Evergetismo relativo agli edifici da spettacolo romani: una rassegna di testi epigrafici della "Baetica"

Numerosos epígrafes latinos de diversas ciudades de la prouincia Baetica se refieren al fenómeno del evergetismo practicado en los edificios de espectáculos. Los teatros, los anfiteatros y los circos -numerosos en esta prouincia romana- eran los mas adecuados lugares públicos para tales actos de propaganda política-social al ser frecuentados por un número muy importante de individuos de todas las clases sociales.---------------------------------------------------------------------Numerose epigrafi latine provenienti da diverse città della Baetica sano relative al fenomeno dell'evergetismo praticato in riferimento ad edifici da spettacolo. Dall'analisi della documentazione risulta evidente che teatri, anfiteatri e circhi, essendo frequentati da un numero notevole di individui appartenenti a tutte le classi sociali, furono considerati luoghi pubblici ideali per I'attuazione di tali atti di propaganda politica e sociale.Artículo revisado por pare

Isolated Metachronous Splenic Metastasis from Colon Cancer: Possible Explanations for This Rare Entity

The incidence of splenic metastases secondary to colorectal cancer is very low; these lesions have been more frequently reported as secondary to breast, lung, and ovarian cancer. Splenic metastases are particularly common in melanoma; their incidence has been reported as being as high as 34% at autopsy [1]. Most cases of secondary splenic metastases have been described in patients with tumors of the left colon while only few cases being reported as originating from right colon tumors (Table 1). The finding of a splenic mass in the absence of a history of malignancy suggests a primary lesion (lymphoma, hematoma, etc.), while a history of oncological disease raises the possibility of a secondary lesion [2]

In Silico Design of New Dual Inhibitors of SARS-CoV-2 MPRO through Ligand- and Structure-Based Methods

The viral main protease is one of the most attractive targets among all key enzymes involved in the life cycle of SARS-CoV-2. Considering its mechanism of action, both the catalytic and dimerization regions could represent crucial sites for modulating its activity. Dual-binding the SARS-CoV-2 main protease inhibitors could arrest the replication process of the virus by simultaneously preventing dimerization and proteolytic activity. To this aim, in the present work, we identified two series' of small molecules with a significant affinity for SARS-CoV-2 M-PRO, by a hybrid virtual screening protocol, combining ligand- and structure-based approaches with multivariate statistical analysis. The Biotarget Predictor Tool was used to filter a large in-house structural database and select a set of benzo[b]thiophene and benzo[b]furan derivatives. ADME properties were investigated, and induced fit docking studies were performed to confirm the DRUDIT prediction. Principal component analysis and docking protocol at the SARS-CoV-2 M-PRO dimerization site enable the identification of compounds 1b,c,i,l and 2i,l as promising drug molecules, showing favorable dual binding site affinity on SARS-CoV-2 M-PRO

One pot-like regiospecific access to 1-aryl-1H-pyrazol-3(2H)-one derivatives and evaluation of the anticancer activity

A set of variously substituted 1-arylpyrazol-3-one derivatives, including the di-ortho-aryl substituted ones, was synthesized as new potential anticancer compounds. To fulfill this aim, herein a regiospecific synthesis was proposed utilizing a new revisited one pot procedure, starting from commercial anilines and easily accessible 2,5-dimethyl-furan-3-one. In the course of the sequential ordered steps, in some cases, a nitro group displacement by chlorine took place to a minor extent. The in vitro screening against the full panel of ~60 human cancer cell lines (NCI) showed a moderate, but promising selective antiproliferative activity against the UO31 renal tumor cell line, only in compounds with the introduction on the phenyl moiety of a -CF3 or two Cl groups

Spectroscopic and in silico studies on the interaction of substituted pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one derivatives with c-myc g4-dna

Herein we describe a combined experimental and in silico study of the interaction of a series of pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one derivatives (PBTs) with parallel G-quadruplex (GQ) DNA aimed at correlating their previously reported anticancer activities and the stabilizing effects observed by us on c-myc oncogene promoter GQ structure. Circular dichroism (CD) melting experiments were performed to characterize the effect of the studied PBTs on the GQ thermal stability. CD measurements indicate that two out of the eight compounds under investigation induced a slight stabilizing effect (2–4 °C) on GQ depending on the nature and position of the substituents. Molecular docking results allowed us to verify the modes of interaction of the ligands with the GQ and estimate the binding affinities. The highest binding affinity was observed for ligands with the experimental melting temperatures (Tms). However, both stabilizing and destabilizing ligands showed similar scores, whilst Molecular Dynamics (MD) simulations, performed across a wide range of temperatures on the GQ in water solution, either unliganded or complexed with two model PBT ligands with the opposite effect on the Tms, consistently confirmed their stabilizing or destabilizing ability ascertained by CD. Clues about a relation between the reported anticancer activity of some PBTs and their ability to stabilize the GQ structure of c-myc emerged from our study. Furthermore, Molecular Dynamics simulations at high temperatures are herein proposed for the first time as a means to verify the stabilizing or destabilizing effect of ligands on the GQ, also disclosing predictive potential in GQ-targeting drug discovery

