Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which...Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which have highlighted DNA methylation patterns as promising biomarkers for early detection,prognosis,and treatment response in lung cancer.Techniques like bisulfite conversion followed by PCR,digital droplet polymerase chain reaction,and next-generation sequencing are commonly used for detecting these methylation patterns,which occur early in the cancer development process and can be detected in non-invasive samples like blood and sputum.Key genes such as SHOX2 and RASSF1A have demonstrated high sensitivity and specificity in clinical studies,making them crucial for diagnostic purposes.However,several challenges remain to be overcome before these biomarkers can be widely adopted for use in clinical practice.Standardizing the assays and validating their effectiveness are critical steps.Additionally,integrating methylation biomarkers with existing diagnostic tools could significantly enhance the accuracy of lung cancer detection,providing a more comprehensive diagnostic approach.Although progress has been made in understanding and utilizing DNA methylation patterns for lung cancer detection,more research and extensive clinical trials are necessary to fully harness their potential.These efforts will help establish the robustness of methylation patterns as biomarkers and therapeutic targets,ultimately leading to better prevention,diagnosis,and treatment strategies for lung cancer.In conclusion,DNA methylation states represent a promising avenue for advancing early detection,accurate diagnosis,and management of lung cancer.展开更多
Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting intervent...Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting interventions at international,regional,national and local levels,wildlife farming is advocated as an alternative approach to minimize pressure on wild populations.For wildlife farming to be an effective conservation tool,the integration of wildlife forensics is inevitable to allow distinction between captive-bred and wild-caught species.To this end,we analyzed methylation rates of skeletal muscle samples(pectoralis major,triceps brachii,gastrocnemius,biceps femoris,and neck muscles)from 60 captive-bred and 30 wild-caught Common Pheasant.A total of 13,507 differentially methylated regions were identified between five wild-caught and five captive-bred individuals through whole-genome methylation sequencing(WGBS).Based on the selected five methylation sites,LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST,quantitative detection technique was developed using methylation-sensitive high-resolution melting curve(MS-HRM)to measure methylation rates.The results showed significant differences in methylation rates at all differential sites between wild-caught and captive-bred individuals(|t|=0.67–33.10,P=0.000–0.042).The discrimination accuracy rate of each locus was highest in the gastrocnemius muscle and lowest in the neck muscle.The discrimination accuracy rate on LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST methylation sites for gastrocnemius muscle was 64.98%,100.00%,68.54%,63.79%,and 63.70%,respectively;and for neck muscle it was 67.42%,68.06%,83.61%,65.04%,and68.85%,respectively.The united discrimination accuracy rate of the five loci were 100.00%for gastrocnemius muscle,99.78%for biceps femoris muscle,97.52%for pectoralis major muscle,93.96%for triceps brachii muscle,and 91.63%for neck muscle,respectively.The panel also revealed excellent repeatability,reproducibility,sensitivity and universality to mammals and avian species.This study establishes an effective,accurate and low-cost identification technology for the identification of wild and farmed Common Pheasant,and also provides a reference for the development of identification methods for other species.展开更多
In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels...In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.展开更多
Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environme...Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.展开更多
BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma me...BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.展开更多
Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the m...Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the mobility and transformation of methylated arsenic in redox-changing paddy fields is crucial for food security.Here,soils including unarsenic contaminated(N-As),low-arsenic(L-As),medium-arsenic(M-As),and high-arsenic(H-As)soils were incubated under continuous anoxic,continuous oxic,and consecutive anoxic/oxic treatments respectively,to profile arsenic methylating process and microbial species involved in the As cycle.Under anoxic-oxic(A-O)treatment,methylated arsenic was significantly increased once oxygen was introduced into the incubation system.The methylated arsenic concentrations were up to 2-24 times higher than those in anoxic(A),oxic(O),and oxic-anoxic(O-A)treatments,under which arsenic was methylated slightly and then decreased in all four As concentration soils.In fact,the most plentiful arsenite S-adenosylmethionine methyltransferase genes(arsM)contributed to the increase in As methylation.Proteobacteria(40.8%-62.4%),Firmicutes(3.5%-15.7%),and Desulfobacterota(5.3%-13.3%)were the major microorganisms related to this process.These microbial increasedmarkedly and played more important roles after oxygen was introduced,indicating that they were potential keystone microbial groups for As methylation in the alternating anoxic(flooding)and oxic(drainage)environment.The novel findings provided newinsights into the reoxidation-driven arsenic methylation processes and the model could be used for further risk estimation in periodically flooded paddy fields.展开更多
Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to envir...Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to environmental chemicals,may alter the spermatogenic epigenome.Here,we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin,bleomycin,vinblastine,and dacarbazine(ABVD).In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes,we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing(WGS)and reduced representation bisulfite sequencing(RRBS).The WGS analysis identified 403 variants following ABVD treatment,including 28 linked to genes crucial for embryogenesis.However,none were found in coding regions,indicating no impact of chemotherapy on protein function.The RRBS analysis identified 99high-quality differentially methylated regions(hqDMRs)for which methylation status changed upon chemotherapy.Those hqDRMs were associated with 87 differentially methylated genes,among which 14 are known to be important or expressed during embryo development.While no variants were detected in coding regions,promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status.These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis,leading to potential developmental disorders or miscarriages.展开更多
The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function a...The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.展开更多
DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Ca...DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.展开更多
AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening o...AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.展开更多
The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study...The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study,we aimed to evaluate the levels of 5-methyl-cytosine(5mC)as a surrogate marker of global DNA methylation in buccal swabs and its potential association with the risk of stunting and cognitive performance.The levels of 5mC were measured using an enzyme-linked immunosorbent assay.The Wechsler Preschool and Primary Scale of Intelligence(WPPSI)was used to measure cognitive function.Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years.In this cross-sectional cohort,the prevalence of stunting was 37%in 138 children aged zero to two years and 30%in 93 children aged over two years.The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children(median,2.84;interquartile range[IQR],2.39–4.62)and children aged less than two years(median,2.81;IQR,2.53–4.62)than those in normal children(median,3.75;IQR,2.80–4.74;P-value,0.028)and children aged over four years(median,4.01;IQR,3.39–4.87;P-value<0.001),respectively.We also found that the average cognitive scores tended to be low in boys and stunted children,although the differences were not statistically significant.Furthermore,the levels of 5mC found in buccal swab and mouthwash DNA were not associated with cognitive scores.展开更多
Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to...Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to bamboo forests,resulting in substantial losses.The underlying cause of bamboo flowering remains elusive.Dynamic fluctuations in DNA methylation govern the transcriptional levels of crucial genes pivotal for plant growth and development.In this study,we conducted comprehensive DNA methylation(by whole-genome bisulfite sequencing)and transcriptome(by RNA-seq)analyses on non-flowering leaves,flowering leaves,and spikelets of Moso bamboo.Our findings revealed a notable reduction in the overall DNA methylation level,particularly CHH methylation,from leaves to spikelets,influencing the expression of differentially regulated genes.Notably,we identified DNA methylation as a regulatory mechanism for numerous flowering-related genes,including SPLs,FT,and SOC1.Specifically,the SPL3f gene,a key regulator of the aging pathway,exhibited hypomethylation and a high expression level in spikelets.Conversely,SOC1c displayed transcriptional silencing attributed to hypermethylation in the CHH context in the leaves of non-flowering plants.DNA methylation may affect the flowering mechanism of Moso bamboo by regulating the expression of key genes.In summary,our results shed light on the dynamic changes in DNA methylation between leaves and spikelets,unraveling an important epigenetic modification mechanism for flowering in Moso bamboo.展开更多
Following the publication of Xu et al.(2022),an error was identified in Figure 1D.Specifically,the top left panel was inadvertently duplicated during figure preparation.To ensure the accuracy and integrity of our publ...Following the publication of Xu et al.(2022),an error was identified in Figure 1D.Specifically,the top left panel was inadvertently duplicated during figure preparation.To ensure the accuracy and integrity of our published work,we request the publication of a corrigendum with the corrected image.We apologize for this oversight and any confusion it may have caused.The amended figure is provided in the updated Supplementary Materials.展开更多
BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role ...BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.展开更多
BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(...BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(GAED)and hepatoid adenocarcinoma(HAC)were previously regarded as gastric adenocarcinoma with primitive enterocyte phenotype(GAPEP).GAPEP is known for its poor prognosis,and the accurate diagnosis of GAPEP directly affects therapeutic decision-making.Despite their poor prognosis and morphological heterogeneity,the molecular drivers of GAPEP,particularly methylation-driven mechanisms,remain poorly explored.AIM To investigate the clinicopathological and molecular characteristics of GAPEP and establish an integrative diagnostic strategy to guide therapeutic decision-making.METHODS Based on the expression profile and morphology,patients were divided into three groups:GAPEP(including GAED and HAC),conventional gastric cancer(CGC),and CGC expressing primitive phenotypic markers.We analyzed clinicopathological features and overall survival.Data from The Cancer Genome Atlas were also analyzed,and functional enrichment analysis was conducted.RESULTS GAPEP showed diverse morphology,and immunohistochemical staining alone was not adequate for accurate diagnosis.Histologically,GAPEP was characterized by large,polygonal tumor cells with supranuclear or subnuclear vacuoles,a“piano keyboard-like”appearance,and clear or eosinophilic cytoplasms.Compared to CGC and CGC expressing primitive phenotypic markers,GAPEP displayed more aggressive clinical features.Molecular analysis showed significant differences in molecular subtypes,TP53 mutation,ERBB2 amplification,ARID1A mutation,MSI status,and CpG island methylator phenotype category.Genomic analysis revealed that TP53 mutations,APC mutations,and ERBB2 amplifications were more frequent in GAPEP.Genes involved in methylation processes were highly upregulated in GAPEP.HAC and GAED shared similar clinicopathological and genetic characteristics.Functional enrichment analysis highlighted the critical role of methylation in the development of GAPEP.CONCLUSION The diversity and aggressiveness of GAPEP are driven by deregulated methylation,necessitating the integration of morphological and immunohistochemical diagnosis.Targeting methylation can provide new therapeutic opportunities for treating this aggressive cancer.展开更多
In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental ...In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental component of treatment,its efficacy varies considerably among individuals.DNA methylation plays a pivotal role in the extinction of fear memories,providing a promising molecular mechanism that could enhance the success of exposure-based interventions.Extensive studies have consistently demonstrated a substantial association between DNA methylation and neuronal plasticity.While DNA methylation holds potential regulatory effects on the effectiveness of exposure therapy,the bidirectional regulatory relationship between it and neuronal activity necessitates addressing several challenges before its widespread clinical application for mental disorders.First,excessive DNA methylation may suppress neural function,and non-selective enhancement of methylation could be counterproductive.Furthermore,due to potential systemic side effects,the use of methylation-modulating agents might disrupt the physiological balance and functionality of other organs and systems.Despite the dynamic interplay between DNA methylation and neuronal activity offering novel insights into the treatment of mental disorders, the strict consideration of target specificity and an appropriate dosing window requirescautious implementation in clinical practice.展开更多
BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge...BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.展开更多
Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and ...Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.展开更多
1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of ca...1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.展开更多
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 s...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.展开更多
文摘Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which have highlighted DNA methylation patterns as promising biomarkers for early detection,prognosis,and treatment response in lung cancer.Techniques like bisulfite conversion followed by PCR,digital droplet polymerase chain reaction,and next-generation sequencing are commonly used for detecting these methylation patterns,which occur early in the cancer development process and can be detected in non-invasive samples like blood and sputum.Key genes such as SHOX2 and RASSF1A have demonstrated high sensitivity and specificity in clinical studies,making them crucial for diagnostic purposes.However,several challenges remain to be overcome before these biomarkers can be widely adopted for use in clinical practice.Standardizing the assays and validating their effectiveness are critical steps.Additionally,integrating methylation biomarkers with existing diagnostic tools could significantly enhance the accuracy of lung cancer detection,providing a more comprehensive diagnostic approach.Although progress has been made in understanding and utilizing DNA methylation patterns for lung cancer detection,more research and extensive clinical trials are necessary to fully harness their potential.These efforts will help establish the robustness of methylation patterns as biomarkers and therapeutic targets,ultimately leading to better prevention,diagnosis,and treatment strategies for lung cancer.In conclusion,DNA methylation states represent a promising avenue for advancing early detection,accurate diagnosis,and management of lung cancer.
