BackgroundThe gene zinc finger homeobox 3 (ZFHX3) encodes a transcription factor with cardiac expression and its genetic variants are associated with atrial fibrillation (AF). We aimed to explore the associations between single nucleotide polymorphisms (SNPs) of ZFHX3 and the risk of AF in a Chinese Han population.MethodsWe genotyped eight SNPs, including seven potentially functional SNPs and one previously reported SNP by using the middle-throughput iPLEX Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models.ResultsWe enrolled a total of 1,593 Chinese Han origin individuals in the study, including 597 AF patients and 996 non-AF controls. Logistic regression analyses revealed that potentially functional SNPs rs6499600 and rs16971436 were associated with a decreased risk of AF (adjusted OR = 0.73, 95% CI: 0.63–0.86, P = 1.07×10−4; adjusted OR = 0.74, 95% CI: 0.56–0.98, P = 0.039, respectively). In addition, rs2106261 showed a robust association with an increased risk of AF (adjusted OR = 1.71, 95% CI: 1.46–2.00, P = 1.85×10−11). After multiple comparisons, rs16971436 conferred a borderline significant association with the risk of AF. Stratification analysis indicated that the risks of AF were statistically different among subgroups of age for rs2106261, and the effect for rs16971436 was more evident in subgroups of patients with coronary artery disease.ConclusionIn summary, our study investigated the role of genetic variants of ZFHX3 in AF and two SNPs (rs2106261, rs6499600) showed significant associations while rs16971436 conferred a borderline significant association with AF risk in Chinese Han populations. However, further large and functional studies are warranted to confirm our findings.
TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca2+-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased. However, the selectively knocked-down TRPM2 with the small interfering RNA technique inhibited the survival and migration of the SCC9 cancer cells, which was independent of the p53-p21 pathway, since the expression of p21 was enhanced after TRPM2 knockdown. Furthermore, the sub-cellular localization of TRPM2 was remarkably different between cancerous and non-cancerous cells. A significant amount of the TRPM2 proteins were located in the nuclei in cancer cells. All these data suggest that TRPM2 is essential for the survival and migration of SCC cancer cells and may be a potential target for the selective treatment of tongue cancer.
Glucose metabolism is a common target for cancer regulation and microRNAs (miRNAs) are important regulators of this process. Here we aim to investigate a tumor‐suppressing miRNA, miR‐33b, in regulating the glucose metabolism of non‐small cell lung cancer (NSCLC). In our study, quantitative real‐time polymerase chain reaction (qRT‐PCR) showed that miR‐33b was downregulated in NSCLC tissues and cell lines, which was correlated with increased cell proliferation and colony formation. Overexpression of miR‐33b through miR‐33b mimics transfection suppressed NSCLC proliferation, colony formation, and induced cell‐cycle arrest and apoptosis. Meanwhile, miR‐33b overexpression inhibited glucose metabolism in NSCLC cells. Luciferase reporter assay confirmed that miR‐33b directly binds to the 3′‐untranslated region of lactate dehydrogenase A (LDHA). qRT‐PCR and Western blot analysis showed that miR‐33b downregulated the expression of LDHA. Moreover, introducing LDHA mRNA into cells over‐expressing miR‐33b attenuated the inhibitory effect of miR‐33b on the growth and glucose metabolism in NSCLC cells. Taken together, these results confirm that miR‐33b is an anti‐oncogenic miRNA, which inhibits NSCLC cell growth by targeting LDHA through reprogramming glucose metabolism.
Epidemiological studies have reported conflicting results on the association of congenital heart defect (CHD) risk in offspring with a maternal history of prior pregnancies and abortions, but no meta-analysis has been reported. We searched MEDLINE and EMBASE from their inception to April 14, 2014, for relevant studies that assessed the association between maternal reproductive history and CHD risk. Two authors independently assessed eligibility and extracted data. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs). Among 1,599 references, 17 case-control studies and one nested case-control study were included in this meta-analysis. The summary OR for the ever versus nulligravidity was 1.18 (95% CI 1.03-1.34). A dose-response analysis also indicated a positive effect of maternal gravidity on CHD risk, and the summary OR for each increment in number of pregnancies was 1.13 (95% CI 1.08-1.18). A history of abortion was associated with a 24% higher risk of CHD, OR = 1.24 (95% CI 1.11-1.38). When stratified by abortion category, CHD risk increased by 18 and 58% with a history of spontaneous abortion and induced abortion, respectively. The summary OR for each increment of one abortion was 1.28 (95% CI 1.18-1.40). In summary, this study provides evidence that increased maternal gravidity was positively associated with a risk of CHDs in offspring. Meanwhile, our results demonstrate a positive association of any history of abortion with an increased risk of CHDs.
Fermented pepper is one of the traditional Chinese fermented vegetables. The production mainly relies on the fermentation by natural microorganisms. This fermentation system is a unique and dynamic microecological environment, and involved microbial communities are very complex. In this study, 454 pyrosequencing was first used to investigate the fungal communities in fresh pepper and different fermentation phases. The results showed that fungal communities in fresh pepper (sample M_0) were more abundant than later fermented phases. Taxa in proportions >0.01% could be assigned to 21 different genera. Taxa in proportions >1% were Trichosporon 24.11%, Rhodotorula 7.4%, Cladosporium 4.26%, Debarvomvces 3.94%, Mucor 2.51% and Cryptococcus 1.86%. There were a large number of unknown fungi (47.99%) in the sample waiting to be identified. Along with the fermentation, microbial communities became less diverse. Hanseniaspora and Pichia became the dominant fungal genera, while Trichosporon decreased from a maximum 24.11% to a minimum 0.1%. On the seventh fermentation day, the percentage of Hanseniaspora reached 89.3%. On the 20th fermentation day, taxa in proportions >1% were Hanseniaspora 69.25%, Unclassified 12.23%, Pichia 8.95%, Debaryomyces 6.22% and Rhodotorula 1.31%.
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