The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin.

BACKGROUND: Obesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown. METHODS: A combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models. RESULTS: MiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats. CONCLUSIONS: Our data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity. SIGNIFICANCE STATEMENT: Up to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.

Grape Pomace-Advances in Its Bioactivity, Health Benefits, and Food Applications.

From a circular economy perspective, the appropriate management and valorization of winery wastes and by-products are crucial for sustainable development. Nowadays, grape pomace (GP) has attracted increasing interest within the food field due to its valuable content, comprising nutritional and bioactive compounds (e.g., polyphenols, organic and fatty acids, vitamins, etc.). Particularly, GP polyphenols have been recognized as exhibiting technological and health-promoting effects in different food and biological systems. Hence, GP valorization is a step toward offering new functional foods and contributing to solving waste management problems in the wine industry. On this basis, the use of GP as a food additive/ingredient in the development of novel products with technological and functional advantages has recently been proposed. In this review, we summarize the current knowledge on the bioactivity and health-promoting effects of polyphenolic-rich extracts from GP samples. Advances in GP incorporation into food formulations (enhancement of physicochemical, sensory, and nutritional quality) and information supporting the intellectual property related to GP potential applications in the food industry are also discussed.

Encuesta burnout (¿estás quemado?) en Especialistas de Cardiología SAC / Burnout Survey among SAC Cardiologists

RESUMEN Introducción. Los profesionales de la salud se encuentran expuestos a un fenómeno ocupacional que resulta del estrés crónico en el ámbito laboral llamado síndrome de burnout (SBO). Este se ha convertido en uno de los riesgos laborales psicosociales más importantes en la sociedad actual y genera costos significativos en el ámbito de la salud. Objetivos. Evaluar la prevalencia de SBO por percepción subjetiva y mediante la aplicación del inventario del síndrome del Desgaste Ocupacional "Burnout" de Maslach (MBI) en los especialistas de cardiología del padrón de la Sociedad Argentina de Cardiología (SAC), y las diferencias acordes al sexo. Material y métodos. Estudio observacional, de corte transversal, mediante una encuesta anónima realizada en abril de 2023 a los especialistas del padrón SAC. Se recabaron datos sobre impresión subjetiva de SBO (sentirse "quemado"), sexo, edad, tiempo de ejercicio profesional. Fue opcional completar el inventario MBI (subescalas) para establecer el diagnóstico de burnout. Resultados. Participaron 756 profesionales, 51,4 % fueron mujeres. El 62 % tenían más de 40 años y el 61 % tenía más de 10 años de ejercicio profesional. Del total de médicos encuestados, el 94,4 % eligió realizar el test de Maslach (MBI), siendo esto más frecuente en las mujeres (96,6 % vs 91,3 %, p < 0,001). La prevalencia de SBO por un MBI de alto puntaje (≥67puntos) fue del 75 % y la prevalencia de percepción de SBO fue del 69 % (p < 0,001). De los que se autopercibieron "quemados" (69 %), el 96,8 % contestó el inventario MBI y se confirmó el diagnóstico de SBO por MBI de alto puntaje en el 78 %. De los que se autopercibieron "no quemados" (31 %), el 89,3 % completó el inventario MBI con diagnóstico de SBO en la subescala cansancio emocional (24 %), despersonalización (18 %) y realización personal (10 %) más allá de no tener la impresión subjetiva de estar "quemado". Los menores de 40 años tuvieron más SBO por MBI de alto puntaje (50 % vs 28 %, p= 0,001) al igual que los profesionales con menos de 10 años en el ejercicio de su profesión (45 % vs 20 % en aquellos con tiempo mayor, p < 0,001). El SBO fue más prevalente en las mujeres que en los hombres, tanto por autopercepción (77 % vs 56 %, p < 0,001) como por el inventario de Maslach (80 % vs 74 %, p=0,001), específicamente en la subescala agotamiento emocional (37 % vs 29 %; p < 0,001) y realización personal (37 % vs 41 %, p < 0,001), sin diferencias por sexo en la esfera de despersonalización. Conclusión. El SBO tiene alta prevalencia entre los cardiólogos encuestados, principalmente en mujeres, tanto por autopercepción como por aplicación del inventario MBI. Por otro lado 1 de cada 4 profesionales encuestados que no se autopercibían "quemados" tuvieron un test positivo para SBO. Teniendo en cuenta la alta prevalencia de SBO entre los especialistas en cardiología es imperioso realizar acciones de prevención e intervención concertadas y sostenidas para transformar esta realidad que impacta desfavorablemente tanto en la salud de los pacientes como en la de los propios médicos.