基金supported by the Fundamental Research Funds for the Central Universities(2572020DR10)Project on the Investigation,Supervision and Industry Regulation of Rare and Endangered Species(2024)。
文摘Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting interventions at international,regional,national and local levels,wildlife farming is advocated as an alternative approach to minimize pressure on wild populations.For wildlife farming to be an effective conservation tool,the integration of wildlife forensics is inevitable to allow distinction between captive-bred and wild-caught species.To this end,we analyzed methylation rates of skeletal muscle samples(pectoralis major,triceps brachii,gastrocnemius,biceps femoris,and neck muscles)from 60 captive-bred and 30 wild-caught Common Pheasant.A total of 13,507 differentially methylated regions were identified between five wild-caught and five captive-bred individuals through whole-genome methylation sequencing(WGBS).Based on the selected five methylation sites,LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST,quantitative detection technique was developed using methylation-sensitive high-resolution melting curve(MS-HRM)to measure methylation rates.The results showed significant differences in methylation rates at all differential sites between wild-caught and captive-bred individuals(|t|=0.67–33.10,P=0.000–0.042).The discrimination accuracy rate of each locus was highest in the gastrocnemius muscle and lowest in the neck muscle.The discrimination accuracy rate on LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST methylation sites for gastrocnemius muscle was 64.98%,100.00%,68.54%,63.79%,and 63.70%,respectively;and for neck muscle it was 67.42%,68.06%,83.61%,65.04%,and68.85%,respectively.The united discrimination accuracy rate of the five loci were 100.00%for gastrocnemius muscle,99.78%for biceps femoris muscle,97.52%for pectoralis major muscle,93.96%for triceps brachii muscle,and 91.63%for neck muscle,respectively.The panel also revealed excellent repeatability,reproducibility,sensitivity and universality to mammals and avian species.This study establishes an effective,accurate and low-cost identification technology for the identification of wild and farmed Common Pheasant,and also provides a reference for the development of identification methods for other species.
基金supported by the National Natural Science Foundation of China(32070607)the National Key Research and Development Program of China(2020YFA0804000)the CAS Project for Young Scientists in Basic Research(YSBR-012).
文摘In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.
基金supported by the National Natural Science Foundation of China,Nos.82271283(to XC),91854115(to JW),31970044(to JW)the Natural Science Foundation of Beijing,No.7202001(to XC)the Scientific Research Project of Beijing Educational Committee,No.KM202010005022(to XC)。
文摘Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.
基金Supported by the Medical Talents of Wuhan Health and Family Planning Commission,No.2017[51](to Yu J)the Medical Talents of Wuhan Hospital of Traditional Chinese and Western Medicine(to Yu J)+1 种基金the Hubei Natural Science Foundation,No.2023AFB1091Wuhan Medical Research Project,No.WX23A36(to Yu J).
文摘BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.
基金supported by the Shandong Province Natural Science Foundation of Major Basic Research Program (No.ZR2020ZD34)the Key Projects of the National Natural Science Foundation of China (No.42230706)+3 种基金the National Natural Science Foundation of China (No.42307164)the China Postdoctoral Science Foundation (Nos.2023TQ0191 and 2023M732060)the Shandong Postdoctoral Science Foundation (No.SDBX2023041)and the Qingdao Postdoctoral Science Foundation (No.QDBSH20230202052).
文摘Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the mobility and transformation of methylated arsenic in redox-changing paddy fields is crucial for food security.Here,soils including unarsenic contaminated(N-As),low-arsenic(L-As),medium-arsenic(M-As),and high-arsenic(H-As)soils were incubated under continuous anoxic,continuous oxic,and consecutive anoxic/oxic treatments respectively,to profile arsenic methylating process and microbial species involved in the As cycle.Under anoxic-oxic(A-O)treatment,methylated arsenic was significantly increased once oxygen was introduced into the incubation system.The methylated arsenic concentrations were up to 2-24 times higher than those in anoxic(A),oxic(O),and oxic-anoxic(O-A)treatments,under which arsenic was methylated slightly and then decreased in all four As concentration soils.In fact,the most plentiful arsenite S-adenosylmethionine methyltransferase genes(arsM)contributed to the increase in As methylation.Proteobacteria(40.8%-62.4%),Firmicutes(3.5%-15.7%),and Desulfobacterota(5.3%-13.3%)were the major microorganisms related to this process.These microbial increasedmarkedly and played more important roles after oxygen was introduced,indicating that they were potential keystone microbial groups for As methylation in the alternating anoxic(flooding)and oxic(drainage)environment.The novel findings provided newinsights into the reoxidation-driven arsenic methylation processes and the model could be used for further risk estimation in periodically flooded paddy fields.
