PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Citation - WoS: 5Citation - Scopus: 7Rational Design of EDTA-Incorporated Nanoflowers as Novel and Effective Endodontic Disinfection Against Biofilms(Springer, 2023-10-03) Aslan, Tugrul; Dadi, Seyma; Kafdag, Ozgur; Temur, Nimet; Ildiz, Nilay; Ocsoy, Ismail; Ustun, YakupThe ethylenediaminetetradiacetic acid (EDTA) is one of the most commonly used irrigation solutions. Although EDTA has a very low antimicrobial property, it is used to remove inorganic part of smear layer in areas of root canal system. Herein, we developed EDTA-incorporated nanoflowers (EDTA NFs), for the first time, as novel and effective irrigation solution with quite high antimicrobial property to provide complete disinfection in root canal system. We both systematically elucidated the formation of the EDTA NFs with various techniques, and their catalytic and antimicrobial activities in the presence of hydrogen peroxide (H2O2) were documented through intrinsic EDTA property and peroxidase-like activities.Article Citation - WoS: 16Citation - Scopus: 18Microfluidic Chip Based Direct Triple Antibody Immunoassay for Monitoring Patient Comparative Response to Leukemia Treatment(Springer, 2020-07-13) Icoz, Kutay; Akar, Unal; Unal, EkremWe report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.Article Citation - WoS: 2Citation - Scopus: 3In Vitro Contact Guidance of Glioblastoma Cells on Metallic Biomaterials(Springer, 2021-03-29) Uzer-Yilmaz, B.Cancer cells' ability to sense their microenvironment and interpret these signals for the regulation of directional adhesion plays crucial role in cancer invasion. Furthermore, given the established influence of mechanical properties of the substrate on cell behavior, the present study aims to elucidate the relationship between the contact guidance of glioblastoma cell (GBM) and evolution of microstructural and mechanical properties of the implants. SEM analyses of the specimens subjected to 5 and 25% of plastic strains revealed directional groove-like structures in micro and submicro-sizes, respectively. Microscale cytoplasmic protrusions of GBMs showed elongation favored along the grooves created via deformation markings on 5% deformed sample. Whereas filopodia, submicro-sized protrusions facilitating cancer invasion, elongated in the direction perpendicular to the deformation markings on the 25% deformed sample, which might lead to easy and rapid retraction. Furthermore, number of cell attachment was 1.7-fold greater on 25% deformed sample, where these cells showed the greatest cellular aspect ratio. The directional attachment and contact guidance of GBMs was reported for the first time on metallic implants and these findings propose the idea that GBM response could be regulated by controlling the spacing of the deformation markings, namely the degree of plastic deformation. These findings can be applied in the design of cell-instructive implants for therapeutic purposes to suppress cancer dissemination.Article Identification of Nonsense Variants in the ATM Gene Mimicking SCID Phenotype: A Brief Report(Springer, 2025-05-16) Firtina, Sinem; Saritas, Merve; Ng, Yuk Yin; Nepesov, Serdar; Kiykim, Ayca; Bozkurt, Selcen; Sayitoglu, MugeSevere combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lymphopenia, it may overlap with other conditions like ataxia-telangiectasia (AT), which also presents with T-cell deficiencies. This study examines two cases of suspected SCID in infants, later identified as AT due to pathogenic variants in the ATM gene. Despite initial negative results from SCID-targeted gene panels, further genetic testing revealed nonsense mutations (p.Y2036X and p.E1996X) in the FAT domain of the ATM gene, confirmed by Sanger sequencing. The patients exhibited significant T-cell lymphopenia and reduced ATM protein activity, indicative of AT. These findings highlight the importance of comprehensive genetic screening beyond common SCID-associated genes, especially in patients with atypical presentations. Early and accurate diagnosis can prevent mismanagement and guide appropriate therapies, improving patient outcomes.Article Citation - WoS: 3Citation - Scopus: 4High-Resolution DIC Analysis of in Situ Strain and Crack Propagation in Coated AZ31 Magnesium Alloys Under Mechanical Loading(Springer, 2025-08-25) Yavuzyegit, Berzah; Karali, Katerina; Davis, Sarah; Morrison, Benjamin; Karabal, Suleyman; Balandiz, Kemal; Blunn, GordonBiodegradable magnesium (Mg) alloys are promising for various biomedical applications but their susceptibility to corrosion poses significant challenges. This study systematically examines the microstructural integrity and failure mechanisms of electrochemically deposited phosphate- and fluorine-rich coatings on AZ31 Mg alloy subjected to three-point bending (3 PB) in both non-corrosive and physiological (HBSS) environments. High-resolution digital image correlation (HR-DIC) combined with scanning electron microscopy (SEM) enables in situ visualization and quantitative analysis of crack initiation, evolution, and propagation within the coatings. Our findings reveal that thinner (5 mu m) coatings are prone to forming dense networks of fine cracks, while thicker (15 mu m) coatings display fewer but wider cracks, with both morphologies strongly governed by localized shear strain. Importantly, cross-sectional analyses after load-holding demonstrate that, while surface cracks initially remain confined within the coating, cracks generated under higher mechanical loading can propagate through the entire coating thickness. These through-thickness cracks create direct pathways for corrosive fluids to access the underlying alloy, serving as initiation sites for stress corrosion cracking within the substrate. Furthermore, our results indicate that fluoride in the coating mitigates rapid corrosion. Overall, the study reveals that coating