Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.

BACKGROUND: This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction. METHODS: The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework. RESULTS: Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability. DISCUSSION: Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis. CONCLUSION: A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.

Review: Presence, distribution and current pesticides used in Spanish agricultural practices.

To guarantee an adequate food supply for the world's growing population, intensive agriculture is necessary to ensure efficient food production. The use of pesticides helps maintain maximum productivity in intensive agriculture by minimizing crop losses due to pests. However, pesticide contamination of surface waters constitutes a major problem as they are resistant to degradation and soluble enough to be transported in water. In recent years, all groups of pesticides defined by the World Health Organization have increased their use and, therefore, their prevalence in the different environmental compartments that can have harmful effects. Despite this effort, there is no rigorous monitoring program that quantifies and controls the toxic effects of each pesticide. However, multiple scientific studies have been published by specialized research groups in which this information is disseminated. Therefore, any attempt to systematize this information is relevant. This review offers a current overview of the presence and distribution of the most widely-used pesticides (insecticides, herbicides, and fungicides) by crop type and an evaluation of the relationships between their uses and environmental implications in Spain. The data demonstrated that there are correlations between the presence of specific pesticides used in the main crops and their presence in the environmental compartments. We have found preliminary data pointing to existing associations between specific pesticides used in the main crops and their presence in environmental compartments within different geographical areas of Spain; this should be the subject of further investigation.

Fast 1H-NMR Species Differentiation Method for Camellia Seed Oils Applied to Spanish Ornamentals Plants. Comparison with Traditional Gas Chromatography.

Camellia genus (Theaceae) is comprised of world famous ornamental flowering plants. C. japonica L. and C. sasanqua Thunb are the most cultivated species due to their good adaptation. The commercial interest in this plant linked to its seed oil increased in the last few years due to its health attributes, which significantly depend on different aspects such as species and environmental conditions. Therefore, it is essential to develop fast and reliable methods to distinguish between different varieties and ensure the quality of Camellia seed oils. The present work explores the study of Camellia seed oils by species and location. Two standardized gas chromatography methods were applied and compared with that of data obtained from proton nuclear magnetic resonance spectroscopy (1H-NMR) for fatty acids profiling. The principal component analysis indicated that the proposed 1H-NMR methodology can be quickly and reliably applied to separate specific Camellia species, which could be extended to other species in future works.

Influence of elaboration process on chemical, biological, and sensory characteristics of European pennyroyal liqueurs.

BACKGROUND: Mentha pulegium is an aromatic and medicinal plant used in different Mediterranean herb-based liqueurs, whose phytochemical composition depends on the elaboration technique used. The aim of this work was to investigate differences in the sensory, chemical, and biological characteristics of pennyroyal liqueurs elaborated by hydro-alcoholic (HI) and aqueous (AI) infusions, percolation (P), maceration (M), and distillation (D) techniques, and by the mixture of spirit with pennyroyal essential oil (EO). The volatile composition determined by gas chromatography-mass spectrometry (GC-MS) and gas chromatography coupled to flame ionization detection (GC-FID), the total phenolic (TPC) and flavonoid (TFC) contents, the antioxidant (AC), and enzyme (α-glucosidase, tyrosinase, and acetylcholinesterase) inhibitory capacities, and the sensory analysis by napping, were evaluated in the liqueurs obtained. RESULTS: Monoterpenes and sesquiterpenes were the main volatiles present in liqueurs. The M, P, HI, and AI liqueurs showed the highest TPC, TFC, and AC values; and pulegone, the main hepatotoxic chemotype, was found in concentrations that gave rise to concern. The D and EO liqueurs stand out for their acceptable pulegone content and greater tyrosinase inhibition. Similar liqueur classifications were achieved by sensory analyses, and physico-chemical and biological analyses using multiple factor and principal component analyses, respectively. CONCLUSION: These results are an important contribution to the identification of the most appropriate elaboration conditions for herbal liqueurs with the healthiest chemical composition and functional properties. © 2020 Society of Chemical Industry.

The Influence of In Vitro Gastrointestinal Digestion on the Chemical Composition and Antioxidant and Enzyme Inhibitory Capacities of Carob Liqueurs Obtained with Different Elaboration Techniques.

