-
Biochimica Et Biophysica Acta.... Jan 2023DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and... (Review)
Review
DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.
Topics: Humans; DNA Methylation; Leukocytes, Mononuclear; Biomarkers, Tumor; Circulating Tumor DNA; Neoplasms; Cell-Free Nucleic Acids
PubMed: 36270476
DOI: 10.1016/j.bbadis.2022.166583 -
Human Reproduction Update Sep 2019A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the...
BACKGROUND
A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the inheritance of such genetic information is accompanied by additional epigenetic marks, or stable heritable information that is not accounted for by variations in DNA sequence. The reversible nature of epigenetic marks coupled with multiple rounds of epigenetic reprogramming that erase the majority of existing patterns have made the investigation of this phenomenon challenging. However, continual advances in molecular methods are allowing closer examination of the dynamic alterations to histone composition and DNA methylation patterns that accompany development and, in particular, how these modifications can occur in an individual's germline and be transmitted to the following generation. While the underlying mechanisms that permit this form of transgenerational inheritance remain unclear, it is increasingly apparent that a combination of genetic and epigenetic modifications plays major roles in determining the phenotypes of individuals and their offspring.
OBJECTIVE AND RATIONALE
Information pertaining to transgenerational inheritance was systematically reviewed focusing primarily on mammalian cells to the exclusion of inheritance in plants, due to inherent differences in the means by which information is transmitted between generations. The effects of environmental factors and biological processes on both epigenetic and genetic information were reviewed to determine their contribution to modulating inheritable phenotypes.
SEARCH METHODS
Articles indexed in PubMed were searched using keywords related to transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits and environmental and biological factors influencing transgenerational modifications. We sought to clarify the role of epigenetic reprogramming events during the life cycle of mammals and provide a comprehensive review of how the genomic and epigenomic make-up of progenitors may determine the phenotype of its descendants.
OUTCOMES
We found strong evidence supporting the role of DNA methylation patterns, histone modifications and even non-protein-coding RNA in altering the epigenetic composition of individuals and producing stable epigenetic effects that were transmitted from parents to offspring, in both humans and rodent species. Multiple genomic domains and several histone modification sites were found to resist demethylation and endure genome-wide reprogramming events. Epigenetic modifications integrated into the genome of individuals were shown to modulate gene expression and activity at enhancer and promoter domains, while genetic mutations were shown to alter sequence availability for methylation and histone binding. Fundamentally, alterations to the nuclear composition of the germline in response to environmental factors, ageing, diet and toxicant exposure have the potential to become hereditably transmitted.
WIDER IMPLICATIONS
The environment influences the health and well-being of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status and the post-translational modification of histones. In evolutionary terms, these changes create the phenotypic diversity that fuels the fires of natural selection. However, rather than being adaptive, such variation may also generate a plethora of pathological disease states ranging from dominant genetic disorders to neurological conditions, including spontaneous schizophrenia and autism.
Topics: Animals; Biological Evolution; DNA Methylation; Epigenesis, Genetic; Genome; Germ Cells; Heredity; Histone Code; Histones; Humans; Mammals; Mutation; Parents; Phenotype
PubMed: 31374565
DOI: 10.1093/humupd/dmz017 -
Cell Death Discovery Apr 2024Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and... (Review)
Review
Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.
PubMed: 38589350
DOI: 10.1038/s41420-024-01935-2 -
Medicinal Research Reviews Mar 2024Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3... (Review)
Review
Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.
