Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 577
Filtrar
1.
Ann Hepatol ; : 101572, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278407

RESUMO

INTRODUCTION AND OBJECTIVE: Due to the high heterogeneity of HCC, which leads to poor prognostic outcomes for patients, there is a need to develop a novel predictive model for accurate classification of HCC in order to improve patient survival rates. MATERIALS AND METHODS: The data of the HCV, cirrhosis, and HCC were obtained from TCGA and GEO databases. Multivariable Cox regression analysis and survival analysis was conducted to assess the prognostic relevance of these differentially expressed genes. Single-cell sequencing was used to explore the intercellular interaction patterns and identify relevant signaling pathways. Drug sensitivity analysis was conducted to determine personalized treatment strategies for patients. RESULTS: In this study, we conducted integrated analysis of hepatitis, cirrhosis, and hepatocellular carcinoma datasets and identified 10 liver disease progression genes associated with prognosis. These genes exhibited significant downregulation in expression as the disease advanced, suggesting their crucial involvement in HCC development. By performing multivariable Cox analysis, we established a prognostic model for liver disease progression to predict the prognosis of HCC patients. The model was validated using ROC analysis, demonstrating good accuracy and stability in prognostic evaluation. Single-cell sequencing analysis revealed that these genes primarily exert their effects through the MIF signaling pathway during HCC progression. Furthermore, we observed that patients in the low-risk group exhibited higher sensitivity to TACE treatment, while patients in the high-risk group showed better response to sorafenib treatment. CONCLUSIONS: In summary, we have elucidated the key genes involved in the progression of liver diseases and established a precise prognostic model for assessing the prognosis of HCC patients. Our study provides novel insights and strategies for the treatment of HCC.

2.
Front Toxicol ; 6: 1438826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39345349

RESUMO

We observed that gestational plus lactational exposure to glyphosate (Gly), as active ingredient, or a glyphosate-based herbicide (GBH) lead to preimplantation losses in F1 female Wistar rats. Here, we investigated whether GBH and/or Gly exposure could impair Hoxa10 gene transcription by inducing epigenetic changes during the receptive stage in rats, as a possible herbicide mechanism implicated in implantation failures. F0 dams were treated with Gly or a GBH through a food dose of 2 mg Gly/kg bw/day from gestational day (GD) 9 up to lactational day 21. F1 female rats were bred, and uterine tissues were analyzed on GD5 (preimplantation period). Transcripts levels of Hoxa10, DNA methyltransferases (Dnmt1, Dnmt3a and Dnmt3b), histone deacetylases (Hdac-1 and Hdac-3) and histone methyltransferase (EZH2) were assessed by quantitative polymerase chain reaction (qPCR). Four CpG islands containing sites targeted by BstUI methylation-sensitive restriction enzyme and predicted transcription factors (TFs) were identified in Hoxa10 gene. qPCR-based methods were used to evaluate DNA methylation and histone post-translational modifications (hPTMs) in four regulatory regions (RRs) along the gene by performing methylation-sensitive restriction enzymes and chromatin immunoprecipitation assays, respectively. GBH and Gly downregulated Hoxa10 mRNA. GBH and Gly increased DNA methylation levels and Gly also induced higher levels than GBH in all the RRs analyzed. Both GBH and Gly enriched histone H3 and H4 acetylation in most of the RRs. While GBH caused higher H3 acetylation, Gly caused higher H4 acetylation in all RRs. Finally, GBH and Gly enhanced histone H3 lysine 27 trimethylation (H3K27me3) marker at 3 out of 4 RRs studied which was correlated with increased EZH2 levels. In conclusion, exposure to GBH and Gly during both gestational plus lactational phases induces epigenetic modifications in regulatory regions of uterine Hoxa10 gene. We show for the first time that Gly and a GBH cause comparable gene expression and epigenetic changes. Our results might contribute to delineate the mechanisms involved in the implantation failures previously reported. Finally, we propose that epigenetic information might be a valuable tool for risk assessment in the near future, although more research is needed to establish a cause-effect relationship.

