Untargeted Metabolomics Analysis Based on LC-QTOF-MS to Investigate the Phenolic Composition of Red and White Wines Elaborated from Sonicated Grapes.

Ultrasounds are considered an emerging technology in the wine industry. Concretely, in 2019, the International Organization of Vine and Wine (OIV) officially approved their use for the treatment of crushed grapes to increase the level of phenolic compound extraction. The main objective of this study was to validate an untargeted metabolomics approach as an analytical tool for identifying novel markers associated with sonication. To do so, the influence of a sonication treatment on the metabolic profile was studied in four typically commercial varietal wines, i.e., two red wines from 'Syrah' and 'Cabernet Sauvignon' grapes and two white wines from 'Macabeo' and 'Airén' grapes. A robust classification and prediction model was created employing supervised techniques such as partial least-squares discriminant analysis (PLS-DA). The findings indicated that the grapes subjected to high-power ultrasound conditions experienced cell wall disruption due to the cavitation phenomenon, resulting in significant changes in various phenolic compounds (including hydroxycinnamic acids and flavonoids) present in these wines compared to wines from non-sonicated grapes. Additionally, new metabolites were tentatively identified through untargeted metabolomics techniques. This study represents the successful application of the untargeted metabolomics approach employing a UHPLC-QTOF system to discern how grape sonication affects bioactive secondary metabolites in wines.

Impact of Lactic Acid Bacteria Fermentation on (Poly)Phenolic Profile and In Vitro Antioxidant and Anti-Inflammatory Properties of Herbal Infusions.

Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of Lactiplantibacillus plantarum of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE2) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders.

Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, i.e., non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant. We evaluated whether UMs, as distinctive functional gut-microbiome signatures, could determine the potential effect of a pomegranate extract (PE) rich in ET-EA on the metabolism of BAs and cholesterol in mild dyslipidaemic overweight-obese individuals, with possible consequences on host-lipid homeostasis and gut health. At the baseline, UM-B presented the highest levels of faecal total and secondary BAs and coprostanol, suggesting that the lipid absorption capacity and gut cytotoxic risk could be augmented in UM-B. PE intake significantly reduced faecal coprostanol and BA production, especially secondary BAs, and modulated the gut microbiome, reducing the gut cytotoxic risk, especially in UM-B individuals. The lowering of faecal microbial coprostanol and BAs and some BA-metabolising bacteria was quantitatively correlated with Uro concentrations, mainly faecal Uro-A. This suggests that PE consumption could exert cardiovascular and gut protection through Uro-A production as a direct driver of the effects and indirectly by reducing the Coriobacteriaceae family and BA pool, known factors involved in the gut absorption of lipids.

Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1ß production.

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1ß production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1ß production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host's innate defence against pathogens while also limiting IL-1ß-dependent inflammatory episodes through immunometabolism modulation.

Percepciones y experiencias de adultos mayores sobre sexualidad y servicios de salud sexual en Colombia

Introducción: Aunque a nivel mundial se ha demostrado que la población adulta mayor mantiene una vida sexual activa, es limitada por estereotipos, cambios fisiológicos resultados del proceso de envejecimiento y la ausencia de estrategias de salud integral para la sexualidad. Objetivo: Documentar la experiencia sexual de los adultos mayores en el país y entender los motivos que promueven o limitan la búsqueda de atención en salud sexual. Metodología: Estudio cualitativo en el que se realizaron 39 entrevistas y 4 talleres virtuales con hombres y mujeres de 50 años y más en Barranquilla, Bogotá, Cali, Medellín, sin excluir personas de otras ciudades. Resultados: Entre los principales hallazgos se evidencia que la población adulta mayor tiene valoraciones positivas frente a la sexualidad y el sexo, pero su desarrollo se ve limitado, especialmente para las mujeres, por los roles de género. La sexualidad en las personas mayores está atravesada por la educación inicial, la transformación de ideas sobre la sexualidad a lo largo de sus trayectorias de vida, las transformaciones del cuerpo, el estado de salud, las prácticas y experiencias sexuales recientes y la manera en la que se aproximan a la dimensión salud sexual con profesionales de la salud. Conclusiones: La heterogeneidad de experiencias, prácticas y valores dados a la sexualidad y al sexo en la vejez requieren de la generación de políticas y programas de atención integral basadas en investigaciones empíricas que superen las concepciones edadistas de la sexualidad. Este estudio es una contribución a la literatura local sobre sexualidad y vejez, así como al diseño de servicios de atención de salud y bienestar de acuerdo con las necesidades, identidades y circunstancias específicas de la población adulta mayor en materia de sexualidad.

