Locus-Specific and Stable DNA Demethylation at the H19/IGF2 ICR1 by Epigenome Editing Using a dCas9-SunTag System and the Catalytic Domain of TET1.

DNA methylation is critically involved in the regulation of chromatin states and cell-type-specific gene expression. The exclusive expression of imprinted genes from either the maternal or the paternal allele is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). Aberrant DNA hyper- or hypomethylation at the ICR1 of the H19/IGF2 imprinting locus is characteristic for the imprinting disorders Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), respectively. In this paper, we performed epigenome editing to induce targeted DNA demethylation at ICR1 in HEK293 cells using dCas9-SunTag and the catalytic domain of TET1. 5-methylcytosine (5mC) levels at the target locus were reduced up to 90% and, 27 days after transient transfection, >60% demethylation was still observed. Consistent with the stable demethylation of CTCF-binding sites within the ICR1, the occupancy of the DNA methylation-sensitive insulator CTCF protein increased by >2-fold throughout the 27 days. Additionally, the H19 expression was increased by 2-fold stably, while IGF2 was repressed though only transiently. Our data illustrate the ability of epigenome editing to implement long-term changes in DNA methylation at imprinting control regions after a single transient treatment, potentially paving the way for therapeutic epigenome editing approaches in the treatment of imprinting disorders.

Aortic dissection detection and thrombus structure quantification using volumetric ultrasound, histology, and scanning electron microscopy.

Aortic dissection occurs when a weakened portion of the intima tears, and a separation of layers propagates along the aortic wall to form a false lumen filled with active blood flow or intramural thrombus. The unpredictable nature of aortic dissection formation and need for immediate intervention leaves limited serial human image data to study the formation and morphological changes that follow dissection. We used volumetric ultrasound examination, histology, and scanning electron microscopy (SEM) to examine intramural thrombi at well-defined timepoints after dissection occurs in apolipoprotein E-deficient mice infused with angiotensin II (n = 71). Stratification of red blood cell (RBC) morphologies (biconcave, intermediate biconcave, intermediate polyhedrocyte, and polyhedrocyte) in the thrombi with scanning electron microscopy (n = 5) was used to determine degree of thrombus deposition/contraction. Very few biconcave RBCs (1.2 ± 0.6%) were in the thrombi, and greater amounts of intermediate biconcave RBCs (25.8 ± 6.7%) were located in the descending thoracic portion of the dissection while more polyhedrocytes (14.6 ± 5.1%) and fibrin (42.3 ± 4.5%; P < .05) were found in the distal suprarenal aorta. Thrombus deposition likely plays some role in patient outcomes, and this multimodality technique can help investigate thrombus deposition and characteristics in experimental animal models and human tissue samples.

Evaluación de las ingestas dietéticas y prácticas alimentarias en niños de 6 a 23 meses en una localidad del noreste argentino / Assessment of dietary intakes and feeding practices in children aged 6­23 months in a town in the Northeast region of Argentina

Introducción. Una alimentación complementaria adecuada en cantidad y calidad resulta esencial durante los primeros dos años de vida. El objetivo del estudio fue evaluar la ingesta de nutrientes y prácticas alimentarias en niños de 6 a 23 meses de una localidad del noreste argentino. Población y métodos. Estudio descriptivo transversal (segundo semestre del 2019). Se evaluaron las ingestas de 24 horas mediante recordatorios a los cuidadores de niños de 6 a 23 meses. Los datos se compararon con las ingestas dietéticas de referencia. Las prácticas alimentarias se evaluaron según los indicadores establecidos por la Organización Mundial de la Salud. Resultados. Se evaluaron 138 niños de 6 a 23 meses de edad. La energía y las vitaminas A, D y E presentaron porcentajes medios de adecuación inferiores al 100 % en todas las edades, mientras que las proteínas alcanzaron una adecuación promedio del 142,8 % y el 168,1 % para los niños de 7-12 meses y de 13-23 meses, respectivamente. Los nutrientes que presentaron una proporción considerable de casos con ingestas por debajo del requerimiento promedio estimado en todos los grupos fueron la energía y la vitamina A. En cuanto a los indicadores de prácticas alimentarias, 50,8 % de los lactantes recibió una dieta mínima aceptable. Conclusiones. Existe una alta prevalencia de inadecuación energética y de nutrientes críticos durante la alimentación complementaria en los niños de 6 a 23 meses incluidos en el estudio. Intervenciones nutricionales que promuevan prácticas alimentarias que mejoren la ingesta de micronutrientes serían de suma importancia para su salud actual y futura.

