ABSTRACT
OBJECTIVE: To screen the differentially expressed microRNA(miRNA) in the serum of patients with occupational pneumoconiosis(hereinafter referred to as pneumoconiosis), and explore their potential target genes and related transcription factors using bioinformatics analysis. METHODS: The pneumoconiosis and miRNA related reports were searched from the Google academic website. The miRNA sequencing or high-throughput microarray data sets based on the serum samplings of pneumoconiosis patients(case group) and normal healthy individuals(control group) were selected to screen for the differentially expressed miRNAs. Serum samples of patients with occupational silicosis and healthy controls were collected, and the relative expression of miRNAs was detected by real-time fluorescence quantitative polymerase chain reaction to verify the differential expression of miRNAs. The target genes of the differentially expressed miRNAs were predicted in the database of miRWalk, analyzed by Gene Ontology(GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway prediction. The transcription factor analysis of target genes was carried out by the database for annotation. RESULTS: Seven differentially expressed miRNAs were screened out and verified. Among them, five were up-regulated and two were down-regulated. GO enrichment analysis and KEGG signaling pathway prediction showed that the up-regulated differentially expressed miRNAs were mainly related to RNA polymerase Ⅱ promoter transcription and extracellular matrix, and were mainly involved in the occurrence and development of pulmonary fibrosis through adhesion plaque, protein digestion and absorption, phosphatidylinositol 3-kinase/protein kinase B and transforming growth factor-β signaling pathways. The down-regulated differentially expressed miRNAs were mainly related to the transcription of RNA polymerase Ⅱ promoter and the activity of DNA sequence specific transcription factors, that were mainly involved in the occurrence and development of pulmonary fibrosis through the signaling pathway of related hormone release. Transcription factor annotation results showed that SMAD family member 3, proto-oncogene JUN, forkhead box O1, early growth factor 1, β-catenin and other transcription factors may have an important relationship with the occurrence and development of pneumoconiosis. CONCLUSION: The seven miRNAs were differentially expressed in the serum of patients with pneumoconiosis. These miRNAs could be used as potential biomarkers for understanding the pathogenesis, the early diagnosis and treatment pneumoconiosis.
ABSTRACT
ABSTRACT:In the present study ,we aimed to identify differentially expressed proteins between induced worms (the infec‐ted mice were treated intragastrically with ED50 PZQ) and uninduced worms (control group) for clarifying the mechanism of PZQ .ED50 PZQ was used to administrate mice that were infected with S .japonicum via intragastric incubation for consecutive‐ly 30 days .Twenty‐one days later ,mice were sacrificed after treatment with 200 mg/kg PZQ for continuously five days ,and the male worms were obtained and some of them were subjected in DMEM medium with different concentrations of PZQ in vitro for 16 hours .Then the worms were washed twice and incubated in PZQ‐free medium for 72 hours .Compared with control group ,the induced worms had lesser sensitivity to PZQ .The survival rate of induced worms was 75 .6% in vitro when the con‐centration of PZQ was 112 mol/L (the concentration was 8 times of uninduced worms Lethal Concentration ) ,significantly higher than that in the uninduced worms (11 .1% ,P<0 .05) ,showing obviously tolerance .The other induced and uninduced worms were acquired and collected for 2D‐DIGE and MALDI‐TOF‐MS ,and combined with bioinformatics to analyse the func‐tion of the identified protein .Thirty differential expression proteins were confirmed between induced and uninduced worms ,in‐cluding 12 proteins up‐regulated and 18 proteins down‐regulated .These proteins respectively ascribed to cytoskeleton‐associat‐ed protein ,glucose and energy metabolism enzymes ,stress proteins ,thioredoxin peroxidase enzymes ,and other protease .Up‐or down‐regulation of these differential proteins indicated that PZQ promote or inhibit the expression of some specific genes . These findings may help to clarify the mechanism of PZQ ,simultaneously ,providing a scientific basis for exploring new vaccine candidate antigens and targets for drug therapy .