文摘Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to environmental chemicals,may alter the spermatogenic epigenome.Here,we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin,bleomycin,vinblastine,and dacarbazine(ABVD).In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes,we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing(WGS)and reduced representation bisulfite sequencing(RRBS).The WGS analysis identified 403 variants following ABVD treatment,including 28 linked to genes crucial for embryogenesis.However,none were found in coding regions,indicating no impact of chemotherapy on protein function.The RRBS analysis identified 99high-quality differentially methylated regions(hqDMRs)for which methylation status changed upon chemotherapy.Those hqDRMs were associated with 87 differentially methylated genes,among which 14 are known to be important or expressed during embryo development.While no variants were detected in coding regions,promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status.These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis,leading to potential developmental disorders or miscarriages.
文摘The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.
基金supported by the Natural Science Foundation of Guangdong Province(Grant Nos.2022A1515111141 and 2023A1515010786)。
文摘DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.
文摘AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.
基金Ministry of Education,Culture,Research,and Technology of the Republic of Indonesia through the Kedaireka 2022 Matching Fund Programme(Grant No.282/E1/KS.060.02/2022)。
文摘The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study,we aimed to evaluate the levels of 5-methyl-cytosine(5mC)as a surrogate marker of global DNA methylation in buccal swabs and its potential association with the risk of stunting and cognitive performance.The levels of 5mC were measured using an enzyme-linked immunosorbent assay.The Wechsler Preschool and Primary Scale of Intelligence(WPPSI)was used to measure cognitive function.Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years.In this cross-sectional cohort,the prevalence of stunting was 37%in 138 children aged zero to two years and 30%in 93 children aged over two years.The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children(median,2.84;interquartile range[IQR],2.39–4.62)and children aged less than two years(median,2.81;IQR,2.53–4.62)than those in normal children(median,3.75;IQR,2.80–4.74;P-value,0.028)and children aged over four years(median,4.01;IQR,3.39–4.87;P-value<0.001),respectively.We also found that the average cognitive scores tended to be low in boys and stunted children,although the differences were not statistically significant.Furthermore,the levels of 5mC found in buccal swab and mouthwash DNA were not associated with cognitive scores.
基金supported by the National Natural Science Foundation of China(Grant No.32160142)the Guangxi Natural Science Foundation(Grant No.2023GXNSFDA026034)+3 种基金the Sugarcane Research Foundation of Guangxi University(Grant No.2022GZA002)the State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(Grant No.SKLCUSAb202302)the National Natural Science Foundation of China(Grant No.31960051)the Natural Science Foundation for Young Scientists of Jiangxi Province(Grant No.20192ACB21005).
文摘Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to bamboo forests,resulting in substantial losses.The underlying cause of bamboo flowering remains elusive.Dynamic fluctuations in DNA methylation govern the transcriptional levels of crucial genes pivotal for plant growth and development.In this study,we conducted comprehensive DNA methylation(by whole-genome bisulfite sequencing)and transcriptome(by RNA-seq)analyses on non-flowering leaves,flowering leaves,and spikelets of Moso bamboo.Our findings revealed a notable reduction in the overall DNA methylation level,particularly CHH methylation,from leaves to spikelets,influencing the expression of differentially regulated genes.Notably,we identified DNA methylation as a regulatory mechanism for numerous flowering-related genes,including SPLs,FT,and SOC1.Specifically,the SPL3f gene,a key regulator of the aging pathway,exhibited hypomethylation and a high expression level in spikelets.Conversely,SOC1c displayed transcriptional silencing attributed to hypermethylation in the CHH context in the leaves of non-flowering plants.DNA methylation may affect the flowering mechanism of Moso bamboo by regulating the expression of key genes.In summary,our results shed light on the dynamic changes in DNA methylation between leaves and spikelets,unraveling an important epigenetic modification mechanism for flowering in Moso bamboo.
文摘Following the publication of Xu et al.(2022),an error was identified in Figure 1D.Specifically,the top left panel was inadvertently duplicated during figure preparation.To ensure the accuracy and integrity of our published work,we request the publication of a corrigendum with the corrected image.We apologize for this oversight and any confusion it may have caused.The amended figure is provided in the updated Supplementary Materials.
文摘BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.
基金Supported by the Startup Fund for Scientific Research,Fujian Medical University,No.2020QH1168Fujian Provincial Science and Technology Innovation Joint Funds,No.2024Y9023the Fujian Provincial Natural Science Foundation of China,No.2024J011644.