Introduction. An adequate quantity and quality of complementary feeding is essential during the first 2 years of life. The objective of this study was to assess dietary intakes and feeding practices in children aged 6­23 months in a town in the Northeast region of Argentina. Population and methods. Descriptive, cross-sectional study (second semester of 2019). Intakes from 24-hour dietary recall interviews conducted among caregivers of children aged 6­23 months were assessed. Data were compared to dietary reference intakes. Feeding practices were assessed as per the World Health Organization's indicators. Results. A total of 138 children aged 6­23 months were assessed. The mean adequacy ratio of energy and vitamins A, D, and E was below 100% for all ages, whereas the protein adequacy for children aged 7-12 and 13-23 months was 142.8% and 168.1%, respectively. A remarkable number of cases had energy and vitamin A intakes below the estimated average requirement. In relation to feeding practice indicators, 50.8% of infants received a minimum acceptable diet. Conclusions. There is a high prevalence of an inadequate level of energy and critical nutrient intake during complementary feeding of the children aged 6­23 months included in the study. Nutritional interventions that promote feeding practices to improve micronutrient intake would be highly important for children's current and future health.

Assessment of dietary intakes and feeding practices in children aged 6-23 months in a town in the Northeast region of Argentina. / Evaluación de las ingestas dietéticas y prácticas alimentarias en niños de 6 a 23 meses en una localidad del noreste argentino.

INTRODUCTION: An adequate quantity and quality of complementary feeding is essential during the first 2 years of life. The objective of this study was to assess dietary intakes and feeding practices in children aged 6-23 months in a town in the Northeast region of Argentina. POPULATION AND METHODS: Descriptive, crosssectional study (second semester of 2019). Intakes from 24-hour dietary recall interviews conducted among caregivers of children aged 6-23 months were assessed. Data were compared to dietary reference intakes. Feeding practices were assessed as per the World Health Organization's indicators. RESULTS: A total of 138 children aged 6-23 months were assessed. The mean adequacy ratio of energy and vitamins A, D, and E was below 100% for all ages, whereas the protein adequacy for children aged 7-12 and 13-23 months was 142.8% and 168.1%, respectively. A remarkable number of cases had energy and vitamin A intakes below the estimated average requirement. In relation to feeding practice indicators, 50.8% of infants received a minimum acceptable diet. CONCLUSIONS: There is a high prevalence of an inadequate level of energy and critical nutrient intake during complementary feeding of the children aged 6-23 months included in the study. Nutritional interventions that promote feeding practices to improve micronutrient intake would be highly important for children's current and future health.

Introducción. Una alimentación complementaria adecuada en cantidad y calidad resulta esencial durante los primeros dos años de vida. El objetivo del estudio fue evaluar la ingesta de nutrientes y prácticas alimentarias en niños de 6 a 23 meses de una localidad del noreste argentino. Población y métodos. Estudio descriptivo transversal (segundo semestre del 2019). Se evaluaron las ingestas de 24 horas mediante recordatorios a los cuidadores de niños de 6 a 23 meses. Los datos se compararon con las ingestas dietéticas de referencia. Las prácticas alimentarias se evaluaron según los indicadores establecidos por la Organización Mundial de la Salud. Resultados. Se evaluaron 138 niños de 6 a 23 meses de edad. La energía y las vitaminas A, D y E presentaron porcentajes medios de adecuación inferiores al 100 % en todas las edades, mientras que las proteínas alcanzaron una adecuación promedio del 142,8 % y el 168,1 % para los niños de 7-12 meses y de 13-23 meses, respectivamente. Los nutrientes que presentaron una proporción considerable de casos con ingestas por debajo del requerimiento promedio estimado en todos los grupos fueron la energía y la vitamina A. En cuanto a los indicadores de prácticas alimentarias, 50,8 % de los lactantes recibió una dieta mínima aceptable. Conclusiones. Existe una alta prevalencia de inadecuación energética y de nutrientes críticos durante la alimentación complementaria en los niños de 6 a 23 meses incluidos en el estudio. Intervenciones nutricionales que promuevan prácticas alimentarias que mejoren la ingesta de micronutrientes serían de suma importancia para su salud actual y futura.

