PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
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Article Citation - WoS: 19Citation - Scopus: 22Absence of Superoxide Dismutase Activity Causes Nuclear Dna Fragmentation During the Aging Process(Academic Press Inc., 2014-02) Muid, Khandaker Ashfaqul; Karakaya, Hüseyin Çaglar; Koç, AhmetSuperoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1Δ and sod2Δ strains. However, ccs1Δ mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1Δ, sod2Δ, and ccs1Δ mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.Article Citation - WoS: 4Citation - Scopus: 7Adding Pneumatic Compression Therapy in Lower Extremity Lymphedema Increases Compliance of Treatment, While Decreasing the Infection Rate(Mary Ann Liebert, Inc, 2022) Soran, Atilla; Toktaş, Osman; Grassi, Ariel; Sezgin, EfeBackground: Lymphedema (LE) is a chronic condition that requires lifelong treatment. Although pneumatic compression therapy (PCT) is one treatment option, current algorithms consider it as an adjunct to standard LE. The purpose of this study is to evaluate the importance of adapting PCT for lower extremity LE (LEL) in relation to patient compliance and rate of infection. Materials and Methods: Patients diagnosed with LEL were followed prospectively. Patient demographics, comorbidities, treatment modality, compliance, infection due to LE, and hospitalization were recorded. LEL patients with no-PCT were also recorded in the same time period to evaluate the treatment compliance and the need for physical therapy visits. The no-PCT group received the standard LE care, whereas the PCT group received the standard LE care plus a new-generation pneumatic compression device. Results: A total of 69 patients were enrolled in this study. The PCT group had 50 patients and no-PCT group had 19 patients. The PCT group had median 58.5 months of LE symptoms, while non-PCT patients had median 23 months of LE symptoms (p = 0.11). Infection rates decreased by 32% and hospitalizations due to infection decreased by 14% after PCT treatment had been initiated. Physical therapy needs decreased by 24% after PCT use. At median 18 months, follow-up compliance for PCT was 84%, but compliance for manual lymphatic drainage was almost half (53%) in no-PCT group. Conclusions: PCT leads to a decrease in infection rate, hospital admissions, and physical therapy (PT) visits in clinically significant LEL. Although there is no cost calculation in this study, it can be correlated to significant cost savings due to a reduction of infection and hospitalization and the need for PT visits. Adoption of PCT offers a superior value proposition to not only patients but also the health care system. Cost analysis should be followed.Article Citation - WoS: 7Citation - Scopus: 10Adjuvant Potency of Astragaloside Vii Embedded Cholesterol Nanoparticles for H3n2 Influenza Vaccine(TÜBİTAK, 2020) Genç, Rukan; Yakuboğulları, Nilgün; Nalbantsoy, Ayşe; Coven, Fethiye; Bedir, ErdalAdjuvants are substances that increase the immune response to a given antigen. In the development of novel vaccine adjuvants/systems, saponins are one of the most attractive molecules due to their altered immunomodulatory activities. In this study, we tried to develop PEG (polyethylene glycol)/cholesterol-based lipid nanoparticles (LNPs) to deliver the Astragaloside VII (AST-VII) and potentiate adjuvant properties of AST-VII for the influenza vaccine. In the formation of PEG/cholesterol/AST-VII-based LNPs (PEG300: Chol-AST-VII LNPs), 3 different primary solvents (acetone, ethanol, and chloroform) were evaluated, employing their effects on hydrodynamic particle size, distribution, surface chemistry, and colloidal stability. Prepared nanoparticles were simply admixtured with inactivated influenza antigen (H3N2) and applied to PMA (phorbol 12-myristate 13-acetate)-ionomycin treated human whole blood to evaluate their cytokine release profile. PEG300: Chol-AST-VII LNPs (80.2 +/- 7.7 nm) were obtained using chloroform as a desolvation agent. Co-treatment of PMA-ionomycin with AST-VII and PEG300: Chol-AST-VII LNPs significantly increased the levels of IL-2 and IFN-gamma, compared to PMA-ionomycin alone. In the presence of H3N2, AST-VII was able to augment IL-17A, while PEG300: Chol-AST-VII LNPs stimulated the production of IFN-gamma. Hemolysis