Application of vascular photobiomodulation therapy in individuals with low back pain and its relationship with global methylation / Aplicação da terapia por fotobiomodulação vascular em indivíduos com lombalgia e sua relação com a metilação global

ABSTRACT BACKGROUND AND OBJECTIVES: Low back pain is among the most disabling conditions worldwide, and among the epigenetic factors, methylation in CpG islands of gene promoter regions can modulate gene expression, potentially correlating with the development of the disease and providing insights into the choice of treatment. The objective of this study was to assess the efficacy of therapy using modified ILIB related to DNA methylation processes in low back pain. Secondary objectives of this study included investigating pain intensity, gender, sociodemographic data, and physical-functional profile. METHODS: This prospective study was conducted in a municipality in the southern region of Brazil. The sample consisted of 30 participants of both genders, with an average age of 41.77 years. The following aspects were analyzed: anthropometric characteristics, global methylation using the ELISA method, pain level, physical activity level, functional disabilities, and hesitancy level related to work and physical activity-related activities. RESULTS: A statistically significant association was observed between methylation levels before and after treatment application for the experimental and placebo groups (p < 0.005), demonstrating a mean responsiveness between methylation and treatment (d = 0.5). However, there were no other statistically significant associations correlated with the other work variables. CONCLUSION: The results obtained in this study suggest the need for further research related to the identification of specific genes in methylation, as well as the standardization of dosimetry used for transcutaneous ILIB laser application in the radial artery.

RESUMO JUSTIFICATIVA E OBJETIVOS: A lombalgia está entre as condições mais incapacitantes no mundo e; dentre os fatores epigenéticos, a metilação em ilhas CpG de regiões promotoras de genes pode modular a expressão gênica permitindo uma possível correlação ao desenvolvimento da doença, como também pode trazer esclarecimentos a respeito do tratamento a ser escolhido. O objetivo deste estudo foi verificar a eficácia da terapia através do uso do ILIB modificado relacionada ao processo de metilação de DNA na lombalgia. Os objetivos secundários deste estudo foram a investigação da intensidade da dor, sexo, dados sociodemográficos e perfil físico-funcional. MÉTODOS: Este estudo, desenvolvido em um município da região sul do Brasil, caracteriza-se como prospectivo. A amostra deste estudo foi composta por 30 participantes, de ambos os sexos, com idade média de 41,77 anos. Foram analisados os seguintes aspectos: características antropométricas, metilação global através do método ELISA, nível de dor, nível de atividade física, incapacidades funcionais e nível de hesitação para realizar atividades relacionada ao trabalho e atividade física. RESULTADOS: Observou-se associação estatisticamente significativa entre os níveis de metilação antes e a após aplicação do tratamento para grupo experimental e placebo (p<0,005) demostrando uma média responsividade entre as variáveis metilação e tratamento (d=0,5). No entanto, não houve nenhuma outra associação estatística correlacionada as demais variáreis do trabalho. CONCLUSÃO: Os resultados obtidos neste estudo sugerem que há necessidade mais estudos relacionados a identificação de genes específicos na metilação, além da necessidade de padronização de dosimetria utilizadas para aplicação do laser ILIB de forma transcutânea, em artéria radial.

HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

Contexto, ser humano y epigenética / Context, human being and epigenetics

Resumen Los últimos años de investigación científica han visto un crecimiento en los estudios que relacionan situaciones de vulnerabilidad (particularmente, durante la vida temprana) con el desarrollo de psicopatologías. Tales disfuncionalidades en la salud mental y en las emociones entienden una sinergia entre factores contextuales y la biología del organismo. Lo que da en llamarse "puente" entre ambas instancias es estudiado por un área de la investigación científica relativamente nueva: la epigenética. La epigenética fue establecida como un interesante factor que permite relacionar, desde un punto de vista biológico, el contexto en que se desarrollan las personas con sus estados emocionales. Este artículo se propone revisar algunos trabajos e integrarlos dentro de una concepción compleja del ser humano, que lo entiende como un sistema de relaciones entre diversas dimensiones que incluyen las esferas genéticas, epigenéticas, neurológicas, emocionales, interaccionales, cognitivas y socioculturales enmarcadas en un contexto particular.

Abstract The discovery of the whole sequence of the human genome in 2001 promised to be a revolution in terms of dealing with diseases and understanding what makes us a "different" species from other animals. However, the scope of this promising discovery was more limited than expected. The information carried by DNA is complex and, furthermore, it does not explain the vast repertoire of functions and dysfunctions that organisms present. For this reason, it began to be thought that it was necessary to change the focus to understand how individuals are formed and develop, and turn the attention paid to DNA to what surrounds that DNA: the environment of the organism (both internal and external). In this way, the studies began to focus on the influence of the context to which organisms are exposed to understand the characteristics of the body and its actions. In thinking about the concept of the body in development, this renewed focus in the environmental influence allows an understanding of it as a permeable and complex system, where dysregulations (diseases) may also be triggered by exogenous events and not only from the endogenous factors. Therefore, in a recursive way, the influence of the human being on the environment transforms the environment that returns to influence the human being. Here is the history of mankind. There are contexts that offer a healthy framework for the growth of its inhabitants and there are others that make life vulnerable and produce lifetime consequences. However, while some people are and feel vulnerable to contexts of adversity, other people are resilient and manage to positively live and growth despite the difficulties that might appear throughout life. Epigenetics has been proposed as one of the molecular mechanisms that explain how those contexts "get under the skin" and trigger phenotypic characteristics. Although the regulation of gene expression by epigenetic mechanisms occurs naturally and constantly in the developing organism, it can also be influenced by environmental factors, such as age, lifestyle, health conditions or social relationships. Epigenetics is sensitive to environmental changes allowing organisms to adapt their physiology and behavior. Unlike the changes that occur in the DNA sequence, epigenetic processes are reversible. One of the most known examples of epigenetic action in determining phenotypes according to the environment is the stress response through the hypothalamus-pituitary-adrenal (HPA) axis. The functioning of the HPA axis and the response to stress can be related to the concepts of vulnerability and trauma. If an emotionally sensitive event is disturbing, it becomes a stressful situation, with the activation of the HPA axis, flooding the bloodstream with cortisol. This allostatic process is the basis of the mechanism of adaptability of humans to traumatic impacts. But if the situation continues to impact, allostasis is systematized and generates an allostatic circuit that produces a residual charge that ends up creating dysfunction in the organism. In this article the involvement of epigenetics in this regulation is discussed and some seminal studies in rodents and humans are presented. The last few years of scientific research have seen an explosive growth of studies linking situations of vulnerability (particularly, during early life) with the development of psychopathologies. Epigenetics was established as an interesting factor that allows to relate, from a biological point of view, the context in which people develop with their emotional states. This article proposes a review of some of these works in order to integrate them into a complex conception of the human being, which understands it as a system of relationships between various dimensions, including genetics, epigenetics, neurology, emotions, social interactions, cognition, and socio-culture, framed in a particular context.