Introduction: Although worldwide has been demonstrated that the older adult population maintains an active sexual life, this is limited by stereotypes, physiological changes resulting from the aging process and the absence of comprehensive health strategies for sexuality. Objective: To document the sexual experience of older adults in the country and to understand the reasons that promote or limit the search for sexual healthcare. Methodology: Qualitative study. Thirty-nine interviews and four virtual workshops were conducted with men and women 50 years of age and older in Barranquilla, Bogotá, Cali, and Medellín, although people from other cities were not excluded. Results: Among the main findings, it is evident that this population has positive evaluations of sexuality and sex, but its development is limited, especially for women, by gender roles. Sexuality in the elderly is formed by their initial education, the transformation of ideas about sexuality throughout their life trajectories, the transformations of their bodies, their state of health, recent sexual practices and experiences, and the way in which they approach this topic with health professionals. Conclusions: The heterogeneity of experiences, practices and values given to sexuality and sex in old age require policies and programs based on empirical research that overcome the ageist conception of sexuality. This study is a contribution to the national literature on sexuality and aging, and to the design of health care and well-being services according to the specific needs, identities and circumstances of the older adult population in terms of sexuality.

Percepciones de proveedores de servicios de salud sobre la salud sexual de los adultos mayores en Colombia

Introducción: La sexualidad y la salud sexual de las personas adultas mayores es una dimensión invisible en la prestación de los servicios de salud. Debido a esto, es importante conocer las percepciones y dificultades del personal de salud para brindar esta atención. Objetivo: Identificar diferencias y similitudes en la percepción que tienen los proveedores de servicios de salud en Colombia sobre la sexualidad y la salud sexual en el adulto mayor. Metodología: Se realizaron 5 grupos focales en Bogotá, Barranquilla, Cali y Medellín donde participaron 19 profesionales de la salud de una institución prestadora de servicios de salud sexual y reproductiva. Resultados: Los profesionales de la salud reconocen la sexualidad como un aspecto importante en la prestación de los servicios de salud en las personas mayores, a pesar de la invisibilidad actual del tema en la atención médica. Reconocen la complejidad de hablar sobre sexualidad en la interacción médico-paciente, en parte por la falta de entrenamiento de los profesionales de la salud y por las propias inhibiciones de los pacientes. Discusión: Persisten obstáculos sociales y teóricos para abordar los temas de sexualidad en consulta, al igual que diferencias de género para el tratamiento de temas de sexualidad y salud sexual. Conclusiones: Los prestadores de servicios de salud son claves para remover barreras a la atención, acompañamiento y comprensión de la salud sexual y la sexualidad de las personas mayores.

Introduction: The sexuality and sexual health of older people is an invisible dimension in the provision of health services. Therefore, it is important to know the perceptions and difficulties of health personnel to provide this care. Objective: To identify differences and similarities in the perception that health service providers in Colombia have about sexuality and sexual health in the elderly. Methodology: A total of 5 focus groups were held in Bogotá, Barranquilla, Cali and Medellín with the participation of 19 health professionals from an institution that provides sexual and reproductive health services. Results: Health professionals recognize sexuality as an important aspect in the provision of health services in the elderly, despite the current invisibility of the issue in medical care. They recognize the complexity of talking about sexuality in the doctor-patient interaction, partly due to the lack of training of health professionals, and due to the patients' own inhibitions. Discussion: Social and theoretical obstacles persist to address sexuality issues in consultation, as well as gender differences for the treatment of sexuality and sexual health issues. Conclusions: Health service providers are key to removing barriers to care, accompaniment and understanding of the sexual health and sexuality of the elderly.

Union Instability and Fertility: An International Perspective.

