Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease.

Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC).

Infliximab induction regimens in steroid-refractory acute severe colitis: a multicentre retrospective cohort study with propensity score analysis.

Background: Accelerated induction regimens of infliximab have been proposed to improve response rates in patients with steroid-refractory acute severe colitis.

Aim: To determine the differences in outcome for acute severe ulcerative colitis between accelerated and standard-dose infliximab METHODS: We collected data on hospitalised patients receiving differing regimens of rescue therapy for steroid-refractory acute severe ulcerative colitis. Our primary outcome was 30-day colectomy rate.

Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies.

Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein-protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type.

Omics Approaches to Identify Potential Biomarkers of Inflammatory Diseases in the Focal Adhesion Complex.

Inflammatory diseases such as inflammatory bowel disease (IBD) require recurrent invasive tests, including blood tests, radiology, and endoscopic evaluation both to diagnose and assess disease activity, and to determine optimal therapeutic strategies. Simple 'bedside' biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex (FAC) has been implicated in the pathogenesis of multiple inflammatory diseases, including IBD, rheumatoid arthritis, and multiple sclerosis.

Identification of critical paralog groups with indispensable roles in the regulation of signaling flow.

Extensive cross-talk between signaling pathways is required to integrate the myriad of extracellular signal combinations at the cellular level. Gene duplication events may lead to the emergence of novel functions, leaving groups of similar genes - termed paralogs - in the genome. To distinguish critical paralog groups (CPGs) from other paralogs in human signaling networks, we developed a signaling network-based method using cross-talk annotation and tissue-specific signaling flow analysis.

Prevention of upper gastrointestinal haemorrhage: current controversies and clinical guidance.

Acute upper gastrointestinal (GI) bleeding is a common medical emergency and associated with significant morbidly and mortality. The risk of bleeding from peptic ulceration and oesophagogastric varices can be reduced by appropriate primary and secondary preventative strategies. Helicobacter pylori eradication and risk stratification with appropriate gastroprotection strategies when used with antiplatelet drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in preventing peptic ulcer bleeding, whilst endoscopic screening and either nonselective beta blockade or endoscopic variceal ligation are effective at reducing the risk of variceal haemorrhage.

Therapeutic advances in the management of chronic hepatitis B infection.

Hepatitis B virus (HBV) is a small nonenveloped DNA virus that is a member of the Hepadnaviridae family. Chronic HBV infection is estimated to effect more than 350 million people worldwide with over 2 billion people being exposed to the virus. Risk factors for chronic infection include age of exposure to the virus, concurrent immunosuppression and HIV infection.