MiR-146b protects against the inflammation injury in pediatric pneumonia through MyD88/NF-κB signaling pathway.
- 作者列表："Zhang L","Dong L","Tang Y","Li M","Zhang M
:Background: Pneumonia is a common respiratory disease worldwide that can be prevented and treated. However, it is considered to be the leading cause of children death. The present study was aimed to explore the functional role and molecular mechanism of miR-146b in the inflammation injury in pediatric pneumonia.Materials and methods: The lipopolysaccharide (LPS)-induced pulmonary injury cell model was established in WI-38 human lung fibroblasts cells. QRT-PCR and Western blot was applied to detect miR-146b and MyD88 expression. ELISA assay was used to analyze the production of pro-inflammatory factors. Cell viability was evaluated by CCK-8 assay. The apoptosis proteins and the downstream genes of NF-κB pathway were detected by Western blot.Results: we displayed that miR-146b was down-regulated, whereas MyD88 was up-regulated in the serum of children patients with pneumonia and in WI-38 cells treated with LPS. Moreover, re-expression of miR-146b suppressed the production of inflammatory factors in the serum of pneumonia patients and WI-38 cells treated with LPS. In addition, elevating miR-146b expression increased WI-38 cell viability and reduced cell apoptosis. More importantly, bioinformatics analysis revealed that MyD88 was a target of miR-146b and could overturn the protective effect of miR-146b on the inflammation injury in LPS-injured WI-38 cells. Furthermore, miR-146b over-expression inhibited the activation of NF-κB signaling pathway by suppressing MyD88.Conclusion: miR-146b attenuated the inflammation injury in pediatric pneumonia through inhibiting MyD88/NF-κB signaling pathway. These preliminarily findings further deepened our understanding of this mechanism and identified new potential therapeutic targets for pediatric pneumonia.
背景: 肺炎是世界范围内常见的可预防和治疗的呼吸系统疾病。然而，它被认为是儿童死亡的主要原因。本研究旨在探讨miR-146b在小儿肺炎炎症损伤中的作用及分子机制。材料与方法: 建立人肺成纤维细胞脂多糖 (LPS) 诱导WI-38 肺损伤模型。应用QRT-PCR和Western blot检测miR-146b和MyD88 的表达。ELISA法分析促炎因子的产生。通过CCK-8 试验评价细胞活力。Western blot检测细胞凋亡蛋白及NF-κ b通路下游基因。结果: 显示miR-146b表达下调，而MyD88 上调血清患儿肺炎和WI-38 细胞脂多糖 (LPS).此外，miR-146b的重新表达抑制了肺炎患者血清和LPS处理WI-38 细胞中炎症因子的产生。此外，提高miR-146b表达增加WI-38 细胞活力和减少细胞凋亡。更重要的是，生物信息学分析发现MyD88 是miR-146b的靶点，可以推翻miR-146b对LPS损伤WI-38 细胞炎症损伤的保护作用。此外，miR-146b过表达通过抑制MyD88 抑制NF-κ b信号通路的激活。结论: miR-146b通过抑制MyD88/NF-κ b信号通路减轻小儿肺炎的炎症损伤。这些初步发现进一步加深了我们对这一机制的理解，并确定了小儿肺炎新的潜在治疗靶点。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.