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Citation - WoS: 59
Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells
(Springer, 2015) Cincin, Zeynep Birsu; Unlu, Miray; Kiran, Bayram; Bireller, Elif Sinem; Baran, Yusuf; Cakmakoglu, Bedia; Baran, Yusuf
Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-kappa B signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.
Citation - WoS: 8
Bioactive sphingolipids in docetaxel-induced apoptosis in human prostate cancer cells
(Elsevier France-editions Scientifiques Medicales Elsevier, 2012) Bassoy, Esen Yonca; Baran, Yusuf; Baran, Yusuf
In this study, we examined the possible roles of ceramide/sphingosine-1-phosphate and ceramide/glucosyleceramide signaling in docetaxel-induced apoptosis by examining expression levels of the glucosyleceramide synthase and sphingosine kinase-1 and ceramide synthase gene family. As confirmed by isobologram analysis, docetaxel in combination with agents that increase intracellular ceramide levels increased the cytotoxic and apoptotic effects of docetaxel synergistically. More importantly, RT-PCR results revealed that expression levels of glucosyleceramide synthase and sphingosine kinase-1 were downregulated and ceramide synthase genes were upregulated in response to docetaxel. This study identifies mechanisms underlying the involvement of ceramide metabolizing genes in docetaxel-induced apoptosis in prostate cancer cells. (c) 2012 Elsevier Masson SAS. All rights reserved.
Citation - WoS: 22
Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action
(Univ Edinburgh, Global Health Soc, 2017) Neergheen-Bhujun, Vidushi; Awan, Almas Taj; Baran, Yusuf; Bunnefeld, Nils; Chan, Kit; Edison Dela Cruz, Thomas; Kagansky, Alexander; Baran, Yusuf
[No Abstract Available]
Citation - WoS: 18
Citation - Scopus: 20
Cryopreservation of a cell-based biosensor chip modified with elastic polymer fibers enabling ready-to-use on-site applications
(Elsevier Advanced Technology, 2021) Ozsoylu, Dua; Isik, Tugba; Demir, Mustafa M.; Schoning, Michael J.; Wagner, Torsten; Demir, Mustafa
An efficient preservation of a cell-based biosensor chip to achieve a ready-to-use on-site system is still very challenging as the chip contains a living component such as adherent mammalian cells. Herein, we propose a strategy called on-sensor cryopreservation (OSC), which enables the adherent cells to be preserved by freezing (-80 degrees C) on a biosensor surface, such as the light-addressable potentiometric sensor (LAPS). Adherent cells on rigid surfaces are prone to cryo-injury; thus, the surface was modified to enhance the cell recovery for OSC. It relies on i) the integration of elastic electrospun fibers composed of polyethylene vinyl acetate (PEVA), which has a high thermal expansion coefficient and low glass-transition temperature, and ii) the treatment with O-2 plasma. The modified sensor is integrated into a microfluidic chip system not only to decrease the thermal mass, which is critical for fast thawing, but also to provide a precisely controlled micro-environment. This novel cryo-chip system is effective for keeping cells viable during OSC. As a proof-of-concept for the applicability of a ready-to-use format, the extracellular acidification of cancer cells (CHO-K1) was evaluated by differential LAPS measurements after thawing. Results show, for the first time, that the OSC strategy using the cryo-chip allows label-free and quantitative measurements directly after thawing, which eliminates additional post-thaw culturing steps. The freezing of the chips containing cells at the manufacturing stage and sending them via a cold-chain transport could open up a new possibility for a ready-to-use on-site system.
Citation - WoS: 35
Effect of Molecular Architecture on Cell Interactions and Stealth Properties of PEG
(Amer Chemical Soc, 2017) Ozer, Imran; Tomak, Aysel; Zareie, Hadi M.; Baran, Yusuf; Bulmus, Volga; Baran, Yusuf
PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which suboptimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. Here we demonstrate that comb-shape poly[oligo(ethylene glycol) methyl ether methacrylate](POEGMA); a stealth polymer alternative, has a more compact structure than PEG and self-organize into nanoparticles in a molecular weight dependent manner. Most notably, we show that comb shape POEGMA promotes significantly higher cellular uptake and exhibits less steric hindrance imposed on the conjugated biomolecule than PEG. Collectively, comb-shape POEGMA offers a versatile alternative to PEG for stealth polymer-biomolecule conjugation applications.
