Migración de neutrófilos en larvas de pez cebra expuestos a extractos de sofrito de tomate

Neutrophils migration in zebrafish larvae exposed to tomato sofrito extracts. The main of this study was to evaluate the anti-inflammatory activity of tomato sofrito extracts, as well as standard compounds present in the Mediterranean diet, using an optimized experimental model based on zebrafish larvae. Neutrophil migration in zebrafish larvae 96 hours post fertilization was induced by a cut in the caudal fin and enhanced by adding lipopolysaccharide and was visualized and quantified by image analysis. The anti-inflammatory effect of tomato extract and the compounds used was correlated by the percentage decrease in the migration of neutrophils. The results showed that, tomato extract showed a reduction in neutrophil migration of 40% compared to the control group. Moreover, chlorogenic acid and cyanidin present in tomato sofrito sauce showed a decrease in neutrophil migration of 66.7% and 62.5% respectively. These percentages are comparable to the results observed in trials with anti-inflammatory drugs such as indomethacin and piroxicam. The results show that tomato sofrito extract has possible anti-inflammatory activity demonstrated by the reduction of neutrophil migration, furthermore the model was sensitive and valid to be applied in complex food matrices

The Zebrafish Embryo as a Model to Test Protective Effects of Food Antioxidant Compounds

t: The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stressinduced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone

Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats

Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response

Efectos de la depleción de la histona H1 en células de cáncer de mama: proliferación y respuesta a interferón

[spa] La histona H1 se une al nucleosoma, situándose en la base, cerca de los sitios de entrada y salida del DNA, siendo una de sus principales funciones descritas, el mantenimiento de una estructura estable y condensada de la cromatina. Los primeros estudios realizados del rol que desempeña H1 en la regulación transcripcional señalaban que H1 era un represor global de la transcripción. Sin embargo, estudios recientes sugieren que H1 desempeña un papel más dinámico y contribuye a una regulación transcripcional específica de genes. Siete variantes de histonas H1 existen en células somáticas humanas (H1.1 a H1.5 que son expresadas de una manera dependiente de la replicación, mientras que H1.0 y H1X son independientes de la replicación). Uno de los principales debates es si dichas variantes de histonas H1 tienen un rol específico o redundante. En este trabajo investigamos esto a través de RNAs interferentes inducibles para inhibir de manera individual y por primera vez de manera simultánea las variantes de la histona H1 en células de cáncer de mama T47D. La inhibición individual de las distintas variantes ocasionó una reducción de la velocidad de crecimiento enc omparación a células parentales. Al inhibir de manera simultánea las variantes H1.2 y H1.4, se observó que la proliferación se ve afectada en mayor medida que al inhibir las variantes H1.2 y H1.4 de manera individual. Debido a que la proliferación celular y adhesión celular son características relacionadas con la tumorogénesis e invasión metastásica, se investigó además los efectos de la depleción de las distintas variantes en la capacidad de formar colonias independientes del anclaje. Nuestros resultados sugieren que la variante H1.2 es esencial para que las células crezcan tanto de manera independiente como dependiente del anclaje, lo que sugiere que al inhibir dicha variante las células posiblemente pierden su capacidad metastásica. La combinación de la depleción de H1.2 y H1.4 indujo una fuerte respuesta a interferón (IFN), efecto que no se observó en depleciones individuales de variantes de histonas H1. Se verificó que la depleción combinada de H1.2 y H1.4 producía la sobreexpresión y síntesis de interferón. Dicha síntesis de IFN indujo la respuesta a IFN en células T47D y activó la ruta JAK-STAT, principal ruta involucrada en la activación de la transcripción de ISGs. Se verificó mediante la combinación de dos RNA interferentes para las variantes H1.4 y H1.2 en T47D(H1.4/H1.2sh) que la respuesta a interferón ocasionada por el multiH1 shRNA, se reproduce al inhibir tanto a nivel de RNA como de proteína únicamente las variantes H1.2 y H1.4. La inhibición de otras combinaciones que incluyen H1.2 con H1.5, H1.4 con H1.5 y triples combinaciones H1.2/H1.5/H1.3 y H1.4/H1.5/H1.3 produjeron, sólo cuando la depleción de H1.2 estuvo involucrada, la sobreexpresión de ISGs a niveles inferiores a los observados en la depleción mH1sh o en la combinación H1.4/H1.2. En las células en las que no se deplecionó H1.2 no se observó la respuesta a interferón. Por otra parte, la combinación de la depleción de H1.2 y H1.4(H1.4/H1.2sh) con el tratamiento con IFNβ comercial produjo un efecto sinérgico en la sobreexpresión de ISGs, lo que sugiere que existen otros mecanismos de inducción de los ISGs además de la estimulación por el IFN sintetizado. Análisis con inhibidores y knock downs constitutivos de sensores y adaptadores de la respuesta a IFN nos sugieren que posiblemente al deplecionar H1.2/H1.4 se desencadena la expresión de dsRNA no codificantes posiblemente formados desde retrovirus endógenos o de secuencias repetitivas de heterocromatina, y que dichos ácidos nucleicos son los causantes de la activación de la respuesta inmune antiviral, que ocasiona los efectos observados como son la síntesis de IFN, sobreexpresión de ISGs, defectos en la proliferación.[eng] Histone H1 binds to linker DNA contributing to higher-order chromatin compaction. In addition, H1 seems to be actively involved in the regulation of nuclear processes such as gene expression control or DNA damage signaling. Seven linker histone H1 variants exist in human somatic cells (H1.1 to H1.5 being expressed in a replication-dependent manner, whereas H1.0 and H1X are replication-independent), with distinct prevalence depending on the cell-type analyzed and along differentiation. It is not well known whether the different variants have specific or redundant roles. We explored this by inducible shRNA- mediated knock-down of each of the H1 variants in breast cancer cells. Knock-down of each H1 variant alters expression of a different reduced subset of genes and affects cell proliferation in a different extent. Although H1.2 is the only variant essential for cells to grow in anchorage-independent conditions, being the H1 that alters the most the proliferative and metastatic properties of cancer cells. Combined depletion of H1.2 and H1.4 has a strong deleterious effect in the cancer cells examined, and induces a strong interferon (IFN) response with up-regulation of many IFN-stimulated genes (ISGs), which is not seen in individual H1 knock-downs. Although H1 participates to repress ISG promoters, its activation upon H1 KD is mainly generated by the activation of the IFN response through cytosolic nucleic acids receptors, IFN synthesis and JAK-STAT pathway activation. The IFN response may be triggered by the expression of noncoding dsRNAs generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific growth-inhibiting IFN response

Factores de riesgo para la infección por SARS Cov 2 e implicación de las nuevas variantes del Virus, alternativas de prevención en Ambato

Introduction: Covid 19 disease is a global health problem, 124 million people infected and 2.73 million deaths. Ecuador did not escape this problem, with 313000 cases and 16478 confirmed deaths. Tungurahua Province has been affected with 10644 cases and 437 confirmed deaths. The assessment of risk factors is essential for the development of effective prevention strategies, especially with the emergence of new variants of the virus in different countries. Objective: Describe the results of the risk factor assessment in the Canton Ambato according to the results of the research projects implemented by the Faculty of Health Sciences of the Technical University of Ambato for further development of community prevention strategies. Material and methods: A cross-cutting descriptive study was carried out, based on the results obtained from the assessment of risk factors in the population of canton Ambato through the execution of research projects of the Faculty of Health Sciences of the Technical University of Ambato in the period October 2020-March 2021. Results: The 18-26 year old etaerios group dominated 58.6%, the female sex by 53.4%, 94.8% of patients self-identified as half-breeds and the normal weight at 75.3%. 1.53% of patients were pregnant. Predominated gestation time from 6 to 9 months at 50%. A history of diagnosing Covid 19 10.12% of patients, 4.3% were treated by their GP, 1.76% in public health homes and 1.51 private. Only 0.25% of cases required hospitalization. Hospitalization lasted up to 15 days in one case (0.25%). 18.9% of patients have had suggestive respiratory symptoms of Covid 19 at the time of the survey, 10.17% with a serious pathological history, predominated HTA 3.3% and Diabetes Mellitus at 2.79%. Conclusions: The most significant risk factors for SARS Cov 2 virus infection in the Ambateña population are: adults over the age of 60, immunocompromised pregnant women, comorities (Arterial Hypertension, Diabetes Mellitus), social factors are not significantly impacting epidemiological control, except in indigenous peoples and communities, where there is also a high prevalence of Diabetes Mellitus and Arterial Hypertension , as in the town of the canton. It is necessary to complete the assessment of the state of immunity in the population to define prevention strategies that help limit the impact of the pandemicIntroducción: La enfermedad Covid 19 constituye un problema de salud de relevancia mundial, 124 millones de personas infectadas y 2,73 millones de muertes. Ecuador no escapó a este problema, con 313000 casos y 16478 muertes confirmadas. La Provincia Tungurahua ha sido afectada con 10644 casos y 437 muertes confirmadas. La evaluación de los factores de riesgo resulta imprescindible para el desarrollo de estrategias de prevención efectivas, más aún con la aparición de nuevas variantes del virus en diferentes países. Objetivo: Describir los resultados de la evaluación de factores de riesgo en el Cantón Ambato según los resultados de los proyectos de investigación ejecutados por la Facultad de Ciencias de la Salud de la Universidad Técnica de Ambato para desarrollo ulterior de estrategias de prevención comunitarias. Material y métodos: Se realizó un estudio descriptivo transversal, a partir de los resultados obtenidos de la evaluación de factores de riesgo en la población del Cantón Ambato a través de la ejecución de proyectos de investigación de la Facultad de Ciencias de la Salud de la Universidad Técnica de Ambato en el periodo octubre 2020-marzo 2021. Resultados: Predominó el grupo etario de 18 a 26 años en el 58,6%, el sexo femenino en el 53,4%, el 94,8 % de los pacientes se autoidentificaron como mestizos y el peso normal en el 75,3%. El 1,53% de las pacientes eran gestantes. Predominó el tiempo de gestación de 6 a 9 meses en el 50%. Antecedentes de diagnóstico de Covid 19 el 10,12% de los pacientes, el 4,3% fueron atendidos por su médico de cabecera, el 1,76 % atendido en casas de salud públicas y el 1,51 privados. Sólo el 0,25% de los casos requirió hospitalización. La hospitalización se prolongó hasta 15 días en un caso (0,25%). El 18,9% de los pacientes ha presentado síntomas respiratorios sugestivos de Covid 19 en el momento de la encuesta, 10,17% con antecedentes patológicos de gravedad, predominó la HTA 3,3% y la Diabetes Mellitus en el 2,79%. Conclusiones: Los factores de riesgo más significativos para la infección por el Virus SARS Cov 2 en la población ambateña son: adultos mayores de 60 años, mujeres embarazadas inmunocomprometidos, comorbilidades (Hipertensión Arterial, Diabetes Mellitus), los factores sociales no están incidiendo significativamente en el control epidemiológico, excepto en los pueblos y comunidades indígenas, donde también existe una alta prevalencia de Diabetes Mellitus e Hipertensión Arterial, al igual que en el resto de la población del cantón. Es necesario completar a evaluación del estado de inmunidad en la población para definir estrategias de prevención que ayuden a limitar el impacto de la pandemi

Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats

Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response

Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats

Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response