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.

Epigenetic regulation mechanism: roles in enamel formation and developmental defects of enamel / 中华口腔医学杂志

Enamel formation is a series of complex physiological processes, which are regulated by critical genes spatially and temporally. These processes involve multiple developmental stages covering ages and are prone to suffer signal interference or gene mutations, ultimately leading to developmental defects of enamel (DDE). Epigenetic modifications have important regulatory roles in gene expression during enarnel development. New technologies including high-throughput sequencing, chromatin immunoprecipitation sequencing (ChIP-seq), and DNA methylation chip are emerging in recent years, making it possible to establish genome-wide epigenetic modification profiles during developmental processes. The regulatory role of epigenetic modification with spatio-temporal pattern, such as DNA methylation, histone modification and non-coding RNA, has significantly expanded our understanding of the regulatory network of enamel formation, providing a new theoretical basis of clinical management and intervention strategy for DDE. The present review briefly describes the enamel formation process of human beings' teeth as well as rodent incisors and summarizes the dynamic characteristics of epigenetic modification during enamel formation. The functions of epigenetic modification in enamel formation and DDE are also emphatically discussed.

Research Progress on Epigenetics in Endometriosis / 中国医学科学院学报

Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.

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.

Significance of preventing developmental origins of diseases in improving population quality / 中华预防医学杂志

More studies show that various diseases, especially chronic non-infectious diseases, have developmental origin. Developmental origins of diseases are mainly due to gametes and early life development stage being exposed to adverse environment, resulting in abnormal modification of epigenetic and stable inheritance to the adult stage, which could make the risk of various long-term diseases of individuals high. The theory of developmental origin provides a new perspective for the occurrence and development of diseases, and also provides a theoretical basis for disease prevention. Attaching importance to maternal and child health care and life-cycle management is conducive to the prevention of developmental diseases and is of great significance to the improvement of population quality.

Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.

Let -7i : A key player and a promising biomarker in diseases / 中南大学学报(医学版)

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small RNAs that regulate gene expression by recognizing homologous sequences and interfering with transcriptional, translational or epigenetic processes. MiRNAs are involved in a variety of disease processes, and regulate the physiological and pathological status of diseases by modulating target cell activity, migration, invasion, apoptosis, autophagy and other processes. Among them, let-7i is highly expressed in various systems, which participates in the process of tumors, cardiovascular and cerebrovascular diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases and other diseases, and plays a positive or negative regulatory role in these diseases through different signal pathways and key molecules. Moreover, it can be used as an early diagnosis and prognostic marker for a variety of diseases and become a potential therapeutic target. As a biomarker, let-7i is frequently tested in combination with other miRNAs to diagnose multiple diseases and evaluate the clinical treatment or prognosis.

Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders / 生理学报

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

Research progress on the role and clinical significance of DNA methylation in early nutritional programming / 生理学报

Early life nutritional environment is not only associated with the growth and development of children, but also affects the health of adults. Numerous epidemiological and animal studies suggest that early nutritional programming is an important physiological and pathological mechanism. DNA methylation is one of the important mechanisms of nutritional programming, which is catalyzed by DNA methyltransferase, a specific base of DNA covalently binds to a methyl group, to regulate gene expression. In this review, we summarize the role of DNA methylation in the "abnormal developmental planning" of key metabolic organs caused by excessive nutrition in early life, resulting in long-term obesity and metabolic disorders in the offspring, and explore the clinical significance of regulating DNA methylation levels through dietary interventions to prevent or reverse the occurrence of metabolic disorders in the early stage in a "deprogramming" manner.

Research Progress of Role and Mechanism of SETD7 in Tumor Occurrence and Progression / 中国肺癌杂志

The occurence and development of tumors is a complicated process, which not only depends on the mutation or deletion of genes, but also is affected by epigenetic regulation. Accumulating evidences have shown that epigenetic modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation, DNA damage response and tumor development. SET domain containing lysine methyltransferase 7 (SETD7) was initially identified as an important lysine methyltransferase, which methylated histone and non-histone proteins. These modifications play fundamental roles. Once this modification disorders, it can directly lead to cell abnormalities and cause many diseases. Studies have shown that SETD7 is related to the occurence and development of various tumors, but the methylation sites of SETD7 and its regulatory mechanism have not been fully elucidated. This article summarizes the research progress of the role of SETD7 on histone and non-histone methylation modification in tumors and the molecular mechanism, in order to provide new therapeutic targets for tumor pathogenesis and diagnosis.
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Programación temprana de la hipertensión arterial / Early programming of hypertension

