Han, H. W. | Search bioRxiv

bioRxiv2020

Generation of tonsil organoids as an ex vivo model for SARS-CoV-2 infection

Palatine tonsil (hereinafter referred to as "tonsil") plays role in the immune systems first line of defense against foreign pathogens. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic since the infection was first reported in China in December 2019. The aim of this study was to establish tonsil epithelial cell-derived organoids and to examine their feasibility as an ex vivo model for SARS-CoV-2 infection. Using an optimized protocol, we achieved 3D tonsil organoid culture from human tonsil tissue that reflects the distinctive characteristics of the tonsil epithelium, such as its cellular composition, histologic properties, and molecular biological features. Notably, we verified that SARS-CoV-2 can infect tonsil organoids with a robust replication efficiency. Furthermore, treatment with remdesivir, an antiviral agent, effectively protected them from viral infection. Therefore, tonsil organoids could be available for investigation of SARS-CoV-2 infection-mediated pathology and for preclinical screening of novel antiviral drug candidates. One-sentence SummaryThis study established tonsil epithelial cell-derived organoids and demonstrated their feasibility as an ex vivo model for SARS-CoV-2 infection.

microbiology↗

bioRxiv2019

Natural naphthoquinones isolated from Lithospermum erythrorhizon suppress dextran sulfate sodium-induced murine experimental colitis

The purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1{beta} and TNF-), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-{kappa}B signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-{kappa}B to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).

biochemistry↗