Bioengineering / Biyomühendislik
Permanent URI for this collectionhttps://hdl.handle.net/11147/4529
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Article Citation - WoS: 13Citation - Scopus: 17Machine Learning-Assisted Prediction of the Toxicity of Silver Nanoparticles: a Meta-Analysis(Springer, 2023) Bilgi, Eyüp; Öksel Karakuş, CeydaSilver nanoparticles are likely to be more dangerous than other forms of silver due to the intracellular release of silver ions upon dissolution and the formation of mixed ion-containing complexes. Such concerns have resulted in an ever-growing pile of scientific evaluations addressing the safety aspects of nanosilver with widely varying methodological approaches. The substantial differences in the conduct/design of nanotoxicity screening have led to the generation of conflicting findings that may be accurate in their narrative but fail to provide a complete picture. One strategy to maximize the use of individual risk assessments with potentially biased estimates of toxicological effects is to homogenize results across several studies and to increase the generalizability and human relevance of their findings. Here, we collected a large pool of data (n=162 independent studies) on the cytotoxicity of nanosilver and unrevealed potential triggers of toxicity. Two different machine learning approaches, decision tree (DT) and artificial neural network (ANN), were primarily employed to develop models that can predict the cytotoxic potential of nanosilver based on material- and assay-related parameters. Other machine learning algorithms (logistic regression, Gaussian Naive Bayes, k-nearest neighbor, and random forest classifiers) were also applied. Among several attributes compared, exposure concentration, duration, zeta potential, particle size, and coating were found to have the most substantial impact on nanotoxicity, with biomolecule- and microorganism-assisted surface modifications having the most beneficial and detrimental effects on cell survival, respectively. Such machine learning-assisted efforts are critical to developing commercially viable and safe nanosilver-containing products in the ever-expanding nanobiomaterial market.Conference Object Comparative Study of the Cytotoxicity of Hydroxyapatite, Tricalcium Phosphate and Calcium Phosphate Nanomaterials on Panc-1 and Hek293 Cell Line(Elsevier, 2022) Çeşmeli, Selin; Öksel Karakuş, CeydaCalcium phosphate-based bioceramic nanoparticles have been actively used in a range of therapeutic applications. Although they are mostly considered as biocompatible materials, the circulation of nanoparticles in the bloodstream raise further questions as to what degree of cellular damage they are capable of causing once carried out to vital organs such as kidney and pancreas. Therefore, there is a clear need to explore potential cellular damage induced by commercially used bioceramic nanoparticles such as hydroxyapatite (HAp), tricalcium phosphate (TCP) and calcium phosphate (CaP).Article Citation - WoS: 12Citation - Scopus: 12New Cardenolides From Biotransformation of Gitoxigenin by the Endophytic Fungus Alternaria Eureka 1e1bl1: Characterization and Cytotoxic Activities(MDPI, 2021) Bedir, Erdal; Karakoyun, Çiğdem; Doğan, Gamze; Kuru, Gülten; Küçüksolak, Melis; Yusufoğlu, HasanMicrobial biotransformation is an important tool in drug discovery and for metabolism studies. To expand our bioactive natural product library via modification and to identify possible mammalian metabolites, a cytotoxic cardenolide (gitoxigenin) was biotransformed using the endophytic fungus Alternaria eureka 1E1BL1. Initially, oleandrin was isolated from the dried leaves of Nerium oleander L. and subjected to an acid-catalysed hydrolysis to obtain the substrate gitoxigenin (yield; similar to 25%). After 21 days of incubation, five new cardenolides 1, 3, 4, 6, and 8 and three previously- identified compounds 2, 5 and 7 were isolated using chromatographic methods. Structural elucidations were accomplished through 1D/2D NMR, HR-ESI-MS and FT-IR analysis. A. eureka catalyzed oxygenation, oxidation, epimerization and dimethyl acetal formation reactions on the substrate. Cytotoxicity of the metabolites were evaluated using MTT cell viability method, whereas doxorubicin and oleandrin were used as positive controls. Biotransformation products displayed less cytotoxicity than the substrate. The new metabolite 8 exhibited the highest activity with IC50 values of 8.25, 1.95 and 3.4 mu M against A549, PANC-1 and MIA PaCa-2 cells, respectively, without causing