PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397

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Start date: 2022Publisher: search.filters.publisher.Springer

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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, Mesude
    Background 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, Aykagan
    ObjectivesThe 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: 2
    Citation - Scopus: 2
    Pangenome 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, Mikail
    This 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
    Citation - WoS: 15
    Citation - Scopus: 18
    Revolutionizing Dermatology: Harnessing Mesenchymal Stem/Stromal Cells and Exosomes in 3D Platform for Skin Regeneration
    (Springer, 2024-05-25) Bicer, Mesude
    Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.
  • Article
    Citation - WoS: 5
    Citation - Scopus: 7
    Rational Design of EDTA-Incorporated Nanoflowers as Novel and Effective Endodontic Disinfection Against Biofilms
    (Springer, 2023-10-03) Aslan, Tugrul; Dadi, Seyma; Kafdag, Ozgur; Temur, Nimet; Ildiz, Nilay; Ocsoy, Ismail; Ustun, Yakup
    The ethylenediaminetetradiacetic acid (EDTA) is one of the most commonly used irrigation solutions. Although EDTA has a very low antimicrobial property, it is used to remove inorganic part of smear layer in areas of root canal system. Herein, we developed EDTA-incorporated nanoflowers (EDTA NFs), for the first time, as novel and effective irrigation solution with quite high antimicrobial property to provide complete disinfection in root canal system. We both systematically elucidated the formation of the EDTA NFs with various techniques, and their catalytic and antimicrobial activities in the presence of hydrogen peroxide (H2O2) were documented through intrinsic EDTA property and peroxidase-like activities.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    Rapamycin and Niacin Combination Induces Apoptosis and Cell Cycle Arrest Through Autophagy Activation on Acute Myeloid Leukemia Cells
    (Springer, 2024-12-23) Subay, Lale Beril; Akcok, Emel Basak Gencer; Akcok, Ismail; Gencer Akçok, Emel Başak
    BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematological malignancy caused by disorders in stem cell differentiation and excessive proliferation resulting in clonal expansion of dysfunctional cells called myeloid blasts. The combination of chemotherapeutic agents with natural product-based molecules is promising in the treatment of AML. In this study, we aim to investigate the anti-cancer effect of Rapamycin and Niacin combination on THP-1 and NB4 AML cell lines.Methods and ResultsThe anti-proliferative effects of Rapamycin and Niacin were determined by MTT cell viability assay in a dose- and time-dependent manner. The combination indexes were calculated by isobologram analysis. Furthermore, apoptosis was investigated by Annexin-V/Propidium Iodide(PI) double staining and cell cycle distribution was measured by PI staining. The expression levels of autophagy-related proteins were detected by western blotting. The combination of Rapamycin and Niacin synergistically decreased cell viability of AML cell lines. The combination treatment induced the apoptotic cell population of THP-1 and NB4 by 4.9-fold and 7.3-fold, respectively. In THP-1 cells, the cell cycle was arrested at the G2/M phase by 10% whereas the NB4 cells were accumulated at the G0/G1 phase. The combination treatment decreased Akt and p-Akt expression. Besides, the ATG7 expression was reduced by combination treatment on THP-1 cells. Similarly, the ATG5 level was downregulated in NB4 cells. The level of LC3B-II/LC3B-I, which is an indicator of autophagy flux, was upregulated in THP-1 and NB4 cells.ConclusionAlthough further studies are required, the combination of Rapamycin and Niacin combats cell proliferation by inducing cellular apoptosis, cell cycle arrest and autophagy activation.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Possible Boron-Rich Amorphous Silicon Borides From Ab Initio Simulations
    (Springer, 2023-03-10) Karacaoglan, Aysegul Ozlem Cetin; Durandurdu, Murat
    ContextBy means of ab initio molecular dynamics simulations, possible boron-rich amorphous silicon borides (BnSi1-n, 0.5 <= n <= 0.95) are generated and their microstructure, electrical properties and mechanical characters are scrutinized in details. As expected, the mean coordination number of each species increases progressively and more closed packed structures form with increasing B concentration. In all amorphous models, pentagonal pyramid-like configurations are observed and some of which lead to the development of B-12 and B11Si icosahedrons. It should be noted that the B11Si icosahedron does not form in any crystalline silicon borides. Due to the affinity of B atoms to form cage-like clusters, phase separations (Si:B) are perceived in the most models. All simulated amorphous configurations are a semiconducting material on the basis of GGA+U calculations. The bulk modulus of the computer-generated amorphous compounds is in the range of 90 GPa to 182 GPa. As predictable, the Vickers hardness increases with increasing B content and reaches values of 25-33 GPa at 95% B concentration. Due to their electrical and mechanical properties, these materials might offer some practical applications in semiconductor technologies.MethodThe density functional theory (DFT) based ab initio molecular dynamics (AIMD) simulations were used to generate B-rich amorphous configurations.
  • 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, Muge
    Severe 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: 3
    Citation - Scopus: 3
    Highly Potent New Probiotic Strains From Traditional Turkish Fermented Foods
    (Springer, 2025-01-21) Yigit, Mehmet Burak; Cebeci, Aysun
    Traditional Turkish fermented foods like boza, pickles, and tarhana are recognized for their nutritional and health benefits, yet the probiotic potential of lactic acid bacteria (LAB) strains isolated from them remains underexplored. Sixty-six LAB strains were isolated from fermented foods using bacterial morphology, Gram staining, and catalase activity. The isolates were differentiated at strain level by RAPD-PCR (Random Amplification of Polymorphic DNA-Polymerase Chain Reaction) and twenty-five strains were selected for further evaluation of acid and bile salt tolerance. Among these, ten strains exhibited high tolerance and were subsequently assessed for adhesion to Caco-2 colorectal carcinoma cells, antimicrobial activity, exopolysaccharide (EPS) production, lysozyme resistance, and hemolytic activity. Using k-means clustering, three strains: Lactiplantibacillus plantarum ES-3, Pediococcus pentosaceus N-1, and Enterococcus faecium N-2 demonstrated superior probiotic characteristics, including significant acid (100% survival at pH3.0) and 0.3% bile salt tolerance (57%, 64%, 67%), strong adhesion to intestinal cells (65%, 88%, 91%), high lysozyme resistance (88%, 88%, 77%), and produced high amounts of EPS. These strains show promising potential as probiotics and warrant further investigation to confirm their functional properties and potential applications.
  • Article
    Citation - WoS: 3
    Citation - Scopus: 4
    High-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, Gordon
    Biodegradable 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.