Yaşam ve Doğa Bilimleri Fakültesi

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Computational Prediction of Functional MicroRNA-mRNA Interactions
(HUMANA PRESS INC, 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA, 01.01.2019) Demirci, Muserref Duygu Sacar; Yousef, Malik; Allmer, Jens; 0000-0003-2012-0598; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
Proteins have a strong influence on the phenotype and their aberrant expression leads to diseases. MicroRNAs (miRNAs) are short RNA sequences which posttranscriptionally regulate protein expression. This regulation is driven by miRNAs acting as recognition sequences for their target mRNAs within a larger regulatory machinery. A miRNA can have many target mRNAs and an mRNA can be targeted by many miRNAs which makes it difficult to experimentally discover all miRNA-mRNA interactions. Therefore, computational methods have been developed for miRNA detection and miRNA target prediction. An abundance of available computational tools makes selection difficult. Additionally, interactions are not currently the focus of investigation although they more accurately define the regulation than pre-miRNA detection or target prediction could perform alone. We define an interaction including the miRNA source and the mRNA target. We present computational methods allowing the investigation of these interactions as well as how they can be used to extend regulatory pathways. Finally, we present a list of points that should be taken into account when investigating miRNA-mRNA interactions. In the future, this may lead to better understanding of functional interactions which may pave the way for disease marker discovery and design of miRNA-based drugs.
Poly(OEGMA)-b-Poly(4-VP) block copolymer nanocarriers for anticancer agent release
(WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, 01.06.2018) Aksit, N. N; Topuzogullari, M.; Isoglu, I. A; El Khatib, M.; Isoglu, S. Dincer; 0000-0002-8697-1654; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
Poly(OEGMA)-b-Poly(4-VP) block copolymer nanocarriers for anticancer agent release
RAFT-mediated synthesis of poly(N-(2-hydroxypropyl)methacrylamide-b-4-vinylpyridine) by conventional and microwave heating
(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2013) Ozdemir, Zeynep; Topuzogullari, Murat; İsoglu, Ismail Alper; Dincer, Sevil; 0000-0003-4435-7776; 0000-0001-5085-5814; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; İsoglu, Ismail Alper; Dincer, Sevil
We report the synthesis of N-(2-hydroxypropyl)methacrylamide (HPMA) macroCTA and HPMA-b-4-Vinylpyridine block copolymers via reversible addition-fragmentation chain transfer (RAFT) reaction. Polymerization was carried out in dimethylformamide (DMF) at 70 C using 4-Cyano-4(thiobenzoylthio) pentanoic acid as chain transfer agent and AIBN as an initiator. Control over molecular weight and composition was achieved by altering the CTA, monomer and initiator feed ratio. The controlled living character of the polymerization was verified with pseudo-first-order kinetic plots, a linear increase of the molecular weight with conversion, and low polydispersities (PDIs B 1.2). Effect of microwave heating on the homo- and copolymer formation was investigated and the rates were significantly higher than those observed under conventional heating conditions. These polymerization reactions were in controlled fashion resulting in polymers with low PDIs, too. These polymers have a great potential to be used in developing delivery vehicles and conjugates for further drug or gene delivery applications
Liver fibrosis staging using CT image texture analysis and soft computing
(ELSEVIER, 2014) Kayaalti, Omer; Aksebzeci, Bekir Hakan; Karahan, Ibrahim Okkes; Deniz, Kemal; Ozturk, Mehmet; Yilmaz, Bulent; Kara, Sadik; Asyali, Musa Hakan; 0000-0001-7476-8141; 0000-0003-2954-1217; AGÜ, Mühendislik Fakültesi, Elektrik - Elektronik Mühendisliği Bölümü; Yilmaz, Bulent; Aksebzeci, Bekir Hakan
Liver biopsy is considered to be the gold standard for analyzing chronic hepatitis and fibrosis; however, it is an invasive and expensive approach, which is also difficult to standardize. Medical imaging techniques such as ultrasonography, computed tomography (CT), and magnetic resonance imaging are non-invasive and helpful methods to interpret liver texture, and may be good alternatives to needle biopsy. Recently, instead of visual inspection of these images, computer-aided image analysis based approaches have become more popular. In this study, a non-invasive, low-cost and relatively accurate method was developed to determine liver fibrosis stage by analyzing some texture features of liver CT images. In this approach, some suitable regions of interests were selected on CT images and a comprehensive set of texture features were obtained from these regions using different methods, such as Gray Level Co-occurrence matrix (GLCM), Laws’ method, Discrete Wavelet Transform (DWT), and Gabor filters. Afterwards, sequential floating forward selection and exhaustive search methods were used in various combinations for the selection of most discriminating features. Finally, those selected texture features were classified using two methods, namely, Support Vector Machines (SVM) and k-nearest neighbors (k-NN). The mean classification accuracy in pairwise group comparisons was approximately 95% for both classification methods using only 5 features. Also, performance of our approach in classifying liver fibrosis stage of subjects in the test set into 7 possible stages was investigated. In this case, both SVM and k-NN methods have returned relatively low classification accuracies. Our pairwise group classification results showed that DWT, Gabor, GLCM, and Laws’ texture features were more successful than the others; as such features extracted from these methods were used in the feature fusion process. Fusing features from these better performing families further improved the classification performance. The results show that our approach can be used as a decision support system in especially pairwise fibrosis stage comparisons.
