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 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 Non-Contact Acoustic Screening for Sleep Apnea: A Subject-Aware Deep Learning Approach(Springer Science and Business Media Deutschland GmbH, 2026-02-11) Aygün Çakıroğlu, M.; Kizilkaya Aydoǧan, E.; Bolatturk, Ö.F.; Aydoğan, S.; Ismailoǧullari, S.; Delice, Y.Purpose: To explore the feasibility of using camera-derived, non-contact audio synchronized with PSG for clinically relevant sleep-apnea classification, and to benchmark compact deep models under a subject-aware design using a previously unstudied, real-world dataset. Methods: Thirty-two adults underwent simultaneous polysomnography (PSG) and camera-based non-contact audio recording. The synchronized audio segments were used to train and compare three compact deep-learning architectures (convolutional, attention-augmented, and transformer-based) under a subject-aware evaluation design that prevented identity leakage. Model performance and calibration were assessed at both segment and subject levels using standard statistical tests. Results: Subject-level evaluation was based on a very small, imbalanced test set of six subjects (one positive). Within this limited yet previously unstudied local dataset, the CNN_trans model achieved an apparent perfect ranking performance (AUC = 1.00; 95% CI 0.00–1.00), though this likely reflects the small, imbalanced test cohort, with recall = 1.00 and precision = 0.55. The wide confidence interval reflects substantial statistical uncertainty, and DeLong comparisons showed no significant AUC difference between CNN_trans and CNN_att (ΔAUC = − 0.042; p = 0.43). Conclusion: PSG-synchronized, non-contact audio supports accurate and well-calibrated sleep-apnea classification with compact deep models. This subject-aware evaluation suggests that contactless acoustic monitoring may have potential clinical relevance, motivating larger, multi-site validation. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2026.Article Deep-Learning Detection of Open-Apex Teeth on Panoramic Radiographs Using YOLO Models(Springer, 2025-12-23) Edik, Merve; Celebi, Fatma; Cukurluoglu, AykaganObjectivesThe use of deep learning in detecting teeth with open apices can prevent the need for additional radiographs for patients. The presented study aims to detect open-apex teeth using You Only Look Once (YOLO)-based deep learning models and compare these models.MethodsA total of 966 panoramic radiographs were included in the study. Open-apex teeth in panoramic radiographs were labeled. During the labeling process, they were divided into 6 classes in the maxilla and mandible, namely incisors, premolars, and molars. AI models YOLOv3, YOLOv4, and YOLOv5 were used. To evaluate the performance of the three detection models, both overall and separately for each class in the test dataset, precision, recall, average precision (mAP), and F1 score were calculated.ResultsYOLOv4 achieved the highest overall performance with a mean average precision (mAP) of 87.84% at IoU (Intersection over Union) 0.5 (mAP@0.5), followed by YOLOv5 with 85.6%, and YOLOv3 with 84.46%. Regarding recall, YOLOv4 also led with 90%, while both YOLOv3 and YOLOv5 reached 89%. Moreover, the F1 score was the highest for YOLOv4 (0.87), followed by YOLOv3 (0.86) and YOLOv5 (0.85).ConclusionsIn this study, YOLOv3, YOLOv4, and YOLOv5 were evaluated for the detection of open-apex teeth, and their mAP, recall, and F1 scores exceeded 84%. Deep learning-based systems can provide faster and more accurate results in the detection of open-apex teeth. This may help reduce the need for additional radiographs from patients and aid dentists by saving time.Article Developing a Label Propagation Approach for Cancer Subtype Classification Problem(Tubitak Scientific & Technological Research Council Turkey, 2022-01-01) Guner, Pinar; Bakir-Gungor, Burcu; Coskun, MustafaCancer is a disease in which abnormal cells grow uncontrollably and invade other tissues. Several types of cancer have various subtypes with different clinical and biological implications. Based on these differences, treatment methods need to be customized. The identification of distinct cancer subtypes is an important problem in bioinformatics, since it can guide future precision medicine applications. In order to design targeted treatments, bioinformatics methods attempt to discover common molecular pathology of different cancer subtypes. Along this line, several computational methods have been proposed to discover cancer subtypes or to stratify cancer into informative subtypes. However, existing works do not consider the sparseness of data (genes having low degrees) and result in an ill-conditioned solution. To address this shortcoming, in this paper, we propose an alternative unsupervised method to stratify cancer patients into subtypes using applied numerical algebra techniques. More specifically, we applied a label propagation based approach to stratify somatic mutation profiles of colon, head and neck, uterine, bladder, and