Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Tribocorrosion and corrosion behavior of stainless steel coated with DLC films in ethanol with different concentrations of water

There has been a recent increase in both the production and consumption of ethanol due to the numerous environmental advantages that it offers, such as the fact that it can be produced from a variety of renewable materials, for instance corn and cellulose, or it can be obtained from sugarcane bagasse and biomass (2nd and 3rd generation ethanol). The result of this is that nowadays ethanol is widely seen as the dominant biofuel – or as a blend component in gasoline or pure fuel - in many countries.However, one disadvantage of the use of ethanol is the high corrosive behavior that occurs when its hygroscopic properties are exposed to a large number of materials. Xiaoyuan Lou and Preet Singh showed that the increase of water concentration in ethanol induces pitting and metal loss. Diamond-Like Carbon (DLC) films may be a solution to this problem due to the fact that they can be deposited inside tubes, offer good protection levels against corrosion, and reduce the friction coefficient and wear.This paper shows the tribocorrosion and corrosion studies of DLC films deposited on stainless steel grade 304 (SS304) substrates in order to gauge its appropriateness usage in the construction of pipelines and fuel storage tanks. The surface morphology was analyzed before and after 14 days of immersion. The tribocorrosion, friction coefficient, and wear rate were studied in ethanol to see the effects of water concentration. The films showed good adherence to the substrates. Corrosion and tribocorrosion results showed that for bare Stainless Steel 304 the increase of the water content increases the corrosion and the friction coefficient. DLC coated samples presented few points of delamination, and the friction coefficient and open circuit potentials were very low compared with the bare sample which was water concentration independent.     

Proteome analysis of tissues by mass spectrometry

Tissues and biofluids are important sources of information used for the detection of diseases and decisions on patient therapies. There are several accepted methods for preservation of tissues, among which the most popular are fresh‐frozen and formalin‐fixed paraffin embedded methods. Depending on the preservation method and the amount of sample available, various specific protocols are available for tissue processing for subsequent proteomic analysis. Protocols are tailored to answer various biological questions, and as such vary in lysis and digestion conditions, as well as duration. The existence of diverse tissue‐sample protocols has led to confusion in how to choose the best protocol for a given tissue and made it difficult to compare results across sample types. Here, we summarize procedures used for tissue processing for subsequent bottom‐up proteomic analysis. Furthermore, we compare protocols for their variations in the composition of lysis buffers, digestion procedures, and purification steps. For example, reports have shown that lysis buffer composition plays an important role in the profile of extracted proteins: the most common are tris(hydroxymethyl)aminomethane, radioimmunoprecipitation assay, and ammonium bicarbonate buffers. Although, trypsin is the most commonly used enzyme for proteolysis, in some protocols it is supplemented with Lys‐C and/or chymotrypsin, which will often lead to an increase in proteome coverage. Data show that the selection of the lysis procedure might need to be tissue‐specific to produce distinct protocols for individual tissue types. Finally, selection of the procedures is also influenced by the amount of sample available, which range from biopsies or the size of a few dozen of mm² obtained with laser capture microdissection to much larger amounts that weight several milligrams.     

Juice and by-products from pomegranate to enrich pancake: characterisation and shelf-life evaluation

In this study, a fortified pancake with all parts of pomegranate as juice and by-products, added in the formulation, was designed. The influence of pomegranate addition on nutritional and sensory quality of pancake, as well as on its shelf-life, was assessed. As one would expect, the enrichment significantly improved the pancake polyphenolic content as compared to the control sample. Surprisingly, pomegranate addition did not affect its sensory quality. In fact, the enriched pancake was greatly appreciated from the sensory point of view. Results also suggested that the addition of pomegranate improved the glycemic index (GI). In fact, while a value of GI equal to 100 was obtained for the control sample, a GI of 71 was measured for the fortified sample. In terms of shelf-life, 30 days were obtained for the enriched pancake, whereas the control sample remained acceptable for about 26 days.     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

Computational intelligence modelling of pharmaceutical tabletting processes using bio-inspired optimization algorithms

