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Carbohydrates comprise the largest fraction of most diets and exert a profound impact on health. Components such as simple sugars and starch supply energy, while indigestible components, deemed dietary fiber, reach the colon to provide food for the tens of trillions of microbes that make up the gut microbiota. The interactions between dietary carbohydrates, our gastrointestinal tracts, the gut microbiome and host health are dictated by their structures. However, current methods for analysis of food glycans lack the sensitivity, specificity and throughput needed to quantify and elucidate these myriad structures. This protocol describes a multi-glycomic approach to food carbohydrate analysis in which the analyte might be any food item or biological material such as fecal and cecal samples. The carbohydrates are extracted by ethanol precipitation, and the resulting samples are subjected to rapid-throughput liquid chromatography (LC)-tandem mass spectrometry (LC-MS/MS) methods. Quantitative analyses of monosaccharides, glycosidic linkages, polysaccharides and alcohol-soluble carbohydrates are performed in 96-well plates at the milligram scale to reduce the biomass of sample required and enhance throughput. Detailed stepwise processes for sample preparation, LC-MS/MS and data analysis are provided. We illustrate the application of the protocol to a diverse set of foods as well as different apple cultivars and various fermented foods. Furthermore, we show the utility of these methods in elucidating glycan-microbe interactions in germ-free and colonized mice. These methods provide a framework for elucidating relationships between dietary fiber, the gut microbiome and human physiology. These structures will further guide nutritional and clinical feeding studies that enhance our understanding of the role of diet in nutrition and health.
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Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.
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Microbioma Gastrointestinal , Desnutrición , Microbiota , Prevotella , Animales , Ratones , Microbioma Gastrointestinal/genética , Aumento de PesoRESUMEN
Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Here we analyse biospecimens from a randomized, controlled trial of a microbiome-directed complementary food (MDCF-2) that produced superior rates of weight gain compared with a calorically more dense conventional ready-to-use supplementary food in 12-18-month-old Bangladeshi children with moderate acute malnutrition4. We reconstructed 1,000 bacterial genomes (metagenome-assembled genomes (MAGs)) from the faecal microbiomes of trial participants, identified 75 MAGs of which the abundances were positively associated with ponderal growth (change in weight-for-length Z score (WLZ)), characterized changes in MAG gene expression as a function of treatment type and WLZ response, and quantified carbohydrate structures in MDCF-2 and faeces. The results reveal that two Prevotella copri MAGs that are positively associated with WLZ are the principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilizing the component glycans of MDCF-2. The predicted specificities of carbohydrate-active enzymes expressed by their polysaccharide-utilization loci are correlated with (1) the in vitro growth of Bangladeshi P. copri strains, possessing varying degrees of polysaccharide-utilization loci and genomic conservation with these MAGs, in defined medium containing different purified glycans representative of those in MDCF-2, and (2) the levels of faecal carbohydrate structures in the trial participants. These associations suggest that identifying bioactive glycan structures in MDCFs metabolized by growth-associated bacterial taxa will help to guide recommendations about their use in children with acute malnutrition and enable the development of additional formulations.
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Alimentos , Microbioma Gastrointestinal , Desnutrición , Polisacáridos , Humanos , Lactante , Bacterias/genética , Bangladesh , Peso Corporal/genética , Heces/microbiología , Microbioma Gastrointestinal/fisiología , Genoma Bacteriano/genética , Desnutrición/microbiología , Metagenoma/genética , Polisacáridos/metabolismo , Aumento de PesoRESUMEN
Preclinical and clinical studies are providing evidence that the healthy growth of infants and children reflects, in part, healthy development of their gut microbiomes1-5. This process of microbial community assembly and functional maturation is perturbed in children with acute malnutrition. Gnotobiotic animals, colonized with microbial communities from children with severe and moderate acute malnutrition, have been used to develop microbiome-directed complementary food (MDCF) formulations for repairing the microbiomes of these children during the weaning period5. Bangladeshi children with moderate acute malnutrition (MAM) participating in a previously reported 3-month-long randomized controlled clinical study of one such formulation, MDCF-2, exhibited significantly improved weight gain compared to a commonly used nutritional intervention despite the lower caloric density of the MDCF6. Characterizing the 'metagenome assembled genomes' (MAGs) of bacterial strains present in the microbiomes of study participants revealed a significant correlation between accelerated ponderal growth and the expression by two Prevotella copri MAGs of metabolic pathways involved in processing of MDCF-2 glycans1. To provide a direct test of these relationships, we have now performed 'reverse translation' experiments using a gnotobiotic mouse model of mother-to-offspring microbiome transmission. Mice were colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains cultured from Bangladeshi infants/children in the study population, with or without P. copri isolates resembling the MAGs. By combining analyses of microbial community assembly, gene expression and processing of glycan constituents of MDCF-2 with single nucleus RNA-Seq and mass spectrometric analyses of the intestine, we establish a principal role for P. copri in mediating metabolism of MDCF-2 glycans, characterize its interactions with other consortium members including Bifidobacterium longum subsp. infantis, and demonstrate the effects of P. copri-containing consortia in mediating weight gain and modulating the activities of metabolic pathways involved in lipid, amino acid, carbohydrate plus other facets of energy metabolism within epithelial cells positioned at different locations in intestinal crypts and villi. Together, the results provide insights into structure/function relationships between MDCF-2 and members of the gut communities of malnourished children; they also have implications for developing future prebiotic, probiotic and/or synbiotic therapeutics for microbiome restoration in children with already manifest malnutrition, or who are at risk for this pervasive health challenge.
