Myelodysplastic syndrome (MDS) is a chronic hematologic disorder characterized by ineffective hematopoiesis, dysplasia of one or more cell lines with or without definite genetic changes. Its diagnosis requires a comprehensive analysis combining morphology, immunology, cytogenetics, and molecular biology findings. In recent years, the development of second-generation sequencing (NGS) has provided great assistance in exploring the molecular pathogenesis of hematological malignancies and guidance for clinical practice. Mutations of a series of gene involved in RNA splicing, DNA methylation, transcriptional regulation, signal transduction, chromatin modification and cohesin complex have been identified as important mechanisms for the development of MDS, among which some mutations have been found to play important roles in the diagnosis, treatment, and prognosis of MDS. This article has provided a comprehensive review the the common molecular genetic abnormalities involved in MDS.
Humans ; Myelodysplastic Syndromes/diagnosis* ; Mutation ; DNA Methylation ; RNA Splicing ; High-Throughput Nucleotide Sequencing

Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation ; Humans ; Space Flight ; Mental Disorders/genetics* ; Epigenesis, Genetic ; Astronauts/psychology* ; Weightlessness/adverse effects* ; Epigenomics

Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue. Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence, influencing diverse physiological activities, including immune response, inflammation, and bone metabolism. Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition. However, the impact of these factors on peri-implantitis remains inconclusive. To address this gap, we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis, specifically focusing on DNA methylation and microRNAs (miRNAs or miRs). We searched for relevant literature on PubMed, Web of Science, Scopus, and Google Scholar with keywords including "epigenetics," "peri-implantitis," "DNA methylation," and "microRNA." DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants. Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis. In addition, we assessed the potential application of DNA methylation and miRNAs in the prevention, diagnosis, and treatment of peri-implantitis, aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition. These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.
Peri-Implantitis/genetics* ; Humans ; Epigenesis, Genetic ; DNA Methylation ; MicroRNAs/genetics*

OBJECTIVES: To evaluate the effect of eye acupuncture on neural function and angiogenesis of ischemic cerebral tissue in rats, and explore the roles of METTL3-mediated m⁶A methylation and the HIF-1α/VEGF-A signal axis in mediating this effect. METHODS: Fifty SD rats were randomized into normal control group, sham-operated group, model group, eye acupuncture group and DMOG (a HIF-1α agonist) group. Rat models of cerebral ischemia/reperfusion injury (CIRI) were established using a modified thread thrombus method, and the changes in neurological deficits of the rats after interventions were evaluated. TTC and Nissl staining were used to examine the changes in infarction size and neuronal injury, and cerebral angiogenesis was detected by double-immunofluorescence staining. m⁶A methylation modification level in the brain tissue was detected by ELISA, and RT-qPCR and Western blotting were used to detect the mRNA and protein expressions of METTL3 and HIF-1α/VEGF-A. RESULTS: Compared with the control and sham-operated rats, the CIRI rats had significantly higher neurological deficit scores with larger cerebral infarction area, a greater number of CD31- and EDU-positive new vessels, higher expression levels of HIF-1α and VEGF-A, reduced number of Nissl bodies and m6A methylation level, and lowered METTL3 protein and mRNA expressions. All these changes were significantly improved by interventions with eye acupuncture after modeling or intraperitoneal injections of DMOG for 7 consecutive days prior to modeling, and the effects of the two interventions were similar. CONCLUSIONS Eye acupuncture can improve neurological deficits in CIRI rat models possibly by promoting cortical angiogenesis via upregulating METTL3-mediated m⁶A methylation and regulating the HIF-1α/VEGF-A signal axis.
Animals ; Rats, Sprague-Dawley ; Methyltransferases/metabolism* ; Reperfusion Injury/physiopathology* ; Methylation ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats ; Vascular Endothelial Growth Factor A/metabolism* ; Brain Ischemia/metabolism* ; Acupuncture Therapy ; Male ; Up-Regulation ; Neovascularization, Physiologic ; Angiogenesis ; Adenosine/analogs & derivatives*