Epigenética y enfermedades crónicas no trasmisibles: un nuevo enfoque preventivo

La prevención de las enfermedades crónicas no trasmisibles de elevada prevalencia a nivel mundial, como la hipertensión arterial, la diabetes mellitus, las enfermedades cardiovasculares y el cáncer, representa una prioridad en salud. La nueva perspectiva brindada por la epigenética sobre el origen intrauterino de las enfermedades que afectarán al ser humano durante la etapa posnatal, obliga a replantearse una nueva visión preventiva, que debe iniciarse desde el período prenatal de la vida. Con el objetivo de estructurar los referentes teóricos que sustentan la relevancia de un nuevo enfoque preventivo de las enfermedades crónicas no trasmisibles, basado en intervenciones modificatorias de los perfiles epigenéticos desfavorables durante la etapa prenatal del desarrollo humano, se realizó una actualizada búsqueda sobre el tema, consultándose 28 referencias bibliográficas. Condiciones maternas durante la gestación, como la malnutrición, el estrés, los hábitos tóxicos y la obesidad, constituyen factores causantes de modificaciones epigenéticas desfavorables, que serán trasmitidas a futuras generaciones e incrementarán en estas el riesgo de enfermedades durante la etapa posnatal de la vida. Se concluye que las intervenciones realizadas durante el período prenatal del desarrollo humano pueden contribuir a la prevención de enfermedades crónicas no trasmisibles, a lo que la epigenética aporta un nuevo enfoque en la prevención de este importante problema de salud.

The prevention of chronic non-communicable diseases with high prevalence around the world, such arterial hypertension, diabetes mellitus, cardiovascular diseases and cancer, represents a health priority. The new perspective given by epigenetics on the intrauterine origin of the diseases that will affect the human being during the post-natal stage, forces us to reconsider a new preventive vision which must begin from the prenatal period of life. With the aim of structuring the theoretical references that support the relevance of a new preventive approach to chronic non-communicable diseases, based on modifying interventions of unfavorable epigenetic profiles during the prenatal stage of the human development, an updated search on the subject was conducted, consulting 28 bibliographic references. Maternal conditions during pregnancy, such as malnourishing, stress, toxic habits and obesity, constitute factors that cause unfavorable epigenetic modifications, which will be transmitted to future generations and will increase in them the risk of disease during the post-natal stage of life. It is concluded that the interventions carried out during the prenatal period of human development can contribute to the prevention of chronic non-communicable diseases, to which epigenetics provides a new approach in the prevention of this important health problem.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

VIH/sida y epigenética / HIV/AIDS and epigenetic

Resumen Desde 1981, el virus de la inmunodeficiencia humana ha afectado a más de 75 millones de personas en el mundo. La prevención, el diagnóstico temprano y, ante todo el empleo de la terapia antirretroviral, ha disminuido su morbimortalidad. Sin embargo, su cura y el desarrollo de una vacuna efectiva aún son objetivos no alcanzables a corto plazo. Una de las barreras para obtener su control es la persistencia crónica de los virus o sus subproductos en los denominados reservorios celulares, lo que induce un proceso inflamatorio crónico complejo que se manifiesta clínicamente como enfermedad cardiovascular, diversos tipos de cáncer, envejecimiento precoz, entre otras patologías. Los procesos intrínsecos que llevan a estos trastornos han estado siendo investigados a profundidad en los últimos años y la epigenética, definida como el estudio de las modificaciones que afectan de manera directa la expresión de los genes, pero sin cambios en la secuencia del ácido desoxirribonuncleico, puede ayudar a desentrañar estos retos. En esta revisión se analizan los mecanismos epigenéticos, como la metilación del ácido desoxirribonuncleico, las modificaciones en histonas y el ácido ribonucleico no codificante, como posibles blancos en el diagnóstico y tratamiento de la inflamación crónica y sus consecuencias clínicas asociadas al virus de inmunodeficiencia humana/sida.

Abstract Since 1981, over 75 million people have been infected with human immunodeficiency virus. The survival rate of patients with this infection has dramatically increased with the use of antiretroviral therapy, and this therapy significantly reduced the incidence of AIDS defining events. Despite recent progress, neither a cure nor a preventive vaccine against human immunodeficiency virus infection is likely to become available soon. Epigenetics is defined as the study of chemical modifications of intrinsic and extrinsic factors of the genetic code regulating gene expression. Three types of epigenetic markers have been found: DNA methylation, post-translational histone modifications, and non-coding RNA (ncRNA). In this review, we analyzed recent research about the relation between epigenetic mechanisms, the persistence of HIV in host cells, the chronic inflammatory response evoked, the cardiovascular diseases associated and premature aging in this population.

