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1.
J Sci Food Agric ; 104(11): 6541-6552, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38520251

RESUMEN

BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 µmol m-2 s-1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Asunto(s)
Bagres , Lactuca , Luz , Hojas de la Planta , Animales , Humanos , Bagres/crecimiento & desarrollo , Bagres/metabolismo , Lactuca/crecimiento & desarrollo , Lactuca/química , Lactuca/efectos de la radiación , Lactuca/metabolismo , Hojas de la Planta/química , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Hojas de la Planta/efectos de la radiación , Células CACO-2 , Antioxidantes/metabolismo , Antioxidantes/análisis , Fenoles/metabolismo , Fenoles/análisis
2.
Hum Psychopharmacol ; 32(3)2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28635119

RESUMEN

OBJECTIVE: This paper describes the misrepresentation of LSD at Portugal's Boom Festival 2014 and the prevention of unintentional consumption of DOx and 25x-NBOMe among LSD consumers attending a drug-checking service. METHODS: Two hundred forty-five drug samples expected to contain LSD were submitted to the drug-checking service for chemical analysis. One hundred ten post-test questionnaires were successfully matched with test results. RESULTS: About 67.3% of the alleged LSD samples tested contained only LSD; 0.8% contained LSD combined with adulterants; 24.1% did not contain LSD but did contain another psychoactive substance, including 11.4% that were 2,5-dimethoxyamphetamine derivatives and 9.8% that were N-benzyl-2,5-dimethoxyphenethylamine derivatives; and no psychoactive substance was detected in 7.8%. The majority of service users who received unexpected test results regarding their alleged LSD (74.2%) reported that they did not intend to consume the drug. Following dissemination of alerts on day 2, a larger than expected proportion of all tests conducted were for LSD, when comparing the 2014 festival to 2012, where no such alert was disseminated. CONCLUSIONS: Although these results support the provision of integrated drug-checking services in party settings, evidence of their utility and effectiveness would be improved through future research incorporating more robust measures of outcomes following provision of drug-checking results.


Asunto(s)
Anfetaminas/análisis , Alucinógenos/análisis , Vacaciones y Feriados , Drogas Ilícitas/análisis , Dietilamida del Ácido Lisérgico/análisis , Detección de Abuso de Sustancias/métodos , Anfetaminas/efectos adversos , Contaminación de Medicamentos/prevención & control , Alucinógenos/efectos adversos , Humanos , Drogas Ilícitas/efectos adversos , Dietilamida del Ácido Lisérgico/efectos adversos , Portugal/epidemiología , Detección de Abuso de Sustancias/normas
3.
Traffic ; 15(10): 1066-82, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24992508

RESUMEN

Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (PIKfyve) that converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2 ] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.


Asunto(s)
Hígado/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Plasmodium berghei/patogenicidad , Animales , Línea Celular Tumoral , Endocitosis , Hígado/parasitología , Ratones , Carga de Parásitos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Plasmodium berghei/fisiología , Transporte de Proteínas , Canales de Potencial de Receptor Transitorio/metabolismo
4.
Membranes (Basel) ; 14(7)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39057665

RESUMEN

The ability to predict the rate of permeation of new compounds across biological membranes is of high importance for their success as drugs, as it determines their efficacy, pharmacokinetics, and safety profile. In vitro permeability assays using Caco-2 monolayers are commonly employed to assess permeability across the intestinal epithelium, with an extensive number of apparent permeability coefficient (Papp) values available in the literature and a significant fraction collected in databases. The compilation of these Papp values for large datasets allows for the application of artificial intelligence tools for establishing quantitative structure-permeability relationships (QSPRs) to predict the permeability of new compounds from their structural properties. One of the main challenges that hinders the development of accurate predictions is the existence of multiple Papp values for the same compound, mostly caused by differences in the experimental protocols employed. This review addresses the magnitude of the variability within and between laboratories to interpret its impact on QSPR modelling, systematically and quantitatively assessing the most common sources of variability. This review emphasizes the importance of compiling consistent Papp data and suggests strategies that may be used to obtain such data, contributing to the establishment of robust QSPRs with enhanced predictive power.

