Objective. From our previous study, we obtained long noncoding RNA (lncRNA) STAT4-AS1, which is related to asthma through high-throughput screening. However, we could not determine the specific mechanism involved and in response to this. We further designed this study. Results. First, we found that lncRNA STAT4-AS1 was downregulated in T cells from patients with asthma when compared to healthy controls. Next, we confirmed that lncRNA STAT4-AS1 was significantly negatively correlated with T helper 17 (TH17) differentiation in vitro experiments. The decreases of STAT4-AS1 promoted TH17 differentiation, while the increases of STAT4-AS1 inhibited TH17 differentiation. Subsequently, through RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and dual luciferase reporter assay, we found that STAT4-AS1 could inhibit the binding of retinoid-related orphan receptor-γt (RORγt) protein with an IL-17A promoter after binding with RORγt protein. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation assay showed that STAT4-AS1 is bonded to RORγt in the cytoplasm, preventing RORγt from entering the nucleus. Conclusion. Overall, STAT4-AS1 directly targets RORγt protein, inhibits the mutual binding of RORγt and IL-17 gene promoter, and eventually inhibits TH17 differentiation. To this end, STAT4-AS1 as a potential target may confer applications in the clinical treatment and diagnosis of TH17-related diseases.

Objective: From our previous study, we obtained long non-coding RNA (lncRNA) STAT4-AS1, which is related to asthma through high-throughput screening. However, we could not determine the specific mechanism involved and in response to this, We further designed this study. Results: First, we found that lncRNA STAT4-AS1 was downregulated in T cells from patients with asthma when compared to healthy controls. Next, we confirmed that lncRNA STAT4-AS1 was significantly negatively correlated with T helper 17 (TH17) differentiation in vitro experiments. The decreases of STAT4-AS1 promoted TH17 differentiation, while the increases of STAT4-AS1 inhibited TH17 differentiation. Subsequently, through RNA pulldown, RNA-binding protein immunoprecipitation (RIP) and dual luciferase reporter assay, we found that STAT4-AS1 could inhibit the binding of retinoid-related orphan receptor-γt (RORγt) protein with IL-17A promoter after binding with RORγt protein. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation assay showed that STAT4-AS1 is bonded to RORγt in the cytoplasm, preventing RORγt from entering the nucleus. Conclusion: Overall, STAT4-AS1 directly targets RORγt protein, inhibits the mutual binding of RORγt and IL-17 gene promoter, and eventually inhibits TH17 differentiation. To this end, STAT4-AS1 as a potential target may confer applications in the clinical treatment and diagnosis of TH17-related diseases.

Lots of epidemiological and clinical studies have shown that human cytomegalovirus (HCMV) is related to the pathogenesis of atherosclerosis. Released by inflammatory cells and vascular smooth muscle cell (VSMCs), metalloproteinases are observed in many pathological vessel conditions, including atherosclerosis and restenosis. This study was designed to investigate the effect of HCMV infection on the expression of metalloproteinases and their involvements in the HCMV‐induced functional changes of VSMCs. Differential metalloproteinase after HCMV infection was assayed using reverse transcription‐polymerase chain reaction (RT‐PCR) microarray. The most significant increased a disintegrin and metalloprotease 9 (ADAM9) was chosen to investigate the mechanism of its specific increase after infection using the treatment of UV‐irradiated replication‐deficient HCMV, HCMV‐infected cell lysate filters or Foscarnet. The function of proliferation, migration, production of inflammatoty factors and phenotypic transformation were determined by using cell counting kit‐8, transwell, Enzyme‐linked immunosorbent assay, RT‐quantitative PCR (qPCR) and Western blot, respectively. Moreover, the effect of ADAM9 deficiency on HCMV replication was also determined using RT‐qPCR and immunofluorescence. The expression levels of 6 genes were upregulated and 14 genes were downregulated at different time points after HCMV infection. Among these, the expression level of ADAM9 increased most significantly at each time point and the abnormal expression of ADAM9 might be induced by the early gene products of HCMV. Further studies found that ADAM9 promoted the proliferation, the migration, the production of inflammatory factors and the transit from the contractile phenotype (decreased ACTA2 expression) to the synthetic phenotype (increased osteopontin [OPN] expression). Knockdown theADAM9 expression could rescue the decreased ACTA2 expression, but has no effect on OPN expression. ADAM‐9 deficiency didn't affect the replication of HCMV. The findings of our study suggest that HCMV infection changed VSMC function through ADAM9 expression, which may contribute to the understanding of the underlying pathological mechanisms of HCMV‐induced atherosclerosis.

Background Insulin-like growth factor 1 receptor (IGF1R) is a newly discovered key receptor that allows RSV to enter cells. RSV and IGF1R fusion triggers PKCζ activation, promoting cell signaling by recruiting nucleolin from the nucleus to the plasma membrane. It is tempting to speculate that other pneumoviruses, including bovine RSV, bind to the IGF1R. Methods Natural products that are effective against IGF1R protein were screened from TargetMol drugs datas by virtual screening. Virtual screening and in vivo and in vitro experiments were carried out. Results The results showed that Tannic acid and Daptomycin had anti-RSV potential through reducing viral loads, inflammation, airway resistance and protecting alveolar integrity. And the IC50 values of tannic acid and daptomycin were the 6 nM and 0.45 µM, respectively. Conclusions Novel small-molecule inhibitors targeting the IGF1R, Tannic acid or Daptomycin, may be effective anti-RSV therapy agents.