Citation - WoS: 10
Effects of cell-mediated osteoprotegerin gene transfer and mesenchymal stem cell applications on orthodontically induced root resorption of rat teeth
(Oxford Univ Press, 2017) Amuk, Nisa Gul; Kurt, Gokmen; Baran, Yusuf; Seyrantepe, Volkan; Yandim, Melis Kartal; Adan, Aysun; Sonmez, Mehmet Fatih; Baran, Yusuf
Aim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). Materials and methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100 g of orthodontic force was applied to upper first molar teeth of rats for 14 days. MSCs and transfected MSC injections were performed at 1st, 6th, and 11th days to the MSC and GT group rats. At the end of experiment, upper first molar teeth were prepared for genetical, scanning electron microscopy (SEM), fluorescent microscopy, and haematoxylin eosin-tartrate resistant acid phosphatase staining histological analyses. Number of total cells, number of osteoclastic cells, number of resorption lacunae, resorption area ratio, SEM resorption ratio, OPG, RANKL, Cox-2 gene expression levels at the periodontal ligament (PDL) were calculated. Paired t-test, Kruskal-Wallis, and chi-square tests were performed. Results: Transferred MSCs showed marked fluorescence in PDL. The results revealed that number of osteoclastic cells, resorption lacunae, resorption area ratio, RANKL, and Cox-2 were reduced after single MSC injections significantly (P < 0.05). GT group showed the lowest number of osteoclastic cells (P < 0.01), number of resorption lacunae, resorption area ratio, and highest OPG expression (P < 0.001). Conclusions: Taken together all these results, MSCs and GT showed marked inhibition and/or repair effects on OIIRR during orthodontic treatment on rats.
Citation - WoS: 63
Hierarchically Structured Metal Oxide/Silica Nanofibers by Colloid Electrospinning
(Amer Chemical Soc, 2012) Horzum, Nesrin; Munoz-Espi, Rafael; Glasser, Gunnar; Demir, Mustafa M.; Landfester, Katharina; Crespy, Daniel; Demir, Mustafa
We present herein a new concept for the preparation of nanofibrous metal oxides based on the simultaneous electrospinning of metal oxide precursors and silica nanoparticles. Precursor fibers are prepared by electrospinning silica nanoparticles (20 nm in diameter) dispersed in an aqueous solution of poly(acrylic acid) and metal salts. Upon calcination in air, the poly(acrylic acid) matrix is removed, the silica nanoparticles are cemented, and nanocrystalline metal oxide particles of 4-14 nm are nucleated at the surface of the silica nanoparticles. The obtained continuous silica fibers act as a structural framework for metal oxide nanoparticles and show improved mechanical integrity compared to the neat metal oxide fibers. The hierarchically nanostructured materials are promising for catalysis applications, as demonstrated by the successful degradation of a model dye in the presence of the fibers.
Citation - WoS: 17
Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model
(Springer, 2017) Isik, Sakine; Karaman, Meral; Adan, Aysun; Kiray, Muge; Bagriyanik, Husnu Alper; Sozmen, Sule Caglayan; Uzuner, Nevin
Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 x 10(6) BMSCs), group IV (sensitized and challenged with OVA and treated with 2 x 10(6) BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 x 10(6) BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.
Citation - WoS: 40
Investigation of Oxygen Permeation through Composites of PMMA and Surface-Modified ZnO Nanoparticles
(Wiley-v C H verlag Gmbh, 2009) Hess, Sandra; Demir, Mustafa M.; Yakutkin, Vladimir; Baluschev, Stanislav; Wegner, Gerhard; Demir, Mustafa
oxygen permeabilities of nanocomposite films consisting of poly(methyl methacrylate) (PMMA) and different amounts of spherical zinc oxide (ZnO) nanoparticles were determined to investigate the barrier effect of this material with respect to particle content. A method was applied which is based on quenching of an excited phosphorescent dye by oxygen. Possible effects of the nanoparticles on the response of the dye molecules were investigated and were ruled out.
