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31.
Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital based case–control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs) in the microRNAs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this study. The hsa-miR-34b/c rs4938723 T>C, pri-miR-124-1 rs531564 C>G, pre-miR-125a rs12975333 G>T and hsa-miR-423 rs6505162 C>A genotypes were determined using Ligation Detection Reaction (LDR) method. Our results demonstrated that hsa-miR-34b/c rs4938723 CC genotype had a decreased risk of ESCC. The association was evident among patients who never drinking. Hsa-miR-423 rs6505162 C>A might associated with a significantly increased risk of ESCC in patients who smoking. These findings indicated that functional polymorphisms hsa-miR-34b/c rs4938723 T>C and hsa-miR-423 rs6505162 C>A might alter individual susceptibility to ESCC. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations are required to confirm current findings.  相似文献   
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The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.  相似文献   
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Breast carcinoma is one of the most commonly diagnosed tumors and also one of the deadliest cancers in the female. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for breast cancer diagnosis and treatment. In this study, we aimed to study the lncRNAs associated with the outcomes in patients using the breast invasive carcinoma datasets from The Cancer Genome Atlas. The Cox proportional hazards regression model was fitted to each lncRNA. Hierarchy clustering was carried out using these survival-related lncRNAs and the log-rank test was carried out for the clustered groups. DNA methylation status was utilized to identify the lncRNAs regulated by epigenetics. Finally, the coexpressed messenger RNA with the potential lncRNAs were utilized to study the possible functions and mechanisms of lncRNAs. In total, 182 lncRNAs had an impact on the survival time of the patients with a cutoff <0.01. The patients were clustered into three groups using these survival-related genes, which performed significantly different prognosis. Two lncRNAs, which were significantly correlated with the outcomes of breast cancer and were regulated by methylation status, were obtained. These two lncRNAs were TP53TG1 and RP5-1061H20.4. We proposed that TP53TG1 was activated by the wild-type TP53 and performed an impact on the PI3Ks family by binding YBX2 in breast cancer.  相似文献   
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前期研究脑表明,脑胶质瘤干细胞(glioma stem cells,GSCs)是胶质瘤发生和发展的重要因素,探索靶向干预GSCs生长有可能成为脑胶质瘤治疗的有效途径之一。该研究旨在阐明两种药物ATRA和Y-分泌酶抑制剂DAPT协同抑制GSCs自我更新的生物学效应。通过用台盼蓝排染法、克隆球形成试验和免疫印迹分析了两种药物的单独使用或联用对GSC样细胞PGCl和PGC2生长、成球能力和自我更新以及干细胞标志物表达的影响。结果发现,单独使用ATRA对PGCl生长有一定的抑制作用,而对PGC2生长几乎没有影响;DAPT对PGCs的生长抑制作用明显强于ATRA。高浓度ATRA(80μmol/L)能诱导PGCs的分化,降低PGCs成球大小,且成球效率降至5%~8%,而正常对照组为32%~35%;同样,DAPT(40μmol/L)也能降低PGCs成球大小,且成球效率降至2%~3%;低浓度ATRA(20μmol/L)和DAPT(5gmol/L)对PGCs自我更新能力和干性没有明显影响,而联合使用后其明显降低PGCs的成球大小,且成球效率降至3%~5%,促进细胞凋亡,并且明显抑制了干细胞标志物Nestin、CDl33、Sox2、Oct4的表达,提高了分化标志物GFAP的表达。该研究证明了低浓度的ATRA和DAPT能协同抑制脑胶质瘤干细胞PGCs的自我更新。研究结果将为脑胶质瘤的临床研究提供实验依据。  相似文献   
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The morphology, ontogeny and molecular phylogeny of Apobakuella fusca gen. n., sp. n. and Parabistichella variabilis gen. n., sp. n., from south China were investigated. Apobakuella fusca, brown colored, demonstrates bakuellid-like infraciliature, and a similar ontogenesis as the genus Bakuella. It is argued, however, that this species represents a novel genus, Apobakuella, which is characterized by two or more marginal rows on the right, several buccal and parabuccal cirri, and lack of frontoterminal and caudal cirri. Phylogenetic analysis based on SSU rRNA gene sequences supports the close relationship of Apobakuella with Neobakuella and Diaxonella within the core Urostylida. By contrast, Parabistichella variabilis has a dominant frontoventral row, few midventral pairs, a long midventral row, and one marginal row on each side. Its morphogenesis exhibits: (1) partial reorganization of the parental adoral membranelles; (2) over six frontoventral-transverse cirri anlagen; (3) intrakinetal development of the midventral row; and (4) very likely, formation of the frontoventral row from the midventral row anlage. Both the morphological characteristics and the SSU rRNA gene sequences suggest that it is incertae sedis among the basal hypotrichs. Further investigation of key taxa with additional molecular markers is required to reveal a better understanding on the phylogeny of Parabistichella.  相似文献   
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The methionine adenosyltransferase gene (MAT) had been isolated from an economic seaweed Undaria pinnatifida by PCR using degenerate primers. The cDNA was 1,491 bp in length with an open reading frame of 1,194 nucleotides, encoding a deduced protein of 397 amino acids. The protein had a predicted molecular weight of 43.2 kDa, and the isoelectric point was 5.244. The sequence contains a 92 bp 5′-untranslated region (UTR) and a 205 bp 3′-UTR. The methionine adenosyltransferase (MAT) sequence of U. pinnatifida (UpMAT) shared 68–92 % identities with the previous published MAT sequences of other species. Phylogenetic analysis indicated that the phylogenetic relationship of UpMAT with some other seaweeds was closer than with those of higher plants. Under different stress conditions, the relative mRNA expression levels of the MAT of U. pinnatifida (UpMAT) were measured by real-time quantitative PCR, and the results demonstrated that the UpMAT might help to protect the alga against various abiotic stresses.  相似文献   
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