PubMed İndeksli Yayınlar Koleksiyonu / PubMed 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 One-Pot, Light-Induced, Liquid Crystal-Templated Synthesis of Nanoporous Silver Films at Room Temperature(TÜBİTAK, 2025) Mert-Balci, F.Nanoporous silver (NPS) films, characterized by a 3-dimensional bicontinuous structure of interconnected nanopores and ligaments, have found widespread use in spectroscopy, plasmonics, solar cells, catalysis, and chemical sensing. Traditionally, NPS films are fabricated via chemical dealloying, where a less noble metal (e.g., Cu or Al) is selectively removed through harsh chemical etching. However, residual traces of these metals can adversely affect the performance of NPS thin films in applications such as plasmonics and catalysis. This paper reports a one-pot, liquid crystal-templated method for synthesizing ultrapure NPS thin films at room temperature for the first time. The process begins with the preparation of an LLC composed of a nonionic surfactant and AgNO<inf>3</inf> that is then coated onto solid substrates. Exposure of the LLC film to ultraviolet light facilitates the in situ synthesis of Ag nanoparticles within the liquid crystal film. Subsequent solvent washing removes the surfactant molecules and any unreacted metal ions, yielding NPS films comprised of densely packed Ag nanoparticles on glass substrates. The resulting NPS films feature a 3-dimensional structure with uniformly distributed, interconnected nanopores. Synthesized under ambient conditions and scalable over large areas, these ultrapure NPS films present a highly promising platform for advanced applications in catalysis, spectroscopy, plasmonics, and biosensing. © TÜBİTAK.Article Subtype-Specific Divergent Roles of Calpain-1 and Calpain-2 in Basal a Triple-Negative Breast Cancer(BMC, 2025) Uner, Goklem; Oztarhan, Gokhan; Kirmizibayrak, Petek BallarBackgroundCAPN-1 and CAPN-2, two ubiquitously expressed calpains, have been implicated in cancer progression, but their distinct roles in breast cancer remain poorly defined. This study aims to define the opposing roles of CAPN-1 and CAPN-2 in breast cancer progression, with a focus on their regulatory impact on cell proliferation. Since these calpains may have different functions in the mammary gland, we aimed to investigate the possible antagonistic roles of CAPN-1 and CAPN-2 in breast cancer progression, focusing on their expression patterns and functional impact on cell proliferation.Methods and resultsWe analyzed breast cancer cell lines using immunoblotting and real-time cellular assays, showing that HCC1937 cells exhibit an opposite expression pattern of CAPN-1 and CAPN-2 compared to non-cancerous breast cells. CAPN-1 promoted cancer cell survival and negatively regulated CAPN-2 at both the protein and mRNA levels, whereas CAPN-2 suppressed proliferation. Additionally, the calpain activator AG-08 triggered cell death through CAPN-2 but not CAPN-1. In silico analysis confirmed higher CAPN-1 and lower CAPN-2 expression levels in breast cancer samples compared to normal tissue.ConclusionsThese findings indicate that CAPN-1 and CAPN-2 may exert antagonistic roles in breast cancer, but importantly, this effect was restricted to HCC1937 cells, representing a basal A TNBC subtype. Validation in additional basal A models and patient-derived samples will be essential to confirm these results. Our study, therefore, provides preliminary, model-specific insights into calpain regulation in TNBC and suggests that future therapeutic strategies should carefully account for subtype heterogeneity.Article Citation - WoS: 1Citation - Scopus: 1Two Key Substitutions in the Chromophore Environment of mKate2 Produce an Enhanced FusionRed-Like Red Fluorescent Protein(Russian Federation Agency Science & innovation, 2025) Ruchkin, D. A.; Gavrikov, A. S.; Kolesov, D., V; Gorokhovatsky, A. Yu.; Chepurnykh, T., V; Mishin, A. S.; Bogdanov, A. M.Red fluorescent proteins (RFPs) are often probes of choice for living tissue microscopy and whole-body imaging. When choosing a specific RFP variant, the priority may be given to the fluorescence brightness, maturation rate, monomericity, excitation/emission wavelengths, and low toxicity, which are rarely combined in an optimal way in a single protein. If additional requirements such as prolonged fluorescence lifetime and/or blinking ability are applied, the available repertoire of probes could dramatically narrow. Since the entire diversity of conventional single-component RFPs belongs to just a few phylogenetic lines (DsRed-, eqFP578-and eqFP611-derived being the major ones), it is not unexpected that their advantageous properties are split between close homologs. In such cases, a systematic mutagenetic analysis focusing on variant-specific amino acid residues can shed light on the origins of the distinctness between related RFPs and may aid in consolidating their strengths in new RFP variants. For instance, the protein FusionRed, despite being efficient in fluorescence labeling thanks to its good monomericity and low cytotoxicity, has undergone considerable loss in fluorescence brightness/lifetime compared to the parental mKate2. In this contribution, we describe a fast-maturing monomeric RFP designed semi-rationally based on the mKate2 and FusionRed templates that outperforms both its parents in terms of molecular brightness, has extended fluorescence lifetime, and displays a spontaneous blinking pattern that is promising for nanoscopy use.