الملخص
Objective To investigate the effects of asbestos exposure on plasma miRNA expression.Methods Plasma samples were collected from control group and asbestos -exposed group (time of exposure >10 years)and three samples from each group were selected to detect differentially expressed miRNA using LC Sciences miRNA Microarray -Single.The target genes of differential miRNA were predicted by three kinds of online software,Target Scan,miRanda and PicTar.GO term enrichment and KEGG pathways were analyzed.Results The results of microarray indicated that there were 40 differential miRNA expression between exposed and control groups(P <0.05),and the signal value of 9 differential miRNA exceeded 500.After analyzing signal pathways of target genes of 5 miRNA,of which the signal values were over 500,these target genes were found mainly involved in pathways associated with cancer and metabolism,including potential function targets of FAS,TP53 and FGFR3.Conclusion Asbestos exposure can result in differentially expressed miRNA in the plasma from workers occupationally exposed to asbestos and the target genes of these miRNA may play important roles in the pathways of cancer.However,the mechanism of these miRNA in asbestos -related diseases needs to be further studied in the future.
الملخص
<p><b>OBJECTIVE</b>To investigate the role of p38 mitogen-activated protein kinases (MAPKs) in the apoptosis of human bronchial epithelial cells (BEAS-2B) induced by refractory ceramic fibers (RCFs).</p><p><b>METHODS</b>BEAS-2B cells were exposed to 10, 20, 40, 80, and 160 µg/cm(2) RCF1, RCF2, and RCF3 for 24 h, and the cell viability was measured by CCK-8 assay. BEAS-2B cells were exposed to 20, 40, and 100 µg/cm(2) RCF1, RCF2, and RCF3 for 24 h, and the cell apoptosis rate was measured by flow cytometry. BEAS-2B cells were exposed to 40 µg/cm(2) RCF1, RCF2, and RCF3, and the expression levels of phospho-p38 MAPK and caspase-3 were measured by Western blot. In each of the above treatments, the BEAS-2B cells were divided into positive control, p38 inhibitor SB203580 intervention, and normal groups.</p><p><b>RESULTS</b>As the concentration of RCFs rose, the RCF exposure groups showed decreased cell viability and increased cell apoptosis rate. After SB203580 intervention, the intervention groups (all concentrations of asbestos + SB, 20, 40, 80, and 160 µg/cm(2)RCF1+SB, and 40, 80, and 160 µg/cm(2) RCF2 and RCF3+SB) had significantly increased cell viabilities (P < 0.05), and the intervention groups (asbestos + SB and 20, 40, and 100 µg/cm(2) RCF1, RCF2, and RCF3 + SB) had significantly decreased cell apoptosis rates (P < 0.05). Compared with the normal group, the RCF (40 µg/cm(2)) exposure and positive control groups had significantly increased expression of phospho-p38 MAPK (P < 0.05), and the RCF (40 µg/cm(2)) exposure group had significantly increased expression of caspase-3 (P < 0.05). The intervention groups (asbestos + SB and 40 µg/cm(2) RCF1, RCF2, and RCF3 + SB) had significantly decreased expression of caspase-3 after SB203580 intervention.</p><p><b>CONCLUSION</b>p38 MAPKs play an important role in RCF-induced apoptosis of BEAS-2B cells.</p>
الموضوعات
Humans , Apoptosis , Bronchi , Cell Biology , Caspase 3 , Metabolism , Cell Line , Ceramics , Toxicity , Epithelial Cells , Metabolism , Pathology , Imidazoles , Pharmacology , Pyridines , Pharmacology , p38 Mitogen-Activated Protein Kinases , Metabolismالملخص
<p><b>OBJECTIVE</b>To screen differently expressed proteins for serum biomarkers by studying serum proteome of population with asbestosis, population exposed to asbestos without asbestosis and population never exposed to asbestos, to further understand the mechanisms of asbestosis.</p><p><b>METHODS</b>The subjects of present study included 37 patients with asbestosis, 254 workers exposed to asbestos and 439 healthy controls. The 2-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-MS/MS) were used to screen and identify the differentially expressed serum proteins among all subjects. ImageMaster6.0 software was utilized to analyze the differentially expressed proteins.</p><p><b>RESULTS</b>Well-qualified gel images of serum proteome were obtained, 21, 34 and 32 differentially expressed spots were found between asbestosis and normal controls, between asbestosis and negative controls or between negative controls and normal controls, respectively. Differentially displayed proteins were identified as cytokines, α1-AT, L-ficolin, etc.</p><p><b>CONCLUSION</b>Exposure to asbestos for a long period could interfere with the immune system of workers exposed to asbestos, and some proteins may serve as the biomarkers for early diagnosis and intervention of asbestosis.</p>
