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Salehiyan</title> <meta name="description" content="Search results for: Narin Salehiyan"> <meta name="keywords" content="Narin Salehiyan"> <meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1, maximum-scale=1, user-scalable=no"> <meta charset="utf-8"> <link href="https://cdn.waset.org/favicon.ico" type="image/x-icon" rel="shortcut icon"> <link href="https://cdn.waset.org/static/plugins/bootstrap-4.2.1/css/bootstrap.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/plugins/fontawesome/css/all.min.css" rel="stylesheet"> <link href="https://cdn.waset.org/static/css/site.css?v=150220211555" rel="stylesheet"> </head> <body> <header> <div class="container"> <nav class="navbar navbar-expand-lg navbar-light"> <a class="navbar-brand" href="https://waset.org"> <img src="https://cdn.waset.org/static/images/wasetc.png" alt="Open Science Research Excellence" title="Open Science Research Excellence" /> </a> <button class="d-block d-lg-none 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action="https://publications.waset.org/abstracts/search"> <div id="custom-search-input"> <div class="input-group"> <i class="fas fa-search"></i> <input type="text" class="search-query" name="q" placeholder="Author, Title, Abstract, Keywords" value="Narin Salehiyan"> <input type="submit" class="btn_search" value="Search"> </div> </div> </form> </div> </div> <div class="row mt-3"> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Commenced</strong> in January 2007</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Frequency:</strong> Monthly</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Edition:</strong> International</div> </div> </div> <div class="col-sm-3"> <div class="card"> <div class="card-body"><strong>Paper Count:</strong> 9</div> </div> </div> </div> <h1 class="mt-3 mb-3 text-center" style="font-size:1.6rem;">Search results for: Narin Salehiyan</h1> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">9</span> Cell Patterns and Tissue Metamorphoses Based on Cell Surface Mechanics</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Salehiyan">Narin Salehiyan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Early stage morphogenesis requires the execution of complex systems that direct the nearby conduct of gatherings of cells. The organization of such instruments has been, for the most part, deciphered through the recognizable proof of moderated groups of flagging pathways that spatially and transiently control cell conduct. In any case, how this data is handled to control cell shape and cell elements is an open territory of examination. The structure that rises up out of differing controls, for example, cell science, material science and formative science, focuses to bond and cortical actin arranges as controllers of cell surface mechanics. In this specific circumstance, a scope of formative marvels can be clarified by the guideline of cell surface pressure. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=cell" title="cell">cell</a>, <a href="https://publications.waset.org/abstracts/search?q=tissue%20damage" title=" tissue damage"> tissue damage</a>, <a href="https://publications.waset.org/abstracts/search?q=morphogenesis" title=" morphogenesis"> morphogenesis</a>, <a href="https://publications.waset.org/abstracts/search?q=cell%20conduct" title=" cell conduct"> cell conduct</a> </p> <a href="https://publications.waset.org/abstracts/170992/cell-patterns-and-tissue-metamorphoses-based-on-cell-surface-mechanics" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/170992.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">81</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">8</span> Glycoside Hydrolase Clan GH-A-like Structure Complete Evaluation</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Salehiyan">Narin Salehiyan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The three iodothyronine selenodeiodinases catalyze the start and end of thyroid hormone impacts in vertebrates. Auxiliary examinations of these proteins have been prevented by their indispensably film nature and the wasteful eukaryotic-specific pathway for selenoprotein blend. Hydrophobic cluster examination utilized in combination with Position-specific Iterated Impact uncovers that their extramembrane parcel has a place to the thioredoxin-fold superfamily for which test structure data exists. Besides, a expansive deiodinase locale imbedded within the thioredoxin overlay offers solid similitudes with the dynamic location of iduronidase, a part of the clan GH-A-fold of glycoside hydrolases. This show can clarify a number of comes about from past mutagenesis examinations and grants unused irrefutable experiences into the auxiliary and utilitarian properties of these proteins. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=glycoside" title="glycoside">glycoside</a>, <a href="https://publications.waset.org/abstracts/search?q=hydrolase" title=" hydrolase"> hydrolase</a>, <a href="https://publications.waset.org/abstracts/search?q=GH-A-like%20structure" title=" GH-A-like structure"> GH-A-like structure</a>, <a href="https://publications.waset.org/abstracts/search?q=catalyze" title=" catalyze"> catalyze</a> </p> <a href="https://publications.waset.org/abstracts/173394/glycoside-hydrolase-clan-gh-a-like-structure-complete-evaluation" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/173394.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">70</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">7</span> Potyviruses Genomic Analysis and Complete Evaluation</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Salehiyan">Narin Salehiyan</a>, <a href="https://publications.waset.org/abstracts/search?q=Ramin%20Ghasemi%20Shayan"> Ramin Ghasemi Shayan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The largest genus of plant viruses, the potyvirus, is responsible for significant crop losses. Potyviruses are aphid sent in a nonpersistent way, and some of them are likewise seed communicated. As significant microorganisms, potyviruses are substantially more examined than other plant infections having a place with different genera, and their review covers numerous parts of plant virology, like utilitarian portrayal of viral proteins, sub-atomic communication with hosts and vectors, structure, scientific classification, development, the study of disease transmission, and determination. Biotechnological utilizations of potyviruses are likewise being investigated. During this last ten years, significant advances have been made in the comprehension of the sub-atomic science of these infections and the elements of their different proteins. Potyvirus multiplication, movement, and transmission, as well as potyvirus/plant compatible interactions, including pathogenicity and symptom determinants, are updated following a general overview of the family Potyviridae and the potyviral proteins. it end the survey giving data on biotechnological uses of potyviruses. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=virology" title="virology">virology</a>, <a href="https://publications.waset.org/abstracts/search?q=poty" title=" poty"> poty</a>, <a href="https://publications.waset.org/abstracts/search?q=virus" title=" virus"> virus</a>, <a href="https://publications.waset.org/abstracts/search?q=genome" title=" genome"> genome</a>, <a href="https://publications.waset.org/abstracts/search?q=genetic" title=" genetic"> genetic</a> </p> <a href="https://publications.waset.org/abstracts/172490/potyviruses-genomic-analysis-and-complete-evaluation" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/172490.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">73</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">6</span> COVID-19 Genomic Analysis and Complete Evaluation</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Salehiyan">Narin Salehiyan</a>, <a href="https://publications.waset.org/abstracts/search?q=Ramin%20Ghasemi%20Shayan"> Ramin Ghasemi Shayan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> In order to investigate coronavirus RNA replication, transcription, recombination, protein processing and transport, virion assembly, the identification of coronavirus-specific cell receptors, and polymerase processing, the manipulation of coronavirus clones and complementary DNAs (cDNAs) of defective-interfering (DI) RNAs is the subject of this chapter. The idea of the Covid genome is nonsegmented, single-abandoned, and positive-sense RNA. When compared to other RNA viruses, its size is significantly greater, ranging from 27 to 32 kb. The quality encoding the enormous surface glycoprotein depends on 4.4 kb, encoding a forcing trimeric, profoundly glycosylated protein. This takes off exactly 20 nm over the virion envelope, giving the infection the appearance-with a little creative mind of a crown or coronet. Covid research has added to the comprehension of numerous parts of atomic science as a general rule, like the component of RNA union, translational control, and protein transport and handling. It stays a fortune equipped for creating startling experiences. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=covid-19" title="covid-19">covid-19</a>, <a href="https://publications.waset.org/abstracts/search?q=corona" title=" corona"> corona</a>, <a href="https://publications.waset.org/abstracts/search?q=virus" title=" virus"> virus</a>, <a href="https://publications.waset.org/abstracts/search?q=genome" title=" genome"> genome</a>, <a href="https://publications.waset.org/abstracts/search?q=genetic" title=" genetic"> genetic</a> </p> <a href="https://publications.waset.org/abstracts/172467/covid-19-genomic-analysis-and-complete-evaluation" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/172467.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">72</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">5</span> Mycoplasmas and Pathogenesis in Preventive Medicine</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Salehiyan">Narin Salehiyan</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The later sequencing of the complete genomes of Mycoplasma genitalium and M. pneumoniae has pulled in significant consideration to the atomic science of mycoplasmas, the littlest self-replicating living beings. It shows up that we are presently much closer to the objective of defining, in atomic terms, the complete apparatus of a self-replicating cell. Comparative genomics based on comparison of the genomic cosmetics of mycoplasmal genomes with those of other microbes, has opened better approaches of looking at the developmental history of the mycoplasmas. There's presently strong hereditary bolster for the speculation that mycoplasmas have advanced as a department of gram-positive microbes by a handle of reductive advancement. Amid this prepare, the mycoplasmas misplaced significant parcels of their ancestors’ chromosomes but held the qualities basic for life. In this way, the mycoplasmal genomes carry a tall rate of preserved qualities, incredibly encouraging quality comment. The critical genome compaction that happened in mycoplasmas was made conceivable by receiving a parasitic mode of life. The supply of supplements from their has clearly empowered mycoplasmas to lose, amid advancement, the qualities for numerous assimilative forms. Amid their advancement and adjustment to a parasitic mode of life, the mycoplasmas have created different hereditary frameworks giving a profoundly plastic set of variable surface proteins to avoid the have safe framework. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=mycoplasma" title="mycoplasma">mycoplasma</a>, <a href="https://publications.waset.org/abstracts/search?q=plasma" title=" plasma"> plasma</a>, <a href="https://publications.waset.org/abstracts/search?q=pathogen" title=" pathogen"> pathogen</a>, <a href="https://publications.waset.org/abstracts/search?q=genome" title=" genome"> genome</a> </p> <a href="https://publications.waset.org/abstracts/174154/mycoplasmas-and-pathogenesis-in-preventive-medicine" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/174154.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">60</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">4</span> Effect of Sodium Chloride Replacement with Potassium Chloride on Qualities of Longan Seasoning Powder</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Charoenphun">Narin Charoenphun</a>, <a href="https://publications.waset.org/abstracts/search?q=Praopen%20Rattanadee"> Praopen Rattanadee</a>, <a href="https://publications.waset.org/abstracts/search?q=Chaiporn%20Phaephiromrat"> Chaiporn Phaephiromrat</a> </p> <p class="card-text"><strong>Abstract:</strong></p> One of the most important intricacies of cooking is seasoning which is the process of adding salt, herbs, or spices to food to enhance the flavor. Sodium chloride (NaCl) was added in seasoning powder for taste-improving and shelf life of products. However, the raised blood pressure caused by eating too much NaCl may damage the arteries leading to the heart. Interestingly, NaCl replacement with other substance is essential for consumer. The objective of this study was to investigate the effects of NaCl replacement with potassium chloride (KCl) on the sensory characteristics and physiochemical properties of longan seasoning powder. Five longan seasoning Powder were replaced sodium chloride with KCl at 0, 25, 50 75 and 100%. Mixture design with 2 replications was performed. Sensory characteristics on overall flavor, saltiness, sweetness, bitterness and overall liking were investigated using 12 descriptive trained panelists. Results revealed that NaCl and KCl had effects on saltiness, bitterness and overall liking. As the level of KCl substituted increased, the overall flavor and sweetness of powdered seasoning from longan were not significantly (p < 0.05). This resulted in the decrease of overall liking of the products. In addition, increasing the level of KCl substituted resulted in the drop of saltiness but out of bitterness of the products. Saltiness of powdered seasoning from longan with replacement levels of 50, 75 and 100% KCl different when compared to that of 0% KCl. Bitterness of powdered seasoning from longan with replacement levels of 50, 75 and 100% KCl different when compared to that of 0% KCl. Moreover, consumer acceptance test was conducted (n=100). In conclusion, the optimum formulation contained of 32.0% longan powder, 28.0% sugar, 15.0% NaCl, 5% KCl, 16.0% pork powder, 3.0% pepper powder, and 3.0% garlic powder that would meet acceptability scores of at least 7 or like moderately. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=longan" title="longan">longan</a>, <a href="https://publications.waset.org/abstracts/search?q=seasoning" title=" seasoning"> seasoning</a>, <a href="https://publications.waset.org/abstracts/search?q=NaCl" title=" NaCl"> NaCl</a>, <a href="https://publications.waset.org/abstracts/search?q=KCl" title=" KCl"> KCl</a> </p> <a href="https://publications.waset.org/abstracts/68520/effect-of-sodium-chloride-replacement-with-potassium-chloride-on-qualities-of-longan-seasoning-powder" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/68520.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">253</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">3</span> Designing of Multi-Epitope Peptide Vaccines for Fasciolosis (Fasciola gigantica) using Immune Epitope and Analysis Resource (IEDB) Server</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Supanan%20Chansap">Supanan Chansap</a>, <a href="https://publications.waset.org/abstracts/search?q=Werachon%20Cheukamud"> Werachon Cheukamud</a>, <a href="https://publications.waset.org/abstracts/search?q=Pornanan%20Kueakhai"> Pornanan Kueakhai</a>, <a href="https://publications.waset.org/abstracts/search?q=Narin%20Changklungmoa"> Narin Changklungmoa</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Fasciola species (Fasciola spp.) is caused fasciolosis in ruminants such as cattle, sheep, and buffalo. Fasciola gigantica (F.gigantica) commonly infects tropical regions. Fasciola hepatica (F.hepatica) in temperate regions. Liver fluke infection affects livestock economically, for example, reduced milk and meat production, weight loss, sterile animals. Currently, Triclabendazole is used to treat liver flukes. However, liver flukes have also been found to be resistant to drugs in countries. Therefore, vaccination is an attractive alternative to prevent liver fluke infection. Peptide vaccines are new vaccine technologies that mimic epitope antigens that trigger an immune response. An interesting antigen used in vaccine production is catepsin L, a family of proteins that play an important role in the life of the parasite in the host. This study aims to identify immunogenic regions of protein and construct a multi-epidetope vaccine using an immunoinformatic tool. Fasciola gigantica Cathepsin L1 (FgCatL1), Fasciola gigantica Cathepsin L1G (FgCatL1G), and Fasciola gigantica Cathepsin L1H (FgCatL1H) were predicted B-cell and Helper T lymphocytes (HTL) by Immune Epitope and Analysis Resource (IEDB) servers. Both B-cell and HTL epitopes aligned with cathepsin L of the host and Fasciola hepatica (F. hepatica). Epitope groups were selected from non-conserved regions and overlapping sequences with F. hepatica. All overlapping epitopes were linked with the GPGPG and KK linker. GPGPG linker was linked between B-cell epitope. KK linker was linked between HTL epitope and B-cell and HTL epitope. The antigenic scores of multi-epitope peptide vaccine was 0.7824. multi-epitope peptide vaccine was non-allergen, non-toxic, and good soluble. Multi-epitope peptide vaccine was predicted tertiary structure and refinement model by I-Tasser and GalaxyRefine server, respectively. The result of refine structure model was good quality that was generated by Ramachandran plot analysis. Discontinuous and linear B-cell epitopes were predicted by ElliPro server. Multi-epitope peptide vaccine model was two and seven of discontinuous and linear B-cell epitopes, respectively. Furthermore, multi-epitope peptide vaccine was docked with Toll-like receptor 2 (TLR-2). The lowest energy ranged from -901.3 kJ/mol. In summary, multi-epitope peptide vaccine was antigenicity and probably immune response. Therefore, multi-epitope peptide vaccine could be used to prevent F. gigantica infections in the future. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=fasciola%20gigantica" title="fasciola gigantica">fasciola gigantica</a>, <a href="https://publications.waset.org/abstracts/search?q=Immunoinformatic%20tools" title=" Immunoinformatic tools"> Immunoinformatic tools</a>, <a href="https://publications.waset.org/abstracts/search?q=multi-epitope" title=" multi-epitope"> multi-epitope</a>, <a href="https://publications.waset.org/abstracts/search?q=Vaccine" title=" Vaccine"> Vaccine</a> </p> <a href="https://publications.waset.org/abstracts/171890/designing-of-multi-epitope-peptide-vaccines-for-fasciolosis-fasciola-gigantica-using-immune-epitope-and-analysis-resource-iedb-server" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/171890.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">79</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">2</span> Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Dilek%20Ozturk">Dilek Ozturk</a>, <a href="https://publications.waset.org/abstracts/search?q=Narin%20Ozturk"> Narin Ozturk</a>, <a href="https://publications.waset.org/abstracts/search?q=Zeliha%20Pala%20Kara"> Zeliha Pala Kara</a>, <a href="https://publications.waset.org/abstracts/search?q=Engin%20Kaptan"> Engin Kaptan</a>, <a href="https://publications.waset.org/abstracts/search?q=Serap%20Sancar%20Bas"> Serap Sancar Bas</a>, <a href="https://publications.waset.org/abstracts/search?q=Nurten%20Ozsoy"> Nurten Ozsoy</a>, <a href="https://publications.waset.org/abstracts/search?q=Alper%20Okyar"> Alper Okyar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=circadian%20rhythm" title="circadian rhythm">circadian rhythm</a>, <a href="https://publications.waset.org/abstracts/search?q=chronotoxicity" title=" chronotoxicity"> chronotoxicity</a>, <a href="https://publications.waset.org/abstracts/search?q=everolimus" title=" everolimus"> everolimus</a>, <a href="https://publications.waset.org/abstracts/search?q=thyroid%20gland" title=" thyroid gland"> thyroid gland</a>, <a href="https://publications.waset.org/abstracts/search?q=thyroid%20hormones" title=" thyroid hormones"> thyroid hormones</a> </p> <a href="https://publications.waset.org/abstracts/71510/relevance-of-dosing-time-for-everolimus-toxicity-on-thyroid-gland-and-hormones-in-mice" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/71510.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">350</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">1</span> Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Narin%20Ozturk">Narin Ozturk</a>, <a href="https://publications.waset.org/abstracts/search?q=Xiao-Mei%20Li"> Xiao-Mei Li</a>, <a href="https://publications.waset.org/abstracts/search?q=Sylvie%20Giachetti"> Sylvie Giachetti</a>, <a href="https://publications.waset.org/abstracts/search?q=Francis%20Levi"> Francis Levi</a>, <a href="https://publications.waset.org/abstracts/search?q=Alper%20Okyar"> Alper Okyar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=circadian%20rhythm" title="circadian rhythm">circadian rhythm</a>, <a href="https://publications.waset.org/abstracts/search?q=chronotoxicity" title=" chronotoxicity"> chronotoxicity</a>, <a href="https://publications.waset.org/abstracts/search?q=everolimus" title=" everolimus"> everolimus</a>, <a href="https://publications.waset.org/abstracts/search?q=mdr1a%3A%3ALuc%20mice" title=" mdr1a::Luc mice"> mdr1a::Luc mice</a>, <a href="https://publications.waset.org/abstracts/search?q=p-glycoprotein" title=" p-glycoprotein"> p-glycoprotein</a> </p> <a href="https://publications.waset.org/abstracts/71521/relevance-of-dosing-time-for-everolimus-toxicity-in-respect-to-the-circadian-p-glycoprotein-expression-in-mdr1aluc-mice" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/71521.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">342</span> </span> </div> </div> </div> </main> <footer> <div id="infolinks" class="pt-3 pb-2"> <div class="container"> <div style="background-color:#f5f5f5;" class="p-3"> <div class="row"> <div class="col-md-2"> <ul class="list-unstyled"> About <li><a href="https://waset.org/page/support">About Us</a></li> <li><a href="https://waset.org/page/support#legal-information">Legal</a></li> <li><a target="_blank" rel="nofollow" href="https://publications.waset.org/static/files/WASET-16th-foundational-anniversary.pdf">WASET celebrates its 16th foundational 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