Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.
Coronaviruses (CoVs) are nonsegmented, single-stranded, positive-sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models. K E Y W O R D S animal model, coronavirus, receptor-binding domain, spike protein, vaccine 1 | INTRODUCTION Coronaviruses (CoVs) are a large family of viruses with some causing mild to moderate illnesses like the common cold and others bringing severe diseases such as Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV). At the end of 2019, emerging infections caused by a novel CoV were reported in Wuhan, China. Most of the early reported cases came from the South China Seafood Wholesale Market in Wuhan, China, which is now closed and disinfected. The virus was identified as a new CoV and officially named by The International Committee on Taxonomy of Viruses as SARS-CoV-2 (previously provisionally named 2019 novel coronavirus or 2019-nCoV by World Health Organization [WHO]), and the disease caused by SARS-CoV-2 received its official name as COVID-19 later on February 11, 2020. 1 As of July 29, 2020, there were 16,341,920 confirmed COVID-19 cases worldwide, including 650,805 deaths. According to the WHO, 226,783 new cases and 4153 new deaths worldwide in the last 24 h. 2 Since the beginning of the new millennium, the rapid emergence and spread of CoVs have caused a grave loss of life and property. One of the most famous examples is the SARS-CoV, which first appeared during the winter of 2002 and caused a viral respiratory illness, namely the SARS. 3,4 The SARS epidemic had serious consequences in 29 regions and countries, with 8096 people being infected worldwide and the mortality rate reaching 9.6%. 5 Later in 2012, the MERS-CoV was first identified in a 60-year-old man who lived in the Kingdom of
Although promising in monitoring low-abundance analytes, most of the DNAzyme walker is only responsive to a specific target. Herein, a universal, ready-to-use platform is developed by coupling nicking-enhanced rolling circle amplification and a self-powered DNAzyme walker (NERSD). It addressed the issues that DNAzyme strands need to be specifically designed for different biosensing system, allowing highly sensitive analysis of various targets with the same DNAzyme walker components. It is also specific owing to target-dependent ligation of the padlock probe and precise cleavage of a substrate by a DNAzyme strand. As typically demonstrated, the strategy has an equivalent capacity with the qRT-PCR kit in distinguishing plasma miR-21 levels of breast cancer patients from normal subjects and is able to differentiate intracellular miR-21 and ATP levels by confocal imaging. The approach characteristic of programmability, flexibility, and generality indicated the potential in all kinds of biosensing and imaging platform.
The role of mast cells in colorectal cancer (CRC) has been an area of intense interest. Mast cell density is closely related to CRC development and prognosis. The identification of mast cell progenitors (MCps) in peripheral blood provides an opportunity to explore the frequency and distribution of mast cells in the circulation and tumour microenvironment of patients with CRC at different disease stages. The aim of the presents study was to investigate the changes of MCps and mast cells in CRC. Flow cytometry was used to measure the circulating frequency of MCps in 37 patients with CRC and 12 healthy control (HC) patients, and the frequency of mast cells in tissue from 15 patients with CRC and 7 patients with haemorrhoids. In the present study, lower levels of circulating MCps in patients with CRC were found, which was significantly related to CRC development. After surgery, the frequency of circulating MCps was significantly increased. However, the frequency of mast cells in tumour tissues was lower than that in adjacent normal tissues and compared with HC tissues and was not associated with CRC progression.
Zika virus (ZIKV) is a neurotropic flavivirus. The outbreak of ZIKV in 2016 created a global health emergency. However, the underlying pathogenic mechanisms remain elusive. We investigated the host response features of in vivo replication in a mouse model of ZIKV infection, by performing a series of transcriptomic and bioinformatic analyses of ZIKV and mock‐infected brain tissue. Tissue damage, inflammatory cells infiltration and high viral replication were observed in the brain tissue of ZIKV infected mice. RNA‐Seq of the brain indicated the activation of ferroptosis pathways. Enrichment analysis of ferroptosis regulators revealed their involvement in pathways such as mineral absorption, fatty acid biosynthesis, fatty acid degradation, PPAR signaling pathway, peroxidase, and adipokinesine signalling pathway. We then identified 12 interacted hub ferroptosis regulators (CYBB, HMOX1, CP, SAT1, TF, SLC39A14, FTL, LPCAT3, FTH1, SLC3A2, TP53, and SLC40A1) that were related to the differential expression of CD8+ T cells, microglia and monocytes. CYBB, HMOX1, SALT, and SLAC40A1 were selected as potential biomarkers of ZIKV infection. Finally, we validated our results using RT‐qPCR and outside available datasets. For the first time, we proposed a possible mechanism of ferroptosis in brain tissue infected by ZIKV in mice and identified the four key ferroptosis regulators.
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