In this article, we analyse the relationship between union instability and cumulated fertility among ever-partnered women in several regions across Europe and the Americas with different patterns of demographic behaviour in terms of fertility levels, union instability and fertility across partnerships. We hypothesise that the relationship between union dissolution and fertility might be less negative in contexts where repartnering is more prevalent. The analysis is performed on a large dataset of 25 countries, combining information from the Harmonised Histories of the Generation and Gender Programme with our own harmonisation of survey data from three Latin American countries. This allows for the inclusion of countries with differing prevalence of union instability as measured by (a) the proportion of women who separated by age 40, and (b) the proportion who repartnered by age 40. We first examine the prevalence of separation and repartnering during reproductive ages across regions, and we estimate the proportion of cumulated fertility attributable to unions of different ranks using a decomposition method. We then analyse the links between union instability and the number of children born by age 40 among ever-partnered and ever-repartnered women, using Poisson regression. Despite observing a high degree of heterogeneity in the proportions of births occurring in the context of repartnering both within and between regions, we find a pattern where a greater prevalence of repartnering by age 40 is accompanied by higher cumulated fertility in second or subsequent unions. Our multivariate findings reveal a negative statistical relationship between separation and cumulated fertility that is partially offset by repartnering in some contexts, and that the time spent in a union during the reproductive lifespan is a key determinant of cumulated fertility, regardless of national context and independently from age at union formation and union rank.

Uso de métodos anticonceptivos de alta eficacia posterior a la interrupción voluntaria del embarazo en Profamilia, 2015-2020

Objetivo: Describir los métodos anticonceptivos reportados por las usuarias de servicios de interrupción voluntaria del embarazo (IVE), antes y posterior a la consulta, y explorar la asociación entre las características sociodemográficas y los antecedentes ginecológicos con la elección de anticonceptivos de alta eficacia posterior a la IVE, con gestaciones menores de 15 semanas, en el departamento de Antioquia, Colombia, en la institución Profamilia, entre el 2015 y el 2020. Metodología: Estudio de corte transversal. Se analizaron los 13 067 registros de consultas de IVE realizadas en Profamilia de la regional Antioquia, del 2015 al 2020. Las variables cualitativas se midieron con frecuencias y porcentajes, y las cuantitativas, con la media y la desviación estándar. Se implementaron modelos de regresión logística para establecer la asociación de las variables independientes con la variable de interés. Resultados: La consulta de IVE contribuyó al incremento del uso de métodos anticonceptivos de alta eficacia. Antes de la IVE, el 53 % de las mujeres no usaban ningún método. Posterior a la interrupción, el 97 % empezó a utilizar métodos de alta eficacia. Además del uso de métodos poco eficaces o el uso de preservativo, obtuvieron una posibilidad 13 veces más alta de elegir un método de alta eficacia. Conclusiones: La educación en métodos anticonceptivos posterior a una IVE es fundamental para promover el uso de opciones muy efectivas, con el fin de disminuir la aparición de nuevos embarazos no deseados que puedan llevar a una IVE recurrente.

Objective: To describe the contraceptive methods reported by users of voluntary termination of pregnancy (VTP) services, before and after consultation, and to examine the association between sociodemographic characteristics and gynecological history with choosing highly effective contraceptive methods after VTP, in gestations shorter than 15 weeks, in the department of Antioquia, Colombia, at the Profamilia institution, from 2015 to 2020. Methodology: This is a cross-sectional study. We analyzed 13 067 records of VTP consultations performed in Profamilia in Antioquia from 2015 to 2020. Qualitative variables were measured with frequencies and percentages, and quantitative variables with the mean and standard deviation. Logistic regression models were implemented to establish the association of the independent variables with the variable of interest. Results: VTP consultation contributed to increased use of highly effective contraceptive methods. Before VTP, 53% of women were not using any method. After the termination, 97% started using highly effective methods. Likewise, those using low efficacy methods or condoms were 13 times more likely to choose a highly effective method. Conclusions: Post-VTP contraceptive education is essential for promoting the use of highly effective methods to reduce the occurrence of new unwanted pregnancies that may lead to repeated VTP

