Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies

Gastric cancer’s bad incidence, prognosis, cellular and molecular heterogeneity amongst others make this disease a major health issue worldwide. Understanding this affliction is a priority for proper patients’ management and for the development of efficient therapeutical strategies. This review gives an overview of major scientific advances, made during the past 5-years, to improve the comprehension of gastric adenocarcinoma. A focus was made on the different actors of gastric carcinogenesis, including, Helicobacter pylori cancer stem cells, tumour microenvironment and microbiota. New and recent potential biomarkers were assessed as well as emerging therapeutical strategies involving cancer stem cells targeting as well as immunotherapy. Finally, recent experimental models to study this highly complex disease were discussed, highlighting the importance of gastric cancer understanding in the hard-fought struggle against cancer relapse, metastasis and bad prognosis.     

Analysis of bacterial diversity in river biofilms using 16S rDNA PCR-DGGE: methodological settings and fingerprints interpretation

Reliability of bacterial diversity assessment using polymerase chain reaction (PCR) denaturing gradient gel electrophoresis (DGGE) analysis of 16S rDNA fragments was evaluated for a particular complex microbial assemblage: river epilithic biofilm. By comparing 3 routine protocols on replicates of one river biofilm sample, we found that common DNA extraction procedures gave comparable diversity (from 28.0 to 30.7 bands detected) and community composition (> 75% of homology) despite differences in the total amount of extracted DNA (from 0.9 to 4.2 microg). Therefore methodological improvements only concerned electrophoretic separation of DNA fragments (range of denaturing gradient from 35% to 70% and migration time=18h) and standardisation of DNA amounts used (PCR-template=50 ng, gel loading=700 ng). Using such a standardised methodology we found a good reproducibility of all steps of the procedure. When an Escherichia coli strain was introduced as a contaminant in a biofilm sample, we were able to recover ribotypes from the strain. As concerns fields sampling, a satisfactory repeatability of banding patterns from neighbouring pebbles (sampling point) allowed discriminating between the biofilm intrasite variability (various points from a cross-profile). These trials confirmed that PCR-DGGE is suitable to assess a reliable genetic fingerprint of epilithic biofilms in the river. Phylogenetic analysis of 40 partial sequences of 16S rDNA from DGGE gels of two sets of river biofilms samples proved evidences for the retrieval of DNA fragments related to phototroph Eukarya. However, in both cases plastidial 16S rDNA represented less than 25% of the analysed operational taxonomic units. Taking into account that Cyanobacteria, as members of the Bacteria, were also detected, sequence analysis of relevant bands from the pattern is required to target "bacteria", i.e. the functional group of prokaryotic microorganisms to which one commonly refers as a key component in sustaining the nutrient turnover.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Poly(vinyl alcohol) functionalization with aldehydes in organic solvents: Shining properties of poly(vinyl acetals)

Poly(vinyl alcohol) has been functionalized with aldehydes in tetrahydrofuran (THF) with a good control of the grafting. A wide library of poly(vinyl acetals) could be obtained in order to study some structure/property correlations. The influence of the aldehyde nature on the functionalization rates has been studied, in particular for optical properties by measurement of the shininess for further applications in the cosmetic field. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40677.     

Development of the Analysis of Fecal Stanols in the Oyster Crassostrea gigas and Identification of Fecal Contamination in Shellfish Harvesting Areas

The objective of this work was to study the effects of washing and purification steps on qualitative and quantitative analysis of fecal stanols in the oyster Crassostrea gigas using either single or a combination of lipid purification steps on silica gel or aminopropyl bonded silica gel (NH₂) or a washing step. Among the three analytical pathways compared, the two including water extraction or NH₂ purification did not lead to higher recoveries and decreased repeatabilities of extractions compared to the single purification on silica gel. This latter led to similar recoveries (ca. 80 %) and repeatabilities (ca. 10 %) for both spiked standards (coprostanol and sitostanol). This analytical pathway has been applied to oysters collected in a harvesting area in Brittany (France) where fecal contaminations are important and allowed to quantify eight stanols in oysters. The relative proportions of fecal stanols of these oysters were combined with principal component analysis in order to investigate the usefulness of their stanol fingerprints to record a fecal contamination and to distinguish its source between human, porcine and bovine contaminations. Oysters non-fecally contaminated by Escherichia coli did not present specific stanol fingerprints while oysters fecally contaminated had a bovine fingerprint, suggesting a contamination of these samples by bovine sources. As a consequence, the method developed here allows the use of stanol fingerprints of oysters as a microbial source tracking tool that can be applied to shellfish harvesting areas subjected to fecal contaminations in order to identify the different sources of contamination and improve watershed management.     

Photo isomerization of cis-cyclooctene to trans-cyclooctene: Integration of a micro-flow reactor and separation by specific adsorption

Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts cis-cyclooctene partly into trans-cyclooctene, leaving an isomeric mixture. Trans-cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO₃/SiO₂ powder, while the cis-isomer stays in the flow. The closed-loop recycling-flow has been presented as systemic approach to enrich the trans-cyclooctene from its cis-isomer. In-flow adsorption in recycling-mode has hardly been reported so that a full theoretical study has been conducted. This insight is used to evaluate three process design options to reach an optimum yield of trans-cyclooctene. These differ firstly in the variation of the individual residence times in the reactor and separator, the additional process option of refreshing the adsorption column under use, and the periodicity of the recycle flow.     

Automatic analysis of human posture equilibrium using empirical mode decomposition

The present study proposes a new approach for the assessment of the human balance control. This approach is based on the decomposition of the center of pressure displacement using empirical mode decomposition (EMD) that provides an effective time-frequency analysis of non-stationary signals. Twenty-eight healthy subjects performed quiet standing in four conditions—feet apart/together with respect to eyes open/closed—while recording the stabilometric signals in the anteroposterior (AP) and mediolateral (ML) directions. The EMD method decomposes each stabilometric signal into several subsignals called intrinsic mode functions (IMFs). Stabilogram-diffusion analysis technique is applied to generate the diffusion curve of each IMF signal. Each diffusion curve is modeled as a second-order system and provides representative features, such as the gain parameter. Analysis of the gain parameter shows the major effect of visual input and feet conditions on the strategy to control/stabilize the balance. Significant differences were found between young and elderly, and between women and men. In addition, the impact of feet position seems to be higher in ML direction than in AP direction.