5.
Plants (Basel) ; 13(3)2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38337960

RESUMEN

Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel's salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.

6.
Sci Immunol ; 8(85): eadd4817, 2023 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-37418548

RESUMEN

Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8+ T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.


Asunto(s)
Linfocitos T CD8-positivos , Melanoma , Humanos , Ratones , Animales , Reprogramación Celular , Células Dendríticas , Antígenos de Neoplasias , Melanoma/terapia , Melanoma/metabolismo
7.
Foods ; 11(19)2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36230011

RESUMEN

Absorption at the intestinal epithelium is a major determinant of cholesterol levels in the organism, influencing the entry of dietary cholesterol and the excretion of endogenous cholesterol. Several strategies are currently being followed to reduce cholesterol absorption, using both pharmacological agents or food ingredients with hypocholesterolemic properties. Coffee has recently been shown to affect cholesterol bioaccessibility, although it has not been shown if this translates into a decrease on cholesterol bioavailability. In this work, coffee obtained with different commercial roasting (light and dark) and grinding (finer and coarser) was evaluated regarding their effect on cholesterol absorption through Caco-2 monolayers, mimicking the intestinal epithelium. The fluorescent dehydroergosterol was used as a sterol model, which was shown to permeate Caco-2 monolayers with a low-to-moderate permeability coefficient depending on its concentration. In the presence of coffee extracts, a 50% decrease of the sterol permeability coefficient was observed, showing their potential to affect sterol bioavailability. This was attributed to an increased sterol precipitation and its deposition on the apical epithelial surface. A higher hypocholesterolemic effect was observed for the dark roasting and finer grinding, showing that the modulation of these technological processing parameters may produce coffees with optimized hypocholesterolemic activity.

8.
Sci Immunol ; 7(69): eabg5539, 2022 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-35245086

RESUMEN

Type 1 conventional dendritic cells (cDC1s) are rare immune cells critical for the induction of antigen-specific cytotoxic CD8+ T cells, although the genetic program driving human cDC1 specification remains largely unexplored. We previously identified PU.1, IRF8, and BATF3 transcription factors as sufficient to induce cDC1 fate in mouse fibroblasts, but reprogramming of human somatic cells was limited by low efficiency. Here, we investigated single-cell transcriptional dynamics during human cDC1 reprogramming. Human induced cDC1s (hiDC1s) generated from embryonic fibroblasts gradually acquired a global cDC1 transcriptional profile and expressed antigen presentation signatures, whereas other DC subsets were not induced at the single-cell level during the reprogramming process. We extracted gene modules associated with successful reprogramming and identified inflammatory signaling and the cDC1-inducing transcription factor network as key drivers of the process. Combining IFN-γ, IFN-ß, and TNF-α with constitutive expression of cDC1-inducing transcription factors led to improvement of reprogramming efficiency by 190-fold. hiDC1s engulfed dead cells, secreted inflammatory cytokines, and performed antigen cross-presentation, key cDC1 functions. This approach allowed efficient hiDC1 generation from adult fibroblasts and mesenchymal stromal cells. Mechanistically, PU.1 showed dominant and independent chromatin targeting at early phases of reprogramming, recruiting IRF8 and BATF3 to shared binding sites. The cooperative binding at open enhancers and promoters led to silencing of fibroblast genes and activation of a cDC1 program. These findings provide mechanistic insights into human cDC1 specification and reprogramming and represent a platform for generating patient-tailored cDC1s, a long-sought DC subset for vaccination strategies in cancer immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos , Factores Reguladores del Interferón , Animales , Reactividad Cruzada , Células Dendríticas , Humanos , Ratones , Ratones Endogámicos C57BL
9.
Food Res Int ; 157: 111399, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35761653

