Optimization and validation of a novel three-dimensional co-culture system in decellularized human liver scaffold for the study of liver fibrosis and cancer

The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as a platform for anti-fibrotic and anti-cancer drug testing. Decellularized 3D scaffolds obtained from healthy and cirrhotic human livers were bioengineered with LX2 and HEPG2 as single and co-cultures for up to 13 days and validated as a new drug-testing platform. Pro-fibrogenic markers and cancer phenotypic gene/protein expression and secretion were differently affected when single and co-cultures were exposed to TGF-β1 with specific ECM-dependent effects. The anti-fibrotic efficacy of Sorafenib significantly reduced TGF-β1-induced pro-fibrogenic effects, which coincided with a downregulation of STAT3 phosphorylation. The anti-cancer efficacy of Regorafenib was significantly reduced in 3D bioengineered cells when compared to 2D cultures and dose-dependently associated with cell apoptosis by cleaved PARP-1 activation and P-STAT3 inhibition. Regorafenib re-versed TGF-β1-induced P-STAT3 and SHP-1 through induction of epithelial mesenchymal marker E-cadherin and downregulation of vimentin protein expression in both co-cultures engrafting healthy and cirrhotic 3D scaffolds. In their complex, the results of the study suggest that this newly proposed 3D co-culture platform is able to reproduce the natural physio-pathological microenvi-ronment and could be employed for anti-fibrotic and anti-HCC drug screening