Carob liqueur is a traditional Mediterranean alcoholic beverage obtained via a wide range of production techniques contributing to the different organoleptic attributes of the final product. The aim of this research was to evaluate the stability of the chemical composition and biological capacities (antioxidant and enzyme inhibition) under in vitro simulated gastrointestinal digestion of liqueurs prepared by flavouring the fig spirit with carob pulp by maceration, distillation, percolation, or aqueous and hydro-alcoholic infusions. For this purpose, the phenolic and furanic compositions, the total phenolic (TPC) and flavonoid (TFC) contents, antioxidant capacity (AC), and enzyme inhibitory potential against acethylcholinesterase, tyrosinase, α-glucosidase and α-amylase enzymes were evaluated. The content of gallic acid decreased after gastrointestinal digestion, while TPC, TFC, and AC significantly increased after each digestion phase. Overall, no significantly different enzyme inhibitions (p < 0.05) were observed among digested liqueurs, with moderate inhibition against acethylcholinesterase and tyrosinase (enzymes related with neurodegenerative diseases), and potent and low inhibitory capacities for α-glucosidase and α-amylase, respectively (ideal conditions employed in antidiabetic therapy). The study indicates that hydro-alcoholic infusion and maceration were the most appropriate methods to obtain liqueurs with higher values of the aforementioned parameters and safe levels of toxic furanics.

Effect of carob variety and roasting on the antioxidant capacity, and the phenolic and furanic contents of carob liquors.

BACKGROUND: The production of the traditional carob liquor from Algarve (Portugal) depends on numerous factors such as carob processing, variety and maceration conditions. An experimental design with 36 runs was created to evaluate the effect of the roasting temperature, particle size, variety of carob and time of maceration on several parameters of carob liquors as gallic acid and total phenolic content, the furanic composition (furfural and 5-(hydroxymethyl)furfural), browning index and in vitro antioxidant capacity. RESULTS: The results revealed that carob variety was the independent variable with the greatest effect on antioxidant capacity, total phenolic and gallic acid content. In particular, AIDA liquors presented the highest results, mainly those prepared with unroasted carob. Meanwhile, Galhosa and Mulata liquors showed the greatest concentrations when the carob pulp was roasted at 150 °C. The furanic composition and browning index were greatly influenced by the carob roasting degree. CONCLUSION: The levels of the main toxic furanics present in carob liquors, furfural and 5-(hydroxymethyl)furfural, suggest a safe consumption of these beverages even in samples of carobs with the maximum roasting degree. The smallest carob particle size favoured the highest phenolic extraction, while the longest maceration periods decreased the concentration of the toxic furanic compounds studied. © 2018 Society of Chemical Industry.

Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and their 4-alkoxy isomers.

Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise for both the prevention and treatment of cancer and metabolic diseases. In this regard, synthetic, functional, and structural investigations into the structure-activity relationships of derivatives of the potent RXR agonist (E)-3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-4-hydroxyphenyl]acrylic acid (CD3254, 9) have been conducted. We recently reported on the characterization of a series of C3'-substituted alkyl ether analogues of 9 (10a-f), which display activities ranging from partial agonists to pure antagonists. The importance of the position of the alkoxy side chain for ligand activity has been further explored with the synthesis of C4'-substituted analogues (11a-f). Here we describe the synthesis of compounds 11a-f, which appear functionally different from their isomeric counterparts, as judged from transactivation assays and fluorescence anisotropy experiments. We also report on the 2.0 A resolution structure of RXR in complex with the parent compound 9, which helps understanding of the impact of the alkyl side chain location on ligand activity.

Selective, potent PPARgamma agonists with cyclopentenone core structure.

A series of analogues of the PPARgamma ligand 15-deoxy-Delta(12,14)-PGJ(2) have been synthesized by functionalization of a 5-alkyl-4-hydroxycyclopentenone core structure obtained by Piancatelli rearrangement of precursor furylcarbinol. Transient transactivation assays indicate that analogues 18 and 20 are selective nanomolar agonists of PPARgamma. This subtype selectivity is lost in derivatives (23, 24) with an alkynyl (oct-1-yn) chain at the C3 position, although the cyclopentenone derivative with cis relative configuration (23) showed greater affinity for PPARalpha.