PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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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 A Small Indole Derivative Isolated From Caper (Capparis Ovata) as an Inducer of P53-Mediated Apoptosis in Prostate Cancer: Comprehensive In Vitro and In Silico Studies(Wiley, 2025-12-31) Acar, Ozden Ozgun; Gazioglu, Isil; Oruc, Hatice; Kale, Elif; Senol, Halil; Topcu, Gulacti; Sen, AlaattinNatural products with stunning chemical diversity have been extensively researched for their anticancer potential for more than fifty years. This study aimed to determine the effect of indole derivative 1H-indole-2-hydroxy-3-carboxylic acid (IHCA), isolated as a novel alkaloid from Capparis ovata, on selected tumor suppressor, apoptotic, and cell cycle regulatory genes, which are known to be important in cancer pathophysiology, on Caco-2 and LNCaP cells in comparison with Taxol. The molecular mechanism of IHCA's anticancer activity is essentially undefined. Different concentrations of IHCA increased the expression levels of apoptosis-related genes, including BCL-2 and TNF-alpha. In addition, the tumor suppressor genes PTEN, P53, and RB were increased in LNCaP and Caco-2 cells. KRAS, an oncogenic gene, was significantly downregulated by IHCA in LNCaP cells. Western blot results showed that the protein expression levels of P53 and PTEN in LNCaP cells were increased when treated with IHCA, whereas CDK4 and TNF-alpha were decreased. Finally, IHCA and doxorubicin significantly increased P53-driven luciferase activity compared to the control. The results strongly suggest that the novel natural compound IHCA has an anticancer effect involving the regulation of the P53 gene and its networks in vitro. The molecular docking and MD simulation analyses reveal that IHCA exhibits superior binding potential to the MDM2 protein compared to Nutlin-3a. MD simulations further confirm that IHCA maintains a more stable and consistent interaction with MDM2, as indicated by lower RMSD values and reduced ligand fluctuation. These results highlight IHCA's potential as a more effective MDM2 inhibitor, suggesting its promise as a lead compound for anticancer drug development.Clinical Trial Registration: Not applicable.Article Citation - WoS: 13Role of Pretty Nanoflowers as Novel Versatile Analytical Tools for Sensing in Biomedical and Bioanalytical Applications(Wiley, 2024-02) Dadi, Seyma; Ocsoy, IsmailIn recent years, an encouraging breakthrough in the synthesis of immobilized enzymes in flower-shaped called "organic-inorganic hybrid nanoflowers (hNFs)" with greatly enhanced catalytic activity and stability were reported. Although, these hNFs were discovered by accident, the enzymes exhibited highly enhanced catalytic activities and stabilities in the hNFs compared with the free and conventionally immobilized enzymes. Herein, we rationally utilized the catalytic activity of the hNFs for analytical applications. In this comprehensive review, we covered the design and use of the hNFs as novel versatile sensors for electrochemical, colorimetric/optical and immunosensors-based detection strategies in analytical perspective. Formation of nanoflowers and their biosensor function in biomedical and bioanalytical applications. imageArticle Citation - WoS: 25Citation - Scopus: 27Progression of Irradiated Mesenchymal Stromal Cells From Early to Late Senescence: Changes in SASP Composition and Anti-Tumour Properties(Wiley, 2023-03-22) Alessio, Nicola; Acar, Mustafa Burak; Squillaro, Tiziana; Aprile, Domenico; Ayaz-Guner, Serife; Di Bernardo, Giovanni; Galderisi, UmbertoGenotoxic injuries converge on senescence-executive program that promotes production of a senescence-specific secretome (SASP). The study of SASP is particularly intriguing, since through it a senescence process, triggered in a few cells, can spread to many other cells and produce either beneficial or negative consequences for health. We analysed the SASP of quiescent mesenchymal stromal cells (MSCs) following stress induced premature senescence (SIPS) by ionizing radiation exposure. We performed a proteome analysis of SASP content obtained from early and late senescent cells. The bioinformatics studies evidenced that early and late SASPs, besides some common ontologies and signalling pathways, contain specific factors. In spite of these differences, we evidenced that SASPs can block in vitro proliferation of cancer cells and promote senescence/apoptosis. It is possible to imagine that SASP always contains core components that have an anti-tumour activity, the progression from early to late senescence enriches the SASP of factors that may promote SASP tumorigenic activity only by interacting and instructing cells of the immune system. Our results on Caco-2 cancer cells incubated with late SASP in presence of peripheral white blood cells strongly support this hypothesis. We evidenced that quiescent MSCs following SIPS produced SASP that, while progressively changed its composition, preserved the capacity to block cancer growth by inducing senescence and/or apoptosis only in an autonomous manner.Article Patient Experiences of Behavioural Therapy for Bipolar Depression: A33 Qualitative Study(Wiley, 2024-12-10) Yilmaz, Sakir; Hancox, Anna; Price, Molly; Regan, Jemma; Dunn, Barney; O'Mahen, Heather; Wright, KimBackgroundAlthough multiple qualitative studies have explored participants' experiences of behavioural activation (BA) for unipolar depression, none have investigated the experiences of BA in people with bipolar