Search results for: interferon alpha and beta receptor subunit 2
1416 Miniaturized PVC Sensors for Determination of Fe2+, Mn2+ and Zn2+ in Buffalo-Cows’ Cervical Mucus Samples
Authors: Ahmed S. Fayed, Umima M. Mansour
Abstract:
Three polyvinyl chloride membrane sensors were developed for the electrochemical evaluation of ferrous, manganese and zinc ions. The sensors were used for assaying metal ions in cervical mucus (CM) of Egyptian river buffalo-cows (Bubalus bubalis) as their levels vary dependent on cyclical hormone variation during different phases of estrus cycle. The presented sensors are based on using ionophores, β-cyclodextrin (β-CD), hydroxypropyl β-cyclodextrin (HP-β-CD) and sulfocalix-4-arene (SCAL) for sensors 1, 2 and 3 for Fe2+, Mn2+ and Zn2+, respectively. Dioctyl phthalate (DOP) was used as the plasticizer in a polymeric matrix of polyvinylchloride (PVC). For increasing the selectivity and sensitivity of the sensors, each sensor was enriched with a suitable complexing agent, which enhanced the sensor’s response. For sensor 1, β-CD was mixed with bathophenanthroline; for sensor 2, porphyrin was incorporated with HP-β-CD; while for sensor 3, oxine was the used complexing agent with SCAL. Linear responses of 10-7-10-2 M with cationic slopes of 53.46, 45.01 and 50.96 over pH range 4-8 were obtained using coated graphite sensors for ferrous, manganese and zinc ionic solutions, respectively. The three sensors were validated, according to the IUPAC guidelines. The obtained results by the presented potentiometric procedures were statistically analyzed and compared with those obtained by atomic absorption spectrophotometric method (AAS). No significant differences for either accuracy or precision were observed between the two techniques. Successful application for the determination of the three studied cations in CM, for the purpose to determine the proper time for artificial insemination (AI) was achieved. The results were compared with those obtained upon analyzing the samples by AAS. Proper detection of estrus and correct time of AI was necessary to maximize the production of buffaloes. In this experiment, 30 multi-parous buffalo-cows were in second to third lactation and weighting 415-530 kg, and were synchronized with OVSynch protocol. Samples were taken in three times around ovulation, on day 8 of OVSynch protocol, on day 9 (20 h before AI) and on day 10 (1 h before AI). Beside analysis of trace elements (Fe2+, Mn2+ and Zn2+) in CM using the three sensors, the samples were analyzed for the three cations and also Cu2+ by AAS in the CM samples and blood samples. The results obtained were correlated with hormonal analysis of serum samples and ultrasonography for the purpose of determining of the optimum time of AI. The results showed significant differences and powerful correlation with Zn2+ composition of CM during heat phase and the ovulation time, indicating that the parameter could be used as a tool to decide optimal time of AI in buffalo-cows.Keywords: PVC Sensors, buffalo-cows, cyclodextrins, atomic absorption spectrophotometry, artificial insemination, OVSynch protocol
Procedia PDF Downloads 2181415 Cervical Ectopic Pregnancy Case Report
Authors: Berrak Yildiz, Hinal Shah, Justine Fernandez, Nazje James, Anna Brown
Abstract:
Cervical ectopic pregnancy, a rare type of ectopic pregnancies, is defined by blastocyst implantation within the cervical canal rather than the endometrium. Its rarity and potential for severe hemorrhage make cervical ectopic pregnancy a diagnostic and therapeutic challenge. A 39-year-old woman, G5P2022, with a history of two cesarean sections and two elective terminations, presented to the emergency department with vaginal bleeding and pelvic pain. Initial assessment showed a beta-hCG level of 2,853 mIU/mL, and transvaginal ultrasound revealed a small, irregular gestational sac at the level of the internal cervical os. Serial betahCG measurements over subsequent visits showed a declining trend, consistent with a nonviable pregnancy. The patient was ultimately treated with methotrexate at a dose of 50 mg/m² (total 100 mg), following which she reported no further symptoms. On follow-up, her beta-hCG level returned to the normal non-pregnant range, with no additional intervention needed. This case highlights the importance of early diagnosis in cervical ectopic pregnancy to avoid complications like hysterectomy. Methotrexate is an effective first-line treatment in hemodynamically stable patients, offering a conservative approach that can preserve fertility. The success in this patient underscores the role of prompt diagnosis and careful management in achieving resolution while minimizing invasive procedures.Keywords: beta-hCG, cervical, ectopic, methotrexate
Procedia PDF Downloads 101414 Investigating the Editing's Effect of Advertising Photos on the Virtual Purchase Decision Based on the Quantitative Electroencephalogram (EEG) Parameters
Authors: Parya Tabei, Maryam Habibifar
Abstract:
