Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
Browse
9 results
Search Results
Now showing 1 - 9 of 9
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 Notum1a Inhibition Promotes Neurogenesis in the Adult Zebrafish Brain(Nature Portfolio, 2025) Kocagoz, Yigit; Erdogan, Nuray Sogunmez; Ozdinc, Sevval; Ipekgil, Dogac; Katkat, Esra; Ozhan, GunesNotum is a carboxylesterase enzyme that modulates extracellular signaling by hydrolyzing palmitoleoyl residues from proteins, thereby influencing key pathways involved in cell differentiation, survival, and proliferation. While notum1 expression has been identified in the brain, its role in adult neurogenesis remains poorly understood. Using the adult zebrafish brain as a model system, we demonstrate that the notum1a homolog is broadly expressed across various brain cell types but is absent in undifferentiated radial glial cells. Pharmacological inhibition of Notum activity with the small molecule inhibitor ABC99 stimulates activation of radial glial cells, leading to increased neurogenesis. A BrdU pulse-chase assay confirms that ABC99-induced proliferation enhances the production of mature neurons. Despite Notum's established role in Wnt signaling, transcriptional analysis following ABC99 treatment reveals no sustained impact on Wnt pathway targets, suggesting that Notum may regulate neurogenesis through alternative mechanisms. Our findings highlight notum1a as a potential modulator of neural progenitor cell dynamics in the adult brain and suggest that targeting Notum could represent a novel therapeutic strategy for neurodegenerative conditions characterized by impaired neurogenesis.Article Citation - WoS: 2Citation - Scopus: 2Tuning Toxicity Profiles of Graphene Oxide Through Imidazole-Oxime Modification: Zebrafish as a Model System(Oxford Univ Press, 2025) Yildirim, Serkan; Kokturk, Mine; Yigit, Aybek; Sahin, Ayse; Kiliclioglu, Metin; Atamanalp, Muhammed; Alak, GoncaThe increasing use of nanotechnology, especially in agriculture and the food industry, has raised concerns about the possible adverse effects of nanomaterials (NMs) on human health and the environment. This study investigates the effects of synthesized graphene oxide (GO) and its derivatives on zebrafish exposed for 96 hr, focusing on morphological changes in brain tissue, histopathology, and immunofluorescent markers such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nucleolar protein 10 (NOP10). Exposure to GO resulted in malformations, DNA damage, and increased NOP10 expression, and it reduced hatching and survival rates. Our results demonstrated that exposure to GO, graphene oxide-oxime (GO-OX), and OX exerted dose-dependent inhibitory effects on hatching and promoted malformations in zebrafish larvae. Histopathological analysis revealed that higher doses led to more pronounced tissue damage, with GO 50 causing severe degeneration and necrosis, while high doses of GO-OX and OX resulted in moderate tissue changes. This was further supported by the increased expression levels of 8-OHdG (marker of oxidative DNA damage) and NOP10 (marker of nucleolar stress), which aligns with the histopathological findings and confirms the neurotoxic effects. Notably, GO-OX treatments consistently mitigated both morphological and neurotoxic effects at all doses, suggesting that oxime functionalization reduces the inherent toxicity of GO. In contrast, treatment with different concentrations of GO-OX derivatives mitigated these adverse effects, reducing them to mild or moderate levels.Review Citation - Scopus: 2Wnt/β-catenin Signaling in Central Nervous System Regeneration(2025) Nazli, D.; Bora, U.; Ozhan, G.The Wnt/β-catenin signaling pathway plays a pivotal role in the development, maintenance, and repair of the central nervous system (CNS). This chapter explores the diverse functions of Wnt/β-catenin signaling, from its critical involvement in embryonic CNS development to its reparative and plasticity-inducing roles in response to CNS injury. We discuss how Wnt/β-catenin signaling influences various CNS cell types-astrocytes, microglia, neurons, and oligodendrocytes-each contributing to repair and plasticity after injury. The chapter also addresses the pathway's involvement in CNS disorders such as Alzheimer's and Parkinson's