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Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural‐tissue‐like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic‐transcription‐factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural‐tissue‐like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Muscle aging is closely related to various epigenetic changes, and exercise has a certain regulatory effect on these epigenetic changes. However, the specific mechanism is not fully understood. OBJECTIVE: To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms, aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS: During the period from June 1st to August 1st, 2023, literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science, PubMed, CNKI, WanFang, and VIP. The search terms used included “skeletal muscle,” “muscle,” “aging,” “older adult,” “aging,” “exercise,” “physical exercise,” “epigenetic,” and “epigenetics” in Chinese as well as “skeletal muscle, muscle, aging, older adult, senescence, age, exercise, sports, physical activity, epigenetic, epigenetics” in English. Boolean logic operators were used to connect the search terms for retrieval, and corresponding strategies were developed. According to the predetermined inclusion and exclusion criteria, 70 eligible articles were selected. RESULTS AND CONCLUSION: Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence, and epigenetic changes in skeletal muscle are an important field. The epigenetic mechanisms of skeletal muscle play an important role in muscle aging, mainly involving DNA methylation, histone modification, regulation of non-coding RNAs, chromatin remodeling, changes in mitochondrial function and expression changes of aging-related genes. Exercise significantly regulates the epigenetics of skeletal muscle, including promoting DNA methylation, muscle histone modification, regulating miRNA expression, and regulating lncRNA expression, regulating muscle factors (such as interleukin-6), regulating mitochondrial function (such as peroxisome proliferators-activated receptors γ co-activator 1α). Future studies are recommended for long-term, cross-diverse populationbased exercise interventions; the application of multi-omics techniques such as proteomics and metabolomics; strengthening the understanding of epigenetic changes at the single-cell level; cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans; strategies for combining exercise and pharmacological interventions to assess their synergistic effects; and epigenetic studies of crosstalk interactions between skeletal muscle and different organs. [ABSTRACT FROM AUTHOR]

Abstract The β‐cell relies predominantly on glucose utilization to generate adenosine triphosphate, which is crucial for both cell viability and insulin secretion. The β‐cell has evolved remarkable metabolic flexibility to productively respond to shifts in environmental conditions and changes in glucose availability. Although these adaptive responses are important for maintaining optimal cellular function, there is emerging evidence that the resulting changes in cellular metabolites can impact the epigenome, causing transient and lasting alterations in gene expression. This review explores the intricate interplay between metabolism and the epigenome, providing valuable insights into the molecular mechanisms leading to β‐cell dysfunction in diabetes. Understanding these mechanisms will be critical for developing targeted therapeutic strategies to preserve and enhance β‐cell function, offering potential avenues for interventions to improve glycemic control in individuals with diabetes.

We report on single case of intraplacental choriocarcinoma (IC) coexisting with feto-maternal hemorrhage from our hospital, a rare malignant tumor that occurs in the chorionic villous trophoblast. To investigate genetic and epigenetic changes to the carcinogenesis of IC, we employed cancer gene panel analysis and whole methylation analysis from a recent case of IC. By Short Tandem Repeats analysis, we confirmed that the tumor of present IC was derived from concurrent normal chorionic villous trophoblast cells. No mutation was found in 145 cancer-related genes. Meanwhile, amplification in MDM2 gene was observed. Furthermore, we observed deferentially methylated CpG sites between tumor and surrounding normal placenta in present IC case. These observations suggest that IC might be arisen as a result of aberrations of methylation rather than of DNA mutations. Further studies are needed to clarify association between aberrant methylation and choriocarcinogenesis. [ABSTRACT FROM AUTHOR]

The β‐cell relies predominantly on glucose utilization to generate adenosine triphosphate, which is crucial for both cell viability and insulin secretion. The β‐cell has evolved remarkable metabolic flexibility to productively respond to shifts in environmental conditions and changes in glucose availability. Although these adaptive responses are important for maintaining optimal cellular function, there is emerging evidence that the resulting changes in cellular metabolites can impact the epigenome, causing transient and lasting alterations in gene expression. This review explores the intricate interplay between metabolism and the epigenome, providing valuable insights into the molecular mechanisms leading to β‐cell dysfunction in diabetes. Understanding these mechanisms will be critical for developing targeted therapeutic strategies to preserve and enhance β‐cell function, offering potential avenues for interventions to improve glycemic control in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Abstract Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural‐tissue‐like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic‐transcription‐factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural‐tissue‐like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

