NMR Spectroscopy Applied to the Metabolic Analysis of Natural Extracts of Cannabis sativa

Cannabis sativa is a herbaceous multiple-use species commonly employed to produce fiber, oil, and medicine. It is now becoming popular for the high nutritional properties of its seed oil and for the pharmacological activity of its cannabinoid fraction in inflorescences. The present study aims to apply nuclear magnetic resonance (NMR) spectroscopy to provide useful qualitative and quantitative information on the chemical composition of seed and flower Cannabis extracts obtained by ultra-sound-assisted extraction, and to evaluate NMR as an alternative to the official procedure for the quantification of cannabinoids. The estimation of the optimal ω-6/ω-3 ratio from the ¹H NMR spectrum for the seed extracts of the Futura 75 variety and the quantitative results from the ¹H and ¹³C NMR spectra for the inflorescence extracts of the Tiborszallasi and Kompolti varieties demonstrate that NMR technology represents a good alternative to classical chromatography, supplying sufficiently precise, sensitive, rapid, and informative data without any sample pre-treatment. In addition, different extraction procedures were tested and evaluated to compare the elaboration of spectral data with the principal component analysis (PCA) statistical method and the quantitative NMR results: the extracts obtained with higher polarity solvents (acetone or ethanol) were poor in psychotropic agents (THC < LOD) but had an appreciable percentage of both cannabinoids and triacylgliceroles (TAGs). These bioactive-rich extracts could be used in the food and pharmaceutical industries, opening new pathways for the production of functional foods and supplements.     

Lower Bound Estimates Without Transversal Ellipticity

We study the validity of Hörmander's inequality for some classes of pseudo-differential operators for which the transversal ellipticity condition does not hold.     

The Cauchy Problem for Hyperbolic Operators with Double Characteristics in Presence of Transition

We study the C ^∞ well-posedness of the Cauchy problem for a class of hyperbolic second order operators with double characteristics in presence of geometric transitions.     

Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin-Targeted Conjugate

This work takes advantage of one of the hallmarks of cancer, that is, the presence of tumor infiltrating cells of the immune system and leukocyte-secreted enzymes, to promote the activation of an anticancer drug at the tumor site. The peptidomimetic integrin ligand cyclo(DKP-RGD) was found to accumulate on the surface of α_vβ₃ integrin-expressing human renal cell carcinoma 786-O cells. The ligand was conjugated to the anticancer drug paclitaxel through a Asn-Pro-Val (NPV) tripeptide linker, which is a substrate of neutrophil-secreted elastase. In vitro linker cleavage assays and cell antiproliferative experiments demonstrate the efficacy of this tumor-targeting conjugate, opening the way to potential therapeutic applications.     

Preliminary Study on New Alternative Binders through Re-Refined Engine Oil Bottoms (REOBs) and Industrial By-Product Additives

Recent studies have worked towards addressing environmental issues such as global warming and greenhouse gas emissions due to the increasing awareness of the depletion of natural resources. The asphalt industry is seeking to implement measures to reduce its carbon footprint and to promote sustainable operations. The reuse of several wastes and by-products is an example of a more eco-friendly activity that fulfils the circular economy principle. Among all possible solutions, the road pavement sector encourages, on one hand, the use of recycled materials as a partial replacement of the virgin lithic skeleton; on the other hand, it promotes the use of recycled materials to substituting for a portion of the petroleum bituminous binder. This study aims to use Re-refined Engine Oil Bottoms (REOBs) as a main substitute and additives from various industrial by-products as a full replacement for virgin bitumen, producing high-performing alternative binders. The REOBs have been improved by utilizing additives in an attempt to improve their specific properties and thus to bridge the gap between REOBs and traditional bituminous binders. An even larger amount of virgin and non-renewable resources can be saved using these new potential alternative binders together with the RAP aggregates. Thus, the reduction in the use of virgin materials is applied at the binder and the asphalt mixture levels. Rheological, spectroscopic, thermogravimetric, and mechanical analysis were used to characterize the properties, composition, and characteristics of the REOBs, REOB-modified binders, and asphalt mixes. Thanks to the rheological investigations of possible alternative binders, 18 blends were selected, since they behaved like an SBS-modified bitumen, and then they were used for producing the corresponding asphalt mixtures. The preliminary mechanical analysis of the asphalt mixtures shows that six mixes have promising responses in terms of stiffness, tensile resistance, and water susceptibility. Nevertheless, the high variability of recycled materials and by-products has to be taken into consideration during the definition of alternative binders and recycled asphalt mixtures. In fact, this study highlights the crucial effects of the chemical composition of the constituents and their compatibility on the behaviour of the final product. This preliminary study represents a first attempt to define alternative binders, which can be used in combination with recycled aggregates for producing more sustainable road materials. However, further analysis is necessary in order to assess the durability and the ageing tendency of the materials.     

Chemical Approaches for Studying the Biology and Pharmacology of Membrane Transporters: The Histidine/Large Amino Acid Transporter SLC7A5 as a Benchmark

The localization of membrane transporters at the forefront of natural barriers makes these proteins very interesting due to their involvement in the absorption and distribution of nutrients and xenobiotics, including drugs. Over the years, structure/function relationship studies have been performed employing several strategies, including chemical modification of exposed amino acid residues. These approaches are very meaningful when applied to membrane transporters, given that these proteins are characterized by both hydrophobic and hydrophilic domains with a different degree of accessibility to employed chemicals. Besides basic features, the chemical targeting approaches can disclose information useful for pharmacological applications as well. An eminent example of this picture is the histidine/large amino acid transporter SLC7A5, known as LAT1 (Large Amino Acid Transporter 1). This protein is crucial in cell life because it is responsible for mediating the absorption and distribution of essential amino acids in peculiar body districts, such as the blood brain barrier and placenta. Furthermore, LAT1 can recognize a large variety of molecules of pharmacological interest and is also considered a hot target for drugs due to its over-expression in virtually all human cancers. Therefore, it is not surprising that the chemical targeting approach, coupled with bioinformatics, site-directed mutagenesis and transport assays, proved fundamental in describing features of LAT1 such as the substrate binding site, regulatory domains and interactions with drugs that will be discussed in this review. The results on LAT1 can be considered to have general applicability to other transporters linked with human diseases.