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

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  • Article
    Dissecting the Strain and Sex Specific Connectome Signatures of Unanesthetized C57BL/6J and DBA/2J Mice Using Magnetic Resonance Imaging
    (Wiley, 2026) Neuberger, Thomas; Kamens, Helen M.; Zhang, Nanyin; Ünsal, Hayreddin Said; Arefin, Tanzil M.
    Mouse models are an essential tool for understanding behavior and disease states in neuroscience research. While genetic and sex-specific effects have been reported in many neurodegenerative and psychiatric illnesses, these factors may also alter baseline neuroanatomical features of mice. This raises the question of whether the observed changes are related to the disease being studied (i.e., pathological differences) or if there are baseline strain or sex differences that may predispose animals to different responses. Over the past decade, tremendous effort has been made to map neural architecture at various scales; however, the complex relationships, including identifying genetic and sex-specific differences in brain structure and function, remain understudied. To bridge this gap, we used C57BL/6J and DBA/2J mice, two of the most widely used inbred mouse strains in neuroscience research, to investigate strain and sex-specific features of the brain connectome in awake animals using magnetic resonance imaging (MRI). By combining resting-state functional MRI and diffusion MRI, we found that the motor, sensory, limbic, and salience networks exhibit significant differences in both functional and structural domains between C57BL/6J and DBA/2J mice. Further, functional and structural properties of the brain were significantly correlated in both strains. Our results underscore the importance of considering these baseline differences when interpreting brain-behavior interactions in mouse models of human disorders.
  • Article
    Comparison of Rapamycin and 3-Methyladenine in Cisplatin-Induced Experimental Cardiotoxicity
    (Wiley, 2026) Kaymak, Emin; Karabulut, Derya; Yalcin, Betul; Guner, Serife Ayaz; Ozturk, Emel; Findik, Fatma; Boyvat, Dudu
    In this study, we evaluated how cisplatin cardiotoxicity affects the histological and endocrine functions of the heart and autophagy while using Rapamycin(Rapa) and 3-methyladenine(3-MA) as autophagy activators and inhibitors. Control, Cisplatin (Cis), 3-methyladenine + Cisplatin (3-MA + Cis) and Rapamycin + Cisplatin (Rapa + Cis). Rapa and 3-MA were administered for 15 days, while a single dose of cisplatin was administered on the 7th day. Natriuretic peptide receptor-A(NPR-A), receptor-B(NPR-B) and biochemically atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) levels were evaluated in heart tissue. Cis caused a statistically significant increase in NPR-A and NPR-B expression, as well as ANP and BNP levels. However, the levels of Beclin-1 and LC3B were not statistically significant. Rapa was more effective than 3-MA + Cis on NPR-A and NPR-B expressions, but did not show the same effect on ANP and NT-proBNP levels. Cis caused an increase in Beclin-1 and LC3B levels, while a decrease was observed in both 3-MA + Cis and Rapa + Cis groups. Our results revealed that Cis cardiotoxicity disrupts autophagy and endocrine function of the heart. It was concluded that by continuing the activator and inhibitor substances after Cis application, more effective results can be obtained in Beclin-1 expression than LC3B expression and that they can be effective in eliminating the toxicity of Cis.
  • Article
    A Novel Dental Implant Nut System Designed to Enhance Primary Stability: Mechanical and Finite Element Analysis
    (Wiley, 2026) Demirbaş, Ahmet Emin; Bal, Burak; Alkan, Alper; Şahin, Mert; Soylu, Emrah
    Purpose: The present study aimed to evaluate, in a preclinical setting, the biomechanical behavior and mechanical performance of a newly developed dental implant nut system designed to address primary stability challenges in the severely resorbed posterior maxilla. Materials and Methods: The evaluation consisted of two complementary stages: an in vitro mechanical experiment and a finite element analysis (FEA). In the experimental phase, polyurethane jaw models simulating a severely atrophic posterior maxilla with approximately 1 mm residual bone height were used. Four groups were prepared: single implant without nut, single implant with nut, double implant without nut, and double implant with nut (n = 10 per group). Primary stability was measured using resonance frequency analysis (RFA) with an Osstell device. In the computational phase, three-dimensional finite element models were constructed from cone-beam computed tomography (CBCT) data of the same configuration to evaluate detachment forces and stress distribution within the bone-implant complex under vertical loading. Results: In single-implant models, mean implant stability quotient (ISQ) values increased from 10.91 +/- 7.35 to 18.27 +/- 7.11 after nut application. In double-implant models, ISQ values increased from 11.13 +/- 4.14 to 19.24 +/- 4.24 (p < 0.05). FEA results revealed that the detachment force increased from 16.5 to 20.33 N in single-implant models and from 15 to 22.3 N in double-implant models. Compressive stresses on the bone were lower in nut-supported configurations, indicating a more favorable load distribution. Conclusion: The nut system was associated with increased implant primary stability and a more favorable stress distribution under the conditions of this preclinical study. These findings should be interpreted as preliminary biomechanical evidence, as no in vivo or clinical validation was performed. Therefore, this design may be considered a mechanical stabilization concept that warrants further investigation through in vivo and clinical studies.
  • 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 Burak
    Dental 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
    BrAIn: A Comprehensive Artificial Intelligence-Based Morphology Analysis System for Brain Organoids and Neuroscience
    (Wiley, 2026-03-12) Polatli, Elifsu; Guner, Huseyin; Bastanlar, Yalin; Karakulah, Gokhan; Evranos, Ali Eren; Kahveci, Burak; Guven, Sinan
    Human-induced pluripotent stem cells (iPSCs) offer transformative potential for biomedical research, with iPSC-derived organoids providing more physiologically relevant models than traditional 2D cell cultures. Among these, brain organoids (BO) are particularly valuable for drug screening, disease modeling, and investigations into molecular pathways. Accurate representation of brain morphology is critical, as more complex organoid structures better mimic the human brain. Deep learning (DL) and machine learning (ML) approaches have become integral to analyzing organoid morphology, yet tools for comprehensive, time-resolved assessments are scarce. Here, we introduce BrAIn, a DL-based application for analyzing the developmental progression of BOs. BrAIn tracks their evolution from embryoid bodies (EBs) and quantifies parameters including area, Feret diameter, perimeter, roundness, and circularity. It also classifies budding and abnormal morphologies of 3D organoids and detects monolayer neural rosette structures, key features of neuronal differentiation. Designed with accessibility in mind, BrAIn provides a no-code interface, enabling researchers of all technical backgrounds to conduct advanced morphological analyses with ease. Our study demonstrates the application of BrAIn to evaluate the effects of different growth conditions-static, orbital shaker, and microfluidic chip-based-on BO development. Orbital shaker cultures resulted in the largest organoids, while chip-based systems achieved more homogeneous growth. Both conditions produced organoids with greater morphological complexity compared to static culture. BrAIn emerges as a robust, user-friendly tool to quantify BO development and explore how versatile growth conditions influence their morphology and maturation.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    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, Alaattin
    Natural 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: 7
    Citation - Scopus: 8
    Sustainability 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, Nigmet
    The 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: 15
    Role of Pretty Nanoflowers as Novel Versatile Analytical Tools for Sensing in Biomedical and Bioanalytical Applications
    (Wiley, 2024-02) Dadi, Seyma; Ocsoy, Ismail
    In 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. image
  • Article
    Citation - WoS: 27
    Citation - Scopus: 28
    Progression 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, Umberto
    Genotoxic 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
    Citation - WoS: 2
    Citation - Scopus: 1
    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, Kim
    BackgroundAlthough 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.