PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article A Capsular Polysaccharide from a Healthy Human Microbiota Member Activates a Lag-3-NK Cell Axis to Restrain Colon Cancer and Augment Immunotherapy(Cell Press, 2025) Weis, Allison M.; Tang, William W.; Stephen-Victor, Emmanuel; Bell, Rickesha; Brown, D. Garrett; Round, June L.Colorectal cancer (CRC) is increasing globally, making identification of preventative measures necessary. Transplantation of the microbiota from CRC and non-CRC patients into mice demonstrates that non-diseased individuals possess organisms that reduce tumor formation and highlights Bacteriodes uniformis as protective. B. uniformis is reduced in humans with CRC, and proactive treatment with B. uniformis slows tumor growth in mice. Natural killer (NK) cells, but not T cells, are required for B. uniformis-mediated protection. CRC is recalcitrant to immunotherapies; however, addition of B. uniformis restores response to alpha-CTLA-4 treatment in an NK cell-dependent manner. We report that high Lag-3 expression is associated with greater survival in CRC patients and that B. uniformis-mediated protection is reliant on Lag-3 in innate cells. Induction of NK cell activity and reduced tumor growth is dependent on a specific B. uniformis capsular polysaccharide. Thus, healthy individuals possess tumor suppressor microbes that prevent cancer development and can be harnessed therapeutically.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 Plasma Proteomic Markers of Interleukin-1β Pathway Associated With Incident Age-Related Macular Degeneration in Persons With Aids(Elsevier, 2025) Hunt, Peter W.; Olshen, Adam B.; Murad, Natalia; Ambayec, Gabrielle C.; Sezgin, Efe; Schneider, Michael F.; Jabs, Douglas A.Objective To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach. Design A nested case-control study (analysis 1) and nested cohort study (analysis 2). Participants Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA). Methods Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality. Main Outcome Measures Incident intermediate-stage AMD; incident cataract; and mortality. Results Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1 beta pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality. Conclusions Upregulation of the IL-1 beta pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1 beta pathway may provide a therapeutic avenue for treatment of AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100794 (c) 2025 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Article Citation - WoS: 4Citation - Scopus: 4Sulfonated Cellulose: a Strategy for Effective Methylene Blue Sequestration(Amer Chemical Soc, 2025) Toy, Mustafa; Recepoglu, Yasar Kemal; Arar, OzgurThis study investigates the sulfonation modification of cellulose for the removal of methylene blue (MB) from aqueous solutions. The prepared biosorbent was characterized, and its sorption capacity, kinetics, and thermodynamics were systematically evaluated. Fourier-transform infrared (FTIR) spectroscopy analyzed structural modifications, while scanning electron microscopy (SEM) examined the surface properties. The optimal sorbent dosage was determined as 0.05 g. MB removal efficiency increased from 11% at pH 1 to 70% at pH 2, reaching 99% within the pH range of 3 to 7. Kinetic studies revealed rapid sorption, achieving 99% removal within 3 min. Among various isotherm models, the Langmuir model provided the best fit (R 2 = 0.9989), indicating monolayer sorption with a maximum capacity of 37.65 mg/g. Thermodynamic analysis showed negative Delta G degrees values, confirming a spontaneous sorption process, while an enthalpy change (Delta H degrees) of -33.5 kJ/mol indicated exothermic behavior. The entropy change (Delta S degrees) of -82.6 J mol-1<middle dot>K-1 suggested decreased disorder during sorption. Regeneration studies demonstrated that 0.2 M HCl combined with ethanol achieved the highest desorption efficiency, and after three cycles, the MB removal efficiency remained above 99%. The presence of -SO3 - groups played a crucial role in MB sorption via ion exchange and may also contribute through hydrogen bonding, thereby enhancing MB sorption. These findings highlight sulfonated cellulose as an efficient and regenerable biosorbent for MB removal, offering valuable insights into its sorption mechanisms.Article Citation - WoS: 3Citation - Scopus: 4Magsity