Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 4A Src/Abl Kinase Inhibitor, Bosutinib, Downregulates and Inhibits Parp Enzyme and Sensitizes Cells To the DNA Damaging Agents(Türk Biyokimya Derneği, 2018) Kırmızıbayrak, Petek Ballar; İlhan, Recep; Yılmaz, Sinem; Günal, Selin; Tepedelen, Burcu ErbaykentBackground: Poly(ADP-ribosyl)ation (PARylation) catalyzed mainly by PARP1 is a highly regulated posttranslational modification associated with several pathways in cellular physiology and genotoxic deoxyribonucleic acid (DNA) damage response. PAR polymers and PARP enzyme function in DNA integrity maintenance and several PARP inhibitors have entered clinical phase studies for cancer therapies. Material and methods: The effect of bosutinib, a dual Src/Abl kinase inhibitor, on PARylation was fluorometrically measured. The cytotoxic and chemosensitizing effects were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of DNA repair proteins and PARP enzyme were examined by immunoblotting. Results: In this study, bosutinib is characterized as a novel PARP inhibitor. Bosutinib inhibited oxidative stress-induced cellular PARylation and nuclear foci formation by downregulating PARP1 levels. Bosutinib was found to be more cytotoxic on Capan1 cells with BRCA2 mutation. Furthermore by acting as a chemosensitizer, bosutinib enhanced the cytotoxicity of doxorubicin (DOXO) and etoposide (ETP) by decreasing phosphorylation of DNA repair enzymes checkpoint kinase 1 (Chk1) and ataxia-telangiectasia mutated (ATM). Conclusion: By inhibition of both PARP and DNA damage checkpoint kinases, bosutinib increased the phospho-H2AX levels, an early indicator of DNA double strand breaks.Conference Object Deep Convolutional Neural Networks for Viability Analysis Directly From Cell Holograms Captured Using Lensless Holographic Microscopy(The Chemical and Biological Microsystems Society (CBMS), 2019) Delikoyun, Kerem; Çine, Ersin; Anıl İnevi, Müge; Özçivici, Engin; Özuysal, Mustafa; Tekin, Hüseyin CumhurCell viability analysis is one of the most widely used protocols in the fields of biomedical sciences. Traditional methods are prone to human error and require high-cost and bulky instrumentations. Lensless digital inline holographic microscopy (LDIHM) offers low-cost and high resolution imaging. However, recorded holograms should be digitally reconstructed to obtain real images, which requires intense computational work. We introduce a deep transfer learning-based cell viability classification method that directly processes the hologram without reconstruction. This new model is only trained once and viability of each cell can be predicted from its hologram. © 2019 CBMS-0001.Conference Object Citation - Scopus: 2Magnetic Levitation-Based Protein Detection Using Lensless Digital Inline Holographic Microscopy(The Chemical and Biological Microsystems Society (CBMS), 2019) Yaman, Sena; Delikoyun, Kerem; Tekin, Hüseyin CumhurWe present a portable protein detection platform based on magnetic levitation principle integrated with a lensless imaging system. In the platform, polymer microspheres are used to capture selectively target proteins and magnetic nanoparticle labels. The imaging system monitors the levitation height change of polymer microspheres with respect to the presence of target protein on their surfaces. This system enables the detection of target proteins down to ng/mL levels in a short time. © 2019 CBMS-0001.Article Citation - WoS: 13Citation - Scopus: 15Cytotoxic Tolerance of Healthy and Cancerous Bone Cells To Anti-Microbial Phenolic Compounds Depend on Culture Conditions(Humana Press, 2019) Karadaş, Özge; Meşe, Gülistan; Özçivici, EnginCarnosol and carnosic acid are polyphenolic compounds found in rosemary and sage with known anti-oxidant, anti-inflammatory, and anti-microbial properties. Here, we addressed the potential use of carnosol and carnosic acid for in vitro bone tissue engineering applications, specifically depending on their cytotoxic effects on bone marrow stromal and stem cells, and osteosarcoma cells in monolayer and 3D cultures. Carnosol and carnosic acid displayed a bacteriostatic effect on Gram-positive bacteria, especially on S. aureus. The viability results indicated that bone marrow stromal cells and bone marrow stem cells were more tolerant to the presence of carnosol compared to osteosarcoma cells. 