Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 393
Revista Digital de Postgrado ; 9(2): 217, ago. 2020. ilus, graf
Article in Spanish | LILACS (Americas), LIVECS | ID: biblio-1103536


Los primeros mil días de vida son parte del Curso de Vida, al tomar en consideración la Epigenética, término postulado por Waddington en 1942: modifica la expresión genética SIN cambiar la secuencia de las bases de ADN. El proyecto internacional llamado DOHaD (Developmental Origins of Health and Disease) u ODSE (Orígenes del Desarrollo de la Salud y Enfermedad), está inserto dentro de la Transición Alimentaria y Nutricional (TAN), que, en países en desarrollo­ocurre en forma muy rápida ­produce tanto la malnutrición por déficit como por exceso; es decir la doble carga nutricional. La TAN es producto en nuestro país, de una urbanización acelerada y anárquica, y de cambios socioculturales, como la incorporación de la mujer al mercado de trabajo con menos tiempo para cocinar; está acompañada de una transición epidemiológica con la emergencia y prevalencia de la obesidad y de las enfermedades crónicas como morbiletalidad. Esta doble carga nutricional se modificó, por la situación país, y prevalece más el déficit que el exceso. Se presenta el PROYECTO FUNDACIÓN BENGOA ­ SVPP ­ SOGV ­ CANIA, cuya meta es: Elaborar una agenda preventiva común contra la malnutrición tanto por déficit como por exceso y sus comorbilidades, bajo el enfoque de los primeros mil días de vida y su efecto sobre todo el curso de vida. Se realizó el diseño y aplicación de tres cuestionarios digitales, que se utilizaran para la elaboración de esta meta. Se consolidó un CONSENSO NACIONAL formado por profesionales de la salud involucrados en los primeros mil días de vida(AU)

The first 1000 days of life is the new paradigm that determines health and nutrition during the life course, based on epidemiological models that incorporate the concept of Epigenetics, term introduced by Waddington, that refers to changes that affect the genetic expression without changing the DNA sequence, within the international program DOHaD/ODSE as well as the Food and Nutrition Transition(FNT). This FNT, product of an accelerated and anarchic urbanization that led to sedentary activities, plus the incorporation of women to the work media, with less time for cooking, with the substitution of the traditional diet for one much more practical and efficient in time and effort. It is accompanied by demographic and epidemiologic changes and transitions. The Double Burden of Nutrition in VENEZUELA has changed due to the effect of the recent crisis with a rise in malnutrition and a fall in obesity/overweight. The current project: Fundación Bengoa- Pediatric Society Venezuela (SVPP) ­ CANIA - Obstetric Society of Venezuela (SOGV) is called Developmental Origins of Health and Disease in Venezuela (DOHaD Venezuela): and by means of a national consensus of medical societies and institutions, its goal is "To elaborate a Preventive Agenda both for Malnutrition and for Overweight and Obesity and its comorbidities, considering the First 1000 Days of life and its effect over the life course"

Humans , Male , Female , Pregnancy in Adolescence , Population Characteristics , Infant, Low Birth Weight , Maternal Mortality , Epigenomics , Cardiovascular Diseases , Epidemiology , Malnutrition , Nutritional Transition
Article in English | WPRIM (Western Pacific) | ID: wprim-762178


PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.

Asthma , Cytokines , Disease Progression , Eosinophils , Epigenomics , Flow Cytometry , Follow-Up Studies , Humans , Inflammation , Interferons , Interleukin-17 , Interleukin-4 , MicroRNAs , Multiplex Polymerase Chain Reaction , Nitric Oxide , Real-Time Polymerase Chain Reaction , Respiratory Function Tests , Spirometry , T-Lymphocyte Subsets , T-Lymphocytes
Article in English | WPRIM (Western Pacific) | ID: wprim-782227


For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the ‘missing’ heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

Air Pollutants , Allergens , Aspirin , Asthma , Base Sequence , DNA Methylation , DNA , Epigenomics , Genome , Histone Code , Hypersensitivity , Methylation , MicroRNAs , Phenotype , Polymorphism, Single Nucleotide , Smoke , Tobacco Products
Annals of Dermatology ; : 122-129, 2020.
Article in English | WPRIM (Western Pacific) | ID: wprim-811086


BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG), which encodes an epidermal protein crucial for the formation of a functional skin barrier, have been identified as a major predisposing factor in the etiopathogenesis of atopic dermatitis (AD). Recent reports of relatively low frequencies of FLG-null mutations among specific ethnic groups with AD necessitated analysis of the epigenetic regulation which may control FLG expression without altering its DNA sequence.OBJECTIVE: The study aimed to identify DNA methylation-dependent regulation of FLG expression.METHODS: Quantitative polymerase chain reaction was performed to determine the restoration of FLG mRNA expression in normal human epidermal keratinocyte (NHEK) cells after treatment with epigenetic modulating agents. Bisulfite genomic sequencing and pyrosequencing analyses of the FLG promoter region were conducted to identify the citical CpG sites relevant to FLG expression. We performed small-scale pilot study for epidermal tissues obtained from Korean patients with severe AD.RESULTS: We here show that DNA methylation in the FLG with non-CpG island promoter is responsible for the transcriptional regulation of FLG in undifferentiated NHEK cells. The methylation frequencies in a single CpG site of the FLG promoter were significantly higher in lesional epidermis than those in matched nonlesional epidermis of subjects with severe AD.CONCLUSION: Our in vitro and clinical studies point to this unique CpG site as a potential DNA methylation marker of FLG, which can be a promising therapeutic target in the complications of filaggrin-related skin barrier dysfunction as well as in AD.

