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    CRISPR-Cas İmmün Sisteminin Biyolojisi, Mekanizması ve Kullanım Alanları
    (Kırıkkale Üniversitesi, 2016) Gün Gök, Zehra; Çağdaş Tunalı, Beste
    Hedeflenmiş nükleazlar genomdüzenlenmesinde yaygın olarak kullanılmaktadır. Kısa süre önce, düzenliaralıklarla bölünmüş palindromik tekrar kümeleri (CRISPRs)-ilişkili Cas9nükleazları genom düzenleme çalışmalarında ilk defa kullanılmış ve o zamandanberi bu alanda devrim yaratmıştır. CRISPR-Cas9 genom düzenleme aracının bubüyük başarısının ardında Cas9’u istenilen DNA lokusuna hedefleyen kılavuzRNA’nın tasarımının basitliği ve CRISPR-Cas9 aracılı DNA kırılmalarının yükseközgüllük ve verimlilikte olması yatmaktadır. Yakın zamanda yapılan bazıçalışmalarda, in vivo hayvanmodellerinde ve ex vivo somatik veuyarılmış pluripotent kök hücrelerinde hastalığa neden olan allellerindüzenlenmesinde CRISPR-Cas9 sistemi başarıyla kullanılarak terapötik genomdüzenlenmesinin klinik uygulamaları için umutları arttırmıştır. Bu derleme ilebu sistemlerden en çok kullanılan CRISPR-Cas9 Tip II sisteminin diğersistemlere göre avantaj ve dezavantajları belirtilmiş ve bu sistemler ileyapılan uygulamalara değinilmiştir. Ayrıca bu derlemede, çeşitli araştırma yada translasyonel uygulamalarda kullanılan ve olağanüstü bir mikrobiyal savunmasisteminden türetilen CRISPR-Cas9’un gelişiminden ve uygulamalarındakizorluklarından bahsedilmiştir.
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    Effects of functional poly(ethylene terephthalate) nanofibers modified with sericin-capped silver nanoparticles on histopathological changes in parenchymal organs and oxidative stress in a rat burn wound model
    (Ankara Univ, 2023) Şahin, Yaşar; Gün Gök, Zehra; Alçığır, Mehmet Eray; Çınar, Miyas
    In this study, it was aimed to investigate the effect of a poly(ethylene terephthalate)-g-poly(hydroxyethyl methacrylate) (PET-g-HEMA) nanofiber wound dressing modified with sericin-coated silver nanoparticles (S-AgNPs) on internal organs, oxidative stress, and biochemical parameters. To establish a burn model, the backs of anesthetized rats were shaved and then third-degree burns were created with a round-bottomed stainless steel rod 2 cm in diameter kept in 100 degrees C water for 20 seconds. The wounds of the negative control group (G1) were covered with standard bandages; the wounds of the positive control group (G2) were covered with silvercel, used as burn wound material; and the wounds of the experimental group (G3) were covered with PET-based dressing material. Histopathological changes in organs (liver, kidneys, heart, pancreas, lungs), total oxidant status (TOS), total antioxidant status (TAS), nitric oxide (NO), and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transpeptidase [GGT], creatine kinase, lactate dehydrogenase [LDH], total protein, albumin, globulin, urea) were examined. Compared with the G1 group, plasma AST, ALT, and GGT levels were found to be significantly decreased in G2 and G3 (P<0.001). Plasma TAS was found to be significantly increased in G2 and G3 compared to G1 (P<0.05). Compared to the G1 group, degenerative and necrotic changes in the liver, kidneys, and pancreas were found to be significantly reduced in G2 and G3 (P<0.05). In conclusion, this work demonstrates that the synthesized PET-based wound dressing material has the capacity to be used commercially.