Análisis del consumo, utilización y aprovechamiento de frutas y verduras entre los años 2019 y 2021 / Analysis of consumption, use and utilization of fruits and vegetables between 2019 and 2021

En 2021 se conmemoró el Año Internacional de las Frutas y Verduras (FyV). Estos alimentos cumplen un rol indispensable en la dieta, sin embargo, un amplio sector de la población no las consume en la variedad y cantidad recomendadas. A esto se suma la problemática de las pérdidas y desperdicios de alimentos, situación que trae consigo un impacto negativo a nivel social, ambiental y económico. El objetivo del presente artículo fue analizar el consumo, utilización y aprovechamiento de FyV desde las perspectivas de salud y sostenibilidad. Para esto, se realizaron cuatro encuestas entre 2019 y 2021 que evaluaron diferentes dimensiones relacionadas con estos alimentos: adecuación del consumo, variedades consumidas, criterios de calidad de FyV apreciados por los consumidores y prácticas de sostenibilidad y consumo responsable. Sólo el 19% de los encuestados presentó consumos adecuados de FyV (5 o más porciones diarias). La variedad de frutas consumidas es menor que la de hortalizas, concentrándose en tres de ellas: manzana, banana y naranja. Los principales factores identificados como limitantes del consumo de FyV fueron el precio, la elevada perecibilidad de estos alimentos y la preferencia hacia otros productos. En relación a las prácticas de alimentación sostenible y los principales criterios de calidad valorados por los consumidores se observó un bajo aprovechamiento de partes comestibles de frutas o verduras, menos del 27% de los encuestados consume la fruta con cáscara, y un mayor desaprovechamiento de partes comestibles de verduras, dónde el 64% de los encuestados tira partes como tallos u hojas, aún cuando existen vías de aprovechamiento con fines no alimenticios. Por último, el factor de calidad más apreciado por los consumidores es la apariencia (30%), el valor nutricional no fue un parámetro de gran valoración (6%)(AU).

In 2021, the International Year of Fruits and Vegetables (FyV) was commemorated. These foods play an essential role in the diet; however, a large sector of the population does not consume them in the recommended variety and quantity. Added to this is the problem of food losses and waste, a situation that brings about a negative impact at a social, environmental and economic level. The objective of this article was to analyze the consumption, use and utilization of F&V from the perspectives of health and sustainability. For achiving this, four surveys were carried out between 2019 and 2021 that evaluated different dimensions: adequacy of consumption, varieties consumed, F&V quality criteria appreciated by consumers, and sustainability practices and responsible consumption. Only 19% of those surveyed presented adequate consumption of F&V (5 or more daily servings). The variety of fruits consumed is less than that of vegetables, concentrating on three of them: apple, banana and orange. The main factors limiting the consumption of F&V were the price, the high perishability of these foods and the preference for other products. In relation to sustainable eating practices and the main quality criteria valued by consumers, a low use of edible parts of fruits or vegetables was observed, less than 27% of respondents consume fruit with peel, and a greater waste of edible parts of vegetables, where 64% of respondents throw away parts such as stems or leaves, even when there are ways of using them for non-food purposes. Finally, the quality factor most appreciated by consumers is appearance (30%), nutritional value was not a highly valued parameter (6%)(AU).

