Research progress on m5C methylation and its prospects in tumor immunotherapy / 口腔疾病防治

@#Epigenetic modification plays an important role in the biological regulatory process of eukaryotic cells. Tumor immunotherapy is an important means and clinical strategy for the treatment of some cancers. 5-Methylcytosine (m5C) is an important component of the epigenetic regulatory network discovered after m6A and has become a new topic for life science research in recent years. The m5C methylation of RNA can affect the fate of the modified RNA molecules and play an important role in various biological processes, including RNA stability, protein synthesis and transcriptional regulation. Recent studies have shown that m5C writers, erasers and readers are related to a variety of cellular biological processes and systemic diseases, including the occurrence, metastasis and tumor immune microenvironment. m5C methylation can widely affect gene expression and the biological process of tumorigenesis and development at multiple levels, but its specific mechanism and potential interaction with other epigenetic modifications in tumor immunotherapy are still unclear, and its regulatory mechanism, risk assessment and role in targeted therapy for malignant tumors need to be further studied. This article will review the dynamic regulatory network of m5C, the biological role of m5C modification in solid tumors and potential targets in tumor immunotherapy.

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.

Expression of EZH2 and H3K27me3 predicts tumor biology of urothelial carcinoma

Background: Enhancer of zeste homolog 2 (EZH2) is one of the major epigenetic modifiers involved in the transcriptional repression of target genes through trimethylation of H3K27 (lysine 27 residue of histone H3). Deregulated expression of both EZH2 and H3K27me3 has been implicated in the biological behavior and prognostic outcome of various malignancies. Aim: To assess the role of EZH2 and H3K27me3 in the carcinogenesis of urothelial carcinoma of urinary bladder. Materials and Methods: One hundred fifty consecutive urothelial carcinoma cases of urinary bladder (54.7% high-grade) were included in this study. Immunohistochemical analysis for EZH2 and H3K27me3 was performed on whole tissue sections. A multiplication score obtained by multiplying staining intensity and proportion of positively stained neoplastic cells was used for assessment. Results: EZH2 showed a significant correlation with the tumor grade and lamina propria invasion (p < 0.001). The cases with high EZH2 expression showed a significantly high proliferative index (Mean- 32.7%; p < 0.001). In contrast, negative and low expression of H3K27me3 was significantly more common in high-grade cases (p = 0.006). The expression of H3K27me3 was significantly associated with lamina propria (p = 0.01) and deep muscle invasion (p = 0.007). EZH2 showed a significantly higher expression in the high-grade invasive areas as compared to the high-grade non-invasive areas of the same tumor (p = 0.03). Conclusions: This study establishes an important role of the key epigenetic regulators EZH2 and H3K27me3 in the pathobiology of urothelial carcinomas. Strong expression of EZH2 and weak expression of H3K27me3 are associated with higher grade, proliferative index and invasive behavior.

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.

EPIGENETICS, SOCIAL DETERMINANTS AND TRANSFORMATION – NATURE AND NURTURE

There is emerging scientic research and evidence which visibly demonstrates that internal body environmental inuences can not only impact genes but also how they are expressed. Scientists have discovered that early experiences can determine how genes are turned on and off and even whether some are expressed at all. Epigenetics is the study of how behaviours and environment can cause changes that affect the way the genes work. Unlike genetic changes, epigenetic changes are reversible and do not change the DNA sequence, but they can change how our body reads a DNA sequence. There is strong inuence of the epigenetics on social life. The ancient Indian systems of Ayurveda and Yoga indeed have strong bases for the same. It would be appropriate to further explore the same through inter disciplinary research

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)

Efecto de la epigenética en la artritis reumatoide / Effect of epigenetics on rheumatoid arthritis

La artritis reumatoide es una enfermedad autoinmune e inflamatoria que afecta de manera predominante a las articulaciones diartrodiales. En esta patología los factores ambientales o conductuales pueden actuar en sinergia con la predisposición genética, acelerando el inicio y la gravedad de la enfermedad. Este vínculo entre el medio ambiente y el genoma está mediado por marcas epigenéticas en el ácido desoxirribonucleico, incluyendo su metilación, la modificación de histonas y la regulación mediada por ácido ribonucleico no codificante. La epigenética puede generar cambios fenotípicos hereditarios, que no están determinados por modificaciones en la secuencia del ácido desoxirribonucleico y, en consecuencia, son reversibles. Por lo tanto la dieta, los medicamentos y otros factores ambientales, tendrían la capacidad de modularlos. La identificación de una desregulación epigenética específica, puede ofrecer una mayor comprensión de la fisiopatología de la enfermedad e influenciar positivamente en la prevención, diagnóstico y desarrollo de nuevas dianas terapéuticas.

Rheumatoid arthritis is an autoimmune and inflammatory disease that predominantly affects the diarthrodial joints. In this pathology, environmental or behavioral factors can act in synergy with genetic predisposition, accelerating the onset and severity of the disease. This link between the environment and the genome is mediated by epigenetic marks on deoxyribonucleic acid, including its methylation, histone modification, and noncoding ribonucleic acid-mediated regulation. Epigenetics can generate heritable phenotypic changes, which are not determined by modifications in the deoxyribonucleic acid sequence and are therefore reversible. Therefore, diet, medications and other environmental factors would have the ability to modulate them. The identification of a specific epigenetic dysregulation can offer a better understanding of the pathophysiology of the disease and positively influence the prevention, diagnosis and development of new therapeutic targets.

