PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 5Citation - Scopus: 5Multiorgan-On for Cancer Drug Pharmacokinetics-Pharmacodynamics (pk-Pd) Modeling and Simulations(Springer/plenum Publishers, 2025) Mohammed, Abdurehman Eshete; Kurucaovali, Filiz; Okvur, Devrim PesenCancer is one of the most common and fatal diseases worldwide and kills millions of people every year. Cancer drug resistance, lack of efficacy, and safety are significant problems in cancer patients. A multiorgan-on-a-chip (MOC) device consisting of breast and liver compartments was designed with AutoCAD software. The MOC molds were printed by a Formlabs Form 2 3D printer. MDA-MB-231, HepG2, and MCF-10 A cells were used for the MOC experiments. The cell lines were cultured at 37 degrees C with 5% CO2, and cell viability was assessed via Alamar blue dye to generate pharmacodynamics (PD) data. Drug concentrations from the cell culture media were analyzed via Agilent 1260 Infinity II HPLC with a Waters Symmetry C18 column and used to generate pharmacokinetics (PK) data. The PK and PD data were modeled and simulated by Monolix and Simulix software, respectively. The safety and efficacy of drug dosing regimens were compared, and the best dosing regimens were selected. This research designed and fabricated a unique MOC consisting of liver and breast compartments that overcomes the need for sealing or assembling. It was used for PK-PD modeling and simulations, and its functionality was proven experimentally. The new MOC will be helpful in preclinical trials to evaluate the efficacy and safety of drugs.Article Citation - WoS: 2Citation - Scopus: 3Development of Mg-Alginate Based Self Disassociative Bio-Ink for Magnetic Bio-Patterning of 3d Tumor Models(Wiley-v C H verlag Gmbh, 2024) Coban, Basak; Baskurt, Mehmet; Sahin, Hasan; Arslan-Yildiz, AhuAlginate forms a hydrogel via physical cross-linking with divalent cations. In literature, Ca2+ is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca-alginate hydrogels. On the other hand, Mg-alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg-alginate as the main component of a bio-ink for the first time to obtain 3D tumor models by magnetic bio-patterning technique. The bio-ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg-alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS-2, and SH-SY5Y cells. Long-term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F-actin expressions are observed successfully in 3D tumor models. Finally, the anti-cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC50 values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio-patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg-alginate hydrogel is successfully used to form bio-patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.Article Citation - WoS: 5Citation - Scopus: 6Beyond Lux: Methods for Species and Photoreceptor-Specific Quantification of Ambient Light for Mammals(Bmc, 2024) McDowell, Richard J.; Didikoğlu, Altuğ; Didikoglu, Altug; Woelders, Tom; Gatt, Mazie J.; Moffatt, Finn; Notash, Saba; Lucas, Robert J.BackgroundLight is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. Light is commonly measured in lux. However, this employs a spectral weighting function for human luminance and is not suitable for 'non-visual' effects of light or use across species. In humans, a photoreceptor-specific (alpha-opic) metrology system has been proposed as a more appropriate way of measuring light.ResultsHere we establish technology to allow this alpha-opic measurement approach to be readily extended across mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. We develop a high-throughput method to derive spectral sensitivities for recombinantly expressed mammalian opsins and use it to establish the spectral sensitivity of melanopsin from 13 non-human mammals. We further address the need for simple measurement strategies for species-specific alpha-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware multichannel light sensor for 'point and click' measurement. We finally demonstrate that species-specific alpha-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species.ConclusionsOur study presents methods for measuring light in species-specific alpha-opic units that are superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.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: 1Citation - Scopus: 1Assessment of the Validity and Reliability of Edinburgh Postpartum Depression Scale in Turkish Men(Walter de Gruyter GmbH, 2024) Alkan, C.; Didikoǧlu, A.; Çöme, O.; Yllmaz, B.; Mevsim, V.Objectives: Perinatal depression (PD) affects individuals during pregnancy and early parenthood, resembling major depression. Recent research highlights paternal perinatal depression (PPD) in fathers. PPD has adverse effects on fathers and their children. This study assesses the Turkish version of the Edinburgh Postnatal Depression Scale (EPDS) for Turkish fathers, aiming to provide a tool for PPD identification. Methods: This methodological study validates the EPDS for Turkish fathers and explores associations with demographic and psychosocial factors. The study involved 295 fathers with infants aged 2 weeks to 12 months. The EPDS, originally designed for perinatal depression and validated in Turkish women, was used. Fathers completed a participant information questionnaire, the EPDS, and the Beck Depression Inventory (BDI) during clinic visits. Data on sociodemographic factors, paternal roles, and pregnancy and postpartum support were collected. Mothers also completed the EPDS. Descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and correlation tests were used. Results: The study included fathers with an average age of 30.5 years, mostly with a high school education or higher. The EPDS had a mean total score of 3.1. Factor analysis suggested a three-factor structure for the