Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Anthraquinones and Macrocyclic Lactones From Endophytic Fungus Penicillium Roseopurpureum and Their Bioactivities(ACG Publications, 2024) Dizmen,B.; Üner,G.; Küçüksolak,M.; Gören,A.C.; Kırmızıbayrak,P.B.; Bedir,E.Endophytic fungi colonize the internal and distinct tissues of the host plants. In recent years, there has been growing interest in endophytic fungi as valuable sources for drug discovery based on their rich metabolic profiles consisting of novel and bioactive compounds. Accordingly, our preliminary study demonstrated that an endophyte, namely Penicillium roseopurpureum isolated from Astragalus angustifolius, had high chemical diversity with an antiproliferative effect. Herein, fermentation of P. roseopurpureum resulted in the production of five new anthraquinone-type compounds (2, 4, 6, 7, 8) together with several known compounds [11-methoxycurvularin (1: epimeric mixture of 1a and 1b), carviolin (3), 11-hydroxycurvularin (5: diastereoisomeric mixture of 5a and 5b) and 1-O-methylemodin (9)]. The structures of the new compounds were established by NMR spectroscopy and HR-MS analysis. Cytotoxicity studies demonstrated that none of the compounds except for 1 and 5 had antiproliferative activity against prostate cancer cell lines. Interestingly, 1 was found as cytotoxic, whereas 5 exhibited cytostatic properties. Also, 7-AAD/Annexin V staining supported these results by showing that 1 caused cellular death, while 5 did not show any increase in dead cell content in comparison to the control. Lastly, cell cycle analysis showed that compounds had distinctive cell cycle arrest patterns. © 2024 ACG Publications.Article Citation - WoS: 7Citation - Scopus: 8Ascorbic Acid Enhances the Metabolic Activity, Growth and Collagen Production of Human Dermal Fibroblasts Growing in Three-Dimensional (3D) Culture(Gazi Üniversitesi, 2023) Dikici, SerkanTissue engineering (TE) enables the development of functional synthetic substitutes to be replaced with damaged tissues and organs instead of the use of auto or allografts. A wide range of biomaterials is currently in use as TE scaffolds. Among these materials, naturally sourced ones are favorable due to being highly biocompatible and supporting cell growth and function, whereas synthetic ones are advantageous because of the high tunability on mechanical and physical properties as well as being easy to process. Alongside the advantages of synthetic polymers, they mostly show hydrophobic behavior that limits biomaterial-cell interaction and, consequently, the functioning of the developed TE constructs. In this study, we assessed the impact of L-Ascorbic acid 2-phosphate (AA2P) on improving the culture conditions of human dermal fibroblasts (HDFs) growing on a three-dimensional (3D) scaffold made of polycaprolactone (PCL) using emulsion templating. Our results demonstrated that AA2P enhances the metabolic activity and growth of HDFs as well as collagen deposition by them when supplemented in their growth medium at 50 µg/mL concentration. It showed a great potential to be used as a growth medium supplement to circumvent the disadvantages of culturing human cells on a synthetic biomaterial that is not favored in default. AA2P's potential to improve cell growth and collagen deposition may prove an effective way to culture human cells on 3D PCL PolyHIPE scaffolds for various TE applications.Article Citation - WoS: 6Citation - Scopus: 6Diagnosis of Ruminant Viral Diseases With Loop-Mediated Isothermal Amplification(Springer, 2023) Ayaz Kök, Sanem; Üstün, Selcen; Taşkent, HümeyraInfectious diseases in livestock industry are major problems for animal health, food safety, and the economy. Zoonotic diseases from farm animals are significant threat to human population as well. These are notifiable diseases listed by the World Organization for Animal Health (OIE). Rapid diagnostic methods can help keep infectious diseases under control in herds. Loop-mediated isothermal amplification (LAMP) is a simple and rapid nucleic acid amplification method that is studied widely for detection of many infectious diseases in the field. LAMP allows biosensing of target DNA or RNA under isothermal conditions with high specificity in a short period of time. An untrained user can analyze results based on color change or turbidity. Here we review LAMP assays to diagnose OIE notifiable ruminant viral diseases in literature highlighting properties of LAMP method considering what is expected from an efficient, field usable diagnostic test.Article Citation - WoS: 1Citation - Scopus: 1Expression Profile of Prostaglandin Enzymes in Cystic Endometrial Hyperplasia in Dogs: the Results of a Hypothesis in Clinical Trial(Kafkas Üniversitesi, 2023) Korlu, Yeşim; Yavaş, Özkan; Aktar, Ahmet; Bozkurt, Berkay; Özyiğit, Musa