RESUMO
The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.
RESUMO
Objective To investigate the effects of psychological stress on small intestinal bacteria and mucosa in mice, and to explore the relationship between small intestinal disfunction and small intestinal bacteria and mucosa under psychological stress. Methods 48 mice were randomly divided into psychological stress group and control group. An animal model with psychological stress was established lodging the mice and a hungry cat in separate layers of a two-layer cage. D-xylose levels in plasma were measured for estimating the damage degree of small intestinal mucosa. A section of the proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as log10[colony forming units/g]. Results D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (3.02±0.85 mmol/L vs 0.94±0.33 mmol/L,P＜0.01).Psychological stress resulted in quantitative alterations in the aerobes (E. coli). There was an increase in the number of E. coli in the proximal small intestinal flora (1.79±0.27 log10(CFU/g) vs 1.32±0.22 log10(CFU/g),P＜0.01), and there was decrease in relative proportion of Lactobacilli and E. coli of stressed mice (0.52±0.56 vs 1.14±1.07,P＜0.05), while there was no significant difference in the anaerobes(Lactobacilli) between the two groups (2.31±0.63 log10(CFU/g) vs 2.41±0.34 log10(CFU/g) P＞0.05). D-xylose concentrations in plasma was significantly and positively correlated with the number of E. coli in the proximal small intestinal flora (r=0.6713,P＜0.05). Conclusion Small intestinal disfunction under psychological stress may be related to dysbacteriosis and the damage of mucosa.
