Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3227

Search results for: cell stimulation

3227 Photoelectrical Stimulation for Cancer Therapy

Authors: Mohammad M. Aria, Fatma Öz, Yashar Esmaeilian, Marco Carofiglio, Valentina Cauda, Özlem Yalçın


Photoelectrical stimulation of cells with semiconductor organic polymers have been shown promising applications in neuroprosthetics such as retinal prosthesis. Photoelectrical stimulation of the cell membranes can be induced through a photo-electric charge separation mechanism in the semiconductor materials, and it can alter intracellular calcium level through both stimulation of voltage-gated ion channels and increase of intracellular reactive oxygen species (ROS) level. On the other hand, targeting voltage-gated ion channels in cancer cells to induce cell apoptosis through calcium signaling alternation is an effective mechanism which has been explained before. In this regard, remote control of the voltage-gated ion channels aimed to alter intracellular calcium by using photo-active organic polymers can be novel technology in cancer therapy. In this study, we used P (ITO/Indium thin oxide)/P3HT(poly(3-hexylthiophene-2,5-diyl)) and PN (ITO/ZnO/P3HT) photovoltaic junctions to stimulate MDA-MB-231 breast cancer cells. We showed that the photo-stimulation of breast cancer cells through photo capacitive current generated by the photovoltaic junctions are able to excite the cells and alternate intracellular calcium based on the calcium imaging (at 8mW/cm² green light intensity and 10-50 ms light durations), which has been reported already to safety stimulate neurons. The control group did not undergo light treatment and was cultured in T-75 flasks. We detected 20-30% cell death for ITO/P3HT and 51-60% cell death for ITO/ZnO/P3HT samples in the light treated MDA-MB-231 cell group. Western blot analysis demonstrated poly(ADP-ribose) polymerase (PARP) activated cell death in the light treated group. Furthermore, Annexin V and PI fluorescent staining indicated both apoptosis and necrosis in treated cells. In conclusion, our findings revealed that the photoelectrical stimulation of cells (through long time overstimulation) can induce cell death in cancer cells.

Keywords: Ca²⁺ signaling, cancer therapy, electrically excitable cells, photoelectrical stimulation, voltage-gated ion channels

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3226 Investigation of Different Stimulation Patterns to Reduce Muscle Fatigue during Functional Electrical Stimulation

Authors: R. Ruslee, H. Gollee


Functional electrical stimulation (FES) is a commonly used technique in rehabilitation and often associated with rapid muscle fatigue which becomes the limiting factor in its applications. The objective of this study is to investigate the effects on the onset of fatigue of conventional synchronous stimulation, as well as asynchronous stimulation that mimic voluntary muscle activation targeting different motor units which are activated sequentially or randomly via multiple pairs of stimulation electrodes. We investigate three different approaches with various electrode configurations, as well as different patterns of stimulation applied to the gastrocnemius muscle: Conventional Synchronous Stimulation (CSS), Asynchronous Sequential Stimulation (ASS) and Asynchronous Random Stimulation (ARS). Stimulation was applied repeatedly for 300 ms followed by 700 ms of no-stimulation with 40 Hz effective frequency for all protocols. Ten able-bodied volunteers (28±3 years old) participated in this study. As fatigue indicators, we focused on the analysis of Normalized Fatigue Index (NFI), Fatigue Time Interval (FTI) and pre-post Twitch-Tetanus Ratio (ΔTTR). The results demonstrated that ASS and ARS give higher NFI and longer FTI confirming less fatigue for asynchronous stimulation. In addition, ASS and ARS resulted in higher ΔTTR than conventional CSS. In this study, we proposed a randomly distributed stimulation method for the application of FES and investigated its suitability for reducing muscle fatigue compared to previously applied methods. The results validated that asynchronous stimulation reduces fatigue, and indicates that random stimulation may improve fatigue resistance in some conditions.

Keywords: asynchronous stimulation, electrode configuration, functional electrical stimulation (FES), muscle fatigue, pattern stimulation, random stimulation, sequential stimulation, synchronous stimulation

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3225 Electromagnetic-Mechanical Stimulation on PC12 for Enhancement of Nerve Axonal Extension

Authors: E. Nakamachi, K. Matsumoto, K. Yamamoto, Y. Morita, H. Sakamoto


In recently, electromagnetic and mechanical stimulations have been recognized as the effective extracellular environment stimulation technique to enhance the defected peripheral nerve tissue regeneration. In this study, we developed a new hybrid bioreactor by adopting 50 Hz uniform alternative current (AC) magnetic stimulation and 4% strain mechanical stimulation. The guide tube for nerve regeneration is mesh structured tube made of biodegradable polymer, such as polylatic acid (PLA). However, when neural damage is large, there is a possibility that peripheral nerve undergoes necrosis. So it is quite important to accelerate the nerve tissue regeneration by achieving enhancement of nerve axonal extension rate. Therefore, we try to design and fabricate the system that can simultaneously load the uniform AC magnetic field stimulation and the stretch stimulation to cells for enhancement of nerve axonal extension. Next, we evaluated systems performance and the effectiveness of each stimulation for rat adrenal pheochromocytoma cells (PC12). First, we designed and fabricated the uniform AC magnetic field system and the stretch stimulation system. For the AC magnetic stimulation system, we focused on the use of pole piece structure to carry out in-situ microscopic observation. We designed an optimum pole piece structure using the magnetic field finite element analyses and the response surface methodology. We fabricated the uniform AC magnetic field stimulation system as a bio-reactor by adopting analytically determined design specifications. We measured magnetic flux density that is generated by the uniform AC magnetic field stimulation system. We confirmed that measurement values show good agreement with analytical results, where the uniform magnetic field was observed. Second, we fabricated the cyclic stretch stimulation device under the conditions of particular strains, where the chamber was made of polyoxymethylene (POM). We measured strains in the PC12 cell culture region to confirm the uniform strain. We found slightly different values from the target strain. Finally, we concluded that these differences were allowable in this mechanical stimulation system. We evaluated the effectiveness of each stimulation to enhance the nerve axonal extension using PC12. We confirmed that the average axonal extension length of PC12 under the uniform AC magnetic stimulation was increased by 16 % at 96 h in our bio-reactor. We could not confirm that the axonal extension enhancement under the stretch stimulation condition, where we found the exfoliating of cells. Further, the hybrid stimulation enhanced the axonal extension. Because the magnetic stimulation inhibits the exfoliating of cells. Finally, we concluded that the enhancement of PC12 axonal extension is due to the magnetic stimulation rather than the mechanical stimulation. Finally, we confirmed that the effectiveness of the uniform AC magnetic field stimulation for the nerve axonal extension using PC12 cells.

