DNA methylation analysis of the SDC2, SEPT9 and VIM genes in fecal DNA for colorectal cancer diagnosis.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide. DNA methylation sites may serve as a new gene signature for colorectal cancer diagnosis. The search for representative DNA methylation sites is urgently needed. This study aimed to systematically identify a methylation gene panel for colorectal cancer diagnosis via tissue and fecal samples. METHODS: A total of 181 fecal and 50 tumor tissue samples were collected. They were obtained from 83 colorectal cancer patients and 98 healthy subjects. These samples were evaluated for DNA methylation of 9 target genes via quantitative bisulfite next-generation sequencing. We employed the rank-sum test to screen the colorectal cancer-specific methylation sites in the tissue and fecal cohorts. A data model was subsequently constructed and validated via the dedicated validation dataset. RESULTS: Compared with the fecal and negative control samples, the colorectal cancer tissue samples presented significantly higher methylation rates for all the selected gene sites. The methylation rates of the tissue and preoperative fecal samples showed the same high and low rates at the same sites. After screening, a panel of 29 loci in the SDC2, SEPT9, and VIM genes proved to be reliable biomarkers for colorectal cancer diagnosis in fecal samples. Logistic regression models were then constructed and validated using this panel. The sensitivity of the model was 91.43% (95% CI = [89.69, 93.17]), the specificity was 100% (95% CI = [100,100]), and the AUC value is 99.31% (95% CI = [99,99.62]). The diagnostic accuracy of the model for stage I and stage II colorectal cancer was 100% (11/11) and 91.3% (21/23), respectively. Overall, this study confirms that the gene locus panel and the model can be used to diagnose colorectal cancer effectively through feces. CONCLUSIONS: Our study identified a set of key methylation sites for colorectal cancer diagnosis from fecal samples, highlighting the importance of using tissue and fecal samples to accurately assess DNA methylation levels to screen for methylation sites, and developing an effective diagnostic model for colorectal cancer.

Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression.

DNA methylation is crucial for chromatin structure, transcription regulation and genome stability, defining cellular identity. Aberrant hypermethylation of CpG-rich regions is common in cancer, influencing gene expression. However, the specific contributions of individual epigenetic modifications to tumorigenesis remain under investigation. In hepatocellular carcinoma (HCC), DNA methylation alterations are documented as in other tumor types. We aimed to identify hypermethylated CpGs in HCC, assess their specificity across other tumor types, and investigate their impact on gene expression. To this end, public methylomes from HCC, other liver diseases, and 27 tumor types as well as expression data from TCGA-LIHC and GTEx were analyzed. This study identified 39 CpG sites that were hypermethylated in HCC compared to control liver tissue, and were located within promoter, gene bodies, and intergenic CpG islands. Notably, these CpGs were predominantly unmethylated in healthy liver tissue and other normal tissues. Comparative analysis with 27 other tumors revealed both common and HCC-specific hypermethylated CpGs. Interestingly, the HCC-hypermethylated genes showed minimal expression in the different healthy tissues, with marginal changes in the level of expression in the corresponding tumors. These findings confirm previous evidence on the limited influence of DNA hypermethylation on gene expression regulation in cancer. It also highlights the existence of mechanisms that allow the selection of tissue-specific methylation marks in normally unexpressed genes during carcinogenesis. Overall, our study contributes to demonstrate the complexity of cancer epigenetics, emphasizing the need of better understanding the interplay between DNA methylation, gene expression dynamics, and tumorigenesis.

UHRF1 knockdown induces cell cycle arrest and apoptosis in breast cancer cells through the ZBTB16/ANXA7/Cyclin B1 axis.

Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is involved in tumorigenicity through DNA methylation in various cancers, including breast cancer. This study aims to investigate the regulatory mechanisms of UHRF1 in breast cancer progression. Herein, we show that UHRF1 is upregulated in breast cancer tissues and cell lines as measured by western blot analysis and immunohistochemistry. Breast cancer cells are transfected with a UHRF1 overexpression plasmid (pcDNA-UHRF1) or short hairpin RNA targeting UHRF1 (sh-UHRF1), followed by detection of cell proliferation, invasion, apoptosis, and cell cycle. UHRF1 overexpression promotes proliferation and invasion and attenuates cell cycle arrest and apoptosis in breast cancer cells, while UHRF1 knockdown shows the opposite effect. Moreover, methylation-specific PCR and ChIP assays indicate that UHRF1 inhibits zinc finger and BTB domain containing 16 (ZBTB16) expression by promoting ZBTB16 promoter methylation via the recruitment of DNA methyltransferase 1 (DNMT1). Then, a co-IP assay is used to verify the interaction between ZBTB16 and the annexin A7 (ANXA7) protein. ZBTB16 promotes ANXA7 expression and subsequently inhibits Cyclin B1 expression. Rescue experiments reveal that ZBTB16 knockdown reverses the inhibitory effects of UHRF1 knockdown on breast cancer cell malignancies and that ANXA7 knockdown abolishes the inhibitory effects of ZBTB16 overexpression on breast cancer cell malignancies. Additionally, UHRF1 knockdown significantly inhibits xenograft tumor growth in vivo. In conclusion, UHRF1 knockdown inhibits proliferation and invasion, induces cell cycle arrest and apoptosis in breast cancer cells via the ZBTB16/ANXA7/Cyclin B1 axis, and reduces xenograft tumor growth in vivo.

Evaluation of Multigene Methylation for Blood-Based Detection of Colorectal Cancer.

Background: Early screening for colorectal cancer (CRC) has the potential to improve patient prognosis, but current screening methods are limited. In this prospective study, we aimed to evaluate the multigene (Septin9, SDC2, KCNQ5, and IKZF1) detection in patient plasma for CRC diagnosis. Methods: Overall, 67 participants were enrolled, including 31 patients with CRC, 17 patients with colorectal polyp, and 19 normal controls who underwent colonoscopy. Carcinoembryonic antigen (CEA) and Septin9, SDC2, KCNQ5, and IKZF1 methylation tests were performed. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of each biomarker. The association between positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed. Results: The positive rate of multigene methylation detection was 87.1% (27/31) in patients with CRC, which was higher than single indicators: CEA (51.61%, 16/31), Septin9 (41.94%, 13/31), SDC2 (41.94%, 13/31), KCNQ5 (58.06%, 18/31), and IKZF1 (32.26%, 10/31). In the colorectal polyp group, the rate of multigene methylation detection is 88.24% (15/17), which was also higher than single indicator: CEA (17.65%, 3/17), Septin9 (11.76%, 2/17), SDC2 (64.71%, 11/17), KCNQ5 (58.82%, 10/17), and IKZF1 (35.29%, 6/17). The ROC curves further showed better diagnostic value of the multigene test for CRC than any single gene. Correlation analysis found that the positive rate of the test was not affected by patients' clinicopathologic characteristics. Conclusion: The combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 tests is preferable to individual gene tests for patients with CRC and polyp.

Comment on, "Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review".

The article "Differential DNA Methylation Associated with Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Systematic Review" by Tomasz Klepinowski et al. offers an in-depth analysis of the relationship between DNA methylation and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). By systematically reviewing databases like PubMed, MEDLINE, Scopus, and Web of Science, the authors identify key genes, including ITPR3, HAMP, INSR, and CDHR5, as potential biomarkers for early DCI diagnosis. Their meticulous adherence to PRISMA guidelines and the STROBE statement for quality assessment enhances the study's credibility. However, the review could be improved by discussing methodological variability, statistical power, and the functional relevance of identified CpG sites. Additional sections on mechanistic pathways, integration with other omics data, clinical translation, and ethical considerations would further strengthen the review, providing a more comprehensive understanding of epigenetic factors in DCI and paving the way for future therapeutic interventions.

Downregulated Expression and Hypermethylation of SIRT1 in Patients with Kashin-Beck Disease-Mediated Chondrocyte Apoptosis May Potentially Be Ameliorated by Selenium Supplement.

