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Archived Theses
Bitki suspansiyon kültürü kaynaklı bitkisel ekstraselüler veziküller
Although extracellular vesicles (EVs) are an ever-present part of life, research of non-mammalian EVs have been severely limited compared to the studies of human EVs. Initial studies of plant EVs already report promising results, such as therapeutic effects for various types of cancers, colitis, immunomodulation, and wound healing. However, there are still many unknowns in plant EV research. A large majority of the articles published in the field fail in adhering to the standards and definitions set in international guidelines of EV research. The abundant contaminants created due to the harsh isolation procedures, lack of adequate controls, and incomplete characterization of the isolated EVs makes these findings questionable. The issues are exacerbated due to a lack of a plant EV isolation method or biomarkers agreed upon by the scientific community. This dissertation attempts to address this issue by providing a complete workflow for the isolation and characterization of true plant EVs using plant cell suspension cultures. Using this workflow, we have isolated and characterized EVs from Nicotiana tabacum, Vitis vinifera and Stevia rebaudiana cell cultures. Proteomic analysis of N. tabacum sEVs revealed the presence of eight proteins suggested as plant EV biomarker candidates. Furthermore, we ran an ortholog protein discovery analysis using proteomes of N. tabacum and seven other plant EV proteomes against top human EV proteins. We identified 116 human proteins with plant orthologues, with 24 of these proteins being present in more than five or more plants. Our findings prove that plant cell suspension cultures can be used for the production of highly pure plant EVs. Plant EVs have considerable potential as therapeutic agents or drug delivery devices, which can be easily, and efficiently produced in a large scale manner. Finally, the biomarkers identified in this study can pave the way for future studies in the field of plant EV research.
Çoklu konut tasarımına esneklik özelliği kazandırabilme kriterlerinin belirlenmesi
Multiple housings are a type of housing that is produced regardless of a specific dweller group and they must be designed with the flexibility to meet the needs of dwellers for change in order to appeal to a wide audience of dwellers who will use the housing. Flexibility is a design parameter that must be considered to ensure the adaptation between the house and the dweller and that the housing can be used for long when the needs for change in the housing arise. From this point on, this thesis aims to determine the criteria that may help to attain flexibility in multiple housings by focusing on the reasons that lead to the need for flexible housing. The chapters and contents of the thesis are as follows: In the first chapter, the intention of doing this study, the extent of the thesis and the methods followed throughout the study are compiled under the title of the thesis method. Existing studies, articles, theses, books are examined. In the second chapter, the flexibility concept is described, classified and the need for flexibility in housings is emphasized. Flexible housing examples from past to present have been examined. In the third chapter, the main reasons for the need for flexibility in housing design are mentioned. In the fourth chapter, flexibility in multi-house production is generally evaluated under the headings of strategies, collaborative planning, modular design. In the fifth chapter, it is aimed to set criteria for flexible multi-housing design in the consideration of the obtained data and the production of two existing multi-housing design is illustrated and evaluated under the criteria. In the sixth final chapter, the overall results of the set criteria to attain flexibility to multi-housing design is put forth.
Silymarin içeren nanopartikül formülasyonu geliştirme ve karaciğer koruyucu etkilerinin değerlendirilmesi
Last decades, many individuals have preferred some medicinal plants to treat the diseases they suffer from and to prevent various diseases. Therefore, recent scientific studies have focused on investigating the effects of plants on diseases. The Silybum marianum, used onwards first ages and whose effects on the liver are known, is one of them. In this study, the effects of Silybum marianum active substances silymarin, and their nanoparticles on the liver disease were observed. While the nanoparticles were prepared using soy lecithin, Silybum marianum extracts, which are active ingredients with the incorporation technique, were obtained from three different sources. In the light of previous studies, it has been seen that it is appropriate to mix soy lecithin and extracts in a 1:1 ratio. While soy lecithin is being prepared, the homogenizer and probe sonicator technique are applied, while Silybum marianum extracts are prepared by solvent extraction method. After incorporation, the probe sonication method was used to mix, decrease the particle size and be a homogenous mixture. Moreover, in order to increase the stability, the freeze-dried technique was used for soy lecithin, extracts, and the final formulations. The characterization of formulation size, zeta potential, and PDI was observed by using the DLS technique, the release profile of three different formulations, and prepared calibration curve were performed by using HPLC. In vivo studies, the procedures were performed on four different groups which were determined as the nanosilymarin formulation applied after the liver damage was induced, the other was treated with pure silymarin formulation under the same condition, the control group (healthy) and the last one who did not receive any treatment after induced liver damage. All groups have six Sprague Dawley, male and young rats. After that, histopathological and HPTLC tests were done. As a result of in vitro, in vivo animal experiments and histopathological studies, it has been observed that nanoparticle-containing standardized seeds are more effective.