Keywords: nerve cell PC12, axonal extension, nerve regeneration, electromagnetic-mechanical stimulation, bioreactor

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3224 Dependence of the Electro-Stimulation of Saccharomyces cerevisiae by Pulsed Electric Field at the Yeast Growth Phase

Authors: Jessy Mattar, Mohamad Turk, Maurice Nonus, Nikolai Lebovka, Henri El Zakhem, Eugene Vorobiev


The effects of electro-stimulation of S. cerevisiae cells in colloidal suspension by Pulsed Electric Fields ‎‎(PEF) with electric field strength E = 20 – 2000 and effective PEF treatment time tPEF = 10^−5 – 1 s were ‎investigated. The applied experimental procedure includes variations in the preliminary fermentation time and ‎electro-stimulation by PEF-treatment. Plate counting was performed.‎ At relatively high electric fields (E ≥ 1000 and moderate PEF treatment time (tPEF > 100 µs), the ‎extraction of ionic components from yeast was observed by conductivity measurements, which can be related to ‎electroporation of cell membranes. Cell counting revealed a dependency of the colonies’ size on the time of ‎preliminary fermentation tf and the power consumption W, however no dependencies were noticeable by varying the initial yeast concentration in the treated suspensions.‎

Keywords: intensification, yeast, fermentation, electroporation, biotechnology

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3223 Stimulation of Nerve Tissue Differentiation and Development Using Scaffold-Based Cell Culture in Bioreactors

Authors: Simon Grossemy, Peggy P. Y. Chan, Pauline M. Doran


Nerve tissue engineering is the main field of research aimed at finding an alternative to autografts as a treatment for nerve injuries. Scaffolds are used as a support to enhance nerve regeneration. In order to successfully design novel scaffolds and in vitro cell culture systems, a deep understanding of the factors affecting nerve regeneration processes is needed. Physical and biological parameters associated with the culture environment have been identified as potentially influential in nerve cell differentiation, including electrical stimulation, exposure to extracellular-matrix (ECM) proteins, dynamic medium conditions and co-culture with glial cells. The mechanisms involved in driving the cell to differentiation in the presence of these factors are poorly understood; the complexity of each of them raises the possibility that they may strongly influence each other. Some questions that arise in investigating nerve regeneration include: What are the best protein coatings to promote neural cell attachment? Is the scaffold design suitable for providing all the required factors combined? What is the influence of dynamic stimulation on cell viability and differentiation? In order to study these effects, scaffolds adaptable to bioreactor culture conditions were designed to allow electrical stimulation of cells exposed to ECM proteins, all within a dynamic medium environment. Gold coatings were used to make the surface of viscose rayon microfiber scaffolds (VRMS) conductive, and poly-L-lysine (PLL) and laminin (LN) surface coatings were used to mimic the ECM environment and allow the attachment of rat PC12 neural cells. The robustness of the coatings was analyzed by surface resistivity measurements, scanning electron microscope (SEM) observation and immunocytochemistry. Cell attachment to protein coatings of PLL, LN and PLL+LN was studied using DNA quantification with Hoechst. The double coating of PLL+LN was selected based on high levels of PC12 cell attachment and the reported advantages of laminin for neural differentiation. The underlying gold coatings were shown to be biocompatible using cell proliferation and live/dead staining assays. Coatings exhibiting stable properties over time under dynamic fluid conditions were developed; indeed, cell attachment and the conductive power of the scaffolds were maintained over 2 weeks of bioreactor operation. These scaffolds are promising research tools for understanding complex neural cell behavior. They have been used to investigate major factors in the physical culture environment that affect nerve cell viability and differentiation, including electrical stimulation, bioreactor hydrodynamic conditions, and combinations of these parameters. The cell and tissue differentiation response was evaluated using DNA quantification, immunocytochemistry, RT-qPCR and functional analyses.

Keywords: bioreactor, electrical stimulation, nerve differentiation, PC12 cells, scaffold

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3222 Direct Current Electric Field Stimulation against PC12 Cells in 3D Bio-Reactor to Enhance Axonal Extension

