Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis

Fibrosis is a progressive and potentially fatal process that can occur in numerous organ systems. Characterised by the excessive deposition of extracellular matrix proteins such as collagens and fibronectin, fibrosis affects normal tissue architecture and impedes organ function. Although a considerable amount of research has focused on the mechanisms underlying disease pathogenesis, current therapeutic options do not directly target the pro-fibrotic process. As a result, there is a clear unmet clinical need to develop new agents. Novel findings implicate a role for epigenetic modifications contributing to the progression of fibrosis by alteration of gene expression profiles. This review will focus on DNA methylation; its association with fibroblast differentiation and activation and the consequent buildup of fibrotic scar tissue. The potential use of therapies that modulate this epigenetic pathway for the treatment of fibrosis in several organ systems is also discussed

Circulating emm types of Streptococcus pyogenes in Scotland: 2011-2015

No abstract available

Organic electrochemical transistor incorporating an ionogel as solid state electrolyte for lactate sensing

Room temperature Ionic liquids (RTILs) have evolved as a new type of solvent for biocatalysis, mainly due to their unique and tunable physical properties.[1] In addition, within the family of organic semiconductor-based sensors, organic electrochemical transistors (OECTs) have attracted particular interest.[2] Here, we present a simple and robust biosensor, based on a OECT, capable of measuring lactic acid using a gel-like polymeric materials that endow RTIL (ionogel)[3] as solid-state electrolyte both to immobilise the enzyme and to serve as a supporting electrolyte.[4] This represents the first step towards the achievement of a fast, flexible, miniaturised and cheap way of measuring lactate concentration in sweat

Evaluation and validation of candidate endogenous control genes for real-time quantitative PCR studies of breast cancer

<p>Abstract</p> <p>Background</p> <p>Real-time quantitative PCR (RQ-PCR) forms the basis of many breast cancer biomarker studies and novel prognostic assays, paving the way towards personalised cancer treatments. Normalisation of relative RQ-PCR data is required to control for non-biological variation introduced during sample preparation. Endogenous control (EC) genes, used in this context, should ideally be expressed constitutively and uniformly across treatments in all test samples. Despite widespread recognition that the accuracy of the normalised data is largely dependent on the reliability of the EC, there are no reports of the systematic validation of genes commonly used for this purpose in the analysis of gene expression by RQ-PCR in primary breast cancer tissues. The aim of this study was to identify the most suitable endogenous control genes for RQ-PCR analysis of primary breast tissue from a panel of eleven candidates in current use. Oestrogen receptor alpha (<it>ESR1</it>) was used a target gene to compare the effect of choice of EC on the estimate of gene quantity.</p> <p>Results</p> <p>The expression and validity of candidate ECs (<it>GAPDH</it>, <it>TFRC</it>, <it>ABL</it>, <it>PPIA</it>, <it>HPRT1</it>, <it>RPLP0</it>, <it>B2M</it>, <it>GUSB</it>, <it>MRPL19</it>, <it>PUM1 </it>and <it>PSMC4) </it>was determined in 6 benign and 21 malignant primary breast cancer tissues. Gene expression data was analysed using two different statistical models. <it>MRPL19 </it>and <it>PPIA </it>were identified as the most stable and reliable EC genes, while <it>GUSB</it>, <it>RPLP0 </it>and <it>ABL </it>were least stable. There was a highly significant difference in variance between ECs. <it>ESR1 </it>expression was appreciably higher in malignant compared to benign tissues and there was a significant effect of EC on the magnitude of the error associated with the relative quantity of <it>ESR1</it>.</p> <p>Conclusion</p> <p>We have validated two endogenous control genes, <it>MRPL19</it> and <it>PPIA</it>, for RQ-PCR analysis of gene expression in primary breast tissue. Of the genes in current use in this field, the above combination offers increased accuracy and resolution in the quantitation of gene expression data, facilitating the detection of smaller changes in gene expression than otherwise possible. The combination identified here is a good candidate for use as a two-gene endogenous control in a broad spectrum of future research and diagnostic applications in breast cancer.</p

