PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
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Article Citation - Scopus: 1Recent Advances in Hydrogel-Based 3D Disease Modeling and Drug Screening Platforms(2025) Bilginer-Kartal, R.; Çoban, B.; Yildirim-Semerci, Ö.; Arslan-Yildiz, A.Three-dimensional (3D) disease modeling and drug screening systems have become important in tissue engineering, drug screening, and development. The newly developed systems support cell and extracellular matrix (ECM) interactions, which are necessary for the formation of the tissue or an accurate model of a disease. Hydrogels are favorable biomaterials due to their properties: biocompatibility, high swelling capacity, tunable viscosity, mechanical properties, and their ability to biomimic the structure and function of ECM. They have been used to model various diseases such as tumors, cancer diseases, neurodegenerative diseases, cardiac diseases, and cardiovascular diseases. Additive manufacturing approaches, such as 3D printing/bioprinting, stereolithography (SLA), selective laser sintering (SLS), and fused deposition modeling (FDM), enable the design of scaffolds with high precision; thus, increasing the accuracy of the disease models. In addition, the aforementioned methodologies improve the design of the hydrogel-based scaffolds, which resemble the complicated structure and intricate microenvironment of tissues or tumors, further advancing the development of therapeutic agents and strategies. Thus, 3D hydrogel-based disease models fabricated through additive manufacturing approaches provide an enhanced 3D microenvironment that empowers personalized medicine toward targeted therapeutics, in accordance with 3D drug screening platforms. © 2025. The Author(s), under exclusive license to Springer Nature Switzerland AG.Article Time-Dependent Effects of Low-Intensity Pulsed Ultrasound on Apoptosis and Autophagy in Malignant Melanoma Stem Cells(Wiley, 2025) Dikici, Omer; Ozdil, Berrin; Yesin, Taha Kadir; Dikici, Aylin; Adali, Yasemin; Aktug, HuseyinCancer stem cells (CSCs) in malignant melanoma contribute to therapeutic resistance and tumour recurrence. While low-intensity pulsed ultrasound (LIPUS) has been proposed as a non-invasive strategy to induce cell death, its effects on CSC-specific apoptotic and autophagic responses remain unclear. This study aimed to explore the time-dependent effects of LIPUS on apoptosis and autophagy in CD133+ melanoma CSCs and CD133- non-stem melanoma cells. Human melanoma cells (CHL-1) were sorted via FACS into CD133+ and CD133- populations. Cells were exposed to LIPUS (1 MHz, 20% duty cycle, 1 W/cm2) for 1, 5, and 10 min. Protein expression levels of Caspase-3, Caspase-8, mTOR, and LC3 were evaluated via immunofluorescence and quantified by image-based analysis. Both cell populations showed significant increases in Casp3, Casp8, mTOR, and LC3 intensities following LIPUS application. Notably, CD133+ cells exhibited delayed but sustained increases in Casp3 and LC3 expression, while CD133- cells responded more rapidly. mTOR activity demonstrated distinct temporal dynamics between the two groups, suggesting differential modulation of autophagy-related pathways. LIPUS triggers temporally distinct apoptotic and autophagic responses in melanoma CSCs and non-stem cancer cells. These findings suggest a potential therapeutic avenue to selectively disrupt CSC survival mechanisms using mechanical stimulation.Article An Analytical Methodology for the Determination of Cadmium Bound To Whey-Proteins by Laser-Induced Breakdown Spectroscopy at Low Pressures(Elsevier, 2026) Erdogrul, Ilayda Yaman; Yalcin, Serife H.In this study, a dried-droplet LIBS methodology for determining cadmium in cow milk has been developed. The performance of the methodology was shown by standard and real protein samples. A standard protein, bovine serum albumin (BSA), and whey protein extracted from skim cow milk were incubated in standard Cd solutions, and the complex solution was filtered through cut-off filters by centrifugation. The unreacted cadmium in the filtrate and Cd-bound protein in the filtered fraction were loaded separately onto a Si-wafer substrate and analyzed via dried-droplet LIBS methodology. Measurements were performed at reduced pressures by taking advantage of the signal enhancement effect. The optimum pressure for most Cd emission lines was found to be 100 mbar. It has been shown that the dried-droplet LIBS methodology at reduced pressures can be used for the identification and determination of free and protein-bound Cd in the whey matrix. The concentration-based detection limit of Cd bound to whey proteins was determined to be 20.2 ng mL- 1, which corresponds to as low as 10 pg in absolute amount with a sample volume of 500 nL. The LOQ value is estimated as 67.3 ng mL- 1 and 33.3 pg, in terms of concentration unit and absolute amount, respectively. The use of small sample volumes is important in the analysis of limited amounts of samples, such as body fluids. Preconcentration studies with multiple loadings of the sample on the same spot resulted in improvements in concentration-based detection. 8 ng mL- 1 Cd in the whey matrix that could not be determined by a single droplet loading due to being below the detection limit; could be determined after 10 consecutive loadings. The methodology may also be applied to the determination of other toxic metals bound to proteins for food quality control.Article Citation - WoS: 1Citation - Scopus: 1Differential Susceptibility and Role for Senescence in Cart Cells Based on Costimulatory Domains(BMC, 2025) Can, Ismail; Siegler, Elizabeth L.; Sirpilla, Olivia L.; Manriquez-Roman, Claudia; Yun, Kun; Stewart, Carli M.; Kenderian, Saad S.Despite the success of chimeric antigen receptor T (CART) cell therapy in hematological malignancies, durable remissions remain low. Here, we report CART senescence as a potential resistance mechanism in 41BB-costimulated CART cell therapy. To mimic cancer relapse, we utilized an in vitro model with repeated CART cell activation cycles followed by rest periods. Using CD19-targeted CART cells with costimulation via 4-1BB-CD3 zeta (BB zeta) or CD28-CD3 zeta (28 zeta), we showed that CART cells undergo functional, phenotypical, and transcriptomic changes of senescence, which is more prominent in BB zeta. We then utilized two additional independent strategies to induce senescence through MYC activation and irradiation. Induction of senescence impaired BB zeta activity but improved 28 zeta activity in preclinical studies. These findings were supported by analyses of independent patient data sets; senescence signatures in CART cell products were associated with non-response to BB zeta but with improved clinical outcomes in 28 zeta treatment. In summary, our study identifies senescence as a potential mechanism of failure predominantly in 41BB-costimulated CART cells.Article Citation - Scopus: 2Flavonoids as Chemosensitizers in Leukemias(2025) Huseynova, N.; Çetinkaya, M.; Baran, Z.; Khalilov, R.; Mammadova, A.; Baran, Y.Flavonoids, a diverse group of natural compounds abundant in plants, fruits, and seeds, are not only responsible for the vibrant colors, fragrances, and flavors found in nature but also possess significant health benefits. Representing a secondary metabolite, these phytonutrients contribute to overall well-being. They have garnered considerable interest due to their diverse biological roles, encompassing antioxidant, anti-inflammatory, and anticancer properties. Flavonoids exert anticancer properties by interfering with different signaling pathways and molecules. Also, they have been demonstrated to exert chemosensitization features, where flavonoids may enhance the effectiveness of chemotherapy, and hold promise for improving cancer treatment outcomes as they have been discovered to make cancer cells more responsive to treatment. Understanding their influence on the regulation of cellular signaling provides a foundation for exploring their potential in combination with different chemotherapy agents and their possible single use for cancer treatment. Besides, they are believed to present a cost-effective approach to cancer therapeutics with possible implications for reducing the side effects of the current chemotherapy regimens, which can be a great therapeutic strategy for treating cancer types, including leukemia. This chapter explores potential approaches for creating anticancer treatments, focusing on leukemia, through integrating flavonoid nutraceuticals with traditional chemotherapy agents. © 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.Article Citation - WoS: 2Citation - Scopus: 2Tuning Toxicity Profiles of Graphene Oxide Through Imidazole-Oxime