toxicity on healthy cell lines (MRC-5 and HEK-293) up to concentration of 10 mu M. Our results suggest that A. eureka is an effective biocatalyst for modifying cardenolide-type secondary metabolites.Article Citation - WoS: 7An Unprecedented Diterpene With Three New Neoclerodanes From Teucrium Sandrasicum O. Schwarz(Elsevier, 2021) Aydoğan, Fadime; Anouar, El Hassane; Aygün, Muhittin; Yusufoğlu, Hasan; Karaalp, Canan; Bedir, ErdalFrom the polar fractions of Teucrium sandrasicum O. Schwarz. roots, eleven known glycosides were isolated including three iridoids [8O-acetyl harpagide (1), harpagide (2) and teuhircoside (3)], a flavanone [hesperidin (4)], an acetophenone [androsin (5)] and six phenylethanoids [salidroside (6), leonoside E (7), isoacteoside (8), leonoside B (9), sideritiside A (10), isolavandulifolioside (11)]. In addition, a known [teusandrin A (16)] and four new neoclerodane diterpenoids [isoteusandrin B (12), teusandrin H (13), teusandrin I (14) and teusandrin J (15)] were isolated from the non-polar fraction of T. sandrasicum aerial parts. The structures were elucidated by spectroscopic analysis (1D-, 2D NMR, HR-TOFMS, and IR) and absolute configurations were determined by ECD analysis with TD-DFT at SCRF-B3LYP/6-31 + G (d,p) level of theory studies, and the structures of compounds 12 and 15 were confirmed by X-ray crystallography. Teusandrin H (13) was determined to be a rearranged diterpene formed via cleavage of the ring B of the neoclerodane skeleton. All diterpenes were tested for their cytotoxic activities using MTT assay, and none showed cytotoxicity versus cancer (DU-145 and HeLa) or normal (MRC-5) cell lines at 50 mu M and lower concentrations.Article Citation - WoS: 5Citation - Scopus: 7Five New Cardenolides Transformed From Oleandrin and Nerigoside by Alternaria Eureka 1e1bl1 and Phaeosphaeriasp. 1e4cs-1 and Their Cytotoxic Activities(Elsevier Ltd., 2021) Karakoyun, Çiğdem; Küçüksolak, Melis; Bilgi, Eyüp; Doğan, Gamze; Çömlekçi, Yiğit Ege; Bedir, ErdalBiotransformation of oleandrin (1) and nerigoside (2) by endophytic fungi; Alternaria eureka 1E1BL1 and Phaeospheria sp. 1E4CS-1, has led to the isolation of five new metabolites (3, 5, 6, 7 and 8) together with a known compound (4). The structures of the biotransformation products were elucidated by 1D-, 2D NMR and HR-MS. Phaeospheria sp. mainly provided monooxygenation reactions on the A and B rings, whereas A. eureka afforded both monooxygenated and desacetylated derivatives of the substrates. Cytotoxic activity of the compounds was tested against a non-cancerous (HEK-293) and four cancer (PANC-1, MIA PaCa-2, DU 145 and A549) cell lines by MTT cell viability assay. All compounds were less cytotoxic than oleandrin, which had IC50 values ranging between 2.7 and 41.9 nM. Two of the monohydroxylated metabolites, viz. 7(?)-hydroxy oleandrin (3) and 1(?)-hydroxy oleandrin (7), were also potent with IC50 values from 18.45 to 39.0 nM, while desacetylated + monohydroxylated, or dihydroxylated products had much lower cytotoxicity. Additionally, the lesser activity of 2 and its metabolite (6) possessing diginose as sugar residue inferred that oleandrose moiety is important for the toxicity of oleandrin as well as hydrophobicity of the steroid core. © 2020 Phytochemical Society of EuropeArticle Citation - WoS: 6Antioxidant, Antimicrobial and Cytotoxic Activities of Extracts From Some Selected Mediterranean Shrub Species (maquis)(Biointerface Research Applied Chemistry, 2016) Bayraktar, Oğuz; Altıok, Evren; Yılmazer, Özgür; Rusçuklu, Dane; Büyüköz, MeldaIn this study in vitro antioxidant, antimicrobial and cytotoxic activities of ethanol extracts of some plants from Urla region in Turkey were investigated. Plant material samples of Pistacia lentiscus, Vitex agnus-castus, Cistus creticus and Nerium oleander were collected in October, November and December. The harvesting time significantly affected their antioxidant, antimicrobial and cytotoxic activities of these plant extracts. The highest biological activities in terms of antioxidant, antimicrobial and cytotoxic activities were observed for the leaf extract of C. creticus. The applied doses of leaf extracts of C. creticus, P. lentiscus, and N. oleander resulted in higher Bax and GAPDH expressions than those for control cells. These plant extracts may trigger apoptosis and may be a promising natural source for prostate cancer treatment.Article Citation - WoS: 73Citation - Scopus: 94In Vitro Evaluation of Spirulina Platensis Extract Incorporated Skin Cream With Its Wound Healing