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Öğe A 3D in vitro co-culture model for evaluating biomaterial-mediated modulation of foreign-body responses(Springer Heidelberg, 2022) Cakmak, Betul; Saglam-Metiner, Pelin; Beceren, Goze; Zhang, Yu S.; Yesil-Celiktas, OzlemThe immune response after implantation of a biomaterial may shorten the functional life of the implant, depending on the degree of the response. In this study, we used a polyacrylamide-alginate (PAAm-Alg) hydrogel, which has been previously characterized as a biocompatible material and shown to enhance regeneration of cartilage in vivo, along with a graphite-enhanced hydrogel (PAAm-Alg-G) as a non-biocompatible counterpart, to evaluate macrophage attachment and polarization to pro- or anti-inflammatory phenotypes. The performance of each biomaterial in the presence of fibroblasts and chondrocytes was validated by an in vitro model which demonstrated modulation of the foreign-body response. A blend of 5% gelatin methacryloyl and 0.1% methacrylated hyaluronic acid was optimized to mimic the extracellular matrix (ECM) and support cell viability, proliferation, migration, and functionality at an initial concentration of 3.25 x 10(5) cells/mL. The PAAm-Alg-G hydrogel localized in the simulated ECM showed cytotoxic and genotoxic effects for both fibroblasts and chondrocytes, while exhibiting a proliferative effect on macrophages with elevated immune response. The M1/M2 ratio was 0.73 for PAAm-Alg hydrogel but 2.64 for PAAm-Alg-G, leading to significant M1 dominance (p < 0.0001), as expected, on day 13. Moreover, loading PAAm-Alg hydrogel with transforming growth factor beta-3 (TGF-beta 3) resulted in a slightly more balanced M1/M2 ratio of 0.87 (p > 0.05). The interleukin-6 (IL-6) concentration secreted in the presence of PAAm-Alg hydrogel (4.58 pg/mL) significantly decreased (p < 0.0001) on day 13, while the increase (p < 0.0001) in interleukin-10 (IL-10) concentration (120.73 pg/mL) confirmed the switch from a pro-inflammatory to an anti-inflammatory response. Predicting immune responses by developing a simplistic yet powerful three-dimensional in vitro model provides advantages in preparing for clinical use of biomaterials. [GRAPHICS] .Öğe Activity and stability enhancement of alpha-amylase treated with sub- and supercritical carbon dioxide(Soc Bioscience Bioengineering Japan, 2011) Senyay-Oncel, Deniz; Yesil-Celiktas, OzlemVarious physical, chemical and genetic approaches have been applied in order to enhance enzyme stability and activity. In this study, the aim was to investigate the capability of sub- and supercritical carbon dioxide to alter the stability and activity of a-amylase as an alternative technique. The effects of operational parameters such as pressure (50-300 bar), temperature (28-80 degrees C), CO2 flow (2-10 gmin(-1)) and time (60-180 min) were evaluated in regard to the activity and stability of fungal based alpha-amylase from Aspergillus oryzea. The activity of untreated enzyme was determined as 17,726 mu mol/ml/min. While both sub- and supercritical conditions enhanced the activity, the increase in flow rate had an adverse effect and the activity was decreased by 28.9% at a flow rate of 10 gmin(-1) under supercritical conditions. Nuclear magnetic resonance (NMR) spectra of untreated enzyme and treated samples exhibiting the lowest and the highest activities were almost identical except for the chemical shifts observed at the lowest activity sample from 4.0 to 4.4 ppm which were assigned to protons of hydrogen-bonded groups. Optimum conditions were determined as 240 bar, 41 degrees C, 4 gmin(-1) CO2 flow and 150 min of process duration yielding 67.7% (29,728 mu mol/ml/min) higher activity than the untreated enzyme providing fundamental basis for enzymatic applications. (C) 2011, The Society for Biotechnology, Japan. All rights reserved.