Design and Synthesis of Novel Thieno[3,2-c]quinoline Compounds with Antiproliferative Activity on RET-Dependent Medullary Thyroid Cancer Cells

RET kinase gain-of-function mutations represent the main cause of the high aggressiveness and invasiveness of medullary thyroid cancer (MTC). The selective inhibition of the RET kinase is a suitable strategy for the treatment of this endocrine neoplasia. Herein, we performed an innovative ligand-based virtual screening protocol using the DRUDITonline web service, focusing on the RET kinase as a biological target. In this process, thieno[3,2-c]quinolines 6a-e and 7a-e were proposed as new potential RET inhibitors. The selected compounds were synthetized by appropriate synthetic strategies, and in vitro evaluation of antiproliferative properties conducted on the particularly aggressive MTC cell line TT(C634R) identified compounds 6a-d as promising anticancer agents, with IC50 values in the micromolar range. Further structure-based computational studies revealed a significant capability of the most active compounds to the complex RET tyrosine kinase domain. The interesting antiproliferative results supported by in silico predictions suggest that these compounds may represent a starting point for the development of a new series of small heterocyclic molecules for the treatment of MTC

The relationship between social networking site use and the internalization of a thin ideal in females: A meta-analytic review

Published: 07 August 2017Previous research has indicated that exposure to traditional media (i.e., television, film, and print) predicts the likelihood of internalization of a thin ideal; however, the relationship between exposure to internet-based social media on internalization of this ideal remains less understood. Social media differ from traditional forms of media by allowing users to create and upload their own content that is then subject to feedback from other users. This meta-analysis examined the association linking the use of social networking sites (SNSs) and the internalization of a thin ideal in females. Systematic searches were performed in the databases: PsychINFO, PubMed, Web of Science, Communication and Mass Media Complete, and ProQuest Dissertations and Theses Global. Six studies were included in the meta-analysis that yielded 10 independent effect sizes and a total of 1,829 female participants ranging in age from 10 to 46 years. We found a positive association between extent of use of SNSs and extent of internalization of a thin ideal with a small to moderate effect size (r = 0.18). The positive effect indicated that more use of SNSs was associated with significantly higher internalization of a thin ideal. A comparison was also made between study outcomes measuring broad use of SNSs and outcomes measuring SNS use solely as a function of specific appearance-related features (e.g., posting or viewing photographs). The use of appearance-related features had a stronger relationship with the internalization of a thin ideal than broad use of SNSs. The finding suggests that the ability to interact with appearance-related features online and be an active participant in media creation is associated with body image disturbance. Future research should aim to explore the way SNS users interact with the media posted online and the relationship linking the use of specific appearance features and body image disturbance.John Mingoia, Amanda D. Hutchinson, Carlene Wilson and David H. Gleave

Antimicrobial activity of aztreonam in combination with old and new β-lactamase inhibitors against mbl and esbl co-producing gram-negative clinical isolates: Possible options for the treatment of complicated infections

none14noMetallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to over-come. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six Enterobacterales and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. E. meningoseptica and C. indologenes were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.openMorroni G.; Bressan R.; Fioriti S.; D'Achille G.; Mingoia M.; Cirioni O.; Di Bella S.; Piazza A.; Comandatore F.; Mauri C.; Migliavacca R.; Luzzaro F.; Principe L.; Lagatolla C.Morroni, G.; Bressan, R.; Fioriti, S.; D'Achille, G.; Mingoia, M.; Cirioni, O.; Di Bella, S.; Piazza, A.; Comandatore, F.; Mauri, C.; Migliavacca, R.; Luzzaro, F.; Principe, L.; Lagatolla, C

Design and synthesis of high affinity compounds for the Hsp60 expression control in carcinogenic processes

First observed in cells exposed to high temperatures, Heat shock proteins (Hsps) are nowadays considered the most important cell “chaperone” complexes over-­expressed in response to a number of cell stress stimuli.1 The chaperone activity is the main function of the eukaryotic Heat shock protein 60 kDa (Hsp60), involved in the capture and refold of unfolded or misfolded proteins. Additional roles in signal transduction,2 senescence activation3 and apoptosis4 have been ascribed to cytosolic Hsp60. During the carcinogenIc process, in vivo studies demonstrated increased levels of human Hsp60 in several organs, such as uterine exocervix,5 large bowel,6 and prostate.6 In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and novel designed antagonists able to specifically block this chaperonine. A preliminary virtual screening of 24 million molecules, available in the Zinc database, was carried out on the ATP-­binding site of a bacterial Hsp60 monomer, the coordinates of which were taken from Protein Data Bank (ID: 1WE3), figure 1. Compounds with high affinity were further refined by other in silico protocols previously and successfully applied by us in the study of several biological targets.7The analysis of virtual screening results highlights the N-­{5-­[1H-­imidazol-­4-­yl-­methyl)-­ amino]-­benzofuran-­3-­yl}-­benzamides of type 1 as interesting series for the inhibition of Hsp60 ATP-­binding site. Selected compounds were prepared in excellent yields, following appropriate synthetic pathways. All compounds are currently tested in order to proof they potential anticancer activity as modulator of Hsp60 function in tumor cells