PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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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 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 Bi-Allelic Variants in OLA1 Cause a Neurodevelopmental Disorder with Joint Hypermobility(Cell Press, 2026-04) Cevik, Sebiha; Alzahrani, Fatema; Sezer, Abdullah; AlAbdi, Lama; Demir, Zanyar; Abdullah, Nor Linda; Alkuraya, Fowzan S.Cytoskeletal organization, cell adhesion, and cell motility are key to neuronal development and functional synapses. Obg-like ATPase 1 (OLA1) regulates cell-matrix adhesion by modulating focal adhesion kinase (FAK) levels, therefore regulating cytoskeletal dynamics and cell motility. To date, however, no Mendelian phenotypes in humans have been linked to OLA1. We identified fourteen individuals from nine families in whom hypermobility-neurodevelopmental disorder with distinct facies is linked to bi-allelic deleterious variants in OLA1. The hypermobility phenotype evoked a diagnosis of Ehlers-Danlos syndrome (EDS) in some affected individuals. The loss-of-function nature of these variants is confirmed in proband-derived fibroblasts, recapitulating the impaired migration and proliferation phenotype previously described in OLA1-deficient cells. To explore the pathogenesis of abnormal neurodevelopment in our probands, we investigated neurons derived from proband fibroblasts and identified impaired adhesion and cytoskeletal control. Modeling ola-1 deficiency in C. elegans revealed reduced neurite numbers compared to the wild type. Additionally, transcriptomic analysis of the ola-1-deficient worms suggested that dysregulation of key signaling pathways results in suppression of microtubule dynamics and axon regrowth, ultimately crippling the regenerative competence of mutant animals compared to wild-type controls. Our results support an autosomal-recessive OLA1-related hypermobility-neurodevelopmental disorder and suggest that dysregulation of key signaling pathways results in the suppression of microtubule dynamics as a potential underlying mechanism.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 GraphUnet-SS: A Novel Deep Learning Model for Protein Secondary Structure Prediction Based on U-Net Architecture(Elsevier Ltd, 2026-04) Aydin, Zafer; Görmez, Yasin; Sabzekar, MostafaArticle 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 Citation - WoS: 1Two-Local Modifications of Sachdev-Ye Model With Quantum Chaos(American Physical Society, 2026-01-27) Hanada, M.; Van Leuven, S.; Oktay, O.; Tezuka, M.The Sachdev-Ye-Kitaev (SYK) model may provide us with a good starting point for the experimental study of quantum chaos and holography in the laboratory. Still, the four-local interaction of fermions makes quantum simulation challenging, and it would be good to search for simpler models that keep the essence. In this paper, we argue that the four-local interaction may not be important by introducing a few models that have two-local interactions. The first model is a generalization of the spin-SYK model, which is obtained by replacing the spin variables with SU(d) generators. Simulations of this class of models might be straightforward on qudit-based quantum devices. We study the case of d=3,4,5,6 numerically and observe quantum chaos already for two-local interactions in a wide energy range. We also introduce modifications of spin-SYK and SYK models that have similar structures as the SU(d) model (e.g., H=∑p,qJpqχpχp+1χqχq+1 instead of the original SYK Hamiltonian H=∑p,q,r,sJpqrsχpχqχrχs), which shows strongly chaotic features although the interaction is essentially two-local. These models may be a good starting point for the quantum simulation of the original SYK model. ©2026 American Physical Society.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.