PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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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 Liposomal Encapsulation of a Synthetic Bromophenol for Antitumor Efficacy and Apoptotic Activity in Cancer Cells(Springer, 2026) Oztanrikulu, Bercem Dilan; Ozdemir, Ekrem; Avci, Bahri; Goksu, Suleyman; Bayrakceken, Handan Uguz; Askin, HakanA novel synthetic bromophenol (BP), inspired by marine-derived natural bromophenols, was evaluated for its antitumor activity and for the enhancement of its in vitro performance through liposomal encapsulation (LipoBP). Etoposide was used as a reference in characterization, release, and loading studies. PEGylated liposomes were employed to improve BP's solubility, bioavailability, and therapeutic potential. The cytotoxicity, apoptosis, and gene expression effects of free BP and LipoBP were assessed in A549 (lung) and MCF-7 (breast) cancer cell lines. WST-8 assays showed that encapsulation significantly increased BP's cytotoxic activity, particularly in A549 cells, while flow cytometry and Annexin V-FITC/PI analyses indicated more pronounced apoptotic induction by LipoBP compared with free BP. qRT-PCR analyses revealed upregulation of proapoptotic genes (BAX, CASP6, CASP3 and CASP9) and downregulation of antiapoptotic/survival genes (BCL-XL, IQSEC2) in both cell lines, indicating activation of intrinsic apoptotic pathways. Plain liposomes exhibited minimal cytotoxicity, confirming their biocompatibility. Liposomal bromophenol, which we have introduced to the literature for the first time, is expected to be a promising nanocarrier system that could be effective in cancer treatment by improving the therapeutic index of new drug candidates such as marine bromophenols.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 Citation - WoS: 8Protective and Therapeutic Effects of Milrinone on Acoustic Trauma in Rat Cochlea(Springer, 2019) Ceylan, Seyit Mehmet; Uysal, Erdal; Altinay, Serdar; Sezgin, Efe; Bilal, Nagihan; Petekkaya, Emine; Gulbagci, Mustafa EmreObjectiveThe aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis.MethodsA total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25mg/kg) in which milrinone was administered 1h before acoustic trauma (AT) and 2h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50mg/kg) in which the drug was administered 1h before AT and 2h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining.ResultsIn terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p>0.05). After 5days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p>0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p<0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p<0.0001).ConclusionWe reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.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 Ranking Circularity Levels in Industrial Parks: A Holistic Approach Incorporating Environmental, Economic and Social Indicators(Springer, 2025) Berk, I.; Ediger, V.Ş.; Öztürk, E.B.; Uctug, F.G.; Kucuker, M.A.; Inan, A.; Aktuna, G.B.This study introduces a circularity ranking system at the meso-level, specifically targeting industrial parks, through the development of the Circular Economy Sustainability Index (CESI). The index comprises five economic-environmental indicators: energy intensity, emission intensity, water intensity, waste intensity, and recycling ratio, as well as a social indicator as a sixth dimension. We utilize CESI to evaluate the circular economy performance of 22 manufacturing firms in the Adana Hacı Sabancı Organized Industrial Zone (AOSB). AOSB, one of the most prominent industrial parks in Türkiye, serves as an excellent case study to assess companies’ circularity performance and identify areas for improvement in the country’s green industrial transformation endeavor. Our findings reveal that waste and recycling indicators are pivotal in determining circularity, contributing 34.6% to the overall score, while the social indicator adds another 16.3%. These results underscore the significance of effective waste management and social responsibility in enhancing circularity. © 2025 Elsevier B.V., All rights reserved.Article Task-Specific Dynamical Entropy Variations in EEG as a Biomarker for Parkinson's Disease Progression(Springer, 2025) Onay, Fatih; Karacali, BilgeUncovering the neuronal mechanisms un-derlying optimal behavioral performance is essential to understand how the brain dynamically adapts to changing conditions. In Parkinson's disease (PD), these neuronal mechanisms are disrupted and lead to impairments in motor coordination and higher-order cognitive functions. This study