was only observed in PEG300: Chol-AST-VII LNPs (250 mu g/mL) treatment. AST-VII and AST-VII-integrated LNPs could be used as efficacious adjuvants for an inactivated H3N2 vaccine in vitro, and cytokine response through Th1/Th17 route was reported.Article Citation - WoS: 9Citation - Scopus: 12Analysis of European Hazelnut (corylus Avellana) Reveals Loci for Cultivar Improvement and the Effects of Domestication and Selection on Nut and Kernel Traits(Springer Verlag, 2019) Frary, Amy; Öztürk, Süleyman Can; Balık, Hüseyin İrfan; Kayalak Balık, Selda; Kızılcı, Gökhan; Doğanlar, Sami; Frary, AnneTurkey is a rich source of European hazelnut (Corylus avellana) germplasm with nearly 400 accessions in the national collection. This genetic material encompasses cultivars, landraces and wild genotypes which were characterized for 12 nut and 13 kernel traits over 2years in the 1990s. Analysis of these attributes revealed both the positive and negative impacts that human selection and breeding have had on hazelnut. Thus, while selection has resulted in larger nuts and kernels, cultivars have fewer nuts per cluster and kernels with larger internal cavities. Breeding has also resulted in a propensity for cultivars to have higher proportions of double kernels and empty nuts, two traits which reduce quality and yield. In addition, it is clear that while selection has successfully increased hazelnut fat content it has not impacted overall flavor, a much more complex trait. The nut and kernel phenotypic data were combined with genotypic data from 406 simple sequence repeat marker alleles for association mapping of the quantitative trait loci (QTL) for the traits. A total of 78 loci were detected in the population with the highest proportions for nut (24%) and kernel (26%) appearance parameters followed by quality (19%), shell thickness (16%) and yield-related (15%) traits. It is hoped that some of the identified QTL will be useful for future breeding of hazelnut for improved nut and kernel yield and quality.Article Citation - WoS: 20Citation - Scopus: 23Apoptotic Effects of Non-Edible Parts of Punica Granatum on Human Multiple Myeloma Cells(SAGE Publications Inc., 2016) Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S.; Rummun, Nawraj; Baran, YusufMultiple 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.Article Citation - WoS: 19Apoptotic Effects of Resveratrol, a Grape Polyphenol, on Imatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells(International Institute of Anticancer Research, 2012-07) Can, Geylani; Çakır, Zeynep; Kartal, Melis; Gündüz, Ufuk; Baran, YusufTo examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). The concentrations of resveratrol that inhibited cell growth by 50% (IC(50)) were calculated as 85 and 122 μM for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 μM resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA-3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA-3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%- and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 μM resveratrol. Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.Article Citation - Scopus: 26Apoptotic Effects of Resveratrol, a Grape Polyphenol, Onimatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells(2012) Can,G.; Cakir,Z.; Kartal,M.; Gunduz,U.; Baran,Y.Aim: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Materials and Methods: Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5- carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). Results: The concentrations of resveratrol that inhibited cell growth by 50% ( IC50) were calculated as 85 and 122 μM for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 μM resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA-3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA- 3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%-and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 μM resveratrol. Conclusion: Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.Article Citation - WoS: 18Citation - Scopus: 19Assessment of Chronological Lifespan Dependent Molecular Damages in Yeast Lacking Mitochondrial Antioxidant Genes(Elsevier Ltd., 2010-09) Demir, Ayşe Banu; Koç, AhmetThe free radical theory of aging states that oxidative damage to biomolecules causes aging and that antioxidants neutralize free radicals and thus decelerate aging. Mitochondria produce most of the reactive oxygen species, but at the same time have many antioxidant enzymes providing protection from these oxidants. Expecting that cells without mitochondrial antioxidant genes would accumulate higher levels of oxidative damage and, therefore, will have a shorter lifespan, we analyzed oxidative damages to biomolecules in young and chronologically aged mutants lacking the mitochondrial antioxidant genes: G. RX2, CCP1, SOD1, GLO4, TRR2, TRX3, CCS1, SOD2, GRX5, and PRX1. Among these mutants, ccp1Δ, trx3Δ, grx5Δ, prx1Δ, mutants were sensitive to diamide, and ccs1Δ and sod2Δ were sensitive to both diamide and menadione. Most of the mutants were less viable in stationary phase. Chronologically aged cells produced higher amount of superoxide radical and accumulated higher levels of oxidative damages. Even though our results support the findings that old cells harbor higher amount of molecular damages, no significant difference was observed between wild type and mutant cells in terms of their damage content. © 2010 Elsevier Inc.Article Citation - WoS: 34Citation - Scopus: 41Autologous Rabbit Adipose Tissue-Derived Mesenchymal Stromal Cells for the Treatment of Bone Injuries With Distraction Osteogenesis(Elsevier Ltd., 2013) Sunay, Özgür; Can, Geylani; Çakır, Zeynep; Denek, Ziya; Kozanoglu, İlknur; Erbil, Güven; Yılmaz, Mustafa; Baran, YusufBackground aims: Adipose tissue-derived mesenchymal stromal cells (MSCs) have a higher capacity for proliferation and differentiation compared with other cell lineages. Although distraction osteogenesis is the most important therapy for treating bone defects, this treatment is restricted in many situations. The aim of this study was to examine the therapeutic potential of adipose tissue-derived MSCs and osteoblasts differentiated from adipose tissue-derived MSCs in the treatment of bone defects. Methods: Bone defects were produced in the tibias of New Zealand rabbits that had previously undergone adipose tissue extraction. Tibial osteotomy was performed, and a distractor was placed on the right leg of the rabbits. The rabbits were placed in control (group I), stem cell (group II) and osteoblast-differentiated stem cell (group III) treatment groups. The rabbits were sacrificed, and the defect area was evaluated by radiologic, biomechanical and histopathologic tests to examine the therapeutic effects of adipose tissue-derived MSCs. Results: Radiologic analyses revealed that callus density and the ossification rate increased in group III compared with group I and group II. In biomechanical tests, the highest ossification rate was observed in group III. Histopathologic studies showed that the quality of newly formed bone and the number of cells active in bone formation were significantly higher in group III rabbits compared with group I and group II rabbits. Conclusions: These data reveal that osteoblasts differentiated from adipose tissue-derived MSCs shorten the consolidation period of distraction osteogenesis. Stem cells could be used as an effective treatment for bone defects.Article Citation - WoS: 16Citation - Scopus: 20Automated Labelling of Cancer Textures in Colorectal Histopathology Slides Using Quasi-Supervised Learning(Elsevier Ltd., 2013-04) Önder, Devrim; Sarıoğlu, Sülen; Karaçalı, BilgeQuasi-supervised learning is a statistical learning algorithm that contrasts two datasets by computing estimate for the posterior probability of each sample in either dataset. This method has not been applied to histopathological images before. The purpose of this study is to evaluate the performance of the method to identify colorectal tissues with or without adenocarcinoma. Light microscopic digital images from histopathological sections were obtained from 30 colorectal radical surgery materials including adenocarcinoma and non-neoplastic regions. The texture features were extracted by using local histograms and co-occurrence matrices. The quasi-supervised learning algorithm operates on two datasets, one containing samples of normal tissues labelled only indirectly, and the other containing an unlabeled collection of samples of both normal and cancer tissues. As such, the algorithm eliminates the need for manually labelled samples of normal and cancer tissues for conventional