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.

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.

Epigenetics, hypersensibility and asthma: what do we know so far?

Abstract In this review, we describe recent advances in understanding the relationship between epigenetic changes, especially DNA methylation (DNAm), with hypersensitivity and respiratory disorders such as asthma in childhood. It is clearly described that epigenetic mechanisms can induce short to long-term changes in cells, tissues, and organs. Through the growing number of studies on the Origins of Health Development and Diseases, more and more data exist on how environmental and genomic aspects in early life can induce allergies and asthma. The lack of biomarkers, standardized assays, and access to more accessible tools for data collection and analysis are still a challenge for future studies. Through this review, the authors draw a panorama with the available information that can assist in the establishment of an epigenetic approach for the risk analysis of these pathologies.

The critical importance of epigenetics in autoimmune-related skin diseases / 医学前沿

Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

Age Estimation Based on DNA Methylation and Its Application Prospects in Forensic Medicine / 法医学杂志

With the improvement of DNA methylation detection techniques, studies on age-related methylation sites have found more age-specific ones across tissues, which improves the sensitivity and accuracy of age estimation. In addition, the establishment of various statistical models also provides a new direction for the age estimation of tissues from different sources. This review summarizes the related studies of age estimation based on DNA methylation from the aspects of detection technology, age-related cytosine phosphate guanine site and model selection in recent years.

The role and treatment strategy of epithelial-mesenchymal transition in radiation-induced pulmonary fibrosis / 中华放射医学与防护杂志

Radiation-induced pulmonary fibrosis (RIPF) is one of the most serious late complications after nuclear radiation accident, bone marrow transplantation pretreatment and thoracic tumor radiotherapy. The formation process of RIPF is complicated and the pathogenesis has not been fully elucidated. Recent studies have shown that radiation-induced epithelial-mesenchymal transition (EMT) of lung epithelial cells is an indispensable segment of RIPF. This article reviews the role of radiation-induced lung EMT in the occurrence and development of RIPF and related drugs with EMT as a potential therapeutic target, providing ideas for the development of therapeutic drugs for RIPF in the future.

Research progress of the relationship between fluorosis and cardiovascular disease / 中华地方病学杂志

Fluorosis is widely prevalent worldwide, and China is one of the countries with a high incidence of endemic fluorosis. In recent years, study on non skeletal damage caused by fluorosis, especially cardiovascular system damage, has gradually increased. Fluoride can cause cardio vascular arteriosclerosis, hypertension and other diseases, while cardiovascular disease have hidden and acute onset, and the mortality rate has increased year by year in recent years. At present, the mechanism of cardiovascular diseases caused by fluoride is not yet clear, and further clarification is needed. This article provides an overview of the effects of fluoride on cardiovascular diseases from three aspect: epidemiological investigation, animals experiment, and in vitro cell experiment. It categorizes and analyzes the pathogenesis, providing new ideas for the study of cardiovascular system damage caused by fluorosis.

Novel insights into histone lysine methyltransferases in cancer therapy:From epigenetic regulation to selective drugs / 药物分析学报

The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.

The epigenetic and non-epigenetic regulation of statins on its anti-tumor effect and its clinical research progress / 药学学报

Statins are a class of hydroxymethylglutaryl-CoA reductase inhibitors (HMG-CoA reductase inhibitors), which are widely used to reduce blood lipid in clinic, and are especially important for the prevention and treatment of cardiovascular diseases. In recent years, many studies at home and abroad believe that statins have a unique role in tumor prevention and treatment, and have been widely concerned. In terms of epigenetic regulation mechanism, statins mainly affect the progress of tumor through DNA methylation, histone modification and miRNA regulation. In addition, statins can also achieve their anti-tumor effects by promoting tumor cell autophagy, regulating tumor cell cycle, and promoting tumor cell apoptosis and other signaling pathways. Therefore, the research on statins provides ideas for the discovery of new anti-tumor treatments. In this paper, the role of statins in the prevention and treatment of common tumors is reviewed, including its mechanism of inhibiting the occurrence and development of tumors through epigenetic regulation and other related mechanisms, as well as its clinical research status.

Advances in the role of epigenetics in tuberculosis / 中华微生物学和免疫学杂志

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis ( Mtb) that seriously endangers human health. Mtb induces epigenetic changes in the host to regulate host genome transcription and immune response, which plays an important role in the growth and replication of Mtb and the development and outcome of TB. Since epigenetic regulation occurs early and is reversible, it has been extensively studied in the pathogenesis of various diseases and has great potential as a molecular target. This paper reviewed the epigenetic changes in host after Mtb infection, including DNA methylation and miRNA, and summarized the role of epigenetics in the pathogenesis of TB and the research progress in potential diagnostic markers.