Authors: E. Nakamachi, S. Tanaka, K. Yamamoto, Y. Morita


In this study, we developed a three-dimensional (3D) direct current electric field (DCEF) stimulation bio-reactor for axonal outgrowth enhancement to generate the neural network of the central nervous system (CNS). By using our newly developed 3D DCEF stimulation bio-reactor, we cultured the rat pheochromocytoma cells (PC12) and investigated the effects on the axonal extension enhancement and network generation. Firstly, we designed and fabricated a 3D bio-reactor, which can load DCEF stimulation on PC12 cells embedded in the collagen gel as extracellular environment. The connection between the electrolyte and the medium using salt bridges for DCEF stimulation was introduced to avoid the cell death by the toxicity of metal ion. The distance between the salt bridges was adopted as the design variable to optimize a structure for uniform DCEF stimulation, where the finite element (FE) analyses results were used. Uniform DCEF strength and electric flux vector direction in the PC12 cells embedded in collagen gel were examined through measurements of the fabricated 3D bio-reactor chamber. Measurement results of DCEF strength in the bio-reactor showed a good agreement with FE results. In addition, the perfusion system was attached to maintain pH 7.2 ~ 7.6 of the medium because pH change was caused by DCEF stimulation loading. Secondly, we disseminated PC12 cells in collagen gel and carried out 3D culture. Finally, we measured the morphology of PC12 cell bodies and neurites by the multiphoton excitation fluorescence microscope (MPM). The effectiveness of DCEF stimulation to enhance the axonal outgrowth and the neural network generation was investigated. We confirmed that both an increase of mean axonal length and axogenesis rate of PC12, which have been exposed 5 mV/mm for 6 hours a day for 4 days in the bioreactor. We found following conclusions in our study. 1) Design and fabrication of DCEF stimulation bio-reactor capable of 3D culture nerve cell were completed. A uniform electric field strength of average value of 17 mV/mm within the 1.2% error range was confirmed by using FE analyses, after the structure determination through the optimization process. In addition, we attached a perfusion system capable of suppressing the pH change of the culture solution due to DCEF stimulation loading. 2) Evaluation of DCEF stimulation effects on PC12 cell activity was executed. The 3D culture of PC 12 was carried out adopting the embedding culture method using collagen gel as a scaffold for four days under the condition of 5.0 mV/mm and 10mV/mm. There was a significant effect on the enhancement of axonal extension, as 11.3% increase in an average length, and the increase of axogenesis rate. On the other hand, no effects on the orientation of axon against the DCEF flux direction was observed. Further, the network generation was enhanced to connect longer distance between the target neighbor cells by DCEF stimulation.

Keywords: PC12, DCEF stimulation, 3D bio-reactor, axonal extension, neural network generation

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3221 Development of Three-Dimensional Bio-Reactor Using Magnetic Field Stimulation to Enhance PC12 Cell Axonal Extension

Authors: Eiji Nakamachi, Ryota Sakiyama, Koji Yamamoto, Yusuke Morita, Hidetoshi Sakamoto


The regeneration of injured central nerve network caused by the cerebrovascular accidents is difficult, because of poor regeneration capability of central nerve system composed of the brain and the spinal cord. Recently, new regeneration methods such as transplant of nerve cells and supply of nerve nutritional factor were proposed and examined. However, there still remain many problems with the canceration of engrafted cells and so on and it is strongly required to establish an efficacious treating method of a central nerve system. Blackman proposed the electromagnetic stimulation method to enhance the axonal nerve extension. In this study, we try to design and fabricate a new three-dimensional (3D) bio-reactor, which can load a uniform AC magnetic field stimulation on PC12 cells in the extracellular environment for enhancement of an axonal nerve extension and 3D nerve network generation. Simultaneously, we measure the morphology of PC12 cell bodies, axons, and dendrites by the multiphoton excitation fluorescence microscope (MPM) and evaluate the effectiveness of the uniform AC magnetic stimulation to enhance the axonal nerve extension. Firstly, we designed and fabricated the uniform AC magnetic field stimulation bio-reactor. For the AC magnetic stimulation system, we used the laminated silicon steel sheets for a yoke structure of 3D chamber, which had a high magnetic permeability. Next, we adopted the pole piece structure and installed similar specification coils on both sides of the yoke. We searched an optimum pole piece structure using the magnetic field finite element (FE) analyses and the response surface methodology. We confirmed that the optimum 3D chamber structure showed a uniform magnetic flux density in the PC12 cell culture area by using FE analysis. Then, we fabricated the uniform AC magnetic field stimulation bio-reactor by adopting analytically determined specifications, such as the size of chamber and electromagnetic conditions. We confirmed that measurement results of magnetic field in the chamber showed a good agreement with FE results. Secondly, we fabricated a dish, which set inside the uniform AC magnetic field stimulation of bio-reactor. PC12 cells were disseminated with collagen gel and could be 3D cultured in the dish. The collagen gel were poured in the dish. The collagen gel, which had a disk shape of 6 mm diameter and 3mm height, was set on the membrane filter, which was located at 4 mm height from the bottom of dish. The disk was full filled with the culture medium inside the dish. Finally, we evaluated the effectiveness of the uniform AC magnetic field stimulation to enhance the nurve axonal extension. We confirmed that a 6.8 increase in the average axonal extension length of PC12 under the uniform AC magnetic field stimulation at 7 days culture in our bio-reactor, and a 24.7 increase in the maximum axonal extension length. Further, we confirmed that a 60 increase in the number of dendrites of PC12 under the uniform AC magnetic field stimulation. Finally, we confirm the availability of our uniform AC magnetic stimulation bio-reactor for the nerve axonal extension and the nerve network generation.

