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 114
  • 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
    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
    Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We
    (Springer, 2026) Shakeri, Raheleh; Mirjalili, Seyedeh Zohreh; Karakus, Ceyda Oksel; Safavi, Maliheh
    Investigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.
  • 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.
  • 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
    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
    Linking RNA Methylation to Structure: A Biophysical Perspective
    (Wiley, 2026) Akgul, Bunyamin; Guler, Gunnur; Saglam, Buket; Akkus, Onur; Akcaoz-Alasar, Azime
    Recent epitranscriptomic studies show that ribonucleic acids (RNAs) are coated with an array of chemical modifications that dictate their cellular fate. Genetic, biochemical, and genomic approaches have been employed to elucidate the molecular details of RNA methylation, one of the most prevalent types of RNA modifications with significant implications for health and disease. Various biochemical approaches have been developed to identify RNA methylations both at the global and nucleotide resolution levels. However, simpler detection methods are needed to assess the global methylation status of synthetic or cellular RNAs. Although significant progress has been made in elucidating the factors involved in writing, erasing, or reading methylated epitopes or structures, the impact of these methyl moieties on the secondary structure of RNAs or macromolecular interactions remains to be fully understood. Typically, biophysical approaches, such as Fourier transformed-infrared (FT-IR) spectroscopy, circular dichroism (CD), and Raman spectroscopy, have been used to study the structures and interactions of macromolecules, including DNA and proteins. Although RNAs harbor similar chemical modifications or structure-mediated functions, the number of RNA studies that employ biophysical approaches is scarce. In this viewpoint article, we present a biophysical perspective that links RNA methylation to structure and propose that FT-IR analyses can be employed to examine global changes in the abundance of cellular RNA m(6)A marks. Additionally, we discuss the potential applications of biophysical approaches that may be employed to gain insight into methylation-mediated changes in RNA structures.
  • Article
    Development of Self-Assembled Peptide Hydrogels Containing Matrix-Metalloproteinase Degradable Motifs for 3D Lung Cancer Models
    (Royal Society of Chemistry, 2026) Tarim, Burcu Sirma; Tamburaci, Sedef; Top, Ayben
    Hydrogel-forming peptides, including matrix metalloproteinase (MMP)-degradable motifs, have been employed to investigate cell-extracellular matrix interactions in vitro. However, their potential in 3D cancer models has been explored only in a few studies. In this study, we used modified MMP-2 degradable motifs (VSLRA or ASLRA) in the design of EDP1 (RVSLRADARVSLRADA) and EDP2 (RASLRADARASLRADA) peptide hydrogelators. The peptides self-assembled into nanofibrillar hydrogels with storage moduli between similar to 300 and similar to 400 Pa. MMP-2 degradation properties of the peptides were confirmed, and a slightly higher MMP-2 responsiveness of the EDP1 hydrogel was observed. The hydrogels were used in the encapsulation of A549 lung adenocarcinoma cancer cells and MRC-5 human lung fibroblast cells. The designed hydrogels supported the proliferation of these cells with high viability and induced cluster formation of encapsulated A549 cells similar to that observed with the RADA hydrogel. However, the hydrogel network structure affected the morphology of the migrated cells in the absence of curcumin. The addition of curcumin decreased the migration and invasion of A549 cells, resulting in a round cell morphology independent of the hydrogel matrices. Anticancer drug tests indicated that cell viability after drug treatment was higher in the 3D hydrogels than in 2D cultures. It was also confirmed that the combinational therapy of doxorubicin and curcumin decreased the cell proliferation and colonization to a greater extent compared to doxorubicin monotherapy. Thus, the hydrogels developed in this study can be used for 3D cancer models or other tissue engineering applications as an alternative to the RADA hydrogel by exploiting the MMP-2 degradation properties.