Base Sequence , Causality , Dermatitis, Atopic , DNA , DNA Methylation , Epidermis , Epigenomics , Ethnic Groups , Gene Expression , Humans , In Vitro Techniques , Keratinocytes , Methylation , Pilot Projects , Polymerase Chain Reaction , Promoter Regions, Genetic , RNA, Messenger , Skin
Belo Horizonte; s.n; 2020. 124 p. ilus, graf, tab.
Thesis in English, Portuguese | LILACS (Americas), BBO | ID: biblio-1099625


A reabsorção radicular externa inflamatória (RREI) é um processo patológico definido como a perda progressiva de tecido mineralizado radicular, dentina e cemento, resultante da combinação entre a lesão às camadas protetoras da superfície externa da raiz e a presença de microrganismos no interior do sistema de canais radiculares. Estudos clínicos demonstraram o papel da idade e de fatores relacionados ao manejo e tratamento do dente avulsionado na etiopatogenia e evolução das RREI após reimplantes. Entretanto, não existem informações sobre a interação destes fatores, bem como poucos estudos avaliaram a influência do perfil genético e imunológico do paciente no padrão de cicatrização após reimplantes dentários. O presente estudo objetivou (1) avaliar a interação de fatores prognósticos para o desenvolvimento da RREI após o reimplante de dentes permanentes, bem como (2) investigar o papel da epigenética nos processos imunomediados das RREI pós-traumáticas. Para estudo dos determinantes clínicos e suas interações, o universo da pesquisa envolveu 427 pacientes (idade média de 12,6 anos) portadores de 581 dentes permanentes reimplantados, com rizogênese completa no momento do trauma, tratados na Clínica de Traumatismos dentários da Faculdade de Odontologia da Universidade Federal de Minas Gerais entre 1994 e 2018. Dados relativos à idade do paciente no momento do trauma, grau de rizogênese, condições de armazenamento e período extra alveolar do dente avulsionado, uso de antibioticoterapia sistêmica, tempo decorrido entre o reimplante e o início da terapia endodôntica radical (TER) e a duração do período de imobilização foram coletados dos prontuários dos pacientes. Tomadas radiográficas realizadas na consulta de início do TER foram utilizadas para diagnóstico da atividade de reabsorção. Sinais radiográficos de RREI foram encontrados em 80,7% da amostra (469 dentes). Os resultados demonstraram que a idade do paciente no momento do trauma e o tempo decorrido até o início do TER representaram importantes fatores prognósticos para a ocorrência de RREI. Além disso foi observada uma interação quantitativa entre estas duas variáveis uma vez que o aumento na idade do paciente atenuou significativamente o efeito do tempo até o início da terapia endodôntica. Este resultado inédito evidencia a maior vulnerabilidade do paciente mais jovem e enfatiza a importância de se considerar estas duas covariáveis conjuntamente durante a tomada de decisão clínica. Para o estudo epigenético, o perfil de metilação do DNA de 22 genes envolvidos na resposta imune foi avaliado em um pool de 08 amostras de fragmentos radiculares de dentes reimplantados portadores de RREI, indicados para exodontia. O grupo controle consistiu em um pool de 06 amostras de tecido ósseo saudável coletado durante a extração cirúrgica de dentes impactados. Os padrões de metilação do DNA dos 22 genes foram quantificados utilizando EpiTect Methyl II Signature Human Cytokine Production PCR Array. Os resultados do estudo da epigenética revelou que o pool de amostras com RREI apresentou nível mais alto de metilação do DNA na região promotora da FOXP3, em comparação com o pool de osso normal (65,95% e 23,43%, respectivamente). Esta é a primeira evidência de uma possível participação de eventos epigenéticos na modulação da RREI e especula-se se o padrão hipermetilado da FOXP3 poderia estar relacionado à presença da infecção endodôntica.