This study aims to elucidate the role of silent information regulator 2 homologue 1 (SIRT1) in cartilage damage in Kashin-Beck disease (KBD) by exploring the correlation between SIRT1 and KBD and the potential effect of SIRT1 expression and methylation on chondrocyte apoptosis. SIRT1 protein expression was detected using IHC, and the mRNA levels of SIRT1, DNMTs, and apoptosis-related genes were measured by RT-qPCR. Methylation levels of SxIRT1 were detected by MALDI-TOF-MS, MSP, and qMSP. Chondrocyte apoptosis was determined by Hoechst 33,342 staining and Annexin V-FITC/PI following selenium (Se) deficiency or T-2 toxin and Se supplement. Both protein and mRNA levels of SIRT1 were reduced in KBD patients, and SIRT1 expression discriminated between KBD and non-KBD with an AUC greater than 0.7. Methylation levels of SIRT1 were significantly elevated in KBD patients, and SIRT1 hypermethylation increased the risk of acquiring KBD 3.879-fold. DNMTs mRNA levels were increased in KBD patients, and further, DNMT1 mRNA levels were decreased, and SIRT1 mRNA levels were increased in the SIRT1 hypomethylation group. Moreover, the SIRT1 expression was negatively correlated with pro-apoptotic genes and positively correlated with anti-apoptotic gene expression, especially in KBD patients. Furthermore, apoptosis rates, DNMT1 mRNA level, and SIRT1 methylation level were increased in chondrocytes treated with Se deficiency and T-2 toxin, but SIRT1 mRNA level was downregulated, whereas the opposite trend was observed in chondrocytes treated with Se supplement. Low SIRT1 expression and CpG hypermethylation in KBD patients are associated with increased disease risk, which mediated chondrocyte apoptosis can be ameliorated by Se supplement.

HOXD12 defines an age-related aggressive subtype of oligodendroglioma.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e-6, p < 0.001, p < 1e-3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were independently prognostic of NOTCH1 and PIK3CA mutations, loss of 15q, MYC activation, and standard histopathological features. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue, particularly within cycling and OPC-like cells, and was associated with a stem-like phenotype. A pan-HOX DNA methylation analysis revealed an age and survival-associated HOX-high signature that was tightly associated with HOXD12 gene body methylation. Overall, HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma.

The d3GHR carrier epigenome in Druze clan longevity.

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health.

Benchmarking sample pooling for epigenomics of natural populations.

DNA methylation (DNAm) is a mechanism for rapid acclimation to environmental conditions. In natural systems, small effect sizes relative to noise necessitates large sampling efforts to detect differences. Large numbers of individually sequenced libraries are costly. Pooling DNA prior to library preparation may be an efficient way to reduce costs and increase sample size, yet there are to date no recommendations in ecological epigenetics research. We test whether pooled and individual libraries yield comparable DNAm signals in a natural system exposed to different pollution levels by generating whole-epigenome data from two invasive molluscs (Corbicula fluminea, Dreissena polymorpha) collected from polluted and unpolluted localities (Italy). DNA of the same individuals were used for pooled and individual epigenomic libraries and sequenced with equivalent resources per individual. We found that pooling effectively captures similar genome-wide and global methylation signals as individual libraries, highlighting that pooled libraries are representative of the global population signal. However, pooled libraries yielded orders of magnitude more data than individual libraries, which was a consequence of higher coverage. We would therefore recommend aiming for a high initial coverage of individual libraries (15×) in future studies. Consequently, we detected many more differentially methylated regions (DMRs) with the pooled libraries and a significantly lower statistical power for regions from individual libraries. Computationally pooled data from the individual libraries produced fewer DMRs and the overlap with wet-lab pooled DMRs was relatively low. We discuss possible causes for discrepancies, list benefits and drawbacks of pooling, and provide recommendations for future epigenomic studies.

Giraffe: A tool for comprehensive processing and visualization of multiple long-read sequencing data.

