Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional bree...Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.展开更多
Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA...Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.展开更多
Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologie...Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulat...A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.展开更多
Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epi...Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epilepsy,structural remodeling and functional disorders in this region have become the focus of research,and the existing evidence mostly focuses on hippocampal sclerosis,a typical neurodegenerative change.However,there is still a lack of systematic analysis of the pathological subtypes under the International League Against Epilepsy(ILAE)classification system in cross-scale molecular events such as epigenetic regulation and microbiome-brain axis.By integrating clinical cohort data and experimental model evidence,this article focuses on the association characteristics between hippocampal sclerosis subtypes and seizure patterns,and reveals the formation of abnormal hippocampal network and the cascading effect of abnormal hippocampus-related neurotransmitters in the formation of epileptogenic network.The study found that specific pathological subtypes showed a significant correspondence with seizure frequency and drug sensitivity,suggesting that hippocampal sclerosis drives epilepsy progression through multidimensional molecular events.In the future,it is necessary to combine spatial transcriptome and targeted metabolomics technology to analyze the cell interaction network in the hippocampal microenvironment,so as to provide a theoretical basis for the development of subtype-specific antiepileptic strategies.展开更多
Epidemiological studies indicate a strong correlation between various types of human cancer and dietary factors,whereas the specific mechanisms remain to be fully elucidated.Epigenetic alterations,such as DNA methylat...Epidemiological studies indicate a strong correlation between various types of human cancer and dietary factors,whereas the specific mechanisms remain to be fully elucidated.Epigenetic alterations,such as DNA methylation,histone modifications,and noncoding RNA,are influenced by dietary components,especially phytochemicals and nutrients that participate in one-carbon metabolism.These alterations significantly impact cancer occurrence and progression.Consequently,epigenetic pathways may mediate the effects of diet on cancer risk.This review synthesizes the current information regarding the association of epigenetic alterations with cancer initiation and development,as well as the mechanisms by which diet exerts its influence on these changes.The goal of this minireview is to enhance the understanding of the roles of diet on epigenetic alterations to improve cancer prevention and treatment through diet.展开更多
Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematic...Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.展开更多
The Jianglang Dome has integral tectonostratigraphic units and contains a suite of high-grade stratiform Cu deposits.However,the formation mechanism of this dome and genetic model of Cu mineralization remain a matter ...The Jianglang Dome has integral tectonostratigraphic units and contains a suite of high-grade stratiform Cu deposits.However,the formation mechanism of this dome and genetic model of Cu mineralization remain a matter of debate.The resolution of these problems hinges on the presence of magmatic intrusions in the core.Here,we report bulk geochemical and zircon U-Pb data of a newly discovered syenite intrusion as well as chalcopyrite Re-Os dating results.We aim to explore genesis of the Jianglang Dome,genetic model of the stratiform Cu deposits,and rare metal mineralization potential of the syenite intrusion.The dated syenite sample yields an emplacement age of 207.1±2.0 Ma,which matches post-collisional extension in the Songpan-Ganze Orogen.The syenite rocks have average high(Zr+Nb+Ce+Y)concentrations of 512 ppm,10000.Ga/Al ratios of 3.97,and crystallization temperatures of 827°C,together with low Mg#values of 1.73;they fi t the A-type granitoid defi nition and a crustal origin.Chalcopyrite separates yield a Re-Os isochron age of 207.1±5.3 Ma,which markedly postdates the formation age of their orehosting rocks(the Liwu Group,ca.553 Ma).Our new age determination,together with previous chalcopyrite Re–Os isochron age of ca.151.1 Ma and sulfi de sulfur isotope(δ^(34)S_(V-CDT)=8.7‰–5.6‰)and tourmaline boron isotope(δ^(11)B=−15.47‰to−5.91‰)data,confi rms multistage epigenetic Cu mineralization related to magmatic-hydrothermal fl uids.Compared with regional ca.209–207 Ma fertile granitoids,the studied syenite intrusion shows unevolved and barren affi nities and negligible rare metal mineralization potential.Combined with residual gravity low anomalies in the core of the Jianglang Dome,which suggest a large deepseated granitic batholith,we prefer thermal doming resulting from magma-induced uplift for the nature of this dome.展开更多
Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a...Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.展开更多
Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcript...Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells.Among the extensive methylation differences across various stages and tissues,we identify tissue-specific differentially methylated regions(tsDMRs)unique to the rumen,which are crucial for regulating epithelial development and energy metabolism.These tsDMRs cluster within super-enhancer regions that overlap with transcription factor(TF)binding sites.Regression models indicate that DNA methylation,along with H3K27me3 and H3K27ac,can be used to predict enhancer activity.Key upstream TFs,including SOX2,FOSL1/2,and SMAD2/3,primarily maintain an inhibitory state through bivalent modifications during fetal development.Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete.Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function,providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.展开更多
Pancreatic cancer(PC)is a highly malignant digestive system cancer that is difficult to diagnose early and is highly resistant to conventional treatments.Recent studies on epigenetics have provided new insights into t...Pancreatic cancer(PC)is a highly malignant digestive system cancer that is difficult to diagnose early and is highly resistant to conventional treatments.Recent studies on epigenetics have provided new insights into the early diagnosis of PC and treatments including immunotherapy.Epigenetic changes can alter gene expression without altering the DNA sequence,involving mechanisms such as DNA methylation,histone modification,and the abnormal expression of noncoding RNAs.These mechanisms play crucial roles in the occurrence,development,and therapeutic response of tumors.This review summarizes progress in epigenetic research on PC and discusses the epigenetic characteristics,underlying mechanisms,early diagnosis,prognostic evaluation,treatment strategies,and future challenges for PC.Strategies targeting epigenetic changes may restore the expression of tumor suppressor genes and regulate the immune microenvironment and may be combined with immune checkpoint inhibitors as a new approach for the precise treatment of PC.However,there are challenges associated with the clinical application of epigenetic therapy,such as the development of resistance and adverse side effects,and challenges in target selection,so new epigenetic drugs and combination treatment strategies are needed.With the development of precision medicine,the integration of epige-netics and clinical medicine research has yielded broadly applicable findings.Interdisciplinary cooperation and advancements in clinical trials will further promote the application of epigenetics in PC research,providing more effective treatment options for patients.In the future,the combined application of epigenetic therapy and immunotherapy,the design of personalized treatment plans,and the development of technologies such as liquid biopsy will likely change the treatment landscape of PC.展开更多
Background:Fibrosis constitutes a significant pathophysiological mechanism in the clinical progression of benign prostatic hyperplasia(BPH)and represents a contributing factor to the ineffectiveness of prevailing phar...Background:Fibrosis constitutes a significant pathophysiological mechanism in the clinical progression of benign prostatic hyperplasia(BPH)and represents a contributing factor to the ineffectiveness of prevailing pharmacological treatments.Emerging evidence suggests a close association between microbial presence and the development of fibrosis.Nonetheless,the potential involvement of microbes within prostatic tissue in the pathogenesis of BPH and prostatic fibrosis,along with the underlying mechanisms,remains unexplored.Methods:Utilizing immunohistochemistry and microbial sequencing,we analyzed the microbes of prostate tissues from BPH patients with different degrees of prostate fibrosis and found that Salmonellaenterica(S.enterica)was enriched in the high degree of prostate fibrosis.We developed prostate cell and animal models infected with the lipopolysaccharide of S.enterica(S.e-LPS)to assess its impact on prostate fibrosis.To elucidate the underlying functional mechanisms,we employed molecular biology techniques,including RNA degradation assays,N6-methyladenosine(m6A)dot blotting,RNA immunoprecipitation,and m6A immunoprecipitation.Results:Microbial diversity differed between low-and high-fibrosis groups,with S.enterica showing the highest mean abundance among the 4 species that differed significantly.S.e-LPS was detected in S.enterica-rich prostate tissue and was found to significantly promote cell proliferation,cell contractility,lipid peroxidation,and the induction of ferroptosis.Animal experiments demonstrated that S.e-LPS infection led to pronounced hyperplasia of the prostatic epithelium,with epithelial thickness increasing to 1.57 times