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    Investigation of the in vitro antibacterial, cytotoxic and in vivo analgesic effects of silver nanoparticles coated with Centella asiatica plant extract
    (Ankara Univ, 2023) Bozkaya, Ogun; Ekici, Hüsamettin; Gün Gök, Zehra; Arat, Esra; Ekici, Seda; Yigitoglu, Mustafa; Vargel, İbrahim
    In recent years, researchers have shown an increased interest in using medicinal plants for the synthesis of silver nanoparticles (AgNPs) having various therapeutic properties. Centella asiatica (CA), a medicinal plant, has been used to treat minor burn wounds, psoriasis, and hypertrophic wounds among many other pathological conditions. The current study aimed to synthesize CA coated AgNPs (CA-AgNPs) with appropriate biocompatibility and various therapeutic properties, including antimicrobial and analgesic activities. The synthesized CA-AgNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, zeta potential measurements, and fourier transform infrared (FT-IR) spectroscopy. The formation of spherical CA-AgNPs was confirmed by a single surface plasmon resonance (SPR) peak emerging at 420 nm wavelength by UV-Vis. The average hydrodynamic diameter and zeta potential of the particles were found to be 29.5 nm and -24.5 mV, respectively. The FT-IR analyses showed that the AgNPs were coated and stabilized by bioactive compounds from the CA extract. MTT cytotoxicity assay revealed that CA-AgNPs at <= 1 mM concentrations exhibited biocompatibility for L929 fibroblast cells. The antimicrobial activity of CA-AgNPs was confirmed by significant inhibition of Staphylococcus aureus and Escherichia coli. In addition, the analgesic effect of CA-AgNPs was investigated for the first time in the literature by tail-flick and hot plate methods, and statistically significant results were obtained for both methods. Taken together, these results suggest that CA-AgNPs can be used as an effective antibacterial and analgesic agent in a variety of biomedical applications, including coating wound dressings.
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    Removal of anionic dyes with glycidyl methacrylate-grafted polyethylene terephthalate (PET) fibers modified with ethylenediamine
    (Springer, 2021) Bozkaya, Ogün; Günay, Kübra; Arslan, Metin; Gün Gök, Zehra
    In this work, the epoxy groups of poly (ethylene terephthalate) PET copolymers grafted with glycidyl methacrylate (GMA) were modified with ethylenediamine (EDA) to form exclusive adsorbent for removal of congo red (CR) and acid violet7 (AV-7) in the aqueous environment. The graft copolymers (GMA-g-PET) were synthesized with different grafting yield by a radical polymerization process with using benzoyl peroxide (Bz(2)O(2)) as radical initiator. Amination of GMA-g-PET fibers using EDA was studied in different solvents, and maximum yield (w/w %) was obtained in the toluene. The grafted and modified fibers were analyzed by CHNS organic elemental analyzer, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance spectroscopy (C-13-NMR). By SEM analysis, the morphological changes have been shown after grafting. The chemical changes after grafting and addition of EDA to the fibers have been proven with FTIR, NMR and elemental analysis. The thermal properties of the grafted and aminated fibers were researched with thermogravimetric analysis and differential scanning calorimeter analysis. The removal of dyes by the EDA-GMA-g-PET fibers was investigated in aqueous medium at different conditions. Optimum conditions of different parameters such as pH of medium, graft yield of GMA on the fibers, adsorption duration, initial concentration of dye molecules and effect of graft yield on amination reaction were examined. The optimum pH of CR and AV-7 removal was found 5 and 3, respectively. The removal yield was found about 100% for both dyes while initial concentration of dyes was changed from 10 to 400 mg/L. Adsorbed dyes with the fibers were desorbed with 1 M NaOH at room conditions.
