PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis(MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, AlaattinBackground/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.Article Citation - WoS: 4Citation - Scopus: 3Unveiling Bone and Dental Regeneration Potential of Quince Seed Mucilage-Nanohydroxyapatite Scaffolds in Rabbit Mandibles(Wiley, 2025) Genc, Cigdem Cetin; Yilmaz-Dagdeviren, Hilal Deniz; Deniz, Yesim; Derkus, Burak; Degirmenci, Alpin; Arslan, Yavuz EmreDonor-side morbidity of autografting for maxillofacial region defect regeneration has directed attention to bioengineered scaffolds. Composite scaffolds that mimic the bone extracellular matrix (ECM) are the potential candidates for defect reconstruction. Herein, a plant-based regenerative hydrogel, quince seed mucilage (QSM), was enriched with the nanohydroxyapatite (nHAp) particles to construct composite scaffolds (QSM/nHAp). The emerging scaffold is able to induce cellular spheroid formation and regenerate the critical-sized bilateral mandibular defects in rabbits. The macroscopic observations, histochemical (HC) and immunohistochemical (IHC) stainings, mu-computer tomography (CT) scanning, quantitative real time-polymerase chain reaction (qRT-PCR) analyses, and scanning electron microscopy (SEM) imaging revealed that all QSM/nHAp scaffolds were swelled with host blood, filled the whole cavity, and sustained cellular infiltration without adverse reactions. The gradual biodegradation profile of the scaffolds improved bone regeneration by releasing nHAp particles from the scaffold. Strikingly, co-development of dental and bone regeneration was observed for all QSM/nHAp groups beginning after day 21. Moreover, QSM/nHAp scaffolds induced expression (> 2-fold) of bone and dental-related gene and protein expressions at the grafted area and sustained a proper platform for maxillofacial remodeling. Therefore, we strongly believe that such biocompatible plant-based constructs, compared with conventional medical devices used in maxillofacial surgery, could support and induce simultaneous bone and dental regeneration due to the intrinsic dynamics of the material.Article Citation - WoS: 2Citation - Scopus: 3Magnetic Levitational Assembly of Differentiated Sh-Sy5y Cells for Aβ-Induced 3d Alzheimer's Disease Modeling and Curcumin Screening(Wiley-v C H verlag Gmbh, 2025) Bilginer-Kartal, Rumeysa; Arslan-Yildiz, AhuAlzheimer's disease is one of the prevalent neurodegenerative diseases and is characterized by amyloid beta aggregate (A beta) accumulation. This study reports an A beta 1-42 induced 3D Alzheimer's disease modeling utilizing differentiated SH-SY5Y spheroids, which is carried out by Magnetic levitation approach, and the neuroprotective effect of Curcumin is further investigated on this model. For this purpose, SH-SY5Y spheroids are differentiated using Retinoic acid-Brain-derived neurotrophic factor sequentially during 3D cell culture. Differentiated spheroids maintained high viability and exhibited significant neuronal characteristics, as evidenced by increasing beta-III tubulin and NeuN expressions. 3D Alzheimer's disease model formation and neurotoxicity of A beta 1-42 aggregates are investigated on un-/differentiated spheroids, resulting in 65% and 51% cell viability, respectively. Characterization of the 3D Alzheimer's disease model is done by immunostaining of Choline acetyltransferase to investigate cholinergic neuron activity loss, showing a 2.2 decrease in fluorescence intensity. Further, Curcumin treatment on the 3D Alzheimer's disease model resulted in augmenting cell viability, confirming neuroprotective effect of Curcumin on A beta 1-42 induced Alzheimer's disease model. This study highlighted the magnetic levitation-based fabrication of A beta 1-42-induced 3D Alzheimer's disease model successfully, offering a promising experimental platform for other neurodegenerative disease research and potential clinical applications.Article Citation - WoS: 2Citation - Scopus: 2Combined Treatment of Ketogenic Diet and Propagermanium Reduces Neuroinflammation in Tay-Sachs Disease Mouse Model(Springer/Plenum Publishers, 2025) Inci, Orhan Kerim; Seyrantepe, VolkanTay-Sachs disease is a rare lysosomal storage disorder caused by beta-Hexosaminidase A enzyme deficiency causing abnormal GM2 ganglioside accumulation in the central nervous system. GM2 accumulation triggers chronic neuroinflammation due to neurodegeneration-based astrogliosis and macrophage activity with the increased expression level of Ccl2 in the cortex of a recently