Organofluorine Hydrazone Derivatives as Multifunctional Anti-Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

A set of novel hydrazone derivatives were synthesized and analyzed for their biological activities. The compounds were tested for their inhibitory effect on the phosphorylating activity of the protein kinase CK2, and their antioxidant activity was also determined in three commonly used assays. The hydrazones were evaluated for their radical scavenging against the DPPH, ABTS and peroxyl radicals. Several compounds have been identified as good antioxidants as well as potent protein kinase CK2 inhibitors. Most hydrazones containing a 4-N(CH₃)₂ residue or perfluorinated phenyl rings showed high activity in the radical-scavenging assays and possess nanomolar IC₅₀ values in the kinase assays.     

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

The AFLATOX® Project: Approaching the Development of New Generation,Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox^® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.     

Surface modification of ultra‐high‐molecular‐weight polyethylene. II. Effect on the physicomechanical and tribological properties of ultra‐high‐molecular‐weight polyethylene/poly(ethylene terephthalate) composites

We performed surface modification of ultra‐high‐molecular‐weight polyethylene (UHMWPE) through chromic acid etching, with the aim of improving the performance of its composites with poly(ethylene terephthalate) (PET) fibers. In this article, we report on the morphology and physicomechanical and tribological properties of modified UHMWPE/PET composites. Composites containing chemically modified UHMWPE had higher impact properties than those based on unmodified UHMWPE because of improved interfacial bonding between the polymer matrix and the fibers and better dispersion of the fibers within the modified UHMWPE matrix. Chemical modification of UHMWPE before the introduction of PET fibers resulted in composites exhibiting improved wear resistance compared to the base material and compared to unmodified UHMWPE/PET composites. On the basis of the morphological studies of worn samples, microploughing and fatigue failure associated with microcracking were identified as the principle wear mechanisms. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Rheology,structure, and properties of ethylene–vinyl acetate/metallocene‐catalyzed ethylene–α‐olefin copolymer blends

The rheology, morphology, thermal, mechanical, and adhesive properties of blends containing ethylene–vinyl acetate and metallocene‐catalyzed ethylene–α‐olefin copolymers, containing butene and octene comonomers, were investigated. On the basis of the thermal and rheological properties and scanning electron microscopy observations, we deduced that these blends were immiscible, both in the solid and melt states over the whole range of compositions. Rheological properties were correlated to blend morphology with the Palierne emulsion model. The butene‐based blends had better mechanical properties, which was attributed to their finer morphology, lower interfacial tension, and better adhesive properties. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 881–889, 2004     

Sediment Delivery Assessment for a Transboundary Mediterranean Catchment: The Example of Nestos River Catchment

Nestos River flows through Bulgaria and Greece and discharges into the North Aegean Sea. Its total catchment area is around 6,200 km², while the mean annual precipitation and runoff are 680 mm and 40 m³/s, respectively. The Hellenic part of the catchment has undergone a substantial hydroelectric development, since two dams associated with major hydropower pumped-storage facilities are in operation. The main objective of the paper is to assess the expected sediment delivery of Nestos R. at the uppermost Thisavros reservoir site. This has been carried out by implementing the Universal Soil Loss Equation in a GIS environment for determining the mean annual soil erosion in conjunction with a suspended sediment measurement program (114 measurements in total) accomplished between 1965 and 1983 adjacent to the dam site. The sediment discharge rating curve between sediment and river discharges in a power form has been constructed using five alternative techniques, namely (a) the linear regression of the log-transformed variables, (b) the same as (a) but with the Ferguson correction, (c) different ratings for the dry and wet seasons of the year, (d) the nonlinear regression, and (e) the broken line interpolation that utilizes different rating parameters for two discharge classes. It is shown that the mean annual sediment yield is almost equal for all rating curve formulations and varies between 178.5 t km⁻² and 203.4 t km⁻² and the highest value results from the broken line interpolation method. Accordingly, the sediment delivery ratios vary slightly between 17% and 19% of the upstream soil erosion.     

Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection‐based delivery of insulin. Neonatal Fc receptor (FcRn)‐mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn‐targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH‐responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH‐sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn‐targeted NPs. Overall, these FcRn‐targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.