This paper explores the challenge of establishing a meaningful connection between a neurotypical therapist and a neurodiverse patient who inhabit different Umwelts, that is, perceptual worlds.1 It discusses how addressing anxiety is crucial in preventing communication difficulties from escalating for individuals with autism who may have heightened stress due to an overgrown amygdala. Embodied mirroring is introduced to focus on perceptions and reduce stress. Furthermore, the potential for epigenetic changes due to unaddressed anxiety is raised. The paper emphasises the importance of responding to individual differences in sensory and perceptual experiences to promote effective communication and positive outcomes in therapy. [ABSTRACT FROM AUTHOR]

Suicide is a serious global public health problem, with a worrying recent increase in suicide rates in both adolescent and adult populations. However, it is essential to recognize that suicide is preventable. A myriad of factors contributes to an individual's vulnerability to suicide. These factors include various potential causes, from psychiatric disorders to genetic and epigenetic alterations. These changes can induce dysfunctions in crucial systems such as the serotonergic, cannabinoid, and hypothalamic–pituitary–adrenal axes. In addition, early life experiences of abuse can profoundly impact an individual's ability to cope with stress, ultimately leading to changes in the inflammatory system, which is a significant risk factor for suicidal behavior. Thus, it is clear that suicidal behavior may result from a confluence of multiple factors. This review examines the primary risk factors associated with suicidal behavior, including psychiatric disorders, early life adversities, and epigenetic modifications. Our goal is to elucidate the molecular changes at the genetic, epigenetic, and molecular levels in the brains of individuals who have taken their own lives and in the plasma and peripheral mononuclear cells of suicide attempters and how these changes may serve as predisposing factors for suicidal tendencies. [ABSTRACT FROM AUTHOR]

Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic‐stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA‐sequencing reveales that cyclic‐stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal‐epithelial transition. Of note, cyclic‐stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin‐2, and YAP), across the cytoskeletal‐to‐nuclear space. Furthermore, stretch‐mediated cytoskeletal‐nuclear mechano‐coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome‐wide ChIP‐sequencing and pharmacological inhibition tests. Single cell RNA‐sequencing further identifies subcluster of mechano‐responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic‐stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic‐stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA‐sequencing reveales that cyclic‐stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal‐epithelial transition. Of note, cyclic‐stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin‐2, and YAP), across the cytoskeletal‐to‐nuclear space. Furthermore, stretch‐mediated cytoskeletal‐nuclear mechano‐coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome‐wide ChIP‐sequencing and pharmacological inhibition tests. Single cell RNA‐sequencing further identifies subcluster of mechano‐responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic‐stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.

Innate lymphoid cells (ILCs) are recently discovered innate immune cells that reside and self-renew in mucosal tissues and serve as the first line of defense against various external insults. They include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer cells. The development and functions of ILC1-3 reflect those of their adaptive immunity TH1, TH2, and TH17 T-cell counterparts. Asthma is a heterogeneous disease caused by repeated exposure to specific allergens or host/environmental factors (e.g., obesity) that stimulate pathogenic pulmonary immune cells, including ILCs. Memory used to be a hallmark of adaptive immune cells until recent studies of monocytes, macrophages, and NK cells showed that innate immune cells can also exhibit greater responses to re-stimulation and that these more responsive cells can be long-lived. Besides, a series of studies suggest that the tissueresident innate lymphoid cells have memory-like phenotypes, such as increased cytokine productions or epigenetic modifications following repetitive exposure to allergens. Notably, both clinical and mouse studies of asthma show that various allergens can generate memory-like features in ILC2s. Here, we discuss the biology of ILCs, their roles in asthma pathogenesis, and the evidence supporting ILC memory. We also show evidence suggesting memory ILCs could help drive the phenotypic heterogeneity in asthma. Thus, further research on memory ILCs may be fruitful in terms of developing new therapies for asthma. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a pandemic in March 2020. During a viral infection, it has been reported that epigenetic changes occur for both sides: Infected cells elicit an antiviral environmental response, which induces and initiates certain pathways for proper response to the virus, while the virus silences the expression of vital genes in the ant-iviral host cell. In this study, we aimed to examine the methylation level of the MX1 gene promoter in different stages in COVID-19 patients compared to the control group. Methods: In total, 470 COVID-19 patients with a positive polymerase chain reaction (PCR) test (235 women and 235 men) were recruited into the study as the test group. Patients were divided based on the World Health Organization (WHO) classification into three groups: moderate, severe, and critical. Moreover, 100 healthy individuals (50 women and 50 men) were selected as the control group. Peripheral white blood cells were collected and PCR was performed using two types of primers designed for methylated and unmethylated states of the MX1 gene. The PCR products were then loaded on agarose gel and the band intensities were calculated by ImageJ software. Results: The results showed a decrease in the methylation of the MX1 gene promoter in moderate and severe groups and an increase in the MX1 gene promoter methylation in the critical group. In addition, the level of methylation was higher in men than in women. Conclusions: Increased methylation of the MX1 gene in the critical group may indicate the role of SARS-CoV-2 in reducing the expression levels of this antiviral gene and thus promoting virus replication and disease progression. [ABSTRACT FROM AUTHOR]

Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic system. Cutaneous malignancies are usually affected by epigenetic changes. However, there is limited knowledge regarding the epigenetic changes associated with cutaneous lymphomas. In this review, we focused on cutaneous T-cell lymphomas such as mycosis fungoides, Sézary syndrome, and anaplastic large cell lymphoma. With regard to epigenetic changes, we summarize the detailed chemical modifications categorized into DNA methylation and histone acetylation and methylation. We also summarize the epigenetic modifications and characteristics of the drug for cutaneous T-cell lymphoma (CTCL). Furthermore, we discuss current research on epigenetic-targeted therapy against cutaneous T-cell lymphomas. Although the current method of treatment with histone deacetylase inhibitors does not exhibit sufficient therapeutic benefits in all cases of CTCL, epigenetic-targeted combination therapy might overcome this limitation for patients with CTCL. [ABSTRACT FROM AUTHOR]

Abstract Background Arsenic toxicity induces a range of metabolic responses in plants, including DNA methylation. The focus of this paper was on the relationship between As-induced stress and plant senescence in the hyperaccumulator Pteris cretica var. Albo-lineata (Pc-Al). We assume difference in physiological parameters and level of DNA methylation in young and old fronds as symptoms of As toxicity. Results The As accumulation of Pc-Al fronds, grown in pots of haplic chernozem contaminated with 100 mg As kg− 1 for 122 days, decreased with age. Content of As was higher in young than old fronds for variants with 100 mg As kg− 1 (2800 and 2000 mg As kg− 1 dry matter, respectively). The highest As content was determined in old fronds of Pc-Al grown in pots with 250 mg As kg− 1. The increase with age was confirmed for determined nutrients – Cu, Mg, Mn, S and Zn. A significant elevation of all analysed nutrients was showed in old fronds. Arsenic accumulation affected DNA methylation status in fronds, but content of 5-methylcytosine (5mC) decreased only in old fronds of Pc-Al (from 25 to 12%). Determined photosynthetic processes showed a decrease of fluorescence, photosynthetic rate and chlorophylls of As treatments in young and old fronds. Water potential was decreased by As in both fronds. Thinning of the sclerenchymatous inner cortex and a reduction in average tracheid metaxylem in the vascular cylinder was showed in roots of As treatment. Irrespective to fronds age, physiological parameters positively correlated with a 5mC while negatively with direct As toxicity. Opposite results were found for contents of Cu, Mg, Mn, S and Zn. Conclusions The results of this paper point to changes in the metabolism of the hyperaccumulator plant Pc-Al, upon low and high exposure to As contamination. The significant impact of As on DNA methylation was found in old fronds. Irrespective to fronds age, significant correlations were confirmed for 5mC and As toxicity. Our analysis of the very low water potential values and lignification of cell walls in roots showed that transports of assimilated metabolites and water between roots and fronds were reduced. As was showed by our results, epigenetic changes could affect studied parameters of the As hyperaccumulator plant Pc-Al, especially in old fronds.

Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC).Methods: We summarized 52 m6A/m5C/m1A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m6A/m5C/m1A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m6A/m5C/m1A-related lncRNAs to construct a prognostic signature of HNSCC.Results: This prognostic signature is based on six m6A/m5C/m1A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (p < 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (p < 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (p < 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden.Conclusion: Our study elucidated how m6A/m5C/m1A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m6A/m5C/m1A-related lncRNAs may become a new choice for immunotherapy of HNSCC.

DNA methylation is one of the epigenetic changes that may affect cell functions, which associated with several steps of cancer progression. Gastric carcinoma is endemic in Iraq with highly association of Epstein Barr Virus infections. Epigenetic changes for gastric carcinoma diagnosis are very important to early diagnose the disease also consider as biomarker to search of the progression of cancer. So detection of methylation of early genes in Epstein barr virus associated gastric carcinoma is very useful to confirm the diagnosis of the disease. The first step is detection of the virus in the fresh and embedded tissues, then search of the methylation pattern of the early genes of the virus that expressed several important proteins that effect the life cycle if the virus also the progression of the disease using conventional polymerase chain reaction. The virus was detected in 20% of tissue samples, while the methylation state was positive in 87.5% in tissues affected with the virus. Highly percentage of the methylation in the early genes of the virus may affect the virus infection which will affect the progression of the cancer.

Maize is a model plant species often used for genetics and genomics research because of its genetic diversity. There are prominent morphological, genetic, and epigenetic variations between tropical and temperate maize lines. However, the genome-wide chromatin conformations of these two maize types remain unexplored. We applied a Hi-C approach to compare the genome-wide chromatin interactions between temperate inbred line D132 and tropical line CML288. A reconstructed maize three-dimensional genome model revealed the spatial segregation of the global A and B compartments. The A compartments contain enriched genes and active epigenome marks, whereas the B compartments are gene-poor, transcriptionally silent chromatin regions. Whole-genome analyses indicated that the global A compartment content of CML288 was 3.12% lower than that of D132. Additionally, global and A/B sub-compartments were associated with differential gene expression and epigenetic changes between two inbred lines. About 25.3% of topologically associating domains (TADs) were determined to be associated with complex domain-level modifications that induced transcriptional changes, indicative of a large-scale reorganization of chromatin structures between the inbred maize lines. Furthermore, differences in chromatin interactions between the two lines correlated with epigenetic changes. These findings provide a solid foundation for the wider plant community to further investigate the genome-wide chromatin structures in other plant species. [ABSTRACT FROM AUTHOR]

Background: Inflammatory skin diseases include a variety of skin diseases, such as seborrheic dermatitis, acne, atopic dermatitis, psoriasis and so on, which are more common and tend to have a significant impact on patients' quality of life. Inflammatory skin diseases often result in physical or psychological distress; however, the pathogenesis of these diseases have not been clearly elucidated. Many factors are involved in the pathogenesis of inflammatory skin diseases, including heredity, environment, immunity, epidermal barrier, mental disorders, infection and so on. In recent years, skin microbiota has been shown to play an important role in inflammatory skin diseases. Aims: To elaborate on the specific mechanisms of inflammatory skin diseases induced by microbiota dysbiosis. Methods: We introduce the function and influence of skin microbiota in inflammatory skin diseases from the following aspects: Immunity, epigenetics, epidermal barrier and treatment. Results: Skin microbiota can affect many aspects of the host, such as Immunity, epigenetics, epidermal barrier, and it plays an important role in the pathogenesis of inflammatory skin diseases. Conclusion: Skin microbiota is extremely important for maintaining the health of skin and the dysbiosis of skin microbiota is an important pathogenesis of inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 has been widely applied to various plant species accelerating the pace of plant genome editing and precision breeding in crops. Unintended effects beyond off-target nucleotide mutations are still somewhat unexplored. We investigated the degree and patterns of epigenetic changes after gene editing. We examined changes in DNA methylation in genome-edited promoters of naturally hypermethylated genes (AT1G72350 and AT1G09970) and hypomethylated genes (AT3G17320 and AT5G28770) from Arabidopsis. Transgenic plants were developed via Agrobacterium-mediated floral dip transformation. Homozygous edited lines were selected from segregated T2 plants by an in vitro digestion assay using ribonucleoprotein complex. Bisulfite sequencing comparisons were made between paired groups of edited and non-edited plants to identify changes in DNA methylation of the targeted loci. We found that directed mutagenesis via CRISPR/Cas9 resulted in no unintended morphological or epigenetic alterations. Phenotypes of wild-type, transgenic empty vector, and transgenic edited plants were similar. Epigenetic profiles revealed that methylation patterns of promoter regions flanking target sequences were identical among wild-type, transgenic empty vector, and transgenic edited plants. There was no effect of mutation type on epigenetic status. We also evaluated off-target mutagenesis effects in the edited plants. Potential off-target sites containing up to 4-bp mismatch of each target were sequenced. No off-target mutations were detected in candidate sites. Our results showed that CRISPR/Cas9 did not leave an epigenetic footprint on either the immediate gene-edited DNA and flanking DNA or introduce off-target mutations.

