Search results for: brain cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4261

Search results for: brain cells

3691 Newly Designed Ecological Task to Assess Cognitive Map Reading Ability: Behavioral Neuro-Anatomic Correlates of Mental Navigation

Authors: Igor Faulmann, Arnaud Saj, Roland Maurer

Abstract:

Spatial cognition consists in a plethora of high level cognitive abilities: among them, the ability to learn and to navigate in large scale environments is probably one of the most complex skills. Navigation is thought to rely on the ability to read a cognitive map, defined as an allocentric representation of ones environment. Those representations are of course intimately related to the two geometrical primitives of the environment: distance and direction. Also, many recent studies point to a predominant hippocampal and para-hippocampal role in spatial cognition, as well as in the more specific cluster of navigational skills. In a previous study in humans, we used a newly validated test assessing cognitive map processing by evaluating the ability to judge relative distances and directions: the CMRT (Cognitive Map Recall Test). This study identified in topographically disorientated patients (1) behavioral differences between the evaluation of distances and of directions, and (2) distinct causality patterns assessed via VLSM (i.e., distinct cerebral lesions cause distinct response patterns depending on the modality (distance vs direction questions). Thus, we hypothesized that: (1) if the CMRT really taps into the same resources as real navigation, there would be hippocampal, parahippocampal, and parietal activation, and (2) there exists underlying neuroanatomical and functional differences between the processing of this two modalities. Aiming toward a better understanding of the neuroanatomical correlates of the CMRT in humans, and more generally toward a better understanding of how the brain processes the cognitive map, we adapted the CMRT as an fMRI procedure. 23 healthy subjects (11 women, 12 men), all living in Geneva for at least 2 years, underwent the CMRT in fMRI. Results show, for distance and direction taken together, than the most active brain regions are the parietal, frontal and cerebellar parts. Additionally, and as expected, patterns of brain activation differ when comparing the two modalities. Furthermore, distance processing seems to rely more on parietal regions (compared to other brain regions in the same modality and also to direction). It is interesting to notice that no significant activity was observed in the hippocampal or parahippocampal areas. Direction processing seems to tap more into frontal and cerebellar brain regions (compared to other brain regions in the same modality and also to distance). Significant hippocampal and parahippocampal activity has been shown only in this modality. This results demonstrated a complex interaction of structures which are compatible with response patterns observed in other navigational tasks, thus showing that the CMRT taps at least partially into the same brain resources as real navigation. Additionally, differences between the processing of distances and directions leads to the conclusion that the human brain processes each modality distinctly. Further research should focus on the dynamics of this processing, allowing a clearer understanding between the two sub-processes.

Keywords: cognitive map, navigation, fMRI, spatial cognition

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3690 Different Cathode Buffer Layers in Organic Solar Cells

Authors: Radia Kamel

Abstract:

Considerable progress has been made in the development of bulk-heterojunction organic solar cells (OSCs) based on a blend of p-type and n-type organic semiconductors. To optimize the interfacial properties between the active layer and the electrode, a cathode buffer layer (CBL) is introduced. This layer can reduce the leakage current, increasing the open-circuit voltage and the fill factor while improving the OSC stability. In this work, the performance of PM6:Y6 OSC with 1-Chloronaphthalene as an additive is examined. To accomplish this, three CBLs PNDIT-F3N-Br, ZrAcac, and PDINO, are compared using the conventional configuration. The device with PNDIT-F3N-Br as CBL exhibits the highest power conversion efficiency of 16.04%. The results demonstrate that modifying the cathode buffer layer is crucial for achieving high-performance OSCs.

Keywords: bulk heterojunction, cathode buffer layer, efficiency, organic solar cells

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3689 A Study on Implementation of Optimal Soldering Temperature Profile through Deformation Analysisin Infrared Lamp Soldering of Photovoltaic Cells

Authors: Taejung Lho, Jonghwan Lee

Abstract:

Most of the photovoltaic (PV) module manufacturers have recently interested in reducing the manufacturing cost. One of available solution is the use of the thin photovoltaic cell because of reducing of raw material cost. Thin PV cells, however, are damaged large deformation which causes possible microcracks inside PV cell, leading to failure problem. In this paper, deformation characteristics by heat conduction in soldering process of PV cells are analyzed through ANSYS software tool. They have been tested for different PV cell thickness and soldering temperature profile. Accordingly optimal soldering process to minimize the deformation of PV cell has been suggested.

