Antioxidant and neuroprotective effects of Hyptis suaveolens,Hyptis pectinata and Hyptis marrubioides in Caenorhabditiselegans

The increasing trend for the use of natural products as sources of pharmacologically active molecules has changed attitudes in the population. Given the existing demand, a credible scientific analysis and validation of the effect of these natural products is necessary. The genus Hyptis Jacq. (Lamiaceae) has about 300 species with wide distribution, among which Hyptis suaveolens, Hyptis pectinata and Hyptis marrubioides (HS, HP, HM, respectively) are used in folk medicine and are commercialized in street markets for treatment of several diseases. This study aims to evaluate the neuroprotective activity, as well as to elucidate some of the cellular mechanisms involved in the pharmacological action of HS/HP/HM plant extracts using Caenorhabditis elegans, as an animal model. For this purpose, we used a C. elegans model of Machado-Joseph disease (MJD), expressing a human mutant ATXN-3 and a C. elegans model of frontotemporal dementia with parkinsonism-17 (FTDP-17), expressing a mutant form of tau protein, and tested ethanolic leaf extracts from HS, HP, and HM. Our data showed that chronic treatment with 1 mg/ mL of HS/HP/HM extracts had a beneficial impact in these diseases since it significantly ameliorated the locomotor defects exhibited by C. elegans. Moreover, with C. elegans model of MJD, the chronic treatment with the Hyptis extracts also increased the animals survival. We observed, in both models, a significant protection against jugloneinduced oxidative damage (by more than 50%), after chronic treatment with these extracts. Using C. elegans reporter strains we also observed a higher induction of gst-4, in HS/HP/HM extract-treated animals upon exposure to oxidative damage. Our findings support an antioxidant and neuroprotective activity of HS, HP e HM, suggesting the activating specific antioxidant enzymes like gst-4.This work was supported by national funds from FCT—Portuguese Foundation for Science and Technology, under the projects PTDC/AGR-ALI/105169/2008, PEst-OE/AGR/UI4033/2014, and INTERACT—ISAC project, no. NORTE-01-0145-FEDER-000017, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020).info:eu-repo/semantics/publishedVersio

Impact of Different Trace Elements on the Growth and Proteome of Two Strains of Granulicella, Class “Acidobacteriia”

Acidobacteria represents one of the most dominant bacterial groups across diverse ecosystems. However, insight into their ecology and physiology has been hampered by difficulties in cultivating members of this phylum. Previous cultivation efforts have suggested an important role of trace elements for the proliferation of Acidobacteria, however, the impact of these metals on their growth and metabolism is not known. In order to gain insight into this relationship, we evaluated the effect of trace element solution SL10 on the growth of two strains (5B5 and WH15) of Acidobacteria belonging to the genus Granulicella and studied the proteomic responses to manganese (Mn). Granulicella species had highest growth with the addition of Mn, as well as higher tolerance to this metal compared to seven other metal salts. Variations in tolerance to metal salt concentrations suggests that Granulicella sp. strains possess different mechanisms to deal with metal ion homeostasis and stress. Furthermore, Granulicella sp. 5B5 might be more adapted to survive in an environment with higher concentration of several metal ions when compared to Granulicella sp. WH15. The proteomic profiles of both strains indicated that Mn was more important in enhancing enzymatic activity than to protein expression regulation. In the genomic analyses, we did not find the most common transcriptional regulation of Mn homeostasis, but we found candidate transporters that could be potentially involved in Mn homeostasis for Granulicella species. The presence of such transporters might be involved in tolerance to higher Mn concentrations, improving the adaptability of bacteria to metal enriched environments, such as the decaying wood-rich Mn environment from which these two Granulicella strains were isolated

Fluorescence studies on new potential antitumoral 1,3-diarylurea derivatives of thieno[3,2-b]pyridines in solution and in nanoliposomes

This work was supported by Fundação para a Ciência e a Tecnologia (Portugal), QREN and FEDER through CFUM, CQ/UM and Project PTDC/QUI/81238/2006 cofinanced by FCT and program FEDER/COMPETE (FCOMP-01-0124-FEDER-007467)

Long-term stability of a non-adapted aerobic granular sludge process treating fish canning wastewater associated to EPS producers in the core microbiome

The tolerance of aerobic granular sludge (AGS) to variable wastewater composition is perceived as one of its greatest advantages compared to other aerobic processes. However, research studies select optimal operational conditions for evaluating AGS performance, such as the use of pre-adapted biomass and the control of wastewater composition. In this study, non-adapted granular sludge was used to treat fish canning wastewater presenting highly variable organic, nutrient and salt levels over a period of ca. 8 months. Despite salt levels up to 14 g NaCl L−1, the organic loading rate (OLR) was found to be the main factor driving AGS performance. Throughout the first months of operation, the OLR was generally lower than 1.2 kg COD m−3 day−1, resulting in stable nitrification and low COD and phosphorous levels at the outlet. An increase in OLR up to 2.3 kg COD m−3 day−1 disturbed nitrification and COD and phosphate removal, but a decrease to average values between 1 and 1.6 kg COD m−3 day−1 led to resuming of those processes. Most of the bacteria present in the AGS core microbiome were associated to extracellular polymeric substances (EPS) production, such as Thauera and Paracoccus, which increased during the higher OLR period. Ammonium-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) species were detected in AGS biomass; while AOB were identified throughout the operation, NOB were no further identified after the period of increased OLR. Different polyphosphate-accumulating organisms (PAOs) were detected along the process: Candidatus Accumulibacter, Tetrasphaera and Gemmatimonas. A non-adapted granular sludge was able to treat the fish canning wastewater and to tolerate salinity fluctuations up to 14 g L−1. Overall, a high microbial diversity associated to EPS producers allowed to preserve bacterial groups responsible for nutrients removal, contributing to the adaptation and long-term stability of the AGS system.info:eu-repo/semantics/publishedVersio