Topics: Humans; Lysine; Histone Demethylases; Monoamine Oxidase Inhibitors; Histones; Neoplasms; Drug Discovery; Enzyme Inhibitors
PubMed: 38014919
DOI: 10.1002/med.22000 -
The Science of the Total Environment Feb 2022Methane, a potent greenhouse gas of global importance, has traditionally been considered as an end product of microbial methanogenesis of organic matter. Paradoxically,... (Review)
Review
Methane, a potent greenhouse gas of global importance, has traditionally been considered as an end product of microbial methanogenesis of organic matter. Paradoxically, growing evidence has shown that some microbes, such as cyanobacteria, algae, fungi, purple non-sulfur bacteria, and cryptogamic covers, produce methane in oxygen-saturated aquatic and terrestrial ecosystems. The non-methanogenesis process could be an important potential contributor to methane emissions. This systematic review summarizes the knowledge of microorganisms involved in the non-methanogenesis process and the possible mechanisms of methane formation. Cyanobacteria-derived methane production may be attributed to either demethylation of methyl phosphonates or linked to light-driven primary productivity, while algae produce methane by utilizing methylated sulfur compounds as possible carbon precursors. In addition, fungi produce methane by utilizing methionine as a possible carbon precursor, and purple non-sulfur bacteria reduce carbon dioxide to methane by nitrogenase. The microbial methane distribution from the non-methanogenesis processes in aquatic and terrestrial environments and its environmental significance to global methane emissions, possible mechanisms of methane production in each open water, water-to-air methane fluxes, and the impact of climate change on microorganisms are also discussed. Finally, future perspectives are highlighted, such as establishing more in-situ experiments, quantifying methane flux through optimizing empirical models, distinguishing individual methane sources, and investigating nitrogenase-like enzyme systems to improve our understanding of microbial methane emission from the non-methanogenesis process.
Topics: Carbon Dioxide; Cyanobacteria; Ecosystem; Methane; Nitrogenase
PubMed: 34740653
DOI: 10.1016/j.scitotenv.2021.151362 -
Frontiers in Cardiovascular Medicine 2022Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like...
Endothelial-mesenchymal transition (EndMT) is a differentiation process in which endothelial cells lose their own characteristics and acquire mesenchymal-like characteristics, which contributes to the formation and development of atherosclerotic plaques. Until now, there is still a lack of effective measures to treat atherosclerosis (AS), so there is an urgent need to understand the underlying mechanisms of AS. In addition, although various studies have shown that EndMT is involved in the pathological stages of cardiovascular diseases, such as myocardial fibrosis, myocardial hypertrophy, and hypertension, the specific molecular mechanisms driving EndMT are still in the exploratory stage. In this review, we review the role of histone modifications (methylation, demethylation and acetylation, deacetylation) on EndMT in cardiovascular disease, aiming to target histone-modifying enzymes to guide cardiovascular disease therapy.
PubMed: 36568553
DOI: 10.3389/fcvm.2022.1022988 -
Hematology (Amsterdam, Netherlands) Dec 2023Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination.
METHOD
Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and 'netmeta' package, after study selection, quality assessment and data extraction.
RESULT
Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)].
CONCLUSION
ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.
Topics: Humans; Arsenic Trioxide; Network Meta-Analysis; Arsenicals; Oxides; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 37908176
DOI: 10.1080/16078454.2023.2274149 -
Cancers Oct 2021The survival rate of head and neck squamous cell carcinoma patients with the current standard of care therapy is suboptimal and is associated with long-term side... (Review)
Review
The survival rate of head and neck squamous cell carcinoma patients with the current standard of care therapy is suboptimal and is associated with long-term side effects. Novel therapeutics that will improve survival rates while minimizing treatment-related side effects are the focus of active investigation. Epigenetic modifications have been recognized as potential therapeutic targets in various cancer types, including head and neck cancer. This review summarizes the current knowledge on the function of important epigenetic modifiers in head and neck cancer, their clinical implications and discusses results of clinical trials evaluating epigenetic interventions in past and ongoing clinical trials as monotherapy or combination therapy with either chemotherapy, radiotherapy or immunotherapy. Understanding the function of epigenetic modifiers in both preclinical and clinical settings will provide insight into a more rational design of clinical trials using epigenetic interventions and the patient subgroups that may benefit from such interventions.