Keywords: photovoltaic (PV) cell, infrared(IR) lamp soldering, optimal soldering temperature profile, deformation, temperature distribution, 3D scanner, ANSYS

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3688 Investigation of Green Dye-Sensitized Solar Cells Based on Natural Dyes

Authors: M. Hosseinnezhad, K. Gharanjig

Abstract:

Natural dyes, extracted from black carrot and bramble, were utilized as photosensitizers to prepare dye-sensitized solar cells (DSSCs). Spectrophotometric studies of the natural dyes in solution and on a titanium dioxide substrate were carried out in order to assess changes in the status of the dyes. The results show that the bathochromic shift is seen on the photo-electrode substrate. The chemical binding of the natural dyes at the surface photo-electrode were increased by the chelating effect of the Ti(IV) ions. The cyclic voltammetry results showed that all extracts are suitable to be performed in DSSCs. Finally, photochemical performance and stability of DSSCs based on natural dyes were studied. The DSSCs sensitized by black carrot extract have been reported to achieve up to Jsc=1.17 mAcm-2, Voc= 0.55 V, FF= 0.52, η=0.34%, whereas Bramble extract can obtain up to Jsc=2.24 mAcm-2, Voc= 0.54 V, FF= 0.57, η=0.71%. The power conversion efficiency was obtained from the mixed dyes in DSSCs. The power conversion efficiency of dye-sensitized solar cells using mixed Black carrot and Bramble dye is the average of the their efficiency in single DSSCs.

Keywords: anthocyanin, dye-sensitized solar cells, green energy, optical materials

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3687 Combined Use of FMRI and Voxel-Based Morphometry in Assessment of Memory Impairment in Alzheimer's Disease Patients

Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

Abstract:

Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

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3686 Cognitive Dysfunctioning and the Fronto-Limbic Network in Bipolar Disorder Patients: A Fmri Meta-Analysis

Authors: Rahele Mesbah, Nic Van Der Wee, Manja Koenders, Erik Giltay, Albert Van Hemert, Max De Leeuw

Abstract:

Introduction: Patients with bipolar disorder (BD), characterized by depressive and manic episodes, often suffer from cognitive dysfunction. An up-to-date meta-analysis of functional Magnetic Resonance Imaging (fMRI) studies examining cognitive function in BD is lacking. Objective: The aim of the current fMRI meta-analysis is to investigate brain functioning of bipolar patients compared with healthy subjects within three domains of emotion processing, reward processing, and working memory. Method: Differences in brain regions activation were tested within whole-brain analysis using the activation likelihood estimation (ALE) method. Separate analyses were performed for each cognitive domain. Results: A total of 50 fMRI studies were included: 20 studies used an emotion processing (316 BD and 369 HC) task, 9 studies a reward processing task (215 BD and 213 HC), and 21 studies used a working memory task (503 BD and 445 HC). During emotion processing, BD patients hyperactivated parts of the left amygdala and hippocampus as compared to HC’s, but showed hypoactivation in the inferior frontal gyrus (IFG). Regarding reward processing, BD patients showed hyperactivation in part of the orbitofrontal cortex (OFC). During working memory, BD patients showed increased activity in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Conclusions: This meta-analysis revealed evidence for activity disturbances in several brain areas involved in the cognitive functioning of BD patients. Furthermore, most of the found regions are part of the so-called fronto-limbic network which is hypothesized to be affected as a result of BD candidate genes' expression.

Keywords: cognitive functioning, fMRI analysis, bipolar disorder, fronto-limbic network

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3685 MARISTEM: A COST Action Focused on Stem Cells of Aquatic Invertebrates

Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

Abstract:

Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

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3684 Offering a Model for Selecting the Most Suitable Type of Thinking for Managers

Authors: H. Emari, Z. Emari

Abstract:

The purpose of this paper is to design an applied framework for strategic thinking which can be applied in all managerial levels and all types of organizational environments. No special applied frame has been presented for this thinking. This paper presents a theoretical framework for the thinking type of a manager by making a historical research and studying the scientific documents about thinking of a strategist. In the new theoretical framework it has been tried to suggest the best type of thinking for a strategist after analyzing the environment of his decisions. So, in this framework, the traditional viewpoint about strategic thinking, which has considered it as a special type of right-brain thinking against other types of right-brain thinking and suggested it for a strategist, was put aside and suggests that the strategist should use a suitable type of thinking under different conditions.

