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 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 Citation - WoS: 2Citation - Scopus: 2Pangenome Analysis and Genome-Guided Probiotic Evaluation of Cyclic Dipeptides Producing Levilactobacillus Brevis DY55bre Strain From a Lactic Acid Fermented Shalgam to Assess Its Metabolic, Probiotic Potentials, and Cytotoxic Effects on Colorectal Cancer Cells(Springer, 2025-10-01) Yetiman, Ahmet E.; Horzum, Mehmet; Kanbur, Ertan; Cadir, Mehmet; Bahar, Dilek; Gurbuz, Serife; Akbulut, MikailThis study investigates the genetic, metabolic, and probiotic characteristics of Levilactobacillus brevis DY55bre, a strain isolated from the traditional Turkish fermented beverage, shalgam. Whole-genome sequencing revealed a circular genome of 2.485 Mb with a GC content of 45.72%, predicted 2791 genes, and multiple CRISPR-Cas systems. Pangenome analysis demonstrated an open structure, with 18.9% core genes and 103 strain-specific genes, highlighting its genetic diversity. The DY55bre exhibits heterofermentative carbohydrate metabolism due to the presence of the araBAD operon and the lack of 1-phosphofructokinase (pfK) and fructose-1,6-bisphosphate aldolase enzymes. Probiotic evaluation revealed firm survival under simulated gastrointestinal conditions, including resistance to acidic pH (as low as 3.0) and bile salts (up to 1%), along with significant adhesion to intestinal epithelial cell lines (HT29;59.3%, Caco-2;87%, and DLD-1;60.8%). The strain exhibited high auto-aggregation (84.55%) and cell surface hydrophobicity (56.69%), essential for gut colonization. Safety assessments confirmed its non-hemolytic nature and absence of horizontally acquired antibiotic resistance genes. Notably, GC-MS analysis identified bioactive cyclic dipeptides, Cyclo(D-Phe-L-Pro) and Cyclo(L-Leu-L-Pro), which demonstrated cytotoxic effects against colorectal cancer cell lines, with IC50 values of 7.71 mg/mL for HT29 and 3.19 mg/mL for DLD-1. The cell-free supernatant exhibited antimicrobial activity against pathogens, likely due to the synergistic effects of cyclic dipeptides, organic acids, and other metabolites. Antioxidant assays revealed significant ABTS+ (76.63%) and DPPH (34.25%) radical scavenging activities, while cholesterol assimilation tests showed a 27.29% reduction. These findings position the DY55bre as a promising candidate for functional foods, nutraceuticals, and therapeutic applications, warranting further in vivo validation.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 - Scopus: 24Analyzing the Nexus Between Environmental Sustainability and Clean Energy for the USA(Springer, 2024-03-22) Dogan, Eyup; Si Mohammed, Kamel; Khan, Zeeshan Anis; BinSaeed, Rima Hassan; Mohammed, Kamel SiEnvironmental sustainability is a key target to achieve sustainable development goals (SDGs). However, achieving these targets needs tools to pave the way for achieving SDGs and COP28 targets. Therefore, the primary objective of the present study is to examine the significance of clean energy, research and development spending, technological innovation, income, and human capital in achieving environmental sustainability in the USA from 1990 to 2022. The study employed time series econometric methods to estimate the empirical results. The study confirmed the long-run cointegrating relationship among CO<inf>2</inf> emissions, human capital, income, R&D, technological innovation, and clean energy. The results are statistically significant in the short run except for R&D expenditures. In the long run, the study found that income and human capital contribute to further aggravating the environment via increasing CO<inf>2</inf> emissions. However, R&D expenditures, technological innovation, and clean energy help to promote environmental sustainability by limiting carbon emissions. The study recommends investment in technological innovation, clean energy, and increasing R&D expenditures to achieve environmental sustainability in the USA. © 2024 Elsevier B.V., All rights reserved.
