Prunus spinosa L. fruit (PSF) ethanol extract, showing a peculiar content of biologically active molecules (polyphenols), was investigated for its wound healing capacity, a typical feature that declines during aging and is negatively affected by the persistence of inflammation and oxidative stress. To this aim, first, PSF anti-inflammatory properties were tested on young and senescent LPS-treated human umbilical vein endothelial cells (HUVECs). As a result, PSF treatment increased miR-146a and decreased IRAK-1 and IL-6 expression levels. In addition, the PSF antioxidant effect was validated in vitro with DPPH assay and confirmed by in vivo treatments in C. elegans. Our findings showed beneficial effects on worms’ lifespan and healthspan with positive outcomes on longevity markers (i.e., miR-124 upregulation and miR-39 downregulation) as well. The PSF effect on wound healing was tested using the same cells and experimental conditions employed to investigate PSF antioxidant and anti-inflammaging ability. PSF treatment resulted in a significant improvement of wound healing closure (ca. 70%), through cell migration, both in young and older cells, associated to a downregulation of inflammation markers. In conclusion, PSF extract antioxidant and anti-inflammaging abilities result in improved wound healing capacity, thus suggesting that PSF might be helpful to improve the quality of life for its beneficial health effects.

The immunogenic potential of α-gliadin protein from two ancient wheats was studied with reference to coeliac disease. To this aim we investigated Graziella Ra® and Kamut® (the latter is considered an ancient relative of modern durum wheat) in comparison to four durum wheat accessions (Senatore Cappelli, Flaminio, Grazia and Svevo). ELISA and Western Blot analyses - carried out by two monoclonal antibodies raised against the α-gliadin peptides p31-49 (LGQQQPFPQQPYPQPQPF) and p56-75 (LQLQPFPQPQLPYPQPQLPY) containing a core region (underlined) reported to be toxic for coeliac patients - always showed an antibody-antigen positive reaction. For all accessions, an α-gliadin gene has also been cloned and sequenced. Deduced amino acid sequences constantly showed the toxic motifs. In conclusion, we strongly recommend that coeliac patients should avoid consuming Graziella Ra® or Kamut®. In fact their α-gliadin not only is as toxic as one of the other wheat accessions, but also occurs in greater amount, which is in line with the higher level of proteins in ancient wheats when compared to modern varieties.

In the present paper, the controversial hypothesis suggesting ancient grains might show lower immunogenic properties and therefore the possibility to introduce them in the diet of wheat-sensitive people, including celiac patients, was investigated. The immunogenic potential of the ancient durum wheats Graziella Ra and Kamut was studied by comparison to the durum accessions Cappelli, Flaminio, Grazia and Svevo. Experiments were carried out with two monoclonal antibodies (mAbs) raised againstα-gliadin peptides p31–49 and p56–75 (the latter containing the overlapping DQ2-Glia-α1 and DQ2-Glia-α2 epitopes), toxic for celiac patients. For all accessions, a fewα-gliadin alleles were also cloned, sequenced and translated into aminoacid sequences. Several aminoacid substitutions or deletions were detected in p31–49, DQ2-Glia-α1 and DQ2-Glia-α2 epitopes, nevertheless, ELISA constantly showed antibody-antigen positive reactions which led us to suggest that mAbs binding was not apparently affected by polymorphisms. Moreover, a few substitutions were also observed in DQ2-Glia-α3 and DQ8-Glia-α1 epitopes. Although some DQ2-Glia-α1 and DQ2-Glia-α2 variants evidenced herein were previously reported to have a diminished or abolished T cell stimulatory capacity, present results cannot confirm that ancient durum wheats would be less CD-toxic. In conclusion, we strongly advice celiac patients from consuming ancient wheats including Graziella Ra or Kamut.

Prunus spinosa fruits (PSF) contain different phenolic compounds showing antioxidant and anti-inflammatory activities. Innovative drug delivery systems such as biomimetic nanoparticles could improve the activity of PSF extract by promoting (i) the protection of payload into the lipidic bilayer, (ii) increased accumulation to the diseased tissue due to specific targeting properties, (iii) improved biocompatibility, (iv) low toxicity and increased bioavailability. Using membrane proteins extracted from human monocyte cell line THP-1 cells and a mixture of phospholipids, we formulated two types of PSF-extract-loaded biomimetic vesicles differing from each other for the presence of either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG). The biological activity of free extract (PSF), compared to both types of extract-loaded vesicles (PSF-DOPCs and PSF-DOPGs) and empty vesicles (DOPCs and DOPGs), was evaluated in vitro on HUVEC cells. PSF-DOPCs showed preferential incorporation of the extract. When enriched into the nanovesicles, the extract showed a significantly increased anti-inflammatory activity, and a pronounced wound-healing effect (with PSF-DOPCs more efficient than PSF-DOPGs) compared to free PSF. This innovative drug delivery system, combining nutraceutical active ingredients into a biomimetic formulation, represents a possible adjuvant therapy for the treatment of wound healing. This nanoplatform could be useful for the encapsulation/enrichment of other nutraceutical products with short stability and low bioavailability.

Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated. We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR-126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells. We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy.

In the present study, Monarda didyma L. essential oil (isolated from the flowering aerial parts of the plant) was examined to characterize its chemotype and to evaluate, in addition to the quali-quantitative chemical analysis, the associated antioxidant and anti-inflammatory activities. The plants were grown in central Italy, Urbino (PU), Marche region. Different analyses (TLC, GC-FID, GC-MS and ¹H-NMR) allowed the identification of twenty compounds among which carvacrol, p-cymene and thymol were the most abundant. On this basis, the chemotype examined in the present study was indicated as Monarda didyma ct. carvacrol. The antioxidant effect was assessed by DPPH assay. Moreover, this chemotype was investigated for the anti-inflammatory effect in an in vitro setting (i.e., LPS-stimulated U937 cells). The decreased expression of pro-inflammatory cytokine IL-6 and the increased expression of miR-146a are suggestive of the involvement of the Toll-like receptor-4 signaling pathway. Although further studies are needed to better investigate the action mechanism/s underlying the results observed in the experimental setting, our findings show that M. didyma essential oil is rich in bioactive compounds (mainly aromatic monoterpenes and phenolic monoterpenes) which are most likely responsible for its beneficial effect.