A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases.

Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity.

Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases.

Objective: Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response.

Design: Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29).

Bile acid profiling in human biological samples: comparison of extraction procedures and application to normal and cholestatic patients.

The role of bile acids in cell metabolism, membrane biology and cell signaling is increasingly recognized, thus making necessary a robust and versatile technique to extract, separate and quantify a large concentration range of these numerous molecular species. HPLC-MS/MS analysis provides the highest sensitivity to detect and identify bile acids. However, due to their large chemical diversity, extraction methods are critical and quite difficult to optimize, as shown by a survey of the literature.

Current smoking differentially affects blood mononuclear cells from patients with Crohn's disease and ulcerative colitis: relevance to its adverse role in the disease.

Background: Epidemiologic data suggest that smoking increases the risk and the severity of Crohn's disease (CD), although it may protect patients with ulcerative colitis (UC). To investigate this paradox, we evaluated the effect of cigarette smoke in the function of blood mononuclear cells from healthy subjects and patients with CD or UC in flare up.

Methods: The production of mediators associated with inflammation but also with protective functions was evaluated by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), following either in vivo or in vitro exposure to cigarette smoke.

C-reactive protein and transesophageal echocardiographic markers of thromboembolism in patients with atrial fibrillation.

Background: To determine whether C-reactive protein (CRP) in combination with a stroke risk stratification scheme can help in identifying transesophageal echocardiographic (TEE) markers of thromboembolism such as left atrial (LA)/left atrial appendage (LAA) thrombus, severe LA/LAA spontaneous echocardiographic contrast (SEC), and aortic plaque ≥ 4 mm.

Methods: Transthoracic echocardiography, TEE, and CRP measurement were performed at admission in 178 patients with non-valvular atrial fibrillation not receiving oral anticoagulant therapy. Patients were classified as at low, moderate, or high risk of thromboembolism based on seven clinical risk stratification schemes (SPAF, CHADS(2), Framingham, Birmingham/NICE, ACC/AHA/ESC 2006 guidelines, ACCP 2008, CHA(2)DS(2)VASc).

Regulation of colon cancer cell proliferation and migration by MD-2 activity.

Evidence suggests that signalling through lipopolysaccharide (LPS) has a significant role in the development of gastrointestinal malignancies. We previously demonstrated the critical role of myeloid differentiation (MD)-2, the essential co-receptor of LPS, for induction of cyclooxygenase (Cox)-2 in intestinal epithelial cells. Cyclooxigenase-2 was suggested to play a key role in colorectal cancer through the effects of prostaglandin (PG) E(2) generated.

Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schizophrenia.

Abnormalities in membrane lipids have been repeatedly reported in patients with schizophrenia. These abnormalities include decreased phosphatidylethanolamine (PE) and n-3 and n-6 polyunsaturated fatty acids in peripheral and brain cell membranes. The present study investigates the hypothesis of an overrepresentation of PE in the external leaflet of the red blood cell (RBC) membrane in patients with schizophrenia.

MD-2 controls bacterial lipopolysaccharide hyporesponsiveness in human intestinal epithelial cells.

Intestinal epithelial cells (IEC) have adapted to the presence of commensal bacteria through a state of tolerance that involves a limited response to lipopolysaccharide (LPS). Low or absent expression of two LPS receptor molecules, the myeloid differentiation (MD)-2 receptor, and toll-like receptor (TLR)4 was suggested to underlie LPS tolerance in IEC. In the present study we performed transfections of TLR4 and MD-2 alone or combined in different IEC lines derived from intestinal cancer (Caco-2, HT-29, and SW837).

Secretory phospholipase A(2) activity and release kinetics of vascular tissue remodelling biomarkers after coronary artery bypass grafting with and without cardiopulmonary bypass.

Background: Cardiopulmonary bypass (CPB) has long been recognised as a main cause of a postoperative complex systemic inflammatory response after coronary artery bypass grafting (CABG).

Methods: We determined the kinetics of peripheral blood release of the novel inflammatory biomarkers secretory phospholipase A(2) (sPLA(2)), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) during the first 6 days following surgery in 16 patients undergoing CABG with (on-pump, n=9) or without (off-pump, n=7) CPB. Kinetic curves for these markers were compared to those of the well-known inflammatory parameters C-reactive protein (CRP) and fibrinogen.

Cytoplasmic phospholipase A2 expression in human colon adenocarcinoma is correlated with cyclooxygenase-2 expression and contributes to prostaglandin E2 production.

