Browsing by Author "Goksel, Tuncay"

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Citation - WoS: 3
Citation - Scopus: 3
Novel Approach Methodologies in Modeling Complex Bioaerosol Exposure in Asthma and Allergic Rhinitis Under Climate Change
(CAMBRIDGE UNIV PRESS, 2025) Esra Atalay-Sahar; Ece Yildiz-Ozturk; Su Ozgur; Arzu Aral; Emre Dayanc; Tuncay Goksel; Ralph Meuwissen; Ozlem Yesil-Celiktas; Ozlem Goksel; Atalay-Sahar, Esra; Dayanc, Emre; Goksel, Tuncay; Aral, Arzu; Ozgur, Su; Yildiz-Ozturk, Ece; Goksel, Ozlem
The undeniable impact of climate change and air pollution on respiratory health has led to increasing cases of asthma allergic rhinitis and other chronic non-communicable immune-mediated upper and lower airway diseases. Natural bioaerosols such as pollen and fungi are essential atmospheric components undergoing significant structural and functional changes due to industrial pollution and atmospheric warming. Pollutants like particulate matter(PMx) polycyclic aromatic hydrocarbons(PAHs) nitrogen dioxide(NO2) sulfur dioxide(SO2) and carbon monoxide(CO) modify the surface and biological properties of atmospheric bioaerosols such as pollen and fungi enhancing their allergenic potentials. As a result sensitized individuals face heightened risks of asthma exacerbation and these alterations likely contribute to the rise in frequency and severity of allergic diseases. NAMs such as precision-cut lung slices(PCLS) air-liquid interface(ALI) cultures and lung-on-a-chip models along with the integration of data from these innovative models with computational models provide better insights into how environmental factors influence asthma and allergic diseases compared to traditional models. These systems simulate the interaction between pollutants and the respiratory system with higher precision helping to better understand the health implications of bioaerosol exposure. Additionally NAMs improve preclinical study outcomes by offering higher throughput reduced costs and greater reproducibility enhancing the translation of data into clinical applications. This review critically evaluates the potential of NAMs in researching airway diseases with a focus on allergy and asthma. It highlights their advantages in studying the increasingly complex structures of bioaerosols under conditions of environmental pollution and climate change while also addressing the existing gaps challenges and limitations of these models.
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.