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Item Platelet proteome changes in dogs with congestive heart failure(BMC, 2020-01-01) Levent, Pinar; Kocaturk, Meric; Akgun, Emel; Saril, Ahmet; Cevik, Ozge; Baykal, Ahmet Tarik; Tanaka, Ryou; Ceron, Jose Joaquin; Yilmaz, ZekiBackgroundPlatelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in congestive heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n =10) and dogs with acute CHF due to myxomatous mitral valve disease (MMVD, n=10) were used. Acute CHF was defined based on the clinical (increased respiratory rate or difficulty breathing) and radiographic findings of pulmonary edema. Dogs Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris.ResultsTotally 104 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in acute CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in acute CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses.ConclusionThis study describes by first time the changes in the protein composition in platelets of dogs with acute CHF due to MMVD. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF caused by MMVD and could be a tool for further investigations about the prevention and treatment of this disease.Item Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression(WILEY, 2020-01-01) Sahan, Ahmet; Akbal, Cem; Tavukcu, Hasan Huseyin; Cevik, Ozge; Cetinel, Sule; Sekerci, Cagri Akin; Sener, Tarik Emre; Sener, Goksel; Tanidir, YilorenA review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg(-1) day(-1)) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.Item Tumor necrosis factor-alpha induced caspase-3 activation-related iNOS gene expression in ADP-activated platelets(TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2017-01-01) Cevik, Ozge; Adiguzel, Zelal; Baykal, Ahmet Tarik; Sener, AzizePlatelets are sensitive cells and are easily activated by different stimulants in the circulation system. It is known that tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and plays a role in inflammation. The role of TNF-a in the apoptotic process in blood platelets is unknown. In order to study the formation of apoptosis in platelets after incubation with TNF-alpha and/or ADP, several biomarkers were chosen: phosphatidylserine (PS) exposure and P-selectin bindingItem Platelets Proteomic Profiles of Acute Ischemic Stroke Patients(PUBLIC LIBRARY SCIENCE, 2016-01-01) Cevik, Ozge; Baykal, Ahmet Tarik; Sener, AzizePlatelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.Item Treatment of glioblastoma by photodynamic therapy with the aid of synthesized silver nanoparticles by green chemistry from Citrus aurantium(MARMARA UNIV, 2021-01-01) Erdogan, Omer; Abbak, Muruvvet; Demirbolat, Gulen Melike; Aksel, Mehran; Pasa, Salih; Donmez Yalcin, Gizem; Cevik, OzgeBlood brain barrier is very important to provide treatment locally for the treatment of glioblastoma. The use of nanoparticles has shown promise for glioblastoma treatments in recent years. In this study, the effect of the combined treatment of silver nanoparticles (AgNPs) synthesized from Citrus aurantium with photodynamic therapy (PDT) was investigated on U87 glioblastoma cells. AgNPs were characterized by FTIR, zeta potential and SEM images. U87 cells were treated with AgNPs (10 mu g/mL) and/or PDT (0.5 mJ/cm(2)) at 24 h. Cells antiproliferative effect, migration levels, colony formation capability, Bax and Bcl-2 protein/gene expression, and caspase-3 activity levels as apoptotic markers were measured. AgNPs size were found at 141 +/- 3 nm and 18.1 +/- 1.3 mV as zeta potential. It was found that cell proliferation, migration and Bcl-2 protein/gene levels decreased, and Bax protein/ gene levels and caspase-3 activity increased via AgNPs and PDT combined treatment. As a result, nanoparticles synthesized from Citrus aurantium are eco-friendly and their size can cross the blood brain barrier. If AgNPs is used with PDT, it may be a new therapy for clinically treatment of glioblastoma in the future.Item Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel(PUBLIC LIBRARY SCIENCE, 2022-01-01) Abas, Burcin Irem; Demirbolat, Gulen Melike; Cevik, OzgeMesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-beta, SMAD, Snail, Slug, beta-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.Item PEG4000 modified liposomes enhance the solubility of quercetin and improve the liposome functionality: in vitro characterization and the cellular efficacy(Scientific and Technological Research Council Turkey, 2022-01-01) Demirbolat, Gulen Melike; Erdogan, Omer; Coskun, Goknil Pelin; Cevik, OzgeQuercetin, a multifunctional therapeutic agent, is used in various types of cancer. However, its therapeutic effect is limited by virtue of poorly aqueous solubility and instability in the physiological medium. To overcome these limitations, we aimed (i) to design quercetin loaded Liposomes with unlinked-PEG4000 with regard to not only surface modification but also solubility enhancement, and (ii) to investigate the antineoplastic effects on HeLa cells. PEG4000 increased the quercetin solubility 2.2 fold. PEG4000 modified Liposomes displayed small particle size (254 +/- 69 nm), low polydispersity index (0.236 +/- 0.018), favorable zeta potential (-35.4 +/- 0.6 mV), high quercetin encapsulation efficiency (87.6 +/- 5.6\%), and drug loading (22.2 +/- 6.9\%). The homogeneity and particle size of stable PEGylated liposomes were proved by transmission electron microscopy. The drug release was reached up to 65.1 +/- 3.8\% in 6 h. The IC50 value of quercetin loaded PEGylated liposomes was 16.3 mu g/mL on HeLa cells, while that of quercetin was 88.3 mu g/mL. PEGylated liposomes remarkably hampered the adherence and colony formation ability of cells according to crystal violet staining tests. The convenience of PEGylated liposomes for the parenteral application was stated by the hemolysis assay. The high-throughput screening assays based on AO/PI staining proved the drastic decrease of viable cell count. Moreover, qPCR tests based on gene expression levels revealed that the quercetin loaded PEGylated liposomes treatment could be more effective than free quercetin on the mitochondrial apoptosis of lieLa cells. These promising results allow considering further in vivo studies for efficient cancer treatment with quercetin loaded PEG4000 modified liposomes.