RESUMEN

Helichrysum italicum (H. italicum) is a halophyte shrub with bright yellow flowers with a strong curry-like aroma. The essential oils of H. italicum have been used in the production of cosmetics and pharmaceuticals, due to their antiallergic and anti-inflammatory properties. In the agri-food sector, H. italicum flowers can be used for seasoning and flavoring food, and as natural food preservatives. Here, we report on the composition, bioactive compounds, and nutritive value of H. italicum flowers. Flowers were mainly composed of carbohydrates (>80 % dry weight), followed by minerals (6.31 ± 0.95 % dw), protein (5.44 ± 0.35 % dw), and lipids (3.59 % ± 0.53 % dw). High percentages of Fe, Zn, Ca, and K were found in the flower material, along with a high content in antioxidants, polyphenols, and carotenoids, as corroborated by the nuclear magnetic resonance (NMR) data. Flowers were mainly composed of saturated fatty acids (SFAs) (54.50 ± 0.95 % of total FA), followed by polyunsaturated fatty acids (PUFAs) (37.73 ± 1.25 % of total FA) and monounsaturated fatty acids (MUFAs) (7.77 ± 0.34 %), as detected by gas chromatography mass spectrometry (GC-MS). The omega-6 PUFA linoleic acid (22.55 ± 0.76 % of total FA) was the most abundant fatty acid found. Flower extracts showed antimicrobial activity against Saccharomyces cerevisiae and Komagataella phaffii, as well as against Gram-negative (Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus) bacteria. H. italicum flower material was nontoxic to human intestinal Caco-2 model cells at concentrations up to 1.0 % w/v.


Asunto(s)
Helichrysum , Aceites Volátiles , Células CACO-2 , Flores/química , Helichrysum/química , Humanos , Valor Nutritivo , Aceites Volátiles/química
10.
Environ Sci Pollut Res Int ; 28(47): 67256-67266, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34247356

RESUMEN

Contributing to the human health risk assessment, the present study aims to evaluate the ability of paralytic shellfish toxins (PSTs) to cross the human intestinal epithelium by using the Caco-2 permeability assay. A crude extract prepared from the PST producer dinoflagellate Gymnodinium catenatum strain, GCAT1_L2_16, and the PST analogue gonyautoxin-5 (GTX-5) prepared from a certified reference material (CRM) were tested. In the conditions of the assay, none of the compounds altered Caco-2 viability, or the integrity of cell monolayers. The GTX-5 apparent permeability coefficients are 0.9×10-7 and 0.6×10-7 cm s-1 for the crude extract and CRM, respectively, thus, <10-6 cm s-1, which indicates that humans absorb this PST analogue poorly. The present study also reveals that, during a 90-min exposure, GTX-5 is not metabolised to a high extent by Caco-2 or retained in the Caco-2 cytoplasm. Since it is known that GTX-5 can be found in the spleen, liver or kidney of the victims, as well as in the urine samples of patients who consumed contaminated seafood, further research is needed to clarify the transport mechanisms involved, permeation time and dose-dependence, and the possible role of intestinal microflora.


Asunto(s)
Dinoflagelados , Toxinas Biológicas , Células CACO-2 , Humanos , Absorción Intestinal , Mariscos/análisis
11.
Pharmaceutics ; 13(10)2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34683857

RESUMEN

Caco-2 monolayers are a common in vitro model used to evaluate human intestinal absorption. The reference protocol requires 21 days post-seeding to establish a stable and confluent cell monolayer, which is used in a single permeability assay during the period of monolayer stability (up to day 30). In this work, we characterize variations in the tightness of the cell monolayer over the stable time interval and evaluate the conditions required for their re-use in permeability assays. The monolayer integrity was assessed through TEER measurements and permeability of the paracellular marker Lucifer Yellow (LY), complemented with nuclei and ZO-1 staining for morphological studies and the presence of tight junctions. Over 150 permeability assays were performed, which showed that manipulation of the cell monolayer in the permeability assay may contribute significantly to the flux of LY, leading to Papp values that are dependent on the sampling duration. The assay also leads to a small decrease in the cell monolayer TEER, which is fully recovered when cell monolayers are incubated with culture media for two full days. When this procedure is followed, the cell monolayers may be used for permeability assays on days 22, 25, and 28, triplicating the throughput of this important assay.

