Pholidota chinensis alleviates azoxymethane/dextran sulfate sodium-induced colorectal carcinogenesis through inhibition of TLR4 and COX-2

Background: Inflammatory bowel disease (IBD) always progresses to colorectal cancer (CRC) which is the second most frequent cause of death by cancer. It is about 2% of population in the lifetime worldwide who at the risk for development of CRC. Oxaliplatin is an effective anticancer drug used for the treatment of advanced CRC; however, it always causes a robust painful neuropathy. Pholidota chinensis is a Chinese folk herbal medicine which was used for treatment of inflammation such as gastroenteritis, duodenal ulcer and bronchitis.Materials and Methods: The azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to induce the colon tumor of mice. The effect of Pholidota chinensis on colon tumorigenesis was evaluated. Immunohistochemistry and semi-quantitative RT-PCR were used to detect the expression of toll-like receptor 4 (TLR4) and cyclooxygenase-2 (COX-2) in colon.Results: Pholidota chinensis can alleviate the colon tumorigenesis. The prevention effects of Pholidota chinensis are similar to oxaliplatin. Specifically, administration of Pholidota chinensis solution suppresses the expression of the proliferating cell nuclear antigen (PCNA), toll-like receptor 4 (TLR4) and cyclooxygenase-2 (COX-2).Conclusion: Our findings suggested that Pholidota chinensis participate in the regulation of colon cancer development through inhibiting the expression of TLR4 and COX-2.Keywords: Pholidota chinensis; colorectal cancer; Toll-like receptor 4; Cyclooxygenase-

Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression

Zinc (Zn)-deficiency (ZD) is implicated in the pathogenesis of human oral-esophageal cancers. Previously, we showed that in ZD mice genetic deletion of cyclooxygenase-2 (Cox-2) enhances N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. By contrast, Cox-2 deletion offers protection in Zn-sufficient (ZS) mice. We hypothesize that ZD activates pathways insensitive to COX-2 inhibition, thereby promoting carcinogenesis. This hypothesis is tested in a Cox-2−/− mouse tongue cancer model that mimics pharmacologic blockade of COX-2 by firstly examining transcriptome profiles of forestomach mucosa from Cox-2−/− and wild-type mice on a ZD vs. ZS diet, and secondly investigating the roles of identified markers in mouse forestomach/tongue preneoplasia and carcinomas. In Cox-2−/− mice exposed to the tongue carcinogen 4-nitroquinoline 1-oxide, dietary ZD elicited tongue/esophagus/forestomach carcinomas that were prevented by ZS. The precancerous ZD:Cox-2−/−vs. ZS:Cox-2−/− forestomach had an inflammatory signature with upregulation of the proinflammation genes S100a8 and S100a9. Bioinformatics analysis revealed overrepresentation of inflammation processes comprising S100a8/a9 and an nuclear factor (NF)-κB network with connectivity to S100A8. Immunohistochemistry revealed co-overexpression of S100A8, its heterodimeric partner S100A9, the receptor for advanced glycation end-products (RAGE), NF-κB p65, and cyclin D1, in ZD:Cox-2−/− forestomach/tongue preneoplasia and carcinomas, evidence for the activation of a RAGE-S100A8/A9 inflammatory pathway. Accumulation of p53 in these carcinomas indicated activation of additional inflammatory pathways. Zn-replenishment in ZD:Cox-2−/−mice reversed the inflammation and inhibited carcinogenesis. Thus, ZD activates alternative inflammation-associated cancer pathways that fuel tumor progression and bypass the antitumor effect of Cox-2 ablation. These findings have important clinical implications, as combination cancer therapy that includes Zn may improve efficacy

Complete mitochondrial genomes of Taenia multiceps, T. hydatigena and T. pisiformis: additional molecular markers for a tapeworm genus of human and animal health significance