Öğe Advances in Glioblastoma Multiforme Treatment: New Models for Nanoparticle Therapy(Frontiers Media Sa, 2018) Ozdemir-Kaynak, Elif; Qutub, Amina A.; Yesil-Celiktas, OzlemThe most lethal form of brain cancer, glioblastoma multiforme, is characterized by rapid growth and invasion facilitated by cell migration and degradation of the extracellular matrix. Despite technological advances in surgery and radio-chemotherapy, glioblastoma remains largely resistant to treatment. New approaches to study glioblastoma and to design optimized therapies are greatly needed. One such approach harnesses computational modeling to support the design and delivery of glioblastoma treatment. In this paper, we critically summarize current glioblastoma therapy, with a focus on emerging nanomedicine and therapies that capitalize on cell-specific signaling in glioblastoma. We follow this summary by discussing computational modeling approaches focused on optimizing these emerging nanotherapeutics for brain cancer. We conclude by illustrating how mathematical analysis can be used to compare the delivery of a high potential anticancer molecule, delphinidin, in both free and nanoparticle loaded forms across the blood-brain barrier for glioblastoma.Öğe Advances in microfluidic synthesis and coupling with synchrotron SAXS for continuous production and real-time structural characterization of nano-self-assemblies(Elsevier, 2021) Ilhan-Ayisigi, Esra; Yaldiz, Burcu; Bor, Gizem; Yaghmur, Anan; Yesil-Celiktas, OzlemMicrofluidic platforms have become highly attractive tools for synthesis of nanoparticles, including lipid nano-self-assemblies, owing to unique features and at least three important aspects inherent to miniaturized micro-devices. Firstly, the fluids flow under controlled conditions in the microchannels, providing well-defined flow profiles and shorter diffusion lengths that play important roles in enhancing the continuous production of lipid and polymer nanoparticles with relatively narrow size distributions. Secondly, various geometries adapted to microfluidic device designs can be utilized for enhancing the colloidal stability of nanoparticles and improving their drug loading. Thirdly, microfluidic devices are usually compatible with in situ characterization methods for real-time monitoring of processes occurring inside the microchannels. This is unlike conventional nanoparticle synthesis methods, where a final solution or withdrawn aliquots are separately analysed. These features inherent to microfluidic devices provide a tool-set allowing not only precise nanoparticle size control, but also real-time analyses for process optimization. In this review, we focus on recent advances and developments in the use of microfluidic devices for synthesis of lipid nanoparticles. We present different designs based on hydrodynamic flow focusing, droplet-based methods and controlled microvortices, and discuss integration of microfluidic platforms with synchrotron small-angle X ray scattering (SAXS) for in situ structural characterization of lipid nano-self-assemblies under continuous flow conditions, along with major challenges and future directions in this research area.Öğe Aligned with sustainable development goals: microwave extraction of astaxanthin from wet algae and selective cytotoxic effect of the extract on lung cancer cells(Taylor & Francis Inc, 2022) Guler, Bahar Aslanbay; Saglam-Metiner, Pelin; Deniz, Irem; Demirel, Zeliha; Yesil-Celiktas, Ozlem; Imamoglu, EsraAstaxanthin is one of the most attractive carotenoid in the cosmetic, food, pharmaceutical, and aquaculture industries due to its strong bioactive properties. Among the various sources, several algae species are considered as rich sources of astaxanthin. Downstream processing of algae involves the majority of the total processing costs. Thus, elimination of high energy involved steps is imperative to achieve cost-effective scale in industry. This study aimed to determine operation conditions for astaxanthin extraction from wet Haematococcus pluvialis using microwave-assisted extraction. The isolated astaxanthin extract was evaluated for cytotoxicity on human lung cancer cells. The microwave-assisted extraction process at 75 degrees C under the power of 700 Watt for 7 min gave the highest astaxanthin yield (12.24 +/- 0.54 mg astaxanthin/g wet cell weight). Based on MTT cell viability and Hoechst 33342 nuclear staining assays on A549 lung cancer cells, astaxanthin inhibited cell growth in dose- and time-dependent manners, where IC50 value was determined as 111.8 +/- 14.8 mu g/mL and apoptotic bodies were observed along with positive control group at 72 hr. These results showed that the treatment with astaxanthin extracted from wet H. pluvialis by microwave-assisted extraction exhibited anti-cancer activity on lung cancer cells indicating a newly potential to be utilized in industry.Öğe Anticancer activities of bioactive peptides derived from rice husk both in free and encapsulated form in chitosan(Elsevier Science Inc, 2021) Ilhan-Ayisigi, Esra; Budak, Gozde; Celiktas, Melih Soner; Sevimli-Gur, Canan; Yesil-Celiktas, OzlemCereal grain-derived protein hydrolysates exert beneficial effects for human health, thus utilization of by-products with high protein content has drawn attention. In this study, hot water extraction of rice husk has been optimized to obtain protein hydrolysate with the highest anticancer activity. The optimum protein value was obtained as 2.40 g/L corresponding to 43.2 g protein/kg dried rice husk under the conditions of 60 degrees C, 2.0 mL/min flow rate and pH 10.0. The protein hydrolysate was encapsulated with chitosan, where the mean particle size of protein hydrolysate (0.3 %) loaded chitosan nanoparticles was 256.4 +/- 33. 4 nm with 89 % encapsulation efficiency and a 65% release at the end of 6 days. Cytotoxicity assays showed that the lowest cell viabilities have been achieved with A549 and MCF7 cells with IC50 values of 1.98 and 3.58 mu g/mL, respectively, whereas nuclear fragmentation and apoptotic bodies were observed through Hoechst 33342 staining. The cytotoxic effect might be associated with the wide variety of peptide/protein subunits ranging from 10 kDa to more than 180 kDa in the protein hydrolysate of rice husk. (C) 2021 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.Öğe Anticancer effects of methanolic, supercritical CO2 rose-mary extracts, carnosic acid and rosmarinic acid(Elsevier Science Bv, 2012) Sevimli-Gur, Canan; Yesil-Celiktas, Ozlem; Vardar-Sukan, Fazilet; Bedir, ErdalÖğe Antimicrobial activity of propolis and gentamycin against methicillin-resistant Staphylococcus aureus in a 3D thermo-sensitive hydrogel(Elsevier, 2019) Gezgin, Yuksel; Kazan, Aslihan; Ulucana, Fulden; Yesil-Celiktas, OzlemThe antibiotic resistance has become a major public health problem globally. Combinatorial administration of natural compounds and antibiotics is an alternative approach, particularly if synergistic effects can be elicited against multi-drug resistant bacteria. The aim of this study was to investigate the combinatorial activity of propolis and gentamycin against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 in three dimensional (3D) thermo-sensitive hydrogel (Poloxamer 407 25% (w/w)) to mimic the microenvironment realistically. Rheological properties, sol-gel transition temperature and the porosity of the hydrogel were determined. Subsequently, thermo-sensitive gel was loaded with propolis and gentamycin for evaluation of the combined effect. The fractional inhibitory concentration indices showed marked synergy and partial synergy without and within 3D termo-sensitive hydrogel at a range of 0.38 to 0.56, respectively. This 3D platform can be utilized to screen potential antimicrobial compounds and readily expanded to other microbial species.Öğe Antimicrobial and wound healing properties of cotton fabrics functionalized with oil-in-water emulsions containing Pinus brutia bark extract and Pycnogenol (R) for biomedical applications(Springer, 2021) Secim-Karakaya, Pelin; Saglam-Metiner, Pelin; Yesil-Celiktas, OzlemTopical formulations containing 1-2% of Pinus brutia bark extract and Pycnogenol (R) have been prepared to investigate the effect of flavonoids on the stability of O/W emulsions, which were subjected to physicochemical and thermal stability tests. The formulations have been applied to cotton fabrics to evaluate antimicrobial properties against Staphylococcus aureus, Escherichia coli, Candida albicans and Aspergillus brasiliensis. Furthermore, prepared cotton fabrics have been tested on keratinocytes seeded in cell culture inserts for wound healing. Results of freeze thaw cycle test indicated enhanced thermo-stability with no major changes in pH and viscosity, likewise the results of centrifugation assay. However, the addition of Pycnogenol (R) has tremendously decreased the viscosity of the topical formulation (10,900 cp.). in terms of antimicrobial activity, 2% P. brutia treated cotton fabrics decreased the proliferation of Aspergillus brasiliensis 78.8%, which were more effective than that of Pycnogenol (R) formulation (62.9%). As for wound healing, 2% P. brutia treated cotton fabrics increased HaCaT keratinocyte cell proliferation and accelerated the cell-free gap closure compared to Pycnogenol (R) and untreated control groups. The obtained results indicate the utilization of pine bark for developing an eco-friendly natural antifungal finish for medical textiles.