that of the sham group,and collagen fibrosis increasing to 2.84 times that of the sham group,thereby exacerbating prostatic tissue fibrosis in rats.Invitro experiments further revealed that S.e-LPS promoted prostate cell fibrosis by inducing ferroptosis.Mechanistically,it was determined that S.e-LPS regulates ferroptosis via AlkB homolog 5(ALKBH5)-mediated m6A modification,which affects the stability of glutathione peroxidase 4(GPX4)mRNA,thereby affecting prostatic fibrosis.Conclusion:The findings of this study suggest that S.enterica promotes prostatic fibrosis through ALKBH5-m6A-GPX4-mediated ferroptosis.This research offers novel insights for the development of new therapeutic targets and personalized strategies for the prevention and treatment of BPH from the perspectives of microbes and epigenetics.展开更多
Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathoge...Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathogenesis.Herein,we review the current progress in genetics and epigenetics to examine genetic variants,susceptibility factors,and the epigenetic regulatory mechanisms implicated in CS.Through an analysis of diverse genetic markers,chromosomal abnormalities,and epigenetic modifications,the correlation between genetic predisposition and environmental influences in CS pathogenesis is elucidated.By integrating these genetic and epigenetic findings,this study aims to clarify the underlying etiology of CS to provide guidance on future clinical interventions and promote the development of personalized therapeutic strategies.展开更多
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,influe...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.展开更多
The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via...The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via heavy metal exposures and nutritional deficits that impact the expression of genes.In the case of the metallothionein(MT)gene,biomarker studies show dietary zinc(Zn)deficits impact MT protein levels in children with autism and are associated with the bioaccumulation of lead and/or mercury in children exhibiting autism/attention deficit/hyperactivity disorders symptomology.The impact of dietary changes on lead and mercury exposures and MT gene behavior could be determined using a randomized test and control group design.Pregnant women serving in the testgroup would participate in a nutritional epigenetics education intervention/course designed to reduce ultra-processed food intake and heavy metal levels in blood while increasing whole food intake and MT and Zn levels.Changes in maternal diet would be measured using data derived from an online diet survey administered to the test and control groups pre-post intervention.Changes in maternal lead,mercury,Zn,and MT levels would be measured via blood sample analyses prior to the intervention and after childbirth via cord blood analyses to determine infant risk factors.展开更多
Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not ...Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.展开更多
To improve understanding of the multifaceted nature of metabolic dysfunction-associated steatotic liver disease(MASLD),the American Association for the Study of Liver Diseases,in collaboration with the European Associ...To improve understanding of the multifaceted nature of metabolic dysfunction-associated steatotic liver disease(MASLD),the American Association for the Study of Liver Diseases,in collaboration with the European Association for the Study of the Liver and the Latin American Association for the Study of the Liver,proposed a broader and more flexible definition,highlighting the role of underlying metabolic dysfunction.MASLD represents the most common chronic liver disease worldwide;however,the impact of the disease goes beyond its epidemiological aspects.Currently,the impact on patients and healthcare syst-ems,due to hepatic and extrahepatic complications,is significant.Recent evidence has demonstrated that epigenetic regulation plays a key role in the development and progression of MASLD.This highly sophisticated regulatory system includes DNA methylation,histone modification,chromatin remodeling,and modulation of non-coding RNA,without causing changes in the primary DNA sequence.Diet,particularly the Westernized diet(characterized by high levels of processed foods,fats,and sugars,but deficient in vitamins and minerals),contributes to the pathogenesis of MASLD through epigenetic modulation at multiple levels.Given the association between diet,epigenetics,and MASLD,this review aims to present some micronutrients and their importance in the prevention and/or treatment of metabolically dysfunction-associated steatotic liver disease.展开更多
Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent researc...Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.展开更多
基金supported by funding from the National Key R&D Program of China(2023ZD0407304)the Sci-Tech Innovation 2030 Agenda(2022ZD0115703)Fundamental Research Funds for Central Non-Profit of Chinese Academy of Agricultural Sciences(Y2023PT20).
