基于网络药理学的谷糠结合态多酚抗乳腺癌机制研究

本研究旨在探讨谷糠结合态多酚(bound phenol of inner shell,BPIS)发挥抗乳腺癌细胞活性的作用机制。首先采用细胞计数法检测BPIS对乳腺癌细胞以及正常乳腺细胞活性的影响;然后综合运用SEA、SIB以及GeneCards等数据库获得BPIS和乳腺癌的相关靶点,并分析活性成分与作用靶点的互作网络以及通路。本研究筛选得到BPIS抗乳腺癌相关靶点39个,主要涉及糖脂代谢和细胞自噬等生物过程以及MAPK、PI3K/AKT、FoxO等多条信号通,表明BPIS抗乳腺癌是多成分、多靶点、多通路协同作用的过程,而与细胞死亡相关的细胞自噬很可能在BPIS抑制乳腺癌过程中发挥主要作用。     

Phylogenetic patterns of diversification in a clade of Neotropical frogs (Anura: Aromobatidae: Mannophryne)

We used partial sequences of mitochondrial 16S and cytochrome oxidase I genes to perform a phylogenetic study of collared frogs (Anura: Aromobatidae: Mannophryne ), a genus endemic to Venezuela and the islands of Trinidad and Tobago. We analysed 1.2 kb from 13 of the 15 described species of Mannophryne . Maximum parsimony, maximum likelihood and Bayesian analyses support the monophyly of Mannophryne . Mannophryne consists of three deeply differentiated clades that split from each other in a relatively short period of time. The diversification of Mannophryne occurred well before the glacial-interglacial periods of the Quaternary. Our data support the taxonomic validity of M. olmonae , a species endemic to Tobago Island. Mannophryne olmonae is more closely related to the continental species Mannophryne riveroi than to the Trinidad island endemic Mannophryne trinitatis . As in most tropical clades of frogs, molecular evidence indicates that species richness in Mannophryne is largely underestimated and, consequently, current priorities for conservation are inadequate.  © 2009 The Linnean Society of London, Biological Journal of the Linnean Society , 2009, 97 , 185–199.     

Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.     

Isolation and characterization of a large,neurite-associated glycoconjugate from neuroblastoma cells

A high molecular weight glycoconjugate has been isolated from neurite-producing neuronal tumor cells in culture and has been designated as I(0) based on its elution characteristics in gel filtration chromatography. This molecule cannot be found in a variety of nonneuronal cells. I(0) is found in the substratum-attached material or cell fraction of neurite-producing neuroblastoma cells, depending upon culture conditions. It is found in the substratum-bound fraction of B104 rat neuroblastoma cells during serum starvation and in the EGTA-detached cell fraction of B104 cells grown in chemically defined N2 medium. It occurs only in the cell fraction of the human neuroblastoma line Platt. Examination of behavioral variants of the B104 rat line further strengthens the association of I(0) with neurite production; the constitutive neurite-producing E(R)B9 variant contains I(0) while the non-neurite-producing E(R)A11 variant does not. I(0) is large, eluting in the void volume of sepharose-CL2B columns. Radioiodination of intact cells with lactoperoxidase shows I(0) to be a cell surface component. Metabolic radiolabeling studies show that it contains a high proportion of polysaccharide to protein, does not contain mannose, and is unsulfated. Alkaline borohydride reduction release two size classes of large polysaccharide chain. The alkaline reduction results, along with the mannose incorporation studies, show the presence of O-glycosidic linkages and few, if any, N-linkages. Resistance to nitrous acid deamination, insensitivity to glycosaminoglycan lyases, and the absence of sulfation, indicate that I(0) does not contain the glycosaminoglycans hyaluronic acid, chondroitin-, dermatan-, or heparin- sulfates. Affinity column chromatography reveals high binding affinity of I(0) to polyornithine and no binding to gelatin (collagen) or the glycosaminoglycans hyaluronate and heparin. These studies describe a unique high molecular weight glycoconjugate on the surface of neurite-producing neuroblastoma cell lines from two species.     

Deep-level diagnostic value of the rDNA-ITS region

The similarity of certain reported angiosperm rDNA internal transcribed spacer (ITS) region sequences to those of green algae prompted our analysis of the deep-level phylogenetic signal in the highly conserved but short 5.8S and hypervariable ITS2 sequences. We found that 5.8S sequences yield phylogenetic trees similar to but less well supported than those generated by a ca. 10-fold longer alignment from rDNA-18S sequences, as well as independent evidence. We attribute this result to our finding that, compared to 18S, the 5.8S has a higher proportion of sites subject to vary and greater among-site substitution rate homogeneity. We also determined that our phylogenetic results are not likely affected by intramolecular compensatory mutation to maintain RNA secondary structure nor by evident systematic biases in base composition. Despite historical homology, there appears to be no ITS2 primary sequence similarity shared sufficient similarity to cluster correctly on the basis of alignability. Our results indicate that groups, however, share sufficient similarity to cluster correctly on the basis of alignability. Our results indicate that ITS region sequences can diagnose organismal origins and phylogenetic relationships at many phylogenetic levels and provide a useful paradigm for molecular evolutionary study.