PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
Browse
405 results
Search Results
Article Tooth Decay Promotes Senescence in Dental Pulp Stem Cells, Modifying Their Biological and Proteomic Profiles(Wiley, 2026) Durukan, Sebahat Melike; Tez, Banu Cicek; Ozcan, Servet; Simsek, Ahmet; Al-Sammarrie, Sura Hilal Ahmed; Gunaydin, Zeynep; Acar, Mustafa BurakDental caries is a prevalent oral health problem that significantly reduces an individual's quality of life; although, it can be effectively managed through restorative treatments. Even in cases where the caries does not reach the pulp, released microbial products from the lesion can still penetrate the pulp chamber, potentially inducing stress on pulp cells. In this study, we conducted a comparative analysis of the biological and proteomic profiles of dental pulp stem cells (DPSCs) isolated from clinically asymptomatic teeth with dentinal caries that had not reached the pulp and isolated from healthy teeth. Following biological evaluations, we examined proteomes of these DPSCs by conducting a shotgun proteomics approach. Our findings show that DPSCs from decayed teeth exhibit a significantly higher proportion of senescent cells. Proteomic profiling revealed upregulation of inflammatory signaling, extracellular matrix remodeling, and senescence-associated secretory phenotype (SASP) related proteins. Additionally, we observed an upregulation in the expression of proteins associated with extracellular matrix (ECM) remodeling and components of the SASP, which are hallmarks of the senescence process. The study reveals that DPSCs can be affected by stress from carious lesions, even when the pulp appears clinically intact. Senescence and inflammatory response in these affected cells may have deleterious effects on other tissues within the organism. Consequently, restorative treatments should consider targeting not only the decayed tissue but also the senescent cells within the pulp that may have been affected by the stress induced by caries.Article The Effect of Video Modeling on Gymnastics-Based Motor Skills in Children with Autism Spectrum Disorder(MDPI, 2026) Bozdag, Berkan; Sonmez, Huseyin Gazi; Turan, Ebru; Aldhahi, Monira I.; Kilinc, Omer; Ergin, Murat; Kocak, Calik VeliBackground and Objectives: While the effectiveness of video modeling (VM) in teaching academic, daily living, and social skills to individuals with Autism Spectrum Disorder (ASD) is frequently investigated, studies examining the use of VM in teaching gymnastics-based motor skills are limited. This study aimed to examine the effects of VM on the acquisition and maintenance of a gymnastics-based motor skills in preschool children with ASD. Methods: The study employed a multiple-probe method across participants in a single-subject research design. Three preschool children diagnosed with mild ASD participated in this study. Baseline, intervention, and follow-up data were systematically collected and analyzed. Social validity data were obtained through semi-structured interviews with parents and special education teachers. Results: The percentage of correct responses increased throughout the VM intervention sessions, and all participants reached the proficiency criterion. Follow-up data collected after the intervention showed that the acquired skill was maintained, and the percentages of correct responses ranged from 80% to 100%. Social validity findings revealed that both teachers and parents perceived VM as an effective and feasible teaching approach for teaching motor skills to children with ASD. Conclusions: The research findings demonstrate that VM is an effective and socially valid teaching method for teaching and maintaining gymnastics-based motor skills in preschool children with ASD. These results contribute to the existing literature by demonstrating the applicability of video modeling in the context of gymnastics-based training.Article Performance Evaluation of Multi-Modal Radar Signal Processing in Dense Co-Existent Environments(MDPI, 2026) Norouzian, Fatemeh; Bekar, Muge; Bekar, Ali; Gashinova, Marina; Pirkani, AnumThe wide-scale deployment of radars, distributed across a platform and across multiple platforms for reliable 360 degrees situational awareness (SA), introduces the challenge of radar interference. Interference can broadly be categorised as self-interference (between radars mounted on the same platform) and mutual interference (signals received from radars on other platforms). Both types of interference impede the reliability of SA delivered by such