failure and the formation of through-thickness cracks play a critical role in facilitating localized corrosion and crack initiation within the alloy under combined mechanical and corrosive environments.Article Functional Combination of Resveratrol and Midostaurin Induces Cytotoxicity to Overcome Acquired Midostaurin Resistance in FLT3-ITD Expressing Acute Myeloid Leukemia Cells(Springer, 2025-08-20) Tecik, Melisa; Adan, AysunThe most important challenge in treating FLT3-ITD AML is the development of resistance to FLT3 inhibitors, such as midostaurin, via both FLT3-dependent and FLT3-independent mechanisms. The study explored the potential cytotoxic effects of combining resveratrol and midostaurin on the sensitization of midostaurin-resistant cells. MTT assay revealed resveratrol's chemo-sensitizing influence on midostaurin-resistant cells, and combination indexes (CI) were calculated using Chou-Talalay's method. Apoptosis induction and cell cycle progression was analyzed by flow cytometry. The apoptotic molecular markers caspase 3, PARP, Bcl-2, and Bax were analyzed using a western blot. Sphingosine kinase-1 (SK-1) expression, total and phosphorylated FLT3, and STAT5A levels were measured using western blotting. Resveratrol enhanced the cytotoxic effects of midostaurin additively in resistant MV4-11MR and MOLM-13MR cells. It effectively reversed midostaurin resistance by inhibiting the activating phosphorylation of FLT3, STAT5A, and modulating the expression of SK-1 while concurrently increasing the levels of cleaved caspase-3 and PARP without noticeable alterations in Bax/Bcl-2 ratios except MV4-11MR cells. Additionally, there was an arrest at the S or G0/G1 phase of the cell cycle, depending on the resistant cells, compared to midostaurin alone, but not to the control group. In conclusion, the FLT3/STAT5A axis and SK-1 might play an important role in the reversal of midostaurin resistance by resveratrol. Therefore, the concurrent administration of resveratrol plus midostaurin could potentially serve as a therapeutic approach to address midostaurin resistance and enhance the overall therapy efficacy for FLT3-ITD AML patients after being validated with future in vivo and ex vivo studies.Article Citation - WoS: 31Citation - Scopus: 34Discovery of Adapalene and Dihydrotachysterol as Antiviral Agents for the Omicron Variant of SARS-CoV-2 Through Computational Drug Repurposing(Springer, 2022-05-04) Fidan, Ozkan; Mujwar, Somdutt; Kciuk, MateuszSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2. [GRAPHICS] .Article Citation - WoS: 3Citation - Scopus: 3Determination of Promising Inhibitors for N-SH2 Domain of SHP2 Tyrosine Phosphatase: An in Silico Study(Springer, 2024-05-13) Akcok, Emel Basak Gencer; Guner, Huseyin; Akcok, Ismail; Gencer Akçok, Emel BaşakThere are many genes that produce proteins related to diseases and these proteins can be targeted with drugs as a potential therapeutic approach. Recent advancement in drug discovery techniques have created new opportunities for treating variety of diseases by targeting disease-related proteins. Structure-based drug discovery is a faster and more cost-effective approach than traditional methods. SHP2 phosphatase, encoded by the PTPN11 gene, has been the focus of much attention due to its involvement in many types of diseases. The biological function of SHP2 is enabled mostly by protein-protein interaction through its SH2 domains. In this study, we report the identification of a potential small molecule inhibitor for the N-SH2 domain of SHP2 by structure-based drug discovery approach. We utilized molecular docking studies, followed by molecular dynamics simulations and MM/PBSA calculations, to analyze compounds retrieved from the Broad's Drug Repurposing Hub and ZINC15 databases. We selected 10 hit compounds with the best docking scores from the libraries and examined their binding properties in the N-SH2 domain. We found that compound CID 60838 (Irinotecan) was the most suitable compound with a binding free energy value of - 64.45 kcal/mol and significant interactions with the target residues in the domain.Article Citation - WoS: 4Citation - Scopus: 5Can Mesenchymal Stem/Stromal Cells and Their Secretomes Combat Bacterial Persisters(Springer, 2023-08-12) Bicer, Mesude; Fidan, OzkanThe increasing number of life-threatening infections caused by persister bacteria is associated with various issues, including antimicrobial resistance and biofilm formation. Infections due to persister cells are often difficult to suppress without the use of last-resort antibiotics. Throughout the world, bacterial persistence and resistance create an unmet clinical demand for the exploration of newly introduced therapeutic approaches. Mesenchymal stem / stromal cells (MSCs) have an antimicrobial activity to protect against bacterial infections, including those caused by bacterial persisters. MSCs have substantial potential to secrete antimicrobial peptides (AMPs), including cathelicidin, beta-defensins, lipocalin-2, hepcidin, indoleamine 2,3-dioxygenase (IDO), cysteine proteases, and inducible nitric oxide synthases (iNOS). MSCs possess the potential to contribute to innate immunity by regulating the immune response. Recently, MSCs and their secreted components have been reported to improve antimicrobial activity. Bactericidal activity by MSCs and their secretomes has been shown to be mediated in part by the secretion of AMPs. Even though they were discovered more than 80 years ago, therapeutic options for persisters are restricted, and there is an urgent need for alternative treatment regimens. Hence, this review intends to critically assess the current literature on the effects of MSCs and their secretomes on persister bacteria. MSCs and their secretome-based therapies could be preferred as an up-and-coming approach to reinforce the antimicrobial efficiency in persister infections.