Browsing by Subject "Nonhuman"
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Item Open Access 15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1(Elsevier, 2017-11) Tunçer, S.; Keşküş, A. G.; Çolakoğlu, M.; Çimen, I.; Yener, C.; Konu, Ö.; Banerjee, S.15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions. Conditioned medium (CM) was obtained from CRC or prostate cancer cell lines re-expressing 15-LOX-1 (15-LOX-1CM). 15-LOX-1CM treated aortic rings from 6-week old C57BL/6 mice showed significantly less vessel sprouting and more organized structure of vascular network. Human umbilical vein endothelial cells (HUVECs) incubated with 15-LOX-1CM showed reduced motility, enhanced expression of intercellular cell adhesion molecule (ICAM-1) and reduced tube formation but no change in proliferation or cell-cycle distribution. HUVECs incubated with 13(S)-HODE partially phenocopied the effects of 15-LOX-1CM, i.e., showed reduced motility and enhanced expression of ICAM-1, but did not reduce tube formation, implying the importance of additional factors. Therefore, a Proteome Profiler Angiogenesis Array was carried out, which showed that Thrombospondin-1 (TSP-1), a matrix glycoprotein known to strongly inhibit neovascularization, was expressed significantly more in HUVECs incubated with 15-LOX-1CM. TSP-1 blockage in HUVECs reduced the expression of ICAM-1 and enhanced cell motility, thereby providing a mechanism for reduced angiogenesis. The anti-angiogenic effects of 15-LOX-1 through enhanced expressions of ICAM-1 and TSP-1 are novel findings and should be explored further to develop therapeutic options.Item Open Access Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio)(Elsevier, 2017-06) Karoglu, Elif Tugce; Halim, Dilara Ozge; Erkaya, Bahriye; Altaytas, Ferda; Arslan-Ergul, Ayca; Konu, Ozlen; Adams, Michelle M.The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.Item Open Access Angiogenic heparin-mimetic peptide nanofiber gel improves regenerative healing of acute wounds(American Chemical Society, 2017) Uzunalli, G.; Mammadov R.; Yesildal, F.; Alhan, D.; Ozturk, S.; Ozgurtas, T.; Güler, Mustafa O.; Tekinay, A. B.Wound repair in adult mammals typically ends with the formation of a scar, which prevents full restoration of the function of the healthy tissue, although most of the wounded skin heals. Rapid and functional recovery of major wound injuries requires therapeutic approaches that can enhance the healing process via overcoming mechanical and biochemical problems. In this study, we showed that self-assembled heparin-mimetic peptide nanofiber gel was an effective bioactive wound dressing for the rapid and functional repair of full-thickness excisional wounds in the rat model. The bioactive gel-treated wounds exhibited increased angiogenesis (p < 0.05), re-epithelization (p < 0.05), skin appendage formation, and granulation tissue organization (p < 0.05) compared to sucrose-treated samples. Increased blood vessel numbers in the gel-treated wounds on day 7 suggest that angiogenesis played a key role in improvement of tissue healing in bioactive gel-treated wounds. Overall, the angiogenic heparin-mimetic peptide nanofiber gel is a promising platform for enhancing the scar-free recovery of acute wounds.Item Open Access Angiogenic peptide nanofibers improve wound healing in STZ-induced diabetic rats(American Chemical Society, 2016-06) Senturk, B.; Mercan, S.; Delibasi, T.; Güler, Mustafa O.; Tekinay, A. B.Low expressions of angiogenic growth factors delay the healing of diabetic wounds by interfering with the process of blood vessel formation. Heparin mimetic peptide nanofibers can bind to and enhance production and activity of major angiogenic growth factors, including VEGF. In this study, we showed that heparin mimetic peptide nanofibers can serve as angiogenic scaffolds that allow slow release of growth factors and protect them from degradation, providing a new therapeutic way to accelerate healing of diabetic wounds. We treated wounds in STZ-induced diabetic rats with heparin mimetic peptide nanofibers and studied repair of full-thickness diabetic skin wounds. Wound recovery was quantified by analyses of re-epithelialization, granulation tissue formation and blood vessel density, as well as VEGF and inflammatory response measurements. Wound closure and granulation tissue formation were found to be significantly accelerated in heparin mimetic gel treated groups. In addition, blood vessel counts and the expressions of alpha smooth muscle actin and VEGF were significantly higher in bioactive gel treated animals. These results strongly suggest that angiogenic heparin mimetic nanofiber therapy can be used to support the impaired healing process in diabetic wounds.Item Open Access Angiogenic peptide nanofibers repair cardiac tissue defect after myocardial infarction(Acta Materialia Inc, 2017) Rufaihah, A. J.; Yasa, I. C.; Ramanujam, V. S.; Arularasu, S. C.; Kofidis, T.; Güler, Mustafa O.; Tekinay, A. B.Myocardial infarction remains one of the top leading causes of death in the world and the damage sustained in the heart eventually develops into heart failure. Limited conventional treatment options due to the inability of the myocardium to regenerate after injury and shortage of organ donors require the development of alternative therapies to repair the damaged myocardium. Current efforts in repairing damage after myocardial infarction concentrates on using biologically derived molecules such as growth factors or stem cells, which carry risks of serious side effects including the formation of teratomas. Here, we demonstrate that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization in cardiovascular tissue after myocardial infarction, without the addition of any biologically derived factors or stem cells. When the GAG mimetic nanofiber gels were injected in the infarct site of rodent myocardial infarct model, increased VEGF-A expression and recruitment of vascular cells was observed. This was accompanied with significant degree of neovascularization and better cardiac performance when compared to the control saline group. The results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair. Statement of Significance We present a synthetic bioactive peptide nanofiber system can enhance cardiac function and enhance cardiovascular regeneration after myocardial infarction (MI) without the addition of growth factors, stem cells or other biologically derived molecules. Current state of the art in cardiac repair after MI utilize at least one of the above mentioned biologically derived molecules, thus our approach is ground-breaking for cardiovascular therapy after MI. In this work, we showed that synthetic glycosaminoglycan (GAG) mimetic peptide nanofiber scaffolds induce neovascularization and cardiomyocyte differentiation for the regeneration of cardiovascular tissue after myocardial infarction in a rat infarct model. When the peptide nanofiber gels were injected in infarct site at rodent myocardial infarct model, recruitment of vascular cells was observed, neovascularization was significantly induced and cardiac performance was improved. These results demonstrate the potential of future clinical applications of these bioactive peptide nanofibers as a promising strategy for cardiovascular repair.Item Open Access Antibacterial electrospun nanofibers from triclosan/cyclodextrin inclusion complexes(Elsevier, 2014) Celebioglu A.; Umu, O. C. O.; Tekinay, T.; Uyar, TamerThe electrospinning of nanofibers (NF) from cyclodextrin inclusion complexes (CD-IC) with an antibacterial agent (triclosan) was achieved without using any carrier polymeric matrix. Polymer-free triclosan/CD-IC NF were electrospun from highly concentrated (160% CD, w/w) aqueous triclosan/CD-IC suspension by using two types of chemically modified CD; hydroxypropyl-beta-cyclodextrin (HPβCD) and hydroxypropyl-gamma-cyclodextrin (HPγCD). The morphological characterization of the electrospun triclosan/CD-IC NF by SEM elucidated that the triclosan/HPβCD-IC NF and triclosan/HPγCD-IC NF were bead-free having average fiber diameter of 520±250nm and 1100±660nm, respectively. The presence of triclosan and the formation of triclosan/CD-IC within the