Pharmacological Activity of Quercetin and 5 Caffeoylquinic Acid Oral Intake in Male Balb/c Mice with Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAC) is a major worldwide cause of death by cancer, it shows high aggressiveness, functional decline, systemic compromise and severe cachexia, which might be counteracted by dietary redox-active phytochemicals. Therefore, our aim was to establish the anticancer effects of the oral intake of quercetin and 5 caffeoylquinic acid. METHODS: LAC-1-bearing male Balb/c mice received quercetin (0-25 µg/kg/d) and 5 caffeoylquinic acid (0-120 µg/kg/d) for three weeks, with different organic and biochemical variables being then compared with ANOVA and the Fisher Test (p <0.05). RESULTS: Quercetin delayed 1.18 fold tumour appearance and increased 8.87 fold non-neoplastic body weight gain, whereas 5 caffeoylquinic acid did it in a lesser extent (1.17 and 2.48 fold, respectively), with tumour weight being consequent with the evolution time. Quercetin induced >1.15 fold tumour hydroperoxides and lipoperoxides, whereas 5 caffeoylquinic acid induced only lipoperoxides. Although both phytochemicals reduced <0.85 fold hydroperoxides and lipoperoxides in the kidney, only quercetin was also antioxidant in the liver. Additionally, 5 caffeoylquinic acid increased >1.15 fold hepatic and renal weights. Although these phytochemicals did not modify telencephalic interleukin 6 production, quercetin augmented 2.51 fold interleukin 6 in the diencephalon, whereas 5 caffeoylquinic acid decreased it 0.43 fold. CONCLUSIONS: Quercetin delayed lung adenocarcinoma appearance and increased the non-neoplastic body weight gain in mice with tumour oxidative stress, without brain interleukin 6 participation. 5 caffeoylquinic acid showed similar effects, although they were weaker. Additionally, quercetin acted as a hepatic and renal antioxidant, whereas 5 caffeoylquinic acid only exerted this effect in the kidney. Therefore, safe oral doses of this flavonoid are promissory to modulate lung cancer progression, with further studies being encouraged.

Effect of cultivation method and processing on total polyphenols content and antioxidant capacity of tomatoes (Solanum lycopersicum)

INTRODUCTION: Tomato is an important dietary source of polyphenols. Factors such as cultivation method and heat can affect its composition. The objective of this study was to determine changes of polyphenol content and antioxidant capacity in tomatoes obtained from different production method (organic vs. conventional), before and after being cooked. METHODS: Total polyphenols and antioxidant capacity were measured in fresh and processed tomatoes from two cultivation methods, using spectrophotometric techniques. RESULTS: Antioxidant capacity was higher (p < 0.05) for fresh and processed samples of organic tomatoes compared with conventional ones (organic 17,82 mg Fe+2/g > conventional 15,39 mg Fe+2/g). No significant difference in polyphenol content according to method of cultivation was found (organic 3,8 μg GAE/g > conventional 3,2 μg GAE/g). Measured parameters were not significantly affected by physical and mechanical processing in tomatoes from both cultivation methods. DISCUSSION: A tendency towards better phytochemical properties in organic tomatoes were found in our study, which is consistent with existing literature. Antioxidant compounds in organic samples appear to be more resistant to processing. CONCLUSION: It is necessary to deepen the study of organic and conventional tomatoes, in order to get more evidence on its nutritional quality

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Effects of bioavailable phenolic compounds from Ilex paraguariensis on the brain of mice with lung adenocarcinoma.

Lung carcinoma is one of the most common cancers and has a high mortality. Recently, we showed that it produces neurological paraneoplastic syndrome, with Ilex paraguariensis (IP) extract exerting palliative effects due to its content of phenolic compounds. It is possible, therefore, that these diet agents can arrive at the brain and exert neuroprotection, after the oral intake of IP. Here, the aim was to investigate the protective role of bioavailable IP compounds on the telencephalon and diencephalon in lung adenocarcinoma-bearing BALB/cJ males. Mice aged 2 months were treated for 3 weeks with 0-100 IP mg·kg-1 ·day-1 . HPLC-UV revealed the presence of chlorogenic acid and quercetin in brain regions, liver, and tumour, in an IP dose-dependent manner. Brain was also evaluated histologically, and interleukin-6 was measured by ELISA. Chlorogenic acid was the major compound found in brain, whereas quercetin was observed at the diencephalon to a lesser extent. Both compounds were involved in IP dose-dependent diencephalic interleukin-6 reduction. Histology suggested cellular protection with less apoptosis in chlorogenic-exposed areas. Taken together, chlorogenic acid and quercetin from dietary IP were bioavailable and bioactive in brain, thereby attenuating lung cancer-related neuroinflammation and damage. These findings support plant-based strategies to improve prognosis.