الموضوعات
Adult , Humans , Male , Asbestosis , Blood , Biomarkers , Blood , Blood Proteins , Metabolism , Case-Control Studies , Electrophoresis, Gel, Two-Dimensional , Proteomicsالملخص
<p><b>OBJECTIVE</b>To explore the biomarkers and mechanism of kidney toxicity induced by trimethyltin chloride (TMT-Cl) through analyzing the differences of protein expression profiles between vero cells and vero cells exposed to TMT-Cl.</p><p><b>METHODS</b>The differences of protein expression levels of three paired samples of vero cells and vero cells exposed to TMT-Cl were compared by two-dimensional gel electrophoresis (2-DE) and liquid chromatography-electrospray ionization-linear trap quadrupole (LC-ESI-LTQ). The differences of expression levels of Annexin A1 and α-Tubulin proteins were validated with western blot assay, and the differences of mRNA expression levels of Annexin A1 and α-Tubulin genes were detected with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).</p><p><b>RESULTS</b>Fifteen spots of differential expression in protein profiles between vero cells and vero cells exposed to TMT-Cl were found, and 9 of these spots were identified by LC-ESI-LTQ. The expression levels of 3 proteins (Annexin A1,similar to RAN protein and a hypothetical protein) increased and the expression levels of 6 proteins(growth factor receptor-bound protein 10, tubulin alpha 6, heterogeneous nuclear ribonucleoprotein, similar to elongation factor SIII p15 subunit, S-adenosylhomocysteine hydrolase and a hypothetical protein) reduced. The expression levels of α-Tubulin protein and mRNA significantly decreased in vero cells exposed to TMT-Cl, as compared with vero cells (P < 0.01). The expression of Annexin A1 protein in all exposure groups was significantly up-regulated, the expression of Annexin A1 mRNA in the groups exposed to 25 and 50 µmol/L TMT-Cl was significantly down-regulated, and The expression of Annexin A1 mRNA in the group exposed to 100 µmol/L TMT-Cl was significantly up-regulated (P < 0.01).</p><p><b>CONCLUSIONS</b>The results of present study suggest that 9 proteins with differential expression detected by LC-ESI-LTQ may be related to the kidney toxicity induced by TMT-Cl, which can serve as the biomarkers of early diagnosis and therapeutic effect for the kidney toxicity induced by TMT-Cl.</p>
الموضوعات
Animals , Chlorocebus aethiops , Electrophoresis, Gel, Two-Dimensional , Gene Expression Profiling , RNA, Messenger , Genetics , Transcriptome , Trimethyltin Compounds , Toxicity , Tubulin , Genetics , Metabolism , Vero Cellsالملخص
<p><b>OBJECTIVE</b>to investigate whether pirfenidone (PFD) presents the antifibrotic effect in silicosis of rats.</p><p><b>METHODS</b>SD rats were randomly divided into five groups: the non-treat group, the normal saline group, the normal saline + PFD group, the SiO2 group, the SiO2 + PFD group. Rats except in the non-treat group were intratracheally instilled with SiO2 (25 mg/ml) or normal saline. The rats in normal saline + PFD group and the SiO2 + PFD group were given PFD (50 mg/kg) orally the next day after instillation and throughout the study. Rats were respectively sacrificed 7, 21, 42 days after instillation. The pathology changes were evaluated by Haematoxylin-eosin (HE), Van Gieson and Foot staining, and the hydroxyproline (HYP) content of pulmonary tissue was determined.</p><p><b>RESULTS</b>compared with the SiO2 group, PFD could relieve the fibrotic changes in the lungs of rats. The fibrotic degree in silicotic lesions of lungs was lower in the SiO2 + PFD group than that of SiO2 group. The HYP content in the lungs of the SiO2 + PFD group [(0.75 ± 0.12) mg/g] was significantly lower than that of the SiO2 group [(1.19 ± 0.17) mg/g] at 42 days after instillation (P < 0.05).</p><p><b>CONCLUSION</b>these data support that PFD has an antifibrotic effect against SiO2 induced lung fibrosis in rats, Which appears to be changing collagen accumulation and inhibiting pulmonary fibrosis.</p>
الموضوعات
Animals , Male , Rats , Hydroxyproline , Metabolism , Lung , Metabolism , Pathology , Pulmonary Fibrosis , Drug Therapy , Metabolism , Pathology , Pyridones , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Silicon Dioxideالملخص