Keywords: nerve regeneration, axonal extension , PC12 cell, magnetic field, three-dimensional bio-reactor

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3220 Isolated Contraction of Deep Lumbar Paraspinal Muscle with Magnetic Nerve Root Stimulation: A Pilot Study

Authors: Shi-Uk Lee, Chae Young Lim


Objective: The aim of this study was to evaluate the changes of lumbar deep muscle thickness and cross-sectional area using ultrasonography with magnetic stimulation. Methods: To evaluate the changes of lumbar deep muscle by using magnetic stimulation, 12 healthy volunteers (39.6±10.0 yrs) without low back pain during 3 months participated in this study. All the participants were checked with X-ray and electrophysiologic study to confirm that they had no problems with their back. Magnetic stimulation was done on the L5 and S1 root with figure-eight coil as previous study. To confirm the proper motor root stimulation, the surface electrode was put on the tibialis anterior (L5) and abductor hallucis muscles (S1) and the hot spots of magnetic stimulation were found with 50% of maximal magnetic stimulation and determined the stimulation threshold lowering the magnetic intensity by 5%. Ultrasonography was used to assess the changes of L5 and S1 lumbar multifidus (superficial and deep) cross-sectional area and thickness with maximal magnetic stimulation. Cross-sectional area (CSA) and thickness was evaluated with image acquisition program, ImageJ software (National Institute of Healthy, USA). Wilcoxon signed-rank was used to compare outcomes between before and after stimulations. Results: The mean minimal threshold was 29.6±3.8% of maximal stimulation intensity. With minimal magnetic stimulation, thickness of L5 and S1 deep multifidus (DM) were increased from 1.25±0.20, 1.42±0.23 cm to 1.40±0.27, 1.56±0.34 cm, respectively (P=0.005, P=0.003). CSA of L5 and S1 DM were also increased from 2.26±0.18, 1.40±0.26 cm2 to 2.37±0.18, 1.56±0.34 cm2, respectively (P=0.002, P=0.002). However, thickness of L5 and S1 superficial multifidus (SM) were not changed from 1.92±0.21, 2.04±0.20 cm to 1.91±0.33, 1.96±0.33 cm (P=0.211, P=0.199) and CSA of L5 and S1 were also not changed from 4.29±0.53, 5.48±0.32 cm2 to 4.42±0.42, 5.64±0.38 cm2. With maximal magnetic stimulation, thickness of L5, S1 of DM and SM were increased (L5 DM, 1.29±0.26, 1.46±0.27 cm, P=0.028; L5 SM, 2.01±0.42, 2.24±0.39 cm, P=0.005; S1 DM, 1.29±0.19, 1.67±0.29 P=0.002; S1 SM, 1.90±0.36, 2.30±0.36, P=0.002). CSA of L5, S1 of DM and SM were also increased (all P values were 0.002). Conclusions: Deep lumbar muscles could be stimulated with lumbar motor root magnetic stimulation. With minimal stimulation, thickness and CSA of lumbosacral deep multifidus were increased in this study. Further studies are needed to confirm whether the similar results in chronic low back pain patients are represented. Lumbar magnetic stimulation might have strengthening effect of deep lumbar muscles with no discomfort.

Keywords: magnetic stimulation, lumbar multifidus, strengthening, ultrasonography

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3219 Bio-Heat Transfer in Various Transcutaneous Stimulation Models

Authors: Trevor E. Davis, Isaac Cassar, Yi-Kai Lo, Wentai Liu


This study models the use of transcutaneous electrical nerve stimulation on skin with a disk electrode in order to simulate tissue damage. The current density distribution above a disk electrode is known to be a dynamic and non-uniform quantity that is intensified at the edges of the disk. The non-uniformity is subject to change through using various electrode geometries or stimulation methods. One of these methods known as edge-retarded stimulation has shown to reduce this edge enhancement. Though progress has been made in modeling the behavior of a disk electrode, little has been done to test the validity of these models in simulating the actual heat transfer from the electrode. This simulation uses finite element software to couple the injection of current from a disk electrode to heat transfer described by the Pennesbioheat transfer equation. An example application of this model is studying an experimental form of stimulation, known as edge-retarded stimulation. The edge-retarded stimulation method will reduce the current density at the edges of the electrode. It is hypothesized that reducing the current density edge enhancement effect will, in turn, reduce temperature change and tissue damage at the edges of these electrodes. This study tests this hypothesis as a demonstration of the capabilities of this model. The edge-retarded stimulation proved to be safer after this simulation. It is shown that temperature change and the fraction of tissue necrosis is much greater in the square wave stimulation. These results bring implications for changes of procedures in transcutaneous electrical nerve stimulation and transcutaneous spinal cord stimulation as well.

Keywords: bioheat transfer, electrode, neuroprosthetics, TENS, transcutaneous stimulation

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3218 A Self-Adaptive Stimulus Artifacts Removal Approach for Electrical Stimulation Based Muscle Rehabilitation

Authors: Yinjun Tu, Qiang Fang, Glenn I. Matthews, Shuenn-Yuh Lee


This paper reports an efficient and rigorous self-adaptive stimulus artifacts removal approach for a mixed surface EMG (Electromyography) and stimulus signal during muscle stimulation. The recording of EMG and the stimulation of muscles were performing simultaneously. It is difficult to generate muscle fatigue feature from the mixed signal, which can be further used in closed loop system. A self-adaptive method is proposed in this paper, the stimulation frequency was calculated and verified firstly. Then, a mask was created based on this stimulation frequency to remove the undesired stimulus. 20 EMG signal recordings were analyzed, and the ANOVA (analysis of variance) approach illustrated that the decreasing trend of median power frequencies was successfully generated from the 'cleaned' EMG signal.

