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, 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
    Semi-Synthetic Sapogenin Derivatives Inhibit Inflammation-Induced Tumorigenic Signaling Alterations in Prostate Carcinogenesis
    (Elsevier Science Inc, 2026) Debelec-Butuner, Bilge; Ozturk, Mert Burak; Tag, Ozgur; Akgun, Ismail Hakki; Bedir, Erdal
    Prostatic inflammation plays a pivotal role in prostate cancer development and progression via altering key cellular mechanisms, including proliferation, metastasis, and angiogenesis. Therefore, the use of antiinflammatory drugs could provide a valid contribution to PCa prevention and treatment. In our research, we explored semi-synthetic derivatives of cycloastragenol (CA) and astragenol (AG) to assess their potential to inhibit inflammation-mediated tumorigenic signaling. Building on our previous findings, which demonstrated their inhibitory activity on NFxB, we discovered that these molecules also suppress inflammation-induced cell proliferation and migration through distinct mechanisms. They effectively alleviated inflammation by reducing levels of ROS, NO, and VEGF expression. Furthermore, these molecules partially restored the expression of AR and the tumor suppressor NKX3.1, both of which are critical in prostate tumorigenesis within an inflammatory microenvironment. They also reversed inflammation-induced activation of Akt and (3-catenin signaling, suggesting their potential to inhibit inflammation-related prostate tumorigenesis. Our study further demonstrated that these molecules exhibited dose-dependent effects on inducing cell cycle arrest and apoptosis, as evidenced by increased p21 and decreased BCL-2 protein levels, leading to activated cell death and suppressed cellular migration. In conclusion, these semi-synthetic sapogenol derivatives demonstrate significant potential as antiinflammatory and anticancer agents, offering a promising approach for targeting prostatic inflammation and inflammation-driven prostate carcinogenesis.
  • 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
    Enhancement of Corchorus Olitorius L. on Osteogenic Differentiation of MC3T3-E1 Pre-Osteoblast Cells by Increasing Alkaline Phosphatase and Hydroxyproline
    (Taylor & Francis Ltd, 2025) Ertugruloglu, Pinar; Baris, Elif; Okkali, Gaye Sumer; Boke Sarikahya, Nazli
    Corchorus olitorius L. (jute mallow or molehiya) belongs to the Malvaceae family valued for its nutritional and medicinal properties. In this study, the potential to enhance osteogenesis in MC3T3-E1(Murine Calvaria-derived 3T3 Subclone E1) pre-osteoblastic cells was investigated to support bone formation and mineralisation. Leaf ethanolic extract was prepared and applied to MC3T3-E1 cells. Osteogenic effects were evaluated through three methods: MTT assays for cell viability, Alizarin Red S staining for calcium deposition, enzymatic analyses for alkaline phosphatase (ALP) and hydroxyproline (HYP). A non-cytotoxic concentration of C. olitorius extract (0.5 mg/mL) significantly increased ALP and HYP levels, promoting osteogenic differentiation in both undifferentiated and differentiated cells. HYP levels were notably elevated in differentiated cells. The findings suggested that C. olitorius extract may be a promising natural agent for enhancing bone health, warranting further in vivo and clinical studies to confirm its therapeutic potential.
  • 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.