TR Dizin İndeksli Yayınlar / TR Dizin Indexed Publications Collection
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Editorial A Thin Film Micro-Extraction Based Salivary Metabolomics and Chemometric Strategy for Rapid Lung Cancer Diagnosis(Galenos Publ House, 2025) Pelit, Levent; Basbinar, Yasemin; Goksel, Ozlem; Goksel, Tuncay; Erbas, İlknur; Pelit, Fusun; Ozdemir, DurmusINTRODUCTION: Lung cancer (LC) remains one of the leading causes of cancer-related mortality worldwide, largely due to the lack of reliable biomarkers for early detection.1 Despite advances in di-agnostic imaging and targeted therapies, the five-year survival rate remains low because most cases are diagnosed at advanced stages. Consequently, the development of sensitive, non-invasive, and cost-effective diagnostic approaches is a major clinical priority. Metabolomics, the comprehensive profiling of small-molecule metabolites, has emerged as a powerful tool for uncovering cancer-associated metabolic alterations, providing insights into tumor biology and facilitating the discovery of novel biomarkers for accurate diagnosis and disease monitoring. Among biological matrices, saliva is a promising diagnostic biofluid because it can be collected non-invasively, is simple to obtain, and reflects systemic and local metabolic changes. Recent studies have demonstrated its potential for detecting various cancers, including lung cancer, highlighting its value for biomarker-based early di-agnosis.2,3 In this study, a novel thin-film microextraction (TFME) technique integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) is introduced for the rapid, selective, and reproducible extraction of salivary metabolites. The developed TFME approach offers high throughput, reduced solvent consumption, and enhanced analytical performance, enabling the identification and quantification of key metabolic biomarkers associated with lung cancer. The objective of this workflow is to advance saliva-based metabolomics toward clinical translation, offering a promising avenue for the early and non-invasive diagnosis of lung cancer. MATERIAL AND METHODS: Synthesis of SiO2 Nanoparticles and TFME blade Preparation: SiO2 nanoparticles were synthesized using the Stöber method, followed by post-coating with tetraethyl orthosilicate, centrifugation, wash-ing with ethanol, and drying. The nanoparticles were incorporated into a polyacrylonitrile (PAN) matrix and coated onto steel TFME blades via a controlled dip-coating process to ensure uniform film thick-ness. Participants and Sample Collection: Saliva samples were collected from 40 histopathologically con-firmed lung cancer patients and 38 healthy volunteers following an overnight fast and an oral rinse. Ethical approval and informed consent were obtained (Ege University Ethics Committee, protocol: 15-11.1/46). Saliva samples were centrifuged, diluted (1:2), and stored at -80 °C until analysis. TFME Sampling and Analysis: A 96-well plate system equipped with PAN/SiO2-coated TFME blades was used for metabolite extraction (Figure 1). Blades were immersed in diluted saliva samples and rotated at 850 rpm for 150 minutes to allow analyte adsorption, followed by desorption of analytes in 0.1% formic acid for 30 minutes. Desorbed solutions were spiked with 0.5 µg/mL ornidazole as an internal standard prior to LC-MS/MS analysis. RESULTS: The TFME method was optimized to detect 18 metabolites in pre-treatment saliva samples from lung cancer patients. Chromatographic evaluation demonstrated that the Inertsil 100 column, employing isocratic elution with ornidazole as the internal standard, provided optimal separation effi-ciency and reproducibility. Extraction parameters, including desorption solution type and pH, were optimized; desorption solution type 2 at pH 8-9 yielding the highest metabolite recovery. Analytical validation indicated robust linearity (R2: 0.9841-0.9975), sensitivity (limit of detection: 0.014-0.97 μg/mL; limit of quantification: 0.046-3.20 μg/mL), precision (%relative standard deviation <20%), and accuracy (85-125% for most metabolites). Pathway analysis revealed significant alterations in the me-tabolism of phenylalanine, purine, tyrosine, histidine, and methionine. The Heatmap visualization showed increased levels of proline, hypoxanthine, phenylalanine, and tyrosine in lung cancer pa-tients. receiver operating characteristic curve analysis highlighted these metabolites as potential