Methylation and transcriptomic expression profiles of HUVEC in the oxygen and glucose deprivation model and its clinical implications in AMI patients

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Дек. 7, 2023

The obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for etiopathology AMI have not been investigated detail. This study aimed explore relationship between pathologically gene expression profile human umbilical vein (HUVECs) subjected oxygen-glucose deprivation (OGD), its clinical implications patients. Illumina Infinium MethylationEPIC BeadChip assay was used genome-wide using Novaseq6000 platform mRNA sequencing 3 pairs HUVEC-OGD control samples. GO KEGG pathway enrichment analyses, as well correlation, causal inference test (CIT), protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget qRT-PCR. ELISA detect four target molecules associated with progression AMI. A total 2,524 differentially expressed (DEGs) 22,148 methylated positions (DMPs) corresponding 6,642 (DMGs) screened (|Δβ|>0.1 detection p < 0.05). After GO, KEGG, CIT, PPI 441 filtered. qRT-PCR confirmed overexpression VEGFA, CCL2, TSP-1, SQSTM1, BCL2L11, TIMP3 genes, downregulation MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, MEIS1. fragments BDNF_1_ (r = 0.931, 0.0001) SQSTM1_2_NEW 0.758, 0.0043) positively correlated expressions MYC_1_ -0.8245, 0.001) negatively correlated. Furthermore, TNFSF10 BDNF elevated peripheral blood patients (p 0.0284 0.0142, respectively). Combined from vitro cellular assays samples, aiming establish potential chain factor (DNA methylation) - mediator (mRNA)-cell outcome (endothelial cell injury)-clinical (AMI), our promising OGD-specific which provided solid basis screening fundamental diagnostic prognostic biomarkers injury Moreover, it furnished first evidence ischemia hypoxia, BNDF regulated blood.

Язык: Английский

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Bioinformatics Analysis of Common Differential Genes of Viral Myocarditis and Dilated Cardiomyopathy: Screening for Potential Pharmacological Compounds

Journal of Cardiovascular Development and Disease, Год журнала: 2022, Номер 9(10), С. 353 - 353

Опубликована: Окт. 15, 2022

(1) Background: The mechanism of viral myocarditis (VMC) progression to dilated cardiomyopathy (DCM) remains unclear. aim this study was identify key genes in the VMC DCM, so as find potential therapeutic drugs and provide insights for future research. (2) Methods: Differential expression analysis GSE4172 GSE17800 from Gene Expression Omnibus (GEO) database performed using GEO2R, which contained genome-wide myocardial biopsies respectively. We used Venn diagram screen common differentially expressed (DEGs). GO functional enrichment KEGG pathway were also performed. Then we conducted protein-protein interaction (PPI) networks STRING identified hub Cytoscape. Finally, cMAP out candidate compounds targeting these genes; (3) Results: In total, 2143 DEGs 1365 DCM found. a total 191 identified. Biological processes involved mainly include GABA-gated chloride ion channel activity Rap1 signaling pathway. A 14 PPI network showed hubs enriched regulation WNT activity. Subgroup Severe cohort revealed 10 clustered GABA activity, extracellular matrix remodeling sarcomere dysfunction. Using cMAP, obtained top medications, but only amlodipine is currently viable; (4) Conclusions: Our finds reveals important role channel, pathway, dysfunction DCM. Amlodipine viable drug preventing

Язык: Английский

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The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 2, 2023

Abstract Polycystic ovary syndrome (PCOS) is associated with infertility, obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, hypertension, cardiovascular problems, neurological and psychological problems cancer. The specific mechanism of PCOS its complications remains unclear. aim this study was to apply a bioinformatics approach reveal related pathways or genes involved in the development complications. next generation squancing (NGS) datset GSE199225 downloaded from gene expression omnibus (GEO) database. Differentially expressed (DEG) analysis performed using DESeq2. g:Profiler utilized analyze functional enrichment, ontology (GO) REACTOME pathway differentially genes. A protein-protein interaction (PPI) network constructed module HiPPIE cytoscape. miRNA-hub regulatory TF-hub were also for research. hub validated receiver operating characteristic (ROC) curve analysis. We have identified 957 DEGs total, including 478 up regulated 479 down gene. GO illustrated that significantly enriched regulation molecular function, developmental process, interferon signaling platelet activation, aggregation. Finally, through analyzing PPI network, modules, we screened HSPA5, PLK1, RIN3, DBN1, CCDC85B, DISC1, AR, MTUS2, LYN TCF4 by Cytoscape software. This uses series technologies obtain hug key These results provide us novel ideas finding biomarkers treatment methods