In pharmaceutical development, it is very useful to exploit the knowledge of the causal relationship between product quality and critical material attributes (CMA) in developing new formulations and products, and optimizing manufacturing processes. With the big data captured in the pharmaceutical industry, computational intelligence (CI) models could potentially be used to identify critical quality attributes (CQA), CMA and critical process parameters (CPP). The objective of this study was to develop computational intelligence models for pharmaceutical tabletting processes, for which bio-inspired feature selection algorithms were developed and implemented for optimisation while artificial neural network (ANN) was employed to predict the tablet characteristics such as porosity and tensile strength. Various pharmaceutical excipients (MCC PH 101, MCC PH 102, MCC DG, Mannitol Pearlitol 200SD, Lactose, and binary mixtures) were considered. Granules were also produced with dry granulation using roll compaction. The feed powders and granules were then compressed at various compression pressures to produce tablets with different porosities, and the corresponding tensile strengths were measured. For the CI modelling, the efficiency of seven bio-inspired optimization algorithms were explored: grey wolf optimization (GWO), bat optimization (BAT), cuckoo search (CS), flower pollination algorithm (FPA), genetic algorithm (GA), particle swarm optimization (PSO), and social spider optimization (SSO). Two-thirds of the experimental dataset was randomly chosen as the training set, and the remaining was used to validate the model prediction. The model efficiency was evaluated in terms of the average reduction (representing the fraction of selected input variables) and the mean square error (MSE). It was found that the CI models can well predict the tablet characteristics (i.e. porosity and tensile strength). It was also shown that the GWO algorithm was the most accurate in predicting porosity. While the most accurate prediction for the tensile strength was achieved using the SSO algorithm. In terms of the average reduction, the GA algorithm resulted in the highest reduction of inputs (i.e. 60%) for predicting both the porosity and the tensile strength.     

The effect of co-encapsulation of Lactobacillus rhamnosus GG ATCC 53103 with inulin on alginate/chitosan matrix: the viability in fermented soy blend and simulated digestive system

This research verified the ability of Lactobacillus rhamnosus encapsulated with inulin to tolerate the simulated digestive system and their viability in a soy blend. Probiotic encapsulated in alginate-chitosan matrix without inulin presented a better encapsulation efficiency (80.92%) than encapsulation with inulin (57.39%). On the 28th day, the count of probiotics decreased by 3.42 and 1.99 logarithmic cycles of free and encapsulated cells without inulin, respectively. In contrast, the microorganisms encapsulated with inulin showed an increase of 1.26 logs CFU g⁻¹. During gastrointestinal simulation, cell counts decreased by 0.78, 1.55 and 1.95 CFU g⁻¹ logs for encapsulated cells without inulin, free and encapsulated with inulin, respectively. Sensory panellists liked the fermented soy blend with encapsulated lactobacilli, and this result shows the possibility to create new probiotic foods of plant origin. Therefore, the alginate/chitosan matrix can be considered adequate for the encapsulation of L. rhamnosus. The inulin reduces the encapsulation efficiency and increases the cell loss in gastrointestinal simulation. Considering cellular losses, the best option for preparing a fermented soy blend is to use L. rhamnosus encapsulated without inulin.     

Metabolism of phospholipids in the yeast Schizosaccharomyces pombe

The fission yeast Schizosaccharomyces pombe is an important model organism for the study of fundamental questions in eukaryotic cell and molecular biology. A plethora of cellular processes are membrane associated and/or dependent on the proper functioning of cellular membranes. Phospholipids are not only the basic building blocks of cellular membranes; they also serve as precursors to numerous signaling molecules. In this review, we describe the biosynthetic pathways leading to major S. pombe phospholipids, how these pathways are regulated, and what is known about degradation and turnover of fission yeast phospholipids. This review also addresses the synthesis, regulation and the role of water-soluble phospholipid precursors. The last chapter of the review is devoted to the use of S. pombe for the biotechnological production of value-added lipid molecules.     

Comparative Analysis of Platelet-Derived Extracellular Vesicles Using Flow Cytometry and Nanoparticle Tracking Analysis

Growing interest in extracellular vesicles (EVs) has prompted the advancements of protocols for improved EV characterization. As a high-throughput, multi-parameter, and single particle technique, flow cytometry is widely used for EV characterization. The comparison of data on EV concentration, however, is hindered by the lack of standardization between different protocols and instruments. Here, we quantified EV counts of platelet-derived EVs, using two flow cytometers (Gallios and CytoFLEX LX) and nanoparticle tracking analysis (NTA). Phosphatidylserine-exposing EVs were identified by labelling with lactadherin (LA). Calibration with silica-based fluorescent beads showed detection limits of 300 nm and 150 nm for Gallios and CytoFLEX LX, respectively. Accordingly, CytoFLEX LX yielded 40-fold higher EV counts and 13-fold higher counts of LA⁺CD41⁺ EVs compared to Gallios. NTA in fluorescence mode (F-NTA) demonstrated that only 9.5% of all vesicles detected in scatter mode exposed phosphatidylserine, resulting in good agreement of LA⁺ EVs for CytoFLEX LX and F-NTA. Since certain functional characteristics, such as the exposure of pro-coagulant phosphatidylserine, are not equally displayed across the entire EV size range, our study highlights the necessity of indicating the size range of EVs detected with a given approach along with the EV concentration to support the comparability between different studies.