Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(...Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.展开更多
Maintaining participants in a trial ultimately without dropout helps keep a study on track,saving time,money,and resources.Since 2015,extensive bioequivalence(BE)studies have been carried out in China,while no researc...Maintaining participants in a trial ultimately without dropout helps keep a study on track,saving time,money,and resources.Since 2015,extensive bioequivalence(BE)studies have been carried out in China,while no research about dropout in healthy volunteers has been reported yet.In this retrospective study,1078 healthy volunteers participating in 18 BE studies from March 2016 to February 2019 in one Chinese hospital were included.Information about the healthy participants and BE studies was recorded for analysis.In terms of the dropout reason,poor compliance,adverse event(AE),and loss of follow-up were found to be the three leading causes of dropout,accounting for 78.7%of all dropouts.In terms of associated factors with active dropout,smoking habit(OR=5.790,P<0.001)was significantly associated with increased risk of active dropout,while older age(OR=0.940,P=0.042)and AE except for SAE(OR=0.321,P=0.004)were significantly associated with a decreased risk of active dropout.Strengthening the education on younger participants and participants with a smoking habit,as well as emphasizing the possible adverse reactions and potential risks,might be strategies to reduce active dropout in healthy participants.展开更多
基金supported by the National Natural Science Foundation of China (21777100, 81803267)。
文摘Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.
基金National Major Scientific and Technological Special Project for Significant New Drugs Development(Grant No.2017ZX09304022)。
文摘Maintaining participants in a trial ultimately without dropout helps keep a study on track,saving time,money,and resources.Since 2015,extensive bioequivalence(BE)studies have been carried out in China,while no research about dropout in healthy volunteers has been reported yet.In this retrospective study,1078 healthy volunteers participating in 18 BE studies from March 2016 to February 2019 in one Chinese hospital were included.Information about the healthy participants and BE studies was recorded for analysis.In terms of the dropout reason,poor compliance,adverse event(AE),and loss of follow-up were found to be the three leading causes of dropout,accounting for 78.7%of all dropouts.In terms of associated factors with active dropout,smoking habit(OR=5.790,P<0.001)was significantly associated with increased risk of active dropout,while older age(OR=0.940,P=0.042)and AE except for SAE(OR=0.321,P=0.004)were significantly associated with a decreased risk of active dropout.Strengthening the education on younger participants and participants with a smoking habit,as well as emphasizing the possible adverse reactions and potential risks,might be strategies to reduce active dropout in healthy participants.