Citation - WoS: 63
Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma
(Elsevier Science Bv, 2011) Firinci, Fatih; Karaman, Meral; Baran, Yusuf; Bagriyanik, Alper; Ayyildiz, Zeynep Arikan; Kiray, Muge; Karaman, Ozkan; Baran, Yusuf
Asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. Mesenchymal stem cells (MSCs) are promising for the development of novel therapies in regenerative medicine. This study aimed to examine the efficacy of MSCs on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: Group 1 (control group, n = 6), Group 2 (ovalbumin induced asthma only, n = 10), Group 3 (ovalbumin induced asthma + MSCs, n = 10), and Group 4 (MSCs only, n = 10). Histological findings (basement membrane, epithelium, subepithelial smooth muscle thickness, numbers of goblet and mast cells) of the airways and MSC migration were evaluated by light, electron, and confocal microscopes. In Group 3, all early histopathological changes except epithelial thickness and all of the chronic changes were significantly ameliorated when compared with Group 2. Evaluation with confocal microscopy showed that no noteworthy amount of MSCs were present in the lung tissues of Group 4 while significant amount of MSCs was detected in Group 3. Serum NO levels in Group 3, were significantly lower than Group 2. The results of this study revealed that MSCs migrated to lung tissue and ameliorated bronchial asthma in murine model. Further studies are needed to evaluate the efficacy of MSCs for the treatment of asthma. (C) 2011 Elsevier B.V. All rights reserved.
Citation - WoS: 13
The roles of macromolecules in imatinib resistance of chronic myeloid leukemia cells by Fourier transform infrared spectroscopy
(Elsevier France-editions Scientifiques Medicales Elsevier, 2013) Baran, Yusuf; Ceylan, Cagatay; Camgoz, Aylin; Baran, Yusuf
Imatinib is a first generation tyrosine kinase inhibitor, which is used for the treatment of chronic myeloid leukemia. However, resistance to imatinib is an important problem. Different mechanisms have been explained for imatinib resistance. In this study, we examined the roles of macromolecules in imatinib resistance in K562 cells at the molecular level using Fourier Transform Infrared (FT-IR) spectroscopy. An amount of 3 mu M imatinib resistant cells were generated by our group and named as K562/IMA-3 cells. Changes in macromolecules in parental and resistant cells were studied by FT-IR spectroscopy. Imatinib resistance caused changes, which indicated decreases in the level of glycogen and increases in the membrane order. The amount of unsaturated lipids increased in the imatinib resistant cells indicating lipid peroxidation. Imatinib resistance caused changes in the lipid/protein ratio. The relative protein content increased with respect to nucleic acids indicating higher transcription and protein expression and structural/organizational changes in the nucleus were evident as revealed by frequency changes in the nucleic acid bands. Changes in the amide bands revealed changes in the proteome of the resistant cells. Protein secondary structural changes indicated that the antiparallel beta sheet's structure increased, however the alpha helix structure, beta sheet structure, random coil structure and turns decreased in the resistant cells. These results indicate that the FT-IR technique provides a suitable method for analyzing drug resistance related structural changes in leukemia and other cancer types. (C) 2013 Elsevier Masson SAS. All rights reserved.
