Targeted nanoparticles for the delivery of novel bioactive molecules to pancreatic cancer cells

Pancreatic cancer (PaCa) is a multifaceted disorder with an extremely poor prognosis. There is an urgent need to identify new and safe drugs as well as to develop novel tumor-targeted controlled release systems for effective treatment of late stage and resistant PaCa. Active targeting via the inclusion of specific ligands on the nanoparticles (NPs) is envisioned to provide a powerful therapeutic strategy. Herein, we present a study on the design and the development of novel DFCencapsulated biocompatible polymeric NPs, functionalized with peptides to selectively bind to Plec-1 (PTP), or densely decorated by low molecular weight organic molecules as alternative targeting ligands (2-ABA), and evaluated a) the impact on ligand binding and b) the in vitro antiproliferative efficacy against a panel of PaCa cells

Rosmarinus officinalis L.: chemical modifications of the essential oil and evaluation of antioxidant and antimicrobial activity.

Rosmarinus officinalis essential oil was separated into its hydrocarbon and oxygenated fractions. The major compounds in the hydrocarbon fraction were α-pinene (44.2%), camphene (24.5%), and limonene (11.7%), while in the oxygenated fraction they were 1,8-cineole (37.6%), camphor (16.5%), and bornyl acetate (21.4%). The hydrocarbon fraction was submitted to a hydroformylation process and the antioxidant activity of the product was screened by the DPPH and β-carotene/linoleic acid tests. The hydroformylated fraction maintained the antioxidant activity of the whole oil. The MIC (minimal inhibitory concentration) and the MBC (minimal bactericidal concentration) of the essential oil, hydrocarbon, oxygenated and hydroformylated fractions were also tested on several microorganisms. Aeromonas sobria and Candida strains were the most susceptible micro-organisms. The hydroformylated fraction exhibited a MBC against Candida strains resistant to the other fractions

Detection of <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (MAP) in animals and human tissue

The aim of this work was the detection of MAP in human with CD and in ovine with natural and experimental PTBC, by in “situ” techniques. ISH showed strong signals in the macrophages infiltrating the mucosal and submucosal layers in PTBC samples and positive signals in macrophages of CD cases. Furthermore, ISPCR signals were more numerous than those obtained by ISH. This result indicate that ISPCR is able to detect also less copies of MAP DNA

Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD)

Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials

Fate of selected pathogens in spiked «SALAME NOSTRANO» produced without added nitrates following the application of NONIT™ technology

This study evaluated the effect of a novel formulation for starter culture associated with specific ripening conditions (NoNit™ technology) vs. a commercial» starter on the fate of selected pathogens and hygiene indicators during the fermentation and ripening of experimentally spiked salame nostrano (Italian dry sausage). Selected strains of Staphylococcus aureus 27R, Escherichia coli CSH26 K 12, Listeria innocua ATCC 33090 and Salmonella Derby 27 were inoculated into salami batter and challenged with two formulations of starter cultures (a commercial formulation and the NoNit™ formulation, consisting of Lactococcus lactis ssp. lactis, strain 340; L. lactis ssp. lactis, strain 16; Lactobacillus casei ssp. casei, strain 208 and Enterococcus faecium strain 614) with ripening at a low temperature. The proposed technology (NoNit™) performed better than the commercial formulation and limited the growth of spiked Escherichia coli, Staphylococcus aureus (including the production of enterotoxin), Salmonella Derby and Listeria innocua, yet maintained the basic product appearance and texture.Supplementary Data 1 : Reduction of selected microorganisms challenged vs. NoNitTM in milk.Supplementary Data 2 : Reduction of selected microorganisms challenged vs. NoNitTM in salami.Supplementary Data 3 : Curve for acidification kinetic for NoNitTM alone and in associations with selected pathogens.A grant from the Sviluppumbria S.p.A., programme iStart 2014, grant n. 28/2014.http://www.elsevier.com/locate/meatsci2019-05-01hj2019Paraclinical Science

Genetic diversity of Italian goat breeds assessed with a medium-density SNP chip

Background: Among the European countries, Italy counts the largest number of local goat breeds. Thanks to the recent availability of a medium-density SNP (single nucleotide polymorphism) chip for goat, the genetic diversity of Italian goat populations was characterized by genotyping samples from 14 Italian goat breeds that originate from different geographical areas with more than 50 000 SNPs evenly distributed on the genome. Results: Analysis of the genotyping data revealed high levels of genetic polymorphism and an underlying North-south geographic pattern of genetic diversity that was highlighted by both the first dimension of the multi-dimensional scaling plot and the Neighbour network reconstruction. We observed a moderate and weak population structure in Northern and Central-Southern breeds, respectively, with pairwise FST values between breeds ranging from 0.013 to 0.164 and 7.49 % of the total variance assigned to the between-breed level. Only 2.11 % of the variance explained the clustering of breeds into geographical groups (Northern, Central and Southern Italy and Islands). Conclusions: Our results indicate that the present-day genetic diversity of Italian goat populations was shaped by the combined effects of drift, presence or lack of gene flow and, to some extent, by the consequences of traditional management systems and recent demographic history. Our findings may constitute the starting point for the development of marker-assisted approaches, to better address future breeding and management policies in a species that is particularly relevant for the medium-and long-term sustainability of marginal regions