Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1β (IL-1β), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1β exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1β expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1β expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1β expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1β expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1β expression. Moreover, ultravioletinactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1β. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1β expression. Moreover, NLRP3/ caspase-1 was involved in GM RNA-induced IL-1β expression. Thus, our study elucidated the critical role of IL-1β in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1β via anti-IL-1β neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1β expression via NLRP3/caspase-1. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'
Purpose. To elucidate the microRNAs existent in exosomes derived from stored red blood cell (RBC) unit and their potential function. Materials and Methods. Exosomes were isolated from the supernatant derived from stored RBC units by sequential centrifugation. Isolated exosomes were characterized by TEM (transmission electron microscopy), western blotting, and DLS (dynamic light scattering). MicroRNA (miRNA) microarray was performed to detect the expression of miRNAs in 3 exosome samples. Results revealed miRNAs that were simultaneously expressed in the 3 exosome samples and were previously reported to exist in mature RBCs. Functions and potential pathways of some detected miRNAs were illustrated by bioinformatic analysis. Validation of the top 3 abundant miRNAs was carried out by qRT-PCR (quantitative reverse transcription‐polymerase chain reaction). Results. TEM and DLS revealed the mean size of the exosomes (RBC-derived) as 64.08 nm. These exosomes exhibited higher abundance of short RNA than the long RNA. 78 miRNAs were simultaneously detected in 3 exosome samples and mature RBCs. Several biological processes might be impacted by these miRNAs, through their target gene(s) enriched in a particular signalling pathway. The top 3 (abundant) miRNAs detected were as follows: miR-125b-5p, miR-4454, and miR-451a. qRT-PCR revealed higher abundance of miR-451a than others. Only miR-4454 and miR-451a abundance tended to increase with increasing storage time. Conclusion. Exosomes derived from stored RBC units possessed multiple miRNAs and, hence, could serve various functions. The function of exosomes (RBC-derived) might be implemented partly by the predominantly enriched miR-451a.
Imported COVID-19 cases pose new challenges for ChinaDear editor , Recently, a letter in your journal predicted the trend of the spread of the novel coronavirus disease 2019 in China, an illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1 , 2 would end after March 20, 2020. 3 Currently, the COVID-19 has spread around the globe, with the center of the epidemic shifting from China to Europe and the United States. 4 As of March 24, 2020, a total of 372,757 cases have been confirmed worldwide, with a death toll of 16,231 (WHO, Coronavirus disease 2019 Situation Report 64, March 24, 2020). Italy, in particular, had thus far diagnosed 63,927 patients, 6077 of whom had lost their lives. That translates to a mortality rate of 9.51%, which is more than twice as high as that of China's 4.02% (3283/81,747). The greater share of elderly patients with confirmed COVID-19 infection in Italy along with the population's significantly higher median age may partly explain the differences in cases and case-fatality rates between the two nations. 5 Countries such as the United States (42,164 cases), Spain (33,089 cases), Germany (29,212 cases), and France (19,615 cases) have seen an explosive increase in confirmed cases, with the rate of growth showing no hint of slowing down.For China-the initial epicenter of the outbreak-two stages of the epidemic have passed ( Fig. 1 A). The first stage is the outbreak period (December 31, 2019 to February 29, 2020), which entailed the period from the first detection of cases to the peak of the epidemic which saw a rapid increase in the number of confirmed cases, and to the time when the growth rate slowed down to less than 200 new confirmed cases per day. In the second stage, which lasted from March 1, 2020 to March 21, 2020, the number of existing cases in most Chinese provinces was reduced to less than 10, respectively, whilst the number of newly confirmed cases in Wuhan, Hubei province, the worst-hit city, was slowly approaching zero. It was during this stage-more specifically on the March 4-that foreign imported cases to appear. During these two stages, the Chinese government, its populous, and its medical professionals had managed to stabilized the deadly epidemic with great deliberation and sacrifices. 6 Currently, however, the situation in China has entered its third stage-recontamination through close contact with foreign infection, as demonstrated by the emergence of second-generation case originated from imported cases first reported in Guangzhou, Guangdong province on March 22, 2020 ( Fig. 1 B). As of March 24, 2020, there were 427 imported cases and 3 second-generation cases originated from imported cases, one each in Beijing, Shanghai and Guangzhou (National Health Commission of the People's Republic of China). It shows that China needs to pay more attention to the control of imported cases and reflect on the measures previously taken against imported cases.
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