Inflammatory external root resorption (IERR) is a pathological process defined as the progressive loss of root mineralized tissue, dentin and cement, resulting from both: damage to the protective layers in the root external surface and the presence of endodontic infection inside the root canal. Clinical studies have demonstrated the role of age and factors related to the management and treatment of avulsed teeth in the etiopathogenesis and progression of RREI. However, there is no information on the interaction of these factors and few studies have evaluated the influence of the patient's genetic and immunological profile on the healing pattern after dental replantation. The present study aimed to (1) evaluate the interaction of prognostic factors for the development of RREI after replantation of permanent teeth, as well as (2) to investigate the role of epigenetics in the immunomediated processes of posttraumatic RREI. To study the clinical determinants and their interactions, the sample comprised 427 patients (mean age 12.6 years) with 581 replanted mature permanent teeth treated at the Dental Trauma Clinic of the Faculty of Dentistry from the Federal University of Minas Gerais between 1994 and 2018. Patients' records were evaluated to collect data such as patient's age at the time of the trauma, storage conditions and extra alveolar period of the avulsed tooth, systemic antibiotic therapy prescription, time elapsed between reimplantation and onset of endodontic therapy (TER) and splinting timing. The presence and index of IERR was assessed radiographically at the visit of pulpectomy. Radiographic signs of IEER were found in 80.7% of the sample (469 teeth) and were absent in 19.7% of cases (112 teeth). The results showed that the patient's age at the time of the trauma and the time that elapsed until the beginning of TER represented important prognostic factors for the occurrence of RREI. In addition, a quantitative interaction was observed between these two variables since the increase in the patient's age significantly attenuated the effect of time until the beginning of endodontic therapy. This is an original result that highlights the greater vulnerability of the younger patients and emphasizes the importance of considering these two covariates together during clinical decision-making. For the epigenetic study, the DNA methylation profile of 22 genes involved in the immune response was evaluated in a pool of 08 samples of root fragments of replanted teeth with RREI, referred to extraction. The control group consisted of a pool of 06 samples of healthy bone tissue collected during surgical extraction of impacted teeth. The DNA methylation pattern was quantified using EpiTect Methyl II Signature Human Cytokine Production PCR Array. The results of the epigenetics study revealed that the sample pool with RREI showed a higher level of DNA methylation in the FOXP3 promoter region, compared to the normal bone pool (65.95% and 23.43%, respectively). This is the first evidence of a possible participation of epigenetic events in the modulation of RREI and it is speculated whether the hypermethylated pattern of FOXP3 could be related to the presence of endodontic infection.

Periodontal Ligament , Root Resorption , Tooth Avulsion , Tooth Replantation , Dentition, Permanent , DNA Methylation , Epigenomics , Cross-Sectional Studies , Anti-Bacterial Agents
Article in English | WPRIM (Western Pacific) | ID: wprim-785344


The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

Adult , Asian Continental Ancestry Group , Biomarkers , China , Consensus , Diagnosis , Diagnosis, Differential , Drug Therapy , Eosinophils , Epidemiology , Epigenomics , Genetics , Humans , Hypersensitivity , Inflammation , International Agencies , Medical Staff , Neck , Phenotype , Precision Medicine
Rev. medica electron ; 41(4): 959-978, jul.-ago. 2019.
Article in Spanish | LILACS (Americas), CUMED | ID: biblio-1094101


RESUMEN La ontogenia humana está basada en fundamentos genéticos y epigenéticos. Con el objetivo de estructurar los referentes teóricos sobre el papel relevante de la epigenética en la ontogenianormal y defectuosa que contribuyan a la promoción de salud y prevención de enfermedad, se realizó la revisión de 37 referencias bibliográficas. La epigenética es el conjunto de procesos químicos dependientes del ambiente que modifican la expresión del ácido desoxirribonucleico, sin alterar su secuencia. Su acción está presente durante toda la vida, especialmente en la prenatal cuando, por modificaciones ambientales intraútero ocurre la programación epigenética que hace al humano susceptible a defectos en la ontogenia, incluso a padecer ulteriormente de enfermedades crónicas no transmisibles. Se han reportado factores ambientales inductores de marcas epigenéticas, entre ellos: alimentación, hábitos tóxicos, estrés, consumo inadecuado de ácido fólico y técnicas de reproducción asistida, todos modificables; su conocimiento constituye un baluarte inestimable en la promoción de salud y prevención de enfermedad.

ABSTRACT Human ontogeny is based in genetic and epigenetic fundaments. 37 bibliographic references were reviewed with the objective of structuring the theoretical referents on the relevant role of epigenetics in normal and defective ontogeny to contribute to health promotion and disease prevention. Epigenetics is the whole of chemical processes depending from the environment that modify the deoxyribonucleic acid expression without modifying its sequence. Its action is present during all lifetime, especially at pre-natal times; when due to intrauterine environmental modifications the epigenetic programming takes place, making humans susceptible to defects in ontogeny, even to subsequently suffer non-communicable chronic diseases. Environmental factors inducing epigenetic marks have been reported: food, toxic habits, stress, folic acid inadequate intake and assisted reproduction techniques, all modifiable. Its knowledge is an invaluable bulkward in health promotion and disease prevention.

