In vitro evaluation of 5-Fluorouracil release by microspheres based on chitosan / Montmorillonite/ Avaliação in vitro da libertação de 5-Fluorouracil por microesferas à base de quitosano / Montmorilonite

5-fluorouracil (5-FU) is one of the most widely used chemotherapeutic compounds for cancer treatment and its rapid metabolization and non-uniform oral absorption are the limitations for its use as an oral chemotherapy. Therefore, this study was performed to evaluate the influence of a 5-fluorouracil (5-FU) nanocomposite microspheres with different diameters to test on a controlled release system in the gastrointestinal environment. 5-FU was incorporated into the chitosan/montmorillonite nanocomposite microspheres through the intercalation method. The microspheres containing the 5-FU were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and optical microscopy (OM). In vitro release fractions at different pHs (1.2, 7.4 and 10.0) were investigated by UV-vis spectroscopy. The release profile of 5-FU for the systems studied was adjusted through the Korsmeyer-Peppas kinetic model, and the results suggested that the mechanism of controlled release at pH 7.4 and 10 occurs by diffusion. In addition, the 5-FU microspheres diameter and roughness directly interfere with the release rate and the released fraction, since the F1 / F2 systems showed a difference in the released fraction of 5-FU of 7.97% and for the systems F3 / F4 the difference was 2.86%. The prepared F1, F2, F3 and F4 systems are suitable for delivery of 5-FU to the gastrointestinal environment in a controlled manner

Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α

<p>Abstract</p> <p>Background</p> <p>Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.</p> <p>Results</p> <p>The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).</p> <p>Conclusion</p> <p>The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.</p

A Comprehensive Peptidome Profiling Technology for the Identification of Early Detection Biomarkers for Lung Adenocarcinoma

The mass spectrometry-based peptidomics approaches have proven its usefulness in several areas such as the discovery of physiologically active peptides or biomarker candidates derived from various biological fluids including blood and cerebrospinal fluid. However, to identify biomarkers that are reproducible and clinically applicable, development of a novel technology, which enables rapid, sensitive, and quantitative analysis using hundreds of clinical specimens, has been eagerly awaited. Here we report an integrative peptidomic approach for identification of lung cancer-specific serum peptide biomarkers. It is based on the one-step effective enrichment of peptidome fractions (molecular weight of 1,000–5,000) with size exclusion chromatography in combination with the precise label-free quantification analysis of nano-LC/MS/MS data set using Expressionist proteome server platform. We applied this method to 92 serum samples well-managed with our SOP (standard operating procedure) (30 healthy controls and 62 lung adenocarcinoma patients), and quantitatively assessed the detected 3,537 peptide signals. Among them, 118 peptides showed significantly altered serum levels between the control and lung cancer groups (p<0.01 and fold change >5.0). Subsequently we identified peptide sequences by MS/MS analysis and further assessed the reproducibility of Expressionist-based quantification results and their diagnostic powers by MRM-based relative-quantification analysis for 96 independently prepared serum samples and found that APOA4 273–283, FIBA 5–16, and LBN 306–313 should be clinically useful biomarkers for both early detection and tumor staging of lung cancer. Our peptidome profiling technology can provide simple, high-throughput, and reliable quantification of a large number of clinical samples, which is applicable for diverse peptidome-targeting biomarker discoveries using any types of biological specimens

Calm counsel: Fiscal Federalism and Provincial Credit Risk

Produced by the Mowat Centre at the School of Public Policy and Governance, University of Toronto.This Mowat Note assesses the risks of a provincial debt crisis and suggests proposals to limit these risks, with particular attention to fiscal federalism

A Good Crisis: Canadian Municipal Credit Conditions After the Lehman Brothers Bankruptcy

This paper is part of the IMFG Papers on Municipal Finance and Governance series. For a full list of papers, please visit http://bit.ly/2ylAa2D.Subnational governments in several countries struggled to borrow on credit markets during and after the global financial crisis of 2008 and 2009. Canadian municipalities were not immune. They, like many governments, were unable to borrow for a brief period after the Lehman Brothers bankruptcy of 2008. But municipal credit conditions improved markedly after the peak of the crisis. Interest rates plunged, demand for long-term bonds increased, and the investor base expanded. Municipal borrowers did not, however, fare as well as the federal and provincial governments, which saw even sharper declines in interest rates. This paper seeks to explain these developments. It links municipal success to factors underpinning low interest rates and stellar municipal creditworthiness, and attributes the superior conditions of federal and provincial borrowers to volatility in global financial markets and patterns of foreign investment in Canada’s government bond markets. The analysis reveals the resilience of Canada’s municipal borrowers in the face of global credit shocks and the virtues of Canada’s tightly regulated system of municipal borrowing.Institute on Municipal Finance and Governanc