fiber structure were confirmed by 1H-NMR, FTIR, XRD, DSC, and TGA studies. The initial 1:1molar ratio of the triclosan:CD was kept for triclosan/HPβCD-IC NF after the electrospinning and whereas 0.7:1molar ratio was observed for triclosan/HPγCD-IC NF and some uncomplexed triclosan was detected suggesting that the complexation efficiency of triclosan with HPγCD was lower than that of HPβCD. The antibacterial properties of triclosan/CD-IC NF were tested against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. It was observed that triclosan/HPβCD-IC NF and triclosan/HPγCD-IC NF showed better antibacterial activity against both bacteria compared to uncomplexed pure triclosan.Item Open Access Antibacterial electrospun zein nanofibrous web encapsulating thymol/cyclodextrin-inclusion complex for food packaging(Elsevier, 2017-10) Aytac Z.; Ipek, S.; Durgun, Engin; Tekinay, T.; Uyar, TamerThymol (THY)/γ-Cyclodextrin(γ-CD) inclusion complex (IC) encapsulated electrospun zein nanofibrous webs (zein-THY/γ-CD-IC-NF) were fabricated as a food packaging material. The formation of THY/γ-CD-IC (1:1 and 2:1) was proved by experimental (X-ray diffraction (XRD), thermal gravimetric analysis (TGA), 1H NMR) and computational techniques. THY/γ-CD-IC (2:1) exhibited higher preservation rate and stability than THY/γ-CD-IC (1:1). It is worth mentioning that zein-THY/γ-CD-IC-NF (2:1) preserved much more THY as observed in TGA and stability of THY/γ-CD-IC (2:1) was higher, as shown by a modelling study. Therefore, much more THY was released from zein-THY/γ-CD-IC-NF (2:1) than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). Similarly, antibacterial activity of zein-THY/γ-CD-IC-NF (2:1) was higher than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). It was demonstrated that zein-THY/γ-CD-IC-NF (2:1) was most effective in inhibiting the growth of bacteria on meat samples. These webs show potential application as an antibacterial food packaging material.Item Open Access Bacteria encapsulated electrospun nanofibrous webs for remediation of methylene blue dye in water(Elsevier, 2017-04) Sarioglu O.F.; Keskin, N. O. S.; Celebioglu A.; Tekinay, T.; Uyar, TamerIn this study, preparation and application of novel biocomposite materials that were produced by encapsulation of bacterial cells within electrospun nanofibrous webs are described. A commercial strain of Pseudomonas aeruginosa which has methylene blue (MB) dye remediation capability was selected for encapsulation, and polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were selected as the polymer matrices for the electrospinning of bacteria encapsulated nanofibrous webs. Encapsulation of bacterial cells was monitored by scanning electron microscopy (SEM) and fluorescence microscopy, and the viability of encapsulated bacteria was checked by live/dead staining and viable cell counting assay. Both bacteria/PVA and bacteria/PEO webs have shown a great potential for remediation of MB, yet bacteria/PEO web has shown higher removal performances than bacteria/PVA web, which was probably due to the differences in the initial viable bacterial cells for those two samples. The bacteria encapsulated electrospun nanofibrous webs were stored at 4 °C for three months and they were found as potentially storable for keeping encapsulated bacterial cells alive. Overall, the results suggest that electrospun nanofibrous webs are suitable platforms for preservation of living bacterial cells and they can be used directly as a starting inoculum for bioremediation of water systems.Item Open Access Bacteria immobilized electrospun polycaprolactone and polylactic acid fibrous webs for remediation of textile dyes in water(Elsevier, 2017-10) Sarioglu O.F.; S. Keskin, N. O.; Celebioglu A.; Tekinay, T.; Uyar, TamerIn this study, preparation and application of novel biocomposite materials for textile dye removal which are produced by immobilization of specific bacteria onto electrospun nanofibrous webs are presented. A textile dye remediating bacterial isolate, Clavibacter michiganensis, was selected for bacterial immobilization, a commercial