Humans , Preventive Health Services , Fetal Development/genetics , Disease Prevention , Epigenomics , Human Genetics , Genetics, Medical , Health Promotion , Impacts on Health , Environmental Hazards , Genetic Code
Rev. cuba. pediatr ; 91(2): e786, abr.-jun. 2019.
Article in Spanish | LILACS (Americas), CUMED | ID: biblio-1003964


Introducción: El exposoma, la epigenética y la microbiota de un individuo son categorías que se interrelacionan y pueden contribuir a una mejor comprensión del proceso salud enfermedad. Objetivo: Exponer la relación entre las categorías mencionadas con enfoque biopsicosocial. Métodos: Búsqueda bibliográfica en Medline, Pubmed, Scielo, LILACS y Cochrane en los últimos cinco años en idioma inglés y español, sobre la relación entre nutrición y aparición de enfermedades, el eje intestino cerebro, la correspondencia entre epigenética y el exposoma y la microbiota intestinal y su relación con algunas afecciones. Resultados: La alimentación adecuada de la madre, en calidad y cantidad, es un seguro de salud para la vida futura del hombre. El eje intestino cerebro puede afectarse por factores de riesgo, de ahí la importancia de regular su funcionamiento para la prevención de enfermedades como la depresión, síndrome de ansiedad, sobrepeso, y otras. El 10 por ciento del riesgo de padecer enfermedades crónicas puede deberse a factores genéticos pero se desconoce que muchas exposiciones humanas al ambiente, podrían iniciar procesos de enfermedad en el futuro. El exposoma es una herramienta útil para evaluar factores de riesgo de enfermedades generadas por el medio ambiente: exposición a productos químicos y contaminantes; el estilo de vida, el nivel socioeconómico y el entorno social de un individuo. Consideraciones finales: La ruptura del equilibrio entre la microbiota intestinal, la epigenética y el exposoma está relacionada con la etiopatogenia de diversas enfermedades, con las características individuales del ser humano y su relación con el medio ambiente(AU)

Introduction: Exposome, epigenetics and microbiota of an individual are categories that are interrelated and can contribute to a better understanding of the health-sickness process. Objective: To deepen the comprehensive analysis of the mentioned categories with a biopsychosocial approach. Methods: A bibliographic search in Medline, Pubmed, Scielo, LILACS and Cochrane databases was made in the last five years in English and Spanish, on the relation between nutrition and diseases onset, the intestine-brain axis, the correspondence between epigenetics and the exposome, and intestinal microbiota and its relation with some conditions. Results: The proper feeding of the mother in quality and quantity is a health insurance for the future life of a person. The intestine -brain axis can be affected by risk factors, hence the importance of regulating its functioning for the prevention of diseases such as depression, anxiety syndrome, overweight, and others. 10 percent of the risk of chronic diseases may be due to genetic factors but it is unknown that many human exposures to the environment could initiate disease processes in the future. The exposome is a useful tool to evaluate risk factors for diseases generated by the environment: exposure to chemicals and contaminants, lifestyle, socioeconomic status and social environment of an individual. Final considerations: The rupture of the equilibrium between intestinal microbiota, epigenetics and exposome is related to the etiopathogenesis of various diseases, with the individual characteristics of human beings and their relationship with the environment(AU)

Health-Disease Process , Epigenomics , Gastrointestinal Microbiome/physiology , Exposome , Intestinal Diseases/complications , Nutritional Sciences
Araçatuba; s.n; 2019. 83 p. graf, tab, ilus.
Thesis in Portuguese | LILACS (Americas), BBO | ID: biblio-1051406


Atualmente, está bem estabelecido que o ambiente fetal está ligado à saúde materna, e estímulos ou agressões anormais durante a vida intra-uterina podem resultar em mudanças na fisiologia e metabolismo da prole, aumentando o risco de doenças na vida adulta. Tal fenômeno é conhecido como programação fetal. Alterações na metilação do DNA e expressão gênica são consideradas mecanismos moleculares responsáveis por esta programação. Estudos anteriores demonstraram que a doença periodontal (DP) materna promove resistência insulínica, aumento nas concentrações plasmáticas de citocinas, redução do conteúdo de GLUT4 e do seu índice de translocação para membrana plasmática em sua prole adulta. E citocinas, como por exemplo, o TNF-α, têm sido relacionadas com a redução da expressão de GLUT4 por meio da ativação do fator de transcrição nuclear κappa B (NF-κB). Além disso, esta citocina pode estimular algumas serinas quinases, incluindo IκB quinase (IKK), c-Jun amino-terminal kinase (JNK) e quinases reguladas por sinais extracelulares (ERKs) que estão envolvidas na resistência insulínica. Tais achados evidenciam a necessidade de realizar mais estudos para verificar os mecanismos envolvidos nestas alterações. Portanto, os objetivos do presente estudo foram avaliar em ratos adultos, proles de ratas com DP: 1) massa corpórea ao longo de 75 dias de idade; 2) glicemia e insulinemia; 3) expressão do RNAm da proteína transportadora de glicose GLUT4 e do IRS1 em muscular esquelético gastrocnêmio (MG); 4) o grau de metilação do DNA na região promotora do gene do GLUT4 em MG; 5) fosforilação das proteínas JNK, IKKα/ß, ERK 1/2, NF-κBp65 e NF-κBp50 e seus conteúdos totais em MG; 6) conteúdo total de TNF-α em MG. As ratas foram divididas em dois grupos: 1) com doença periodontal (DP), no qual esta doença foi induzida por meio de ligadura com fio de seda ao redor do 1º molar inferior; 2) ratas controle (CN). Após 7 dias da colocação da ligadura, as ratas de ambos os grupos foram colocadas para acasalamento, verificou-se diariamente, por esfregaço vaginal, o dia da copulação. As ratas prenhas foram separadas em caixas individuais. Quando os filhotes machos destas ratas completaram 75 dias, realizaram-se os experimentos: 1) glicemia e insulinemia; 2) expressão do RNAm do GLUT4 e do IRS1 em MG; 3) o grau de metilação do DNA na região promotora do gene do GLUT4 em MG; 4) fosforilação das proteínas JNK, IKKα/ß, ERK 1/2, NF-κBp65 e NF-κBp50 e seus conteúdos totais em MG; 5) conteúdo total de TNF-α em MG. Os resultados demonstraram que a doença periodontal materna promove na sua prole adulta baixo peso ao nascimento (BPN), resistência insulínica, aumento do conteúdo total de TNF-α em MG, aumento do grau de fosforilação de IKKα/ß, ERK 1/2, NF-κBp65 (grau de fosforilação e conteúdo) e NF-κBp50 em MG, diminuição na expressão gênica da proteína transportadora de glicose GLUT4 e aumento na expressão gênica do IRS1; porém não promove nessa prole alteração no grau de metilação do DNA na região promotora do gene do GLUT4, e no grau de fosforilação da proteína JNK em MG. Portanto, este estudo é de fundamental importância para o entendimento de alguns dos mecanismos envolvidos na relação entre a doença periodontal materna e resistência à insulina na prole adulta. Além disso, mostra que a saúde bucal materna ideal pode ajudar a prevenir doenças futuras na prole adulta(AU)

It is well established that the fetal environment is linked to maternal health, and abnormal stimuli or aggressions during intrauterine life can result in changes in the physiology and metabolism of offspring, increasing the risk of disease in adult life, this phenomenon is known as fetal programming. Changes in DNA methylation and gene expression are considered molecular mechanisms responsible for this programming. Previous studies have demonstrated that maternal periodontal disease (PD) promotes insulin resistance, increased plasma concentrations of cytokines, reduced GLUT4 content and its plasma membrane translocation index in its adult offspring. And cytokines, such as TNF-α, have been linked to reduced GLUT4 expression through the activation of nuclear transcription factor kappa B (NF-κB). In addition, this cytokine can stimulate some serine kinases including IκB kinase (IKK), c-Jun amino-terminal kinase (JNK) and extracellular signal­regulated kinases (ERKs) that are involved in insulin resistance. These findings evidenced the need for further studies to verify the mechanisms involved in these changes. Therefore, the objectives of the present study were to evaluate in adult rats, offspring of rats with PD: 1) birth weight and during the 75 days of age; 2) glycemia and insulinemia; 3) GLUT4 and IRS1 mRNA expression in skeletal muscle gastrocnemius (MG); 4) the degree of DNA methylation in the promoter region of the GLUT4 gene in MG; 5) phosphorylation of JNK, IKKα/ß, ERK 1/2, NF-κBp65 and NF-κBp50 proteins and their total contents in MG; 6) TNF-α content in MG. Female Wistar rats were distributed into a control group and an experimental periodontal disease group, in which the disease is induced by ligation with silk thread around the 1st molar. Seven days after ligature placement, animals from both groups mated and daily vaginal smears were taken to verify the presence of sperm. Pregnant rats were kept in individual cages. The body weights of the offspring were measured once weekly from birth until 75 days of age. When male offspring of these rats completed 75 days, the experiments were performed: 1) glycemia and insulinemia; 2) GLUT4 and IRS1 mRNA expression in skeletal muscle gastrocnemius (MG); 3) the degree of DNA methylation in the promoter region of the GLUT4 gene in MG; 4) phosphorylation of JNK, IKKα/ß, ERK 1/2, NF-κBp65 and NF-κBp50 proteins and their total contents in MG; 5) TNF-α content in MG. The results demonstrated that maternal periodontal disease promotes in its adult offspring low birth weight (LBW), insulin resistance, increased TNF-α content in MG, increased IKKα/ß, ERK 1/2, NF-κBp65 (phosphorylation status and content) and NF-κBp50 phosphorylation status in the MG, decrease in gene expression of GLUT4 and increase in IRS1 gene expression; but does not promote in this progeny change in the degree of DNA methylation in the promoter region of the GLUT4 gene, and JNK phosphorylation status in MG. Therefore, this study is of fundamental importance for the understanding of some of the mechanisms involved in the relationship between maternal periodontal disease and insulin resistance in adult offspring. In addition, it shows that ideal maternal oral health can help prevent future illnesses in adult offspring(AU)