Decision-making is an important cognitive function that can be defined as the process of choosing an option among available options to achieve a specific goal. Consumer ‘need’ is the main reason for purchasing decisions. Human decision-making while buying products online is subject to various factors, one of which is the quality and effect of advertising photos. Advertising photo editing can have a significant impact on people's virtual purchase decisions. This technique helps improve the quality and overall appearance of photos by adjusting various aspects such as brightness, contrast, colors, cropping, resizing, and adding filters. This study, by examining the effect of editing advertising photos on the virtual purchase decision using EEG data, tries to investigate the effect of edited images on the decision-making of customers. A group of 30 participants were asked to react to 24 edited and unedited images while their EEG was recorded. Analysis of the EEG data revealed increased alpha wave activity in the occipital regions (O1, O2) for both edited and unedited images, which is related to visual processing and attention. Additionally, there was an increase in beta wave activity in the frontal regions (FP1, FP2, F4, F8) when participants viewed edited images, suggesting involvement in cognitive processes such as decision-making and evaluating advertising content. Gamma wave activity also increased in various regions, especially the frontal and parietal regions, which are associated with higher cognitive functions, such as attention, memory, and perception, when viewing the edited images. While the visual processing reflected by alpha waves remained consistent across different visual conditions, editing advertising photos appeared to boost neural activity in frontal and parietal regions associated with decision-making processes. These Findings suggest that photo editing could potentially influence consumer perceptions during virtual shopping experiences by modulating brain activity related to product assessment and purchase decisions.Keywords: virtual purchase decision, advertising photo, EEG parameters, decision Making
Procedia PDF Downloads 481413 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation
Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich
Abstract:
Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance
Procedia PDF Downloads 1581412 Development and Characterization of Site Specific Peptide Conjugated Polymeric Nanoparticles for Efficient Delivery of Paclitaxel
Authors: Madhu Gupta, Vikas Sharma, Suresh P. Vyas
Abstract:
CD13 receptors are abundantly overexpressed in tumor cells as well as in neovasculature. The CD13 receptors were selected as a targeted site and polymeric nanoparticles (NPs) as a targeted delivery system. By combining these, a cyclic NGR (cNGR) peptide ligand was coupled on the terminal end of polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) and prepared the dual targeted-NPs (cNGR-PEG-PTX-NPs) to enhance the intracellular delivery of anticancer drug to tumor cells and tumor endothelial cells via ligand-receptor interaction. In-vitro cytotoxicity studies confirmed that the presence of cNGR enhanced the cytotoxic efficiency by 2.8 folds in Human Umbilical Vein Endothelial (HUVEC) cells, while cytotoxicity was improved by 2.6 folds in human fibrosarcoma (HT-1080) cells as compared to non-specific stealth NPs. Compared with other tested NPs, cNGR-PEG-PTX-NPs revealed more cytotoxicity by inducing more apoptosis and higher intracellular uptake. The tumor volume inhibition rate was 59.7% in case of cNGR-PEG-PTX-NPs that was comparatively more with other formulations, indicating that cNGR-PEG-PTX-NPs could more effectively inhibit tumor growth. As a consequence, the cNGR-PEG-PTX-NPs play a key role in enhancing tumor therapeutic efficiency for treatment of CD13 receptor specific solid tumor.Keywords: cyclic NGR, CD13 receptor, targeted polymeric NPs, solid tumor, intracellular delivery
Procedia PDF Downloads 4361411 Vegan Low Glycemic Index Diet in Appetite Reduction Among Polycystic Ovarian Syndrome (PCOS) Patients Carrying Melanocortin 4 Receptor (MC4R) Variants of (rs12970134), and (rs17782313): A Mini Review
Authors: Jumanah S. Alawfi
Abstract:
Polycystic ovary syndrome (PCOS) is a common endocrinopathy among females in their reproductive years. The incidence cases are nearly 1.55 million among females across the globe, with 0.43 million associated disability-adjusted life-years (DALYs). This syndrome is associated with intricate mechanisms typically characterized by insulin resistance (IR), infertility, overweight and/or obesity. Lifestyle interventions are often prescribed as an adjective treatment. Nonetheless, obesity is a complex disease that encompasses multiple dimensions, such as excessive energy intake and genetics. The melanocortin 4 receptor mutation (MC4R) is an important mediator in appetite. There is emerging evidence that suggests its role in the Body Mass Index (BMI) among PCOS subjects, which poses the question of obesity and/or overweight among the PCOS patients who carry the MC4R variants may be caused by overconsumption. Thereby, using other satiety techniques may be beneficial as a part of personalized nutrition. Therefore, the aim of the current mini-review is to discuss the effect of the vegan low glycemic diet on reducing appetite among PCOS patients. The review shows that there is a gap in the knowledge of the effect of the vegan diet on PCOS patients who carry MC4R variants which need further research.Keywords: polycystic ovarian syndrome (PCOS), Appetite, Melanocortin 4 Receptor Mutation (MC4R)., Obesity
