ABSTRACT
Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved human bronchial epithelial cells and examined whether they could be used as a model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research. Our hBO contain basal, club, ciliated, and goblet cells. Angiotensin-converting enzyme 2 (ACE2), which is a receptor for SARS-CoV-2, and transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike (S) protein of SARS-CoV-2, were highly expressed. After SARS-CoV-2 infection, not only the intracellular viral genome, but also progeny virus, cytotoxicity, pyknotic cells, and moderate increases of the type I interferon signal could be observed. Treatment with camostat, an inhibitor of TMPRSS2, reduced the viral copy number to 2% of the control group. Furthermore, the gene expression profile in SARS-CoV-2-infected hBO was obtained by performing RNA-seq analysis. In conclusion, we succeeded in generating hBO that can be used for SARS-CoV-2 research and COVID-19 drug discovery. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/115600v2_ufig1.gif" ALT="Figure 1"> View larger version (99K): org.highwire.dtl.DTLVardef@13a6908org.highwire.dtl.DTLVardef@1c59300org.highwire.dtl.DTLVardef@362167org.highwire.dtl.DTLVardef@1cb31ed_HPS_FORMAT_FIGEXP M_FIG C_FIG
ABSTRACT
Botulinum toxin A (BTX-A) was used in adult cerebral palsy patients for chronic pain treatment. Five patients (quadriplegia 3, diplegia 1, and athetosis 1 with an average age of 47) were all classified as GMFCS level IV. As a treatment for neck and trunk muscle pain, BTX-A injections were administered with a total dose below 6 units per kilogram of body weight. To investigate the efficacy of BTX-A, the Visual Analogue Scale and Modified Tsui Scale were used to evaluate the patients before and at regular monthly follow-ups after their injections. We found significant improvement in the Visual Analogue Scale scores at 1 month after initial injection and also found the same difference at the second injection. Also, although we found improvement in the Modified Tsui Scale scores at 1 month after injection, these improvements did not last as long as the Visual Analogue Scale improvements. BTX-A has been used in a growing number of indications for the treatment of muscle spasticity including blepharospasm, facial spasm and spasmodic torticollis. We found that BTX-A may also be useful in treating patients with cerebral palsy suffering from chronic pain.