Prostat kanseri hücre hatlarında MEISi-2 tedavisinin etkinliği
MEIS proteins are histrocally associated with tumorigenesis, metastasis and invasion in cancer. MEIS and associated PBX-HOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be mis-regulated in various cancers. Bionformatical analyses suggest their upregulation in leukemia/lymphoma, thymoma, pancreas, glioma, and glioblastoma, and downregulation in cervical, uterine, rectum and colon cancers. However, every cancer type includes, at least, a subtype with high MEIS expression. In addition, studies highligh that MEIS proteins and associated factors may function as diagnostic or therapeutic biomarkers for various diseases. In this study, the function of MEIS1-2-3 proteins in prostate cancer (PCa) cell lines was investigated in vitro. In addition, MEIS inhibitors (MEISi-2), the first in its class, the MEIS homeodomain inhibitor has been shown to have a potent chemotherapeutic agent potential in PC-3, DU145, 22Rv-1 and LNCaP, prostate cancer cell lines. The effects on MEIS inhibitors in PCa cell lines are that reveal cytotoxicity and reduce cell viability. Also, intracellular ROS levels and MEIS protein expression were upregulated post MEISi-2 treatment. Also, MEISi-2 treatment resulted in slightly increase of Pca cell migration and the alteration of cell cycle of Pca cell lines. Overall, it is the first time that Pca cell lines necessitate basal MEIS1/2/3 expression for survical in vitro.
Buğday (Triticum aestivum L.) kaynaklı ekzozomların yara iyileşmesi üzerine etkisi
Wound healing is the main physiological process which undergoes homeostasis, inflammation, proliferation, migration and tissue remodeling. Acute injuries usually heal in a short period of time but chronic illnesses associated with infection and prolonged inflammation, may resulted with the life-threatening infections, limb amputations that presents a serious challenge for the current technology. Although wound healing has been studied for decades, improved drugs are not still effective enough due to their high cost, low efficiency, having patient specific response, requiring wound care facilities and severe side effects. In this sense, developing new, safe, self-applicable, effective and cheap wound care products is still an attractive area of international research. Cell to cell communication is compulsory in order to sustain tissue homeostasis but most communication mechanisms between cells requires a coordination of the receptors and the signaling molecules. Recently, nano vesicle mediated cell communication become prominence because of the ability to shuttle different molecules from producing cells to the target cells via extracellular vesicles called exosomes. Previous studies reported that, exosomes released from plants such as grape, grapefruit, ginger and carrot have anti-inflammatory and anti-cancer properties. Although the underlying mechanisms of wound healing process of plant exosomes are still unknown. For this reason, in this study, for the first time, rate limiting factors of wound regeneration such as cell proliferation, migration, angiogenesis, gene and growth factor expression cell migration and proliferation was stimulated by using wheat derived exosomes by using both in vitro and in vivo approaches. According to the results, wheat exosomes increased cell proliferation, migration and angiogenesis, have anti-inflammatory effect, increased essential growth factor, and gene expression levels of HDF, HUVEC and HACAT cells in vitro. Moreover, wheat exosome-containing hydrogel formulations improved wound healing and histopathological rates in vivo. All in all, this research indicates a brand-new scope for wound healing therapeutics using wheat derived exosomes for the first time.
