Phd Degree / Doktora
Permanent URI for this collectionhttps://hdl.handle.net/11147/2869
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Doctoral Thesis Investigations on the Prebiotic Activity of Xylan and Xylooligosaccharides Using in Vitro Mouse Fecal Culture and Ex Vivo Mouse Colon Model(01. Izmir Institute of Technology, 2024) Sabancı, Kevser; Büyükkileci, Ali Oğuz; Güleç, ŞükrüKsilan (KS) ve onun hidroliz ürünü olan ksilooligosakkaritler (KOS), prebiyotik özellikleriyle tanınmaktadır. KS'nin, KOS ve inüline (INU) göre daha yavaş bir şekilde kullanıldığı ve bağırsak mikrobiyotası üzerinde farklı etkiler gösterdiği gözlemlenmiştir. Ancak, KS'nin fizyolojik etkilerine yönelik araştırmalar hâlâ sınırlıdır. Bu çalışma, KS'nin kolondaki kullanımını ve mikrobiyota üzerindeki etkilerini, fare tabanlı in vitro ve ex vivo modeller kullanarak araştırmayı amaçlamıştır. In vitro çalışmalar, BALB/c fare dışkı inokulumu kullanılarak KOS, KS, INU ve KOS+KS ile INU+KS kombinasyonlarının etkilerini değerlendirmiştir. İyi bilinen bir prebiyotik olan INU, karşılaştırma amacıyla çalışmaya dahil edilmiştir. Sonuçlar, test edilen tüm prebiyotiklerin Bifidobacteria ve Lactobacillus popülasyonlarını önemli ölçüde artırırken, Enterococcus, Staphylococcus ve Clostridium sensu stricto popülasyonlarını çeşitli oranlarda azalttığını göstermiştir. Oligomerik KOS, özellikle Bifidobacteria ve Lactobacillus popülasyonlarını artırırken, polimerik KS daha çok Bacteroides türlerinin büyümesini desteklemiştir. Ex vivo modelde ise farelerin sekum, proksimal ve distal kolon bölümlerinde KS ve KOS'un lokalize etkileri incelenmiştir. Bulgular, her iki prebiyotiğin tüm bağırsak segmentlerinde metabolize edilerek kısa zincirli yağ asidi üretimine yol açtığını ve Bacteroides ile Bifidobacteria popülasyonlarını desteklediğini ortaya koymuştur. KS, tüm bağırsak bölümlerinde daha yüksek Bacteroides büyümesi ile ilişkilendirilmiş olup, sekumda yavaş fermantasyon göstererek prebiyotik aktivitenin distal kolona kadar uzanabileceğine işaret etmektedir. Bu bulgular, prebiyotiklerin bağırsak sağlığında potansiyel uygulamaları ile prebiyotik dinamiklerinin anlaşılmasına önemli katkılar sunmaktadır.Doctoral Thesis Physiologic Effects of the Golden Thistle (scolymus Hispanicus L.) Hydromethanolic Extracts: Outcomes of Phytochemical Health Benefits(01. Izmir Institute of Technology, 2022) Özel Taşcı, Cansu; Güleç, Şükrü; Büyükkileci, Ali Oğuz; Güleç, Şükrü; Büyükkileci, Ali OğuzThis dissertation aimed to screen the beneficial health effects of a hydromethanolic extract (GTE) obtained from the golden thistle (S. hispanicus L.) on different health conditions, including type 2 diabetes, inflammation, cancer, and wound healing. First, 1 mg/mL GTE resulted in 6.94% chlorogenic acid (CGA) bioavailability with (1.82±0.07)x10-6 cm/s apparent permeability on differentiated CaCo-2 cells. Then, 1 mg/mL GTE prompted 39.4-42.6% less glucose efflux and 49-66% less GLUT2 mRNA expressions on CaCo-2 cells. In the systemic inflammation model, pre-treatments of 50-500 μg/mL GTE reduced some inflammatory markers after 0.5 μg/mL lipopolysaccharide (LPS) inflammation induction for 12 h on RAW 264.7 cells. Reductions in 30-53%, 32-45% and 16-36% ranges for nitric oxide, tumor necrosis factor-α, and interleukin-6 (IL-6) were determined, respectively. Additionally, same GTE concentrations were pre-treated with the CaCo-2 cells in the colonic inflammation model. 15.5-19.5% and 8.7-17.3% less IL-6 and IL-8 cytokine releases were detected from CaCo-2 cells, respectively. The wound healing model of 3T3-L1 mouse fibroblasts revealed that 40-80 μg/mL root bark extract resulted in enhanced wound closures with significant differences in the cell cycle distributions. As the most significant result, G2 phase distributions were 1.8% and 12.5% in the negative and positive control samples, respectively. The root bark extract treatments of 10, 40, and 80 μg/mL resulted in 6.6%, 7.1%, and 9.1% in increasing concentrations. Finally, 4 mg/mL GTE application to CaCo-2 human adenocarcinoma cells caused 78.4% reduced cell viability, a cell cycle arrest, and increased early and late apoptotic properties. Overall results suggest that S. hispanicus L. has functional molecules that influence cellular regulations and have potential beneficial health effects.Doctoral Thesis Xylan Based Composite Nanoparticles and Biofoams for Drug Delivery and Tissue Engineering(01. Izmir Institute of Technology, 2022) Zeybek, Nüket; Büyükkileci, Ali OğuzXylan is a hemicellulosic polysaccharide, which can be obtained from forest and agricultural wastes. Similar to some other polysaccharides, xylan can find application in drug delivery and tissue engineering due to its availability, structural diversity, biocompatibility, biodegradability, and low cost. In the first part of the study, xylan-based nanoparticles were developed for colontargeted oral drug delivery. Xylan is resistant to digestion and absorption in the upper GIT and is degraded by hydrolysis of glycosidic