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Evidence is accumulating that perturbed postnatal development of the gut microbiome contributes to childhood malnutrition1-4. Designing effective microbiome-directed therapeutic foods to repair these perturbations requires knowledge about how food components interact with the microbiome to alter its expressed functions. Here we use biospecimens from a randomized, controlled trial of a microbiome-directed complementary food prototype (MDCF-2) that produced superior rates of weight gain compared to a conventional ready-to-use supplementary food (RUSF) in 12-18-month-old Bangladeshi children with moderate acute malnutrition (MAM)4. We reconstructed 1000 bacterial genomes (metagenome-assembled genomes, MAGs) present in their fecal microbiomes, identified 75 whose abundances were positively associated with weight gain (change in weight-for-length Z score, WLZ), characterized gene expression changes in these MAGs as a function of treatment type and WLZ response, and used mass spectrometry to quantify carbohydrate structures in MDCF-2 and feces. The results reveal treatment-induced changes in expression of carbohydrate metabolic pathways in WLZ-associated MAGs. Comparing participants consuming MDCF-2 versus RUSF, and MDCF-2-treated children in the upper versus lower quartiles of WLZ responses revealed that two Prevotella copri MAGs positively associated with WLZ were principal contributors to MDCF-2-induced expression of metabolic pathways involved in utilization of its component glycans. Moreover, the predicted specificities of carbohydrate active enzymes expressed by polysaccharide utilization loci (PULs) in these two MAGs correlate with the (i) in vitro growth of Bangladeshi P. copri strains, possessing differing degrees of PUL and overall genomic content similarity to these MAGs, cultured in defined medium containing different purified glycans representative of those in MDCF-2, and (ii) levels of carbohydrate structures identified in feces from clinical trial participants. In the accompanying paper5, we use a gnotobiotic mouse model colonized with age- and WLZ-associated bacterial taxa cultured from this study population, and fed diets resembling those consumed by study participants, to directly test the relationship between P. copri, MDCF-2 glycan metabolism, host ponderal growth responses, and intestinal gene expression and metabolism. The ability to identify bioactive glycan structures in MDCFs that are metabolized by growth-associated bacterial taxa will help guide recommendations about use of this MDCF for children with acute malnutrition representing different geographic locales and ages, as well as enable development of bioequivalent, or more efficacious, formulations composed of culturally acceptable and affordable ingredients.
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BACKGROUND: Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. OBJECTIVES: The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. METHODS: This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. Dietary recalls were mapped to the Davis Food Glycopedia to estimate monosaccharide intake. Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). RESULTS: Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). CONCLUSIONS: Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. This trial is registered at www. CLINICALTRIALS: gov as NCT02367287.
