New Synthetic Endocannabinoid as Anti-Inflammaging Cosmetic Active: an In Vitro Study on a Reconstructed Skin Model

Endocannabinoids have been recently appointed as interesting cosmetic actives in regulating inflammaging, a state of chronic low-grade inflammation, known for being involved in many senescence\u2019s manifestations, included skin aging. The aim of this study was to assess the anti-inflammaging activity of a new synthetic endocannabinoid, Isopalmide\uae, on a reconstructed skin model, on which inflammaging has been reproduced through UVA radiation and light mechanical stress. We tested Isopalmide\uae both as a single active and conveyed in a cosmetic product, in comparison with Anandamide, a well-known natural endocannabinoid with anti-inflammatory action. The anti-inflammaging activity of topically applied products has been assessed, after 6 hours of treatment post-irradiation, through the transcriptional modification of genes involved in the NF-\u3baB pathway and the epigenetic pathway targeting miRs as potential biomarkers of inflammaging: miR-21, miR-126 and miR-146a. The results confirmed the anti-inflammatory action of Anandamide which inhibits NF-\u3baB, while Isopalmide\uae showed its anti-inflammaging activity through the establishment of an inflammatory/anti-inflammatory balance by maintaining NF-\u3baB inactive in the cytoplasm and active in the nucleus. The anti-inflammaging activity was shown also by the cosmetic product containing Isopalmide

Comparison of presepsin, procalcitonin, interleukin-8 and C-reactive protein in predicting bacteraemia in febrile neutropenic adult patients with haematological malignancies

Bacterial infections represent life-threatening complications in patients with febrile neutropenia (FN). Diagnostic biomarkers of infections may help to differentiate bacteraemia from non-bacteraemia FN. We aimed to evaluate the utility of procalcitonin (PCT), presepsin (PS), C-reactive protein (CRP) and interleukin-8 (IL-8) as biomarkers of bacteraemia in adult FN patients with haematological malignancies. Concentrations of PCT, PS, CRP and IL-8 were prospectively measured in 36 FN episodes experienced by 28 oncohaematological patients. 11 out of 36 episodes were classified as bacteraemia. PCT was the best biomarker to predict bacteraemia with the area under the curve (AUC) ROC of 0,9; specificity 100% and positive predictive value 100%, while the most sensitive was IL-8 (90,9%) with AUC ROC of 0,88 and negative predictive value 95,2%. All patients with PCT concentrations above 1,6 \u3bcg/l had bacteraemia. Patients with IL-8 concentrations superior to 170 pg/ml had a 40 times higher risk for bacteraemia than the ones with lower levels. Patients with PS concentrations superior to 410 pg/ml had 24 times higher risk for bacteraemia than the patients with lower levels. PCT has higher accuracy than CRP, IL-8 and PS in predicting bacteraemia in adult hematologic patients with FN

Mapping and Monitoring Urban Environment through Sentinel-1 SAR Data: A Case Study in the Veneto Region (Italy)

Focusing on a sustainable and strategic urban development, local governments and public administrations, such as the Veneto Region in Italy, are increasingly addressing their urban and territorial planning to meet national and European policies, along with the principles and goals of the 2030 Agenda for the Sustainable Development. In this regard, we aim at testing a methodology based on a semi-automatic approach able to extract the spatial extent of urban areas, referred to as \u201curban footprint\u201d, from satellite data. In particular, we exploited Sentinel-1 radar imagery through multitemporal analysis of interferometric coherence as well as supervised and non-supervised classi\ufb01cation algorithms. Lastly, we compared the results with the land cover map of the Veneto Region for accuracy assessments. Once properly processed and classi\ufb01ed, the radar images resulted in high accuracy values, with an overall accuracy ranging between 85% and 90% and percentages of urban footprint di\ufb00ering by less than 1%\u20132% with respect to the values extracted from the reference land cover map. These results provide not only a reliable and useful support for strategic urban planning and monitoring, but also potentially identify a solid organizational data\ufb02ow process to prepare geographic indicators that will help answering the needs of the 2030 Agenda (in particular the goal 11 \u201cSustainable Cities and Communities\u201d)

