WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Gamma Secretase Inhibitors, DAPT and MK0752, Exhibit Synergistic Anticancer Effects with Cisplatin and Docetaxel in 2D and 3D Models of Breast Cancer(TÜBİTAK Scientific & Technological Research Council of Turkey, 2025) Telli, Kubra; Gubat, Johannes; D'Arcy, Padraig; Ozuysal, Ozden YalcinBackground/aim: Breast cancer remains a major malignancy among women, and severe side effects and the development of acquired drug resistance frequently hinder current therapeutic strategies. The Notch signaling pathway, a key regulator of cell fate, is commonly dysregulated in breast cancer and associated with poor prognosis. Gamma-secretase inhibitors (GSIs) block Notch receptor activation and have shown potential anticancer efficacy. This study aimed to investigate the synergistic activity of two commonly used GSIs, DAPT and MK0752, combined with docetaxel or cisplatin in both 2D and 3D breast cancer models. Materials and methods: Triple-negative, highly metastatic MDA-MB-231 and ER+/PR+ MCF-7 breast cancer cell lines were treated with DAPT or MK0752 alone or in combination with docetaxel or cisplatin. Drug efficacy and potential synergism were evaluated in 2D monolayer cultures and 3D spheroid models. Sequential treatment strategies were also assessed, where docetaxel or cisplatin was administered prior to GSI exposure. Results: Both MDA-MB-231 and MCF-7 cell lines exhibited notable sensitivity to DAPT and MK0752 combinations with docetaxel or cisplatin in 2D and 3D cultures. Synergistic enhancement of cytotoxicity was observed, particularly in sequential treatment regimens. Pretreatment with docetaxel or cisplatin followed by GSI exposure demonstrated superior growth inhibition compared with either monotherapy or simultaneous combination treatments. Conclusion: This study highlights the therapeutic potential of combining GSIs with standard chemotherapeutics to overcome drug resistance in breast cancer. The observed synergy and sequencing effects provide a strong basis for further mechanistic and translational investigations to optimize GSI-based combinational therapy strategies.Article Quantum Calculus of Fibonacci Divisors and Fermion-Boson Entanglement for Infinite Hierarchy of N=2 Supersymmetric Golden Oscillators(Pleiades Publishing Ltd, 2025) Pashaev, O. K.The quantum calculus with two bases, represented by powers of the golden and silver ratios, relates the Fibonacci divisor derivative with Binet formula for the Fibonacci divisor number operator, acting in the Fock space of quantum states. It provides a tool to study the hierarchy of golden oscillators with energy spectrum in the form of Fibonacci divisor numbers. We generalize this model to the supersymmetric number operator and corresponding Binet formula for the supersymmetric Fibonacci divisor number operator. The operator determines Hamiltonian of the hierarchy of supersymmetric golden oscillators, acting in fermion-boson Hilbert space and belonging to N = 2 supersymmetric algebra. The eigenstates of the super Fibonacci divisor number operator are double degenerate and can be characterized by a point on the super-Bloch sphere. By introducing the supersymmetric Fibonacci divisor annihilation operator, we construct the hierarchy of supersymmetric coherent states as eigenstates of this operator. The entanglement of fermions with bosons in these states is calculated by the concurrence, represented as the Gram determinant and expressed in terms of the hierarchy of golden exponential functions. We show that the reference states and the corresponding von Neumann entropy measuring the fermion-boson entanglement are characterized completely by powers of the golden ratio. We give a geometrical classification of entangled states by the Frobenius ball and interpret the concurrence as the double area of a parallelogram in a Hilbert space.Article The Temperature Dependence of Elastic Constants and Zener Anisotropy in Single Crystal KTaO3 Below Room Temperature(Pleiades Publishing Ltd, 2025) Li, C. H.; Ding, X. D.; Carpenter, M. A.; Aktas, O.We present the first experimental report of the complete elastic tensor of incipient ferroelectric KTaO3 between 9.6 and 307 K, using resonant ultrasound spectroscopy (RUS). The elastic constants C-11 and C-44, as well as the bulk and shear moduli increase roughly linearly upon cooling. Deviations from such dependence are a result of impurities. Zener anisotropy factor is 0.697 at room temperature and decreases to 0.627 at 9.6 K, indicating increasing elastic anisotropy. The temperature dependence of C-12 is anomalous with no stiffening on cooling, which could be a result of different defect species influencing C-12 but not the other constants, possibly due to defect anisotropy. The values of elastic constants and anisotropy are compared at room temperature and below 10 K with the literature reporting experimental results and density functional theory calculations.Article Hydrothermal Synthesis of Zeolite T From Bentonite Clay: Catalytic Applications and Molecular Docking Analysis(National Information & Documentation Centre-NIDOC, 2025) Taib, H.; Lefrada, L.; Belfennache, D.; Belghit, M. Y.; Benbouzid, M.; Yilmaz, S.; A.Ali, MohamedZeolites are essential materials in modern industries due to their uses as cation exchangers, selective adsorbents, and catalysts. In this study,we report novel procedures for producing zeolite T, which is distinguished by its round crystals that closely resemble Saharan flowers. An investigation was conducted on the hydrothermal synthesis of T zeolite in alkaline aqueous solutions without templates. Zeolite T crystals were synthesized via hydrothermal methods with clay-based aluminosilicate gel containing 1Al2O3, 25SiO2, 6.5Na2O, 2.25K2O, and 350 H2O. Zeolite crystals were formed at a temperature of 130 degrees C, with crystallization durations of 3 and 5 days, respectively, using processed natural bentonite clay as the starting material. A range of analytical methods, such as XRD, FTIR, Raman, SEM, ATD-EDX, BET, ATG, and NH3-TPD, were used to observe the crystallization stages of zeolite T grains.During the synthesis of Zeolite T, samples were collected at various intervals, with the samples taken after three and five days of reaction being particularly noteworthy. The T1 zeolite is identified as a mixture of T2 zeolite and other impurities present in the reaction medium, indicating that T1 zeolite serves as a precursor phase to T2 zeolite (T1 is a germination phase). The analysis revealed that a treatment temperature of 130 degrees C for 5 days is optimal. The nucleation of zeolite T from treated bentonite commenced after 3 days. The results indicate that zeolite T2, composed of uniform crystalline grains formed over 5 days, yields a mesoporous structure with a size of 1.35 mu m and a molar ratio of 1.78 between molar quantities of silica and aluminum of this zeolite (T Zeolite). An analysis of the BET (surface area) revealed a value of 95.75 m2g-1, accompanied by a pore volume of 0.010 cm3g-1. Moreover, the examination of TPD-NH3 desorption revealed a restricted occurrence of the acidic site of Br & oslash;nsted, while a significant number of acidic sites of Lewis were detected. The obtained crystalline zeolite T was examined for its ability to catalyze the Hantzsch reaction. In addition, T2 zeolite prepared was used as a catalyst in the synthesis of the 1,1'-(4-(5-bromo-2-thiophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-diyl)bis(ethan-1-one) (BTDDB) due to the acidity sites (Lewis and Br & oslash;nsted acid) in the structure of the zeolite. The result of the reaction has shown a good percentage in the synthetic of BTDDB The results of FTIR, UV, 13C NMR, and 1H NMR spectrum analyses revealed that the structure of the 1,4-dihydropyridine compound was well-defined, and the use of molecular docking and density functional theory (DFT) analysis revealed better performance in the inhibition of the macromolecular targets aminodeoxyfutalosine nucleosidase and DNA gyrase subunit B.Article Assessment of Cytotoxic Potentials of Isoindole-Derived Compounds With Epoxy Alcohol Functionalities on Different Cancer Cell Lines and Molecular Docking Analysis(Maik Nauka/Interperiodica/Springer, 2025) Yetiskin, Egehan; Gundogdu, Ozlem; Mete, Derya; Kishali, Nurhan H.; Kara, Yunus; Sanli-Mohamed, GulsahObjective: Isoindoline and epoxycyclohexane derivatives are known to exert beneficial effects on various inflammatory pathologies, including cancer. This study uniquely evaluates the cytotoxic potential of four synthesized isoindoline derivatives against five different cancer cell lines. Methods: Cancer cell lines were treated with varying concentrations of each derivative and incubated for 24, 48, and 72 h. Cytotoxicity was assessed via cell growth inhibition assays and cell membrane damage tests. Additionally, molecular docking studies were conducted to examine the interaction of the compounds with key cancer-related proteins: human tankyrase 1, c-MET, estrogen receptor alpha, androgen receptor, and EGFR. Results and Discussion: The epoxy alcohol derivatives demonstrated a dose-dependent cytotoxic effect, inhibited cell proliferation, and induced membrane damage in adenocarcinoma cell lines. Apoptosis rates and in vitro wound healing assays further supported their antiproliferative potential. Conclusions: These findings suggest that epoxy isoindole derivatives may serve as promising anticancer agents for the treatment of cervical, lung, prostate, and breast cancers due to their cytotoxic and antiproliferative activities. Molecular docking results corroborated their potential mechanism of action.Article Citation - WoS: 5Citation - Scopus: 6Hydrocolloids for Tissue Engineering and 3d Bioprinting(World Scientific Publ Co Pte Ltd, 2024) Yildirim-Semerci, Ozum; Onbas, Rabia; Bilginer-Kartal, Rumeysa; Arslan-Yildiz, AhuHydrocolloids, derived from plants, marine, and microbial sources, have become research favorites due to their unique properties. This article provides an overview of the extraction methods, from chemical to enzymatic, to obtain hydrocolloids. Distinctive properties of hydrocolloids, such as high swelling capacity, tunable features, and rapid gelation ability, have gained significant attention recently and have started to be used in tissue engineering and 3D bioprinting. Hydrocolloids will play substantial roles in advancing biomedical products and contributing to improving human health.Review Citation - WoS: 1Citation - Scopus: 2Organ-On Platforms for Drug Development, Cellular Toxicity Assessment, and Disease Modeling(Tubitak Scientific & Technological Research Council Turkey, 2024) Khurram, Muhammad Maaz; Cinel, Gokturk; Yesil Celiktas, Ozlem; Bedir, ErdalOrgans-on-chips (OoCs) or microphysiological platforms are biomimetic systems engineered to emulate organ structures on microfluidic devices for biomedical research. These microdevices can mimic biological environments that enable cell-cell interactions on a small scale by mimicking 3D in vivo microenvironments outside the body. Thus far, numerous single and multiple OoCs that mimic organs have been developed, and they have emerged as forerunners for drug efficacy and cytotoxicity testing. This review explores OoC platforms to highlight their versatility in studies of drug safety, efficacy, and toxicity. We also reflect on the potential of OoCs to effectively portray disease models for possible novel therapeutics, which is difficult to achieve with traditional 2D in vitro models, providing an essential basis for biologically relevant research.Article Mkate2-k67r/R197h-extra-bright Red Fluorescent Biomarker of New Generation. X-Ray Structure and Molecular Dynamic Properties(Maik Nauka/interperiodica/springer, 2024) Goryacheva, E. A.; Rossokhin, A. V.; Ruchkin, D. A.; Bogdanov, A. M.; Artemyev, I. V.; Pletneva, N. V.; Plenev, V. Z.Objective: Cell biology continuously shows the need for new fluorescent tags with advanced properties. The object of our current study is a new genetically encoded monomeric red fluorescent biomarker mKate2-K67R/R197H (lambda ex/lambda em 579/603 mn), designed from commercial biomarker mKate2 by two R197H/K67R mutations. The mKate2 precursor, a far-red fluorescent protein, is nearly 3-fold brighter than the previously designed mKate. Compared with commercial mKate2, the double mutant mKate2-K67R/R197H (alternative names FusionRed2 and Diogenes) exhibits an additional similar to 1.6-fold increase in fluorescence brightness and represents the next generation of extra-bright red fluorescent probes offering novel possibilities for fluorescent imaging of proteins in living cells and animals. Methods: The paper presents the results of X-ray and molecular dynamics study of new bright biomarker mKate2-K67R/R197H. Results and Discussion: The three dimensional structure of new advanced red fluorescent biomarker mKate2-K67R/R197H has been studied by X-ray method at 1.5 angstrom resolution supported by molecular dynamics (MD) study The principal structural fold of the protein is an 11-stranded beta-barrel. The nearest chromophore environment (<= 4 angstrom) comprises 18 tightly packed residues. Conclusions: The MD study showed that the brightness of mKate2-K67R/R197H and its mKate2 precursor correlates with the dipole moments of the amino acid environments of the chromophores. The higher the dipole moment, the higher the brightness of biomarker.Article Citation - WoS: 4Citation - Scopus: 3Expression Patterns of M6a Rna Methylation Regulators Under Apoptotic Conditions in Various Human Cancer Cell Lines(TUBITAK, 2024) Alasar, Azime Akçaöz; Sağlam, Buket; Vatansever, İpek Erdoğan; Akgül, BünyaminBackground/aim: Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m6A RNA modifiers under apoptotic conditions across various cancer cell lines. Materials and methods: Initially, we quantified the abundance of m6A RNA modifiers in cervical (HeLa and ME180), breast (MCF7 and MDA-MB-231), lung (A549 and H1299), and colon (Caco-2 and HCT116) cancer cell lines using qPCR. Subsequently, we induced apoptosis using cisplatin and tumor necrosis factor-alpha (TNF-α) to activate intrinsic and extrinsic pathways, respectively, and assessed apoptosis rates via flow cytometry. Further, we examined the transcript abundance of m6A RNA modifiers under apoptotic conditions in cervical, breast, and lung cancer cell lines using qPCR. Results: Overall, treatment with cisplatin increased the abundance of m 6A modifiers, whereas TNF-α treatment decreased their expression in cervical, breast, and lung cancer cell lines. Specifically, cisplatin-induced apoptosis, but not TNF-α-mediated apoptosis, resulted in decreased abundance of METTL14 and FTO transcripts. Additionally, cisplatin treatment drastically reduced the abundance of IGF2BP2 and IGF2BP3 readers. Conclusion: These results suggest that the differential response of cancer cells to apoptotic inducers may be partially attributed to the expression of m6A RNA modifiers.Article Citation - WoS: 1Citation - Scopus: 1Investigation of Cytotoxic Properties of Some Isoindole-Related Compounds Bearing Silyl and Azide Groups With in Vitro and in Silico Studies(Taylor & Francis, 2023) Tan, Ayşe; Köse, Aytekin; Mete, Derya; Şanlı Mohamed, Gülşah; Kışhalı, Nurhan H.; Kara, YunusThis study aims to evaluate the synthesis of isoindole-1,3-dione analogues and their cytotoxic potential. A549 and HeLa cells exposed to 250-100-50-25 mu M doses of each derivative were incubated for 24, 48, and 72 h. The cytotoxicity of the isoindole-1,3-dione derivatives was analyzed using the cell growth inhibition assay and the cell membrane damage test. (3aR,5R,6R,7aS)-5-Azido-2-benzyl-6-hydroxyhexahydro-1H-isoindole-1,3(2H)-dione (1d), (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-ethylhexahydro-1H-isoindole-1,3(2H)-dione (2a), and (3aR,5R,6R,7aS)-5-azido-6-((tert-butyldiphenylsilyl)oxy)-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (2b) compounds inhibited the growth of the A549 and HeLa cells caused membrane damage and exhibited a dose-dependent cytotoxic effect on lung and cervical carcinoma cells. The effect of tert-butyldiphenylsilyl (TBDPS) groups on cytotoxicity was observed in compounds 2a and 2b, but not in the other compounds. Considering the effect of groups attached to the nitrogen atom, the best activity was exhibited in 2b molecule to which the methyl group is attached. Additionally, the interactions of compounds (3aR,5R,6R,7aS)-5-azido-6-hydroxy-2-methylhexahydro-1H-isoindole-1,3(2H)-dione (1b), 1d, 2a and 2b with mammalian rapamycin target, human ribosomal S6 kinase 1 and human epidermal growth factor receptor were investigated by molecular docking studies, . According to the docking results, 2a and 2b compounds containing a TBDPS group have stronger binding energies than 1b and 1d compounds against all target receptors.