diseases, psychiatric disorders, and traumatic brain injury (TBI), highlighting potential Wnt-based therapeutic approaches. Lastly, zebrafish are presented as a promising model organism for studying CNS regeneration and neurodegenerative diseases, offering insights into future research and therapeutic development. © 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.Article Gypsophila Eriocalyx Roots Inhibit Proliferation, Migration, and Tgf-Β Signaling in Melanoma Cells(Walter de Gruyter GmbH, 2025) Azbazdar, Yagmur; Ozhan, Gunes; Helvacioglu, SelinObjectives: Melanoma is a highly malignant and serious form of skin cancer. In addition to the standard treatments, complementary approaches, including phytotherapy, are also used to alleviate symptoms and improve patient well- being. This study aims to investigate the anticancer effects of Gypsophila eriocalyx (GE), an endemic species from Türkiye, on melanoma cells. We set out to determine the efficacy of GE in inhibiting melanoma cell proliferation, migration, and growth, and to explore its underlying mechanisms. Methods: We examined the impact of GE on the prolifera- tion of two melanoma cell lines, Malme-3M and SK-MEL-28, and assessed its developmental toxicity in zebrafish em- bryos. Next, we evaluated GE’s influence on colony forma- tion and wound healing in melanoma cells, as well as its ability to induce apoptosis and affect the TGF-β/Smad signaling pathway, by measuring pathway reporter activity and target gene expression. Results: GE inhibited cell proliferation in melanoma cell lines at concentrations 104 to 488 times lower than those required for normal non-malignant L929 fibroblast cells. In zebrafish embryos, GE demonstrated developmental toxicity only at concentrations above 50 μg/mL. GE treatment significantly impaired the colony formation and wound healing abilities of melanoma cells, indicating reduced pro- liferation and migration. Moreover, GE induced apoptosis in melanoma cells and inhibited the TGF-β/Smad signaling pathway, as evidenced by decreased pathway reporter activity and target gene expression. Conclusions: This study highlights the potential of GE as a novel therapeutic agent in melanoma treatment by demon- strating its ability to inhibit tumor growth and progressionArticle Citation - WoS: 1Citation - Scopus: 2<i>tubg1</I> Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model(Springer, 2024) Cark, Ozge; Katkat, Esra; Aydogdu, Ipek; Iscan, Evin; Oktay, Yavuz; Ozhan, GunesDevelopment of the multilayered cerebral cortex relies on precise orchestration of neurogenesis, neuronal migration, and differentiation, processes tightly regulated by microtubule dynamics. Mutations in tubulin superfamily genes have been associated with tubulinopathies, encompassing a spectrum of cortical malformations including microcephaly and lissencephaly. Here, we focus on gamma-tubulin, a pivotal regulator of microtubule nucleation encoded by TUBG1. We investigate its role in brain development using a zebrafish model with somatic tubg1 mutation, recapitulating features of TUBG1-associated tubulinopathies in patients and mouse disease models. We demonstrate that gamma-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between gamma-tubulin and canonical Wnt/beta-catenin signaling, with gamma-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that gamma-tubulin could be a potential target for further research in neurodevelopmental disorders, although challenges such as mode of action, specificity, and potential side effects must be addressed.Article Citation - WoS: 6Citation - Scopus: 6A Novel 2-Aminophenalenone Fluorescent Probe Designed for Monitoring H2o2 for in Vitro and in Vivo Bioimaging(Elsevier, 2024) Saygılı, Ecem; Ersöz Gülseven, Esra; Kıbrıs, Erman; Çakan Akdoğan, Gülçin; Üçüncü, MuhammedA significant compound in living organisms, hydrogen peroxide (H2O2) plays a dual role as a signalling molecule in cellular communication and as a pivotal biomarker in assessing disease and oxidative stress. Thus, the detection of abnormal changes in H2O2 levels is essential to understanding its function and involvement in biological systems. The growing demand to meet the specific needs for applications, particularly in biological systems, has sharpened focus on highly sensitive, highly