systems, particularly in dense environments where numerous radars operate simultaneously within the same frequency band. This work presents a comprehensive evaluation of a multi-modal beamforming approach that combines unfocused synthetic aperture radar with the traditional Multiple-Input, Multiple-Output beamformer to enhance radar resolution and suppress interference. Additionally, various aspects of sensor configurations defining hardware and software capabilities of state-of-the-art radars are discussed, and a systematic analysis of signal-to-interference-plus-noise ratio at each step of the processing is presented. Extensive simulations and experimental results in both automotive and maritime environments are shown to validate the effectiveness of the proposed approach.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 Citation - WoS: 1Citation - Scopus: 1Targeting Cholinergic Dysfunction and Neuroinflammation through Rationally Designed Thieno[3,2-d]Pyrimidine Hybrids(Academic Press Inc Elsevier Science, 2026-07) Acar, Ozden Ozgun; Acar, Busra; Senol, Halil; Tokali, Feyzi Sinan; Sen, Alaattin; Demir, Yeliz; Cakir, FurkanNeurodegenerative diseases involve the convergence of cholinergic dysfunction, neuronal loss, and sustained neuroinflammatory responses, necessitating the development of multifunctional therapeutic agents. In this study, a series of novel thieno[3,2-d]pyrimidine-phenolic Mannich base hybrids were rationally designed, synthesized, and evaluated as dual cholinesterase inhibitors with neuroprotective and anti-neuroinflammatory potential. The synthesized compounds exhibited potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants in the low nanomolar range. Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. Molecular docking and molecular dynamics simulations supported the experimental findings, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations further confirmed their superior binding affinities compared with donepezil. Cytotoxicity profiling in SH-SY5Y neuronal cells and RAW 264.7 and THP-1 immune cells identified a narrow sub-cytotoxic concentration window (EC05-EC10 = 1.2-2.1 mu M), ensuring biological effects independent of nonspecific cell damage. Within this range, both compounds exerted pronounced antineuroinflammatory activity. Notably, compound 9 significantly downregulated pro-inflammatory mediators, reducing IL-1 beta, IL-6, and NF-kappa B1 gene expression by up to 2.78-, 3.37-, and 4.84-fold, respectively. Consistently, it suppressed nitric oxide production in LPS-stimulated macrophages to levels comparable with ascorbic acid and markedly decreased Iba1 expression in activated THP-1 cells. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders.Article Parametric Study on the Behavior of CFRP-Strengthened Reinforced Concrete Deep Beams with Cut Circular Web Openings in Shear Spans(Nature Portfolio, 2026-02-17) Yagmur, ErenWeb openings in reinforced concrete deep beams are often necessary for functional purposes but substantially reduce structural performance. Carbon fiber-reinforced polymer (CFRP) strengthening is commonly employed to mitigate these effects. Previous studies typically examined openings in regions without stirrups or assumed closed stirrup configurations, overlooking the frequent stirrup damage that occurs in practice due to the high shear reinforcement in deep beams. In this study, three specimens from a prior experimental program were modeled in ABAQUS, and the numerical results were validated against experimental data. Openings of varying diameters were introduced by cutting reinforcements, and the beams were subsequently strengthened with CFRP laminates, and a parametric study was conducted. Results showed that increasing opening diameter markedly reduces load-carrying capacity and energy absoption, while thicker CFRP laminates partially restore performance. For example, a 300 mm opening in a 500 mm high unstrengthened beam reduced load capacity by 56% and energy absorption by 87%. Even when the opening diameter was less than one-third of the beam height, 1.8 mm CFRP laminates provided only limited improvement. Deep beam performance was strongly influenced by web opening size, and the effectiveness of CFRP strengthening was limited when stirrup integrity was compromised.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 Citation - Scopus: 4Integrated Querying and Version Control of Context-Specific Biological Networks(Oxford University Press, 2020-01-01) Coşkun, Mustafa; Grama, Ananth; Koyutürk, Mehmet; Cowman, Tyler