Association between peripheral blood WBCs C3aR mRNA level and plasma C3a, C3aR, IL-1ß concentrations and acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The relationship between C3a-C3aR, IL-1ß, and the acute exacerbation of chronic obstructive pulmonary disease is still unclear. This study aims to explore the expression levels of C3aR in peripheral blood WBCs and the concentrations of C3a, C3aR, and IL-1ß in plasma in healthy controls and patients with chronic obstructive pulmonary disease (COPD). METHODS: WBCs C3aR level in the peripheral blood, the concentrations of C3a, C3aR, and IL-1ß in plasma were measured in 60 patients with acute exacerbation of COPD (AECOPD), 30 patients with stable COPD (SCOPD), and 30 healthy controls. The baseline characteristics and clinical data collected from enrolled patients, including age, gender, laboratory indicators, and lung function. We analyzed the correlation between C3a, C3aR, IL-1ß, and lung function indicators (forced expiratory volume in the first second as a percentage of predicted value, FEV1%pred) in the AECOPD group. RESULTS: The white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP) of patients in COPD were higher than in healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were higher than in SCOPD and healthy controls (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3aR, and IL-1ß in AECOPD combined with respiratory failure were higher than in the non-respiratory failure group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD with high-risk were higher than in the low-risk group (P < 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in AECOPD were negatively correlated with FEV1pred%. The peripheral blood WBCs C3aR mRNA, the plasma C3a and C3aR in AECOPD were positively correlated with IL-1ß. CONCLUSION: The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1ß in COPD patients were significantly related to the risk of disease deterioration. The C3a-C3aR axis may be involved in airway inflammation in patients with COPD.

CpG methylation participates in regulation of hepatitis B virus gene expression in host sperm and sperm-derived embryos.

AIM: This study was undertaken to investigate relationship between hepatitis B virus (HBV) CpG methylation and HBV gene transcription in sperm and sperm-derived embryos. METHODS: HBV-infected patient sperm and HBV plasmid-transfected donor sperm were subjected to interspecific in vitro fertilization, methylation-specific PCR, bisulfite sequencing PCR, reverse transcription PCR and real-time quantitative PCR. RESULTS: Positive methylation bands for CpG islands II and III in the HBV genome were observed in patient sperm but not in controls, and methylation percentages of CpG sites varied among different patient sperm samples. After fertilization, CpG sites were highly demethylated in embryos. Transcriptional levels of HBV X and S genes increased with decrease in CpG site methylation percentages. CONCLUSION: HBV CpG sites can be methylated in patient sperm before maturation. Methylation of CpG islands II and III participates in transcriptional regulation of HBV X and S genes, respectively, in sperm and sperm-derived embryos.

Mutations and CpG islands among hepatitis B virus genotypes in Europe.

BACKGROUND: Hepatitis B virus (HBV) genotypes have a distinct geographical distribution and influence disease progression and treatment outcomes. The purpose of this study was to investigate the distribution of HBV genotypes in Europe, the impact of mutation of different genotypes on HBV gene abnormalities, the features of CpG islands in each genotype and their potential role in epigenetic regulation. RESULTS: Of 383 HBV isolates from European patients, HBV genotypes A-G were identified, with the most frequent being genotype D (51.96%) in 12 countries, followed by A (39.16%) in 7 countries, and then E (3.66%), G (2.87%), B (1.57%), F (0.52%) and C (0.26%). A higher rate of mutant isolates were identified in those with genotype D (46.7%) followed by G (45.5%), and mutations were associated with structural and functional abnormalities of HBV genes. Conventional CpG island I was observed in genotypes A, B, C, D and E. Conventional islands II and III were detected in all A-G genotypes. A novel CpG island IV was found in genotypes A, D and E, and island V was only observed in genotype F. The A-G genotypes lacked the novel CpG island VI. "Split" CpG island I in genotypes D and E and "split" island II in genotypes A, D, E, F and G were observed. Two mutant isolates from genotype D and one from E were found to lack both CpG islands I and III. CONCLUSIONS: HBV genotypes A-G were identified in European patients. Structural and functional abnormalities of HBV genes were caused by mutations leading to the association of genotypes D and G with increased severity of liver disease. The distribution, length and genetic traits of CpG islands were different between genotypes and their biological and clinical significances warrant further study, which will help us better understand the potential role of CpG islands in epigenetic regulation of the HBV genome.

CpG islands of hepatitis B virus genome isolated from Chinese patients.

There are differences in the distribution and length of HBV CpG islands and the viral mutations contribute greatly to the development of HBV-related diseases. However, little is known regarding the effects of such difference and mutations in HBV genotypes B and C sequences on the regulation of HBV gene expression and their clinical outcomes. To study the distribution, length and genetic trait of CpG islands in normal and mutant sequences of HBV genotypes B and C, 320 HBV isolates from Chinese patients were retrieved from GenBank. Programs CLUSTALX 1.83 and MethPrimer were employed to perform multiple sequence alignments and to predict CpG islands, respectively. 72.0% genotype B isolates contained three conventional CpG islands, and 76.1% genotype C only contained CpG islands II and III. 14.6% genotype B and 7.5% genotype C contained three novel CpG islands. In genotype B, lengths of conventional CpG islands between normal and mutant isolates exhibited substantial variations, but in genotype C, those were relatively stable. CpG island II could be "truncated" or "split". "Truncated" region mutations were associated with structural and functional abnormalities of HBV genes. Rate of "split" CpG island II in genotype B was much higher than that in genotype C. In the majority of isolates from HCC and HBV-ACLF, genotype C lacked CpG island I and novel islands. Distribution, length and genetic trait of CpG islands in HBV genotypes B and C might affect their methylation status, and further affect regulation of HBV gene expression, leading to different clinical outcomes.