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Microbioma Gastrointestinal , Masculino , Femenino , Adulto , Humanos , Monosacáridos , Estudios Transversales , Fibras de la Dieta , Ingestión de Alimentos , Dieta , Heces/química , InflamaciónRESUMEN
Carbohydrates are the most abundant biomolecules in nature, and specifically, polysaccharides are present in almost all plants and fungi. Due to their compositional diversity, polysaccharide analysis remains challenging. Compared to other biomolecules, high-throughput analysis for carbohydrates has yet to be developed. To address this gap in analytical science, we have developed a multiplexed, high-throughput, and quantitative approach for polysaccharide analysis in foods. Specifically, polysaccharides were depolymerized using a nonenzymatic chemical digestion process followed by oligosaccharide fingerprinting using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS). Both label-free relative quantitation and absolute quantitation were done based on the abundances of oligosaccharides produced. Method validation included evaluating recovery for a range of polysaccharide standards and a breakfast cereal standard reference material. Nine polysaccharides (starch, cellulose, ß-glucan, mannan, galactan, arabinan, xylan, xyloglucan, chitin) were successfully quantitated with sufficient accuracy (5-25% bias) and high reproducibility (2-15% CV). Additionally, the method was used to identify and quantitate polysaccharides from a diverse sample set of food samples. Absolute concentrations of nine polysaccharides from apples and onions were obtained using an external calibration curve, where varietal differences were observed in some of the samples. The methodology developed in this study will provide complementary polysaccharide-level information to deepen our understanding of the interactions of dietary polysaccharides, gut microbial community, and human health.
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Glicómica , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados , Polisacáridos/química , Cromatografía Liquida/métodos , Oligosacáridos/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Pyoderma gangrenosum (PG) is an uncommon, idiopathic, neutrophilic dermatosis characterised by large necrotic ulcers. Occasionally, patients develop atypical presentations, including pustular, bullous, and vegetative lesions. Bullous pyoderma gangrenosum (BPG) is considered an extremely rare form. We describe a case of BPG in a 76-year-old man, with active oncological history, including a recent diagnosis of hairy cell leukemia. Diagnosis of PG was delayed because of atypical clinical presentation that mimicked necrotising fasciitis. The patient was treated with diverse intravenous antibiotics and several surgical procedures. The suspicion of neutrophilic dermatosis arose from the histopathological studies. In the setting of mandatory clinico-pathological correlation, the aim of this report is to point out the morphological characteristics that allow recognition of this uncommon variant of pyoderma gangrenosum.
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Increases in snack consumption associated with Westernized lifestyles provide an opportunity to introduce nutritious foods into poor diets. We describe two 10-wk-long open label, single group assignment human studies that measured the effects of two snack prototypes containing fiber preparations from two sustainable and scalable sources; the byproducts remaining after isolation of protein from the endosperm of peas and the vesicular pulp remaining after processing oranges for the manufacture of juices. The normal diets of study participants were supplemented with either a pea- or orange fiber-containing snack. We focused our analysis on quantifying the abundances of genes encoding carbohydrate-active enzymes (CAZymes) (glycoside hydrolases and polysaccharide lyases) in the fecal microbiome, mass spectrometric measurements of glycan structures (glycosidic linkages) in feces, plus aptamer-based assessment of levels of 1,300 plasma proteins reflecting a broad range of physiological functions. Computational methods for feature selection identified treatment-discriminatory changes in CAZyme genes that correlated with alterations in levels of fiber-associated glycosidic linkages; these changes in turn correlated with levels of plasma proteins representing diverse biological functions, including transforming growth factor type ß/bone morphogenetic protein-mediated fibrosis, vascular endothelial growth factor-related angiogenesis, P38/MAPK-associated immune cell signaling, and obesity-associated hormonal regulators. The approach used represents a way to connect changes in consumer microbiomes produced by specific fiber types with host responses in the context of varying background diets.
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Microbioma Gastrointestinal , Microbiota , Fibras de la Dieta/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Polisacáridos/metabolismo , ProteomaRESUMEN
The molecular complexity of the carbohydrates consumed by humans has been deceptively oversimplified due to a lack of analytical methods that possess the throughput, sensitivity, and resolution required to provide quantitative structural information. However, such information is becoming an integral part of understanding how specific glycan structures impact health through their interaction with the gut microbiome and host physiology. This work presents a detailed catalogue of the glycans present in complementary foods commonly consumed by toddlers during weaning and foods commonly consumed by American adults. The monosaccharide compositions of over 800 foods from diverse food groups including Fruits, Vegetables, Grain Products, Beans, Peas, Other Legumes, Nuts, Seeds; Sugars, Sweets and Beverages; Animal Products, and more were obtained and used to construct the "Davis Food Glycopedia" (DFG), an open-access database that provides quantitative structural information on the carbohydrates in food. While many foods within the same group possessed similar compositions, hierarchical clustering analysis revealed similarities between different groups as well. Such a Glycopedia can be used to formulate diets rich in specific monosaccharide residues to provide a more targeted modulation of the gut microbiome, thereby opening the door for a new class of prophylactic or therapeutic diets.
