Sürdürülebilir Yeşil Kampüs Koleksiyonu / Sustainable Green Campus Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7755

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2018 - 20192

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Author: search.filters.author.Bedir, Erdal

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  • Master Thesis
    Fungal Biotransformation of Novel 20(27)- Octanor Cycloastragenol and Biological Activities of the Purified Metabolites
    (Izmir Institute of Technology, 2019) Duman, Seda; Bedir, Erdal; Çağır, Ali
    Biotransformation is the chemical modifications performed by enzymes or living organisms. The difficulty and high cost of enzyme isolation and purification makes it more advantageous to use whole cell systems as biocatalysts. Microbial biocatalysts are particularly interesting in the modification of complex molecules such as steroids and triterpenoids, which can catalyze stereo- and regio- selective reactions that are difficult or impossible to perform with chemical reactions. Specially, ability of endophytic microorganisms to produce specific enzymes for adaptation to their environment by tolerating toxic defense metabolites, makes them interesting for biotransformation studies. Telomeres are nucleotide structures located at the end of chromatids shortening with each cell division. Telomerase is a reverse transcriptase enzyme, and it helps to replenish telomere ends that are truncated by aging and stress factors. The telomerase activators (TA) with their potentials are suggested encouraging agents for healthy aging, and they are projected to generate a huge market in the future. Cycloastragenol is the only natural product in the sector marketed as a potent telomerase activator. In this study, by using endophytic fungi, the biotransformation studies were performed on 20(27)-octanor cycloastragenol. As a result, 14 biotransformation products, were isolated by chromatographic studies, and the structures of the metabolites were established by spectral methods. Based on the literature survey, 13 compounds turned out to be new for nature. Seven metabolites were screened for telomerase activation. In these screenings, metabolites showed telomerase activation ranging from 5.43 to 12.36 fold at doses ranging from 0.1 to 30 nM compared to the control cells treated with DMSO.
  • Master Thesis
    Investigating Immunomodulator Mechanisms of Astragalus Saponins
    (Izmir Institute of Technology, 2018) Yakuboğulları, Nilgün; Yakuboğulları, Nilgün; Bedir, Erdal; Sağ, Duygu
    Adjuvants are chemical/biological substances that are used in vaccines to increase immunogenicity of antigens. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response with antigen specific antibody response. The main goals of this thesis are synthesis of immunologically active analogs of AST VII and identifying immunomodulatory mechanism of actions of AST VII. The impact of AST VII and its synthesized analogs (dicarboxylic AST VII: DC-AST VII and dodecylamine conjugated AST VII: DAC-AST VII) on the cytokine release profile of human whole blood cells (hWB), dendritic cell maturation and subsequently T cell activation were analyzed by using flow cytometry and ELISA. IL-1 and IL-17A cytokines were substantially induced on hWB following treatments of the compounds. The most potent compounds were: DAC-AST VII (3.32 fold) for production of IL-1, AST VII (5.05 fold) for production of IL-17A. AST VII was more effective than DAC-AST VII (7.52 fold versus 1.34) in IL-1 production in BMDCs (bone marrow derived dendritic cells). The co-stimulation with AST VII and LPS enhanced dendritic cell maturation and activation by upregulating MHC II, CD86 and CD80, as well as IL-12 induction. All compounds were able to activate CD4+ and CD8+ T cells via increasing CD44 expression. Inflammasome activation may have a role in AST VII induced IL-1 secretion, dendritic cell maturation and T cell activation. However, more detailed molecular mechanism studies are warranted to substantiate our findings and to put forward signaling pathways involved.