supervised learning and significantly reduces the expert intervention. Several texture feature vector datasets corresponding to different extraction parameters were tested within the proposed framework. The Independent Component Analysis dimensionality reduction approach was also identified as the one improving the labelling performance evaluated in this series. In this series, the proposed method was applied to the dataset of 22,080 vectors with reduced dimensionality 119 from 132. Regions containing cancer tissue could be identified accurately having false and true positive rates up to 19% and 88% respectively without using manually labelled ground-truth datasets in a quasi-supervised strategy. The resulting labelling performances were compared to that of a conventional powerful supervised classifier using manually labelled ground-truth data. The supervised classifier results were calculated as 3.5% and 95% for the same case. The results in this series in comparison with the benchmark classifier, suggest that quasi-supervised image texture labelling may be a useful method in the analysis and classification of pathological slides but further study is required to improve the results.Article Citation - WoS: 6Citation - Scopus: 6Bioactive Sphingolipids in Response To Chemotherapy: a Scope on Leukemias(Bentham Science Publishers B.V., 2011) Ekiz, Hüseyin Atakan; Baran, YusufSphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias. © 2011 Bentham Science Publishers Ltd.Article Citation - WoS: 5Citation - Scopus: 7A Biodesign Approach To Obtain High Yields of Biosimilars by Anti-Apoptotic Cell Engineering: A Case Study To Increase the Production Yield of Anti-Tnf Alpha Producing Recombinant Cho Cells(Humana Press, 2018-01) Gülce İz, Sultan; Anıl İnevi, Müge; Sağlam Metiner, Pelin; Ayyıldız Tamiş, Duygu; Kisbet, NazlıRecent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid with polyethylenimine (PEI) reagent at the ratio of 1:6 (DNA:PEI). In conclusion, the anti-apoptotic efficacy of the Bcl-xL expressing plasmid in humanized anti-TNF-α MAb producing stable CHO cells is compatible with curative effect for high efficiency recombinant protein production. Thus, this model can be used for large-scale production of biosimilars through transient Bcl-xL gene expression as a cost-effective method.Article Citation - WoS: 11Citation - Scopus: 16Bisphosphonate Treatment and Radiotherapy in Metastatic Breast Cancer(Humana Press, 2008-09) Ural, Ali Uğur; Avcu, Ferit; Baran, YusufPatients with advanced breast cancer frequently develop metastasis to bone. Bone metastasis results in intractable pain and high risk of pathologic fractures due to osteolysis. The treatment of breast cancer patients with bone metastases requires a multidisciplinary approach. Radiotherapy is an established treatment for metastatic bone pain. It may be delivered either as a localized low dose treatment for localized bone pain or systemically for more widespread symptoms. Bisphosphonates have been shown to reduce morbidity and bone pain from bone metastases when given to patients with metastatic bone disease. In vivo studies indicate that early bisphosphonates administration in combination with radiotherapy improves remineralization and restabilization of osteolytic bone metastases in animal tumor models. This review focused on a brief discussion about biology of bone metastases, the effects of radiotherapy and bisphosphonate therapy, and possible mechanisms of combination therapy in metastatic breast cancer patients.Article Citation - WoS: 22Citation - Scopus: 28Caffeic Acid Phenethyl Ester Triggers Apoptosis Through Induction of Loss of Mitochondrial Membrane Potential in Ccrf-Cem Cells(Springer Verlag, 2011) Avcı, Çığır Biray; Gündüz, Cumhur; Baran, Yusuf; Şahin, Fahri; Yılmaz, Sunde; Doğan, Zeynep Özlem; Saydam, GürayPurpose CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death. Methods Trypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope. Results We detected the time-and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells. Conclusion This in vitro data by being supported with clinical data may open the way of the potential use of CAPE for the treatment of leukemia.Review Citation - WoS: 19Citation - Scopus: 22Cancer Stem Cells in Tumor Modeling: Challenges and Future Directions(John Wiley and