3.
Epigenomics ; 16(18): 1253-1264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39297700

RESUMO

Aim: Promoter methylation of LINE-1 may be affected by prematurity, but there is little evidence in the literature.Materials & methods: Blood from premature and full-term neonates on days 0, 5, 30 and 90 was analyzed for DNA methylation percentage in a promoter region of the LINE-1, after bisulfite conversion and pyrosequencing.Results: Premature infants, as a whole, showed significantly lower methylation percentage at birth, but this difference diminished over time. However, the subgroup of extremely premature (<28 weeks gestational age) had higher methylation percentages, similar to full-term newborns.Conclusion: This research underscores the critical role of prematurity on the methylation pattern of LINE-1. These findings underline the complexity of epigenetic regulation in prematurity and emphasize the need for further studies.


Premature birth can have significant effects on a baby's development and long-term health. This study investigates how being born prematurely affects a process called DNA methylation, which can influence how genes are turned on or off. Specifically, we examined the LINE-1 promoter, a frequently occurring region of DNA known for its role in regulating gene activity.We collected blood samples from both premature and full-term newborns at birth and at several points in the early months of life. Our findings showed that premature babies have lower levels of LINE-1 promoter methylation at birth compared with full-term babies. These differences in methylation could possibly affect the babies' development and health as they grow.Our research highlights the need for continued study in this area to explore how these epigenetic changes impact long-term health and to develop strategies to mitigate these effects.


Assuntos
Metilação de DNA , Recém-Nascido Prematuro , Elementos Nucleotídeos Longos e Dispersos , Regiões Promotoras Genéticas , Humanos , Recém-Nascido , Feminino , Masculino , Epigênese Genética , Idade Gestacional
5.
J Nutr Biochem ; 134: 109739, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154791

RESUMO

The objective of our study was to investigate the impact of neonatal overfeeding on cognitive functions and neurosteroidogenesis in male rats. Offspring were assigned to either small litters (SL; 4 pups/mother), resulting in increased milk intake and body weight gain, or normal litters (NL; 10 pups/mother). On postnatal day (PND) 21, half of the male rats were euthanized, while the remaining were kept under standard conditions (4 rats/cage) until PND70. At this stage, subjects underwent assessments for locomotor activity, anxiety levels via the elevated plus maze, and episodic-like memory (ELM) tests. By PND90, the rats were euthanized for brain dissection. Utilizing micropunch techniques, dentate gyrus (DG), CA1, and CA3 regions were extracted for analysis of mRNA expression and methylation patterns. At PND21, SL rats exhibited increased body and adipose tissue weights, alongside elevated cholesterol, glucose, and triglyceride levels compared to NL counterparts. By PND90, although metabolic disparities were no longer evident, SL rats demonstrated heightened anxiety-like behavior and diminished performance in ELM tests. Early life changes included a decreased expression of aromatase (P450arom) and 3α-HSD in CA1, with increased levels in CA3 and DG among SL rats. Additionally, PND90 rats from SL exhibited increased P450arom and decreased 5α-reductase 1 (5αR-1) expression in DG. Notably, some of these variations were correlated with changes in methylation patterns of their promoter regions. Our findings reveal that neonatal overfeeding exerts a long-term adverse effect on cognitive abilities and neurosteroidogenic pathways, underscoring the lasting impact of nutritional experiences during critical early postnatal development periods.

6.
Front Cell Infect Microbiol ; 14: 1369226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086605

RESUMO

Objective: The study delved into the epigenetic factors associated with periodontal disease in two lineages of mice, namely C57bl/6 and Balb/c. Its primary objective was to elucidate alterations in the methylome of mice with distinct genetic backgrounds following systemic microbial challenge, employing high-throughput DNA methylation analysis as the investigative tool. Methods: Porphyromonas gingivalis (Pg)was orally administered to induce periodontitis in both Balb/c and C57bl/6 lineage. After euthanasia, genomic DNA from both maxilla and blood were subjected to bisulfite conversion, PCR amplification and genome-wide DNA methylation analysis using the Ovation RRBS Methyl-Seq System coupled with the Illumina Infinium Mouse Methylation BeadChip. Results: Of particular significance was the distinct methylation profile observed within the Pg-induced group of the Balb/c lineage, contrasting with both the control and Pg-induced groups of the C57bl/6 lineage. Utilizing rigorous filtering criteria, we successfully identified a substantial number of differentially methylated regions (DMRs) across various tissues and comparison groups, shedding light on the prevailing hypermethylation in non-induced cohorts and hypomethylation in induced groups. The comparison between blood and maxilla samples underscored the unique methylation patterns specific to the jaw tissue. Our comprehensive methylome analysis further unveiled statistically significant disparities, particularly within promoter regions, in several comparison groups. Conclusion: The differential DNA methylation patterns observed between C57bl/6 and Balb/c mouse lines suggest that epigenetic factors contribute to the variations in disease susceptibility. The identified differentially methylated regions associated with immune regulation and inflammatory response provide potential targets for further investigation. These findings emphasize the importance of considering epigenetic mechanisms in the development and progression of periodontitis.


