Biology subjects

Stoeckl, J.

Publications and source records attributed to Stoeckl, J..

3 recordsLinked to original sources

bioRxiv2024

Nebulized 2-deoxylated glucose analogues inhibit respiratory viral infection in advanced in vitro airway models

Respiratory viral infections caused by rhinoviruses (RVs), influenza A virus (IAV) and endemic corona viruses (HCoV) result in a serious strain on healthcare systems and public health, underscoring an urgent need for inhaled broad-spectrum antiviral therapies. However, their development is challenging, as no standardized in vitro methodologies that can fully replicate the in vivo environment have been established. In this work, we aimed to investigate the antiviral and anti-inflammatory effect of three 2-deoxylated glucose analogues (2-DGA): 2-deoxy-D-glucose, 2-fluoro-2-dexoy-D-glucose and 2-fluoro-2-dexoy-D-mannose (2-FDM), by utilizing advanced in vitro air-liquid interface (ALI) airway models. We demonstrated that commonly used ALI models have variable susceptibility to RV, IAV and HCoV infection. Further, we showed that 2-DGA have an anti-inflammatory effect and suppress respiratory viral replication in models mimicking the upper and lower respiratory airways. Moreover, we confirmed that 2-DGA can be delivered via nebulization in vitro, highlighting their potential to be used as broad-spectrum inhaled antivirals. Finally, our results demonstrate the importance of incorporating complex in vitro methodologies, such as primary cell ALI cultures and aerosol exposure, at an early stage of drug development.

microbiology↗

bioRxiv2024

Developing and characterising decellularized extracellular matrix hydrogels to bio-fabricate female reproductive tissues

This study investigated the development and characterization of decellularized extracellular matrix (dECM) hydrogels tailored for the bio-fabrication of female reproductive tissues, specifically targeting cortex, endometrium, medulla, and oviduct tissues. We aimed to evaluate the cytocompatibility, biomechanical properties, and overall efficacy of these dECMs in promoting cell viability, proliferation, and differentiation. Our findings revealed that these dECMs exhibited high biocompatibility with embryo development and cell viability, supporting micro vascularization and cellular differentiation without the need for external growth factors. These hydrogels displayed biomechanical properties that closely mimicked native tissues, which was vital for maintaining their functional integrity and supporting cellular activities. The printability assessments showed that dECMs, particularly those from cortex tissues, achieved high precision in replicating the intended structures, though challenges such as low porosity remained. The bioprinted constructs demonstrated robust cell growth, with over 97% viability observed by day 7, indicating their suitability for cell culture. This work represented a significant advancement in reproductive tissue bio-fabrication, demonstrating the potential of dECM-based hydrogels in creating structurally and functionally viable tissue constructs. By tailoring each dECM to match the unique biomechanical properties of different tissues, we paved the way for more effective and reliable applications in reproductive medicine and tissue engineering. HighlightsO_LIDeveloped decellularized extracellular matrix (dECM) bio-inks for bio-fabrication of female reproductive tissues. C_LIO_LIDemonstrated high biocompatibility with embryo development and cell viability. C_LIO_LIAchieved accurate bioprinting, maintaining structural integrity. C_LIO_LIPromoted micro vascularization and cell differentiation without added growth factors. C_LI

bioengineering↗

bioRxiv2022

Host-directed therapy with 2-Deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2

Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways such as glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), we assessed the dose-dependent inhibition of viral replication of minor- and major-receptor group RVs in epithelial cells. 2-DG disrupted RV infection cycle by inhibiting template negative-strand as well as genomic positive-strand RNA synthesis, resulting in less progeny virus and RV-mediated cell death. Assessment of 2-DGs intracellular kinetics revealed that after a short-exposure to 2-DG, the active intermediate, 2-DG6P, is stored intracellularly for several hours. Finally, we confirmed the antiviral effect of 2-DG on pandemic SARS-CoV-2 and showed for the first time that 2-DG also reduces replication of endemic human coronaviruses (HCoVs). These results provide further evidence that 2-DG could be utilized as a broad-spectrum antiviral. HIGHLIGHTSO_LI2-DG inhibits replication of minor- and major-group rhinoviruses in epithelial cells including human nasal epithelial cell. C_LIO_LI2-DG disrupts rhinovirus infection cycle and reduces rhinovirus-mediated cell death in vitro. C_LIO_LI2-DG treatment attenuates viral load of endemic coronaviruses in vitro. C_LI

microbiology↗