Lanthanide-based organic salts: Synthesis, characterization, and cytotoxicity studies

This work was supported by Fundação para a Ciência e a Tecnologia through projects (PEst-C/LA0006/2013, PTCD/CTM-NAN/120658/2010, two contracts under Investigador FCT (L. C. Branco and I. M. Marrucho), a doctoral fellowship Andreia Forte (PD/BD/109625/2015), and by the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/MAR/04292/2020 granted to MARE—Marine and Environmental Sciences Centre and Solchemar company.The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C. The magnetic moments obtained for the Gd(III) salts were, as expected, smaller than those obtained for the Tb(III)-based compounds. The values for Gd(III) and Tb(III) magnetic salts are in the range of 6.55–7.30 MB and 8.22–9.34 MB, respectively. It is important to note a correlation between the magnetic moments obtained for lanthanides, and the structural features of the cation. The cytotoxicity of lanthanide-based salts was also evaluated using 3T3, 293T, Caco2, and HepG2 cells, and it was revealed that most of the prepared compounds are not toxic.info:eu-repo/semantics/publishedVersio

Boosting antimicrobial activity of ciprofloxacin by functionalization of mesoporous silica nanoparticles

Mesoporous silica nanoparticles (MSNs) are very promising nanomaterials for treating bacterial infections when combined with pharmaceutical drugs. Herein, we report the preparation of two nanomaterials based on the immobilization of ciprofloxacin in mesoporous silica nanoparticles, either as the counter-ion of the choline derivative cation (MSN-[Ch][Cip]) or via anchoring on the surface of amino-group modified MSNs via an amide bond (MSN-Cip). Both nanomaterials were characterized by TEM, FTIR and solution 1H NMR spectroscopies, elemental analysis, XRD and N2 adsorption at 77 K in order to provide the desired structures. No cytotoxicity from the prepared mesoporous nanoparticles on 3T3 murine fibroblasts was observed. The antimicrobial activity of the nanomaterials was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Klebsiella pneumoniae) bacteria and the results were promising against S. aureus. In the case of B. subtilis, both nanom aterials exhibited higher antimicrobial activity than the precursor [Ch][Cip], and in the case of K. pneumoniae they exhibited higher activity than neutral ciprofloxacin.info:eu-repo/semantics/publishedVersio

Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

<p>Abstract</p> <p>Background</p> <p>We investigated the effects of the signaling molecules, cyclic AMP (cAMP) and protein-kinase C (PKC), on gap junctional intercellular communication (GJIC) between thymic epithelial cells (TEC).</p> <p>Results</p> <p>Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC.</p> <p>Conclusions</p> <p>Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.</p

Genome and metabolome ms-based mining of a marine strain of Aspergillus affinis

Aspergillus section Circumdati encompasses several species that express both beneficial (e.g., biochemical transformation of steroids and alkaloids, enzymes and metabolites) and harmful compounds (e.g., production of ochratoxin A (OTA)). Given their relevance, it is important to analyze the genetic and metabolic diversity of the species of this section. We sequenced the genome of Aspergillus affinis CMG 70, isolated from sea water, and compared it with the genomes of species from section Circumdati, including A. affinis’s strain type. The A. affinis genome was characterized considering secondary metabolites biosynthetic gene clusters (BGCs), carbohydrate-active enzymes (CAZymes), and transporters. To uncover the biosynthetic potential of A. affinis CMG 70, an untargeted metabolomics (LC-MS/MS) approach was used. Cultivating the fungus in the presence and absence of sea salt showed that A. affinis CMG 70 metabolite profiles are salt dependent. Analyses of the methanolic crude extract revealed the presence of both unknown and well-known Aspergillus compounds, such as ochratoxin A, anti-viral (e.g., 3,5-Di-tert-butyl-4-hydroxybenzoic acid and epigallocatechin), anti-bacterial (e.g., 3-Hydroxybenzyl alcohol, L-pyroglutamic acid, lecanoric acid), antifungal (e.g., L-pyroglutamic acid, 9,12,13-Trihydroxyoctadec-10-enoic acid, hydroxyferulic acid), and chemotherapeutic (e.g., daunomycinone, mitoxantrone) related metabolites. Comparative analysis of 17 genomes from 16 Aspergillus species revealed abundant CAZymes (568 per species), secondary metabolite BGCs (73 per species), and transporters (1359 per species). Some BGCs are highly conserved in this section (e.g., pyranonigrin E and UNII-YC2Q1O94PT (ACR toxin I)), while others are incomplete or completely lost among species (e.g., bikaverin and chaetoglobosins were found exclusively in series Sclerotiorum, while asperlactone seemed completely lost). The results of this study, including genome analysis and metabolome characterization, emphasize the molecular diversity of A. affinis CMG 70, as well as of other species in the section Circumdati.SUPPLEMENTARY MATERIAL : Table S1: Gene annotation, Table S2: Carbohydrate active enzymes prediction, Table S3: Secreted proteins, Table S4: Transporter’s prediction, Table S5: Biosynthetic Gene Clusters, Table S6: Summary of genomic features of Circumdati genomes, Table S7: Comparison of CAZymes families between A. affinis CMG 70 and ATCC MYA-4773, Table S8: Full list of compounds, Table S9: List of the significantly differential compounds, File S1: matched spectral library compounds.The authors acknowledge financial support from the Portuguese Foundation for Science and Technology (FCT) to CESAM (UIDB/50017/2020+UIDP/50017/2020), Marta Tacão (CEECIND/00977/2020) and the PhD grants of M. Gonçalves (SFRH/BD/129020/2017) and S. Hilário (SFRH/BD/137394/2018).https://www.mdpi.com/journal/jofam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Exploring the correlations between epi indicators of COVID-19 and the concentration of pharmaceutical compounds in Wastewater Treatment Plants in Northern Portugal

