Role of Exosomal miR-205-5p Cargo in Angiogenesis and Cell Migration.

Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying a diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs in hyperglycemia or inflammation. In fact, sEVs release has been associated with the promotion of physio-pathological processes. Among the sEVs cargo, microRNAs play an essential role in cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim of this study is to understand the specific role of sEVs containing miR-205-5p under high glucose conditions. ARPE-19 cells were cultured with high glucose (HG) for 5 days. sEVs were isolated and characterized. sEVs from ARPE-19 were used for angiogenesis and cell proliferation. HG increased sEVs release but downregulated miR-205-5p cargo expression compared to the control. sEVs from HG-treated ARPE-19 cells promoted tube formation and migration processes. In contrast, miR-205-5p overexpression (by mimic transfection) decreased angiogenesis and cell migration. Our results demonstrate how ARPE-19 cells respond to HG challenge by increasing sEVs with weak miR-205-5p cargo. The absence of this miRNA in sEVs is enough to promote angiogenesis. In contrast, restoring sEVs-miR-205-5p levels decreased it. These findings open new possibilities in sEVs-based therapies containing miR-205-5p against angiogenesis.

[Use of ribavirin in viruses other than hepatitis C. A review of the evidence]. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

A New Depigmenting-Antifungal Methylated Grindelane from Grindelia chiloensis.

The new methylated grindelane diterpenoid, 7ß-hydroxy-8(17)-dehydrogrindelic acid (1b), together with the known 7α-hydroxy-8(17)-dehydrogrindelic acid (2a), 6-oxogrindelic acid (3a), 4ß-hydroxy-6-oxo-19-norgrindelic (4a), 19-hydroxygrindelic acid (5a), 18-hydroxygrindelic acid (6a), 4α-carboxygrindelic acid (7a), 17-hydroxygrindelic acid (8a), 6α-hydroxygrindelic acid (9a), 8,17-bisnor-8-oxagrindelic acid (10a), 7α,8α-epoxygrindelic acid (11a), and strictanonic acid (12a) as methyl esters were obtained from an Argentine collection of Grindelia chiloensis (Cornel.) Cabrera. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl3 extract from the aerial parts and their pure compounds were evaluated for their antifungal and depigmenting effects. Methyl ester derivative of 10a (10b) exhibited a remarkable mycelial growth inhibition against Botritis cinerea with an IC50 of 13.5 µg ml-1 . While the new grindelane 1b exerted a clear color reduction of the yellow-orange pigment developed by Fusarium oxysporum against UV-induced damage.

Oxidative-Induced Angiogenesis Is Modulated by Small Extracellular Vesicle miR-302a-3p Cargo in Retinal Pigment Epithelium Cells.

Extracellular vesicles are released from cells under diverse conditions. Widely studied in cancer, they are associated with different diseases playing major roles. Recent reports indicate that oxidative damage promotes the release of small extracellular vesicle (sEVs) from the retinal pigment epithelium (RPE), with an angiogenic outcome and changes in micro-RNA (miRNA) levels. The aim of this study was to determine the role of the miRNA miR-302a-3p, included within RPE-released sEVs, as an angiogenic regulator in cultures of endothelial cells (HUVEC). ARPE-19 cell cultures, treated with H2O2 to cause an oxidative insult, were transfected with a miR-302a-3p mimic. Later, sEVs from the medium were isolated and added into HUVEC or ARPE-19 cultures. sEVs from ARPE-19 cells under oxidative damage presented a decrease of miR-302a-3p levels and exhibited proangiogenic properties. In contrast, sEVs from miR-302a-3p-mimic transfected cells resulted in control angiogenic levels. The results herein indicate that miR-302a-3p contained in sEVs can modify VEGFA mRNA expression levels as part of its antiangiogenic features.

Two New Furanoeremophilanes from Senecio santelisis.