Keywords: strategic thinking, systemic thinking, lateral thinking, intuitive thinking, hybrid thinking

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3683 Psychological Intervention for Partners Post-Stroke: A Case Study

Authors: Natasha Yasmin Felles, Gerard Riley

Abstract:

Background and Aims: Relationship breakdown is typical when one partner lives with an acquired brain injury caused by issues like a stroke. Research has found that the perception of relationship satisfaction decreases following such an injury among non-injured partners. Non-injured partners also are found to experience caregiver stress/burden as they immediately have to take the role of a caregiver along with being a partner of the injured. Research has also found that the perception of a continuous relationship, i.e. the perception of the relationship to be essentially the same as it was before the injury, also changes among those caregiving partners. However, there is a lack of available intervention strategies that can help those partners with both individual and relationship difficulties. The aim of this case study was to conduct a pilot test of an intervention aimed to explore whether it is possible to support a partner to experience greater continuity within the relationship poststroke, and what benefits such a change might have. Method: A couple, where one partner experienced an acquired brain injury poststroke were provided with Integrated Behavioural Couples Therapy for 3-months. The intervention addressed goals identified as necessary by the couple and by the formulation of their individual and relationship difficulties, alongside the goal of promoting relationship continuity. Before and after measures were taken using a battery of six questionnaires to evaluate changes in perceptions of continuity, stress, and other aspects of the relationship. Results: Both quantitative and qualitative data showed that relationship continuity was improved after the therapy, as were the measures of stress and other aspects of the relationship. The stress felt by the person with the acquired brain injury also showed some evidence of improvement. Conclusion: The study found that perceptions of relationship continuity can be improved by therapy and that improving these might have a beneficial impact on the stress felt by the carer, their satisfaction with the relationship and overall levels of conflict and closeness within the relationship. The study suggested the value of further research on enhancing perceptions of continuity in the relationship after an acquired brain injury. Currently, the findings of the study have been used to develop a pilot feasibility study to collect substantive evidence on the impact of the intervention on the couples and assess its feasibility and acceptability, which will help in further developing a specific generalized relationship continuity intervention, that will be beneficial in preventing relationship breakdown in the future.

Keywords: acquired brain injury, couples therapy, relationship continuity, stroke

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3682 Cumulus Cells of Mature Local Goat Oocytes Vitrified with Insulin Transferrin Selenium and Heat Shock Protein 70

Authors: Izzatul Ulfana, Angga Pratomo Cahyadi, Rimayanti, Widjiati

Abstract:

Freezing oocyte could cause temperature stress. Temperature stress triggers cell damage. Insulin Transferrin Selenium (ITS) and Heat Shock Protein 70 (HSP70) had been used to prevent damage to the oocyte after freezing. ITS and HSP70 could cause the difference protective effect. The aim of this research was to obtain an effective cryoprotectant for freezing local goat oocyte in cumulus cells change. The research began by collecting the ovary from a local slaughterhouse in Indonesia, aspiration follicle, in vitro maturation and the freezing had been used vitrification method. Examination of the morphology cells by native staining method. Data on the calculation morphology oocyte analyzed by Kruskall-Wallis Test. After the Kruskall-Wallis Test which indicated significance, followed by Mann-Whitney Test to compare between treatment groups. As a result, cryoprotectant ITS has the best culumus cells after warming

Keywords: Insulin Transferrin Selenium, Heat Shock Protein 70, cryoprotectant, vitrification

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3681 Determination of the Toxicity of a Lunar Dust Simulant on Human Alveolar Epithelial Cells and Macrophages in vitro

Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

Abstract:

Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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3680 Effects of the Natural Compound on SARS-CoV-2 Spike Protein-Mediated Metabolic Alteration in THP-1 Cells Explored by the ¹H-NMR-Based Metabolomics Approach

Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

Abstract:

Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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3679 Effectiveness of Opuntia ficus indica Cladodes Extract for Wound-Healing

Authors: Giuffrida Graziella, Pennisi Stefania, Coppa Federica, Iannello Giulia, Cartelli Simone, Lo Faro Riccardo, Ferruggia Greta, Brundo Maria Violetta

Abstract:

Cladode chemical composition may vary according to soil factors, cultivation season, and plant age. The primary metabolites of cladodes are water, carbohydrates, and proteins. The carbohydrates in cladodes are divided into two types: structural and storage. Polysaccharides from Opuntia ficus‐indica (L.) Mill plants build molecular networks with the capacity to retain water; thus, they act as mucoprotective agents. Mucilage is the main polysaccharide of cladodes; it contains polymers of β‐d‐galacturonic acid bound in positions (1–4) and traces of R‐linked l‐rhamnose (1-2). Mucilage regulates both the cell water content during prolonged drought and the calcium flux in the plant cells. The in vitro analysis of keratinocytes in monolayer, through the scratch-wound-healing assay, provided promising results. After 48 hours of exposure, the wound scratch was almost completely closed in cells treated with cladode extract. After 72 hours, the treated cells reached complete confluence, while in the untreated cells (negative control) the confluence was reached after 96 hours. We also added a positive control group of cells treated with colchicine, which inhibited wound closure for a more comprehensive analysis.

Keywords: cladodes, metabolites, polysaccharide, scratch-wound-healing assay

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3678 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

Abstract:

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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3677 The Mechanism of Parabacteroides goldsteinii on Immune Modulation and Anti-Obsogenicity

Authors: Yu-Ling Tsai, Chih-Jung Chang, Chia-Chen Lu, Eric Wu, Chuan-Sheng Lin, Tzu-Lung Lin, Hsin-Chih Lai

Abstract:

It is urgent that novel anti-obesity measures that are safe, effective and widely available are developed for counteracting the rapidly growing obesity epidemics. In the present study, we show that a probiotic bacterium Parabacteroides goldsteinii screened through culture under the high molecular weight polysaccharides prepared from two iconic medicinal fungi, the Ganoderma lucidum and the Hirsutella sinensis, reduced body weight by ca. 20% in high-fat diet (HFD)-fed mice. The bacterium also decreased intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Notably, oral administration of live, but not high temperature-killed, P. goldsteinii to HFD fed mice considerably reduces weight gain and obesity-associated metabolic disorders. A three months feeding of the mice with P. goldsteinii did not show any aberrant side effects, indicating the safety of this bacterium. Transcriptome analysis indicated that P. goldsteinii enhances immunity in resting dendritic cells, but reduces inflammation in lipopolysaccharide (LPS)-induced dendritic cells. On top, Naïve T-cells were skewed towards regulatory T-cells after encountering with dendritic cells (DCs) pretreated with P. goldsteinii. These results indicated P. goldsteinii showed anti-inflammatory effects and can work as a potential probiotic ameliorating obesogenicity and related metabolic syndromes.

Keywords: Parabacteroides goldsteinii, gut microbiome, obesity, immune modulation

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3676 Anti-cancer Activity of Cassava Leaves (Manihot esculenta Crantz.) Against Colon Cancer (WiDr) Cells in vitro

Authors: Fatma Zuhrotun Nisa, Aprilina Ratriany, Agus Wijanarka

Abstract:

Background: Cassava leaves are widely used by the people of Indonesia as a vegetable and treat various diseases, including anticancer believed as food. However, not much research on the anticancer activity of cassava leaves, especially in colon cancer. Objectives: the aim of this study is to investigate anti-cancer activity of cassava leaves (Manihot esculanta C.) against colon cancer (WiDr) cells in vitro. Methods: effect of crude aqueous extract of leaves of cassava and cassava leaves boiled tested in colon cancer cells widr. Determination of Anticancer uses the MTT method with parameters such as the percentage of deaths. Results: raw cassava leaf water extract gave IC50 of 63.1 mg / ml. While the water extract of boiled cassava leaves gave IC50 of 79.4 mg/ml. However, there is no difference anticancer activity of raw cassava leaves or cancer (p> 0.05). Conclusion: Cassava leaves contain a variety of compounds that have previously been reported to have anticancer activity. Linamarin, β-carotene, vitamin C, and fiber were thought to affect the IC50 cassava leaf extract against colon cancer cells WiDr.