Intervención educativa en estudiantes de Enfermería sobre epigenética y prevención preconcepcional de enfermedades crónicas

Introducción: la prevención de las enfermedades crónicas no trasmisibles de elevada prevalencia a nivel mundial, representa una prioridad en salud; en este sentido, la epigenética aporta una nueva perspectiva a la prevención de las mismas. Objetivo: evaluar la efectividad de una intervención educativa en estudiantes de la Licenciatura en Enfermería de la Universidad de Ciencias Médicas de Matanzas, a fin de incrementar el nivel de conocimientos en epigenética y prevención preconcepcional de enfermedades crónicas, realizada entre abril y julio de 2022. Materiales y métodos: se realizó un estudio de intervención que constó de tres etapas, en un universo de 54 estudiantes de primer y tercer años del curso regular diurno de la Licenciatura en Enfermería. Se empleó una encuesta para medir los conocimientos de los mismos en epigenética y prevención preconcepcional de enfermedades crónicas. Resultados: el nivel de conocimientos en epigenética y prevención preconcepcional de enfermedades crónicas previo a la intervención, fue calificado de malo. Conclusión: después de la implementación del programa educativo, se elevaron los conocimientos sobre epigenética y prevención preconcepcional de enfermedades crónicas en estudiantes de Licenciatura en Enfermería, demostrándose así su efectividad.

Introduction: the prevention of chronic non-preventable diseases of high-prevalence worldwide represents a health priority; in this sense, epigenetics brings a new perspective to their prevention. Objective: to assess the effectiveness of an educative intervention carried out between April and July 2022 in students of the Nursing degree from Matanzas University of Medical Sciences, with the aim of increasing their level of knowledge on epigenetics and preconception prevention of chronic diseases. Materials and methods: a three-stage intervention study was carried out, in a universe of 54 students of first and third years of the regular day-time course of the Nursing degree. A survey was used to measure their knowledge on epigenetics and preconception prevention of chronic diseases. Results: the level of knowledge on epigenetics and preconception prevention of chronic diseases prior to intervention was qualified as bad. Conclusion: after the implementation of the educative program, the knowledge on epigenetics and preconception prevention of chronic diseases increased in students of the Nursing degree, thus demonstrating its effectiveness.

La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Fisiopatología de la programación fetal y su repercusión en la salud futura / Pathophysiology of fetal programming and its impact on the future health

Resumen ANTECEDENTES: Durante la vida intrauterina, las alteraciones en el microambiente fetal causadas por desequilibrios nutricionales y metabólicos de la madre pueden dejar huellas epigenéticas y efectos persistentes en la vida adulta de su hijo que habrán de predisponerlo a enfermedades crónicas futuras. OBJETIVO: Llevar a cabo una revisión sistemática de la fisiopatología de la programación fetal y su repercusión en la salud futura del feto. METODOLOGÍA: Búsqueda en la base de datos de PubMed de artículos publicados, en los últimos 10 años, en inglés o español, con los MeSH "fetal programming"; "pathophysiology", con su correspondiente traducción. Se incluyeron artículos originales y de revisión con criterios PRISMA para revisiones sistemáticas. RESULTADOS: Se encontraron 38 artículos, y se agregaron 7 de información complementaria y sustento para la discusión. En su análisis queda clara la relación entre las condiciones fisiopatológicas reportadas de desnutrición, sub y sobrealimentación, diabetes mellitus gestacional, obesidad, resistencia a la insulina, glucocorticoides y preeclampsia con enfermedades de la infancia, adolescencia y adultez. Se encontró evidencia de disruptores endocrinos, melatonina y disbiosis con enfermedades de la infancia y vida adulta. Así mismo, la interrupción de la angiogénesis durante el desarrollo pulmonar que conduce a hipertensión arterial pulmonar y enfisema, todo ello originado por la programación fetal epigenética. Se encontraron diferencias en el patrón de metilación de placentas prematuras en comparación con las de término. CONCLUSIONES: Las anormalidades que sobrevienen durante el embarazo modifican la programación fetal y dan pie a las enfermedades que aparecerán durante la infancia, adolescencia y adultez, como consecuencia de los cambios en el patrón de metilación de los genes.

Abstract BACKGROUND: During intrauterine life, alterations in the fetal microenvironment caused by maternal nutritional and metabolic imbalances may leave epigenetic imprints and persistent effects on fetal adult life that will predispose the fetus to future chronic diseases. OBJECTIVE: To carry out a systematic review of the pathophysiology of fetal programming and its impact on the future health of the fetus. METHODOLOGY: Search in the PubMed database of articles published in the last 10 years, in English or Spanish, with the MeSH "fetal programming"; "pathophysiology", with their corresponding translation. Original and review articles with PRISMA criteria for systematic reviews were included. RESULTS: Thirty-eight articles were found, and seven were added for complementary information and support for discussion. In their analysis the relationship between the reported pathophysiological conditions of under-, under- and over-nutrition, gestational diabetes mellitus, obesity, insulin resistance, glucocorticoids and pre-eclampsia with diseases of childhood, adolescence and adulthood is clear. Evidence of endocrine disruptors, melatonin and dysbiosis was found with diseases of childhood and adulthood. Also, disruption of angiogenesis during lung development leads to pulmonary arterial hypertension and emphysema, all caused by epigenetic fetal programming. Differences were found in the methylation pattern of preterm placentas compared to term placentas. CONCLUSIONS: Abnormalities that occur during pregnancy modify fetal programming and give rise to the diseases that will appear during childhood, adolescence, and adulthood, because of changes in the methylation pattern of genes.

Diabetes materna y deficiencia de zinc: riesgos para la descendencia / Maternal diabetes and zinc deficiency, risks for the offspring

Resumen ANTECEDENTES: Cuando la mujer embarazada tiene déficit de zinc, esta carencia puede ser un factor que contribuya a la aparición de alteraciones en el feto, como las malformaciones congénitas y otros trastornos del desarrollo. OBJETIVO: Identificar los aspectos relevantes del estado actual del conocimiento de las complicaciones de la diabetes en la mujer embarazada y el déficit de zinc en el feto. Además, explicar cuál es la posible consecuencia de la deficiencia del micronutriente, entre otras causas moleculares subyacentes. METODOLOGÍA: Revisión bibliográfica efectuada en las bases de datos de Google, PubMed-Medline y SciELO de artículos publicados en inglés o español del año 2012 al 2022, con los MeSH: Maternal diabetes; Hyperglycemia; Zinc deficiency; Congenital malformations; Epigenetics; con su correspondiente traducción al español. Criterios de selección: artículos originales, estudios prospectivos, de revisión bibliográfica, metanálisis, capítulos de libro y reportes de la Asociación Americana de Diabetes (ADA) y la Asociación Latinoamericana de Diabetes (ALAD). RESULTADOS: Se localizaron 187 artículos de los que se excluyeron 126 no adecuados para el tema de la revisión, duplicados o en idioma diferente al inglés y español. CONCLUSIONES: El análisis bibliográfico evidenció que los trastornos metabólicos provocados por la hiperglucemia de la madre, el déficit de zinc, la alteración de su homeostasis y su interacción con el desequilibrio redox, la inflamación de bajo grado, la activación apoptósica y las modificaciones epigenéticas producen un ambiente intrauterino adverso que condiciona la aparición de malformaciones y otros trastornos del desarrollo en la descendencia.

