ABSTRACT
Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
Subject(s)
Animals , Mice , Inflammation , NF-kappa B/metabolism , Particulate Matter/toxicity , Signal Transduction , Sirtuin 2/metabolism , Transcription Factor RelA/metabolismABSTRACT
Objective:To investigate the effect of intercellular adhesion molecule-1 (ICAM1) targeted miR-133a-5p on lipopolysaccharide (LPS)-induced alveolar epithelial A549 cell injury.Methods:Dual lucife-rase reporter assay was used to verify the ICAM1 targeted effect of miR-133a-5p.A549 cells were induced by LPS in vitro and divided into the control group, LPS group, LPS+ negative control(miR-NC) group, LPS+ miR-133a-5p group, LPS+ small interfering RNA(si)-NC group, and LPS+ si-ICAM1 group.The expression levels of miR-133a-5p and ICAM1 mRNA were detected by real-time fluorescent quantitative PCR.Apoptosis was detected by flow cytometry.The expression levels of ICAM1, Bcl-2, Bax and cleaved caspase-3 protein that could activate cysteine were detected by Western blot.The expression levels of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were detected by enzyme linked immunosorbent assay kit. Results:Compared with the control group, the LPS group had a decreased expression level of miR-133a-5p (0.39±0.04 vs.1.00±0.09) in A549 cells, increased expression of ICAM1 (0.86±0.08 vs.0.39±0.03), an increased apoptotic rate [(27.65±2.47)% vs.(8.13±0.89)%], and increased secretion of IL-6 [(624.59 ± 51.42) ng/L vs.(194.25±18.43) ng/L] and TNF-α [(548.35±51.42) ng/L vs.(174.26±19.43) ng/L]. The differences were significant (all P<0.05). Compared with the LPS+ miR-NC group, the apoptosis rate of A549 cells [(13.46±1.38)% vs.(28.71±2.54)%] in LPS+ miR-133a-5p group were significantly decreased, and the secretion of IL-6 [(296.43±23.51) ng/L vs.(635.86±55.41) ng/L] and TNF-α [(321.14±30.56) ng/L vs.(563.24±49.52) ng/L] was significantly decreased (all P<0.05). Compared with LPS+ si-NC group, the apoptosis rate of A549 cells [(13.65±1.64)% vs.(23.51±2.33)%] in LPS+ si-ICAM1 group was significantly decreased, and the secretion of IL-6 [(324.15±29.41) ng/L vs.(625.39±52.59) ng/L] and TNF-α [(334.65±20.46) ng/L vs.(534.97±51.42) ng/L] were significantly decreased (all P<0.05). Conclusions:miR-133a-5p can alleviate LPS-induced alveolar epithelial cell injury, and the mechanism may be related to down-regulation of ICAM1 expression.
ABSTRACT
Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases.Recently, children′s NCP cases have gradually increased, and children′s fever outpatient department has become the first strategic pass to stop the epidemic.Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection.This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities.The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period.
ABSTRACT
Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children′s NCP cases have gradually increased, and children′s fever outpatient department has become the first strategic pass to stop the epidemic. Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis; triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children′s fever in outpatient department during the novel coronavirus pneumonia epidemic period.
ABSTRACT
Objective To investigate the prevalent feature of children with Mycoplasma pneumoniae (MP) infection in Xi'an region from Jan.2015 to Dec.2016.Methods From Jan.2015 to Dec.2016,9 648 cases with acute lower respiratory tract infection in xijing hospital were given serum test of the antibody of Mycoplasma pneumoniae by ELISA.Results A total of 9 648 cases with lower respiratory tract infection in children in xijing hospital received MP antibody detection,the positive cases were 2 971,the total positive rate was 30.79 ％.MP-IgM antibody positive rates between different age groups had significant differences,in which infants' group has the lowest(7.00 ％),and with the age growing,the positive rate increased.The positive rates in different age groups of toddler,preschool age,and school age were 27.29 ％,36.10 ％ and 37.76 ％ respec tively.The positive rates of MP-IgM antibody in different quarter were different.The highest antibody positive rate was found in the first quarter (January-March),followed by the fourth quarter,the third quarter and the second quarter.The difference was statistically significant (P＜0.01).Conclusion There was MP infection prevalence in Xi'an from 2015 to 2016.The positive rate in children increased with the age,the peak of infection was in the first quarter,so the detection and prevention of MP should be strengthened at that time of the year.