Indirect evidence of microbial modulation induced by encapsulated A. muciniphila

info:eu-repo/semantics/publishedVersio

The budget of carbon in the farming of the Amazon river prawn and tambaqui fish in earthen pond monoculture and integrated multitrophic systems

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In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure

This article belongs to the Special Issue Toxicity of Nanomaterials and Legacy Contaminants: Risks to the Environment and Human Health.Considering the increasing emergence of new contaminants, such as nanomaterials, mixing with legacy contaminants, including metal(loid)s, it becomes imperative to understand the toxic profile resulting from these interactions. This work aimed at assessing and comparing the individual and combined hepatotoxic and neurotoxic potential of titanium dioxide nanoparticles (TiO2NPs 0.75-75 mg/L), cerium oxide nanoparticles (CeO2NPs 0.075-10 μg/L), arsenic (As 0.01-2.5 mg/L), and mercury (Hg 0.5-100 mg/L) on human hepatoma (HepG2) and neuroblastoma (SH-SY5Y) cells. Viability was assessed through WST-1 (24 h) and clonogenic (7 days) assays and it was affected in a dose-, time- and cell-dependent manner. Higher concentrations caused greater toxicity, while prolonged exposure caused inhibition of cell proliferation, even at low concentrations, for both cell lines. Cell cycle progression, explored by flow cytometry 24 h post-exposure, revealed that TiO2NPs, As and Hg but not CeO2NPs, changed the profiles of SH-SY5Y and HepG2 cells in a dose-dependent manner, and that the cell cycle was, overall, more affected by exposure to mixtures. Exposure to binary mixtures revealed either potentiation or antagonistic effects depending on the composition, cell type and time of exposure. These findings prove that joint toxicity of contaminants cannot be disregarded and must be further explored.This research was funded by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia in the framework of the project POCI-01-0145-FEDER-029651. This work was also financed by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of projects UIDB/04750/2020 and LA/P/0064/2020. This work was also developed within the scope of the project CICECO- Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC). A.T. Reis thanks the financial support of FCT through individual Grant SFRH/BPD/122112/2016. C.B. Lopes and A.C. Estrada acknowledge their research position funded by national funds (OE), through FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19.info:eu-repo/semantics/publishedVersio

Synthesis, molecular Docking and biological evaluation of new 1-Aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenylureas as Potent Type II VEGFR-2 Tyrosine Kinase inhibitors

The vascular endothelial growth factor receptor 2 (VEGFR-2) is a tyrosine kinase receptor, expressed primarily in endothelial cells, and is activated by the specific binding of VEGF to the VEGFR-2 extracellular regulatory domain. Once activated, VEGFR-2 undergoes autophosphorylation, triggering signaling pathways leading to endothelial cell proliferation and subsequent angiogenesisY1 Small molecules may act as inhibitors by competing for the ATP-binding s'1te of the VEGFR-2 intracellular tyrosine kinase domain, thereby preventing the intracellular signa ling that leads to angiogenesis. [ZJ Here, we present the synthesis of new 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas la-c, as potent type 11 VEGFR-2 inhibitors based on molecular docking (Figure A) and biological evaluation including enzymatic assays using the VEGFR-2 tyrosine kinase domain (ICso=l0-28 nM) and studies in human umbilical vein endothelial cells (HUVECs). The latter included cell viability (MTS), proliferation (BrdU) and Western blot for total and phosphorylated VEGFR-2 (Figure B). The predicted docked poses were analyzed in detail and a plausible explanation for compounds 1 potency was obtained base9 on the simultaneous presence of a S-linker and the arylurea moiety in the meta position as a new substitution pattern for the type 11 VEGFR-2 inhibitors. These chemical features place the thieno[3,2-b]pyridine and the terminal aryl ring in close superimposition to a pyrrolo[3,2-d]pyrimidine derivative. The presence of hydrofobic substituents (F and Me) in the terminal aryl ring is also important. For these compounds a significant inhibition in HUVECs proliferation upon VEGF stimulation was observed at low concentrations (0.5-1.0 IJ.M) without affecting cell viability. Westernblot analysis demonstrated that compounds 1 significantly the inhibited VEGFR-2 phosphorylation at 1.0 jlM, thus confirming their anti-angiogenic potential

Tensile strain hardening of a metakaolin based fibre reinforced composite

Portland cement concrete is the most used building material in the world. However, its manufacture is energy-intensive and it is susceptible to harsh environments. Alternative binder systems without ordinary Portland cement, such as geopolymers or alkali-activated materials, are recently new in the Civil Engineered world. These alternative binder systems seek, among other characteristics, improved durability and environmental efficiency. The attaining of strain hardening and multiple cracking typical of Strain Hardening Cementitious Composites (SHCC) using these alternative binder systems is very attractive from a conceptual point of view, since additional endurance to certain harsh or extreme environments, as well as enhanced durability, are usually expected as two of the main outcomes. In the present work, the behaviour of two different composites was studied: an existing Engineered Cementitious Composite (ECC) and a new composite based on an alternative binder prepared with metakaolin. Polyvinyl alcohol (PVA) fibres were used in both materials. A series of experiments, including compressive and direct tensile testing were carried out to characterize and compare the mechanical properties of both materials. The results showed that the alternative binder composite, when subjected to uniaxial tension, developed multiple cracks at steadily increasing tensile stress and strain, which is also typical of ECCs showing strain hardening behaviour. The development of fibre reinforced geopolymer or alkali-activated materials showing strain hardening ability in tension may still be considered as a novel research topic, with great potential for creating new and interesting developments for Civil Engineering and structural applications, particularly the ones subjected to harsh environments