Résumé
Objective To analyze the correlation between P73 gene G4C14-to-A4T14 double nucleotide polymorphism and the risk of lung cancer in Guangdong population. Methods Genotype analysis of P73 gene polymorphism in peripheral blood of 642 patients with lung cancers (including 450 NSCLC patients and 192 SCLC patients) and 354 normal controls was performed with HRM method (high-resolution fusion curve). Results HRM genotyping results showed that the distribution of P73 genotypes in 450 NSCLC patients was as follows: GC/GC 280 (62.3%), GC/AT 155 (34.4%), and AT/AT 15 (3.3%). P73 genotypes in 192 SCLC patients were 118 GC/GC (61.5%), 67 GC/AT (34.9%) and 7 AT/AT (3.6%). The P73 genotypes of 354 normal controls were 192 GC/GC (53.1%), 136 GC/AT (38.5%), and 26 AT/AT (8.4%). AT/AT homozygous genotypes significantly reduced the risk of NSCLC (OR=0.393；95% CI:0.037-0.873；P=0.001) and SCLC (OR=0.428；95%CI:0.050-0.880；P<0.001) compared with non-carriers. Conclusion The results of the present study indicated that the polymorphism of P73 G4C14-A4T14 may be a modification factor for the susceptibility of lung cancer in Guangdong province, and the increased GC content in the P73 gene may increase the risk of lung cancer.
Résumé
In anaerobic bottles fermentation,glucose,fructose,xylose,lactose,maltose,sucrose and sugar alcohols could be used to produce succinic acid with Actinobacillus succinogenes. When sorbitol was utilized as the carbon source in the batch fermentation,more succinate and ethanol were produced compared with those using glucose,while producing less acetate and formate. The metabolic flux analysis results showed that the flux partitioning at PEP node was stable when glucose was replaced by sorbitol,but the flux partitioning at PYR and AcCoA nodes changed a lot because more reducing power(NADH) was generated to meet the more requirement the synthesis of succinate and ethanol.
Résumé
Succinic acid has received a great deal of attention as an important green chemical stock for the manufacture of synthetic resins, biodegradable polymers and chemical intermediates. In this paper, the breeding mechanism of Actinobacillus succinogenes based on metabolic flux analysis was demonstrated to improve the yield of succinic acid by fermentation. After the NTG treatment, mutants from A. succinogenes CGMCC 1593 which were able to grow in medium containing concentrations of about 50-100 mmol/L of sodium monofluoroacetate were obtained. Among them, a mutant SF-9 was selected for producing more succinic acid and less acetic acid. When fermentations were conducted in a 5 L bioreactors, the final succinic acid concentration of SF-9 (34.8 g/L) increased 23.4%, and the mass ratio of succinic acid/acetic acid increased from 3.3 to 9 compared with those of the parent strain. Based on the metabolic flux analysis of A. succinogenes, PEP was found to be a key node which has an important effect on the production of succinic acid, and the flux ratio of by-productions (acetic, formic, lactic acid) was influenced by PYR node. Compared with the parent strain, the flux to succinic acid of mutant (A. succinogenes SF-9) was significantly increased, while the flux to by-productions had an obvious decline. Therefore, PEP and PYR are not rigid nodes in the metabolic regulation of A. succinogenes.