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An in-depth understanding of the relevant cell types and mechanisms of lung regeneration has an important positive effect on the prevention and treatment of lung diseases.This review summarizes the recent advances in the classification, characteristics, and mechanisms of self-renewal and differentiation of lung epithelial stem cells.Lung epithelial stem cells include basal cells, club cells, pulmonary neuroendocrine cells, bronchioloalveolar stem cells, distal airway stem cells and alveolar epithelial stem cells.Mechanisms include Wnt, notch, innate immune signaling pathways and others related to growth factors and transcription factors.
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AIM: To investigate the therapeutic effect of endothelial progenitor cell-conditioned medium (EPC-CM) on the lung structure of neonatal rat exposed to hyperoxia, and to explore the mechanisms.METHODS: Bone marrow-derived endothelial progenitor cells (EPCs) were collected from new born Sprague-Dawley (SD) rats and the EPCs were identified.The conditioned medium from the passage 3 EPCs was collected.Newborn SD rats (n=40) were randomly divided into 4 groups.The rats in room air group were exposed to the room air (21% O2) for 21 d.The rats in hyperoxia group were exposed to hyperoxia (85% O2) for 21 d.The rats in endothelial cell basal medium (EBM) group were exposed to hyperoxia for 21 d, and received 100 μL EBM on postnatal day 14 (P14) in a single intratracheal (IT) injection.The rats in EPC-CM group were exposed to hyperoxia for 21 d, and received 100 μL EPC-CM on P14 in a singlie IT injection.The rats were sacrified on the 21st day.The left lungs were excised, placed in 4% paraformaldehyde, serially dehydrated in ethanol and embedded by paraffin.Serial sectioning of the paraffin-embedded left lung tissues was prepared for 5 μm thickness, and stained with hematoxylin and eosin.The pulmonary radical alveolar count (RAC) and alveolar mean linear intercept (MLI) were then calculated.The microvascular density was determined by FVIII immunostaining.The mRNA expression of KGF, VEGF, SP-A and SP-C in the right lung tissues was detected by real-time fluorescence quantitative PCR.RESULTS: The cultured cells had typical EPC morphological characteristics, and had the abilities to bind to FITC-UEA-1 and uptake DiI-ac-LDL.The body weight of the rats on day 21, RAC, MLI and microvascular density were significantly lower in hyperoxia group and EBM group than those in room air group (P<0.05).The EPC-CM group had significantly higher RAC and microvascular density than those in hyperoxia group and EBM group (P<0.05), but the body weight and MLI had no significant difference.The mRNA expression levels of KGF, VEGF, SP-A and SP-C in hyperoxia group and EBM group were significantly lower than those in room air group (P<0.05).The mRNA expression levels of KGF, VEGF, SP-A and SP-C in EPC-CM group were significantly higher than those in hyperoxia group and EBM group (P<0.05).CONCLUSION: EPC-CM promotes the lung alveolarization and microvascular formation in neonatal rats exposed to hyperoxia.These benefits may be correlated with the increased KGF and VEGF mRNA expression.
