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  1. Article ; Online: Proposing novel natural compounds against Alzheimer’s disease targeting acetylcholinesterase

    Münteha Girgin / Sevim Isik / Nigar Kantarci-Carsibasi

    PLoS ONE, Vol 18, Iss

    2023  Volume 4

    Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder considered as a global public health threat influencing many people. Despite the concerning rise in the affected population, there is still a shortage of potent and safe therapeutic agents. The aim ...

    Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder considered as a global public health threat influencing many people. Despite the concerning rise in the affected population, there is still a shortage of potent and safe therapeutic agents. The aim of this research is to discover novel natural source molecules with high therapeutic effects, stability and less toxicity for the treatment of AD, specifically targeting acetylcholinesterase (AChE). This research can be divided into two steps: in silico search for molecules by systematic simulations and in vitro experimental validations. We identified five leading compounds, namely Queuine, Etoperidone, Thiamine, Ademetionine and Tetrahydrofolic acid by screening natural molecule database, conducting molecular docking and druggability evaluations. Stability of the complexes were investigated by Molecular Dynamics simulations and free energy calculations were conducted by Molecular Mechanics Generalized Born Surface Area method. All five complexes were stable within the binding catalytic site (CAS) of AChE, with the exception of Queuine which remains stable on the peripheral site (PAS). On the other hand Etoperidone both interacts with CAS and PAS sites showing dual binding properties. Binding free energy values of Queuine and Etoperidone were -71.9 and -91.0 kcal/mol respectively, being comparable to control molecules Galantamine (-71.3 kcal/mol) and Donepezil (-80.9 kcal/mol). Computational results were validated through in vitro experiments using the SH-SY5Y(neuroblastoma) cell line with Real Time Cell Analysis (RTCA) and cell viability assays. The results showed that the selected doses were effective with half inhibitory concentrations estimated to be: Queuine (IC50 = 70,90 μM), Etoperidone (IC50 = 712,80 μM), Thiamine (IC50 = 18780,34 μM), Galantamine (IC50 = 556,01 μM) and Donepezil (IC50 = 222,23 μM), respectively. The promising results for these molecules suggest the development of the next step in vivo animal testing and provide hope for natural ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 540
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Microglia Mediated Neuroinflammation in Parkinson’s Disease

    Sevim Isik / Bercem Yeman Kiyak / Rumeysa Akbayir / Rama Seyhali / Tahire Arpaci

    Cells, Vol 12, Iss 1012, p

    2023  Volume 1012

    Abstract: Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in ... ...

    Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation of intracellular protein α-synuclein are the pathological characterizations. Neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. It is a complex network of interactions comprising immune and non-immune cells in addition to mediators of the immune response. Microglia, the resident macrophages in the CNS, take on the leading role in regulating neuroinflammation and maintaining homeostasis. Under normal physiological conditions, they exist as “homeostatic” but upon pathological stimuli, they switch to the “reactive state”. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes are used to classify microglial activity with each phenotype having its own markers and released mediators. When M1 microglia are persistent, they will contribute to various inflammatory diseases, including neurodegenerative diseases, such as PD. In this review, we focus on the role of microglia mediated neuroinflammation in PD and also signaling pathways, receptors, and mediators involved in the process, presenting the studies that associate microglia-mediated inflammation with PD. A better understanding of this complex network and interactions is important in seeking new therapies for PD and possibly other neurodegenerative diseases.
    Keywords Parkinson’s Disease ; neuroinflammation ; microglial activation ; α-synuclein ; M1 phenotype ; M2 phenotype ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression

    Merve Zaim / Sevim Isik

    Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Abstract Background DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of ... ...

    Abstract Abstract Background DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. Methods and results For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Conclusion Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.
    Keywords Human mesenchymal stem cells ; Neural differentiation ; Neurite outgrowth ; DNA topoisomerase IIβ ; Rho GTPases ; Neurodegeneration ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
    Subject code 571
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Boronic Acid vs. Folic Acid: A Comparison of the bio-recognition performances by Impedimetric Cytosensors based on Ferrocene cored dendrimer

    Dervisevic, Muamer / Mehmet Şenel / Sevim Isik / Tugba Sagir

    Biosensors & bioelectronics. 2017 May 15, v. 91

    2017  

    Abstract: A comparative study is reported where folic acid (FA) and boronic acid (BA) based cytosensors and their analytical performances in cancer cell detection were analyzed by using electrochemical impedance spectroscopy (EIS) method. Cytosensors were ... ...

    Abstract A comparative study is reported where folic acid (FA) and boronic acid (BA) based cytosensors and their analytical performances in cancer cell detection were analyzed by using electrochemical impedance spectroscopy (EIS) method. Cytosensors were fabricated using self-assembled monolayer principle by modifying Au electrode with cysteamine (Cys) and immobilization of ferrocene cored polyamidiamine dendrimers second generation (Fc-PAMAM (G2)), after which electrodes were modified with FA and BA. Au/Fc-PAMAM(G2)/FA and Au/Fc-PAMAM(G2)/BA based cytosensors showed extremely good analytical performances in cancer cell detection with linear range of 1×102 to 1×106cellsml−1, detection limit of 20cellsml−1 with incubation time of 20min for FA based electrode, and for BA based electrode detection limit was 28cellsml−1 with incubation time of 10min. Next to excellent analytical performances, cytosensors showed high selectivity towards cancer cells which was demonstrated in selectivity study using human embryonic kidney 293 cells (HEK 293) as normal cells and Au/Fc-PAMAM(G2)/FA electrode showed two times better selectivity than BA modified electrode. These cytosensors are promising for future applications in cancer cell diagnosis.
    Keywords biosensors ; cysteamine ; detection limit ; dielectric spectroscopy ; electrodes ; folic acid ; gold ; humans ; kidneys ; neoplasm cells ; neoplasms
    Language English
    Dates of publication 2017-0515
    Size p. 680-686.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2017.01.030
    Database NAL-Catalogue (AGRICOLA)