reactive textile dye, Setazol Blue BRF-X, was selected as the target contaminant, and electrospun polycaprolactone (PCL) and polylactic acid (PLA) nanofibrous polymeric webs were selected for bacterial integration. Bacterial adhesion onto nanofibrous webs was monitored by scanning electron microscopy (SEM) imaging and optical density (OD) measurements were performed for the detached bacteria. After achieving sufficient amounts of immobilized bacteria on electrospun nanofibrous webs, equivalent web samples were utilized for testing the dye removal capabilities. Both bacteria/PCL and bacteria/PLA webs have shown efficient remediation of Setazol Blue BRF-X dye within 48 h at each tested concentration (50, 100 and 200 mg/L), and their removal performances were very similar to the free-bacteria cells. The bacteria immobilized webs were then tested for five times of reuse at an initial dye concentration of 100 mg/L, and found as potentially reusable with higher bacterial immobilization and faster dye removal capacities at the end of the test. Overall, these findings suggest that electrospun nanofibrous webs are available platforms for bacterial integration and the bacteria immobilized webs can be used as starting inocula for use in remediation of textile dyes in wastewater systems.Item Open Access Biocompatibility studies on lanthanum oxide nanoparticles(Royal Society of Chemistry, 2015) Brabu, B.; Haribabu, S.; Revathy, M.; Anitha, S.; Thangapandiyan, M.; Navaneethakrishnan, K. R.; Gopalakrishnan, C.; Murugan, S. S.; Kumaravel, T. S.Lanthanum oxide nanoparticles (LONP), a rare earth metal oxide, have unique properties that make them a suitable candidate for several biomedical applications. We investigated certain key in vitro and in vivo biocompatibility endpoints on LONP. LONP were cytotoxic in in vitro assays and predominantly exerted their action via release of reactive oxygen species. These nanoparticles were neither irritants nor sensitizers in a rabbit model. LONP extracts did not exert any acute systemic toxicity effects in mice. On the other hand LONP exerted toxicity to the liver following oral administration, suggesting that these particles are absorbed from the gastrointestinal (GI) tract and deposited in the hepatobiliary system. LONP did not induce any mutation in the Ames test both in the presence or absence of S-9. These observations provide a base line biocompatibility and toxicity data on LONP. The current findings will also be useful in defining standards for nanoparticle containing devices. © The Royal Society of Chemistry.Item Open Access Biological properties of extracellular vesicles and their physiological functions(Taylor & Francis, 2015) Yáñez-Mó, M.; Siljander, P. R. M.; Andreu, Z.; Zavec, A. B.; Borràs, F. E.; Buzas, E. I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; Colás, E.; Cordeiro-Da, S. A.; Fais, S.; Falcon-Perez, J. M.; Ghobrial, I. M.; Giebel, B.; Gimona, M.; Graner, M.; Gursel, I.; Gursel, M.; Heegaard, N. H. H.; Hendrix, A.; Kierulf, P.; Kokubun, K.; Kosanovic, M.; Kralj-Iglic, V.; Krämer-Albers, E. M.; Laitinen, S.; Lässer, C.; Lener, T.; Ligeti, E.; Line, A.; Lipps, G.; Llorente, A.; Lötvall, J.; Manček-Keber, M.; Marcilla, A.; Mittelbrunn, M.; Nazarenko, I.; Nolte-'t Hoen, E. N. M.; Nyman, T. A.; O'Driscoll, L.; Olivan, M.; Oliveira, C.; Pállinger, E.; Del Portillo, H. A.; Reventós, J.; Rigau, M.; Rohde, E.; Sammar, M.; Sánchez-Madrid, F.; Santarém, N.; Schallmoser, K.; Ostenfeld, M. S.; Stoorvogel, W.; Stukelj, R.; Grein V. D. S.G.; Helena,ü V. M.; Wauben, M. H. M.; De Wever, O.In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells.While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.Item Open Access Biosystems engineering of prokaryotes with tumor-killing capacities(Bentham Science Publishers Ltd., 2016) Kalyoncu, E.; Olmez, T. T.; Ozkan, A. D.; Sarioglu, O. F.Certain bacteria selectively attack tumor tissues and trigger tumor shrinkage by producing toxins and modulating the local immune system, but their clinical utility is limited because of the dangers posed by systemic infection. Genetic engineering