Objetivo: Descrever os métodos anticoncepcionais referidos pelas usuárias de serviços de interrupção voluntária da gravidez (IVG), antes e depois da consulta, e estudar a associação entre as características sociodemográficas e os antecedentes ginecológicos com a eleição de anticoncepcionais de alta eficiência depois da IVG, com gestações menores de 15 semanas, no departamento de Antioquia, Colômbia, na instituição Profamilia, entre 2015 e 2020. Metodologia: Estudo de corte transversal. Analisaram-se os 13067 registros de consultas de IVG realizadas em Profamilia na sede Antioquia, de 2015 a 2020. As variáveis qualitativas mediram-se com frequências e porcentagens, e as quantitativas com a média e o desvio padrão. Implementaram-se modelos de regressão logística para estabelecer a associação das variáveis independentes com a variável de interesse. Resultados: A consulta de IVG contribuiu ao incremento do uso de métodos anticoncepcionais de alta eficiência. Antes da IVG, o 53% das mulheres não usavam nenhum método. Depois da interrupção, o 97% começou a usar métodos de alta eficiência. Além do uso de métodos pouco eficientes ou o uso da camisinha, obtiveram uma possibilidade 13 vezes maior de escolher um método de alta eficiência. Conclusões: A educação em métodos anticoncepcionais posterior a uma IVG é fundamental para promover o uso de opções muito efetivas, com o fim de diminuir a aparição de novas gravidezes não desejadas que podem levar a uma IVG recorrente.

Effect of Resistant Dextrin on Intestinal Gas Homeostasis and Microbiota.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production.

Real clinical experience after one year of treatment with tolvaptan in patients with autosomal dominant polycystic kidney disease.

Background: Tolvaptan (TV) is the first vasopressin-receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD). No publications report TV experience in real clinical practice during the first year of treatment. Methods: A prospective study of an initial cohort of 220 rapidly progressing patients treated with TV for 12 months. The tolerability of TV, the evolution of the estimated glomerular filtration rate (eGFR), analytical parameters, and blood pressure were analyzed. Results: A total of 163 patients (78.2%) received TV for 1 year. The main causes of treatment withdrawal were the aquaretic effects (11%), eGFR deterioration (5%), and hepatic toxicity (2.3%). eGFR decreased significantly after 1 month of treatment without further changes. The decrease in eGFR in the first month was higher in patients with an initially higher eGFR. The eGFR drop during the first year of treatment with TV was lower than that reported by patients in the 2 years prior to TV treatment (-1.7 ± 7.6 vs. -4.4 ± 4.8 mL/min, p = 0.003). Serum sodium and uric acid concentrations increased, and morning urinary osmolality decreased in the first month, with no further changes. Blood pressure decreased significantly without changes in antihypertensive medication. Conclusion: TV treatment is well tolerated by most patients. Liver toxicity is very rare and self-limited. TV reduces eGFR in the first month without showing further changes during the first year of treatment. Patients with a higher starting eGFR will suffer a greater initial drop, with a longer recovery. We suggest using the eGFR observed after a month of treatment as the reference for future comparisons and calculating the rate of eGFR decline in patients undergoing TV treatment.

Lunularin Producers versus Non-producers: Novel Human Metabotypes Associated with the Metabolism of Resveratrol by the Gut Microbiota.

We describe here for the first time the consistent observation of two metabotypes associated with resveratrol metabolism by the human gut microbiota, that is, lunularin (LUNU)-producers and LUNU non-producers. In healthy volunteers (n = 195), resveratrol was reduced to dihydroresveratrol, which only in the LUNU-producer metabotype was sequentially dehydroxylated at the 5-position to yield LUNU and the 3-position to produce 4-hydroxydibenzyl. These metabolites (also 3,4'-dihydroxy-trans-stilbene in some LUNU-producers) were detected in the urine and (or) feces of 74% of volunteers after consuming resveratrol, while 26% lacked these dehydroxylase activities. The LUNU non-producer metabotype was more prevalent in females (P < 0.05) but independent of individuals' BMI and age. A 4-styrylphenol reductase in both metabotypes converted stilbenes to their corresponding dibenzyls, while no 4-dehydroxylation in stilbenes or dibenzyls was observed. 4-Hydroxy-trans-stilbene, pinosylvin, dihydropinosylvin, 3-hydroxydibenzyl, and 3-hydroxy-trans-stilbene were not detected in vivo or in vitro. Further research on LUNU metabotypes, their associated gut microbiota, and their impact on health is worthwhile.

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells' ABC-mediated chemoresistance.

Economic burden of female genital mutilation in 27 high-prevalence countries.

BACKGROUND: Female genital mutilation (FGM) is a traditional harmful practice affecting 200 million women and girls globally. Health complications of FGM occur immediately and over time, and are associated with healthcare costs that are poorly understood. Quantifying the global FGM-related burden is essential for supporting programmes and policies for prevention and mitigation. METHODS: Health complications of FGM are derived from a meta-analysis and stratified by acute, uro-gynaecological, obstetric and psychological/sexual. Treatment costs are calculated from national cohort models of 27 high-burden countries over 30 years. Savings associated with full/partial abandonment are compared with a current incidence reference scenario, assuming no changes in FGM practices. RESULTS: Our model projects an increasing burden of FGM due to population growth. As a reference scenario assuming no change in practices, prevalent cases in 27 countries will rise from 119.4 million (2018) to 205.8 million (2047). Full abandonment could reduce this to 80.0 million (2047), while partial abandonment is insufficient to reduce cases. Current incidence economic burden is US$1.4 billion/year, rising to US$2.1 billion/year in 2047. Full abandonment would reduce the future burden to US$0.8 billion/year by 2047. CONCLUSION: FGM is a human rights violation, a public health issue and a substantial economic burden that can be avoided through effective prevention strategies. While decreasing trends are observed in some countries, these trends are variable and not consistently observed across settings. Additional resources are needed to prevent FGM to avoid human suffering and growing costs. The findings of this study warrant increased political commitment and investment in the abandonment of FGM.

Lignocellulose-Degrading Enzymes: A Biotechnology Platform for Ferulic Acid Production from Agro-Industrial Side Streams.

Biorefining by enzymatic hydrolysis (EH) of lignocellulosic waste material due to low costs and affordability has received enormous interest amongst scientists as a potential strategy suitable for the production of bioactive ingredients and chemicals. In this study, a sustainable and eco-friendly approach to extracting bound ferulic acid (FA) was demonstrated using single-step EH by a mixture of lignocellulose-degrading enzymes. For comparative purposes of the efficiency of EH, an online extraction and analysis technique using supercritical fluid extraction-supercritical fluid chromatography-mass spectrometry (SFE-SFC-MS) was performed. The experimental results demonstrated up to 369.3 mg 100 g-1 FA release from rye bran after 48 h EH with Viscozyme L. The EH of wheat and oat bran with Viscoferm for 48 h resulted in 255.1 and 33.5 mg 100 g-1 of FA, respectively. The release of FA from bran matrix using supercritical fluid extraction with carbon dioxide and ethanol as a co-solvent (SFE-CO2-EtOH) delivered up to 464.3 mg 100 g-1 of FA, though the extractability varied depending on the parameters used. The 10-fold and 30-fold scale-up experiments confirmed the applicability of EH as a bioprocessing method valid for the industrial scale. The highest yield of FA in both scale-up experiments was obtained from rye bran after 48 h of EH with Viscozyme L. In purified extracts, the absence of xylose, arabinose, and glucose as the final degradation products of lignocellulose was proven by high-performance liquid chromatography with refractive index detection (HPLC-RID). Up to 94.0% purity of FA was achieved by solid-phase extraction (SPE) using the polymeric reversed-phase Strata X column and 50% EtOH as the eluent.

Differential Effects of Western and Mediterranean-Type Diets on Gut Microbiota: A Metagenomics and Metabolomics Approach.

Our aim was to determine the effect of diet on gut microbiota, digestive function and sensations, using an integrated clinical, metagenomics and metabolomics approach. We conducted a cross-over, randomised study on the effects of a Western-type diet versus a fibre-enriched Mediterranean diet. In 20 healthy men, each diet was administered for 2 weeks preceded by a 2-week washout diet. The following outcomes were recorded: (a) number of anal gas evacuations; (b) digestive sensations; (c) volume of gas evacuated after a probe meal; (d) colonic content by magnetic resonance imaging; (e) gut microbiota taxonomy and metabolic functions by shotgun sequencing of faecal samples; (f) urinary metabolites using untargeted metabolomics. As compared to a Western diet, the Mediterranean diet was associated with (i) higher number of anal gas evacuations, (ii) sensation of flatulence and borborygmi, (iii) larger volume of gas after the meal and (iv) larger colonic content. Despite the relatively little difference in microbiota composition between both diets, microbial metabolism differed substantially, as shown by urinary metabolite profiles and the abundance of microbial metabolic pathways. The effects of the diet were less evident in individuals with robust microbiotas (higher beta-diversity). To conclude, healthy individuals tolerate dietary changes with minor microbial modifications at the composition level but with remarkable variation in microbial metabolism.

Highly-Efficient Release of Ferulic Acid from Agro-Industrial By-Products via Enzymatic Hydrolysis with Cellulose-Degrading Enzymes: Part I-The Superiority of Hydrolytic Enzymes Versus Conventional Hydrolysis.

Historically Triticum aestívum L. and Secale cereále L. are widely used in the production of bakery products. From the total volume of grain cultivated, roughly 85% is used for the manufacturing of flour, while the remaining part is discarded or utilized rather inefficiently. The limited value attached to bran is associated with their structural complexity, i.e., the presence of cellulose, hemicellulose, and lignin, which makes this material suitable mostly as a feed supplement, while in food production its use presents a challenge. To valorize these materials to food and pharmaceutical applications, additional pre-treatment is required. In the present study, an effective, sustainable, and eco-friendly approach to ferulic acid (FA) production was demonstrated through the biorefining process accomplished by non-starch polysaccharides degrading enzymes. Up to 11.3 and 8.6 g kg-1 of FA was released from rye and wheat bran upon 24 h enzymatic hydrolysis with multi-enzyme complex Viscozyme® L, respectively.

Novel Urinary Biomarkers of Orange Juice Consumption, Interindividual Variability, and Differences with Processing Methods.

Untargeted metabolomics identified urinary biomarkers able to discriminate between the intake of fresh hand-squeezed and industrially processed orange juices. Processing led to an upregulation in the excretion of hydroxy-polymethoxyflavone sulfates, abscisic acid, and sinapic acid 4'-glucuronide. The demethylated polymethoxyflavone metabolites were produced with a significant interindividual variability suggesting that they could originate from gut microbiota metabolism. No correlation between the excretion levels of flavanone and polymethoxyflavone metabolites was observed, showing that gut microbiota metabolism differences could be behind the interindividual variability. Subjects with a high excretion level of hesperetin conjugates could be low or high polymethoxyflavone excretors. Flavanone phase II metabolites were primarily glucuronides, while those of demethylated polymethoxyflavones were mainly sulfates. A comparative study with the available demethylated polymethoxyflavone standards suggested that the metabolites produced in humans could be tentatively 4'-hydroxy- and/or 3'-hydroxy-polymethoxyflavone sulfates. This study is the first to describe the bioavailability and metabolism of citrus juice polymethoxyflavones in humans.

Blood Orange Juice Consumption Increases Flow-Mediated Dilation in Adults with Overweight and Obesity: A Randomized Controlled Trial.