Ochratoxin A (OTA) is a mycotoxin produced by fungi and occurs naturally in various foodstuffs and some animal-derived products. This mycotoxin can cause deleterious effects on kidney, liver, central nervous, and immune system. However, potential mechanisms regarding how OTA disrupts the mammalian oocyte quality have not been clearly defined. In this study, we proved that OTA weakened oocyte quality by impairing oocyte meiotic maturation. We found that female mice treated with 1 mg/kg body weight OTA by intraperitoneal (IP) injection for 7 days displayed ovarian dysfunction and decreased offspring number. We also found that OTA treatment at 7.5 μM for 16 h decreased the rate of first polar body extrusion by disrupting spindle and chromosome alignment. In addition, OTA caused oxidative stress by inducing the accumulation of reactive oxygen species and consumption of antioxidants during meiosis, consequently resulting in oocytes apoptosis. Mitochondrial damage and insufficient energy supply were also observed in OTA-pretreated oocytes, which led to the meiotic failure of oocyte. Moreover, the epigenetic modifications were also affected, showing with altered 5 mC, 5hmC, H3K9ac, and H3K9me3 levels in mice oocytes. In summary, these results showed that OTA could decrease oocyte maturation and fertility by inducing oxidative stress and epigenetic changes. • Ochraoxin A decreased reproductive capacity of female mice. • OTA induced oxidative stress and apoptosis in oocytes. • OTA induced metabolic disorder of energy during meiotic progression of oocytes. • The epigenetic modifications of oocyte changed after OTA treated. • OTA decreased reproductive capacity of female mice by reducing oocyte quality. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine whether feeding rats a diet without added Cu increases oxidation of macromolecules in tissues, as well as epigenetic changes in the brain. The rats were divided into two groups: the Cu-6.5 group which was fed a diet with a standard content of Cu in mineral mixture – 6.5 mg Cu from CuCO3 per kg of diet; and the Cu-0 group which was fed a diet with a mineral mix without Cu supplementation. At the end of the experiment the rats were weighed and blood samples were collected. Finally, the rats were euthanized and then the liver, small intestine, spleen, kidneys, heart, brain, lung, testes and leg muscles were removed and weighed. In the blood of Cu-0 rats the lower Cp activity and greater GPx and CAT activity than in Cu-6.5 rats were noticed. In the liver, lungs, heart and testes of Cu-0 rats, a decreased content of Cu were noticed. Application of Cu-0 diets resulted in increased LOOH level in the small intestine, liver, and heart, as well as increased MDA content in the liver, spleen, lungs, brain and testes. The Cu-0 treatment caused a decrease in SOD activity in the heart, lungs and testes of the rats and a decrease in CAT activity in the small intestine. In the brain and testes of rats from the Cu-0 treatment, lower content of GSH + GSSG was observed. The brain of rats from the Cu-0 treatment showed an increase in the level of PCs, 8-OHdG, Casp 8 and DNA methylation. The research has shown that a deficiency of Cu in the diet impairs the body's antioxidant defences, which in turn leads to increased lipid oxidation in the liver, small intestinal wall, heart, spleen, lungs, brain and testes, as well as to oxidation of proteins and DNA in the brain. A deficiency of Cu in the diet also increases methylation of cytosine in the brain. [ABSTRACT FROM AUTHOR]