Assuntos
Metilação de DNA , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis , Animais , Porphyromonas gingivalis/genética , Camundongos , Periodontite/microbiologia , Epigênese Genética , Doenças Periodontais/microbiologia , Suscetibilidade a Doenças , Infecções por Bacteroidaceae/microbiologia , Epigenoma
7.
Eur J Oral Sci ; 132(5): e13009, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39075736

RESUMO

This study aimed to investigate the relationship between epigenetic mechanisms and oral mucositis (OM) in paediatric patients with acute lymphoblastic leukaemia. Oral cells were collected from 76 participants, including 15 healthy individuals, 10 patients with acute lymphoblastic leukaemia but without a history of OM and 51 acute lymphoblastic leukaemia patients with a history of OM (35 with active OM and 16 who had recovered from OM). Global DNA methylation in the miR-9-1 and miR-9-3 genes was performed. Seven polymorphisms rs1801131, rs1801133 (MTHFR), rs2228611 (DNMT1), rs7590760, rs1550117 (DNMT3A), rs6087990, rs2424913 (DNMT3B) were genotyped and an analysis of association with global DNA methylation was performed. The global methylation levels were lower in cancer patients recovered from OM than in the other groups. A higher frequency of unmethylated profile for miR-9-1 and partially methylated profile for miR-9-3 was observed in cancer patients regardless of OM history compared to healthy patients. The GG genotype of the rs2228611 (DNMT1) polymorphism was associated with higher levels of global methylation in cancer patients irrespective of OM. It was concluded that global methylation is associated with mucosal recovery. The effect of DNMT1 genotype on the global DNA methylation profile, as well as the methylation profile of miR-9-1 and miR-9-3 in cancer patients is independent of OM.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Epigênese Genética , MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Estomatite , Humanos , Criança , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estomatite/genética , Feminino , Masculino , MicroRNAs/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Pré-Escolar , Genótipo , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A/genética , DNA Metiltransferase 3B , Polimorfismo de Nucleotídeo Único , Adolescente , Estudos de Casos e Controles , Metilenotetra-Hidrofolato Redutase (NADPH2)
8.
Front Plant Sci ; 15: 1407700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978517

RESUMO

Rubber tree (Hevea brasiliensis) is reproduced by bud grafting for commercial planting, but significant intraclonal variations exist in bud-grafted clones. DNA methylation changes related to grafting may be partly responsible for intraclonal variations. In the current study, whole-genome DNA methylation profiles of grafted rubber tree plants (GPs) and their donor plants (DPs) were evaluated by whole-genome bisulfite sequencing. Data showed that DNA methylation was downregulated and DNA methylations in CG, CHG, and CHH sequences were reprogrammed in GPs, suggesting that grafting induced the reprogramming of DNA methylation. A total of 5,939 differentially methylated genes (DMGs) were identified by comparing fractional methylation levels between GPs and DPs. Transcriptional analysis revealed that there were 9,798 differentially expressed genes (DEGs) in the DP and GP comparison. A total of 1,698 overlapping genes between DEGs and DMGs were identified. These overlapping genes were markedly enriched in the metabolic pathway and biosynthesis of secondary metabolites by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Global DNA methylation and transcriptional analyses revealed that reprogramming of DNA methylation is correlated with gene expression in grafted rubber trees. The study provides a whole-genome methylome of rubber trees and an insight into the molecular mechanisms underlying the intraclonal variations existing in the commercial planting of grafted rubber trees.