Abstract BACKGROUND: When pregnant women are deficient in zinc, this deficiency may be a contributing factor to foetal disorders, such as congenital malformations and other developmental disorders. OBJECTIVE: To identify the relevant aspects of the current state of knowledge of the complications of diabetes in pregnant women and zinc deficiency in the foetus. In addition, to explain the possible consequences of micronutrient deficiency, among other underlying molecular causes. METHODOLOGY: Bibliographic review carried out in Google, PubMed-Medline and SciELO databases of articles published in English or Spanish from 2012 to 2022, with the MeSH: Maternal diabetes; Hyperglycemia; Zinc deficiency; Congenital malformations; Epigenetics; with their corresponding translation into Spanish. Selection criteria: original articles, prospective studies, literature reviews, meta-analyses, book chapters and reports of the American Diabetes Association (ADA) and the Latin American Diabetes Association (ALAD). RESULTS: 187 articles were located of which 126 unsuitable for the review topic, duplicates or in language other than English and Spanish were excluded. CONCLUSIONS: The literature review evidenced that metabolic disorders caused by maternal hyperglycemia, zinc deficiency, alteration of its homeostasis and its interaction with redox imbalance, low-grade inflammation, apoptotic activation and epigenetic modifications produce an adverse intrauterine environment that conditions the appearance of malformations and other developmental disorders in the offspring.

El rol epigenético de la radiación ultravioleta y estrés oxidativo en la formación de cataratas / The Epigenetic Role of Ultraviolet Radiation and Oxidative Stress in Cataract Formation

El ojo humano es altamente expuesto a luz de todo tipo de ondas electromagnéticas, la tensión metabólica en la eliminación del daño celular, así como su acumulación, constituyen el mayor estrés oxidativo debido a radiación ultravioleta. El objetivo del la revisión fue documentar la nueva evidencia científica en epigenética con respecto a la radiación ultravioleta y estrés oxidativo en la formación de cataratas. Se realiza una revisión de la literatura comprendida del 1ro de mayo del 2021 al 1ro de mayo 2022 con meta buscadores en inglés y español. El daño bioquímico acumulable a nivel de las histonas es considerado el primer insulto ambiental en la formación de cataratas. El potencial inmunomodulador de las células del epitelio del lente humano es un blanco terapéutico prometedor, debido a ser la principal línea celular afectada en radiación por rayos ultravioleta. El avance tecnológico, bioquímico y fisiológico permitirá promover una solución diferente, por otro concepto distinto de cirugía, para la cura de la entidad más prevalente en el mundo por ceguera reversible: catarata(AU)

The human eye is highly exposed to light of all types of electromagnetic waves, the metabolic stress in the elimination of cellular damage, as well as its accumulation, constitute the major oxidative stress due to ultraviolet radiation. The objective was to document the new scientific evidence in epigenetics regarding ultraviolet radiation and oxidative stress in cataract formation. A review of the literature from May 1, 2021 to May 1, 2022 was performed with meta-search engines in English and Spanish. Cumulative biochemical damage at the histone level is considered the primary environmental insult in cataract formation. The immunomodulatory potential of human lens epithelium cells is a promising therapeutic target, due to being the main cell line affected in ultraviolet radiation. The technological, biochemical and physiological advance will allow promoting a different solution, by a different concept of surgery, for the cure of the most prevalent condition in the world for reversible blindness: cataract(AU)

Síndrome de Angelman

Introducción: El síndrome de Angelman es un trastorno del neurodesarrollo hereditario poco frecuente que afecta a 1 de cada 10 mil a 24 mil nacimientos. Esta condición incluye retraso del desarrollo, discapacidad intelectual, discapacidad severa para hablar, problemas con el movimiento y el equilibrio (ataxia), epilepsia y cabeza muy pequeña. Las personas con síndrome de Angelman parecen estar siempre de buen humor y sonríen mucho. Objetivo: Sistematizar los conocimientos sobre las características del síndrome de Angelman, los aspectos clínicos y genéticos de la enfermedad y las estrategias de tratamientos actuales. Método: Se realizó una revisión bibliográfica en la Universidad Regional Autónoma de los Andes, mediante la búsqueda en bases de datos tanto nacionales como internacionales, como PubMed, Scopus, SciELO, Web of Science y Google Scholar. Para la investigación se empleó una estrategia de búsqueda. Se encontraron 45 artículos, de los cuales 15 fueron seleccionados para esta revisión. Resultados: Se elaboró un texto sintetizado donde se abordaron aspectos tales como: etiología, diagnóstico, principales síntomas clínicos y tratamiento de este trastorno genético. Conclusiones: Por su naturaleza de necesidades clínicas que no son satisfechas en cuanto al área motora, la comunicación, el sueño y el comportamiento, el síndrome de Angelman hace necesario que los profesionales de enfermería desarrollen un plan de acción que permita un diagnóstico precoz y desarrollen un plan de cuidados específico para el individuo y el entorno íntimo de actuación para responder a las necesidades a demanda.

