PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer Using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive In Silico Study(Bentham Science Publ Ltd, 2026) Yucel, Muhsin Samet; Akcok, IsmailBackground Histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are crucial therapeutic targets in cancer research with their interconnected roles in regulating protein homeostasis and cellular processes. The interaction of these proteins within the cytosolic complex plays a critical role in regulating cancer cell survival and progression. Notably, current studies highlight that the simultaneous inhibition of HDAC6 and Hsp90 can produce synergistic effects and offer a promising therapeutic potential for combating malignant cancers.Objective The objective of this study was to explore potential compounds that can inhibit both HDAC6 and Hsp90 proteins.Methods In this study, a number of in-silico computational techniques were employed. A total of 791 molecules, sharing at least 30% similarity with previously identified four HDAC inhibitors, were obtained from the ZINC15 database and subjected to docking on HDAC6 and Hsp90 proteins. The top eight ligands demonstrating the best binding scores against both targets, with panobinostat and ganetespib serving as reference compounds for HDAC6 and Hsp90, respectively, were selected for further analysis. Subsequently, ADME prediction and molecular dynamics simulations were conducted on the selected ligands.Results A detailed molecular docking, molecular dynamics simulations and ADME studies have revealed that ZINC27653366 exhibited the highest inhibitory potential against both Hsp90 and HDAC6 target proteins, making it the most promising inhibitor.Conclusion In conclusion, although additional in vitro and in vivo studies are required for the validation, in silico evaluation of ZINC27653366 may position it as a promising candidate for the treatment of different types of cancers.Article Unveiling the Therapeutic Role of 3D-Cultured Mesenchymal Stem Cells in Diabetic Foot Ulcers through Transcriptomic Integration and Fibroblast Modulation(Springer, 2026-03-31) Ozturk, Esengul; Bicer, MesudeBackground Diabetic foot ulcers (DFUs) are among the most severe complications of diabetes mellitus and remain difficult to manage due to chronic inflammation, defective angiogenesis, delayed tissue repair, which increase the risk of recurrence and limb amputation. Standard treatments, such as debridement, infection management, pressure off-loading and revascularization, are commonly used, however; these interventions often inadequate to fully restore effective wound repair. Mesenchymal stem cells (MSCs) have attracted remarkable interest due to their potential regenerative ability and paracrine activity. Nevertheless, the molecular interaction between MSCs and fibroblasts under hyperglycemic conditions has not been fully elucidated. Objective This study aimed to examine differentially expressed genes (DEGs) associated with DFUs and MSC-related regenerative mechanisms using transcriptomic datasets (such as GSE143735, GSE199939, and GSE217709). Methods and results Differentially expressed genes and protein-protein interaction (PPI) network analysis were performed to determine central regulatory genes. Four key genes including CXCL1, MMP9, THBS1, and POSTN were recognized as hub genes related to inflammatory response, extracellular matrix reorganization, and angiogenesis. For experimental validation, L929 murine fibroblasts were exposed to high-glucose conditions to set-up an in vitro diabetic model and subsequently treated with MSCs with/without a 3D platform. Hyperglycemic conditions significantly reduced fibroblast proliferation and migration downregulated the expression of the identified hub genes and enhanced apoptotic activity. MSC treatment partially increased cellular function, while MSCs embedded into 3D culture enhanced a more pronounced recovery in both gene expression patterns and functional assays. Conclusions These findings suggest that high glucose impair fibroblast functions for wound repair, while 3D-cultured MSCs enhance regenerative responses and may represent a promising strategy for diabetic wound healing.Article TEffectBayes: A Nextflow Pipeline for Exploring the Potential Effect of Transposable Elements in Gene Regulatory Network with Multi-Omic Bayesian Network Model(Springer Heidelberg, 2026-03-10) Karakülah, Gökhan; Güner, Hüseyin; Kutlu, Necati KaanTransposable elements (TEs) are critical contributors