Özgür; Özalp, Gözde RabiaThe expressions of prostaglandin synthesis enzymes and estrogen, progesterone receptors in canine cystic endometrial hyperplasia (CEH) were reported in this manuscript. Uterine tissue samples were collected from bitches with CEH (n=5), CEH-P (Cystic endometrial hyperplasia-Pyometra) (n=5) and healthy-negative control group, CG (n=5). Immunohistochemistry was carried out for the estrogen (ER) and progesterone receptor (PR) detection. Shock-frozen samples were utilized in mRNA extraction and Real-Time PCR was performed. Gene expression of PTGS2/COX2, PTGES, PTGER4, PGFS, PTGFR and PGR were detected higher in the CEH group compared with CG. The PGFS and PTGFR (FP) mRNA expressions were significantly increased in CEH compared with other groups. Expression of progesterone receptor mRNA (PGR) was highest in CEH and statistically different from the CEH-P group (P<0.05). No PR immunostaining was observed. ER staining had been detected in endometrial glands, endometrial stoma and myometrium, however hyperplasic glands in propria mucosa had lower or no ER scores. Based on the results of this study, the high levels of prostaglandin enzymes and low ER scores in CEH could be a preliminary step for the next stages of severe differentiation of endometrium.Conference Object On-Chip 3d Cell Culture Platform for Tumor Modeling and Drug Screening(Mary Ann Liebert, 2022) Yıldırım, Özüm; Arslan Yıldız, AhuThree-dimensional (3D) cell culture allows cell-cell and cellmatrix interactions and provides more in vivo like models rather than 2D cell culture which cannot fully mimic native tissue. 3D cell culture on microfluidics allows formation of 3D structures that mimic the physiological and chemical microenvironment for cells[1]. These microfluidic platforms also downsize bench-top laboratory to a microchip, require miniaturized reagent, and are convenient for dynamic drug screening[2]. In this study, a microfluidic platform was designed which is housing a PLLCL scaffold fabricated by electrospinning methodology.Conference Object Biofabrication by Magnetic Levitational Assembly of Cells Into Defined 3d Cellular Structures(Mary Ann Liebert, 2022) Arslan Yıldız, AhuIn the field of tissue engineering 3D (three dimensional) cell culture studies have increased over the years since they are the closest models of real tissues. Compared to the 2D models, there is a big improvement on cell growth, morphology, differentiation, gene and protein expression when 3D system is utilized. Because of these advantages 3D cell culture is commonly used for tissue engineering, artificial organ technologies, regenerative medicine, drug development, drug screening and stem cell studies. Despite promising advances in these areas, there are still unmet needs to completely fulfill all requirements. Sophisticated tools, methodologies and materials are still required for further development in tissue engineering; especially for cellular assembly, single cell level control, easy control over biofabrication system, direct forward cellular imaging and analysis. Recently, magnetic levitation technology that overcomes most of the above mentioned problems, has been utilized for the formation of 3D cellular structures. Magnetic levitational assembly of cells provide rapid, simple, cost-effective 3D cell culture formation while ensuring scaffold-free microenvironment.Conference Object Development of New Generation Hydrocolloid Bio-Ink for 3d Bioprinting(Mary Ann Liebert, 2022) Arslan Yıldız, AhuBioprinting enables the production of 3-dimensional (3D) structures by combining bioinks, living cells, extracellular matrix (ECM) components, biochemical factors, proteins, drugs; and it has recently become one of the most promising techniques in the field of tissue engineering. The successful production of the 3D structure to be created by 3D bioprinting technology depends on the properties of the bio-ink to be used. Hydrogel/hydrocolloid materials used as bio-inks are developed using synthetic and natural polymers where they have the necessary rheological properties for printing, they also have biocompatibility, low toxicity and support for cell attachment. Natural hydrogels, which have the ability to mimic the extracellular matrix structure and function at a high rate, are highly preferred bioink materials for bioprinting applications.Conference Object Development of 3d Cardiac Models Via Magnetic Manipulation for Drug Screening Studies(Mary Ann Liebert, 2022) Önbaş, Rabia; Arslan Yıldız, AhuDrug discovery and development process comprise of preclinical and clinical phases that are very intensive, long, and expensive research phases. However, drug candidates can fail in clinical trials. Toxicity is the major reason that leads to about 30% of drug development