Background: Arsenic toxicity induces a range of metabolic responses in plants, including DNA methylation. The focus of this paper was on the relationship between As-induced stress and plant senescence in the hyperaccumulator Pteris cretica var. Albo-lineata (Pc-Al). We assume difference in physiological parameters and level of DNA methylation in young and old fronds as symptoms of As toxicity. Results: The As accumulation of Pc-Al fronds, grown in pots of haplic chernozem contaminated with 100 mg As kg− 1 for 122 days, decreased with age. Content of As was higher in young than old fronds for variants with 100 mg As kg− 1 (2800 and 2000 mg As kg− 1 dry matter, respectively). The highest As content was determined in old fronds of Pc-Al grown in pots with 250 mg As kg− 1. The increase with age was confirmed for determined nutrients – Cu, Mg, Mn, S and Zn. A significant elevation of all analysed nutrients was showed in old fronds. Arsenic accumulation affected DNA methylation status in fronds, but content of 5-methylcytosine (5mC) decreased only in old fronds of Pc-Al (from 25 to 12%). Determined photosynthetic processes showed a decrease of fluorescence, photosynthetic rate and chlorophylls of As treatments in young and old fronds. Water potential was decreased by As in both fronds. Thinning of the sclerenchymatous inner cortex and a reduction in average tracheid metaxylem in the vascular cylinder was showed in roots of As treatment. Irrespective to fronds age, physiological parameters positively correlated with a 5mC while negatively with direct As toxicity. Opposite results were found for contents of Cu, Mg, Mn, S and Zn. Conclusions: The results of this paper point to changes in the metabolism of the hyperaccumulator plant Pc-Al, upon low and high exposure to As contamination. The significant impact of As on DNA methylation was found in old fronds. Irrespective to fronds age, significant correlations were confirmed for 5mC and As toxicity. Our analysis of the very low water potential values and lignification of cell walls in roots showed that transports of assimilated metabolites and water between roots and fronds were reduced. As was showed by our results, epigenetic changes could affect studied parameters of the As hyperaccumulator plant Pc-Al, especially in old fronds. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 has been widely applied to various plant species accelerating the pace of plant genome editing and precision breeding in crops. Unintended effects beyond off-target nucleotide mutations are still somewhat unexplored. We investigated the degree and patterns of epigenetic changes after gene editing. We examined changes in DNA methylation in genome-edited promoters of naturally hypermethylated genes (AT1G72350 and AT1G09970) and hypomethylated genes (AT3G17320 and AT5G28770) from Arabidopsis. Transgenic plants were developed via Agrobacterium -mediated floral dip transformation. Homozygous edited lines were selected from segregated T2 plants by an in vitro digestion assay using ribonucleoprotein complex. Bisulfite sequencing comparisons were made between paired groups of edited and non-edited plants to identify changes in DNA methylation of the targeted loci. We found that directed mutagenesis via CRISPR/Cas9 resulted in no unintended morphological or epigenetic alterations. Phenotypes of wild-type, transgenic empty vector, and transgenic edited plants were similar. Epigenetic profiles revealed that methylation patterns of promoter regions flanking target sequences were identical among wild-type, transgenic empty vector, and transgenic edited plants. There was no effect of mutation type on epigenetic status. We also evaluated off-target mutagenesis effects in the edited plants. Potential off-target sites containing up to 4-bp mismatch of each target were sequenced. No off-target mutations were detected in candidate sites. Our results showed that CRISPR/Cas9 did not leave an epigenetic footprint on either the immediate gene-edited DNA and flanking DNA or introduce off-target mutations. [ABSTRACT FROM AUTHOR]