文摘Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.
文摘Epigenetics is the discipline of regulating cellular activity through chemical modification or modulation of noncoding RNAs without altering the nucleotide sequence.Studies on this topic include the exploration of DNA methylation,histone modification,noncoding RNA regulation,and chromatin remodeling.Derived from the apical tissues of young permanent teeth,stem cells from apical papilla are odontogenic adult stem cells with high proliferation,self-renewal capacity,and differentiation potential.These cells play crucial roles in root formation and development.This article focuses on the two epigenetic regulatory mechanisms of histone modifications and non-coding RNA.This review summarizes,generalizes,and evaluates the status of research on the epigenetic regulation of the multidirectional differentiation of stem cells from the apical papilla,aiming to explore the mechanisms underlying the multidirectional differentiation process of these stem cells.
基金supported by the National Natural Science Foundation of China(Nos.82271158,82301312,82071045,82101219,82071048).
文摘Hearing loss,which currently affects more than 430 million individuals globally and is projected to exceed 700 million by 2050,predominantly manifests as sensorineural hearing loss(SNHL),for which existing technologies such as hearing aids and cochlear implants fail to restore natural auditory function.Research focusing on protecting inner ear hair cells(HCs)from harmful factors through the regulation of epigenetic modifications has gained significant attention in otology for its role in regulating gene expression without altering the DNA sequence,suggesting potential strategies for preventing and treating SNHL.By synthesizing relevant studies on the inner ear,this review summarizes the emerging roles of histone modifications,DNA methylation,and noncoding RNAs in HC damage,with a focus on their therapeutic potential through epigenetic modulation.Moreover,this review examines the therapeutic potential of epigenetic regulation for the prevention and treatment of SNHL,emphasizing the application of small-molecule epigenetic compounds and their efficacy in modulating gene expression to preserve and restore auditory function.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
文摘A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.
文摘Objective As the core unit of the limbic system,the hippocampus is involved in the regulation of higher neural activity by integrating emotional encoding and memory storage functions.In the pathological process of epilepsy,structural remodeling and functional disorders in this region have become the focus of research,and the existing evidence mostly focuses on hippocampal sclerosis,a typical neurodegenerative change.However,there is still a lack of systematic analysis of the pathological subtypes under the International League Against Epilepsy(ILAE)classification system in cross-scale molecular events such as epigenetic regulation and microbiome-brain axis.By integrating clinical cohort data and experimental model evidence,this article focuses on the association characteristics between hippocampal sclerosis subtypes and seizure patterns,and reveals the formation of abnormal hippocampal network and the cascading effect of abnormal hippocampus-related neurotransmitters in the formation of epileptogenic network.The study found that specific pathological subtypes showed a significant correspondence with seizure frequency and drug sensitivity,suggesting that hippocampal sclerosis drives epilepsy progression through multidimensional molecular events.In the future,it is necessary to combine spatial transcriptome and targeted metabolomics technology to analyze the cell interaction network in the hippocampal microenvironment,so as to provide a theoretical basis for the development of subtype-specific antiepileptic strategies.
文摘Epidemiological studies indicate a strong correlation between various types of human cancer and dietary factors,whereas the specific mechanisms remain to be fully elucidated.Epigenetic alterations,such as DNA methylation,histone modifications,and noncoding RNA,are influenced by dietary components,especially phytochemicals and nutrients that participate in one-carbon metabolism.These alterations significantly impact cancer occurrence and progression.Consequently,epigenetic pathways may mediate the effects of diet on cancer risk.This review synthesizes the current information regarding the association of epigenetic alterations with cancer initiation and development,as well as the mechanisms by which diet exerts its influence on these changes.The goal of this minireview is to enhance the understanding of the roles of diet on epigenetic alterations to improve cancer prevention and treatment through diet.