failures. Recently, the withdrawal rate of drugs from the market was increased to 33.3%from5.1%due to cardiotoxicity. When the drug fails at phase I, the reasons are probably related to 2-dimensional (2D) cell culture studies that do not represent the real tissue physiology; therefore, they provide misdirected data about the efficacy and toxicity of drug.Article Citation - WoS: 5Citation - Scopus: 5Screening of Cytotoxicity and Dna Topoisomerase Iia Inhibitory Activity of Turkish Onosma Species(TÜBİTAK, 2021) Güzel, Özge; Duman, Seda; Yılmaz, Sinem; Karakoyun, Çiğdem; Kul, Demet; Pirhan, Ademi Fahri; Bedir, ErdalOnosma L., the largest genus of Boraginaceae, is represented by 105 species in Turkey with an endemism rate of 52%. Phytochemical studies indicate that Boraginaceae plants mainly comprise naphthoquinones with a wide range of biological activities including anticancer, antiinflammatory, wound healing, and antioxidant effects. However, few taxa of the genus Onosma have been investigated in detail for their bioactivities. Considering the high rate of endemism and an inadequate number of bioactivity screening studies in literature, we aimed to evaluate the cytotoxic effects and topoisomerase inhibitory activities of some Onosma species growing in southwestern Turkey. Here, we describe a comprehensive cytotoxic activity screening study on petroleum ether, dichloromethane, and methanol extracts of the roots of 20 identified and one unidentified Onosma taxa. The MTT cell viability assay has been performed to investigate the cytotoxicity of the extracts against seven cancer cell lines (MCF-7, HeLa > Hep G2, A549, Capan-1, HCC-1937, and DU-145) and a noncancerous cell line (MRC-5), while doxorubicin was served as a positive standard. The petroleum ether extracts of O. aksoyii Aytac&Turkmen, O. isaurica Boiss. and Heldr., O. taurica Pallas ex Willd. var. taurica and O. alborosea Fisch. & C.A. Mey subsp. alborosea var. alborosea were determined as the most active ones based on their IC50 values. DNA topoisomerase Ila inhibition assay was conducted on the petroleum ether and dichloromethane extracts of these four active species, and almost all tested extracts demonstrated strong inhibition on the enzyme at a concentration of 0.1 mg/mL. Our cytotoxicity screening results were consistent with the findings of the topoisomerase Ila inhibition test. This study advocates the significant role of Onosma species in the field of anticancer drug discovery.Article Citation - WoS: 6Citation - Scopus: 8A “sweet” Way To Increase the Metabolic Activity and Migratory Response of Cells Associated With Wound Healing: Deoxy-Sugar Incorporated Polymer Fibres as a Bioactive Wound Patch(TÜBİTAK, 2022) Dikici, SerkanThe selection of a wound dressing is crucial for successful wound management. Conventional dressings are preferable for the treatment of simple wounds. However, a bioactive wound dressing that supports wound management and accelerates the healing process is required when it comes to treating non-self-healing wounds. 2-deoxy-D-ribose (2dDR) is a small deoxy sugar that naturally occurs in human body. Although we have previously demonstrated that 2dDR can be used to induce neovascularisation and accelerates wound healing in vitro and in vivo, the literature on small sugars is conflicting, and the knowledge on how 2dDR achieves its biological activity is very limited. In this study, several small sugars including D-glucose (DG), 2-deoxy-D-glucose (2dDG), 2deoxy-L-ribose (2dLR) were compared to 2dDR by investigating their effects on the metabolic activities of both human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts (HDFs). Then, for the first time, a two-dimensional (2D) scratch wound healing model was used to explore the migratory response of HDFs in response to 2dDR treatment. Finally, 2dDR was incorporated into Poly(3-hydroxybutyrate-co3-hydroxyvalerate) (PHBV) polymer fibres via electrospinning, and the metabolic activity of both types of cells in vitro was investigated in response to sugar release via Alamar Blue assay. The results demonstrated that 2dDR was the only sugar, among others, that enhances the metabolic activity of both HDMECs and HDFs and the migratory response of HDFs in a 2D scratch assay in a dose-dependent manner. In addition to direct administration, 2dDR was also found to increase the metabolic activity of HDMECs and HDFs over 7 days when released from polymer fibres. It is concluded that 2dDR is a potential pro-angiogenic agent that has a positive impact not only on endothelial cells but also fibroblasts, which take a key role in wound healing. It could easily be introduced into polymeric scaffolds to be released quickly to enhance the metabolic activity and the migratory response of cells that are associated with angiogenesis and wound healing.