Copper nanoparticles supported on activated carbon have been found to catalyze the multicomponent synthesis of indolizines from pyridine-2-carbaldehyde derivatives, secondary amines, and terminal ...alkynes in dichloromethane; in the absence of solvent, however, heterocyclic chalcones are formed. We provide compelling evidence that both processes take place through aldehyde–amine–alkyne coupling intermediates. In contrast to other well-known mechanisms for chalcone formation from aldehydes and alkynes, a new reaction pathway involving propargyl amines as intermediates that do not undergo rearrangement is presented. The formation of indolizines or chalcones is driven by inductive and solvent effects, with a wide array of both being reported. In both reactions, the nanoparticulate catalyst has been shown to be superior to some commercially available copper catalysts, and it could be recycled in the case of the chalcone synthesis.
The spice saffron is made from the dried stigmas of the plant
L. The main use of saffron is in cooking, due to its ability to impart colour, flavour and aroma to foods and beverages. However, from ...time immemorial it has also been considered a medicinal plant because it possesses therapeutic properties, as illustrated in paintings found on the island of Santorini, dated 1627 BC. It is included in Catalogues of Medicinal Plants and in the European Pharmacopoeias, being part of a great number of compounded formulas from the 16th to the 20th centuries. The medicinal and pharmaceutical uses of this plant largely disappeared with the advent of synthetic chemistry-produced drugs. However, in recent years there has been growing interest in demonstrating saffron's already known bioactivity, which is attributed to the main components-crocetin and its glycosidic esters, called crocins, and safranal-and to the synergy between the compounds present in the spice. The objective of this work was to provide an updated and critical review of the research on the therapeutic properties of saffron, including activity on the nervous and cardiovascular systems, in the liver, its antidepressant, anxiolytic and antineoplastic properties, as well as its potential use as a functional food or nutraceutical.
Interleukin 4 (IL-4) induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL) cells. MicroRNAs (miRNAs) regulate mRNA and protein expression, and several miRNAs, deregulated ...in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC), and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p), miR-500a (3p), miR-502 (3p), and miR-532 (3p and 5p) genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.
Background
The impact of coronavirus disease 2019 (COVID‐19) in haematological patients (HP) has not been comprehensively reported.
Methods
We analysed 39 patients with SARS‐CoV‐2 infection and ...haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non‐cancer patients with COVID‐19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome.
Results
The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty‐seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non‐cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID‐19 therapy were not predictors of outcome.
Conclusion
Mortality of COVID‐19 is significantly higher in patients with haematological malignancies compared to non‐cancer patients. The impact of persistent viral shedding must be considered in order to re‐start therapies and maintain infectious control measures.
The emerging field of precision medicine is rapidly growing, fostered by the advances in genome mapping and molecular diagnosis. In general, the translation of these advances into precision ...treatments relies on the use of biological macromolecules, whose structure offers a high specificity and potency. Unfortunately, due to their complex structure and limited ability to overcome biological barriers, these macromolecules need to be administered via injection. The scientific community has devoted significant effort to making the oral administration of macromolecules plausible thanks to the implementation of drug delivery technologies. Here, an overview of the current situation and future prospects in the field of oral delivery of biologics is provided. Technologies in clinical trials, as well as recent and disruptive delivery systems proposed in the literature for local and systemic delivery of biologics including peptides, antibodies, and nucleic acids, are described. Strategies for the specific targeting of gastrointestinal regions—stomach, small bowel, and colon—cell populations, and internalization pathways, are analyzed. Finally, challenges associated with the clinical translation, future prospects, and identified opportunities for advancement in this field are also discussed.
Oral drug delivery technologies contribute to precision medicine by enabling the targeted delivery of biologics. The harsh environment of the gastrointestinal tract and the complex structure of macromolecules make their formulation a critical challenge. An overview of the current situation, future prospects, barriers to clinical translation, and identified opportunities for advancement in the field is provided.