Procedia PDF Downloads 1281410 Effect of Birks Constant and Defocusing Parameter on Triple-to-Double Coincidence Ratio Parameter in Monte Carlo Simulation-GEANT4
Authors: Farmesk Abubaker, Francesco Tortorici, Marco Capogni, Concetta Sutera, Vincenzo Bellini
Abstract:
This project concerns with the detection efficiency of the portable triple-to-double coincidence ratio (TDCR) at the National Institute of Metrology of Ionizing Radiation (INMRI-ENEA) which allows direct activity measurement and radionuclide standardization for pure-beta emitter or pure electron capture radionuclides. The dependency of the simulated detection efficiency of the TDCR, by using Monte Carlo simulation Geant4 code, on the Birks factor (kB) and defocusing parameter has been examined especially for low energy beta-emitter radionuclides such as 3H and 14C, for which this dependency is relevant. The results achieved in this analysis can be used for selecting the best kB factor and the defocusing parameter for computing theoretical TDCR parameter value. The theoretical results were compared with the available ones, measured by the ENEA TDCR portable detector, for some pure-beta emitter radionuclides. This analysis allowed to improve the knowledge of the characteristics of the ENEA TDCR detector that can be used as a traveling instrument for in-situ measurements with particular benefits in many applications in the field of nuclear medicine and in the nuclear energy industry.Keywords: Birks constant, defocusing parameter, GEANT4 code, TDCR parameter
Procedia PDF Downloads 1471409 Immunolabeling of TGF-β during Muscle Regeneration
Authors: K. Nikovics, D. Riccobono, M. Oger, H. Morin, L. Barbier, T. Poyot, X. Holy, A. Bendahmane, M. Drouet, A. L. Favier
Abstract:
Muscle regeneration after injury (as irradiation) is of great importance. However, the molecular and cellular mechanisms are still unclear. Cytokines are believed to play fundamental role in the different stages of muscle regeneration. They are secreted by many cell populations, but the predominant producers are macrophages and helper T cells. On the other hand, it has been shown that adipose tissue derived stromal/stem cell (ASC) injection could improve muscle regeneration. Stem cells probably induce the coordinated modulations of gene expression in different macrophage cells. Therefore, we investigated the patterns and timing of changes in gene expression of different cytokines occurring upon stem cells loading. Muscle regeneration was studied in an irradiated muscle of minipig animal model in presence or absence of ASC treatment (irradiated and treated with ASCs, IRR+ASC; irradiated not-treated with ASCs, IRR; and non-irradiated no-IRR). We characterized macrophage populations by immunolabeling in the different conditions. In our study, we found mostly M2 and a few M1 macrophages in the IRR+ASC samples. However, only few M2b macrophages were noticed in the IRR muscles. In addition, we found intensive fibrosis in the IRR samples. With in situ hybridization and immunolabeling, we analyzed the cytokine expression of the different macrophages and we showed that M2d macrophage are the most abundant in the IRR+ASC samples. By in situ hybridization, strong expression of the transforming growth factor β (TGF-β) was observed in the IRR+ASC but very week in the IRR samples. But when we analyzed TGF-β level with immunolabeling the expression was very different: many M2 macrophages showed week expression in IRR+ASC and few cells expressing stronger level in IRR muscles. Therefore, we investigated the MMP expressions in the different muscles. Our data showed that the M2 macrophages of the IRR+ASC muscle expressed MMP2 proteins. Our working hypothesis is that MMP2 expression of the M2 macrophages can decrease fibrosis in the IRR+ASC muscle by capturing TGF-β.Keywords: adipose tissue derived stromal/stem cell, cytokine, macrophage, muscle regeneration
Procedia PDF Downloads 2301408 A Recognition Method of Ancient Yi Script Based on Deep Learning
Authors: Shanxiong Chen, Xu Han, Xiaolong Wang, Hui Ma
Abstract:
Yi is an ethnic group mainly living in mainland China, with its own spoken and written language systems, after development of thousands of years. Ancient Yi is one of the six ancient languages in the world, which keeps a record of the history of the Yi people and offers documents valuable for research into human civilization. Recognition of the characters in ancient Yi helps to transform the documents into an electronic form, making their storage and spreading convenient. Due to historical and regional limitations, research on recognition of ancient characters is still inadequate. Thus, deep learning technology was applied to the recognition of such characters. Five models were developed on the basis of the four-layer convolutional neural network (CNN). Alpha-Beta divergence was taken as a penalty term to re-encode output neurons of the five models. Two fully connected layers fulfilled the compression of the features. Finally, at the softmax layer, the orthographic features of ancient Yi characters were re-evaluated, their probability distributions were obtained, and characters with features of the highest probability were recognized. Tests conducted show that the method has achieved higher precision compared with the traditional CNN model for handwriting recognition of the ancient Yi.Keywords: recognition, CNN, Yi character, divergence