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Fabaceae , Alimentos , Animales , Dieta , Frutas , Monosacáridos , Polisacáridos , VerdurasRESUMEN
The Sarajevo Canton Winter Field Campaign 2018 (SAFICA) was a project that took place in winter 2017-2018 with an aim to characterize the chemical composition of aerosol in the Sarajevo Canton, Bosnia and Herzegovina (BiH), which has one of the worst air qualities in Europe. This paper presents the first characterization of the metals in PM10 (particulate matter aerodynamic diameters ≤10 µm) from continuous filter samples collected during an extended two-months winter period at the urban background Sarajevo and remote Ivan Sedlo sites. We report the results of 18 metals detected by inductively coupled plasma mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (ETAAS). The average mass concentrations of metals were higher at the Sarajevo site than at Ivan Sedlo and ranged from 0.050 ng/m3 (Co) to 188 ng/m3 (Fe) and from 0.021 ng/m3 (Co) to 61.8 ng/m3 (Fe), respectively. The BenMAP-CE model was used for estimating the annual BiH health (50% decrease in PM2.5 would save 4760+ lives) and economic benefits (costs of $2.29B) of improving the air quality. Additionally, the integrated energy and health assessment with the ExternE model provided an initial estimate of the additional health cost of BiH's energy system.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Bosnia y Herzegovina , Polvo/análisis , Monitoreo del Ambiente/métodos , Metales/análisis , Material Particulado/análisis , Estaciones del AñoRESUMEN
This evidence map was developed to identify, summarize, and communicate to key stakeholders the findings of evidence on interventions to reduce exposure to household air pollution (HAP). The map synthesizes evidence from 48 literature reviews published on technological and sociocultural interventions and others (potentialities of public policies like incentives) to address health, environmental and economic impacts associated to HAP. Furthermore, this map seeks to inform decision-making processes on strategic interventions and most effective policies. Main results: Most of the existing HAP interventions to address indoor air quality have been focused on evaluating improved stove interventions that still use solid fuels (n = 39). It has been identified that Interventions with clean fuels (LPG, electricity, and others) are the most effective in impacting the health outcomes and reducing household air pollutants. Only six reviews analyzed or reported outcomes of sociocultural interventions (health education) aimed at reducing air pollution in homes; some showed positive impacts on health. Three reviews reported the effects of changes in people's behaviors when cooking food, which have improved indoor air quality. All authors agree on the importance of changing behavior and community practices as an essential element for the sustainability of improved kitchen interventions. Four reviews evaluated at the synergy between policies to reduce household air pollution and outdoor pollution, as well as other environmental health concerns. These reviews allow the conclusion that synergies between policies are much more effective at reducing air pollution and its impacts on the health of communities.
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Humanos , Contaminación del Aire Interior/prevención & control , Enfermedades Respiratorias , Contaminación del Aire Interior/efectos adversosRESUMEN
Changing food preferences brought about by westernization that have deleterious health effects1,2-combined with myriad forces that are contributing to increased food insecurity-are catalysing efforts to identify more nutritious and affordable foods3. Consumption of dietary fibre can help to prevent cardiovascular disease, type 2 diabetes and obesity4-6. A substantial number of reports have explored the effects of dietary fibre on the gut microbial community7-9. However, the microbiome is complex, dynamic and exhibits considerable intra- and interpersonal variation in its composition and functions. The large number of potential interactions between the components of the microbiome makes it challenging to define the mechanisms by which food ingredients affect community properties. Here we address the question of how foods containing different fibre preparations can be designed to alter functions associated with specific components of the microbiome. Because a marked increase in snack consumption is associated with westernization, we formulated snack prototypes using plant fibres from different sustainable sources that targeted distinct features of the gut microbiomes of individuals with obesity when transplanted into gnotobiotic mice. We used these snacks to supplement controlled diets that were consumed by adult individuals with obesity or who were overweight. Fibre-specific changes in their microbiomes were linked to changes in their plasma proteomes indicative of an altered physiological state.