ABSTRACT Background. Healthcare professionals are exposed to an occupational phenomenon as a result of chronic stress in the workplace called burnout syndrome (BOS). Burnout has become one of the most important psychosocial occupational hazards today and generates significant health care costs. Objectives. The aim of our study was to evaluate the subjective perception of the prevalence of BOS among cardiologists of the Argentine Society of Cardiology (SAC) using Maslach Burnout Inventory (MBI), and the differences between sexes. Methods. We conducted an observational, cross-sectional study using an anonymous survey distributed among specialists of the SAC register in April 2023. The information collected included the subjective impression of BOS (feeling "burned out"), sex, age and years of practice. The participants could optionally complete the MBI (subscales) to establish the diagnosis of BOS. Results. A total of 756 professionals participated in the survey; 51.4% were women. Sixty-two percent of the participants were >40 years old, and 61 % had been practicing medicine for more than 10 years. Of all the physicians surveyed, 94.4% completed the MBI, with women more likely to do so than men (96.6% vs. 91.3%, p < 0.001). The prevalence of BOS, assessed by a high MBI score (≥ 67), was 75%, while 69% reported feeling burned out (p < 0.001). Of those who felt burned out (69 %), 96.8 % completed the MBI, and 78% of them received a diagnosis of BOS based on high MBI scores. Of the 31 % who did not feel burned out, 89.3 % completed the MBI. Burnout syndrome was diagnosed in the emotional exhaustion subscale in 24 %, in the depersonalization subscale in 18%, and in the personal accomplishment subscale in 10%. The diagnosis of BOS made by high MBI score was more common in survey participants under 40 years than in older participants (50 % vs. 28 %, p < 0.001) and in professionals who have been practicing medicine for less than 10 years (45 % vs. 20 % in those with more years of practice, p < 0.001). Women were more likely to experience BOS according to their own perception (77 % vs. 56 %, p < 0.001) and MBI score (80 % vs. 74 %, p < 0.001), specifically in the emotional exhaustion (37 % vs. 29 %, p < 0.001) and personal accomplishment (37 % vs. 41 %, p < 0.001) subscales, with No differences by sex in the depersonalization sphere. Conclusion. Burnout syndrome was found to be prevalent among the surveyed cardiologists, particularly in female participants, as indicated by both their own perception and the MBI assessment. In addition, 1 out of 4 professionals surveyed who did not feel "burned out" tested positive for BOS. Given the high prevalence of BOS among cardiologists, coordinated and sustained prevention and intervention actions should be undertaken to change this reality that negatively impacts both patient and physician health.

Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice.

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.

Nutraceutical and Pharmaceutical Behavior of Bioactive Compounds of Miracle Oilseeds: An Overview.

India plays an important role in the production of oilseeds, which are mainly cultivated for future extraction of their oil. In addition to the energic and nutritional contribution of these seeds, oilseeds are rich sources of bioactive compounds (e.g., phenolic compounds, proteins, minerals). A regular and moderate dietary supplementation of oilseeds promotes health, prevents the appearance of certain diseases (e.g., cardiovascular diseases (CVDs), cancers) and delays the aging process. Due to their relevant content in nutraceutical molecules, oilseeds and some of their associated processing wastes have raised interest in food and pharmaceutical industries searching for innovative products whose application provides health benefits to consumers. Furthermore, a circular economy approach could be considered regarding the re-use of oilseeds' processing waste. The present article highlights the different oilseed types, the oilseeds-derived bioactive compounds as well as the health benefits associated with their consumption. In addition, the different types of extractive techniques that can be used to obtain vegetable oils rich from oilseeds, such as microwave-assisted extraction (MAE), ultrasonic-assisted extraction (UAE) and supercritical fluid extraction (SFE), are reported. We conclude that the development and improvement of oilseed markets and their byproducts could offer even more health benefits in the future, when added to other foods.

