A functional SNP regulated by miR-196a-3p in the 3'UTR of FGF2 is associated with bone mineral density in the Chinese population.

Previous studies have identified FGF2 as a susceptibility gene for osteoporosis in Caucasians. Evaluating the genetic associations in different ethnicities is necessary. Moreover, elucidating the functional mechanism for the susceptibility loci is important to offer new targets for therapeutic studies. Here, we genotyped 10 SNPs in FGF2 and tested for associations with bone mineral density (BMD) in a discovery sample of 1,300 Chinese subjects. Nominally significant results were subjected to replication in another sample of 1,039 Chinese subjects. We identified one SNP rs1048201:C>T in FGF2 3'untranslated region significantly associated with spine BMD (combined cohorts, P = 1.53×10-3 ). Expression quantitative trait locus analyses revealed that rs1048201 also affected FGF2 gene expression (P = 7.03×10-4 ). Bioinformatics prediction suggested that rs1048201 T allele could disrupt miRNA binding. Luciferase assay validated that the C allele had a repressive effect on FGF2 gene expression. We found that hsa-miR-196a-3p affected expression on both mRNA and protein levels of FGF2. In conclusion, our study provided evidence that a functional SNP rs1048201 was associated with BMD, and SNP rs1048201:C>T variant may act by affecting binding of hsa-miR-196a-3p. The SNP-modified posttranscriptional gene regulation by miRNA could be a potentially pathogenetic mechanism of osteoporosis.

Impact of environmental factors on the toxicity of Bacillus thuringiensis var. israelensis IPS82 to Chironomus kiiensis.

To determine the feasibility of microbiological control of chironomid larvae in water sources for the city of Shenzhen, China, the toxicity characteristics of Bacillus thuringiensis var. israelensis (Bti) IPS82 on Chironomus kiiensis Tokunaga were studied. Tests on fermentation products of IPS82 showed good correlations between toxicity, cell density, dissolved oxygen, and the spore-forming phase. In this study, bioassays were carried out with different stage larvae. Results showed that the LC50s (24 h postexposure) were 8.2, 15.2, 24.7, and 38.6 mg/liter for the 1st, 2nd, 3rd, and 4th instars, respectively. Tests on environmental factors influencing toxicity of Bti to C. kiiensis showed that sunlight is the most important factor, shortening the half-life of Bti from 21 days in dark to 10 days under sunlight. Temperature variations (15-30 degrees C) caused no impact on toxicity, but a 16% increase in larval mortality was observed at 35 degrees C. The toxicity of IPS82 was greatest at a pH of 7. In field trials, dosages above 100 mg/liter were effective in the control of C. kiiensis. Our study indicated that it is feasible to use Bti to control C. kiiensis in city source water.

[Security of dual cancer-specific targeting vector and its cytotoxic effect when harbored].

BACKGROUND & OBJECTIVE: The xenograft tumor mass in nude mice could be completely eliminated using the targeting dual gene-virotherapy strategy. Now, the most important point is to improve its security. This study was to construct dual cancer-specific targeting adenovirus called TD55 to evaluate its security, and construct TD55-TRAIL to explore its antitumor effect. METHODS: Plasmid pTD55 was constructed through replacing E1A promoter with promoter of human telomerase reverse transcriptase and deleting E1B 55KD gene, and plasmid pTD55-TRAIL was constructed by inserting TRAIL gene into pTD55. Adenoviruses TD55 and TD55-TRAIL were obtained through homologous recombination in 293 cells. Cytotoxic effects of TD55 and TD55-TRAIL on human colon cancer cell lines SW620 and HCT116, human lung cancer cell line A549, and human embryonic lung cell lines MRC5 and WI38 were detected by crystal violet staining and MTT assay. Tumor cell apoptosis was detected by flow cytometry. RESULTS: Cytotoxic effects of TD55-TRAIL on MRC5 and WI38 cells were weaker than those of ZD55-TRAIL. The virus proliferation ability of ZD55-TRAIL in normal cells is 3-5 times stronger than those of TD55 and TD55-TRAIL. The apoptosis rate of TD55-TRAIL-infected SW620 cells was 3.3 times as high as that of TD55-infected SW620 cells. CONCLUSIONS: TD55-TRAIL has better security than ZD55-TRAIL in normal cells. So, the security of medication will be improved with dual targeting vector TD55. TD55-harbored gene as TD55-TRAIL has stronger effect than TD55 in inducing apoptosis of tumor cells.