Electrical and thermal properties of polyimide/silica nanocomposite

The electrical and thermal properties of thin films of polyimide/silica nanocomposites prepared via sol–gel process were studied as a function of nanosilica particles content, temperature and applied field frequency. It was found that the dielectric constant and dielectric loss of the nanocomposites decrease with both the frequency and the nanosilica content, while increase with temperature. The AC-conductivity measured in frequency range 200 kHz–1.5 MHz decreases with the filler concentration and increases with increasing temperature. For the (25 wt%) nanocomposite, it was found that the AC-conductivity increases with temperature, and the Cole–Cole plots showed that the calculated activation energy and relaxation time decrease with temperature. The observed thermal conductivity increases gently with temperature. The empirical universal law was used to fit the observed electrical data under the measuring conditions

Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line

AbstractMany molecular mechanisms contribute to the development of doxorubicin resistance and different cancers can express wide and diverse arrays of drug-resistance genes. The aim of this study was to identify the changes in gene expression associated with the development of doxorubicin resistance in MCF7 breast cancer cell line. The doxorubicin resistant MCF7 cell line was developed by stepwise selection of MCF7 cells and was tested using the MTT assay. The alterations in gene expression were examined using the real-time based PCR array. The findings showed an up-regulation of many phase I/II metabolizing genes, specifically, the CYP1A1 and the CYP1A2 that were up-regulated by 206- and 96-fold respectively. Drug efflux pump genes were also up-regulated profoundly. TOP2A was strongly down-regulated by 202-fold. Many other changes were observed in genes crucial for cell cycle, apoptosis and DNA repair. The findings of this project imply that the development of doxorubicin resistance is a multi-factorial process

Hypoxia-induced gene expression pattern in doxorubicin resistant MCF7 cells

Purpose: To investigate hypoxia-induced gene expression pattern in doxorubicin-resistant human breast cancer cells (MCF7). Methods: Human breast cancer cells (MCF7) were exposed to 60 episodes of 8 h hypoxia thrice a week for three months. Chemo-resistance to doxorubicin was assessed using 3-(4,5-dimethylthiazol-2- yl)-2, 5-diphenyl tetrazolium bromide (MTT) cell proliferation assay. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to assess gene expression pattern in doxorubicinresistant cells on exposure to hypoxia. Results: Hypoxia significantly increased the resistance of MCF7 cells to doxorubicin, with a maximum of 16.42-fold enhancement after 25 episodes of 8-h hypoxia, while the resistance thereafter significantly decreased with prolonged episodes of hypoxia (p < 0.05). Gene expression analysis revealed significant changes in 42 genes. The expressions of 10 of these genes were significantly upregulated, while those of 32 genes were significantly down-regulated (p < 0.05). Cytochrome P450 family 1, subfamily A, member1 (CYP1A1) was the most conspicuous upregulated gene (13.32-fold), while breast cancer gene 1 (BRCA1) was the most down-regulated (8.23-fold). Gene expression analysis after 60 episodes of 8-h hypoxia revealed the upregulation of CYP1A1 (5.77-fold). Similarly, 27 genes were significantly down-regulated, with BRCA2 as the most down-regulated gene (8.11-fold). Topoisomerase (DNA) II alpha (TOP2A) was the most down-regulated among genes involved in drug metabolism and resistance (6.37-fold), while cyclin-dependent kinase 2 (CDK2) was the most profoundly downregulated among genes involved in cell cycle regulation (3.56-fold). Conclusion: These results indicate that development of resistance to doxorubicin by MCF7 cells after short-term hypoxia results from the upregulation of genes responsible for the metabolism of doxorubicin and for shifting the cells to alternative pathway driven principally by EGF and ESR2. The observed down-regulation is an adaptation of the MCF7 cells to survive under long-term hypoxia

Allelic frequency of PON1 Q192R, CYP2C19*2 and CYP2C19*17 among Jordanian patients taking clopidogrel

Purpose: To investigate the influence of allelic frequencies of PON1 Q192R, CYP2C19*2 and CYP2C19*17 genetic polymorphisms on the response to clopidogrel among Jordanian patients.Methods: Polymorphisms in CYP2C19 were assessed among 148 patients using PCR-RFLP assay.Results: The CYP2C19*2, CYP2C19*17, and PON1 Q192R allele frequencies were 9.8, 28.72 and 28.7 %, respectively. On the genotyping side, the frequencies of CYP2C19*1/1* and CYP2C19*1/2* were 80.4 and 19.6 %, respectively, but none of the patients had CYP2C19*2/2* genotype. The genotype frequencies CYP2C19*17 were 47.97, 46.62 and 5.41 % for wild-type C-C, heterozygote C-T, and the mutant T-T, respectively. PON1 genotype was 42.7 % for QQ, and 57.8 % for QR. None of the patients had RR genotype.Conclusion: Relative to other populations, the observed allelic frequencies are consistent with the values reported for Caucasian and Middle Eastern populations.Keywords: CYP2C9 polymorphisms, Clopidogrel, Genotype, Allele frequency, PON1 gene

Electrothermal and Optical Properties of Hybrid Polymer Composites

The Electrothermal and optical properties of hybrid polymer composites made of poly (ethylene oxide) (PEO) matrix filled with different zinc oxide (ZnO) concentrations (0, 2, 4, 6 and 12 wt %), and strengthened with iodine (0.1 wt %) have been investigated. The electrical properties have been studied using the impedance technique as a function of ZnO concentrations, applied frequency ranges from 10 KHz to 3 MHz, and temperature in range (25-55 ˚C). The AC electrical properties showed frequency, temperature, and zinc oxide dependence. It was found that with increasing the ZnO concentration and with decreasing the applied frequency the dielectric loss and dielectric constant will be increased. The determined activation energy decreases with increasing the ZnO content and iodine charge complexes. The thermal conductivity has been studied, and it was found that the thermal conductivity increases with both ZnO concentration and temperature. The optical properties have been examined as a function of ZnO concentration, and applied UV-wavelength ranges from 300 to 800 nm. The determined optical dispersion parameters, such as the optical energy and refractive index are discussed

The effect of cycling hypoxia on MCF-7 cancer stem cells and the impact of their microenvironment on angiogenesis using human umbilical vein endothelial cells (HUVECs) as a model

Background Breast cancer is the most common type of cancer among females. Hypoxia mediates cancer hallmarks and results from reduced oxygen level due to irregularities in tumor vascularization or when the tumor size prevents oxygen diffusion and triggers angiogenesis to compensate for low oxygen. Cancer stem cells (CSCs) are a rare subpopulation, able to self-renew and to give rise to tumor-initiating cells. It is proposed that CSCs’ secretions help to recruit endothelial cells via angiogenic factors to establish tumor vascularization. In the tumor microenvironment, the effect of hypoxia on CSCs and the impact of their secretions on triggering angiogenesis and tumor vascularization remain questionable. In this study, three-dimensional (3D) CSCs derived from MCF-7 were directly exposed to repetitive long-term cycles of hypoxia to assess its effect on CSCs and then to evaluate the role of the hypoxic CSCs’ (CSCsHYP) secretions in angiogenesis using (HUVECs) as a model for tumor neovascularization response. Methods CSCs derived from MCF-7 cell-line were expanded under repetitive, strictly optimized, long-term/continuous and intermittent hypoxic shots for almost four months to assess hypoxic effect on CSCs, sorted based on CD44+/CD24− biomarkers. Hypoxic phenotype of CSCsHYP was evaluated by assessing the acquired chemoresistance using MTT assay and elevated stemness properties were assessed by flow cytometry. To evaluate the effect of the secretions from CSCsHYP on angiogenesis, HUVECs were exposed to CSCsHYP conditioned-medium (CdM)—in which CSCs had been previously grown—to mimic the tumor microenvironment and to assess the effect of the secretions from CSCsHYP on the HUVECs’ capability of tube formation, migration and wound healing. Additionally, co-culture of CSCsHYP with HUVECs was performed. Results CSCsHYP acquired higher chemoresistance, increased stemness properties and obtained greater propagation, migration, and wound healing capacities, when compared to CSCs in normoxic condition (CSCsNOR). HUVECs’ tube formation and migration abilities were mediated by hypoxic (CSCs) conditioned media (CdM). Discussion This study demonstrates that chemoresistant and migrational properties of CSCs are enhanced under hypoxia to a certain extent. The microenvironment of CSCsHYP contributes to tumor angiogenesis and migration. Hypoxia is a key player in tumor angiogenesis mediated by CSCs

An Analysis on the Detection of Biological Contaminants Aboard Aircraft

The spread of infectious disease via commercial airliner travel is a significant and realistic threat. To shed some light on the feasibility of detecting airborne pathogens, a sensor integration study has been conducted and computational investigations of contaminant transport in an aircraft cabin have been performed. Our study took into consideration sensor sensitivity as well as the time-to-answer, size, weight and the power of best available commercial off-the-shelf (COTS) devices. We conducted computational fluid dynamics simulations to investigate three types of scenarios: (1) nominal breathing (up to 20 breaths per minute) and coughing (20 times per hour); (2) nominal breathing and sneezing (4 times per hour); and (3) nominal breathing only. Each scenario was implemented with one or seven infectious passengers expelling air and sneezes or coughs at the stated frequencies. Scenario 2 was implemented with two additional cases in which one infectious passenger expelled 20 and 50 sneezes per hour, respectively. All computations were based on 90 minutes of sampling using specifications from a COTS aerosol collector and biosensor. Only biosensors that could provide an answer in under 20 minutes without any manual preparation steps were included. The principal finding was that the steady-state bacteria concentrations in aircraft would be high enough to be detected in the case where seven infectious passengers are exhaling under scenarios 1 and 2 and where one infectious passenger is actively exhaling in scenario 2. Breathing alone failed to generate sufficient bacterial particles for detection, and none of the scenarios generated sufficient viral particles for detection to be feasible. These results suggest that more sensitive sensors than the COTS devices currently available and/or sampling of individual passengers would be needed for the detection of bacteria and viruses in aircraft

The crosstalk between adenosine A2B receptor and insulin signalling in rat skeletal muscle cells

Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. Insulin therapy might be affected by specific metabolic enzymes and transporters. There are conflicting reports in the literature on the role of adenosine receptor A2B (AR2B) in skeletal and cardiac muscle glucose metabolism. This study aims to find out if there is an association between AR2B and insulin signalling, especially the metabolic pathways (AKT-GSK). Differentiated L6 cell rat muscle cells were treated with insulin, adenosine agonist NECA, selective AR2B antagonist PSB 603 and combinations between these reagents, the expression of AKT2, GSK3α, and GSK3β were measured by qPCR hydrolysis probe technique. Insulin increases AKT2, GSK3α and GSK3β mRNA expression, while AR2B antagonist inhibits AKT2 GSK3α and GSK3β mRNA expression and combining AR2B antagonist with insulin diminish insulin action and decrease AKT2 GSK3α and GSK3β mRNA expression, which means a strong relationship between AR2B and insulin action. Furthermore AR2B agonist may be a good candidate as an anti-diabetic drug