PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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 Liposomal Encapsulation of a Synthetic Bromophenol for Antitumor Efficacy and Apoptotic Activity in Cancer Cells(Springer, 2026) Oztanrikulu, Bercem Dilan; Ozdemir, Ekrem; Avci, Bahri; Goksu, Suleyman; Bayrakceken, Handan Uguz; Askin, HakanA novel synthetic bromophenol (BP), inspired by marine-derived natural bromophenols, was evaluated for its antitumor activity and for the enhancement of its in vitro performance through liposomal encapsulation (LipoBP). Etoposide was used as a reference in characterization, release, and loading studies. PEGylated liposomes were employed to improve BP's solubility, bioavailability, and therapeutic potential. The cytotoxicity, apoptosis, and gene expression effects of free BP and LipoBP were assessed in A549 (lung) and MCF-7 (breast) cancer cell lines. WST-8 assays showed that encapsulation significantly increased BP's cytotoxic activity, particularly in A549 cells, while flow cytometry and Annexin V-FITC/PI analyses indicated more pronounced apoptotic induction by LipoBP compared with free BP. qRT-PCR analyses revealed upregulation of proapoptotic genes (BAX, CASP6, CASP3 and CASP9) and downregulation of antiapoptotic/survival genes (BCL-XL, IQSEC2) in both cell lines, indicating activation of intrinsic apoptotic pathways. Plain liposomes exhibited minimal cytotoxicity, confirming their biocompatibility. Liposomal bromophenol, which we have introduced to the literature for the first time, is expected to be a promising nanocarrier system that could be effective in cancer treatment by improving the therapeutic index of new drug candidates such as marine bromophenols.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.Review Citation - WoS: 69Nanoparticle-Protein Corona Complex: Understanding Multiple Interactions Between Environmental Factors, Corona Formation, and Biological Activity(TAYLOR & FRANCIS LTD, 2021) Tomak, Aysel; Tomak, Aysel; Çesmeli, Selin; Öksel Karakuş, Ceyda; Hanoglu, Bercem D.; Winkler, David; Oksel Karakus, CeydaThe surfaces of pristine nanoparticles become rapidly coated by proteins in biological fluids, forming the so-called protein corona. The corona modifies key physicochemical characteristics of nanoparticle surfaces that modulate its biological and pharmacokinetic activity, biodistribution, and safety. In the two decades since the protein corona was identified, the importance of nanoparticles surface properties in regulating biological responses have been recognized. However, there is still a lack of clarity about the relationships between physiological conditions and corona composition over time, and how this controls biological activities/interactions. Here we review recent progress in characterizing the structure and composition of protein corona as a function of biological fluid and time. We summarize the influence of nanoparticle characteristics on protein corona composition and discuss the relevance of protein corona to the biological activity and fate of nanoparticles. The aim is to provide a critical summary of the key factors that affect protein corona formation (e.g. characteristics of nanoparticles and biological environment) and how the corona modulates biological activity, cellular uptake, biodistribution, and drug delivery. In addition to a discussion on the importance of the characterization of protein corona adsorbed on nanoparticle surfaces under conditions that mimic relevant physiological environment, we discuss the unresolved technical issues related to the characterization of nanoparticle-protein corona complexes during their journey in the body. Lastly, the paper offers a perspective on how the existing nanomaterial toxicity data obtained from in vitro studies should be reconsidered in the light of the presence of a protein corona, and how recent advances in fields, such as proteomics and machine learning can be integrated into the quantitative analysis of protein corona components.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: 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.