bonds by the colon microbiota; this makes it prominent in targeted drug delivery to the colon. The drug carrier was combined with a polymeric micelles system to increase the bioavailability of hydrophobic bioactive molecules in the colon targeting. The model hydrophobic molecule, curcumin, was loaded in the core of the triblock copolymer P-123 micelles by the thin-film hydration method. Curcumin-loaded micelles were coated with xylan supported by chitosan and tripolyphosphate using the ionic gelation method. In another approach, xylan was also used to coat curcumin-loaded mesoporous silica nanoparticles to prevent premature drug release in the upper GIT in colon-targeted delivery. In both approaches, the drugcontaining structures were maintained up to the colon and the drug was released upon bacterial hydrolysis of xylan. In the second part, xylan-based biofoams were synthesized by the oil in water emulsion templated method. Several physicochemical and mechanical tests have shown that at the optimal conditions foams with promising properties could be synthesized. Besides, to develop a more effective tissue therapy by utilizing the synergistic effect of the drug delivery and scaffold system, a model drug was successfully loaded into biofoams. This study showed that xylan is a promising feedstock for the synthesis of stable and biocompatible materials in biomedical applications, which reveals its potential capability in drug carriers and scaffolds.Doctoral Thesis Prebiotic Oligosaccharide Production From Hazelnut Wastes(Izmir Institute of Technology, 2017) Sürek, Ece; Büyükkileci, Ali OğuzTurkey is the world leader in hazelnut production and a large amount of wastes is produced during its harvesting and processing. Obtaining valuable products from hazelnut by-products can add value to those. In this study, xylooligosaccharide (XOS), which has prebiotic potential and not manufactured in Turkey, was selected as the target product. Hazelnut wastes (shell, green leafy cover and pruning wastes) are suitable sources for production of XOS. Although there are some studies on valorization of hazelnut wastes, there is no study about XOS production. In this study, xylan in the shell was hydrolyzed to XOS by autohydrolysis and enzymatic hydrolysis at different conditions. The highest XOS yield was obtained as 62.93% after autohydrolysis at 190 oC for 5 min. The content of XOS with low degree of polymerization (DP<6) increased from 10.13 to 32.74% after hydrolysis with xylanase. XOS from enzymatic hydrolysis was purified by ultrafiltration through 10 and 2 kDa size membranes. The percent of low DP-XOS in liquor was increased after ultrafiltration; however monomers could not be separated. Prebiotic activity and stability of XOS were determined under different conditions. The growth of probiotic bacteria was observed after in vitro fermentation of XOS. XOS showed a good stability to food production and gastrointestinal digestion conditions. The objective of this study was to produce of a high value product such as XOS with prebiotic potential from hazelnut wastes by autohydrolysis and enzymatic hydrolysis. This study was highly original since XOS has been produced from hazelnut wastes for the first time.Doctoral Thesis Polysaccharide Based Packaging Film for Fresh Cut Produce(Izmir Institute of Technology, 2017) Şamlı, Merve; Harsa, Hayriye Şebnem; Büyükkileci, Ali OğuzIn this thesis, agro industrial wastes such as bracts and leaves of artichoke were used to develop biodegradable packaging materials for fresh-cut artichokes. As flim forming materials; cellulose, hemicellulose, lignin and wax fractions were extracted by using mild alkaline treatment applied to artichoke wastes. Carboxy methyl cellulose was chemically synthesized from extracted cellulose fiber. A mechanical process (Masuko Supermasscolloider, at-100 um grind size via 5 times feeding) with minimum environmental impact was selected to obtain cellulose micro fibrils with micro sized dimensions (50-200 um in length and 10-30 um in width).These fractions used as polysaccharide sources in film forming solutions. Different combinations of these polysaccharide based film materials were optimized using General Factorial Design and four film combinations were selected among the films produced.elected films were MFC and CMC based having good elasticity (16 % strain), tensile strength and low gas permeability properties (150mlO2/m2.day).Different concentrations of additives such as wax, stearic acid, chitosan were used with the glycerol addition of plasticizer. SEM analyses of selected films showed films showed films having smooth surface and dense structure by looking their cross sectional area. Thermal analyses proved sealabilitiy of films obtained by extracted fractions from artichoke at 200-250 oC temperature intervals. But, presence of MFC in films hindered the heat sealing ability. Therefore, MFC and CMC based films successfully showed optimal properties when they were combined with glycerol, stearic acid and wax.