Keywords: EMG, FES, stimulus artefacts, self-adaptive

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3217 The Effect of Combined Fluid Shear Stress and Cyclic Stretch on Endothelial Cells

Authors: Daphne Meza, Louie Abejar, David A. Rubenstein, Wei Yin


Endothelial cell (ECs) morphology and function is highly impacted by the mechanical stresses these cells experience in vivo. Any change in the mechanical environment can trigger pathological EC responses. A detailed understanding of EC morphological response and function upon subjection to individual and simultaneous mechanical stimuli is needed for advancement in mechanobiology and preventive medicine. To investigate this, a programmable device capable of simultaneously applying physiological fluid shear stress (FSS) and cyclic strain (CS) has been developed, characterized and validated. Its validation was performed both experimentally, through tracer tracking, and theoretically, through the use of a computational fluid dynamics model. The effectiveness of the device was evaluated through EC morphology changes under mechanical loading conditions. Changes in cell morphology were evaluated through: cell and nucleus elongation, cell alignment and junctional actin production. The results demonstrated that the combined FSS-CS stimulation induced visible changes in EC morphology. Upon simultaneous fluid shear stress and biaxial tensile strain stimulation, cells were elongated and generally aligned with the flow direction, with stress fibers highlighted along the cell junctions. The concurrent stimulation from shear stress and biaxial cyclic stretch led to a significant increase in cell elongation compared to untreated cells. This, however, was significantly lower than that induced by shear stress alone, indicating that the biaxial tensile strain may counteract the elongating effect of shear stress to maintain the shape of ECs. A similar trend was seen in alignment, where the alignment induced by the concurrent application of shear stress and cyclic stretch fell in between that induced by shear stress and tensile stretch alone, indicating the opposite role shear stress and tensile strain may play in cell alignment. Junctional actin accumulation was increased upon shear stress alone or simultaneously with tensile stretch. Tensile stretch alone did not change junctional actin accumulation, indicating the dominant role of shear stress in damaging EC junctions. These results demonstrate that the shearing-stretching device is capable of applying well characterized dynamic shear stress and tensile strain to cultured ECs. Using this device, EC response to altered mechanical environment in vivo can be characterized in vitro.

Keywords: cyclic stretch, endothelial cells, fluid shear stress, vascular biology

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3216 Hydrogen Peroxide: A Future for Well Stimulation and Heavy Oil Recovery

Authors: Meet Bhatia


Well stimulation and heavy oil recovery continue to be a hot topic in our industry, particularly with formation damage and viscous oil respectively. Cyclic steam injection has been recognised for most of the operations related to heavy oil recovery. However, the cost of implementation is high and operation is time-consuming, moreover most of the viscous oil reservoirs such as oil sands, Bitumen deposits and oil shales require additional treatment of well stimulation. The use of hydrogen peroxide can efficiently replace the cyclic steam injection process as it can be used for both well stimulation and heavy oil recovery simultaneously. The decomposition of Hydrogen peroxide produces oxygen, superheated steam and heat. The increase in temperature causes clays to shrink, destroy carbonates and remove emulsion thus it can efficiently remove the near wellbore damage. The paper includes mechanisms, parameters to be considered and the challenges during the treatment for the effective hydrogen peroxide injection for both conventional and heavy oil reservoirs.

Keywords: hydrogen peroxide, well stimulation, heavy oil recovery, steam injection

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3215 Effect of Naphtha on the Composition of a Heavy Crude, in Addition to a Cycle Steam Stimulation Process

Authors: A. Guerrero, A. Leon, S. Munoz, M. Sandoval


The addition of solvent to cyclic steam stimulation is done in order to reduce the solvent-vapor ratio at late stages of the process, the moment in which this relationship increases significantly. The study of the use of naphtha in addition to the cyclic steam stimulation has been mainly oriented to the effect it achieves on the incremental recovery compared to the application of steam only. However, the effect of naphtha on the reactivity of crude oil components under conditions of cyclic steam stimulation or if its effect is the only dilution has not yet been considered, to author’s best knowledge. The present study aims to evaluate and understand the effect of naphtha and the conditions of cyclic steam stimulation, on the remaining composition of the improved oil, as well as the main mechanisms present in the heavy crude - naphtha interaction. Tests were carried out with the system solvent (naphtha)-oil (12.5° API, 4216 cP @ 40° C)- steam, in a batch micro-reactor, under conditions of cyclic steam stimulation (250-300 °C, 400 psi). The characterization of the samples obtained was carried out by MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) and NMR (Nuclear Magnetic Resonance) techniques. The results indicate that there is a rearrangement of the microstructure of asphaltenes, resulting in a decrease in these and an increase in lighter components such as resins.

Keywords: composition change, cyclic steam stimulation, interaction mechanism, naphtha

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3214 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


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

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3213 Bioreactor for Cell-Based Impedance Measuring with Diamond Coated Gold Interdigitated Electrodes

Authors: Roman Matejka, Vaclav Prochazka, Tibor Izak, Jana Stepanovska, Martina Travnickova, Alexander Kromka


Cell-based impedance spectroscopy is suitable method for electrical monitoring of cell activity especially on substrates that cannot be easily inspected by optical microscope (without fluorescent markers) like decellularized tissues, nano-fibrous scaffold etc. Special sensor for this measurement was developed. This sensor consists of corning glass substrate with gold interdigitated electrodes covered with diamond layer. This diamond layer provides biocompatible non-conductive surface for cells. Also, a special PPFC flow cultivation chamber was developed. This chamber is able to fix sensor in place. The spring contacts are connecting sensor pads with external measuring device. Construction allows real-time live cell imaging. Combining with perfusion system allows medium circulation and generating shear stress stimulation. Experimental evaluation consist of several setups, including pure sensor without any coating and also collagen and fibrin coating was done. The Adipose derived stem cells (ASC) and Human umbilical vein endothelial cells (HUVEC) were seeded onto sensor in cultivation chamber. Then the chamber was installed into microscope system for live-cell imaging. The impedance measurement was utilized by vector impedance analyzer. The measured range was from 10 Hz to 40 kHz. These impedance measurements were correlated with live-cell microscopic imaging and immunofluorescent staining. Data analysis of measured signals showed response to cell adhesion of substrates, their proliferation and also change after shear stress stimulation which are important parameters during cultivation. Further experiments plan to use decellularized tissue as scaffold fixed on sensor. This kind of impedance sensor can provide feedback about cell culture conditions on opaque surfaces and scaffolds that can be used in tissue engineering in development artificial prostheses. This work was supported by the Ministry of Health, grants No. 15-29153A and 15-33018A.