Third-generation sequencing techniques have become increasingly popular due to their capacity to produce long, high-quality reads. Effective comparative analysis across various samples and sequencing platforms is essential for understanding biological mechanisms and establishing benchmark baselines. However, existing tools for long-read sequencing predominantly focus on quality control (QC) and processing for individual samples, complicating the comparison of multiple datasets. The lack of comprehensive tools for data comparison and visualization presents challenges for researchers with limited bioinformatics experience. To address this gap, we present Giraffe (https://github.com/lrslab/Giraffe_View), a Python3-based command-line tool designed for comparative analysis and visualization across diverse samples and platforms. Giraffe facilitates the assessment of read quality, sequencing bias, and genomic regional methylation proportions for both DNA and direct RNA sequencing reads. Its effectiveness has been demonstrated in various scenarios, including comparisons of sequencing methods (whole genome amplification vs. shotgun), sequencing platforms (Oxford Nanopore Technology, ONT vs. Pacific Biosciences, PacBio), tissues (kidney marrow with and without blood), and biological replicates (kidney marrows).

Methylome-wide association study of multidimensional resilience.

Although resilient youth provide an important model of successful adaptation to adversity, we know relatively little about the origins of their positive outcomes, particularly the role of biological mechanisms. The current study employed a series of methylome-wide association studies to identify methylomic biomarkers of resilience in a unique sample of 276 twins within 141 families residing in disadvantaged neighborhoods. Results revealed methylome-wide significant differentially methylated probes (DMPs) for social and academic resilience and suggestive DMPs for psychological resilience and resilience across domains. Pathway analyses informed our understanding of the biological underpinnings of significant differentially methylated probes. Monozygotic twin difference analyses were then employed to narrow in on DMPs that were specifically environmental in origin. Our findings suggest that alterations in the DNA methylome may be implicated in youth resilience to neighborhood adversity and that some of the suggestive DMPs may be environmentally engendered. Importantly, our ability to replicate our findings in a well-powered sample was hindered by the scarcity of twin samples with youth exposed to moderate to substantial levels of adversity. Thus, although preliminary, the present study is the first to identify DNA methylation biomarkers of academic and social resilience.

Blood-based HYAL2 methylation as a potential marker for the preclinical detection of coronary heart disease and stroke.

BACKGROUND: Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population. METHODS: In a prospective nested case-control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant. RESULTS: Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per - 10% methylation: 1.35-1.64, p ≤ 0.045 for HYAL2_CpG_1, HYAL2_CpG_2 and HYAL2_CpG_3 in CHD; ORs per - 10% methylation: 0.76-1.64, p ≤ 0.033 for HYAL2_CpG_2 and HYAL2_CpG_4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively]. CONCLUSIONS: This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases.

A study on the methylation patterns of DIO3 in patients with heart failure and its correlation with key clinical parameters.

Objective: This study aimed to analyze the methylation pattern of deoxyribonucleic acid (CpG) sites in the DIO3_FA26 promoter region of patients with heart failure (HF) and explore the correlation between differential CpG methylation levels and various clinical parameters. Methods: Peripheral blood specimens were collected from 20 patients with HF and 20 healthy individuals. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to identify and detect the CpG sites in the DIO3_FA26 promoter region. CpG methylation levels were compared between patients with HF and healthy controls and patients with HF with different levels of cardiac function. Results: The methylation level of DIO3_FA26_CpG_17.18 in patients with HF was significantly lower than that in the healthy control group (P = 0.0002). Among patients with HF and cardiac function levels of I/II and III/IV, methylation levels of DIO3_FA26_CpG_24.25.26.27 (P = 0.0168) were significantly lower in those with III/IV cardiac function compared to those with I/II cardiac function. Conclusion: The methylation level of DIO3_FA26_CpG_17.18 is significantly reduced in patients with HF, and that of DIO3_FA26_CpG_24.25.26.27 is significantly decreased in patients with III/IV cardiac function. Variations in DIO3_FA26 methylation levels influence coagulation, liver and kidney functions, and routine blood indexes, including D-dimer, albumin, calcium, and hemoglobin. This study provides clinical evidence for the involvement of DIO3_FA26 methylation in the occurrence and development of HF and proposes novel targets for HF prevention and treatment.

Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age.

