6'-O-Lactose Ester Surfactants as an Innovative Opportunity in the Pharmaceutical Field: From Synthetic Methods to Biological Applications

Glycolipid surfactants are biocompatible and biodegradable compounds characterized by potential applications in various sectors including pharmaceuticals, cosmetics, agriculture, and food production. A specific overview regarding synthetic methodologies and properties of 6'-lactose-based surfactants is presented herein, particularly all the synthetic approaches to this class of lactose esters, such as enzymatic and traditional organic syntheses. Moreover, detailed descriptions of physicochemical data and biocompatibility properties of these molecules, that is, surface tension, critical micelle concentration, emulsifying ability, foaming, particle size distribution, biocompatibility, and safety, are described. Biological applications with a focus on permeability enhancing, antimicrobial activity, and antibiofilm properties of 6'-lactose-based esters are also reported

Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents

A small library of sugar-based (i.e., glucose, mannose and lactose) monoesters containing hydrophobic aliphatic or aromatic tails were synthesized and tested. The antimicrobial activity of the compounds against a target panel of Gram-positive, Gram-negative and fungi was assessed. Based on this preliminary screening, the antibiofilm activity of the most promising molecules was evaluated at different development times of selected food-borne pathogens (E. coli, L. monocytogenes, S. aureus, S. enteritidis). The antibiofilm activity during biofilm formation resulted in the following: mannose C10 > lactose biphenylacetate > glucose C10 > lactose C10. Among them, mannose C10 and lactose biphenylacetate showed an inhibition for E. coli 97% and 92%, respectively. At MICs values, no toxicity was observed on Caco-2 cell line for all the examined compounds. Overall, based on these results, all the sugar-based monoesters showed an interesting profile as safe antimicrobial agents. In particular, mannose C10 and lactose biphenylacetate are the most promising as possible biocompatible and safe preservatives for pharmaceutical and food applications

Phosphodiesterase Type 5 Inhibitors, Sport and Doping

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors

The Synthetic Cannabinoid URB447 Exerts Antitumor and Antimetastatic Effect in Melanoma and Colon Cancer

The endocannabinoid system is widespread through the body and carries out a wide variety of functions. However, its involvement in other pathologies, such as cancer, still needs further attention. We aim to investigate the role of CB2 receptor during melanoma and colorectal cancer (CRC) aggressiveness and metastatic growth in the liver. We used the synthetic cannabinoid URB447, a known CB2 agonist and CB1 antagonist drug, and studied prometastatic ability of mouse B16 melanoma and MCA38 CRC cells, by means of proliferation, apoptosis, cell cycle, migration and matrix degradation in vitro upon URB447 treatment. We reported a dose-dependent viability decrease in both tumor types. This result is partly mediated by apoptotic cell death and cell cycle arrest in G1/G0 phase, as observed through flow cytometry. Melanoma and CRC cell migration was affected in a dose-dependent fashion as observed through scratch assay, whereas the secretion of matrix degrading proteins metalloprotease 2 (MMP2) and 9 (MMP9) in tumor cells did not significantly change. Moreover, daily treatment of tumor bearing mice with URB447 decreased the development of liver metastasis in a melanoma model in vivo. This proof of concept study points out to the synthetic cannabinoid URB447 as a potential candidate for deeper studies to confirm its potential as antitumor therapy and liver metastasis treatment for CRC and melanoma.This research was funded by EITB Maratoia-BIOEF (BIO18/IC/003), and the Spanish Ministry of Science and Innovation (MINECOR20/P66/AEI/10.13039/501100011033)

Prevalence of Coxiella burnetii in cows' and ewes' bulk tank milk samples from selected dairy farms of Central Italy

The prevalence of Coxiella burnetii, the causative agent of Q fever, in cattle and sheep raw milk farms was determined in Central Italy, an area in which dairy production plays an important economic role. Milk samples (n. 189), collected from 66 dairy farms in 2012–2013, were tested by a commercial real-time PCR assay. Seventeen dairy farms had at least one positive milk sample; percent positive was higher for cattle (50%) than sheep (21%) farms. Concerning milk, 15% of samples tested overall gave a positive result, with the highest percentage of positivity observed for bovine milk compared with sheep milk (41% and 12%, respectively). In the only bovine farm repeatedly sampled during the study, C. burnetii contamination was persistently found for almost a year. The prevalence calculated for the sheep farms showed a discontinuous trend with a maximum peak in February. The results obtained underline the widespread presence of the pathogen in the considered geographical area, giving new epidemiological information. Since the milk route of elimination is a potential vehicle of infection for farmers, veterinarians and for dairy stakeholders in general, BTM screening by real-time PCR can be applied as a useful surveillance tool both for the identification of infected flocks and implementation of control programmes

Synthesis and Biological Characterization of the New Glycolipid Lactose Undecylenate (URB1418)

As a follow-up to our previous studies on glycolipid surfactants, a new molecule, that is lactose 6'-O-undecylenate (URB1418), was investigated. To this end, a practical synthesis and studies aimed at exploring its specific properties were carried out. URB1418 showed antifungal activities against Trichophyton rubrum F2 and Candida albicans ATCC 10231 (MIC 512 μg/mL) and no significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. At the same time, it presented anti-inflammatory properties, as documented by the dose-dependent reduction in LPS-induced NO release in RAW 264.7 cells, while a low antioxidant capacity in the range of concentrations tested (EC50 > 200 µM) was also observed. Moreover, URB1418 offers the advantage of being more stable than the reference polyunsaturated lactose esters and of being synthesized using a "green" procedure, involving an enzymatic method, high yield and low manufacturing cost. For all these reasons and the absence of toxicity (HaCaT cells), the new glycolipid presented herein could be considered an interesting compound for applications in various fields

The synthetic cannabinoid URB447 exerts antitumor effect in colon carcinoma and reduces liver metastasis in mice

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Genomics of the genus Bifidobacterium reveals species-specific adaptation to the glycan-rich gut environment

Bifidobacteria represent one of the dominant microbial groups that occur in the gut of various animals, being particularly prevalent during the suckling period of humans and other mammals. Their ability to compete with other gut bacteria is largely attributed to their saccharolytic features. Comparative and functional genomic as well as transcriptomic analyses have revealed the genetic background that underpins the overall saccharolytic phenotype for each of the 47 bifidobacterial (sub)species representing the genus Bifidobacterium, while also generating insightful information regarding carbohydrate resource sharing and crossfeeding among bifidobacteria. The abundance of bifidobacterial saccharolytic features in human microbiomes supports the notion that metabolic accessibility to dietary and/or host-derived glycans is a potent evolutionary force that has shaped the bifidobacterial genome

Studi di linguistica slava. Nuove prospettive e metodologie di ricerca

The present paper examines the Russian discourse markers мол and дескать as Renarrative markers that generally are considered conventional means to indicate information sources. Etymologically, they derive from verba dicendi. In this paper, relying on a large amount of occurrences taken from Russian Italian bilingual corpus composed by the author, a qualitative analysis of their semantics is carries out. They can express different meanings: referring to someone else's text with accurate or inaccurate quoting, pointing to their information source, expressing doubts about the reliability of transmitted information, interpreting gestures through verbal means and sometimes have contact-establishing and intensifying functions. The survey allows to affirm that these markers indicate evidentiality, because they create a distance between the information and the person which communicates this information and make an important contribution to evaluate the truthfulness of a proposition