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health and play an important role in tissue engineering and regenerative medicine because of their multidirectional differentiation potential and self-renewal ability. The cellular microenvironment regulates the fate of stem cells and can be modified using various optimization techniques. These methods can influence the cellular microenvironment, activate disparate signaling pathways, and induce different biological effects. "Epigenetic regulation" refers to the process of influencing gene expression and regulating cell fate without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate pivotal transcription factors governing DMSCs differentiation into osteo-/odontogenic lineages. The most important sites of histone methylation in tooth organization were found to be H3K4, H3K9, and H3K27. Histone methylation affects gene expression and regulates stem cell differentiation by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial signaling pathways associated with osteogenic differentiation are susceptible to modulation via histone methylation modifications. A deeper understanding of the regulatory mechanisms governing histone methylation modifications in osteo-/odontogenic differentiation and immune-inflammatory responses of DMSCs will facilitate further investigation of the epigenetic regulation of histone methylation in DMSC-mediated tissue regeneration and inflammation. Here is a concise overview of the pivotal functions of epigenetic histone methylation at H3K4, H3K9, and H3K27 in the regulation of osteo-/odontogenic differentiation and renewal of DMSCs in both non-inflammatory and inflammatory microenvironments. This review summarizes the current research on these processes in the context of tissue regeneration and therapeutic interventions.
Mesenchymal Stem Cells/physiology* ; Humans ; Osteogenesis/genetics* ; Histones/metabolism* ; Cell Differentiation/physiology* ; Methylation ; Odontogenesis/genetics* ; Epigenesis, Genetic

Human naïve pluripotent stem cells (PSCs) hold great promise for embryonic development studies. Existing induction and culture strategies for these cells, heavily dependent on MEK inhibitors, lead to widespread DNA hypomethylation, aberrant imprinting loss, and genomic instability during extended culture. Here, employing high-content analysis alongside a bifluorescence reporter system indicative of human naïve pluripotency, we screened over 1,600 chemicals and identified seven promising candidates. From these, we developed four optimized media-LAY, LADY, LUDY, and LKPY-that effectively induce and sustain PSCs in the naïve state. Notably, cells reset or cultured in these media, especially in the LAY system, demonstrate improved genome-wide DNA methylation status closely resembling that of pre-implantation counterparts, with partially restored imprinting and significantly enhanced genomic stability. Overall, our study contributes advancements to naïve pluripotency induction and long-term maintenance, providing insights for further applications of naïve PSCs.
Humans ; DNA Methylation/drug effects* ; Genomic Instability ; Pluripotent Stem Cells/metabolism* ; Cell Culture Techniques/methods* ; Cells, Cultured

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Epigenetics refers to a heritable phenomenon that dynamically modulates gene expression without altering the DNA sequence, through molecular mechanisms such as DNA methylation, histone modification, non-coding RNA, chromatin remodeling, and RNA modifications. In plants, these modifications are extensively involved in key biological processes, including flowering time, gametogenesis, stress responses, and immune defenses. Over the past few decades, the research on epigenetics has gradually shifted from fundamental studies primarily conducted in Arabidopsis thaliana to investigations in various crop species such as rice and tomato. This transition has revealed the multifaceted roles of epigenetic regulation in shaping agronomic traits. This review integrates current knowledge of epigenetic regulatory mechanisms and their functions in plant responses to both biotic and abiotic stresses. Epigenetic editing tools such as CRISPR-dCas9 enable targeted DNA methylation or histone acetylation. Emerging transformation technologies, including magnetic nanoparticles and virus-based delivery systems, have the potential to overcome the bottlenecks of plant regeneration, offering new possibilities for precise epigenetic editing. In future agriculture, it is essential to further elucidate multi-layered epigenetic regulatory mechanisms at the single-cell level, develop efficient delivery systems, and leverage artificial intelligence to advance the application of epigenetic breeding for sustainable agricultural development.
Epigenesis, Genetic/genetics* ; Crops, Agricultural/genetics* ; Plant Breeding/methods* ; DNA Methylation/genetics* ; Gene Editing ; Disease Resistance/genetics* ; CRISPR-Cas Systems