Objective To investigate the accumulation of mutations and single nucleotide polymorphisms ( SNPs) in the displacement loop ( D-loop ) of mitochondrial DNA ( mtDNA ) might be associated with cancer risk and disease outcome.Methods We obtained cancerous and noncancerous liver tissues from 49 HBV-related HCC patients at the Fourth Hospital of Hebei Medical University.mtDNA of the liver tissues was extracted with Mitochondrial DNA Extraction Kit.Mutation and polymorphism were confirmed by repeated analysis.We assessed the prediction power of D-loop SNPs in hepatocellular carcinoma ( HCC) patients.Results No mutation in these HCC patients had prediction power for post-operational survival, whereas one SNP site ( nucleotide 150 C/T ) was identified by the log-rank test for statistically significant prediction of HCC survival.In an overall multivariate analysis, allele 150 was identified as an independent predictor of HCC outcome.The length of survival of patients with allele 150C was significantly shorter than that of patients with allele 150T (relative risk, 0.246;95% CI, 0.070–0.861; P=0.028).Conclusions The analysis of genetic polymorphisms in the mitochondrial D-loop helps to identify patient subgroups at high risk of a poor disease outcome.

Aspergillosis ; complications ; Aspergillus ; Chemical and Drug Induced Liver Injury ; complications ; microbiology ; Humans

PURPOSE: T helper (Th) 17 cells play a critical role in the development of asthma, but the underlying mechanism of how interleukin (IL)-17 is regulated in allergic airway inflammation is poorly understood. In this study, we investigated the impact of Bcl11b on Th17 response in asthma. METHODS: Blood samples from patients with mild asthma (MA) and severe asthma (SA) were collected. Expression of Bcl11b, IL-4, IL-5, IL-13, IL-17A and transforming growth factor (TGF)-β1 were determined in CD4+ T cells and plasma by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Relative mRNA and protein levels of Bcl11b, IL-17A and genes involved in the TGF/Smad signaling pathway were examined by PCR, ELISA and western blot analysis in house dust mite (HDM)-challenged mice. Ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes was achieved by nucleofection of Bcl11b expression plasmid. RESULTS: We found significantly decreased Bcl11b but increased IL-17A and TGF-β1 expression in patients with asthma and a strongly negative correlation between Bcl11b and these 2 cytokines in SA patients. Similar expression patterns of Bcl11b, IL-17A and TGF-β1 were also found in mice with HDM-induced allergic airway inflammation. We demonstrated further that Smad2/3 phosphorylation was increased in HDM-challenged mice and that ectopic expression of Bcl11b in HDM-stimulated primary mouse splenocytes reduced Smad2 phosphorylation and IL-17 expression. CONCLUSIONS: Our findings demonstrate a potential effect of Bc111b in controlling IL-17-mediated inflammation in asthma and suggest that Bc111b may be a useful therapeutic target for asthma.
Animals ; Asthma* ; Blotting, Western ; Cytokines ; Ectopic Gene Expression ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Interleukin-13 ; Interleukin-17* ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Mice ; Phosphorylation ; Plasma ; Plasmids ; Polymerase Chain Reaction ; Pyroglyphidae ; RNA, Messenger ; T-Lymphocytes ; Transforming Growth Factors

Cardiovascular System/pathology* ; Constriction, Pathologic/genetics* ; Point Mutation ; Neurofibromin 1/genetics* ; Animals ; Mice

Objective: To investigate the relationship between the mutations in precore/core (preC/C) region of hepatitis B virus (HBV) gene and the postoperative survival in patients with hepatocellular carcinoma. Methods: A total of 81 cases in HBV associated hepatocellular carcinoma (HBV-HCC) patients with cancer tissue genomic DNA were extracted. The preC/C region of HBV was amplified and sequenced, and survival-associated HBV mutations were identified according to the NCBI database. The relationships between the mutations in the preC/C region and HCC survival was analyzed with the Kaplan-Meier method and the Cox proportional hazards model. Eleven mutational sites were identified as statistically significant independent predictors of HBV-HCC postoperative survival. Results: The portal vein thrombosis, tumor TNM classification and size were identified as statistically significant independent predictors of survival in HBV-HCC patients. In the research, we found that seven mutational sites in preC/C region of HBV were associated with independent risk factors for postoperative survival in patients of HBV-HCC. The following five mutational sites were identified as statistically significant independent predictors of HBV-HCC survival: 1915, 2134, 2176, 2221, 2260. The mutational site of 1979 and 2245 were identified for the association with survival at a borderline significance level. Conclusions The portal vein thrombosis, tumor TNM classification, size and seven mutational sites in the PreC/C region were identified as independent predictors of postoperative survival in HCC patients.