Nicotiana tabacum cv. Xanthi hücre süspansiyon kültüründen solanesol üretimi ve ölçek büyütme çalışmaları
Plants are important sources for wide range of different chemical compounds used in the production of fragrances, pigments, flavors, industrial feedstock, antimicrobials and pharmaceuticals. These chemicals are known as plant secondary metabolites which are generally responsible for the protection of the plant against environmental stress factors. Solanesol is a non-cyclic terpene found mainly in Solanaceae family plants and known to have highest accumulation in Nicotiana tabacum (tobacco) with 0.04-3.6 percent of leaf dry weight. It has antimicrobial, anti-cancer and anti-inflammatory effects that is mainly used as a precursor of Coenzyme Q-10. It is mainly extracted from the plants instead of chemical synthesis due to its long carbon chains. Secondary metabolites are generally extracted from whole plants which require large lands for growth, optimal environmental conditions and it is also labor intensive. Therefore, using plant cell suspension culture systems for the production of secondary metabolites has become one of the most important tools. In this study, it was aimed to achieve solanesol extraction from Nicotiana tabacum cv. Xanthi cell suspension culture and process scale-up of the suspension cultures. To our knowledge, this is the first study in the literature that focuses on the production of solanesol from tobacco cell suspension culture instead of whole tobacco plant or tobacco waste. N. tabacum cv. Xanthi callus cell lines were used to initiate the cell suspension culture which was maintained throughout the study. Optimal pH of the cell suspension cultures were determined as 6, cells were in log phase between days 1-11 and in stationary phase between days 11-15 according to the fresh weight, dry weight, pH and sugar consumption analysis. Optimal subculture period was determined as 7 to 9 days. Solanesol was extracted from N. tabacum cv. Xanthi cell suspension cultures for the first time in literature and had the average production of 14.56 ± 4.71 mg/ml which was the 1.46 percent of the dry weight. Scale-up parameters were optimized for growing plant cell suspension cultures in a stirred-tank bioreactor. This study will be the foundation for large-scale production of solanesol from N. tabacum cv. Xanthi cell suspension cultures.
Yüzeyde zenginleştirilmiş raman saçılımı kullanılarak 2D hücre kültüründe ilaçların hücresel metabolizma üzerindeki etkisinin incelenmesi
Raman spektroskopisi (RS), etiketsiz bir numuneden moleküler düzeyde bilgi sağlayan güçlü bir titreşim spektroskopik tekniktir. yüzeyde zenginliştirilmiş Raman saçılımı (SERS), Raman Spektroskopisinin oldukça hassas bir modudur ve yüzeydeki moleküler bileşimi veya çok yakın çevresindeki soy metal partiküllerin boyutu, saniyede iki büyüklükten daha az büyüklükte tanımlanmasına yardımcı olabilir. Metformin (MET), mitokondriyal solunum zinciri kompleksi I, hücre proliferasyonu, protein sentezi ve glukoneogenezi etkileyen bir ilaç molekülüdür. 6-Merkaptopürin (6-MP), antijen uyarımını takiben serideki nükleik asit metabolizması ve protein senteziyle ilgisi ve hücreler üzerindeki sitotoksik aktivitesi ile düzenlenebilen immünosüpresif özelliklere sahiptir. Bu çalışmada, SERS'in ilaçların hücre metabolizması üzerindeki etkisini izleyebilme potansiyeli, model ilaçlar olarak metformin ve 6-Merkaptopurin kullanılarak araştırılmıştır. Çalışma için iki hücre hattı, A549 ve Beas-2b seçildi. Ortalama boyutu 50 nm olan altın nanopartiküller, SERS substratları olarak seçildi. Metformin tedavisinde nükleik asitler, amino asitler ve fosfolipid zirveleri değişti. Bu değişikliğin nedeni, proliferasyonun inhibisyonunu ve protein sentezini ve lipid ve kolesterol biyosentezinin baskılanmasını sağlayan MET mekanizmalarıdır. Nükleik asitlere ve proteinlere karşılık gelen SERS pikleri, 6-Merkaptopürin tedavisi ile değiştirildi. Gözlemlenen spektral değişiklikler, de novo purin sentezinin ve protein sentezinin engellenmesine atfedilir. Hücrelerin artan konsantrasyonlarda ilaç moleküllerine maruz kalması üzerine gözlemlenen spektral modeldeki değişiklikler, bilinen ilaç metabolizması mekanizmalarıyla ilişkilendirilmeye çalışılır. Sonuçlar, MET ve 6-MP durumunda gösterildiği gibi, SERS'in ilaç moleküllerine maruz kalması üzerine hücresel düzeyde metabolik değişiklikleri izlemek için kullanılabileceğini göstermektedir.
Diz için fiziksel egzersizlerin verimliliğinin bıofedbackkullanılmasının artırılması
Impairments occurred in the knee result in the decline of the quality of daily activities such as walking, running, sitting, and standing. Depending on the level of impairment, physical exercises are subscripted to regain strength, flexibility, and range of motion. The efficiency of the exercises can be improved by supplying a feedback mechanism during the exercises. Meanwhile, some improvements can be obtained when the knee joint range of motion is assessed during the exercises. The development of automated systems having feedbacks and motion assessments is gaining increased demand. This thesis work aims to improve the efficiency of physical exercises for the knee by quantifying the knee joint range of motion with the use of two micro-electro-mechanical orientation sensors, and by giving audio feedback by playing predetermined dialogues with the use of an audio player module. Fifteen volunteers are enrolled to analyze the effectiveness of the audio feedback on three physical exercises namely sit-to-stand, squat, and seated leg flexion-extension. The Wilcoxon rank-sum test results for seated leg flexion-extension exercise, sit-to-stand, and squat exercise shows that the addition of audio feedback shows a statistically significant difference in sit-to-stand (p=.01) and squat exercises (p<.001) but not in seated leg flexion-extension exercise (p=.15). The System Usability Scale (SUS) results show that exercise with audio feedback (SUS score=83.0) has a higher score than exercise without audio feedback (SUS score=72.2), but this increase is not statistically significant (p=0.14). The addition of audio feedback in closed chained exercises may increase the efficiency of the physical exercises. This improvement may be seen more drastic in the exercises that do not end with the movement of locking the knee in full flexion or extension. Future studies are planned to compare the designed system with video-based feedback systems used in physical therapy and to examine the effects of audio feedback on knee-based physical therapy with volunteers requiring physical rehabilitation rather than healthy volunteers.
Kemik doku mühendisliğinde diş germ kaynaklı kök hücreler: Osteo-odontojenik potansiyel
Bone tissue engineering (BTE) needs a reliable stem cell source, appropriate 3D scaffolds and growth factors. Mesenchymal stem cells (MSCs) are attractive stem cell sources for BTE since their differentiation can be controlled and they have high clonogenic capacity. In particular, dental tissue derived MSCs are favorable candidates due to their high osteogenic capacity, easy access, no donor site morbidity and availability of human source without any ethical problems. Aim of this study was to determine most appropriate and applicable dental stem cell source for BTE by comparing clonogenic characteristics and osteogenic differentiation capability of dental germ stem cell (TGSC), dental follicle stem cell (DFSC) and stem cell from apical papilla (SCAP) tissues and to obtain bone-like tissue by seeding the cells with higher osteogenic capacity on fibrous PBS:PLGA composite scaffold. For these purposes, dental germ, follicle and apical papilla tissues of third molars were extracted from 6-month-old pigs due to their similarities to humans and stem cells from these tissues were isolated by explant culture. Mesenchymal characteristics of cells were proved and differentiation studies were performed. Their osteogenic differentiation potential in cell culture plates and on the fibrous composite PBS:PLGA scaffolds which were fabricated by wet spinning were detected in terms of mineral deposition, ALP activity and gene expressions. The best scaffolds were chosen as a result of degradation analysis, mechanical analysis and cell viability test. These studies showed that stem cells from three different sources had great osteogenic differentiation capacity in tissue culture plates but SCAP achieved higher and faster osteogenic differentiation. However, all cells had similar mineralization and bone marker expression on scaffold at the end of 21 days of osteogenic induction. Also, wet spun 20 percent PBS:PLGA (1:1) scaffold was shown to be an excellent candidate for BTE due to its good mechanical properties and physiological features.
Plastik olmayan silt içeriğinin kumların sismik sıvılaşmasına etkisi
Earthquakes are one of the important problems of Turkey because of being in a seismically active region. During earthquakes, loose, saturated, cohesionless soils could significantly lose their shear strength because of great excess pore water pressures generated and act like fluid, which is called soil liquefaction. Liquefaction is one of the most significant and worth researching phenomena in geotechnical engineering and it has been studied by researchers for decades. Liquefaction occurs mostly on sandy soils, but the soils in situ include a certain amount of silt. In this study, the effects of non-plastic silt contents on the liquefaction potential of sands were investigated experimentally at the Soil Mechanics Laboratory of Yeditepe University. The clean sand was mixed with silt at three different fines contents (i.e. FC = 5 percent, 15 percent, and 35 percent). Cyclic Direct Simple Shear (CDSS) tests were performed on each soil under 100 kPa vertical effective stress at a wide range of different relative densities (Dr) and under three different cyclic stress ratios (i.e. CSR = 0.1, 0.12 and 0.14). The results were compared with that of the clean sand (i.e. FC = 0%), and the change in the seismic liquefaction potential was investigated. In conclusion, it was observed that liquefaction resistance of silty sands with 5 percent fines content is greater than the resistance of clean sand and liquefaction resistance of silty sands with 35 percent fines content is smaller than the resistance of clean sands. In addition, it has been observed that liquefaction resistance of silty sands with 15 percent fines content decreases on soils where the relative density is less than 45 percent compared to the resistance of clean sands and liquefaction resistance of silty sands with 15 percent fines content increases on soils where the relative density is higher than 45 percent compared to the resistance of clean sands.