Tumour-infiltrating lymphocytes bear the 75 kDa tumour necrosis factor receptor.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with a variety of immunological properties. The identification of two receptors for this molecule, i.e. the 75 kDa and the 55 kDa TNF receptors (TNF-R), recently clarified the mechanisms through which this cytokine provides its wide range of immunomodulatory activities. In this study we have investigated the expression and the functional properties of these receptors on tumour-infiltrating lymphocytes (TILs) recovered from 17 patients with solid cancers (melanoma, colorectal carcinoma and lung cancer). To this end, TIL lines and freshly isolated TILs were evaluated for (a) the expression and the functional role of TNF receptors following culture in the presence of interleukin 2 (IL-2) and (b) the production of TNF-alpha following culture with IL-2 and the role of this cytokine in IL-2-driven TIL proliferation. Flow cytometry analysis demonstrated that TILs bear the 75 kDa TNF-R. Moreover, TIL lines express detectable messages for TNF-alpha and release this cytokine. Functional in vitro studies have shown that anti-TNF-alpha, as well as anti-75 kDa TNF-R antibodies, are able to inhibit the IL-2-induced TIL proliferation. These data demonstrate that TILs are equipped with a fully functional TNF-R system and suggest a putative role for this receptor and its ligand in the activation and expression of TILs following immunotherapy with IL-2

Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-β Regulation within Lung Fibroblasts

Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-β production in lung fibroblasts. EVs were isolated from supernatants of M0, M1, and M2 macrophages and quantified using nanoscale flow cytometry prior to fibroblast stimulation. The concentration of TGF-β in fibroblast supernatants was measured using ELISA assays. The expression levels of miRNA-19a-3p and miRNA-425-5p were assessed via TaqMan-qPCR. TGF-β production after stimulation with M0-derived EVs and with M1-derived EVs increased significantly compared to untreated fibroblasts. miRNA-425-5p, but not miRNA-19a-3p, was significantly upregulated in M2-derived EVs compared to M0- and M1-derived EVs. This study demonstrates that EVs derived from both M0 and M1 polarized macrophages induce the production of TGF-β in fibroblasts, with potential regulation by miRNA-425-5p

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial

Aprospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (RHDS) versus conventional chemotherapy with rituximab (CHOP-R) as firstline therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13- year estimates of 77.0% and 36.8% for complete remission versus no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (P<0.001), along with younger age (P=0.002) and female sex (P=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma

Endophytic Bacteria and Essential Oil from Origanum vulgare ssp. vulgare Share Some VOCs with an Antibacterial Activity

Medicinal aromatic plants’ essential oils (EOs) are mixtures of volatile compounds showing antimicrobial activity, which could be exploited to face the emerging problem of multi-drug resistance. Their chemical composition can depend on the interactions between the plant and its endophytic microbiota, which is known to synthesize volatile organic compounds (VOCs). However, it is still not clear whether those volatile metabolites can contribute to the composition of the aroma profile of plants’ EOs. The aims of this study were to characterize medicinal plant O. vulgare ssp. vulgare bacterial endophyte VOCs, evaluating their ability to antagonize the growth of opportunistic human pathogens belonging to the Burkholderia cepacia complex (Bcc) and compare them with O. vulgare EO composition. Many of the tested endophytic strains showed (i) a bactericidal and/or bacteriostatic activity against most of Bcc strains and (ii) the production of VOCs with widely recognized antimicrobial properties, such as dimethyl disulfide, dimethyl trisulfide, and monoterpenes. Moreover, these monoterpenes were also detected in the EOs extracted from the same O. vulgare plants from which endophytes were isolated. Obtained results suggest that endophytes could also play a role in the antibacterial properties of O. vulgare ssp. vulgare and, potentially, in determining its aromatic composition