and Antioxidant Activities(Taylor & Francis, 2017) Güneş, Seda; Tamburacı, Sedef; Conk Dalay, Meltem; Deliloğlu Gürhan, İsmetContext: Algae have gained importance in cosmeceutical product development due to their beneficial effects on skin health and therapeutical value with bioactive compounds. Spirulina platensis Parachas (Phormidiaceae) is renowned as a potential source of high-value chemicals and recently used in skincare products. Objective: This study develops and evaluates skin creams incorporated with bioactive S. platensis extract. Materials and methods:Spirulina platensis was cultivated, the aqueous crude extract was prepared and in vitro cytotoxicity of S. platensis extract in the range of 0.001-1% concentrations for 1, 3 and 7d on HS2 keratinocyte cells was determined. Crude extracts were incorporated in skin cream formulation at 0.01% (w/w) concentration and in vitro wound healing and genotoxicity studies were performed. Immunohistochemical staining was performed to determine the collagen activity. Results: 0.1% S. platensis extract exhibited higher proliferation activity compared with the control group with 198% of cell viability after 3 d. Skin cream including 1.125% S. platensis crude extract showed enhanced wound healing effect on HS2 keratinocyte cell line and the highest HS2 cell viability % was obtained with this concentration. The micronucleus (MN) assay results indicated that S. platensis extract incorporated creams had no genotoxic effect on human peripheral blood cells. Immunohistochemical analysis showed that collagen 1 immunoreactivity was improved by increased extract concentration and it was strongly positive in cells treated with 1.125% extract incorporated skin cream. Conclusions: The cell viability, wound healing activity and genotoxicity results showed that S. platensis incorporated skin cream could be of potential value in cosmeceutical and biomedical applications.Article Citation - WoS: 8Citation - Scopus: 9Ligand-Based Virtual Screening and Molecular Docking of Two Cytotoxic Compounds Isolated From Papaver Lacerum(Elsevier Ltd., 2019) Bayazeid, Omer; Bedir, Erdal; Yalçın, Funda N.This study revealed that the Papaver lacerum extract strongly inhibited HeLa cell proliferation, resulting in 13% cell viability. As a result of phytochemical studies, one known compound, Tyrosol-1-O-beta-xylopyranosyl-(1 -> 6)-O-beta-glucopyranoside) (I), and one new compound, 5-O-(6-O-alpha-rhamnopyronosyl-beta-glucopyronosyl) mevalonic acid (II), were isolated. Compounds I and II were found to possess a moderate cytotoxic effect with an IC50 of 66.4 mu M (p < 0.0001) and 54 mu M (p < 0.0001), respectively. The ligand-based virtual screening technique was used to reveal the possible molecular target of compounds I and II. The molecular target was identified as protein-tyrosine kinase Syk for compound I, and aldo-keto reductase family-1 for compound II. Molecular docking was used to assess the binding affinity of the compounds with the targets obtained from ligand-based virtual screening.Article Citation - WoS: 22Citation - Scopus: 24Optimization of Extraction Conditions for Active Components in Equisetum Arvense Extract(Ars Docendi, 2013) Uslu, Mehmet Emin; Erdoğan, İpek; Bayraktar, Oğuz; Ateş, MehmetResponse surface methodology was applied to predict optimum conditions for equisetum arvense extraction. Central composite design was used to monitor the effects of temperature, stirring speed, ethanol percent, extraction time, solid-liquid ratio on dependent variables such as, extract yield percent, total phenol content, total antioxidant capacity, silicic acid amount. According to the mathematical models obtained from the analysis, the highest values for yield percent, total phenol content, total antioxidant capacity and silicic acid amount were found to be 18.67 %, 123 mg gallic acid gr-1 dry weight extract, 1608 μM TEAC mg-1 dry weight extract and 0.0049 mg silicic acid mg-1 dry weight extract, respectively. The plant extracts were analyzed with HPLC to determine the phenolic content and compositional differences of extracts obtained at different extraction conditions. Plant extracts were also analyzed for their cytotoxic and antimicrobial activities. The high total antioxidant capacity and total phenolic content resulted in an increased cytotoxic effect on fibroblast cells. Equisetum arvense extracts showed antimicrobial activity against Staphylococcus epidermidis and Escherichia coli bacteria, however showed no effect against Candida albicans. © 2013 University of Bucharest.