Exploiting Visual Languages Generation and UML Meta Modeling to Construct Meta-CASE Workbenches

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Natural compounds for pediatric cancer treatment

There is a tremendous need in clinics to impair cancer progression through noninvasive therapeutic approaches. The use of natural compounds to achieve this is of importance to improve the quality of life of young patients during their treatments. This review will address the "status of the art" related to the potential of natural compounds that are undergoing investigation in combination with standard therapeutic protocols in preclinical and clinical studies and their importance for pediatric cancer treatment. The early studies of drug discovery of these natural compounds discussed here include the main targets, the cellular signaling pathways involved, and the potential modes of action. We also focus on some promising natural compounds that have shown excellent results in vitro and in vivo: Chebulagic acid, Apigenin, Norcantharidin, Saffron/Crocin, Parthenolide, Longikaurin E, Lupeol, Spongistatin 1, and Deoxy-variolin B. Additionally, we introduce the effects of several compounds from nutraceutical and functional foods, to underline their potential use as adjuvant therapies to improve therapeutic benefits. For this purpose, we have selected several compounds: Agaritine, Ganoderma and GL6 peptide, Diallyl trisulfide and Ajoene from garlic, Epigallocatechin gallate from green tea, Curcumin, Resveratrol, and Quercetin

Exploiting XPG for Visual Languages Definition, Analysis and Development

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Molecular signals from primordial clouds at high redshift

The possibility to detect cosmological signals from the post-recombination Universe is one of the main aims of modern cosmology. In a previous paper we emphasized the role that elastic resonant scattering through LiH molecules can have in dumping primary CBR anisotropies and raising secondary signals. Here we extend our analysis to all the evolutionary stages of a primordial cloud, starting with the linear phase, through the turn-around and to the non linear collapse. We have done calculations for proto-clouds in a CDM scenario and, more generally, for a set of clouds with various masses and various turn-around redshifts, in this case without referring to any particular structure formation scenario. We found that the first phase of collapse, for $t/t_{free-fall}=0.05\div 0.2$ is the best one for simultaneous detection of the first two LiH rotational lines. The observational frequency falls between 30 and 250 GHz and the line width ${\Delta \nu\over \nu}$ is between $10^{-5}$ and $10^{-4}$. As far as we know this is the most favourable process to detect primordial clouds before they start star formation processes.Comment: 26 pages, uuencoded compressed postscript, 7 figures included. Accepted for publication in Ap.

A competitive cell-permeable peptide impairs Nme-1 (NDPK-A) and Prune-1 interaction: therapeutic applications in cancer.

The understanding of protein–protein interactions is crucial in order to generate a second level of functional genomic analysis in human disease. Within a cellular microenvironment, protein–protein interactions generate new functions that can be defined by single or multiple modes of protein interactions. We outline here the clinical importance of targeting of the Nme-1 (NDPK-A)–Prune-1 protein complex in cancer, where an imbalance in the formation of this protein–protein complex can result in inhibition of tumor progression. We discuss here recent functional data using a small synthetic competitive cell-permeable peptide (CPP) that has shown therapeutic efficacy for impairing formation of the Nme-1–Prune-1 protein complex in mouse preclinical xenograft tumor models (e.g., breast, prostate, colon, and neuroblastoma). We thus believe that further discoveries in the near future related to the identification of new protein–protein interactions will have great impact on the development of new therapeutic strategies against various cancers

Vesuvio: Rete Sismica Digitale

In the tex

The ghrelin paradox in the control of equine chondrocyte function: The good and the bad

Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-7-10-11\u202fmol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100\u202fng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide staining. The presence of GHS-R1a on chondrocytes was detected by Western Blot. The involvement of the GHS-R1a in the ghrelin effect against LPS-induced cytotoxicity was examined by pretreating chondrocytes with D-Lys3-GHRP-6, a specific GHS-R1a antagonist, and by using des-acyl ghrelin (DAG, 10-7and 10-9\u202fmol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7\u202fmol/L ghrelin protects against LPS-induced cellular damage. The protective effect of ghrelin depends on the interaction with the GHS-R1a since it is significantly reduced by D-Lys3-GHRP-6. The negative action of ghrelin involves caspase activation and could be due to an interaction with a GHS-R type different from the GHS-R1a recognized by both low ghrelin concentrations and DAG. DAG, in fact, induces a dose-dependent decrease in chondrocyte viability and exacerbates LPS-induced damage. These data indicate that ghrelin protects chondrocytes against LPS-induced damage via interaction with GHS-R1a and suggest the potential utility of local GHS-R1a agonist administration to treat articular inflammatory diseases such as OA

Epigenetics and immune cells in medulloblastoma

: Medulloblastoma (MB) is a highly malignant childhood tumor of the cerebellum. Transcriptional and epigenetic signatures have classified MB into four molecular subgroups, further stratified into biologically different subtypes with distinct somatic copy-number aberrations, driver genes, epigenetic alterations, activated pathways, and clinical outcomes. The brain tumor microenvironment (BTME) is of importance to regulate a complex network of cells, including immune cells, involved in cancer progression in brain malignancies. MB was considered with a "cold" immunophenotype due to the low influx of immune cells across the blood brain barrier (BBB). Recently, this assumption has been reconsidered because of the identification of infiltrating immune cells showing immunosuppressive phenotypes in the BTME of MB tumors. Here, we are providing a comprehensive overview of the current status of epigenetics alterations occurring during cancer progression with a description of the genomic landscape of MB by focusing on immune cells within the BTME. We further describe how new immunotherapeutic approaches could influence concurring epigenetic mechanisms of the immunosuppressive cells in BTME. In conclusion, the modulation of these molecular genetic complexes in BTME during cancer progression might enhance the therapeutic benefit, thus firing new weapons to fight MB

Arterial stiffness and hand osteoarthritis: a novel relationship?

SummaryObjectiveOsteoarthritis (OA) and vascular stiffening may share elements of common pathogenesis, but their potential relatedness has been the focus of little prior inquiry. We tested the hypothesis that these two aging-associated conditions are related to each other.MethodWe analyzed cross-sectional data from 256 participants of the Baltimore Longitudinal Study of Aging (BLSA), a study of normative aging. All underwent measurement of arterial pulse wave velocity (PWV), an index of vascular stiffness, as well as hand radiographs that were graded for evidence of OA. Twenty total joints across three joint groups (distal interphalangeal [DIP], proximal interphalangeal [PIP], carpal-metacarpal [CMC]) were each assigned a Kellgren–Lawrence grade (K–L) of 0 (normal) through 4 (severe), with K–L grades ≥2 considered evidence of definite OA. Radiographic hand OA was defined as definite OA changes in at least two of the three anatomic hand sites (DIP, PIP, CMC). OA burden was represented by the total number of affected OA joints, and a cumulative K–L grade was aggregated across all hand joint groups. The relationship of PWV with these three measures of hand OA was assessed by linear regression.ResultsUpon univariate analysis, the presence of radiographic hand OA (β=218.1, P<0.01), the total number of OA joints (β=32.9, P<0.01), and the cumulative K–L grade across all joint groups (β=12.2, P<0.01) were each associated with increased PWV. These associations, however, were no longer significant in age-adjusted models.ConclusionAlthough significant individual relationships between PWV and several measures of hand OA were observed, these associations were largely attributable to the confounding effect of age

Paullinia cearensis (Sapindaceae) nueva especie de Brasil

La nueva especie Paullinia cearensis Somner &amp; Ferrucci (Sapindaceae-Paullinieae) del nordeste de Brasil se describe, ilustra, y compara con sus parientes más cercanos.