bi-omarkers, with proline exhibiting the highest diagnostic performance [area under the curve (AUC): 0.946], followed by hypoxanthine (AUC: 0.933) and phenylalanine (AUC: 0.905) CONCLUSION: The findings of this study demonstrate that the TFME approach is a reliable and effi-cient platform for metabolomic profiling in lung cancer. Using pre-treatment saliva samples, the method achieved a sensitivity exceeding 90% for detecting newly diagnosed histopathologically con-firmed patients. Among the metabolites analyzed, proline, hypoxanthine, and phenylalanine showed strong diagnostic potential, consistent with the pathway analyses implicating purine and phenylala-nine metabolism. These results underscore the potential of salivary metabolomics as a non-invasive screening alternative in the absence of validated early lung cancer biomarkers. Additionally, TFME’s high-throughput capacity, cost-effectiveness, and environmental sustainability support its feasibility for routine clinical application.Article Citation - WoS: 1Citation - Scopus: 2Lacoo3 Is a Promising Catalyst for the Dry Reforming of Benzene Used as a Surrogate of Biomass Tar(Tubitak Scientific & Technological Research Council Turkey, 2024) Çağlar, Başar; Üner, DenizTar build-up is one of the bottlenecks of biomass gasification processes. Dry reforming of tar is an alternative solution if the oxygen chemical potential on the catalyst surface is at a sufficient level. For this purpose, an oxygen-donor perovskite, $LaCoO_3$, was used as a catalyst for the dry reforming of tar. To circumvent the complexity of the tar and its constituents, the benzene molecule was chosen as a model compound. Dry reforming of benzene vapor on the $LaCoO_3$ catalyst was investigated at temperatures of 600, 700, and 800 °C; at $CO_2/C_6H_6$ ratios of 3, 6, and 12; and at space velocities of 14,000 and 28,000 h–1. The conventional Ni(15 wt.%)/$Al_2O_3$ catalyst was also used as a reference material to determine the relative activity of the $LaCoO_3$ catalyst. Different characterization techniques such as X-ray diffraction, $N_2$ adsorption-desorption, temperature-programmed reduction, and oxidation were used to determine the physicochemical characteristics of the catalysts. The findings demonstrated that the $LaCoO_3$ catalyst has higher $CO_2$ conversion, higher $H_2$ and CO yields, and better stability than the Ni(15 wt.%)/γ-$Al_2O_3$ catalyst. The improvement in activity was attributed to the strong capacity of $LaCoO_3$ for oxygen exchange. The transfer of lattice oxygen from the surface of the $LaCoO_3$ catalyst facilitates the oxidation of carbon and other surface species and leads to higher conversion and yields.Article Citation - WoS: 3Citation - Scopus: 3Β-Ketoenamine-linked covalent organic framework for efficient iodine capture(Tubitak Scientific & Technological Research Council Turkey, 2024) Büyükçakır, OnurExploring the materials that effectively capture radioactive iodine is crucial in managing nuclear waste produced from nuclear power plants. In this study, a β-ketoenamine-linked covalent organic framework (bCOF) is reported as an effective adsorbent to capture iodine from both vapor and solution. The bCOF’s high porosity and heteroatom-rich skeleton offer notable iodine vapor uptake capacity of up to 2.51g $g^{–1}$ at 75 °C under ambient pressure. Furthermore, after five consecutive adsorption-desorption cycles, the bCOF demonstrates high reusability performance with significant iodine vapor capacity retention. The adsorption mechanism was also investigated using various ex situ structural characterization techniques, and these mechanistic studies revealed the existence of a strong chemical interaction between the bCOF and iodine. The bCOF also showed good iodine uptake performance of up to 512 mg $g^{–1}$ in cyclohexane with high removal efficiencies. The bCOF’s performance in adsorbing iodine from both vapor and solution makes it a promising material to be used as an effective adsorbent in capturing radioactive iodine emissions from nuclear power plants.Article Citation - WoS: 5Citation - Scopus: 5Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2d) and Three-Dimensional (3d) Models for Breast Cancer(Galenos Publishing House, 2021) Aydın,M.; Özdemir,E.; Altun,Z.; Kılıç,S.; Aktaş,S.Objective: Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells in two dimensions (2D) and three dimensions (3D). Materials and Methods: With this aim, breast