Keywords: bio-impedance measuring, bioreactor, cell cultivation, diamond layer, gold interdigitated electrodes, tissue engineering

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3212 Differential Antibrucella Activity of Bovine and Murine Macrophages

Authors: Raheela Akhtar, Zafar Iqbal Chaudhary, Yongqun Oliver He, Muhammad Younus, Aftab Ahmad Anjum


Brucella abortus is an intracellular pathogen affecting macrophages. Macrophages release some components such as lysozymes (LZ), reactive oxygen species (ROS) and reactive nitrite intermediates (RNI) which are important tools against intracellular survival of Brucella. The antibrucella activity of bovine and murine macrophages was compared following stimulation with Brucella abortus lipopolysaccharides. Our results revealed that murine macrophages were ten times more potent to produce antibrucella components than bovine macrophages. The differential production of these components explained the differential Brucella killing ability of these species that was measured in terms of intramacrophagic survival of Brucella in murine and bovine macrophages.

Keywords: bovine macrophages, Brucella abortus, cell stimulation, cytokines, Murine macrophages

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3211 Effect of Grayanotoxins on Skeletal Muscle Cell C2C12

Authors: Bayan Almofty, Yuto Yamaki, Tadamasa Terai, Sadahito Uto


Myopathy (muscles disease) treatment are expected in the field of regenerative medicine and applied research of cultured muscle to bio actuator is performed in Biomedical Engineering as applied research of cultured muscle. This study is about cultured myoblast C2C12 from mouse skeletal muscle and a mechanism of cultured muscle contraction by electric stimulation is investigated. Grayanotoxins (GTXs) belong to neurotoxins known to enhance the permeability of cell membrane for Na ions. Grayanotoxins are extracted from a famous Pieris japonica and Ericaceae as a phytotoxin. We investigated the functional role of GTXs on muscle cells (C2C12) contraction and membrane potential. A change in membrane potential is measured using a micro glass tube electrode contraction of myotubes is induced by applying an external electrical stimulation. The contraction and membrane potential change induced by injection of current using the micro glass electrode are also measured. From the result, contraction and membrane potential of muscle cells was affected by GTXs treatment, suggesting that the diverse chemical structures of GTXs are responsible for contraction and membrane potential of muscle cells.

Keywords: skeletal muscle, C2C12, myoblast, myotubes, contraction, Grayanotoxins, membrane potential, neurotoxins, phytotoxin

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3210 Stem Cell Fate Decision Depending on TiO2 Nanotubular Geometry

Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki


In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

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3209 Obsessive-Compulsive Disorder: Development of Demand-Controlled Deep Brain Stimulation with Methods from Stochastic Phase Resetting

Authors: Mahdi Akhbardeh


Synchronization of neuronal firing is a hallmark of several neurological diseases. Recently, stimulation techniques have been developed which make it possible to desynchronize oscillatory neuronal activity in a mild and effective way, without suppressing the neurons' firing. As yet, these techniques are being used to establish demand-controlled deep brain stimulation (DBS) techniques for the therapy of movement disorders like severe Parkinson's disease or essential tremor. We here present a first conceptualization suggesting that the nucleus accumbens is a promising target for the standard, that is, permanent high-frequency, DBS in patients with severe and chronic obsessive-compulsive disorder (OCD). In addition, we explain how demand-controlled DBS techniques may be applied to the therapy of OCD in those cases that are refractory to behavioral therapies and pharmacological treatment.

Keywords: stereotactic neurosurgery, deep brain stimulation, obsessive-compulsive disorder, phase resetting

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3208 The Effects of Transcranial Direct Current Stimulation on Brain Oxygenation and Pleasure during Exercise

Authors: Alexandre H. Okano, Pedro M. D. Agrícola, Daniel G. Da S. Machado, Luiz I. Do N. Neto, Luiz F. Farias Junior, Paulo H. D. Nascimento, Rickson C. Mesquita, John F. Araujo, Eduardo B. Fontes, Hassan M. Elsangedy, Shinsuke Shimojo, Li M. Li


The prefrontal cortex is involved in the reward system and the insular cortex integrates the afferent inputs arriving from the body’ systems and turns into feelings. Therefore, modulating neuronal activity in these regions may change individuals’ perception in a given situation such as exercise. We tested whether transcranial direct current stimulation (tDCS) change cerebral oxygenation and pleasure during exercise. Fourteen volunteer healthy adult men were assessed into five different sessions. First, subjects underwent to a maximum incremental test on a cycle ergometer. Then, subjects were randomly assigned to a transcranial direct current stimulation (2mA for 15 min) intervention in a cross over design in four different conditions: anode and cathode electrodes on T3 and Fp2 targeting the insular cortex, and Fpz and F4 targeting prefrontal cortex, respectively; and their respective sham. These sessions were followed by 30 min of moderate intensity exercise. Brain oxygenation was measured in prefrontal cortex with a near infrared spectroscopy. Perceived exertion and pleasure were also measured during exercise. The asymmetry in prefrontal cortex oxygenation before the stimulation decreased only when it was applied over this region which did not occur after insular cortex or sham stimulation. Furthermore, pleasure was maintained during exercise only after prefrontal cortex stimulation (P > 0.7), while there was a decrease throughout exercise (P < 0.03) during the other conditions. We conclude that tDCS over the prefrontal cortex changes brain oxygenation in ventromedial prefrontal cortex and maintains perceived pleasure during exercise. Therefore, this technique might be used to enhance effective responses related to exercise.

Keywords: affect, brain stimulation, dopamine neuromodulation, pleasure, reward, transcranial direct current stimulation

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3207 System for Mechanical Stimulation of the Mesenchymal Stem Cells Supporting Differentiation into Osteogenic Cells

Authors: Jana Stepanovska, Roman Matejka, Jozef Rosina, Marta Vandrovcova, Lucie Bacakova


The aim of this study was to develop a system for mechanical and also electrical stimulation controlling in vitro osteogenesis under conditions more similar to the in vivo bone microenvironment than traditional static cultivation, which would achieve good adhesion, growth and other specific behaviors of osteogenic cells in cultures. An engineered culture system for mechanical stimulation of the mesenchymal stem cells on the charged surface was designed. The bioreactor allows efficient mechanical loading inducing an electrical response and perfusion of the culture chamber with seeded cells. The mesenchymal stem cells were seeded to specific charged materials, like polarized hydroxyapatite (Hap) or other materials with piezoelectric and ferroelectric features, to create electrical potentials for stimulating of the cells. The material of the matrix was TiNb alloy designed for these purposes, and it was covered by BaTiO3 film, like a kind of piezoelectric material. The process of mechanical stimulation inducing electrical response is controlled by measuring electrical potential in the chamber. It was performed a series of experiments, where the cells were seeded, perfused and stimulated up to 48 hours under different conditions, especially pressure and perfusion. The analysis of the proteins expression was done, which demonstrated the effective mechanical and electrical stimulation. The experiments demonstrated effective stimulation of the cells in comparison with the static culture. This work was supported by the Ministry of Health, grant No. 15-29153A and the Grant Agency of the Czech Republic grant No. GA15-01558S.

Keywords: charged surface, dynamic cultivation, electrical stimulation, ferroelectric layers, mechanical stimulation, piezoelectric layers

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3206 Global Analysis of HIV Virus Models with Cell-to-Cell

Authors: Hossein Pourbashash


Recent experimental studies have shown that HIV can be transmitted directly from cell to cell when structures called virological synapses form during interactions between T cells. In this article, we describe a new within-host model of HIV infection that incorporates two mechanisms: infection by free virions and the direct cell-to-cell transmission. We conduct the local and global stability analysis of the model. We show that if the basic reproduction number R0 1, the virus is cleared and the disease dies out; if R0 > 1, the virus persists in the host. We also prove that the unique positive equilibrium attracts all positive solutions under additional assumptions on the parameters.

Keywords: HIV virus model, cell-to-cell transmission, global stability, Lyapunov function, second compound matrices

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3205 The Effectiveness of Transcranial Electrical Stimulation on Brain Wave Pattern and Blood Pressure in Patients with Generalized Anxiety Disorder

Authors: Mahtab Baghaei, Seyed Mahmoud Tabatabaei


Aim & Background: Electrical stimulation of transcranial direct current is considered one of the treatment methods for mental disorders. The aim of this study was to evaluate the effectiveness of transcranial electrical stimulation on the delta, theta, alpha, beta and systolic and diastolic blood pressure in patients with generalized anxiety disorder. Materials and Methods: The present study was a double-blind intervention with a pre-test and post-test design on people with generalized anxiety disorder in Tabriz in 1400. In this study, 30 patients with generalized anxiety disorder were selected by purposive sampling method based on the criteria specified in DSM-5 and randomly divided into an experimental group (n = 15) and a control group (n = 15). The experimental group received two sessions of 30 minutes of electrical stimulation of transcranial direct current with an intensity of 2 mA in the area of the lateral dorsal prefrontal cortex, and the control group also received artificial stimulation. Results: The results showed that transcranial electrical stimulation reduces delta and theta waves and increases beta and alpha brain waves in the experimental group. On the other hand, this method also showed a significant decrease in systolic and diastolic blood pressure in these patients (p <0.01). Conclusion: The results show that transcranial electrical stimulation has a statistically significant effect on brain waves and blood pressure, and this non-invasive method can be used as one of the treatment methods in people with generalized anxiety disorder.

Keywords: transcranial direct current electrical stimulation, brain waves, systolic blood pressure, diastolic blood pressure

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3204 Evaluation of the Laser and Partial Vibration Stimulation on Osteoporosis

Authors: Ji Hyung Park, Dong-Hyun Seo, Young-Jin Jung, Han Sung Kim


The aim of this study is to evaluate the effects of the laser and partial vibration stimulation on the mice tibia with morphological characteristics. Twenty female C57BL/6 mice (12 weeks old) were used for the experiment. The study was carried out on four groups of animals each consisting of five mice. Four groups of mice were ovariectomized. Animals were scanned at 0 and 2 weeks after ovariectomy by using micro-computed tomography to estimate morphological characteristics of tibial trabecular bone. Morphological analysis showed that structural parameters of multi-stimuli group appear significantly better phase in BV/TV, BS/BV, Tb.Th, Tb.N, Tb.Sp, and than single stimulation groups. However, single stimulation groups didn’t show significant effect on tibia with Sham group. This study suggests that multi-stimuli may restrain the change as the degenerate phase on osteoporosis in the mice tibia.

Keywords: laser, partial vibration, osteoporosis, in-vivo micro-CT, mice

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3203 Comparison between Effects of Free Curcumin and Curcumin Loaded NIPAAm-MAA Nanoparticles on Telomerase and Pinx1 Gene Expression in Lung Cancer Cells

Authors: Y. Pilehvar-Soltanahmadi, F. Badrzadeh, N. Zarghami, S. Jalilzadeh-Tabrizi, R. Zamani


Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR. MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu-6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of curcumin-loaded NIPAAm-MAA increased while expression of the PinX1 gene became elevated. The results showed that curcumin loaded NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down-regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA could be the good carrier for such kinds of hydrophobic agent.