can be used to minimize the risks associated with tumor-targeting pathogens, as well as to increase their efficiency in killing tumor cells. Advances in genetic circuit design have led to the development of bacterial strains with enhanced tumor-targeting capacities and the ability to secrete therapeutics, cytotoxic proteins and prodrug-cleaving enzymes, which allows their safe and effective use for cancer treatment. The present review details the recent advances in the design and application of these modified bacterial strains.Item Open Access Characterization of a novel zebrafish (Danio rerio) gene, wdr81, associated with cerebellar ataxia, mental retardation and dysequilibrium syndrome (CAMRQ)(BioMed Central Ltd., 2015) Doldur-Balli, F.; Ozel, M. N.; Gulsuner, S.; Tekinay, A. B.; Ozcelik, T.; Konu, O.; Adams, M. M.Background: WDR81 (WD repeat-containing protein 81) is associated with cerebellar ataxia, mental retardation and disequilibrium syndrome (CAMRQ2, [MIM 610185]). Human and mouse studies suggest that it might be a gene of importance during neurodevelopment. This study aimed at fully characterizing the structure of the wdr81 transcript, detecting the possible transcript variants and revealing its expression profile in zebrafish, a powerful model organism for studying development and disease. Results: As expected in human and mouse orthologous proteins, zebrafish wdr81 is predicted to possess a BEACH (Beige and Chediak-Higashi) domain, a major facilitator superfamily domain and WD40-repeats, which indicates a conserved function in these species. We observed that zebrafish wdr81 encodes one open reading frame while the transcript has one 5' untranslated region (UTR) and the prediction of the 3' UTR was mainly confirmed along with a detected insertion site in the embryo and adult brain. This insertion site was also found in testis, heart, liver, eye, tail and muscle, however, there was no amplicon in kidney, intestine and gills, which might be the result of possible alternative polyadenylation processes among tissues. The 5 and 18 hpf were critical timepoints of development regarding wdr81 expression. Furthermore, the signal of the RNA probe was stronger in the eye and brain at 18 and 48 hpf, then decreased at 72 hpf. Finally, expression of wdr81 was detected in the adult brain and eye tissues, including but not restricted to photoreceptors of the retina, presumptive Purkinje cells and some neurogenic brains regions. Conclusions: Taken together these data emphasize the importance of this gene during neurodevelopment and a possible role for neuronal proliferation. Our data provide a basis for further studies to fully understand the function of wdr81.Item Open Access Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement(John Wiley & Sons, Inc., 2008) Kenar, H.; Kocabas, A.; Aydınlı, Atilla; Hasirci, V.Proper cell attachment and distribution, and thus stronger association in vivo between a bone implant and native tissue will improve the success of the implant. In this study, the aim was to achieve promotion of attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing chemical and topographical cues on poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) film surfaces. As the chemical cues, either alkaline phosphatase was covalently immobilized on the film surface to induce deposition of calcium phosphate minerals or fibrinogen was adsorbed to improve cell adhesion. Microgrooves and micropits were introduced on the film surface by negative replication of micropatterned Si wafers. Both chemical cues improved cell attachment and even distribution on the PHBV films, but Fb was more effective especially when combined with the micropatterns. Cell alignment (<10° deviation angle) parallel to chemically modified microgrooves (1, 3, or 8 μm groove width) and on 10 μm-thick Fb lines printed on the unpatterned films was achieved. The cells on unpatterned and 5 μm-deep micropitted films were distributed and oriented randomly. Results of this study proved that microtopographies on PHBV can improve osseointegration when combined with chemical cues, and that