Antiulcerogenic Potential of the Ethanolic Extract of Ceiba speciosa (A. St.-Hil.) Ravenna Evaluated by In Vitro and In Vivo Studies

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.     

Synthesis and applications of some new antioxidant and anticorrosive additives for Egyptian diesel motor oils

Pyrimidine‐5‐carboxylate derivative Ia was utilised as a key intermediate for the synthesis of new pyrimidine derivatives. Thiopyrimidine derivative Ia undergo N‐methylation using methyl iodide afforded III. Methylsulfanyl moiety in II was easily removed when reacted with phenyl hydrazine and thiosemicarbazide afforded pyrimidine derivatives IV and VI, respectively. The reaction on nitrogen atom in Ia using 1,3‐dibromo‐propane, benzoyl chloride, phosphorous oxychloride afforded VIII, IX and X, respectively. The reaction using 1,3‐dibromo‐propane or 1,2‐dibromo‐ethane furnished the formation of the corresponding fused cycles containing sulfur. Representative compounds of the synthesised products were evaluated as antioxidant and corrosion inhibitors for gasoline lube oils. Copyright © 2010 John Wiley & Sons, Ltd.     

In situ FTIR spectroelectrochemistry of poly[2-(3-thienyl)ethyl acetate] and its hydrolyzed derivatives

Poly[2-(3-thienyl)ethyl acetate] (PTEtAc) was chemically synthesized and transformed to partially hydrolyzed PTEtAc (PTEtAcOH) and poly[2-(3-thienyl)ethanol] (PTEtOH). The influence of the acetoxy and hydroxyl terminal functionalities in the side groups on the electrochemical properties of these polyalkylthiophenes was studied by cyclic voltammetry and in situ FTIR spectroelectrochemistry. The cyclic voltammograms point to a chemically reversible behaviour of the p-doping process for PTEtAc and PTEtAcOH, while for PTEtOH the redox activity of the polymer film is lost during consecutive potential scans.The attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to investigate the p-doping of the three different type of thiophene polymer films. In situ FTIR spectra taken at different electrode potentials in a cyclovoltammetric scan display the doping induced changes of the polymer pattern. Important differences in the behaviour of the polymers were observed and interpreted in terms of different film structures.     

Synthesis and evaluation of some new oxazolones and imidazolones as antioxidant additives for Egyptian lubricating oils

Oxazolone derivative 2 was utilized as a key intermediate for synthesis of some new oxazolone and imidazolone derivatives. Reaction of oxazolone derivative 2 with diamines under different conditions afforded the corresponding imidazolone derivatives 3-8, respectively. Moreover, oxazolone 2 reacted with some heterocyclic amines in glacial acetic acid giving the corresponding imidazolone derivatives 9-14, respectively. Cyclocondensation of thiosemicarbazide with compound 2 in dry pyridine afforded compound 15. Addition of secondary amines to olefin double bond of compound 2 gave the corresponding addition products 16-19, respectively. Michael addition of compound 2 with some active methylene compounds afforded oxazolone derivatives 20-23, respectively. These prepared products were evaluated as antioxidant and corrosion inhibitors for gasoline lubricating oil and compounds 6a-c, 10 and 15 exhibited the highest antioxidant and anticorrosive activities. The effect of concentration of additives was studied to recommend the optimum concentration to be used. The results showed, for additive 15, 0.1 g for 1 L oil was the more effective concentration. Measurements for thermal analysis and of surface tension of oil after oxidation were also carried out.     

Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model

The IDH1^R132H mutation in glioma results in the neoenzymatic function of IDH1, leading to the production of the oncometabolite 2-hydroxyglutarate (2-HG), alterations in energy metabolism and changes in the cellular redox household. Although shifts in the redox ratio NADPH/NADP⁺ were described, the consequences for the NAD⁺ synthesis pathways and potential therapeutic interventions were largely unexplored. Here, we describe the effects of heterozygous IDH1^R132H on the redox system in a CRISPR/Cas edited glioblastoma model and compare them with IDH1 wild-type (IDH1^wt) cells. Besides an increase in 2-HG and decrease in NADPH, we observed an increase in NAD⁺ in IDH1^R132H glioblastoma cells. RT-qPCR analysis revealed the upregulation of the expression of the NAD⁺ synthesis enzyme nicotinamide phosphoribosyltransferase (NAMPT). Knockdown of NAMPT resulted in significantly reduced viability in IDH1^R132H glioblastoma cells. Given this dependence of IDH1^R132H cells on NAMPT expression, we explored the effects of the NAMPT inhibitors FK866, GMX1778 and GNE-617. Surprisingly, these agents were equally cytotoxic to IDH1^R132H and IDH1^wt cells. Altogether, our results indicate that targeting the NAD⁺ synthesis pathway is a promising therapeutic strategy in IDH mutant gliomas; however, the agent should be carefully considered since three small-molecule inhibitors of NAMPT tested in this study were not suitable for this purpose.     