Neuroprotective Effect of Ilex Paraguariensis Intake on Brain Myelin of Lung Adenocarcinoma-Bearing Male Balb/c Mice.

Ilex paraguariensis (IP) is widely consumed as tea with high nutritional value. This plant contains several bioactive phenolic compounds, which are antioxidant and anti-inflammatory. On the other hand, lung adenocarcinoma (LAC) deleteriously involves neoplastic progression, inflammatory paraneoplastic syndromes, and death. Given that brain is a frequent target of this illness, our objective was to determine the neuroprotective effect of IP consumption in LAC-bearing mice. They were orally treated with 50 mg of IP extract/kg/day (IP50) for 3 weeks. Results (phenolic compounds, lipid peroxides, interleukin 6-IL-6-, tumor necrosis factor alpha -TNFα-, and luxol-stained myelination) were compared with respect to untreated controls (C) by the T test. IP50 significantly lowed brain IL-6 (2858.12 ± 57.81 pg g-1 vs. 3801.30 ± 27.34 pg g-1), whereas other variables differed in a less extent. C brains showed demyelination (low luxol-staining contrast between gray and white matters), with IP50 increasing myelination (P < 0.05). In conclusion, LAC deleterious effects on murine brain were prevented by dietary IP, which is an original discovery to develop a nutritional approach against cancer neurological compromise.

Evaluación de las condiciones de desamargado en húmedo de quinoa (Chenopodium quinoa Willd) / Evaluation of wet de-bittering conditions of quinoa (Chenopodium quinoa Willd)

Introducción: los granos de quinoa presentan en su episperma saponinas, compuestos con actividad antinutricional y que le otorgan sabor amargo al grano, por lo que deben desamargarse previo a su consumo. La falta de precisión acerca de las condiciones más adecuadas para realizarlo por método húmedo, evidencia la necesidad de contar con información que aporte claridad. Objetivo: el objetivo del trabajo fue evaluar las condiciones de desamargado vía húmeda en granos de quinoa, con el fin de comparar su efectividad con un método cuantitativo. Materiales y métodos: se evaluaron como variables el tiempo, relación agua/granos y temperatura. Para determinar el contenido de saponinas residuales, se utilizó el método de la espuma (estimación afrosimétrica) y se compararon los resultados con espectrofotometría. Resultados y discusión: todas las variables ejercieron un efecto significativo y una correlación negativa sobre el contenido de saponinas. La interacción de las variables permitió establecer las condiciones de extracción que tuvieron mayor eficiencia: 6 minutos, relación masa granos/solvente 10 mL/g, independientemente de la temperatura. Por espectrofotometría, se observó la misma tendencia. Conclusiones: la conjugación de estas condiciones permite realizar lavados en tiempos breves, con una cantidad de agua determinada y sin la necesidad de aplicar temperatura. El método demostró ser sencillo, práctico y eficiente para la remoción de las saponinas

Introduction: quinoa grains present in its episperm saponins, compounds with antinutritional activity that give bitter flavor to the grain. Therefore, they must be previously removed for their consumption. The lack of precision about the most appropriate conditions to perform it by wet method, demonstrates the need to have information that provides clarity. Aim: the aim of this work was to evaluate the conditions of wet de-bittering in grains of quinoa, in order to compare its effectiveness with a quantitative method. Materials and methods: Time, water/grain mass ratio and temperature were evaluated as variables. To determine the content of saponins, foam method (afrosimetric estimation) was used and the data obtained by spectrophotometric method was used to compare. Results and discussion: All the variables presented a significant effect and a negative correlation on the saponin content. The interaction between the variables allowed establishing the conditions of extraction that had greater efficiency: 6 minutes, solvent/grain mass ratio 10:1, independently of the temperature. The same tendency was observed by spectrophotometry. Conclusions: the conjugation of these conditions enables to carry out washes in short periods of time, with a certain amount of water and without the need to apply temperature. The method proved to be simple, practical and efficient for the removal of saponins

Pharmacology and Toxicology of Polyphenols with Potential As Neurotropic Agents in Non-communicable Diseases.

