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) Büyükkileci, Ali Oğuz; Güleç, Şükrü; Büyükkileci, Ali Oğuz; Güleç, Şükrü; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyKsilan (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) Güleç, Şükrü; Büyükkileci, Ali Oğuz; Büyükkileci, Ali Oğuz; Güleç, Şükrü; Büyükkileci, Ali Oğuz; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyThis 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) Büyükkileci, Ali Oğuz; Büyükkileci, Ali Oğuz; 03.08. Department of Food Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyXylan 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.