Polyethylenimine Modified and Non-Modified Polymeric Micelles Used for Nasal Administration of Carvedilol
(AMER SCIENTIFIC PUBLISHERS, 2015) Kahraman, Emine; Karagoz, Ayse; Dinçer, Sevil; Ozsoy, Yildiz; 0000-0002-6887-6549; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Dinçer, Sevil
This study evaluates the ability of polyethylenimine-modified and non-modified polymeric micelles to enhance permeation through the nasal mucosa for a highly hydrophobic model drug. Carvedilol was loaded into polyethylenimine-modified and non-modified micelles by direct dissolution. Formulations were characterised by critical micelle concentration, micelle particle size and distribution, zeta potential, morphological structure and entrapment efficiency. The drug entrapment efficiency was determined to be as high as 77.14%, while micelle particle sizes and zeta potentials were within the range of 140.0-279.9 nm and (-40.6)-(+25.9) mV, respectively. In vitro studies showed 100% release of carvedilol from micelles in 120 hours. Ex vivo permeation studies showed that the drug in polyethylenimine non-modified micelles passed more efficiently than the drug in polyethylenimine modified micelles. These results demonstrated that polyethylenimine modified micelles did not significantly affect the permeation of the drug when compared to polyethylenimine non-modified micelles. On the contrary, the drug in poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 micelles, the polyethylenimine non-modified micelles, showed the highest permeation rate through bovine nasal mucosa. In conclusion, poly(L-lactide)-block-methoxy poly(ethylene glycol) 5000 polymeric micelles maybe useful as novel drug carriers that increase the permeation through the nasal mucosa.
TACTILE SENSITIVITY and CAPABILITY OF SOFT-SOLID TEXTURE DISCRIMINATION
(WILEY, 2015) Aktar, Tugba; Ettelaie, Rammile; Chen, Jianshe; Holmes, Melvin; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, Tugba
The sensation and perception of food texture is regulated by tactile-dominated mechanisms and therefore, it is believed that one’s capability in discriminating food textural properties could be related to one’s tactile sensitivity. However, evidence to support this hypothesis is currently not available. This work aims to test this hypothesis by examining tactile sensitivity of individuals’ (touch detection threshold and two-point discrimination threshold) and texture discrimination capability. A range of soft-solid food samples with controlled firmness and elastic moduli were designed for textural discrimination tests. A total of 32 healthy subjects threshold of touch detection was found to be 0.028 g for the fingertip and 0.013 g for the tongue. Similarly, the mean threshold of two-point discrimination was 1.42 mm and 0.62 mm for the fingertip and tongue, respectively. Threshold for firmness discrimination (compressing until yielding) of the gel samples was 13.3% for the fingertip and 11.1% for the tongue. However, the elasticity discrimination threshold (by gentle pressing) of the population was found to be much smaller at 2.3% and 1.2% for the fingertip and the tongue respectively. Results show that tongue is slightly more sensitive than the fingertip in discriminating food texture (P < 0.05). An expected correlation between individual’s capability of texture discrimination and their tactile sensitivity was not observed.
Combination of the Simple Additive (SAW) Approach and Mixture Design to Determine Optimum Cocoa Combination of the Hot Chocolate Beverage
(TAYLOR & FRANCIS INC, 2015) DOGAN, Mahmut; Aktar, Tugba; Toker, Omer Said; Tatlisu, Nevruz Berna; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, Tugba
Physicochemical (pH, brix, and color), sensory (color, taste, odor, mouthfeeling, consistency, bitter flavor, and general acceptability), and rheological properties of the hot chocolate beverages including different cocoa combinations were investigated in the present study. Cocoa type significantly affected all of the properties. Simple additive weighting approach was applied to obtain one score from seven different sensory parameters and simple additive weighting score was used in mixture design to determine optimum cocoa type or cocoa combination. Ostwald de Waele model described the flow behavior of the hot chocolate beverage samples with R2 values ranged between 0.818 and 0.999. The consistency coefficient (K) and apparent viscosity at shear rate 50 s−1 (η50) were significantly affected by cocoa type found in the formulation of the beverage. The mixture design approach was performed in order to determine variation of the responses (physicochemical, sensory, and rheological parameters) as a function of cocoa concentration. Simple additive weighting scores were satisfactorily described by established equation as a function of cocoa concentration to be used in the formulation of the hot chocolate beverage (R2 = 0.8645).
A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells
(GALENOS YAYINCILIK, ERKAN MOR, MOLLA GURANI CAD 21-1, FINDIKZADE, ISTANBUL 34093, TURKEY, 2015) Gokbulut, Aysun Adan; Yasar, Mustafa; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Objective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, Izmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase.
An update on molecular biology and drug resistance mechanisms of multiple myeloma
(ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA, 2015) Mutlu, Pelin; Kiraz, Yagmur; Gunduz, Ufuk; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Multiple myeloma (MM), a neoplasm of plasma cells, is the second most common hematological malignancy. Incidance rates increase after age 40. MM is most commonly seen in men and African-American population. There are several factors to this, such as obesity, environmental factors, family history, genetic factors and monoclonal gammopathies of undetermined significance (MGUS) that have been implicated as potentially etiologic. Development of MM involves a series of complex molecular events, including chromosomal abnormalities, oncogene activation and growth factor dysregulation. Chemotherapy is the most commonly used treatment strategy in MM. However, MM is a difficult disease to treat because of its marked resistance to chemotherapy. MM has been shown to be commonly multidrug resistance (MDR)-negative at diagnosis and associated with a high incidence of MDR expression at relapse. This review deals with the molecular aspects of MM, drug resistance mechanisms during treatment and also possible new applications for overcoming drug resistance. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A
(Kluwer Academic Publishers, 2015) Kaymaz, Burçin Tezcanlı; Günel, Nur Selvi; Ceyhan, Metin; Çetintaş, Vildan Bozok; Özel, Buket; Yandım, Melis Kartal; Kıpçak, Sezgi; Aktan, Çağdaş; Gökbulut, Aysun Adan; Baran, Yusuf; Can, Buket Kosova; 0000-0003-2659-4129; 0000-0003-0573-4276; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Baran, Yusuf
BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR-1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumor-suppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy.
EVALUATION OF THE SENSORY CORRELATION BETWEEN TOUCH SENSITIVITY AND THE CAPACITY TO DISCRIMINATE VISCOSITY
(WILEY, 2015) Aktar, Tugba; Chen, Jianshe; Ettelaie, Rammile; Holmes, Melvin; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü
The capacity to discriminate the viscous nature of food materials is critically important in the sensory evaluation and subsequent perception of food texture and acceptability. It is generally assumed that this capability is closely linked to individual's tactile sensitivity, which in itself is a function of the individual's specific capabilities due to experience, age, lifestyle and health status for example. However, no experimental evidence is yet available to validate or disprove this assumption. By comparing the touch sensitivity and the capability of viscosity discrimination among individuals (using finger and tongue sensory perception), this work aims to establish if a correlation exists. Semmes-Weinstein monofilaments were used for touch sensitivity tests of the index fingers and tongue surfaces. A series of syrup solutions were prepared to give a wide range of viscosities with a viscosity scale factor of 1.20.009. A total of 30 healthy subjects (16 female and 14 male; mean age 29.9 +/- 9 years; mean body mass index 22.5 +/- 2.9kg/m(2)) participated in this study. A similar touch sensitivity threshold, 0.023 and 0.021g, was observed for the index fingertip and for the tongue, respectively. However, the tongue appears to be more sensitive to touch than the fingertips when the force range they cover was compared. The viscosity discrimination threshold was found to be approximately 53% for the index fingertip and around 47% for the tongue. By comparing individual capabilities of viscosity discrimination against touch sensitivity, no significant correlation was observed between the two factors. The results from this work suggest that the capability to discriminate viscosity differences is more likely attributed to experience and is little influenced by one's physiological capability of tactile sensation, e.g., the touch sensitivity. Practical ApplicationsThe capability to discriminate differences in viscosity and the subsequent perception is an important factor for food texture appreciation. Establishment of the underlying factors that characterize the variation in the ability for such discrimination across individuals is not only critically important for our fundamental understanding of the viscosity perception but is also hugely important for the food industry in development of new food products, and in particular for specific food design for individuals with special needs, e.g., elderly, dysphagia patients, etc. Differential threshold for certain tastes and aroma compounds has been investigated. However, little has been reported in the literature about the tactile interpretation of viscosity sensation and perception. Findings from this work could provide new insight for researchers in the food industry and in food development by giving them flexibility to redesign their ingredients especially the one that has thickening effect on the product viscosity. Methodologies used in this experiment could also be applied for general food sensory studies in establishing relationships between sensory psychology and sensory physiology and especially the threshold studies with a similar approach of finding just noticeable difference values of any stimuli. The method could also be applicable to sensory capability studies of some particular groups such as elderly people to assess how weakened physiology affects their sensory capability.
Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling
(SAGE PUBLICATIONS LTD1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2016) Adan, Aysun; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Baran, Yusuf; Adan, Aysun
Fisetin and hesperetin, naturally occurring flavonoids, have been reported as novel antioxidants with chemopreventive/chemotherapeutic potential against various types of cancer. However, their mechanism of action in CML is still unknown. This particular study aims to evaluate the therapeutic potentials of fisetin and hesperetin and their effects on cell proliferation, apoptosis, and cell cycle progression in human K562 CML cells. The results indicated that fisetin and hesperetin inhibited cell proliferation and triggered programmed cell death in these cells. The latter was confirmed by mitochondrial membrane depolarization and an increase in caspase-3 activation. In addition to that, we have detected S and G2/Mcell cycle arrests and G0/G1 arrest upon fisetin and hesperetin treatment, respectively. To identify the altered genes and genetic networks in response to fisetin and hesperetin, whole-genome microarray analysis was performed. The microarray gene profiling analysis revealed some important signaling pathways including JAK/STAT pathway, KIT receptor signaling, and growth hormone receptor signaling that were altered upon fisetin and hesperetin treatment. Moreover, microarray data suggested potential candidate genes for targeted CML therapy. Fisetin and hesperetin significantly modulated the expression of genes involved in cell proliferation and division, apoptosis, cell cycle regulation, and other significant cellular processes such as replication, transcription, and translation. In conclusion, our results suggest that fisetin and hesperetin as potential natural agents for CML therapy.
Ceramide is a key factor that regulates the crosstalk between TGF-beta and sonic hedgehog signaling at the basal cilia to control cell migration and tumor metastasis
(ELSEVIER SCI LTDTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND, 2016) Gencer, Salih; Ogretmen, Besim; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Gencer, Salih
Ceramide is a key factor that regulates the crosstalk between TGF-beta and sonic hedgehog signaling at the basal cilia to control cell migration and tumor metastasis
Ceramide is A Key Factor That Regulates The Crosstalk Between TGF-beta and Sonic Hedgehog Signaling at The Basal Cilia To Control Cell Migration and Tumor Metastasis
(WILEY111 RIVER ST, HOBOKEN 07030-5774, NJ, 2016) Gencer, Salih; Oleinik, Natalia; Dany, Mohammed; Ogretmen, Besim; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Gencer, Salih
Ceramide is A Key Factor That Regulates The Crosstalk Between TGF-beta and Sonic Hedgehog Signaling at The Basal Cilia To Control Cell Migration and Tumor Metastasis
Molecular mechanisms of drug resistance and its reversal in cancer
(Taylor and Francis, 2016) Kartal Yandım, Melis; Adan Gökbulut, Aysun; Baran, Yusuf; 0000-0003-0573-4276; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Baran, Yusuf
Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.
A novel signaling pathway that governs tumor metastasis: ceramide regulates direct crosstalk between TGF-beta and sonic hedgehog signaling
(WILEY111 RIVER ST, HOBOKEN 07030-5774, NJ, 2016) Gencer, Salih; Ogretmen, B.; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü
A novel signaling pathway that governs tumor metastasis: ceramide regulates direct crosstalk between TGF-beta and sonic hedgehog signaling
T cells in tumor microenvironment
(SAGE PUBLICATIONS LTD1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2016) Kiraz, Yagmur; Baran, Yusuf; Nalbant, Ayten; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Baran, Yusuf
Tumors progress in a specific area, which supports its development, spreading or shrinking in time with the presence of different factors that effect the fate of the cancer cells. This specialized site is called "tumor microenvironment" and has a composition of heterogenous materials. The immune cells are also residents of this stromal, cancerous, and inflammatory environment, and their types, densities, or functional differences are one of the key factors that mediate the fate of a tumor. T cells as a vital part of the immune system also are a component of tumor microenvironment, and their roles have been elucidated in many studies. In this review, we focused on the immune system components by focusing on T cells and detailed T helper cell subsets in tumor microenvironment and how their behaviors affect either the tumor or the patient's outcome.
Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells
(SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2016) Kiraz, Yagmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.
A molecular and biophysical comparison of macromolecular changes in imatinib-sensitive and imatinib-resistant K562 cells exposed to ponatinib
(SAGE PUBLICATIONS LTD, 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND, 2016) Yandim, Melis Kartal; Ceylan, Cagatay; Elmas, Efe; Baran, Yusuf; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü;
Chronic myeloid leukemia (CML) is a type of hematological malignancy that is characterized by the generation of Philadelphia chromosome encoding BCR/ABL oncoprotein. Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib, are used for the frontline therapy of CML. Development of resistance against these TKIs in the patients bearing T315I mutation is a major obstacle in CML therapy. Ponatinib, the third-generation TKI, is novel drug that is effective even in CML patients with T315I mutation. The exact mechanism of ponatinib in CML has been still unknown. In this study, we aimed to determine the potential mechanisms and structural metabolic changes activated by ponatinib treatment in imatinib-sensitive K562 human CML cell lines and 3 mu M-imatinib-resistant K562/IMA3 CML cell lines generated at our lab. Apoptotic and antiproliferative effects of ponatinib on imatinib-sensitive and 3 mu M-imatinib-resistant K562/IMA3 CML cells were determined by proliferation and apoptosis assays. Additionally, the effects of ponatinib on macromolecules and lipid profiles were also analyzed using Fourier transform infrared spectroscopy (FTIR). Our results revealed that ponatinib inhibited cell proliferation and induced apoptosis as determined by loss of mitochondrial membrane potential, increased caspase-3 enzyme activity, and transfer of phosphatidylserine to the plasma membrane in both K562 and K562/IMA-3 cells. Furthermore, cell cycle analyses revealed that ponatinib arrested K562 and K562/IMA-3 cells at G1 phase. Moreover, ponatinib treatment created a more ordered nucleic acid structure in the resistant cells. Although the lipid to protein ratio increased in imatinib-sensitive K562 cells with a little decrease in the K562/IMA-3 cells, ponatinib treatment indicated significant changes in the lipid composition such as a significant increase in the cellular cholesterol amounts much more in the K562/IMA-3 cells than the sensitive counterparts. Unsaturation in lipids was higher in the resistant cells; however, increases in lipids without phosphate and the number of acyl chains were much higher in the K562 cells. Taken together, all these results showed powerful antiproliferative and apoptotic effects of ponatinib in both imatinib-sensitive and imatinib-resistant CML cells in a dose-dependent manner, and hence, the use of ponatinib for the treatment of TKI-resistant CML patients may be an effective treatment approach in the clinic. More importantly, these results showed that FTIR spectroscopy can detect drug-induced physiological changes in cancer drug resistance.
A methodology to evaluate the sensory properties of instant hot chocolate beverage with different fat contents: multi-criteria decision-making techniques approach
(SPRINGERONE NEW YORK PLAZA, SUITE 4600 , NEW YORK, NY 10004, UNITED STATES, 2016) Dogan, Mahmut; Aslan, Duygu; Aktar, Tugba; Sarac, Meryem Goksel; 0000-0001-8417-868X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Aktar, Tugba
The multi-criteria decision-making techniques are applied in many areas such as integrated manufacturing systems, evaluation of technology investment, water and agriculture management and energy planning. However, there are very few studies in the field of food. In this work, the selection of optimum fat content in the model beverage of instant hot chocolate beverage was evaluated based on sensory analyses by performing multi-criteria decision techniques (analytic hierarchy process, simple additive weighting, technique for order preference by similarity to ideal solution and elimination et choixtraduisant la realite-elimination and choice translating reality). The wettability, solubility, bulk density, soluble solids, pH, color values, and rheological and sensory properties of the nine samples were evaluated. According to the results of multi-criteria decision techniques, sample S2 which had a relatively high amount of fat content was the most preferred beverage among the samples. Study showed that the use of different fat contents of milk and cocoa powder positively affected the rheological parameters and preferences of consumers. The findings may be considered to improve dairy and cocoa-based products formulation by the food industry.

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