PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection

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Now showing 1 - 10 of 106
  • Article
    Alterations in Secondary Lipids Are Associated with Neuroinflammation in the Brain of Neu1-Deficient Mice
    (Springer, 2026) Ada, Ebru; Seyrantepe, Volkan
    Neu1 (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, Volkan
    Tay-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
    Dimensionality Effects in Anisotropic Single Layers TiSe5 and TiTe5: a Comparative Study of 2D Sheets and 1D Nanochains
    (IOP Publishing Ltd, 2026) Can Dogan, Kadir; Kutay Tamdogan, Omer; Bozkurt, Yagmur; Cetin, Zebih; Yagmurcukardes, Mehmet
    In this study, we present a comprehensive first-principles investigation of the structural, vibrational, and electronic properties of titanium pentachalcogenide structures in both two-dimensional (2D) and one-dimensional (1D) nanochain (NC) forms. Total energy and geometry optimizations reveal that the 2D TiX5 (X = Se, Te) structures exhibit in-plane anisotropy arising from the trigonal prismatic TiX3 units interconnected via the chalcogenide chains. Phonon band dispersions and elastic tensor elements confirm the dynamical and mechanical stability of the 2D layers, respectively. Electronically, while TiTe5 is a metal, TiSe5 possesses direct band gap semiconducting behavior. In addition, free-standing 1D NC counterparts, which are sub-units of the 2D structures, are investigated by means of their stability. Three stable 1D NCs, namely TiTe5-NC, TiSe7-NC, and TiTe7-NC, are found to be composed of edge-sharing TiX6-like units with either five- or seven-fold coordination. The dynamically stable 1D NCs are shown to be semiconductors with relatively larger band gaps as compared to 2D layers. Predicted Raman spectra reveal clear signatures of vibrational mode evaluations as a result of quantum confinement from the 2D layer to the 1D NC. Moreover, finite-temperature ab-initio quantum molecular dynamics simulations at 300 K confirm the thermal stability of both the 2D TiX5 layers and 1D NC derivatives, showing that the Ti-based systems retain their structural integrity under ambient conditions and are feasible candidates for experimental synthesis. Our findings highlight the formation of stable semiconducting 1D NCs of Ti-pentachalcogenides from their 2D counterparts.
  • Article
    Citation - WoS: 1
    Citation - Scopus: 1
    Biophysical Assessment of Protein Stability in Ethanol-Stressed Environments via UV Absorption and Fluorescence Spectroscopies
    (Elsevier, 2026) Akyuz, Ersed; Vorob'ev, Mikhail M.; Guler, Gunnur
    Maintaining 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.
  • Article
    Therapeutic Targeting of Neuroinflammation in Sphingolipidosis
    (Pergamon-Elsevier Science Ltd, 2025) Ada, Ebru; Seyrantepe, Volkan
    Lysosomal storage diseases (LSDs) are a class of hereditary metabolic disorders primarily caused by lysosomal enzyme defects, leading to the accumulation of undegraded substrates. Sphingolipidoses, a subset of LSDs, are primarily associated with profound involvement of the central nervous system (CNS), characterized by progressive neurodegeneration due to massive sphingolipid accumulation. A common pathological feature among many CNS-involved LSDs is the early activation of microglia and astrocytes, which often precedes and predicts regions of subsequent neuronal loss. The extent to which neuroinflammation disrupts CNS homeostasis appears to be determined by its onset, magnitude, and duration. Although neuroinflammatory processes are increasingly recognized as critical contributors to disease progression in sphingolipidoses, the molecular mechanisms underlying glial activation and the initiation of inflammatory cascades remain incompletely understood. Therefore, mouse models of sphingolipidoses have been instrumental in elucidating these pathogenic processes and provide valuable platforms for evaluating therapeutic strategies. This review critically examines the role of neuroinflammation in sphingolipidoses, summarizes insights derived from pre-clinical models, and discusses the therapeutic potential of anti-inflammatory interventions to mitigate CNS pathology and improve clinical outcomes.