Язык: Английский

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Characterization of testosterone and androgen receptor action in human and rhesus macaque heart muscle cells

Опубликована: Янв. 1, 2024

Androgens are sex steroid hormones that influence various processes in reproductive tissues and peripheral organs. Their lipophilic nature enables free diffusion through the plasma membrane. In cytoplasm, testosterone (T) binds to its receptor, androgen receptor (AR), complex then translocates nucleus for activation or inhibition of gene expression. Although effects androgens studied greatly healthy diseased tissues, little is known about their cellular molecular action cardiovascular system. Clinical research reported impact high low T levels on human heart vasculature, but data currently conflicting. Additionally, most triggered by muscle cells were researched using rodents. These models vastly contributed our understanding biological processes, though partially limited due differences physiology humans. This work focused studying male physiological (25 nM) supraphysiological (100 concentrations primate cardiomyocytes (CMs) rhesus macaque origin. For first time, AR was detected CM nuclei tissue. Notably, no signal female cells. further vitro studies we used an induced pluripotent stem cell (iPSC) model. iPSCs translocated T. A directed cardiac differentiation protocol optimized generate CMs from lines. Non-treated showed cytoplasmic staining while T-treated displayed mostly nuclear signals. treatment abundance iPSC-CMs. Interestingly, AR-V7 isoform with T-binding capabilities iPSC-CMs left ventricular Since may also exhibit AR-independent action, generated a clonal knock-out (KO) iPSC line investigate effects. Further analysis KO fewer after differentiation, higher proliferation rate, more disorganized contractile apparatus compared wild-type (WT) The differentially expressed genes WT highlighted immature state CMs. While 24 hours resulted decrease Ca2+ current density, 48 exposure did not result significant changes between treated non- groups Overall, has shown drastic effect itself than treatment. That why hypothesized conversion other androgens. LC- MS/MS demonstrated culture media addition confirming assumption. Moreover, androstenedione, weaker T, samples, almost none rhesus. conclusion, this demonstrates relevant / system proliferation, cytoskeleton organization, electrophysiological parameters, expression

Язык: Английский

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CoordinatedTbx3 / Tbx5transcriptional control of the adult ventricular conduction system

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

The cardiac conduction system (CCS) orchestrates the electrical impulses that enable coordinated contraction of chambers. T-box transcription factors

Язык: Английский

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Coordinated Tbx3 / Tbx5 transcriptional control of the adult ventricular conduction system

Опубликована: Ноя. 21, 2024

The cardiac conduction system (CCS) orchestrates the electrical impulses that enable coordinated contraction of chambers. T-box transcription factors TBX3 and TBX5 are required for development associated with overlapping distinct human diseases. We evaluated role Tbx3 Tbx5 in murine ventricular (VCS). engineered a compound Tbx3:Tbx5 conditional knockout allele both genes located cis on mouse chromosome 5. Conditional deletion transcriptional system, using VCS-specific Mink:Cre, caused loss VCS function molecular identity. Combined deficiency adult led to defects, including prolonged PR QRS intervals elevated susceptibility tachycardia. These electrophysiologic defects occurred prior detectable alterations contractility or histologic morphology, indicative primary defect. double cardiomyocytes revealed shift towards non-CCS-specialized working myocardium, suggesting reprogramming their cellular Furthermore, optical mapping propagation. Collectively, these findings indicate coordinate control fate function, implications understanding disorders humans.

Язык: Английский

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Coordinated Tbx3 / Tbx5 transcriptional control of the adult ventricular conduction system

Опубликована: Ноя. 21, 2024

The cardiac conduction system (CCS) orchestrates the electrical impulses that enable coordinated contraction of chambers. T-box transcription factors TBX3 and TBX5 are required for development associated with overlapping distinct human diseases. We evaluated role Tbx3 Tbx5 in murine ventricular (VCS). engineered a compound Tbx3:Tbx5 conditional knockout allele both genes located cis on mouse chromosome 5. Conditional deletion transcriptional system, using VCS-specific Mink:Cre, caused loss VCS function molecular identity. Combined deficiency adult led to defects, including prolonged PR QRS intervals elevated susceptibility tachycardia. These electrophysiologic defects occurred prior detectable alterations contractility or histologic morphology, indicative primary defect. double cardiomyocytes revealed shift towards non-CCS-specialized working myocardium, suggesting reprogramming their cellular Furthermore, optical mapping propagation. Collectively, these findings indicate coordinate control fate function, implications understanding disorders humans.

Язык: Английский

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The identification of key genes and pathways in polycystic ovary syndrome by bioinformatics analysis of next-generation sequencing data

Middle East Fertility Society Journal, Год журнала: 2024, Номер 29(1)

Опубликована: Ноя. 28, 2024

Abstract Background Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder. The specific molecular mechanism of PCOS remains unclear. aim this study was to apply bioinformatics approach reveal related pathways or genes involved in the development PCOS. Methods next-generation sequencing (NGS) dataset GSE199225 downloaded from gene expression omnibus (GEO) database and NGS analyzed obtained vitro culture patients’ muscle cells healthy lean control women. Differentially expressed (DEG) analysis performed using DESeq2. g:Profiler utilized analyze ontology (GO) REACTOME differentially genes. A protein–protein interaction (PPI) network constructed module HiPPIE cytoscape. miRNA-hub regulatory TF-hub were constructed. hub validated by receiver operating characteristic (ROC) curve analysis. Results We have identified 957 DEG total, including 478 upregulated 479 downregulated gene. GO terms illustrated that significantly enriched regulation function, developmental process, interferon signaling platelet activation, signaling, aggregation. top 5 HSPA5, PLK1, RIN3, DBN1, CCDC85B DISC1, AR, MTUS2, LYN, TCF4 might be associated with gens HSPA5 KMT2A, together corresponding predicted miRNAs (e.g., hsa-mir-34b-5p hsa-mir-378a-5p), TF RCOR3 TEAD4) found correlated Conclusions These uses data obtain key its complications. Also provides novel ideas for finding biomarkers treatment methods

Язык: Английский

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Screening of the key genes and signaling pathways for schizophrenia using bioinformatics and next generation sequencing data analysis

Italian Journal of Medicine, Год журнала: 2024, Номер 18(4)

Опубликована: Дек. 18, 2024

Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Researchers have identified numerous proteins associated with occurrence and development of schizophrenia. This study aimed identify potential core genes pathways involved in schizophrenia through exhaustive bioinformatics next generation sequencing (NGS) data analyses using GSE106589 NGS neural progenitor cells neurons obtained from healthy controls patients The were downloaded Gene Expression Omnibus database. was processed by DESeq2 package R software, differentially expressed (DEGs) identified. ontology (GO) enrichment analysis REACTOME pathway carried out biological functions DEGs. Protein-protein interaction network, module, micro-RNA (miRNA)-hub gene regulatory transcription factor (TF)-hub drug-hub network performed hub genes, miRNA, TFs, drug molecules. Potential analyzed receiver operating characteristic curves package. In this investigation, an overall 955 DEGs identified: 478 remarkably upregulated 477 distinctly downregulated. These enriched for GO terms mainly multicellular organismal process, G protein-coupled receptor ligand binding, regulation cellular processes, amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A, BTK considered genes. MiRNA-hub TF-hub constructed successfully predicted key miRNAs, molecules diagnosis treatment. On whole, findings investigation enhance our understanding molecular mechanisms provide targets further investigation.

Язык: Английский

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TMT-based proteomic analysis of radiation lung injury in rats

Clinical Proteomics, Год журнала: 2024, Номер 21(1)

Опубликована: Дек. 1, 2024

Язык: Английский

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