Codon usage bias of the phosphoprotein gene of spring viraemia of carp virus and high codon adaptation to the host.

In this study, we calculated the relative synonymous codon usage (RSCU) value and the effective number of codons (ENC) value to carry out principal component analysis (PCA) and correlation analysis of the codon usage pattern of the phosphoprotein gene (P gene) of spring viraemia of carp virus (SVCV). The synonymous codon usage pattern in P genes is geography-specific, based on PCA analysis. The high correlation between (G + C)1,2 % and (G + C)3 % suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage and base components in P genes. At least 40 out of 59 synonymous codons are similarly selected in all functional genes within five complete SVCV genomes, and the hosts based on the RSCU data. These results not only provide insight into variations in the codon usage pattern of SVCV but also may help in understanding the processes governing the evolution of SVCV.

Association of CYP3A polymorphisms with the pharmacokinetics of cyclosporine A in early post-renal transplant recipients in China.

AIM: To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS: One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clinical indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4*1G, CYP3A5*3C, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T polymorphisms. Whole blood trough concentrations of CsA at time zero (C(0)) were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted C(0) (C(0)/dose) based on several clinical indices. RESULTS: The CYP3A5*3C polymorphism influenced the C(0) and C(0)/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs (CYP3A4*1G, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T). In a univariate analysis using Pearson's correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA C(0)/dose. In the multiple regression model, CYP3A5*3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA C(0)/dose. CONCLUSION: CYP3A5*3C correlates with the C(0)/dose of CsA on the seventh day after renal transplantation. The allele is a putative indicator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.

Hypoxia-reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocyets and the protective effect of prostaglandin E.

The aim of the present study was to investigate the effect of prostaglandin (PG) E1 on hypoxia/re-oxygenation (H/R) apoptosis and the expression of bcl-2 and bax in cultured neonatal rat cardiomyocytes. The H/R model was made using the first generation of cultured neonatal rat cardiomyocytes. Hypoxia/re-oxygenation apoptosis was studied by electron microscopy and agarose gel electrophoresis. The percentage of apoptotic cells was measured by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL). The expression of bcl-2 and bax was detected by in situ hybridization and immunohistochemical staining. Most cells of the H/R group tested by electron microscopy showed cytoplasmic concentration, nuclear chromatin condensation and margination. Prostaglandin E1 (5, 15 and 45 microg/L) relieved the injury. The results of DNA electrophoresis in the H/R group showed a typical DNA ladder and the DNA ladder decreased gradually corresponding with increasing doses of PGE1. The TUNEL staining showed that the total number of apoptotic cells in the H/R group was much more than that in the PGE1 (45 microg/L) group. The results of in situ hybridization and immunohistochemical staining showed that the bcl-2 content in the H/R group was lower than that in the control group; bax content showed the reverse. Compared with the H/R group, bcl-2 content was significantly higher in the PGE1 (5, 15 and 45 microg/L) groups. However, bax content in the PGE1 (5, 15 and 45 microg/L) groups was significantly lower than that in the H/R group. 6. In conclusion, H/R injury can induce cardiomyocyte apoptosis. Prostaglandin E1 obviously has anti-apoptotic effects on cardiomyocytes and the mechanisms probably involve the inhibition of bax expression and increased expression of bcl-2.

Effect of G(alphaq/11) protein and ATP-sensitive potassium channels on prostaglandin E(1) preconditioning in rat hearts.

AIM: To investigate the effect of G(alphaq/11) signaling pathway and ATP-sensitive potassium channels (K(ATP) channels) on prostaglandin E1 (PGE1) induced early and delay-preconditioning protection in rat hearts. METHODS: Two series of experiments were performed in Wistar rat hearts. In the first series of experiment, all rats were pretreated with PGE1 40 min or 23 h 20 min before the experiment. Ischemia-reperfusion injury was induced by 30 min coronary artery occlusion followed by 90 min reperfusion. Hemodynamics, infarct size, and scores of ventricular arrhythmias were measured. The expression of G(alphaq/11) protein in the heart was measured by Western blot analysis in the second series. RESULTS: Preconditioning with PGE1 (25 microg/kg) markedly reduced infarct size, left ventricular end-diastolic pressure, and scores of ventricular arrhythmia. The effect of PGE1 was significantly attenuated by glibenclamide (1 mg/kg, ip), a nonselective K(ATP) channel inhibitor. PGE1 caused a significant increase in the expression of G(alphaq/11) protein. CONCLUSION: Activations of G(alphaq/11) signal pathway and K(ATP) channel played significant roles in the cardioprotection of PGE1 preconditioning in rat heart and might be an important mechanism of signal transduction pathway during the PGE1 preconditioning.