breast tumors. We evaluated the performance of our method by comparing it to the baseline methods. Extensive experiments demonstrate that our approach highly renders tumor classification tasks by largely outperforming the state-of-the-art unsupervised and supervised approaches.Letter Citation - WoS: 18Yemen's Triple Emergency: Food Crisis Amid a Civil War and COVID-19 Pandemic(Elsevier, 2021-11) Hashim, Hashim Talib; Miranda, Adriana Viola; Babar, Maryam Salma; Essar, Mohammad Yasir; Hussain, Hasham; Ahmad, Shoaib; Basalilah, Ashraf Fhed MohammedYemen has been termed as the world's worst humanitarian crisis by the United Nations. About 20.1 million (more than 50% of population) Yemenis are facing hunger and 10 million are severely food insecure according to reports by the World Food Programme. With the spread of COVID-19, the situation in Yemen has worsened and humanitarian aid from other countries has become the basis of life for hundreds of thousands of Yemenis after the threat of famine. Yemen is practically one of the poorest countries in the world. It has structural vulnerabilities that have developed over a protracted period of conflict and poor governance and more than 50% live in starving, they suffer for getting one meal a day. To prevent a total collapse of Yemen's food crises, the government and the international community should act now more decisively.Article Citation - WoS: 19Citation - Scopus: 19Understanding and Tailoring Excited State Properties in Solution-Processable Oligo(p-Phenyleneethynylene)s: Highly Fluorescent Hybridized Local and Charge Transfer Character via Experiment and Theory(Amer Chemical Soc, 2021-10-13) Usta, Hakan; Cosut, Bunyemin; Alkan, FahriRod-shaped oligo(p-phenyleneethynylene) (OPE) offers an attractive p-framework for the development of solution-processable highly fluorescent molecules having tunable hybridized local and charge transfer (HLCT) excited states and (reverse) intersystem crossing ((R)ISC) channels. Herein, an HLCT oligo(p-phenyleneethynylene) library was studied for the first time in the literature in detail systematically via experiment and theory. The design, synthesis, and full characterization of a new highly fluorescent (Phi(PL-solution) similar to 1) sky blue emissive 4',4 ''-((2,5-bis((2-ethylhexyl)oxy)-1,4-phenylene)bis(ethyne-2,1-diyl))bis(N,N-diphenyl-[1,1'-bi-phenyl]-4-amine) (2EHO-TPA-PE) was also reported. The new molecule consists of a D'-Ar-pi-D-pi-Ar-D' molecular architecture with an extended pi-spacer and no acceptor unit, and detailed structural, physicochemical, single-crystal, and optoelectronic characterizations were performed. A high solid-state quantum efficiency (Phi(PL-solution) similar to 0.8) was achieved as a result of suppressed exciton-phonon/vibronic couplings (no pi-pi interactions and multiple (14 per dimeric form) strong C-H center dot center dot center dot pi interactions). Strong solution-phase/solid-state dipole-dependent tunable excited state behavior (local excited (LE) -> HLCT -> charge transfer (CT)) and decay dynamics covering a wide spectral region were demonstrated, and the CT state was observed to be highly fluorescent despite extremely large Stokes shift (similar to 130 nm)/fwhm (similar to 125 nm) and significant charge separation (0.75 charge.nm). Employing the Lippert-Mataga model, along with detailed photophysical studies and TDDFT calculations, key relationships between molecular design-electronic structure-exciton characteristics were elucidated with regards to HLCT and hot exciton channel formations. The interstate coupling between CT and LE states and the interplay of this coupling with respect to medium polarity were explored. A key relationship between excited-state symmetry breaking process and the formation of HLCT state was discussed for TPA-ended rod-shaped OPE p-systems. (R)ISC-related delayed fluorescence (tau similar to 2-6 ns) processes were evident following the prompt decays (similar to 0.4-0.9 ns) both in the solution and in the solid-state. As a unique observation, the delayed fluorescence could be tuned and facilitated via small dielectric changes in the medium. Our results and the molecular engineering perspectives presented in this study may provide unique insights into the structural and electronic factors governing tunable excited state and hot-exciton channel formations in OPEs for (un)conventional solution-processed luminescence applications.Article Citation - WoS: 1Citation - Scopus: 1Tomatidine, a Steroidal Alkaloid, Synergizes With Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells(Humana Press inc, 2024-07-11) Ayvaz, Havva Berre; Yenigul, Munevver; Akcok, Emel Basak Gencer; Gencer Akçok, Emel BaşakBackgroundAcute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy.MethodsAnti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels.ResultsCisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 mu M tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected.ConclusionsTogether, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.