PubMed: 34680389
DOI: 10.3390/cancers13205241 -
European Review For Medical and... Mar 2021Abnormal DNA methylation plays a critical role in acute myeloid leukemia (AML) pathogenesis and hypomethylating agents (HMAs) such as decitabine (5-aza-29-deoxycytidine)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Abnormal DNA methylation plays a critical role in acute myeloid leukemia (AML) pathogenesis and hypomethylating agents (HMAs) such as decitabine (5-aza-29-deoxycytidine) and azacitidine (5-azacytidine) are considered efficacious for treating AML. This study aimed to identify if HMAs have therapeutic advantages compared with conventional care regimens (CCR) or placebo in elderly AML patients.
MATERIALS AND METHODS
We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to November July 15, 2020. Randomized controlled trials that compared the efficacy and adverse events associated with HMAs, CCR, or placebo were searched. RevMan 5.3 software was used to calculate the hazard ratio (HR) and risk ratio (RR) with a 95% confidence interval (CI).
RESULTS
Seven trials with a total of 1966 participants were included. Meta-analyses showed that the overall survival of HMAs was better than that of CCR [HR=0.76, 95% CI (0.69-0.85), (p<0.01)], and the complete remission rate of elderly AML patients was increased by HMAs compared with CCR [RR=1.46, 95%CI (1.08-1.99), p=0.01)]. HMA treatment showed higher incidence of neutropenia [RR=1.30 (95%CI 1.07-1.59, p=0.008)], thrombocytopenia [RR=1.14 (95%CI 1.01-1.59, p=0.04)], and pneumonia [RR=1.37 (95%CI 1.06-1.76, p=0.02)] compared with CCR.
CONCLUSIONS
Although HMAs cause a higher incidence of adverse events such as neutropenia, thrombocytopenia, and pneumonia, demethylation drugs are well-tolerated and effective for treating AML in the elderly.
Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; Humans; Leukemia, Myeloid, Acute; Randomized Controlled Trials as Topic
PubMed: 33829444
DOI: 10.26355/eurrev_202103_25421 -
The Science of the Total Environment Jun 2020The fate and transport of Hg species in natural aquatic environment are strongly affected by photochemical transformation of Hg, Hg, and MeHg. Migration of Hg is... (Review)
Review
The fate and transport of Hg species in natural aquatic environment are strongly affected by photochemical transformation of Hg, Hg, and MeHg. Migration of Hg is determined by its complexation with organic and inorganic ligands that are widely present in the water. The presence of dissolved organic matter (DOM) is closely related to photochemical reactions of Hg. DOM can strongly bind to mercury (e.g., Hg and MeHg), thus affecting its speciation, mobility and toxicity, eventually dominating its bioavailability. This review summarizes extensive studies on photochemical behaviors of Hg including: (1) photo-oxidation; (2) photo-reduction; (3) photochemical methylation; and (4) MeHg photo-degradation. Photo-oxidation of Hg is mostly caused by oxidative free radicals (e.g., •OH, CO, O, and O), while photo-reduction of Hg is more complicated and it involves two pathways: (1) primary processes (direct photolysis of Hg or ligand-metal charge transfer of Hg-DOM complex); and (2) secondary processes (reduction of Hg-DOM complex induced by free radicals derived from DOM photolysis). Photochemical methylation of inorganic Hg occurs as follows: (1) Hg complexes with methyl donors (e.g., acetic acid, tert-butyl, alcohols, etc.) to form intermediates, followed by (2) an intramolecular methyl transfer. MeHg photo-degradation is the leading pathway for MeHg demethylation and it primarily proceeds via four different pathways. The information on DOM was also mentioned, but DOM is not the only factor that affects the photochemical behaviors of Hg. Other influencing factors such as: (1) pH value; (2) dissolved oxygen; (3) cations (Fe, K) and anions (NO, HCO, CO, Cl); and (4) suspended substance cannot be ignored.
PubMed: 32143045
DOI: 10.1016/j.scitotenv.2020.137540