From an Argentine collection of Senecio santelisis Phil., the new furanoeremophilanoids, (10betaH)-6beta-acetoxy-1alpha-hydroxyfuranoeremophilan-9-one (1) and (10betaH)-1alpha-hydroxy-6beta-(propanoyloxy)furanoeremophilan-9-one (2), together with the known (10alphaH)-6beta-acetoxy-1alpha-hydroxyfuranoeremophilan-9-one (3), (10alphaH)-1alpha,6beta-diacetoxyfuranoeremophilan-9-one (4), and (10alphaH)-1alpha-hydroxy-6beta-(propanoyloxy)furanoeremophilan-9-one (5) were isolated. Their structures and relative configurations were established on the basis of spectroscopic analysis. CHCl3 Extract and pure compounds were evaluated for their antifungal activity. Compound 5 exhibited remarkable mycelial growth inhibition against B. cinerea with an IC(50) value of 21.4 microg/ml.

Use of ribavirin in viruses other than hepatitis C. A review of the evidence. / Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia.

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitisC virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus.

Bioactive plants from Argentina and Bolivia.

Antibacterial and molluscicidal activities of methanol and chloroform extracts of 16 plant species belonging to the families Compositae and Melastomataceae were evaluated. The chloroform extract of Vernonanthura tweediana and the methanol extract of Senecio santelisis resulted to be very toxic to brine shrimp nauplii (LC(50)=1 microg/ml). Chloroform extracts of S. santelisis and Senecio leucostachys as well as the methanol extract of Wedelia subvaginata displayed molluscicidal effects on Biomphalaria peregrina showing LC(100)<100 microg/ml. Moderate antibacterial action was produced by the chloroform extracts of Flaveria bidentis, Grindelia scorzonerifolia and Vernonia incana against two strains of Staphylococcus aureus.

Seed mass maturity in the terrestrial bromeliad Hechtia perotensis (Bromeliaceae), endemic to Mexico / Madurez de las semillas en la bromelia terrestre Hechtia perotensis (Bromeliaceae), endémica de México

Abstract Introduction: H. perotensis is a plant with a high potential for ecological restoration because it yields thousands of seeds and grows under low levels of rain, poor soils and contrasting temperatures. However, little is known of the seed mass maturity (high seed germination, low seed fresh weight and low seed moisture content) in this species. Objective: Assess seed germination in the laboratory of H. perotensis during seed development and along the floral stalk (infructescence) in two sites one in rocky location and another near a lake. The hypothesis was that there is a time after flowering in which seeds have highest germination and fresh weight and that the apical, centre and base of the infructescence are different in seed germination and fresh weight in both sites. Methods: Capsules were collected in two sites one in rocky land (Frijol Colorado, Perote, Veracruz) and another near one lake (Alchichica, Puebla), in the months of August, September and November 2016 and January 2017. A repeated measure design (RMD) was used to analyze the effects of infructescence section on seed weight, moisture content and seed germination (41, 87, 152 and 215 days after flowering). Each evaluation time comprised five replicates, each one with 15 seeds. Results: Difference in seed germination, seed weight and moisture content between sections of the infructescence was not significant. However, significant differences were found not only between first and last sample dates, but mainly between first and second dates. Eighty-seven days after flower pollination seed moisture content was lower than 20 % and up to 80 % of seed germinated in both sites of sampling. Conclusions: In this study it was found that the moisture content of H. perotensis seed can be used as an indicator of the physiological maturity of the seed and it is also related to germination of the seed.

Resumen Introducción: H. perotensis es una planta con un alto potencial para la restauración ecológica debido a que produce miles de semillas y crece con niveles bajos de lluvia, suelos pobres y temperaturas contrastantes. Sin embargo, el desarrollo de la madurez de las semillas (germinación alta, baja humedad y bajo peso fresco de semilla) en esta especie es muy poco conocido. Objetivo: Evaluar la germinación en el laboratorio de las semillas de H. perotensis, durante el desarrollo de la semilla y a lo largo del tallo floral (infrutescencia) en dos sitios; uno en un área rocosa y otro cerca de un lago. La hipótesis fue que hay un tiempo después de la floración, en el que las semillas presentan la mayor germinación y menor peso fresco, y que las secciones apical, central y base de la infrutescencia, la germinación y el peso fresco de la semilla son diferentes en los dos sitios. Métodos: se recolectaron las cápsulas en dos sitios uno en un área rocosa (Frijol Colorado, Perote, Veracruz) y otro cerca de un lago (Alchichica, Puebla), en los meses de Agosto, Septiembre y Noviembre de 2016 y Enero de 2017. Se usó un diseño de medidas repetidas (DMR) para analizar los efectos de la sección de la infrutescencia sobre el peso fresco de la semilla, el contenido de humedad y la germinación de la semilla (41, 87, 152 y 215 días, después de la floración). Cada tiempo de evaluación comprendió cinco réplicas y 15 semillas. Resultados: La diferencia en la germinación de la semilla, el peso de la semilla y el contenido de humedad entre las secciones de la infrutescencia no fue significativa. Sin embargo, se encontraron diferencias significativas entre las fechas de muestreo inicial y final, pero sobre todo entre la primera y la segunda fecha. Asimismo, ochenta y siete días después de la polinización de las flores, el contenido de humedad de las semillas fue inferior al 20 % y superior al 80 % en la germinación de las semillas en ambos sitios de muestreo. Conclusiones: en este estudio se encontró que el contenido de humedad de la semilla de H. perotensis, puede usarse como un indicador de la madurez fisiológica de la semilla y también está relacionado con la germinación de la semilla.

