RESUMEN
COVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using a variety of normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of highly epithelial cells. Notably, infection with SARS-CoV-2 in cancer cell lines, bronchial organoids, and patient nasal epithelium, induces metabolic and transcriptional changes consistent with epithelial to mesenchymal transition (EMT), including upregulation of ZEB1 and AXL, resulting in an increased EMT score. Additionally, a transcriptional loss of genes associated with tight junction function occurs with SARS-CoV-2 infection. The SARS-CoV-2 receptor, ACE2, is repressed by EMT via TGFbeta, ZEB1 overexpression and onset of EGFR TKI inhibitor resistance. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state, associated with a loss of tight junction components with acute respiratory distress syndrome-protective effects. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect. These observations highlight the utility of aerodigestive and, especially, lung cancer model systems in exploring the pathogenesis of SARS-CoV-2 and other respiratory viruses, and offer important insights into the potential mechanisms underlying the morbidity and mortality of COVID-19 in healthy patients and cancer patients alike.
RESUMEN
The purpose of the humanistic spirit of TCM is to focus on the ethics. The key of TCM lies in adhering to and absorbing the essence of Chinese philosophy, which contains speculative thought, life value and meaning from practice. From the perspective of life ethics, the essence of the humanistic spirit of traditional Chinese medicine culture is the highest value of human, mercy from doctors, sincerity of patients, salvation of the people and the world, which is also there flection on the self-aknowlegement, the concept of life and death, the quality of life and the harmonious development of human and nature. The Strategy of Health China encourages the humanistic spirit of TCM from the view of ethics, changing the concept of disease-centered to health-centered with the following main methods: the moral sublimation of doctors self-improvement and striving for perfection, integrity of patients, respect of life and awareness of health, internalization consciousness of life ethics and the atmosphere construction of humanistic spirit of TCM.