Unravelling the phytochemical composition and the pharmacological properties of an optimized extract from the fruit from <em>Prunus mahaleb</em> L.: From traditional liqueur market to the pharmacy shelf

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RADIATIVE RECOMBINATION IN THE PRESENCE OF A FEW CYCLE LASER PULSE

We have investigated the laser-assisted radiative recombination in the presence of a few-cycle pulse with the aim of demonstrating means of controlling such process. Within the Coulomb-Volkov approach already employed to describe the radiative recombination assisted by a monochromatic laser field, we have found that the emitted photon spectrum is affected by both the cycle number n(c) and the carrier-envelope relative phase.. In particular, it has been shown that the minimum and the maximum values of the emitted photon energy may be controlled by varying nc and.. Finally, it has been found that the enhancement of radiative recombination occurring in the presence of a monochromatic field, takes place also by using a few-cycle laser pulse

Urban Regeneration and Soft Mobility: The Case Study of the Rimini Canal Port in Italy

The increasing need to reduce emissions and the environmental impact of urban areas to meet European decarbonisation goals motivates the selection of the Rimini Canal Port as a case study within the FRAMESPORT project, part of the European Interreg Italy–Croatia programme. A preliminary historical–documental and urban regulations analysis of the context allowed the identification of the main criticalities and potentials through a SWOT analysis. The central role of the stakeholders enabled the creation of a successful participatory co-design process developed through online surveys. Critical issues that emerged during the data collection phase were prioritised through a BOCR model, a powerful multi-criteria analysis tool. The project phase then focused on the resolution of the two main critical issues that emerged: the improvement of cycle/pedestrian paths, and the raising of the flooding docks in the Canal Port area. This article intends to demonstrate the strong influence of soft mobility in urban regeneration projects, and how an improvement of the quality of cycle/pedestrian paths can increase the quality of urban spaces. The new paths create a green infrastructure that contributes to a reduction in pollutant emissions through the promotion of sustainable mobility systems and an increase in green urban spaces

Graminex pollen: phenolic pattern, colorimetric analysis and protective effects in immortalized prostate cells (PC3) and rat prostate challenged with LPS

Prostatitis, a general term describing prostate inflammation, is a common disease that could be sustained by bacterial or non-bacterial infectious agents. The efficacy of herbal extracts with antioxidant and anti-inflammatory effects for blunting the burden of inflammation and oxidative stress, with possible improvements in clinical symptoms, is under investigation. Pollen extracts have been previously reported as promising agents in managing clinical symptoms related to prostatitis. The aim of the present work was to evaluate the protective effects of Graminex pollen (GraminexTM, Deshler, OH, USA), a commercially available product based on standardized pollen extracts, in rat prostate specimens, ex vivo. In this context, we studied the putative mechanism of action of pollen on multiple inflammatory pathways, including the reduction of prostaglandin E2 (PGE2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFB), and malondialdehyde (MDA), whose activities were significantly increased by inflammatory stimuli. We characterized by means of chromatographic and colorimetric studies the composition of Graminex pollen to better correlate the activity of pollen on immortalized prostate cells (PC3), and in rat prostate specimens challenged with Escherichia coli lipopolysaccharide (LPS). We found that Graminex pollen was able to reduce radical oxygen species (ROS) production by PC3 cells and MDA, NFB mRNA, and PGE2 levels, in rat prostate specimens. According to our experimental evidence, Graminex pollen appears to be a promising natural product for the management of the inflammatory components in the prostate

Benzo[b]tiophen-3-ol derivatives as effective inhibitors of human monoamine oxidase: design, synthesis, and biological activity

A series of benzo[b]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors in vitro as well as ex vivo in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed

Mobile elites at Frattesina: flows of people in a Late Bronze Age &#8216;port of trade&#8217; in northern Italy

Following a mid twelfth-century BC demographic crisis, Frattesina, in northern Italy, arose as a prominent hub linking continental Europe and the Mediterranean, as evidenced by the remarkable variety of exotic materials and commodities discovered at the site. Debate persists, however, about the extent to which migrants influenced the foundation and development of Frattesina. The authors present the results of strontium isotope analyses, which suggest significant migration to the site, particularly of elites, mostly from within a 50km radius. Among these non-indigenous people, the authors identify a \u2018warrior-chief\u2019, whom they interpret as representing a new, more hierarchical society

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy

Metabolomic Profiling, Antioxidant and Antimicrobial Activity of Bidens pilosa

Bidens pilosa L. (fam. Asteraceae) is an annual herb used globally in phytotherapy and each plant material or the whole plant have been declared to be effective. Therefore, the aim of the present study was to conduct metabolomic profiling of different plant materials, including the quali-quantitative composition of phenolic compounds. The intrinsic scavenging/reducing properties and antimicrobial effects of the extracts were assayed against numerous bacterial, Candida and dermatophytes species, whereas docking runs were conducted for tentatively unravelling the mechanism of action underlying antimicrobial effects. Oligosaccharide, disaccharide and fatty acids were present at higher concentrations in root rather than in the other plant parts. Monoglycerides were more abundant in stem than in the other plant parts, whereas peptide and diterpenoid were prominent in leaf and root, respectively. By contrast, amino acids showed very different distribution patterns in the four plant parts. Regarding the phenolic composition, appreciable levels of caftaric acid were found in most of the analyzed methanol extracts, that were also particularly efficacious as antiradical and anti-mycotic agents against C. albicans and dermatophytes. The docking experiments also showed a micromolar affinity of caftaric acid towards the lanosterol 14α-demethylase, deeply involved in fungal metabolism. In conclusion, the present study corroborates the B. pilosa as a phytotherapy remedy against infectious disease

Venous endotelin-1 (ET-1) and brain natriuretic peptide (BNP) plasma levels during 6-month bosentan treatment for pulmonary arterial hypertension

Objective: Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. Setting and patients: Twenty-five patients with PAH (idiopathic n = 16, CTD n = 9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1 18.7 pg/ml). Results: Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435 ± 85) m to 467 ± 77 m, p > 0.001) and an improvement in WHO class (from 2.4 ± 0.5 to 2 ± 0.6 p > 0.01), with a significant decrease in BNP (from 87 ± 33 pg/ml to 67 ± 41 pg/ml, p = 0.006) and a trend towards lower ET-1 plasma levels (from 17.7 ± 5 pg/ml to 16 ± 6 pg/ml, p = ns). Improvement in effort tolerance (Δ distance) was not correlated to modification in ET-1 (ΔET-1) and BNP (ΔBNP) plasma levels, while we found a significant correlation between ΔET-1 and ΔBNP (r = 0.63, p = 0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41 ± 10 years vs Gr.2: 50 ± 9 years, p = 0.04), had less effort capacity (6MWT distance, Gr.1: 469 ± 76 m, vs Gr.2: 398 ± 82 m, p = 0.03), and showed a trend towards higher BNP values (Gr.1: 82 ± 41 pg/ml vs Gr.2: 92 ± 23 pg/ml, p = 0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: + 32 ± 24 m, Gr.2: + 32 ± 21 m p = 0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: - 0.5 ± 0.5, Gr.2: - 0.3 ± 0.4 p = 0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: - 6 ± 41 pg/ml, Gr.2: - 34 ± 19 pg/ml p = 0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2 ± 4.6 pg/ml, Gr.2: - 3.8 ± 6.6 pg/ml p = 0.09). Conclusions: Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy. © 2008 Elsevier B.V. All rights reserved