Modification: Zebrafish as a Model System(Oxford Univ Press, 2025) Yildirim, Serkan; Kokturk, Mine; Yigit, Aybek; Sahin, Ayse; Kiliclioglu, Metin; Atamanalp, Muhammed; Alak, GoncaThe increasing use of nanotechnology, especially in agriculture and the food industry, has raised concerns about the possible adverse effects of nanomaterials (NMs) on human health and the environment. This study investigates the effects of synthesized graphene oxide (GO) and its derivatives on zebrafish exposed for 96 hr, focusing on morphological changes in brain tissue, histopathology, and immunofluorescent markers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nucleolar protein 10 (NOP10). Exposure to GO resulted in malformations, DNA damage, and increased NOP10 expression, and it reduced hatching and survival rates. Our results demonstrated that exposure to GO, graphene oxide-oxime (GO-OX), and OX exerted dose-dependent inhibitory effects on hatching and promoted malformations in zebrafish larvae. Histopathological analysis revealed that higher doses led to more pronounced tissue damage, with GO 50 causing severe degeneration and necrosis, while high doses of GO-OX and OX resulted in moderate tissue changes. This was further supported by the increased expression levels of 8-OHdG (marker of oxidative DNA damage) and NOP10 (marker of nucleolar stress), which aligns with the histopathological findings and confirms the neurotoxic effects. Notably, GO-OX treatments consistently mitigated both morphological and neurotoxic effects at all doses, suggesting that oxime functionalization reduces the inherent toxicity of GO. In contrast, treatment with different concentrations of GO-OX derivatives mitigated these adverse effects, reducing them to mild or moderate levels.Article Durable ZrB2–ZrC Composite Materials as Advanced Electrodes for High-Performance Supercapacitors(Amer Chemical Soc, 2025) Paksoy, Aybike; Gungor, Ahmet; Yildirim, Ipek Deniz; Arabi, Seyedehnegar; Erdem, Emre; Balci-Cagiran, OzgeBoride and carbide-based materials attract increasing attention as promising options for energy storage applications. This research focuses on synthesizing pure boride and carbide compounds of zirconium (ZrB2 and ZrC) and their composite powders using mechanical activation-assisted route and subsequent heating processes. The chemical and microstructural characterization results indicate that the synthesized composite powders are of high purity, possess submicron-scale particle sizes (below 400 nm), and exhibit a high surface area of up to 9.41 m2/g. Supercapacitor devices, using the resulting powders as symmetrical electrodes, exhibit high energy density values ranging from 5.8 to 8.8 Wh/kg. The ZrB2-15 wt % ZrC composite sample achieves the highest power density at 155 W/kg, compared to 118 W/kg for the pure ZrB2 sample. Cycling tests demonstrate exceptional capacitance retention (99.4-99.9%) and cyclic stability, even after 5000 cycles, highlighting the high durability of the composite samples. These findings show that ZrB2-ZrC composites exhibit high energy and power density values and excellent cycling performance, making them strong candidates for use in high-performance supercapacitor devices.Article Citation - WoS: 1Citation - Scopus: 1The Role of Trna Fragments on Neurogenesis Alteration by H2o2-Induced Oxidative Stress(Springernature, 2025) Karacicek, Bilge; Katkat, Esra; Binokay, Leman; Ozhan, Gunes; Karakulah, Goekhan; Genc, SerminTransfer RNAs (tRNAs) are small non-coding RNA molecules transcribed from tRNA genes. tRNAs cleaved into a diverse population tRNA fragments (tRFs) ranging in length from 18 to 40 nucleotides, they interact with RNA binding proteins and influence the stability and translation. Stress is one of the reasons for tRFs cleavage. In our study, we modeled oxidative stress conditions with hydrogen peroxide (H2O2) exposure and dealt with one of the frequently expressed tRF in the hippocampus region of the brain, which is tRF-Glu-CTC. For this purpose, neural stem cells (NSCs) were exposed to H2O2, and tRF-Glu-CTC levels were increased in various H(2)O(2 )concentrations. A decrease was seen in microtubule-associated protein 2 (MAP2) marker expression. To understand the H(2)O(2)oxidative stress condition on the expression of tRNA fragments, 72 hpf zebrafish embryos exposed to different H(2)O(2 )concentrations, an increase in the