Sons Inc, 2021) Dogan,E.; Kisim,A.; Bati-Ayaz,G.; Kubicek,G.J.; Pesen-Okvur,D.; Miri,A.K.Microfluidic tumors-on-chips models have revolutionized anticancer therapeutic research by creating an ideal microenvironment for cancer cells. The tumor microenvironment (TME) includes various cell types and cancer stem cells (CSCs), which are postulated to regulate the growth, invasion, and migratory behavior of tumor cells. In this review, the biological niches of the TME and cancer cell behavior focusing on the behavior of CSCs are summarized. Conventional cancer models such as 3D cultures and organoid models are reviewed. Opportunities for the incorporation of CSCs with tumors-on-chips are then discussed for creating tumor invasion models. Such models will represent a paradigm shift in the cancer community by allowing oncologists and clinicians to predict better which cancer patients will benefit from chemotherapy treatments. © 2021 The Authors. Advanced NanoBiomed Research published by Wiley-VCH GmbH.Article Citation - WoS: 1Citation - Scopus: 1Canine Oocyte Nuclear Maturation With Nano-Ozone (nzs) Supplementation: the Alterations of Antioxidant, and Oxidant Status and Cdk1, Cyclin B1 Expressions(Elsevier, 2024) Bari, O.; Sabanci, A. U.; Avci, G.; Bozkurt, B.; Ustuner, B.; Denk, B.; Ozalp, G. R.This study aims to evaluate the effects of nano-ozone solution (NZS) on canine oocyte nuclear maturation, associated with the alterations of antioxidant and oxidant status and cyclin-dependent kinase 1 (CDK1), cyclin B1 gene expressions. Oocytes were cultured in four distinct concentrations of NZS (0.5, 1, 2, and 5 mu g/mL) and parthenogenetically activated. The rates of oocytes arrested at the Germinal Vesicle (GV), Germinal Vesicle Breakdown (GVBD), Metaphase I (MI), and Metaphase II (MII) stages were statistically different among groups (P < 0.05). The oocytes cultured in 1 g/mL NZS yielded the best oocyte maturation rate at the MI and MII stages; however, the lowest maturation and high degeneration rates were observed in Group E. The measurements of Malondialdehyde (MDA), reduced Glutathione (GSH), Superoxide Dismutase (SOD), and Ferric Reducing/Antioxidant Power assay (FRAP) were performed from IVM culture media. No statistical difference was observed in SOD and MDA results (P > 0.05). GSH levels were statistically significant between Group AGroup E (p = 0.003), Group B-Group E (p = 0.045), and Group E-Group D (p = 0.021). The culture media in Group D and Group E had high FRAP concentrations and significantly differed between groups (P < 0.05). CDK1, and cyclin B1 genes, which are subunits of maturation-promoting factor (MPF), are upregulated in Group B and Group C, while are downregulated in oocytes of Group E. This study showed that low, controlled doses of NZS (1 g/mL) supplementation could improve the meiotic competence of canine oocytes and lead to positive response in expressions of CDK1 and cyclin B1 on the gene level.Article Citation - WoS: 2Citation - Scopus: 2Changes in Protein Profiles of Multiple Myeloma Cells in Response To Bortezomib(Informa Healthcare, 2013-05) Turan, Taylan; Şanlı Mohamed, Gülşah; Baran, YusufThe objective of this study was to determine the changes in protein profiles of U-266 multiple myeloma cells in response to bortezomib. Bortezomib inhibited cell proliferation and increased the loss of mitochondrial membrane potential and caspase-3 activity in a dose-dependent manner. DECODON Delta2D Version 4.3 software demonstrated 37 differentially expressed protein spots: five proteins were newly formed, 10 proteins were lost, 12 proteins were up-regulated and 10 proteins were down-regulated in bortezomib-treated cells as compared to untreated cells. Some of the identified proteins after mass spectrometric analysis were as follows: apoptosis regulatory protein Siva (newly formed), caspase recruitment domain-containing protein 14 (lost), Ras-related protein Rab-25 (up-regulated), nuclear factor κB (NF-κB) p105 subunit (down-regulated). In summary, differentially expressed proteins of MM U-266 cells in response to bortezomib were analyzed and identified. The data obtained from this study may indicate the use of bortezomib for the treatment of various diseases.Article Citation - WoS: 6Citation - Scopus: 5Charmm Force Field Generation for a Cationic Thiophene Oligomer With Fftk(Springer, 2021) Kıbrıs, Erman; Nalıncı Barbak, Nehir; Elmacı Irmak, NuranIn the present work, CHARMM force field parameters are generated for a cationic oligomer of N, N, N-trimethyl-3-(4-methylthiophen-3-yl) oxy) propan-1-aminium) which has the potential for sensing biological molecules such as nucleic acids, nucleobases. We have used ffTK (force field tool kit) to obtain potential parameters. MD simulations are performed for 20-mer and its complexes with AMP and ATP. The simulation results are analyzed to see the number of phosphates in adenosine nucleotides effects on the structure of the backbone of oligomer. The UV-VIS calculations for the conformers which possess the most probable radius of gyration are carried out and compared to the experimental ones to validate the generated force field. Recent studies have shown that, biologically important anions (ATP, AMP, vb.) change the spectroscopic properties of cationic polythiophenes (CPT) in the solutions. This work aims to generate CHARMM compatible force field parameters for a CPT to explain experimental studies. The type of interactions will be investigated deeply to lead new biosensor studies by examining the formation and the structure of complexes that consist of a oligothiophene and biological molecules, ATP, AMP by molecular dynamic simulations.Article Citation - WoS: 7Citation - Scopus: 8Checkpoint Deficient Rad53-11 Yeast Cannot Accumulate Dntps in Response To Dna Damage(Elsevier Ltd., 2007) Koç, Ahmet; Merrill, Gary F.Deoxyribonucleotide pools are maintained at levels that support efficient and yet accurate DNA replication and repair. Rad53 is part of a protein kinase regulatory cascade that, conceptually, promotes dNTP accumulation in four ways: (1) it activates the transcription of ribonucleotide reductase subunits by inhibiting the Crt1 repressor; (2) it plays a role in relocalization of ribonucleotide reductase subunits RNR2 and RNR4 from nucleus to cytoplasm; (3) it antagonizes the action of Sml1, a protein that binds and inhibits ribonucleotide reductase; and (4) it blocks cell-cycle progression in response to DNA damage, thus preventing dNTP consumption through replication forks. Although several lines of evidence support the above modes of Rad53 action, an effect of a rad53 mutation on dNTP levels has not been directly demonstrated. In fact, in a previous study, a rad53-11 mutation did not result in lower dNTP levels in asynchronous cells or in synchronized cells that entered the S-phase in the presence of the RNR inhibitor hydroxyurea. These anomalies prompted us to investigate whether the rad53-11 mutation affected dNTP levels in cells exposed to a DNA-damaging dose of ethylmethyl sulfonate (EMS). Although dNTP levels increased by 2- to 3-fold in EMS treated wild-type cells, rad53-11 cells showed no such change. Thus, the results indicate that Rad53 checkpoint function is not required for dNTP pool maintenance in normally growing cells, but is required for dNTP pool expansion in cells exposed to DNA-damaging agents.Article Citation - WoS: 3Citation - Scopus: 3Cloning, Expression, and Activity Analysis of Human Cathepsin C in the Yeast Pichia Pastoris(TUBITAK, 2017) Dağlıoğlu, CenkThe yeast Pichia pastoris expression system was investigated for the production of human cathepsin C (CatC) recombinant protein. The full-length CatC cDNA, corresponding to amino acids 12-475, was synthesized from interleukin-2 (IL-2) stimulated human peripheral blood mononuclear cells and subcloned in the pGEM-T cloning vector. After confirming the DNA sequence of the insert, the gene was cloned into the pPICZαA expression vector under the control of the methanol-inducible alcohol oxidase (AOX1) promoter and transformed to P. pastoris X-33 cells. The expressed protein was secreted into the culture medium through the α-factor mating signal sequence of the expression vector. Analysis of the culture supernatant revealed that the recombinant human CatC was secreted as a 58-kDa molecule, indicating that human CatC was accumulated in the culture supernatant as proform composed of the residual propart, the activation peptide, and the heavy and light chains. Extracellular recombinant proCatC was further activated by cysteine endoprotease papain in vitro and its activity was confirmed by assays using a synthetic substrate.