Animals , Rats , Periodontal Diseases , Protein Kinases , Insulin Resistance , Tumor Necrosis Factor-alpha , Glucose Transporter Type 4 , Oral Health , Rats, Wistar , Epigenomics , Inflammation
Univ. med ; 60(2): 1-25, 2019. ilus, tab
Article in Spanish | LILACS (Americas), COLNAL | ID: biblio-994578


Para acortar la brecha entre lo molecular y la clínica, el personal de atención médica debe tener un conocimiento básico de los mecanismos moleculares que gobiernan la identidad celular, mediante la activación selectiva de genes. La expresión diferencial de genes permite a las células sintetizar las proteínas requeridas para cumplir con sus funciones biológicas, y ello posibilita a las células responder a estímulos internos y externos. Para esto se debe tener primero acceso a los genes que codifican las proteínas, determinando el fenotipo celular. Modificaciones en la estructura de la cromatina permiten a la maquinaria transcripcional tener acceso a secuencias de ADN. El ADN es transcripto en ARNm, que sufre diversas modificaciones antes de salir del núcleo para ser traducido en una proteína en el citoplasma. Cualquier desregulación en alguno de los procesos asociados se presenta como una patología. A inicios del siglo XXI se reportó la secuenciación del genoma humano, y sorprendentemente uno de los principales hallazgos fue que solo un 2% de la secuencia codifica para proteínas, lo cual dejó un interrogante sobre cómo funcionan y se regulan los procesos genéticos que llevan a la identidad celular. Desde entonces las investigaciones han permitido utilizar los principios que rigen estos procesos para ampliar el conocimiento de los mecanismos asociados a enfermedades. Gracias a estos avances, se ha buscado determinar aplicaciones clínicas dirigidas a los procesos involucrados en la expresión génica diferencial, lograr una mejor comprensión sobre los procesos patológicos de la enfermedad y desarrollar herramientas diagnósticas.

To narrow the gap between the bench and the clinic, healthcare personnel should have a basic understanding of molecular mechanisms ruling cell identity, since it establishes the key differences between health and disease states. Differential gene expression allows for protein synthesis required for the cell's biological function. In this process genes are selected from the entire genome to meet the cell's biological functioning and respond to internal and external stimuli. To this end, first the chromatin must be remodeled for the transcriptional machinery to gain access to DNA sequences coding for particular genes. DNA can then be transcribed into mRNA, followed by different processes leading to mature mRNA leaving the nucleus for protein synthesis in the cytoplasm. Any dysregulation in these processes results in disease. In the beginning of this millennium the human genome project sequenced the whole genome. Surprisingly, one of the main findings was only 2% of the genome represented protein coding sequences, which raised the question about the remainder of the genome and cell identity. Based on principles derived from the human genome project many investigations have shed light on mechanisms associated with disease. Thanks to advancements in differential gene expression, researchers are seeking for a better understanding in pathological processes associated with disease and the development of diagnostic tools.

Humans , Epigenomics , Acetylation , Methylation
Article in Korean | WPRIM (Western Pacific) | ID: wprim-762195


Air pollution does harm to the respiratory tracts. Fine particulate matter (PM(2.5)) attacks the lung directly passing through mucosal ciliary clearance, causes new-onset asthma, or exacerbates asthma symptoms in children. Oxidative stresses, immunologic changes, allergic sensitization, and epigenetic modification are associated with bronchial asthma. Furthermore, it causes respiratory tract infection and lung function decline. We have to protect the children who are more vulnerable to PM(2.5) than adults. We will investigate individual exposure, influences by the components of air pollution, and genetic susceptibility.

Adult , Air Pollution , Asthma , Child , Epigenomics , Genetic Predisposition to Disease , Humans , Lung , Oxidative Stress , Particulate Matter , Respiratory System , Respiratory Tract Infections
Article in English | WPRIM (Western Pacific) | ID: wprim-762171


Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) has attracted a great deal of attention because of its association with severe asthma. However, it remains widely underdiagnosed in asthmatics as well as the general population. Upon pharmacological inhibition of cyclooxygenase 1 by NSAIDs, production of anti-inflammatory prostaglandin E2 and lipoxins ceases, while release of proinflammatory cysteinyl leukotrienes increases. To determine the underlying mechanisms, many studies have attempted to elucidate the genetic variants, such as single nucleotide polymorphisms, responsible for alterations of prostaglandins and leukotrienes, but the results of these genetic studies could not explain the whole genetic pathogenesis of NERD. Accordingly, the field of epigenetics has been introduced as an additional contributor to genomic alteration underlying the development of NERD. Recently, changes in CpG methylation, as one of the epigenetic components, have been identified in target tissues of NERD. This review discusses in silico analyses of both genetic and epigenetic components to gain a better understanding of their complementary roles in the development of NERD. Although the molecular mechanisms underlying NERD pathogenesis remain poorly understood, genetic and epigenetic variations play significant roles. Our results enhance the understanding of the genetic and epigenetic mechanisms involved in the development of NERD and suggest new approaches toward better diagnosis and management.