基金Supported by Quzhou Science and Technology Plan Project,No.2024K076.
文摘Diabetic retinopathy(DR)is a major microvascular complication of diabetes,with its pathogenesis involving metabolic memory,epigenetic dysregulation,and multi-cellular microenvironmental disorders.This study systematically invest-igates the mechanism by which curcumol ameliorates DR through regulation of the FTO/MAFG-AS1 epigenetic axis and reveals its therapeutic potential in tar-geting the retinal microenvironment via a nano-delivery system.Experimental results demonstrate that curcumol activates the demethylase activity of FTO,sta-bilizing the expression of the long non-coding RNA MAFG-AS1,thereby inhi-biting high glucose-induced retinal endothelial cell inflammation,migration,and vascular leakage.Single-cell transcriptomic analysis further uncovered the dual role of FTO in DR:On the one hand,it promotes pathological angiogenesis in endothelial cells,while on the other hand,it exerts protective effects through MAFG-AS1-mediated antioxidative and anti-inflammatory functions.Moreover,this study proposes a multidimensional epigenetic regulatory network based on histone lactylation,N6-methyladenosine modification,and DNA methylation,and verifies that curcumol delays DR progression by coordinately modulating these modifications.To overcome the limitations of conventional therapies,this study innovatively designed a macrophage membrane-coated nano-delivery system,significantly enhancing the retinal targeting and bioavailability of curcumol.Finally,the study advocates a paradigm shift from passive treatment to early prevention,proposing a three-tiered intervention strategy that integrates epigenetic biomarkers with artificial intelligence-based risk assessment.These findings not only elucidate the multi-target regulatory mechanisms of curcumol but also provide a theoretical foundation for the development of precision therapies for DR based on epigenetic remodeling and microenvironmental synergistic intervention.
基金supported by the National Natural Science Foundation of China(Nos.41902068,42272106)Young Scholars Development Fund of Southwest Petroleum University(No.201499010083)China Geological Survey Project(Nos.DD20230338,DD20242494)。
文摘The Jianglang Dome has integral tectonostratigraphic units and contains a suite of high-grade stratiform Cu deposits.However,the formation mechanism of this dome and genetic model of Cu mineralization remain a matter of debate.The resolution of these problems hinges on the presence of magmatic intrusions in the core.Here,we report bulk geochemical and zircon U-Pb data of a newly discovered syenite intrusion as well as chalcopyrite Re-Os dating results.We aim to explore genesis of the Jianglang Dome,genetic model of the stratiform Cu deposits,and rare metal mineralization potential of the syenite intrusion.The dated syenite sample yields an emplacement age of 207.1±2.0 Ma,which matches post-collisional extension in the Songpan-Ganze Orogen.The syenite rocks have average high(Zr+Nb+Ce+Y)concentrations of 512 ppm,10000.Ga/Al ratios of 3.97,and crystallization temperatures of 827°C,together with low Mg#values of 1.73;they fi t the A-type granitoid defi nition and a crustal origin.Chalcopyrite separates yield a Re-Os isochron age of 207.1±5.3 Ma,which markedly postdates the formation age of their orehosting rocks(the Liwu Group,ca.553 Ma).Our new age determination,together with previous chalcopyrite Re–Os isochron age of ca.151.1 Ma and sulfi de sulfur isotope(δ^(34)S_(V-CDT)=8.7‰–5.6‰)and tourmaline boron isotope(δ^(11)B=−15.47‰to−5.91‰)data,confi rms multistage epigenetic Cu mineralization related to magmatic-hydrothermal fl uids.Compared with regional ca.209–207 Ma fertile granitoids,the studied syenite intrusion shows unevolved and barren affi nities and negligible rare metal mineralization potential.Combined with residual gravity low anomalies in the core of the Jianglang Dome,which suggest a large deepseated granitic batholith,we prefer thermal doming resulting from magma-induced uplift for the nature of this dome.
基金supported by grants from the Deutsche Forschungsgemeinschaft(DFG)to MW.
文摘Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.
基金funded by the Science and Technology Major Project of the Inner Mongolia Autonomous Region of China to the State Key Laboratory of Reproductive Regulation(2023KYPT0010 and 2021ZD0048)STI 2030-Major Projects(2023ZD0407504)of China+1 种基金the development plan for young scientific and technological talents in colleges and universities of Inner Mongolia Autonomous Region of China(NMGIRT2204)the National Natural Science Foundation of China(32160172).
文摘Epigenetic regulation in the rumen,a unique ruminant organ,remains largely unexplored compared with other tissues studied in model species.In this study,we perform an in-depth analysis of the epigenetic and transcriptional landscapes across fetal and adult bovine tissues as well as pluripotent stem cells.Among the extensive methylation differences across various stages and tissues,we identify tissue-specific differentially methylated regions(tsDMRs)unique to the rumen,which are crucial for regulating epithelial development and energy metabolism.These tsDMRs cluster within super-enhancer regions that overlap with transcription factor(TF)binding sites.Regression models indicate that DNA methylation,along with H3K27me3 and H3K27ac,can be used to predict enhancer activity.Key upstream TFs,including SOX2,FOSL1/2,and SMAD2/3,primarily maintain an inhibitory state through bivalent modifications during fetal development.Downstream functional genes are maintained mainly in a stable repressive state via DNA methylation until differentiation is complete.Our study underscores the critical role of tsDMRs in regulating distal components of rumen morphology and function,providing key insights into the epigenetic regulatory mechanisms that may influence bovine production traits.
基金National Natural Science Foundation of China,No.82304628Natural Science Foundation of Zhejiang Province,No.LQ23H160047.
文摘Pancreatic cancer(PC)is a highly malignant digestive system cancer that is difficult to diagnose early and is highly resistant to conventional treatments.Recent studies on epigenetics have provided new insights into the early diagnosis of PC and treatments including immunotherapy.Epigenetic changes can alter gene expression without altering the DNA sequence,involving mechanisms such as DNA methylation,histone modification,and the abnormal expression of noncoding RNAs.These mechanisms play crucial roles in the occurrence,development,and therapeutic response of tumors.This review summarizes progress in epigenetic research on PC and discusses the epigenetic characteristics,underlying mechanisms,early diagnosis,prognostic evaluation,treatment strategies,and future challenges for PC.Strategies targeting epigenetic changes may restore the expression of tumor suppressor genes and regulate the immune microenvironment and may be combined with immune checkpoint inhibitors as a new approach for the precise treatment of PC.However,there are challenges associated with the clinical application of epigenetic therapy,such as the development of resistance and adverse side effects,and challenges in target selection,so new epigenetic drugs and combination treatment strategies are needed.With the development of precision medicine,the integration of epige-netics and clinical medicine research has yielded broadly applicable findings.Interdisciplinary cooperation and advancements in clinical trials will further promote the application of epigenetics in PC research,providing more effective treatment options for patients.In the future,the combined application of epigenetic therapy and immunotherapy,the design of personalized treatment plans,and the development of technologies such as liquid biopsy will likely change the treatment landscape of PC.
基金supported by the National Key Research and Development Program of China(2022YFC3600700)the National Natural Science Foundation of China(82370778)+2 种基金the Hubei Provincial Natural Science Foundation of China(2023AFA061)the Fundamental Research Funds for the Central Universities(2042024kf1043)the Young Top-Notch Talent Cultivation Program of Hubei Province(for Prof.Zeng XT).
