Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer Cells

Cancer is the second leading cause of deaths worldwide. Despite concerted efforts to improve the current therapies, the prognosis of cancer remains dismal. Highly selective or specific blocking of only one of the signaling pathways has been associated with limited or sporadic responses. Using targeted agents to inhibit multiple signaling pathways has emerged as a new paradigm for anticancer treatment. Icariside II, a flavonol glycoside, is one of the major components of Traditional Chinese Medicine Herba epimedii and possesses multiple biological and pharmacological properties including anti-inflammatory, anti-osteoporosis, anti-oxidant, anti-aging, and anticancer activities. Recently, the anticancer activity of Icariside II has been extensively investigated. Here, in this review, our aim is to give our perspective on the current status of Icariside II, and discuss its natural sources, anticancer activity, molecular targets and the mechanisms of action with specific emphasis on apoptosis pathways which may help the further design and conduct of preclinical and clinical trials.Icariside II has been found to induce apoptosis in various human cancer cell lines of different origin by targeting multiple signaling pathways including STAT3, PI3K/AKT, MAPK/ERK, COX-2/PGE2 and β-Catenin which are frequently deregulated in cancers, suggesting that this collective activity rather than just a single effect may play an important role in developing Icariside II into a potential lead compound for anticancer therapy. This review suggests that Icariside II provides a novel opportunity for treatment of cancers, but additional investigations and clinical trials are still required to fully understand the mechanism of therapeutic effects to further validate it in anti-tumor therapy.     

REDHORSE-REcombination and Double crossover detection in Haploid Organisms using next-geneRation SEquencing data

Background

Next-generation sequencing technology provides a means to study genetic exchange at a higher resolution than was possible using earlier technologies. However, this improvement presents challenges as the alignments of next generation sequence data to a reference genome cannot be directly used as input to existing detection algorithms, which instead typically use multiple sequence alignments as input. We therefore designed a software suite called REDHORSE that uses genomic alignments, extracts genetic markers, and generates multiple sequence alignments that can be used as input to existing recombination detection algorithms. In addition, REDHORSE implements a custom recombination detection algorithm that makes use of sequence information and genomic positions to accurately detect crossovers. REDHORSE is a portable and platform independent suite that provides efficient analysis of genetic crosses based on Next-generation sequencing data.

Results

We demonstrated the utility of REDHORSE using simulated data and real Next-generation sequencing data. The simulated dataset mimicked recombination between two known haploid parental strains and allowed comparison of detected break points against known true break points to assess performance of recombination detection algorithms. A newly generated NGS dataset from a genetic cross of Toxoplasma gondii allowed us to demonstrate our pipeline. REDHORSE successfully extracted the relevant genetic markers and was able to transform the read alignments from NGS to the genome to generate multiple sequence alignments. Recombination detection algorithm in REDHORSE was able to detect conventional crossovers and double crossovers typically associated with gene conversions whilst filtering out artifacts that might have been introduced during sequencing or alignment. REDHORSE outperformed other commonly used recombination detection algorithms in finding conventional crossovers. In addition, REDHORSE was the only algorithm that was able to detect double crossovers.

Conclusion

REDHORSE is an efficient analytical pipeline that serves as a bridge between genomic alignments and existing recombination detection algorithms. Moreover, REDHORSE is equipped with a recombination detection algorithm specifically designed for Next-generation sequencing data. REDHORSE is portable, platform independent Java based utility that provides efficient analysis of genetic crosses based on Next-generation sequencing data. REDHORSE is available at http://redhorse.sourceforge.net/.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1309-7) contains supplementary material, which is available to authorized users.     

Highly sensitive ethanol chemical sensor based on Ni-doped SnO₂ nanostructure materials

Due to potential applications of semiconductor transition doped nanostructure materials and the important advantages of synthesis in cost-effective and environmental concerns, a significant effort has been consummated for improvement of Ni-doped SnO(2) nanomaterials using hydrothermal technique at room conditions. The structural and optical properties of the low-dimensional (average diameter, 52.4 nm) Ni-doped SnO(2) nanostructures were demonstrated using various conventional techniques such as UV/visible spectroscopy, FT-IR spectroscopy, X-ray powder diffraction (XRD), and Field-emission scanning electron microscopy (FE-SEM). The calcined doped material is an attractive semiconductor nanoparticle for accomplishment in chemical sensing by simple I-V technique, where toxic chemical (ethanol) is used as a target chemical. Thin-film of Ni-doped SnO(2) nanostructure materials with conducting coating agents on silver electrodes (AgE, surface area, 0.0216 cm(2)) revealed higher sensitivity and repeatability. The calibration plot is linear (R, 0.8440) over the large dynamic range (1.0 nM-1.0 mM), where the sensitivity is approximately 2.3148 μA cm(-2) mM(-1) with a detection limit of 0.6 nM, based on signal/noise ratio in short response time. Consequently on the basis of the sensitive communication among structures, morphologies, and properties, it is exemplified that the morphologies and the optical characteristics can be extended to a large scale in doping nanomaterials and proficient chemical sensors applications.     

N-Glycans mutations rule oligomeric assembly and functional expression of P2X3 receptor for extracellular ATP

N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor.     

Degradation pathway, toxicity and kinetics of 2,4,6-trichlorophenol with different co-substrate by aerobic granules in SBR

The present study deals with cultivation of 2,4,6-trichlorophenol (TCP) degrading aerobic granules in two SBR systems based on glucose and acetate as co-substrate. Biodegradation of TCP containing wastewater starting from 10 to 360 mg L⁻¹ with more than 90% efficiency was achieved. Sludge volume index decreases as the operation proceeds to stabilize at 35 and 30 mL g⁻¹ while MLVSS increases from 4 to 6.5 and 6.2 g L⁻¹ for R1 (with glucose as co-substrate) and R2 (with sodium acetate as co-substrate), respectively. FTIR, GC and GC/MS spectral studies shows that the biodegradation occurred via chlorocatechol pathway and the cleavage may be at ortho-position. Haldane model for inhibitory substrate was applied to the system and it was observed that glucose fed granules have a high specific degradation rate and efficiency than acetate fed granules. Genotoxicity studies shows that effluent coming from SBRs was non-toxic.     

Bioassay to detect <Emphasis Type="Italic">Ascophyllum nodosum</Emphasis> extract-induced cytokinin-like activity in <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis>

Ascophyllum nodosum, a brown macroalga, is the most widely used seaweed in agriculture. We report a rapid method for the detection of cytokinin-like activity in plants treated with a commercial A. nodosum liquid concentrate (Stimplex®) using a transgenic line of Arabidopsis carrying the ARR5 promoter fused to ß-glucuronidase (GUS) reporter gene. Based on GUS activity assay, an increase in cytokinin-like activity was detected in plants grown in vitro treated with 3 mL L^?1 Stimplex®, whereas foliar spray treatments showed similar cytokinin-like activity at a concentration of 5 mL L^?1. Histochemical staining showed Stimplex®-induced GUS activity in leaf as well as in the root tissues. Taken together, our results suggest that Stimplex® contains compounds that may elicit endogenous cytokinin-like activity. Furthermore, it is shown that this bioassay can be used for rapid screening of extracts that can stimulate cytokinin-like activities using Arabidopsis AAR5::GUS reporter transgenic plants.