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Environmental Pollution (Barking, Essex... Jun 2024Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly... (Review)
Review
Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly utilized to produce epoxy resins, polycarbonate plastics, and other products. Mounting evidence has shown that BPs, especially BPA, may enter into the human body and participate in the development of human diseases mediated by nuclear hormone receptors. Moreover, BPA may negatively affect human health at the epigenetic level through processes such as DNA methylation and histone acetylation. Recent studies have demonstrated that, as part of epigenetics, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), have vital impacts on BP-related diseases, such as reproductive system diseases, nervous system diseases, digestive system diseases, endocrine system diseases, and other diseases. Moreover, based on the bioinformatic analysis, changes in ncRNAs may be relevant to normal activities and functions and BP-induced diseases. Thus, we conducted a meta-analysis to identify more promising ncRNAs as biomarkers and therapeutic targets for BP exposure and relevant human diseases. In this review, we summarize the regulatory functions of ncRNAs induced by BPs in human diseases and latent molecular mechanisms, as well as identify prospective biomarkers and therapeutic targets for BP exposure and upper diseases.
PubMed: 38942269
DOI: 10.1016/j.envpol.2024.124447 -
Current Opinion in Plant Biology Jun 2024Flowering plants exhibit unique DNA methylation dynamics during development. Particular attention can be focused on seed development and the embryo, which represents the... (Review)
Review
Flowering plants exhibit unique DNA methylation dynamics during development. Particular attention can be focused on seed development and the embryo, which represents the starting point of the sporophytic life cycle. A build-up of CHH methylation is now recognized as highly characteristic of embryo development. This process is thought to occur in order to silence potentially harmful transposable element expression, though roles in promoting seed dormancy and dessication tolerance have also been revealed. Recent studies show that increased CHH methylation in embryos inhabits both novel loci, unmethylated elsewhere in the plant, as well as shared loci, exhibiting more dense methylation. The role of DNA methylation in cis-regulatory gene regulation in plants is less well established compared to mammals, and here we discuss both transposable element regulation and the potential role of DNA methylation in dynamic gene expression.
PubMed: 38941722
DOI: 10.1016/j.pbi.2024.102593 -
PloS One 2024A differentially methylated region (DMR) is a genomic region that has significantly different methylation patterns between biological conditions. Identifying DMRs...
A differentially methylated region (DMR) is a genomic region that has significantly different methylation patterns between biological conditions. Identifying DMRs between different biological conditions is critical for developing disease biomarkers. Although methods for detecting DMRs in microarray data have been introduced, developing methods with high precision, recall, and accuracy in determining the true length of DMRs remains a challenge. In this study, we propose a normalized kernel-weighted model to account for similar methylation profiles using the relative probe distance from "nearby" CpG sites. We also extend this model by proposing an array-adaptive version in attempt to account for the differences in probe spacing between Illumina's Infinium 450K and EPIC bead array respectively. We also study the asymptotic results of our proposed statistic. We compare our approach with a popular DMR detection method via simulation studies under large and small treatment effect settings. We also discuss the susceptibility of our method in detecting the true length of the DMRs under these two settings. Lastly, we demonstrate the biological usefulness of our method when combined with pathway analysis methods on oral cancer data. We have created an R package called idDMR, downloadable from GitHub repository with link: https://github.com/DanielAlhassan/idDMR, that allows for the convenient implementation of our array-adaptive DMR method.
Topics: DNA Methylation; Humans; CpG Islands; Oligonucleotide Array Sequence Analysis; Mouth Neoplasms; Algorithms; Software; Computer Simulation
PubMed: 38941289
DOI: 10.1371/journal.pone.0306036 -
Age and Ageing Jun 2024Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study...
BACKGROUND
Epigenetic ageing is among the most promising ageing biomarkers and may be a useful marker of physical function decline, beyond chronological age. This study investigated whether epigenetic age acceleration (AA) is associated with the change in frailty scores over 7 years and the 7-year risk of incident frailty and persistent Activities of Daily Living (ADL) disability among 560 Australians (50.7% females) aged ≥70 years.
METHODS
Seven AA indices, including GrimAge, GrimAge2, FitAge and DunedinPACE, were estimated from baseline peripheral-blood DNA-methylation. Frailty was assessed using both the 67-item deficit-accumulation frailty index (FI) and Fried phenotype (Fried). Persistent ADL disability was defined as loss of ability to perform one or more basic ADLs for at least 6 months. Linear mixed models and Cox proportional-hazard regression models were used as appropriate.