Keywords: boiled cassava leaves, cassava leaves raw, anticancer activity, colon cancer, IC50

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3675 No Histological and Biochemical Changes Following Administration of Tenofovir Nanoparticles: Animal Model Study

Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu

Abstract:

Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.

Keywords: tenofovir nanoparticles, liver, kidney, blood cells

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3674 Zinc Oxide Nanoparticles as Support for Classical Anti-cancer Therapies

Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

Abstract:

Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

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3673 Perovskite Solar Cells Penetration on Electric Grids Based on the Power Hardware in the Loop Methodology

Authors: Alaa A. Zaky, Bandar Alfaifi, Saleh Alyahya, Alkistis Kontou, Panos Kotsampopoulos

Abstract:

In this work, we present for the first time the grid-integration of 3rd generation perovskite solar cells (PSCs) based on nanotechnology in fabrication. The effect of this penetration is analyzed in normal, fault and islanding cases of operation under different irradiation conditions using the power hardware in the loop (PHIL) methodology. The PHL method allows the PSCs connection to the electric grid which is simulated in the real-time digital simulator (RTDS), for laboratory validation of the PSCs behavior under conditions very close to real.

Keywords: perovskite solar cells, power hardware in the loop, real-time digital simulator, smart grid

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3672 Microencapsulation for Enhancing the Survival of S. thermophilus and L. bulgaricus during Spray Drying of Sweetened Yoghurt

Authors: Dibyakanta Seth, Hari Niwas Mishra, Sankar Chandra Deka

Abstract:

Microencapsulation is an established method of protecting bacteria from the adverse conditions. An improved extrusion spraying technique was used to encapsulate mixed bacteria culture of S. thermophilus and L. bulgaricus using sodium alginate as the coating material. The effect of nozzle air pressure (200, 300, 400 and 500 kPa), sodium alginate concentration (1%, 1.5%, 2%, 2.5% and 3% w/v), different concentration of calcium chloride (0.1, 0.2, 1 M) and initial cell loads (10⁷, 10⁸, 10⁹ cfu/ml) on the viability of encapsulated bacteria were investigated. With the increase in air pressure the size of microcapsules decreased, however the effect was non-significant. There was no significant difference (p > 0.05) in the viability of encapsulated cells when the concentration of calcium chloride was increased. Increased level of sodium alginate significantly increased the survival ratio of encapsulated bacteria (P < 0.01). Encapsulation with 3% alginate was treated as optimum since a higher concentration of alginate increased the gel strength of the solution and thus was difficult to spray. Under optimal conditions 3% alginate, 10⁹ cfu/ml cell load, 20 min hardening time in 0.1 M CaCl2 and 400 kPa nozzle air pressure, the viability of bacteria cells was maximum compared to the free cells. The microcapsules made at the optimal condition when mixed with yoghurt and subjected to spray drying at 148°C, the survival ratio was 2.48×10⁻¹ for S. thermophilus and 7.26×10⁻¹ for L. bulgaricus. In contrast, the survival ratio of free cells of S. thermophilus and L. bulgaricus were 2.36×10⁻³ and 8.27×10⁻³, respectively. This study showed a decline in viable cells count of about 0.5 log over a period of 7 weeks while there was a decline of about 1 log in cultures which were incorporated as free cells in yoghurt. Microencapsulation provided better protection at higher acidity compared to free cells. This study demonstrated that microencapsulation of yoghurt culture in sodium alginate is an effective technique of protection against extreme drying conditions.

Keywords: extrusion, microencapsulation, spray drying, sweetened yoghurt

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3671 Cord Blood Hematopoietic Stem Cell Expansion Ability of Mesenchymal Stem Cells Isolated From Different Sources

Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

Abstract:

Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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3670 NK Cells Expansion Model from PBMC Led to a Decrease of CD4+ and an Increase of CD8+ and CD25+CD127- T-Reg Lymphocytes in Patients with Ovarian Neoplasia

Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

Abstract:

T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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3669 The Effect of Acid Treatment of PEDOT: PSS Anode for Organic Solar Cells

Authors: Ismail Borazan, Ayse Celik Bedeloglu, Ali Demir, David Carroll

Abstract:

In this project, PEDOT:PSS layer was treated with formic acid, sulphuric acid, and hydrochloric acid, methanol, acetone, and dichlorobenzene:methanol. The resistivity measurements with 2-probes were carried out and the best-chosen method was employed to make an organic solar cell device.

