Revealing the roles of TLR7, a nucleic acid sensor for COVID-19 in pan-cancer.

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus's nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 (or its causing virus SARS-CoV-2) has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We applied the computational framework in a few databases, including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), lung gene expression data of mice infected with SARS-CoV-2, and the like. As a result, TLR7 expression was found to be higher in the lung of mice infected with SARS-CoV-2 than that in the control group. The analysis in the Opentargets database also confirmed the association between TLR7 and COVID-19. There are also a few exciting findings in cancers. First, the most common type of TLR7 was "Missense" at the genomic level. Second, TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types compared to normal tissues, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with mismatch repair (MMR), microsatellite instability (MSI), and tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Third, abnormal expression of TLR7 could predict the survival of Brain Lower Grade Glioma (LGG), Lung adenocarcinoma (LUAD), Skin Cutaneous Melanoma (SKCM), Stomach adenocarcinoma (STAD), and Testicular Germ Cell Tumors (TGCT) patients, respectively. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Study on component-target-pathway multiple interactive network to reveal mechanism of Houttuynia cordata in treatment

Objective: To analyze the molecular biological mechanism of Houttuynia cordata in treatment of viral pneumonia based on network pharmacology, and to evaluate its feasibility in prevention and treatment of Corona Virus Disease 2019 (COVID-19).

Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor.

Introduction: In December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum. Methods: Using TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58. Results: The expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was "mutation." In the protein-protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE-821, Itraconazole, JNJ-42756493, IWR-1, and Linsitinib. Discussion: In conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.

Protective Effect of Fluorofenidone Against Acute Lung Injury Through Suppressing the MAPK/NF-κB Pathway

Acute lung injury (ALI) is a severe disease that presents serious damage and excessive inflammation in lungs with high mortality without effective pharmacological therapy. Fluorofenidone (AKFPD) is a novel pyridone agent that has anti-fibrosis, anti-inflammation, and other pharmacological activities, while the effect of fluorofenidone on ALI is unclarified. Here, we elucidated the protective effects and underlying mechanism of fluorofenidone on lipopolysaccharide (LPS)-induced ALI. In this study, fluorofenidone alleviated lung tissue structure injury and reduced mortality, decreased the pulmonary inflammatory cell accumulation and level of inflammatory cytokines IL-1β, IL-6, and TNF-α in the bronchoalveolar lavage fluid, and attenuated pulmonary apoptosis in LPS-induced ALI mice. Moreover, fluorofenidone could block LPS-activated phosphorylation of ERK, JNK, and P38 and further inhibited the phosphorylation of IκB and P65. These results suggested that fluorofenidone can significantly contrast LPS-induced ALI through suppressing the activation of the MAPK/NF-κB signaling pathway, which indicates that fluorofenidone could be considered as a novel therapeutic candidate for ALI.

Characteristics of Angiotensin I-converting enzyme 2, type II transmembrane serine protease 2 and 4 in tree shrew indicate it as a potential animal model for SARS-CoV-2 infection.

Angiotensin I-converting enzyme 2 (ACE2), type II transmembrane serine protease 2 and 4 (TMPRSS2 and TMPRSS4) are important receptors for SARS-CoV-2 infection. In this study, the full-length tree shrewACE2 gene was cloned and sequenced, and its biological information was analyzed. The expression levels of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs of the tree shrew were detected. The results showed that the full-length ACE2 gene in tree shrews was 2,786 bp, and its CDS was 2,418 bp, encoding 805 amino acids. Phylogenetic analysis based on the CDS of ACE2 revealed that tree shrews were more similar to rabbits (85.93%) and humans (85.47%) but far from mice (82.81%) and rats (82.58%). In silico analysis according to the binding site of SARS-CoV-2 with the ACE2 receptor of different species predicted that tree shrews had potential SARS-CoV-2 infection possibility, which was similar to that of rabbits, cats and dogs but significantly higher than that of mice and rats. In addition, various tissues or organs of tree shrews expressed ACE2, TMPRSS2 and TMPRSS4. Among them, the kidney most highly expressed ACE2, followed by the lung and liver. The esophagus, lung, liver, intestine and kidney had relatively high expression levels of TMPRSS2 and TMPRSS4. In general, we reported for the first time the expression of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs in tree shrews. Our results revealed that tree shrews could be used as a potential animal model to study the mechanism underlying SARS-CoV-2 infection.

A Retrospective Cohort Study on the Clinical Course of Patients With Moderate-Type COVID-19.

Background: A large number of people contracted moderate-type COVID-19 around the world. However, to our knowledge no studies have covered the clinical course of patients with moderate-type COVID-19. This study describes the clinical course of moderate-type patients with COVID-19 from Wuhan City and Yiyang City, and explores factors relevant to the length of hospitalization and symptoms relief. Methods: The study analyzed the clinical course of 107 moderate-type patients with COVID-19 from the outbreak area (Wuhan) and the imported area (Yiyang), and used automatic linear modeling and multivariate linear regression analysis to explore the factors relevant to the length of hospitalization and symptoms relief. Furthermore, we created a scoring system to value the length of hospitalization and symptoms relief. Results: Lymphopenia, elevated C-reactive protein, increased LDH, bilateral lung GGO (ground glass opacity), and lung consolidation were more likely to appear in ordinary inpatients with moderate-type COVID-19 from Wuhan (P < 0.05), compared to infected medical staff from Wuhan and ordinary inpatients with moderate-type COVID-19 from Yiyang. Meanwhile, the length of hospitalization and symptoms relief was longer in ordinary patients with moderate-type COVID-19 from Wuhan (P < 0.05). Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO were linearly related to the length of hospitalization (P < 0.05); onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation were linearly related to the length of symptoms relief (P < 0.05). By using the scoring system, we found that the time of hospitalization and symptoms relief lengthened as the scores increased. Conclusions: This study described the clinical course of patients with moderate-type COVID-19, and found that ordinary patients with moderate-type COVID-19 in outbreak areas were more serious and needed stronger treatment and longer treatment time. Onset of symptoms to admission, ESR, leucocytes count, and bilateral lung GGO can be effective predictors of the length of hospitalization. And onset of symptoms to admission, leucocytes count, bilateral lung GGO, and lung consolidation can be effective predictors of the amount of time until symptoms relief. Most importantly, we have created a scoring system, which could contribute to the diagnosis and treatment of COVID-19.

COVID-19 in a patient with long-term use of glucocorticoids: A study of a familial cluster.

Clusters of patients with novel coronavirus disease 2019 (COVID-19) have been successively reported globally. Studies show clear person-to-person transmission. The average incubation period is 2-14 days, and mostly 3-7 days. However, in some patients, this period may be longer. Here, we report a familial cluster of COVID-19 where a 47-year-old woman with long-term use of glucocorticoids did not develop any symptoms within the 14-day quarantine period but was confirmed with COVID-19 by tested positive of antibody on day 40 after she left Wuhan. Almost at the same time, her father and sister were diagnosed with COVID-19. The results suggest that the long-term use of glucocorticoids might cause atypical infections, a long incubation period, and extra transmission of COVID-19.