A flexible service selection for executing virtual services

[EN] With the adoption of a service-oriented paradigm on the Web, many software services are likely to fulfil similar functional needs for end-users. We propose to aggregate functionally equivalent software services within one single virtual service, that is, to associate a functionality, a graphical user interface (GUI), and a set of selection rules. When an end user invokes such a virtual service through its GUI to answer his/her functional need, the software service that best responds to the end-user s selection policy is selected and executed and the result is then rendered to the end-user through the GUI of the virtual service. A key innovation in this paper is the flexibility of our proposed service selection policy. First, each selection policy can refer to heterogeneous parameters (e.g., service price, end-user location, and QoS). Second, additional parameters can be added to an existing or new policy with little investment. Third, the end users themselves define a selection policy to apply during the selection process, thanks to the GUI element added as part of the virtual service design. This approach was validated though the design, implementation, and testing of an end-to-end architecture, including the implementation of several virtual services and utilizing several software services available today on the Web.This work was partially supported in part by SERVERY (Service Platform for Innovative Communication Environment), a CELTIC project that aims to create a Service Marketplace that bridges the Internet and Telco worlds by merging the flexibility and openness of the former with the trustworthiness and reliability of the latter, enabling effective and profitable cooperation among actors.Laga, N.; Bertin, E.; Crespi, N.; Bedini, I.; Molina Moreno, B.; Zhao, Z. (2013). A flexible service selection for executing virtual services. World Wide Web. 16(3):219-245. doi:10.1007/s11280-012-0184-2S219245163Aggarwal, R., Verma, K., Miller, J., and Milnor, W.: Constraint Driven Web Service Composition in METEOR-S. In Proceedings of the 2004 IEEE international Conference on Services Computing (September 2004). IEEE Computer Society, Washington, DC, 23–30.Apple Inc. Apple app store.: Available at: www.apple.com/iphone/appstore/ , accessed on May 22nd, 2012.Atzeni, P., Catarci, T., Pernici, B.: Multi-Channel adaptive information Systems. World Wide Web 10(4), 345–347 (2007)Baresi, L., Bianchini, D., Antonellis, V.D., Fugini, M.G., Pernici, B., Plebani, P.: Context-aware Composition of e-Service. In Technologies for E-Services: Third International Workshop, vol. 2819, 28–41, TES 2003, Berlin, German, 2003.Ben Hassine, A., Matsubara, S., Ishida, T.: In Proceedings of the 5th international conference on The Semantic Web (ISWC’06), Isabel Cruz, Stefan Decker, Dean Allemang, Chris Preist, and Daniel Schwabe (Eds.). Springer-Verlag, Berlin, Heidelberg, 130–143 (2006).Blum, N., Dutkowski, S., Magedanz, T.: InSeRt - An Intent-based Service Request API for Service Exposure in Next Generation Networks. In Proceedings of 32nd Annual IEEE Software Engineering Workshop. Porto Sani Resort, Kassandra, Greece, 2008 pp21–30.Boussard, M., Fodor, S., Crespi, N., Iribarren, V., Le Rouzic, J.P., Bedini, I., Marton, G., Moro Fernandez, D., Lorenzo Duenas, O., Molina, B.: SERVERY: the Web-Telco marketplace. ICT-Mobile Summit 2009, Santander (2009)Cabrera, Ó., Oriol, M., Franch, X., Marco, J., López, L., Fragoso, O., Santaolaya, R.: WeSSQoS: A Configurable SOA System for Quality-aware Web Service Selection. CoRR 2011, abs/1110.5574.Casati, F., Ilnicki, S., Jin, L., Krishnamoorthy, V., Shan, M.: Adaptive and Dynamic Service Composition in eFlow. Lecture Notes in Computer Science, Volume 1789/2000, 13–31, 2000.Cibrán, M. A., Verheecke, B., Vanderperren, W., Suvée, D., and Jonckers, V.: “Aspect-oriented Programming for Dynamic Web Service Selection, Integration and Management.” In Proc. World Wide Web 2007, pp. 211–242.Crespi, N., Boussard, M. Fodor, S.: Converging Web 2.0 with telecommunications. eStrategies Projects, Vol. 10, 108–109. British Publishers, ISSN 1758–2369, June 2009.Dey, A.K., Salber, D., Abowd, G.D.: A conceptual framework and a toolkit for supporting the rapid prototyping of context-aware applications. Hum. Comput. Interact. 16, 1–67 (2001)Ding, Q., Li, X., and Zhou, X.: Reputation Based Service Selection in Grid Environment. In Proceedings of the 2008 international Conference on Computer Science and Software Engineering - Volume 03 (December. 2008). CSSE. IEEE Computer Society, Washington, DC, 58–61.Fielding, R.T.: Architectural Styles and the Design of Network-based Software Architectures. Thesis dissertation, 2000.Franch, X., Grünbacher, P., Oriol, M., Burgstaller, B., Dhungana, D., López, L., Marco, J., Pimentel, J.: Goal-driven Adaptation of Service-Based Systems from Runtime Monitoring Data. REFS 2011.Frolund, S., Koisten, J.: QML: A Language for Quality of Service Specification. HP Labs technical reports. Available at http://www.hpl.hp.com/techreports/98/HPL-98-10.html , accessed on May 22nd, 2012.Google. Android market.: Available at: www.android.com/market/ , accessed on May 22nd, 2012.Google. Intents and Intent Filters.: Available at http://developer.android.com/guide/topics/intents/intents-filters.html , accessed on May 22nd, 2012.Gu, X., Nahrstedt, K., Yuan, W., Wichadakul, D., Xu, D.: An Xml-Based Quality of Service Enabling Language for the Web. Technical Report. UMI Order Number: UIUCDCS-R-2001-2212., University of Illinois at Urbana-Champaign.Laga, N., Bertin, E., and Crespi, N.: Building a User Friendly Service Dashboard: Automatic and Non-intrusive Chaining between Widgets. In Proceedings of the 2009 Congress on Services - I (July 06–10, 2009). SERVICES. IEEE Computer Society, Washington, DC, 484–491.Laga, N., Bertin, E., and Crespi, N.: Business Process Personalization Through Web Widgets. In Proceedings of the 2010 IEEE international Conference on Web Services (July 05–10, 2010). ICWS. IEEE Computer Society, Washington, DC, 551–558.Liu, Y., Ngu, A. H., and Zeng, L. Z.: QoS computation and policing in dynamic web service selection. In Proceedings of the 13th international World Wide Web Conference on Alternate Track Papers &Amp; Posters (New York, NY, USA, May 19–21, 2004). WWW Alt. ’04. ACM, New York, NY, 66–73.Malik, Z., Bouguettaya, A.: Rater credibility assessment in Web services interactions. World Wide Web 12(1), 3–25 (2009)Martin, D. et al.: OWL-S: Semantic Markup for Web Services. W3C member submission, available at http://www.w3.org/Submission/2004/SUBM-OWL-S-20041122/ , accessed on May 22nd, 2012.Nestler, T., Namoun, A., Schill, A.: End-user development of service-based interactive web applications at the presentation layer. EICS 2011: 197–206.Newcomer, E.: Understanding Web Services: XML, Wsdl, Soap, and UDDI. Addison, Wesley, Boston, Mass., May 2002.O’Reilly, T.: What Is Web 2.0, Design Patterns and Business Models for the Next Generation of Software.Piessens, F., Jacobs, B., Truyen, E., Joosen, W.: Support for Metadata-driven Selection of Run-time Services in .NET is Promising but Immature. vol. 3, no. 2, Special issue: .NET: The Programmer’s Perspective: ECOOP Workshop, 27–35. 2003.Rasch, K;, Li, F., Sehic, S., Ayani R., and Dustdar, S.: “Context-driven personalized service discovery in pervasive environments,” in Proc World Wide Web, 2011, pp. 295–319.Reichl, P.: From ‘Quality-of-Service’ and ‘Quality-of-Design’ to ‘Quality-of-Experience’: A holistic view on future interactive telecommunication ser-vices. In 15th International Conference on Software, Telecommunications and Computer Networks, 2007. Soft-COM 2007. Sept. 2007. vol., no.,1–6, 27–29.Rolland, C., Kaabi, R.S., Kraiem, N.: On ISOA: Intentional Services Oriented Architecture. In Advanced Information Systems Engineering, volume 4495/2007, 158–172, June 2007.Sanchez, A., Carro, B., Wesner, S.: Telco services for end customers: European Perspective. In Communications Magazine. IEEE 46(2), 14–18 (2008)Santhanam, G. R., Basu, S., and Honavar, V.: On Utilizing Qualitative Preferences in Web Service Composition: A CP-net Based Approach. In Proceedings of IEEE Congress on Services, Services - Part I, vol., no.,538–544, 2008.Spanoudakis, G., Mahbub, K., Zisman, A.: A Platform for Context Aware Runtime Web Service Discovery. In Proc IEEE ICWS, 2007, pp233-240.Tsesmetzis, D., Roussaki, I., Sykas, E.: Modeling and Simulation of QoS-aware Web Service Selection for Provider Profit Maximization. Simulation 83(1), 93–106 (2007)Wang, P., Chao, K., Lo, C., Farmer, R., and Kuo, P.: A Reputation-Based Service Selection Scheme. In Proceedings of the 2009 IEEE international Conference on E-Business Engineering (October 21–23, 2009). ICEBE. IEEE Computer Society, Washington, DC, 501–506.Wang, H., Yang, D., Zhao, Y., and Gao, Y.: Multiagent System for Reputation--based Web Services Selection. In Proceedings of the Sixth international Conference on Quality Software (October 27–28, 2006). QSIC. IEEE Computer Society, Washington, DC, 429–434.Wholesale Applications Community.: WAC Informational Whitepaper. Available at http://www.wholesaleappcommunity.com/About-Wac/BACKGROUND%20TO%20WAC/whitepaper.pdf , accessed on May 22nd, 2012.Windows Marketplace.: Available at http://marketplace.windowsphone.com/default.aspx , accessed on May 22nd, 2012.Xu, Z., Martin, P., Powley, W., Zulkernine, F.: Reputation-Enhanced QoS-based Web Services Discovery. Web Services, 2007. In proceedings of IEEE International Conference on Web Services, ICWS 2007. 249, 256, 9–13 July 2007.Yu, Q., Bouguettaya,A.: “Multi-attribute optimization in service selection”. In Proc World Wide Web,2012, pp. 1–31.Yu, T., Zhang, Y., Lin, K. Efficient algorithms for Web services selection with end-to-end QoS constraints. ACM Transaction Web 1, 1. Article 6, 26 pages. (May 2007),

