Activité anti-inflammatoire des feuilles dBorassus aethiopum Mart. (Arecaceae)

Le rônier est un palmier très utilisé dans la pharmacopée traditionnelle ; Le calcinât des feuilles est utilisé en boisson dans l’eau pour traiter la bilharziose viscérale. La tigelle de la noix germée en décoction lutte contre l’impuissance sexuelle, une activité anti-inflammatoire avec une inhibition de 70% de l’oedème induite par la carragénine a été révélée dans les extraits d’inflorescences mâles. La méthode de l’oedème induit par la carragénine de Winter a été utilisée sur des rats de souche Wistar pour mettre en évidence l’activité antiinflammatoire des feuilles de Borassus aethiopum. L’extrait d’acétate d’éthyle et sa fraction F1 à la dose 30 mg/kg ont une activité anti-inflammatoire voisine de celle de l’aspirine à 30 mg/kg; cette activité (exprimée en pourcentage d’inhibition) est respectivement de 79,21%, 73,16 et 92,53% à la première heure. Ainsi à la cinquième heure ces pourcentages sont 69,18%, 54,59% et 58,75% respectivement pour la référence, l’extrait d’acétate d’éthyle et la fraction F1.Mots clés: Borassus aethiopum Mart, feuilles et activité anti-inflammatoire

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.111813Ysciescopu

Distribution and Regulation of the Mobile Genetic Element-Encoded Phenol-Soluble Modulin PSM-mec in Methicillin-Resistant Staphylococcus aureus

The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus

Flood Risk Assessment for Urban Drainage System in a Changing Climate Using Artificial Neural Network

Changes in rainfall patterns due to climate change are expected to have negative impact on urban drainage systems, causing increase in flow volumes entering the system. In this paper, two emission scenarios for greenhouse concentration have been used, the high (A1FI) and the low (B1). Each scenario was selected for purpose of assessing the impacts on the drainage system. An artificial neural network downscaling technique was used to obtain local-scale future rainfall from three coarse-scale GCMs. An impact assessment was then carried out using the projected local rainfall and a risk assessment methodology to understand and quantify the potential hazard from surface flooding. The case study is a selected urban drainage catchment in northwestern England. The results show that there will be potential increase in the spilling volume from manholes and surcharge in sewers, which would cause a significant number of properties to be affected by flooding

Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

<p>Abstract</p> <p>Background</p> <p>The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown.</p> <p>Methods</p> <p>High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC).</p> <p>Results</p> <p>On a genome-wide profile, SCCs showed higher frequency of gains than ACs (<it>p </it>= 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (<it>P </it>< 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,<it>MDS1, PIK3CA </it>and <it>TP73L</it>, were observed in SCC (<it>P </it>< 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: <it>LOC389174 </it>(3q26.2),<it>KCNMB3 </it>(3q26.32),<it>EPHB3 </it>(3q27.1), <it>MASP1 </it>and <it>SST </it>(3q27.3), <it>LPP </it>and <it>FGF12 </it>(3q28), and <it>OPA1</it>,<it>KIAA022</it>,<it>LOC220729</it>, <it>LOC440996</it>,<it>LOC440997</it>, and <it>LOC440998 </it>(3q29), all of which were significantly targeted in SCC (<it>P </it>< 0.05). Among these same genes, high-level amplifications were detected for the gene, <it>EPHB3</it>, at 3q27.1, and <it>MASP1 </it>and <it>SST</it>, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs.</p> <p>Conclusion</p> <p>Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of the squamous cell carcinoma of the lung.</p

Inactivation of Staphylococcal Phenol Soluble Modulins by Serum Lipoprotein Particles

Staphylococcus aureus virulence has been associated with the production of phenol soluble modulins (PSM). PSM are known to activate, attract and lyse neutrophils. However, the functional characterizations were generally performed in the absence of human serum. Here, we demonstrate that human serum can inhibit all the previously-described activities of PSM. We observed that serum can fully block both the cell lysis and FPR2 activation of neutrophils. We show a direct interaction between PSM and serum lipoproteins in human serum and whole blood. Subsequent analysis using purified high, low, and very low density lipoproteins (HDL, LDL, and VLDL) revealed that they indeed neutralize PSM. The lipoprotein HDL showed highest binding and antagonizing capacity for PSM. Furthermore, we show potential intracellular production of PSM by S. aureus upon phagocytosis by neutrophils, which opens a new area for exploration of the intracellular lytic capacity of PSM. Collectively, our data show that in a serum environment the function of PSM as important extracellular toxins should be reconsidered

DECK: Distance and environment-dependent, coarse-grained, knowledge-based potentials for protein-protein docking

<p>Abstract</p> <p>Background</p> <p>Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom) pairs in the non-interaction state.</p> <p>Results</p> <p>The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK) potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the D<smcaps>OCKGROUND</smcaps> resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results.</p> <p>Conclusions</p> <p>A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of the potentials.</p

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease