BACKGROUND: Cluster of differentiation 8 positive (CD8 + ) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8 + T cell exhaustion mediated by HCC exosomes remain poorly understood. METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p ( miR-27b-3p ) and thymocyte selection-associated high mobility group box ( Tox ) by Pparα . In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p , Pparα , and T cell exhaustion-related molecules ( Tox , Havcr2 , and Pdcd1 ) were detected using quantitative reverse transcription polymerase chain reaction analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis. RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p . The overexpressed Pparα from HCC cells was delivered to CD8 + T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo , acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions. CONCLUSIONS HCC-derived exosomes deliver Pparα to T cells and promote CD8 + T cell exhaustion and malignant progression of HCC via the miR-27b-3p /TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
MicroRNAs/metabolism* ; PPAR alpha/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Liver Neoplasms/genetics* ; CD8-Positive T-Lymphocytes/immunology* ; Exosomes/metabolism* ; Animals ; Cell Line, Tumor ; Mice ; High Mobility Group Proteins/genetics* ; Male ; T-Cell Exhaustion

Objective:To summarize the evidence for the link between rheumatoid arthritis and risk of vertebral fractures or vertebral deformities with a meta-analysis, so as to provide objective proof for early preventing and the development of vertebral deformity and fractures.Methods:Wanfang,CNKI,VIP,PUBMED,Springlink and Elsevier were retrieved for all publications relating to rheumatoid arthritis and vertebral fractures in women.According to inclusion and exclusion criteria,two investigators collected their data individually,then statistical analysis was performed using Stata 12.0 software.Results: Eight case-control studies were enrolled, including 86 741 participants,2 258 of them with RA.The results of Meta-analysis showed that a higher incidence of vertebral fractures in RA,and Odds ratio was 3.70 with a 95%confidence interval(2.47-5.55,P<0.000 1).The publication bias analysis did not reveal any evidence of obvious asymmetry, and the sensitivity analysis showed that omission of any individual study made no significant difference for all comparison models,suggesting that our results were statistically robust.Conclusion:RA may be one of the risk factors for the vertebral fractures.

Objective:To investigate the expression profile variation of long non-coding RNA( lncRNA) in the peripheral blood mononuclear cells of rheumatoid arthritis ( RA ) and healthy controls, and explore the role of lncRNA in the pathogenesis of RA.Methods:A total of 12 RA patients and 11 age-matched healthy controls from University Hospital of Hubei University for Nationalities were recruited.Using lncRNA microarray technology to detect differently expressed lncRNAs in 3 cases of RA PBMCs and 3 cases of healthy controls.GO and Pathway analysis was performed.The coding-non-coding gene co-expression networks of lncRNA and mRNA was constructed based on the correlation analysis,and then searched lncRNA in pathogenesis of RA through the cis-analysis and trans-analysis.Results:A total of 1 615 deregulated lncRNAs and 878 deregulated mRNAs were detected in RA patients.GO analysis of different expressed mRNA may involve in metal ion binding,protein kinase binding,nucleotide binding,regulation of transcription,et al.Pathway analysis of different expressed mRNA may involve in TNF signaling pathway,B cell receptor signaling pathway,pancreatic cancer,system lupus erythematosus endometrial cancer,et al.REL,SMAD3 and ETS1 may play an important role in the pathogenesis and development of RA through cis-analysis and trans-analysis.As the NONHSAG027875,FR378506 and NONHSAT031501 also had the similar function,and they may be related to the pathogenesis and development of RA.Conclusion:Differentially expressed lncRNAs may exert a partial role in RA,and may provide potential targets for future treatment of RA.

Objective:To observe the effect of Yiqiyangyin Decoction( YQYY) on bleomycin-induced rats pulmonary fibrosis and the expression of Smad2 and Smad7.Methods:Sixty male SD rats were randomly divided into normal group,model group,YQYY group,hormone group,YQYY plus hormone group.The rats in the normal group injected saline via the trachea,the rest rats injected ble-omycin(5 mg/kg).From the second day of injection,YQYY group were treated with YQYY decoction(1 ml/100 g);hormone group were given 35%Prednisone acetate solution(1 ml/100 g);YQYY plus hormone group were treated with the mixture of YQYY decoction and hormone (1 ml/100 g);normal group and model group were given equivalent saline.After twenty-eight days,all the rats were killed,the rat lung histopathology was examined with HE staining and detect Smad2/Smad7 protein with immunohistochemical staining.Results:Compared with normal group, the model group rats alveolitis and pulmonary fibrosis scores were significantly increased;compared with model group,the hormone group,YQYY group,YQYY plus hormone group rats alveolitis and lung fibrosis scores were reduced,and the lung injury of YQYY group reduced obviously.The expression of Smad2 protein of model group in alveolar epithelial cells and the fibroblasts was significantly higher than normal group;compared with model group,the positive expression of Smad2 in hormone group,YQYY group,YQYY plus hormone group were reduced,the Smad2 of YQYY group was the lowest.Compared with normal group,the smad7 protein of model group decreased significantly;compared with model group,Smad7 protein expression in hormone group, YQYY group, YQYY plus hormone group were increased, the Smad7 expression of YQYY group was highest.Conclusion:Yiqiyangyin decoction has a good intervention and therapeutic effect on bleomycin-induced rats pulmonary fibrosis,its mechanism may be related to inhibiting the inflammatory reaction,reduce the formation and deposition of collagen and the intervention of Smad signal pathway.