12.
Food Chem ; 345: 128732, 2021 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-33341558

RESUMEN

Edible wild plants are part of the ethnobotanical and gastronomic heritage of different geographical areas. Corema album (L.) D. Don is an endemic species of the dune systems of the Atlantic coast of the Iberian Peninsula. The aerial parts of Corema album are a source of nutrients and antioxidants. The Corema album white berry (Portuguese crowberry) is rich in calcium, iron, and zinc. The plant also shows high phenolic content and antioxidant capacity associated with the leaves, fruit, and flowers. The presence of organic acids, namely phenolic acids, such as hydroxycinnamic acids, and long chain polyunsaturated fatty acids (PUFAs) omega-3 and omega-6 has also been confirmed. Toxicity studies evaluated by cell viability tests with human intestinal epithelium model cells (Caco-2) have shown that, at low concentrations, plant extracts may present beneficial effects.


Asunto(s)
Ericaceae/química , Hidroxibenzoatos/análisis , Minerales/análisis , Plantas Comestibles/química , Antioxidantes/análisis , Células CACO-2 , Frutas/química , Humanos , Extractos Vegetales/toxicidad , Hojas de la Planta/química
13.
Bio Protoc ; 10(10): e3619, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-33659292

RESUMEN

Ectopic expression of transcription factor combinations has been recently demonstrated to reprogram differentiated somatic cells towards the dendritic cell (DC) lineage without reversion to a multipotent state. DCs have the ability to induce potent and long-lasting adaptive immune responses. In particular, conventional type 1 DCs (cDC1s) excel on antigen cross-presentation, a critical step for inducing CD8+ T cell cytotoxic responses. The rarity of naturally occurring cDC1s and lack of in vitro methodologies for the generation of pure cDC1 populations strongly hinders the study of cDC1 lineage specification and function. Here, we describe a protocol for the generation of induced DCs (iDCs) by lentiviral-mediated expression of the transcription factors PU.1, IRF8 and BATF3 in mouse embryonic fibroblasts. iDCs acquire DC morphology, cDC1 phenotype and transcriptional signatures within 9 days. iDCs generated with this protocol acquire functional ability to respond to inflammatory stimuli, engulf dead cells, process and cross-present antigens to CD8+ T cells. DC reprogramming provides a simple and tractable system to generate high numbers of cDC1-like cells for high content screening, opening new avenues to better understand cDC1 specification and function. In the future, faithful induction of cDC1 fate in fibroblasts may lead to the generation of patient-specific DCs for vaccination.

14.
Helicobacter ; 14(6): 559-70, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19889074

RESUMEN

BACKGROUND: Helicobacter pylori cell surface is composed of lipopolysaccharides (LPSs) yielding structures homologous to mammalian Lewis O-chains blood group antigens. These structures are key mediators in the definition of host-microbial interactions and known to change their expression pattern in response to environmental pressure. AIMS: The present work is focused on the identification of new H. pylori cell-surface glycosides. Special attention is further devoted to provide insights on the impact of in vitro subcultivation on H. pylori cell-surface phenotypes. METHODS: Cell-surface glycans from H. pylori NCTC 11637 and two clinical isolates were recovered from the aqueous phase resulting from phenol:water extraction of intact bacteria. They were evaluated in relation to their sugars and glycosidic-linkages composition by CG-MS, size-exclusion chromatography, NMR, and Mass Spectrometry. H. pylori glycan profile was also monitored during subcultivation in vitro in agar and F12 liquid medium. RESULTS: All three studied strains produce LPS expressing Lewis epitopes and express bioaccumulate amylose-like glycans. Bioaccumulation of amylose was found to be enhanced with the subcultivation of the bacterium on agar medium and accompanied by a decrease in the expression of LPS O-chains. In contrast, during exponential growth in F12 liquid medium, an opposite behavior is observed, that is, there is an increase in the overall amount of LPS and decrease in amylose content. CONCLUSIONS: This work shows that under specific environmental conditions, H. pylori expresses a phase-variable cell-surface alpha-(1-->4)-glucose moiety.