Connecting nutritional deprivation and pubertal inhibition via GRK2-mediated repression of kisspeptin actions in GnRH neurons.

BACKGROUND: Perturbations in the timing of puberty, with potential adverse consequences in later health, are increasingly common. The underlying neurohormonal mechanisms are unfolded, but nutritional alterations are key contributors. Efforts to unveil the basis of normal puberty and its metabolic control have focused on mechanisms controlling expression of Kiss1, the gene encoding the puberty-activating neuropeptide, kisspeptin. However, other regulatory phenomena remain ill-defined. Here, we address the putative role of the G protein-coupled-receptor kinase-2, GRK2, in GnRH neurons, as modulator of pubertal timing via repression of the actions of kisspeptin, in normal maturation and conditions of nutritional deficiency. METHODS: Hypothalamic RNA and protein expression analyses were conducted in maturing female rats. Pharmacological studies involved central administration of GRK2 inhibitor, ßARK1-I, and assessment of gonadotropin responses to kisspeptin or phenotypic and hormonal markers of puberty, under normal nutrition or early subnutrition in female rats. In addition, a mouse line with selective ablation of GRK2 in GnRH neurons, aka G-GRKO, was generated, in which hormonal responses to kisspeptin and puberty onset were monitored, in normal conditions and after nutritional deprivation. RESULTS: Hypothalamic GRK2 expression increased along postnatal maturation in female rats, especially in the preoptic area, where most GnRH neurons reside, but decreased during the juvenile-to-pubertal transition. Blockade of GRK2 activity enhanced Ca+2 responses to kisspeptin in vitro, while central inhibition of GRK2 in vivo augmented gonadotropin responses to kisspeptin and advanced puberty onset. Postnatal undernutrition increased hypothalamic GRK2 expression and delayed puberty onset, the latter being partially reversed by central GRK2 inhibition. Conditional ablation of GRK2 in GnRH neurons enhanced gonadotropin responses to kisspeptin, accelerated puberty onset, and increased LH pulse frequency, while partially prevented the negative impact of subnutrition on pubertal timing and LH pulsatility in mice. CONCLUSIONS: Our data disclose a novel pathway whereby GRK2 negatively regulates kisspeptin actions in GnRH neurons, as major regulatory mechanism for tuning pubertal timing in nutritionally-compromised conditions.

Selective loss of kisspeptin signaling in oocytes causes progressive premature ovulatory failure.