Introduction: Angelman Syndrome is a rare inherited neurodevelopmental disorder that affects 1 in 10,000 to 24,000 newborns. This condition includes developmental desability, intellectual disability, severe speech disability, movement and balance problems (ataxia), seizures and very small head. People with Angelman Syndrome always seem to be in a good mood and smile a lot. Objective: To systematize knowledge about the characteristics of Angelman Syndrome, clinical and genetic aspects of the disease and current treatment strategies. Method: A bibliographic review was carried out at the Universidad Regional Autónoma de los Andes, by searching in national and international databases such as PubMed, Scopus, SciELO, Web of Science and Google Scholar. For the investigation a search strategy was used. Forty-five articles were found, of which 15 were selected for this review. Results: A synthesized text was elaborated where aspects such as etiology, diagnosis, main clinical symptoms and treatment of this genetic disorder were addressed. Conclusions: Due to its nature of clinical needs that are not met in terms of the motor area, communication, sleep and behavior, Angelman syndrome makes it necessary for nursing professionals to develop an action plan that allows an early diagnosis and develop a plan specific care for the individual and the intimate environment of action to respond to the needs on demand.

Introdução: A síndrome de Angelman é um distúrbio hereditário raro do neurodesenvolvimento que afeta 1 em 10.000 a 24.000 nascimentos. Essa condição inclui atraso no desenvolvimento, deficiência intelectual, deficiência grave da fala, problemas de movimento e equilíbrio (ataxia), epilepsia e cabeça muito pequena. Pessoas com síndrome de Angelman parecem estar sempre de bom humor e sorrir muito. Objetivo: Sistematizar o conhecimento sobre as características da síndrome de Angelman, os aspectos clínicos e genéticos da doença e as estratégias atuais de tratamento. Método: Foi realizada revisão bibliográfica na Universidad Regional Autónoma de los Andes, por meio de busca em bases de dados nacionais e internacionais, como PubMed, Scopus, SciELO, Web of Science e Google Acadêmico. Para a investigação, foi utilizada uma estratégia de busca. Foram encontrados 45 artigos, dos quais 15 foram selecionados para esta revisão. Resultados: Foi elaborado um texto sintetizado onde foram abordados aspectos como: etiologia, diagnóstico, principais sintomas clínicos e tratamento desta doença genética. Conclusões: Devido à sua natureza de necessidades clínicas não satisfeitas ao nível da área motora, comunicação, sono e comportamento, a síndrome de Angelman torna necessário que os profissionais de enfermagem desenvolvam um plano de ação que permita o diagnóstico precoce e desenvolvam um plano de cuidados específico para o indivíduo e o ambiente íntimo de ação para responder às necessidades sob demanda.

Perspectivas con dianas para el tratamiento de la artritis reumatoide / Perspectives with targets for the treatment of rheumatoid arthritis

La artritis reumatoide se clasifica como una enfermedad articular autoinmune crónica poliarticular sistémica que afecta principalmente a manos y pies. El objetivo de este trabajo es mostrar información publicada que contribuye a direccionar el manejo de la artritis reumatoide con nuevos fármacos, a partir del conocimiento de aspectos novedosos relacionados con la fisiopatología y los avances recientes sobre un grupo importante de dianas para el tratamiento de esta enfermedad. Las modificaciones epigenéticas pueden regular la expresión génica sin alterar la secuencia del ADN. La regulación de los ARN no codificantes (ncRNA), la metilación del ADN, la metilación del ARN y las modificaciones de las histonas se consideran los principales mecanismos de las regulaciones epigenéticas. Numerosas investigaciones han establecido que varias anomalías en estos mecanismos terminan en el desarrollo de la AR. Este trabajo resume nuevas dianas, que incluyen proteínas, pequeños metabolitos moleculares y reguladores de la epigenética. Son dianas moleculares prometedoras para el descubrimiento de fármacos que alivien la aparición de enfermedades y resuelvan la falta de respuesta y las respuestas parciales, así como los efectos adversos de los FARME actuales. Es innegable que aún se necesitan mayores esfuerzos para definir con mayor precisión las vías de señalización subyacentes afectadas por estas moléculas recién descubiertas y para desarrollar métodos de terapia apropiados(AU)

Rheumatoid arthritis is classified as a systemic polyarticular chronic autoimmune joint disease that mainly affects the hands and feet. The objective of this work is to show published information that contributes to directing the management of RA with new drugs. Epigenetic modifications can regulate gene expression without altering the DNA sequence. Regulation of non-coding RNAs (ncRNAs), DNA methylation, RNA methylation, and histone modifications are considered the main mechanisms of epigenetic regulations. Numerous investigations have established that various abnormalities in these mechanisms lead to the development of RA. This work summarizes new targets, including proteins, small molecular metabolites and regulators of epigenetics. They are promising molecular targets for drug discovery to alleviate disease onset and resolve non-response and partial responses, as well as adverse effects of current DMARDs. It is undeniable that further efforts are still needed to further define the underlying signaling pathways affected by these newly discovered molecules and to develop appropriate therapy methods(AU)

Epigenética y estilos de vida saludables de la Enfermedad Arterial Periférica / Epigenetics and healthy lifestyles of Peripheral Arterial Disease / Epigenética e Estilos de Vida Saudáveis na Doença Arterial Periférica

RESUMEN La Enfermedad Arterial Periférica (EAP) se caracteriza por la oclusión progresiva de las arterias de las extremidades inferiores, afectando a gran parte de la población mundial. Se conoce que los factores de riesgo más reconocidos de la enfermedad y el estilo de vida pueden producir cambios epigenéticos que influyen en el desarrollo de la EAP. Por lo anterior; el propósito de este estudio, fue evidenciar la relación entre la epigenética y el estilo de vida, asociado a la EAP a partir de una revisión. La búsqueda se realizó en las bases de datos de PubMed, Cochrane, Science Direct y Google Scholar; eligiendo solo artículos en espanol e inglés publicados en los últimos I0 anos. Se encontró que aquellas personas con comportamientos saludables como realizar actividad física, buena alimentación y dejar de fumar, inducen cambios epigenéticos como la expresión de miARN, metilación del ADN y modificación de histonas, procesos implicados en el desarrollo y progresión de la EAP. La epigenética vislumbra la necesidad de nuevas estrategias que conduzcan a la prevención, tratamiento y autocuidado de los comportamientos saludables para mejorar la calidad de vida de las personas y reducir la carga por esta enfermedad.

