Pyrazoles as potential modulators of inflammation through the inhibition of COX2 activity and human leukocytes' oxidative burst

The inflammatory process is a complex and tightly regulated cascade of events that involves the production of prostaglandins (PG) by the inducible isoform cyclooxygenase 2 (COX-2) and the production of reactive pro-oxidant species. When the production of these mediators becomes excessive, it can lead to chronic inflammation and associated diseases such as diabetes, rheumatoid arthritis, and cancer. Unfortunately, many existing anti-inflammatory agents are associated with unwanted side effects. Therefore, there is a critical need to discover new and effective compounds that can modulate the inflammatory cascade. In this study, an extensive panel of structurally related pyrazoles holding diverse structures and substitutions were tested in vitro against human COX-2, and ex vivo in human whole blood, through the measurement of prostaglandin E2 (PGE2) production. Their potential inhibitory effect against human leukocytes’ oxidative burst was also studied. The results showed that some of the tested compounds had a significant inhibitory effect on COX2 activity, and pyrazoles 4 and 11 (Figure 1) excelled as the most potent inhibitors, with IC50 < 25 µM. Nonetheless, among the tested compounds only 1 was able to inhibit both the COX-2 activity and the PGE2 production. The tested pyrazoles, namely pyrazole 4, also demonstrated a potential inhibitory effect (IC50 < 5 µM) against human leukocytes’ oxidative burst. These results represent a significant contribution for the design and development of new anti-inflammatory molecules.info:eu-repo/semantics/publishedVersio

Life Design Counseling outcome and process: a case study with an adolescent

This article aims to explore the relationship between clients' narrative transformation and the promotion of vocational decidedness and career maturity in a mid-adolescent case of Life Design Counseling (LDC). To assess LDC outcomes the Vocational Certainty Scale and the Career Maturity Inventory — Form C were used before and after the intervention. To intensively analyze the process of LDC change two measures of narrative change were used: the Innovative Moments Coding System (IMCS), as a measure of innovation emergence, and the Return to the Problem Coding System (RPCS), as a measure of ambivalence towards change. The results show that the three LDC sessions produced a significant change in vocational certainty but not in career maturity. Findings confirm that the process of change, according to the IMCS, is similar to the one observed in previous studies with adults. Implications for future research and practice are discussed.Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and when applicable co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013)University of Lisbon. CICPS

Time dependent clustering of time series

In this work we consider the problem of clustering time series. Contrary to other works on this topic, our main concern is to let the most important observations, for instance the most recent, have a larger weight on the analysis. This is done by defining similarities measures between two time series, based on Pearson's correlation coefficient, which uses the notion of weighted mean and weighted covariance, where the weights increase monotonically with the time. We use these measures, which are metrics between time series, as a similarity or dissimilarity index between the $n$ time series to be clustered. We apply a very well known partitional method, the K-means, with some adaptations to make it able to choose the number of clusters

Evolving biofilm inhibition and eradication in clinical settings through plant-based antibiofilm agents

Background After almost 100 years since evidence of biofilm mode of growth and decades of intensive investigation about their formation, regulatory pathways and mechanisms of antimicrobial tolerance, nowadays there are still no therapeutic solutions to eradicate bacterial biofilms and their biomedical related issues. Purpose This review intends to provide a comprehensive summary of the recent and most relevant published studies on plant-based products, or their isolated compounds with antibiofilm activity mechanisms of action or identified molecular targets against bacterial biofilms. The objective is to offer a new perspective of most recent data for clinical researchers aiming to prevent or eliminate biofilm-associated infections caused by bacterial pathogens. Methods The search was performed considering original research articles published on PubMed, Web of Science and Scopus from 2015 to April 2023, using keywords such as antibiofilm, antivirulence, phytochemicals and plant extracts. Results Over 180 articles were considered for this review with a focus on the priority human pathogens listed by World Health Organization, including Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Inhibition and detachment or dismantling of biofilms formed by these pathogens were found using plant-based extract/products or derivative compounds. Although combination of plant-based products and antibiotics were recorded and discussed, this topic is currently poorly explored and only for a reduced number of bacterial species. Conclusions This review clearly demonstrates that plant-based products or derivative compounds may be a promising therapeutic strategy to eliminate bacterial biofilms and their associated infections. After thoroughly reviewing the vast amount of research carried out over years, it was concluded that plant-based products are mostly able to prevent biofilm formation through inhibition of quorum sensing signals, but also to disrupt mature biofilms developed by multidrug resistant bacteria targeting the biofilm extracellular polymeric substance. Flavonoids and phenolic compounds seemed the most effective against bacterial biofilms.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 and UIDP/04469/2020, and by LABBELS – Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020. The authors also acknowledge FCT for the PhD grant (UI/BD/151243/2021) to Eduarda Silva and for Scientific Employment Stimulus 2017 (CEECIND/01507/2017) provided to Ana Margarida Sousa.info:eu-repo/semantics/publishedVersio

Freeze‑dried Nannochloropsis oceanica biomass protects eicosapentaenoic acid (EPA) from metabolization in the rumen of lambs

Research Areas: Science & Technology ; Other TopicsEicosapentaenoic acid (EPA) from freeze-dried biomass of Nannochloropsis oceanica microalgae resists ruminal biohydrogenation in vitro, but in vivo demonstration is needed. Therefore, the present study was designed to test the rumen protective effects of N. oceanica in lambs. Twenty-eight lambs were assigned to one of four diets: Control (C); and C diets supplemented with: 1.2% Nannochloropsis sp. oil (O); 12.3% spray-dried N. oceanica (SD); or 9.2% N. oceanica (FD), to achieve 3 g EPA /kg dry matter. Lambs were slaughtered after 3 weeks and digestive contents and ruminal wall samples were collected. EPA concentration in the rumen of lambs fed FD was about 50% higher than lambs fed SD or O diets. Nevertheless, the high levels of EPA in cecum and faeces of animals fed N. oceanica biomass, independently of the drying method, suggests that EPA was not completely released and absorbed in the small intestine. Furthermore, supplementation with EPA sources also affected the ruminal biohydrogenation of C18 fatty acids, mitigating the shift from the t10 biohydrogenation pathways to the t11 pathways compared to the Control diet. Overall, our results demonstrate that FD N. oceanica biomass is a natural rumen-protected source of EPA to ruminants.info:eu-repo/semantics/publishedVersio

A study towards drug discovery for the management of type 2 diabetes: Mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2’- and C-4’ of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.This work received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013, and “Programa Operacional Competitividade e Internacionalização” (COMPETE) (POCI-01-0145-FEDER-029241). Thanks are due to University of Aveiro, Instituto Politécnico de Bragança, FCT/ MEC for the financial support to the QOPNA (FCT UID/QUI/ 00062/2013) and CIMO (UID/AGR/00690/2013) research Units through national funds and where applicable co-financed by the FEDER, within the PT2020 Partnership Agreement, and also to the Portuguese NMR Network. Sónia Rocha acknowledges FCT the financial support for the PhD grant (PD/BD/ 145169/2019), in the ambit of “QREN – POPH – Tipologia 4.1 – Formação Avançada”, co-sponsored by Fundo Social Europeu (FSE) and by national funds of Ministério da Ciência, Tecnologia e Ensino Superior (MCTES).info:eu-repo/semantics/publishedVersio

Acetonitrile adducts of tranexamic acid as sensitive ions for quantification at residue levels in human plasma by UHPLC-MS/MS

The quantitative analysis of pharmaceuticals in biomatrices by liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) is often hampered by adduct formation. The use of the molecular ion resulting from solvent adducts for quantification is uncommon, even if formed in high abundance. In this work, we propose the use of a protonated acetonitrile adduct for the quantitative analysis of tranexamic acid (TXA) by LC-MS/MS. The high abundance of the protonated acetonitrile adduct [M + ACN + H]+ was found to be independent of source-dependent parameters and mobile phase composition. The results obtained for TXA analysis in clinical samples were comparable for both [M + ACN + H]+ and [M + H]+ , and no statistically significant differences were observed. The relative stability and structure of the [M + ACN + H]+ ions were also studied by analyzing probable structures from an energetic point of view and by quantum chemical calculations. These findings, and the studied fragmentation pathways, allowed the definition of an acetimidium structure as the best ion to describe the observed acetonitrile protonated adduct of TXA.info:eu-repo/semantics/publishedVersio

Cyclic voltammetric analysis of 2-styrylchromones: Relationship with the antioxidant activity