generated Tay-Sachs disease mouse model Hexa-/-Neu3-/-. Propagermanium blocks the neuroinflammatory response induced by Ccl2, which is highly expressed in astrocytes and microglia. The ketogenic diet has broad potential usage in neurological disorders, but the knowledge of the impact on Tay-Sach disease is limited. This study aimed to display the effect of combining the ketogenic diet and propagermanium treatment on chronic neuroinflammation in the Tay-Sachs disease mouse model. Hexa-/-Neu3-/- mice were placed into the following groups: (i) standard diet, (ii) ketogenic diet, (iii) standard diet with propagermanium, and (iv) ketogenic diet with propagermanium. RT-PCR and immunohistochemistry analyzed neuroinflammation markers. Behavioral analyses were also applied to assess phenotypic improvement. Notably, the expression levels of neuroinflammation-related genes were reduced in the cortex of 140-day-old Hexa-/-Neu3-/- mice compared to beta-Hexosaminidase A deficient mice (Hexa-/-) after combined treatment. Immunohistochemical analysis displayed correlated results with the RT-PCR. Our data suggest the potential to implement combined treatment to reduce chronic inflammation in Tay-Sachs and other lysosomal storage diseases.Article Citation - WoS: 7Citation - Scopus: 7Periodate-Mediated Cross-Linking for the Preparation of Catechol Conjugated Albumin Nanoparticles Used for in Vitro Drug Delivery(Amer Chemical Soc, 2025) Argitekin, Eda; Erez, Ozlem; Cakan-Akdogan, Gulcin; Akdogan, YasarConjugation of serum albumin protein with catechol-containing dopamine molecules provides an alternative method for the preparation of albumin nanoparticles (NPs). A commonly used desolvation method utilizes glutaraldehyde as a cross-linking agent. Here, the catechol cross-linking mechanism is used instead of glutaraldehyde providing advantages to prevent toxicity and an undesirable reaction of glutaraldehyde with cargo molecules. Covalent cross-linking between dopamine conjugated bovine serum albumin (D-BSA) proteins was obtained in the presence of sodium periodate (NaIO4) as an oxidizer. As a result, spherical D-BSA NPs with a uniform size distribution of around 100 nm in diameter and negative zeta potential around -28 mV were prepared. Optimal conditions were reached when a dopamine:IO4 - molar ratio of 2:1, pH 7.4 of the medium, and acetone as the desolvating agent were used. Furthermore, the obtained NPs display antioxidant properties, have rapid biodegradability in the presence of trypsin, and have a high doxorubicin (DOX) loading (9.1%) with a sustainable drug release. DOX loaded D-BSA NPs also caused up to 90% breast cancer cell (MCF-7) death within 24 h. These results show that drug carrying albumin NPs can alternatively be prepared via covalently cross-linked catechol groups and used in drug delivery studies.Article Long-Term Outcomes of Türkiye's First Population-Based Mammography Screening Program: a Decade of Breast Cancer Detection and Survival Analysis in Bahçeşehir(Bmc, 2025) Ozcinar, Beyza; Aribal, Erkin; Cabioglu, Neslihan; Gurdal, Sibel Ozkan; Varol, Gamze; Akyurt, Nuran; Ozmen, VahitBackgroundThe Bah & ccedil;e & scedil;ehir population-based mammography screening program (BMSP) is an example of T & uuml;rkiye's first population-based screening program. This study aims to reveal the successful implementation of population-based secreening program in one of the low- and middle-income countries, T & uuml;rkiye and long-term results of patients diagnosed with breast cancer during BMSP. MethodsThis study was conducted between 2009 and 2019, in the Bah & ccedil;e & scedil;ehir county of Istanbul. Women between the ages of 40 and 69 living in this region were invited every two years to undergo clinical breast examination (CBE) and mammography screening. All data was recorded in a dedicated software program. Women diagnosed with breast cancer were followed as a separate cohort. ResultsDuring the 10-year screening period, 8,825 women were screened and 146 (1.7%) breast cancers were detected. The median age at diagnosis for these patients was 52.9 years (40-69). The risk of breast cancer was 1.39 times higher (95% CI: 1.01-1.93) in women aged >= 50 compared to those less than 50 years (p = 0.045). The Cox regression analysis revealed that age at first birth, and number of births were significant predictors of breast cancer risk (p < 0.001, and p = 0.011). The breast cancer rate tends to increase as the breast density category progresses from A to D (p < 0.001). The median follow-up time for 146 breast cancer patients