Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Self-Assembled Peptide Hydrogels with Cell Attachment Motifs for 3D Lung Cancer Model: Evaluation of Cell-Matrix Interactions and Drug Response(John Wiley and Sons Inc, 2026) Sırma Tarım, B.; Tamburaci, S.; Top, A.3D cancer models can mimic the tumor microenvironment, serving as a physiologically relevant platform to investigate the behavior of tumors and test anticancer therapeutics. Although bioactive peptide hydrogels have been widely evaluated for tissue engineering applications, their potential in 3D cancer models has been confirmed in only a few studies. In this study, self-assembling peptide hydrogels containing LDV (IBP1) and LDV and IKVAV cell attachment motifs (IBP2), and the control hydrogel without adhesion units (KLEI) were used for lung cancer modeling. The peptides self-assembled into hydrogels in a cell culture medium with storage moduli of ∼700–1500 Pa. The IBP1 and IBP2 hydrogels enhanced A549 cell proliferation and induced the formation of spheroids with average diameters between ∼70 and ∼150 µm. The cells in KLEI hydrogel with the highest stiffness exhibited mesenchymal-type migration, independent of the cell population, whereas transformation to mesenchymal migration necessitated a specific cell population in the IBP2 hydrogel. The cells in the IBP1 and IBP2 hydrogels with enhanced cell-cell interactions demonstrated higher resistance to docetaxel (DTX). Thus, our results indicate that these bioactive hydrogels can serve as a promising platform for in vitro assessment of cancer mechanisms and drug screening. © 2026 Wiley-VCH GmbH.Article Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain(John Wiley and Sons Inc, 2026) Nazli, D.; Ipekgil, D.; Poyraz, Y.K.; Can, K.; Okmen, I.; Turhanlar-Sahin, E.; Ozhan, G.Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD. © 2026 Wiley Periodicals LLC.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 Effect of Irradiation on Total Biophenol and Antioxidant Activity During Storage of Natural Black Table Olives Obtained Using Starter Culture(John Wiley and Sons Inc, 2024) Irmak,Ş.; Öztürk Güngör,F.; Susamci,E.; Sevim,D.; Köseoğlu,O.In this study, it was aimed to determine the effects of different production and preservation methods on the shelf life and quality of the Gemlik variety of natural black table olives produced with low salt (2%). For this purpose, olives were processed by the traditional Turkish style dry salted black olive by using a starter culture. The MAP (Modified atmosphere packaging, 60% N2 and 40% CO2), vacuum and for the first time gamma irradiation methods (1, 3 and 5 kGy) were applied in the preservation of table olives. The 5 kGy irradiation treatment reduced the total phenolic amount and DPPH antioxidant activity of olives more than other irradiation doses. The pH (4.3–4.83) and titratable acidity (0.68–1.02%) of the samples changed in accordance with the legal regulations during the storage period (pH max. 5 and acidity min 0.3%). At the end of the fermentation and storage, total phenolic content and antioxidant activity decreased significantly (p-value <0.05). During the storage period, the total phenolic content in natural fermented olives (without starter culture) decreased from 232 to 144 mgCAE/100 g and in starter culture added table olives from 200 to 138 mgCAE/100 g. In addition, the antioxidant activity was changed between 60.94 and 47.14 μmolTE/100 g oil. As a result of the study, it was ensured that black table olives produced with less salt (2%) could be stored on the shelves for 6 months without using any preservatives. In addition, radiation effect on quality was relatively similar to other treatments (vacuum and MAP). © 2024 AOCS.Article Citation - Scopus: 6Sequence Identification and in Silico Characterization of Novel Thermophilic Lipases From Geobacillus Species(John Wiley and Sons Inc, 2024) Sürmeli,Y.; Tekedar,H.C.; Şanlı-Mohamed,G.Microbial lipases are utilized in various biotechnological areas, including pharmaceuticals, food, biodiesel, and detergents. In this study, we cloned and sequenced Lip21 and Lip33 genes from Geobacillus sp. GS21 and Geobacillus sp. GS33, then we in silico and experimentally analyzed the encoded lipases. For this purpose, Lip21 and Lip33 were cloned, sequenced, and their amino acid sequences were investigated for determination of biophysicochemical characteristics, evolutionary relationships, and sequence similarities. 3D models were built and computationally affirmed by various bioinformatics tools, and enzyme-ligand interactions were investigated by docking analysis using six ligands. Biophysicochemical property of Lip21 and Lip33 was also determined experimentally and the results demonstrated that they had similar isoelectric point (pI) (6.21) and Tm (75.5°C) values as Tm was revealed by denatured protein analysis of the circular dichroism spectrum and pI was obtained by isoelectric focusing. Phylogeny analysis indicated that Lip21 and Lip33 were the closest to lipases from Geobacillus sp. SBS-4S and Geobacillus thermoleovorans, respectively. Alignment analysis demonstrated that S144–D348–H389 was catalytic triad residues in Lip21 and Lip33, and enzymes possessed a conserved Gly-X-Ser-X-Gly motif containing catalytic serine. 