Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

Single-cell RNA profiling of ACE2, the SARS-CoV-2 receptor, had proposed multiple tissue cells as the potential targets of SARS-CoV-2, the novel coronavirus causing the COVID-19 pandemic. However, most were not echoed by the patients clinical manifestations, largely due to the lack of protein expression information of ACE2 and co-factors. Here, we incorporated the protein information to analyse the expression of ACE2, together with TMPRSS2 and Furin, two proteases assisting SARS-CoV-2 infection, at single cell level in situ, which we called protein-proofed single-cell RNA (pscRNA) profiling. Systemic analysis across 36 tissues revealed a rank list of candidate cells potentially vulnerable to SARS-CoV-2. The top targets are lung AT2 cells and macrophages, then cardiomyocytes and adrenal gland stromal cells, followed by stromal cells in testis, ovary and thyroid. Whereas, the polarized kidney proximal tubule cells, liver cholangiocytes and intestinal enterocytes are less likely to be the primary SARS-CoV-2 targets as ACE2 localizes at the apical region of cells, where the viruses may not readily reach. Actually, the stomach may constitute a physical barrier against SARS-CoV-2 as the acidic environment in normal stomach (pH < 2.0) could completely inactivate SARS-CoV-2 pseudo-viruses. These findings are in concert with the clinical characteristics of prominent lung symptoms, frequent heart injury, and uncommon intestinal symptoms and acute kidney injury. Together, we provide a comprehensive view on the potential SARS-CoV-2 targets by pscRNA profiling, and propose that, in addition to acute respiratory distress syndrome, attentions should also be paid to the potential injuries in cardiovascular, endocrine and reproductive systems during the treatment of COVID-19 patients.

Expression and clinical significance of endostatin and angiostatin in pterygium / 中国基层医药

Objective:To investigate the expression and clinical significance of endostatin (ES) and angiostatin (AS) in pterygium.Methods:From January 2016 to December 2018, 60 cases (60 eyes) of pterygium tissue and 60 cases (60 eyes) of normal human conjunctival tissue were selected from the eye surgery of Traditional Chinese Medicine Hospital of Yiwu.HE staining was used to observe the morphological changes of pterygium and normal conjunctival tissue.Western blot was used to measure ES and AS protein levels in the tissues of pterygium group and control group.Results:HE staining showed that in the normal bulbar conjunctival tissue, the stromal layer was connective tissue and the epithelial layer was columnar epithelium; in the pterygium, the basal layer had a large number of new blood vessels, fibroblasts, collagen fibers, and inflammatory cells infiltrated around the blood vessels; the epithelium showed different degrees of hyperplasia.The protein levels of ES and AS in pterygium tissues[(0.35±0.12), (0.62±0.17)] were higher than those in the control group [(0.13±0.08), (0.16±0.09)]( t=11.816, 18.524, P=0.000, 0.000). The protein levels of ES and AS in the pterygium tissues of the recurrent group [(0.63±0.15), (0.87±0.21)] were higher than those in the initial group [(0.22±0.11), (0.45±0.16)]( t=17.073, 12.323, P=0.000, 0.000). There was positive correlation between ES and AS in pterygium ( r=0.571, P=0.000). Conclusion:The levels of ES and AS in pterygium tissue are increased, and ES and AS may be involved in the occurrence and recurrence of pterygium.

UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis solution of adjuvant arthritis rats: Application to geniposide pharmacodynamic study.

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P. Therefore, S1P can also be potentially used as a pharmacodynamic marker to study adjuvant arthritis (AA) rats. In the current study, a UHPLC-MS/MS method combined with the microdialysis sampling technique (using FTY720 phosphate as an internal standard) was adopted and validated to measure S1P levels in the hemodialysis fluid and joint cavity dialysates of AA rats after oral administration of GE. A S1P concentration-time curve in the dialysate was established in this study. It was demonstrated that GE exerted an anti-inflammatory effect by reducing AA-induced elevated S1P levels. It is showed that changes in S1P concentrations over time can be used to monitor the pharmacodynamic effects of GE in treating AA rats in pharmacodynamic studies.

Effects of sphingosine-1-phosphate andits receptors on angiogenesis in autoimmune diseases / 中国药理学通报

Sphingosine-1-phosphate(S1P) is an important bioactive lipid produced from cell membrane sphingomyelin metabolism process.S1P and cell membrane surface S1P receptors(S1PR1-5) are G protein coupled receptors(GPCRs), which influence the formation of new blood vessels in the immune system via combining the related inflammatory signaling pathway.This review describes briefly the effects of S1P and S1PRs on autoimmune disease angiogenesis through intracellular signal transduction, such as rheumatoid arthritis, multiple sclerosis, colitis, systemic lupus erythematosus.Further research will be a new therapeutic target on vascular inflammation of autoimmune diseases.

Correlation analysis of human papilloma virus 16/18 infection and the expression of Rb and p16 protein in bladder cancer tissue / 国际检验医学杂志

Objective To investigate the correlation between human papilloma virus(HPV) 16/18 infection and the expression of Rb and p16 protein in bladder cancer tissue,and to analyze the relationship between HPV infection and the incidence of bladder cancer.Methods The expression of HPV16/18 E6 and E7 gene encoded protein,RB and p16 were detected by immunohistochemical method in 40 cases of bladder cancer and 40 cases of normal bladder tissues,and the correlation between them and pathological grading,stage of international union of cancer(UICC),whether recurrence or not after receiving surgery was analyzed.Results In bladder cancer tissues,HPV16/18 E6 and E7 gene encoded protein,RB and p16 positive rates were 65%,47.5%,42.5%,compared with the positive rate of normal bladder tissue samples(22.5%,92.5%,87.5%),the differences were statistically significant(P0.05).The expression of HPV16/18 E6 and E7 gene encoded protein and Rb,p16 protein were not significantly correlated(P>0.05),The expression of Rb and p16 protein were negatively correlated(P<0.05).Conclusion HPV 16/18 infection is related to the occurrence and development of bladder cancer,but its mechanism might not be related to the abnormal expression of Rb and p16 protein.