microgrooves and cell adhesive protein lines on PHBV can guide selective osteoblast adhesion and alignment.Item Open Access Chondrogenic differentiation of mesenchymal stem cells on glycosaminoglycan-mimetic peptide nanofibers(American Chemical Society, 2016) Yaylaci, S .U.; Sen, M.; Bulut, O.; Arslan, E.; Güler, Mustafa O.; Tekinay, A. B.Glycosaminoglycans (GAGs) are important extracellular matrix components of cartilage tissue and provide biological signals to stem cells and chondrocytes for development and functional regeneration of cartilage. Among their many functions, particularly sulfated glycosaminoglycans bind to growth factors and enhance their functionality through enabling growth factor-receptor interactions. Growth factor binding ability of the native sulfated glycosaminoglycans can be incorporated into the synthetic scaffold matrix through functionalization with specific chemical moieties. In this study, we used peptide amphiphile nanofibers functionalized with the chemical groups of native glycosaminoglycan molecules such as sulfonate, carboxylate and hydroxyl to induce the chondrogenic differentiation of rat mesenchymal stem cells (MSCs). The MSCs cultured on GAG-mimetic peptide nanofibers formed cartilage-like nodules and deposited cartilage-specific matrix components by day 7, suggesting that the GAG-mimetic peptide nanofibers effectively facilitated their commitment into the chondrogenic lineage. Interestingly, the chondrogenic differentiation degree was manipulated with the sulfonation degree of the nanofiber system. The GAG-mimetic peptide nanofibers network presented here serve as a tailorable bioactive and bioinductive platform for stem-cell-based cartilage regeneration studies.Item Open Access Cornea engineering on polyester carriers(John Wiley & Sons, Inc., 2006) Zorlutuna, P.; Tezcaner, A.; Kiyat, I.; Aydınlı, Atilla; Hasirci, V.In this study, biodegradable polyester based carriers were designed for tissue engineering of the epithelial and the stromal layers of the cornea, and the final construct was tested in vitro. In the construction of the epithelial layer, micropatterned films were prepared from blends of biodegradable and biocompatible polyesters of natural (PHBV) and synthetic (P(L/DL)LA) origin, and these films were seeded with D407 (retinal pigment epithelial) cells. To improve cell adhesion and growth, the films were coated with fibronectin. To serve as the stromal layer of the cornea, highly porous foams of P(L/DL)LA-PHBV blends were seeded with 3T3 fibroblasts. Cell numbers on the polyester carriers were significantly higher than those on the tissue culture polystyrene control. The cells and the carriers were characterized scanning electron micrographs showed that the foam was highly porous and the pores were interconnected. 3T3 Fibroblasts were distributed quite homogeneously at the seeding site, but probably because of the high thickness of the carrier (∼6 mm); they could not sufficiently populate the core (central parts of the foam) during the test duration. The D407 cells formed multilayers on the micropatterned polyester film. Immunohistochemical studies showed that the cells retained their phenotype during culturing; D407 cells formed tight junctions characteristic of epithelial cells, and 3T3 cells deposited collagen type I into the foams. On the basis of these results, we concluded that the micropatterned films and the foams made of P(L/DL)LA-PHBV blends have a serious potential as tissue engineering carriers for the reconstruction of the epithelial and stromal layers of the cornea.Item Open Access Cytotoxic activity of resveratrol in different cell lines evaluated by MTT and NRU assays(Turkish Pharmacists Association, 2016) Anlar, H. G.; Bacanli, M.; Kutluk, B.; Başaran, A. A.; Başaran, N.Oxidative stress is the state of imbalance between the level of antioxidant defence system and production of reactive oxygen species (ROS) and is involded in the progression of several diseases such as inflammation, cancer, neurodegenerative disorders and cardiovascular diseases. It is suggested that plant polyphenols may act