Asunto(s)
Amilosa/metabolismo , Helicobacter pylori/metabolismo , Amilosa/química , Infecciones por Helicobacter/microbiología , Helicobacter pylori/química , Humanos , Lipopolisacáridos/metabolismo , Polisacáridos/química , Polisacáridos/metabolismo
15.
Front Immunol ; 10: 2809, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31921109

RESUMEN

Cell reprogramming concepts have been classically developed in the fields of developmental and stem cell biology and are currently being explored for regenerative medicine, given its potential to generate desired cell types for replacement therapy. Cell fate can be experimentally reversed or modified by enforced expression of lineage specific transcription factors leading to pluripotency or attainment of another somatic cell type identity. The possibility to reprogram fibroblasts into induced dendritic cells (DC) competent for antigen presentation creates a paradigm shift for understanding and modulating the immune system with direct cell reprogramming. PU.1, IRF8, and BATF3 were identified as sufficient and necessary to impose DC fate in unrelated cell types, taking advantage of Clec9a, a C-type lectin receptor with restricted expression in conventional DC type 1. The identification of such minimal gene regulatory networks helps to elucidate the molecular mechanisms governing development and lineage heterogeneity along the hematopoietic hierarchy. Furthermore, the generation of patient-tailored reprogrammed immune cells provides new and exciting tools for the expanding field of cancer immunotherapy. Here, we summarize cell reprogramming concepts and experimental approaches, review current knowledge at the intersection of cell reprogramming with hematopoiesis, and propose how cell fate engineering can be merged to immunology, opening new opportunities to understand the immune system in health and disease.


Asunto(s)
Reprogramación Celular/inmunología , Inmunidad , Animales , Células Dendríticas/citología , Células Dendríticas/inmunología , Hematopoyesis , Humanos , Inmunoterapia
16.
Int J Drug Policy ; 73: 88-95, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31398488

RESUMEN

BACKGROUND: Drug checking services are being implemented in recreational settings across the world, however these projects are frequently accused of a lack of evidence concerning their impact on people who use drugs. This paper describes the implementation of a drug checking service at the Boom Festival 2016 and explores the impact of this service on its users' behavioural intentions. METHODS: 753 drug samples were submitted to the drug checking service for chemical analysis. All drug checking users were invited to fill a pre-analysis and a post-analysis questionnaire. 310 pre- and post-analysis questionnaires answered by users of the service were successfully matched. RESULTS: When the test results were "unexpected" (N = 86), 94.3% of the service users reported that they would not to take the drug. When the test result indicated the sample contained "the expected substance plus adulterants" (N = 41) 32% of users stated they would not take it. When the test result was "only the expected substance" (N = 370), as anticipated, 98% of the participants reported they would take it. There was a statistically significant association between users' behavioural intentions and drug-checking result (χ2(2) = 350,042, p < .001). CONCLUSIONS: These results support the hypothesis that providing drug checking services in large-scale festivals helps users to better manage their drug use and deal with drug adulteration. The data corroborates the supposition that when provided with objective information about the content of their drugs, some users consider health protecting behaviours. Additionally, these results can contribute to the design of tailored harm reduction interventions that take into consideration clients' characteristics, profiles and motivations.


