Search results for: Sertoli cell only syndrome (SCOS)
937 Membrane-Localized Mutations as Predictors of Checkpoint Blockade Efficacy in Cancer
Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell
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Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers
Procedia PDF Downloads 109936 Laser-Hole Boring into Overdense Targets: A Detailed Study on Laser and Target Properties
Authors: Florian Wagner, Christoph Schmidt, Vincent Bagnoud
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Understanding the interaction of ultra-intense laser pulses with overcritical targets is of major interest for many applications such as laser-driven ion acceleration, fast ignition in the frame of inertial confinement fusion or high harmonic generation and the creation of attosecond pulses. One particular aspect of this interaction is the shift of the critical surface, where the laser pulse is stopped and the absorption is at maximum, due to the radiation pressure induced by the laser pulse, also referred to as laser hole boring. We investigate laser-hole boring experimentally by measuring the backscattered spectrum which is doppler-broadened because of the movement of the reflecting surface. Using the high-power, high-energy laser system PHELIX in Darmstadt, we gathered an extensive set of data for different laser intensities ranging from 10^18 W/cm2 to 10^21 W/cm2, two different levels of the nanosecond temporal contrast (10^6 vs. 10^11), elliptical and linear polarization and varying target configurations. In this contribution we discuss how the maximum velocity of the critical surface depends on these parameters. In particular we show that by increasing the temporal contrast the maximum hole boring velocity is decreased by more than a factor of three. Our experimental findings are backed by a basic analytical model based on momentum and mass conservation as well as particle in cell simulations. These results are of particular importance for fast ignition since they contribute to a better understanding of the transport of the ignitor pulse into the overdense region.Keywords: laser-hole boring, interaction of ultra-intense lasers with overcritical targets, fast ignition, relativistic laser motter interaction
Procedia PDF Downloads 405935 Circadian Expression of MicroRNAs in Colon and Its Changes during Colorectal Tumorigenesis
Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova
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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis
Procedia PDF Downloads 167934 Bluetooth Communication Protocol Study for Multi-Sensor Applications
Authors: Joao Garretto, R. J. Yarwood, Vamsi Borra, Frank Li
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Bluetooth Low Energy (BLE) has emerged as one of the main wireless communication technologies used in low-power electronics, such as wearables, beacons, and Internet of Things (IoT) devices. BLE’s energy efficiency characteristic, smart mobiles interoperability, and Over the Air (OTA) capabilities are essential features for ultralow-power devices, which are usually designed with size and cost constraints. Most current research regarding the power analysis of BLE devices focuses on the theoretical aspects of the advertising and scanning cycles, with most results being presented in the form of mathematical models and computer software simulations. Such computer modeling and simulations are important for the comprehension of the technology, but hardware measurement is essential for the understanding of how BLE devices behave in real operation. In addition, recent literature focuses mostly on the BLE technology, leaving possible applications and its analysis out of scope. In this paper, a coin cell battery-powered BLE Data Acquisition Device, with a 4-in-1 sensor and one accelerometer, is proposed and evaluated with respect to its Power Consumption. First, evaluations of the device in advertising mode with the sensors turned off completely, followed by the power analysis when each of the sensors is individually turned on and data is being transmitted, and concluding with the power consumption evaluation when both sensors are on and respectively broadcasting the data to a mobile phone. The results presented in this paper are real-time measurements of the electrical current consumption of the BLE device, where the energy levels that are demonstrated are matched to the BLE behavior and sensor activity.Keywords: bluetooth low energy, power analysis, BLE advertising cycle, wireless sensor node
Procedia PDF Downloads 91933 Communication Tools Used in Teaching and Their Effects: An Empirical Study on the T. C. Selcuk University Samples
Authors: Sedat Simsek, Tugay Arat
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Today's communication concept, which has a great revolution with the printing press which has been found by Gutenberg, has no boundary thanks to advanced communication devices and the internet. It is possible to take advantage in many areas, such as from medicine to social sciences or from mathematics to education, from the computers that was first produced for the purpose of military services. The use of these developing technologies in the field of education has created a great vision changes in both training and having education. Materials, which can be considered as basic communication resources and used in traditional education has begun to lose its significance, and some technologies have begun to replace them such as internet, computers, smart boards, projection devices and mobile phone. On the other hand, the programs and applications used in these technologies have also been developed. University students use virtual books instead of the traditional printed book, use cell phones instead of note books, use the internet and virtual databases instead of the library to research. They even submit their homework with interactive methods rather than printed materials. The traditional education system, these technologies, which increase productivity, have brought a new dimension to education. The aim of this study is to determine the influence of technologies in the learning process of students and to find whether is there any similarities and differences that arise from the their faculty that they have been educated and and their learning process. In addition to this, it is aimed to determine the level of ICT usage of students studying at the university level. In this context, the advantages and conveniences of the technology used by students are also scrutinized. In this study, we used surveys to collect data. The data were analyzed by using SPSS 16 statistical program with the appropriate testing.Keywords: education, communication technologies, role of technology, teaching
Procedia PDF Downloads 303932 Iron Response Element-mRNA Binding to Iron Response Protein: Metal Ion Sensing
Authors: Mateen A. Khan, Elizabeth J. Theil, Dixie J. Goss
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Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.Keywords: IRE-mRNA, IRP1, binding, ionic strength
Procedia PDF Downloads 128931 Self-Organized TiO₂–Nb₂O₅–ZrO₂ Nanotubes on β-Ti Alloy by Anodization
Authors: Muhammad Qadir, Yuncang Li, Cuie Wen
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Surface properties such as topography and physicochemistry of metallic implants determine the cell behavior. The surface of titanium (Ti)-based implant can be modified to enhance the bioactivity and biocompatibility. In this study, a self-organized titania–niobium pentoxide–zirconia (TiO₂–Nb₂O₅–ZrO₂) nanotubular layer on β phase Ti35Zr28Nb alloy was fabricated via electrochemical anodization. Energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle measurement techniques were used to investigate the nanotubes dimensions (i.e., the inner and outer diameters, and wall thicknesses), microstructural features and evolution of the hydrophilic properties. The in vitro biocompatibility of the TiO₂–Nb₂O₅–ZrO₂ nanotubes (NTs) was assessed by using osteoblast cells (SaOS2). Influence of anodization parameters on the morphology of TiO₂–Nb₂O₅–ZrO₂ NTs has been studied. The results indicated that the average inner diameter, outer diameter and the wall thickness of the TiO₂–Nb₂O₅–ZrO₂ NTs were ranged from 25–70 nm, 45–90 nm and 5–13 nm, respectively, and were directly influenced by the applied voltage during anodization. The average inner and outer diameters of NTs increased with increasing applied voltage, and the length of NTs increased with increasing anodization time and water content of the electrolyte. In addition, the size distribution of the NTs noticeably affected the hydrophilic properties and enhanced the biocompatibility as compared with the uncoated substrate. The results of this study could be considered for developing nano-scale coatings for a wide range of biomedical applications.Keywords: Titanium alloy, TiO₂–Nb₂O₅–ZrO₂ nanotubes, anodization, surface wettability, biocompatibility
Procedia PDF Downloads 155930 Rapid Weight Loss in Athletes: A Look at Suppressive Effects on Immune System
Authors: Nazari Maryam, Gorji Saman
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For most competitions, athletes usually engage in a process called rapid weight loss (RWL) and subsequent rapid weight gain (RWG) in the days preceding the event. Besides the perfection of performance, weight regulation mediates a self-image of being “a real athlete” which is mentally important as a part of the pre-competition preparation. This feeling enhances the focus and commitment of the athlete. There is a large body of evidence that weight loss, particularly in combat sports, results in several health benefits. However, intentional weight loss beyond normal levels might have unknown negative special effects on the immune system. As the results show, a high prevalence (50%) of RWL is happening among combat athletes. It seems that energy deprivation and intense exercise to reach RWL results in altered blood cell distribution through modification of body composition that, in turn, changes B and T-Lymphocyte and/or CD4 T-Helper response. Moreover, it may diminish IgG antibody levels and modulate IgG glycosylation after this course. On the other hand, some studies show suppression of signaling and regulation of IgE antibody and chemokine production are responsible for immunodeficiency following a period of low-energy availability. Some researchers hypothesize that severe glutamine depletion, which occurs during exercise and calorie restriction, is responsible for this immune system weakness. However, supplementation by this amino acid is not prescribed yet. Therefore, weight loss is achieved not only through chronic strategies (body fat losses) but also through acute manipulations prior to competition should be supervised by a sports nutritionist to minimize side effects on the immune system and other body systems.Keywords: athletes, immune system, rapid weight loss, weight loss strategies
Procedia PDF Downloads 120929 Influence of Age on Some Testicular and Spermatic Parameters in Kids and Bucks in Local Breed Arbia in Algeria
Authors: Boukhalfa Djemouai, Belkadi Souhila, Safsaf Boubakeur
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To increase the profitability of the national herd so that it can meet the needs of the population, Algeria has proceeded to the introduction of new reproductive biotechnologies, including artificial insemination on natural heat, by induction and heat synchronization. This biotechnology uses the male way for the creation and dissemination of genetic progress. The study has focused on 30 goat kids and bucks local breed aged between 03 and 24 months, divided into 03 groups 03-06 months[Grp 1; n=9], 07-10 months [Grp 2; n=13] and 11-24 months [Grp 3; n=8], in order to determine the influence of age on testicular evolution by measurements of testis and scrotum, and the epididymis sperm parameters evaluation. These parameters are influenced by age variations (sperm and spermocytogram). The examined parameters have focused on testicular weight (grams), the scrotal circumference (cm), mass mobility (%), vitality rate (%), sperm concentration (x 109), and percentage of abnormal spermatozoa (%). The ANOVA reveals a significance effect of age on parameters: testis weight, scrotal circumference, sperm concentration, motility varying between high (p < 0.01) to very high significance (p < 0.001), while in viability and abnormalities no significance was observed between all groups. The value of these parameters increased significantly until the age of 02 years, while that of sperm abnormalities has increased in Grp2. The histological study of testicular development shows that the genetic spermatozoa function characterized by cell proliferation, which is more and more intense starting from the age of 05 months and can be considered as an age of puberty in the local breed goat Arbia and increases with animal age.Keywords: kids and bucks, epididymis sperm, testicular measurements, Arbia breed
Procedia PDF Downloads 132928 Ergosterol Biosynthesis: Non-Conventional Method for Improving Process
Authors: Madalina Postaru, Alexandra Tucaliuc, Dan Cascaval, Anca Irina Galaction
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Ergosterol (ergosta-5,7,22-trien-3β-ol) is the precursor of vitamin D2 (ergocalciferol), known as provitamin D2 as it is converted under UV radiation to this vitamin. The natural sources of ergosterol are mainly the yeasts (Saccharomyces sp., Candida sp.), but it can be also found in fungus (Claviceps sp.) or plants (orchids). As ergosterol is mainly accumulated in yeast cell membranes, especially in free form in the plasma-membrane, and the chemical synthesis of ergosterol does not represent an efficient method for its production, this study aimed to analyze the influence of aeration efficiency on ergosterol production by S. cerevisiae in batch and fed-batch fermentations, by considering different levels of mixing intensity, aeration rate, and n-dodecane concentration. Our previous studies on ergosterol production by S. cerevisiae in batch and fed-batch fermentation systems indicated that the addition of n-dodecane led to the increase of almost 50% of this sterol concentration, the highest productivity being reached for the fed-batch process. The experiments were carried out in a laboratory stirred bioreactor, provided with computer-controlled and recorded parameters. In batch fermentation system, the study indicated that the oxygen mass transfer coefficient, kLa, is amplified for about 3 times by increasing the volumetric concentration of n-dodecane from 0 to 15%. Moreover, the increase of dissolved oxygen concentration by adding n-dodecane leads to the diminution for 3.5 times of the produced alcohol amount. In fed-batch fermentation process, the positive influence of hydrocarbon on oxygen transfer rate is amplified mainly at its higher concentration level, as the result of the increased yeasts cells amount. Thus, by varying n-dodecane concentration from 0 to 15% vol., the kLa value increase becomes more important than for the batch fermentation, being of 4 timesKeywords: ergosterol, yeast fermentation, n-dodecane, oxygen-vector
Procedia PDF Downloads 119927 Crystallization Based Resolution of Enantiomeric and Diastereomeric Derivatives of myo-Inositol
Authors: Nivedita T. Patil, M. T. Patil, M. S. Shashidhar, R. G. Gonnade
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Cyclitols are cycloalkane polyols which have raise attention since they have numerous biological and pharmaceutical properties. Among these, inositols are important cyclitols, which constitute a group of naturally occurring polyhydric alcohols. Myo, scyllo, allo, neo, D-chiro- are naturally occurring structural isomer of inositol while other four isomers (L-chiro, allo, epi-, and cis-inositol) are derived from myo-inositol by chemical synthesis. Myo-inositol, most abundant isomer, plays an important role in signal transduction process and for the treatment of type 2 diabetes, bacterial infections, stimulation of menstruation, ovulation in polycystic ovary syndrome, improvement of osteogenesis, and in treatment of neurological disorders. Considering the vast application of the derivatives, it becomes important to supply these compounds for further studies in quantitative amounts, but the synthesis of suitably protected chiral inositol derivatives is the key intermediates in most of the synthesis which is difficult. Chiral inositol derivatives could also be of interest to synthetic organic chemists as they could serve as potential starting materials for the synthesis