Hemp seeds (HS) constitute a rich nutrient source and contain γ‐linolenic acid (GLA, 18:3, n‐6), which is a healthy fatty acid (FA). The objectives of this research are i) to look for GLA‐rich ...varieties of unhusked hemp seeds (UHS) and commercial hulled hemp seeds (HHS); ii) to check the influence of different extracting systems on both oil yield and FA profiles; iii) to test a simultaneous oil extraction/GLA‐enrichment process looking to improve GLA content. Hop and European hackberry seeds (both from Cannabaceae family) are also analyzed for comparative purposes. GLA is the most discriminant FA among UHS varieties, ranging in both UHS and HHS seeds from 0.5% to 4.5% of total FA, while hop seeds are the richest GLA source from Cannabaceae (7.2% of total FA). The extraction system selected for hemp seeds processing has a clear influence on oil yields, although, the FA profiles are slightly modified. The use of n‐hexane and n‐hexane:acetone in extractions allows an improvement in oil yields at the same GLA percentage. A process comprising saponification and subsequent cooling allows the improvement of GLA percentage in both hemp and hop seeds extracts at values higher than 10% of total FA, at high yields (>70%).
Practical Applications: The global HS market increases significantly year after year and the demand of hemp products is increasing rapidly. The natural GLA sources in nature are limited, and although hemp contains GLA, this reaches low percentages in the oil. Hemp is a well‐established crop with highly standardized agricultural technologies, thus, the development of any well‐designed processes feasible for application in oil extraction industries, would allow the development of new GLA‐based functional seed oils. This would boost the development of the agricultural and food industries dedicated to revaluing hemp products.
In this study, gamma linolenic acid (GLA) occurrence is checked in hemp, hop, and European hackberry seeds. Different extracting systems are checked for oil extraction with the goal to improve GLA content. A process comprising saponification and subsequent cooling allowed improvement in GLA percentage in both hemp and hop seeds extracts at values higher than 10% of total FA, at high yields (>70%).
This paper reviews the effect of organic and inorganic coatings on magnetic nanoparticles. The ferromagnetic-like behaviour observed in nanoparticles constituted by materials which are non-magnetic ...in bulk is analysed for two cases: (a) Pd and Pt nanoparticles, formed by substances close to the onset of ferromagnetism, and (b) Au and ZnO nanoparticles, which were found to be surprisingly magnetic at the nanoscale when coated by organic surfactants. An overview of theories accounting for this unexpected magnetism, induced by the nanosize influence, is presented. In addition, the effect of coating magnetic nanoparticles with biocompatible metals, oxides or organic molecules is also reviewed, focusing on their applications.
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•Nanocarriers can be designed to target specific immune cells.•Nanovaccines may help fighting diseases that are elusive to traditional vaccines.•Nanocarriers can bias the immune ...response from humoral to cellular.•Autoimmune disease treatments can be improved with nanotechnology-based approaches.•The use of nanocarriers may help to avoid ADAs formation against biotherapeutics.
Nowadays, nanotechnology-based modulation of the immune system is presented as a cutting-edge strategy, which may lead to significant improvements in the treatment of severe diseases. In particular, efforts have been focused on the development of nanotechnology-based vaccines, which could be used for immunization or generation of tolerance. In this review, we highlight how different immune responses can be elicited by tuning nanosystems properties. In addition, we discuss specific formulation approaches designed for the development of anti-infectious and anti-autoimmune vaccines, as well as those intended to prevent the formation of antibodies against biologicals.
Forest area is increasing in temperate biomes through active and passive restoration of old fields. Despite the large extension of restored forests, the success of contrasting restoration strategies ...(active – planted forests ‐ vs. passive – secondary forests ‐) over time has never been evaluated in Mediterranean forests.