STUDY QUESTION: Does direct kisspeptin signaling in the oocyte have a role in the control of follicular dynamics and ovulation? SUMMARY ANSWER: Kisspeptin signaling in the oocyte plays a relevant physiological role in the direct control of ovulation; oocyte-specific ablation of kisspeptin receptor, Gpr54, induces a state of premature ovulatory failure in mice that recapitulates some features of premature ovarian insufficiency (POI). WHAT IS KNOWN ALREADY: Kisspeptins, encoded by the Kiss1 gene, are essential for the control of ovulation and fertility, acting primarily on hypothalamic GnRH neurons to stimulate gonadotropin secretion. However, kisspeptins and their receptor, Gpr54, are also expressed in the ovary of different mammalian species, including humans, where their physiological roles remain contentious and poorly characterized. STUDY DESIGN, SIZE, DURATION: A novel mouse line with conditional ablation of Gpr54 in oocytes, named OoGpr54-/-, was generated and studied in terms of follicular and ovulatory dynamics at different age-points of postnatal maturation. A total of 59 OoGpr54-/- mice and 47 corresponding controls were analyzed. In addition, direct RNA sequencing was applied to ovarian samples from 8 OoGpr54-/- and 7 control mice at 6 months of age, and gonadotropin priming for ovulatory induction was conducted in mice (N = 7) from both genotypes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte-selective ablation of Gpr54 in the oocyte was achieved in vivo by crossing a Gdf9-driven Cre-expressing transgenic mouse line with a Gpr54 LoxP mouse line. The resulting OoGpr54-/- mouse line was subjected to phenotypic, histological, hormonal and molecular analyses at different age-points of postnatal maturation (Day 45, and 2, 4, 6 and 10-11 months of age), in order to characterize the timing of puberty, ovarian follicular dynamics and ovulation, with particular attention to identification of features reminiscent of POI. The molecular signature of ovaries from OoGpr54-/- mice was defined by direct RNA sequencing. Ovulatory responses to gonadotropin priming were also assessed in OoGpr54-/- mice. MAIN RESULTS AND THE ROLE OF CHANCE: Oocyte-specific ablation of Gpr54 caused premature ovulatory failure, with some POI-like features. OoGpr54-/- mice had preserved puberty onset, without signs of hypogonadism. However, already at 2 months of age, 40% of OoGpr54-/- females showed histological features reminiscent of ovarian failure and anovulation. Penetrance of the phenotype progressed with age, with >80% and 100% of OoGpr54-/- females displaying complete ovulatory failure by 6- and 10 months, respectively. This occurred despite unaltered hypothalamic Gpr54 expression and gonadotropin levels. Yet, OoGpr54-/- mice had decreased sex steroid levels. While the RNA signature of OoGpr54-/- ovaries was dominated by the anovulatory state, oocyte-specific ablation of Gpr54 significantly up- or downregulated of a set of 21 genes, including those encoding pituitary adenylate cyclase-activating polypeptide, Wnt-10B, matrix-metalloprotease-12, vitamin A-related factors and calcium-activated chloride channel-2, which might contribute to the POI-like state. Notably, the anovulatory state of young OoGpr54-/- mice could be rescued by gonadotropin priming. LARGE SCALE DATA: N/A. . LIMITATIONS, REASONS FOR CAUTION: Conditional ablation of Gpr54 in oocytes unambiguously caused premature ovulatory failure in mice; yet, the ultimate molecular mechanisms for such state of POI can be only inferred on the basis of RNAseq data and need further elucidation, since some of the molecular changes observed in OoGpr54-/- ovaries were secondary to the anovulatory state. Direct translation of mouse findings to human disease should be made with caution since, despite the conserved expression of Kiss1/kisspeptin and Gpr54 in rodents and humans, our mouse model does not recapitulate all features of common forms of POI. WIDER IMPLICATIONS OF THE FINDINGS: Deregulation of kisspeptin signaling in the oocyte might be an underlying, and previously unnoticed, cause for some forms of POI in women. STUDY FUNDING/COMPETING INTEREST(S): This work was primarily supported by a grant to M.P. and M.T.-S. from the FiDiPro (Finnish Distinguished Professor) Program of the Academy of Finland. Additional financial support came from grant BFU2017-83934-P (M.T.-S.; Ministerio de Economía y Competitividad, Spain; co-funded with EU funds/FEDER Program), research funds from the IVIRMA International Award in Reproductive Medicine (M.T.-S.), and EFSD Albert Renold Fellowship Programme (S.T.R.). The authors have no conflicts of interest to declare in relation to the contents of this work. TRIAL REGISTRATION NUMBER: N/A.

Kisspeptins and the neuroendocrine control of reproduction: Recent progress and new frontiers in kisspeptin research.

In late 2003, a major breakthrough in our understanding of the mechanisms that govern reproduction occurred with the identification of the reproductive roles of kisspeptins, encoded by the Kiss1 gene, and their receptor, Gpr54 (aka, Kiss1R). The discovery of this unsuspected reproductive facet attracted an extraordinary interest and boosted an intense research activity, in human and model species, that, in a relatively short period, established a series of basic concepts on the physiological roles of kisspeptins. Such fundamental knowledge, gathered in these early years of kisspeptin research, set the scene for the more recent in-depth dissection of the intimacies of the neuronal networks involving Kiss1 neurons, their precise mechanisms of regulation and the molecular underpinnings of the function of kisspeptins as pivotal regulators of all key aspects of reproductive function, from puberty onset to pulsatile gonadotropin secretion and the metabolic control of fertility. While no clear temporal boundaries between these two periods can be defined, in this review we will summarize the most prominent advances in kisspeptin research occurred in the last ten years, as a means to provide an up-dated view of the state of the art and potential paths of future progress in this dynamic, and ever growing domain of Neuroendocrinology.