of several natural products and their analogs. Thus, obtaining chiral myo-inositol derivatives in a more eco-friendly way is need for current inositol chemistry. Thus, the resolution of nonracemates by preferential crystallization of enantiomers has not been reported as a method for inositol derivatives. We are optimistic that this work might lead to the development of the two tosylate enantiomers as synthetic chiral pool molecules for organic synthesis. Resolution of racemic 4-O-benzyl 6-O-tosyl myo-inositol 1, 3, 5 orthoformate was successfully achieved on multigram scale by preferential crystallization, which is more scalable, eco-friendly method of separation than other reported methods. The separation of the conglomeric mixture of tosylate was achieved by suspending the mixture in ethyl acetate till the level of saturation is obtained. To this saturated clear solution was added seed crystal of the desired enantiomers. The filtration of the precipitated seed was carried out at its filtration window to get enantiomerically enriched tosylate, and the process was repeated alternatively. These enantiomerically enriched samples were recrystallized to get tosylate as pure enantiomers. The configuration of the resolved enantiomers was determined by converting it to previously reported dibenzyl ether myo-inositol, which is an important precursor for mono- and tetraphosphates. We have also developed a convenient and practical method for the preparation of enantiomeric 4-O and 6-O-allyl myo-inositol orthoesters by resolution of diastereomeric allyl dicamphante orthoesters on multigram scale. These allyl ethers can be converted to other chiral protected myo-inositol derivatives using routine synthetic transformations. The chiral allyl ethers can be obtained in gram quantities, and the methods are amenable to further scale-up due to the simple procedures involved. We believe that the work described enhances the pace of research to understand the intricacies of the myo-inositol cycle as the methods described provide efficient access to enantiomeric phosphoinositols, cyclitols, and their derivatives from the abundantly available myo-inositol as a starting material.Keywords: cyclitols, diastereomers, enantiomers, myo-inositol, preferential crystallization, signal transduction
Procedia PDF Downloads 141926 Mathematical Modelling and AI-Based Degradation Analysis of the Second-Life Lithium-Ion Battery Packs for Stationary Applications
Authors: Farhad Salek, Shahaboddin Resalati
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The production of electric vehicles (EVs) featuring lithium-ion battery technology has substantially escalated over the past decade, demonstrating a steady and persistent upward trajectory. The imminent retirement of electric vehicle (EV) batteries after approximately eight years underscores the critical need for their redirection towards recycling, a task complicated by the current inadequacy of recycling infrastructures globally. A potential solution for such concerns involves extending the operational lifespan of electric vehicle (EV) batteries through their utilization in stationary energy storage systems during secondary applications. Such adoptions, however, require addressing the safety concerns associated with batteries’ knee points and thermal runaways. This paper develops an accurate mathematical model representative of the second-life battery packs from a cell-to-pack scale using an equivalent circuit model (ECM) methodology. Neural network algorithms are employed to forecast the degradation parameters based on the EV batteries' aging history to develop a degradation model. The degradation model is integrated with the ECM to reflect the impacts of the cycle aging mechanism on battery parameters during operation. The developed model is tested under real-life load profiles to evaluate the life span of the batteries in various operating conditions. The methodology and the algorithms introduced in this paper can be considered the basis for Battery Management System (BMS) design and techno-economic analysis of such technologies.Keywords: second life battery, electric vehicles, degradation, neural network
Procedia PDF Downloads 65925 Chitosan Hydrogel Containing Nitric Oxide Donors with Potent Antibacterial Effect
Authors: Milena Trevisan Pelegrino, Bruna De Araujo Lima, Mônica H. M. Do Nascimento, Christiane B. Lombello, Marcelo Brocchi, Amedea B. Seabra
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Nitric oxide (NO) is a small molecule involved in a wide range of physiological and pathophysiological processes, including vasodilatation, control of inflammatory pain, wound healing, and antibacterial activities. As NO is a free radical, the design of drugs that generates therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, in an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial and biocompatibility properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior, and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications, at physiological and skin temperatures. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL-1 of hydrogel, which correspondents to 1 mmol·L-1 of GSNO). Interesting, the concentration range in which the NO-releasing hydrogel demonstrated antibacterial effect was not found toxic to Vero mammalian cell. Thus, GSNO-PL/CS hydrogel is suitable biomaterial for topical NO delivery applications.Keywords: antimicrobial, chitosan, biocompatibility, S-nitrosothiols
Procedia PDF Downloads 185924 Comparison of Acetylcholinesterase Reactivators Cytotoxicity with Their Structure
