RESUMO
The vitamin K antagonist is a commonly prescribed effective oral anticoagulant with a narrow therapeutic range, and the dose requirements for different patients varied greatly. In recent years, studies on human intestinal microbiome have provided many valuable insights into disease development and drug reactions. A lot of studies indicated the potential relationship between microbiome and the vitamin K antagonist. Vitamin K is absorbed by the gut, and the intestinal bacteria are a major source of vitamin K in human body. A combined use of the vitamin K antagonist and antibiotics may result in an increase in INR, thus elevating the risk of bleeding, while vitamin K supplementation can improve stability of anticoagulation for oral vitamin K antagonist treatment. Recently, how intestinal bacteria affect the response of the vitamin K antagonist remains unclear. In this review, we reviewed the research, focusing on the physiology of vitamin K in the anticoagulation treatment, and investigated the potential pathways of intestinal bacteria affecting the reaction of the vitamin K antagonist.
RESUMO
TEA domain family members (TEADs) play important roles in tumor progression. Till now, the genomic status of TEADs in patients with glioma has not been well investigated. To confirm whether the genomic status of TEADs could affect the prognosis of patients with glioma, the copy number variation (CNV), mutation and expression data of glioma cohorts in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas were comprehensively analyzed. Results showed that TEAD CNV frequency in lower grade gliomas (LGGs) was higher than in glioblastoma multiforme (GBM). Multivariate cox regression analysis showed that TEAD4 CNV increase was significantly associated with overall survival (OS) and disease-free survival (DFS) in LGGs (OS p = 0.022, HR = 1.444, 95% CI: 1.054-1.978; DFS p = 0.005, HR = 1.485, 95% CI: 1.124-1.962), while not in GBM. Patients with TEAD4 CNV increase showed higher expression level of TEAD4 gene. In LGG patients with IDH mutation, those with higher TEAD4 expression levels had shorter OS and DFS. Integrating TEAD4 CNV increase, IDH mutations, TP53 mutation, ATRX mutation and 1p19q co-deletion would separate patients with LGG into four groups with significant differences in prognosis. These study results suggested that TEAD4 variations were independent predictive biomarkers for the prognosis in patients with LGG with IDH mutation.
RESUMO
As constituents of lysosomes, lysosomal membrane proteins play important roles in lysosome-related autophagy and apoptosis. In a recent proteomic study of lysosomal proteins, we identified transmembrane protein 192 (TMEM192) as a novel lysosomal membrane protein candidate. Using specific anti-TMEM192 antibody and lysosomal markers, the lysosomal localization of TMEM192 was determined by immunofluorescence. TMEM192 shows a wide expression pattern in mouse tissues. Interestingly, TMEM192 was found to be highly expressed in tumor cell lines, while it was not expressed or was detected at low levels in normal cell lines. By knockdown of TMEM192 expression using specific siRNAs, we found that TMEM192-deficient HepG2 hepatoma cells show growth inhibition and increased apoptosis. Autophagy was shown to be activated through detection of LC3II expression. Increased apoptosis was inhibited by blocking the expression of the key autophagy gene Atg7 in TMEM192-deficient HepG2 cells. The results suggest that TMEM192 is important for tumor cell growth and proliferation. TMEM192 deficiency can induce autophagy in tumor cells, and can further activate apoptosis by the mitochondrial pathway through autophagy. TMEM192 promotion of autophagy may be a new route for tumor therapy.