Platform: a Hybrid Magnetic Levitation-Based Lensless Holographic Microscope Platform for Liquid Density and Viscosity Measurements(Royal Soc Chemistry, 2025) Ince, Oyku Doyran; Tekin, H. CumhurThe viscosity and density of liquids are the most extensively studied material properties, as their accurate measurement is critical in various industries. Although developments in micro-viscometers have overcome the limitations of traditional bulky methods, more accessible technologies are required. Here, we introduce a novel magnetic levitation-based method to measure the viscosity and density of solutions in a microcapillary channel. This principle exploits microparticles as microsensors to correlate levitation time and height with solutions' viscosity and density, using buoyancy and drag forces. The platform has an integrated lensless holographic microscope, providing a hybrid system for in situ and precise measurements. By utilizing this hybrid technology, portable, rapid and cost-effective measurements can be conducted. This platform enables viscosity and density measurements within 7 minutes, achieving high accuracies of at least 97.7% and 99.9%, respectively, across an operation range of 0.84-5.09 cP and 1.00-1.09 g cm-3. The platform is utilized to clearly distinguish differences in the spent cell culture medium across various cell lines. This method, as presented, can be readily applied to measure a diverse array of liquids in multiple domains, encompassing biotechnology, medicine, and engineering.Article Citation - WoS: 1Tcgex: a Powerful Visual Interface for Exploring and Analyzing Cancer Gene Expression Data(Springernature, 2025) Kus, M. Emre; Sahin, Cagatay; Kilic, Emre; Askin, Arda; Ozgur, M. Mert; Karahanogullari, Gokhan; Ekiz, H. AtakanAnalyzing gene expression data from the Cancer Genome Atlas (TCGA) and similar repositories often requires advanced coding skills, creating a barrier for many researchers. To address this challenge, we developed The Cancer Genome Explorer (TCGEx), a user-friendly, web-based platform for conducting sophisticated analyses such as survival modeling, gene set enrichment analysis, unsupervised clustering, and linear regression-based machine learning. TCGEx provides access to preprocessed TCGA data and immune checkpoint inhibition studies while allowing integration of user-uploaded data sets. Using TCGEx, we explore molecular subsets of human melanoma and identify microRNAs associated with intratumoral immunity. These findings are validated with independent clinical trial data on immune checkpoint inhibitors for melanoma and other cancers. In addition, we identify cytokine genes that can be used to predict treatment responses to various immune checkpoint inhibitors prior to treatment. Built on the R/Shiny framework, TCGEx offers customizable features to adapt analyses for diverse research contexts and generate publication-ready visualizations. TCGEx is freely available at https://tcgex.iyte.edu.tr, providing an accessible tool to extract insights from cancer transcriptomics data.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 Citation - Scopus: 2Turkmednli: a Turkish Medical Natural Language Inference Dataset Through Large Language Model Based Translation(Peerj inc, 2025) Ogul, Iskender Ulgen; Soygazi, Fatih; Bostanoglu, Belgin ErgencNatural language inference (NLI) is a subfield of natural language processing (NLP) that aims to identify the contextual relationship between premise and hypothesis sentences. While high-resource languages like English benefit from robust and rich NLI datasets, creating similar datasets for low-resource languages is challenging due to the cost and complexity of manual annotation. Although translation of existing datasets offers a practical solution, direct translation of domain-specific datasets presents unique challenges, particularly in handling abbreviations, metric conversions, and cultural alignment. This study introduces a pipeline for translating a medical NLI dataset into Turkish, which is a low-resource language. Our approach employs fine-tuning the Llama-3.1 model with selected samples from the Medical Abbreviation dataset (MeDAL) to extract and resolve medical abbreviations. Consequently, NLI pairs are refined with extracted abbreviations and subjected to metric correction. Later, the processed sentences are then translated using Facebook's No Language Left Behind (NLLB) translation model. To ensure quality, we conducted comprehensive evaluations using both machine learning models and medical expert review. Our results show that BERTurk achieved 75.17% accuracy on TurkMedNLI test data and 76.30% on the normalized test set, while BioBERTurk demonstrated comparable performance with 75.59% accuracy on test data and 72.29% on the normalized dataset. Medical experts further validated the translations through manual assessment of sampled sentences. This work demonstrates the effectiveness of large language models in adapting domain-specific datasets for low-resource languages, establishing a foundation for future research in multilingual biomedical NLP.Article Radially Aligned Carbon Nanotube Glass Fiber Composites as Ion-Selective Microelectrodes(Amer Chemical Soc, 2025) Onder, Ahmet; Ng, Zhi Kai; Tsang, Siu Hon; Alagappan, Palaniappan; Teo, Edwin Hang Tong; Yildiz, Umit HakanDetection of ions is challenging due to their small size, rapid diffusion, and high mobility, especially for assaying in samples of low volumes. Among the traditional analytical methods, potentiometric ion-selective electrodes (ISE) have become a popular choice for detecting ions as they are cost-effective, user-friendly and can be miniaturized, making them useful for on-site analysis. In this context, radially aligned carbon nanotubes (RACNT) directly grown on glass fibers (GF) via the chemical vapor deposition method is investigated as a solid contact material for the fabrication of ion-selective microelectrodes (mu ISE) upon incorporating specific ionophores within a polymeric encapsulation membrane. As an illustration, sensitive detection of ammonium ions is accomplished by the fabricated mu ISE (plasticized PVC membrane containing nonactin ionophores), which yielded a LOD and a linear response range between 7.5 x 10-6 and 1.0 x 10-5 to 1.0 x 10-1 M, respectively. The mu ISE fabricated with RACNT-GF as an interface material exhibited improvements in LOD and enhanced the detection selectivity as compared to a conventional ISE fabricated using planar solid contact materials such as graphite. We hypothesize that the fabricated mu ISE with a high surface area and mechanical durability maximize the accommodation of ionophores in the barrier membrane for yielding improved potentiometric responses. Experimental results illustrate that the mu ISE possesses the potential to be utilized for the fabrication of selective and sensitive ISE upon incorporation of specific ionophores with RACNT-GF composites.Article Citation - WoS: 1Citation - Scopus: 1Imbalance in Redox Homeostasis Is Associated With Neurodegeneration in the Murine Model of Tay-Sachs Disease(Springer, 2025) Basirli, Hande; Ates, Nurselin; Seyrantepe, VolkanBackgroundTay-Sachs disease is a neurodegenerative disorder characterized by a build-up of GM2 ganglioside in the brain, which results in progressive central nervous system dysfunction. Our group recently generated Hexa-/-Neu3-/- mice, a murine model with neuropathological abnormalities similar to the infantile form of Tay-Sachs disease. Previously, we reported progressive neurodegeneration with neuronal loss in the brain sections of Hexa-/-Neu3-/- mice. However, the relationship between the severity of neurodegeneration and the imbalance in redox homeostasis was not yet clarified in Hexa-/-Neu3-/- mice. Here, we evaluated whether neurodegeneration is associated with oxidative stress in the tissues and cells of Hexa-/-Neu3-/- mice and neuroglia cells from Tay-Sachs patients.Methods and resultsCell death and oxidative stress-related markers were evaluated in four brain regions and fibroblasts of 5-month-old WT, Hexa-/-, Neu3-/-, and Hexa-/-Neu3-/- mice and human neuroglia cells using Western blot, RT-PCR, and immunohistochemistry analyses. We further analyzed oxidative stress levels in the samples using flow cytometry analyses. We discovered neuronal death, alterations in intracellular ROS levels, and damaging effects of oxidative stress, especially in the cerebellum and fibroblasts of Hexa-/-Neu3-/- mice.ConclusionsOur results showed that alteration in redox homeostasis might be related to neurodegeneration in the murine model of Tay-Sachs Disease. These findings suggest that targeting the altered redox balance and increased oxidative stress might be a rational therapeutic approach for alleviating neurodegeneration and treating Tay-Sachs disease.