to gene regulatory networks, yet their repetitive and abundant nature complicates efforts to elucidate their precise regulatory roles. While existing computational tools facilitate systematic identification of associations between TEs and gene expression, these methods typically cannot account for confounding variables or capture causal and directional interactions. To address these limitations, we developed TEffectBayes, a Nextflow-based pipeline leveraging a multi-omic Bayesian network (BN) framework designed to systematically infer directional, probabilistic regulatory dependencies involving TEs. TEffectBayes integrates diverse omics datasets, including RNA-seq-derived gene and locus-specific TE expression, along with ChIP-seq-based histone modification data processed via custom R and Python scripts. Integrated multi-omic datasets are subsequently employed to build gene-centric Bayesian models, enabling robust inference of context-dependent, probabilistic relationships between TEs, chromatin modifications, and gene expression. TEffectBayes thus provides a reproducible and scalable computational framework for unraveling the complex regulatory landscape shaped by TEs. In summary, TEffectBayes supports systematic prioritization of TE-chromatin-gene regulatory candidates for downstream benchmarking and experimental validation, enabling hypothesis-driven follow-up studies in diverse biological contexts. The pipeline, along with comprehensive user tutorials and example datasets, is publicly accessible at https://github.com/nkaan-kutlu/TEffectBayes.Article Integrative Bioinformatics Prediction of West Nile Virus-Derived microRNAs Reveals Potential Host Regulatory Interactions(Elsevier Sci Ltd, 2026-08) Demirci, Muserref Duygu Sacar; Orhan, Mehmet Emin; Erginkoc, Altay Nida; Saçar Demirci, Müşerref DuyguWest Nile virus (WNV) is a mosquito-borne flavivirus linked to severe neuroinvasive disease. Although host and vector microRNAs (miRNAs) have been implicated in viral infection, the presence and functional relevance of WNV-encoded miRNAs remain largely unexplored. Here, we developed an integrative bioinformatics pipeline that combines multiple miRNA prediction algorithms with secondary structure screening and host transcriptomic data to identify high-confidence candidate WNV-derived mature miRNAs. Overlap-based confidence scoring and differential expression support from RNA-seq datasets prioritized a small subset of putative miRNA-mRNA interactions with potential roles in infection-associated gene regulation. A competitive endogenous RNA network constructed from predicted mRNA, lncRNA, and circRNA targets highlighted pathways involving innate immunity, GPCR and Wnt signaling, RNA degradation, and viral replication. Together, these findings provide a reproducible computational workflow and nominate testable regulatory interactions for future experimental validation.Article Borax-Doped Fe2O3 and CeO2 Nanoparticles Regulate Dose-Dependently Inflammation, the Cell Cycle, and Migration in LPS-Activated THP-1 Cells(Wiley-VCH Verlag GmbH, 2026-03) Sulak, Mine; Ceylan Ekiz, Yağmur; Şen, Alaattin; Acar, Büşra; Çelik Turgut, Gurbet; Aktaş Pepe, NihanThis study examined the biological effects of borax-doped Fe2O3 and CeO2 nanoparticles (NPs) on lipopolysaccharide (LPS)-activated THP-1 cells. The morphology and composition of the nanocomposites were confirmed via scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX). Cell viability (resazurin and crystal violet assays), apoptosis/necrosis (annexin V/propidium iodide [PI]), cell cycle (flow cytometry), migration (scratch assay), and inflammatory response (Iba1 immunofluorescence staining, inducible nitric oxide synthase [iNOS] activity, and RT-PCR) were evaluated. The particle sizes ranged from 21.34 to 33.47 nm (Fe2O3-B-NPs) and 31.07 to 36.62 nm (CeO2-B-NPs). The IC10 and IC50 dose ranges were defined for each nanocomposite and applied across different cell lines to evaluate dose-dependent biological effects. Fe2O3-B-NPs altered cell cycle progression, increasing the number of S phase cells. Both nanocomposites promoted migration at low doses but inhibited it at high doses. CeO2-B-NPs reduced Iba1 levels, whereas Fe2O3-B-NPs increased inflammatory marker levels at higher concentrations. CeO2-B-NPs suppressed TNF-alpha and IL-1 beta gene expression at the IC50 dose, while both nanocomposites reduced iNOS activity. These results indicate that the dose-dependent effects of nanocomposites should be carefully