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

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

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases / 医学前沿

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Roles of m6A modification in neurological diseases / 中南大学学报(医学版)

N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications for eukaryotic mRNA. Under the catalytic regulation of relevant enzymes, m6A participates in the body's pathophysiological processes via mediating RNA transcription, splicing, translation, and decay. In the past, we mainly focused on the regulation of m6A in tumors such as hematological tumors, cervical cancer, breast cancer. In recent years, it has been found that m6A is enriched in mRNAs of neurogenesis, cell cycle, and neuron differentiation. Its regulation in the nervous system is gradually being recognized. When the level of m6A modification and the expression levels of relevant enzyme proteins are changed, it will cause neurological dysfunction and participate in the occurrence and conversion of neurological diseases. Recent studies have found that the m6A modification and its associated enzymes were involved in major depressive disorder, Parkinson's disease, Alzheimer's disease, Fragile X syndrome, amyotrophic lateral sclerosis, and traumatic brain injury, and they also play a key role in the development of neurological diseases and many other neurological diseases. This paper mainly reviewed the recent progress of m6A modification-related enzymes, focusing on the impact of m6A modification and related enzyme-mediated regulation of gene expression on the central nervous system diseases, so as to provide potential targets for the prevention of neurological diseases.

Research Advances of Immunotherapy for Follicular Lymphoma --Review / 中国实验血液学杂志

Follicular lymphoma is an indolent malignant tumor originating from lymph nodes and lymphoid tissues, which may affect the patients' quality of survival due to the recurrence and progression. In recent years, with the deepening understand of the molecular biology and signaling pathways, many new targeted drugs for follicular lymphoma have been discovered, such as monoclonal antibodies, checkpoint inhibitors, epigenetic regulation related targeted therapies and signaling pathway inhibitors. In this review, the new progress of immunotherapy for follicular lymphoma is summarized briefly.

Epigenetic regulation of microglia-mediated innate immune memory and neurological diseases / 生理学报

Microglia have the ability to mediate innate immune memory and can be reprogrammed by primary stimuli to enhance or inhibit the immune response of microglia to secondary stimuli. Inflammatory stimulation is an important factor for microglia to mediate innate immune memory. Single or repeated stimulation can induce microglia to form different phenotypes. Microglia-mediated innate immune response is involved in the regulation of immune memory. Enhancer modification is a key pathway of microglia epigenetic regulation, and the H3K27ac enhancer marker is closely related to immune training. TGF-β1 mediates the interaction between IL-10 and IL-1β, thereby influencing the microglial phenotype. Microglia glycolysis activity is increased after immune training, and oxidative phosphorylation is associated with immune tolerance. Innate immune memory is closely associated with neurodegenerative diseases, brain tumors, brain damage and psychosis. Further study on the mechanism of microglia-mediated innate immune memory is helpful to understand the occurrence and development of central nervous system diseases and provide new options for the treatment of central nervous system diseases.

Consensus and controversy on research progress and clinical practice of vascular calcification / 生理学报

Vascular calcification is an active and complex pathological process regulated by several factors. Vascular calcification is closely related to the incidence and mortality of the cardiovascular disease, chronic kidney disease and other diseases, which affects multiple organs and systems, thus affecting people's health. Therefore, more and more attention is paid to vascular calcification. At present, the pathogenesis and clinical practice of vascular calcification have been continuously improved, which mainly includes calcium and phosphorus imbalance theory, vascular smooth muscle cell transdifferentiation theory, bone homeostasis imbalance theory, epigenetic regulation theory, inflammation theory, extracellular matrix theory, new cell fate theory and so on. However, there are still many unsolved problems. Since the occurrence and development of vascular calcification affect multiple organs and systems, this expert consensus gathered clinicians and basic research experts engaged in the study of vascular calcification in order to summarize the progress of various disciplines related to vascular calcification in recent years. The purpose of this consensus is to systematically summarize the latest research progress, treatment consensus and controversy of vascular calcification from the aspects of epidemiology, pathogenesis, prevention and treatment, so as to provide theoretical basis and clinical enlightenment for in-depth research in this field.

Integrated metabolism and epigenetic modifications in the macrophages of mice in responses to cold stress / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.