The COVID-19 pandemic caused by the SARS-CoV-2 virus led to changes in the lifestyle and human behaviour, which resulted in different consumption patterns of some classes of pharmaceuticals including curative, symptom-relieving, and psychotropic drugs. The trends in the consumption of these compounds are related to their concentrations in wastewater systems, since incompletely metabolised drugs (or their metabolites back transformed into the parental form) may be detected and quantified by analytical methods. Pharmaceuticals are highly recalcitrant compounds and conventional activated sludge processes implemented in wastewater treatment plants (WWTP) are ineffective at degrading these substances. As a results, these compounds end up in waterways or accumulate in the sludge, being a serious concern given their potential effects on ecosystems and public health. Therefore, it is crucial to evaluate the presence of pharmaceuticals in water and sludge to assist in the search for more effective processes. In this work, eight pharmaceuticals from five therapeutic classes were analysed in wastewater and sludge samples collected in two WWTP located in the Northern Portugal, during the third COVID-19 epidemic wave in Portugal. The two WWTP demonstrated a similar pattern with respect to the concentration levels in that period. However, the drugs loads reaching each WWTP were dissimilar when normalising the concentrations to the inlet flow rate. Acetaminophen (ACET) was the compound detected at highest concentrations in aqueous samples of both WWTP (98. 516 g L1 in WWTP2 and 123. 506 g L1in WWTP1), indicating that this drug is extensively used without the need of a prescription, known of general public knowledge as an antipyretic and analgesic agent to treat pain and fever. The concentrations determined in the sludge samples were below 1.65 µg g1 in both WWTP, the highest value being found for azithromycin (AZT). This result may be justified by the physico-chemical characteristics of the compound that favour its adsorption to the sludge surface through ionic interactions. It was not possible to establish a clear relationship between the incidence of COVID-19 cases in the sewer catchment and the concentration of drugs detected in the same period. However, looking at the data obtained, the high incidence of COVID-19 in January 2021 is in line with the high concentration of drugs detected in the aqueous and sludge samples but prediction of drug load from viral load data was unfeasible.This study was supported by the Competitiveness and Internationalisation Operational Programme, Lisbon Regional Operational Programme and Algarve Regional Operational Programme with the support of FEDER, through the Incentive Scheme: research and development activities and investment in testing and optimisation (upscaling) infrastructures in the context of COVID-19, through the Project “SARS CONTROL: Evaluation of the impacts of SARS-CoV-2 on the urban water cycle and the downstream effects on Public Health" (Ref. 070076). Acknowledge is also due to the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS – Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020. Strategic funding from FCT to cE3c and BioISI Research Units (UIDB/00329/2020 and UIDB/04046/2020) and to the Associate Laboratory CHANGE (LA/P/0121/2020) is also gratefully acknowledged. ARS holds an FCT grant SFRH/BD/131905/2017 and COVID/BD/151951/2021.ARLR and MFRP acknowledge the financial support from LA/P/0045/2020 (ALiCE), UIDB/50020/2020 and UIDP/50020/2020 (LSRE-LCM), funded by national funds through FCT/MCTES (PIDDAC). ARLR acknowledges FCT funding under DL57/2016 Transitory Norm Programme.info:eu-repo/semantics/publishedVersio

Is the air we breathe while sleeping conditioning our sleep quality?

Human exposure to air pollution: high variability of air pollutants concentration within a city; people spend more than 90% of their time in indoor environments; high variability of patterns of spaces’ occupation within the population. What do we know now? Sleep has a vital role in human welfare; low ventilation rates; breathing area closer to potential sources of pollutants; lack of studies about exposure during sleep. Why sleep matters – the economic costs of insufficient sleep: sleep has an overall impact on the countries’ richness; lower productivity levels and higher mortality risks related to insufficient sleep can result in substantial economic losses to modern economies; insufficient sleep among its populations cost the 5 OECD countries under consideration (USA, UK, Japan, Germany and Canada) up to $680 billion of economic output lost every year. The aim of this study: Do indoor air quality influences sleep quality?info:eu-repo/semantics/publishedVersio

Impacto da qualidade do ar interior nos parâmetros cardiorrespiratórios durante o sono

