Yazar "Kocanci, Fatma Gonca" seçeneğine göre listele

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    Anti-inflammatory and antioxidative actions of tacrolimus (FK506) on human microglial HMC3 cell line
    (Wiley, 2024) Kocanci, Fatma Gonca; Goksu, Azize Yasemin
    Microglial cells are indispensable for the normal development and functioning of neurons in the central nervous system, where they play a crucial role in maintaining brain homeostasis by surveilling the microenvironment for signs of injury or stress and responding accordingly. However, in neurodegenerative diseases, the density and phenotypes of microglial cells undergo changes, leading to chronic activation and inflammation. Shifting the focus from neurons to microglia in drug discovery for neurodegenerative diseases has become an important therapeutic target. This study was aimed to investigate the potential of Tacrolimus (FK506) an FDA-approved calcineurin inhibitor, to modulate the pathology of neurodegenerative diseases through anti-inflammatory and antioxidative effects on microglial activation. The human microglia clone 3 (HMC3) cells were exposed to 1 mu g/mL LPS in the presence and absence of doses of FK506. Survival rates of cells were determined using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) method. Morphological evaluation of cells showed that FK506 restored the normal morphology of activated microglia. Furthermore, FK506 treatment increases the total antioxidant capacity and reduces the total oxidative capacity, indicating its potential antioxidant effects. Data from ELISA and RT-PCR analyses showed that LPS abolished its promoting effects on the release of proinflammatory IL-1 beta and IL-6 cytokines in HMC3 cells, reflecting the anti-inflammatory effect of FK506. These findings support the idea that FK506 could be a promising therapeutic agent for neurodegenerative diseases by modulating microglial activation and reducing inflammation and oxidative stress.
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    Chemical Composition and Neurotherapeutic Potential of Glaucium corniculatum Extracts
    (Wolters Kluwer Medknow Publications, 2021) Kocanci, Fatma Gonca; Aslim, Belma
    Background: The discovery of natural agents that suppress neural apoptosis is of strategic importance for the treatment of neurodegenerative diseases. Glaucium corniculatum has been used as a traditional medicine because of its memory-enhancing and neuroprotective properties. However, there has not been a study about this plant's apoptosis suppressive properties until now. Objectives: The present study examines the possible suppressive effects on apoptosis of three different G. corniculatum extracts (chloroform, methanol, and water) in neuronal-differentiated PC12 (dPC12) cells induced by hydrogen peroxide (H2O2) and presents the first association of compound content differences in extracts with the suppressive property. Materials and Methods: The chemical composition of these extracts was analyzed by Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy. The changes caused by the extracts in apoptotic markers were examined by real-time quantitative polymerase chain reaction and Western blot. Results: Extracts contained alkaloid, fatty acid, alcohol, alkane hydrocarbon, ester, ether, alkane, alkene, aliphatic, aromatic, and phenolic compounds with different relative proportions. In all the three extracts, the major compound was allocriptopine. Oleamide and 2-monopalmitin were the major fatty acids, respectively, identified in water and methanol extracts. Extracts were suppressed H2O2-induced apoptosis via decreasing the expression of Bax, Caspase-3 and -9, while increasing Bcl-2, in a concentration-dependent manner. The water extract showed the highest apoptosis suppression while methanol was the second. Conclusion: G. corniculatum extracts suppress apoptosis in dPC12 cells and allocriptopine, oleamide, and 2-monopalmitin may be responsible of apoptosis suppressive effect.