Renal fibrosis is a common outcome of various renal injuries, leading to structural destruction and functional decline of the kidney, and is also a critical prognostic indicator and determinant in renal diseases therapy. Hypoxia is induced in different stress and injuries in kidney, and the hypoxia inducible factors (HIFs) are activated in the context of hypoxia in response and regulation the hypoxia in time. Under stress and hypoxia conditions, HIF-1α increases rapidly and regulates intracellular energy metabolism, cell proliferation, apoptosis, and inflammation. Through reprogramming cellular metabolism, HIF-1α can directly or indirectly induce abnormal accumulation of metabolites, changes in cellular epigenetic modifications, and activation of fibrotic signals. HIF-1α protein expression and activity are regulated by various posttranslational modifications. The drugs targeting HIF-1α can regulate the downstream cascade signals by inhibiting HIF-1α activity or promoting its degradation. As the renal fibrosis is affected by renal diseases, different diseases may trigger different mechanisms which will affect the therapy effect. Therefore, comprehensive analysis of the role and contribution of HIF-1α in occurrence and progression of renal fibrosis, and determination the appropriate intervention time of HIF-1α in the process of renal fibrosis are important ideas to explore effective treatment strategies. This study reviews the regulation of HIF-1α and its mediated complex cascade reactions in renal fibrosis, and lists some drugs targeting HIF-1α that used in preclinical studies, to provide new insight for the study of the renal fibrosis mechanism. [Display omitted] • HIF-1α is related to abnormal metabolites and activation of fibrotic signals. • Complex post-translational modifications regulate stability and function of HIF-1α. • Targeting HIF-1α may be a potential strategy for alleviating renal fibrosis. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of short (~22 nucleotides [nt]), single-stranded RNA oligonucleotides that are regulatory in nature and are often dysregulated in various diseases, including cancer. miRNAs can act as oncomiRs (miRNAs associated with cancer) or tumor suppressor miRNAs and have the potential to be a diagnostic, prognostic, noninvasive biomarker for these diseases. MicroRNA-221 (miR-221) and microRNA-222 (miR-222) are homologous miRNAs, located on the human chromosome Xp11.3, which factored significantly in impairment in the regulation of a wide range of cancers. In this review, we have highlighted the most consistently reported dysregulated miRNAs that trigger human tissues to express cancerous features and surveyed the role of those miRNAs in metastasis, apoptosis, angiogenesis, and tumor prognosis. Also, we applied the causes of drug resistance and the role of coordinated actions of these miRNAs to epigenetic changes and selected miRNAs as a potential type of cancer treatment. [ABSTRACT FROM AUTHOR]

Environmental stress such as genotoxic agents can cause DNA damage either indirectly through the generation of reactive oxygen species or directly by interactions with the DNA molecule. Damage to the genetic material may cause mutations and ultimately cancer. Genotoxic mutation can be prevented either by apoptosis or DNA repair. In response to DNA damage, cells have evolved DNA damage responses (DDR) to detect, signal, and repair DNA lesions. Epigenetic mechanisms play critically important roles in DDR, which requires changes in chromatin structure and dynamics to modulate DNA accessibility. Incorporation of histone variants into chromatin is considered as an epigenetic mechanism. Canonical histones can be replaced with variant histones that change chromatin structure, stability, and dynamics. Recent studies have demonstrated involvement of nearly all histone variants in environmental-stress-induced DNA damage repair through various mechanisms, including affecting nucleosome dynamics, carrying variant-specific modification, promoting transcriptional competence or silencing, mediating rearrangement of chromosomes, attracting specific repair proteins, among others. In this review, we will focus on the role of histone variants in DNA damage repair after exposure to environmental genotoxic agents. Understanding the mechanisms regulating environmental exposure-induced epigenetic changes, including replacement of canonical histones with histone variants, will promote the development of strategies to prevent or reverse these changes. [ABSTRACT FROM AUTHOR]

DNA methylation is one of the epigenetic changes that may affect cell functions, which associated with several steps of cancer progression. Gastric carcinoma is endemic in Iraq with highly association of Epstein Barr Virus infections. Epigenetic changes for gastric carcinoma diagnosis are very important to early diagnose the disease also consider as biomarker to search of the progression of cancer. So detection of methylation of early genes in Epstein barr virus associated gastric carcinoma is very useful to confirm the diagnosis of the disease. The first step is detection of the virus in the fresh and embedded tissues, then search of the methylation pattern of the early genes of the virus that expressed several important proteins that effect the life cycle if the virus also the progression of the disease using conventional polymerase chain reaction. The virus was detected in 20% of tissue samples, while the methylation state was positive in 87.5% in tissues affected with the virus. Highly percentage of the methylation in the early genes of the virus may affect the virus infection which will affect the progression of the cancer. [ABSTRACT FROM AUTHOR]