RESULTS
Accelerated GrimAge, GrimAge2, FitAge and DunedinPACE at baseline were associated with increasing FI scores per year (adjusted-Beta ranged from 0.0015 to 0.0021, P < 0.05), and accelerated GrimAge and GrimAge2 were associated with an increased risk of incident FI-defined frailty (adjusted-HRs 1.43 and 1.39, respectively, P < 0.05). The association between DunedinPACE and the change in FI scores was stronger in females (adjusted-Beta 0.0029, P 0.001 than in males (adjusted-Beta 0.0002, P 0.81). DunedinPACE, but not the other AA measures, was also associated with worsening Fried scores (adjusted-Beta 0.0175, P 0.04). No associations were observed with persistent ADL disability.
CONCLUSION
Epigenetic AA in later life is associated with increasing frailty scores per year and the risk of incident FI-defined frailty.
Topics: Humans; Female; Activities of Daily Living; Male; Aged; Frailty; Frail Elderly; Epigenesis, Genetic; Geriatric Assessment; Aging; Risk Factors; Aged, 80 and over; Disability Evaluation; DNA Methylation; Age Factors; Risk Assessment; Time Factors; Functional Status
PubMed: 38941117
DOI: 10.1093/ageing/afae127 -
Alternative Therapies in Health and... Jun 2024Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone...
Study on the Mechanism of Xianling Gubao Capsule Regulating Runt-Related Transcription Factor 2 (RUNX2) and Promoting Osteoblast Differentiation by N6-Methyladenosine (m6A) Methyltransferase-Like 3 (METTL3).
BACKGROUND
Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and a higher risk of fractures. It is a significant public health concern, particularly among postmenopausal women and older adults. The imbalance between bone formation and resorption is the fundamental cause of OP. Current clinical drugs for OP have limited efficacy and can cause side effects. Therefore, there is a need to explore alternative treatments and investigate their mechanisms to improve OP management. The Xianling Gubao capsule, a traditional Chinese medicine, is commonly used to treat OP by tonifying the kidney. However, the specific mechanism of action of the Xianling Gubao capsule in improving OP remains unclear, necessitating further research in this area.
METHODS
The N6-methyladenosine (m6A) content was evaluated by dot blot and m6A ribonucleic acid (RNA) methylation assay kit. The contents of methyltransferase-like 3 (METTL3), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and bone gamma-carboxyglutamate protein (BGLAP) were appraised by quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) and western blot. The bilateral ovariectomy (OVX) method was used to establish an animal model of OP. OP bone marrow mesenchymal stem cells (OP-BMSCs) were extracted from mice in the OVX group by the whole bone marrow method. METTL3 overexpression and control vectors were transfected to OP-BMSCs using X-tremeGENE HP DNA Transfection Reagent. The ALP activity in OP-BMSCs was assessed by ALP staining. The calcium nodules in OP-BMSCs were detected by Alizarin Red S (ARS) assay. The Xianling Gubao capsule solution was employed to gavage mice, and the drug-containing serum was used to treat OP-BMSCs. Dot blot allows for the assessment of relative levels of m6A modification. The m6A RNA methylation assay kit is a specialized kit designed to quantitatively measure m6A levels in RNA samples. qRT-PCR allows for the measurement of mRNA levels of target genes. Western blot is used to detect and quantify specific proteins in a sample, and provides information about protein expression levels. OVX mimics the hormonal changes occurring in postmenopausal women and leads to bone loss and osteoporotic conditions in animals. This model allows for the investigation of the effects of the Xianling Gubao capsule on OP in a controlled experimental setting.
RESULTS
The m6A modification and METTL3, RUNX2, ALP, and BGLAP levels were reduced in bone samples of patients with OP and OVX mice compared with the corresponding control groups. Upregulated METTL3 enhanced the osteogenic ability of OP-BMSCs. METTL3 overexpression obviously increased m6A modification and METTL3, RUNX2, ALP, and BGLAP levels in OP-BMSCs. Xianling Gubao capsule treatment could weaken the impact of OP in mice by regulating the m6A modification and METTL3, RUNX2, ALP, and BGLAP levels. Serum containing Xianling Gubao capsule could enhance the osteogenic capability of OP-BMSCs and boost METTL3, RUNX2, ALP, and BGLAP levels. Treatment with the Xianling Gubao capsule shows promising effects in attenuating the impact of OP. The capsule is found to regulate m6A modification and increase the levels of METTL3, RUNX2, ALP, and BGLAP in OP-BMSCs. This indicates that the Xianling Gubao capsule may rescue the diminished osteogenic capability of OP-BMSCs by modulating METTL3. These findings suggest that the Xianling Gubao capsule has the potential to be an effective drug for the treatment of OP.
CONCLUSION
Taken together, the m6A modification and contents of osteogenic-related factors were reduced in OP. Upregulated METTL3 improved the osteogenic ability, m6A modification, and osteogenic-related factor abundances in OP-BMSCs. Xianling Gubao capsule rescued the diminished osteogenic capability of OP-BMSCs by modulating METTL3 and might serve as an effective drug for OP. The Xianling Gubao capsule, as a traditional Chinese medicine, could potentially complement existing therapeutic approaches for OP. By targeting the m6A modification pathway and promoting osteogenic differentiation, the capsule may help to expedite bone formation and repair, which are critical for managing OP and reducing the risk of fractures.
PubMed: 38940781
DOI: No ID Found -
The Journal of Clinical Endocrinology... Jun 2024Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or...
CONTEXT
Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential.
OBJECTIVE
To characterize the molecular landscape and deregulated pathways in APT.
METHODS
Whole exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000.
RESULTS
A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT.
CONCLUSIONS
APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation.
PubMed: 38940486
DOI: 10.1210/clinem/dgae441 -
Epigenomics Jun 2024
PubMed: 38940212
DOI: 10.1080/17501911.2024.2365615 -
Frontiers in Bioscience (Landmark... May 2024Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences.... (Review)
Review
Epigenetics refers to heritable changes in gene expression and function that impact nuclear processes associated with chromatin, all without altering DNA sequences. These epigenetic patterns, being heritable traits, are vital biological mechanisms that intricately regulate gene expression and heredity. The application of chemical labeling and single-cell resolution mapping strategies has significantly facilitated large-scale epigenetic modifications in nucleic acids over recent years. Notably, epigenetic modifications can induce heritable phenotypic changes, regulate cell differentiation, influence cell-specific gene expression, parentally imprint genes, activate the X chromosome, and stabilize genome structure. Given their reversibility and susceptibility to environmental factors, epigenetic modifications have gained prominence in disease diagnosis, significantly impacting clinical medicine research. Recent studies have uncovered strong links between epigenetic modifications and the pathogenesis of metabolic cardiovascular diseases, including congenital heart disease, heart failure, cardiomyopathy, hypertension, and atherosclerosis. In this review, we provide an overview of the progress in epigenetic research within the context of cardiovascular diseases, encompassing their pathogenesis, prevention, diagnosis, and treatment. Furthermore, we shed light on the potential prospects of nucleic acid epigenetic modifications as a promising avenue in clinical medicine and biomedical applications.
Topics: Humans; Epigenesis, Genetic; Cardiovascular Diseases; DNA Methylation; Animals
PubMed: 38940023
DOI: 10.31083/j.fbl2906205 -
Current Drug Delivery Jun 2024Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter...
Drug transporters are critical factors influencing the pharmacokinetics of drugs under hypoxic conditions. Studies have shown significant changes in drug transporter levels in the hypoxic environment. In addition to being regulated by HIF-1, nuclear receptors, and inflammatory factors, hypoxia can also regulate transporters through epigenetic modifications, thereby affecting drug absorption, distribution, metabolism, and excretion. In recent years, increasing attention has been paid to the role of epigenetic modifications in regulating drug transporters under hypoxic conditions at high altitude. In this paper, we comprehensively review the effects of hypoxia on drug transporters and epigenetic modifications and explore the regulatory mechanism of epigenetic modifications on drug transporter expression under hypoxic conditions. The aim is to provide a reference for exploring the epigenetic regulation mechanism of drug transporter expression in the hypoxic environment at high altitude, and then guide the study of pharmacokinetics and promote effective and safe medication at high altitude.
PubMed: 38939986
DOI: 10.2174/0115672018295087240620061102 -
Frontiers in Bioscience (Scholar... Jun 2024
Topics: Metals, Heavy; Epigenesis, Genetic; Plants; Stress, Physiological
PubMed: 38939977
DOI: 10.31083/j.fbs1602013