PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7645

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Now showing 1 - 10 of 1187
  • Article
    Anticancer Properties of Newly Synthesized Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors
    (Wiley, 2026) Kaya, Meltem; Kara, Yunus; Sanli-Mohamed, Gulsah
    The 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, Hakan
    A 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, Mohammad
    Due 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.
  • Correction
    Development of Tissue-Engineered Vascular Grafts from Decellularized Parsley Stems (Vol 20, Pg 338, 2024)
    (Royal Society Chemistry, 2024) Cevik, Merve; Dikici, Serkan
  • 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 Yalcin
    Background/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, Gunes
    Notum 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, Gregory
    Conservatively 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, Nur
    Objectives 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
    Iron Oxide Nanocube Assembly on Silver Nanowire Templates to Enhance Magnetic Hyperthermia Performance
    (Royal Society of Chemistry, 2026) Arica, Tugce A.; Tiryaki, Ecem; Sadeghi, Ehsan; Mannir, Abubakar R.; Balci, Sinan; Pellegrino, Teresa
    Iron oxide nanocubes (IONCs) represent one of the benchmark magnetic nanoparticles able to most efficiently convert magnetic energy into heat for magnetic hyperthermia cancer treatment, and their heat losses can be further increased by controlling their assembly through the synthesis of ordered structures. However, achieving the alignment of nanoparticles with one-dimensional chain or columnar structures into long arrays to then study their magnetic heat losses still remains a significant challenge. This study exploits silver nanowires as high-surface-area anisotropic templates for the controlled chaining of IONCs. The surfaces of the IONCs were purposely functionalized with polyethyleneimine (IONCs@PEI) and interacted with silver nanowire (AgNW) surfaces via electrostatic attraction. Here, alternating current (AC) magnetometry was employed to compare the heating performance expressed as specific absorption rate values between individually coated IONCs@PEI and AgNWs@IONCs@PEI composites at various magnetic field strengths and frequencies. SAR values reveal that clustering of IONCs on AgNW surfaces improves the heating efficiency at an applied magnetic field strength of 24 kA m-1, regardless of the applied frequencies, with SAR values of AgNWs@IONCs@PEI composites outperforming those of individual IONCs@PEI. Moreover, dynamic hysteresis loops showed that the coercive field of AgNWs@IONCs@PEI increased significantly at 24 kA m-1, indicating the existence of strong magnetic dipolar interactions between nanoparticles. This study shows an innovative approach for guiding the orientation of magnetic nanoparticles using one-dimensional templates to enhance their heating performance.
  • Article
    Relationships Between Light Exposure and Aspects of Cognitive Function in Everyday Life
    (Springer Nature, 2025) Didikoglu, Altug; Woelders, Tom; Bickerstaff, Lucien; Mohammadian, Navid; Johnson, Sheena; van Tongeren, Martie; Lucas, Robert J.
    Light exposure can modulate cognitive function, yet its effects outside of controlled laboratory settings remain insufficiently explored. To examine the relationship between real-world light exposure and cognitive performance, we assessed personal light exposure and measured subjective sleepiness, vigilance, working memory, and visual search performance over 7 days of daily life, in a convenience sample of UK adults (n = 58) without significant circadian challenge (shiftwork or jet-lag). A subset of participants (n = 41) attended an in-lab session comprising a battery of pupillometric and psychophysical tests aimed to quantify melanopsin-driven visual responses. We find significant associations between recent light exposure and subjective sleepiness. Recent light exposure was also associated with reaction times for both psychomotor vigilance and working memory tasks. In addition, higher daytime light exposure and an exposure pattern with reduced fragmentation were linked to improved cognitive performance across visual search, psychomotor vigilance, and working memory tasks. Higher daytime light exposure and earlier estimated bedtimes were associated with stronger relationships between recent light exposure and subjective sleepiness. These results provide real world support for the notion that intra- and inter-individual differences in light exposure meaningfully influence aspects of cognition, with beneficial effects of short-term bright light and of habitual light exposure patterns characterized by brighter daytimes, earlier rest phase, and greater intra- and inter-daily stability.