Prognostic factors of health-related quality of life in patients after tibial plafond fracture. A pilot study.

BACKGROUND: Tibial plafond fractures are a uncommon injury, and the outcomes described in literature are generally poor. The purposes were to determine the effect of the tibial plafond fractures on general health-related quality of life, and to examine the factors that influence these outcomes. METHODS: Retrospective study of 43 patients with average age of 45.6 (range 18-69) years who were also invited for a clinical and radiological reassessment. The primary outcome measure was quality of life assessed by the Short Form-36 questionnaire. Visual analogue scale for pain, and motion of both ankle and subtalar joints were also assessed. Radiological evaluation was performed to assess bone healing, fracture reduction quality, and tibial alignment. RESULTS: The mean follow-up at last visit was 8.1 (range, 4-12) years. Patients who had suffered plafond fracture had significantly poorer quality of life compared with age- and gender-matched general population of our country regardless of the treatment method used. Multivariate analyses showed that the age had influence on the emotional outcomes, educational level and fracture pattern on physical outcomes, and marital status, fracture reduction quality, and ankle motion on both physical and mental component summaries. CONCLUSION: Tibial plafond fractures have a significant negative impact on general health-related quality of life regardless of the operative treatment used which reflects injury severity. In addition, psychosocial characteristics of patients may influence the outcomes.

Uso de ribavirina en virus distintos de la hepatitis C. Una revisión de la evidencia / Use of ribavirin in viruses other than hepatitis C. A review of the evidence

La ribavirina es una molécula con actividad antiviral sobre diferentes virus. Ha encontrado su hueco en la práctica clínica de forma casi exclusiva para el tratamiento del virus de la hepatitis C, pero existen otras enfermedades que podrían beneficiarse de su empleo. Su disponibilidad para administración por vía oral, por vía intravenosa e inhalada es una característica beneficiosa. En este trabajo se realiza una revisión de las indicaciones en las principales agencias del medicamento (española, europea y americana), así como de otras posibles indicaciones, principalmente sobre fiebres hemorrágicas y coronavirus

Ribavirin is a molecule with antiviral activity against different viruses. In clinical practice, it has made its niche almost exclusively for the treatment of the hepatitis C virus. However, there are other diseases in which it could be of benefit and it has the advantage of being suitable for oral, intravenous and inhaled administration. We conducted a review of the indications of the main drug agencies (Spanish, European and American) and other possible indications, mainly haemorrhagic fevers and coronavirus

Utilización del trámite de la libreta sanitaria laboral como estrategia de vacunación de los solicitantes / Use of labor health record as a strategy to vaccinate applicants

En la División Promoción y Protección de la Salud del Hospital Ramos Mejía de la Ciudad de Buenos Aires, se utiliza el otorgamiento de la Libreta Sanitaria Laboral como estrategia para indicar y aplicar a los solicitantes las vacunas correspondientes al calendario. La población recibe así vacunas que noson exigidas por ley, lo que representa una oportunidad ganada.

Vasorelaxant activity of phthalazinones and related compounds.

Several series of dihydrostilbenamide, imidazo[2,1-a]isoindole, pyrimido[2,1-a]isoindole and phthalazinone derivatives were obtained and their vasorelaxant activity was measured on isolated rat aorta rings pre-contracted with phenylephrine (10(-5)M). Some phthalazinones attained, practically, the total relaxation of the organ at micromolar concentrations. For the most potent compound 9h (EC(50)=0.43microM) the affinities for alpha(1A), alpha(1B) and alpha(1D) adrenergic sub-receptors were determined.

Manoyl oxide diterpenoids from Grindelia scorzonerifolia.

Two new norditerpenoids, 4beta-hydroxy-19-normanoyl oxide (1) and 4alpha-hydroxy-18-normanoyl oxide (2), the new 18-O-alpha-l-arabinopyranosylmanoyl oxide (3a), and the known diterpenoids jhanol (4) and 18-hydroxy-13-epi-manoyl oxide (5) were isolated, together with other common plant constituents from an Argentine collection of Grindelia scorzonerifolia. The structures of the new compounds were established by extensive 1D and 2D NMR techniques and chemical transformations. Structural features of compounds 2 and 4 were verified by X-ray crystallographic analyses. The insecticidal effect of compound 3a was evaluated against the polyphagous pest Spodoptera frugiperda. Pupal and adult malformations leading to death occurred when 3a was incorporated in a larval diet at a concentration of 100 ppm.

Morbilidad bucal: su relación con el estado nutricional en niños de 2 a 5 años de la Consulta de Nutrición del Hospital Pediátrico Docente de Centro Habana / Oral morbidity: its relationship with the nutritional status of 2-5 years-old children

En el presente trabajo se describe la morbilidad de las principales afecciones bucales y su relación con el estado nutricional y peso al nacer en niños de 2 a 5 años de edad. Se realizó un estudio descriptivo transversal donde se evaluaron 230 niños, de ellos 115 eutróficos y 115 desnutridos, según tablas de referencia cubana de peso y talla, exámenes bioquímicos y exámenes clínicos, utilizándose como variables: estado nutricional, peso al nacer, índice coe-d, retardo del brote dentario, lesiones de esmalte, maloclusión e índice PMA. Para su procesamiento estadístico se aplicaron pruebas Chi cuadrado con un nivel de confiabilidad del 95 por ciento (alfa 0,05). Se concluye que el índice coe-d fue de 0,14 para los eutróficos y de 0,71 para los desnutridos. El brote dentario estuvo retardado en el 2,63 por ciento en los eutróficos, mientras que los desnutridos fue del 39,4 por ciento y estuvo más retardado en los bajo peso al nacer, desnutridos, con el 75 por ciento. Solo aparecieron lesiones de esmalte en el grupo de desnutridos (22,60 por ciento) y se incrementó en los bajo peso de este grupo (34,61 por ciento). El porcentaje de maloclusión en el grupo eutrófico fue de 36,52 por ciento, en los desnutridos 62,6 por ciento y aumentó en los de bajo peso, con el 84,61 por ciento. Se apreció como trastorno periodontal el 26,92 por ciento de gingivitis moderada en niños desnutridos de bajo peso(AU)

The present paper describes the morbidity of the main oral diseases and their relationship with nutritional status and low birthweight in 2-5 years-old children. A cross-sectional descriptive study was conducted to evaluate 230 children - 115 eutrophic and 115 undernourished- according to the Cuban weight-size reference tables, biochemical and clinical examinations, using variables such as nutritional status, birthweight, coe-d index, dental eruption retardation, dental enamel lesions, malocclusion, and PMA index. For statistical processing, Chi-square test with a 95 percent confidence interval (alpha 0,05) was applied. It was concluded that coe-d index was 0,14 for eutrophics and 0,71 for undernourished. 2,63 percent of eutrophics and 39,47 percent of the undernourished showed dental eruption retardation. The retardation was more remarkable in low-birthweight undernourished children amounting to 75 percent. Dental enamel lesions only occurred in the undernourished group (22,60 percent), mainly in low birthweighted (34,61 percent). The malocclusion percentage was 36,52 percent in the eutrophics, 62,6 percent in the undernourished and 84,61 percent in the low-birthweighted. Mild gingivitis accounted for 26,92 percent as periodontal disorder in low birthweight undernourished children(AU)