Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Green Synthesis of Nanostructured Bioactive Glass for Dental Applications(01. Izmir Institute of Technology, 2023) Tüncer, Melisa; Yücesoy, Deniz Tanıl; Öksel Karakuş, CeydaBioactive glass is a biomaterial commonly used in dental care products and bone tissue engineering applications due to its biocompatibility, bone-forming ability, and remineralization capability. Bioactive glasses form a hydroxyapatite-like layer on dentinal tubules by releasing calcium and phosphorus ions after interaction with saliva. Bioactive 45S5 glass traditionally synthesized by wet chemical methods which require high-temperature heating and the use of a strong acid catalyst, bringing into question of the possibility of introducing toxic acid residues into the final product. Therefore, there is a need to develop environmental-friendly bioactive glass synthesis methods or to modify existing ones in a way to uplift their environmental friendliness. To satisfy this need, we greenized the traditional sol-gel method by replacing the acid catalyst with an environment-friendly alternative and successfully used it for the synthesis of nanostructured 45S5 bioactive glass. First, physicochemical characterization of the synthesized bioactive glasses was performed. Then, the apatite formation capability of bioglasses were investigated in saliva. Next, the mineralization kinetics of bioglasses were tested in Ca/P buffer. In vitro toxicity tests were performed to assess the cytotoxic potential of the synthesized bioactive glass. All analyses were repeated for the traditional synthesis method for comparison purposes. The results confirmed that green synthesis is more advantageous in terms of bioactivity and functionality required for dental applications. Increasing the safety and functionality of bioglass at the same time during the production phase has critical importance for ensuring the sustainability of current applications as well as creating new uses in the biomedical fieldMaster Thesis Development of a Natural Tubular Scaffold From Decellularized Parsley Stems To Be Used in Vascular Tissue Engineering Applications(01. Izmir Institute of Technology, 2024) Çevik, Merve; Dikici, Serkan; Özçivici, EnginCardiovascular diseases (CVD) are usually associated with narrowing or blockage of blood vessels and are the leading cause of death globally. By 2030, the annual incidence of CVD-related deaths is estimated to increase 23.3 million. Considering the advancements in endovascular surgery, the use of vascular grafts in cardiovascular surgery is becoming increasingly common. Autografts are the gold standard but have limitations, including limited tissue availability and complications from vessel isolation. Recently, synthetic grafts have emerged as alternatives, though they often fail due to thrombosis, atherosclerosis, intimal hyperplasia, or infection. Thrombosis, the main cause of post-implantation failure, is associated with damage or absence of the endothelial cell lining on the luminal surface of the vascular graft. To overcome the limitations mentioned so far, tissue-engineered vascular grafts (TEVG) have come into prominence. The use of decellularized plant tissues in tissue engineering applications has recently gained great importance. Accordingly, in this study, we fabricated tubular scaffolds from decellularized parsley stems and evaluated them in vitro as potential TEVGs. Our results demonstrated that native plant DNA was successfully removed, and biocompatible tubular biomaterials were successfully fabricated via chemical decellularization of parsley stems. The decellularized parsley stems showed suitable mechanical and biological properties for use as TEVG material. Finally, they were found to provide a convenient environment to form a pseudo-endothelium by recellularization with human endothelial cells prior to implantation. This study is the pioneer in the literature that reports on the potential of parsley stems to be used as a potential TEVG biomaterial.Master Thesis Investigation of Antimicrobial, Antioxidant and Cytotoxic Properties of Some Green Leaf Plants(2023) Çetin, Elif Nur; Baysal, Ayşe Handan; Özen, Fatma BanuThe present study aims to investigate the chemical composition, antimicrobial activity, antioxidant properties, and cytotoxic activity of extracts obtained from leaf samples that are discarded as waste products. For this purpose, two different green leaves were selected: one is the grape (Vitis vinifera) leaf, a by-product from the winemaking process, and the other is the cauliflower (Brassica oleracea, var. botrytis) leaf, which is a waste product of cauliflower, and they were subjected to related tests. Both leaf samples were extracted by water because of its easy accessibility and environmentally friendly properties. Leaf extracts were examined according to their total phenolic content and subjected to chemical characterization by Liquid chromatography-quadrupole time-of-flight tandem mass spectrometry system. The promising antioxidant activities of the water-extracted leaf samples were authenticated through DPPH and ABTS assays. Antimicrobial and antibiofilm activities were examined against some Gram-positive (Bacillus cereus, Listeria innocua, and Carnobacterium divergens) and Gram-negative (Escherichia coli, Serratia liquefaciens, and Salmonella Typhimurium) strains, and two fungi (Saccharomyces cerevisiae and Candida albicans) species. Both tested leaf extracts showed a dose-dependent antimicrobial activity, while the antimicrobial activity of grape leaf extract was slightly higher. However, their activities against biofilm formation were varying in different bacterial and fungi species. The cytotoxic activity of the leaf extracts was examined on the mouse fibroblast cell (L929) line. According to the presented results, neither of the leaf extract samples used in the study showed any unwholesome effects on the cell line at any time point.Master Thesis Development of Microfluidic Devices for Investigating Small Molecule Induced Chemotaxis of Dendritic Cells(01. Izmir Institute of Technology, 2023) Khurram, Muhammad Maaz; Bedir, Erdal; Tekin, Hüseyin CumhurMicrofluidics is the core branch of science and technology in which interdisciplinary research is conducted with a low amount of samples in microchannels ranging from 10-100 μm. The main objective of this thesis is to design and fabricate a chemotaxis microfluidic device (CMD) from the poly-methyl methacrylate (PMMA) substrate to analyze the immune cell behavior against cancer cells. The patterns of the three-layered CMD were generated using laser ablation. During the fabrication, Power (P) and Speed (S) values were varied to determine the optimal P-S combination. Then, the structural properties of microfluidic channels in the CMD were examined via microscope. The mechanical properties and liquid handling abilities of CMDs were also investigated through tensile and leakage tests, respectively. Moreover, cell viability of DC2.4 dendritic cells (DCs) and B16-F10 murine melanoma (B16-F10) cells in CMDs sterilized through either autoclaving or UV treatment were determined to test the suitability of CMDs via Live/Dead Assay. The highest cell viability for DCs and B16-F10 was obtained in autoclaved CMDs. For the maturation of DCs before seeding into CMD, DCs were stimulated with lipopolysaccharide (LPS) and Astragaloside VII (AST-VII) at various concentrations. While the cytotoxicity of LPS and AST-VII were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the expression levels of specific chemokine receptors were also analyzed through flow cytometry. Lastly, stimulated DCs and B16-F10 were simultaneously cultured in the CMD, and the migratory behavior of DCs against B16-F10 was time-dependently studied. Consequently, CMD that provided cost-effective and rapid analysis of intercellular interactions was successfully developed.Master Thesis The Investigation of Intestinal Zinc and Glucose Metabolism Due To Increased Glucose Amount in Obesity(2023) Divrik, Bengisan; Güleç, Şükrü; Büyükkileci, Ali OğuzObesity is defined as an excessive accumulation of adipose tissue within the human body. The global prevalence of obesity has seen a marked increase, and our country is no exception to this trend. The pathogenesis of obesity is intricately linked to the consumption of glucose, a phenomenon in which glucose absorption plays a pivotal role via the enterocytes of the intestinal lining. In individuals with obesity, both dietary and blood glucose levels are elevated, thereby intensifying the exposure of enterocyte cells to glucose. This thesis results delved into the interactions between high-glucose-associated zinc metabolism and zinc-dependent glucose metabolism within enterocyte cells. Results revealed a correlation between elevated glucose concentrations and reduced zinc levels within the cells, coupled with the regulation of mRNA levels on zinc transporters. Additionally, observed a reduction in cellular 2-deoxy-glucose uptake upon zinc treatment. Also, indicated that zinc treatments, whether administered to the basolateral or both apical and basolateral sides of the cells, led to the regulation of mRNA levels for glucose transporters, compared to control groups. Remarkably, also observed that specific treatments involving zinc on the polarized sides of Caco-2 cells increased the efflux of glucose from these cells. In conclusion, results suggest that zinc may play a pivotal role in the development of obesity concerning glucose metabolism.Master Thesis Molecular Evolutionary and Population Genetics Analyses of Human H1n1 Ha and Na Genes in Pandemic and Non-Pandemic Years(2023) Naycı, Kıvanç; Sezgin, EfeThe 1918 H1N1 pandemic, known as Spanish Flu, is one of the deadliest pandemics on recorded history. It is estimated that the Spanish Flu pandemic affected over 500 million people across the globe, and the death toll is estimated to be between 20 to 50 million. Ever since this, scientists worked hard to find an effective vaccine for influenza, but its very rapidly evolving nature made this task quite the challenge. In this thesis we performed molecular evolution and population genetics analyses on 35714 hemagglutinin and 36302 neuraminidase nucleotide sequences to better understand the evolution of these proteins. The Tajima's D values showed strong positive selection on the pandemic year of 2009 and the BEAST analysis results also suggested there was a greater exponential growth compared to other years. The relaxation of selection and lack of exponential population growth was inferred from the calculations for 2021 sequences, whereas the positive selection on the hemagglutinin and neuraminidase proteins was evident for the 2022 sequences. Outgroup tests also confirmed the positive selection was acting on the pandemic and non-pandemic years, the tests also confirmed the divergence of human influenza neuraminidase from the swine influenza neuraminidase. HA2 part of hemagglutinin and 475-500 nt part of neuraminidase proteins were found to be the most conserved parts of these proteins. In conclusion, the positive selection on these two proteins returned after the year 2021, which was a very unusual year for influenza that caused the positive selection on the virus and the exponential growth rates of the virus to decline. The most conserved regions can be a good candidate for small molecule/drug and vaccine studies.Master Thesis Polymorphisms in Reverse-Cholesterol Transport Pathway Related Genes and Their Relationship With Complex Heart Diseases in Human Populations(01. Izmir Institute of Technology, 2023) Yasdı, Burak Kaan; Sezgin, EfeCardiovascular diseases have been one of the major causes of mortality worldwide. Genetic factors within the underlying mechanisms are extensively studied but still remain unclear at certain points of views. This master's thesis investigates the genetic factors as single nucleotide polymorphisms and their relationship with complex heart diseases in human populations. The study employs a comprehensive approach integrating molecular genetics, epidemiology and biostatistics to analyze diver range of genetic variations within the reverse cholesterol pathway (RCT) playing a role in the cholesterol homeostatis. In a systematic review perspective, by conducting meta-analyses of existing clinical data in literature, the study aims to examine and identify single nucleotide polymorphisms with an increased risk of complex heart disease. Furthermore, the study aims to enrich the set of variants related to coronary heart disease (CHD) and high-density lipoprotein cholesterol (HDL-C) by determination of additional variants in linkage disequilibrium pairs and functional annotation of variants with potential effects. Publicly available clinical data regarding to the relationships of variants and their effects enabled us to explore the underlying genetic factors of higher CHD risk. The findings have the potential to improve future research directions, clinical practice, and public health initiatives aimed at reducing the global burden of cardiovascular diseases.Master Thesis Enhancing L-Asparaginase Catalytic Activity for Improved Antileukemic Activity: a Computational Study on Thermococcus Kodakarensis L-Asparaginase Mutations(2023) Ekmekci, Pelinsu; Eraltuğ, Nur Başak Sürmeli; Karataş, DenizIn this study, thermostable Thermococcus kodakarensis L-asparaginase (TkA) enzyme, which lacks glutaminase activity, was studied for its structural and dynamic properties. The structural and dynamic properties of TkA, was investigated in its apo state and with the L-asparagine ligand to understand how the active site and general structure of the TkA enzyme changes with ligand binding and what effect this interaction has on the general behavior of the enzyme. T11E, T55E and D86S mutants of TkA were examined by molecular docking and molecular dynamics simulations. Binding results for molecular docking indicate that the structure is largely conserved, with root mean square deviation (RMSD) scores of −5.2 to −5.7 nm for wildtype TkA and mutants. RMSD and root mean square fluctuations (RMSF) data obtained as a result of molecular dynamics studies showed that the