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    Synthesis of carrageenan coated silver nanoparticles by an easy green method and their characterization and antimicrobial activities
    (Springer, 2021) Gün Gök, Zehra; Karayel, Mine; Yigitoglu, Mustafa
    The aim of the present work was to synthesize carrageenan coated silver nanoparticles (CA-AgNPs) using carrageenan as reducing and stabilizing agent. For this purpose, 10 mL of 0.35% (w/v) carrageenan solution was mixed with 10 mL AgNO3 solution at different concentrations (1, 5 and 10 mM), and the resulting mixture was stirred at 100 degrees C at high speed for 2 h. The formation of CA-AgNPs was proven with the surface plasmon peaks observed at approximately 420 nm. The sizes and zeta potentials of CA-AgNPs were determined by Zeta-Sizer. Negative zeta potentials of CA-AgNPs indicated that the obtained AgNPs were stable. With scanning electron microscope (SEM) and transmission electron microscope analysis, it was seen that CA-AgNPs have spherical structure. According to the energy dispersion spectrometer analysis based on SEM images, it was observed that the samples were elementally composed of carbon, oxygen, sulfur, potassium and silver. The chemical structures of CA-AgNPs were determined by Fourier transform infrared spectroscopy, and it was proved that the carbonyl and OH groups of carrageenan were involved in formation and stabilizing of AgNPs, respectively. According to thermal gravimetric analysis, it has been observed that CA-AgNPs were thermally more stable than pure carrageenan. Antibacterial activity of CA-AgNPs against gram-positive and gram-negative bacteria was investigated with agar well diffusion and liquid test. It has been observed that CA-AgNPs synthesized with 1 mM AgNO3 did not have an antibacterial activity on Escherichia coli and Staphylococcus aureus. Inhibition zones of varying diameters were observed in the 5 mM and 10 mM S-AgNPs groups. The synthesized CA-AgNPs (5 and 10 mM) have the capacity to be used in wound dressing materials or topical agents applied to burns and wounds due to their antibacterial effects and stability.
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    Synthesis, characterization and in vitro release analysis of pluronic F127 copolymer micelles containing quercetin as a hydrophobic drug
    (Springer Science and Business Media Deutschland GmbH, 2024) İspir, Elif; İnal, Murat; Gün Gök, Zehra; Yiğitoğlu, Mustafa
    The object of the present study is to develop a new controlled drug release system by loading quercetin into pluronic F127 micelles. For the experimental studies, first of all, the critical micelle concentration (CMC) of the pluronic F127 copolymer was found as 4.5% g/mL at 25 °C, since the micelle-forming surfactants formed micelles at concentrations equal to or higher than the CMC. Afterward, with thin-film hydration method, three micelle groups with different polymer/quercetin ratios were formed. In this procedure, pluronic F127 polymer dissolved in ethanol at 30–40 °C and different amount of quercetin was added to the polymer solution. The polymer-quercetin solutions were evaporated in the evaporator at 40 °C for 2 h to obtain a film. The resulting film was hydrated by adding of ultrapure water and the micelle suspensions were obtained after filtration. According to Malvern Zetasizer measurement and transmission electron microscope (TEM) analysis, quercetin loaded micelles were determined to have particle sizes between 40 and 50 nm. It was determined by fourier-transform infrared spectroscopy (FTIR) analysis that quercetin was physically found into pluronic F127 micelles without any chemical reaction. It was determined by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyzes that quercetin was present in amorphous form as a solid solution instead of in crystalline form in the micelles. Thermogravimetric analysis (TGA) analysis showed that loading quercetin into the micelles did not affect the thermal stability of the PF127 copolymer. The drug loading amounts for micelles were found between 1.95% and 3.3% (mg/mg) for different micelles groups and there was not much difference in the percentage of encapsulation efficiency values thought to the groups. In vitro release profiles of quercetin-loaded micelles were investigated in pH 7.4 phosphate buffer solution and at 37 °C. When the release results were examined in general, it was seen that the release rates of all formulations were almost the same after 168 h. The kinetic parameters of the release results of the micelles in different formulations were calculated according to the Peppas equation and it was determined that the quercetin release in each micelle formulation did not comply with Fick’s law, according to the calculated n parameter. Quercetin-loaded polymeric micelles obtained in this study offer advantages due to their easy synthesis methods and slow release profiles and they can used to successfully encapsulation of hydrophobic active ingredients like quercetin. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023.