3D structure analysis indicated that Lip21 and Lip33 highly resembled each other and they were α/β hydrolase-fold enzymes with large lid domains. BANΔIT analysis results showed that Lip21 and Lip33 had higher thermal stability, compared to other thermostable Geobacillus lipases. Docking results revealed that Lip21- and Lip33-docked complexes possessed common residues (H112, K115, Q162, E163, and S141) that interacted with the substrates, except paranitrophenyl (pNP)-C10 and pNP-C12, indicating that these residues might have a significant action on medium and short-chain fatty acid esters. Thus, Lip21 and Lip33 can be potential candidates for different industrial applications. © 2023 International Union of Biochemistry and Molecular Biology, Inc.Article Citation - Scopus: 6Functional Characterization of a Novel Cyp119 Variant To Explore Its Biocatalytic Potential(John Wiley and Sons Inc, 2022) Sakalli, T.; Surmeli, N.B.Biocatalysts are increasingly applied in the pharmaceutical and chemical industry. Cytochrome P450 enzymes (P450s) are valuable biocatalysts due to their ability to hydroxylate unactivated carbon atoms using molecular oxygen. P450s catalyze reactions using nicotinamide adenine dinucleotide phosphate (NAD(P)H) cofactor and electron transfer proteins. Alternatively, P450s can utilize hydrogen peroxide (H2O2) as an oxidant, but this pathway is inefficient. P450s that show higher efficiency with peroxides are sought after in industrial applications. P450s from thermophilic organisms have more potential applications as they are stable toward high temperature, high and low pH, and organic solvents. CYP119 is an acidothermophilic P450 from Sulfolobus acidocaldarius. In our previous study, a novel T213R/T214I (double mutant [DM]) variant of CYP119 was obtained by screening a mutant library for higher peroxidation activity utilizing H2O2. Here, we characterized the substrate scope; stability toward peroxides; and temperature and organic solvent tolerance of DM CYP119 to identify its potential as an industrial biocatalyst. DM CYP119 displayed higher stability than wild-type (WT) CYP119 toward organic peroxides. It shows higher peroxidation activity for non-natural substrates and higher affinity for progesterone and other bioactive potential substrates compared to WT CYP119. DM CYP119 emerges as a new biocatalyst with a wide range of potential applications in the pharmaceutical and chemical industry. © 2021 International Union of Biochemistry and Molecular Biology, Inc.Article Citation - Scopus: 4Quasi-Supervised Strategies for Compound-Protein Interaction Prediction(John Wiley and Sons Inc, 2022) Çakı, O.; Karaçalı, B.In-silico compound-protein interaction prediction addresses prioritization of drug candidates for experimental biochemical validation because the wet-lab experiments are time-consuming, laborious and costly. Most machine learning methods proposed to that end approach this problem with supervised learning strategies in which known interactions are labeled as positive and the rest are labeled as negative. However, treating all unknown interactions as negative instances may lead to inaccuracies in real practice since some of the unknown interactions are bound to be positive interactions waiting to be identified as such. In this study, we propose to address this problem using the Quasi-Supervised Learning (QSL) algorithm. In this framework, potential interactions are predicted by estimating the overlap between a true positive dataset of compound-protein pairs with known interactions and an unknown dataset of all the remaining compound-protein pairs. The potential interactions are then identified as those in the unknown dataset that overlap with the interacting pairs in the true positive dataset in terms of the associated similarity structure. We also address the class-imbalance problem by modifying the conventional cost function of the QSL algorithm. Experimental results on GPCR and Nuclear Receptor datasets show that the proposed method can identify actual interactions from all possible combinations. © 2021 Wiley-VCH GmbH.Article Citation - Scopus: 13Her2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual Ph-Sensitive Dox Release(John Wiley and Sons Inc, 2022) Bayram, N.N.; Ulu, G.T.; Topuzoğulları, M.; Baran, Y.; Dinçer, İşoğlu, S.Here, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition−fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide–doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery. © 2021 Wiley-VCH GmbHArticle Interpersonal Trust, Invention, and Innovation Across European Regions(John Wiley and Sons Inc, 2023) Dindaroğlu, BurakMany studies in economics and regional science claim a positive link between interpersonal trust and innovation by demonstrating a positive effect of trust on patenting. This contrasts many findings from organization level studies on trust and innovation, who report a variety of findings including inverted-U type relations. A possible explanation is that trust exhibits different roles in invention and innovation, as the former relies on knowledge commons while the latter directly embeds commercialization and the market context. This study attempts to reconcile the two set of findings by studying indicators of invention and innovation in relation to trust at the same unit of observation, by using the regional variation in Europe. I study the relationship between interpersonal trust and patent applications (a measure of invention), trademark applications (a composite indicator) and the share of innovative sales in turnover by SMEs (a direct indicator of commercialization), across European regions. I show that trust positively affects trademark applications with an effect that is comparable to that on patent applications. However, trust exhibits an inverted-U type relationship with innovative sales. Results collectively point to a strong role of trust in all three creative activities, including a negative effect at the higher end when the indicator is directly contingent on commercialization and sales. I also estimate the extent of spatial spillovers in the effect of trust on all three creative outcomes. © 2023 Wiley Periodicals LLC.