PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Self-Assembled Peptide Hydrogels with Cell Attachment Motifs for 3D Lung Cancer Model: Evaluation of Cell-Matrix Interactions and Drug Response(John Wiley and Sons Inc, 2026) Sırma Tarım, B.; Tamburaci, S.; Top, A.3D cancer models can mimic the tumor microenvironment, serving as a physiologically relevant platform to investigate the behavior of tumors and test anticancer therapeutics. Although bioactive peptide hydrogels have been widely evaluated for tissue engineering applications, their potential in 3D cancer models has been confirmed in only a few studies. In this study, self-assembling peptide hydrogels containing LDV (IBP1) and LDV and IKVAV cell attachment motifs (IBP2), and the control hydrogel without adhesion units (KLEI) were used for lung cancer modeling. The peptides self-assembled into hydrogels in a cell culture medium with storage moduli of ∼700–1500 Pa. The IBP1 and IBP2 hydrogels enhanced A549 cell proliferation and induced the formation of spheroids with average diameters between ∼70 and ∼150 µm. The cells in KLEI hydrogel with the highest stiffness exhibited mesenchymal-type migration, independent of the cell population, whereas transformation to mesenchymal migration necessitated a specific cell population in the IBP2 hydrogel. The cells in the IBP1 and IBP2 hydrogels with enhanced cell-cell interactions demonstrated higher resistance to docetaxel (DTX). Thus, our results indicate that these bioactive hydrogels can serve as a promising platform for in vitro assessment of cancer mechanisms and drug screening. © 2026 Wiley-VCH GmbH.Article Alterations in Secondary Lipids Are Associated with Neuroinflammation in the Brain of Neu1-Deficient Mice(Springer, 2026) Ada, Ebru; Seyrantepe, VolkanNeu1 (lysosomal sialidase 1) is essential for removing sialic acid from oligosaccharides and glycoconjugates. Neu1 deficiency impairs lysosomal digestion, leading to sialidosis and sialoglycoprotein accumulation. It also increases lipids, including gangliosides GM3, GD3, GM4, and LM1, in the kidney, liver, and spleen. Neu1-/- mice display symptoms resembling Type II sialidosis, including enlarged spleen and liver, kidney issues, neurological problems, spinal defects, and oligosaccharide buildup. The study examined secondary lipid alterations and inflammation in the cortex and cerebellum of these mice. Lipidomic, molecular, and immunohistochemical analyses of tissues from 2 and 5 M Neu1-/- mice revealed reduced levels of lipids, including PC, PE, PS, and CL, along with increased pro-inflammatory cytokines and loss of oligodendrocytes and neurons. Signs of astrogliosis and microgliosis emerged in specific brain regions. These results indicate that reduced levels of glycerophospholipids could serve as an indicator of inflammation in sialidosis mice. Future research should investigate therapies targeting these lipid changes, as modulating glycerophospholipids might slow disease progression in sialidosis patients.Article Mass Spectrometric Profiling Reveals Alterations in N-Glycans and O-Glycans in Tay-Sachs Disease Under Autophagy-Induced Conditions(Springer, 2025) Can, Melike; Basirli, Hande; Jin, Chunsheng; Karlsson, Niclas G.; Bojar, Daniel; Seyrantepe, VolkanTay-Sachs disease is a rare neurodegenerative disorder caused by mutations in the HEXA gene. The HEXA gene encodes the alpha-subunit of the enzyme beta-hexosaminidase A, which degrades GM2 ganglioside. Previously, we identified impaired autophagy in the brains of a mouse model of Tay-Sachs disease, which exhibited neuropathological and clinical abnormalities. Moreover, we demonstrated autophagosome clearance in Tay-Sachs cells under lithium-induced conditions. Here, we further aimed to evaluate N- and O-glycan changes in these cells and examine whether glycan alterations are linked to ER stress. The profiles of N- and O-glycans were analyzed using LC-MS/MS in fibroblasts and neuroglial cells from 5-month-old Hexa-/-Neu3-/- mice and neuroglial cells from Tay-Sachs patients under lithium induction and nutrient deprivation. The expression levels of ER stress-related markers were assessed using qRT-PCR and Western blot analyses. We demonstrated higher levels of high mannose and lower levels of complex types of N-glycans, along with increased O-glycan levels in Tay-Sachs cells. Compared to control groups, we observed upregulated expression of endoplasmic reticulum (ER) stress-related markers, CHOP and ATF-6, in Tay-Sachs cells. Our study demonstrated that autophagy induction causes the degradation of accumulated high-mannose N-glycans and O-glycans, which is associated with the downregulation of ER stress-related genes in Tay-Sachs cells. Our study is the first to show this phenomenon in Tay-Sachs cells and suggests the presence of ER stress-mediated autophagy. Therefore, targeting glycans through autophagy induction could offer therapeutic benefits to patients with Tay-Sachs disease in future studies.Article Development of Self-Assembled Peptide Hydrogels Containing Matrix-Metalloproteinase Degradable Motifs for 3D Lung Cancer Models(Royal Society of Chemistry, 2026) Tarim, Burcu Sirma; Tamburaci, Sedef; Top, AybenHydrogel-forming peptides, including matrix metalloproteinase (MMP)-degradable motifs, have been employed to investigate cell-extracellular matrix interactions in vitro. However, their potential in 3D cancer models has been explored only in a few studies. In this study, we used modified MMP-2 degradable motifs (VSLRA or ASLRA) in the design of EDP1 (RVSLRADARVSLRADA) and EDP2 (RASLRADARASLRADA) peptide hydrogelators. The peptides self-assembled into nanofibrillar hydrogels with storage moduli between similar to 300 and similar to 400 Pa. MMP-2 degradation properties of the peptides were confirmed, and a slightly higher MMP-2 responsiveness of the EDP1 hydrogel was observed. The hydrogels were used in the encapsulation of A549 lung adenocarcinoma cancer cells and MRC-5 human lung fibroblast cells. The designed hydrogels supported the proliferation of these cells with high viability and induced cluster formation of encapsulated A549 cells similar to that observed with the RADA hydrogel. However, the hydrogel network structure affected the morphology of the migrated cells in the absence of curcumin. The addition of curcumin decreased the migration and invasion of A549 cells, resulting in a round cell morphology independent of the hydrogel matrices. Anticancer drug tests indicated that cell viability after drug treatment was higher in the 3D hydrogels than in 2D cultures. It was also confirmed that the combinational therapy of doxorubicin and curcumin decreased the cell proliferation and colonization to a greater extent compared to doxorubicin monotherapy. Thus, the hydrogels developed in this study can be used for 3D cancer models or other tissue engineering applications as an alternative to the RADA hydrogel by exploiting the MMP-2 degradation properties.Article Enhanced Osteoconductive Properties of Quince Seed Hydrocolloid-Based Composite Scaffolds Enriched With Bioactive Glass for Bone Tissue Engineering(Wiley-VCH Verlag GmbH, 2025) Yilmaz-Dagdeviren, Hilal Deniz; Zheng, Kai; Boccaccini, Aldo Roberto; Arslan Yildiz, AhuBioactive composite scaffolds enhance osteoconduction and mineralization, offering potential for bone regeneration. In this study, polysaccharide-based Quince Seed Hydrocolloid (QSH) was combined with Gelatin (Gel), mesoporous bioactive glass nanoparticles (MBGNs), and 45S5 bioactive glass (BG) to fabricate osteoconductive scaffolds. QSH/Gel/BG and QSH/Gel/MBGN composites were characterized for chemical composition, mechanical behavior, and in vitro bioactivity. FTIR and SEM-elemental mapping confirmed homogeneous bioactive glass incorporation. BET analysis revealed a >3-fold increase in surface area for MBGN-containing scaffolds compared to BG and pristine QSH/Gel samples, attributed to the nanoscale mesoporous structure of MBGNs. Swelling tests showed a hydrophilic nature in all scaffolds, with MBGN composites exhibiting the highest swelling ratio (2094 +/- 571%), nearly twice that of BG composites (1105 +/- 56%). Compression tests indicated similar elastic moduli for MBGN and BG containing scaffolds (2330 and 2140 Pa). Human osteosarcoma cell cultures (28 days) demonstrated high viability (>70%) and osteoconductive response in all composites. Alizarin Red staining and SEM mapping revealed greater mineral accumulation in MBGN-containing scaffolds (Ca/P: 2.53). Overall, both composites supported a 3D osteoconductive microenvironment, while MBGN scaffolds exhibited superior long-term cell viability and mineralization potential, emphasizing their suitability for bone tissue engineering applications.Article Geogenic Determinants of Indoor Radon Exposure in Izmir (West Türkiye)(Pergamon-Elsevier Science Ltd, 2026) Alkan, Turkan; Simsek, Celalettin; Sac, Murat; Uzelli, Taygun; Taskin, NurcihanRadon, a naturally occurring product of uranium decay, is the second leading cause of lung cancer. I(center dot)zmir Province in western T & uuml;rkiye, situated within the Aegean extensional regime, comprises complex fault-bounded basins that favor indoor radon accumulation. This study evaluates the spatial variability and geogenic controls of indoor radon to delineate radon-prone zones with public-health relevance. Indoor radon was measured in 79 dwellings distributed across major lithologies and structural settings; detectors were deployed in basements to capture soil-gas infiltration. Concentrations ranged from 12 to 366.5 Bq/m3 (mean 118 Bq/m3), exceeding the national average of 81 Bq/m3; 32 % of sites surpassed the EPA