ABSTRACT Peripheral Arterial Disease (PAD) is characterized by the progressive occlusion of the arteries of the lower extremities, affecting a large part of the world population. It is known that the most recognized risk factors for disease and lifestyle can produce epigenetic changes that influence the development of PAD. Therefore, the purpose of this study was to demonstrate the relationship between epigenetics and lifestyle, associated with PAD, based on a review. The search was carried out in the databases of PubMed, Cochrane, Science Direct, and Google Scholar, choosing only articles in Spanish and English published in the last I0 years. It was found that those people with healthy behaviors such as physical activity good nutrition, and quitting smoking, induce epigenetic changes such as miRNA expression and DNA methylation and histone modification, processes involved in the development and progression of PAD. Epigenetics envisions the need for new strategies that lead to the prevention, treatment, and self-care of healthy behaviors to improve people's quality of life and reduce the burden of this disease.

RESUMO A Doença Arterial Periférica (DAP) é caracterizada pela oclusão progressiva das artérias das extremidades inferiores, afectando uma grande proporção da população mundial. Sabe-se que os factores de risco mais reconhecidos para a doença e estilo de vida podem levar a mudanças epigenéticas que influenciam o desenvolvimento do DAP. Portanto, o objectivo deste estudo era demonstrar a relação entre epigenética e estilo de vida associado ao DAP, com base numa revisão. A pesquisa foi realizada nas bases de dados da PubMed, Cochrane, Science Direct e Google Scholar, escolhendo apenas artigos em espanhol e inglês publicados nos últimos 10 anos. Verificámos que pessoas com comportamentos saudáveis tais como actividade física, boa nutrição e cessação do tabagismo induzem alterações epigenéticas tais como expressão do miRNA, metilação do ADN e modificação do historial, processos envolvidos no desenvolvimento e progressão do DAP. A epigenética prevê a necessidade de novas estratégias que conduzam à prevenção, tratamento e autocuidado de comportamentos saudáveis para melhorar a qualidade de vida das pessoas e reduzir o peso desta doença.

Obesidade genética não sindrômica: histórico, fisiopatologia e principais genes / Non-syndromic genetic obesity: history, pathophysiology and key genes

A obesidade é definida pelo excesso de gordura corporal acumulada no tecido adiposo quando o indivíduo atinge valores de IMC igual ou superior a 30 Kg/m2. Constitui um dos principais fatores de risco para várias doenças não transmissíveis (DNTs) como por exemplo, diabetes mellitus tipo 2 (DM2), doenças cardiovasculares, hipertensão arterial, acidente vascular cerebral e até mesmo o câncer. Embora a obesidade esteja diretamente relacionada com o consumo calórico excessivo em relação ao gasto energético diário, sua etiologia pode estar associada aos baixos níveis de atividade física, às alterações neuroendócrinas e aos fatores genéticos. Considerando o componente genético, esta pode ser classificada como sindrômicas e estar associada às alterações cromossômicas estruturais ou numéricas, ou como não sindrômica, quando relacionada, principalmente, com os polimorfismos de nucleotídeos simples (SNPs) em alelos que atuam como herança monogênica, ou ainda com a interação vários genes (poligênica multifatorial). Apesar de existirem muitas etiologias diferentes, normalmente a obesidade é tratada a partir da mesma abordagem, desconsiderando a fisiologia que a desencadeou. Dessa forma, o objetivo do presente trabalho foi abordar a obesidade genética não sindrômica por meio a) da descrição breve de perspectiva histórica sobre seu entendimento; b) da exposição dos principais mecanismos moleculares envolvidos com o controle de peso; c) da compilação dos principais genes e SNPs relacionados; d) da definição dos principais genes; e e) da abordagem das principais perspectivas de intervenção.

Obesity is defined as excess body fat accumulated in the adipose tissue when the individual reaches BMI values equal to or greater than 30 kg/m2. It is one of the main risk factors for several non-communicable diseases (NCDs), such as Type 2 Diabetes mellitus (T2D), cardiovascular diseases, high blood pressure, stroke and even cancer. Although obesity is directly related to excessive calorie intake in relation to daily energy expenditure, its etiology may be associated with low levels of physical activity, neuroendocrine changes, and genetic factors. Considering the genetic component, it can be classified as syndromic and be associated with chromosomal or numerical changes, or as non-syndromic and being related mainly to single nucleotide polymorphisms (SNPs) in alleles that act as monogenic inheritance, or with an interaction of several genes (multifactorial polygenic). Although there are many different etiologies, obesity is usually treated using the same approach, disregarding the physiology that triggered it. Thus, the aim of this study was to address non-syndromic genetic obesity through a) a brief description of a historical perspective on its understanding; b) the exposure of the main molecular mechanisms involved in weight control, c) the compilation of the key genes and related SNPs, d) the definition of the key genes and e) the approach of the main intervention representations.

El desafío para el desarrollo del sistema nervioso central en la reproducción humana asociada con la diabetes / The challenge for the development of the central nervous system in human reproduction associated with diabetes

Introducción: Los hijos de madres con diabetes presentan una mayor incidencia de trastornos del neurodesarrollo como autismo, actividad cognitiva baja, déficit de atención, esquizofrenia y otras enfermedades del espectro autista. Objetivo: Explicar los mecanismos moleculares que subyacen en la aparición de los trastornos del neurodesarrollo en hijos de gestantes con diabetes. Métodos: Se llevó a cabo una revisión de la literatura que aparece en las bases de datos electrónicas Google, MEDLINE/PubMed y SciELO. Se revisaron artículos publicados entre los años 2000 y 2020. Las palabras clave utilizadas fueron: hiperglucemia, neurodesarrollo, malformaciones congénitas y epigenética. Resultados: Se pone de manifiesto el alto riesgo que representa la hiperglucemia durante el desarrollo intrauterino. El riesgo relativo que tienen los hijos de madres con diabetes pregestacional de presentar malformaciones del sistema nerviosos central es 15,5 veces mayor que en gestantes sin diabetes. El hipocampo es especialmente sensible a cambios en los niveles de glucosa. La diabetes materna puede dejar una impronta negativa para la capacidad de procesar información, adquirir habilidades y poseer un comportamiento social adecuado en la descendencia. Conclusiones: Las alteraciones en el metabolismo condicionadas por la hiperglucemia, el estrés oxidativo, la inflamación de bajo grado y las modificaciones epigenéticas crean un fatal engranaje que sustenta el desarrollo anómalo en hijos de gestantes con diabetes(AU)