Öğe Application of beta-glucuronidase-immobilised silica gel formulation to microfluidic platform for biotransformation of beta-glucuronides(Springer, 2018) Muderrisoglu, Cahit; Sargin, Sayit; Yesil-Celiktas, OzlemTo improve the efficiency of reactions of beta-glucuronidase (GUS)-assisted glucuronic acid (GluA) removal within a microfluidic system. beta-glucuronidase from Helix pomatia was immobilised and characterised in silica-based sol-gel monoliths. Efficiency of the GUS-doped silica monoliths was tested for hydrolysis of p-Nitrophenyl-beta-d-glucuronide (pNP-GluA) in both ml-scaled medium via batch reactions and microfluidic environment via continuous-flow reactions. In the microfluidic platform, within a duration of 150 min of continuous operation (flow rate: 1 A mu L/min), the obtained highest pNP yield was almost 50% higher than that of the corresponding batchwise reaction. However, increased flow rates (3, 5, and 10 A mu L/min) resulted in lower conversion yields compared to 1 A mu L/min. The microfluidic platform demonstrated continuous hydrolytic activity for 7 days with considerable reaction yields while using a small amount of the enzyme. These results revealed that usage of the microreactors has considerable potential to efficiently obtain bioactive GluA-free aglycons from various plant-derived beta-glucuronides for pharmaceutical applications. [GRAPHICS] .Öğe A bioactivity based comparison of Echinacea purpurea extracts obtained by various processes(Elsevier Science Bv, 2014) Yildiz, Ece; Karabulut, Dilan; Yesil-Celiktas, OzlemEchinacea species is provided as dietary supplements for various infectious and immune related disorders and has a potential role in cancer prevention. The aim of this study was to optimize the extraction of total flavonoids using different extraction methods and investigate the cytotoxic effects on various cancer cell lines (CaCo-2, MCF-7, A549, U87MG, and HeLa) and VERO (African green monkey) as a non-cancerous cell line. Box-Behnken statistical design was used to evaluate the effect of pressure (100-200 bar), temperature (40-80 degrees C) and ethanol as co-solvent (6-20 wt%) at a flow rate of 15 g/min for 60 min in supercritical CO2 extraction and the effect of temperature (60-100 degrees C), time (5-15 min) and power (300-900W) in microwave-assisted extraction. Optimum extraction conditions were elicited as 300 bar, 80 degrees C and 13% co-solvent yielding 0.472 mg rutin equivalent total flavonoids/g extract in SC-CO2 extraction, whereas 60 degrees C, 10 min and 300W yielded the highest (0.202 mg rutin equivalent) total flavonoids in microwave-assisted extraction. Additional trials with subcritical water (0.022 mg/g) and Soxhlet extraction with methanol (0.238 mg/g) yielded lower flavonoid contents. The exposures upto 50 mu g/ml of extracts revealed no significant inhibition on the proliferation of both tested cancer cells and healthy VERO cells. (C) 2014 Elsevier B.V. All rights reserved.Öğe The Breadth and Intensity of Supercritical Particle Formation Research with an Emphasis on Publication and Patent Disclosures(Amer Chemical Soc, 2010) Yesil-Celiktas, Ozlem; Senyay, DenizThe drawbacks of the conventional mechanical treatments for particle micronization often resulting in product damage or performance degradation have highlighted the need for alternative particle formation processes. The aim of this study was to shed light on the trends of the scientific studies and innovations in the field of particle formation using supercritical fluids (SCF) in order to observe the progress of science and technology and to satisfy the need for a global view of research activities. The publications in the ISI Web and the patents in a patent database were screened using nine different keywords in title or topics. A total of 939 journal publication and 206 patent disclosures between 1980-2009, with the contributions of 3588 authors and 604 innovators, were found to focus on particle formation using SCF. The results showed that the majority of the publication (59.2%) and patent (40.3%) disclosures were related to antisolvent precipitation and rapid expansion of SCF (18.3, 16%). Patents originating from United States (56.8%) were dominating, followed by those from the European Union (30.1%) and Japan (9.2%). The analysis revealed the appetite of the companies for commercialization (73.8%), which can be interpreted as an indicator of upcoming industrial applications.