<p><b>OBJECTIVE</b>To investigate abnormal liver function associated with polymorphism of GSTT1, GSTM1 and CYP2E1 in workers exposed to N, N-dimethylformamide.</p><p><b>METHODS</b>Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case. One hundred and twenty five control subjects with similar work tasks were selected from the same factory. Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR, and for CYP2E1 PstI by PCR-RFLP assay.</p><p><b>RESULTS</b>The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control, with an odds ratio (OR) of 2.34,95% CI: 1.29-4.29 (P=0.005). For GSTT1 and CYP2E1 PstI, the frequencies of genotypes showed no significant difference between case and control.</p><p><b>CONCLUSION</b>GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N, N-dimethylformamide.</p>
الموضوعات
Adult , Female , Humans , Male , Chemical and Drug Induced Liver Injury , Genetics , Cytochrome P-450 CYP2E1 , Genetics , Dimethylformamide , Genotype , Glutathione Transferase , Genetics , Occupational Exposure , Polymorphism, Geneticالملخص
<p><b>OBJECTIVE</b>To investigate the apoptosis rate and the reactive oxygen species (ROS) level induced by chrysotile fibers in BEAS-2B cells and the blockage effect of free radical scavengers on the induction of chrysotile fibers.</p><p><b>METHODS</b>The cell survival rate, the morphological variation of BEAS-2B cells, the apoptosis rate, the expression levels of gene caspase-3 and the ROS generation level were measured by using trypan blue phagocytosis, hematoxylin and eosin staining, oligonucleosomal DNA fragmentation assay, FCM, RT-PCR and fluorescent probe DCFH-DA in the suspension (0, 5, 10, 20, 100 and 200 microg/cm(2)) and the filtrate (0, 100, 200, 400, 800 and 1600 microg/ml) of chrysotile fibers. Addition of free radical scavengers such as catalase, dimethyl sulfoxide and mannitol prevented the radical generation and gene expression.</p><p><b>RESULTS</b>Survival rates of BEAS2B cells treated by the suspension (0, 5 and 10 microg/cm(2)) and the filtrate (0, 100 and 200 microg/ml) of chrysotile fibers for 24 hours were above 90%. The apoptotic rates of BEAS-2B were increased with the concentration of suspension and filtrate from chrysotile fibers (P < 0.05). Otherwise, caspase-3 mRNA and ROS were stimulated by chrysotile fibers. Free radical scavengers such as CAT, DMSO and mannitol could reduce these stimulations. The ROS blocking rate of suspension of chrysotile fibers was 23.7%, 21.6% and 11.2% respectively, and that of filtrate was 37.9%, 40.3% and 10.6% respectively.</p><p><b>CONCLUSION</b>Apoptosis is induced in BEAS-2B cells exposed to chrysotile fibers suspension and filtrate. Generation of ROS plays an important role in chrysotile fibers-induced BEAS-2B cell apoptosis.</p>
الموضوعات
Humans , Apoptosis , Asbestos, Serpentine , Toxicity , Cell Line , Drug Antagonism , Epithelial Cells , Metabolism , Pathology , Free Radical Scavengers , Pharmacology , Oxidative Stress , Reactive Oxygen Species , Metabolismالملخص
<p><b>OBJECTIVE</b>To investigate the hepatotoxic effects of N, N-dimethylformamide (DMF) in the workers of a synthetic leathers factory, and the effects on liver function of covariates such as alcohol consumption and other factors.</p><p><b>METHODS</b>The workers were classified into three groups (low, high and the control) by the concentration of DMF in workplace which was determined in the past two years. A questionnaire was drawn up for relevant demographic characteristics and other factors influencing liver function. The bloods were collected for laboratory test which included parameters especially relevant to the liver (ALT AST and gamma GT).</p><p><b>RESULTS</b>Low and high-exposure groups were significantly associated with elevated ALT and gamma GT, and high-exposure group was significantly associated with elevated Liver index. Modeling by stepwise regression analysis demonstrated that high concentration of DMF and BMI were associated with and elevated ALT, gamma GT and Liver index, besides DMF and BMI, the elevation of ALT was also associated with high TRIG. AST was only associated with alcohol consumption. The AST/ALT ration < 1 was present in 86.7% of the exposure workers of liver function abnormal.</p><p><b>CONCLUSION</b>DMF can cause liver function alternations even if air concentration of DMF was below PC-TWA. Besides the levels of DMF exposure, obesity (BMI) and alcohol consumption are covariates alternating liver function. Liver index can be a parameter for assessment liver function, and the AST/ALT ration < 1 may serve as markers of risk in health screening programs.</p>