MicroRNAs Up-Regulated by CagA of Helicobacter pylori Induce Intestinal Metaplasia of Gastric Epithelial Cells

CagA of Helicobacter pylori is a bacterium-derived oncogenic protein closely associated with the development of gastric cancers. MicroRNAs (miRNAs) are a class of widespread non-coding RNAs, many of which are involved in cell growth, cell differentiation and tumorigenesis. The relationship between CagA protein and miRNAs is unclear. Using mammalian miRNA profile microarrays, we found that miRNA-584 and miRNA-1290 expression was up-regulated in CagA-transformed cells, miRNA-1290 was up-regulated in an Erk1/2-dependent manner, and miRNA-584 was activated by NF-κB. miRNA-584 sustained Erk1/2 activities through inhibition of PPP2a activities, and miRNA-1290 activated NF-κB by knockdown of NKRF. Foxa1 was revealed to be an important target of miRNA-584 and miRNA-1290. Knockdown of Foxa1 promoted the epithelial-mesenchymal transition significantly. Overexpression of miRNA-584 and miRNA-1290 induced intestinal metaplasia of gastric epithelial cells in knock-in mice. These results indicate that miRNA-584 and miRNA-1290 interfere with cell differentiation and remodel the tissues. Thus, the miRNA pathway is a new pathogenic mechanism of CagA