Exercise training can significantly improve skeletal muscle mitochondrial function and has been proven to be highly relevant to alterations in skeletal muscle DNA methylation. However, it remains unclear whether late-in-life exercise has an effect on promoter methylation of PGC-1α, a key regulator of mitochondrial biogenesis. Here we employed two distinct exercise modalities, constant medium intensity exercise training (CMIT) and high-intensity interval exercise training (HIIT), to investigate their impacts on PGC-1α expression and methylation regulation in skeletal muscle of aged mice. The results revealed a notable decrease in PGC-1α expression in skeletal muscle of aged mice, accompanied by elevated methylation levels of the PGC-1α promoter, and increased DNA methyltransferase (DNMT) protein expressions. However, both forms of exercise training significantly corrected PGC-1α epigenetic changes, increased PGC-1α expression, and ameliorated skeletal muscle reduction. Furthermore, exercise training led to elevated expression of proteins related to mitochondrial biogenesis and energy metabolism in skeletal muscle, improving mitochondrial structure and function. In conclusion, late-in-life exercise improved skeletal muscle function, morphology, and mitochondria biogenesis, which may be associated with hypomethylation in promoters of PGC-1α and increased content of skeletal muscle PGC-1α. Notably, there was no clear difference between HIIT and CMIT in PGC-1α expression and skeletal muscle function.

Unraveling the genetic and epigenetic landscape governing intramuscular fat deposition in rabbits: Insights and implications.

Intramuscular fat (IMF) content is a predominant factor recognized to affect rabbit meat quality, directly impacting flavor, juiciness, and consumer preference. Despite its significance, the major interplay of genetic and epigenetic factors regulating IMF in rabbits remains largely unexplored. This review sheds light on this critical knowledge gap, offering valuable insights and future directions. We delve into the potential role of established candidate genes from other livestock (e.g. PPARγ, FABP4, and SCD) in rabbits, while exploring the identified novel genes of IMF in rabbits. Furthermore, we explored the quantitative trait loci studies in rabbit IMF and genomic selection approaches for improving IMF content in rabbits. Beyond genetics, this review unveils the exciting realm of epigenetic mechanisms modulating IMF deposition. We explored the potential of DNA methylation patterns, histone modifications, and non-coding RNA-mediation as fingerprints for selecting rabbits with desirable IMF levels. Additionally, we explored the possibility of manipulating the epigenetic landscape through nutraceuticals interventions to promote favorable IMF depositions. By comprehensively deciphering the genomic and epigenetic terrain of rabbit intramuscular fat regulation, this study aims to assess the existing knowledge regarding the genetic and epigenetic factors that control the deposition of intramuscular fat in rabbits. By doing so, we identified gaps in the current research, and suggested potential areas for further investigation that would enhance the quality of rabbit meat. This can enable breeders to develop targeted breeding strategies, optimize nutrition, and create innovative interventions to enhance the quality of rabbit meat, meet consumer demands and increase market competitiveness.

Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.

The progressive degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is accompanied by the formation of a broad array of cytoplasmic and nuclear neuronal inclusions (protein aggregates) largely containing RNA-binding proteins such as TAR DNA-binding protein 43 (TDP-43) or fused in sarcoma/translocated in liposarcoma (FUS/TLS). This process is driven by a liquid-to-solid phase separation generally from proteins in membrane-less organelles giving rise to pathological biomolecular condensates. The formation of these protein aggregates suggests a fundamental alteration in the mRNA expression or the levels of the proteins involved. Considering the role of the epigenome in gene expression, alterations in DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA modifications become highly relevant to understanding how this pathological process takes effect. In this review, we explore the evidence that links epigenetic mechanisms with the formation of protein aggregates in ALS. We propose that a greater understanding of the role of the epigenome and how this inter-relates with the formation of pathological LLPS in ALS will provide an attractive therapeutic target.

Genome-wide DNA methylation sequencing reveals the involvement of ferroptosis in hepatotoxicity induced by dietary exposure to food-grade titanium dioxide.

BACKGROUND: Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. METHODS: Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. RESULTS: Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. CONCLUSIONS: Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo.

Dietary Pattern's Role in Hepatic Epigenetic and Dietary Recommendations for the Prevention of NAFLD.