Asunto(s)
Contaminación de Medicamentos/prevención & control , Consumidores de Drogas/estadística & datos numéricos , Drogas Ilícitas/análisis , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Femenino , Reducción del Daño , Humanos , Masculino , Persona de Mediana Edad , Música , Portugal , Encuestas y Cuestionarios , Adulto Joven
17.
Colloids Surf B Biointerfaces ; 180: 319-325, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31071572

RESUMEN

Biological systems are the result of the interactions established among their many distinct molecules and molecular assemblies. The high concentration of small molecules dissolved in the aqueous media alter the water properties with important consequences in the interactions established. In this work, the effects of high concentrations of the disaccharide trehalose on the solubility of a homologous series of fluorescent amphiphiles (NBD-Cn, n=4-16) and on their interaction with a lipid bilayer and a serum protein are quantitatively characterized. Both kinetic and equilibrium aspects are reported for a better understanding of the effects observed. The aqueous solubility of the most hydrophobic amphiphiles (n ≥ 8) is strongly increased by 1 M trehalose, while no signifcant effect is observed for the most polar amphiphile (n = 4). This results from a decrease in the magnitude of the hydrophobic effect at molecular crowding conditions. A small decrease is observed on the equilibrium association with serum albumin. This is most significant for amphiphiles with longer alkyl chains, in agreement with their increased solubility in the aqueous media containing trehalose. The effects on the association of the amphiphiles with lipid bilayers are influenced by both equilibrium and kinetic aspects. On the one hand, the decreased magnitude of the hydrophobic effect leads to a decrease in the affinity of the amphiphiles towards the membrane. However, this tendency may be overbalanced by the effects on the kinetics of the interaction (insertion/desorption) due to the increase in the viscosity of the aqueous media. It is shown that the distribution of amphiphilic drugs in the crowded biological media is significantly different from that predicted from studies in dilute solutions and that the effects are dependent on the solute's hydrophobicity.


Asunto(s)
Sustancias Macromoleculares/química , Tensoactivos/química , Animales , Bovinos , Fluorescencia , Calor , Cinética , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Albúmina Sérica Bovina/química , Solubilidad , Agua/química
18.
Sci Immunol ; 3(30)2018 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-30530727

RESUMEN

Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1-like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of DC specification programs and serve as a platform for the development of patient-specific DCs for immunotherapy.


Asunto(s)
Células Presentadoras de Antígenos/inmunología , Fibroblastos/inmunología , Animales , Células Cultivadas , Células HEK293 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos
20.
Nutrition ; 32(7-8): 834-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27036611

RESUMEN

OBJECTIVE: A large body of evidence has confirmed a multitude of health benefits of plant products and their derived formulations. Echinacea purpurea (L.) Moench is a good example, widely used due to its therapeutic properties. In the present study, the chemical composition of the different samples and antioxidant properties of E. purpurea hydroethanolic and aqueous extracts obtained from dry or fresh raw material were evaluated and compared with dietary supplements based on the same plant (tablets and syrup), to determine the most active phytopharmacologic preparation or formulation. METHODS: Chemical composition of the different samples was assessed through the determination of free sugars, organic acids and tocopherols. The in vitro antioxidant properties were determined using four assays: 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals scavenging activity, reducing power, inhibition of b-carotene bleaching and inhibition of lipid peroxidation by thiobarbituric acid reactive substances (TBARS) assay. Total phenolics and flavonoids were also determined. RESULTS: Overall, the hydroethanolic extract of fresh plant revealed the highest activity, directly related with its higher contents in phenolic (229.22 ± 4.38 mg gallic acid equivalent [GAE]/mL), flavonoids (124.83 ± 7.47 mg GAE/mL), organic acids (8.89 ± 0.10 g/100 g), and tocopherols (4.55 ± 0.02 mg/100 g). Tablets followed by syrup revealed the worst effect, positively correlated with the lowest abundance in bioactive molecules. The weak in vitro antioxidant potential of commercial phytopharmacologic formulations could be related to their chemical composition, including the addition of excipients. CONCLUSION: Further studies are necessary to deepen knowledge on this area, namely focusing on in vivo experiments, to establish upcoming guidelines to improve the quality and bioavailability of phytopharmacologic formulations.


Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Echinacea/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Compuestos de Bifenilo , Suplementos Dietéticos , Peroxidación de Lípido/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Picratos , Tocoferoles
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