Parasitic Plants Striga and Phelipanche Dependent upon Exogenous Strigolactones for Germination Have Retained Genes for Strigolactone Biosynthesis

Abstract Strigolactones are plant hormones with multiple functions, including regulating various aspects of plant architecture such as shoot branching, facilitating the colonization of plant roots by arbuscular mycorrhizal fungi, and acting as seed germination stimulants for certain parasitic plants of the family Orobanchaceae. The obligate parasitic species Phelipanche aegyptiaca and Striga hermonthica require strigolactones for germination, while the facultative parasite Triphysaria versicolor does not. It has been hypothesized that P. aegyptiaca and S. hermonthica would have undergone evolutionary loss of strigolactone biosynthesis as a part of their mechanism to enable specific detection of exogenous strigolactones. We analyzed the transcriptomes of P. aegyptiaca, S. hermonthica and T. versicolor and identified genes known to act in strigolactone synthesis (D27, CCD7, CCD8, and MAX1), perception (MAX2 and D14) and transport (PDR12). These genes were then analyzed to assess likelihood of function. Transcripts of all strigolactone-related genes were found M. Das et al. 1152 in P. aegyptiaca and S. hermonthica, and evidence points to their encoding functional proteins. Gene open reading frames were consistent with homologs from Arabidopsis and other strigolactone-producing plants, and all genes were expressed in parasite tissues. In general, the genes related to strigolactone synthesis and perception appeared to be evolving under codon-based selective constraints in strigolactone-dependent species. Bioassays of S. hermonthica root extracts indicated the presence of strigolactone class stimulants on germination of P. aegyptiaca seeds. Taken together, these results indicate that Phelipanche aegyptiaca and S. hermonthica have retained functional genes involved in strigolactone biosynthesis, suggesting that the parasites use both endogenous and exogenous strigolactones and have mechanisms to differentiate the two

Assessment of a Novel VEGF Targeted Agent Using Patient-Derived Tumor Tissue Xenograft Models of Colon Carcinoma with Lymphatic and Hepatic Metastases

The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents

Dvl2-Dependent Activation of Daam1 and RhoA Regulates Wnt5a-Induced Breast Cancer Cell Migration

The Dishevelled (Dvl) and Dishevelled-associated activator of morphogenesis 1 (Daam1) pathway triggered by Wnt5a regulates cellular polarity during development and tissue homoeostasis. However, Wnt5a signaling in breast cancer progression remains poorly defined.We showed here that Wnt5a activated Dvl2, Daam1 and RhoA, and promoted migration of breast cancer cells, which was, however, abolished by Secreted Frizzled-related protein 2 (sFRP2) pretreatment. Dominant negative Dvl2 mutants or Dvl2 siRNA significantly decreased Wnt5a-induced Daam1/RhoA activation and cell migration. Ectopic expression of N-Daam1, a dominant negative mutant, or Daam1 siRNA remarkably inhibited Wnt5a-induced RhoA activation, stress fiber formation and cell migration. Ectopic expression of dominant negative RhoA (N19) or C3 exoenzyme transferase, a Rho inhibitor, decreased Wnt5a-induced stress fiber formation and cell migration.Taken together, we demonstrated for the first time that Wnt5a promotes breast cancer cell migration via Dvl2/Daam1/RhoA

Determination of relevance between surface free energy and adsorption capacity of cement particles

ABSTRACT The compatibility between superplasticizer and cement was influenced by the adsorption capacity of cement particles. This study investigated the relevance between the adsorption capability and surface free energy. Adsorption capacity and surface free energy of both sulphoaluminate cement and portland cement were measured. The adsorption capacity of cement particles was measured by ultraviolet spectrophotometry. The test showed that particles of sulphoaluminate cement adsorbed more molecules of superplasticizer than portland cement particles. The weight of superplasticizer adsorbed by 2g of sulphoaluminate cement and portland cement were 0.28mg and 0.159mg respectively. Surface free energy of cement particles was calculated by contact angle and the contact angles were determined by the thin-layer wicking technique and washburn equation which is theoretical basis of thin-layer wiching technique presented by Chibowski E. The sulphoaluminate cement, portland cement's surface free energy were 51.46 mJ·m-2 and 49.36 mJ·m-2 respectively. The results showed that the higher adsorption capacity of particles was usual accompanied by higher surface free energy. The fluidity of cement paste was influenced by the adsorption capacity of cement particles because the more molecules of superplasticizer was adsorbed by cement particles there were lacking superplasticizer in the paste. The macro-behaviour of higher adsorption capacity is that the cement paste need more superplasticizer to reach the needed fluidity