We studied how restoration strategy determined forest restoration success. We evaluated which restoration strategy resulted in forests more like references (i.e. forests with continuous canopy cover since at least the 1940s) in terms of structure, diversity, functional composition, and dynamics. We then assessed whether active restoration accelerated forest recovery compared to passive restoration.
We studied a chronosequence of recovery in four forest types (mountain and Mediterranean pine forests and mesic and Mediterranean oak forests) using the data of the Spanish Forest Inventory in central Spain. Each plot was classified as planted, secondary or reference forest. We modelled the response ratios of 11 forest attributes and a multifunctionality index as a function of restoration strategy, forest age, and abiotic and biotic constraints.
Secondary forests showed a greater likeness to references than planted forests in oak forests while minor differences between secondary and planted forests were found in pine forests. The recovery speed of most forest attributes in secondary and planted forests was similar. Multifunctionality was higher, and increased more rapidly, in planted than in secondary forests in Mediterranean oak forests. However, multifunctionality was similar for both restoration strategies in the other forest types.
Synthesis and applications. The long‐term assessment of forest recovery in Mediterranean abandoned fields indicated that both planted forests and natural forest succession are successful restoration strategies, depending on the aim and the forest type. In our research, restoration strategy did not influence the magnitude and speed of forest recovery in pine forests. However, in oak forests, natural forest succession led to forests more alike to references, but planted forests can maximize and accelerate recovery of forest multifunctionality.
Foreign Language Resumen
La superficie forestal está aumentando en zonas templadas gracias a la restauración activa y pasiva de campos agrícolas abandonados. A pesar de la extensión de los bosques restaurados, el éxito de la restauración activa – bosques plantados ‐ vs. la restauración pasiva – bosques secundarios ‐ no se ha evaluado a largo plazo en ambientes mediterráneos.
En este trabajo se analizó (1) qué estrategia de restauración condujo a bosques más parecidos a las referencias (bosques con una cubierta arbórea constante desde al menos 1946) atendiendo a la estructura, la diversidad, la composición funcional y la dinámica forestal; y (2) si la restauración activa aceleró la recuperación respecto a la restauración pasiva.
Establecimos una cronosecuencia de recuperación con los datos del Inventario Forestal Nacional para cuatro tipos de bosque del centro de España (pinares de montaña y mediterráneos, y bosques de quercíneas mésicos – rebollares ‐ y mediterráneos – encinares ‐). Las parcelas se clasificaron en bosques plantados, secundarios o referencias. Modelizamos los ratios de respuesta a la restauración de 11 atributos forestales y un índice de multifuncionalidad en función de la estrategia de restauración, la edad del bosque y los condicionantes ambientales.
Los bosques secundarios fueron más parecidos a las referencias que las plantaciones en los rebollares y encinares. Las diferencias entre bosques plantados y secundarios fueron menores en los pinares. La velocidad de recuperación de la mayoría de los atributos forestales fue parecida en ambas estrategias. La multifuncionalidad fue mayor y aumentó más rápidamente en bosques plantados que en bosques secundarios en los encinares, pero fue similar para ambas estrategias en los otros bosques.
Síntesis y aplicaciones. El análisis de la recuperación a largo plazo de bosques en campos abandonados mediterráneos mostró que tanto las plantaciones como la sucesión natural pueden ser estrategias exitosas según el objetivo y el tipo de bosque a restaurar. La estrategia de restauración no determinó la magnitud y la velocidad de recuperación en los pinares. Sin embargo, la sucesión natural generó bosques más parecidos a las referencias en bosques de quercíneas, mientras que las plantaciones en encinares favorecieron la recuperación de la multifuncionalidad.
The long‐term assessment of forest recovery in Mediterranean abandoned fields indicated that both planted forests and natural forest succession are successful restoration strategies, depending on the aim and the forest type. In our research, restoration strategy did not influence the magnitude and speed of forest recovery in pine forests. However, in oak forests, natural forest succession led to forests more alike to references, but planted forests can maximize and accelerate recovery of forest multifunctionality.
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