Biological functions of eukaryotic FRD superfamily members from published experiments.

<p>Biological functions of eukaryotic FRD superfamily members from published experiments.</p

Maximum likelihood phylogeny of the FRD superfamily.

<p>A. Phylogram of the NOX family rooted to DUOX genes (outgroup not shown). The tree topology suggests lineage-specific gene duplications in all major taxonomic clades. The NOX1-3 and NOX4 subfamilies possibly diverged before the emergence of metazoans. B. Phylogeny of eukaryotic gene families of the FRE group and the NOX group. According to this model, the DUOX family and NOX family form sister clades, but not the EF-hands containing protein families NOX5 and DUOX. C. Phylogenetic tree of the FRD superfamily. The tree topology proposes that the metazoan STEAP family (red) emerges from the bacterial clade at the base of the YedZ family. The gene AM1_3152 from the cyanobacterium <i>Acaryochloris marina</i> (strain MBIC 11017) (UniProtKB: B0CEP3) was probably obtained from an ancestral gene of the eukaryotic NOX5 family. Explanation: The names of gene families and gene groups are indicated with curly brackets. Branch colors correspond to those of the listed taxonomic groups.</p

Sequence conservation logos and the proposed structure of the ferric reductase domain of protein groups from the FRD superfamily.

<p>A. Transmembrane domains TM3 to TM5 - as predicted for human cytochrome b-245 heavy chain (NOX2) - are indicated by gray rectangles. The cladogram indicates the phylogenetic relationship of the analyzed homologous groups. In the conservation logos, the height of the stacks indicates sequence conservation; the width of the stacks is proportional to the fraction of amino acids, thus narrowed within gapped regions. B. Proposed structure of ferric reductase domain with conserved amino acid residues corresponding to the annotation in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058126#pone-0058126-g004" target="_blank">figure 4A</a>.</p

Domain architecture of FRD superfamily members.

<p>Models of domain architectures are mapped to the phylogenetic gene trees of bacterial (A) and eukaryotic (B) FRD homologs. Tree branch colors correspond to the color code of the models (see highlight color of model identifiers). The three conserved domains of the ‘eukaryotic structural core’ are colored, and other predicted domains are given in black. Domain forms indicate their function; rounded rectangle = binding of electron donor/hydrogen acceptor: FAD-binding, NADPH-binding (M3), FMN (M4); triangle = electron transfer agent: Ferredoxin/Fer2 (M8), Rieske (M4), DOMON (M10), peroxidase-like domain (M15); circle = regulation of enzyme activity: EF-hands (M14–M16); hexagon = protein-protein interaction: NADPH-oxidase-like domain (M16), SH3 (M17); ellipse = transport of small solutes: MSF (M6).</p

A model of the evolutionary history of the FRD superfamily.

<p>The ancestral system may have used reduced quinol to produce soluble ferrous ions and progressed into a highly regulated system that generates immunologically potent ROS by using NADPH as electron source.</p

Phyletic profile and molecular function of the FRD superfamily.

<p>On the left-hand side, phyletic profile for 47 species: gene copy numbers are plotted in accordance with the species phylogeny (left) and gene families: The number of NOX homologs of a species is given in red cells, FRE homologs in blue cells, and preNOX in orange ones. Some cells are merged according to the family hierarchy. The number of predicted homologs is given in the last column of the phyletic profile. On the right-hand side, gene copies are represented by lines which link the corresponding species and protein families; the thickness of these lines indicates the number of gene copies. Colored lines flag experimentally confirmed gene functions: red = ROS-generating NADPH oxidase activity; blue = metalloreductase activity. Black circles mark species that possess p22phox homologs.</p

Propofol inhibits proliferation, migration, and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells

<div><p>Propofol is an intravenous sedative hypnotic agent of which the growth-inhibitory effect has been reported on various cancers. However, the roles of propofol in endometrial cancer (EC) remain unclear. This study aimed to explore the effects of propofol on EC in vitro and in vivo. Different concentrations of propofol were used to treat Ishikawa cells. Colony number, cell viability, cell cycle, apoptosis, migration, and invasion were analyzed by colony formation, MTT, flow cytometry, and Transwell assays. In addition, the pcDNA3.1-Sox4 and Sox4 siRNA plasmids were transfected into Ishikawa cells to explore the relationship between propofol and Sox4 in EC cell proliferation. Tumor weight in vivo was measured by xenograft tumor model assay. Protein levels of cell cycle-related factors, apoptosis-related factors, matrix metalloproteinases 9 (MMP9), matrix metalloproteinases 2 (MMP2) and Wnt/β-catenin pathway were examined by western blot. Results showed that propofol significantly decreased colony numbers, inhibited cell viability, migration, and invasion but promoted apoptosis in a dose-dependent manner in Ishikawa cells. Moreover, propofol reduced the expression of Sox4 in a dose-dependent manner. Additionally, propofol significantly suppressed the proportions of Ki67+ cells, but Sox4 overexpression reversed the results. Furthermore, in vivo assay results showed that propofol inhibited tumor growth; however, the inhibitory effect was abolished by Sox4 overexpression. Moreover, propofol inhibited Sox4 expression via inactivation of Wnt/β-catenin signal pathway. Our study demonstrated that propofol inhibited cell proliferation, migration, and invasion but promoted apoptosis by regulation of Sox4 in EC cells. These findings might indicate a novel treatment strategy for EC.</p></div

Funnel and filled funnel plots for studies investigating the effect of <i>CHRNA3</i> gene polymorphism rs1051730 (A and B) and <i>AGPHD1</i> gene polymorphism rs8034191 (C and D) on the risk of lung cancer.

<p>Funnel and filled funnel plots for studies investigating the effect of <i>CHRNA3</i> gene polymorphism rs1051730 (A and B) and <i>AGPHD1</i> gene polymorphism rs8034191 (C and D) on the risk of lung cancer.</p

The baseline characteristics of all qualified studies in this meta-analysis.

<p><i>Abbreviations:</i> NSCLC, non-small-cell lung cancer; SLCC, lung squamous cell carcinoma; NA, not available.</p>*<p>Mixed ethnicity included Caucasian, African-American and Hispanic.</p

Overall and subgroup analyses of <i>CHRNA3</i> gene rs1051730 polymorphism with the odds of developing lung cancer under allelic and dominant models.

<p><i>Abbreviations:</i> NA, not available; OR, odds ratio; 95% CI, 95% confidence interval; NSCLC, non-small-cell lung cancer; LSCC, lung squamous cell carcinoma.</p>*<p>Matched on age or sex or smoking.</p