Molecular subtypes based on DNA sensors predict prognosis and tumor immunophenotype in hepatocellular carcinoma.

DNA sensors play crucial roles in inflammation and have been indicated to be involved in antitumor or tumorigenesis, while it is still unclear whether DNA sensors have potential roles in the prognosis and immunotherapy of hepatocellular carcinoma (HCC). Herein, The Cancer Genome Atlas and Gene Expression Omnibus databases were used to analyze RNA sequencing data and clinical information. A total of 14 DNA sensors were collected and performed consensus clustering to determine their molecular mechanisms in HCC. Two distinct molecular subtypes (Clusters C1 and C2) were identified and were associated with different overall survival (OS). Immune subtype analysis revealed that C1 was mainly characterized by inflammation, while C2 was characterized by lymphocyte depletion. Immune scoring and immunomodulatory function analysis confirmed the different immune microenvironment of C1 and C2. Notably, significant differences in "Hot Tumor" Immunophenotype were observed between the two subtypes. Moreover, the prognostic model based on DNA sensors is capable of effectively predicting the OS of HCC patients. Besides, the chemotherapeutic drug analysis showed the different sensitivity of two subtypes. Taken together, our study shows that the proposed DNA sensors were a reliable signature to predict the prognosis and immunotherapy response with potential application in the clinical decision and treatment of HCC.

Effect of Rheum palmatum L. on NF-κB signaling pathway of mice with acute liver failure.

OBJECTIVE: To explore the regulation effect of Rheum palmatum (R. palmatum) L. on NF-κB signaling pathway of ALF mice. METHODS: The intraperitoneal injection of d-GalN/LPS was employed for the model building. Mice in the treatment group and positive control group were given the R. palmatum L. and bifendate before the model building. Mice in the normal group were given the intraperitoneal injection of equivalent normal saline for continuously 3 d. After 16 h of model building, the blood was collected from eyeballs of mice and then mice were executed. The measurement was performed on the content of ALT, AST, NO and Il-1ß in the serum of mice in each group, as well as the activity of Caspase 3 and Caspase 8 in the liver tissue. HE staining was employed to detect the pathological morphology of liver; and the western blot was used to detect the expression of iNOS, COX-2, Bax, Bcl-2, PCNA, NF-κB p65 and IκBα. RESULTS: The content of ALT, AST, NO and Il-1ß in the serum and the activity of Caspase 3 and Caspase 8 in the liver tissue were increased in the mice of ALF model group. Besides, the expression of iNOS, COX-2 and Bax was increased, the expression of Bcl-2 and PCNA was decreased, the phosphorylation of NF-κB p65 and IκBα was significant and the treatment group of R. palmatum L. could inhibit such change. CONCLUSIONS: Through NF-κB signaling pathway, the R. palmatum L. could reduce the content of enzyme of liver function and inflammation factor in the serum of ALF mice, regulate the expression of cell apoptosis-related protein and improve the symptoms of ALF mice.