was 95.3 months. The 10-year breast cancer specific survival rate was 85%. ConclusionsThis study demonstrates that with a committed team and sufficient infrastructure, screening mammography can be effectively carried out in T & uuml;rkiye, leading to early detection and lower mortality rates. The recommended age to commence screening is 40 years old.Article Phenotypically Plastic Drug-Resistant Chronic Myeloid Leukaemia Cell Line Displays Enhanced Cellular Dynamics in a Zebrafish Xenograft Model(Wiley, 2024) Baykal, Seda; Yuce, Zeynep; Ozhan, GunesUnderstanding the mechanisms by which cancer cells switch between different adaptive states and evade therapeutic interventions is essential for clinical management. In this study, the in vivo cellular dynamics of a new chronic myeloid leukaemia cell line displaying altered phenotype and resistance to tyrosine kinase inhibitors were investigated in correlation with their parental cells for invasiveness/metastasis, angiogenic potential and population kinetics. We showed that the cells exhibiting drug resistance and plastic phenotype possess an increased capacity for invasion compared to their parental cells, that exposure to imatinib mesylate has the potential to enhance cellular motility and that in a leukaemic cell population, even a minority of plastic cells exhibit improved migratory ability. Furthermore, we show that these plastic cells have angiogenic and extravasation potential. The present study provides significant insights into the cellular dynamics displayed by a TKI-resistant, phenotypically plastic CML cell line, using a zebrafish (Danio rerio) xenograft model.Article Citation - WoS: 5Citation - Scopus: 6A Comparative Study of Metaheuristic Feature Selection Algorithms for Respiratory Disease Classification(MDPI, 2024) Gürkan Kuntalp, D.; Özcan, N.; Düzyel, Okan; Kababulut, F.Y.; Kuntalp, M.The correct diagnosis and early treatment of respiratory diseases can significantly improve the health status of patients, reduce healthcare expenses, and enhance quality of life. Therefore, there has been extensive interest in developing automatic respiratory disease detection systems. Most recent methods for detecting respiratory disease use machine and deep learning algorithms. The success of these machine learning methods depends heavily on the selection of proper features to be used in the classifier. Although metaheuristic-based feature selection methods have been successful in addressing difficulties presented by high-dimensional medical data in various biomedical classification tasks, there is not much research on the utilization of metaheuristic methods in respiratory disease classification. This paper aims to conduct a detailed and comparative analysis of six widely used metaheuristic optimization methods using eight different transfer functions in respiratory disease classification. For this purpose, two different classification cases were examined: binary and multi-class. The findings demonstrate that metaheuristic algorithms using correct transfer functions could effectively reduce data dimensionality while enhancing classification accuracy. © 2024 by the authors.Article Citation - WoS: 3Citation - Scopus: 3The Effect of Co-Delivery of Oxygen and Anticancer Drugs on the Viability of Healthy and Cancer Cells Under Normoxic and Hypoxic Conditions(Wiley-v C H verlag Gmbh, 2024) Kehr, Nermin SedaHypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O2 supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O2 and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O2 release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O2 and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions. The synthesis of pH-sensitive perfluorocarbon-based nanomaterials containing oxygen and anticancer drugs is reported. These nanomaterials provide oxygen release within 14 d and pH-dependent sustained release of anticancer drugs over 30 d. Co-delivery of oxygen and anticancer drugs by pH-sensitive nanomaterials promotes the viability of healthy cells compared to malignant cells under hypoxic conditions. imageArticle Citation - WoS: 1Citation - Scopus: 1Optimization of Biotransformation Processes of <i>camarosporium Laburnicola</I> To Improve Production Yields of Potent Telomerase Activators(Bmc, 2024) Kuecueksolak, Melis; Coban, Hasan Bugra; Bedir, ErdalBackground Telomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02). Results DoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01). Conclusion Following a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.