Öğe Characterization, immobilization, and activity enhancement of cellulase treated with supercritical CO2(Springer, 2015) Senyay-Oncel, Deniz; Yesil-Celiktas, OzlemEnzyme activity enhancement represents a great opportunity for biotechnological production, while recovery of most enzymes from media, possible loss of catalytic activity in reactions, and denaturation occur. In this study, the activity and stability enhancement, kinetic parameters, and thermal inactivation for cellulose hydrolysis of supercritical carbon dioxide (SC-CO2)-treated and untreated cellulase from Trichoderma longibrachiatum as a model enzyme are presented, and the activity enhancement capability of SC-CO2 for cellulase after consecutive enzymatic reactions is discussed. The pH and temperature stability were pH 5 and 50 A degrees C for the enzymatic reaction, whereas the kinetic parameter values, V (max) and K (m), were calculated using the Michaelis-Menten model. The optimal operational parameters were determined to be 54 A degrees C, 180 bar, and 10 g/min CO2 flow rate for 120 min, yielding 48.3 % higher activity (9.27 mu mol/ml/min) than for untreated enzyme. In addition, SC-CO2-treated cellulase with the highest activity was immobilized on NaY zeolite, and consecutive reactions were carried out. The presented results suggest that enzymes as catalysts in biochemical applications can be improved by using supercritical fluids as potential media.Öğe A COMPARATIVE STUDY OF ANTIOXIDANT PROPERTIES OF EXTRACTS OBTAINED FROM RENEWABLE FORESTRY AND AGRICULTURAL RESOURCES(Parlar Scientific Publications (P S P), 2009) Yesil-Celiktas, OzlemRenewable forestry and agricultural resources collected from various locations of Turkey were subjected to evaluation as potential phytochemicals. Antioxidant activities of 4 pine bark extracts (Pinus brutia, Pinus sylvestris, Pinus nigra and Pinus pinea), a commercial product (Pycnogenol (R)), and 3 industrial extracts of olive leaves (olive leaf extract, olive leaf juice and olive mill wastewater pulp) were determined using in vitro antioxidant activity, radical scavenging assays and P-carotene bleaching method. P. brutia extract revealed the highest activity (936.6 mg GAE/g extract; EC(50): 8.1 mu g/ml), whereas pine bark extracts showed higher activities than the industrial extracts of olive leaf. Additionally, extent of lipid peroxidation in cooked turkey meat was the lowest in P. brutia extract (0.92 to 3.78 mg MDA/kg) during 7 days of storage. Results presented here indicate that bark of Pinus species other than P. maritima and olive leaves offer the prospects of new bio-resources to be utilized in the industry.Öğe A comparative study on extraction processes of Stevia rebaudiana leaves with emphasis on antioxidant, cytotoxic and nitric oxide inhibition activities(Elsevier Science Bv, 2015) Yildiz-Ozturk, Ece; Nalbantsoy, Ayse; Tag, Ozgur; Yesil-Celiktas, OzlemIn this paper, the extraction conditions yielding the highest steviol glycosides from the leaves of Stevia rebaudiana were determined using microwave (MAE) and ultrasonically assisted extraction (UAE) and biological activities of the extracts along with analyses of the residue from the extraction process were investigated. Under optimum conditions, 21.21 mg glycosides/g dried leaf in MAE and 14.90 mg glycosides/g dried leaf in UAE were quantified by HPLC analyses. After extraction, total chlorophyll, carotenoid contents and total dietary fibers were quantified as 15.14 mg/100 g, 2.93 mg/100 g and 6.5% in the raffinate phase. The total phenols were determined as 80.13 and 86.47 mg gallic acid/g extract, whereas the total flavonoids were 111.16 and 126.70 mg quercetin/g extract and DPPH radical scavenging activities were 91.39 and 92.40%, respectively. The extracts exhibited no cytotoxicity against healthy cell line and macrophage RAW 264.7 cells. The IC50 values were 68 mu g/ml and >100 mu g/ml for MAE and UAE. Overall, obtained results suggest that stevia extracts and its residue can be utilized holistically on industrial scale. (C) 2015 Elsevier B.V. All rights reserved.Öğe Continuous Microfluidic Production of Citrem-Phosphatidylcholine Nano-Self-Assemblies for Thymoquinone Delivery(Mdpi, 2021) Ilhan-Ayisigi, Esra; Ghazal, Aghiad; Sartori, Barbara; Dimaki, Maria; Svendsen, Winnie Edith; Yesil-Celiktas, Ozlem; Yaghmur, AnanLamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip. In this study, nanoparticle tracking analysis (NTA) and synchrotron small-angle X-ray scattering (SAXS) were employed to characterize TQ-free and TQ-loaded citrem/SPC nanodispersions. Microfluidic synthesis led to formation of TQ-free and TQ-loaded nanoparticles with mean sizes around 115 and 124 nm, and NTA findings indicated comparable nanoparticle size distributions in these nanodispersions. Despite the attractiveness of the microfluidic chip for continuous production of citrem/SPC nano-self-assemblies, it was not efficient as comparable mean nanoparticle sizes were obtained on employing a batch (discontinuous) method based on low-energy emulsification method. SAXS results indicated the formation of a biphasic feature of swollen lamellar (L-alpha) phase in coexistence with an inverse bicontinuous cubic Pn3m phase in all continuously produced TQ-free and TQ-loaded nanodispersions. Further, a set of SAXS experiments were conducted on samples prepared using the batch method for gaining further insight into the effects of ethanol and TQ concentration on the structural features of citrem/SPC nano-self-assemblies. We discuss these effects and comment on the need to introduce efficient microfluidic platforms for producing nanocarriers for delivering TQ and other therapeutic agents.Öğe Cytotoxic and Nitric Oxide Inhibition Activities of Propolis Extract along with Microencapsulation by Complex Coacervation(Springer, 2016) Onbas, Rabia; Kazan, Aslihan; Nalbantsoy, Ayse; Yesil-Celiktas, OzlemIn this study, cytotoxicity of ethanol extract of propolis (EEP) originating from Sivas, Turkey was screened against several cancer cell lines, namely PC-3, U87MG, A-549, mPANC96, CaCo-2, MCF-7, HeLa, MDA-MB-231 and a non-tumor cell line HEK293 by MTT assay. The inhibition levels of inducible nitric oxide synthase (iNOS) were also determined by using RAW 264.7 macrophage cells following lipopolysaccharide (LPS) treatment. EEP exhibited significant cytotoxic nitric oxide inhibition activities with an IC50 value of 0.1 +/- 0.1 mu g/ml indicating a high potential as an anti-inflammatory agent. In spite of these promising results and the fact that propolis is a highly nutritive substance, its low solubility and bitter taste limit the applications as a natural supplement. Encapsulation might serve as a good strategy in order to overcome these problems. Complex coacervation was applied where the main focus was on surfactant type, polymer ratio (alginate: gelatin), stirring rate and concentration of core material. The mean particle size of unloaded microparticles were 22.62 mu m obtained with gelatin: alginate ratio of 1: 1 at a stirring rate of 1400 rpm with 2 ml of 1 % (w/v) sodium carboxymethyl cellulose (Na-CMC), whereas addition of EEP at a concentration of 100 mg/ml increased the mean particle size to 36.44 mu m and yielded an encapsulation efficiency of 98.77 %. The cytotoxicities of EEP loaded microparticles were also assessed both on MCF-7 and MDA-MB-231 where similar results were achieved as free EEP which can enhance the possible use of propolis extract in the industry as a natural supplement.