Polymorphisms of CYP1A1 I462V and GSTM1 genotypes and lung cancer susceptibility in Mongolian

Aim: To study the genotype of cytochrome P450 1A1(CYP1A1) I462V and glutathions S-transferase M1( GSTM1) and the relationship of the genetic polymorphism of them with the susceptibility of lung cancer in Mongolia of China. 

Methods: Allele-specific PCR and a multiplex PCR were employed to identify the genotypes of I462V of CYP1A1 and GSTM1 in a case-control study of 210 lung cancer patients with bronchoscopy diagnosis and 210 matched controls free of malignancy.

Results: The frequencies of the variant CYP1A1(Val/Val) genotypes and GSTM1(-) in lung cancer groups were higher than that in control groups (15.24% vs 7.4% and 56.67% vs 40.95% ). The individuals who carried with CYP1A1(Val/Val) or GSTM1(-) genotype had a significantly higher risk of lung cancer, the OR is 2.56 and 1.89 respectively. Stratified histologically the relative risk increased to 2.6 - fold when the patients carried with two valine alleles than the ones carried one valine allele in cases of SCC. GSTM1(-) genotype is the risk factor of SCC (OR=2.39) and AC(OR=2.16). The presence of at least one Val allele of CYP1A1 and GSTM1(-), the risk of lung cancer was increased, the OR was 4.15 for one Val allele and GSTM1(-) and 2.67 for two Val alleles and GSTM1 Considering ages and smoking status, the risk of lung cancer increased when the age less than 50 who carried with CYP1A1 valine (one or two) alleles or the age during the 51 to 65 who carried with GSTM1(-) genotype. The light smokers with CYP1A1 valine alleles and GSTM1(-) have a high risk for lung cancer. No association was found between the light and heavy drinkers with the susceptibility of lung cancer and the genetic polymorphisms of CYP1A1 I462V and GSTM1(-). 

Conclusion: The valine allele of CYP1A1 was the risk factors of lung cancer especially for SCC and GSTM1(-) also was the risk factor of lung cancer and especially for SCC and AC of Mongolian, China. Light smoking has a influence each other with genotype of CYP1A1 I462V and GSTM1(-) and susceptibility of lung cancer. No relationship was found between the susceptibility of lung cancer and drinkers with genetic polymorphisms of CYP1A1 I462V and GSTM1(-). The influence of genotypes on the susceptibility of lung cancer may depend on the ages. There may be a synergetic interaction between CYP1A1 valine allele and GSTM1(-) genotypes on the elevated susceptibility of lung cancer. So do those genotypes with light smokers. Key words polymorphism; genotype; lung cancer; cytochrome P450；glutathione S-transferase Abbreviations: SCC, squamous cell carcinoma; AC, adenocarcinoma; SCLC, small cell lung cancer; LCLC, large cell lung cance

Effect of ammonia on the immune response of mud crab (Scylla paramamosain) and its susceptibility to mud crab reovirus

Ammonia is one of the major environmental pollutants that affect the growth and physiological functions of organisms. In the present study, the effects of ammonia on the immune response and pathogen resistance of mud crab reovirus (MCRV) in mud crab were investigated. Mud crab were exposed to four different ammonia concentrations (0, 2.5, 5 and 10 mg L-1 ammonia-N) for 7 d. The result showed that aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity significantly increased after 5 and 10 mg L-1 ammonia exposure. The hepatopancreas superoxide dismutase (SOD), catalase (CAT), and total antioxidative capacity (T-AOC) in ammonia-N group were significantly lower than those in the control group, while the levels of malondialdehyde (MDA) were significantly higher than those in the control group. Significant reductions in total hemocyte counts (THC) were observed after ammonia exposure. After 7d ammonia exposure, mud crabs were injected 100 μL MCRV at 105 copies/g body weight. The mortality of mud crabs in ammonia-N group were significantly higher than those in the control group. All these results suggested that ammonia in water caused a depression in the immune response, and increased susceptibility to MCRV infection

Bioconversion of Raw Glycerol From Waste Cooking-Oil-Based Biodiesel Production to 1,3-Propanediol and Lactate by a Microbial Consortium

Waste cooking oil (WCO) is a sustainable alternative to raw vegetable oils and fats for biodiesel production considering both environmental and economic benefits. Raw glycerol from WCO-based biodiesel production (GWCO) is difficult to utilize via biological method, as multiple toxic impurities have inhibitory effects on microbial growth especially for pure cultures. In this work, four microbial consortia were selected from activated sludge by 30 serial transfers under different conditions. The obtained consortia exhibited lower diversity and species difference with the transfers. The consortium LS30 exhibited unique advantages for bioconversion of GWCO to 1,3-propanediol (1,3-PDO) and lactate (LA). Moreover, the fermentation could be performed economically under microaerobic and non-sterile conditions. The consortium consisted of 57.97% Enterobacter and 39.25% Escherichia could effectively convert 60 g/L GWCO to 1,3-PDO and LA in batch fermentation. In addition, this consortium exhibited better tolerance to fatty acid-derived crude glycerol (100 g/L), which demonstrated that specific toxic impurities in GWCO did pose a great challenge to microbial growth and metabolism. In fed batch fermentation, 27.77 g/L 1,3-PDO and 14.68 g/L LA were achieved. Compared with the consortium, a long lag phase in cell growth associated with a decreased glycerol consumption was observed in four single-strain fermentations. Furthermore, neither the consortium DL38 with excellent glycerol tolerance nor consortium C2-2M with high yield of 1,3-PDO could effectively transform GWCO into valuable products. The results demonstrated that the selected microbial consortium has the advanced adaptability to the toxic impurities in GWCO compared with other reported consortia and isolated single strain. This process can contribute to added-value use of GWCO

Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody.</p> <p>Methods</p> <p>DNA-PKcs epitopes were predicted and cloned. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA damage repair was analyzed by comet assay and immunofluorescence detection of γH2AX foci. The radiosensitization in vivo was determined on Balb/c athymic mice transplanted tumours of HeLa cells.</p> <p>Results</p> <p>Four epitopes of DNA-PKcs have been predicted and expressed as the antigens, and a specific human anti-DNA-PKcs scFv antibody gene, anti-DPK3-scFv, was obtained by screening the phage antibody library using the DNA-PKcs peptide DPK3. The specificity of anti-DPK3-scFv was verified, <it>in vitro</it>. Transfection of HeLa cells with the anti-DPK3-scFv gene resulted in an increased sensitivity to IR, decreased repair capability of DNA double-strand breaks (DSB) detected by comet assay and immunofluorescence detection of γH2AX foci. Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. Measurement of the growth and apoptosis rates showed that anti-DPK3-scFv enhanced the sensitivity of tumours transplanted in Balb/c athymic mice to radiation therapy.</p> <p>Conclusion</p> <p>The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential.</p