Authors: Lubica Muckova, Petr Jost, Jaroslav Pejchal, Daniel Jun
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The development of acetylcholinesterase reactivators, i.e. antidotes against organophosphorus poisoning, is an important goal of defence research. The aim of this study was to compare cytotoxicity and chemical structure of 5 currently available (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) and 4 newly developed compounds (K027, K074, K075, and K203). In oximes, there could be at least four important structural factors affecting their toxicity, including the number of oxime groups in the molecule, the position of oxime group(s) on pyridinium ring, the length of carbon linker, and the substitution by oxygen or insertion of the double bond into the connection chain. The cytotoxicity of tested substances was measured using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT assay) in SH-SY5Y cell line. Toxicity was expressed as toxicological index IC₅₀. The tested compounds showed different cytotoxicity ranging from 1.5 to 27 mM. K027 was the least, and methoxime was the most toxic reactivator. The lowest toxicity was found in a monopyridinium reactivator and bispyridinium reactivators with simple 3C carbon linker. Shortening of connection chain length to 1C, incorporation of oxygen moiety into 3C compounds, elongation of carbon linker to 4C and insertion of a double bond into 4C substances increase AChE reactivators' cytotoxicity. Acknowledgements: This work was supported by a long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence.Keywords: acetylcholinesterase, cytotoxicity, organophosphorus poisoning, reactivators of acetylcholinesterase
Procedia PDF Downloads 307923 Synthesis and in vitro Characterization of a Gel-Derived SiO2-CaO-P2O5-SrO-Li2O Bioactive Glass
Authors: Mehrnaz Aminitabar, Moghan Amirhosseinian, Morteza Elsa
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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO2-CaO-P2O5 glass with nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of opposite effect of Sr and Li of the dissolution of BG in the SBF but also, stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S BG exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.Keywords: antibacterial activity, bioactive glass, sol-gel, strontium
Procedia PDF Downloads 121922 Removal of Nickel and Vanadium from Crude Oil by Using Solvent Extraction and Electrochemical Process
Authors: Aliya Kurbanova, Nurlan Akhmetov, Abilmansur Yeshmuratov, Yerzhigit Sugurbekov, Ramiz Zulkharnay, Gulzat Demeuova, Murat Baisariyev, Gulnar Sugurbekova
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Last decades crude oils have tended to become more challenge to process due to increasing amounts of sour and heavy crude oils. Some crude oils contain high vanadium and nickel content, for example Pavlodar LLP crude oil, which contains more than 23.09 g/t nickel and 58.59 g/t vanadium. In this study, we used two types of metal removing methods such as solvent extraction and electrochemical. The present research is conducted for comparative analysis of the deasphalting with organic solvents (cyclohexane, carbon tetrachloride, chloroform) and electrochemical method. Applying the cyclic voltametric analysis (CVA) and Inductively coupled plasma mass spectrometry (ICP MS), these mentioned types of metal extraction methods were compared in this paper. Maximum efficiency of deasphalting, with cyclohexane as the solvent, in Soxhlet extractor was 66.4% for nickel and 51.2% for vanadium content from crude oil. Percentage of Ni extraction reached maximum of approximately 55% by using the electrochemical method in electrolysis cell, which was developed for this research and consists of three sections: oil and protonating agent (EtOH) solution between two conducting membranes which divides it from two capsules of 10% sulfuric acid and two graphite electrodes which cover all three parts in electrical circuit. Ions of metals pass through membranes and remain in acid solutions. The best result was obtained in 60 minutes with ethanol to oil ratio 25% to 75% respectively, current fits into the range from 0.3A to 0.4A, voltage changed from 12.8V to 17.3V.Keywords: demetallization, deasphalting, electrochemical removal, heavy metals, petroleum engineering, solvent extraction
Procedia PDF Downloads 326921 Investigating the Effect of the Psychoactive Substances Act 2016 on the Incidence of Adverse Medical Events in Her Majesty’s Prison (HMP) Leeds
Authors: Hayley Boal, Chloe Bromley, John Fairfield
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Novel Psychoactive Substances (NPS) are synthetic compounds designed to reproduce effects of illicit drugs. Cheap, potent, and readily available on UK highstreets from so-called ‘head shops’, in recent years their use has surged and with it have emerged side effects including seizures, aggression, palpitations, coma, and death. Rapid development of new substances has vastly outpaced pre-existing drug legislation but the Psychoactive Substances Act 2016 rendered all but tobacco, alcohol, and amyl nitrates, illegal. Drug use has long been rife within prisons, but the absence of a reliable screening tool alongside the availability of NPS makes them ideal for prison use. Here we examine the occurrence of NPS-related adverse side effects within HMP Leeds, comparing May-September of 2015 and 2017 using daily reports distributed amongst prison staff summarising medical and behavioural incidents of the previous day. There was a statistically-significant rise of over 200% in the use of NPS between 2015 and 2017: 0.562 and 1.149 incidents per day respectively. In 2017, 38.46% incidents required ambulances, fallen from 51.02% in 2015. Although the most common descriptions in both years were ‘seizure’ and ‘unresponsive’, by 2017 ‘inhalation by staff’ had emerged. Patterns of NPS consumption mirrored the prison regime, peaking when cell doors opened, and prisoners could socialise. Despite limited data, the Psychoactive Substances Act has clearly been an insufficient deterrent to the prison population; more must be done to understand and address substance misuse in prison. NPS remains a significant risk to prisoners’ health and wellbeing.Keywords: legislation, novel psychoactive substances, prison, spice