selective molecular sensors and, in turn, heightened interest in these diagnostic tools with innovative designs. In our study, 2-aminophenalenone (2-AP) was used for the first time as a fluorophore in a fluorescent probe. The 2-APB molecule obtained from the reaction of 2-AP with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzyl chloroformate exhibited a highly selective and sensitive (i.e. 62 nM) detection profile for H2O2 compared with the other reactive oxygen species, anions, and metal cations. Moreover, offering naked-eye detection in aqueous solutions, 2-APB demonstrated excellent sensing performance, detection and real-time monitoring in relation to exogenous H2O2 in cells and endogenous H2O2 in zebrafish embryos. © 2024 Elsevier B.V.Article Citation - WoS: 12Citation - Scopus: 13Lc-esi-ms/Ms Analysis of Secondary Metabolites of Different St. John's Wort (hypericum Perforatum) Extracts Used as Food Supplements and Evaluation of Developmental Toxicity on Zebrafish (danio Rerio) Embryos and Larvae(Elsevier, 2023) Atalar, Mehmet Nuri; Köktürk, Mine; Altındağ, Fikret; Özhan, Güneş; Özen, Tevfik; Demirtaş, İbrahim; Gülçin, İlhamiHypericum perforatum (St. John's wort) belongs to the Hypericaceae family and is one of the best known Hypericum species worldwide. It is a very popular and valuable medicinal plant widely distributed in Anatolia. Hypericum perforatum contains many bioactive components that play a role in activities has been used as a food supplement. The extracts are used within safe dose range that are harmless and effective for health. When the SJW1, SJW2 and SJW3 fractions of St. John's Wort extracts were exposed to zebrafish embryos and larvae at different concentrations (5, 10, 100, and 300 µg/mL), the survival rates at 96th hour were determined as 83.3, 27.5 and 2.5%, respectively. No significant changes were found in the malformation rates, and the larval emergence was found to be above 80% at 96th hour for all extracts. No caspase-3 expression was found at the 96th hour in the larvae. Similar secondary components of extracts were observed except quantitative differences. The use of samples in doses of 10 µg/mL and below as food supplement may be harmless, however, threshold dose values of H. perforatum extracts lower toxic doses may be due to the different amounts of secondary metabolites. © 2023Article Citation - WoS: 10Citation - Scopus: 10An in Vivo Zebrafish Model Reveals Circulating Tumor Cell Targeting Capacity of Serum Albumin Nanoparticles(Elsevier, 2022) Çakan Akdoğan, Gülçin; Ersöz, Esra; Sözer, Sümeyra Çiğdem; Gelinci, EmineNanoparticles are promising tools of drug delivery in modern medicine. There is a need for fast and reliable models for in vivo validation of newly developed nanocarriers. Here, we report a fast and easy zebrafish larval model to study the biodistribution and cancer cell targeting capacity of serum albumin nanoparticles in vivo. Fluorescently tagged Bovine Serum Albumin Nanoparticles (BSA-NPs) delivered intravenously to the zebrafish larvae, can be used to study the biodistribution via live imaging. We showed that the BSA-NPs were instantly distributed to the larval vasculature including the brain, without causing any toxicity. The clearance of nanoparticles from the body occurred within few days, which gives sufficient time to study anti-cancer efficiency of the BSA-NPs. Next, we asked whether the BSA-NPs can target the cancer cells in circulation. We established a circulating tumor cell (CTC) xenograft model and described a quantitative method for colocalization and cancer cell death analysis in the intact live organism. We showed that BSA-NPs effectively found and localized to MCF7 cells in vasculature which were killed upon doxorubicin delivery. Interestingly, folic acid coating of BSA-NPs caused faster colocalization but did not increase the overall cell death. This is the first report of the biodistribution, toxicity and anti-cancer effectiveness of serum albumin-based nanoparticles in the zebrafish model. Moreover, here we report for the first time that BSA-NPs are able to target the CTCs in an in vivo model. The zebrafish CTC model and the analysis protocol reported here can be used to assess CTC targeting capacity of nanoparticles and devise patient specific CTC targeting tests.