Citation - WoS: 68
Sorption Efficiency of Chitosan Nanofibers toward Metal Ions at Low Concentrations
(Amer Chemical Soc, 2010) Horzum, Nesrin; Boyaci, Ezel; Eroglu, Ahmet E.; Shahwan, Talal; Demir, Mustafa M.; Demir, Mustafa
Chitosan fibers showing narrow diameter distribution with a mean of 42 nm were produced by electrospinning and utilized for the sorption of Fe(III), Cu(II), Ag(I), and Cd(II) ions from aqueous solutions. The ion concentrations in the supernatant solutions were determined using inductively coupled plasma-mass spectrometry (ICP-MS). The filtration efficiency of the fibers toward these ions was studied by both batch and microcolumn methods. High efficiency in sorption of the metal ions was obtained in the both methods. The effects of sorbent amount (0.10-0.50 mg), shaking time (15-120 min), initial metal ion concentration (10.0-1000.0 mu g.L-1), and temperature (25 and 50 degrees C) on the extent of sorption were examined. The sorbent amount did not significantly alter the efficiency of sorption; however, shaking time, temperature, and metal ion concentration were found to have a strong influence on sorption. By virtue of its mechanical integrity, the applicability of the chitosan mat in solid phase extraction under continuous flow looks promising.
Citation - WoS: 12
STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells
(Elsevier France-editions Scientifiques Medicales Elsevier, 2013) Kiper, Hatice Demet; Kaymaz, Burcin Tezcanli; Gokbulut, Aysun Adan; Selvi, Nur; Avci, Cigir Biray; Kosova, Buket; Saydam, Guray
In this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. (C) 2013 Elsevier Masson SAS. All rights reserved.
Citation - WoS: 32
Therapeutic applications of bioactive sphingolipids in hematological malignancies
(Wiley, 2010) Ekiz, Huseyin Atakan; Baran, Yusuf; Baran, Yusuf
Sphingolipids are sphingosine-based lipid molecules that have important functions in cellular signal transduction and in a variety of cellular processes including proliferation, differentiation, programmed cell death (apoptosis) and responses to stressful conditions. Ceramides, dihydroceramide, sphingosine and sphingosine-1-phosphate are examples of those bioactive sphingolipids. They have a major impact on determination of the cell fate by contributing to the cell survival or cell death through apoptosis. Despite the number of carbon atoms in the fatty acid chain changes the physiological role; ceramides generally exert suppressive roles on the cell proliferation. There have been several enzymes identified in this pathway that are responsible for the conversion of ceramide into other sphingolipid derivatives. Those,derivatives also have differential roles on those cellular process. Sphingosine-1-phosphate is an example of such sphingolipid derivatives which has antiapoptotic effects. As they have significant impacts particularly on the cell death and survival, bioactive sphingolipids have a great potential to be targets in cancer therapy. Increasing number of studies indicates that sphingolipid derivatives are important in the progression of hematological malignancies, and they are also involved in the resistance to current chemotherapeutic options. This review compiles the current knowledge in this area for enlightening the therapeutic potentials of bioactive sphingolipids in various leukemias.
Citation - WoS: 70
Toward Transparent Nanocomposites Based on Polystyrene Matrix and PMMA-Grafted CeO₂ Nanoparticles
(Amer Chemical Soc, 2011) Parlak, Onur; Demir, Mustafa M.; Demir, Mustafa
The association of transparent polymer and nanosized pigment particles offers attractive optical materials for various potential and existing applications. However, the particles embedded into polymers scatter light due to refractive index (RI) mismatch and reduce transparency of the resulting composite material. In this study, optical composites based on polystyrene (PS) matrix and poly(methyl methacrylate) (PMMA)-grafted CeO2 hybrid particles were prepared. CeO2 nanoparticles with an average diameter of 18 +/- 8 nm were precipitated by treating Ce(NO3)center dot 6H(2)O with urea in the presence of a polymerizable surfactant, 3-methacyloxypropyltrimethoxy silane. PMMA chains were grafted on the surface of the nanoparticles upon free radical in situ solution polymerization. While blending of unmodified CeO2 particles with PS resulted in opaque films, the transparency of the composite films was remarkably enhanced when prepared by PMMA-grafted CeO2 hybrid particles, particularly those having a PMMA thickness of 9 nm. The improvement in transparency is presumably due to the reduction in RI mismatch between CeO2 particles and the PS matrix when using PMMA chains at the interface.

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