Wnt/β-catenin signalling induces MLL to create epigenetic changes in salivary gland tumours

We show that activation of Wnt/{beta}-catenin and attenuation of Bmp signals, by combined gain- and loss-of-function mutations of {beta}-catenin and Bmpr1a, respectively, results in rapidly growing, aggressive squamous cell carcinomas (SCC) in the salivary glands of mice. Tumours contain transplantable and hyperproliferative tumour propagating cells, which can be enriched by fluorescence activated cell sorting (FACS). Single mutations stimulate stem cells, but tumours are not formed. We show that {beta}-catenin, CBP and Mll promote self-renewal and H3K4 tri-methylation in tumour propagating cells. Blocking {beta}-catenin-CBP interaction with the small molecule ICG-001 and small-interfering RNAs against {beta}-catenin, CBP or Mll abrogate hyperproliferation and H3K4 tri-methylation, and induce differentiation of cultured tumour propagating cells into acini-like structures. ICG-001 decreases H3K4me3 at promoters of stem cell-associated genes in vitro and reduces tumour growth in vivo. Remarkably, high Wnt/{beta}-catenin and low Bmp signalling also characterize human salivary gland SCC and head and neck SCC in general. Our work defines mechanisms by which {beta}-catenin signals remodel chromatin and control induction and maintenance of tumour propagating cells. Further, it supports new strategies for the therapy of solid tumours

A Bi-Functional Anti-Thrombosis Protein Containing Both Direct-Acting Fibrin(ogen)olytic and Plasminogen-Activating Activities

Direct-acting fibrin(ogen)olytic agents such as plasmin have been proved to contain effective and safety thrombolytic potential. Unfortunately, plasmin is ineffective when administered by the intravenous route because it was neutralized by plasma antiplasmin. Direct-acting fibrin(ogen)olytic agents with resistance against antiplasmin will brighten the prospect of anti-thrombosis. As reported in ‘Compendium of Materia Medica’, the insect of Eupolyphaga sinensis Walker has been used as traditional anti-thrombosis medicine without bleeding risk for several hundreds years. Currently, we have identified a fibrin(ogen)olytic protein (Eupolytin1) containing both fibrin(ogen)olytic and plasminogen-activating (PA) activities from the beetle, E. sinensis. Objectives: To investigate the role of native and recombinant eupolytin1 in fibrin(ogen)olytic and plasminogen-activating processes. Methods and Results: Using thrombus animal model, eupolytin1 was proved to contain strong and rapid thrombolytic ability and safety in vivo, which are better than that of urokinase. Most importantly, no bleeding complications were appeared even the intravenous dose up to 0.12 µmol/kg body weight (3 times of tested dose which could completely lyse experimental thrombi) in rabbits. It is the first report of thrombolytic agents containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities. Conclusions: The study identified novel thrombolytic agent with prospecting clinical potential because of its bi-functional merits containing both plasmin- and PA-like activities and unique pharmacological kinetics in vivo

Wastewater nutrient removal in a mixed microalgae bacteria culture: effect of light and temperature on the microalgae bacteria competition

[EN] The aim of this study was to evaluate the effect of light intensity and temperature on nutrient removal and biomass productivity in a microalgae¿bacteria culture and their effects on the microalgae¿bacteria competition. Three experiments were carried out at constant temperature and various light intensities: 40, 85 and 125¿µE¿m¿2¿s¿1. Other two experiments were carried out at variable temperatures: 23¿±¿2°C and 28¿±¿2°C at light intensity of 85 and 125¿µE¿m¿2¿s¿1, respectively. The photobioreactor was fed by the effluent from an anaerobic membrane bioreactor. High nitrogen and phosphorus removal efficiencies (about 99%) were achieved under the following operating conditions: 85¿125¿µE¿m¿2¿s¿1 and 22¿±¿1°C. In the microalgae¿bacteria culture studied, increasing light intensity favoured microalgae growth and limited the nitrification process. However, a non-graduated temperature increase (up to 32°C) under the light intensities studied caused the proliferation of nitrifying bacteria and the nitrite and nitrate accumulation. Hence, light intensity and temperature are key parameters in the control of the microalgae¿bacteria competition. Biomass productivity significantly increased with light intensity, reaching 50.5¿±¿9.6, 80.3¿±¿6.5 and 94.3¿±¿7.9¿mgVSS¿L¿1¿d¿1 for a light intensity of 40, 85 and 125¿µE¿m¿2¿s¿1, respectivelyThis research work was possible because of Projects CTM2011-28595-C02-01 and CTM2011-28595-C02-02 [funded by the Spanish Ministry of Economy and Competitiveness jointly with the European Regional Development Fund and the Generalitat Valenciana GVA-ACOMP2013/203]. 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Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study

<p>Abstract</p> <p>Background</p> <p>Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication.</p> <p>Methods</p> <p>We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index.</p> <p>Results</p> <p>D-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers.</p> <p>Conclusions</p> <p>The results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.</p