Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway

BACKGROUND AND PURPOSE Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS Toluquinol inhibited LEC proliferation,migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependentmanner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by personal funding by FP7-PEOPLE-2013-IEF Marie Curie Postdoctoral Fellowship (MGC). Acknowledged are the supporting grants from the Action de Recherche Concertée (ARC) (Université de Liège), the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS), the Foundation Against Cancer (foundation of public interest), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the Interuniversity Attraction Poles Programme-Belgian Science Policy (all from Belgium) and the Plan National Cancer (« Service Public Federal » from Belgium). Research in the lab of A.R.Q. and M.A.M. was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER)

Fishery biomass trends of exploited fish populations in marine ecoregions, climatic zones and ocean basins

Highlights: • 1st global long-term fishery biomass trends evaluation of 1300 exploited marine populations. • Decline in average fishery biomass observed across oceans and climate zones. • Systemic wide-spread overfishing of the world's coastal and continental shelf water. Abstract: This contribution presents time series of the ‘fishery biomass’ of fish populations, defined as the weight (whole-body, wet weight) of the in-water part of a fishable population, i.e., that part of a population (also called ‘stock’) that is exposed to a certain fishing gear. Detailed data of this type are only available for a limited number of species that are targets of the fisheries in the waters of economically developed regions, such as Europe, the USA, Canada or Australia. However, similar fishery biomass assessments are generally lacking for developing countries, even for many of their most heavily fished species. Here, an estimation of the long-term fishery biomass trends of 1320 fish and invertebrate populations for 483 species exploited by fisheries in the 232 coastal Marine Ecoregions (MEs) around the world was undertaken. Fishery biomass trends were derived using the Bayesian CMSY stock assessment method applied to the global fisheries catch database for 1950–2014 as reconstructed by the Sea Around Us for every maritime fishing country in the world. Overall, the results suggest a consistent decline in the fishery biomass of exploited populations, in virtually all climatic zones and ocean basins in the world. The only zone with currently higher fishery biomass than in 1950 is the northern Pacific polar-boreal zone, likely due to environmental changes that occurred in the region positively affecting fish populations, combined with prudent management of the fisheries. For populations in MEs that are known to have highly questionable catch statistics, the results suggested smaller declines in fishery biomass than likely occurred in reality, implying that these results do not exaggerate declining trends in fishery biomass. This study used informative Bayesian priors to improve the trend analyses in areas where systematic stock assessments were conducted. The use of these independent assessments reduced the uncertainty associated with the findings of this study

In-situ trace metal (Cd, Pb, Cu) speciation along the Po River plume (Northern Adriatic Sea) using submersible systems

Highlights • In-situ trace metal speciation in the Adriatic Sea by submersible voltammetric sensors • Metal species distribution mainly affected by Po River outflow. • Metal dynamic concentrations below legal limits • Cu dynamic concentrations toxic to sensitive phytoplankton Abstract Information on the distribution and speciation of trace metals is of critical importance for our ability to interpret the links between the bioavailability and uptake of an element, and its biogeochemical cycle in coastal environments. Within the framework of the European Project “In-situ automated Monitoring of Trace metal speciation in Estuaries and Coastal zones in relation with the biogeochemical processes (IMTEC)”, the chemical speciation of Cd, Pb and Cu was carried out along the Po River plume in the period 27 October – 2 November 2002. During the cruise, five Voltammetric In-situ Profiling systems and one Multi Physical Chemical Profiler, as well as conventional voltammetric instruments, were successfully applied in order to evaluate the distribution of Cd, Pb and Cu between different fractions (free ion, dynamic, colloidal, dissolved and particulate fractions) and to assess the evolution of these fractions during estuarine mixing and in the water column. Dynamic concentrations were 0.05–0.2 nmol L−1 Cd, 0.02–0.2 nmol L−1 Pb, and 0.15–4.0 nmol L−1Cu. Cd was mainly present as dynamic fraction (40–100% of the dissolved Cd). High proportions of Pb (~70%) and Cu (~80%) were present as colloids probably of biogenic origin. Principal components analysis reveals a strong influence of the Po River discharge on the spatial and vertical distributions of metal species. Almost all the metal fractions globally decreased following the salinity gradient. Metal concentrations are far below (at least one order of magnitude lower) the Environmental Quality Standard established by the Italian law. However, the Cu dynamic fraction showed concentrations likely to be toxic to sensitive phytoplankton community and to have negative effects on larva development of coastal macroinvertebrate species (toxicity data extracted from literature)

Tannin- caprolactam and Tannin- PEG formulations as outdoor wood preservatives: Weathering properties

International audienceAbstractKey messageThis article presents the leaching, fire and weathering resistance improvements of samples treated with tannin-based wood preservatives added of caprolactam. PEG-added formulations show limited applicability. The FT-IR and13C-NMR analyses of the caprolactam-added formulations show some evidences of copolymerization.ContextTannin-boron wood preservatives are known for their high resistance against leaching, biological attacks, fire as well as for the good mechanical properties that they impart to wood. These properties promoted these formulations for being a candidate for the protection of green buildings. However, the low elasticity of these polymers and their dark colour implied limited weathering resistances.AimsThe aim of the study is to find suitable additives for tannin-based formulations to overcome their limited weathering resistances, without compromising the other properties.MethodsTreatment, leaching and fire tests, dimensional stability as well as artificial and natural weathering of the timber treated with caprolactam-added and PEG-added formulations were performed. FT-IR and 13C-NMR of the formulations were presented.ResultsThe presence of caprolactam improved the properties of the formulation with particularly significant results in terms of resistance against leaching and dimensional stability. These enhancements were imparted also to the weathering resistance of the tannin-caprolactam formulations. Indeed, the colour changes during the artificial and natural exposures were stable for longer periods. FT-IR and 13C-NMR investigations of the advanced formulations were led, and covalent copolymerization of the caprolactam with the tannin-hexamine polymer was observed.ConclusionThe tannin formulations with caprolactam improved the durability of the wood specimens, while the PEG-tannin presented strong application drawbacks

A stellar overdensity associated with the Small Magellanic Cloud

We report the discovery of a stellar over-density 8$^{\circ}$ north of the center of the Small Magellanic Cloud (Small Magellanic Cloud Northern Over-Density; SMCNOD) using data from the first two years of the Dark Energy Survey (DES) and the first year of the MAGellanic SatelLITEs Survey (MagLiteS). The SMCNOD is indistinguishable in age, metallicity and distance from the nearby SMC stars, being primarly composed of intermediate-age stars (6 Gyr, Z=0.001), with a small fraction of young stars (1 Gyr, Z=0.01). The SMCNOD has an elongated shape with an ellipticity of 0.6 and a size of $\sim$ 6x2 deg. It has an absolute magnitude of $M_V \cong$ -7.7, $r_h = 2.1$ kpc, and $\mu_V(r<r_h)$ = 31.2 mag arcsec$^{-2}$. We estimate a stellar mass of $\sim 10^5$ $M_{\odot}$, following a Kroupa mass function. The SMCNOD was probably removed from the SMC disk by tidal stripping, since it is located near the head of the Magellanic Stream, and the literature indicates likely recent LMC-SMC encounters. This scenario is supported by the lack of significant HI gas. Other potential scenarios for the SMCNOD origin are a transient over-density within the SMC tidal radius or a primordial SMC satellite in advanced stage of disruption.Comment: 14 pages, 10 color figure