PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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 Dimensionality Effects in Anisotropic Single Layers TiSe5 and TiTe5: a Comparative Study of 2D Sheets and 1D Nanochains(IOP Publishing Ltd, 2026) Can Dogan, Kadir; Kutay Tamdogan, Omer; Bozkurt, Yagmur; Cetin, Zebih; Yagmurcukardes, MehmetIn this study, we present a comprehensive first-principles investigation of the structural, vibrational, and electronic properties of titanium pentachalcogenide structures in both two-dimensional (2D) and one-dimensional (1D) nanochain (NC) forms. Total energy and geometry optimizations reveal that the 2D TiX5 (X = Se, Te) structures exhibit in-plane anisotropy arising from the trigonal prismatic TiX3 units interconnected via the chalcogenide chains. Phonon band dispersions and elastic tensor elements confirm the dynamical and mechanical stability of the 2D layers, respectively. Electronically, while TiTe5 is a metal, TiSe5 possesses direct band gap semiconducting behavior. In addition, free-standing 1D NC counterparts, which are sub-units of the 2D structures, are investigated by means of their stability. Three stable 1D NCs, namely TiTe5-NC, TiSe7-NC, and TiTe7-NC, are found to be composed of edge-sharing TiX6-like units with either five- or seven-fold coordination. The dynamically stable 1D NCs are shown to be semiconductors with relatively larger band gaps as compared to 2D layers. Predicted Raman spectra reveal clear signatures of vibrational mode evaluations as a result of quantum confinement from the 2D layer to the 1D NC. Moreover, finite-temperature ab-initio quantum molecular dynamics simulations at 300 K confirm the thermal stability of both the 2D TiX5 layers and 1D NC derivatives, showing that the Ti-based systems retain their structural integrity under ambient conditions and are feasible candidates for experimental synthesis. Our findings highlight the formation of stable semiconducting 1D NCs of Ti-pentachalcogenides from their 2D counterparts.Article A Machine Learning Model for Predicting Oligoclonal Band Positivity Using Routine Cerebrospinal Fluid and Serum Biochemical Markers(Oxford University Press Inc, 2025) Gözgöz, Hazar; Orhan, Oğuzhan; Akan Konuk, Başak; Akan, PınarOBJECTIVE: To develop and validate a machine learning model for predicting oligoclonal band (OCB) positivity using routine cerebrospinal fluid (CSF) and serum biochemical markers to improve the diagnostic accuracy and efficiency of assessing intrathecal immunoglobulin G (IgG) synthesis. METHODS: In this retrospective study (n = 1709), an ensemble model was developed using 8 refined CSF and serum parameters. Combining optimized CatBoost, XGBoost, and LightGBM classifiers, the model was trained and evaluated using a 2-phase workflow, including 5-fold cross-validation and validation on independent internal (n = 342) and external (n = 49) cohorts. RESULTS: The developed ensemble model achieved a receiver operating characteristic-area under the curve (ROC-AUC) of 0.902 on the internal test set, significantly outperforming the conventional IgG index (ROC-AUC, 0.795). At its optimal threshold, the model demonstrated an accuracy of 0.830, with a sensitivity of 0.714 and a specificity of 0.916. On the external validation cohort, it achieved 90% accuracy and 96% sensitivity. CONCLUSIONS: A novel machine learning ensemble model accurately predicts OCB positivity using routine laboratory data and demonstrates superior performance compared with the IgG index. This approach represents a significant step in applying artificial intelligence in laboratory medicine, with the potential to enhance diagnostic efficiency. Prospective, multicenter validation is essential for broader clinical implementation. © The Author(s) 2025.Article One-Pot, Light-Induced, Liquid Crystal-Templated Synthesis of Nanoporous Silver Films at Room Temperature(TÜBİTAK, 2025) Mert-Balci, F.Nanoporous silver (NPS) films, characterized by a 3-dimensional bicontinuous structure of interconnected nanopores and ligaments, have found widespread use in spectroscopy, plasmonics, solar cells, catalysis, and chemical sensing. Traditionally, NPS films are fabricated via chemical dealloying, where a less noble metal (e.g., Cu or Al) is selectively removed through harsh chemical etching. However, residual traces of these metals can adversely affect the performance of NPS thin films in applications such as plasmonics and catalysis. This paper reports a one-pot, liquid crystal-templated method for synthesizing ultrapure NPS thin films at room temperature for the first time. The process begins with the preparation of an LLC composed of a nonionic surfactant and AgNO<inf>3</inf> that is then coated onto solid substrates. Exposure of the LLC film to ultraviolet light facilitates the in situ synthesis of Ag nanoparticles within the liquid crystal film. Subsequent solvent washing removes the surfactant molecules and any unreacted metal ions, yielding NPS films comprised of densely packed Ag nanoparticles on glass substrates. The resulting NPS films feature a 3-dimensional structure with uniformly distributed, interconnected nanopores. Synthesized under ambient conditions and scalable over large areas, these ultrapure NPS films present a highly promising platform for advanced applications in catalysis, spectroscopy, plasmonics, and biosensing. © TÜBİTAK.Article Subtype-Specific Divergent Roles of Calpain-1 and Calpain-2 in Basal a Triple-Negative Breast Cancer(BMC, 2025) Uner, Goklem; Oztarhan, Gokhan; Kirmizibayrak, Petek BallarBackgroundCAPN-1 and CAPN-2, two ubiquitously expressed calpains, have been implicated in cancer progression, but their distinct roles in breast cancer remain poorly defined. This study aims to define the opposing roles of CAPN-1 and CAPN-2 in breast cancer progression, with a focus on their regulatory impact on cell proliferation. Since these calpains may have different functions in the mammary gland, we aimed to investigate the possible antagonistic roles of CAPN-1 and CAPN-2 in breast cancer progression, focusing on their expression patterns and functional impact on cell proliferation.Methods and resultsWe analyzed breast cancer cell lines using immunoblotting and real-time cellular assays, showing that HCC1937 cells exhibit an opposite expression pattern of CAPN-1 and CAPN-2 compared to non-cancerous breast cells. CAPN-1 promoted cancer cell survival and negatively regulated CAPN-2 at both the protein and mRNA levels, whereas CAPN-2 suppressed proliferation. Additionally, the calpain activator AG-08 triggered cell death through CAPN-2 but not CAPN-1. In silico analysis confirmed higher CAPN-1 and lower CAPN-2 expression levels in breast cancer samples compared to normal tissue.ConclusionsThese findings indicate that CAPN-1 and CAPN-2 may exert antagonistic roles in breast cancer, but importantly, this effect was restricted to HCC1937 cells, representing a basal A TNBC subtype. Validation in additional basal A models and patient-derived samples will be essential to confirm these results. Our study, therefore, provides preliminary, model-specific insights into calpain regulation in TNBC and suggests that future therapeutic strategies should carefully account for subtype heterogeneity.Article Citation - WoS: 1Citation - Scopus: 1Imbalance in Redox Homeostasis Is Associated With Neurodegeneration in the Murine Model of Tay-Sachs Disease(Springer, 2025) Basirli, Hande; Ates, Nurselin; Seyrantepe, VolkanBackgroundTay-Sachs disease is a neurodegenerative disorder characterized by a build-up of GM2 ganglioside in the brain, which results in progressive central nervous system dysfunction. Our group recently generated Hexa-/-Neu3-/- mice, a murine model with neuropathological abnormalities similar to the infantile form of Tay-Sachs disease. Previously, we reported progressive neurodegeneration with neuronal loss in the brain sections of Hexa-/-Neu3-/- mice. However, the relationship between the severity of neurodegeneration and the imbalance in redox homeostasis was not yet clarified in Hexa-/-Neu3-/- mice. Here, we evaluated whether neurodegeneration is associated with oxidative stress in the tissues and cells of Hexa-/-Neu3-/- mice and neuroglia cells from Tay-Sachs patients.Methods and resultsCell death and oxidative stress-related markers were evaluated in four brain regions and fibroblasts of 5-month-old WT, Hexa-/-, Neu3-/-, and Hexa-/-Neu3-/- mice and human neuroglia cells using Western blot, RT-PCR, and immunohistochemistry analyses. We further analyzed oxidative stress levels in the samples using flow cytometry analyses. We discovered neuronal death, alterations in intracellular ROS levels, and damaging effects of oxidative stress, especially in the cerebellum and fibroblasts of Hexa-/-Neu3-/- mice.ConclusionsOur results showed that alteration in redox homeostasis might be related to neurodegeneration in the murine model of Tay-Sachs Disease. These findings suggest that targeting the altered redox balance and increased oxidative stress might be a rational therapeutic approach for alleviating neurodegeneration and treating Tay-Sachs disease.