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Fibras de la Dieta/farmacología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Vida Libre de Gérmenes , Bocadillos , Adolescente , Adulto , Animales , Bacteroides/efectos de los fármacos , Bacteroides/aislamiento & purificación , Proteínas Sanguíneas/análisis , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Obesidad/microbiología , Sobrepeso/microbiología , Proteoma/análisis , Proteoma/efectos de los fármacos , Adulto JovenRESUMEN
The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.
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Antineoplásicos Fitogénicos/química , Proliferación Celular/efectos de los fármacos , Cissus/química , Proteínas de Neoplasias/genética , Transcriptoma , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Apigenina/química , Apigenina/aislamiento & purificación , Apigenina/farmacología , Bioensayo , Supervivencia Celular/efectos de los fármacos , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavanonas/farmacología , Flavonas/química , Flavonas/aislamiento & purificación , Flavonas/farmacología , Perfilación de la Expresión Génica , Humanos , Quempferoles/química , Quempferoles/aislamiento & purificación , Quempferoles/farmacología , Masculino , Análisis por Micromatrices , Proteínas de Neoplasias/clasificación , Proteínas de Neoplasias/metabolismo , Células PC-3 , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/aislamiento & purificación , Triterpenos Pentacíclicos/farmacología , Extractos Vegetales/química , Resveratrol/química , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Ácido BetulínicoRESUMEN
Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata's leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.
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Bromeliaceae/química , Ácidos Cumáricos/farmacología , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Extractos Vegetales/química , Inhibidores de Proteínas Quinasas/farmacología , Bioensayo , Muerte Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Ácidos Cumáricos/química , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Humanos , Células MCF-7 , Proteínas Quinasas Activadas por Mitógenos/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Células PC-3 , Fenoles/farmacología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
Greater understanding of the spatial relationships between members of the human gut microbiota and available nutrients is needed to gain deeper insights about community dynamics and expressed functions. Therefore, we generated a panel of artificial food particles with each type composed of microscopic paramagnetic beads coated with a fluorescent barcode and one of 60 different dietary or host glycan preparations. Analysis of 160 Bacteroides and Parabacteroides strains disclosed diverse strain-specific and glycan-specific binding phenotypes. We identified carbohydrate structures that correlated with binding by specific bacterial strains in vitro and noted strain-specific differences in the catabolism of glycans that mediate adhesion. Mixed in vitro cultures revealed that these adhesion phenotypes are maintained in more complex communities. Additionally, orally administering glycan beads to gnotobiotic mice confirmed specificity in glycan binding. This approach should facilitate analyses of how strains occupying the same physical niche interact, and it should advance the development of synbiotics, more nutritious foods, and microbiota-based diagnostics.
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Bacterias/metabolismo , Microbioma Gastrointestinal/fisiología , Polisacáridos/metabolismo , Animales , Bacterias/clasificación , Bacterias/genética , Bacteroides , Alimentos , Tracto Gastrointestinal/microbiología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Polisacáridos/administración & dosificaciónRESUMEN
INTRODUCCIÓN: El ingreso de menores en unidades de hospitalización de psiquiatría de adultos constituye un problema debido a la ausencia de recursos adecuados y de datos epidemiológicos. OBJETIVO: Describir y analizar las características sociodemográficas y clínicas de los menores que ingresaron en la Unidad de Hospitalización Breve de Psiquiatría en Cáceres. Sujetos y métodos: Estudio observacional, descriptivo y retrospectivo. La muestra estuvo definida por pacientes de edades comprendidas entre los 12 y los 18 años, hospitalizados en la unidad de psiquiatría. El periodo de evaluación fue entre el 1 de enero del 2014 y el 31 de diciembre del 2018. RESULTADOS: Se incluyeron 79 pacientes. La edad media fue de 15,72 (± 1,65) años. El 93,6% presentaron antecedentes psiquiátricos personales. El diagnóstico al alta más frecuente en los varones fueron los trastornos destructivos del control de impulsos; en las mujeres los trastornos afectivos. El 40,6% presentaron antecedentes de consumo de sustancias, siendo más frecuente en varones, lo cual empeoraba el pronóstico. La estancia media fue de 5,4 (± 4,7) días. La prolongación de la estancia media se relacionó con los antecedentes de ingresos psiquiátricos previos, el número de diagnósticos al alta, un mayor número de fármacos al alta y aquellos que recibieron antipsicóticos inyectables de liberación prolongada (p < 0,005 en todos los casos). CONCLUSIONES: El estudio identifica el perfil sociodemográfico y clínico del menor ingresado en la unidad de psiquiatría y cómo la estancia hospitalaria se asoció con antecedentes psiquiátricos previos y una complejidad diagnóstica y clínica
