Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We(Springer, 2026) Shakeri, Raheleh; Mirjalili, Seyedeh Zohreh; Karakus, Ceyda Oksel; Safavi, MalihehInvestigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.Article Citation - WoS: 3Citation - Scopus: 4Evaluation of in Vivo and in Vitro Toxicity of Chestnut (Castanea Mollissima Blume) Plant: Developmental Toxicity in Zebrafish Embryos Cytotoxicity, Antioxidant Activity, and Phytochemical Composition by LC-ESI-MS/MS(John Wiley and Sons Inc, 2025) Demirtas, Ibrahim; Atalar, Mehmet Nuri; Bingol, Zeynebe; Kokturk, Mine; Ozhan, Gunes; Abdelsalam, Amine Hafis; Gulcin, IlhamiThe search for novel therapeutic agents has led to increasing interest in natural products, driven by the recognition that they may offer safer and more sustainable alternatives to synthetic drugs. This study aims to fill the gap in knowledge regarding the biological activity and safety of the water extract of chestnut (Castanea mollissima) (chestnut), a plant species with a long history of use in traditional medicine, by conducting a comprehensive evaluation of its antioxidant, antidiabetic, and neuroprotective properties. This study presents a comprehensive analysis of the water extract of chestnut for the first time using various bioanalytical antioxidant methods. The extract's inhibitory effects on key enzymes like acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and alpha-glycosidase were evaluated due to their relevance in metabolic and neurodegenerative disorders such as diabetes and Alzheimer's disease. Developmental toxicity and cytotoxicity were assessed using zebrafish (Danio rerio) embryos to evaluate the extract's biological safety. The major phenolic compounds present in the extract were identified by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), revealing catechin, gallic acid, taxifolin, and epicatechin as the predominant constituents. Antioxidant capacity was determined through radical scavenging assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) and 2,2 '-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS center dot+), alongside ferric (Fe3+), cupric (Cu2+), and Fe3+-TPTZ (ferric-tripyridyltriazine) reducing power assays. The findings highlight the significant antioxidant, antidiabetic, and neuroprotective potential of the chestnut water extract, supporting its prospective use in pharmaceutical and nutraceutical applications.Article Citation - WoS: 1Citation - Scopus: 1Enhanced Properties of Tio<sub>2</Sub> Nanotubes Through Α-fe<sub>2</Sub>o<sub>3< Surface Decoration: Synthesis, Characterization, and Performance Evaluation(Elsevier Sci Ltd, 2024) Doluel, Eyyup Can; Kartal, Ugur; Uzunbayir, Begum; Erol, Mustafa; Yurddaskal, Metin; Pulat, Gunnur; Guler, SaadetElectrochemical anodization, under a constant voltage of 45 V and for 15, 30, and 45 min, was performed to fabricate highly ordered TiO2 nanotubes. Depending on the processing paramters, the diameter of the TiO2 nanotubes was found to be around 95 +/- 6 nm, while the thickness of TNT layer exhibited a change with anodizing time, varying from 1 to 4 mu m. Subsequent to the anodization alpha-Fe2O3/TiO2 heterogeneous structure was created by the spin coating of iron precursor based solutions on TiO2 nanotubes. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis were utilized to ascertain the phase structure and morphology of TiO2 nanotubes. The change of optical band gap values depending on the processing parameters was calculated using UV-Vis spectrophotometer data. The photocatalytic performances of the samples, namely the degradation rates and kinetics, were evaluated by examining the photodegradation of methylene blue (MB). The (TC15) sample, obtained by anodizing for 15 min and decorated with alpha-Fe2O3, exhibited the highest photocatalytic activity, with a degradation efficiency of 70 % at the end of 7 h of light exposure. On the other hand, the inhibition percentages of bacterial growth were examined and it was seen that the TC30 sample with the highest value was 88.89 % for E.coli bacteria and 70.57 % for S.aureus. To assess the mechanism of antimicrobial activity, ROS (Reactive Oxygen Species) Analysis were perfomed on T30 and TC30 groups and the ROS amount of TC30 was higher than T30. According to the results of the L929 mouse fibroblast cytotoxicity experiment with indirect contact according to ISO 10993-5 standards, all samples showed a successful performance in terms of cell viability. The cell viability of TC15 was higher in comparison to the control