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    Zs.A 2275: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article: Highly sensitive detection of cancer cells with an electrochemical cytosensor based on boronic acid functional polythiophene

    Dervisevic, Muamer / Mehmet Senel / Sevim Isik / Tugba Sagir

    Biosensors & bioelectronics. 2017 Apr. 15, v. 90

    2017  

    Abstract: The detection of cancer cells through important molecular recognition target such as sialic acid is significant for the clinical diagnosis and treatment. There are many electrochemical cytosensors developed for cancer cells detection but most of them ... ...

    Abstract The detection of cancer cells through important molecular recognition target such as sialic acid is significant for the clinical diagnosis and treatment. There are many electrochemical cytosensors developed for cancer cells detection but most of them have complicated fabrication processes which results in poor reproducibility and reliability. In this study, a simple, low-cost, and highly sensitive electrochemical cytosensor was designed based on boronic acid-functionalized polythiophene. In cytosensors fabrication simple single-step procedure was used which includes coating pencil graphite electrode (PGE) by means of electro-polymerization of 3-Thienyl boronic acid and Thiophen. Electrochemical impedance spectroscopy and cyclic voltammetry were used as an analytical methods to optimize and measure analytical performances of PGE/P(TBA0.5Th0.5) based electrode. Cytosensor showed extremely good analytical performances in detection of cancer cells with linear rage of 1×101 to 1×106 cellsmL−1 exhibiting low detection limit of 10 cellsmL−1 and incubation time of 10min. Next to excellent analytical performances, it showed high selectivity towards AGS cancer cells when compared to HEK 293 normal cells and bone marrow mesenchymal stem cells (BM-hMSCs). This method is promising for future applications in early stage cancer diagnosis.
    Keywords bone marrow ; carbon electrodes ; detection limit ; dielectric spectroscopy ; electrochemistry ; neoplasm cells ; neoplasms ; sialic acid ; stem cells
    Language English
    Dates of publication 2017-0415
    Size p. 6-12.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2016.10.100
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2275: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Preparation and characterization of amine functional nano-hydroxyapatite/chitosan bionanocomposite for bone tissue engineering applications

    Atak, Besir Hakan / Berna Buyuk / Guven Cetin / Mehmet Senel / Merve Huysal / Sevim Isik / Wolfgang Metzger

    Carbohydrate polymers. 2017 May 15, v. 164

    2017  

    Abstract: In this study, three different types of scaffolds including a uniquely modified composite scaffold – namely chitosan (CTS), nano-hydroxyapatite/chitosan composite (CTS+nHAP), and amine group (NH2) modified nano-hydroxyapatite/chitosan composite (CTS+nHAP- ...

    Abstract In this study, three different types of scaffolds including a uniquely modified composite scaffold – namely chitosan (CTS), nano-hydroxyapatite/chitosan composite (CTS+nHAP), and amine group (NH2) modified nano-hydroxyapatite/chitosan composite (CTS+nHAP-NH2) scaffolds – were synthesized for bone tissue engineering (BTE) purposes. As results of the study, it was found that all scaffold types were biodegradable with CTS and CTS+nHAP scaffolds losing up to 15% of their initial weight, while the CTS+nHAP-NH2 scaffold showing 10% of weight loss after six weeks of lysozyme treatment. In addition, all three types of scaffolds were shown to be biocompatible, and amongst them CTS+nHAP-NH2 scaffolds supported the most cell proliferation in WST-1 assay and expressed the least and acceptable level of cytotoxicity in lactate dehydrogenase (LDH) test for human bone mesenchymal stem cells (hBM-MSCs). Finally, during osteoinductivity assessment, CTS+nHAP-NH2 nearly tripled initial alkaline phosphatase (ALP) activity when whereas both CTS and CTS+nHAP scaffolds only doubled. These results indicate that all synthesized scaffold types under investigation have certain potential to be used in bone tissue engineering approaches with CTS+nHAP-NH2 scaffold being the most promising and applicable one. In the future, we plan to intensify our studies on osteogenic differentiation on our scaffolds on a detailed molecular level and to include in vivo studies for pre-clinical purposes.
    Keywords alkaline phosphatase ; biodegradability ; bone formation ; bones ; cell proliferation ; chitosan ; cytotoxicity ; humans ; in vivo studies ; lactate dehydrogenase ; lysozyme ; nanocomposites ; stem cells ; tissue engineering ; weight loss
    Language English
    Dates of publication 2017-0515
    Size p. 200-213.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2017.01.100
    Database NAL-Catalogue (AGRICOLA)

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