9.
Epigenetics ; 19(1): 2375030, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967279

RESUMO

The mechanisms by which the ageing process is associated to an unhealthy lifestyle and how they play an essential role in the aetiology of systemic arterial hypertension have not yet been completely elucidated. Our objective is to investigate the influence of NOS3 polymorphisms [-786T > C and (Glu298Asp)] on systolic blood pressure (SBP) and diastolic blood pressure (DBP) response, differentially methylated regions (DMRs), and physical fitness of adult and older women after a 14-week combined training intervention. The combined training was carried out for 14 weeks, performed 3 times a week, totalling 180 minutes weekly. The genotyping experiment used Illumina Infinium Global Screening Array version 2.0 (GSA V2.0) and Illumina's EPIC Infinium Methylation BeadChip. The participants were separated into SNP rs2070744 in TT (59.7 ± 6.2 years) and TC + CC (60.0 ± 5.2 years), and SNP rs17999 in GluGlu (58.8 ± 5.7 years) and GluAsp + AspAsp (61.6 ± 4.9 years). We observed an effect of time for variables BP, physical capacities, and cholesterol. DMRs related to SBP and DBP were identified for the rs2070744 and rs17999 groups pre- and decreased numbers of DMRs post-training. When we analysed the effect of exercise training in pre- and post-comparisons, the GluGlu SNP (rs17999) showed 10 DMRs, and after enrichment, we identified several biological biases. The combined training improved the SBP and DBP values of the participants regardless of the SNPs. In addition, exercise training affected DNA methylation differently between the groups of NOS3 polymorphisms.


Assuntos
Pressão Sanguínea , Metilação de DNA , Exercício Físico , Óxido Nítrico Sintase Tipo III , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/genética , Pressão Sanguínea/genética , Idoso , Hipertensão/genética , Epigênese Genética
10.
Methods Mol Biol ; 2827: 1-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985259

RESUMO

Plant cell, tissue, and organ cultures (PCTOC) have been used as experimental systems in basic research, allowing gene function demonstration through gene overexpression or repression and investigating the processes involved in embryogenesis and organogenesis or those related to the potential production of secondary metabolites, among others. On the other hand, PCTOC has also been applied at the commercial level for the vegetative multiplication (micropropagation) of diverse plant species, mainly ornamentals but also horticultural crops such as potato or fruit and tree species, and to produce high-quality disease-free plants. Moreover, PCTOC protocols are important auxiliary systems in crop breeding crops to generate pure lines (homozygous) to produce hybrids for the obtention of polyploid plants with higher yields or better performance. PCTOC has been utilized to preserve and conserve the germplasm of different crops or threatened species. Plant genetic improvement through genetic engineering and genome editing has been only possible thanks to the establishment of efficient in vitro plant regeneration protocols. Different companies currently focus on commercializing plant secondary metabolites with interesting biological activities using in vitro PCTOC. The impact of omics on PCTOC is discussed.


Assuntos
Células Vegetais , Técnicas de Cultura de Tecidos , Técnicas de Cultura de Células/métodos , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Melhoramento Vegetal/métodos , Células Vegetais/metabolismo , Desenvolvimento Vegetal/genética , Plantas/genética , Plantas/metabolismo , Técnicas de Cultura de Tecidos/métodos
11.
Methods Mol Biol ; 2827: 323-350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985280

