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: 6Citation - Scopus: 7Sustainability Assessment of Denim Fabric Made of PET Fiber and Recycled Fiber From Postconsumer PET Bottles Using LCA and LCC Approach With the EDAS Method(Wiley, 2024-11-01) Fidan, Fatma Sener; Aydogan, Emel Kizilkaya; Uzal, NigmetThe textile industry is under pressure to adopt sustainable production methods because its contribution to global warming is expected to rise by 50% by 2030. One solution is to increase the use of recycled raw material. The use of recycled raw material must be considered holistically, including its environmental and economic impacts. This study examined eight scenarios for sustainable denim fabric made from recycled polyethylene terephthalate (PET) fiber, conventional PET fiber, and cotton fiber. The evaluation based on the distance from average solution (EDAS) multicriteria decision-making method was used to rank scenarios according to their environmental and economic impacts, which are assessed using life cycle assessment and life cycle costing. Allocation, a crucial part of evaluating the environmental impact of recycled products, was done using cut-off and waste value. Life cycle assessments reveal that recycled PET fiber has lower freshwater ecotoxicity and fewer eutrophication and acidification impacts. Cotton outperformed PET fibers in human toxicity. Only the cut-off method reduces potential global warming with recycled PET. These findings indicated that recycled raw-material life cycle assessment requires allocation. Life cycle cost analysis revealed that conventional PET is less economically damaging than cotton and recycled PET. The scenarios were ranked by environmental and economic impacts using EDAS. This ranking demonstrated that sustainable denim fabric production must consider both economic and environmental impacts. Integr Environ Assess Manag 2024;00:1-19. (c) 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).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: 17Citation - Scopus: 21Finite Element Analysis of the Stress Distribution Associated With Different Implant Designs for Different Bone Densities(Wiley, 2022-06-06) Kurtulus, Ikbal Leblebicioglu; Kilic, Kerem; Bal, Burak; Kilavuz, Ahmet; Leblebicioğlu Kurtuluş, IkbalPurpose The main objective of this study was to investigate the influence of implant design, bone type, and abutment angulation on stress distribution around dental implants. Materials and methods Two implant designs with different thread designs, but with the same length and brand were used. The three-dimensional geometry of the bone was simulated with four different bone types, for two different abutment angulations. A 30 degrees oblique load of 200 N was applied to the implant abutments. Maximum principal stress and minimum principal stresses were obtained for bone and Von misses stresses were obtained for dental implants. Results The distribution of the load was concentrated at the coronal portion of the bone and implants. The stress distributions to the D4 type bone were higher for implant models. Increased bone density and increased cortical bone thickness cause less stress on bone and implants. All implants showed a good distribution of forces for non-axial loads, with higher stresses concentrated at the crestal region of the bone-implant interface. In implant types using straight abutments there was a decrease in stress as the bone density decreased. The change in the abutment angle also caused an increase in stress. Conclusions The use of different implant threads and angled abutments affects the stress on the surrounding bone and implant. In addition, it was observed that a decrease in density in trabecular bone and a decrease in cortical bone thickness increased stress.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: 1Citation - Scopus: 1ConVarT: Search Engine for Missense Variants Between Humans and Other Organisms(Wiley, 2022-11) Pir, Mustafa S.; Cevik, Sebiha; Kaplan, Oktay I.ConVarT (https://convart.org/) is a search engine for searching for conjugate variants between humans and other species. The search engine is based on matching conjugate variants called MatchVars between species. Matching equivalent variants requires correct alignment of orthologous proteins with the use of multiple sequence alignments (MSA). Indeed, the ConVarT pipeline has performed over a million MSAs and integrated variants and variant-specific annotations (pathogenicity, phenotypic variants; etc.) into the corresponding positions on MSAs. When a clinically relevant variant is discovered whose functional relevance is unknown, ConVarT offers clinician scientists the possibility to search for a MatchVar in other species and to look for functional data on that variant. Fortunately, ConVarT enables users to paste a protein sequence in FASTA format to search for human orthologous proteins. A pairwise sequence alignment (PSA) is then performed between the provided protein sequence and the human orthologous protein, allowing users to visualize human variants on the PSA. Here, we describe the step-by-step usage of ConVarT.