INTRODUCTION: The admission of minors into adult psychiatric units is a problem and is due to the lack of adequate resources and epidemiology data. OBJECTIVE: The aim of this study is to describe and analyse the sociodemographic and clinical characteristics of minors that were admitted into the Short-Stay Psychiatric Hospitalisation Unit of Caceres, Spain. MATERIALS AND METHODS: A retrospective, observational, and descriptive study was conducted on a sample of patients between 12 and 18 years-old admitted to the Psychiatric Unit. The study period was between January 1, 2014 and December 31, 2018. RESULTS: A total of 79 patients, with a mean age of 15.72 (± 1.65) years, were included. Almost all of them (93.6%) had a personal psychiatric history. The most common diagnoses at discharge in males were disruptive, impulse-control and conduct disorders, and mood disorders in females. A history of substance consumption was present in 40.6%, and was more common in males, which led to a worse prognosis. The mean stay was 5.4 (± 4.7) days. Prolongation of the mean stay was associated with a history of previous psychiatric admissions, the number of diagnoses at discharge, a greater number of drugs at discharge, and those that received long-acting injectable antipsychotic drugs (p < 0.005 in all cases). CONCLUSIONS: The study identified the sociodemographic and clinical profile of the minor admitted to the Psychiatric Unit, and how the hospital stay was associated with previous psychiatric history, as well as diagnostic and clinical complexity
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Humanos , Masculino , Femenino , Niño , Adolescente , Hospitalización , Servicio de Psiquiatría en Hospital/estadística & datos numéricos , Psiquiatría del Adolescente/métodos , Psiquiatría Infantil/métodos , Epidemiología Descriptiva , Estudios Retrospectivos , Tiempo de InternaciónRESUMEN
INTRODUCTION: The admission of minors into adult psychiatric units is a problem and is due to the lack of adequate resources and epidemiology data. OBJECTIVE: The aim of this study is to describe and analyse the sociodemographic and clinical characteristics of minors that were admitted into the Short-Stay Psychiatric Hospitalisation Unit of Caceres, Spain. MATERIALS AND METHODS: A retrospective, observational, and descriptive study was conducted on a sample of patients between 12 and 18 years-old admitted to the Psychiatric Unit. The study period was between January 1, 2014 and December 31, 2018. RESULTS: A total of 79 patients, with a mean age of 15.72 (± 1.65) years, were included. Almost all of them (93.6%) had a personal psychiatric history. The most common diagnoses at discharge in males were disruptive, impulse-control and conduct disorders, and mood disorders in females. A history of substance consumption was present in 40.6%, and was more common in males, which led to a worse prognosis. The mean stay was 5.4 (± 4.7) days. Prolongation of the mean stay was associated with a history of previous psychiatric admissions, the number of diagnoses at discharge, a greater number of drugs at discharge, and those that received long-acting injectable antipsychotic drugs (p < 0.005 in all cases). CONCLUSIONS: The study identified the sociodemographic and clinical profile of the minor admitted to the Psychiatric Unit, and how the hospital stay was associated with previous psychiatric history, as well as diagnostic and clinical complexity.
Asunto(s)
Hospitalización , Menores , Adolescente , Niño , Femenino , Hospitales Psiquiátricos , Humanos , Tiempo de Internación , Masculino , Alta del Paciente , Estudios Retrospectivos , EspañaRESUMEN
The 2018 NASA Health and Air Quality Applied Science Team (HAQAST) "Indicators" Tiger Team collaboration between NASA-supported scientists and civil society stakeholders aimed to develop satellite-derived global air pollution and climate indicators. This Commentary shares our experience and lessons learned. Together, the team developed methods to track wildfires, dust storms, pollen counts, urban green space, nitrogen dioxide concentrations and asthma burdens, tropospheric ozone concentrations, and urban particulate matter mortality. Participatory knowledge production can lead to more actionable information but requires time, flexibility, and continuous engagement. Ground measurements are still needed for ground truthing, and sustained collaboration over time remains a challenge.
RESUMEN
The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.