level of tRF-Glu-CTC was observed in all concentrations of H(2)O(2 )compared to control. Subsequently, neurogenesis markers were figured out via Calb2a (calbindin 2a) in situ hybridization (ISH) and HuC/D immunofluorescence staining (IF) staining experiments. Under H(2)O(2 )exposure, a decline was observed in Calb2a and HuC/D markers. To understand the inhibitory role of tRF-Glu-CTC on neurogenesis, NSCs were transfected via tRF-Glu-CTC inhibitor, and neurogenesis markers (ss III-tubulin, MAP2, and GFAP) were determined with qRT-PCR and IF staining. tRF-Glu-CTC inhibitor reversed the diminished neuronal markers expression under the exposure of H2O2. Gene Ontology (GO) enrichment analysis showed us that targets of tRF-Glu-CTC are generally related to neuronal function and synaptic processes.Article Citation - WoS: 10Citation - Scopus: 9Quantifying Hydrogen Bonding Using Electrically Tunable Nanoconfined Water(Nature Portfolio, 2025) Wang, Ziwei; Bhattacharya, Anupam; Yagmurcukardes, Mehmet; Kravets, Vasyl; Diaz-Nunez, Pablo; Mullan, Ciaran; Mishchenko, ArtemHydrogen bonding plays a crucial role in biology and technology, yet it remains poorly understood and quantified despite its fundamental importance. Traditional models, which describe hydrogen bonds as electrostatic interactions between electropositive hydrogen and electronegative acceptors, fail to quantitatively capture bond strength, directionality, or cooperativity, and cannot predict the properties of complex hydrogen-bonded materials. Here, we introduce a concept of hydrogen bonds as elastic dipoles in an electric field, which captures a wide range of hydrogen bonding phenomena in various water systems. Using gypsum, a hydrogen bond heterostructure with two-dimensional structural crystalline water, we calibrate the hydrogen bond strength through an externally applied electric field. We show that our approach quantifies the strength of hydrogen bonds directly from spectroscopic measurements and reproduces a wide range of key properties of confined water reported in the literature. Using only the stretching vibration frequency of confined water, we can predict hydrogen bond strength, local electric field, O-H bond length, and dipole moment. Our work also introduces hydrogen bond heterostructures - a class of electrically and chemically tunable materials that offer stronger, more directional bonding compared to van der Waals heterostructures, with potential applications in areas such as catalysis, separation, and energy storage.Article Citation - WoS: 2Citation - Scopus: 2Modulating Cancer Stem Cell Characteristics in CD133+ Melanoma Cells through Hif1α, KLF4, and SHH Silencing(Amer Chemical Soc, 2025) Ozdil, Berrin; Güler, Günnur; Avci, Cigir Biray; Calik-Kocaturk, Duygu; Gorgulu, Volkan; Uysal, Aysegul; Guler, Gunnur; Aktug, HuseyinMalignant melanoma is a highly aggressive form of skin cancer, partly driven by a subset of cancer stem cells (CSCs) with remarkable capacities for self-renewal, differentiation, and resistance to therapy. In this study, we examined how silencing three key genes-Hif1 alpha, KLF4, and SHH-affects CSC characteristics. Using small interfering RNA (siRNA)-based approaches, we observed significant changes at both the gene and protein levels, shedding light on how these pathways influence melanoma progression. Our results demonstrated that silencing these genes reduces the stem-like features of CSCs. Notably, Hif1 alpha silencing triggered a marked decrease in hypoxia-related gene expression, while targeting SHH led to a reduction in Gli1, a downstream effector of SHH signaling, highlighting its potential as a therapeutic target. We also observed changes in epigenetic markers such as HDAC9 and EP300, which play crucial roles in maintaining stemness and regulating gene expression. Interestingly, these interventions appeared to reprogram CSCs, pushing them toward a phenotype distinct from both traditional CSCs and non-stem cancer cells (NCSCs). Our findings emphasize the importance of targeting key signaling pathways in melanoma CSCs and underscore the value of mimicking the tumor microenvironment in experimental models. By revealing the dynamic plasticity of melanoma CSCs, this study offers fresh insights into potential therapeutic strategies, particularly using siRNA to modulate pathways associated with tumor progression and stem cell behavior.