文摘Background:Fibrosis constitutes a significant pathophysiological mechanism in the clinical progression of benign prostatic hyperplasia(BPH)and represents a contributing factor to the ineffectiveness of prevailing pharmacological treatments.Emerging evidence suggests a close association between microbial presence and the development of fibrosis.Nonetheless,the potential involvement of microbes within prostatic tissue in the pathogenesis of BPH and prostatic fibrosis,along with the underlying mechanisms,remains unexplored.Methods:Utilizing immunohistochemistry and microbial sequencing,we analyzed the microbes of prostate tissues from BPH patients with different degrees of prostate fibrosis and found that Salmonellaenterica(S.enterica)was enriched in the high degree of prostate fibrosis.We developed prostate cell and animal models infected with the lipopolysaccharide of S.enterica(S.e-LPS)to assess its impact on prostate fibrosis.To elucidate the underlying functional mechanisms,we employed molecular biology techniques,including RNA degradation assays,N6-methyladenosine(m6A)dot blotting,RNA immunoprecipitation,and m6A immunoprecipitation.Results:Microbial diversity differed between low-and high-fibrosis groups,with S.enterica showing the highest mean abundance among the 4 species that differed significantly.S.e-LPS was detected in S.enterica-rich prostate tissue and was found to significantly promote cell proliferation,cell contractility,lipid peroxidation,and the induction of ferroptosis.Animal experiments demonstrated that S.e-LPS infection led to pronounced hyperplasia of the prostatic epithelium,with epithelial thickness increasing to 1.57 times that of the sham group,and collagen fibrosis increasing to 2.84 times that of the sham group,thereby exacerbating prostatic tissue fibrosis in rats.Invitro experiments further revealed that S.e-LPS promoted prostate cell fibrosis by inducing ferroptosis.Mechanistically,it was determined that S.e-LPS regulates ferroptosis via AlkB homolog 5(ALKBH5)-mediated m6A modification,which affects the stability of glutathione peroxidase 4(GPX4)mRNA,thereby affecting prostatic fibrosis.Conclusion:The findings of this study suggest that S.enterica promotes prostatic fibrosis through ALKBH5-m6A-GPX4-mediated ferroptosis.This research offers novel insights for the development of new therapeutic targets and personalized strategies for the prevention and treatment of BPH from the perspectives of microbes and epigenetics.
基金Supported by the National Natural Science Foundation of China,No.82460940Major Project of Gansu Province Joint Fund,No.23JRRA1519+2 种基金Key Science and Technology Project of Gansu Province,No.21ZD4FA009Natural Science Foundation of Gansu Province,No.24JRRA1040Gansu Province Famous Traditional Chinese Medicine Inheritance Studio Project。
文摘Congenital scoliosis(CS)is a prevalent spinal deformity with a multifaceted etiology that remains incompletely understood.Recent advances in genetic and epigenetic research have provided novel insights into CS pathogenesis.Herein,we review the current progress in genetics and epigenetics to examine genetic variants,susceptibility factors,and the epigenetic regulatory mechanisms implicated in CS.Through an analysis of diverse genetic markers,chromosomal abnormalities,and epigenetic modifications,the correlation between genetic predisposition and environmental influences in CS pathogenesis is elucidated.By integrating these genetic and epigenetic findings,this study aims to clarify the underlying etiology of CS to provide guidance on future clinical interventions and promote the development of personalized therapeutic strategies.
基金supported by the Basic Public Welfare Research Project of Zhejiang Province(No.LGF22H140007)the Research and Development Project of Stomatology Hospital Affiliated to Zhejiang University School of Medicine(No.RD2022JCXK01)+1 种基金the National Natural Science Foundation of China(No.82301072)the Postdoctoral Science Foundation of China(Nos.2021TQ0277 and 2022M722741)。
文摘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.