2-Styrylchromones (2-SC) are a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), whose occurrence in nature has been reported. Recently, several 2-SC derivatives were demonstrated to have antioxidant properties, namely, xanthine oxidase inhibition, hepatoprotection against pro-oxidant agents in cellular and non-cellular systems and scavenging activity against reactive oxygen and reactive nitrogen species (ROS and RNS). Considering these antioxidant properties, it may be hypothesised that the electrochemical redox behaviour of 2-SC contributes significantly to their activity. To test this hypothesis, the electrochemical behaviour of different 2-SC was studied, together with a number of flavonoids with well-known antioxidant activities, by cyclic voltammetry, and the results correlated to their ability to scavenge ROS and RNS. The results obtained showed that 2-SC with a catecholic B-ring have a low oxidation peak potential corresponding to the oxidation of the 30,40-OH (catechol) moiety. The compounds with a phenolic B-ring have a common peak, with oxidation potential values of about +0.4/+0.5 V versus Ag/AgCl, corresponding to the oxidation of the 40-OH. The oxidation of the hydroxyl substituents in the A-ring generated peaks of higher potentials (+0.7/+0.8 V vs Ag/AgCl). The results from the scavenging assays were in agreement with those obtained from the cyclic voltammetry, that is, higher scavenging effects corresponded to lower values of oxidation potentials, with significant correlation coefficients. The values obtained for the studied flavonoids are in accordance with the literature, and reflect their relative antioxidant activity, when compared to the studied 2-SC. Thus, in this family of compounds, oxidation potentials obtained by cyclic voltammetry seem to be applicable as a general indicator of radical scavenging activity.The authors acknowledge FCT and FEDER financial support for the Project POCI/QUI/59284/2004. Ana Gomes acknowledges FCT and FSE her Ph.D. Grant (SFRH/BD/23299/2005)

Purification of mercury-contaminated water using new AM-11 and AM-14 microporous silicates

Water is an essential resource on Earth and the maintenance of its quality led to the incentive of water reuse programmes. Among the most relevant contaminants, mercury is recognized for its toxicity and biomagnifica- tions along the food chain, reason why its removal from aqueous solutions was studied in this essay using two microporous materials for the first time. The ability of a niobium silicate, called AM-11 (Aveiro-Manchester No 11), and of a vanadium silicate, AM-14 (Aveiro-Manchester No 14), were assessed under batch conditions, at fixed temperature and pH. These microporous materials were synthesized and characterized by SEM, PXRD, ICP- OES, TGA and elemental analysis. Because of their excellent ion exchange properties, equilibrium and kinetics assays were performed using only a few mg dm−3 of material. The most relevant two- and three-parameter isotherms were used to fit the experimental data. Langmuir isotherm adjusted better the AM-11 data (deviation of 3.58 %, Radj 2 =0.980, AIC=52.8), predicting a maximum uptake of 161 mg g−1, while the AM-14 data were better fitted by the Temkin model (deviation of 3.92 %, Radj 2 =0.985, AIC=54.2). The kinetic study was per- formed using Elovich, pseudo-first order and pseudo-second order models. The pseudo–second order and Elovich equations provided the best fits for both materials. The Elovich equation achieved a better correlation in the initial branch while the pseudo-second order expression was more efficient for the horizontal branch. The in- traparticle diffusivities of counter ions were also assessed using a kinetic model based on the Nernst-Plank equations. Performance of these two microporous materials to remove mercury has been compared with other sorbents, highlighting their potential as ion exchangerspublishe

Automatic solid-phase extraction by programmable flow injection coupled to chromatographic fluorimetric determination of fluoroquinolones

Fluoroquinolones are broad-spectrum bactericidal agents applied for the treatment of human and veterinary diseases. Their common use and their incorrect disposal foster environmental contamination, namely in water resources, increasing the risk of antimicrobial resistance. Hence, a method based on automatic solid-phase extraction coupled to liquid chromatography and fluorimetric detection is proposed for the determination of fluoroquinolones in environmental waters. For the solid-phase extraction procedure, a commercially available molecularly imprinted polymer targeting fluoroquinolones was trapped inside a flow-through extraction column, integrated into a programmable flow injection system using multisyringe flow injection analysis, where all steps concerning sorbent conditioning, sample loading, matrix removal, and analyte elution were performed under computer control. The eluate resulting from the sample preparation was collected and transferred at-line to chromatographic analysis using a reversed-phase monolithic column coupled to a fluorimetric detector, and isocratic elution with methanol-phosphoric acid (pH 3.0; 5.0 mM) (17.5:82.5, v/v) at a flow rate of 3.5 mL min-1. Sample treatment and chromatographic analysis were performed in tandem, with sample throughput limited by the sample treatment step. Calibration curves based on fluorescence intensity vs. analyte mass were obtained in the range of 10 to 1000 pg for norfloxacin, ciprofloxacin, and enrofloxacin with LOD values of 6-19 ng L-1 for a sample volume of 100 mL, and RSD < 11% at 0.7 ¿g L-1. The method was successfully applied to estuarine river water analysis.info:eu-repo/semantics/publishedVersio