A COMPARSION OF METHODS TO EXAMINE DOUBLE AND SINGLE LEG DROP JUMP PERFORMANCE

The purpose of this study was to compare the use of both a force platform and Optojump photocell system (Microgate, Bolzano, Italy) to examine double leg and single leg drop jumps. Thirteen physically active individuals performed 5 double leg drop jumps and 5 single leg drop jumps from a height of 0.3 m. Ground contact time (CT), flight height (FH) and reactive strength index (RSI) were calculated concurrently for both jump types. Despite intraclass correlation coefficients for all variables being very close to 1, a significant systematic difference was consistently observed between both devices with the Optojump system overestimating CT and underestimating both FH and RSI for both jump types. Both devices demonstrated excellent test- retest reliability with all ICCs for CT, FH and RSI above 0.940

The synthesis and biological evaluation of lanostane and cholestane-type natural products

The main objective of this thesis is to outline the synthetic chemistry involved in the preparation of a range of novel lanostane and cholestane derivatives, and subsequent investigation into their biological activity in cancer cells. The biological results obtained throughout the project have driven the strategic synthesis of new compounds, in an effort to optimise the anti cancer potential of lanostane and cholestane derivatives. The first chapter begins with an overview of steroidal compounds and details a literature review of the natural sources of these moieties, as well as their biosynthesis and reported synthetic derivatives. The biological activity of interesting natural and synthetic analogues is also discussed. In addition, an insight into some currently prescribed pharmaceutical compounds, with functional groups relevant to this project, is presented. The second chapter discusses the methods employed for the synthesis of these novel lanostane and cholestane derivatives, and comprises three main sections. Firstly, various oxidation products of lanosterol are synthesised, mainly via epoxidations of the C-8,9 and C- 24,25 alkenes, and also allylic oxidations at these positions. Secondly, amine derivatives of lanosterol are formed by cleaving the lanostane side chain, thereby yielding a new cholestane nucleus, and performing several reductive aminations on the resulting key aldehyde intermediates. Various amines such as piperidine, morpholine, diethylamine and aniline are employed in the reductive amination reactions to yield novel cholestane steroids with amine side chains. Finally, starting from stigmasterol and proceeding with the same methodology of cleaving the steroidal side chain and subsequently performing reductive aminations, novel cholestane derivatives of the biologically active amines are synthesised. The cytotoxicity of these compounds against CaCo-2 and U937 cell lines is presented in terms of percentage viability of cells, IC50 value and apoptosis. The MTT assay is used to determine the percentage viability of cells, and the IC50 data is generated from the MTT results. Apoptosis is measured in terms of fold increase relative to a carrier control. In summary, the compounds formed are discussed in terms of chemical synthesis, spectroscopic interpretation and biological activity. The main reaction pathways involved in the chemistry within this project are various oxidations and reductive amination. The final chapter is a detailed account of the full experimental procedures for the compounds synthesised during this work, including characterisation using spectroscopic and analytical data

Building Scaffolds for Tubular Tissue Engineering.

Hollow organs and tissue systems drive various functions in the body. Many of these hollow or tubular systems, such as vasculature, the intestines, and the trachea, are common targets for tissue engineering, given their relevance to numerous diseases and body functions. As the field of tissue engineering has developed, numerous benchtop models have been produced as platforms for basic science and drug testing. Production of tubular scaffolds for different tissue engineering applications possesses many commonalities, such as the necessity for producing an intact tubular opening and for formation of semi-permeable epithelia or endothelia. As such, the field has converged on a series of manufacturing techniques for producing these structures. In this review, we discuss some of the most common tissue engineered applications within the context of tubular tissues and the methods by which these structures can be produced. We provide an overview of the general structure and anatomy for these tissue systems along with a series of general design criteria for tubular tissue engineering. We categorize methods for manufacturing tubular scaffolds as follows: casting, electrospinning, rolling, 3D printing, and decellularization. We discuss state-of-the-art models within the context of vascular, intestinal, and tracheal tissue engineering. Finally, we conclude with a discussion of the future for these fields

C-reactive protein binds to alphaIIbbeta3.

C-reactive protein binds to alphaIIbbeta3

Advances in mesenchymal stem cell-mediated gene therapy for cancer

Mesenchymal stem cells have a natural tropism for tumours and their metastases, and are also considered immunoprivileged. This remarkable combination of properties has formed the basis for many studies investigating their potential as tumour-specific delivery vehicles for suicide genes, oncolytic viruses and secreted therapeutic proteins. The aim of the present review is to discuss the range of approaches that have been used to exploit the tumour-homing capacity of mesenchymal stem cells for gene delivery, and to highlight advances required to realize the full potential of this promising approach