Browsing by Author "Kilic, E."

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Open Access
A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold
(Royal Society of Chemistry, 2016) Tansik, G.; Kilic, E.; Beter, M.; Demiralp, B.; K.Sendur, G.; Can, N.; Ozkan, H.; Ergul, E.; Güler, Mustafa O.; Tekinay, A. B.
Biomineralization of the extracellular matrix (ECM) plays a crucial role in bone formation. Functional and structural biomimetic native bone ECM components can therefore be used to change the fate of stem cells and induce bone regeneration and mineralization. Glycosaminoglycan (GAG) mimetic peptide nanofibers can interact with several growth factors. These nanostructures are capable of enhancing the osteogenic activity and mineral deposition of osteoblastic cells, which is indicative of their potential application in bone tissue regeneration. In this study, we investigated the potential of GAG-mimetic peptide nanofibers to promote the osteogenic differentiation of rat mesenchymal stem cells (rMSCs) in vitro and enhance the bone regeneration and biomineralization process in vivo in a rabbit tibial bone defect model. Alkaline phosphatase (ALP) activity and Alizarin red staining results suggested that osteogenic differentiation is enhanced when rMSCs are cultured on GAG-mimetic peptide nanofibers. Moreover, osteogenic marker genes were shown to be upregulated in the presence of the peptide nanofiber system. Histological and micro-computed tomography (Micro-CT) observations of regenerated bone defects in rabbit tibia bone also suggested that the injection of a GAG-mimetic nanofiber gel supports cortical bone deposition by enhancing the secretion of an inorganic mineral matrix. The volume of the repaired cortical bone was higher in GAG-PA gel injected animals. The overall results indicate that GAG-mimetic peptide nanofibers can be utilized effectively as a new bioactive platform for bone regeneration. © 2016 The Royal Society of Chemistry.
Open Access
Supramolecular GAG-like self-assembled glycopeptide nanofibers Induce chondrogenesis and cartilage regeneration
(American Chemical Society, 2016) Yaylaci, U. S.; Ekiz, M. S.; Arslan, E.; Can, N.; Kilic, E.; Ozkan, H.; Orujalipoor, I.; Ide, S.; Tekinay, A. B.; Güler, Mustafa O.
Glycosaminoglycans (GAGs) and glycoproteins are vital components of the extracellular matrix, directing cell proliferation, differentiation, and migration and tissue homeostasis. Here, we demonstrate supramolecular GAG-like glycopeptide nanofibers mimicking bioactive functions of natural hyaluronic acid molecules. Self-assembly of the glycopeptide amphiphile molecules enable organization of glucose residues in close proximity on a nanoscale structure forming a supramolecular GAG-like system. Our in vitro culture results indicated that the glycopeptide nanofibers are recognized through CD44 receptors, and promote chondrogenic differentiation of mesenchymal stem cells. We analyzed the bioactivity of GAG-like glycopeptide nanofibers in chondrogenic differentiation and injury models because hyaluronic acid is a major component of articular cartilage. Capacity of glycopeptide nanofibers on in vivo cartilage regeneration was demonstrated in microfracture treated osteochondral defect healing. The glycopeptide nanofibers act as a cell-instructive synthetic counterpart of hyaluronic acid, and they can be used in stem cell-based cartilage regeneration therapies.
Open Access
The cancer genome explorer (TCGEx): a powerful visual interface for sophisticated analyses of high throughput cancer data
(John Wiley & Sons Ltd., 2024-06-26) Kus, M. E; Sahin, C.; Kilic, E.; Askin, A.; Özgür, Mustafa M.; Karahanogullari, G.; Aksit, A.; O'Connell, R.; Ekiz, H. A.
Analyzing high-throughput genomics data requires programming expertise, and it remains challenging for many experimental researchers. While visual interfaces have eased access to this data, their limited flexibility in accommodating complex custom analyses remains a significant hurdle. To address these shortcomings, we have developed The Cancer Genome Explorer (TCGEx), a web-based R/Shiny application that can work with preprocessed The Cancer Genome Atlas (TCGA) transcriptomics data and user-provided external datasets. TCGEx serves as a centralized hub, offering a diverse array of analytical tools including survival modeling, exploratory graphing, gene set enrichment, gene-to-gene correlation, dimensionality reduction, and machine learning. Our utilization of TCGEx in investigating gene expression profiles within human primary and metastatic melanoma revealed distinctive tumor subsets characterized by unique immune signatures and survival outcomes. Delving deeper, we explored miRNA networks associated with intratumoral immunity, harnessing TCGEx's machine learning algorithms. Aligning with existing literature, our study highlighted miR-155 as among the prominently upregulated miRNAs in immune-enriched melanoma biopsies. Intriguingly, heightened miR-155 levels correlated with transcriptomic enrichment in lipid catabolism pathways and depletion in ribonucleoside catabolism pathways. Expanding our inquiry to previously published datasets from melanoma immunotherapy trials, we discerned transcriptomic patterns linked to therapeutic benefits. While our study predominantly focused on immune-associated noncoding RNAs within the melanoma tumor microenvironment, TCGEx extends its capabilities to investigate 32 other TCGA cancer projects as well as user-uploaded external datasets. In essence, TCGEx emerges as a powerful and adaptable platform facilitating the analysis of high-throughput cancer data.