mutants had a stability close to that of the WT TkA enzyme, between 0.15 and 0.16 nm. In general, solvent accessible surface area (SASA) and radius of gyration analysis results support this analysis, while the D86S mutant gave more effective results than other mutants with SASA value of 260.38 nm2 /ns and radius of gyration values of 2.61 nm/ns. The total interaction energy of the ligand and WT TkA was -337.98 kJ/mol, while the interaction energy for D86S mutant was larger, at -363.03 kJ/mol. In conclusion, the study showing how the structure and dynamics of the TkA enzyme are affected by thebinding of L-asparagine ligand helps to understand the stability and functional behavior of the enzyme.Master Thesis Image-Based Bioassays in Microfluidic Devices(Izmir Institute of Technology, 2023) Doyran, Öykü; Teki̇n, Hüseyi̇n CumhurSon zamanlarda, mikroakışkan uygulamalar, tıbbi bozuklukların teşhisini ve izlenmesini amaçlayan minyatür cihazlarla, standart laboratuvar prosedürlerinin yerini almıştır. İyi tanınan geleneksel mikroskobik teknikler, hala alışılagelmiş olarak mikroakışkan teknolojilerinde görüntüleme için kullanılmaktadır. Ancak bu mikroskopların hantal ve pahalı yapıları, yeni nesil hasta başı test cihazları ile uyumlu değildir. Minyatür cihazlarda optik elemanların uygulanması, ölçüm doğruluğu ve kesinliğinin yanı sıra taşınabilir enstrümantasyon sunar. Spesifik olarak, lenssiz görüntüleme teknolojilerinin mikro teknolojilerle entegrasyonu, yeni cihazlar geliştirmenin yolunu açmıştır. Bu tezde entegre lenssiz holografik mikroskopların iki farklı uygulaması sunulmuştur. İlk uygulama, boyutlarına ve morfolojilerine göre kanda sirküle eden tümör mikroembolilerini lökositlerden ayırmak, saflaştırmak ve izole etmek için yeni bir lenssiz holografik mikroskop entegreli mikroakışkan tabanlı filtreleme yönteminin geliştirilmesini içermektedir. Geliştirilen yöntem, mikrofiltrasyon ve lenssiz holografik mikroskop teknolojilerinin avantajlarını kullanarak, ticari hücre ayırma cihazlarıyla karşılaştırılabilir şekilde kanda sirküle eden tümör mikroemboli ayırma verimliliği ve saflığı sağlamıştır. Ayrıca, lenssiz holografik mikroskop entegre manyetik levitasyon tabanlı sıvı viskozitesi ve özkütle ölçümü olarak başka bir yeni yöntem tanıtılmıştır. Bu yöntemde, sıvıların özkütle ve viskozitelerini belirlemek için mikrosensör olarak mikropartiküller ölçüm yapılacak sıvı içinde kullanılmıştır. Bu parçacıkların levitasyon yüksekliği ve hızı sıvının özkütlesi ve viskozitesi ile ilişkilendirilmiştir. Bu tez kapsamında sunulan, mikroakışkan tabanlı teknolojilere entegre lenssiz holografik mikroskop sistemleri, uygun maliyetli ve taşınabilir görüntü tabanlı yeni cihazların geliştirilmesinin önünü açabilecektir.Master Thesis Effect of Gold Nanorod Properties on Lspr Response(01. Izmir Institute of Technology, 2023) Kılıç, Şebnem; Bulmuş Zareie, Esma Volga; Tekin, Hüseyin CumhurOptical qualities make gold nanorods (GNRs) excellent for plasmonic biosensors. Localized surface plasmon resonance (LSPR) phenomenon which occurs on GNR surfaces enables the creation of highly sensitive biosensors. The physical properties such as aspect ratio and size are directly related to the LSPR response of GNRs. The aim of this study is to investigate the impact of the aspect ratio (AR) and the interparticle distance on the localized surface plasmon resonance (LSPR) response of GNRs decorated glass sensor chips. For this aim, GNRs were first synthesized using a seed-mediated growth method. The effect of AgNO3 concentration on the AR of GNRs was investigated. It was observed that increasing AgNO3 concentration resulted in GNRs with higher AR and a red shift in the longitudinal plasmon peak wavelength. GNRs with an AR of 4, 6 and 8 were successfully synthesized. Next, the effect of the stabilizer molecule type and molecular weight on the distribution of GNRs on the silanized glass surface was investigated. It was found that the APTES modified glass surfaces cannot be coated with CTAB stabilized GNRs. Using GNRs stabilized with PEG5K resulted in a more homogeneous distribution of GNRs on the glass surface with respect to GNRs stabilized with PEG2K. The interparticle distance between GNRs on the glass surface was successfully controlled by simply concentrating or diluting the GNR solution used for coating the glass surfaces. It was observed that the LSPR peak shifts decreased upon binding of analytes as the interparticle distance between GNRs decreased in the studied range. On the other hand, as the AR decreased, the LSPR response of the GNRs shifted blue. The results presented in this thesis may contribute to future research to improve the potential of LSPR-based biosensors for diverse biomedical and diagnostic applications.