Cellular senescence is a tumor suppressive response that has become recognized as a major contributor of tissue aging. Senescent cells undergo a stable proliferative arrest that protects against neoplastic transformation, but acquire a secretory phenotype that has long-term deleterious effects. Studies are still unraveling the effector mechanisms that underlie these senescence responses with the goal to identify therapeutic interventions. Such effector mechanisms have been linked to the dramatic remodeling in the epigenetic and chromatin landscape that accompany cellular senescence. We discuss these senescence-associated epigenetic changes and their impact on the senescence phenotypes, notably the proliferative arrest and senescence associated secretory phenotype (SASP). We also explore possible epigenetic targets to suppress the deleterious effects of senescent cells that contribute towards aging. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies, including in vitro fertilization ( IVF), are now frequently used, and increasing evidence indicates that IVF causes gene expression changes in children and adolescents that increase the risk of metabolic diseases. Although such gene expression changes are thought to be due to IVF-induced epigenetic changes, the mechanism remains elusive. We tested whether the transcription factor ATF7-which mediates stress-induced changes in histone H3K9 tri- and dimethylation, typical marks of epigenetic silencing-is involved in the IVF-induced gene expression changes. IVF up- and downregulated the expression of 688 and 204 genes, respectively, in the liver of 3-week-old wild-type ( WT) mice, whereas 87% and 68% of these were not changed, respectively, by IVF in ATF7-deficient ( Atf7 −/−) mice. The genes, which are involved in metabolism, such as pyrimidine and purine metabolism, were upregulated in WT mice, but not in Atf7 −/− mice. Of the genes whose expression was upregulated by IVF in WT mice, 37% were also upregulated by a loss of ATF7. These results indicate that ATF7 is a key factor in establishing the memory of IVF effects on metabolic pathways. [ABSTRACT FROM AUTHOR]

DNA methylation is an important epigenetic modification that may contribute to environmentally induced phenotypic variations by regulating gene expression. Chemically induced male sterility (CIMS) lines in wheat (Triticum aestivum L.) can transform from sterile to fertile, induced by a chemical hybridising agent during anther development. So far, little is known about the DNA methylation variation of CIMS in wheat. TAA1 regulates pollen wall development, probably through converting fatty acids to fatty alcohol in wheat. We investigated the DNA methylation pattern of the TAA1 gene in the core promoter region by using the bisulfite genomic sequencing method, and higher methylation was observed in CIMS. The expression levels of the TAA1 gene were also evaluated by real time quantitative reverse transcriptase PCR analysis, which revealed that the expression levels of the TAA1 gene were down regulated in CIMS. The aliphatic composition of the anther underwent accumulation in line 1376-CIMS, revealed by gas chromatography–mass spectrometry, including increments of tetradecanoic acid, hexadecanoic acid and octadecanoic acid. Scanning electron microscopy revealed that anther and pollen wall formation was significantly altered in 1376-CIMS. These results suggested that DNA methylation of the TAA1 gene may be involved in the sterility–fertility transition of CIMS. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) has become one of the most critical health problems in many countries, including Japan. Liver injury in ALD ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular carcinoma. Many factors are thought to contribute to the development and progression of ALD, particularly insulin resistance, generation of reactive oxygen species during alcohol metabolism, adipokines from visceral adipose tissue, and endotoxin derived from the gut. Although the pathogenesis of ALD has been widely investigated, the precise mechanisms are yet to be elucidated and many questions remain. This article reviews the possible mechanisms for the development of ALD identified to date. [ABSTRACT FROM AUTHOR]

AbstractEMT and MET comprise the processes by which cells transit between epithelial and mesenchymal states, and they play integral roles in both normal development and cancer metastasis. This article reviews these processes and the molecular pathways that contribute to them. First, we compare embryogenesis and development with cancer metastasis. We then discuss the signaling pathways and the differential expression and down‐regulation of receptors in both tumor cells and stromal cells, which play a role in EMT and metastasis. We further delve into the clinical implications of EMT and MET in several types of tumors, and lastly, we discuss the role of epigenetic events that regulate EMT/MET processes. We hypothesize that reversible epigenetic events regulate both EMT and MET, and thus, also regulate the development of different types of metastatic cancers.