PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Semi-Synthetic Sapogenin Derivatives Inhibit Inflammation-Induced Tumorigenic Signaling Alterations in Prostate Carcinogenesis(Elsevier Science Inc, 2026) Debelec-Butuner, Bilge; Ozturk, Mert Burak; Tag, Ozgur; Akgun, Ismail Hakki; Bedir, ErdalProstatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of antiinflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (CA) and astragenol (AG) to assess their potential to inhibit inflammation-mediated tumorigenic signaling. Building on our previous findings, which demonstrated their inhibitory activity on NFxB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and (3-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration. In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as antiinflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.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 Enhancement of Corchorus Olitorius L. on Osteogenic Differentiation of MC3T3-E1 Pre-Osteoblast Cells by Increasing Alkaline Phosphatase and Hydroxyproline(Taylor & Francis Ltd, 2025) Ertugruloglu, Pinar; Baris, Elif; Okkali, Gaye Sumer; Boke Sarikahya, NazliCorchorus olitorius L. (jute mallow or molehiya) belongs to the Malvaceae family valued for its nutritional and medicinal properties. In this study, the potential to enhance osteogenesis in MC3T3-E1(Murine Calvaria-derived 3T3 Subclone E1) pre-osteoblastic cells was investigated to support bone formation and mineralisation. Leaf ethanolic extract was prepared and applied to MC3T3-E1 cells. Osteogenic effects were evaluated through three methods: MTT assays for cell viability, Alizarin Red S staining for calcium deposition, enzymatic analyses for alkaline phosphatase (ALP) and hydroxyproline (HYP). A non-cytotoxic concentration of C. olitorius extract (0.5 mg/mL) significantly increased ALP and HYP levels, promoting osteogenic differentiation in both undifferentiated and differentiated cells. HYP levels were notably elevated in differentiated cells. The findings suggested that C. olitorius extract may be a promising natural agent for enhancing bone health, warranting further in vivo and clinical studies to confirm its therapeutic potential.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: 5Citation - Scopus: 7Targeting the Panoptosome Using Necrostatin-1 Reduces Panoptosis and Protects the Kidney Against Ischemia-Reperfusion Injury in a Rat Model of Controlled Experimental Nonheart-Beating Donor(Elsevier Science inc, 2024) Dokur, Mehmet; Uysal, Erdal; Kucukdurmaz, Faruk; Altinay, Serdar; Polat, Sait; Batcioglu, Kadir; Yeni, Sema Nur DokurPurpose. Reducing renal ischemia is crucial for the function and survival of grafts from non- heartbeat donors, as it leads to inflammatory responses and tubulointerstitial damage. The primary concern with organs from nonheartbeat donors is the long warm ischemia period and reperfusion injury following renal transplantation. This study had two main goals; one goal is to determine how Necrostatin-1 targeting the PANoptosome affects PANoptosis in the nonheartbeating donor rat model. The other goal is to fi nd out if Necrostatin-1 can protect the kidney from ischemic injury for renal transplantation surgery. Methods. Twenty-four rats were grouped randomly as control and Necrostatin-1 in this experimental animal study, and we administered 1.65 mg/kg of Necrostatin-1 intraperitoneally to the experimental group for 30 minutes before cardiac arrest. We removed the rats' left kidneys and measured various oxidative stress marker measures such as malondialdehyde, superoxide dismutase, catalase, GPx, and 8-hydroxy-2-deoxyguanosine levels. We then subjected the tissues to immunohistochemical analysis, electron microscopy, and histopathological analysis. Findings. The Necrostatin-1 group had a lower total tubular injury score (P < .001) and less Caspase-3, gasdermin D, and mixed lineage kinase domain-like protein expression. Additionally, the apoptotic index of the study group was lower (P < .001). Furthermore, the study group had higher levels of superoxide dismutase and GPx (P < .05), whereas malondialdehyde levels were reduced (P = .009). Electron microscopy also revealed a significant improvement in tissue structure in the Necrostatin-1 group. Conclusion. Necrostatin-1 protects against ischemic acute kidney injury in nonheart-beating donor rats by inhibiting PANoptosis via the blockade of RIPK1. As a result of this, Necrostatin1 