BACKGROUND: Epidemiological studies have indicated an inverse association between citrus fruit consumption and cardiovascular disease (CVD) risk. There is, however, a paucity of data concerning effects of blood orange juice (BOJ) intake on endothelial function and cardiovascular risk biomarkers. OBJECTIVES: We examined short-term effects of BOJ on endothelial function, blood pressure, lipid profile, and inflammatory markers in healthy participants of European origin who were overweight or obese. METHODS: In a randomized, controlled, single-blind, crossover trial, 15 men and women (age: 28.7 ± 6.5 y; BMI: 28.3 ± 3.1 kg/m2) consumed BOJ or a sugar-matched control drink (CD) (200 mL twice daily) for 2 wk with a washout period of 1 wk. Endothelial function, measured as flow-mediated dilation (FMD) (primary outcome), and the secondary outcomes blood pressure, anthropometric measures, lipid profile, inflammatory markers, markers of vasodilation and vasoconstriction, and urinary flavanone metabolites were evaluated prior to and at the end of each treatment period following an overnight fast. Changes between treatments over time were assessed using repeated-measures ANOVA. RESULTS: The results demonstrate a significant increase in FMD following BOJ consumption (pre: 8.15% ± 2.92%; post: 10.2% ± 3.31%; P = 0.002) compared with CD (pre: 8.11% ± 2.52%; post: 7.77% ± 2.43%; time × treatment interaction: P = 0.001). Concurrent significant increases in urinary hesperetin-3'-glucuronide and hesperetin-7-glucuronide were observed following BOJ supplementation only (time × treatment interaction: P ≤ 0.01). Baseline blood pressure, lipid profile, high-sensitivity C-reactive protein, and endothelin-1 were generally within healthy ranges and unaffected by the intervention. CONCLUSIONS: A 2-wk consumption of BOJ exerted favorable effects on endothelial function in healthy women and men who were overweight or obese, which is likely mediated by the combined actions of anthocyanin and flavanone metabolites on mechanisms that contribute to enhancing NO bioavailability. This trial was registered at clinicaltrials.gov as NCT03611114.

First exploratory study on the metabolome from plasma exosomes in patients with paroxysmal nocturnal hemoglobinuria.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in which patients are at increased risk of thrombosis. The mechanisms underlying the associated thrombosis risk are still poorly understood, although it is known that Eculizumab, the drug of choice for symptomatic patients, prevents thrombotic events. Exosomes are extracellular vesicles that can carry and disseminate genetic material, tumor biomarkers and inflammatory mediators. To date, the metabolite cargo of plasma exosomes from PNH patients has not yet been explored. In this pilot trial, we compared the metabolome of plasma exosomes from PNH patients with that of healthy subjects in order to provide further insights into this rare disease. RESULTS: We used a non-targeted metabolomics approach with UPLC-ESI-QTOF-MS/MS and GC-MS platforms. Multivariate analyses revealed the differential occurrence (p < .001) of 78 metabolites in plasma exosomes from PNH patients vs healthy control subjects. Remarkably, prostaglandin F2-alpha (6.1-fold), stearoyl arginine (5.3-fold) and 26-hydroxycholesterol-3-sulfate (11.2-fold) were higher in PNH patients vs healthy controls (p < .001). CONCLUSIONS: This is the first description on the differential metabolite cargo occurring in plasma exosomes from PNH patients. Our results could contribute to the search for possible prognostic biomarkers of thrombotic risk in patients with PNH. Further research in a larger cohort to validate these results is warranted.

Differential miRNA expression profile and proteome in plasma exosomes from patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a clonal disease of blood cells caused by the lack of glycosyl phosphatidyl inositol anchored proteins bound to the cell membrane. In consequence, erythrocytes lead to intravascular hemolysis upon complement activation, which promotes high risk of thrombosis, intravascular hemolytic anemia, and bone marrow failure in patients. The mechanisms of thrombosis in PNH are still poorly understood. Treatment with eculizumab reduces intravascular hemolysis and thrombotic risk, but not in all cases. Exosomes are extracellular vesicles released by cells and whose secretion is closely related to the inflammatory status. They participate in cell communication by activating signaling pathways and transferring genetic material and proteins to host cells. In consequence, exosomes may serve as surrogate biomarkers for the prognosis and/or diagnosis of a disease. Isolation of exosomes was carried out from healthy controls and from three groups of PNH patients, i.e. i) with no eculizumab treatment; ii) under treatment with eculizumab that have not suffered thrombosis; and iii) under treatment with eculizumab but that have suffered thrombosis. The miRNAome and proteome was analyzed using plasma focus miRNAs PCR panel and LC-MS analysis respectively. We found differential expression of miRNAs miR-148b-3p, miR-423-3p, miR29b-3p, miR15b-5p, let-7e-5p, miR126-3p, miR-125b-5p and miR-376c-3p as well as hemoglobin, haptoglobin, protein S and C4-binding protein in healthy controls vs PNH patients. Our results warrant further research and provide new information on the content of exosomes that could play a role in the hypercoagulable state in this disease.