RESUMO

This chapter describes a step-by-step protocol for rapid serological quantification of global DNA methylation by enzyme-linked immunosorbent assay (ELISA) in plant tissue culture specimens. As a case study model, we used the coconut palm (Cocos nucifera), from which plumules were subjected to somatic embryogenesis followed by embryogenic calli multiplication. DNA methylation is one of the most common epigenetic markers in the regulation of gene expression. DNA methylation is generally associated with non-expressed genes, that is, gene silencing under certain conditions, and the degree of DNA methylation can be used as a marker of various physiological processes, both in plants and in animal cells. Methylation consists of adding a methyl radical to carbon 5 of the DNA cytosine base. Herein, the global DNA methylation was quantified by ELISA with antibodies against methylated cytosines using a commercial kit (Zymo-Research™). The method allowed the detection of methylation in total DNA extracts from coconut palm embryogenic calli (arising from somatic embryogenesis) cultivated in liquid or solid media by using antibodies against methylated cytosines and enzymatic development with a colorimetric substrate. Control samples of commercially provided Escherichia coli bacterial DNA with previously known methylation percentages were included in the ELISA test to construct an experimental methylation standard curve. The logarithmic regression of this E. coli standard curve allowed methylation quantification in coconut palm samples. The present ELISA methodology, applied to coconut palm tissue culture specimens, is promising for use in other plant species and botanical families. This chapter is presented in a suitable format for use as a step-by-step laboratory procedure manual, with theoretical introduction information, which makes it easy to apply the protocol in samples of any biological nature to evaluate DNA global methylation associated with any physiological process.


Assuntos
Metilação de DNA , Ensaio de Imunoadsorção Enzimática , Epigênese Genética , Ensaio de Imunoadsorção Enzimática/métodos , DNA de Plantas/genética , Cocos/genética , Técnicas de Cultura de Tecidos/métodos , Técnicas de Embriogênese Somática de Plantas/métodos
12.
Metabolites ; 14(7)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39057684

RESUMO

Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of several hormones, cytokines, and growth factors related to fetal fat mass growth. One of the molecular mechanisms of GDM influencing these factors is epigenetic alterations, such as DNA methylation (DNAm). This review will examine the role of DNAm as a potential biomarker for monitoring fetal growth during pregnancy in women with GDM. This information is relevant since it may provide useful new biomarkers for the diagnosis, prognosis, and treatment of fetal growth and its later-life health consequences.

13.
Toxics ; 12(7)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39058128

RESUMO

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been associated with cancer, such as ADAMTS9 and C18ORF8. Gestation and delivery data were obtained from the POSGRAD study. Exposure to As was measured in urine during pregnancy. Gene methylation was performed by sodium bisulfite sequencing; 26 CpG sites for the C18ORF8 gene and 21 for ADAMTS9 were analyzed. These sites are located on the CpG islands near the start of transcription. Sociodemographic characteristics were obtained by a questionnaire. The statistical analysis was performed using multiple linear regression models adjusted for potential confounders. Newborns with an As exposure above 49.4 µg g-1 showed a decrease of 0.21% on the methylation rate in the sites CpG15, CpG19, and CpG21 of the C18ORF8 gene (adjusted ß = -0.21, p-value = 0.02). No statistically significant association was found between prenatal exposure to As and methylation of the ADAMTS9 gene. Prenatal exposure to As was associated with decreased DNA methylation at the CpG15, CpG19, and CpG21 sites of the C18ORF8 gene. These sites can provide information to elucidate epigenetic mechanisms associated with prenatal exposure to As and cancer.

14.
Epigenomics ; 16(11-12): 809-820, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884343

RESUMO

Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects.Results:  LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05).Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.


[Box: see text].


Assuntos
Metilação de DNA , Hiperlipoproteinemia Tipo II , Proteína Associada a Proteínas Relacionadas a Receptor de LDL , Pró-Proteína Convertase 9 , Receptores de LDL , Humanos , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteína Associada a Proteínas Relacionadas a Receptor de LDL/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/etiologia , Ilhas de CpG , Proteínas Adaptadoras de Transdução de Sinal
15.
Development ; 151(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828854

RESUMO

The neural plate border (NPB) of vertebrate embryos is segregated from the neural plate (NP) and epidermal regions, and comprises an intermingled group of progenitors with multiple fate potential. Recent studies have shown that, during the gastrula stage, TFAP2A acts as a pioneer factor in remodeling the epigenetic landscape required to activate components of the NPB induction program. Here, we show that chick Tfap2a has two highly conserved binding sites for miR-137, and both display a reciprocal expression pattern at the NPB and NP, respectively. In addition, ectopic miR-137 expression reduced TFAP2A, whereas its functional inhibition expanded their territorial distribution overlapping with PAX7. Furthermore, we demonstrate that loss of the de novo DNA methyltransferase DNMT3A expanded miR-137 expression to the NPB. Bisulfite sequencing revealed a markedly elevated presence of non-canonical CpH methylation within the miR-137 promoter region when comparing NPB and NP samples. Our findings show that miR-137 contributes to the robustness of NPB territorial restriction in vertebrate development.


