) antibodies. The results clearly showed that the mean of immune titers was significantly (p= 0.03) higher in trail group than control one. The coefficient of variance percentages were 55% and 39% for control and trial groups respectively, this illustrates that homogeneity of immunity titers in the trail group was much better comparing with control group. The values of geometric means of titers in the control group and trial group were reported 3820 and 8133, respectively. The crude mortality rate in the experimental group was two times lower comparing with control group (14% and 28% respectively, p = 0.005

Keywords: probiotic, broiler chicken, infectious bursal disease, immunity, ELISA test

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Authors: Chadlia Ounissi, Maher Gzam, Tahani Hallek, Salah Mahmoudi, Mabrouk Montacer

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This work consists of a morphological study of the coastal domain at the central fringe of the Gulf of Gabes, Southeast of Tunisia, belonging to the structural domain of the maritime Jeffara. The diachronic study of tidal mouths in the study area and the observation of morphological markers revealed the existence of hydro-sedimentary processes leading to sedimentary accumulation and filling of the estuarine system. This filling process is materialized by the genesis of a sandy cord and the lateral migration of the tidal mouth. Moreover, we have been able to affirm, by the use of satellite images, that the dominant and responsible current at this particular coastal morphology is directed to the North, having constituted a controversy on the occurrence of what is previously mentioned in the literature. The speed of the lateral displacement of the channel varies as a function of the hydrodynamic forcing. Wave-dominated sites recorded the fastest speed (18 m/year) in the image of the mouth of Wadi el Melah. Tidal dominated sites in the Wadi Zerkine satellite image recorded a very low lateral migration (2 m / year). This variation in speed indicates that the intensity of the coastal current is uneven along the coast. This general pattern of hydrodynamic circulation, to the north, of the central fringe of the Gulf of Gabes, is disturbed by hydro-sedimentary cells.

Keywords: tidal mouth, direction of current, filling, sediment transport, Gulf of Gabes

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Authors: Hasan Basri Jumin, Danil Endriand Basri

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Isolated protoplast from embryogenic callus of orange Jessamine (Murraya paniculata L. (Jack) cultured and maintained under growth chamber at the temperature +25oC. The parameter observed are the plating efficiency, the number of spherical embryos, heard-shaped embryos-like structure, shoot formation, and plantlets obtained. Treatment was arranged with 0.0, 0.001, 0.01, 0.1 or 1.0 mg 1-1 Naphthalene acetic acid (NAA), and 0, 300, 500 mg 1/l malt extract (ME) and 0.M sorbitol in the medium with 2.5 % sucrose. Interaction between 0.001 mg/l NAA and 500 mg/l was observed the higher percentage of planting efficiency. For embryo development from callus, the media was added to 0.0 mg/l, 0.001 mg/l, 0.01 ,mg/l, 0.1 mg/l, 1.0 mg/l NAA, and 1.0 %, 2.0 %, 3.0 %, 4.0 % sucrose. Media supplemented with 0.01mg/l NAA, and 1.0% sucrose was found to be a suitable medium for the development of spherical somatic embryos. A combination of 0.1 mg/ indole acetic acid (IAA) and 0.1 mg/l zeatin constituted the spherical somatic embryo became heart-shaped embryos-like structure. A combination between GA3 0.1 mg 1/l GA3 and 0.1 mg 1-1 zeatin is looking high, growing the heart-shaped embryos-like structure to form a shoot. Cells were developed into spherical embryos and grew into heart-shaped embryos, and then spherical somatic embryos developed into shoot formation. Sequence from single protoplast to plantlets was obtained by using a low concentration of plant growth regulator and sucrose; This recovery of single protoplast to be completed plantlets is a new technology in plant cell culture, and this could be used in genetic engineering in citrus.

Keywords: heart-shaped-embryos-like-structure, Muraya-paniculata, plant-growth-regulator, spherical- somatic-embryo, single protoplast, glucose

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Authors: Hasan Afarnegan, Ali Shahraki, Jafar Shahraki

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Paraquat is widely used as a strong nitrogen-based herbicide for controlling of weeds in agriculture. This poison is extremely toxic for humans which induces several – organ failure by accumulation in cells and many instances of death occurred due to its poisoning. Paraquat metabolized primarily in the liver. The purpose of this study was to assess the effects of aquatic extract of levisticum officinale on oxidative status and biochemical factors in hepatocytes exposed to paraquat. Our results determined that hepatocytes destruction induced by paraquat is mediated by reactive oxygen species (ROS) production, lipid peroxidation and decrease of mitochondrial membrane potential were significantly (P<0.05) prevented by aquatic extract of Levisicum officinale (100, 200 and 300 µg/ml). These effects of paraquat also prevented via antioxidants and ROS scavengers (α-tocopherol, DMSO, manitol), mitochondrial permeability transition (MPT) pore sealing compound (carnitine).MPT pore sealing compound inhibited the hepatotoxicity, indicating that paraquat induced cell death via mithochondrial pathway. Pretreatment of hepatocytes with aquatic extracts of Levisticum officinale, antioxidants and ROS scavengers also blocked hepatic cell death caused by paraquat, suggesting that oxidative stress may be directly induced decline of mithochondrial membrane potential. In conclusion, paraquat hepatotoxicity can be attributed to oxidative stress and continued by mithochondrial membrane potential disruption. Levisticum officinale aquatic extract, presumably due to its strong antoxidant properties, could protect the destructive effects of paraquat on rat hepatocytes.

Keywords: hepatocyte protection, levisticum officinale, oxidative stress, paraquat

Procedia PDF Downloads 223

Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

Procedia PDF Downloads 139

Authors: P. Bublíkova, P. Halodova, H. K. Namburi, J. Stodolna, J. Duchon, O. Libera

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Neutron radiation-induced microstructural changes cause degradation of mechanical properties and the lifetime reduction of reactor internals during nuclear power plant operation. Investigating the effects of neutron irradiation on mechanical properties of the irradiated material (hardening, embrittlement) is challenging and time-consuming. Although the fast neutron spectrum has the major influence on microstructural properties, the thermal neutron effect is widely investigated owing to Irradiation-Assisted Stress Corrosion Cracking firstly observed in BWR stainless steels. In this study, 300-series austenitic stainless steels used as material for NPP's internals were examined after neutron irradiation at ~ 15 dpa. Although several nanoindentation experimental publications are available to determine the mechanical properties of ion irradiated materials, less is available on neutron irradiated materials at high dpa tested in hot-cells. In this work, we present particular methodology developed to determine the mechanical properties of neutron irradiated steels by nanoindentation technique. Furthermore, radiation-induced damage in the specimens was investigated by High Resolution - Transmission Electron Microscopy (HR-TEM) that showed the defect features, particularly Frank loops, cavity microstructure, radiation-induced precipitates and radiation-induced segregation. The results of nanoindentation measurements and associated nanoscale defect features showed the effect of irradiation-induced hardening. We also propose methodologies to optimized sample preparation for nanoindentation and microscotructural studies.

Keywords: nanoindentation, thermal neutrons, radiation hardening, transmission electron microscopy

Procedia PDF Downloads 158