Procedia PDF Downloads 1611407 On the Fourth-Order Hybrid Beta Polynomial Kernels in Kernel Density Estimation
Authors: Benson Ade Eniola Afere
Abstract:
This paper introduces a family of fourth-order hybrid beta polynomial kernels developed for statistical analysis. The assessment of these kernels' performance centers on two critical metrics: asymptotic mean integrated squared error (AMISE) and kernel efficiency. Through the utilization of both simulated and real-world datasets, a comprehensive evaluation was conducted, facilitating a thorough comparison with conventional fourth-order polynomial kernels. The evaluation procedure encompassed the computation of AMISE and efficiency values for both the proposed hybrid kernels and the established classical kernels. The consistently observed trend was the superior performance of the hybrid kernels when compared to their classical counterparts. This trend persisted across diverse datasets, underscoring the resilience and efficacy of the hybrid approach. By leveraging these performance metrics and conducting evaluations on both simulated and real-world data, this study furnishes compelling evidence in favour of the superiority of the proposed hybrid beta polynomial kernels. The discernible enhancement in performance, as indicated by lower AMISE values and higher efficiency scores, strongly suggests that the proposed kernels offer heightened suitability for statistical analysis tasks when compared to traditional kernels.Keywords: AMISE, efficiency, fourth-order Kernels, hybrid Kernels, Kernel density estimation
Procedia PDF Downloads 691406 Cancer Stem Cell-Associated Serum Proteins Obtained by Maldi TOF/TOF Mass Spectrometry in Women with Triple-Negative Breast Cancer
Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso
Abstract:
Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells
Procedia PDF Downloads 2131405 Initiation of Paraptosis-Like PCD Pathway in Hepatocellular Carcinoma Cell Line by Hep88 mAb through the Binding of Mortalin (HSPA9) and Alpha-Enolase
Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul
Abstract:
Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase
Procedia PDF Downloads 3601404 Behavioral Effects of Oxidant and Reduced Chemorepellent on Mutant and Wild-Type Tetrahymena thermophila
Authors: Ananya Govindarajan
Abstract:
Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent
Procedia PDF Downloads 1311403 The Effect of Temperature and Salinity on the Growth and Carotenogenesis of Three Dunaliella Species (Dunaliella sp. Lake Isolate, D. salina CCAP 19/18, and D. bardawil LB 2538) Cultivated under Laboratory Conditions
Authors: Imen Hamed, Burcu Ak, Oya Işık, Leyla Uslu, Kubilay Kazım Vursavuş
Abstract:
In this study, 3 species of Dunaliella (Dunaliella sp. Salt Lake isoalte (Tuz Gölü), Dunaliella salina CCAP19/18, and Dunaliella bardawil LB 2538) and their optical density, dry matter, chlorophyll a, total carotenoids, and β-carotene production were investigated in a batch system. The aim of this research was to compare carotenoids, and β-carotene production were investigated in a batch those 3 species. Therefore 2 stress factors were used: 2 different temperatures (20°C and 30°C) and 2 different salinities (30‰, and 60‰) were tested over a 17-day study. The highest growth and chlorophyll a was reported for Dunaliella sp. under 20°C/30‰ and 20°C/60‰ conditions respectively followed by D. bardawil and D. salina. Significant differences were noticed (p<0.05) for the other 3 species. The growth decreased as temperature and salinity increased since the lowest growth was noticed for the 30°C/60‰ group. The chlorophyll a content decreased also as temperature increased however when the NaCl concentration increased an augmentation of the content was noticed . In the 17th day of experiment the highest carotenoids concentration was reported for D. bardawil 20°C/30‰ (65,639±0,400 μg.mL−1) and the most important β carotene concentration was for D. salina 20°C/60‰ (8,98E-07±0,013 mol/L).Keywords: Dunaliella sp., Dunaliella salina, Dunaliella bardawil, growth, pigments, stress factors
Procedia PDF Downloads 3141402 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta
Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel
Abstract:
Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant
Procedia PDF Downloads 3161401 Dietary Gluten and the Balance of Gut Microbiota in the Dextran Sulphate Sodium Induced Colitis Model
Authors: Austin Belfiori, Kevin Rinek, Zach Barcroft, Jennifer Berglind
Abstract:
Diet influences the composition of the gut microbiota and host's health. Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). To study the role of gut microbiota in intestinal inflammation, the microbiome of control mice (C57BL6) given a gluten-containing standard diet versus C57BL6 mice given the gluten-free (GF) feed (n=10 in each group) was examined. All mice received the 3% DSS for 5 days. Throughout the study, feces were collected and processed for DNA extraction and MiSeq Illumina sequencing of V4 region of bacterial 16S rRNA gene. Alpha and beta diversities and compositional differences at phylum and genus levels were determined in intestinal microbiota. The mice receiving the GF diet showed a significantly increased abundance of Firmicutes and a decrease of Bacteroides and Lactobacillus at phylum level. Therefore, the gluten free diet led to reductions in beneficial gut bacteria populations. These findings indicate a role of wheat gluten in dysbiosis of the intestinal microbiota.Keywords: gluten, colitis, microbiota, DSS, dextran sulphate sodium
Procedia PDF Downloads 2101400 The Association between Affective States and Sexual/Health-Related Status among Men Who Have Sex with Men in China: An Exploration Study Using Social Media Data
Authors: Zhi-Wei Zheng, Zhong-Qi Liu, Jia-Ling Qiu, Shan-Qing Guo, Zhong-Wei Jia, Chun Hao
Abstract:
Objectives: The purpose of this study was to understand and examine the association between diurnal mood variation and sexual/health-related status among men who have sex with men (MSM) using data from MSM Chinese Twitter messages. The study consists of 843,745 postings of 377,610 MSM users located in Guangdong that were culled from the MSM Chinese Twitter App. Positive affect, negative affect, sexual related behaviors, and health-related status were measured using the Simplified Chinese Linguistic Inquiry and Word Count. Emotions, including joy, sadness, anger, fear, and disgust were measured using the Weibo Basic Mood Lexicon. A positive sentiment score and a positive emotions score were also calculated. Linear regression models based on a permutation test were used to assess associations between affective states and sexual/health-related status. In the results, 5,871 active MSM users and their 477,374 postings were finally selected. MSM expressed positive affect and joy at 8 a.m. and expressed negative affect and negative emotions between 2 a.m. and 4 a.m. In addition, 25.1% of negative postings were directly related to health and 13.4% reported seeking social support during that sensitive period. MSM who were senior, educated, overweight or obese, self-identified as performing a versatile sex role, and with less followers, more followers, and less chat groups mainly expressed more negative affect and negative emotions. MSM who talked more about sexual-related behaviors had a higher positive sentiment score (β=0.29, p < 0.001) and a higher positive emotions score (β = 0.16, p < 0.001). MSM who reported more on their health status had a lower positive sentiment score (β = -0.83, p < 0.001) and a lower positive emotions score (β = -0.37, p < 0.001). The study concluded that psychological intervention based on an app for MSM should be conducted, as it may improve mental health.Keywords: affect, men who have sex with men, sexual related behavior, health-related status, social media
Procedia PDF Downloads 1611399 A Systematic Review for the Association between Active Smoking and Latent Tuberculosis Infection
Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh
Abstract:
Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.Keywords: latent tuberculosis infection, systematic review, active smoking, model
Procedia PDF Downloads 2561398 Serum Interlukin-8 and Immunomodulation in Beta Thalassemia Patients
Authors: Shahira El Shafie, Hanaa Eldash, Engy Ghabbour, Mohamed Eid
Abstract:
Several immunologic defects can be found in patients with beta-thalassemia, among which the impairment of neutrophil phagocytic function is of utmost importance. Attention has been directed to the role of proinflammatory cytokines in neutrophil chemotaxis and phagocytosis. Interleukin-8 (IL-8) is an important chemotactic and activation peptide for neutrophils; changes in IL-8 level and potential correlation with neutrophil function can be relevant to immunomodulation pathophysiology in beta-thalassemia patients. This case-control study aimed to evaluate IL-8 level and to assess granulocyte recruitment, as markers of immunomodulation, in poly-transfused thalassemia patients attending Fayoum University Hospitals. The study was conducted on 50 patients with ß thalassemia and 32 age-matched controls. 21/50 patients were transfused more than ten times, and 29/50 were transfused in a lower frequency. Patients and controls were subjected to thorough history taking and clinical examination, measurement of IL-8 level using human IL-8 ELISA kit, and Rebuck skin window technique (RSWT) to assess granulocyte recruitment. Our data showed statistically significant higher levels of IL-8 in ß thalassemia patients compared to control with a much higher difference in patients transfused more than ten times. Neutrophil recruitment was significantly lower in ß thalassemia patients compared to control at 4 hours and 24 hours test time. Although IL-8, the main chemotactic pro-inflammatory cytokine showed a higher level in thalassemia patients, neutrophils recruitment was significantly lower, especially in those receiving more than ten transfusion times. Our findings suggest a possible role of other neutrophil chemotactic factors, defective neutrophil response, or increased IL-8 as compensation of abnormal function. We recommend the use of IL-8 and Rebuck skin window technique as useful markers of immunomodulation in thalassemia and further study for these biomarkers to assess their clinical implications and impact on the management of thalassemia patients.Keywords: beta-thalassemia, Interleukin-8, Rebuck skin window technique, immunomodulation
Procedia PDF Downloads 1851397 Production of Keratinase and Its Insilico Characterization