Cytoplasmic phospholipase A2 (cPLA2) has a key role in prostaglandin production. The role of cPLA2 in intestinal tumorigenesis has been suggested, however, contradictory data are found in the literature. We evaluated cPLA2 and cyclooxygenase-2 (COX-2) protein expression in 65 colon carcinomas by immunohistochemistry, and in eight colorectal cancer cell lines by Western Blot.

Circulating secretory phospholipase A2 activity predicts recurrent events in patients with severe acute coronary syndromes.

Objectives: The purpose of this study was to determine the prognostic value of circulating secretory phospholipase A2 (sPLA2) activity in patients with acute coronary syndromes (ACS).

Background: The plasma level of type IIA sPLA2 is a risk factor for coronary artery disease (CAD) and is associated with adverse outcomes in patients with stable CAD. The prognostic impact of sPLA2 in patients with ACS is unknown.

Cytoplasmic phospholipase A2 alpha overexpression in stromal cells is correlated with angiogenesis in human colorectal cancer.

In colorectal cancer, cyclooxygenase-2 (COX-2) overexpression in stromal cells induces angiogenesis through EP2 prostaglandin E2 receptor signaling. Cytoplasmic phospholipase A2 (PLA2) alpha preferentially hydrolyses arachidonic acid, which is the limiting substrate for prostaglandin production, from membrane phospholipids. We therefore investigated a possible relationship between cytoplasmic PLA2 and COX-2 overexpression in stromal cells, angiogenesis and microsatellite instability in 48 human colorectal adenocarcinomas.

Cyclooxygenase-2 and its role in colorectal cancer development.

Cyclooxygenase 2 (COX-2), also called prostaglandin endoperoxide synthase 2, is involved in colorectal tumor development. This review deals with particular questions raised in this field such as the mechanisms of COX-2 related tumor promotion, the role of the different types of cells (epithelial and interstitial) expressing COX-2, the factors that trigger COX-2 induction, and the clinical potential of selective COX-2 inhibitors to treat or prevent colorectal tumors. Several mechanisms of COX-2 related tumor promotion have been identified.

Cytosolic phospholipase A2-p11 interaction controls arachidonic acid release as a function of epithelial cell confluence.

Madin-Darby canine kidney type II cells were shown to release low amounts of AA (arachidonic acid) and prostaglandin E2 in response to various stimuli when analysed after cell confluence. In contrast, non-confluent Madin-Darby canine kidney type II cells released much higher amounts of AA and prostaglandin E2. In both stationary and non-confluent cells, AA was released by type IV cPLA2 (cytosolic phospholipase A2), as shown by the use of specific inhibitors and by analysis of the profile of fatty acids released.

Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release.

Accumulating evidence suggests that some heat shock proteins (Hsps), in particular the 72-kDa inducible Hsp70, associate to the cell membrane and might be secreted through an unknown mechanism to exert important functions in the immune response and signal transduction. We speculated that specialized structures named lipid rafts, known as important platforms for the delivery of proteins to the cell membrane, might be involved in the unknown mechanism ensuring membrane association and secretion of Hsp70. Lipid rafts are sphingolipid-cholesterol-rich structures that have been mainly characterized in polarized epithelial cells and can be isolated as detergent-resistant microdomains (DRMs).

Mucinous colon carcinomas with microsatellite instability have a lower microvessel density and lower vascular endothelial growth factor expression.

We determined the association between cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) expression, microvessel density (MVD) and microsatellite instability (MSI) or the histological type in colon adenocarcinomas. Sixty-six cases were studied, 28 MSI+ and 38 MSI-. MSI phenotype was determined using polymerase chain reaction.

COX-2, inflammatory secreted PLA2, and cytoplasmic PLA2 protein expression in small bowel adenocarcinomas compared with colorectal adenocarcinomas.

Cyclooxygenase-2 (COX-2), human synovial inflammatory secreted phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) are involved in eicosanoid production and also seem to participate in colorectal tumorigenesis. As there are no data regarding these enzymes in human small bowel tumors, we wanted to determine whether they were involved in human small bowel tumorigenesis, and whether their expression was different in small bowel compared to colorectal adenocarcinomas, as suggested by animal studies. We studied their protein expression by immunohistochemistry in 25 small bowel adenocarcinomas and compared it to 48 colorectal adenocarcinomas.