Anti-Inflammatory Agents, Non-Steroidal , Asthma , Computer Simulation , Cyclooxygenase 1 , Diagnosis , Dinoprostone , Epigenomics , Genetics , Leukotrienes , Lipoxins , Methylation , Polymorphism, Single Nucleotide , Prostaglandins
Article in English | WPRIM (Western Pacific) | ID: wprim-762147


Environmental variations induced by industrialization and climate change partially explain the increase in prevalence and severity of allergic disease. One possible mechanism is the increase in allergen production leading to more exposure and sensitization in susceptible individuals. House dust mites (HDMs) are important sources of allergens inducing asthma and rhinitis, and experimentally they have been demonstrated to be very sensitive to microenvironment modifications; therefore, global or regional changes in temperature, humidity, air pollution or other environmental conditions could modify natural HDM growth, survival and allergen production. There is evidence that sensitization to HDMs has increased in some regions of the world, especially in the subtropical and tropical areas; however, the relationship of this increase with environmental changes is not so clear as has reported for pollen allergens. In this review, we address this point and explore the effects of current and predicted environmental changes on HDM growth, survival and allergen production, which could lead to immunoglobulin E (IgE) sensitization and allergic disease prevalence. We also assess the role of adjuvants of IgE responses, such as air pollution and helminth infections, and discuss the genetic and epigenetic aspects that could influence the adaptive process of humans to drastic and relatively recent environmental changes we are experiencing.

Air Pollution , Allergens , Asthma , Climate Change , Dust , Epigenomics , Helminths , Humans , Humidity , Hypersensitivity , Immunoglobulin E , Immunoglobulins , Pollen , Prevalence , Pyroglyphidae , Rhinitis
Article in English | WPRIM (Western Pacific) | ID: wprim-742450


BACKGROUND: The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients. METHODS: Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years. RESULTS: We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1). CONCLUSION: This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

Biomarkers , DNA Methylation , DNA , Epigenomics , Humans , Lung Neoplasms , Lung , Methods , Methylation , Prognosis
Article in English | WPRIM (Western Pacific) | ID: wprim-742363


During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

Chromatin Assembly and Disassembly , DNA Methylation , Embryonic Development , Epigenomics , Female , Fertility , Fertilization , Histone Code , Humans , Infertility , Infertility, Male , Male , Pregnancy , Reproductive Techniques, Assisted , RNA , Spermatozoa
Article in English | WPRIM (Western Pacific) | ID: wprim-742360


Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM.

Apoptosis , Congenital Abnormalities , DNA Fragmentation , Epigenomics , Fertilization in Vitro , Germ Cells , Humans , Infertility , Infertility, Male , Inflammation , Leydig Cells , Male , Male , Medicine, Chinese Traditional , Microcirculation , Oxidative Stress , Sertoli Cells , Testis , Trace Elements , Vitamins
Journal of Experimental Hematology ; (6): 1711-1716, 2019.
Article in Chinese | WPRIM (Western Pacific) | ID: wprim-781408


Abstract  The physiological hematopoiesis depends on the programmed expression of a series of gene regulated by mechanisms at various levels. Currently, the epigenetic regulation has been considered as the most important mechanism during hematopoietic differentiation, resulting in a specific epigenomic landscape in the hematopoietic stem/progenitor cells. We try to concisely review the epigenetic mechanisms, including the genomic methylation, the histone modifications and the expression profiles of noncoding RNA, illustrating briefly the differentiation from the hematopoietic stem/progenitor cells to to the erythroid, myeloid and lymphoid cells.

Cell Differentiation , Epigenesis, Genetic , Epigenomics , Hematopoiesis , Hematopoietic Stem Cells
Repert. med. cir ; 28(3): 145-151, 2019.
Article in Spanish | LILACS (Americas), COLNAL | ID: biblio-1046730


La obesidad en este momento representa una de las peores amenazas del sector salud. El acelerado aumento de la prevalencia y mortalidad a causa de enfermedades cardiovasculares establece un precedente histórico como problema de salud pública mundial. La elevada incidencia de obesidad y enfermedades crónicas ha llevado a múltiples áreas de la salud a entender y buscar un detonante claro que explique esta patología. Existen numerosas causas que explican su comportamiento agresivo, progresivo y crónico. Sin embargo, ninguna de ellas satisface como el solo factor desencadenante que ofrezca un tratamiento único que genere una reducción de su rápida expansión. En este artículo se buscan explicar las principales causas relacionadas con esta entidad así como los mecanismos que lo demuestran, para lograr entender el abordaje adecuado de los pacientes que acuden buscando el manejo de la obesidad (modelo COD2).