NAFLD has emerged as a significant public health concern, with its prevalence increasing globally. Emphasizing the complex relationship between dietary patterns and epigenetic modifications such as DNA methylation or miRNA expression can exert a positive impact on preventing and managing metabolic disorders, including NAFLD, within the 2030 Sustainable Development Goals. This review aims to evaluate the influence of dietary patterns on hepatic epigenetic gene modulation and provide dietary recommendations for the prevention and management of NAFLD in the general population. METHODS: Comprehensive screening and eligibility criteria identified eleven articles focusing on epigenetic changes in NAFLD patients through dietary modifications or nutrient supplementation. RESULTS AND DISCUSSION: Data were organized based on study types, categorizing them into evaluations of epigenetic changes in NAFLD patients through dietary pattern modifications or specific nutrient intake. CONCLUSIONS: The study highlights the importance of dietary interventions in managing and preventing NAFLD, emphasizing the potential of dietary patterns to influence hepatic epigenetic gene modulation. This study provides valuable insights and recommendations to mitigate the risk of developing NAFLD: (i) eat a primarily plant-based diet; (ii) increase consumption of high-fiber foods; (iii) consume more polyunsaturated and monounsaturated fatty acids; (iv) limit processed foods, soft drinks, added sugars, and salt; and (v) avoid alcohol.

Unlocking Plant Resilience: Advanced Epigenetic Strategies Against Heavy Metal and Metalloid Stress.

The escalating threat of heavy metal and metalloid stress on plant ecosystems requires innovative strategies to strengthen plant resilience and ensure agricultural sustainability. This review provides important insights into the advanced epigenetic pathways to improve plant tolerance to toxic heavy metals and metalloid stress. Epigenetic modifications, including deoxyribonucleic acid (DNA) methylation, histone modifications, and small ribonucleic acid (RNA) engineering, offer innovative avenues for tailoring plant responses to mitigate the impact of heavy metal and metalloid stress. Technological advancements in high-throughput genome sequencing and functional genomics have unraveled the complexities of epigenetic regulation in response to heavy metal and metalloid contamination. Recent strides in this field encompass identifying specific epigenetic markers associated with stress resilience, developing tools for editing the epigenome, and integrating epigenetic data into breeding programs for stress-resistant crops. Understanding the dynamic interaction between epigenetics and stress responses holds immense potential to engineer resilient crops that thrive in environments contaminated with heavy metals and metalloids. Eventually, harnessing epigenetic strategies presents a promising trajectory toward sustainable agriculture in the face of escalating environmental challenges. Plant epigenomics expands, the potential for sustainable agriculture by implementing advanced epigenetic approaches becomes increasingly evident. These developments lay the foundation for understanding the growing significance of epigenetics in plant stress biology and its potential to mitigate the detrimental effects of heavy metal and metalloid pollution on global agriculture.

Epigenetic alteration of uterine Leukemia Inhibitory Factor gene after glyphosate or a glyphosate-based herbicide exposure in rats.

Glyphosate-based herbicides (GBHs) or its active ingredient, glyphosate (Gly), induce implantation failure in rats. We aimed to elucidate a mechanism of action of these compounds assessing the transcriptional and epigenetic status of the receptivity marker, leukemia inhibitory factor (Lif) gene. F0 rats were orally exposed to GBH or Gly at 3.8 or 3.9mg Gly/kg/day, respectively, from gestational day (GD) 9 until weaning. F1 females were mated and uterine samples collected at GD5. Methylation-sensitive restriction enzymes (MSRE) sites and transcription factors were in silico predicted in regulatory regions of Lif gene. DNA methylation status and histone modifications (histone 3 and 4 acetylation (H3Ac and H4Ac) and H3 lysine-27-trimethylation (H3K27me3)) were assessed. GBH and Gly decreased Lif mRNA levels and caused DNA hypermethylation. GBH increased H3Ac levels, whereas Gly reduced them; both compounds enhanced H3K27me3 levels. Finally, both GBH and Gly induced similar epigenetic alterations in the regulatory regions of Lif.