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Objective To study the effect of transplanted endothelial progenitor cell (EPC) on hyperoxia-induced lung injury in neonatal rats.Methods Rat bone marrow mononuclear cells were cultured in endothelial cell growth medium to obtain EPCs,which were identified by morphology,phagocytosis and CD34+ analyses.Sixty neonatal Sprague-Dawley rats were allowed to acclimate in room air for 24 h after birth,and were then divided into four groups (15 per group),including the air group,the hyperoxia group,the EPCs transplantation group and the N ω-nitro-L-arginine methyl ester (L-NAME) intervention group.Neoborn rats in the Air and Hyperoxia groups were fed in the room air or hyperoxia (85％ oxygen) for 28 days.For rats in transplantation group were exposed continuously to hyperoxia for 28 days,and got an EPC (1 × 105 cells) injection on the 21st day.Rats in Intervention group were exposed continuously to hyperoxia for 28 days,got an EPC (1 × 105 cells) injection on the 21st day,and a daily injection of L-NAME from day 21 to day 28,with a daily dose of 20 mg/kg.Levels of circulating CD34+ cells and serum VEGF expression were detected.Specimens from lung tissues were analyzed by immunohistochemistry or immunofluorescence.The expression of vascular endothelial growth factor (VEGF),VEGF receptor 2 (VEGFR2) and eNOS were detected by realtime polymerase chain reaction and Western-blotting.NO production were detected by nitrate reductase assay.One way ANOVA and Bonferroni test were used for statistical analysis.Results (1) The cultured cells had a typical cobblestone appearance; double positive cell binding of fluorescein Ulex Europaeus agglutinin-1 and uptake of Dil-labeled acetylated low density lipoprotein accounted for approximately 85％ of the total number of cells.CD34+ cells accounted for 68.2％-72.4％ of total cultured cells.(2) Circulating CD34+ cells in the air group,hyperoxia group,EPC transplantation group and L NAME intervention group were (1.91 ± 0.34)％,(1.06 ± 0.10)％,(1.47 ± 0.06)％ and (0.77 ± 0.11)％ (F=32.710,P=0.000).The number of circulating CD34+ cells in the hyperoxia group was lower than the air group,in the EPC transplantation group the number of these cells was higher than the hyperoxia group,and in the L-NAME intervention group the number of these cells was lower than that in the EPC transplantation group,and the differences between these two groups were statistically significant (P ＜ 0.05,respectively).Serum VEGF in the four groups was (7.90±2.72),(6.38±0.72),(14.00± 1.66) and (11.70± 1.91) pg/ml,respectively.The difference between the four groups was statistically significant (F=22.809,P=0.000),and serum VEGF in the EPC transplantation group was higher than that in the hyperoxia group (P ＜ 0.05).(3) Transplanted EPCs could engraft in pulmonary vascular endothelium and alveolar interstitium,and L-NAME intervention significantly reduced the engraftment of EPCs in the lungs (10.7±0.47 / field vs 16.95±0.5 /field,t=17.820,P=0.000).(4) There were significant differences in the radial alveolar count (RAC) and number of microvessels between the four groups (F=859.580 or 211.150,P=0.000,respectively).RAC and the number of microvessels in the hyperoxia group were less than those in the air group (7.98±0.23 vs 13.12±0.20,3.98±0.42 vs 9.50±0.22,P ＜ 0.05,respectively).The number of microvessels in the EPC transplantation group was 5.40±0.41,being higher than that in the hyperoxia group (P＜0.05).(5) VEGF mRNA in lungs in the hyperoxia group was lower than that in the air group (0.23 ± 0.16 vs 1.05 ± 0.33,P ＜ 0.05); in the EPC transplantation group,VEGF mRNA was higher than that in the hyperoxia group (0.69 ± 0.09 vs 0.23 ± 0.16,P ＜ 0.05); and in the L-NAME intervention group,VEGF mRNA was lower than that in the EPC transplantation group (0.31 ±0.08 vs 0.69±0.09,P ＜ 0.05).VEGF protein in the lungs in the hyperoxia group was lower than the air group (0.52±0.01 vs 0.82±0.01,P ＜ 0.05),and was higher in the EPC transplantation group than the hyperoxia group (0.58±0.05 vs 0.52±2501,P ＜ 0.05).VEGFR2 mRNA in the hyperoxia group was lower than the air group (0.35±0.13 vs 1.07±0.45,P ＜ 0.05).eNOS mRNA in the hyperoxia group was lower than the air group (0.46±0.10 vs 1.05±0.36,P ＜ 0.05).eNOS protein in the hyperoxia group was lower than the air group (0.32±0.01 vs 0.51 ±0.03,P ＜ 0.05),and was higher in the EPC transplantation group than the hyperoxia group (0.86±0.02 vs 0.32±0.01,P ＜ 0.05).Conclusion Transplanted EPC can engraft in the lung tissue,improving alveolar and pulmonary vascular development,which may be associated with upregulation of the expression of eNOS and VEGF in lung.