New standards at European Union level on water reuse for agricultural irrigation: Are the Spanish wastewater treatment plants ready to produce and distribute reclaimed water within the minimum quality requirements?

The new European regulation on minimum quality requirements (MQR) for water reuse (EU, 2020/741) was launched in May 2020 and describes the directives for the use of reclaimed water for agricultural irrigation. This Regulation will be directly applicable in all Member States from 26 June 2023. Since its publication in 2020, concerns have raised about potential non-compliance situations in water reuse systems. The present study represents a case study where three different water reuse systems have been monitored to establish their compliance with the MQR. Each water reuse system includes a wastewater treatment plant (WWTP), a distribution/storage system and an end-user point, where water is used for irrigation of leafy greens. The selected water reuse systems allowed us to compare the efficacy of water treatments implemented in two WWTPs as well as the impact of three different irrigation systems (drip, furrow and overhead irrigation). The presence and concentration of indicator microorganisms (Escherichia coli and C. perfringens spores) as well as pathogenic bacteria (Shiga toxin-producing, E. coli (STEC), E. coli O157:H7, and Salmonella spp.) were monitored in different sampling points (influent and effluent of the WWTPs, water reservoirs located at the distribution system and the end-user point at the irrigation system as well as in the leafy greens during their growing cycle. Average levels of E. coli (0.73 ± 1.20 log cfu E. coli/100 mL) obtained at the point where the WWTP operator delivers reclaimed water to the next actor in the chain, defined in the European regulation as the 'point of compliance', were within the established MQR (<1 log cfu/100 mL) (EU, 2020/741). On the other hand, average levels of E. coli at the end-user point (1.0 ± 1.2 log cfu/100 mL) were below the recommended threshold (2 log cfu E. coli/100 mL) for irrigation water based on the guidance document on microbiological risks in fresh fruits and vegetables at primary production (EC, 2017/C_163/01). However, several outlier points were observed among the samples taken at the irrigation point, which were linked to a specific cross-contamination event within the distribution/storage system. Regarding pathogenic bacteria, water samples from the influent of the WWTPs showed a 100% prevalence, while only 5% of the effluent samples were positive for any of the monitored pathogenic bacteria. Obtained results indicate that reclaimed water produced in the selected water reuse system is suitable to be used as irrigation water. However, efforts are necessary not only in the establishment of advance disinfection treatments but also in the maintenance of the distribution/storage systems.

Molecular diagnosis of polycystic ovary syndrome in obese and non-obese women by targeted plasma miRNA profiling.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is diagnosed based on the clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, such as obesity and insulin resistance. miRNA have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical tools. METHODS: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean, non-PCOS/obese, PCOS/lean, and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800 human miRNA panel, followed by targeted quantitative real-timePCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs, and build classification algorithms, considering PCOS and obesity as major categories. RESULTS: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p, and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial least absolute shrinkage and selection operator regression and decision-tree models were built to reliably discriminate PCOS vs non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers. CONCLUSIONS: We define herein a robust method for molecular classification of PCOS based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS but also discrimination between PCOS and obesity. CAPSULE: We define a novel protocol, based on plasma miRNA profiling, for molecular diagnosis of PCOS. This tool not only allows proper discrimination of the condition in non-obese women but also permits distinction between PCOS and obesity, which often display overlapping clinical presentations.

Spray-drying encapsulation of microwave-assisted extracted polyphenols from Moringa oleifera: Influence of tragacanth, locust bean, and carboxymethyl-cellulose formulations.