Keywords: organic solar cells, PEDOT:PSS, polymer electrodes, resistivity

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3668 Chromosomes Are Present in a Fixed Region on the Equatorial Plate Within the Interphase of Cell Division

Authors: Chunxiao Wu, Dongyun Jiang, Tao Jiang, Luxia Xu, Qian Xu, Meng Zhao, Qin Zhu, Zhigang Guo, Jinlan Pan, Suning Chen

Abstract:

The stability and evolution of human genetics depends on chromosomes (and chromosome-chromosome interactions). We wish to understand the spatial location of chromosomes in dividing cells in order to understand the relationship between chromosome-chromosome interactions and to further investigate the role of chromosomes and their impact on cell biological behavior. In this study, we explored the relative spatial positional relationships of chromosomes [t (9;22) and t (15;17)] in B-ALL cells by using the three-dimensions DNA in situ fluorescent hybridization (3D-FISH) method. The results showed that chromosomes [t (9;22) and t (15;17)] showed relatively stable spatial relationships. The relative stability of the spatial location of chromosomes in dividing cells may be relevant to disease.

Keywords: chromosome, human genetics, chromosome territory, 3D-FISH

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3667 Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery

Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

Abstract:

Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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3666 Biocompatible Beta Titanium Alloy Ti36Nb6Ta as a Suitable Material for Bone Regeneration

Authors: Vera Lukasova, Eva Filova, Jana Dankova, Vera Sovkova, Matej Daniel, Michala Rampichova

Abstract:

Proper bone implants should promote fast adhesion of cells, stimulate cell differentiation and support the formation of bone tissue. Nowadays titanium is used as a biocompatible material capable of bone tissue integration. This study was focused on comparison of bioactive properties of two titanium alloys - beta titanium alloy Ti36Nb6Ta and standard medical titanium alloy Ti6A14V. The advantage of beta titanium alloy Ti36Nb6Ta is mainly that this material does not contain adverse elements like vanadium or aluminium. Titanium alloys were sterilized in ethanol, placed into 48 well plates and seeded with porcine mesenchymal stem cells. Cells were cultivated for 14 days in standard growth cultivation media with osteogenic supplements. Cell metabolic activity was quantified using MTS assay (Promega). Cell adhesion on day 1 and cell proliferation on further days were verified immunohistochemically using beta-actin monoclonal antibody and secondary antibody conjugated with AlexaFluor®488. Differentiation of cells was evaluated using alkaline phosphatase assay. Additionally, gene expression of collagen I was measured by qRT-PCR. Porcine mesenchymal stem cells adhered and spread well on beta titanium alloy Ti36Nb6Ta on day 1. During the 14 days’ time period the cells were spread confluently on the surface of the beta titanium alloy Ti36Nb6Ta. The metabolic activity of cells increased during the whole cultivation period. In comparison to standard medical titanium alloy Ti6A14V, we did not observe any differences. Moreover, the expression of collagen I gene revealed no statistical differences between both titanium alloys. Therefore, a beta titanium alloy Ti36Nb6Ta promotes cell adhesion, metabolic activity, proliferation and collagen I expression equally to standard medical titanium alloy Ti6A14V. Thus, beta titanium is a suitable material that provides sufficient biocompatible properties. This project was supported by the Czech Science Foundation: grant No. 16-14758S.

Keywords: beta titanium alloy, biocompatibility, differentiation, mesenchymal stem cells

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3665 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity

Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

Abstract:

Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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3664 Mutational and Evolutionary Analysis of Interleukin-2 Gene in Four Pakistani Goat Breeds

Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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3663 Human Endogenous Retrovirus Link With Multiple Sclerosis Disease Progression

Authors: Sina Mahdavi

Abstract:

Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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3662 In Vitro Effect of Cobalt(II) Chloride (CoCl₂)-Induced Hypoxia on Cytokine Production by Human Breast Cancer Cells

Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

Abstract:

Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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