Obesity is currently considered as one of the major life-threatening conditions affecting the healthcare system. The accelerated increase in prevalence and mortality due to cardiovascular diseases establishes an historical precedent as a global public health issue. The increased incidence of obesity and chronic diseases, has led multiple health researchers to try to identify a clear triggering factor contributing to obesity. There are numerous causes which explain its aggressive, progressive and chronic behavior. However, they do not satisfactorily elucidate a unique triggering factor which would determine a unique treatment to help decelerate its rapid expansion. This article seeks to explain the major causal factors and mechanisms leading to obesity, in order to find the most appropriate approach for obese patients seeking treatment options (COD2 model).

Obesity , Diet , Sedentary Behavior , Epigenomics
São Paulo; s.n; s.n; 2019. 90 p. tab, graf.
Thesis in English | LILACS (Americas) | ID: biblio-1048416


Breast cancer is the most frequent cancer in women worldwide. Paternal consumption of a highfat diet has been shown to program breast cancer risk in female offspring. Orange juice is widely consumed and is known for its content of bioactive compounds that may have a role in regulating epigenetic processes. Therefore, the aim of the present study was to evaluate the effects of paternal obesity and orange juice consumption on female offspring susceptibility to chemically-induced breast carcinogenesis. Three-week-old C57BL/6 male mice were distributed in control (CO), control-orange juice (CJ), obese (OB) and obese-orange juice (OJ) groups, fed either a standard chow or a high-fat/high-sugar diet (45% lard-based diet supplemented with sweetened condensed milk), with water or orange juice, for 11 weeks before mating. Female offspring were weaned onto standard chow until 7 weeks of age and then were initiated with 7,12-dimethyl-benzo[a]anthracene to induce mammary tumors. CJ female offspring presented higher multiplicity of mammary tumors (p≤0.05) compared to CO offspring. Female offspring from OB group showed higher tumor latency (p≤0.05), lower tumor incidence (p≤0.05), higher multiplicity of tumors (p≤0.05), lower cell proliferation (Ki67) in the mammary ducts (p≤0.05) and lower global levels of H3K27me3 in the mammary gland (p≤0.05) when compared to CO offspring. No differences (p≥0,05) were observed between OB and OJ female offspring regarding these parameters. Consumption of orange juice by non-obese fathers during preconception increased susceptibility of female offspring to mammary carcinogenesis. Although paternal consumption of a high-fat/high-sugar diet during preconception decreased incidence and increased latency of tumors, the multiplicity of lesions increased. In addition, the data indicates that the response to orange juice consumption depends of the paternal metabolic context

O câncer de mama é o mais frequente entre as mulheres em todo o mundo. Foi demonstrado que o consumo paterno de uma dieta hiperlipídica aumenta o risco de câncer de mama nas filhas. O suco de laranja é amplamente consumido e é conhecido pelo seu conteúdo de compostos bioativos que podem ter um papel na regulação dos processos epigenéticos. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade paterna e do consumo de suco de laranja na suscetibilidade da prole feminina à carcinogênese mamária quimicamente induzida. Camundongos C57BL/6 machos com três semanas de idade foram distribuídos nos grupos controle (CO), controle de suco de laranja (CJ), obeso (OB) e obeso suco de laranja (OJ), alimentados com ração controle ou com ração hiperlipídica e hiperglicídica (45% das calorias proveniente de lipídeos, a base de banha de porco) suplementada com leite condensado, com água ou suco de laranja, durante 11 semanas antes do acasalamento. A prole feminina foi desmamada e recebeu ração controle até 7 semanas de idade e, então, foi iniciada com 7,12- dimetil-benzo[a]antraceno para induzir tumores mamários. A prole feminina CJ apresentou maior multiplicidade de tumores mamários (p≤0.05) em relação a prole feminina CO. A prole feminina OB apresentou maior latência tumoral (p≤0.05), menor incidência tumoral (p≤0.05), maior multiplicidade de tumores (p≤0.05), menor proliferação celular (Ki67) nos ductos mamários (p≤0.05) e menores níveis globais de H3K27me3 na glândula mamária (p≤0.05), quando comparada a prole feminina CO. Não foram observadas diferenças (p≥0,05) entre a prole feminina do OB e OJ em relação a esses parâmetros. O consumo de suco de laranja por pais não obesos durante o período pré-concepcional aumentou a susceptibilidade da prole feminina à carcinogênese mamária. Embora o consumo paterno de uma dieta hiperlipídica e hiperglicídica durante a preconcepção tenha diminuído a incidência e aumentado a latência, a multiplicidade dos tumores mamários aumentou. Ainda, os resultados indicam que a resposta ao consumo de suco de laranja depende do contexto metabólico paterno

Animals , Male , Mice , Breast Neoplasms/diet therapy , Citrus sinensis/classification , Fathers/classification , Diet, High-Fat/adverse effects , Fruit and Vegetable Juices/analysis , Beginning of Human Life , Epigenomics , Obesity/physiopathology