evaluated.Article Thermal Stresses in SOFC Stacks: The Role of Mismatch Among Thermal Conductivity of Adjacent Components(Tubitak Scientific & Technological Research Council Turkey, 2021-06-30) Aydin, Ozgur; Matsumoto, Go; Shiratori, YusukeGenerating power from renewable biogas in solid oxide fuel cells (SOFCs) is an environment-friendly, efficient, and promising energy conversion process. Biogas can be used in SOFCs via a reforming process for which dry reforming is more suitable as the reforming agent exists in the biogas mixture. Biogas can be directly reformed to H-2 -rich fuel stream in the anode chamber of a SOFC by the heat released during power generation. Exploiting the heat and water produced in the SOFC for internal reforming of biogas makes the energy conversion process very efficient; however, various challenges are reported. Thus, indirect internal reforming is opted for which a separate reforming domain is required. In an indirect internal reformer operating at usual conditions, dry reforming rate is quite high in the inlet and it decreases steeply toward the fuel outlet. Great temperature gradients develop over the reformer, since the dry reforming reaction is strongly endothermic. The abruptly varying rate of the reforming reaction affects the temperature fields in the adjacent components of SOFC and hence intolerable thermal stresses emerge on the SOFC components. In our preceding study, we graded the reforming domain, homogenized the temperature profile over the reforming domain, and executed performance and durability experiments. However, most of the experiments failed due to fracturing SOFC components hinting at existence of thermal stresses. In that study, we focused on minimizing the temperature gradients within the reforming domain; namely, we neglected the other processes. To eliminate the thermal stresses, we modeled the entire module of SOFC equipped with a reformer featuring a graded reforming domain. We found that the mismatch between the thermal conductivities of the adjacent module components is the major reason for the thermal stresses. When the mismatch is eliminated, thermal stresses disappear even if the reforming domain is not graded.Article Citation - WoS: 9Citation - Scopus: 9Therapeutic Potential of Nitrogen-Substituted Oleanolic Acid Derivatives in Neuroinflammatory and Cytokine Pathways: Insights From Cell-Based and Computational Models(Wiley-VCH Verlag GmbH, 2025-04-22) Turgut, Gurbet Celik; Pepe, Nihan Aktas; Ekiz, Yagmur Ceylan; Senol, Halil; Sen, AlaattinThis study was conducted to investigate the mechanism of the potential and anti-inflammatory properties of nitrogen-substituted oleanolic acid derivatives that can be used to treat neuroinflammatory diseases. Nitrogen-containing oleanolic acid derivatives have been evaluated for their anti-neuroinflammatory effects in vitro in neuronal and monocytic cell lines at nontoxic doses, and the production of cytokines (TNF-alpha, IL-6 and IL-17), the inflammatory enzyme induced nitric oxide synthase (iNOS) and NF-kappa B signalling under LPS-stimulated conditions, and the expression of genes associated with Alzheimer's disease have been assessed. In addition, molecular docking and molecular dynamics simulation assessments are conducted in silico. Key protein markers of neurodegenerative diseases, especially Alzheimer's disease and neuroinflammation, TAU protein levels, and microglial activation, as well as ionised calcium-binding adaptor protein-1 (IBA1) levels, were significantly reduced with the addition of oleanolic acid derivatives. LPS-induced NF-kappa B luciferase reporter activity and iNOS activity were significantly inhibited, approaching the levels in uninduced controls. The mRNA expression of proinflammatory cytokines critical for neuroinflammation, such as TNF-alpha, NF-kappa B, IL-6 and IL-17, was reduced twofold to sevenfold. Furthermore, the molecular docking and MD simulation analyses revealed potential interactions with the TNF-alpha and NF-kappa B proteins. These findings underscore the potential of oleanolic acid derivatives, particularly compound 16, as candidates for further development as therapeutic agents for neurodegenerative diseases associated with chronic inflammation.Article Citation - WoS: 3Citation - Scopus: 3Theoretical Investigation of Substituent Effects on the Relative Stabilities and Electronic Structure of [BnXn]2- Clusters(Springer, 2021-11-29) Tahaoglu, Duygu; Alkan, Fahri; Durandurdu, MuratIn this study, we provide a theoretical evaluation of relative stabilities and electronic structure for [BnXn](2-) clusters (n = 10, 12, 13, 14, 15, 16). Structural and electronic characteristics of [BnXn](2-) clusters are examined by comparison with the [B12X12](2-) counterparts with a focus on the substituent effects (X = H, F, Cl, Br, CN, BO, OH, NH2) on the electronic structure, electron detachment energies, formation enthalpies, and charge distributions. For the electronic structure and electron detachment energies, substituent effects on boron clusters are shown to follow a very similar trend to the mesomeric and inductive effects (+/- M and +/- I) of pi-conjugated systems, and the most stable derivatives in terms of HOMO/LUMO and electron detachment energies are calculated for CN and BO substituents due to strong -M effects. In the case of formation enthalpies for larger boron clusters (n >= 13), the icosahedral barrier is shown to increase with the halogen and CN substitution, whereas it is possible to reduce the icosahedral barrier for the cases of X = OH and NH2. It is shown that this reduction results from destabilizing the [B12X12](2-) cluster with electronic (+ M) and symmetry effects induced by OH and NH2 ligands.Article Citation - WoS: 1Citation - Scopus: 2The Impact of COVID-19 on Healthcare Utilization in Turkey(Elsevier, 2024-09) Ugur, Zeynep B.; Durak, AysenurObjectives: This study investigates the impact of the COVID-19 pandemic on healthcare utilization in Turkey. Methods: We utilized individual-level data derived from Turkish Statistical Institute 's annual surveys between 2014 and 2022 and estimated probit regression models. Results: We find that COVID-19 pandemic reduced healthcare utilization by 11.8% after taking into account a large set of background variables. Although our study finds that the elderly and those with health problems are more likely to use healthcare services under normal circumstances, the COVID-19 pandemic has caused notable drops in the healthcare utilization among the elderly (-6.5%) and those with health problems (-3.8%). Although those without health insurance had lower utilization of healthcare services before the pandemic, during the pandemic they were not particularly hit. Conclusion: We conclude that the pandemic did not lower the healthcare utilization in Turkey because of the supply constraints. Also, the evidence points to the reduced demand due to the fear of contagion rather than financial concerns.Article Citation - WoS: 19Citation - Scopus: 21Resveratrol Triggers Anti-Proliferative and Apoptotic Effects in FLT3-LTD Acute Myeloid Leukemia Cells via Inhibiting Ceramide Catabolism Enzymes(Humana Press inc, 2022-01-20) Ersoz, Nur Sebnem; Adan, AysunResveratrol possesses well-defined anti-carcinogenic activities. However, how resveratrol exerts its anti-leukemic actions by modulating anti-apoptotic ceramide catabolism enzymes, mainly sphingosine kinase (SK-1) and glucosylceramide synthase (GCS), in FLT3-ITD AML remains unclear. Resveratrol, SKI II (SK inhibitor) and PDMP (GCS inhibitor) were evaluated alone or in combinations for their effect on cell proliferation (MTT assay), apoptosis (annexin V-FITC/PI staining by flow cytometry) and cell cycle progression (PI staining by flow cytometry) in MOLM-13 and MV4-11 cells. The combination indexes (CIs) were calculated based on cell proliferation data using CompuSyn software. Caspase-3 and PARP activation, changes in SK-1 and GCS levels by resveratrol alone or PARP cleavage in co-treatments were determined by western blot. Resveratrol and inhibitors alone inhibited cell proliferation in a dose- and time-dependent manner. Resveratrol downregulated SK-1 and GCS expression in both cell lines. It induced apoptosis by phosphatidylserine (PS) exposure together with caspase-3 and PARP cleavage and arrested the cell cycle slightly at the S phase. Co-administrations intensified resveratrol's effect by inhibiting cell proliferation synergistically (A CI of < 1) or additively (A CI 1.0-1.1) and inducing apoptosis via PS relocalization and PARP cleavage. Resveratrol plus SKI II did not affect cell cycle progression significantly, however, resveratrol plus PDMP blocked cycle progression at G0/G1 and S phases for MOLM-13 cells and MV4-11 cells, respectively. Overall, resveratrol may inhibit FLT3-ITD AML cell proliferation by inhibiting ceramide catabolism and be evaluated as a chemopreventive after detailed analysis of the crosstalk between resveratrol and ceramide catabolism pathway.