文摘BACKGROUND Gastric adenocarcinoma with primitive phenotypes has recently attracted increasing attention due to its aggressive nature and challenging diagnosis.Gastric adenocarcinoma with enteroblastic differentiation(GAED)and hepatoid adenocarcinoma(HAC)were previously regarded as gastric adenocarcinoma with primitive enterocyte phenotype(GAPEP).GAPEP is known for its poor prognosis,and the accurate diagnosis of GAPEP directly affects therapeutic decision-making.Despite their poor prognosis and morphological heterogeneity,the molecular drivers of GAPEP,particularly methylation-driven mechanisms,remain poorly explored.AIM To investigate the clinicopathological and molecular characteristics of GAPEP and establish an integrative diagnostic strategy to guide therapeutic decision-making.METHODS Based on the expression profile and morphology,patients were divided into three groups:GAPEP(including GAED and HAC),conventional gastric cancer(CGC),and CGC expressing primitive phenotypic markers.We analyzed clinicopathological features and overall survival.Data from The Cancer Genome Atlas were also analyzed,and functional enrichment analysis was conducted.RESULTS GAPEP showed diverse morphology,and immunohistochemical staining alone was not adequate for accurate diagnosis.Histologically,GAPEP was characterized by large,polygonal tumor cells with supranuclear or subnuclear vacuoles,a“piano keyboard-like”appearance,and clear or eosinophilic cytoplasms.Compared to CGC and CGC expressing primitive phenotypic markers,GAPEP displayed more aggressive clinical features.Molecular analysis showed significant differences in molecular subtypes,TP53 mutation,ERBB2 amplification,ARID1A mutation,MSI status,and CpG island methylator phenotype category.Genomic analysis revealed that TP53 mutations,APC mutations,and ERBB2 amplifications were more frequent in GAPEP.Genes involved in methylation processes were highly upregulated in GAPEP.HAC and GAED shared similar clinicopathological and genetic characteristics.Functional enrichment analysis highlighted the critical role of methylation in the development of GAPEP.CONCLUSION The diversity and aggressiveness of GAPEP are driven by deregulated methylation,necessitating the integration of morphological and immunohistochemical diagnosis.Targeting methylation can provide new therapeutic opportunities for treating this aggressive cancer.
基金Supported by the General Program of the Joint Fund Project Under the Liaoning Provincial Science and Technology Plan,No.2024-MSLH-104Research Project Plan of the Qingpu Branch of Zhongshan Hospital,No.QYT2023-02Research Topic of the Shanghai Qingpu District Health Commission,No.QWJ2024-10.
文摘In the contemporary research landscape of mental illness treatment,fear-related disorders such as post-traumatic stress disorder continue to pose significant challenges.Although exposure therapy remains a fundamental component of treatment,its efficacy varies considerably among individuals.DNA methylation plays a pivotal role in the extinction of fear memories,providing a promising molecular mechanism that could enhance the success of exposure-based interventions.Extensive studies have consistently demonstrated a substantial association between DNA methylation and neuronal plasticity.While DNA methylation holds potential regulatory effects on the effectiveness of exposure therapy,the bidirectional regulatory relationship between it and neuronal activity necessitates addressing several challenges before its widespread clinical application for mental disorders.First,excessive DNA methylation may suppress neural function,and non-selective enhancement of methylation could be counterproductive.Furthermore,due to potential systemic side effects,the use of methylation-modulating agents might disrupt the physiological balance and functionality of other organs and systems.Despite the dynamic interplay between DNA methylation and neuronal activity offering novel insights into the treatment of mental disorders, the strict consideration of target specificity and an appropriate dosing window requirescautious implementation in clinical practice.
基金Supported by National Natural Science Foundation of China,No.82360231Yunnan Basic Research Program General Project,No.202401AT070075+1 种基金Dali Basic Research Program Key Project,No.202301A020021Youth Special Project for Basic Research of Local Universities in Yunnan Province,No.202301BA070001-127.
文摘BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.
文摘Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.
基金supported by the Beijing Nova Program of Science and Technology(grant number:20230484397)the National Natural Science Foundation of China(grant number:82273726).
文摘1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.
基金supported by the National Natural Science Foundation of China(Nos.82274211 and 82474190)the Natural Science Foundation of Tianjin(Nos.24JCZDJC00120 and 24PTLYHZ00280)Liaoning Provincial Department of Education Basic Research Projects for Higher Education Institutions(No.LJ212510163021)。
文摘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.