action level of 148 Bq/m3. Highest values cluster in Bornova, Buca, and Kemalpas, a, coincident with fault-controlled sedimentary basins and permeable units. Spatial mapping highlights the dominant influence of lithology and fault proximity on radon distribution and underscores the limitations of uniform, national-scale mitigation policies. We advocate targeted, geology-aware health policies and urban-planning measures for monitoring and mitigation in geogenically vulnerable districts. These findings contribute to medical geology by providing region-specific evidence of radon risk in one of T & uuml;rkiye's most seismically active metropolitan areas. These outputs provide decision-ready evidence for monitoring, mitigation, and building-code updates in seismically active metropolitan settings.Article Analytical Methodology for Monitoring and Distribution Pattern Analysis of Polycyclic Aromatic Hydrocarbons in River Basins Based on Chemometrics(Wiley, 2025) Yildirim, Ebru calkan; Pelit, Fusun; Ozdemir, Durmus; Kazan, Aysegul; Tasdelen, Ozge; Baycan, NevalWith the increase in urbanization and industrialization, the environmental quality of river basins, which serve as a crucial source of irrigation for agricultural activities, has been deteriorating progressively. Thus, monitoring persistent toxic substances in urban water resources is crucial for maintaining ecological stability and protecting human health. In recent years, particular attention has been directed toward the prevention of polyaromatic hydrocarbons (PAHs), highlighting the importance of analyzing these compounds in water samples through more environmentally sustainable techniques. In this study, we report a green, rapid, cost-effective and simple dispersive liquid-liquid extraction (DLLME) method to monitor PAHs in river waters taken from 21 stations located within the geographical boundaries of the Gediz River Basin in Izmir Province, T & uuml;rkiye. Methodological parameters were optimized by chemometric techniques including Plackett-Burman (PBD) and Box-Behnken design. The method's accuracy was tested upon spiked river samples, and the recoveries ranged from 80% to 102%. The calibration curves were linear, with correlation coefficients greater than 0.98. The limit of detection values were between 0.01 and 0.05 ng mL-1. The reproducibility (RSD%) varied from 4.0% to 19%. Multivariate classification methods such as principal component analysis (PCA) and hierarchical cluster analysis (HCA), along with the supervised classification method partial least squares discriminant analysis (PLS-DA) were applied to elucidate the general distribution patterns of individual PAHs in the basin water samples. The chemometric evaluation conducted across four seasons revealed that PAH contamination was higher in the fall and winter months, resulting in a clear separation from spring and summer samples by using the first two principal components.Article Citation - WoS: 8The Effects of Halofuginone on Wound Healing in the Rat Nasal Mucosa(Sage Publications Inc, 2020) Ceylan, Seyit Mehmet; Uysal, Erdal; Sokucu, Mehmet; Sezgin, Efe; Kanmaz, Mahmut Alper; Yurtseven, Duygu Gok; Bilal, NagihanBackground Halofuginone is an alkaloid febrifugine analogue and bioactive molecule that was isolated incidentally from the Dichroa febrifuga plant. The therapeutic efficacy of halofuginone in parasitic infections, scleroderma, inflammation, and fibrosis-related diseases, as well as in some types of cancer, has been previously reported. The effects of halofuginone on nasal mucosal damage are not yet known. Objective The aim of this study was to investigate the potential effect of topically applied halofuginone on wound healing in the mechanically injured nasal mucosa of rats. Methods A unilateral mucosal wound was created in the nasal cavity of 32 rats (aged 4 weeks) using the brushing technique. These rats were randomly divided into 4 groups. Although the control group did not receive an intervention, a dry pad, a saline-impregnated pad, or a pad impregnated with halofuginone were placed in the rats of the other 3 groups and left for 5 minutes. Rats were sacrificed on the 14th day, and a histological examination was performed. The nasal mucosa was assessed via hematoxylin-eosin and Masson's trichrome staining. Results There were no statistically significant differences in epithelial thickness, inflammation, goblet cell formation, and epithelial disarray values between the halofuginone group and the control group (P > .05). The subepithelial thickness was significantly decreased in the saline-treated group and the halofuginone-treated group (P < .05), but a significantly lower level of subepithelial fibrosis was only observed in the halofuginone group compared to the other groups (P < .05). Conclusions Topical halofuginone administration reduces the development of fibrosis and subepithelial edema after experimentally induced nasal mucosal injury, but it does not exert therapeutic or preventive effects on epithelial damage, inflammation, and goblet cell hyperplasia.Article A Fiber-Driven Finite Element Model for Predicting Residual Limb Soft Tissue Deformation: Applications in Prosthetic Socket Design(Springer, 2025) Wang, Ling; Qiu, Ziyan; Tang, Lei; Huang, Fuhao; Wei, Pingping; Mihcin, Senay; Li, DichenPurposeChanges in residual limb volume and shape pose significant challenges in achieving and maintaining an accurate and comfortable fit for prosthetic socket. While numerous techniques for measuring residual limb volume have been proposed, their clinical application remains limited by insufficient resolution and the inability to perform in-socket measurements. To address this issue, this study develops a novel method for predicting residual limb soft tissue deformation to guide prosthetic socket design.MethodsA three-dimensional (3D) finite element (FE) model of the human thigh was developed to simulate the soft tissue deformation during daily activities, driven by muscle contraction to replicate natural biomechanics. The model included hard tissue and muscle components, with the muscle modeled as a structure of evenly distributed, contractile fibers that generate movement. Parameters controlling fiber contraction were iteratively adjusted to best match the calculated tissue deformation and that observed in physical muscle models.ResultsThe optimized FE model significantly improved the accuracy of predicting dynamic soft tissue deformation, with average errors of 0.83% and 1.86% for tissue expansion and contraction regions, respectively. For various gait patterns, the average differences in equivalent volume and cross-sectional area changes were also less than 0.83% and 1.86%, respectively.ConclusionThe model demonstrated consistent prediction accuracy across different gait data. The fiber-driven soft tissue model developed offers a valuable tool for pre-design simulations of prosthetic sockets and orthoses. It is equally applicable to other wearable devices that interface with the skin, providing a robust framework for improving device design and functionality.Article Citation - WoS: 1Citation - Scopus: 1Biophysical Assessment of Protein Stability in Ethanol-Stressed Environments via UV Absorption and Fluorescence Spectroscopies(Elsevier, 2026) Akyuz, Ersed; Vorob'ev, Mikhail M.; Guler, GunnurMaintaining the structure and functionality of proteins is crucial in applications ranging from food preservation to pharmaceutical formulation. Ethanol, while commonly used as a solvent and preservative, can induce structural changes in proteins depending on its concentration and the specific structure of the protein itself. This study investigates the structural effects of ethanol on three types of model proteins, namely bovine serum albumin (BSA), beta-Lactoglobulin (beta-Lg), and beta-Casein (beta-Cn), by using UV-Vis spectroscopy and fluorescence spectroscopy. The conformational responses of proteins in water-EtOH solutions of various ethanol concentrations (0-10 %, v/v) were analyzed through absorbance and emission spectral changes. At increasing ethanol concentration, UV absorption data showed distinct protein-dependent spectral changes. beta-Lg and beta-Cn exhibited strong hypochromism (an absorbance decrease of similar to 25 %) and red-shifting at 222 nm and 220 nm, respectively, indicating partial unfolding and solvent exposure of aromatic residues. BSA demonstrated subtle changes, and consistent quenching in fluorescence with a continuous blue-shifting to 330 nm, suggesting a moderate overall stability and local rearrangements in its structure. beta-Cn exhibited red-shifted fluorescence and quenching, reflecting its flexible, disordered structure and heterogeneous response to solvent conditions. Statistical analysis revealed that while fluorescence spectroscopy was highly sensitive to the intrinsic differences between proteins (p < 0.001), the ethanol-induced conformational changes were too subtle to be detected as a statistically significant treatment effect. The consistency of these trends indicates a rational underlying mechanism of interaction. This reflects the subtle nature of the effect at the tested concentrations rather than the absence of an effect. Moreover, these results unveil the protein-specific effects of ethanol and strongly emphasize the importance of solvent composition in maintaining protein integrity. Ethanol concentrations up to 5 % may offer protein stability whereas high ethanol levels (>= 5-10 %) promote structural perturbations. These results will be useful for both basic scientific research, such as biophysical studies and the advancement of optical techniques, and various industrial uses.