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1.
Aging (Albany NY) ; 122021 Jan 10.
Article in English | MEDLINE | ID: covidwho-1022288

ABSTRACT

Both lung adenocarcinoma and coronavirus disease 2019 would cause pulmonary inflammation. Angiotensin-converting enzyme 2, the functional receptor of SARS-CoV-2, also plays a key role in lung adenocarcinoma. To study the risk of SARS-CoV-2 infection in lung adenocarcinoma patients, mRNA and microRNA profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus followed by bioinformatics analysis. A network which regards angiotensin-converting enzyme 2 as the center was structured. In addition, via immunological analysis to explore the essential mechanism of SARS-CoV-2 susceptibility in lung adenocarcinoma. Compared with normal tissue, angiotensin-converting enzyme 2 was increased in lung adenocarcinoma patients. Furthermore, a total of 7 correlated differently expressed mRNAs (ACE2, CXCL9, MMP12, IL6, AZU1, FCN3, HYAL1 and IRAK3) and 5 correlated differently expressed microRNAs (miR-125b-5p, miR-9-5p, miR-130b-5p, miR-381-3p and miR-421) were screened. Interestingly, the most frequent toll-like receptor signaling pathway was enriched by mRNA (interlukin 6) and miRNA (miR-125b-5p) sets simultaneously. In conclusion, it was assumed that miR-125b-5p-ACE2-IL6 axis could alter the risk of SARS-CoV-2 infection in lung adenocarcinoma patients.

2.
Sci Adv ; 2020 Dec 04.
Article in English | MEDLINE | ID: covidwho-960993

ABSTRACT

Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Herein we demonstrated that lungs originated from different types of PF patients including coronavirus disease 2019, systemic sclerosis associated interstitial lung disease and idiopathic pulmonary fibrosis, and mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor ß1 (TGF-ß1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support that MBD2 could be a viable target against pulmonary fibrosis in clinical settings.

3.
Small ; 16(46): e2004237, 2020 11.
Article in English | MEDLINE | ID: covidwho-891902

ABSTRACT

Prevention and intervention methods are urgently needed to curb the global pandemic of coronavirus disease-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Herein, a general pro-antigen strategy for subunit vaccine development based on the reversibly formulated receptor binding domain of SARS-CoV-2 spike protein (S-RBD) is reported. Since the poor lymph node targeting and uptake of S-RBD by antigen-presenting cells prevent effective immune responses, S-RBD protein is formulated into a reversible nanogel (S-RBD-NG), which serves as a pro-antigen with enhanced lymph node targeting and dendritic cell and macrophage accumulation. Synchronized release of S-RBD monomers from the internalized S-RBD-NG pro-antigen triggers more potent immune responses in vivo. In addition, by optimizing the adjuvant used, the potency of S-RBD-NG is further improved, which may provide a generally applicable, safer, and more effective strategy for subunit vaccine development against SARS-CoV-2 as well as other viruses.


Subject(s)
Antigens, Viral/immunology , /prevention & control , Immunity , Nanogels/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Animals , Cell Line , Dendritic Cells/metabolism , Immunization , Lymph Nodes/immunology , Macrophages/metabolism , Mice , Nanogels/ultrastructure , Neutralization Tests , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry
5.
Front. Psychiatry ; (11)20200721.
Article in English | ELSEVIER | ID: covidwho-706101

ABSTRACT

Background: A novel coronavirus (COVID-19) outbreak has occurred in China, and national medical workers have been thrown into this silent battle. Paediatric medical workers have been an important part of this battle and under enormous pressure. This paper evaluates the depression, anxiety, and stress of paediatric medical staff during the epidemic and examines related impact factors. Methods: We conducted this study using online questionnaires via social networking software during the week of Feb. 17 to Feb. 23, 2020. The 21-item Depression Anxiety Stress Scale (DASS), which is a revised, simplified version of the original DASS developed by Lovibond et al., was used in this study. Results: Among all 2,031 respondents, 14.81%, 18.3%, and 9.98% had depression, anxiety and stress symptoms, respectively. Males, doctors, individuals aged between 31‑60 years, those with senior job titles, those who had contact with patients with confirmed or suspected cases of COVID-19, those who worked on the clinical frontlines fighting the epidemic and those who had experience combating similar outbreaks were more likely to have depression, anxiety or stress symptoms. Respondents in Beijing and Chongqing had lower negative psychological symptom scores than the national average. Conclusion: During the COVID-19 outbreak, depression, anxiety and stress are present to varying degrees among paediatric medical workers across the country. Psychological crisis interventions should be implemented to protect the mental health of paediatric medical workers during and after the epidemic.

6.
Genes Dis ; 2020 Apr 14.
Article in English | MEDLINE | ID: covidwho-101703

ABSTRACT

A novel coronavirus appeared in Wuhan, China has led to major outbreaks. Recently, rapid classification of virus species, analysis of genome and screening for effective drugs are the most important tasks. In the present study, through literature review, sequence alignment, ORF identification, motif recognition, secondary and tertiary structure prediction, the whole genome of SARS-CoV-2 were comprehensively analyzed. To find effective drugs, the parameters of binding sites were calculated by SeeSAR. In addition, potential miRNAs were predicted according to RNA base-pairing. After prediction by using NCBI, WebMGA and GeneMark and comparison, a total of 8 credible ORFs were detected. Even the whole genome have great difference with other CoVs, each ORF has high homology with SARS-CoVs (>90%). Furthermore, domain composition in each ORFs was also similar to SARS. In the DrugBank database, only 7 potential drugs were screened based on the sequence search module. Further predicted binding sites between drug and ORFs revealed that 2-(N-Morpholino)-ethanesulfonic acid could bind 1# ORF in 4 different regions ideally. Meanwhile, both benzyl (2-oxopropyl) carbamate and 4-(dimehylamina) benzoic acid have bene demonstrated to inhibit SARS-CoV infection effectively. Interestingly, 2 miRNAs (miR-1307-3p and miR-3613-5p) were predicted to prevent virus replication via targeting 3'-UTR of the genome or as biomarkers. In conclusion, the novel coronavirus may have consanguinity with SARS. Drugs used to treat SARS may also be effective against the novel virus. In addition, altering miRNA expression may become a potential therapeutic schedule.

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