may offer novel opportunities for protecting donor kidneys from renal ischemia-reperfusion injury during transplantation in patients with end-stage kidney disease requiring a renal transplantation.Article Comprehensive Analysis Of<i> Gjb1</I> in Breast Cancer: Its Implications in Survival and Molecular Mechanisms(int inst Anticancer Research, 2024) Ozcivici, Engin; Mese, GulistanBackground/Aim: Breast cancer is the leading cause of cancer-related mortality among women worldwide. The connexin (Cx) family, including GJB1 (Cx32), plays complex roles in tumor progression depending on cellular context and cancer subtype. While Cx32 overexpression has been linked to lymph node metastasis, its effects on survival and molecular processes remain unclear. Herein, we aimed to investigate the role of GJB1 in breast cancer by examining its impact on survival and cellular processes in addition to its expression pattern in tumor subtypes, using public datasets. Materials and Methods: We conducted a comprehensive analysis of GJB1 in breast cancer using METABRIC patient dataset, Cancer Cell Line Encylopedia, and other publicly available databases. We examined the association between GJB1 expression and patient survival, performed differential gene expression analysis, and explored gene set enrichment to identify biological processes associated with high GJB1 expression. Results: GJB1 was significantly down-regulated in breast cancer tissues compared to normal tissues. However, patients with high GJB1 expression had significantly poorer survival compared to those with low expression, with the median survival reduced by over 25 months. Gene ontology (GO) analysis revealed that down- regulated genes in the GJB1-high group were enriched in extracellular matrix components and membrane junctions, while up-regulated genes were associated with mitochondrial function and cellular respiration. Conclusion: Our findings suggest a dual role for GJB1 in breast cancer. Although it is generally down-regulated, high GJB1 expression is associated with poorer survival, implying a potential oncogenic role. Further studies are needed to clarify the role of GJB1 in breast cancer and explore its therapeutic implications.Article Citation - WoS: 2Citation - Scopus: 2Exploring the Use of Water-Extracted Flaxseed Hydrocolloids in Three-Dimensional Cell Culture(Mary Ann Liebert, inc, 2024) Yildirim-Semerci, Ozum; Bilginer-Kartal, Rumeysa; Arslan-Yildiz, AhuPlant-derived hydrocolloids offer promising prospects in biomedical applications. Among these, Flaxseed hydrocolloid (FSH) can form a soft, elastic, and biocompatible hydrocolloid with tunable viscosity and superior swelling capacity, making it an attractive scaffold. This study introduces a green extraction method for FSH, employing a single-step aqueous extraction process and fabrication of FSH scaffold. Despite growing interest, the pristine form of FSH has not been investigated for sustainable long-term three-dimensional (3D) cell culture. Here, FSH scaffolds were thoroughly characterized for their morphological, chemical, mechanical, and biological properties. 3D cell culture experiments were conducted using NIH-3T3 mouse fibroblast cells, and cell viability was assessed using live/dead and Alamar Blue assays. High cell viability was sustained for long term compared with 2D cell culture. Cell adhesion and 3D cellular morphology on FSH scaffold for 30 days were monitored by scanning electron microscopy analysis. Also, collagen type-I and F-actin expressions were analyzed by immunostaining after 30 days of culture, resulting in 5- and 4-fold increments of fluorescence intensity, respectively. Results indicate sustained cell viability in the long term and favorable cell-material interaction, demonstrating the potential of FSH as a scaffold. This study emphasizes the importance of the green extraction approach, improving the biocompatibility and functionality of FSH tissue engineering applications. Impact Statement Flaxseed hydrocolloid (FSH) is a promising scaffold for biomedical applications due to its biocompatibility and tunable properties. This study introduces a green extraction method for FSH and evaluates its use in 3D cell culture with NIH-3T3 mouse fibroblast cells. The findings indicate high cell viability and enhanced cell-material interactions over 30 days, highlighting the potential of FSH for tissue engineering.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.