BACKGROUND: The central nervous system (CNS) is involved in organic integration. Nervous modulation via bioactive compounds can modify metabolism in order to prevent systemic noncommunicable diseases (NCDs). Concerning this, plant polyphenols are proposed as neurotropic chemopreventive/ therapeutic agents, given their redox and regulating properties. OBJECTIVE: To review polyphenolic pharmacology and potential neurological impact on NCDs. METHOD: First, polyphenolic chemistry was presented, as well as pharmacology, i.e. kinetics and dynamics. Toxicology was particularly described. Then, functional relevance of these compounds was reviewed focusing on the metabolic CNS participation to modulate NCDs, with data being finally integrated. RESULTS: Oxidative stress is a major risk factor for NCDs. Polyphenols regulate the redox biology of different organic systems including the CNS, which participates in metabolic homeostasis. Polyphenolic neurotropism is determined by certain pharmacological characteristics, modifying nervous and systemic physiopathology, acting on several biological targets. Nonetheless, because these phytochemicals can trigger toxic effects, they should not be recommended indiscriminately. CONCLUSION: Summing up, the modulating effects of polyphenols allow for the physiological role of CNS on metabolism and organic integration to be utilized in order to prevent NCDs, without losing sight of the risks.

[Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids]. / Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides.

OBJECTIVE: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. MATERIALS AND METHODS: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. RESULTS: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. CONCLUSIONS: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

OBJETIVO: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. MATERIAL Y MÉTODOS: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. RESULTADOS: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. CONCLUSIONES: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Physical Activity of German Children and Adolescents 2003-2012: The MoMo-Study.

Organized and unorganized physical activity (PA) hold an important role in the daily life of children and adolescents. Regular representative tracking of PA in different settings is important to evaluate social trends and implemented interventions. In this paper, representative PA data of German children and adolescents from the MoMo Baseline-Study (2004, n = 4528) are compared to those of Wave 1 (2010, n = 3994). Participants aged 4-17 were drawn out of 167 sample points in Germany and the data was weighted to ensure representativeness. PA was measured via questionnaire and was differentiated between organized (sports clubs and schools) and unorganized (unorganized sports and playing outside). Organized PA in extracurricular activities and sports clubs increased by eight percent, while unorganized PA decreased by seven percent. In addition to sports clubs, schools became a more prevalent setting for participation in physical activity in Germany.

Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides / Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids

Resumen: Objetivo: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. Material y métodos: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. Resultados: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. Conclusiones: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Abstract: Objective: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. Materials and methods: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. Results: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. Conclusions: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

[Regional oxidative stress in encephalon of female mice with polyphenolic exposure from tea extracts in oral overweight plant-based treatment].

Polyphenols provide by diet may act as antioxidant in the Central Nervous System and exert a protective effect on metabolic diseases. The aim of this study was to establish tea extract effects on oxidative status and murine overweight in accordance with polyphenolic availability in different encephalic regions. METHODS: Balb/c mice (female, n>3) with overweight received for 15 days 100 mg/Kg/d of extract from Lantana grisebachii, Aspidosperma quebracho-blanco, or Ilex paraguariensis extracts and control group (received water without extract). Body weight gain was recorded regularly. Polyphenols, hydroperoxides (HP), lipid peroxides (LP), and superoxide anion (SO) were measured in brain (telencephalon and diencephalon), midbrain, brainstem and cerebellum. Results were compared by ANOVA followed by the Tukey test (P<0.05). RESULTS: A. quebracho-blanco-based treatment decreased weight gain and increased polyphenols in brainstem (p<0.02), although it concomitantly increased SO and LP in this region (p=0.0029 and p=0.0280, respectively). L. grisebachii-based treatment reduced oxidative markers differentially in each region (p<0.05). I. paraguariensis-based treatment oxidized midbrain and cerebellum, although it was antioxidant in the brainstem (p<0.05). All treatments were antioxidant in telencephalon (p=0.0029). CONCLUSIONS: The A. quebracho-blanco extract was active on overweight and increased polyphenols in brainstem, with safe functional derivatives being required to avoid oxidative stress. Other extracts affected oxidative status in a region-dependent manner.