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    Combination Treatment with Cromolyn Sodium and Masitinib Displays Cell-Protective Effect and Shows Additive Anti-Oxidative Actions on an in vitro Neurodegenerative Model
    (Springer/Plenum Publishers, 2021) Erol, A. Yasemin Goksu; Kocanci, Fatma Gonca; Demir-Dora, Devrim; Uysal, Hilmi
    [Abstract Not Available]
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    Cromolyn sodium and masitinib combination inhibits fibroblast-myofibroblast transition and exerts additive cell-protective and antioxidant effects on a bleomycin-induced in vitro fibrosis model
    (John Wiley & Sons Ltd, 2024) Goksu, Azize Yasemin; Dirol, Hulya; Kocanci, Fatma Gonca
    Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. While recent studies have suggested the potential efficacy of tyrosine kinase inhibitors in managing IPF, masitinib, a clinically used tyrosine kinase inhibitor, has not yet been investigated for its efficacy in fibrotic lung diseases. In a previous study on an in vitro neurodegenerative model, we demonstrated the synergistic antitoxic and antioxidant effects of masitinib combined with cromolyn sodium, an FDA-approved mast cell stabilizer. This study aims to investigate the anti-fibrotic and antioxidant effects of the masitinib-cromolyn sodium combination in an in vitro model of pulmonary fibrosis. Fibroblast cell cultures treated with bleomycin and/or hydrogen peroxide (H2O2) were subjected to masitinib and/or cromolyn sodium, followed by assessments of cell viability, morphological and apoptotic nuclear changes, triple-immunofluorescence labeling, and total oxidant/antioxidant capacities, besides ratio of Bax and Bcl-2 mRNA expressions as an indication of apoptosis. The combined treatment of masitinib and cromolyn sodium effectively prevented the fibroblast myofibroblast transition, a hallmark of fibrosis, and significantly reduced bleomycin / H2O2-induced apoptosis and oxidative stress. This study is the first to demonstrate the additive anti-fibrotic, cell-protective, and antioxidant effects of the masitinib-cromolyn sodium combination in an in vitro fibrosis model, suggesting its potential as an innovative therapeutic approach for pulmonary fibrosis. Combination therapy may be more advantageous in that both drugs could be administered in lower doses, exerting less side effects, and at the same time providing diverse mechanisms of action simultaneously. Illustration of the Anti-Fibrotic and Antioxidant Effects of Masitinib and Cromolyn Sodium in a Pulmonary Fibrosis ModelThis graphical abstract presents an overview of the experimental design and methodologies used to investigate the anti-fibrotic and antioxidant effects of masitinib and cromolyn sodium in a bleomycin/H2O2-induced pulmonary fibrosis model. Fibroblast cultures were treated with bleomycin and/or H2O2 24 hours after the experiment began, followed by the application of masitinib and/or cromolyn sodium 48 hours later. Multiple assessments-including cell viability assays, morphological evaluation, nuclear DNA staining, immunofluorescence staining, measurements of total oxidant and antioxidant capacities, and analysis of Bax/Bcl-2 mRNA expression levels-were performed to evaluate the effects on fibroblast-to-myofibroblast transition, apoptosis, and oxidative stress.image
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    Effect of Pimecrolimus on apoptotic pathways in H2O2-treated neuron like differentiated-SH-SY5Y cells: a molecular docking and mechanistic study
    (Oxford Univ Press, 2025) Kocanci, Fatma Gonca
    Neurodegenerative diseases (NDs), including Alzheimer's and Parkinson's, are marked by progressive neuronal loss, driven largely by oxidative stress and apoptosis. Developing neuroprotective strategies to counteract these processes is critical for managing such disorders. This study explores the neuroprotective effects of pimecrolimus, a calcineurin inhibitor, in mitigating hydrogen peroxide (H2O2)-induced cytotoxicity in neuron-like differentiated SH-SY5Y (d-SH-SY5Y) cells. The investigation focuses on apoptosis modulation, cell viability, and molecular docking interactions with apoptotic proteins.SH-SY5Y cells were differentiated with retinoic acid and treated with H2O2 (250 mu M) alone or in combination with pimecrolimus (0.01, 0.1, and 1 mu M) for 24 h. Cell viability was assessed using lactate dehydrogenase (LDH) assays. Additionally, malondialdehyde (MDA) levels were measured to assess oxidative stress in SH-SY5Y cells following the treatment conditions. Molecular docking analyses evaluated pimecrolimus' interactions with bax, bcl-2, caspase-3 and caspase-8 proteins, using Venetoclax as a positive control. Apoptosis-related protein levels were analyzed via ELISA, qRT-PCR, and immunofluorescence staining (cleaved caspase-3 and DAPI).Molecular docking showed strong binding of pimecrolimus to bax, bcl-2, caspase-3 and caspase-8, with comparable binding energies to Venetoclax. LDH and MDA assays demonstrated significant reductions in H2O2-induced cytotoxicity with pimecrolimus. ELISA and qRT-PCR revealed that H2O2 increased pro-apoptotic bax, caspase-3 and caspase-8 levels while decreasing anti-apoptotic bcl-2 levels. Pimecrolimus co-treatment reversed these effects in a dose-dependent manner. Immunofluorescence confirmed reduced apoptosis and cell death with pimecrolimus.Pimecrolimus effectively mitigates oxidative stress and apoptosis in H2O2-treated d-SH-SY5Y cells. These findings suggest its potential as a neuroprotective agent for managing (NDs).
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    Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin
    (Springer, 2025) Kocanci, Fatma Gonca; Sarban, Hamiyet Eciroglu; Yildiz, Fatma
    Neurodegenerative diseases (ND), marked by progressive neuronal degeneration, often involve dysregulation of acetylcholinesterase (AChE), a key enzyme in cholinergic neurotransmission. AChE inhibition is a well-established therapeutic strategy for Alzheimer's disease (AD), the most prevalent ND, as it aims to restore impaired cholinergic function. However, the effects of calcineurin inhibitors (CNIs), primarily used as immunosuppressants, on AChE activity remain largely unexplored. Recent evidence suggests CNIs possess neuroprotective properties, highlighting their potential for ND treatment. This study evaluated the binding affinities of FDA-approved CNIs-Tacrolimus (Tac), Pimecrolimus (Pim), Cyclosporine A (Csa), and Voclosporin (Voc)-to AChE via molecular docking and molecular dynamic simulation. AChE inhibition was assessed in vitro using the Ellman method and in H2O2-induced degenerative neuron-like SH-SY5Y cells via ELISA and qRT-PCR. Neuroprotection was examined through MTT assays and neurite analysis. Additionally, the antiapoptotic effect was examined by ELISA analysis measuring caspase-3. Docking studies confirmed strong AChE binding for all CNIs, with Voc exhibiting the highest affinity. Voc demonstrated superior in vitro AChE inhibition, surpassing galantamine at low concentrations. Cellular assays showed that CNIs, particularly Voc, significantly inhibited AChE expression at the gene level. Moreover, Voc markedly restored cell viability and reduced neuronal degeneration in H2O2-treated cells. These findings suggest CNIs, especially Voc, as promising candidates for ND treatment, targeting AChE overactivity and oxidative stress.Graphical AbstractCreated in BioRender. Hamiyet Eciroglu Sarban, (2025) https://BioRender.com/q77r137
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    Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration
    (Wiley, 2024) Goksu, Azize Yasemin; Kocanci, Fatma Gonca; Akinci, Ersin; Demir-Dora, Devrim; Erendor, Fulya; Sanlioglu, Salih; Uysal, Hilmi
    A common pathological hallmark of neurodegenerative disorders is neuronal cell death, accompanied by neuroinflammation and oxidative stress. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. The gene therapy field shows long-term promise for treating a wide range of neurodegenerative diseases (ND). In this study, we aimed to investigate the in vitro efficacy of transduction of microglia using lentiviral gene therapy vectors encoding VIP (LentiVIP). Additionally, we tested the protective effects of the secretome derived from LentiVIP-infected immortalized human microglia HMC3 cells, and cells treated with Synthetic VIP (SynVIP), against toxin-induced neurodegeneration. First, LentiVIP, which stably expresses VIP, was generated and purified. VIP secretion in microglial conditioned media (MG CM) for LentiVIP-infected HMC3 microglia cells was confirmed. Microglia cells were activated with lipopolysaccharide, and groups were formed as follows: 1) Control, 2) SynVIP-treated, or 3) LentiVIP-transduced. These MG CM were applied on an in vitro neurodegenerative model formed by differentiated (d)-SH-SY5Y cells. Then, cell survival analysis and apoptotic nuclear staining, besides measurement of oxidative/inflammatory parameters in CM of cells were performed. Activated MG CM reduced survival rates of both control and toxin-applied (d)-SH-SY5Y cells, whereas LentiVIP-infected MG CM and SynVIP-treated ones exhibited better survival rates. These findings were supported by apoptotic nuclear evaluations of (d)-SH-SY5Y cells, alongside oxidative/inflammatory parameters in their CM. LentiVIP seems worthy of further studies for the treatment of ND because of the potential of gene therapy to treat diseases effectively with a single injection. Cultured microglial cells were activated with LPS, and then grouped as: 1) Control, 2) SynVIP-treated, or 3) LentiVIP-transduced microglia. Subsequently, conditioned media of microglial groups were applied on differentiated-SH-SY5Y cells that were exposed to MPTP (a neurotoxin) or not. Several analysis and tests were performed to investigate the protective effects of SynVIP or LentiVIP against toxicity of MPTP or microglial secretome. image
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    Phytochemical examination of Cistus laurifolius extract and its impact on cytotoxicity, apoptosis and oxidative stress in colorectal and breast cancer cell lines
    (Elsevier Gmbh, 2024) Yildiz, Fatma; Sarban, Hamiyet Eciroglu; Kocanci, Fatma Gonca; Gungor, Meltem; Yucel, Ersin; Yucel, Dilge
    Introduction: Colon and breast cancer are the most common types of cancer worldwide. This study investigatesd the anticancer properties of Cistus laurifolius L. leaf extract on breast cancer (MCF-7) and human colon cancer (Caco-2) cell lines. Methods: The research involved meticulous collection, drying and processing of C. laurifolius leaves to extract bioactive compounds, subsequently analyzed for phenolic content using advanced LC-MS/MS technology. Cell viability of the extract on MCF-7 and Caco-2 cells was demonstrated by MTT test. Levels of critical apoptotic markers (Bad, Bax/Bcl-2, Bax/Bcl-xl, Caspase-9) and Total Antioxidant Capacity (TAC) and Total Oxidant Capacity (TOC), which affect the antioxidant system, were evaluated by the ELISA method. Identification of phenolic compounds, including quercetin and rutin, through target prediction analysis enriches our understanding of bioactive molecules. Results: The results of the study showed that C. laurifolius extract inhibited cell proliferation time and dose-dependent on Caco-2 and MCF-7 cells (P<0.05). TAC, Bax/Bcl-2 and Bax/Bcl-xl ratios in MCF-7 and Caco-2 cells increased in a dose-dependent manner compared to the control group. In MCF-7 cells, TAC (p<0.05; p<0.01), Bax/Bcl-2 (p<0.001; p<0.0001) and Bax-Bcl-xl (p<0.01) ratios increased at 24 h compared to the control group. In Caco-2 cells, TAC (p<0.001), Bax/Bcl-2 ratios increased at 48 h (p<0.05), while Bax-Bcl-xl ratios decreased (p<0.01; p<0.001) compared to the control group. Conclusion: C. laurifolius leaf extracts emerge as a promising anticancer candidate, hindering cell proliferation and inducing apoptosis in colon and breast cancer cells. The classification of bioactive molecules may facilitate further clinical therapeutic interventions targeting colon and breast cancer.
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    Pimecrolimus protects neuron-like SH-SY5Y cells against anti-inflammatory and anti-oxidant effects of both microglial secretome and hydrogen peroxide
    (Wiley, 2024) Kocanci, Fatma Gonca; Erol, Azize Yasemin Goksu; Yildiz, Fatma; Eciroglu, Hamiyet
    Calcineurin inhibitors have been found to exhibit a preventive role against neuroinflammation, which represents a crucial underlying mechanism in neurodegenerative diseases (ND). Additionally, they possess suppressive effects on the activation of apoptotic pathways, which constitute another mechanism underlying such diseases. Given that pimecrolimus, a calcineurin inhibitor, impedes the synthesis of pro-inflammatory cytokines, such as interleukin (IL)-2, IL-4, and IL-10, and influences apoptotic processes, it is noteworthy to test its potential neuroprotective properties. Thus, the objective of this investigation was to assess the potential protective effects of pimecrolimus against the degenerative consequences of both microglial secretomes and hydrogen peroxide (H2O2), an oxidant agent. The survival rates of HMC3 microglia cells, neuron-like differentiated SH-SY5Y (d-SH- SY5Y) cells, and their co-culture were determined using the 3-( 4,5-Dimethylthiazol- 2- yl)- 2,5- Diphenyltetrazolium Bromide (MTT) method. Furthermore, the levels of pro-inflammatory cytokines IL-1 beta and IL-6, and anti-inflammatory cytokine IL-10 were measured using ELISA kits, besides total antioxidant and oxidant capacities in conditioned media of cells. Additionally, the effect of pimecrolimus on neurite length in these cell groups was evaluated through morphological observations. This study revealed, for the first time, that pimecrolimus exerts preventive effects on neurodegenerative processes by virtue of its anti-inflammatory and -antioxidant activities. It holds promise as a potential treatment option for ND.
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    Role of Fatty Acid Chemical Structures on Underlying Mechanisms of Neurodegenerative Diseases and Gut Microbiota
    (Wiley, 2021) Kocanci, Fatma Gonca
    Neurodegenerative diseases have been found to be closely related to common mechanisms such as protein aggregation, neural oxidative stress, neuroinflammation, mitochondrial dysfunction, and gut microbiota dysbiosis. Although there are some drugs that can temporarily reduce symptoms, there is no cure for these diseases. Therefore, the discovery of molecules that can halt the pathology of these diseases is urgently needed in the present time. Fatty acids show positive effects on the pathology of neurodegenerative diseases, depending on the degree of unsaturation and the shortness of the hydrocarbon chain. Understanding the effects of different structures of fatty acids on the underlying mechanisms of neurodegenerative diseases and the balance of gut microbiota can produce positive implications for the development of future treatments. The present review focuses on the role of different fatty acids on underlying mechanisms of neurodegenerative diseases, gut microbiota balance, and gut-brain axis.