cancer cells with different features (4T1, MDA-MB231, MCF-7) were growth in 2D and 3D dimensions. The cytotoxic and cell death effects under different conditions, durations and doses were evaluated with WST-1, trypan-blue, colony counts. Apoptotic effects were investigated with flow cytometric Annexin-V-PI and immunohistochemical (Ki-67, caspase 3, 8, 9) methods. Results: After free DOX and LipoDOX were applied, the proliferation index of three cell lines reduced. Intrinsic and extrinsic apoptotic pathways were activated in both 2D and 3D models. However, this effect was observed at lower levels in the 3D model due to the difficulty of diffusion of DOX into the spheroids. Additionally, the suitability of the 3D model for breast cancer cells was supported by formation of ductus-like structures and spheroids. Cell deaths were not observed significantly with the DOX-loaded microbubbles due to rising of MBs to the surface and not reaching spheroids held in matrigel of 3D model. Conclusion: DOX and LipoDOX showed anti-proliferative and apoptosis-inducing effects in breast cancer cells. However, these effects indicated variability depending on the cell lines and 2D or 3D model types. ©Copyright 2021 by the the Turkish Federation of Breast Diseases Societies.Letter Prof. Dr. O. Yavuz Ataman(TÜBİTAK, 2021) Eroğlu, Ahmet EminProf. Dr. O. Yavuz Ataman passed away on August 15, 2020, in Ankara. He was an academic as well as a social figure throughout his life. He had remarkable achievements in academy as a researcher, an educator, and an administrator. He was known for his unique approaches to the events in all aspects of life. With his beloved character, he was really special. With Prof. Ataman's passing away, the chemistry and especially analytical chemistry community have lost a very special member.Article Citation - WoS: 11Citation - Scopus: 13Effect of Cnt Incorporation on Pan/Ppy Nanofibers Synthesized by Electrospinning Method(TÜBİTAK, 2020) İnce Yardımcı, Atike; Tanoğlu, Metin; Yılmaz, Selahattin; Selamet, YusufIn this study, carbon nanotubes (CNTs) added polyacrylonitrile/polypyrrole (PAN/PPy) electrospun nanofibers were produced. Average diameters of the nanofibers were measured as 268 and 153 nm for 10 and 25 wt% of PPy contents, respectively. A relatively higher strain to failure values (23.3%) were observed for the low PPy content. When as-grown CNTs (1 and 4 wt%) were added into the PAN/PPy blends, disordered nanofibers were observed to form within the microstructure. To improve the interfacial properties of CNTs/PAN/PPy composites, CNTs were functionalized with H2SO4/HNO3/HCl solution. The functionalized CNTs were well dispersed within the nanofibers and aligned along the direction of nanofibers. Therefore, beads formation on nanofibers decreased. The impedance of the nanofibers was found to decrease with the PPy content and CNT addition. These nanofibers had a great potential to be used as an electrochemical actuator or a tissue engineering scaffold.Article Citation - WoS: 6Citation - Scopus: 6Therapeutic Potentials of Inhibition of Jumonji C Domain-Containing Demethylases in Acute Myeloid Leukemia(Aves, 2020) Koca, Duygu; Hastar, Nurcan; Engür, Selin; Kiraz, Yağmur; Ulu, Gizem Tuğçe; Çekdemir, Demet; Baran, YusufAcute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases.Article Citation - WoS: 2Citation - Scopus: 3A Novel Natural Product, Kl-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells(Turkish Society of Hematology, 2015) Adan Gökbulut, Aysun; Yaşar, Mustafa; Baran, YusufObjective: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by naturin natural Products, İzmir, Turkey), on 232B4 chronic lymphocytic leukemia (CLL) cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. Materials and Methods: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. Results: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. Conclusion: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.Article Citation - WoS: 21Citation - Scopus: 22Effects of Spaceflight on Cells of Bone Marrow Origin(Aves, 2013) Özçivici, EnginOnce only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types.Article Citation - WoS: 4Citation - Scopus: 7The Importance of Protein Profiling in the Diagnosis and Treatment of Hematologic Malignancies(Galenos Yayıncılık, 2011) Şanlı Mohamed, Gülşah; Turan, Taylan; Ekiz, Hüseyin Atakan; Baran, YusufProteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed.