Formamidines with antinociceptive and antiinflammatory activities

Pursuing our investigations on 7-amino-2,3-polymethyleneindole derivatives, a set of 7-(dimethylaminomethylene)-amino-2,3-polymethyleneindoles, together with some other aryl or cycloalkyl substituted formamidines, were prepared and tested for analgesic and antiinflammatory activities. Several compounds resulted endowed with one or both of these activities; the indole derivatives 1 and 2 exhibited a good degree of both of them

Human adenocarcinoma cell line sensitivity to essential oil phytocomplexes from pistacia species: A multivariate approach

Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus var. chia (mastic gum), P. terebinthus, P. vera, and P. integerrima, was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC50 = 138.5 \ub5g/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents

Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage

Aminosalicylates, corticosteroids and immunosuppressants are currently the therapeutic choices in inflammatory bowel diseases (IBD), however, with limited remission and often serious side effects. Meanwhile complementary and alternative medicine (CAM) use is increasing, particularly herbal medicine. Boswellia serrata is a traditional Ayurvedic remedy with anti-inflammatory properties, of interest for its usefulness in IBDs. The mechanism of this pharmacological potential of Boswellia serrata was investigated in colonic epithelial cell monolayers exposed to H2O2 or INF-\u3b3+TNF-\u3b1, chosen as in vitro experimental model of intestinal inflammation. The barrier function was evaluated by the transepithelial electrical resistance (TEER) and paracellular permeability assay, and by the tight junction proteins (zonula occludens-1, ZO-1 and occludin) immunofluorescence. The expression of phosphorylated NF-\u3baB and reactive oxygen species (ROS) generation were determined by immunoblot and cytofluorimetric assay, respectively. Boswellia serrata oleo-gum extract (BSE) and its pure derivative acetyl-11-keto-\u3b2-boswellic acid (AKBA), were tested at 0.1-10 \u3bcg/ml and 0.027\u3bcg/ml, respectively. BSE and AKBA safety was demonstrated by no alteration of intestinal cell viability and barrier function and integrity biomarkers. H2O2 or INF-\u3b3+TNF-\u3b1 treatment of Caco-2 cell monolayers significantly reduced TEER, increased paracellular permeability and caused the disassembly of tight junction proteins occludin and ZO-1. BSE and AKBA pretreatment significantly prevented functional and morphological alterations and also the NF-\u3baB phosphorylation induced by the inflammatory stimuli. At the same concentrations BSE and AKBA counteracted the increase of ROS caused by H2O2 exposure. Data showed the positive correlation of the antioxidant activity with the mechanism involved in the physiologic maintenance of the integrity and function of the intestinal epithelium. This study elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD

Plumbagin Induces Cell Cycle Arrest and Apoptosis in A431 Cisplatin-Resistant Cancer Cells

The onset of drug resistance represents the leading cause of chemotherapy failure in clinics. In the last decades, natural compounds have emerged as possible anticancer strategies used either alone or in combination with chemotherapeutic drugs, in order to overcome drug resistance. In fact, plant-derived therapies present biological activity and minimal side effects showing promising roles in the resensitization of resistant cancer cells. This work was aimed at investigating the anticancer potential of the natural naphthoquinone plumbagin in a cisplatin-resistant cancer cell line. The results indicated cytotoxic and pro-oxidant activity of plumbagin in both sensitive (A431wt) and cisplatin-resistant (A431/Pt) human cervix squamous carcinoma cell lines. Moreover, plumbagin treatment induced cell cycle arrest and apoptosis in A431/Pt cells and the inhibition of retinoblastoma complex, suggesting a stronger activity on the cisplatin-resistant cell line. Taken together, the data indicate appreciable in vitro anticancer activity of plumbagin, suggesting that this natural compound could become a tool to overcome cisplatin resistance. Although further studies are necessary, this work underlines a promising role of plumbagin in the resensitization of cisplatin-resistant cancer cells

Pregnane X receptor and constitutive androstane receptor modulate differently CYP3A-mediated metabolism in earlyand late-stage cholestasis

AIM: To ascertain whether cholestasis affects the expression of two CYP3A isoforms (CYP3A1 and CYP3A2) and of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). METHODS: Cholestasis was induced by bile duct ligation in 16 male Wistar rats; whereas 8 sham-operated rats were used as controls. Severity of cholestasis was assessed on histological examination of liver sections, and serum concentrations of albumin, AST, ALT, GGT, ALPK and bilirubin. Gene and protein expressions of PXR, CAR, CYP3A1 and CYP3A2 were assessed by means of qRT-PCR and Western blot, respectively. Alterations in CYP3A activity were measured by calculating the kinetic parameters of 4-OH and 1'-OH-midazolam hydroxylation, marker reactions for CYP3A enzymes. RESULTS: The mRNA and protein expression of CYP3A1 increased significantly in mild cholestasis (P < 0.01). At variance, mRNA and protein expression of CYP3A2 didn't change in mild cholestasis, whereas the expression and activity of both CYP3A1 and CYP3A2 decreased dramatically when cholestasis became severe. Consistently with these observations, the nuclear expression of both PXR and CAR, which was measured because they both translocate into the cell nucleus after their activation, virtually disappeared in the late stage of cholestatic injury, after an initial increase. These results indicate that early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently, probably as consequence of the different activation of PXR and CAR. CONCLUSION: Early- and late-stage cholestasis affects CYP3A-mediated drug metabolism differently. PXR and CAR might be targeted therapeutically to promote CYP3A-mediated liver detoxification

NEW MOHO MAP OF ITALY

In complex tectonics regions, seismological, geophysical, and geodynamic modeling require accurate definition of the Moho geometry. Various active and passive seismic experiments performed in the central Mediterranean region revealed local information on the Moho depth, in some cases used to produce interpolated maps. In this paper, we present a new and original map of the 3-D Moho geometry obtained by integrating selected high-quality controlled source seismic and teleseismic receiver function data. The very small cell size makes the retrieved model suitable for detailed regional studies, crustal corrections in teleseismic tomography, advanced 3-D ray tracing in regional earthquake location, and local earthquake tomography. Our results show the geometry of three different Moho interfaces: the European, Adriatic-Ionian, and Tyrrhenian. The three distinct Moho are fashioned following the Alpine and Apennines subduction, collision, and back-arc spreading and show medium- to high-frequency topographic undulations reflecting the complexity of the geodynamic evolution

Kinematic variables of table vault on artistic gymnastics

Resumo O salto sobre a mesa é uma prova da ginástica artística, tanto no setor masculino quanto no setor feminino. Embora existam inúmeras combinações para a realização de um salto, podemos separá-los em três grupos: reversões, Yurchenko e Tsukahara. Acredita-se que as variáveis cinemáticas do salto podem variar de acordo com o tipo de abordagem ou posição corporal do ginasta, porem pouco se têm estudado acerca das reais diferenças entre os três grupos de saltos, comparando-os e descrevendo os comportamentos em diferentes fases. Assim, o objetivo deste estudo foi organizar de maneira crítica, objetiva e sistemática as variáveis cinemáticas mais relevantes para o performance no salto sobre a mesa. Foi realizada uma meta-análise nas bases de dados Pubmed, Sport Discus and Web of Science sobre o assunto. A partir das referências bibliográficas resultantes, foi descrita e analisada a cinemática do salto sobre a mesa. O salto foi caracterizado em sete fases de análise. A maior parte dos estudos é descritiva, e alguns não abordam todas as fases. As diferenças entre as variáveis dos saltos de acordo com os grupos de saltos, nível técnico e gênero foram analisadas somente em estudos mais recentes. Ainda há lacunas na pesquisa sobre as variáveis cinemáticas do salto sobre a mesa, para fornecer informação abrangente sobre as possibilidades de saltos neste aparelho da ginástica artística. Concluiu-se que as variáveis cinemáticas do salto sobre a mesa dependem do tipo de salto e devem ser consideradas para a melhora da performance técnica. Mais pesquisas são necessárias para que uma interface entre o conhecimento da biomecânica e a aplicação prática seja abrangente ao técnico de ginástica.Abstract The table vault is an event of male and female Artistics Gymnastics. Although it can be performed in a variety of rotations and body positions in different phases, it can be separated in three groups: handspring, Yurchenko and Tsukahara. It is believed that kinematic variables of vault may vary according to group of vault or gymnast body position, but few studies compares the real differences among the three groups of vaults, comparing and describing the variables in different phases. Vault kinematic variables could be diversifying according to the approach or position of the vaulting, but little has been studied about the biomechanical differences, comparing and describing behaviours at different stages. The aim of this study was to organize critical, objective and to systematize the most relevant kinematic variables to performance on vaulting. A Meta analysis over the basis Pubmed, Sport Discus and Web of Science were performed about this issue. From the selected references, we described and analyzed the kinematics of the table vault. Vault can be characterized in seven phases of analysis. Most of the studies are descriptive, and some do not descript all phases. Differences among vault variables according to group vaults, technical level and gender were analysed only in recent studies. There still gaps of knowledge about kinematic variables of table vault, in order to provide comprehensive information about all possibilities of vaults in this gymnastic event. It is concluded that kinematic variables of table vault depends upon vault group and may be considered to the improvement of technical performance. More researches are needed to approach the coaching interface with biomechanics applicable knowledge

A GeoNode-based platform for an effective exploitation of advanced DInSAR measurements

This work presents the development of an efficient tool for managing, visualizing, analysing, and integrating with other data sources, the deformation time-series obtained by applying the advanced differential interferometric synthetic aperture radar (DInSAR) techniques. To implement such a tool we extend the functionalities of GeoNode, which is a web-based platform providing an open source framework based on the Open Geospatial Consortium (OGC) standards, that allows development of Geospatial Information Systems (GIS) and Spatial Data Infrastructures (SDI). In particular, our efforts have been dedicated to enable the GeoNode platform to effectively analyze and visualize the spatio/temporal characteristics of the DInSAR deformation time-series and their related products. Moreover, the implemented multi-thread based new functionalities allow us to efficiently upload and update large data volumes of the available DInSAR results into a dedicated geodatabase. The examples we present, based on Sentinel-1 DInSAR results relevant to Italy, demonstrate the effectiveness of the extended version of the GeoNode platform

Diterpenoid Alkaloids and Phenol Glycosides from Aconitum Naviculare (Brühl) Stapf

Phytochemical investigation of the aerial parts of Aconitum naviculare, a medicinal plant used in traditional Nepalese medicine, led to the isolation and characterization of two new diterpenoid alkaloids, navirine B (1), and navirine C (2), along with (+) chellespontine (3), kaempferol-7-O-β-D-glucopyranosyl(1→3)α-L-rhamnopyranoside (4), kaempferol-7-O α-L-rhamnopyranoside,3-O-β-D-glucopyranoside (5), p-coumaric-4-O-β-D-glucopyranoside acid (6), and ferulic-4-O-β-D-glucopyranoside acid (7). The structures of the isolated compounds were elucidated on the basis of extensive analyses of 1D and 2D NMR spectra (HMQC, HMBC, COSY, ROESY) and HR-MS data. The antiproliferative activity of alkaloids 1–3 against human tumor cell lines (LoVo and 2008) was also evaluated

Modeling Surface Energy Fluxes over a Dehesa (Oak Savanna) Ecosystem Using a Thermal Based Two-Source Energy Balance Model (TSEB) I

Savannas are among the most variable, complex and extensive biomes on Earth, supporting livestock and rural livelihoods. These water-limited ecosystems are highly sensitive to changes in both climatic conditions, and land-use/management practices. The integration of Earth Observation (EO) data into process-based land models enables monitoring ecosystems status, improving its management and conservation. In this paper, the use of the Two-Source Energy Balance (TSEB) model for estimating surface energy fluxes is evaluated over a Mediterranean oak savanna (dehesa). A detailed analysis of TSEB formulation is conducted, evaluating how the vegetation architecture (multiple layers) affects the roughness parameters and wind profile, as well as the reliability of EO data to estimate the ecosystem parameters. The results suggest that the assumption of a constant oak leaf area index is acceptable for the purposes of the study and the use of spectral information to derive vegetation indices is sufficiently accurate, although green fraction index may not reflect phenological conditions during the dry period. Although the hypothesis for a separate wind speed extinction coefficient for each layer is partially addressed, the results show that taking a single oak coefficient is more precise than using bulk system coefficient. The accuracy of energy flux estimations, with an adjusted Priestley–Taylor coefficient (0.9) reflecting the conservative water-use tendencies of this semiarid vegetation and a roughness length formulation which integrates tree structure and the low fractional cover, is considered adequate for monitoring the ecosystem water use (RMSD ~40W m-2)