Browsing by Author "Yesil-Celiktas, Ozlem"

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Citation - WoS: 7
Citation - Scopus: 7
Organotypic lung tissue culture as a preclinical model to study host- influenza A viral infection: A case for repurposing of nafamostat mesylate
(Elsevier Ltd, 2024) Pelin Saglam-Metiner; Ece Yildiz-Ozturk; Aslı Tetik Vardarlı; Candan Çiçek; Ozlem Keskin Goksel; Tuncay Göksel; Beril Tezcanli; Ozlem Yesil-Celiktas; Yesil-Celiktas, Ozlem; Goksel, Tuncay; Saglam-Metiner, Pelin; Cicek, Candan; Yildiz-Ozturk, Ece; Tetik-Vardarli, Aslı; Goksel, Ozlem
Reliable and effective models for recapitulation of host-pathogen interactions are imperative for the discovery of potential therapeutics. Ex vivo models can fulfill these requirements as the multicellular native environment in the tissue is preserved and be utilized for toxicology vaccine infection and drug efficacy studies due to the presence of immune cells. Drug repurposing involves the identification of new applications for already approved drugs that are not related to the prime medical indication and emerged as a strategy to cope with slow pace of drug discovery due to high costs and necessary phases to reach the patients. Within the scope of the study broad-spectrum serine protease inhibitor nafamostat mesylate was repurposed to inhibit influenza A infection and evaluated by a translational ex vivo organotypic model in which human organ-level responses can be achieved in preclinical safety studies of potential antiviral agents along with in in vitro lung airway culture. The safe doses were determined as 10 µM for in vitro whereas 22 µM for ex vivo to be applied for evaluation of host-pathogen interactions which reduced virus infectivity increased cell/tissue viability and protected total protein content by reducing cell death with the inflammatory response. When the gene expression levels of specific pro-inflammatory anti-inflammatory and cell surface markers involved in antiviral responses were examined the significant inflammatory response represented by highly elevated mRNA gene expression levels of cytokines and chemokines combined with CDH5 downregulated by 5.1-fold supported the antiviral efficacy of NM and usability of ex vivo model as a preclinical infection model. © 2024 Elsevier B.V. All rights reserved.
Citation - WoS: 5
Citation - Scopus: 5
Supercritical CO2 extraction of an immunosuppressant produced by solid-state fermentation
(ELSEVIER SCI LTD, 2018) Ilknur Alpak; Ruhan Askin Uzel; Sayit Sargin; Ozlem Yesil-Celiktas; Uzel, Ruhan Askin; Yesil-Celiktas, Ozlem; Sargin, Sayit; Askin Uzel, Ruhan; Alpak, Ilknur
Mycophenolic acid (MPA) is a secondary metabolite of Penicillium species with diverse biological properties and has clinical applications mainly as an immunosuppressive agent. Production of MPA was carried out using Penicillium brevicompactum (DSM 2215) by solid-state fermentation (SSF). Six different carbon sources (wheat bran rice husk rice bran potato peel and rice husk - rice bran rice bran-potato peel mixture) were examined by SSF in order to obtain the highest yield of mycophenolic acid. Rice bran-potato peel mixture was determined as the best solid substrate and used in scale up studies which was applied in the tray bioreactor. Supercritical CO2 and soxhlet extractions were analyzed for the recovery of MPA from the fermentation broth. The highest recovery (0.47 g MPA/100 g substrate) was obtained by supercritical CO2 at 30 MPa 50 degrees C at a CO2 flow rate of 15 g/min with 10% ethanol as co-solvent for 3 h. The results obtained by the scale-up in bioreactor and optimization of supercritical CO2 entrained with ethanol can provide basis for the production of the immunosuppresant compound on industrial scale.