EPDS in Turkish fathers, including anhedonia, anxiety, and depression. Confirmatory factor analysis validated the three-factor structure, with acceptable model fit indices. Positive correlations were found between fathers' EPDS scores, maternal EPDS scores, and paternal BDI scores. The EPDS effectively discriminated between different levels of depression severity. Various factors, such as education level and lack of support during pregnancy and after childbirth, were associated with higher EPDS scores. Conclusions: These findings emphasize the significance of assessing and addressing PPD in fathers, supporting the use of the EPDS as a valid tool in the Turkish context. The three-factor structure aligns with international research, highlighting the importance of a multi-dimensional approach to PPD assessment. Early intervention can mitigate PPD's impact on fathers, mothers, and children, benefiting mental health and well-being. © 2024 Walter de Gruyter GmbH, Berlin/Boston.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.Review Citation - WoS: 3Citation - Scopus: 4Long Non-Coding Rna-Mediated Modulation of Endoplasmic Reticulum Stress Under Pathological Conditions(Wiley, 2024) Ciftci, Yusuf Cem; Yurtsever, Yigit; Akgul, BunyaminEndoplasmic reticulum (ER) stress, which ensues from an overwhelming protein folding capacity, activates the unfolded protein response (UPR) in an effort to restore cellular homeostasis. As ER stress is associated with numerous diseases, it is highly important to delineate the molecular mechanisms governing the ER stress to gain insight into the disease pathology. Long non-coding RNAs, transcripts with a length of over 200 nucleotides that do not code for proteins, interact with proteins and nucleic acids, fine-tuning the UPR to restore ER homeostasis via various modes of actions. Dysregulation of specific lncRNAs is implicated in the progression of ER stress-related diseases, presenting these molecules as promising therapeutic targets. The comprehensive analysis underscores the importance of understanding the nuanced interplay between lncRNAs and ER stress for insights into disease mechanisms. Overall, this review consolidates current knowledge, identifies research gaps and offers a roadmap for future investigations into the multifaceted roles of lncRNAs in ER stress and associated diseases to shed light on their pivotal roles in the pathogenesis of related diseases.Review Citation - WoS: 10Citation - Scopus: 12Genetic and Biotechnological Approaches To Improve Fruit Bioactive Content: a Focus on Eggplant and Tomato Anthocyanins(Mdpi, 2024) Cammareri, Maria; Frary, Amy; Frary, Anne; Grandillo, SilvanaAnthocyanins are a large group of water-soluble flavonoid pigments. These specialized metabolites are ubiquitous in the plant kingdom and play an essential role not only in plant reproduction and dispersal but also in responses to biotic and abiotic stresses. Anthocyanins are recognized as important health-promoting and chronic-disease-preventing components in the human diet. Therefore, interest in developing food crops with improved levels and compositions of these important nutraceuticals is growing. This review focuses on work conducted to elucidate the genetic control of the anthocyanin pathway and modulate anthocyanin content in eggplant (Solanum melongena L.) and tomato (Solanum lycopersicum L.), two solanaceous fruit vegetables of worldwide relevance. While anthocyanin levels in eggplant fruit have always been an important quality trait, anthocyanin-based, purple-fruited tomato cultivars are currently a novelty. As detailed in this review, this difference in the anthocyanin content of the cultivated germplasm has largely influenced genetic studies as well as breeding and transgenic approaches to improve the anthocyanin content/profile of these two important solanaceous crops. The information provided should be of help to researchers and breeders in devising strategies to address the increasing consumer demand for nutraceutical foods.Article Citation - WoS: 1Citation - Scopus: 1Association Mapping and Candidate Gene Identification for Yield Traits in European Hazelnut (<i>corylus Avellana</I> L.)(John Wiley & Sons Ltd, 2024) Baytar, Asena Akkoese; Yanar, Ertugrul Gazi; Frary, Anne; Doganlar, SamiEuropean hazelnut (Corylus avellana L.) is an important nut crop due to its nutritional benefits, culinary uses, and economic value. T & uuml;rkiye is the leading producer of hazelnut, followed by Italy and the United States. Quantitative trait locus studies offer promising opportunities for breeders and geneticists to identify genomic regions controlling desirable traits in hazelnut. A genome-wide association analysis was conducted with 5,567 single nucleotide polymorphisms on a Turkish core set of 86 hazelnut accessions, revealing 189 quantitative trait nucleotides (QTNs) associated with 22 of 31 traits (p < 2.9E-07). These QTNs were associated with plant and leaf, phenological, reproductive, nut, and kernel traits. Based on the close physical distance of QTNs associated with the same trait, we identified 23 quantitative trait loci. Furthermore, we identified 23 loci of multiple QTs comprising chromosome locations associated with more than one trait at the same position or in close proximity. A total of 159 candidate genes were identified for 189 QTNs, with 122 of them containing significant conserved protein domains. Some candidate matches to known proteins/domains were highly significant, suggesting that they have similar functions as their matches. This comprehensive study provides valuable insights for the development of breeding strategies and the improvement of hazelnut and enhances the understanding of the genetic architecture of complex traits by proposing candidate genes and potential functions.
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