Keywords: curcumin, NIPAAm-MAA, PinX1, telomerase, lung cancer cells

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3202 Single-Cell Visualization with Minimum Volume Embedding

Authors: Zhenqiu Liu


Visualizing the heterogeneity within cell-populations for single-cell RNA-seq data is crucial for studying the functional diversity of a cell. However, because of the high level of noises, outlier, and dropouts, it is very challenging to measure the cell-to-cell similarity (distance), visualize and cluster the data in a low-dimension. Minimum volume embedding (MVE) projects the data into a lower-dimensional space and is a promising tool for data visualization. However, it is computationally inefficient to solve a semi-definite programming (SDP) when the sample size is large. Therefore, it is not applicable to single-cell RNA-seq data with thousands of samples. In this paper, we develop an efficient algorithm with an accelerated proximal gradient method and visualize the single-cell RNA-seq data efficiently. We demonstrate that the proposed approach separates known subpopulations more accurately in single-cell data sets than other existing dimension reduction methods.

Keywords: single-cell RNA-seq, minimum volume embedding, visualization, accelerated proximal gradient method

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3201 Ovarian Stimulation and Oocyte Cryopreservation for Fertility Preservation in Adolescent Females at the Royal Children’s Hospital: A Case Series

Authors: Kira Merigan


BACKGROUND- Fertility preservation (FP) measures are increasingly recognised as an important consideration for children and adolescents planned to undergo potentially damaging gonadotoxic therapy. Worldwide, there are very few documented cases of FP in young females by way of ovarian stimulation and oocyte cryopreservation.AIM – To report a case series of mature oocyte cryopreservation in 5post-pubertal adolescents aged 14-17 years old, with varied medical conditions requiring gonadotoxic treatment. SETTING-These cases took place via a multidisciplinary team approach at The Royal Children’s Hospital, a large tertiary centre in Melbourne, Australia. INTERVENTION– Ovarian stimulation and oocyte collection was performed as detailed in each case. RESULTS –Across the 5 patients, 3-28 oocytes were retrieved. We report pre-treatment workup, complications, and delays to treatment. CONCLUSION- Oocyte cryopreservation may be a safe alternative to ovarian tissue cryopreservation (OTC) in the adolescent population

Keywords: fertility preservation, adolescent, ovarian stimulation, oocyte cryopreservation

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3200 Effects of Transcranial Direct Current Stimulation on Post-Stroke Dysphagia

Authors: Ehsan Kaviani, Azin Golmoradizade


Introduction: Traditionally, tendons are considered to only contain tenocytes that are responsible for the maintenance, repair, and remodeling of tendons. Stem cells, which are termed tendon-derived stem cells, so this study we investigate the effect of transcranial direct current stimulation combined with swallowing training on post-stroke dysphagia. Methods: This review article is about effects of transcranial direct current stimulation (tDCS) on post-stroke dysphagia that were extracted from Science Direct, Pro quest, and Pub med Data Bases. 15 articles had been selected according to inclusion criteria from 2014 to 2019, and 6 of them had been deleted by exclusion criteria. Results: The results of our systematic review suggest that tDCS may represent a promising novel treatment for post-stroke dysphagia. However, to date, little is known about the optimal parameters of tDCS for relieving post-stroke dysphagia. Further studies are warranted to refine this promising intervention by exploring the optimal parameters of tDCS. Conclusion: anodal tDCS over the affected hemisphere may be as effective as cathodal tDCS on the unaffected hemisphere to enhance recovery after subacute ischemic stroke and anodal tdcs applied over the affected pharyngeal motor cortex can enhance the outcome of swallowing training in post-stroke dysphagia.

Keywords: dysphagia, stroke, cortical stimulation, transcranial direct current stimulation

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3199 Up-Regulation of SCUBE2 Expression in Co-Cultures of Human Mesenchymal Stem Cell and Breast Cancer Cells

Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi


Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.

Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2

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3198 The Functional Roles of Right Dorsolateral Prefrontal Cortex and Ventromedial Prefrontal Cortex in Risk-Taking Behavior

Authors: Aline M. Dantas, Alexander T. Sack, Elisabeth Bruggen, Peiran Jiao, Teresa Schuhmann


Risk-taking behavior has been associated with the activity of specific prefrontal regions of the brain, namely the right dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC). While the deactivation of the rDLPFC has been shown to lead to increased risk-taking behavior, the functional relationship between VMPFC activity and risk-taking behavior is yet to be clarified. Correlational evidence suggests that the VMPFC is involved in valuation processes that involve risky choices, but evidence on the functional relationship is lacking. Therefore, this study uses brain stimulation to investigate the role of the VMPFC during risk-taking behavior and replicate the current findings regarding the role of the rDLPFC in this same phenomenon. We used continuous theta-burst stimulation (cTBS) to inhibit either the VMPFC or DLPFC during the execution of the computerized Maastricht Gambling Task (MGT) in a within-subject design with 30 participants. We analyzed the effects of such stimulation on risk-taking behavior, participants’ choices of probabilities and average values, and response time. We hypothesized that, compared to sham stimulation, VMPFC inhibition leads to a reduction in risk-taking behavior by reducing the appeal to higher-value options and, consequently, the attractiveness of riskier options. Right DLPFC (rDLPFC) inhibition, on the other hand, should lead to an increase in risk-taking due to a reduction in cognitive control, confirming existent findings. Stimulation of both the rDLPFC and the VMPFC led to an increase in risk-taking behavior and an increase in the average value chosen after both rDLPFC and VMPFC stimulation compared to sham. No significant effect on chosen probabilities was found. A significant increase in response time was observed exclusively after rDLPFC stimulation. Our results indicate that inhibiting DLPFC and VMPFC separately leads to similar effects, increasing both risk-taking behavior and average value choices, which is likely due to the strong anatomical and functional interconnection of the VMPFC and rDLPFC.

Keywords: decision-making, risk-taking behavior, brain stimulation, TMS

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