In this work, polyphenols from Moringa oleifera (Mor) leaves were extracted by microwave-assisted extraction (MAE) and encapsulated by spray-drying (SD). Particularly, we explored the influence of tragacanth gum (TG), locust bean gum (LBG), and carboxymethyl-cellulose (CMC) as wall-materials on the physicochemical behavior of encapsulated Mor. Single or combined wall-material treatments (100:00 and 50:50 ratios, and total solid content 1%) were tested. The results showed the wall-material had a significant effect on the process yield (55.7-68.3%), encapsulation efficiency (24.28-35.74%), color (yellow or pale-yellow), total phenolic content (25.17-27.49 mg GAE g-1 of particles), total flavonoid content (23.20-26.87 mg QE g-1 of particles), antioxidant activity (DPPH• = 5.96-6.95 mg GAE g-1; ABTS•+ = 5.61-6.18 mg TE g-1 of particles), and particle size distribution (D50 = 112-1946 nm) of the encapsulated Mor. On the other hand, SEM analysis showed smooth and spherical particles, while TGA and DSC analyses confirmed the encapsulation of bioactive compounds based on the changes in thermal peaks. Finally, XRD analysis showed that the particles have an amorphous behavior. The encapsulated Mor produced with individual TG or CMC demonstrated better properties than those obtained from mixed gums. Thus, TG or CMC might be feasible wall materials for manufacturing encapsulated Mor that conserve the phenolic content and antioxidant activity.

Evolution of Flavors in Extra Virgin Olive Oil Shelf-Life.

Extra virgin olive oil (EVOO) is one of the most distinctive ingredients of the Mediterranean diet. There are many properties related to this golden ingredient, from supreme organoleptic characteristics to benefits for human health. EVOO contains in its composition molecules capable of exerting bioactivities such as cardio protection, antioxidant, anti-inflammatory, antidiabetic, and anticancer activity, among others, mainly caused by unsaturated fatty acids and certain minor compounds such as tocopherols or phenolic compounds. EVOO is considered the highest quality vegetable oil, which also implies a high sensory quality. The organoleptic properties related to the flavor of this valued product are also due to the presence of a series of compounds in its composition, mainly some carbonyl compounds found in the volatile fraction, although some minor compounds such as phenolic compounds also contribute. However, these properties are greatly affected by the incidence of certain factors, both intrinsic, such as the olive variety, and extrinsic, such as the growing conditions, so that each EVOO has a particular flavor. Furthermore, these flavors are susceptible to change under the influence of other factors throughout the oil's shelf-life, such as oxidation or temperature. This work offers a description of some of the most remarkable compounds responsible for EVOO's unique flavor and aroma, the factors affecting them, the mechanism that lead to the degradation of EVOO, and how flavors can be altered during the shelf-life of the oil, as well as several strategies suggested for the preservation of this flavor, on which the quality of the product also depends.

Scientific Approaches on Extraction, Purification and Stability for the Commercialization of Fucoxanthin Recovered from Brown Algae.

The scientific community has corroborated the numerous beneficial activities of fucoxanthin, such as its antioxidant, anti-inflammatory, anticancer or neuroprotective effects, among others. These properties have attracted the attention of nutraceutical, cosmetic and pharmacological industries, giving rise to various possible applications. Fucoxanthin may be chemically produced, but the extraction from natural sources is considered more cost-effective, efficient and eco-friendly. Thus, identifying suitable sources of this compound and giving a general overview of efficient extraction, quantification, purification and stabilization studies is of great importance for the future production and commercialization of fucoxanthin. The scientific research showed that most of the studies are performed using conventional techniques, but non-conventional techniques begin to gain popularity in the recovery of this compound. High Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR) and spectroscopy techniques have been employed in the quantification and identification of fucoxanthin. The further purification of extracts has been mainly accomplished using purification columns. Finally, the stability of fucoxanthin has been assessed as a free molecule, in an emulsion, or encapsulated to identify the variables that might affect its further industrial application.

Bioactive Compounds and Quality of Extra Virgin Olive Oil.

(1) Background: Extra virgin olive oil (EVOO) is responsible for a large part of many health benefits associated to Mediterranean diet as it is a fundamental ingredient of this diet. The peculiarities of this golden, highly valued product are in part due to the requirements that must be met to achieve this title, namely, it has to be obtained using exclusively mechanical procedures, its free acidity cannot be greater than 0.8%, it must not show sensory defects, and it has to possess a fruity taste. (2) Methods: All these characteristics are key factors to EVOO quality, thus the chemical composition of these many health-promoting compounds, such as unsaturated fatty acids (which are also the major compounds, especially oleic acid), as well as minor components such as tocopherols or phenolic compounds (which behave as natural antioxidants) must be preserved. (3) Results: Due to the presence of all these compounds, the daily consumption of EVOO entails health benefits such as cardioprotective, antioxidant, anti-inflammatory, anti-tumor properties or acting as regulator of the intestinal microbiota, among others. (4) Conclusions: Taking all together, conserving EVOO chemical composition is essential to preserve its properties, so it is worth to control certain factors during storage like exposure to light, temperature, oxygen presence or the chosen packaging material, to maintain its quality and extend its shelf-life until its consumption.

Neonatal exposure to androgens dynamically alters gut microbiota architecture.

Gonadal steroids strongly contribute to the metabolic programming that shapes the susceptibility to the manifestation of diseases later in life, and the effect is often sexually dimorphic. Microbiome signatures, together with metabolic traits and sex steroid levels, were analyzed at adulthood in neonatally androgenized female rats, and compared with those of control male and female rats. Exposure of female rats to high doses of androgens on early postnatal life resulted in persistent alterations of the sex steroid profile later on life, namely lower progesterone and higher estradiol and estrone levels, with no effect on endogenous androgens. Neonatally androgenized females were heavier (10% at early adulthood and 26% at adulthood) than controls and had impaired glucose homeostasis observed by higher AUC of glucose in GTT and ITT when subjected to obesogenic manipulations. Androgenized female displayed overt alterations in gut microbiota, indicated especially by higher Bacteroidetes and lower Firmicutes abundance at early adulthood, which disappeared when animals were concurrently overfed at adulthood. Notably, these changes in gut microbiota were related with the intestinal expression of several miRNAs, such as miR-27a-3p, miR-29a-5p, and miR-100-3p. Our results suggest that nutritional and hormonal disruption at early developmental periods not only alters the metabolic programming of the individual later in life but also perturbs the architecture of gut microbiota, which may interact with the host by a cross-talk mediated by intestinal miRNAs; phenomena that may contribute to amplify the metabolic derangement caused by obesity, as seen in neonatally androgenized female rats.

Nanosystems of plant-based pigments and its relationship with oxidative stress.

Plant-based pigments are widely present in nature, they are classified depending on their chemical structure as tetrapyrroles, carotenoids, polyphenolic compounds, and alkaloids and are extensively used in medicine, food industry, clothes, and others. Recently they have been investigated due to their role in the areas of food processing, food safety and quality, packaging, and nutrition. Many studies indicate a relationship between bioactive pigments and Non-Communicable Diseases derived from oxidative stress. Their biological applications can help in preventing oxidative injuries in the cell caused by oxygen and nitrogen reactive species. Those pigments are easily degraded by light, oxygen, temperature, pH conditions, among others. Nanotechnology offers the possibility to protect bioactive ingredients and increase its bioavailability after oral administration. Safety to humans (mainly evaluated from toxicity data) is the first concern for these products. In the present work, we present a comprehensive outlook of the most important plant-based pigments used as food colorants, the principal nanotechnology systems prepared with them, and the relationship of these compounds with the oxidative stress and related Non-Communicable Disease.

Technological Application of Tannin-Based Extracts.

