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 Epigallocatechin Gallate and Punicalagin Combination Reduces Aβ Aggregation and Promotes Neurogenesis in Adult Zebrafish Brain(John Wiley and Sons Inc, 2026) Nazli, D.; Ipekgil, D.; Poyraz, Y.K.; Can, K.; Okmen, I.; Turhanlar-Sahin, E.; Ozhan, G.Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral alterations. The pathogenesis of AD involves the accumulation of amyloid-beta (Aβ) plaques and the hyperphosphorylated tau proteins, which disrupt neuronal function and trigger neuroinflammation. This study explores the therapeutic potential of epigallocatechin gallate (EGCG) and punicalagin (PU) in mitigating Aβ-induced toxicity using an adult zebrafish model of AD. Our results demonstrate that the EGCG + PU combination significantly reduces Aβ accumulation, protects against cellular damage, suppresses acetylcholinesterase (AChE) activity, and normalizes the expression of amyloidogenic and AD-related genes. Additionally, EGCG + PU treatment alleviates neuroinflammation by suppressing glial activation, including reductions in L-plastin and proinflammatory cytokine expression, while promoting neuronal recovery through mechanisms of neurogenesis and neuroprotection. Notably, the combination treatment restored neuronal density and improved behavioral outcomes by alleviating anxiety- and aggression-like behaviors associated with Aβ toxicity. These results underscore the synergistic neuroprotective effects of EGCG + PU, highlighting their potential as a novel therapeutic approach for mitigating the pathological, behavioral, and inflammatory aspects of AD. © 2026 Wiley Periodicals LLC.Article Valorization of Recycled Waste in Green/White Purification and LC-QTOF/MS Analysis of Beverages Adulterated with Incapacitating Drugs(Elsevier B.V., 2026) Anilanmert, Beril; Yonar, Fatma Cavus; Er, Elif Ozturk; Pekcaliskan, Elif Yılmaz; Cengiz, SalihIncapacitating drugs constitute a growing threat for the community, since victims may drink adulterated beverages without noticing. A validated eco-friendly/economical purification/analysis kit prototype, along with an LC-QToF/MS method has been developed in coke and mixed fruit-juice, for simultaneous determination of 10 drugs used for incapacitating victims (zaleplone, zolpidem, zopiclone, mephedrone, fentanyl, phenytoin, thiopental, sertraline, ketamine and GHB). A combination of two different waste nut-shells which yielded the highest recovery for these drugs were directly used as adsorbent after grinding and modification and a reusable separation apparatus recycled from waste were utilized for the first time in a toxicological analysis. In the method, after adding the adsorbent on to the sample, pH was adjusted. Following 25-min (min) automatic vortexing for adsorption, matrix was removed easily, using the separation apparatus. After 25-min desorption via cold ultrasonication using 500 μL methanol, a 9.5-min LC-QToF/MS analysis was performed. The validated method in fruit-juice and coke, extraordinarily gave successful results also in urine and saliva. Assessment tools for greenness/whiteness and pictograms confirmed the environmental friendliness of the method kit. © 2025 Elsevier B.V.Article FTIR Spectroscopy Coupled With Chemometrics for Evaluating Functional Food Efficacy in an in Vitro Model of Iron Deficiency Anemia(Elsevier Science Ltd, 2026) Dalyan, Eda; Cavdaroglu, Cagri; Ozen, Banu; Gulec, SukruVibrational spectroscopy offers a rapid, cost-effective approach for studying biological systems. This study employs Fourier Transform Infrared (FTIR) spectroscopy, combined with Soft Independent Modeling of Class Analogy (SIMCA), to evaluate treatment outcomes for iron deficiency anemia (IDA). The model was built using spectra from healthy and anemic cells, then validated with cells treated with commonly used iron supplements. In calibration, 9 of 10 control and all IDA samples were correctly classified; 14 of 15 validation samples were identified as healthy. The model was applied to cells treated with protein-iron complexes. All samples treated with a 60:1 protein-iron ratio matched the healthy group, while 3 of 4 treated with a 10:1 ratio matched the IDA group. These results were further supported by iron-regulated gene expression of transferrin receptor (TFR) and (Ankyrin Repeat Domain 37) ANKRD37. FTIR coupled with chemometrics enables rapid assessment of functional effects and shows potential for screening functional ingredients in anemia-targeted food products.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 Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We(Springer, 2026) Shakeri, Raheleh; Mirjalili, Seyedeh Zohreh; Karakus, Ceyda Oksel; Safavi, MalihehInvestigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.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 Chloroaluminum Phthalocyanine Loaded Bovine Serum Albumin Nanoparticles as a Dual-Functional Nanoplatform for Sono-Photodynamic Cancer Therapy(Elsevier, 2026) Akyol-Karpuzcu, Cansu; Nartas, Eylem Doga; Calibasi-Kocal, Gizem; Akdogan, YasarChloroaluminum phthalocyanine (ClAlPc) loaded bovine serum albumin (BSA) nanoparticles (NPs) were synthesized as a dual-functional platform for photodynamic and sonodynamic therapies (PDT and SDT). ClAlPc loading did not disturb the morphology of the BSA NPs. Their spherical structure, with a size around 200 nm, was preserved upon ClAlPc loading (1 %w/w). Singlet oxygen productions in the presence of ClAlPc loaded BSA NPs or free ClAlPc were determined by ultraviolet absorption (UV-vis) spectroscopy and electron paramagnetic resonance (EPR) spectroscopy. While a slower rate of singlet oxygen formation rate after both PDT and SDT was detected by UV-vis measurements in the presence of ClAlPc loaded BSA NPs, EPR results showed a similar rate of singlet oxygen formation for both ClAlPc loaded BSA NPs and free ClAlPc. Confocal microscopy confirmed the efficient cellular uptake and perinuclear localization of the ClAlPc loaded BSA NPs in HCT-116 cancer cells. In vitro cytotoxicity studies demonstrated a dose and time dependent photo-and sonotoxic effects in the presence of ClAlPc loaded BSA. In particular, simultaneous application of light and ultrasound as sono-photodynamic therapy (SPDT) resulted in 15 % cell viability in the presence of ClAlPc loaded BSA NPs, which is much lower than individual PDT and SDT results, confirming the effect of the combination therapy on cell viability. In comparison, free ClAlPc reduced cell viability to 27 %. These findings suggest that ClAlPc loaded BSA NPs is a promising "one-for-two" nanoplatform for combined cancer therapy to reduce the limitations of both methods.Article Linking RNA Methylation to Structure: A Biophysical Perspective(Wiley, 2026) Akgul, Bunyamin; Guler, Gunnur; Saglam, Buket; Akkus, Onur; Akcaoz-Alasar, AzimeRecent epitranscriptomic studies show that ribonucleic acids (RNAs) are coated with an array of chemical modifications that dictate their cellular fate. Genetic, biochemical, and genomic approaches have been employed to elucidate the molecular details of RNA methylation, one of the most prevalent types of RNA modifications with significant implications for health and disease. Various biochemical approaches have been developed to identify RNA methylations both at the global and nucleotide resolution levels. However, simpler detection methods are needed to assess the global methylation status of synthetic or cellular RNAs. Although significant progress has been made in elucidating the factors involved in writing, erasing, or reading methylated epitopes or structures, the impact of these methyl moieties on the secondary structure of RNAs or macromolecular interactions remains to be fully understood. Typically, biophysical approaches, such as Fourier transformed-infrared (FT-IR) spectroscopy, circular dichroism (CD), and Raman spectroscopy, have been used to study the structures and interactions of macromolecules, including DNA and proteins. Although RNAs harbor similar chemical modifications or structure-mediated functions, the number of RNA studies that employ biophysical approaches is scarce. In this viewpoint article, we present a biophysical perspective that links RNA methylation to structure and propose that FT-IR analyses can be employed to examine global changes in the abundance of cellular RNA m(6)A marks. Additionally, we discuss the potential applications of biophysical approaches that may be employed to gain insight into methylation-mediated changes in RNA structures.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.