Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Anticancer Properties of Newly Synthesized Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors(Wiley, 2026) Kaya, Meltem; Kara, Yunus; Sanli-Mohamed, GulsahThe anticancer activity of a series of newly synthesized pyrrole derivatives was systematically evaluated in HeLa cervical cancer cells, focusing on their potential as tyrosine kinase inhibitors and modulators of the mTOR signaling pathway. This study builds on our previous synthetic work by investigating the biological effects of seven structurally characterized compounds (d1-d7). Among them, compounds d1 and d3 exhibited the most potent cytotoxicity, with IC50 values of 140.6 mu M and 366.4 mu M, respectively, after 48 h of treatment. Both compounds significantly impaired cell cycle progression-d1 induced S-phase arrest, while d3 caused G1-phase arrest-and markedly suppressed cell migration in wound healing assays. Mechanistically, these effects were accompanied by reduced phosphorylation of p70S6K (Thr389, Ser421/424) and increased p-4EBP1, indicating inhibition of mTORC1 signaling. These findings suggest that d1 and d3 are promising lead compounds with dual antiproliferative and anti-migratory activity in cervical cancer, mediated through modulation of the PI3K/Akt/mTOR axis.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 Hydrogeochemical Assessment and Health Risks of Groundwater in Sahand Volcanic Foreland (NW Iran): Arsenic Speciation and Heavy Metal Risk Indicators(Academic Press Inc Elsevier Science, 2026) Ghayurdoost, Farhad; Zarghami, Mahdi; Sadeghfam, Sina; Jabraili-Andaryan, Nasser; Nikmaram, Sara; Baba, Alper; Mosaferi, MohammadDue to the toxic nature of arsenic (As) and its elevated concentrations in many water resources, numerous studies have focused on understanding its origin, distribution, and impacts. This study aimed to identify the dominant As species in groundwater of the Sahand Volcanic Foothills, assess water quality indices, and examine heavy metal (HM) concentrations to address rising concerns about groundwater contamination. A total of 21 groundwater samples were collected and analyzed in accordance with world health organization (WHO) guidelines. Although most samples fell within acceptable ranges, several (notably S10, S20, and S21) exhibited elevated levels of total dissolved solids (TDS), electrical conductivity (EC), and HMs, particularly iron (Fe) and As. Hydrochemical assessments using Piper, Gibbs, Stiff, and Schoeller diagrams indicated that geochemical processes resulting from rock dissolution were the main factors controlling groundwater chemistry, with limited influence from anthropogenic pollution. According to the groundwater quality index (GWQI), most samples were categorized as "good" to "excellent," though some areas ranged from "moderate" to "very poor." HM pollution indices revealed that As concentrations exceeded permissible limits. Health risk assessments further showed that both oral and dermal exposure posed significant carcinogenic and non-carcinogenic risks, especially for children. Speciation analysis indicated that arsenate (As V) was the dominant form of As, consistent with oxidizing aquifer conditions, and is less biologically hazardous than arsenite (As III). The study highlights the necessity of continuous groundwater monitoring, effective pollution source management, and implementation of protective regulations to mitigate environmental and health risks in the region.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 Notum1a Inhibition Promotes Neurogenesis in the Adult Zebrafish Brain(Nature Portfolio, 2025) Kocagoz, Yigit; Erdogan, Nuray Sogunmez; Ozdinc, Sevval; Ipekgil, Dogac; Katkat, Esra; Ozhan, GunesNotum is a carboxylesterase enzyme that modulates extracellular signaling by hydrolyzing palmitoleoyl residues from proteins, thereby influencing key pathways involved in cell differentiation, survival, and proliferation. While notum1 expression has been identified in the brain, its role in adult neurogenesis remains poorly understood. Using the adult zebrafish brain as a model system, we demonstrate that the notum1a homolog is broadly expressed across various brain cell types but is absent in undifferentiated radial glial cells. Pharmacological inhibition of Notum activity with the small molecule inhibitor ABC99 stimulates activation of radial glial cells, leading to increased neurogenesis. A BrdU pulse-chase assay confirms that ABC99-induced proliferation enhances the production of mature neurons. Despite Notum's established role in Wnt signaling, transcriptional analysis following ABC99 treatment reveals no sustained impact on Wnt pathway targets, suggesting that Notum may regulate neurogenesis through alternative mechanisms. Our findings highlight notum1a as a potential modulator of neural progenitor cell dynamics in the adult brain and suggest that targeting Notum could represent a novel therapeutic strategy for neurodegenerative conditions characterized by impaired neurogenesis.Article A Physics-Informed Neural Network (PINN) Approach to Over-Equilibrium Dynamics in Conservatively Perturbed Linear Equilibrium Systems(MDPI, 2025) Dutta, Abhishek; Mukherjee, Bitan; Hosen, Sk Aftab; Turan, Meltem; Constales, Denis; Yablonsky, GregoryConservatively perturbed equilibrium (CPE) experiments yield transient concentration extrema that surpass steady-state equilibrium values. A physics-informed neural network (PINN) framework is introduced to simulate these over-equilibrium dynamics in linear chemical reaction networks without reliance on extensive time-series data. The PINN incorporates the reaction