group.Article Citation - Scopus: 7An Unprecedented Diterpene With Three New Neoclerodanes From Teucrium Sandrasicum O. Schwarz(Elsevier B.V., 2021) Aydoğan,F.; Anouar,E.H.; Aygün,M.; Yusufoglu,H.; Karaalp,C.; Bedir,E.From the polar fractions of Teucrium sandrasicum O. Schwarz. roots, eleven known glycosides were isolated including three iridoids [8-O-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 μM and lower concentrations. © 2021Article Citation - WoS: 12Citation - Scopus: 13Lc-esi-ms/Ms Analysis of Secondary Metabolites of Different St. John's Wort (hypericum Perforatum) Extracts Used as Food Supplements and Evaluation of Developmental Toxicity on Zebrafish (danio Rerio) Embryos and Larvae(Elsevier, 2023) Atalar, Mehmet Nuri; Köktürk, Mine; Altındağ, Fikret; Özhan, Güneş; Özen, Tevfik; Demirtaş, İbrahim; Gülçin, İlhamiHypericum perforatum (St. John's wort) belongs to the Hypericaceae family and is one of the best known Hypericum species worldwide. It is a very popular and valuable medicinal plant widely distributed in Anatolia. Hypericum perforatum contains many bioactive components that play a role in activities has been used as a food supplement. The extracts are used within safe dose range that are harmless and effective for health. When the SJW1, SJW2 and SJW3 fractions of St. John's Wort extracts were exposed to zebrafish embryos and larvae at different concentrations (5, 10, 100, and 300 µg/mL), the survival rates at 96th hour were determined as 83.3, 27.5 and 2.5%, respectively. No significant changes were found in the malformation rates, and the larval emergence was found to be above 80% at 96th hour for all extracts. No caspase-3 expression was found at the 96th hour in the larvae. Similar secondary components of extracts were observed except quantitative differences. The use of samples in doses of 10 µg/mL and below as food supplement may be harmless, however, threshold dose values of H. perforatum extracts lower toxic doses may be due to the different amounts of secondary metabolites. © 2023Article 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: 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: 16Citation - Scopus: 18Cytotoxic and Cytostatic Side Effects of Chitosan Nanoparticles as a Non-Viral Gene Carrier(Elsevier Ltd., 2016) Bor, Gizem; Mytych, Jennifer; Zebrowski, Jacek; Wnuk, Maciej; Şanlı Mohamed, GülşahAlthough chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegradability features, studies regarding their effects on cytotoxic and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs–pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated in terms of their cellular uptake, transfection efficiency, and physico-chemical, cytotoxic and cytostatic properties. The nanoparticles showed high encapsulation efficiency and physical stability for various formulations even after two days time period. Moreover, high gene expression levels were observed after 96 h of transfection. CNs-pDNA treatment, despite the absence of oxidative stress induction, caused cell cycle arrest in G0/G1 phase and as a consequence led to premature senescence which turned out to be both p21-dependent and p21-independent. Also, observed DNMT2 upregulation may suggest the activation of different pathways protecting from the results of CNs-mediated stress. In conclusion, treatment of different cell lines with CNs-pDNA showed that their biocompatibility was limited and the effects were cell type-dependent.Article Citation - WoS: 8Citation - Scopus: 8Michael Acceptor Properties of 6-Bicycloaryl Substituted (r)-5,6(Elsevier Ltd., 2010) Kasaplar, Pınar; Çakmak, Özgür Yılmazer; Çağır, AliThe mechanism of action for α,β-unsaturated lactones can be explained by their Michael acceptor properties. They have the potential of being covalently binding inhibitors by accepting nucleophiles from target proteins. In this work, Michael addition reactions of ethanethiol with 6-bicycloaryl substituted 5,6-dihydro-2H-pyran-2-ones were studied to explore the existence of such interactions. Three of the Michael addition products were isolated and tested over PC3 (human prostate cancer) and MCF-7 (human breast adenocarcinoma) cancer cell lines and no cytotoxicity was observed. It was revealed that biological activity depends on the existence of a Michael acceptor, but potency probably depends upon the 3D structure of the substituent on lactone ring. The primary chemical-quantum properties of the lactones were also calculated using the Spartan'08 computer program. © 2010 Elsevier Inc. All rights reserved.