BackgroundBrain metastases (BM) from hepatocellular carcinoma (HCC) are extremely rare and are associated with a poor prognosis. The aim of this study was to define clinical outcome and prognostic determinants in patients with BM from HCC.MethodsBetween January 1994 and December 2009, all patients with HCC and BM treated in Sun Yat-sen University Cancer Center were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors.ResultsForty-one patients were diagnosed with BM from HCC, an incidence of 0.47%. The median age at diagnosis of BM was 48.5 years. Thirty-three patients (80.5%) developed extracranial metastases at diagnosis of BM, and 30 patients (73.2%) had hepatitis B. Intracranial hemorrhage occurred in 19 patients (46.3%). BM were treated primarily either with whole brain radiation therapy (WBRT; 5 patients), stereotactic radiosurgery (SRS; 7 patients), or surgical resection (6 patients). The cause of death was systemic disease in 17 patients and neurological disease in 23. Patients in a high RPA (recursive partitioning analysis) class, treated with conservatively and without lung metastases, tended to die from neurological disease. Median survival after the diagnosis of BM was 3 months (95% confidence interval: 2.2-3.8 months). In multivariate analysis, the presence of extracranial metastases, a low RPA class and aggressive treatment, were positively associated with improved survival.ConclusionsBM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive treatment. The clinical implication of extracranial metastases in HCC patients with BM needs further assessment.

Chop and ER stress are implicated in asthma pathogenesis, which involves regulation of M2 programming in macrophages.

Sirt6 which is implicated in the control of aging, cancer, and metabolism, has been shown to have anti-fibrosis function in heart and liver. However, whether Sirt6 inhibits idiopathic pulmonary fibrosis remains elusive. Epithelial to mesenchymal transition has been found to be involved in the pathogenesis of idiopathic pulmonary fibrosis. In the present study, forced expression of Sirt6 significantly abrogated TGF-β1-induced epithelial to mesenchymal transition-like phenotype and cell behaviors in A549 cells. Additionally, activation of TGF-β1/Smad3 signaling pathway and binding of Smad3-Snail1 were ameliorated by overexpression of wild-type Sirt6 but not mutant Sirt6 (H133Y) without histone deacetylase activity. Meanwhile, upregulation of epithelial to mesenchymal transition-related transcription factors by TGF-β1 were also restored by overexpression of wild-type Sirt6 but not mutant Sirt6. Furthermore, in vivo study showed that lung targeted delivery of Sirt6 using adeno-associated virus injection blunted bleomycin-induced pulmonary epithelial to mesenchymal transition and fibrosis. Overall, our findings unravel that Sirt6 acts as a key modulator in epithelial to mesenchymal transition process, suggesting Sirt6 may be an attractive potential therapeutic target for idiopathic pulmonary fibrosis.

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs that could serve as novel biomarkers for the diagnosis and treatment of diseases. We hypothesized that circRNAs of CD4 + T cells are involved in asthma. Objective:In this study, we investigated the circRNA expression profile and the possible mechanism by which hsa_circ_0005519 participates in asthma. Methods:The expression profiles of circRNAs in CD4 + T cells were revealed by circRNA microarray. Hsa_circ_0005519 expression in CD4 + T cells was confirmed in asthmatic patients (n = 65) and healthy subjects (n = 30). Hsa-let-7a-5p, the target of hsa_circ_0005519, was predicted by online algorithms and verified by a dual-luciferase reporter assay. Correlation assays between the expression of hsa_ circ_0005519 and hsa-let-7a-5p, the mRNA levels of interleukin (IL)-13 and IL-6 in CD4 + T cells, and the clinical characteristics of asthmatic patients were performed.The role of hsa_circ_0005519 in proinflammatory cytokine expression was investigated in CD4 + T cells from asthmatic patients in vitro. Hsa_circ_0005519 expression in PBMCs was determined in another cohort including 30 asthmatic patients and 24 controls. Correlation assays of hsa_circ_0005519 expressions between CD4 + T cells and PBMCs were performed.Results: Hsa_circ_0005519 was up-regulated and negatively correlated with hsalet-7a-5p expression in CD4 + T cells of asthmatic patients. Both the fraction of exhaled nitric oxide (FeNO) and the peripheral blood eosinophil ratio were positively correlated with hsa_circ_0005519 expression in CD4 + T cells. These outcomes were also different in asthmatic patients with low vs high hsa_circ_0005519 levels. Hsa_ circ_0005519 expressions between CD4 + T cells and PBMCs were concordant in asthmatic patients. Mechanistically, hsa_circ_0005519 might bind to hsa-let-7a-5p and relieve suppression for IL-13/IL-6 in CD4 + T cells. Conclusions and clinical relevance:Our data suggest that hsa_circ_0005519 may induce IL-13 and IL-6 expression by regulating hsa-let-7a-5p in CD4 + T cells to affect asthma. And hsa_circ_0005519 may be a potential biomarker of asthma. K E Y W O R D Sasthma, CD4 + T cells, hsa_circ_0005519, hsa-let-7a-5p, PBMCs