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 Citation - WoS: 1Citation - Scopus: 2Lacoo3 Is a Promising Catalyst for the Dry Reforming of Benzene Used as a Surrogate of Biomass Tar(Tubitak Scientific & Technological Research Council Turkey, 2024) Çağlar, Başar; Üner, DenizTar build-up is one of the bottlenecks of biomass gasification processes. Dry reforming of tar is an alternative solution if the oxygen chemical potential on the catalyst surface is at a sufficient level. For this purpose, an oxygen-donor perovskite, $LaCoO_3$, was used as a catalyst for the dry reforming of tar. To circumvent the complexity of the tar and its constituents, the benzene molecule was chosen as a model compound. Dry reforming of benzene vapor on the $LaCoO_3$ catalyst was investigated at temperatures of 600, 700, and 800 °C; at $CO_2/C_6H_6$ ratios of 3, 6, and 12; and at space velocities of 14,000 and 28,000 h–1. The conventional Ni(15 wt.%)/$Al_2O_3$ catalyst was also used as a reference material to determine the relative activity of the $LaCoO_3$ catalyst. Different characterization techniques such as X-ray diffraction, $N_2$ adsorption-desorption, temperature-programmed reduction, and oxidation were used to determine the physicochemical characteristics of the catalysts. The findings demonstrated that the $LaCoO_3$ catalyst has higher $CO_2$ conversion, higher $H_2$ and CO yields, and better stability than the Ni(15 wt.%)/γ-$Al_2O_3$ catalyst. The improvement in activity was attributed to the strong capacity of $LaCoO_3$ for oxygen exchange. The transfer of lattice oxygen from the surface of the $LaCoO_3$ catalyst facilitates the oxidation of carbon and other surface species and leads to higher conversion and yields.Article Citation - WoS: 3Citation - Scopus: 3Β-Ketoenamine-linked covalent organic framework for efficient iodine capture(Tubitak Scientific & Technological Research Council Turkey, 2024) Büyükçakır, OnurExploring the materials that effectively capture radioactive iodine is crucial in managing nuclear waste produced from nuclear power plants. In this study, a β-ketoenamine-linked covalent organic framework (bCOF) is reported as an effective adsorbent to capture iodine from both vapor and solution. The bCOF’s high porosity and heteroatom-rich skeleton offer notable iodine vapor uptake capacity of up to 2.51g $g^{–1}$ at 75 °C under ambient pressure. Furthermore, after five consecutive adsorption-desorption cycles, the bCOF demonstrates high reusability performance with significant iodine vapor capacity retention. The adsorption mechanism was also investigated using various ex situ structural characterization techniques, and these mechanistic studies revealed the existence of a strong chemical interaction between the bCOF and iodine. The bCOF also showed good iodine uptake performance of up to 512 mg $g^{–1}$ in cyclohexane with high removal efficiencies. The bCOF’s performance in adsorbing iodine from both vapor and solution makes it a promising material to be used as an effective adsorbent in capturing radioactive iodine emissions from nuclear power plants.Article Citation - WoS: 5Citation - Scopus: 8Textural, Rheological, Melting Properties, Particle Size Distribution, and Nmr Relaxometry of Cocoa Hazelnut Spread With Inulin-Stevia Addition as Sugar Replacer(John Wiley and Sons Inc, 2024) Berk,B.; Cosar,S.; Mazı,B.G.; Oztop,M.H.This study investigated the influence of substituting 60, 80, and 100% of the sugar in traditional cocoa hazelnut paste (control) formulation with inulin-stevia (90:10, w/w) mixture on textural and rheological characteristics, melting behavior, water activity (aw), particle size distribution (PSD), and color. Textural, rheological, melting properties, and color of samples were analyzed after 1, 2, and 3 months of storage at 11°C. Nuclear magnetic resonance (NMR) relaxometry experiments were also performed to understand the interaction of new ingredients with oil. Replacement of sugar with inulin-stevia gave darker color, reduced Casson yield stress, and changed the textural parameters and melting profile of the samples depending on the level but did not create a remarkable effect on PSD and Casson plastic viscosity. Increasing inulin-stevia content yielded lower aw and higher T2a values indicating decreased mobility of water. Complete removal of sugar caused low spreadability. The results showed that an 80% replacement level yielded a product with similar textural parameters and fat-melting mouth feeling compared to control sample. Cocoa hazelnut spreads prepared with inulin and stevia showed good textural stability during storage. © 2024 The Authors. Journal of Texture Studies published by Wiley Periodicals LLC.