文摘The prevalence of autism and attention deficit/hyperactivity disorders is increasing worldwide.Recent studies suggest the excessive intake of ultra-processed food plays a role in the inheritance of these disorders via heavy metal exposures and nutritional deficits that impact the expression of genes.In the case of the metallothionein(MT)gene,biomarker studies show dietary zinc(Zn)deficits impact MT protein levels in children with autism and are associated with the bioaccumulation of lead and/or mercury in children exhibiting autism/attention deficit/hyperactivity disorders symptomology.The impact of dietary changes on lead and mercury exposures and MT gene behavior could be determined using a randomized test and control group design.Pregnant women serving in the testgroup would participate in a nutritional epigenetics education intervention/course designed to reduce ultra-processed food intake and heavy metal levels in blood while increasing whole food intake and MT and Zn levels.Changes in maternal diet would be measured using data derived from an online diet survey administered to the test and control groups pre-post intervention.Changes in maternal lead,mercury,Zn,and MT levels would be measured via blood sample analyses prior to the intervention and after childbirth via cord blood analyses to determine infant risk factors.
文摘Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.
文摘To improve understanding of the multifaceted nature of metabolic dysfunction-associated steatotic liver disease(MASLD),the American Association for the Study of Liver Diseases,in collaboration with the European Association for the Study of the Liver and the Latin American Association for the Study of the Liver,proposed a broader and more flexible definition,highlighting the role of underlying metabolic dysfunction.MASLD represents the most common chronic liver disease worldwide;however,the impact of the disease goes beyond its epidemiological aspects.Currently,the impact on patients and healthcare syst-ems,due to hepatic and extrahepatic complications,is significant.Recent evidence has demonstrated that epigenetic regulation plays a key role in the development and progression of MASLD.This highly sophisticated regulatory system includes DNA methylation,histone modification,chromatin remodeling,and modulation of non-coding RNA,without causing changes in the primary DNA sequence.Diet,particularly the Westernized diet(characterized by high levels of processed foods,fats,and sugars,but deficient in vitamins and minerals),contributes to the pathogenesis of MASLD through epigenetic modulation at multiple levels.Given the association between diet,epigenetics,and MASLD,this review aims to present some micronutrients and their importance in the prevention and/or treatment of metabolically dysfunction-associated steatotic liver disease.
文摘Diabetic neuropathy (DN) and impaired wound healing in diabetic foot ulcers(DFUs) are major complications of diabetes mellitus, driven by complex molecularmechanisms, including epigenetic modifications. Recent research highlights therole of epigenetic markers including DNA methylation, histone modifications,and non-coding RNAs in regulating inflammatory responses, neuronal degeneration,and tissue repair. This review explores the epigenetics of DN and DFUs,emphasizing key regulatory pathways that influence disease progression andwound healing outcomes. Genome-wide DNA methylation studies reveal acceleratedepigenetic aging and metabolic memory effects in DN, contributing tosensory neuron dysfunction and neuropathic pain. Epigenetic dysregulation ofinflammatory mediators such as Toll-like receptors and the Nod-like receptorfamily, pyrin domain-containing 3 inflammasome further exacerbates neuronaldamage and delays wound healing. Additionally, histone deacetylases play apivotal role in oxidative stress regulation via the Nrf2 pathway, which is critical for both neuronal protection and angiogenesis in DFUs. Non-coding RNAs, particularly microRNAs (miRNAs),long non-coding RNAs (lncRNAs), and circular RNAs, are emerging as central regulators of the epigeneticcrosstalk between DN and DFUs. Several miRNAs, including miR-146a-5p and miR-518d-3p, are implicated inneuropathy severity, while lncRNAs such as nuclear enriched abundant transcript 1 modulate angiogenesis andwound repair. Cellular reprogramming of DFU fibroblasts has also been shown to induce pro-healing miRNAsignatures, offering potential therapeutic avenues. Furthermore, recent whole-genome and transcriptomic analysesof DFU-derived monocytes and Charcot foot lesions reveal unique epigenetic signatures that may serve as biomarkersfor early detection and personalized interventions. This epigenetic interplay between DN and DFUpathogenesis not only enhances our knowledge of disease mechanisms but also opens avenues for targetedepigenetic therapies to improve clinical outcomes.