Tannins are polyphenolic compounds naturally found in vegetables. Their presence in nature has prompted their historical use in many different ways. The revision of their traditional utilization has allowed their further modification aiming for an industrial application. Sometimes these modifications have implied the addition of harmful substances such as formaldehyde, classified as a carcinogen of category B1. In other cases, these natural tannins have been replaced by synthetic compounds that threaten human and animal health and damage the environment. Therefore, currently, both academy and industry are searching for the substitution of these unsafe complexes by the increasing inclusion of tannins, natural molecules that can be obtained from several and diverse renewable resources, modified using harmless additives. To achieve promising results, cost-efficient and eco-friendly extraction methods have been designed. Once these green alternatives have been isolated, they have been successfully applied to many fields with very assorted aims of utilization such as coagulants, adhesives, floatation agents, tannings, dyes, additives, or biomolecules. Therefore, this review offers a global vision of the full process that involves the tannin's technological application including an overview of the most relevant tannin sources, effective extraction methods, and their utilization in very diverse fields.

The Potential of Seaweeds as a Source of Functional Ingredients of Prebiotic and Antioxidant Value.

Two thirds of the world is covered by oceans, whose upper layer is inhabited by algae. This means that there is a large extension to obtain these photoautotrophic organisms. Algae have undergone a boom in recent years, with consequent discoveries and advances in this field. Algae are not only of high ecological value but also of great economic importance. Possible applications of algae are very diverse and include anti-biofilm activity, production of biofuels, bioremediation, as fertilizer, as fish feed, as food or food ingredients, in pharmacology (since they show antioxidant or contraceptive activities), in cosmeceutical formulation, and in such other applications as filters or for obtaining minerals. In this context, algae as food can be of help to maintain or even improve human health, and there is a growing interest in new products called functional foods, which can promote such a healthy state. Therefore, in this search, one of the main areas of research is the extraction and characterization of new natural ingredients with biological activity (e.g., prebiotic and antioxidant) that can contribute to consumers' well-being. The present review shows the results of a bibliographic survey on the chemical composition of macroalgae, together with a critical discussion about their potential as natural sources of new functional ingredients.

Glucosinolates: Molecular structure, breakdown, genetic, bioavailability, properties and healthy and adverse effects.

Glucosinolates are a large group of plant secondary metabolites with nutritional effects and biologically active compounds. Glucosinolates are mainly found in cruciferous plants such as Brassicaceae family, including common edible plants such as broccoli (Brassica oleracea var. italica), cabbage (B. oleracea var. capitata f. alba), cauliflower (B. oleracea var. botrytis), rapeseed (Brassica napus), mustard (Brassica nigra), and horseradish (Armoracia rusticana). If cruciferous plants are consumed without processing, myrosinase enzyme will hydrolyze the glucosinolates to various metabolites, such as isothiocyanates, nitriles, oxazolidine-2-thiones, and indole-3-carbinols. On the other hand, when cruciferous are cooked before consumption, myrosinase is inactivated and glucosinolates could be partially absorbed in their intact form through the gastrointestinal mucosa. This review paper summarizes the glucosinolate molecular breakdown, their genetic aspects from biosynthesis to precursors, their bioavailability (assimilation, absorption, and elimination of these molecules), their sensory properties, identified healthy and adverse effects, as well as the impact of processing on their bioavailability.

Benzoxaboroles as dynamic covalent receptors for bioconjugation and transport of nucleosides and related drugs: Proof of action in HeLa cells.

In this work we describe not previously explored binding studies on the reversible interaction of benzoxaborole with ligands of medical and pharmaceutical interest such as nucleosidic drugs gemcitabine and capecitabine, as well as the hydrophobic chemotherapeutic doxorubicin. We include functional derivatives of benzoxaborole such as a near infrared fluorescent boronolectine, Cy-Bx, The dynamic covalent interaction in physiological conditions was assessed by spectroscopic techniques yielding moderate to high binding affinities. The cytotoxic activity of the drugs upon conjugation to the boronolectins was evaluated revealing significant influence of the bioconjugation status on the cellular viability. The availability of the conjugate for cellular uptake and localization in the model cancer cell line HeLa was assessed by fluorescence imaging. Benzoxaborole and the fluorescent boronolectin Cy-Bx, proved to be versatile conjugation tools for 1,2 and 1,3-diol containing pharmacophores as well as bioisosteric forms such as 1,2-hydroxyamino, envisioning these small boronolectins as components in systems for drug release with tracking capability.