depression. This is of particular interest because qualitative studies concerning the experience of receiving therapy can help inform the theory of change underpinning the intervention.AimThe purpose of this study was to explore the experiences and perspectives of individuals with bipolar disorder who received a course of one-to-one BA for bipolar depression. We sought to explore participants' experience of the effects of BA therapy, both proximally and distally.MethodSemi-structured interviews were conducted with nine individuals meeting research diagnostic criteria for bipolar I or II disorder who had received up to 20 sessions of BA adapted for bipolar depression. Thematic analysis using a framework approach was used to explore and describe the experiences of participants.ResultsParticipants' perspectives on the impact of therapy were categorized under four subthemes: client behaviour inside and outside sessions, changes in clients' perspectives, the impact on symptoms and impact on life and functioning.ConclusionsParticipants' accounts of the impact of therapy were broadly consistent with the theory underpinning a behavioural approach. Participants described a central role for perspective change, and particularly increased acceptance of the self and mood states, as facilitating behavioural changes and more distal benefits. Process evaluations embedded in future trials may include quantitative measures of key processes described by our participants, as well as those clearly implied by the behavioural theory of depression.Article Citation - WoS: 33Citation - Scopus: 37In Silico Evaluation of Food-Derived Carotenoids Against SARS-CoV Drug Targets: Crocin Is a Promising Dietary Supplement Candidate for COVID-19(Wiley, 2022-05-11) Mujwar, Somdutt; Sun, Lei; Fidan, OzkanThe current COVID-19 pandemic is severely threatening public healthcare systems around the globe. Some supporting therapies such as remdesivir, favipiravir, and ivermectin are still under the process of a clinical trial, it is thus urgent to find alternative treatment and prevention options for SARS-CoV-2. In this regard, although many natural products have been tested and/or suggested for the treatment and prophylaxis of COVID-19, carotenoids as an important class of natural products were underexplored. The dietary supplementation of some carotenoids was already suggested to be potentially effective in the treatment of COVID-19 due to their strong antioxidant properties. In this study, we performed an in silico screening of common food-derived carotenoids against druggable target proteins of SARS-CoV-2 including main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase. Molecular docking results revealed that some of the carotenoids had low binding energies toward multiple receptors. Particularly, crocin had the strongest binding affinity (-10.5 kcal/mol) toward the replication complex of SARS-CoV-2 and indeed possessed quite low binding energy scores for other targets as well. The stability of crocin in the corresponding receptors was confirmed by molecular dynamics simulations. Our study, therefore, suggests that carotenoids, especially crocin, can be considered an effective alternative therapeutics and a dietary supplement candidate for the prophylaxis and treatment of SARS-CoV-2. Practical applications In this study, food-derived carotenoids as dietary supplements have the potential to be used for the prophylaxis and/or treatment of SARS-CoV-2. Using in silico techniques, we aimed at discovering food-derived carotenoids with inhibitory effects against multiple druggable sites of SARS-CoV-2. Molecular docking experiments against main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP-ribose phosphatase resulted in a few carotenoids with multitarget inhibitory effects. Particularly, crocin as one of the main components of saffron exhibited strong binding affinities to the multiple drug targets including main protease, helicase, replication complex, mutant spike protein of lineage B.1.351, and ADP-ribose phosphatase. The stability of the crocin complexed with these drug targets was further confirmed through molecular dynamics simulations. Overall, our study provides the preliminary data for the potential use of food-derived carotenoids, particularly crocin, as dietary supplements in the prevention and treatment of COVID-19.Article Citation - WoS: 7Citation - Scopus: 7Diagnosis Melanoma With Artificial Intelligence Systems: A Meta-Analysis Study and Systematic Review(Wiley, 2025-06-06) Erturk Zararsiz, Gozde; Yerlitas Tastan, Serra Ilayda; Celik Gurbulak, Elif; Erakcaoglu, Aleyna; Yilmaz Isikhan, Selen; Demirbas, Abdullah; Zararsiz, GoekmenBackgroundOne of the most promising and rapidly advancing research areas in recent years is using dermoscopic images for automatic diagnosis with artificial intelligence and machine learning methods.ObjectiveThis study aimed to synthesize the existing studies for the clinical use of applications made with artificial intelligence methods and to summarize the predictive performance of deep learning and hybrid models-based algorithms in all these studies with a large-scale meta-analysis.MethodThe literature review was conducted between January 2006 and May 2024, and meta-analysis data were created by scanning the Web of Science (WOS), Scopus and MEDLINE databases. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist.ResultsA total of 2722 articles were evaluated. Data from 78 diagnostic tests from 39 primary studies meeting the inclusion and exclusion criteria were assessed. The pooled SROC overall model AUC was 0.96 [95% CI: 0.94-0.98], sensitivity was 0.89 [95% CI: 0.85-0.91] and specificity was 0.92 [95% CI: 0.90-0.94]. In the subgroup analyses, the pooled AUC was 0.98 [95% CI: 0.96-0.99] for HYBRID models.ConclusionRecent studies have suggested that artificial intelligence algorithms and machine learning methods should be used extensively in medicine to assist physicians, especially in diagnosing melanoma. The ability of HYBRID model algorithms to predict diseases is promising. In particular, the performance of HYBRID models was found to be high. This information can assist clinicians in interpreting the most appropriate algorithms for diagnosing melanoma.Article Citation - WoS: 5Citation - Scopus: 6Capturing B Type Acute Lymphoblastic Leukemia Cells Using Two Types of Antibodies(Wiley, 2018-11-20) Icoz, Kutay; Gercek, Tayyibe; Murat, Ayseguel; Ozcan, Servet; Unal, EkremOne way to monitor minimal residual disease (MRD) is to screen cells for multiple surface markers using flow cytometry. In order to develop an alternative microfluidic based method, isolation of B type acute lymphoblastic cells using two types of antibodies should be investigated. The immunomagnetic beads coated with various antibodies are used to capture the B type acute lymphoblastic cells. Single beads, two types of beads and surface immobilized antibody were used to measure the capture efficiency. Both micro and nanosize immunomagnetic beads can be used to capture B type acute lymphoblastic cells with a minimum efficiency of 94% and maximum efficiency of 98%. Development of a microfluidic based biochip incorporating immunomagnetic beads and surface immobilized antibodies for monitoring MRD can be an alternative to current cost and time inefficient laboratory methods. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2737, 2019Article Citation - WoS: 3Citation - Scopus: 3Biochemical, Pharmacological, and Toxicological Attributes of Caper (Capparis Ovata) Flowering Buds and Berries Pickles(Wiley, 2022-07-30) Ozgun-Acar, Ozden; Celik-Turgut, Gurbet; Guner, Huseyin; Sezer, Serdar; Sen, AlaattinCapparis ovata is a natural plant that grows widely in Turkey and its flowering buds and berry pickle are used in traditional medicine. Thus, the current study was expanded to evaluate the biochemical, pharmacological, and toxicological aspects of the Capparis ovata water extract (COWE). To determine the biochemical properties of COWE, mineral and fatty acid content, elemental analysis, flavonoid/phenolic content, radical-scavenging capacity, and pesticide analysis were performed. Furthermore, to find out whether it had anti-inflammatory properties, reverse transcription-polymerase chain reaction (RT-PCR) and nuclear factor kappa B (NF-kappa B) luciferase activity tests were conducted. Whole-genome transcriptomic profiling was carried out at a dose level of 500 mg/kg COWE to understand its pharmacological effect. Transaminases in serum were tested, and quantitative polymerase chain reaction (qPCR) was done using a custom design array that included the stress and molecular toxicology pathway to establish its toxicological qualities. As a result of the evaluations, it was observed that COWE has a high mineral and unsaturated fatty acid content, flavonoid/phenolic content, and radical-scavenging ability. It significantly inhibited NF-kappa B transcriptional activity as well as inflammatory cytokine expression in T-lymphoblast cells. Whole-genome transcriptomic profiling depicted that COWE modulates immune responses by upregulating natural killer cell activation, cellular response to type I interferon, B-cell proliferation and differentiation, and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Molecular Toxicology Pathfinder RT2 Profiler PCR array analysis revealed that COWE at or lower dose of 500 mg/kg/day did not cause a comparatively adverse effect. According to the findings, COWE is a rich source of nutrients and can be used as an adjunct therapy for various inflammatory diseases.Article Citation - WoS: 4Citation - Scopus: 2Biochemical Characterization and Genome Analysis of Pseudomonas Loganensis Sp. Nov., a Novel Endophytic Bacterium(Wiley, 2025-08) Karaman, Melisa Z.; Yetiman, Ahmet E.; Zhan, Jixun; Fidan, OzkanPseudomonas species are highly adaptable, thriving in diverse environments and exhibiting remarkable genetic and metabolic diversity. While some strains are pathogenic, others have significant ecological and industrial applications. Bioinformatics and biochemical analyses, including antibiotic sensitivity testing, revealed that Pseudomonas loganensis sp. nov. can tolerate NaCl concentrations up to 5% and pH ranges between 5 and 9. Antibiogram results corroborated genome data, demonstrating resistance to vancomycin, ampicillin, methicillin, oxacillin, and penicillin G. Phylogenetic analysis based on 16S rRNA, rpoB, rpoD, and gyrB genes, combined with average nucleotide identity (ANI) comparisons, confirmed P. loganensis sp. nov. as a novel species within the Pseudomonas genus. Genome analysis further revealed the presence of turnerbactin and carotenoid gene clusters. Turnerbactin, known to contribute to nitrogen fixation in plants, highlights the strain's potential as a biofertilizer. Additionally, the carotenoid gene cluster suggests potential applications in industrial carotenoid production. The discovery of a trehalose synthase (treS) gene indicates the capability for one-step conversion of maltose into trehalose, underscoring its potential utility in trehalose production.