Introduction: Children, whose mothers suffer from diabetes, have higher incidence of neurodevelopmental disorders such as autism, low cognitive activity, attention deficit, schizophrenia and other autism spectrum diseases. Objective: To explain the molecular mechanisms that underlie the appearance of neurodevelopmental disorders in children of pregnant women with diabetes. Methods: A review of the literature that appears in Google, MEDLINE/PubMed and SciELO electronic databases, was carried out. Articles published from 2000 to 2020 were reviewed. The keywords used were hyperglycemia, neurodevelopment, congenital malformations, and epigenetics. Results: The high risk that hyperglycemia represents during intrauterine development is highlighted. The relative risk that children of mothers with pregestational diabetes have of presenting malformations of the central nervous system is 15.5 times higher than in pregnant women without diabetes. The hippocampus is especially sensitive to changes in glucose levels. Maternal diabetes can leave negative print on the ability to process information, acquire skills and have appropriate social behavior in their children. Conclusions: Alterations in metabolism conditioned by hyperglycemia, oxidative stress, low-grade inflammation and epigenetic modifications create a fatal mechanism that supports abnormal development in children of pregnant women with diabetes(AU)

Mecanismos epigenéticos involucrados en la génesis del autismo / Epigenetic mechanisms involved in the genesis of autism

Resumen El autismo es un trastorno del neurodesarrollo de base neurobiológica, caracterizado por alteración en la interacción social y la comunicación, intereses restringidos y conductas estereotipadas. Se relaciona con trastornos en la sinaptogénesis y a multiples etiologías. La identificación de factores epigenéticos implicados en la génesis del autismo permiten una mejor comprensión de los mecanismos moleculares invo lucrados. Nuestro objetivo fue analizar los mecanismos epigenéticos relacionados al desarrollo del autismo, puntualizando entidades específicas y sus mecanismos fisiopatológicos. Analizamos de qué manera se rela cionan los trastornos en la metilación del ADN, la modificación de las histonas, la remodelación cromosómica y la regulación mediada por el ARN no codificantes con diversos síndromes genéticos como el frágil X, Rett, Mecp2patías, Phelam McDermid, tóxicos prenatales como el alcohol, ácido valproico, cannabis y ambientales cómo el estrés materno, todos ellos asociados a una mayor prevalencia de autismo. En conclusión, el recono cimiento de estos mecanismos abre nuevas posibilidades para la prevención, y probablemente en un futuro, en las entidades genéticas, permitirá el desarrollo de tratamientos específicos con modificaciones a la medida de cada entidad.

Abstract Autism is a neurobiological developmental disorder characterized by poor social interaction and communication, narrow interests, and stereotyped behaviors. It has been associated with disorders of synaptogenesis and multiple etiologies. The iden tification of the epigenetic factors involved in the genesis of autism allows a better understanding of the molecular mechanisms involved. Our objective was to analyze the epigenetic mechanisms related to the development of autism, specifying specific entities and their pathophysiological mechanisms. We analyze how DNA methylation disorders, histone modification, remodeling and chromosomal regulation mediated by non-coding RNA are related to various genetic syndromes such as fragile X, Rett, Pathias Mecp2, Phelam McDermid, prenatal toxins such as alcohol, valproic. acid, cannabis, and environmental toxins such as maternal stress, all associated with a higher prevalence of autism. In conclusion: the recognition of these mechanisms opens up new possibilities for preven tion and it is likely that, in genetic entities, it will allow the development of specific treatments with modifications tailored to each entity.

Programación temprana de la hipertensión arterial / Early programming of hypertension

La hipertensión arterial (HTA) es un factor de riesgo modificable de enfermedad cardiovascular (ECV) y debe incluirse dentro del estudio de los orígenes del desarrollo de la salud y enfermedad (DOHaD). Durante el desarrollo intrauterino y perinatal, diferentes factores ambientales impactan en la programación temprana de las enfermedades crónicas no transmisibles (ECNT). En esta revisión se resume la evidencia que vincula los cambios adaptativos y la plasticidad del feto a factores ambientales desfavorables alterando el fenotipo adulto en el desarrollo de HTA. Estos cambios adaptativos responden a cambios epigenéticos que favorecen el desarrollo de HTA y ECV en la edad adulta con implicancias intergeneracionales. Por último, se mencionan estrategias preventivas para limitar o revertir algunas de las variables que pueden producir alteraciones en la programación del desarrollo que conducen a HTA en etapas más tardías de la vida.

Hypertension (HTN) is a modifiable risk factor for cardiovascular disease (CVD) and should be included in the study of developmental origins of health and disease (DOHaD). During intrauterine and perinatal development, different environmental factors have an impact on the early programming of noncommunicable diseases (NCDs). This review provides a summary of the evidence that connects the fetus' plasticity and adaptive changes to unfavorable environmental factors that alter the adult phenotype in the development of HTN. Such adaptive changes result from epigenetic changes that favor the development of HTN and CVD in adulthood with intergenerational implications. Lastly, we mention preventive strategies to limit or reverse any variable that may alter developmental programming leading to HTN later in life.

Response and tolerance mechanism of food crops under high temperature stress: a review / Mecanismo de resposta e tolerância de culturas alimentares sob estresse de alta temperatura: uma revisão

High temperature stress events are critical factors inhibiting crop yield. Meanwhile, world population is growing very rapidly and will be reached up to 9 billion by 2050. To feed increasing world population, it is challenging task to increase about 70% global food productions. Food crops have significant contribution toward global food demand and food security. However, consequences from increasing heat stress events are demolishing their abilities to survive and sustain yield when subjected to extreme high temperature stress. Therefore, there is dire need to better understand response and tolerance mechanism of food crops following exposure to heat stress. Here, we aimed to provide recent update on impact of high temperature stress on crop yield of food crops, pollination, pollinators, and novel strategies for improving tolerance of food crop under high temperature stress. Importantly, development of heat-resistant transgenic food crops can grant food security through transformation of superior genes into current germplasm, which are associated with various signaling pathways as well as epigenetic regulation in response to extreme high temperature stress.

Eventos de estresse de alta temperatura são fatores críticos que inibem o rendimento das culturas. Enquanto isso, a população mundial está crescendo muito rapidamente e atingirá até 9 bilhões em 2050. Para alimentar a crescente população mundial, é uma tarefa desafiadora aumentar cerca de 70% da produção global de alimentos. As culturas alimentares têm uma contribuição significativa para a procura global de alimentos e a segurança alimentar. No entanto, as consequências do aumento de eventos de estresse por calor estão destruindo suas habilidades de sobreviver e manter a produção quando submetidos a estresse de alta temperatura. Portanto, há uma necessidade urgente de entender melhor o mecanismo de resposta e tolerância das safras de alimentos após a exposição ao estresse por calor. Aqui, nosso objetivo foi fornecer atualizações recentes sobre o impacto do estresse de alta temperatura no rendimento de culturas de alimentos, polinização, polinizadores e novas estratégias para melhorar a tolerância de culturas de alimentos sob estresse de alta temperatura. É importante ressaltar que o desenvolvimento de culturas alimentares transgênicas resistentes ao calor pode garantir segurança alimentar por meio da transformação de genes superiores em germoplasma atual, que estão associados a várias vias de sinalização, bem como à regulação epigenética em resposta ao estresse de alta temperatura extrema.

Triagem biológica de inibidores de sirtuína 2 (TcSir2rp1) candidatos a antichagásicos / Biological screening of sirtuin 2 inhibitors (TcSir2rp1) antichagasic candidates

A doença de Chagas é causada pelo Trypanosoma cruzi, e atualmente, acomete entre 6 a 7 milhões de pessoas em todo o mundo. A quimioterapia disponível para seu o tratamento se baseia apenas em dois fármacos, nifurtimox e benznidazol, com mais de 50 anos de descoberto. Estes fármacos apresentam eficácia limitada, pois são pouco efetivos na fase crônica e apresentam alta toxicidade, resultando em efeitos adversos graves. Esse panorama mostra a necessidade de novas abordagens terapêuticas contra essa doença. Nesse sentido, a inibição de vias bioquímicas essencias para o parasita se mostram como uma boa sugestão para identificação de compostos promissores candidatos a novos agentes quimioterápicos. A sirtuína 2 (Sir2) são enzimas reguladoras que participam de mecanismos epigenéticos em tripanossomatídeos, e no T. cruzi possuem um papel fundamental em todos os seus estágios evolutivos, devido a este fato, se apresentam como um alvo promissor na busca por novos fármacos contra a doença de Chagas. Neste sentido propomos a busca de inibidores da Sir2 proteína 1 do T. cruzi (TcSir2rp1) que é geneticamente validada como alvo farmacológico, por meio da estratégia de triagem biológica. Realizou-se a expressão da enzima recombinante por biologia molecular em um sistema de transformação utilizando cepa de Escherichia coli Artic Express (DE3). Foi feita a purificação e a confirmação da obtenção da proteína recombinante se deu por gel SDS-PAGE. Após a obtenção da enzima os parâmetros cinéticos foram determinados por experimentos de fluorimetria. A triagem foi realizada para um conjunto de 82 compostos, previamente sintetizados pelo nosso grupo de pesquisa, como inibidores da TcSir2p1 em dose única de 100 µM. Os ensaios foram realizados em triplicata e em experimentos independentes. Dentre os 82 compostos testados, 20 apresentaram inibições maior que 50% contra a enzima TcSir2rp1, na dose de 100 µM. Dentre estes, se destacaram 3 compostos derivados de chalconas, para os quais foi determinada a potência. O composto 1 foi o que mais potente, apresentando valor de IC50 de 11,65 µM, já os compostos 3 e 5 foram menos potentes (IC50= 38,50 µM e 19,85 µM, respectivamente). Diante dos resultados obtidos, pode-se concluir que a estratégia de triagem biológica é promissora na identificação de inibidores da TcSir2p1 candidatos a agentes anti- T. cruzi

Chagas disease is caused by Trypanosoma cruzi, and currently affects 6 to 7 million people worldwide. The chemotherapy available for its treatment is based on only two drugs, nifurtimox and benznidazole, with more than 50 years of discovery. These drugs have limited efficacy, as they are ineffective in the chronic phase and have high toxicity, resulting in serious adverse effects. This panorama shows the need for new therapeutic approaches against this disease. In this sense, the inhibition of essential biochemical pathways for the parasite proves to be a good suggestion for the identification of promising compounds candidates for new chemotherapeutic agents. Sirtuin 2 (Sir2) are regulatory enzymes that participate in epigenetic mechanisms in trypanosomatids, and in T. cruzi they have a fundamental role in all their evolutionary stages, due to this fact, they present themselves as a promising target in the search for new drugs against Chagas disease. In this sense, we propose the search for inhibitors of Sir2 protein 1 of T. cruzi (TcSir2rp1) which is genetically validated as a pharmacological target, through the biological screening strategy. The expression of the recombinant enzyme was performed by molecular biology in a transformation system using strain of Escherichia coli Artic Express (DE3). Purification was performed and confirmation of obtaining the recombinant protein was performed by SDS-PAGE gel. After obtaining the enzyme, the kinetic parameters were determined by fluorimetry experiments. Screening was performed for a set of 82 compounds, previously synthesized by our research group, as TcSir2p1 inhibitors in a single dose of 100 µM. Assays were performed in triplicate and in independent experiments. Among the 82 compounds tested, 20 showed inhibitions greater than 50% against the enzyme TcSir2rp1, at a dose of 100 µM. Among these, 3 compounds derived from chalcones stood out, for which the potency was determined. Compound 1 was the most potent, with an IC50 value of 11.65 µM, while compounds 3 and 5 were less potent (IC50= 38.50 µM and 19.88 µM, respectively). In view of the results obtained, it can be concluded that the biological screening strategy is promising in the identification of TcSir2p1 inhibitors candidates for anti-T. cruzi agents