Projeto IPL/2017/E2SLEEP/ESTeSL/711030Os efeitos da poluição ambiental na saúde estão amplamente documentados, havendo evidências dos efeitos a longo e a curto prazo que se relacionam com maiores taxas de morbilidade e mortalidade, principalmente de causa cardiovascular e respiratória. No entanto, as evidências sobre os efeitos da qualidade do ar interior (QAI) no sono são ainda limitadas. Durante o sono NREM e REM existem diferentes mediadores ao nível da função autonómica, podendo conduzir a características distintas ao nível da frequência cardíaca (FC), respiratória (FR) e pressão arterial. O presente estudo tem o objetivo de avaliar a existência de correlações entre determinados parâmetros cardiorrespiratórios durante o sono e a QAI.info:eu-repo/semantics/publishedVersio

Será a estrutura do sono vulnerável a contaminantes microbiológicos do ar interior?

Projeto IPL/2017/E2SLEEP/ESTeSL/711030Os humanos passam um terço da sua vida a dormir, sendo do conhecimento geral que o sono desempenha um papel fundamental no bem-estar e desempenho físico e cognitivo. Nas últimas décadas, o estudo do impacto da qualidade do ar interior (QAI) na saúde dos ocupantes tem aumentado significativamente, porém, a investigação nesta área tem sido direcionada principalmente para microambientes onde os indivíduos realizam as suas atividades durante o dia. Apesar de limitadas, existem algumas evidências relacionadas com o impacto da QAI nalguns parâmetros do sono, no entanto, estudos com uma caracterização abrangente dos contaminantes ambientais, nomeadamente microbiológicos, são ainda inexistentes. O presente trabalho tem o objetivo de avaliar os efeitos da exposição microbiológica na estrutura do sono.info:eu-repo/semantics/publishedVersio

Impacto da qualidade do ar interior nos parâmetros cardiorrespiratórios durante o sono

Projeto IPL/2017/E2SLEEP/ESTeSL/711030Os efeitos da poluição ambiental na saúde estão amplamente documentados, havendo evidências dos efeitos a longo e a curto prazo que se relacionam com maiores taxas de morbilidade e mortalidade, principalmente de causa cardiovascular e respiratória. No entanto, as evidências sobre os efeitos da qualidade do ar interior (QAI) no sono são ainda limitadas. Durante o sono NREM e REM existem diferentes mediadores ao nível da função autonómica, podendo conduzir a características distintas ao nível da frequência cardíaca (FC), respiratória (FR) e pressão arterial. O presente estudo tem o objetivo de avaliar a existência de correlações entre determinados parâmetros cardiorrespiratórios durante o sono e a QAI.info:eu-repo/semantics/publishedVersio

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs)1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in Sao Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.Brazilian Ministry of HealthUniv Fed Rio de Janeiro, Lab Virol Mol, Dept Genet IB, Rio De Janeiro, RJ, BrazilFdn Med Trop Amazonas, Manaus, Amazonas, BrazilLAPI Univ Fed Bahia, Hosp Univ Prof Edgar Santos, Lab Pesquisa, Salvador, BA, BrazilLab Cent Saude Publ Ceara Lacen CE, Fortaleza, Ceara, BrazilLab Cent Saude Publ Dist Fed, Setor Grandes Areas Norte SGAN 601, Brasilia, DF, BrazilUniv Fed Minas Gerais UFMG, Fac Med, Lab Imunol & Biol Mol DIP, Belo Horizonte, MG, BrazilLab Cent Saude Publ Mato Grosso Sul, Campo Grande, MS, BrazilLab Cent Saude Publ Pernambuco, Recife, PE, BrazilLab Municipal Curitiba, Curitiba, PR, BrazilFiocruz MS, Lab AIDS & Imunol Mol, Dept Imunol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Carga Viral, Rio de Janeiro, RJ, BrazilInst Biol Exercito, Rio De Janeiro, RJ, BrazilLab Cent Saude Publ Rio Grande Sul, Porto Alegre, RS, BrazilLab Hosp Nossa Senhora Conceicao, Porto Alegre, RS, BrazilLab Cent Saude Publ Santa Catarina, Florianopolis, SC, BrazilUNESP, Lab Biol Mol Hemocentro Botucatu, Fac Med, Botucatu, SP, BrazilUniv Estadual Campinas, Lab Pesquisa AIDS, Hosp Clin, Campinas, SP, BrazilInst Adolfo Lutz Sao Jose do Rio Preto, Lab Biol Mol, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilInst Adolfo Lutz Cent, Lab Retrovirus, Ctr Virol, Nucleo Doencas Sanguineas & Sexuais, Sao Paulo, SP, BrazilMinist Saude, Dept Vigilancia Prevencao & Controle DST AIDS & H, Setor Adm Fed Sul SAFS 02, Secretaria Vigilancia Saude, Brasilia, DF, BrazilUniv Brasilia, Programa Pos Grad Saude Colet, Fac Med, Fac Ciencias Saude, Brasilia, DF, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilBMH: TC 298/12Web of Scienc