Procedia PDF Downloads 189920 Evaluation of the Diagnostic Potential of IL-2 after Specific Antigen Stimulation with PE35 (Rv3872) and PPE68 (Rv3873) for the Discrimination of Active and Latent Tuberculosis
Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani
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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.Keywords: IL-2, PE35, PPE68, tuberculosis
Procedia PDF Downloads 409919 Conjugated Linoleic Acid (CLA) Health Benefits and Sources
Authors: Hilal Ahmad Punoo
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Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid with two conjugated double bonds. Of more than a dozen isomers of CLA found naturally in dairy and meat products from ruminants, c-9, t-11 and t-10, c-12 are the two isomers with known physiological importance, including anticarcinogenic, antidiabetic, antilipogenic, and antiatherosclerotic effects. Conjugated linoleic acids (CLA) may influence the onset and severity of several chronic diseases, including various cancers, atherosclerosis, obesity, bone density loss, and diabetes. These findings are of special interest to the agriculture community, because dietary sources of CLA are almost exclusively beef and dairy products. Thus, a better understanding of the specific isomers and mechanisms responsible for these positive effects of CLA on human health would be both prudent and economically beneficial. To date, research related to the advantages of CLA consumption on human health has been conducted using experimental laboratory animals and cell culture systems. These data consistently show that relatively low levels of CLA can influence risk of cancer. Further, very recent investigations suggest that the predominate CLA isoform (cis-9, trans-11 CLA or rumenic acid) found in beef and milk fat possesses anticarcinogenic effects but does not alter body composition; the trans-10, cis-12 CLA has been shown to inhibit lipogenesis. Clearly, further work, especially using human subjects, will be required to characterize the potential benefits of CLA consumption on human health. Moreover, we suggest that foods naturally containing high amounts of CLA (e.g., beef and dairy products) be considered as meeting the definition of functional foods.Keywords: conjugated linoleic acid, potential health benefits, fats, animals, humans
Procedia PDF Downloads 308918 Improving Biodegradation Behavior of Fabricated WE43 Magnesium Alloy by High-Temperature Oxidation
Authors: Jinge Liu, Shuyuan Min, Bingchuan Liu, Bangzhao Yin, Bo Peng, Peng Wen, Yun Tian
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WE43 magnesium alloy can be additively manufactured via laser powder bed fusion (LPBF) for biodegradable applications, but the as-built WE43 exhibits an excessively rapid corrosion rate. High-temperature oxidation (HTO) was performed on the as-built WE43 to improve its biodegradation behavior. A sandwich structure including an oxide layer at the surface, a transition layer in the middle, and the matrix was generated influenced by the oxidation reaction and diffusion of RE atoms when heated at 525 ℃for 8 hours. The oxide layer consisted of Y₂O₃ and Nd₂O₃ oxides with a thickness of 2-3 μm. The transition layer is composed of α-Mg and Y₂O₃ with a thickness of 60-70 μm, while Mg24RE5 could be observed except α-Mg and Y₂O₃. The oxide layer and transition layer appeared to have an effective passivation effect. The as-built WE43 lost 40% weight after the in vitro immersion test for three days and finally broke into debris after seven days of immersion. The high-temperature oxidation samples kept the structural integrity and lost only 6.88 % weight after 28-day immersion. The corrosion rate of HTO samples was significantly controlled, which improved the biocompatibility of the as-built WE43 at the same time. The samples after HTO had better osteogenic capability according to ALP activity. Moreover, as built WE43 performed unqualified in cell adhesion and hemolytic test due to its excessively rapid corrosion rate. While as for HTO samples, cells adhered well, and the hemolysis ratio was only 1.59%.Keywords: laser powder bed fusion, biodegradable metal, high temperature oxidation, biodegradation behavior, WE43
Procedia PDF Downloads 105917 Management of Femoral Neck Stress Fractures at a Specialist Centre and Predictive Factors to Return to Activity Time: An Audit
Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey
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Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D
Procedia PDF Downloads 183916 Eco-Friendly Control of Bacterial Speck on Solanum lycopersicum by Azadirachta indica Extract
Authors: Navodit Goel, Prabir K. Paul
