Cannabinoidi e patologie intestinali

Negli ultimi anni, numerose evidenze hanno suggerito che il legame dei cannabinoidi endogeni ai recettori CB1 e CB2 è in grado di controllare in condizioni fisiologiche la motilità intestinale. Per meglio caratterizzare il ruolo del sistema endocanabinoide nella regolazione della motilità intestinale anche in condizioni patologiche abbiamo studiato il ruolo di questi durante (i) un’ ipersecrezione intestinale indotta da tossina colerica nel topo (ii) un’ infiammazione intestinale indotta da olio di croton nel topo e (iii) in pazienti affetti da colite ulcerosa. I nostri risultati indicano che il sistema cannabinoide endogeno svolge un ruolo protettivo sia in un modello di dismotilità intestinale indotto da un agente infiammatorio che nel modello di ipersecrezione indotta dalla tossina colerica. Inoltre, è stato dimostrato che la palmitoiletanolamide, un analogo strutturale dell’anandamide, riduce la motilità intestinale durante una flogosi intestinale. Infine, studi effettuati su pazienti affetti da colite ulcerosa hanno evidenziato un aumento dei livelli intestinali di anandamide e di palimitoiletanolamide. Alla luce di questi risultati è ipotizzabile che il sistema endocannabinoide endogeno svolga un ruolo protettivo in alcune patologie del tratto digerente

Antispasmodic saponins from bulbs of red onion, Allium cepa L. var. Tropea

A phytochemical analysis of the polar extract from the red bulbs of Allium cepa L. var. Tropea, typical of Calabria, a southern region of Italy, was performed extensively for the first time, leading to the isolation of four new furostanol saponins, named tropeoside A1/A2 (1a/1b) and tropeoside B1/B2 (3a/3b), along with the respective 22-O-methyl derivatives (2a/2b and 4a/4b), almost certainly extraction artifacts. High concentrations of ascalonicoside A1/A2 (5a/5b) and ascalonicoside B (6), previously isolated from Allium ascalonicum Hort., were also found. This is the first report of furostanol saponins in this A. cepa variety. The chemical structures of the new compounds were established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses. High concentrations of quercetin, quercetin 4(I)-glucoside, taxifolin, taxifolin 7-glucoside, and phenylalanine were also isolated. The new saponins were found to possess antispasmodic activity in the guinea pig isolated ileum; such an effect might contribute to explaining the traditional use of onion in the treatment of disturbances of the gastrointestinal tract

Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol.

There are anecdotal reports that some Cannabis preparations may be useful for bladder dysfunctions. Here, we investigated the effect of a number of non-psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV) and cannabichromene (CBC) on mouse bladder contractility in vitro. CBG, THCV, CBD and CBDV, but not CBC, at concentration ranging from 10−8M to 10−4M, decreased (with similar potency), the contractions induced by acetylcholine without significantly modifying the contractions induced by electrical stimulation. The rank order of efficacy was CBG=THCV>CBD>CBDV. In depth studies on CBG showed that the effect of this phytocannabinoid on acetylcholine-induced contractions was not affected by CB1or CB2receptor antagonists. Additionally, CBG also reduced acetylcholine-induced contractions in the human bladder

Lasing mode pattern of a quantum cascade photonic crystal surface-emitting microcavity laser

The identification of the lasing mode within a quantum cascade photonic crystal microcavity laser emitting at λ ~8 µm is presented. The symmetry of the lasing mode is determined by the position of nodal lines within micro-bolometer camera measurements of its polarized spatial distribution. Full three-dimensional finite-difference time-domain simulations are also performed, and the resulting vertically emitted radiation field pattern is seen to follow the experimental results closely

LSD1 mediates MYCN control of epithelial-mesenchymal transition through silencing of metastatic suppressor NDRG1 gene

Neuroblastoma (NB) with MYCN amplification is a highly aggressive and metastatic tumor in children. The high recurrence rate and resistance of NB cells to drugs urgently demands a better therapy for this disease. We have recently found that MYCN interacts with the lysine-specific demethylase 1 (LSD1), a histone modifier that participates in key aspects of gene transcription. In cancer cells, LSD1 contributes to the genetic reprogramming that underlies to Epithelial-Mesenchymal Transition (EMT) and tumor metastasis. Here, we show that LSD1 affects motility and invasiveness of NB cells by modulating the transcription of the metastasis suppressor NDRG1 (N-Myc Downstream-Regulated Gene 1). At mechanistic level, we found that LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene and inhibits its expression. Pharmacological inhibition of LSD1 relieves repression of NDRG1 by MYCN and affects motility and invasiveness of NB cells. These effects were reversed by overexpressing NDRG1. In NB tissues, high levels of LSD1 correlate with low levels of NDRG1 and reduced patients survival. Collectively, our findings elucidate a mechanism of how MYCN/LSD1 control motility and invasiveness of NB cells through transcription regulation of NDRG1 expression and suggest that pharmacological targeting of LSD1 represents a valuable approach for NB therapy

Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon

Colorectal cancer is an increasingly important cause of death in Western countries. Endocannabinoids inhibit colorectal carcinoma cell proliferation in vitro. In this paper, we investigated the involvement of endocannabinoids on the formation of aberrant crypt foci (ACF, earliest preneoplastic lesions) in the colon mouse in vivo. ACF were induced by azoxymethane (AOM); fatty acid amide hydrolase (FAAH) and cannabinoid receptor messenger ribonucleic acid (mRNA) levels were analyzed by the quantitative reverse transcription polymerase chain reaction (RT-PCR); endocannabinoid levels were measured by liquid chromatography–mass spectrometry; caspase-3 and caspase-9 expressions were measured by Western blot analysis. Colonic ACF formation after AOM administration was associated with increased levels of 2-arachidonoylglycerol (with no changes in FAAH and cannabinoid receptor mRNA levels) and reduction in cleaved caspase-3 and caspase-9 expression. The FAAH inhibitor N-arachidonoylserotonin increased colon endocannabinoid levels, reduced ACF formation, and partially normalized cleaved caspase-3 (but not caspase-9) expression. Notably, N-arachidonoylserotonin completely prevented the formation of ACF with four or more crypts, which have been show to be best correlated with final tumor incidence. The effect of N-arachidonoylserotonin on ACF formation was mimicked by the cannabinoid receptor agonist HU-210. No differences in ACF formation were observed between CB1 receptor-deficient and wild-type mice. It is concluded that pharmacological enhancement of endocannabinoid levels (through inhibition of endocannabinoid hydrolysis) reduces the development of precancerous lesions in the mouse colon. The protective effect appears to involve caspase-3 (but not caspase-9) activation

An updated overview on nanonutraceuticals: focus on nanoprebiotics and nanoprobiotics

Over the last few years, the application of nanotechnology to nutraceuticals has been rapidly growing due to its ability to enhance the bioavailability of the loaded active ingredients, resulting in improved therapeutic/nutraceutical outcomes. The focus of this work is nanoprebiotics and nanoprobiotics, terms which stand for the loading of a set of compounds (e.g., prebiotics, probiotics, and synbiotics) in nanoparticles that work as absorption enhancers in the gastrointestinal tract. In this manuscript, the main features of prebiotics and probiotics are highlighted, together with the discussion of emerging applications of nanotechnologies in their formulation. Current research strategies are also discussed, in particular the promising use of nanofibers for the delivery of probiotics. Synbiotic-based nanoparticles represent an innovative trend within this area of interest. As only few experimental studies on nanoprebiotics and nanoprobiotics are available in the scientific literature, research on this prominent field is needed, covering effectiveness, bioavailability, and safety aspects.The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007. E. B. Souto acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Protein substitutions as new-generation pharmanutrition approach to managing phenylketonuria

Phenylketonuria (PKU), an autosomal recessive inherited metabolic disorder, is caused by a mutation in the phenylalanine hydroxylase (PAH) gene on the 12th chromosome. Defective PAH activity ultimately leads to increased phenylalanine (Phe) blood concentrations (hyperphenylalaninemia) that harm the brain. The primary purpose of PKU treatment is to maintain the blood Phe level to prevent certain undesired effects. Hence, lifelong medical nutrition therapy is recommended for these patients. The usefulness of natural protein sources may be limited, as they are based on individual Phe tolerance, and a patient’s daily protein requirements are supported by Phe-free amino acid mixtures. A few PKU treatment centers recently started using supplemental casein glycomacropeptide, pegvaliase, or large neutral amino acids, and some patients are treated by responding to tetrahydrobiopterin, which works as a pharmaceutical chaperone (prescribed as sapropterin dihydrochloride). This review discusses the efficacy and safety considerations of basic medical nutrition approaches and newgeneration protein substitutes that are used to treat PKU

THE SECTION OF TORRE PICCHIO (TERNI, UMBRIA, CENTRAL ITALY):A VILLAFRANCHIAN SITE RICH IN VERTEBRATES, MOLLUSCS,OSTRACODS AND PLANTS

Fluvial deposits of the S. Maria di Ciciliano Formation crop out near Montecastrilli (Terni), in the southwestern branch of the Tiberino Basin.  Many specimens of plants ("mummified" woods, fruits and seeds), freshwater molluscs, ostracods, vertebrate bones and coprolites were collected at Torre Picchio. This small outcrop contains a fairly rich record of fruits and seeds, among which about 50 species were identified; the most frequent invariably belong to submerged, floating and emergent aquatic herbs, possibly because these were buried not far from their place of growth, thus representing the ancient local vegetation.  The fruits and seeds of woody plants, including several exotic elements, were transported from neighbouring areas and indicate a paleoclimate similar to the present day, though slightly wetter.  Among molluscs, three distinct assemblages were found, indicating fluvial, swampy and lacustrine environment, respectively.  They contain taxa of biochronological interest, most of them typical of Early Pleistocene deposits (late Villafranchian), but making their first appearance in the Late Pliocene (Middle Villafranchian). One species, Margarifera (Pseudunio) auricularia, represents the oldest record everywhere, since it was known, so far, only from the Middle Pleistocene upwards.  As palaeoenvironmental indicators, the ostracods complete the information given by molluscs.  Vetrebrates are represented by large and small mammals, rare birds, reptiles, amphibians and some fishes.  A great number of coprolites was collected as well.  The mammal assemblage shows affinities with the Costa S. Giacomo and Olivola F. U. (Middle and Late Villafranchian, Late Pliocene). Mimomys medasensis, an Iberoccitane element, is signaled for the first time in Italy.  From the geological point of view, the S. Maria di Ciciliano Fm. is interfingering with the marine Chiani-Tevere Fm., which is mostly Santernian in age and lies unconformably on the Middle Pliocene cycle. Only in some areas representing a structural low, the continuous transition between the lower portion of this unit and Late Pliocene deposits may be observed before the heteropic episodes.  This fact suggests some inconsistencies between chronostratigraphy and biochronology in the examined area because some taxa indicate a latest Pliocene age.  A heterochrony in the extinction of some species of plants and animals is suggested as a possible solution to the problem.&nbsp