kinetics, stoichiometric invariants, and equilibrium constraints directly into its loss function, ensuring that the learned solution strictly satisfies physical conservation laws. Applied to three- and four-species reversible mechanisms (both acyclic and cyclic), the PINN surrogate matches conventional ODE integration results, reproducing the characteristic early concentration extrema (maxima or minima) in unperturbed species and the subsequent relaxation to equilibrium. It captures the timing and magnitude of these extrema with high accuracy while inherently preserving total mass. Through the physics-informed approach, the model achieves accurate results with minimal data and a compact network architecture, highlighting its parameter efficiency.Article K41-A Enhances the Antiproliferative Efficacy of Cisplatin in Neuroblastoma by Modulating Apoptosis and Autophagy(Oxford University Press, 2026) Sanlav, Gamze; Kum Ozsengezer, Selen; Altun, Zekiye; Bedir, Erdal; Aktas, Safiye; Olgun, NurObjectives Neuroblastoma (NB), the most common extracranial tumor in childhood, has a poor prognosis, especially in cases with MYC gene amplification. Cisplatin (CDDP) is widely used in treatment, but its effectiveness is limited due to chemotherapy resistance. Autophagy plays a dual role in cancer progression, either promoting survival or contributing to cell death.Methods This study explores the anticancer effects of K41-A, a polycyclic polyether molecule, alone and in combination with CDDP in SH-SY5Y and KELLY NB cell lines, the HE-IOC1 noncancerous cochlear cell line, and the NB xenograft model.Key findings For the first time, we demonstrate that K41-A, either alone or combined with CDDP, significantly inhibits cell proliferation selectively in NB cells, sparing noncancerous cells. This study confirmed that K41-A alone and in combination with CDDP induced changes in both apoptotic and autophagic cell death components in NB, resulting in antiproliferative activity in vitro and in vivo. In addition, the combination with CDDP enhanced the therapeutic efficacy of K41-A.Conclusions These results highlight the potential of K41-A as a candidate drug for the treatment of NB.Article Temporal Coherence of Single Photons Emitted by Hexagonal Boron Nitride Defects at Room Temperature(Amer Chemical Soc, 2026) Martinez-Pons, Juan Vidal; Kim, Sang Kyu; Behrens, Max; Izquierdo-Molina, Alejandro; Menendez Rua, Adolfo; Pacal, Serkan; Anton-Solanas, CarlosColor centers in hexagonal boron nitride (hBN) emerge as promising quantum light sources at room temperature, with potential applications in quantum communications, among others. The temporal coherence of emitted photons (i.e., their capacity to interfere and distribute photonic entanglement) is essential for many of these applications. Hence, it is crucial to study and determine the temporal coherence of this emission under different experimental conditions. In this work, we report the coherence time of the single photons emitted by an hBN defect in a nanocrystal at room temperature, measured via Michelson interferometry. The visibility of this interference vanishes when the temporal delay between the interferometer arms is a few hundred femtoseconds, highlighting that the phonon dephasing processes are 4 orders of magnitude faster than the spontaneous decay time of the emitter. We also analyze the single photon characteristics of the emission via correlation measurements, defect blinking dynamics, and its Debye-Waller factor. Our room temperature results highlight the presence of a strong electron-phonon coupling, suggesting the need to work at cryogenic temperatures to enable quantum photonic applications based on photon interference.Article Interaction of Hazelnut-Derived Polyphenols With Biodegradable Film Matrix: Structural, Barrier, and Functional Properties(Multidisciplinary Digital Publishing Institute (MDPI), 2026) Hızır-Kadı, I.; Demircan, E.; Özçelik, B.The study presents a sustainable approach to valorizing hazelnut processing by-products, specifically skins and shells, through their conversion into bioactive polyphenol-rich extracts using pressurized hot water extraction (PHWE), an environmentally friendly green technology. PHWE yielded extracts with total phenolic contents of 25.4 mg GAE/g dw (shell) and 83.7 mg GAE/g dw (skin), which were incorporated into biodegradable poly(vinyl alcohol)/carboxymethyl cellulose (PVA/CMC) films at concentrations of 1–3% (w/v). The resulting composites were comprehensively characterized in terms of structural, mechanical, thermal, and barrier properties. FTIR, DSC, and XRD analyses demonstrated strong hydrogen bonding, increased thermal stability, and reduced crystallinity due to polyphenol–polymer interactions. Phenolic incorporation enhanced UV-blocking capability, increased antioxidant activity by up to five-fold, and reduced oxygen permeability from 0.048 to 0.015 (cm3·mm·m−2·day−1·atm−1) (69% reduction, p < 0.05), compared to neat PVA while maintaining desirable transparency (>70%). Optimal formulations (HSkE-II) exhibited a 39% increase in elongation at break and improved flexibility without compromising film integrity. Application tests using fresh-cut apples, watermelon, and chicken revealed significant reductions in microbial growth (up to ~1.2 log CFU/g), lipid oxidation, and weight loss during storage, confirming the films’ potential for active food packaging. This work highlights an efficient valorization strategy for nut industry by-products and demonstrates their functional integration into sustainable biodegradable packaging systems. © 2025 by the authors.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.