Authors: Akshita Bhardwaj
Abstract:
Keratinase is an enzyme obtained from extracellular sources that is involved in biodegradation of keratin. It is a member of a group of proteases that can break down keratin into amino acids. Keratinases are produced only in the presence of substrate that contain keratin. It attacked the disulfide bond of substrate and involve in keratin degradation. Human hair, feathers, animal hard tissues, horns, claws, and hooves all contain keratin.. It exists in two form alpha keratin (found in soft tissues) and beta keratin (found in hard tissue). By taking part in the degradation of keratin, keratinases derived from microbial sources, often referred to as microbial keratinases, are important in the process of turning wastes containing keratin into products with added value. Chicken feathers contain high level of keratin protein content than other sources and became a suitable protein source. Keratinase production occurs at near alkaline pH and thermophilic temperatures. The bioprocessing of keratinous waste benefits greatly from the use of keratinases. Additionally, it lessens the issue caused by poultry excrement. The use of feather meal, along with keratinase, improves the digestion of proteins and amino acids.Keywords: mili litre (ml), micro litre (Ul), TCA - trichloroacetic acid, OD - optical density
Procedia PDF Downloads 751396 Investigating the Combined Medicinal Effects of Withania Somnifera (Ashwaghandha) and Murraya Koenigii (Curry Pata) in Vitro
Authors: Sadia Roshan, Kulsoom Sughra, Shazia Shamas, Shamaila Irum, Haleema Sadia
Abstract:
To evaluate synergistic medicinal effects of Withania somnifera (Ashwaghandha) and Murraya koenigii (Curry pata) in vitro. Antimicrobial activity was determined using the disc diffusion method against five bacterial and two fungal strains. The antioxidant activity was evaluated by the DPPH assay. The antidiabetic activity was evaluated by alpha-glucosidase inhibition assay and alpha-amylase inhibition assay. Synergistic antibacterial activity was observed against all the strains of bacteria, either Gram-positive or Gram-negative and fungi under study conditions. The maximum antibacterial activity was displayed by combined extract against E. coli i.e. 26±0.4mm. Maximum antifungal activity was shown by combined extract against Aspergillus niger, i.e., 17.3±0.5mm. The antioxidant activity of the combined extract was also significant. Alpha-glucosidase inhibition and alpha-amylase inhibition assays also showed synergism. Results indicate that Withania somnifera and Murraya koengii have medicinal properties. The combined extract of both plants is more potent than their individual extracts, suggesting that these can work in synergism. The research suggests that different plant extracts could be used in combination to increase their medicinal activities by many folds, thus giving an insight into future use of herbal medication.Keywords: withania somnifera, murraya koenigii, antimicrobial activity, gram-positive bacetria, gram-negative bacteria
Procedia PDF Downloads 781395 The Omicron Variant BA.2.86.1 of SARS- 2 CoV-2 Demonstrates an Altered Interaction Network and Dynamic Features to Enhance the Interaction with the hACE2
Authors: Taimur Khan, Zakirullah, Muhammad Shahab
Abstract:
The SARS-CoV-2 variant BA.2.86 (Omicron) has emerged with unique mutations that may increase its transmission and infectivity. This study investigates how these mutations alter the Omicron receptor-binding domain's interaction network and dynamic properties (RBD) compared to the wild-type virus, focusing on its binding affinity to the human ACE2 (hACE2) receptor. Protein-protein docking and all-atom molecular dynamics simulations were used to analyze structural and dynamic differences. Despite the structural similarity to the wild-type virus, the Omicron variant exhibits a distinct interaction network involving new residues that enhance its binding capacity. The dynamic analysis reveals increased flexibility in the RBD, particularly in loop regions crucial for hACE2 interaction. Mutations significantly alter the secondary structure, leading to greater flexibility and conformational adaptability compared to the wild type. Binding free energy calculations confirm that the Omicron RBD has a higher binding affinity (-70.47 kcal/mol) to hACE2 than the wild-type RBD (-61.38 kcal/mol). These results suggest that the altered interaction network and enhanced dynamics of the Omicron variant contribute to its increased infectivity, providing insights for the development of targeted therapeutics and vaccines.Keywords: SARS-CoV-2, molecular dynamic simulation, receptor binding domain, vaccine
Procedia PDF Downloads 201394 Persistent Organochlorine Pesticides (POPs) in Water, Sediment, Fin Fishes (Schilbes mystus and Hemichromis fasciatus) from River Ogun, Lagos, Nigeria
Authors: Edwin O. Clarke, Akintade O. Adeboyejo
Abstract:
Intensive use of pesticides resulted in dispersal of pollutants throughout the globe. This study was carried out to investigate persistent Organochlorine pesticides (POPs) in water, sediment and fin fishes, Schilbes mystus and Hemichromis fasciatus from two different sampling stations along River Ogun between the month of June 2012 and January 2013. The Organochlorine pesticides analyzed include DDT (pp’1,1,1-trichloro-2,2-bis-(4-chlorophenyl) ethane), DDD, DDE (pp1,1-dichloro-2, 2-bis-(4-chlorophenyl) ethylene, HCH (gamma 1,2,3,4,5,6-hexachlorocylohexane, HCB hexachlorobenzene),Dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a octahydro- 1,4,5,8 dimethanonaphthalene). The analysis was done using Gas Chromatograph with Electron Capture Detector. In water sample, the result showed that PPDDT, Endrin aldehyde, Endrin ketone concentrations were high in both stations. The mean value of Organochlorine analyzed in water range from Beta BHC (0.50±0.10µg/l) to PP DDT (162.86±0.21µg/l) in Kara sample station and Beta BHC (0.20±0.07µg/l) to Endrin Aldehyde (76.47±0.02µg/l) in Odo-Ogun sample station. The levels of POPs obtained in sediments ranged from 0.40±0.23µg/g (Beta BHC) to 259.90 ± 1.00µg/kg (Endosulfan sulfate) in Kara sample station and 0.64±0.00µg/g (Beta BHC) to 379.77 ±0.15 µg/g (Endosulfan sulfate) in Odo-Ogun sample station. The levels of POPs obtained in fin fish samples ranged from 0.29±0.00µg/g (Delta BHC) to 197.87 ± 0.31µg/g (PP DDT) in Kara sample station and in Odo-Ogun sample station the mean value for fish samples range from 0.29 ± 0.00 µg/g (Delta BHC) to 197.87 ± 0.32 µg/g (PP DDT). The study showed that the accumulation of POPs affect the environment and reduce water quality. The results showed that the concentrations were found to exceed the maximum acceptable concentration of 0.10µg/l value set by the European Union for the protection of freshwater aquatic life and this can be hazardous if the trend is not checked.Keywords: hazardous, persistent, pesticides, biomes
Procedia PDF Downloads 2911393 Genetics of Atopic Dermatitis: Role of Cytokines Genes Polymorphisms
Authors: Ghaleb Bin Huraib, Fahad Al Harthi, Misbahul Arfin, Abdulrahman Al-Asmari
Abstract:
Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin disease characterized by severe itching and recurrent relapsing eczema-like skin lesions, affecting up to 20% of children and 10% of adults in industrialized countries. AD is a complex multifactorial disease, and its exact etiology and pathogenesis have not been fully elucidated. The aim of this study was to investigate the impact of gene polymorphisms of T helper cell subtype Th1 and Th2 cytokines, interferon-gamma (IFN-γ), interleukin-6 (IL-6) and transforming growth factor (TGF)-β1on AD susceptibility in a Saudi cohort. One hundred four unrelated patients with AD and 195 healthy controls were genotyped for IFN-γ (874A/T), IL-6 (174G/C) and TGF-β1 (509C/T) polymorphisms using ARMS-PCR and PCR-RFLP technique. The frequency of genotypes AA and AT of IFN-γ (874A/T) differed significantly among patients and controls (P 0.001). The genotype AT was increased while genotype AA was decreased in AD patients as compared to controls. AD patients also had higher frequency of T containing genotypes (AT+TT) than controls (P = 0.001). The frequencies of allele T and A were statistically different in patients and controls (P = 0.04). The frequencies of genotype GG and allele G of IL-6 (174G/C) were significantly higher while genotype GC and allele C were lower in AD patients than controls. There was no significant difference in the frequencies of alleles and genotypes of TGF-β1 (509C/T) polymorphism between patient and control groups. These results showed that susceptibility to AD is influenced by presence or absence of genotypes of IFN-γ (874A/T) and IL-6 (174G/C) polymorphisms. It is concluded that T-allele and T-containing genotypes (AT+TT) of IFN-γ (874A/T) and G-allele and GG genotype ofIL-6 (174G/C) polymorphisms are susceptible to AD in Saudis.On the other hand, the TGF-β1 (509C/T) polymorphism may not be associated with AD risk in Saudi population however further studies with large sample size are required to confirm these findings.Keywords: atopic dermatitis, interferon-γ, interleukin-6, transforming growth factor-β1, polymorphism
Procedia PDF Downloads 1171392 Insight2OSC: Using Electroencephalography (EEG) Rhythms from the Emotiv Insight for Musical Composition via Open Sound Control (OSC)
Authors: Constanza Levicán, Andrés Aparicio, Rodrigo F. Cádiz
Abstract:
The artistic usage of Brain-computer interfaces (BCI), initially intended for medical purposes, has increased in the past few years as they become more affordable and available for the general population. One interesting question that arises from this practice is whether it is possible to compose or perform music by using only the brain as a musical instrument. In order to approach this question, we propose a BCI for musical composition, based on the representation of some mental states as the musician thinks about sounds. We developed software, called Insight2OSC, that allows the usage of the Emotiv Insight device as a musical instrument, by sending the EEG data to audio processing software such as MaxMSP through the OSC protocol. We provide two compositional applications bundled with the software, which we call Mapping your Mental State and Thinking On. The signals produced by the brain have different frequencies (or rhythms) depending on the level of activity, and they are classified as one of the following waves: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), gamma (30-50 Hz). These rhythms have been found to be related to some recognizable