Araştırma Çıktıları

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    Associations of meningioma molecular subgroup and tumor recurrence
    (OXFORD UNIV PRESS INC, 2021-01-01) Youngblood, Mark W.; Miyagishima, Danielle F.; Jin, Lan; Gupte, Trisha; Li, Chang; Duran, Daniel; Montejo, Julio D.; Zhao, Amy; Sheth, Amar; Tyrtova, Evgeniya; Ozduman, Koray; Iacoangeli, Francesco; Peyre, Matthieu; Boetto, Julien; Pease, Matthew; Avsar, Timucin; Huttner, Anita; Bilguvar, Kaya; Kilic, Turker; Pamir, M. Necmettin; Amankulor, Nduka; Kalamarides, Michel; Erson-Omay, E. Zeynep; Gunel, Murat; Moliterno, Jennifer
    Background. We and others have identified mutually exclusive molecular subgroups of meningiomas
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    CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes
    (PUBLIC LIBRARY SCIENCE, 2015-01-01) Avsar, Timucin; Durasi, Ilknur Melis; Uygunoglu, Ugur; Tutuncu, Melih; Demirci, Nuri Onat; Saip, Sabahattin; Sezerman, O. Ugur; Siva, Aksel; Turanli, Eda Tahir
    Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10(-5)) which is important in the immune cell migration, renin-angiotensin (p=6.88x10(-5)) system that induces Th17 dependent immunity, notch signaling (p=1.83x10(-10)) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10(-5)). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.
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    Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis
    (TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2021-01-01) Avsar, Timucin; Celikyapi Erdem, Gokce; Terzioglu, Gokhan; Tahir Turanli, Eda
    Cuprizone, copper chelator, treatment of mouse is a toxic model of multiple sclerosis (MS) in which oligodendrocyte death, demyelination and remyelination can be observed. Understanding T and B cell subset as well as their cytokines involved in MS pathogenesis still requires further scrutiny to better understand immune component of MS. The study presented here, aimed to evaluate relevant cytokines, lymphocytes, and gene expressions profiles during demyelination and remyelination in the cuprizone mouse model of MS. Eighty male C57BL/6J mice fed with 0.2\% cuprizone for eight weeks. Cuprizone has been removed from the diet in the following eight weeks. Cuprizone treated and control mice sacrificed biweekly, and corpus callosum of the brain was investigated by staining. Lymphocyte cells of mice analyzed by flow cytometry with CD3e, CD11b, CD19, CD80, CD86, CD4, CD25 and FOXP3 antibodies. IFNgamma, IL-1alpha, IL-2, IL-5, IL-6, IL-10, IL-17, TNF-alpha cytokines were analyzed in plasma samples. Neuregulin 1 (Nrg1), ciliary neurotrophic factor (Cntf) and C-X-C chemokine receptor type 4 (Cxcr4) gene expressions in corpus callosum sections of the mice brain were quantified. Histochemistry analysis showed that demyelination began at the fourth week of cuprizone administration and total demyelination occurred at the twelfth week in chronic model. Remyelination occurred at the fourth week of following withdrawal of cuprizone from diet. The level of mature and activated T cells, regulatory T cells, T helper cells and mature B cells increased during demyelination and decreased when cuprizone removed from diet. Further, both type 1 and type 2 cytokines together with the proinflammatory cytokines increased. The level of oligodendrocyte maturation and survival genes showed differential gene expression in parallel to that of demyelination and remyelination. In conclusion, for the first-time, involvement of both cellular immune response and antibody response as well as oligodendrocyte maturation and survival factors having role in demyelination and remyelination of cuprizone mouse model of MS have been shown.