Research progress on food-derived antioxidants for alleviating toxicity of endocrine disrupting chemicals / 环境与职业医学

Endocrine disrupting chemicals (EDCs) are a class of chemical substances widely present in daily-life environment, and can enter human body through various pathways, posing a threat to reproductive development and health. Oxidative stress (OS) is one of the most important fundamental mechanisms underlying the reproductive toxicity of EDCs. Numerous studies have found that exposure to EDCs can increase the levels of reactive oxygen species (ROS) in human reproductive system and reduce the activity and quantity of multiple enzymatic antioxidants, leading to oxidative stress and inducing damage to the reproductive system at various levels such as DNA and cells. Many research results have shown that supplementing food-derived non-enzymatic antioxidants can reduce ROS levels and increase the activity of enzymatic antioxidants, thereby reduce OS levels, and further repair EDCs-induced reproductive damage. In addition, many food-derived antioxidants are important elements involved in reproductive physiological activities and have protective effects on reproductive health. This paper summarized the reproductive toxicity of EDCs, including damage to reproductive cells, interference with hormone action, and influence on reproductive-related epigenetic regulation, elaborated the relationship between OS and reproductive toxicity of EDCs, and further summarized the alleviating effects and related mechanisms of food-derived antioxidants such as vitamins, trace elements, and plant polyphenols and pigments against reproductive toxicity of EDCs, aiming to provide a theoretical and scientific basis for prevention and treatment against reproductive toxicity of EDCs.

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.

Research progress on relationship between N6-adenylate methylation modification and cell transformation and associated mechanism / 环境与职业医学

As a reversible and dynamic epigenetic marker, N6-adenylate methylation (m6A) modification is the most common mRNA modification in eukaryotes. This paper briefly described how m6A can influence RNA splicing, stability, and translation after transcription, and then participate in a variety of signaling pathways and biological and pathological processes, regulating cell proliferation, apoptosis, epithelial mesenchymal transformation (EMT) processes, and tumor invasion and metastasis. In addition, according to current studies, m6A methyltransferases (writers) are believed to promote EMT and tumor development, and readers and erasers both promote and inhibit EMT in different research objects. In this review, we summarized the mechanism of m6A modification and its role in cell transformation, and pointed out the direction of disease treatment.

Research progress on the role of environmentally induced DNA methylation in congenital cleft lip and/or palate / 口腔疾病防治

@#Congenital cleft lip and/or palate (CL/P) is a common malformation of maxillofacial development. At present, it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmental factors. Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congenital malformations. As one of the important epigenetic modifications, DNA methylation has been widely and deeply studied in many fields, but as a link between the individual and the environment, its application in CL/P is limited. Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate. Stimulation of folate deficiency, smoking, pollutant exposure and other environmental factors can induce changes in the state of DNA methylation, thus affecting gene expression in the development of lip and palate and leading to the occurrence of deformities.

Advances on the correlation between hypoxia inducible factor and epigenetic modification / 国际儿科学杂志

Hypoxia inducible factor(HIF)is a key factor in the regulation of oxygen homeostasis, and its expression level is mainly influenced by oxygen concentration in the adaptation of the body to chronic hypoxia, with which many pediatric diseases are closely associated.The response to hypoxia can be altered by HIF and its mediated downstream signaling pathways, in addition to epigenetic modifications such as regulation of overall methylation or histone modification levels to adapt to hypoxic environments.Previous studies have shown that the transcriptional activity and stability of HIF are interrelated with various histone modifications including methylation/demethylation, hydroxylation, deacetylation, phosphorylation, and lactylation, which makes the study of epigenetic modification correlation deserves to be explored in depth as an important potential target for regulating HIF expression levels.

Advances in epigenetic regulation of Chinese hamster ovary cells / 生物工程学报

Chinese hamster ovary (CHO) cells play an irreplaceable role in biopharmaceuticals because the cells can be adapted to grow in suspension cultures and are capable of producing high quality biologics exhibiting human-like post-translational modifications. However, gene expression regulation such as transgene silencing and epigenetic modifications may reduce the recombinant protein production due to the decrease of expression stability of CHO cells. This paper summarized the role of epigenetic modifications in CHO cells, including DNA methylation, histone modification and miRNA, as well as their effects on gene expression regulation.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

Chromatin Remodeling Factor SMARCA5 is Essential for Hippocampal Memory Maintenance via Metabolic Pathways in Mice / 神经科学通报·英文版

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Excellent appearance of Dao-di Ginseng Radix et Rhizoma and interaction mechanism between genetic and environmental factors: a review / 中国中药杂志

Dao-di medicinal materials produced in a specific environment always present excellent appearance and high quality. Because of the unique appearance, Ginseng Radix et Rhizoma is regarded as a paradigm in the research on excellent appearance. This paper systematically summarized the research progress in the genetic and environmental factors influencing the formation of the excellent appearance of Ginseng Radix et Rhizoma, aiming to provide reference for the quality improvement of Ginseng Radix et Rhizoma and the scientific connotation of Dao-di Chinese medicinal materials. The Ginseng Radix et Rhizoma with high quality generally has a robust and long rhizome, a large angle between branch roots, and the simultaneous presence of a robust basal part of rhizome, adventitious roots, rhizome bark with circular wrinkles, and fibrous roots with pearl points. The cultivated and wild Ginseng Radix et Rhizoma have significant differences in the appearance and no significant difference in the population genetic diversity. The differences in the appearance are associated with cell wall modification, transcriptional regulation of genes involved in plant hormone transduction, DNA methylation, and miRNA regulation. The rhizosphere soil microorganisms including Fusarium and Alternaria, as well as the endophytes Trichoderma hamatum and Nectria haematococca, may be the key microorganisms affecting the growth and development of Panax ginseng. Cultivation mode, variety, and root exudates may be the main factors influencing the stability of rhizosphere microbial community. Ginsenosides may be involved in the formation of the excellent appearance. However, most of the available studies focus on the partial or single factors in the formation of Dao-di medicinal materials, ignoring the relationship within the complex ecosystems, which limits the research on the formation mechanism of Dao-di medicinal materials. In the future, the experimental models for the research involving genetic and environmental factors should be established and mutant materials should be developed to clarify the internal relationship between factors and provide scientific support for the research on Dao-di medicinal materials.

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

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

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

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

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

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

Research progress of m6A methylation in prostate cancer / 亚洲男科学杂志(英文版)

N6-methyladenosine (m6A) is a ubiquitous RNA modification in mammals. This modification is "written" by methyltransferases and then "read" by m6A-binding proteins, followed by a series of regulation, such as alternative splicing, translation, RNA stability, and RNA translocation. At last, the modification is "erased" by demethylases. m6A modification is essential for normal physiological processes in mammals and is also a very important epigenetic modification in the development of cancer. In recent years, cancer-related m6A regulation has been widely studied, and various mechanisms of m6A regulation in cancer have also been recognized. In this review, we summarize the changes of m6A modification in prostate cancer and discuss the effect of m6A regulation on prostate cancer progression, aiming to profile the potential relevance between m6A regulation and prostate cancer development. Intensive studies on m6A regulation in prostate cancer may uncover the potential role of m6A methylation in the cancer diagnosis and cancer therapy.

Recent Insights into Mechanisms Governing Breast Cancer Dormancy / 肿瘤防治研究

Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.

Research advances on the role of epigenetic modifications in the long-term progression of alcoholic liver disease / 药学学报

There are more than 60 million alcoholic liver disease (ALD) patients in China, which has become a public health problem that cannot be ignored. Moreover, the social problem of "alcohol culture" is still hardly to solve, so that safe and effective prevention and treatment for ALD are in urgent need clinically. Previous studies on ALD have focused on the direct damaging effects of alcohol and its toxic metabolites, while recent studies have shown that the pathogenesis of ALD also include alcohol metabolic reprogramming and endogenous metabolites disorder. Although the endogenous metabolites have no direct toxicity, its long-term effect should not be ignored. These endogenous metabolites could change epigenetic modifications, cause widespread and persistent abnormal gene expression and signal pathway activation abnormally to promote metabolic reprogramming and stamp it as "metabolic memory", which manifest pathological changes and promote ALD, especially liver fibrosis/cirrhosis and liver cancer. Based on this, the article reviews the important epigenetic modifications caused by related metabolites in ALD and their associated effects. The role of traditional Chinese medicine (TCM) and its active ingredients in regulating epigenetics was also analyzed. The results suggest that regulation of epigenetics and alteration of "metabolic memory" may be a novel mechanism of TCM in the prevention and treatment of ALD.

Advances in histone epigenetic enzyme inhibitors based on proteomics / 药学学报

As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.

Role of DNA methylation in the pathogenesis of ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

The occurrence and development of many eye diseases are closely related to genetic and environmental factors, among which epigenetic modification is an important bridge connecting genetic and environmental factors. It can affect the levels of related genes by influencing gene transcription or translation, thereby playing a role in the pathogenesis of ocular diseases. DNA methylation is an important part of epigenetic modification which is usually regulated by three processes: de novo methylation, maintenance methylation, and demethylation, and plays an essential role in regulating gene expression. At present, researchers have conducted that DNA methylation plays an important role in repair of damage to corneal endothelium, mitochondrial dynamics regulation and diabetic retinopathy, oxidative stress response and cataracts and other eye diseases, providing new ideas in the treatment of related ocular diseases. This study presented a brief review of the role of DNA methylation in the development of related ocular diseases and provided new perspectives and directions for the screening, diagnosis, and treatment of eye diseases.

Visión general y perspectivas futuras del estudio de las variaciones epigenéticas / Overview and future perspectives of the study of epigenetic variations / Visão geral e perspectivas futuras do estudo das variações epigenéticas / Reconocimiento a la trayectoria del Prof. Dr. Juan Miguel Castagnino†

Resumen Los cambios epigenéticos juegan en el organismo un papel importante en el control de la expresión génica, durante el desarrollo y a lo largo de toda la vida, sobre todo durante el envejecimiento. En los últimos años se han acumulado evidencias que avalan la participación de los procesos epigenéticos en el desarrollo y evolución de diversas enfermedades como procesos tumorales, enfermedades genéticas, cardiovasculares y neurodegenerativas. Además, los marcadores epigenéticos (metilación del ADN, modificaciones en las histonas y los ARN no codificantes) podrían indicar la predisposición del individuo a determinados procesos patológicos. La administración de fármacos epigenéticos ha demostrado ser eficiente en el tratamiento de enfermedades tales como la aterosclerosis, neoplasias, procesos neurodegenerativos, enfermedades hepáticas, etc. En este artículo se abordarán algunos ejemplos de la contribución que las modificaciones epigenéticas dan a la patogenia de las enfermedades neurodegenerativas y cardiovasculares. En el futuro, la bioquímica clínica será frecuentemente utilizada en los análisis epigenéticos y ayudará al diseño de fármacos y estrategias terapéuticas dirigidas a modificar el epigenoma.

Abstract In the organism, epigenetic changes play an important role in the control of gene expression, during its development and throughout life, especially during ageing. In recent years, evidence has accumulated that supports the participation of epigenetic processes in the development and evolution of various diseases such as tumor processes, genetic, cardiovascular and neurodegenerative diseases. In addition, epigenetic markers (DNA methylation, histone modifications and non-coding RNAs) could indicate the predisposition to certain pathological processes. The administration of epigenetic drugs has proven to be efficient in the treatment of diseases such as atherosclerosis, neoplasms, neurodegenerative processes, liver diseases, etc. In this article we will address some examples of the contribution that epigenetic modifications give to the pathogenesis of neurodegenerative and cardiovascular diseases. In the future, clinical biochemistry will be frequently used in epigenetic analyzes and will help design drugs and therapeutic strategies aimed to modify the epigenome.

Resumo As alterações epigenéticas têm no organismo um papel importante no controle da expressão gênica durante o desenvolvimento e ao longo de toda a vida, principalmente durante o envelhecimento. Nos últimos anos, foram acumuladas evidências que demonstram a participação dos processos epigenéticos no desenvolvimento e evolução de diversas doenças como, por exemplo, processos tumorais, doenças genéticas, cardiovasculares e neurodegenerativas. Além disso, os marcadores epigenéticos (metilação do DNA, modificações nas histonas e nos RNA não codificantes), poderiam indicar a predisposição do indivíduo a determinados processos patologicos. A administração de fármacos epigenéticos demonstrou ser eficiente no tratamento de doenças tais como a aterosclerose, neoplasias, processos neurodegenerativos, doenças hepáticas, etc. Neste estudo abordaremos alguns exemplos da contribuição que as alterações epigenéticas dão à patogenia das doenças neurodegenerativas e cardiovasculares. No futuro, a bioquímica clínica será frequentemente utilizada nas análises epigenéticas e ajudará ao desenho de medicamentos e estratégias terapêuticas dirigidas a modificar o epigenoma.

DNA methylation in bryophytes as a biomarker for monitoring environmental pollution

Rapidly growing industrialization and increased need for transportation have led to environmental pollution, particularly heavy metals. Efficient monitoring would help planning effective strategies to curb such increasing pollution. In this context, we studied the epigenetic changes in the bryophyte Greater Fork-moss, Dicranum majus Turner so as to use to monitor the environmental stress conditions due to accumulation of heavy metals and toxic organic compounds. The hypothesis is that the DNAm (DNA methylation) signatures reflect changes in the environmental conditions, and thus could serve as an alternate monitoring tool to study environmental pollution. The vegetative form of D. majus was collected from two different geographical locations where one was near the main road (MR) and another in the forest area (FS). DNAm rate was found 10.41±2.009 and 23.37±2.94 in MR and FS, respectively (P <0.005). The only difference between the two samples were traffic related pollutants. Thus, the reuslts suggest that vehicle pollution induces epigenetic changes in bryophytes, particularly DNA methylation, and could serve as a valuable biomarker to assess pollution risk due to vehicle traffic.

Utilidad de la técnica de MS-MLPA en el diagnóstico de los síndromes de Beckwith-Wiedemann y Silver-Russell / Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome

Resumen Introducción: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. Objetivo: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. Métodos: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. Resultados: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. Conclusiones: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Abstract Introduction: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. Objective: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. Methods: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. Results: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. Conclusions: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.