mental states. For example, the delta rhythm is predominant in a deep sleep, while beta and gamma rhythms have higher amplitudes when the person is awake and very concentrated. Our first application (Mapping your Mental State) produces different sounds representing the mental state of the person: focused, active, relaxed or in a state similar to a deep sleep by the selection of the dominants rhythms provided by the EEG device. The second application relies on the physiology of the brain, which is divided into several lobes: frontal, temporal, parietal and occipital. The frontal lobe is related to abstract thinking and high-level functions, the parietal lobe conveys the stimulus of the body senses, the occipital lobe contains the primary visual cortex and processes visual stimulus, the temporal lobe processes auditory information and it is important for memory tasks. In consequence, our second application (Thinking On) processes the audio output depending on the users’ brain activity as it activates a specific area of the brain that can be measured using the Insight device.Keywords: BCI, music composition, emotiv insight, OSC
Procedia PDF Downloads 3221391 Characterization of Bovine SERPIN- Alpha-1 Antitrypsin (AAT)
Authors: Sharique Ahmed, Khushtar Anwar Salman
Abstract:
Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor
Procedia PDF Downloads 4891390 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer
Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner
Abstract:
Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab
Procedia PDF Downloads 911389 Antidepressant-Like Effects of EQC-34, a 5HT3 Receptor Antagonist in Neurobehavioral Mouse Model of Depression
Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj
Abstract:
Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin
Procedia PDF Downloads 4321388 The Role of Chemerin and Myostatin after Physical Activity
Authors: M. J. Pourvaghar, M. E. Bahram
Abstract:
Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. Chemerin is an adipocyne that plays a role in the regulation of the adipocyte function and the metabolism of glucose in the liver and musculoskeletal system. Most likely, chemerin is involved in obesity-related disorders such as type 2 diabetes and cardiovascular disease. Aerobic exercises reduce the level of chemerin and cause macrophage penetration into fat cells and inflammatory factors. Several efforts have been made to clarify the cellular and molecular mechanisms of hypertrophy and muscular atrophy. Myostatin, a new member of the TGF-β family, is a transforming growth factor β that its expression negatively regulates the growth of the skeletal muscle; and the increase of this hormone has been observed in conditions of muscular atrophy. While in response to muscle overload, its levels decrease after the atrophy period, TGF-β is the most important cytokine in the development of skeletal muscle. Myostatin plays an important role in muscle control, and animal and human studies show a negative role of myostatin in the growth of skeletal muscle. Separation of myostatin from Golgi begins on the ninth day of the onset period and continues until birth at all times of muscle growth. Higher levels of myostatin are found in obese people. Resistance training for 10 weeks could reduce levels of plasma myostatin.Keywords: chemerin, myostatin, obesity, physical activity
Procedia PDF Downloads 3081387 Acute Phase Proteins, Proinflammatory Cytokines and Oxidative Stress Biomarkers in Sheep with Pneumonic Pasteurellosis
Authors: Wael M. El-Deeb
Abstract:
The aim of this study was to assess the pathophysiological importance of lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress markers in sheep with pneumonic pasteurellosis. Blood samples were collected from 36 Pasteurellamultocida-infected sheep, together with 20 healthy controls. Samples for bacteriological examination (nasal swabs, bronchoalveolar lavage) were collected from all animals and subjected to bacteriological examinations. Moreover, heart blood and lung samples were collected from the dead pneumonic sheep and subjected also to bacteriological examinations. A lipid profile was determined, along with a blood picture and other biochemical parameters. The acute phase proteins (fibrinogen, haptoglobin, serum amyloid A), the proinflammatory cytokine tumour necrosis factor-alpha, interleukins (IL-1α, IL-1β, IL-6), interferon-gamma and the oxidative stress markers malondialdehyde, super oxide dismutase, glutathione and catalase were also measured. The examined biochemical parameters were increased in the pneumonic sheep, except for cholesterol and high-density lipoprotein cholesterol (HDL-c), which were significantly lower than control group. Acute phase proteins and cytokines were significantly higher in the pneumonic sheep when compared to the healthy sheep. There was a significant increase in the levels of malondialdehyde; however, a significant decrease in the levels of super oxide dismutase, glutathione and catalase was observed. The present study shed the light on the possible pathphysiological role of lipid profile, acute phase proteins (APPs), proinflammatory cytokines and oxidative stress markers in pneumonic pasteurelosis in sheep.Keywords: acute phase proteins, sheep, pasteurella, interleukins, stress
Procedia PDF Downloads 389