The influence of hubs in the structure of a neuronal network during an epileptic seizure

In this work, we propose changes in the structure of a neuronal network with the intention to provoke strong synchronization to simulate episodes of epileptic seizure. Starting with a network of Izhikevich neurons we slowly increase the number of connections in selected nodes in a controlled way, to produce (or not) hubs. We study how these structures alter the synchronization on the spike firings interval, on individual neurons as well as on mean values, as a function of the concentration of connections for random and non-random (hubs) distribution. We also analyze how the post-ictal signal varies for the different distributions. We conclude that a network with hubs is more appropriate to represent an epileptic state.     

Characterization of Biocatalysts Prepared with Thermomyces lanuginosus Lipase and Different Silica Precursors,Dried using Aerogel and Xerogel Techniques

The use of lipases in industrial processes can result in products with high levels of purity and at the same time reduce pollutant generation and improve both selectivity and yields. In this work, lipase from Thermomyces lanuginosus was immobilized using two different techniques. The first involves the hydrolysis/polycondensation of a silica precursor (tetramethoxysilane (TMOS)) at neutral pH and ambient temperature, and the second one uses tetraethoxysilane (TEOS) as the silica precursor, involving the hydrolysis and polycondensation of the alkoxide in appropriate solvents. After immobilization, the enzymatic preparations were dried using the aerogel and xerogel techniques and then characterized in terms of their hydrolytic activities using a titrimetric method with olive oil and by the formation of 2-phenylethyl acetate in a transesterification reaction. The morphological properties of the materials were characterized using scanning electron microscopy, measurements of the surface area and pore size and volume, thermogravimetric analysis, and exploratory differential calorimetry. The results of the work indicate that the use of different silica precursors (TEOS or TMOS) and different drying techniques (aerogel or xerogel) can significantly affect the properties of the resulting biocatalyst. Drying with supercritical CO₂ provided higher enzymatic activities and pore sizes and was therefore preferable to drying, using the xerogel technique. Thermogravimetric analysis and differential scanning calorimetry analyses revealed differences in behavior between the two biocatalyst preparations due to the compounds present.     

Photodynamic Activity on Biofilm in Endotracheal Tubes of Patients Admitted to an Intensive Care Unit

Ventilator-associated pneumonia (VAP) is an infection that arises after endotracheal intubation affecting patients under intensive care. The presence of the endotracheal tube (ETT) is a risk factor since it is colonized by multispecies biofilm. Antimicrobial photodynamic therapy (aPDT) could be a strategy to decontaminate ETTs. We verify if methylene blue (MB) associated with external illumination of the ETT could be an alternative to destroy biofilm. We performed an in vitro and ex vivo study. In vitro study was performed with P. aeruginosa biofilm grew over ETT for 7 days. After treatment, the surviving cells were cultured for 3 days and the biofilm was analyzed by crystal violet absorbance. Ex vivo study employed ETT obtained from extubated patients. aPDT was performed with MB (100 µm ) and red LED (λ = 640±20 nm). We quantified the biofilm thickness and used scanning electron microscopy and fluorescence technique to verify morphological and functional changes after aPDT. Our results showed that bacteria remain susceptible to aPDT after sequential treatments. We also attested that aPDT can reduce biofilm thickness, disrupt biofilm attachment from ETT surface and kill microbial cells. These data suggest that aPDT should be investigated to decrease VAP incidence via ETT decontamination.     

Terroir Effect on the Phenolic Composition and Chromatic Characteristics of Mencía/Jaen Monovarietal Wines: Bierzo D.O. (Spain) and Dão D.O. (Portugal)

‘Mencía’/‘Jaen’ it’s an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different “terroirs” on the phenolic composition and chromatic characteristics of ‘Mencía’/‘Jaen’ monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from ‘Jaen’ and ‘Mencía’ to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.     

Production of Verbascoside,Isoverbascoside and Phenolic Acids in Callus,Suspension, and Bioreactor Cultures of Verbena officinalis and Biological Properties of Biomass Extracts

Callus, suspension and bioreactor cultures of Verbena officinalis were established, and optimized for biomass growth and production of phenylpropanoid glycosides, phenolic acids, flavonoids and iridoids. All types of cultures were maintained on/in the Murashige and Skoog (MS) media with 1 mg/L BAP and 1 mg/L NAA. The inoculum sizes were optimized in callus and suspension cultures. Moreover, the growth of the culture in two different types of bioreactors—a balloon bioreactor (BB) and a stirred-tank bioreactor (STB) was tested. In methanolic extracts from biomass of all types of in vitro cultures the presence of the same metabolites—verbascoside, isoverbascoside, and six phenolic acids: protocatechuic, chlorogenic, vanillic, caffeic, ferulic and rosmarinic acids was confirmed and quantified by the HPLC-DAD method. In the extracts from lyophilized culture media, no metabolites were found. The main metabolites in biomass extracts were verbascoside and isoverbascoside. Their maximum amounts in g/100 g DW (dry weight) in the tested types of cultures were as follow: 7.25 and 0.61 (callus), 7.06 and 0.48 (suspension), 7.69 and 0.31 (BB), 9.18 and 0.34 (STB). The amounts of phenolic acids were many times lower, max. total content reached of 26.90, 50.72, 19.88, and 36.78 mg/100 g DW, respectively. The highest content of verbascoside and also a high content of isoverbascoside obtained in STB (stirred-tank bioreactor) were 5.3 and 7.8 times higher than in extracts from overground parts of the parent plant. In the extracts from parent plant two iridoids—verbenalin and hastatoside, were also abundant. All investigated biomass extracts and the extracts from parent plant showed the antiproliferative, antioxidant and antibacterial activities. The strongest activities were documented for the cultures maintained in STB. We propose extracts from in vitro cultured biomass of vervain, especially from STB, as a rich source of bioactive metabolites with antiproliferative, antioxidant and antibacterial properties.     

Characterization of the Zwitterionic Intermediate in 1,1‐Carboboration of Alkynes

The reaction of a Lewis acidic borane with an alkyne is a key step in a diverse range of main group transformations. Alkyne 1,1‐carboboration, the Wrackmeyer reaction, is an archetypal transformation of this kind. 1,1‐Carboboration has been proposed to proceed through a zwitterionic intermediate. We report the isolation and spectroscopic, structural and computational characterization of the zwitterionic intermediates generated by reaction of B(C₆F₅)₃ with alkynes. The stepwise reactivity of the zwitterion provides new mechanistic insight for 1,1‐carboboration and wider B(C₆F₅)₃ catalysis. Making use of intramolecular stabilization by a ferrocene substituent, we have characterized the zwitterionic intermediate in the solid state and diverted reactivity towards alkyne cyclotrimerization.     

Determination of phenolic compounds,in vitro antioxidant activity and characterization of secondary metabolites in different parts of Passiflora cincinnata by HPLC-DAD-MS/MS analysis

Abstract

Ethanol extracts of different parts of Passiflora cincinnata were obtained by maceration. The total phenolic and flavonoid contents were evaluated. The antioxidant activities were determined by β-carotene-linoleic acid bleaching test, 2,2-diphenyl-1-picrylhydrazil (DPPH), and 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging. The crude ethanol stem extract showed the highest amount of total polyphenols (45.53?mg gallic acid equivalent/g) while the highest total flavonoid contents (1.42?mg of quercetin equivalent/g) were observed in the leaf extract. The lowest IC₅₀ (25.65?μg/ml) by the DPPH method was observed for the stem extract. The ABTS method showed a significant antioxidant activity for all investigated extracts. The secondary metabolite composition of ethanol extracts was assessed by HPLC-DAD-MS/MS analysis, leading to the identification of fourteen secondary metabolites in P. cincinnata extracts. These results showed the potentiality of this species as a source of phenolic compounds and antioxidants.     

Evaluation of the cytotoxicity on breast cancer cell of extracts and compounds isolated from Hyptis pectinata (L.) poit

Abstract

Hyptis pectinata is a herb popularly used in Brazil for the treatment of inflammations, pain, bacterial infections and cancer. In the present study, inflorescences (MPIn), leaves (MPL), branches (MPB), root (MPR) extracts and three compounds isolated from MPIn were assayed against breast tumor cell lines. The structures of the three compounds (pectinolide J, hyptolide and pectinolide E) were determined by means of spectroscopic analysis. Pectinolide J was isolated for the first time. The MPIn, MPL and MPR exhibited specific antiproliferative activity on tumor cell lines when compared to normal cell lines with IC₅₀ of 52.01?±?0.64, 45.91?±?0.02?μg/mL and 82.84?±?0.03?μg/mL, respectively. Although the isolated substances did not present good antiproliferative activity, when the three were associated, a greater biological effect was observed, suggesting a synergistic effect. Hyptolide (5.6?±?0.4?μg/mL) showed IC₅₀ sufficiently low to be considered as a drug prototype.     

Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

Development of Phenothiazine Hybrids with Potential Medicinal Interest: A Review

The molecular hybridization approach has been used to develop compounds with improved efficacy by combining two or more pharmacophores of bioactive scaffolds. In this context, hybridization of various relevant pharmacophores with phenothiazine derivatives has resulted in pertinent compounds with diverse biological activities, interacting with specific or multiple targets. In fact, the development of new drugs or drug candidates based on phenothiazine system has been a promising approach due to the diverse activities associated with this tricyclic system, traditionally present in compounds with antipsychotic, antihistaminic and antimuscarinic effects. Actually, the pharmacological actions of phenothiazine hybrids include promising antibacterial, antifungal, anticancer, anti-inflammatory, antimalarial, analgesic and multi-drug resistance reversal properties. The present review summarizes the progress in the development of phenothiazine hybrids and their biological activity.