1 Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in 3 Hubei province of China and has draw significant public health attention. The same as 4 severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into 5 host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to 6 dissect the ACE2-expressing cell composition and proportion and explore a potential 7 route of the 2019-nCov infection in digestive system infection, 4 datasets with 8 single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed.9
ObjectiveSince December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.DesignFive datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.ResultsCell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.ConclusionThis study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.
Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an "Off−On" release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.
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