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Objective To study the regulatory role of chemerin in infant with respiratory syncytial virus (RSV) pneumonia by investigating the level of serum chemerin,pro-inlfammatory cytokine (TNF-α, IL-17), and anti-inlfammatory cytokine (IL-10, TGF-β). Methods The serum level of chemerin,TNF-α,IL-1,IL-10,TGF-βwere tested in 82 RSV pneumonia inpatients (17 severe RSV pneumonia cases,65 mild cases) and 40 controls by ELISA and the severity of the RSV pneumonia was evaluated using a scoring system. Results The serum level of chemerin of RSV pneumonia cases were (610.45±106.63pg/ml) which were signiifcantly higher than the control(337.24±43.37 pg/ml). Chemerin level of severe RSV pneumonia group is signiifcantly higher than mild cases as well [(786.62±82.59 pg/ml)vs (539.98±65.86 pg/ml)P<0.01 ]. Signiifcant positive correlations were found be-tween serum chemerin level and TNF-α,IL-17 level (r=0.81,r=0.61;P<0.01) while the serum level of chemerin is negatively correlated with IL-10, TGF-β(r=-0.80,r=-0.75;P<0.01). Conclusions The level of chemerin increased in RSV pneumonia patients,and related to clinical severity after RSV infection. These results indicate that chemerin may play an important role in the pathogenesis of RSV pneumonia and to the severity of the infection.
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Objective To investigate the role of indoleamine 2,3-dioxygenase(IDO)in asthma.Methods The mouse asthma model was induced by ovalbumin(OVA).IDO expression was detected on the level of protein and mRNA respectively.Distribution and maturation of dendritic cells were detected by the immunofluorescence method.Results (1)The symptoms and lung inflammation in the model group were more serious than control group.The serum total IgE was significantly higher in the model group than that in the control group,165.50 ± 30.13 ng/ml vs.94.45 ± 28.30 ng/ml(P ＜ 0.05).(2)IDO expression in the model group was lower than that in control group.On the level of protein,mean intergrated optical density was 11.38 ± 6.05 in the model group vs.23.62 ± 8.92 in the control group(P ＜ 0.05);on the level of mRNA,IDO expression of the model group was 33% of the control group(P ＜ 0.05).(3)CD11c+CD86+ cells were distributed in alveolar wall and around small vessels.The quantity of CD11c+CD86+ cells in lungs of the model group were significantly smaller than that in the control group.The median intergrated fluorescence intensity was 9961.86(range,7 406.52 ～ 12 724.98)in the model group vs.15974.60(range,10 006.39 ～ 16 171.46)in the control group(P ＜ 0.05).Conclusions IDO expression is low and matured dendritic cells are less in situ in the asthma model.These suggest that less matured DCs may produce less IDO,which may play an important role in asthma.
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Congenital cystic lung lesions are a group of congenital lung diseases with low incidence. These include congenital cystic adenomatoid malformation,bronchogenic cyst,congenital lobar emphysema and pulmonary sequestration. These malformations occur during the period of lung development stimulated by various factors. Manifestations of the diseases are very similar,but the pathogenesis and pathology are very different. Congenital cystic adenomatoid malformations are thought to be the results of the cessation of bronchiolar maturation with overgrowth of mesenchymal elements and without development of alveoli. There are 5 pathological types of congenital cystic adenomatoid malformations. Bronchogenic cysts are the results of abnormal budding from a segment of the tracheobronchial tree during embryo development,and the buds with no communication with normal tracheobronchial tree. Congenital lobar emphysema is a term reserved for hyperinflation of alveoli from idiopathic reasons or extrinsic compression,as well as pathological changes of the bronchial wall. Pulmonary sequestrations account for parts of nonfunctioning lung tissue that mostly do not communicate with normal bronchoalveolar tree and vascularized by a systemic artery,two types(intralobar and extralobar sequestration)are described.
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OBJECTIVE To develop the countermeasures how to strengthen disinfection and isolation in the basic(medical) and health institutions.METHODS Through investigation,to analyze the current situation and problem of disinfection and isolation in the basic medical and health institutions.RESULTS There were some problems of the(disinfection) and isolation in the basic medical and health institutions and some possibility for patient catching(nosocomial) infection.CONCLUSIONS It is very important for strictly observing Medical Instrument Surveillance and Management Regulations published by the State Council and Hospital Infection Management Standards,Disinfection Technology Standards and Disinfection Management Methods published by Ministry of Health,and strengthening the management of disinfection and isolation in the basic medical and health institutions.