Öğe Cytotoxic responses of carnosic acid and doxorubicin on breast cancer cells in butterfly-shaped microchips in comparison to 2D and 3D culture(Springer, 2017) Yildiz-Ozturk, Ece; Gulce-Iz, Sultan; Anil, Muge; Yesil-Celiktas, OzlemTwo dimensional (2D) cell culture systems lack the ability to mimic in vivo conditions resulting in limitations for preclinical cell-based drug and toxicity screening assays and modelling tumor biology. Alternatively, 3D cell culture systems mimic the specificity of native tissue with better physiological integrity. In this regard, microfluidic chips have gained wide applicability for in vitro 3D cancer cell studies. The aim of this research was to develop a 3D biomimetic model comprising culture of breast cancer cells in butterfly-shaped microchip to determine the cytotoxicity of carnosic acid and doxorubicin on both estrogen dependent (MCF-7) and independent (MDAMB231) breast cancer cells along with healthy mammary epithelial cells (MCF-10A) in 2D, 3D Matrigel (TM) and butterfly-shaped microchip environment. According to the developed mimetic model, carnosic acid exhibited a higher cytotoxicity towards MDAMB 231, while doxorubicin was more effective against MCF-7. Although the cell viabilities were higher in comparison to 2D and 3D cell culture systems, the responses of the investigated molecules were different in the microchips based on the molecular weight and structural complexity indicating the importance of biomimicry in a physiologically relevant matrix.Öğe Cytotoxic, antimicrobial and nitric oxide inhibitory activities of supercritical carbon dioxide extracted Prunus persica leaves(Springer, 2020) Koyu, Halil; Kazan, Aslihan; Nalbantsoy, Ayse; Yalcin, Husniye Tansel; Yesil-Celiktas, OzlemDifferent parts of Prunus persica as fruits, flowers, leaves and kernels have been consumed with dietary and therapeutic purposes traditionally. During fruit production, remarkable amount of leaves which can hold important bioactive groups as phenolics, have been left unutilized. the aim of this study was to investigate cytotoxic, antimicrobial and nitric oxide inhibitory activities of supercritical carbondioxide extracts of Prunus persica leaves. Among studied cell lines, supercritical carbon dioxide extract which was processed at 150 bar, 60 degrees C, and 6% co-solvent ethanol, exhibited remarkable cytotoxic activity against HeLa, MPanc-96 and MCF-7 cell lines with IC50 values of 12.22 mu g/ml, 28.17 mu g/ml and 35.51 mu g/ml respectively, whereas IC50 value of conventional solvent extract was above 50 mu g/ml. Minimum inhibitory concentration values determined for antibacterial and antifungal activities against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Candida albicans were found as 62.50 mu g/ml. Strong nitric oxide inhibition was achieved with IC50 of 9.30 mu g/ml. the promising results revealed that Prunus persica leaves may have remarkable potential as supplement both for drug and food industries. This study is the first report revealing cytotoxic, antimicrobial and nitric oxide inhibitory activity of supercritical carbon dioxide extract of Prunus persica leaves.Öğe Cytotoxicity of Silica Nanoparticles with Transcaucasian Nose-Horned Viper, Vipera ammodytes transcaucasiana, Venom on U87MG and SHSY5Y Neuronal Cancer Cells(Humana Press Inc, 2018) Celen, Cigdem; Kececiler, Ceren; Karis, Mert; Gocmen, Bayram; Yesil-Celiktas, Ozlem; Nalbantsoy, AyseHighly bioactive compounds of the snake venom make them particular sources for anticancer agent development. They contain very rich peptide-protein structures. Therefore, they are very susceptible to environmental conditions such as temperature, pH, and light. In this study, Vipera ammodytes transcaucasiana venom was encapsulated in PAMAM-G4 dendrimer by sol-gel method in order to prevent degradation of venom contents from the environmental conditions. For this purpose, nanoparticles were prepared by sol-gel methodology and SEM analyses were performed. U87MG and SHSY5Y neuronal cancer cell lines were treated with different concentrations of venom-containing nanoparticles and cytotoxicity was determined by MTT assay. IC50 values of nanoparticles with snake venom were calculated as 37.24 and 44.64g/ml for U87MG and SHSY5Y cells, respectively. The IC50 values of nanoparticles with snake venom were calculated as 10.07 and 7.9g/ml for U87MG and SHSY5Y cells, respectively. As a result, nanoparticles with V. a. transcaucasiana venom showed remarkably high cytotoxicity. Encapsulation efficiency of nanoparticles with 1mg/ml snake venom was determined as %67 via BCA protein analysis. In conclusion, this method is found to be convenient and useful for encapsulating snake venom as well as being suitable for drug delivery systems.
