ABSTRACT
【Objective】 To investigate the effects of miR-126-3p targeting chemokine receptor 1 (CCR1) in exosomes derived from bone marrow mesenchymal stem cells (BMSC) on the proliferation, migration, and invasion of lung cancer cells. 【Methods】 BMSC cells were cultured; exosomes were extracted and identified by the exosomal marker proteins CD63 and TSG101. After exosome culture of A549 cells for different durations (0, 24, 48, and 72 h), cell survival rate was detected by CCK-8, mRNA levels of miR-126-3p and CCR1 were detected by qRT-PCR, and cell migration and invasion abilities were detected by Transwell assay. The relative expressions of CCR1, epithelial cadherin (E-cad), neural cadherin (N-cadherin), and Vimentin were detected by Western blotting. 【Results】 Exosomes had round or oval cup-shaped structures with bright edges and dark middle, with a particle size distribution of about 152 nm, expressing CD63 and TSG101 proteins. The expression of miR-126-3p in exosomes was higher than that in A549 cells. The expression of miR-126-3p was low in A549 cells and that of CCR1 mRNA was high. However, after co-culture with exosomes, the expression of miR-126-3p in A549 cells was increased, while the expression of CCR1 was decreased. A549 cells were cocultured with exosomes for 0, 24, 48, and 72 h. The survival rate, migration and invasion abilities, CCR1 gene and protein expression levels, and N-cad and Vimentin protein expression levels of A549 cells decreased gradually with the extension of culture time. The level of miR-126-3p and the expression of E-cad protein increased gradually with the extension of culture time. 【Conclusion】 The co-culture of exosomes derived from bone marrow mesenchymal stem cells with A549 cells can increase the expression level of miR-126-3p, and miR-126-3p can reduce the proliferation, migration, and invasion of A549 cells by targeting the inhibition of CCR1 expression.
ABSTRACT
The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
ABSTRACT
Objective To systematically investigate the efficacy and safety of sublingual immunotherapy( SLIT) in the treatment of a-dults with seasonal allergic rhinitis( SAR) .Methods Literature was retrieved online in CNKI,CBM,VIP,Wanfang data,PubMed,EMBase, Medline,Cochrane Library,et al.After screening literature,data collection and assessment quality,randomized controlled trials relevant to our study were selected independently based on inclusion and exclusion criteria by two researchers.Statistical analyses were conducted by RevMan 5.2 software.Results A total of 13 RCTs were enrolled.The meta-analysis revealed that SLIT provided a significant improvement in aspect of reducing Symptom Scores(SS) and Medication Scores (MS)of adults with SAR,the difference had statistical significance(P<0.000 01). Compared to placebo,SLIT could increase the rate of adverse events( AEs) in the treatment of adults with SAR compared to placebo.The fre-quently reported AEs during clinical trials were oral pruritus,tongue edema,ear pruritus,throat irritation,et al.Conclusion Sublingual im-munotherapy could improve the symptoms significantly and reduce the SS and MS in the treatment of adults with SAR.And its safety could be well tolerated.
