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Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.
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<p><b>OBJECTIVE</b>To explore the relationship between G2139A,G3091A, T663A, and T3593C single nucleotide polymorphisms (SNPs), which are located at the promoter region,13th exon, and 2nd intron of epithelial sodium channel (ENaC) gene, and their haplotypes with essential hypertension (EH) in Kazakhs in Xinjiang.</p><p><b>METHODS</b>A case-control study was conducted including 252 EH patients (EH group) and 254 normotensive subjects (NT group) among Kazakhs in Xinjiang. The four genetic polymorphisms were identified by polymerase chain reaction - restriction fragment length polymorphism. The distribution of the genotypes and alleles in all subjects and the different frequency of these four SNPs between EH group and NT group were analyzed. The linkage disequilibrium and haplotypes of these four SNPs were analyzed.</p><p><b>RESULTS</b>These four SNPs of alpha ENaC gene existed in Xinjiang Kazakhs. In all subjects, the distribution frequencies of genotypes AA, AG, and GG at G2139A were 26.2%, 52.3%, and 21.5%, respectively, and those of alleles (A, G) were 52.37% and 47.63%. The distribution frequencies of genotypes AA, AG, and GG at G3091A were 19.0%, 52.5%, and 28.5%, respectively, and those of and alleles (A, G) were 45.56% and 59.44%. The distribution frequencies of genotypes AA, AG, and GG at T663A were 15.6%, 49.9%, and 34.5%, respectively, and those of alleles (A, G) were 40.53% and 59.47%. The distribution frequencies of genotypes TT, TC, and CC at T3593C were 88.5%, 10.5%, and 1.0%, respectively, and those of alleles (T, C) were 93.77% and 6.23%. The distribution of genotypes at these four SNPs were all consistent with Hardy-Weinberg equilibrium in this population (P0.05). The distribution frequencies of genotypes and alleles about these four genetic polymorphisms were not significantly different between the EH group and NT group (P0.05). However, the frequencies of two haplotypes were found to be significantly different between these two groups (P0.05). The haplotype frequency which included 2139G, 3091A, 663G, and 3593T alleles was significantly increased in EH group (P0.01), while the haplotype frequency which included 2139A, 3091A, 663A, and 3593C alleles was significantly increased in NT group (P0.05).</p><p><b>CONCLUSIONS</b>The haplotypes that are composed of G2139A, G3091A, T663A, and T3593C polymorphisms of alphaENaC gene may play an important role in the development of EH among Kazakhs in Xinjiang. The haplotypes that are composed of 2139G, 3091A, 663G, and 3593T alleles may aggravate the development of EH. The haplotypes that composed of 2139A, 3091A, 663A, and 3593C alleles may decrease the risk of EH among Kazakhs.</p>