New Synthesized Derivatives from N-Substituted-4-Oxo-[1] Benzopyrano [4,3-c] Pyrazole Influenced Proliferation, Viability, Spreading and Invasion of Human Liver Tumor Cells

Background/Aim: There is an unsatisfied clinical demand to develop new anticancer agents. The aim of the current study was to synthesize new coumarin derivatives using two different synthetic methodologies and to evaluate their anticancer activity. Materials and methods: Four coumarin derivatives were synthesized and evaluated for their anticancer activities. The structures of all compounds were confirmed by infrared (IR), UV-vis, Nuclear magnetic resonance (NMR) 13C NMR, 1H NMR, and high-resolution mass spectrometry (HRMS) analysis. All the synthesized compounds (4, 5, 8 and 9) were analyzed for their anti-proliferative (MTT and LDH assays and cell cycle studied with flow cytometry) and anti-invasive activity (spreading and invasion tests) on human hepatoma cell lines Huh-7 in vitro. Doxorubicin was used as control in order to compare their anti-tumoral effects. Results. All the synthesized compounds are potential inhibitors of proliferation, viability, spreading and invasion of human liver tumor cells with a 50% inhibitory Concentration range,  IC50=10.37 μM to 12.94 μM. Conclusion. This study could lead to the identification of a new target therapy for human Hepatocellular carcinoma (HCC) or other cancers

Dynamic Contact Angle Analysis of Protein Adsorption on Polysaccharide Multilayer’s Films for Biomaterial Reendothelialization

Atherosclerosis is a major cardiovascular disease. One of the side effects is restenosis. The aim of this work was to study the coating of stents by dextran derivates based polyelectrolyte’s multilayer (PEM) films in order to increase endothelialization of injured arterial wall after stent implantation. Films were composed with diethylaminoethyl dextran (DEAE) as polycation and dextran sulphate (DS) as polyanion. One film was composed with 4 bilayers of (DEAE-DS)4 and was labeled D−. The other film was the same as D− but with an added terminal layer of DEAE polycation: (DEAE-DS)4-DEAE (labeled D+). The dynamic adsorption/desorption of proteins on the films were characterized by dynamic contact angle (DCA) and atomic force microscopy (AFM). Human endothelial cell (HUVEC) adhesion and proliferation were quantified and correlated to protein adsorption analyzed by DCA for fibronectin, vitronectin, and bovine serum albumin (BSA). Our results showed that the endothelial cell response was optimal for films composed of DS as external layer. Fibronectin was found to be the only protein to exhibit a reversible change in conformation after desorption test. This behavior was only observed for (DEAE-DS)4 films. (DEAE-DS)4 films could enhance HUVEC proliferation in agreement with fibronectin ability to easily change from conformation

Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression.

International audienceThe therapeutic potential of low molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed was investigated on vascular smooth muscle cell (VSMC) and human vascular endothelial cell (HUV-EC-C) proliferation and migration in vitro and in a rat model of intimal hyperplasia. Sprague-Dawley rats were subjected to balloon injury in the thoracic aorta followed by two weeks' treatment with either LMWF (5mg/kg/day) or vehicle. Morphological analysis and proliferating cell nuclear antigen immunostaining at day 14 indicated that LMWF prevented intimal hyperplasia in rat thoracic aorta as compared with vehicle (neo-intima area, 3±0.50 versus 5±0.30mm, <0.01). In situ zymography showed that LMWF significantly decreased the activity of matrix metalloproteinase (MMP)-2 in the neo-intima compared to vehicle. The in vitro study demonstrated that 10μg/ml LMWF increased HUV-EC-C migration by 45±5% but reduced VSMC migration by 40±3%. LMWF also increased MMP-2 mRNA expression in HUV-EC-Cs and reduced it in VSMCs. MMP-2 level in the conditioned medium from cells incubated with 10μg/ml LMWF was 5.4-fold higher in HUV-EC-C, but 6-fold lower in VSMCs than in untreated control cells. Furthermore, decreasing MMP-2 expression in HUV-EC-Cs or VSMCs by RNA interference resulted in reduced LMWF-induced effects on cell migration

Angiogenic properties of the chemokine RANTES/CCL5

International audienc

Mediator levels and activities in salivary samples from men and women.

<p>n indicates number of subjects studied.</p

Mediator levels and activities in salivary samples from all subjects.

<p>n indicates number of subjects studied.</p

Mediator levels and activities in salivary samples from young (≤40 years) and old (>40 years) subjects.

<p>n indicates number of subjects studied and</p>*<p>indicates values significantly different from young subjects (P<0.05).</p

Relationship between age and mediators of inflammation in saliva from healthy subjects.

<p>Panel a: lysozyme activity, b: PGE₂, c: LTB₄ (with inset showing ≤40 years) and d: MMP-9 activity. Diagonal lines are the regression correlations when shown to be significant.</p