Postharvest storage and cooking techniques affect the stability of glucosinolates and myrosinase activity of Andean mashua tubers (Tropaeolum tuberosum)

The identification and quantification of Glucosinolates (Gls) via UPLC^® MS-MS/PDA/qToF in ten mashua cultivars was carried out. Gls total contents were within the 4.9–54.2 μmol g⁻¹ dry matter range, of which 96–99% corresponded to glucoaubrietin. Other less abundant Gls were glucotropaeolin and tentatively two isomers of hydroxybenzyl Gls. Postharvest refrigeration and shade storage conditions increased the content of Gls up to day 6 in 39.7% and 51.5% respectively. Sun exposure increased the Gls content in 40% up to day 3 but from day 6 considerable losses were attained (92% at day 15). Low correlation levels (R²) between the Gls and myrosinase (MYR) activity of 0.57, 0.28 and 0.39 for the refrigeration, shade and sun exposure treatments were obtained. The cooking regimes tested, boiling, microwaving and baking totally inactivated MYR without affecting the Gls content.     

Regulatory Proteolysis in Arabidopsis-Pathogen Interactions

Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is simultaneously used both by plant cells, to recognize and inactivate invading pathogens, and by microbes, to overcome the immune system of the plant and successfully colonize host cells. In this review, we present available results on the group of proteases in the model plant Arabidopsis thaliana whose functions in microbial pathogenesis were confirmed. Pathogen-derived proteolytic factors are also discussed when they are involved in the cleavage of host metabolites. Considering the wealth of review papers available in the field of the ubiquitin-26S proteasome system results on the ubiquitin cascade are not presented. Arabidopsis and its pathogens are conferred with abundant sets of proteases. This review compiles a list of those that are apparently involved in an interaction between the plant and its pathogens, also presenting their molecular partners when available.     

Schizosaccharomyces pombe Arc3 is a conserved subunit of the Arp2/3 complex required for polarity, actin organization, and endocytosis

We characterized the Schizosaccharomyces pombe arc3 gene, whose product shares sequence homology with that of the budding yeast ARC18 and human ARPC3/p21 subunits of the Arp2/3 complex. Our data showed that Arc3p co-localizes with F-actin patches at the cell ends, but not with F-actin cables or the equatorial actin ring, and binds other subunits of the Arp2/3 complex. Gene deletion analysis showed that arc3 is essential for viability. When arc3 expression was repressed, F-actin patches became dispersed throughout the cell with greatly reduced mobility. Furthermore, in arc3-repressed cells, endocytosis was also inhibited. Human ARPC3 rescued the viability of the Sz. pombe arc3 null mutant; in addition, ARPC3 also localized to F-actin patches in human cells. These data suggest that Arc3p is an evolutionarily conserved subunit of the Arp2/3 complex required for proper F-actin organization and efficient endocytosis.     

Reference-Guided De Novo Genome Assembly of the Flour Beetle Tribolium freemani

The flour beetle Tribolium freemani is a sibling species of the model organism and important pest Tribolium castaneum. The two species are so closely related that they can produce hybrid progeny, but the genetic basis of their differences has not been revealed. In this work, we sequenced the T. freemani genome by applying PacBio HiFi technology. Using the well-assembled T. castaneum genome as a reference, we assembled 262 Mb of the T. freemani genomic sequence and anchored it in 10 linkage groups corresponding to nine autosomes and sex chromosome X. The assembly showed 99.8% completeness of conserved insect genes, indicating a high-quality reference genome. Comparison with the T. castaneum assembly revealed that the main differences in genomic sequence between the two sibling species come from repetitive DNA, including interspersed and tandem repeats. In this work, we also provided the complete assembled mitochondrial genome of T. freemani. Although the genome assembly needs to be ameliorated in tandemly repeated regions, the first version of the T. freemani reference genome and the complete mitogenome presented here represent useful resources for comparative evolutionary studies of related species and for further basic and applied research on different biological aspects of economically important pests.     

Layered specifications to support reusability and integrability

Building systems by integrating components and building systems by reusing components are but two sides of the same coin. In both cases one faces the problem of producing systems out of prefabricated parts, either parts which have been designed for a different environment than the one they will be used in now, or parts which have been designed for a yet undefined target system.This situation differs from classical software design situations. It demands that in parts engineering as well as in systems engineering, certain interface decisions are postponed to a rather late point in time. This is only permissible, though, if other aspects are very precisely specified. Having the right model of specification of both, the target (system) and source (component) will substantially aid the retrieval and integration problem.This article argues for a layered approach towards system specification. It will show, how relational specifications will help system designers not to bind themselves too early into premature decisions and how designs aiming for heavy reuse can grow by stepwise enriching specifications.