as antioxidants and therefore it has anti-cancer activities. Resveratrol (RV), is a naturally occuring polyphenolic compound which is found in many plant species including grapes, nuts, blueberries and raspberries. Data indicated that it has anti-oxidant, anti-inflamatory and anti-cancer activities. But there are also some studies reported that RV has not protective effects aganist cancer. In this study, the cytotoxicity of RV in human breast adenocarcinoma (MDA-MB 231), human cervical cancer (HeLa) and Chinese hamster lung fibroblast (V79) cells were evaluated by Neutral Red uptake assay (NRU) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays after incubation at 24 h. We obtained more or the less same results by two cytotoxicity assays. In the concentrations between 2-400 μM, RV seemed not to induce a pronounced cytotoxicity in all cell types. Even at highest concentrations, it showed almost no cytotoxic effects. So the IC50 values were not calculated at the studied concentrations.Item Open Access Cytotoxic and bioactive properties of different color tulip flowers and degradation kinetic of tulip flower anthocyanins(Pergamon Press, 2013) Sagdic, O.; Ekici, L.; Ozturk, I.; Tekinay, T.; Polat, B.; Tastemur, B.; Bayram, O.; Senturk, B.This study was conducted to determine the potential use of anthocyanin-based extracts (ABEs) of wasted tulip flowers as food/drug colorants. For this aim, wasted tulip flowers were samples and analyzed for their bioactive properties and cytotoxicity. Total phenolic contents of the extracts of the claret red (126.55. mg of gallic acid equivalent (GAE)/g dry extract) and orange-red (113.76. mg GAE/g dry extract) flowers were the higher than those of the other tulip flowers. Total anthocyanin levels of the violet, orange-red, claret red and pink tulip flower extracts were determined as 265.04, 236.49, 839.08 and 404.45. mg pelargonidin 3-glucoside/kg dry extract, respectively and these levels were higher than those of the other flowers. The extracts were more effective for the inhibition of Listeria monocytogenes, Staphylococcus aureus and Yersinia enterocolitica compared to other tested bacteria. Additionally, the cytotoxic effects of five different tulip flower extracts on human breast adenocarcinoma (MCF-7) cell line were investigated. The results showed that the orange red, pink and violet extracts had no cytotoxic activity against MCF-7 cell lines while yellow and claret red extracts appeared to be toxic for the cells. Overall, the extracts of tulip flowers with different colors possess remarkable bioactive and cytotoxic properties. © 2013 Elsevier Ltd.Item Open Access Demographically-based evaluation of genomic regions under selection in domestic dogs(Public Library of Science, 2016) Freedman, A. H.; Schweizer, R. M.; Vecchyo, D. Ortega-Del; Han, E.; Davis, B. W.; Gronau, I.; Silva, P. M.; Galaverni, M.; Fan, Z.; Marx, P.; Lorente-Galdos, B.; Ramirez, O.; Hormozdiari, F.; Alkan C.; Vilà, C.; Squire K.; Geffen, E.; Kusak, J.; Boyko, A. R.; Parker, H. G.; Lee C.; Tadigotla, V.; Siepel, A.; Bustamante, C. D.; Harkins, T. T.; Nelson, S. F.; Marques Bonet, T.; Ostrander, E. A.; Wayne, R. K.; Novembre, J.Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. © 2016, Public Library of Science. All Rights Reserved.Item Open Access Design of a novel MRI compatible manipulator for image guided prostate interventions(IEEE, 2005-02) Krieger, A.; Susil, R. C.; Ménard, C.; Coleman, J. A.; Fichtinger, G.; Atalar, Ergin; Whitcomb, L. L.This paper reports a novel remotely actuated manipulator for access to prostate tissue under magnetic resonance imaging guidance (APT-MRI) device, designed for use in a standard high-field MRI scanner. The device provides three-dimensional MRI guided needle placement with millimeter accuracy under physician control. Procedures enabled by this device include MRI guided needle biopsy, fiducial marker placements, and therapy delivery. Its compact size allows for use in both standard cylindrical and open configuration MRI scanners. Preliminary in vivo canine experiments and first clinical trials are reported.