investigates neuronal dynamics during a lower-limb pedaling task by analyzing the dynamical entropy of EEG signals in healthy controls (HC), PD patients, and PD patients with freezing of gait (PDFOG). We examined both average entropy changes and entropy variability across trials to characterize task-specific neural adaptations across disease progression. Results showed that PD and PDFOG patients exhibited decreased levels of permutation entropy in frontal and parietal regions, which may be associated with loss of cognitive adapta-tion due to altered information processing. Additionally, Vasicek's entropy variability in both PD groups was significantly diminished in occipital and left frontal regions, suggesting reduced cognitive capacity to dy-namically allocate neuronal resources during task engagement. We extended this analysis to the classification of groups using LDA and SVM classifiers, where entropy-derived features achieved a classification accuracy of up to 96.15% when distinguishing HC from PDFOG patients. This dynamical entropic framework provides a novel approach for capturing neural complexity changes during task performance, revealing subtle cognitive-motor impairments in PD. Understanding the maintenance of cognitive information processing and flexibility in response to motor and cognitive task demands could be a useful tool to track PD diagnosis and progression in addition to resting-state analyses.Article Comparative Proteomic Analysis of Dental-Origin Stem Cells: Insights Into Regenerative Potential(Springer, 2025) Tez, Banu Cicek; Durukan, Sebahat Melike; Yildir, Selin Kubra; Cokkececi, Murat; Boyvat, Dudu; Altinsoy, Nilay; Ozcan, ServetTeeth are a significant source of stem cells and have clinical importance for regenerative medicine. A human tooth harbors different kinds of stem cells in the dental pulp (DPSC) or the periodontal ligament (PDLSC). Also exfoliated teeth in childhood contain a special type of stem cells in their pulp called Stem cells from Human Exfoliated Deciduous teeth (SHED). All these stem cells have features and capacities that vary depending on their niche. Here we investigated the proteomic properties of three types of stem cells that originated from human teeth. We isolated and cultured the DPSCs, PDLSCs, and SHED cells. After validating MSC populations via immunophenotyping, we performed a mass spectrometry-based proteomic approach to identify and relatively quantify whole cell and secreted proteins. Identified proteins were evaluated by using Gene Ontology and Reactome pathway analysis tools. Our data reveal that SHED cells represented inflammation, hypoxia, and nutrient deficiency-associated ontologies in both their secretome and whole-cell proteomes. The whole-cell proteome of PDLSCs consisted of differentiation and proliferation-associated molecules while their secretory molecules were mainly associated with inflammation, ECM organization, and immune response. Among dental-originated stem cells, DPSCs appeared to be the healthiest and clinically relevant in terms of proteomic properties with their proliferation, growth factor signaling, and stemness-associated molecules in their secretome and whole-cell proteome. Obtained results demonstrated that every type of stem cell from dental origin has unique proteomic features that are altered by their location and physiological conditions. The findings may help researchers improve the dental stem-cell-based regenerative medicine approaches.Article Citation - WoS: 7Citation - Scopus: 9A Holistic Overview of the Applications of Grace-Observed Terrestrial Water Storage in Hydrology and Climate Science(Springer, 2025) Khorrami, Behnam; Gunduz, OrhanTerrestrial Water Storage (TWS) represents a vital element of the hydrological cycle, with its fluctuations significantly impacting the climate of the Earth and its ecological balance. Since its launch in 2002, the Gravity Recovery and Climate Experiment (GRACE) satellite mission has revolutionized the ability to observe and analyze large-scale mass changes within Earth's system components. This paper offers a comprehensive and current overview of GRACE satellite gravimetry, highlighting its relevance to hydrological and climate-related studies. It outlines the fundamental measurement principles of the GRACE mission, provides an in-depth explanation of GRACE data products (including spherical harmonic and mascon solutions), examines emerging trends in GRACE-based research, and reviews key applications in hydrology and climate science. Additionally, it addresses the major challenges in utilizing GRACE data and explores promising avenues for future research and applications.