<p>Abstract</p> <p>Background</p> <p>Mitochondrial genomes provide a rich source of molecular variation of proven and widespread utility in molecular ecology, population genetics and evolutionary biology. The tapeworm genus <it>Taenia </it>includes a diversity of tapeworm parasites of significant human and veterinary importance. Here we add complete sequences of the mt genomes of <it>T. multiceps</it>, <it>T. hydatigena </it>and <it>T. pisiformis</it>, to a data set of 4 published mtDNAs in the same genus. Seven complete mt genomes of <it>Taenia </it>species are used to compare and contrast variation within and between genomes in the genus, to estimate a phylogeny for the genus, and to develop novel molecular markers as part of an extended mitochondrial toolkit.</p> <p>Results</p> <p>The complete circular mtDNAs of <it>T. multiceps</it>, <it>T. hydatigena </it>and <it>T. pisiformis </it>were 13,693, 13,492 and 13,387 bp in size respectively, comprising the usual complement of flatworm genes. Start and stop codons of protein coding genes included those found commonly amongst other platyhelminth mt genomes, but the much rarer initiation codon GTT was inferred for the gene <it>atp</it>6 in <it>T. pisiformis</it>. Phylogenetic analysis of mtDNAs offered novel estimates of the interrelationships of <it>Taenia</it>. Sliding window analyses showed <it>nad</it>6, <it>nad</it>5, <it>atp</it>6, <it>nad</it>3 and <it>nad</it>2 are amongst the most variable of genes per unit length, with the highest peaks in nucleotide diversity found in <it>nad</it>5. New primer pairs capable of amplifying fragments of variable DNA in <it>nad</it>1, <it>rrn</it>S and <it>nad</it>5 genes were designed <it>in silico </it>and tested as possible alternatives to existing mitochondrial markers for <it>Taenia</it>.</p> <p>Conclusions</p> <p>With the availability of complete mtDNAs of 7 <it>Taenia </it>species, we have shown that analysis of amino acids provides a robust estimate of phylogeny for the genus that differs markedly from morphological estimates or those using partial genes; with implications for understanding the evolutionary radiation of important <it>Taenia</it>. Full alignment of the nucleotides of <it>Taenia </it>mtDNAs and sliding window analysis suggests numerous alternative gene regions are likely to capture greater nucleotide variation than those currently pursued as molecular markers. New PCR primers developed from a comparative mitogenomic analysis of <it>Taenia </it>species, extend the use of mitochondrial markers for molecular ecology, population genetics and diagnostics.</p

PHOLIDOTA CHINENSIS ALLEVIATES AZOXYMETHANE/DEXTRAN SULFATE SODIUM-INDUCED COLORECTAL CARCINOGENESIS THROUGH INHIBITION OF TLR4 AND COX-2

Inflammatory bowel disease (IBD) always progresses to colorectal cancer (CRC) which is the second most frequent cause of death by cancer. It is about 2% of population in the lifetime worldwide who at the risk for development of CRC. Oxaliplatin is an effective anticancer drug used for the treatment of advanced CRC, however, it always causes a robust painful neuropathy. Pholidota chinensis is a Chinese folk herbal medicine which was used for treatment of inflammation such as gastroenteritis, duodenal ulcer and bronchitis. In the present study, we examined the role of Pholidota chinensis in inflammation-related colon tumorigenesis which was induced by azoxymethane (AOM)/dextran sulfate sodium (DSS) in mice. We found that Pholidota chinensis can alleviate the colon tumorigenesis. The prevention effects of Pholidota chinensis is similar to oxaliplatin. Specifically, administration of Pholidota chinensis solution suppresses the expression of the proliferating cell nuclear antigen (PCNA), toll-like receptor 4 (TLR4) and cyclooxygenase-2 (COX-2). Our findings suggested that Pholidota chinensis participate in the regulation of colon cancer development through inhibiting the expression of TLR4 and COX-2

Analysing the Coupled Effects of Compressive and Diffusion Induced Stresses on the Nucleation and Propagation of Circular Coating Blisters in the Presence of Micro-cracks

This paper presents the delamination of coating with micro-cracks under compressive residual stress coupled with diffusion induced stress. Micro-cracks in coating provide a passage for corrosive species towards the coating-substrate interface which in turn produces diffusion induced stress in the coating. Micro-cracks contract gradually with increasing compressive residual stress in coating due to thermal expansion mismatch which blocks the species diffusion towards the interface. This behaviour reduces the diffusion induced stress in the coating while the compressive residual stress increases. With further increase in compressive residual stress, micro-cracks reach to the point, where they cannot be constricted any further and a high compressive residual stress causes the coating to buckle away from the substrate resulting in delamination and therefore initiating blistering. Blistering causes the contracted micro-cracks to wide open again which increases diffusion induced stress along with high compressive residual stress. The high resultant stress in coating causes the blister to propagate in an axis-symmetric circular pattern. A two-part theoretical approach has been utilised coupling the thermodynamic concepts with the mechanics concepts. The thermodynamic concepts involve the corrosive species transportation through micro-cracks under increasing compression, eventually causing blistering, while the fracture mechanics concepts are used to treat the blister growth as circular defect propagation. The influences of moduli ratio, thickness ratio, thermal mismatch ratio, poisson’s ratio and interface roughness on blister growth are discussed. Experiment is reported for blistering to allow visualisation of interface and to permit coupled (diffusion and residual) stresses in the coating over a full range of interest. The predictions from model show excellent, quantitative agreement with the experimental results

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.