Novel diastereoisomers of C21H20O3 obtained from the cathodic reduction of methyl (2E)-3-[2-(2-{2-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}ethyl)phenyl]prop-2-enoate

The diastereoisomeric title compounds, 5 and 6, were obtained as a result of intramolecular electrohydrocyclisation of methyl (2E)-3-[2- (2-{2-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}ethyl)phenyl]prop-2-enoate. The common feature of the molecular structures is the presence of a central, eight-membered, –C(H)–C(H)–C C–(CH2)2–C C, ring appended to a cyclopentenyl and two phenyl rings. This study represents an unprecedented structural characterisation of such an atomic/bonding arrangement. The distinctive feature of the structures relates to the conformation of the central rings, i.e. approximating a boat in 5 and a chair in 6. This difference in molecular conformations arises from the different configurations at the methine-C atoms of the cyclopentenyl ring, i.e. R- and S-(or S- and R-) in 5 as opposed to R- and R- (or S- and S-) in 6. In each case, the hydroxyl-OH forms an intramolecular hydrogen-bond to the adjacent carbonyl-O atom so the molecular packing in each of 5 and 6 is sustained by non-conventional interactions. A three-dimensional architecture in 5 arises from a combination of phenyl-C–H…O(carbonyl) and methyl- and methylene-C–H…p contacts. In the crystal of 6, supramolecular chains with a zig-zag topology along the c-axis are formed via methyl-C–H…O(hydroxyl); the chains pack with no directional interactions between them

Histological assessment of paxgene tissue fixation and stabilization reagents

Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic experiments with PAXgene-fixed and paraffin embedded tissue derived biomolecules. But, for this technology to be accepted for use in both clinical and basic research, it is essential that its adequacy for preserving morphology and antigenicity is validated relative to formalin fixation. It is our aim to assess the suitability of PAXgene tissue fixation for (immuno)histological methods. Normal human tissue specimens (n = 70) were collected and divided into equal parts for fixation either with formalin or PAXgene. Sections of the obtained paraffin-embedded tissue were cut and stained. Morphological aspects of PAXgene-fixed tissue were described and also scored relative to formalin-fixed tissue. Performance of PAXgene-fixed tissue in immunohistochemical and in situ hybridization assays was also assessed relative to the corresponding formalin-fixed tissues. Morphology of PAXgene-fixed paraffin embedded tissue was well preserved and deemed adequate for diagnostics in most cases. Some antigens in PAXgene-fixed and paraffin embedded sections were detectable without the need for antigen retrieval, while others were detected using standard, formalin fixation based, immunohistochemistry protocols. Comparable results were obtained with in situ hybridization and histochemical stains. Basically all assessed histological techniques were found to be applicable to PAXgene-fixed and paraffin embedded tissue. In general results obtained with PAXgene-fixed tissue are comparable to those of formalin-fixed tissue. Compromises made in morphology can be called minor compared to the advantages in the molecular pathology possibilities

High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal, Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options

Anodic methoxylation of cinnamate esters

The present work describes the electrochemical oxidation of methyl cinnamate ring methoxylated derivatives in neutral or basic methanolic solution. In the electrochemical studies cyclic voltammetry and preparative electrolyses under controlled potential or current conditions in divided or undivided cells were used. The influence of current density, cell type, electrode material, solvent, substrate and base concentration was investigated for methyl 4-methoxycinnamate.The products result from aromatic ring and side chain methoxylation, however, nuclear methoxylation products were observed in higher yields when the number of methoxy groups in the aromatic ring was increased. The structure of the products is dependent on the work-up procedures