[Bioavailability of phenolic compounds and redox state of murine liver and kidney as sex-dependent responses to phytoextracts.]

BACKGROUND: Plant extracts can be obtained to carry bioactive compounds, useful for prevention and treatment of different illnesses. This also supports the intake of teas as functional beverages. Nonetheless, it is incompletely known whether these extracts can act as effective sources and vehicles de phenolic compounds (phenolics/polyphenols) to reach their targets. OBJECTIVE: To establish whether phytoextract ingestion modified in a sex-dependent manner the phenolic bioavailability and redox response in liver and kidney. METHOD: BALB/C mice ingested for a month 100 mg/Kg/d of extracts (tea-like) from Aspidosperma quebracho-blanco (AQB), Lantana grisebachii (LG) or Ilex paraguariensis (IP). Then, phenolics, peroxides and nitrites were analyzed by spectrophotometry. Also, phenolic permeation from digested and undigested extracts was evaluated in vitro with a rat jejunum-based assay. RESULTS: Phenolic permeation depended on extract digestion. In males, IP showed a special time course of hepatic phenolics, whereas all extracts decreased renal phenolics at 15 days. Extracts induced hepatic lipoperoxides at 15 days. LG reduced renal hydroperoxides at 15 days and hepatic nitrites at 30 days, whereas AQB and IP reduced renal lipoperoxides and nitrites at 30 days. In females, extracts reduced hydroperoxides, with LG and AQB also reducing lipoperoxides. IP increased renal lipoperoxides at 30 days. CONCLUSION: IP was a relevant phenolic source. Sex-dependent responses were found in all variables, which should be considered to prevent misleading generalizations in phytodrug bioprospecting.

Motorik-Module (MoMo) - the KiGGS Wave 2 module to survey motor performance and physical activity.

Initially, the Motorik-Module (MoMo) Longitudinal Study was surveyed between 2003 and 2006 using a sub-sample from the baseline German Health Interview and Examination Survey for Children and Adolescents (KiGGS). The federal representative sub-sample of KiGGS consisted of 4,528 children and adolescents aged 4 to 17. To date, there have been two further survey waves: 2009-2012 (Wave 1) and 2015-2017 (Wave 2). MoMo Wave 2 consists of motor performance tests, anthropometric measurements, questionnaire-based information collection on activity habits and motion sensor data. Initial results of MoMo Wave 2 will be published in the second half of 2018. The total size of the Wave 2 sample is estimated to reach 5,200 participants. As its central goal, the MoMo longitudinal survey aims to contribute towards the long-term improvement of child and adolescent health in Germany. A focus will be on developmental (age-related) and periodic (over time) trends in motor performance and physical activity, underlying factors and the impacts on physical and mental health in the development of children and adolescents.

Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.

Selective CB2 receptor agonists. Part 1: the identification of novel ligands through computer-aided drug design (CADD) approaches.

Computer-aided drug design scaffold hopping strategies were utilized to identify new classes of CB2 agonists when compounds of an established series with low nanomolar potency were challenging to optimize for good drug-like properties. Use of ligand-based design strategies through BI Builder (a tool for de novo design) and PharmShape (a virtual screening software package) approaches led to the discovery of new chemotypes. Specifically, compounds containing azetidine-, proline-, and piperidine-based cores were found to have low nanomolar and picomolar CB2 agonist activities with drug-like properties considered appropriate for early profiling.

Selective CB2 receptor agonists. Part 3: the optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model.

A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.