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.Article Citation - WoS: 1Citation - Scopus: 1Comparison of Magnetic Seed and Rfid Methods in the Localization of Non-Palpable Breast Lesions(Wolters Kluwer Medknow Publications, 2024) Sanli, Ahmet Necati; Sanli, Deniz E. Tekcan; Golshan, Mehra; Sezgin, Efe; Celik, Varol; Aydogan, FatihBackground: Many methods have been developed for localizing non-palpable breast lesions. This study investigated the success rate and surgical results of the magnetic seed (Magseed) and radiofrequency identification (RFID) method, which are relatively new compared to standard wire-guided localizations. Materials and Methods: 20 simulation (10 Magseed, 10 RFID) models were created using turkey breasts and raisins. Raisins containing magnetic seed and RFID tags were placed on the turkey breast. Sentimag (R) probe was used for the Magseed group, and Faxitron LOCalizer (TM) System device was used in the RFID group. Both methods were evaluated in terms of accuracy in detecting breast lesion localization, operation times, excised tissue weights, total resection volume, surgical margin negativity, and re-excision rates. Results: Lesion localization success in both techniques was 100%. While procedure times were statistically significantly shorter in the Magseed group, incision lengths were shorter in the RFID group (P = 0.013, P = 0.007, respectively). No statistically significant difference was found between the groups for the weight of the removed parts, total resection volume, and surgical margin distance (P > 0.05). Conclusion: In this feasibility study, it was concluded that neither the RFID nor Magseed methods had a significant advantage over each other, in terms of localization detection and surgical margin negativity, and both methods could be used successfully for localization.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: 1Citation - Scopus: 2The Impact of Genetic Variants Related To the Fatty Acid Metabolic Process Pathway on Milk Production Traits in Jersey Cows(Taylor & Francis inc, 2024) Ardicli, Sena; Senturk, Nursen; Bozkurt, Berkay; Babayev, Huseyn; Selvi, Tugce; Skolnick, Stephen; Cobanoglu, OzdenThe synthesis of fatty acids plays a critical role in shaping milk production characteristics in dairy cattle. Thus, identifying effective haplotypes within the fatty acid metabolism pathway will provide novel and robust insights into the genetics of dairy cattle. This study aimed to comprehensively examine the individual and combined impacts of fundamental genes within the fatty acid metabolic process pathway in Jersey cows. A comprehensive phenotypic dataset was compiled, considering milk production traits, to summarize a cow's productivity across three lactations. Genotyping was conducted through PCR-RFLP and Sanger sequencing, while the association between genotype and phenotype was quantified using linear mixed models. Moderate biodiversity and abundant variation suitable for haplotype analysis were observed across all examined markers. The individual effects of the FABP3, LTF and ANXA9 genes significantly influenced both milk yield and milk fat production. Additionally, this study reveals novel two-way interactions between genes in the fatty acid metabolism pathway that directly affect milk fat properties. Notably, we identified that the GGAAGG haplotype in FABP3xLTFxANXA9 interaction may be a robust genetic marker concerning both milk fat yield and percentage. Consequently, the genotype combinations highlighted in this study serve as novel and efficient markers for assessing the fat content in cow's milk. [GRAPHICS]Article Citation - WoS: 2Citation - Scopus: 2Gas Phase Fragmentation Behavior of Proline in Macrocyclic B7 Ions(American Chemical Society, 2023) Taşoğlu, Çağdaş; Arslanoğlu, Alper; Yalçın, TalatThefragmentation characteristics of b (7) ionsproduced from proline-containing heptapeptides have been studiedin detail. The study has utilized the following C-terminally amidatedmodel peptides: PA(6), APA(5), A(2)PA(4), A(3)PA(3), A(4)PA(2), A(5)PA, A(6)P, PYAGFLV, PAGFLVY, PGFLVYA, PFLVYAG,PLVYAGF, PVYAGFL, YPAGFLV, YAPGFLV, YAGPFLV, YAGFPLV, YAGFLPV, YAGFLVP,PYAFLVG, PVLFYAG, A(2)PXA(3), and A(2)XPA(3) (where X = C, D, F, G, L, V, and Y, respectively). The resultshave shown that b (7) ions undergo head-to-tailcyclization and form a macrocyclic structure. Under the collision-induceddissociation (CID) condition, it generates nondirect sequence ionsregardless of the position of the proline and the neighboring aminoacid residues. This study highlights the unusual and unique fragmentationbehavior of proline-containing heptapeptides. Following the head-to-tailcyclization, the ring opens up and places the proline residue in theN-terminal position while forming a regular oxazolone form of b (2) ions for all peptide series. Then, the fragmentationreaction pathway is followed by the elimination of proline with itsC-terminal neighbor residue as an oxazolone (e.g., PXoxa) for all proline-containing peptide series.