3D culture conditions increased this tolerance further for healthy cells, while not affecting the cytotoxic potential of carnosol for osteosarcoma cells. Carnosic acid was found to be more cytotoxic for all cell types used in the study. Results suggest that phenolic compounds might have potential use as anti-microbial and anti-carcinogenic agents for bone tissue engineering with further optimization for controlled release.Conference Object Citation - WoS: 1Microbial Transformation of Ruscogenins by Cunninghamella Blakesleeana(Georg Thieme Verlag, 2016) Özçınar, Özge; Tağ, Özgür; Kıvçak, Bijen; Bedir, ErdalThe natural product drug discovery process involves the isolation of new molecules from natural sources, investigation of their biological activities, and semi-synthesis of more active analogs. Microbial transformation plays a vital role in the preparation of new oxygenated derivatives, and has frequently been used as microbial model of mammalian drug metabolism [1,2]. It has been proved that the hydroxylation of steroidal compounds is catalyzed by cytochrome P450 monoxygenase systems, which exist in all eucaryotic microorganisms [3]. Cunninghamella genus has been widely used in transformation of steroids [4,5]. The major steroidal saponins of Ruscus aculeatus, ruscogenin and neoruscogenin, has strong anti-inflammatory activities, acts as an anti-elastase, and decreases capillary permeability [6]. In the present study microbial transformation of Neoruscogenin:Ruscogenin (78:22) mixture by Cunninghamella blakesleeana fungus afforded three new compounds. The structures were elucidated by LC-MS, 1D- and 2D NMR analyses as shown below. Mainly oxydation products were obtained from neoruscogenin by C. blakesleana. As far as can be ascertained from the literature, this is the first microbial transformation study performed on neoruscogenin.Conference Object Role of Connexin 32 on Gap Junctions in Breast Cancer Cells With Varying Metastatic Potential.(American Society for Cell Biology, 2017) Uğur, Deniz; Özçivici, Engin; Meşe, Gülistan[No abstract available]Conference Object Investigating the Role of Connexin 32 in Cell Cycle, Cell Viability and Epithelial To Mesenchymal Transition of Normal Breast and Breast Cancer Cells(American Society for Cell Biology, 2017) Adak, Aslı; Özçivici, Engin; Meşe, Gülistan[No abstract available]Conference Object Bioassay Guided Isolation of Naphthoquinones From Onosma Aksoyii, Investigation of Their Cytotoxic Properties(Georg Thieme Verlag, 2019) Kul, Demet; Karakoyun, Çiğdem; Yılmaz, Sinem; Pirhan, Ademi Fahri; Bedir, ErdalThe genus Onosma L. (Boraginaceae) includes about 230 species, distributed mainly in the Mediterranean region and Central Asia. Major constituents of Onosma species are alkaloids, naphthoquinones, polyphenols, phytosterols, terpenoids and fatty acids [1], [2]. Naphthoquinones are naturally widespread secondary metabolites deriving from some higher plants, fungi and bacteria. They exhibit significant biological activities such as cytotoxicity, antimalarial, antibacterial, antifungal and wound healing [2], [3]. Recently naphthoquinone derivatives have also been recognized as potent topoisomerase inhibitors [4].Conference Object Semi-Synthetic Studies on Astragaloside Vii and Immunomodulatory Activities of the Derivatives(Georg Thieme Verlag, 2019) Yakuboğulları, Nilgün; Sağ, Duygu; Çağır, Ali; Bedir, ErdalAdjuvants have been used in vaccine sector since 1920s to increase the immunogenicity of antigens, reduce the dosage and minimize frequency of immunizations [1]. The use of saponins as adjuvant in the prophylactic/therapeutic human and veterinary vaccines, and investigation of their immunomodulatory activities have gained importance in recent years [2],[3]. Astragaloside VII (AST VII), a triterpenoid saponin isolated from Astragalus species, stimulates Th1 mediated immune response, antigen-specific antibody response and splenocyte proliferation.Conference Object A Validated Uhplc-Cad Method for Quantitative Determination of Astragaloside Vii(Georg Thieme Verlag, 2019) Kurt, Mustafa Ünver; Tağ, Özgür; Bedir, ErdalAstragaloside VII (AST VII) [Fig 1], the first tridesmosidic saponin identified in nature [1], possesses potent immunostimulatory/adjuvant effects [2]. Based on the promising adjuvant properties comparable to current adjuvants (i.e. Alum and QS-21), our team has decided to carry out further studies on AST VII including semi-synthesis studies to discover and develop new human/animal vaccine adjuvants [2]–[5]. Since more than 450 Astragalus species grow wildly in Turkish flora, one of the first challenges of this adjuvant development project is to examine these species by efficient analytical methods to find AST VII rich plant materials and select the rich species for possible cultivation and/or pilot production studies. Thus, aim of this study was to develop a UHPLC method coupled with the Charged Aerosol Detector (CAD) in order to determine AST VII content simultaneously, precisely and sensitively in Astragalus samples. A fifteen minutes method was developed using C18 (100 mm x 4 mm x 3 µm) column, eluting with gradient Water:Acetonitrile mixtures at 0.75 mL/min flow rate. The linear regression analysis of calibration plots showed good linear relationship with r 2=0.9995 in concentrations ranging from 52 to 208 μg/mL. The method was validated for its calibration curve, specificity, precision and robustness. The recovery was found to be in the range of 98.17 to 101.86%. As a conclusion, for the first time, a UHPLC method was validated to quantify AST VII utilizing CAD for its detection.