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Tomato (Solanum lycopersicum) is attacked by Pseudomonas syringae pv. tomato causing speck lesions on the leaves leading to severe economic casualty. In the present study, aqueous fruit extracts of Azadirachta indica (neem) were sprayed on a single node of tomato plants grown under controlled contamination-free conditions. The treatment of plants was performed with neem fruit extract either alone or along with the pathogen. The parameters of observation were activities of polyphenol oxidase (PPO) and lysozyme, and isoform analysis of PPO; both at the treated leaves as well as untreated leaves away from the site of extract application. Polyphenol oxidase initiates phenylpropanoid pathway resulting in the synthesis of quinines from cytoplasmic phenols and production of reactive oxygen species toxic to broad spectrum microbes. Lysozyme is responsible for the breakdown of bacterial cell wall. The results indicate the upregulation of PPO and lysozyme activities in both the treated and untreated leaves along with de novo expression of newer PPO isoenzymes (which were absent in control samples). The appearance of additional PPO isoenzymes in bioelicitor-treated plants indicates that either the isoenzymes were expressed after bioelicitor application or the already expressed but inactive isoenzymes were activated by it. Lysozyme activity was significantly increased in the plants when treated with the bioelicitor or the pathogen alone. However, no new isoenzymes of lysozyme were expressed upon application of the extract. Induction of resistance by neem fruit extract could be a potent weapon in eco-friendly plant protection strategies.Keywords: Azadirachta indica, lysozyme, polyphenol oxidase, Solanum lycopersicum
Procedia PDF Downloads 288915 Antihyperglycemic Potential of Chrysin and Diosmin alone or in Combination against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms
Authors: Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O Saleh, Manal Badawi
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Background: Diabetes is a metabolic disease that affects a wide range of people worldwide and results in serious complications. Streptozotocin (STZ) causes selective cytotoxicity in the pancreatic β-cell, and it has been extensively used to induce diabetes mellitus in rats. The present study investigated the effects of diosmin and chrysin alone or in combination with each other on glucose level and on liver in STZ diabetic rats. Methods: In this study, rats were divided into six experimental groups (normal, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with glycazide (10 mg/kg B.W, oral), treated STZ-diabetic with diosmin (100 mg/kg B. W., oral), treated STZ-diabetic with chrysin (80 mg/kg B.W., oral), treated STZ-diabetic with diosmin (50 mg/kg B.W, oral) + chrysin (40 mg/kg B.W., oral). After 2 weeks blood samples were withdrawn and glucose was measured. Animals were anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for dissecting liver. Results: Throughout the experimental period, all treatments significantly (P<0.05) lowered serum glucose, AST, ALT, triglyceride, cholesterol, IL-6, TNF-α and IL-1β. Moreover, the treated diabetic rats showed higher levels of reduced glutathione (P<0.05) in the liver compared to the diabetic control rats and inhibited diabetes-induced elevation in the levels of malondialdehyde in liver. The results of this study clearly demonstrated that diosmin and chrysin possess several treatment-oriented properties, including the control of hyperglycemia, antioxidant effects and anti-inflammatory effects. Conclusion: Considering these observations, it appears that diosmin and chrysin may be a useful supplement to delay the developmentof diabetes and its complications.Keywords: diabetes, streptozocin, chrysin, rat, diosmin, cytokines
Procedia PDF Downloads 265914 Encapsulation of Probiotic Bacteria in Complex Coacervates
Authors: L. A. Bosnea, T. Moschakis, C. Biliaderis
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Two probiotic strains of Lactobacillus paracasei subsp. paracasei (E6) and Lactobacillus paraplantarum (B1), isolated from traditional Greek dairy products, were microencapsulated by complex coacervation using whey protein isolate (WPI, 3% w/v) and gum arabic (GA, 3% w/v) solutions mixed at different polymer ratio (1:1, 2:1 and 4:1). The effect of total biopolymer concentration on cell viability was assessed using WPI and GA solutions of 1, 3 and 6% w/v at a constant ratio of 2:1. Also, several parameters were examined for optimization of the microcapsule formation, such as inoculum concentration and the effect of ionic strength. The viability of the bacterial cells during heat treatment and under simulated gut conditions was also evaluated. Among the different WPI/GA weight ratios tested (1:1, 2:1, and 4:1), the highest survival rate was observed for the coacervate structures made with the ratio of 2:1. The protection efficiency at low pH values is influenced by both concentration and the ratio of the added biopolymers. Moreover, the inoculum concentration seems to affect the efficiency of microcapsules to entrap the bacterial cells since an optimum level was noted at less than 8 log cfu/ml. Generally, entrapment of lactobacilli in the complex coacervate structure enhanced the viability of the microorganisms when exposed to a low pH environment (pH 2.0). Both encapsulated strains retained high viability in simulated gastric juice (>73%), especially in comparison with non-encapsulated (free) cells (<19%). The encapsulated lactobacilli also exhibited enhanced viability after 10–30 min of heat treatment (65oC) as well as at different NaCl concentrations (pH 4.0). Overall, the results of this study suggest that complex coacervation with WPI/GA has a potential to deliver live probiotics in low pH food systems and fermented dairy products; the complexes can dissolve at pH 7.0 (gut environment), releasing the microbial cells.Keywords: probiotic, complex coacervation, whey, encapsulation
Procedia PDF Downloads 297913 Relationship between Hepatokines and Insulin Resistance in Childhood Obesity
Authors: Mustafa Metin Donma, Orkide Donma
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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity
Procedia PDF Downloads 176912 The Role of Micro-Ribonucleic Acid-182 and Micro-Ribonucleic Acid-214 in Cisplatin Resistance of Triple-Negative Breast Cancer Cells
Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul
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Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX
Procedia PDF Downloads 131911 Anticancer Activity of Calyx of Diospyros kaki Thunb. through Downregulation of Cyclin D1 Protein Level in Human Colorectal Cancer Cells
Authors: Jin Boo Jeong
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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer
Procedia PDF Downloads 312910 Experimental Correlation for Erythrocyte Aggregation Rate in Population Balance Modeling
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
Procedia PDF Downloads 355909 Avoiding Gas Hydrate Problems in Qatar Oil and Gas Industry: Environmentally Friendly Solvents for Gas Hydrate Inhibition
Authors: Nabila Mohamed, Santiago Aparicio, Bahman Tohidi, Mert Atilhan
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Qatar's one of the biggest problem in processing its natural resource, which is natural gas, is the often occurring blockage in the pipelines caused due to uncontrolled gas hydrate formation in the pipelines. Several millions of dollars are being spent at the process site to dehydrate the blockage safely by using chemical inhibitors. We aim to establish national database, which addresses the physical conditions that promotes Qatari natural gas to form gas hydrates in the pipelines. Moreover, we aim to design and test novel hydrate inhibitors that are suitable for Qatari natural gas and its processing facilities. From these perspectives we are aiming to provide more effective and sustainable reservoir utilization and processing of Qatari natural gas. In this work, we present the initial findings of a QNRF funded project, which deals with the natural gas hydrate formation characteristics of Qatari type gas in both experimental (PVTx) and computational (molecular simulations) methods. We present the data from the two fully automated apparatus: a gas hydrate autoclave and a rocking cell. Hydrate equilibrium curves including growth/dissociation conditions for multi-component systems for several gas mixtures that represent Qatari type natural gas with and without the presence of well known kinetic and thermodynamic hydrate inhibitors. Ionic liquids were designed and used for testing their inhibition performance and their DFT and molecular modeling simulation results were also obtained and compared with the experimental results. Results showed significant performance of ionic liquids with up to 0.5 % in volume with up to 2 to 4 0C inhibition at high pressures.Keywords: gas hydrates, natural gas, ionic liquids, inhibition, thermodynamic inhibitors, kinetic inhibitors
Procedia PDF Downloads 1320908 Complex Management of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Abdullah A. Al Qurashi, Hattan A. Hassani, Bader K. Alaslap
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Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an uncommon, inheritable cardiac disorder characterized by the progressive substitution of cardiac myocytes by fibro-fatty tissues. This pathologic substitution predisposes patients to ventricular arrhythmias and right ventricular failure. The underlying genetic defect predominantly involves genes encoding for desmosome proteins, particularly plakophilin-2 (PKP2). These aberrations lead to impaired cell adhesion, heightening the susceptibility to fibrofatty scarring under conditions of mechanical stress. Primarily, ARVD/C affects the right ventricle, but it can also compromise the left ventricle, potentially leading to biventricular heart failure. Clinical presentations can vary, spanning from asymptomatic individuals to those experiencing palpitations, syncopal episodes, and, in severe instances, sudden cardiac death. The establishment of a diagnostic criterion specifically tailored for ARVD/C significantly aids in its accurate diagnosis. Nevertheless, the task of early diagnosis is complicated by the disease's frequently asymptomatic initial stages, and the overall rarity of ARVD/C cases reported globally. In some cases, as exemplified by the adult female patient in this report, the disease may advance to terminal stages, rendering therapies like Ventricular Tachycardia (VT) ablation ineffective. This case underlines the necessity for increased awareness and understanding of ARVD/C to aid in its early detection and management. Through such efforts, we aim to decrease morbidity and mortality associated with this challenging cardiac disorder.Keywords: arrhythmogenic right ventricular dysplasia, cardiac disease, interventional cardiology, cardiac electrophysiology
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