Assuntos
Metilação de DNA , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs , Placa Neural , Fator de Transcrição AP-2 , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Embrião de Galinha , Metilação de DNA/genética , Placa Neural/metabolismo , Placa Neural/embriologia , Fator de Transcrição AP-2/metabolismo , Fator de Transcrição AP-2/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A/metabolismo , Regiões Promotoras Genéticas/genética , Sítios de Ligação
16.
Plant J ; 119(3): 1197-1209, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38864847

RESUMO

Plants continuously endure unpredictable environmental fluctuations that upset their physiology, with stressful conditions negatively impacting yield and survival. As a contemporary threat of rapid progression, global warming has become one of the most menacing ecological challenges. Thus, understanding how plants integrate and respond to elevated temperatures is crucial for ensuring future crop productivity and furthering our knowledge of historical environmental acclimation and adaptation. While the canonical heat-shock response and thermomorphogenesis have been extensively studied, evidence increasingly highlights the critical role of regulatory epigenetic mechanisms. Among these, the involvement under heat of heterochromatic suppression mediated by transcriptional gene silencing (TGS) remains the least understood. TGS refers to a multilayered metabolic machinery largely responsible for the epigenetic silencing of invasive parasitic nucleic acids and the maintenance of parental imprints. Its molecular effectors include DNA methylation, histone variants and their post-translational modifications, and chromatin packing and remodeling. This work focuses on both established and emerging insights into the contribution of TGS to the physiology of plants under stressful high temperatures. We summarized potential roles of constitutive and facultative heterochromatin as well as the most impactful regulatory genes, highlighting events where the loss of epigenetic suppression has not yet been associated with corresponding changes in epigenetic marks.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Resposta ao Choque Térmico/genética , Temperatura Alta , Metilação de DNA , Plantas/genética , Plantas/metabolismo , Heterocromatina/genética , Heterocromatina/metabolismo
17.
Front Mol Biosci ; 11: 1385140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745909

RESUMO

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-). Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA sequencing assays were performed on 13 bone marrows from Hispanic children with B-cell ALL. Partek Flow was used for transcript mapping and quantification, followed by differential expression analysis using DEseq2. DNA methylation analyses were performed with Partek Genomic Suite and Genome Studio. Gene expression and differential methylation were compared between patients with MRD-/- and MRD+/+ at the end of induction chemotherapy. Overexpressed and hypomethylated genes were selected and validated by RT-qPCR in samples of an independent validation cohort. The predictive ability of the genes was assessed by logistic regression. Survival and Cox regression analyses were performed to determine the association of genes with death. Results: DAPK1, BOC, CNKSR3, MIR4435-2HG, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in MRD+/+ patients. Overexpression was also validated by RT-qPCR. DAPK1, BOC, ASCL2, and CNKSR3 can predict refractoriness, but MIR4435-2HG is the best predictor. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. Finally, MIR4435-2HG overexpression, together with MRD+, are associated with poorer survival, and together with overexpression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype. Conclusion: MIR4435-2HG is a potential predictive biomarker of treatment response and death in children with B-cell ALL.

18.
Environ Epigenet ; 10(1): dvae005, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779494

RESUMO

In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic review of the literature, what epigenetic alterations are associated with pesticide exposure. We performed a systematic review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and ß-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethane and p,p'-dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as CDKN2AIGF2, WRAP53α and CDH1, while CDKN2B and H19 were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.

19.
Ann Hepatol ; 29(4): 101506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38710471

RESUMO

INTRODUCTION AND OBJECTIVES: Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors. PATIENTS AND METHODS: 12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq. RESULTS: Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response. CONCLUSIONS: In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI.


Assuntos
Metilação de DNA , Epigênese Genética , Perfilação da Expressão Gênica , Transplante de Fígado , Fígado , Traumatismo por Reperfusão , Transplante de Fígado/efeitos adversos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Perfilação da Expressão Gênica/métodos , Transcriptoma , Adulto , Idoso
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA