Ciência da disseminação em DOHaD para a promoção da saúde nas futuras gerações / Dissemination Science in DOHaD for health promotion in future generations

Após o reconhecimento de princípios evolutivos e da epigenética associada à plasticidade do desenvolvimento, a ciência de DOHaD (Origens Desenvolvimentistas da Saúde e Doença) floresceu. Segundo DOHaD, a exposição a condições adversas no início da vida, como a subnutrição, leva a respostas adaptativas para aumentar as chances de sobrevivência imediata e posterior, as quais podem aumentar o risco de doenças crônicas não transmissíveis (DCNT) no curso da vida. Outros insultos como obesidade (materna e paterna) na preconcepção e gestação, diabetes gestacional, aleitamento e a alimentação inadequada na infância podem induzir respostas não adaptativas e aumentar o risco de doenças, independentemente do ambiente posterior. A exposição à desreguladores endócrinos, substâncias tóxicas e poluentes também podem ter efeitos de longo prazo. Esses efeitos são mediados por alterações epigenéticas, as quais se tornam mais sensíveis nesse período crítico de desenvolvimento de intensa reorganização. Diante da transição nutricional e coexistência das diferentes formas de desnutrição nos países de baixa e média renda (PBMR); do aumento global das DCNT, cujo impacto social e econômico é maior nesses países; da fraca contribuição de fatores genéticos fixos na etiologia dessas doenças; e da ineficácia das atuais intervenções, a implementação de DOHaD representa uma estratégia potencial para beneficiar as futuras gerações. Considerando que a disseminação de DOHaD não têm acompanhado seu florescimento científico, esse trabalho teve como objetivo o desenvolvimento de um ebook direcionado para nutricionistas e um artigo relativo aos impactos da pandemia de COVID-19 na perspectiva de DOHaD, a fim de aproximar a ciência destes profissionais e fomentar sua implementação. Trata-se de uma revisão narrativa de literatura a partir artigos científicos em inglês e português, publicados nas bases de dados SciELO, PubMed e BVS, sem limite de data. O trabalho evidenciou que o desafio da dupla carga de doenças e das diferentes formas de desnutrição nos PBMR, foi agravado pela pandemia, tornando imperativo medidas de intervenção por seu provável impacto no ciclo intergeracional de DCNT e desenvolvimento dos países. A aproximação dessa ciência do nutricionista, propicia uma formação mais ampla e integrativa, através de capacitação técnica e habilidades interpessoais, capazes de acionar as fragilidades biopsicossociais, e melhor intervir, equacionando resultados de curto e longo prazo, a fim de interromper o ciclo intergeracional de DCNT, assim como otimizar o capital humano, a capacidade de produção e renda da futura geração. Conclui-se que o material desenvolvido é de grande valia, dado que a disseminação desse conhecimento deve se estender aos nutricionistas de todas as áreas e ser multiplicado

After evolutionary and epigenetics principles associated with the plasticity of development were recognized, DOHaD (Developmental Origins of Health and Disease) science flourished. According to DOHaD, the exposure to adverse conditions at the beginning of life, like undernutrition, leads to adaptive responses to increased immediate and later odds of survival, which may increase the risk of noncommunicable diseases (NCD) during life. Other conditions such as obesity (maternal and paternal) in preconception and pregnancy, gestational diabetes, lactation, and inadequate nourishment during infancy can induce non-adaptive responses and increased risk of diseases, regardless of the upcoming environment. The exposure to endocrine disruptors, and toxic and pollutant substances can also have long-term effects. Those effects are mediated by epigenetic changes, which become more sensitive during this critical period of development under intense reorganization. Considering the nutritional transition and coexistence of the different forms of undernutrition in the low- and middle-income countries (LMIC); the global increase of NCDs, with a higher social and economic impact in those countries; the weak contribution of fixed genetic factors in the etiology of those diseases; and the inefficacy of current interventions, the implementation of DOHaD represents a potential strategy to benefit future generations. Considering that the dissemination of DOHaD have not followed its scientific progress, the goal of the present work was to develop an e-book targeting nutritionists and an article about the impacts of the COVID-19 pandemic in the perspective of DOHaD, intended to drive the science closer to those professionals and foster its implementation. It is a narrative review of the literature regarding scientific articles published in English and Portuguese on the data bases SciELO, PubMed and BVS, with no date limit. The work has highlighted that the challenge of the double burden of the diseases and the several forms of undernutrition in the LMIC, was aggravated by the pandemic, making intervention measures imperative due to its likely impact on the intergenerational cycle of NCD and the development of countries. By inching closer to nutritionists this science provides larger and more integrative education through technical training and interpersonal abilities that help activate biopsychosocial fragilities, and better intervention; providing short- and long-term results aiming to interrupt the NCD intergenerational cycle, as well as optimize the human capital, the work and income capacity of the future generation. It is concluded that the material developed is of great value, given that the dissemination of this knowledge should reach all nutritionists from all areas and be multiplied

Breaking the Cycle of Health Inequities: The Bioethics of Data.

Social epigenomics measures the mechanisms through which place and context change our biology. Big data science connects, analyzes, and allows inferences from previously disconnected data. Precision medicine promises individually-tailored treatments. Together, these emerging fields are changing the way we discover, decipher, and deliver new science to populations. However, differential participation in and uptake (by adopter type-from innovators to laggards) of the discovering, deciphering, and delivering of these new mechanisms may exacerbate health disparities. Innovators and early adopters are generally from higher-resourced environments. This leads to data and findings biased towards those environments. Such biased data in turn continue to be used to generate new discoveries, further obscuring potentially underrepresented populations, and creating a nearly inescapable cycle of health inequity. We argue that equitable access to representative data is of special moral (bioethical) importance, necessary to break the cycle of health inequities.

Necessity of Epigenetic Epidemiology Studies on the Carcinogenesis of Lung Cancer in Never Smokers.

Based on epidemiological and genomic characteristics, lung cancer in never smokers (LCNS) is a different disease from lung cancer in smokers. Based on current research, the main risk factor for LCNS may be air pollution. A recent case-control study in Koreans reported that nitrogen dioxide (NO2) may be a risk factor for LCNS. Additionally, a cohort study showed that exposure to NO2 was associated with significant hypomethylation. Thus, epigenetic epidemiology studies are needed in the near future to evaluate the carcinogenesis of LCNS according to chronic exposure to air pollution and/or viral infections.

PALTEM: What Parameters Should Be Collected in Disaster Settings to Assess the Long-Term Outcomes of Famine?

Evidence suggests that nutritional status during fetal development and early life leaves an imprint on the genome, which leads to health outcomes not only on a person as an adult but also on his offspring. The purpose of this study is to bring forth an overview of the relevant parameters that need to be collected to assess the long-term and transgenerational health outcomes of famine. A literature search was conducted for the most pertinent articles on the epigenetic effects of famine. The results were compiled, synthesized and discussed with an expert in genetics for critical input and validation. Prenatal and early life exposure to famine was associated with metabolic, cardiovascular, respiratory, reproductive, neuropsychiatric and oncologic diseases. We propose a set of parameters to be collected in disaster settings to assess the long-term outcomes of famine: PALTEM (parameters to assess long-term effects of malnutrition).

Framing Strategies to Avoid Mother-Blame in Communicating the Origins of Chronic Disease.

Evolving research in epigenetics and the developmental origins of health and disease offers tremendous promise in explaining how the social environment, place, and resources available to us have enduring effects on our health. Troubling from a communications perspective, however, is the tendency in framing the science to hold mothers almost uniquely culpable for their offspring's later disease risk. The purpose of this article is to add to the conversation about avoiding this unintended outcome by (1) discussing the importance of cognitive processing and issue frames, (2) describing framing challenges associated with communicating about developmental origins of health and disease and offering principles to address them, and (3) providing examples of conceptual metaphors that may be helpful in telling this complex and contextual story for public health.

Buscando entre la basura genómica para descifrar nuevos mecanismos patogénicos en la diabetes mellitus / Searching through junk DNA for novel pathogenic mechanisms underlying diabetes mellitus

En los últimos años han surgido nuevas tecnologías que permiten definir la función de partes del genoma que no contienen genes codificantes de proteínas. Hasta hace poco tiempo el genoma no codificante era considerado como “DNA basura”. Sin embargo, actualmente se sabe que contiene las instrucciones necesarias para establecer mecanismos epigenéticos que determinan qué genes deben activarse o silenciarse en diferentes contextos celulares, y cómo se transmite esta información a las células descendientes. La disección del genoma no codificante permitirá comprender cómo ciertas variaciones de secuencia contribuyen al desarrollo de la diabetes tipo 2, una enfermedad de la que aún desconocemos los mecanismos moleculares patogénicos. La manipulación de mecanismos epigenéticos también puede facilitar la plasticidad celular con el fin de desarrollar terapias regenerativas para la diabetes tipo 1

During recent years new technologies have emerged that enable decoding of the genomic portions that do not encode for proteins. Not long ago this part of the genome was often referred to as “junk DNA”. However, we now know that it contains the instructions to establish epigenetic mechanisms that determine which genes should become active or silenced in different cellular contexts, and that enable this information to be transmitted to offspring cells. A thorough dissection of the noncoding genome will enable us to understand how certain sequence variants contribute to the development of type 2 diabetes, a disease for which the molecular mechanisms remain unknown. Manipulation of epigenetic mechanisms can also be exploited to harness cellular plasticity for regenerative therapies in type 1 diabetes

MicroRNAs as novel epigenetic biomarkers for human cancer

MicroRNAs (miRNAs) are regulatory, non-coding RNAs that are approximately 22 nucleotides in length. Nearly 1000 unique miRNAs encoded in the human genome have been identified, shedding new light on the posttranscriptional regulation of more than one-third of human genes. These miRNAs are involved in numerous biological processes, including development, differentiation, apoptosis, homeostasis and stem cell biology. Aberrant miRNA expression patterns also play a substantial role in carcinogenesis. It is believed that genetic and epigenetic regulation is responsible for changes in miRNA expression in cancer development, however the exact mechanisms remain unclear. miRNAs are involved in almost all aspects of cancer biology such as apoptosis, invasion, metastasis and angiogenesis. Thanks to this wide range of biological functions, the analysis of changes in overall miRNA expression occurring within human tumours has helped identify miRNA signatures associated with diagnosis, staging, progression, prognosis and response to treatment. This positions miRNA- targeting therapeutics as a novel and promising tool for cancer treatment (AU)