  • Article
    Citation - WoS: 1
    From Chemistry to Clinic: Polysaccharide-Bioceramic Composites for Tissue Engineering Applications
    (Mary Ann Liebert, Inc, 2025) Yakubogullari, Nilgun; Yilmaz-Dagdeviren, Hilal Deniz; Arslan-Yildiz, Ahu
    Composite scaffolds combining polysaccharides and bioceramics represent next-generation scaffolds extensively investigated in tissue engineering (TE) and biomedical applications. Polysaccharides such as chitosan, hyaluronic acid, and pectin mimic the extracellular matrix components with their tunable physicochemical properties, enabling a favorable microenvironment for cell adhesion, proliferation, and cell-matrix interactions. On the other hand, bioceramics, including calcium phosphate, hydroxyapatite, and bioactive glasses, enhance the mechanical properties of the material and offer structural integrity and osteoconductive properties. While they have generally been preferred to be used in bone TE and dental applications, various studies have also demonstrated their potential in cartilage regeneration, wound healing, and broader biomedical applications. Recent advancements in material design and scaffold fabrication techniques, particularly 3D printing and electrospinning, have provided precise engineering of materials and fabrication of scaffolds for desirable mechanical properties and biological performance. These innovations foster the development of patient-specific scaffolds, thereby paving the way for applications in personalized medicine. This review critically summarizes alternative polysaccharides, bioceramics, and composite materials used in TE and biomedical applications. It also highlights advanced fabrication strategies and finally explores the translational potential of these biocomposites. By integrating emerging technologies, this review aims to provide alternative and sustainable materials for the development of next-generation scaffolds that meet clinical needs.Impact Statement This study introduces polysaccharide-bioceramic composites with enhanced mechanical and biological properties for tissue engineering. Beyond bone and dental repair, their applications increasingly extend to wound healing, cartilage, cardiac, and muscle regeneration with drug delivery, angiogenesis, and neurogenesis. By mimicking the native extracellular matrix, these composites support cell growth and tissue regeneration, offering a versatile platform for advanced regenerative therapies.
  • Article
    Enhanced Catalytic Performance of Rhizomucor Miehei Lipase on Di-N and Diethylhexyl Phthalates: Insights Into Substrate Specificity and Immobilization Strategy
    (Taylor & Francis Ltd, 2025) Balci, Esin; Rosales, Emilio; Curras, Marta Pazos; Sofuoglu, Aysun; Sanroman, M. A.
    Di-n-butyl (DnBP) and Diethylhexyl Phthalates (DEHP), known as potential endocrine disruptors, are priority pollutants categorized by many regulatory agencies. Enzymatic degradation is a green and efficient approach to remove PEs in the environment. In this study, the DnBP and DEHP degradation performance of Rhizomucor miehei lipase (palatase) in free and immobilized forms on Halloysite nanoclays (HNCs) in an aqueous system was investigated. Upon enzyme immobilization, the alterations in the palatase's secondary structure were examined using the circular dichroism (CD) analysis. The binding affinity of DnBP and DEHP to palatase was evaluated with molecular docking approaches. The enzyme's immobilization efficiency and relative activity were found to be 80.3% and 87.8%, respectively. CD results revealed that palatase retained its secondary structure to a significant extent. HNCs-palatase (HNCs-P) exhibited a high stability, as the structural integrity of palatase was mostly preserved. Both free palatase (FP) and HNCs-P fully degraded DnBP and DEHP (100 mg/L) to phthalic acid and a degradation pathway of DnBP and DEHP was suggested. Immobilization prevented the enzyme inhibition caused by the accumulation of metabolites. After seven consecutive uses, HNCs-P was still able to degrade DnBP (63.3%) and DEHP (72.8%). Molecular docking results showed that DEHP had a higher affinity for palatase than DnBP. This study suggests that enzyme immobilization onto HNCs can increase their stability and catalytic performance. FP and HNCs-P effectively hydrolyse ester bonds responsible for phthalate toxicity. Considering their high efficiency, FP and HNCs-P can be used as potential phthalate degraders in various environmental remediation processes.
  • Article
    A Comprehensive MicroRNA-Seq Transcriptomic Analysis of Tay-Sachs Disease Mice Revealed Distinct MiRNA Profiles in Neuroglial Cells
    (Springernature, 2025) Kaya, Beyza; Orhan, Mehmet Emin; Yanbul, Selman; Demirci, Muserref Duygu Sacar; Demir, Secil Akyildiz; Seyrantepe, Volkan
    Tay-Sachs disease (TSD) is a rare lysosomal storage disorder marked by the progressive buildup of GM2 in the central nervous system (CNS). This condition arises from mutations in the HEXA gene, which encodes the alpha subunit of the enzyme beta-hexosaminidase A. A newly developed mouse model for early-onset TSD (Hexa-/-Neu3-/-) exhibited signs of neurodegeneration and neuroinflammation, evidenced by elevated levels of pro-inflammatory cytokines and chemokines, as well as significant astrogliosis and microgliosis. Identifying disease-specific microRNAs (miRNAs) may aid the development of targeted therapies. Although previous small-scale studies have investigated miRNA expression in some regions of GM2 gangliosidosis mouse models, thorough profiling of miRNAs in this innovative TSD model remains to be done. In this study, we employed next-generation sequencing to analyze the complete miRNA profile of neuroglial cells from Hexa-/-Neu3-/- mice. By comparing KEGG and Reactome pathways associated with neurodegeneration, neuroinflammation, and sphingolipid metabolism in Hexa-/-Neu3-/- neuroglial cells, we discovered new microRNAs and their targets related to the pathophysiology of GM2 gangliosidosis. For the first time, our findings showed that miR-708-5p, miR-672-5p, miR-204-5p, miR-335-5p, and miR-296-3p were upregulated, while miR-10 b-5p, miR-615-3p, miR-196a-5p, miR-214-5p, and miR-199a-5p were downregulated in Hexa-/-Neu3-/- neuroglial cells in comparison to age-matched wild-type (WT). These specific changes in miRNA expression deepen our understanding of the disease's neuropathological characteristics in Hexa-/-Neu3-/- mice. Our study suggests that miRNA-based therapeutic strategies may improve clinical outcomes for TSD patients.
  • Article
    Citation - WoS: 7
    Citation - Scopus: 9
    A Holistic Overview of the Applications of Grace-Observed Terrestrial Water Storage in Hydrology and Climate Science
    (Springer, 2025) Khorrami, Behnam; Gunduz, Orhan
    Terrestrial 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.
  • Article
    Biologically Informed Decision-Making for PMRT in PT3N0M0 Luminal Breast Cancers (Protocol MF22-02): International Multicenter Real-World Data
    (Cig Media Group, Lp, 2025) Soran, Atilla; Gultekin, Melis Bahadir; Venkatesulu, Bhanu Prasad; Barry, Parul Nafees; King, Caleb; Bhargava, Rohit; Vargo, John Austin
    Two hundred and 2 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, HER2 negative BC who underwent mastectomy were retrospectively analyzed. Patients were divided into 2 groups: PMRT (n = 130) and no PMRT (n = 69). Groups were compared in terms of overall survival (OS), loco-regional recurrence (LRR) rate, and distant metastases (DM) in light of Magee Equations Score (MS). At a median follow-up of 51.3 months for the no PMRT group and 65.9 months for the PMRT group (P =.041), 9% (n = 6) of patients from the no PMRT group and 2% (n = 3) from the PMRT group developed LRR (P = 0.047). There was no difference in local recurrence (1% in no PMRT group vs. 2% in PMRT group; P =.7) and distant recurrence (7% in no PMRT group vs. 3% in PMRT group; P =.16) in patients who received PMRT and no PMRT. Further comparison of the LRR in the no PMRT and PMRT groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; P =.64). However, among patients with an MS >= 18, no PMRT group had a higher LRR rate compared to the PMRT group (11% vs. 2%; P =.01). In patients with an MS >= 18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95% CI 0.05-0.79; P =.02). Patients with MS <18 experience a comparable rate of recurrence irrespective of PMRT, while those with MS >= 18 have higher rates of LRR and thus should not omit PMRT. Background: Current guidelines do not list definitive recommendations for postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). Increased data suggests de-escalation of radiation therapy (RT) in genomically defined biologically favorable luminal BCs. The goal of this study is to determine whether PMRT can be safely omitted for this specific subgroup of patients. Methods and materials: Two hundred and 2 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, HER2 negative BC who underwent mastectomy were retrospectively analyzed. No patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. Patients were divided into 2 groups: PMRT (n = 130) and no PMRT (n = 69). Groups were compared in terms of overall survival (OS), loco-regional recurrence (LRR) rate, and distant metastases (DM) in light of the Magee Equations Score (MS), menopausal status/age, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy. Results: The majority of the patients had invasive ductal carcinoma (49%, n = 98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the 2 groups (P =.82, P =.28, P =.12, respectively). LVI was 19% (n = 39), and it was greater in the PMRT group (25% vs. 10%; P =.01). Patients in the PMRT group received more chemotherapy (66% vs. 30%; P <.001), had more grade 3 tumors (28% vs. 9%, P =.005), and were more premenopausal (49% vs. 22%; P =.0001). At a median follow-up of 51.3 months for the no PMRT group and 65.9 months for the PMRT group (P =.041), 9% (n = 6) of patients from the no PMRT group and 2% (n = 3) from the PMRT group developed LRR (P =.047). There was no difference in local recurrence (1% in no PMRT group vs. 2% in PMRT group; P =.7) and distant recurrence (7% in no PMRT group vs. 3% in PMRT group; P =.16) in patients who received PMRT and no PMRT. Further comparison of the LRR in the no PMRT and PMRT groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; P =.64). However, among patients with an MS >= 18, no PMRT group had a higher LRR rate compared to the PMRT group (11% vs. 2%; P =.01). In patients with an MS >= 18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95% CI 0.05-0.79; P =.02). Conclusions: Our findings imply that when considering PMRT for patients with pT3N0M0, HR-positive, and HER2-negative BC, clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS < 18 experience a comparable rate of recurrence irrespective of PMRT, while those with MS >= 18 have higher rates of LRR and thus should not omit PMRT. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.