Araştırma Çıktıları
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Item Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, ErcumentThe SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.Item Melatonin in preservation solutions prevents ischemic injury in rat kidneys(PUBLIC LIBRARY SCIENCE, 2022-01-01) Coskun, Abdurrahman; Yegen, Cumhur; Arbak, Serap; Attaallah, Wafi; Gunal, Omer; Elmas, Merve Acikel; Ucal, Yasemin; Can, Ozge; Bas, Banu; Yildirim, Zeynep; Seckin, Ismail; Demirci, Sibel; Serteser, Mustafa; Ozpinar, Aysel; Belce, Ahmet; Basdemir, Gulcin; Moldur, Derya Emel; Derelioglu, Ecenur Izzete; Yozgatli, Tahir Koray; Erdemgil, Yigit; Unsal, IbrahimTransplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCI which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.Item Differences between Solution and Membrane Forms of Chitosan on the In Vitro Activity of Fibroblasts(GALENOS PUBL HOUSE, 2015-01-01) Uslu, Bahar; Biltekin, Burcu; Denir, Secnur; Ozbas-Turan, Suna; Arbak, Serap; Akbuga, Julide; Bilir, AyhanBackground: Chitosan, a linear polysaccharide, has been recently used in biomedical applications. In vitro studies have demonstrated its effect on cellular growth and its stimulatory action on cellular layer formation. Aims: The present study aims to compare the proliferative effects of chitosan in two forms, membranous and solution forms, on Swiss 3T3 mouse embryonic fibroblasts. Study Design: In vitro study. Methods: Three experimental groups were formed: cells were cultured in a normal medium without chitosan (Control Group)Item SARS-CoV-2 isolation and propagation from Turkish COVID-19 patients(2004-01-01) Tastan, Cihan; Yurtsever, Bulut; Karakus, Gozde Sir; Kancagi, Derya Dilek; Demir, Sevda; Abanuz, Selen; Seyis, Utku; Yildirim, Mulazim; Kuzay, Recai; Elibol, Omer; Arbak, Serap; Elmas, Merve Acikel; Birdogan, Selcuk; Sezerman, Osman Ugur; Kocagoz, Aye Sesin; Yalcin, Koray; Ovali, ErcumentThe novel coronavirus pneumonia, which was named later as coronavirus disease 2019 (COVID-19), is caused by the severe acute respiratory syndrome coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. In May, over 150,000 cases in Turkey, and 5.5 million cases around the world have been declared. Due to the urgent need for a vaccine and antiviral drug, isolation of the virus is crucial. Here, we report 1 of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology,and cell culture tropism of the virus that will be available to the research communities.Item Early Onset of Atherosclerosis of The Carotid Bifurcation in Newborn Cadavers(PREMCHAND SHANTIDEVI RESEARCH FOUNDATION, 2016-01-01) Uslu, Bahar; Cakmak, Yusuf Ozgur; Sehirli, Umit; Keskinoz, Elif Nedret; Cosgun, Erdal; Arbak, Serap; Yalin, AymelekIntroduction: The anatomy of arterial bifurcations affects blood flow and has a significant role in the development of vascular disease. Therefore, it is important to know the structural characteristics of the Common Carotid Artery (CCA) and its branches for early onset of atherosclerosis in newborns. Aim: The present study was conducted to evaluate the characteristics of CCA in newborn cadavers. Materials and Methods: Eight carotid arteries obtained from newborn cadavers were used. The outflow to inflow area ratios was calculated to evaluate vessel diameters. Additionally, scanning electron and light microscopic investigations were conducted with tissue samples. The brachial artery of each cadaver was used as controls. Correlation between area ratios and atherosclerotic endothelial damage was determined. Results: Light microscopic investigations demonstrated that control group sections showed no positivity for Oil red O staining, while carotid bifurcation regions depicted widespread occurrence of intimal lipid accumulations. Scanning electron microscopic examination of control group sections presented regular endothelial topography, while carotid bifurcation region topography exhibited numerous blood cells and separated endothelial cells. Fibrin accumulation on endothelial surface in low area ratios was another important finding in the examination of its endothelial surface degeneration. The above-mentioned morphological findings seemed to be quite parallel to outflow to inflow area ratio data favouring low area and degeneration. Conclusion: The correlation between area ratios and the histological characteristic of cerebral vessels of newborn cadavers indicate that early stages of atherosclerosis began in early embryologic life.Item Preclinical Assessment of Efficacy and Safety Analysis of CAR-T Cells (ISIKOK-19) Targeting CD19-Expressing B-Cells for the First Turkish Academic Clinical Trial with Relapsed/Refractory ALL and NHL Patients(GALENOS YAYINCILIK, 2020-01-01) Tastan, Cihan; Kancagi, Derya Dilek; Turan, Raife Dilek; Yurtsever, Bulut; Cakirsoy, Didem; Abanuz, Selen; Yilanci, Muhammet; Seyis, Utku; Ozer, Samed; Mert, Selin; Kayhan, Cavit Kerem; Tokat, Fatma; Elmas, Merve Acikel; Birdogan, Selcuk; Arbak, Serap; Yalcin, Koray; Sezgin, Aslihan; Kizilkilic, Ebru; Hemsinlioglu, Cansu; Ince, Umit; Ratip, Siret; Ovali, ErcumentObjective: Relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are the focus of studies on hematological cancers. Treatment of these malignancies has undergone recent transformation with the development of new gene therapy and molecular biology techniques, which are safer and well-tolerated therapeutic approaches. The CD19 antigen is the most studied therapeutic target in these hematological cancers. This study reports the results of clinical-grade production, quality control, and in vivo efficacy processes of ISIKOK-19 cells as the first academic clinical trial of CAR-T cells targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey. Materials and Methods: We used a lentiviral vector encoding the CD19 antigen-specific antibody head (FMC63) conjugated with the CD8-CD28-CD3 zetaItem A New Hypothesis on the Frequency Discrimination of the Cochlea(AVES, 2017-01-01) Bulut, Erdogan; Uzun, Cem; Ozturk, Levent; Turan, Pinar; Kanter, Mehmet; Arbak, SerapOBJECTIVE: Medial olivocochlear efferent (MOCE) neurons innervate outer hair cells (OHCs) of the cochlea, which in turn leads to basilar membrane motion. We hypothesized that MOCE-induced alterations in basilar membrane motion, independent of traveling waves, is responsible for the cochlear frequency discrimination of sound. MATERIALS and METHODS: Eleven guinea pigs underwent bilateral otoscopic and audiologic evaluations under general anesthesia. The study comprised two parts. Part I (n=11) included spontaneous otoacoustic emission (SOAE) recordings with or without contralateral pure-tone acoustic stimuli (1 and 8 kHz) at 60 dB sound pressure level (SPL). Part II involved pure-tone (1 or 8 kHz) acoustic trauma in the right ears of two randomly selected subgroups (G1: 1 kHzItem Morphological evaluation of the effects of exercise on high-fat-diet-induced liver damage in rats(AVES, 2020-01-01) Elmas, Merve Acikel; Atay, Nilsu; Ozakpinar, Ozlem Bingol; Arbak, Serap; Kolgazi, Meltem; Sener, Goksel; Ercan, FerihaBackground/Aims: This study was aimed to investigate the protective effects of swimming on nonalcoholic fatty liver disease associated with high-fat-diet-induced obesity using microscopic and biochemical parameters. Materials and Methods: Sprague-Dawley male rats were fed either standard chow (STD groupItem p-Coumaric acid has an ameliorative effect on peptic ulcer: a macroscopic, microscopic and biochemical analysis(MARMARA UNIV, FAC MEDICINE, 2021-01-01) Kolgazi, Meltem; Oztosun, Gulsen; Yalcin, Muge; Unan, Zehra Neslisah; Arsoy, Edanur; Oral, Simge; Cilingir, Sumeyye; Acikel Elmas, Merve; Arbak, SerapObjective: p-Coumaric acid is commonly found in edible plants in nature and is known to be an effective antioxidant. This study aimed to investigate the therapeutic effects of p-coumaric acid on ethanol-induced gastric ulcer model Materials and Methods: After an 18-hour starvation period, the ulcer was induced in male Sprague-Dawley (250-300) rats by intragastric administration of 75\% ethanol. An hour after ulcer induction, p-coumaric acid (250 mg/kg) suspended in 1 ml tween-80 was administered intragastrically. The control and ulcer groups received 1 ml tween-80, One hour later, all rats were euthanized and stomach samples were collected for macroscopic examination, histological evaluation, and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), and glutathione (GSH) levels. Results: Ethanol induction resulted in gastric epithelial and mucosa' injury, increased MPO activity and MDA levelsItem Ameliorating effects of exercise on disrupted epididymal sperm parameters in high fat diet-induced obese rats(MARMARA UNIV, FAC MEDICINE, 2019-01-01) Acikel Elmas, Merve; Arbak, Serap; Ercan, FerihaObjective: Obesity causes male infertility problems and affects the sperm quality. Recent studies have shown that exercise has positive effects on male fertility. The present study aimed to show the effects of swimming exercise on the epididymal sperm number, motility and morphology in hight fat diet (HFD)-induced obese rats. Materials and Methods: Four experimental groups (n=8 in each group) were formed. Standard (STD) and STD+Exercise (STD+EXC) groups were fed with standard rat diet (6\% of calories as fat)