Validation de nouvelles perspectives pour le dimensionnement des techniques de traitement des eaux pluviales par comparaison d'un modèle de dimensionnement à HEC-HMS

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Toxicological and anti-tumor effects of a linden extract (Tilia platyphyllos Scop.) in a HPV16-transgenic mouse model

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. platyphyllos Scop. have shown in vitro antioxidant, anti-inflammatory and antitumor properties. The aim of this work was to evaluate the therapeutic properties of a hydroethanolic extract obtained from T. platyphyllos in HPV16-transgenic mice. The animals were divided into eight groups according to their sex and phenotype. Four groups of female: HPV+ exposed to linden (HPV linden; n = 6), HPV+ (HPV water; n = 4), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 4) and four groups of male: HPV+ exposed to linden (HPV linden; n = 5), HPV+ (HPV water; n = 5), HPV- exposed to linden (WT linden; n = 5) and HPV- (WT water; n = 7). The linden (Tilia platyphyllos Scop.) extract was orally administered at a dose of 4.5 mg/10 mL per animal (dissolved in water) and changed daily for 33 days. The hydroethanolic extract of T. platyphyllos consisted of protocatechuic acid and (-)-epicatechin as the most abundant phenolic acid and flavonoid, respectively, and was found to be stable during the studied period. In two male groups a significant positive weight gain was observed but without association with the linden extract. Histological, biochemical, and oxidative stress analyses for the evaluation of kidney and liver damage support the hypothesis that the linden extract is safe and well-tolerated under the present experimental conditions. Skin histopathology does not demonstrate the chemopreventive effect of the linden extract against HPV16-induced lesions. The linden extract has revealed a favourable toxicological profile; however, additional studies are required to determine the chemopreventive potential of the linden extract. This journal isThis work was supported by the project IBERPHENOL, project number 0377_IBERPHENOL_6_E; Interact R&D project, operation number NORTE-01-0145-FEDER-000017, National Funds by FCT – Portuguese Foundation for Science and Technology, under the project UIDB/04033/2020 (CITAB), and project UIDB/ CVT/00772/2020 (CECAV) and the post-graduation grant SFRH/ BD/136747/2018 and 2020.04789.BD; the authors are also grateful to FCT, Portugal and FEDER under programme PT2020 for financial support to CIMO (UIDB/00690/2020) and L. Barros acknowledges the national funding by FCT, P. I., through the institutional scientific employment program-contract. The authors would like to thank Cantinho das Aromáticas organic farmers from Vila Nova de Gaia (Portugal) for providing the samples. This work was financially supported by: Base Funding - UIDB/00511/2020 of the Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE - funded by national funds through the FCT/MCTES (PIDDAC).info:eu-repo/semantics/publishedVersio

Suitability of the predatory mites Iphiseiodes zuluagai and Euseius concordis in controlling Polyphagotarsonemus latus and Tetranychus bastosi on Jatropha curcas plants in Brazil

One of the most promising plant species for biofuel production in Brazil is the physic nut Jatropha curcas. Major phytosanitary problems include the attack of two pest mite species, the broad mite Polyphagotarsonemus latus and the spider mite Tetranychus bastosi. Owing to pesticide-related problems, there is an increasing demand for sustainable environmental-friendly control methods such as biological control. In this study we evaluated the suitability of the predatory mite species Iphiseiodes zuluagai and Euseius concordis in controlling P. latus and T. bastosi on J. curcas. The number of T. bastosi killed by I. zuluagai was lower than the number of P. latus consumed.Euseius concordis preyed upon both T. bastosi and P. latus but the number of prey killed was always lower in comparison with I. zuluagai. However, P. latus and T. bastosi are suitable for the development of I. zuluagai and E. concordis as oviposition of both predators did not differ in relation to prey species. The preference of I. zuluagai for leaves of plants infested by either P. latus or T. bastosi, combined with the higher values for predation obtained by this predatory mite when fed on P. latus, compared to those values obtained by E. concordis, suggests that I. zuluagai can be more efficient than E. concordis in reducing populations of P. latus and T. bastosi under field conditions. Furthermore, we report here on the first record of predatory mites associated with P. latus and T. bastosi on native J. curcas plants in Brazil. In conclusion, we emphasize the crucial importance of predatory mites as agents of natural biological control of mite pests on J. curcas in small farms

Plasma pTau-217 and N-terminal tau (NTA) enhance sensitivity to identify tau PET positivity in amyloid-β positive individuals

INTRODUCTION: We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers. METHODS: In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18F]AZD4694 and tau-PET with [18F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aβ+ individuals. RESULTS: Highest associations with tau positivity in Aβ+ individuals were found for plasma pTau-217 (AUC [CI95%] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI95%] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95% = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity. DISCUSSION: The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice. Highlights: We found that in a cohort without pre-selection pTau-181, pTau-217, and NTA-tau showed the highest association with tau PET positivity. We found that in Aβ+ individuals pTau-217 and NTA-tau showed the highest association with tau PET positivity. Combining pTau-217 and NTA-tau resulted in the strongest agreement with the tau PET-based classification

Inclusion of a pH‑responsive amino acid‑based amphiphile in methotrexate‑loaded chitosan nanoparticles as a delivery strategy in cancer therapy

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promising approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pH-responsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials. Outstandingly the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-sensitive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent

A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload

BACKGROUND: It has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described. METHODS: The study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region. RESULTS: Eighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 ± 0.14 × 10(6)/ml), in comparison with subjects carrying only one copy of those alleles (0.46 ± 0.19 × 10(6)/ml) and subjects without any copy of those alleles (0.79 ± 0.15 × 10(6)/ml;p = 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 ± 0.14; 0.45 ± 0.21 and 0.41 ± 0.17 × 10(6)/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p = 0.0009). CONCLUSION: The present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed