Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis DOI Creative Commons

Cheng-Fei Bi,

Jia Liu, Xiao Hu

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. It characterized high morbidity and mortality one of the major diseases that seriously hang over global human health. Autophagy crucial regulator in complicated pathophysiological processes sepsis. The activation autophagy known be great significance for protecting sepsis induced dysfunction. Recent research has demonstrated N6-methyladenosine (m6A) methylation well-known post-transcriptional RNA modification controls epigenetic gene expression well number biological In addition, m6A affects stability, export, splicing translation transcripts involved autophagic process. Although it been suggested regulates metabolic more frequently seen progression pathogenesis, underlying molecular mechanisms m6A-modified have not thoroughly elucidated. present article fills this gap providing an review its potential role development novel therapeutics.

Language: Английский

Identification and validation of m6A RNA methylation and ferroptosis-related biomarkers in sepsis: transcriptome combined with single-cell RNA sequencing DOI Creative Commons

Jinshuai Lu,

Jianhao Wang, Kun Han

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Background Sepsis, a systemic inflammatory response syndrome triggered by infection, is associated with high mortality rates and an increasing global incidence. While N 6 -methyladenosine (m A) RNA methylation ferroptosis are implicated in diseases, their specific genes mechanisms sepsis remain unclear. Methods Transcriptomic datasets of sepsis, along m A-related A-RGs) ferroptosis-related (FRGs), were sourced from public databases. Differentially expressed (DEGs) identified between the control groups, A-RGs analyzed through weighted gene co-expression network analysis (WGCNA) to uncover A module genes. These then intersected DEGs FRGs identify candidate Biomarkers using two machine learning methods, receiver operating characteristic (ROC) curves, expression validation, followed development nomogram. Further in-depth analyses biomarkers performed, including functional enrichment, immune infiltration, drug prediction, molecular docking. Single-cell was conducted distinct cell clusters evaluate biomarker at single-cell level. Finally, reverse transcription–quantitative PCR (RT-qPCR) employed validate clinical samples. Results DPP4 TXN as key biomarkers, showing higher samples, respectively. The nomogram incorporating these demonstrated strong diagnostic potential. Enrichment highlighted involvement spliceosome function antigen processing presentation. Differential types revealed significant correlations cells, such macrophages activated dendritic cells. Drug predictions gambogenic acid valacyclovir potential treatments, which successfully docked biomarkers. that predominantly CD4 + memory CD16 CD14 monocytes. further validated Conclusions for insights into infiltration therapeutic level, offering novel perspectives treatment.

Language: Английский

Citations

0
N6-methyladenosine modification: Regulatory mechanisms and therapeutic potential in sepsis DOI Open Access
Wei Wang, Huaili Wang, Tongwen Sun

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115719 - 115719

Published: Oct. 14, 2023

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection and characterized multiple biological clinical features. N6-methyladenosine (m6A) modification the most common type of RNA modifications in eukaryotes plays an important regulatory role various processes. Recently, m6A has been found be involved regulation immune responses sepsis. In addition, several studies have shown that sepsis-induced dysfunctions, including cardiovascular dysfunction, acute lung injury (ALI), kidney (AKI) etc. Considering complex pathogenesis sepsis lack specific therapeutic drugs, may bond pathophysiological process even targets. This review systematically highlights recent advances regarding roles sheds light on their use as treatment targets for

Language: Английский

Citations

7
Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome DOI Creative Commons
Junhao Yin, Jiayao Fu, Jiabao Xu

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28645 - e28645

Published: March 29, 2024

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged a pivotal player immune regulation. Its dysregulation been implicated pathogenesis of various autoimmune conditions. However, implications m6A within microenvironment Sjögren's syndrome (SS), chronic disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate expression profiles regulatory genes SS. Our cohort comprised 220 patients diagnosed with SS 62 healthy individuals, enabling comprehensive evaluation peripheral blood at transcriptomic level. We report significant association between altered key regulators, these changes closely tied activation CD4

Language: Английский

Citations

1
Analysis of lactate metabolism-related genes and their association with immune infiltration in septic shock via bioinformatics method DOI Creative Commons
Huimin Jiang,

Yun Ren,

Jiale Yu

et al.

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: July 26, 2023

Background: Lactate, as an essential clinical evaluation index of septic shock, is crucial in the incidence and progression shock. This study aims to investigate differential expression, regulatory relationship, diagnostic efficacy, immune infiltration lactate metabolism-related genes (LMGs) Methods: Two sepsis shock datasets (GSE26440 GSE131761) were screened from GEO database, common differentially expressed (DEGs) two out. LMGs selected GeneCards DEGs (LMDEGs) determined by integrating LMGs. Protein-protein interaction networks, mRNA-miRNA, mRNA-RBP, mRNA-TF networks constructed using STRING, miRDB, ENCORI, CHIPBase databases, respectively. Receiver operating characteristic (ROC) curves for each LMDEGs evaluate efficacy expression changes relation Finally, analysis was performed ssGSEA CIBERSORT. Results: identified 10 LMDEGs, including LDHB, STAT3, LDHA, GSR, FOXM1, PDP1, GCDH, GCKR, ABCC1, CDKN3. Enrichment revealed that significantly enriched pathways such pyruvate metabolism, hypoxia pathway, immune-inflammatory pathways. PPI based on well 148 pairs mRNA-miRNA interactions, 243 mRNA-RBP 119 interactions established. ROC eight (LDHA, CDKN3, LDHB) with consistent patterns had area under curve (AUC) ranging 0.662 0.889. The results CIBERSORT both showed significant differences various cells, CD8 T natural killer CDKN3 associated cells. Conclusion: are response have a certain accuracy

Language: Английский

Citations

2
The Role of m6A Methylation Genes in Predicting Poor Prognosis in Sepsis: Identifying Key Biomarkers and Therapeutic Targets DOI Creative Commons

Shaokang Wang,

Siye Shen,

Na Cheng

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Abstract Sepsis is one of the leading causes death among seriously ill patients worldwide, affecting more than 30 million people annually and accounting for 1–2% hospitalizations. By analyzing GEO data set, this study explored relationship between m6A methylation gene poor prognosis sepsis, aiming at early detection providing basis timely intervention, so as to improve survival rate patients. GSE54514 transcriptome were extracted from database 31 with sepsis 72 without death. Key genes screened by DEGs, LASSO RF algorithms, then METTL3, WTAP RBM15 further verified qRT-PCR. The constructed nomogram model showed high accuracy in predicting These three are mainly involved chemokine signaling pathway, differentiation monocytes T cells, phagocytosis immune cells. Through analysis infiltrations, identification subtype, ratio clinical samples, it was found that probability immunosuppression score subtype lower higher. Finally, through inhibition METTL3 mouse model, protective effect demonstrated spleen cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) HE staining. findings provide potential biomarkers targets precision diagnosis treatment.

Language: Английский

Citations

0
The role of m6A methylation genes in predicting poor prognosis in sepsis: identifying key biomarkers and therapeutic targets DOI Creative Commons

Shaokang Wang,

Siye Shen,

Na Cheng

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Dec. 19, 2024

Sepsis is one of the leading causes death among seriously ill patients worldwide, affecting more than 30 million people annually and accounting for 1–2% hospitalizations. By analyzing gene expression omnibus (GEO) data set, our team explored relationship between m6A methylation poor prognosis sepsis. The purpose this present study to examine new detection markers with prognosis, provide theoretical basis timely intervention improve survival rate patients. First, GSE54514 transcriptome were extracted from GEO database 31 sepsis related 72 survivors. Key genes screened differentially expressed (DEGs), least absolute shrinkage selection operator (LSAAO) random forest (RF). And then, METTL3, WTAP RBM15 further verified by quantitative reverse transcription PCR (qRT-PCR). constructed nomogram model showed high accuracy in predicting death. These three are mainly involved chemokine signaling pathway, differentiation monocytes T cells, phagocytosis immune cells. analysis that a score subtype linked lower immunosuppression higher rates clinical samples, suggesting better responses outcomes these Finally, protective effect METTL3 was demonstrated mouse applied inhibitor, conducting cell flow cytometry analysis, enzyme-linked immunosorbent assay (ELISA) hematoxylin–eosin (HE) staining. In conclusion, findings potential biomarkers targets early precision diagnosis treatment.

Language: Английский

Citations

0
Unveiling Key Biomarkers and Mechanisms in Septic Cardiomyopathy: A Comprehensive Transcriptome Analysis DOI Creative Commons
Dandan Zhao,

Jinqiang Zhuang,

Liping Wang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 11451 - 11467

Published: Dec. 1, 2024

Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis effective therapies. This study aimed identify hub biomarkers in SCM explore their potential mechanisms.

Language: Английский

Citations

0
Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis DOI Creative Commons

Cheng-Fei Bi,

Jia Liu, Xiao Hu

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 18, 2023

Sepsis is defined as a life-threatening organ dysfunction caused by dysregulated host response to infection. It characterized high morbidity and mortality one of the major diseases that seriously hang over global human health. Autophagy crucial regulator in complicated pathophysiological processes sepsis. The activation autophagy known be great significance for protecting sepsis induced dysfunction. Recent research has demonstrated N6-methyladenosine (m6A) methylation well-known post-transcriptional RNA modification controls epigenetic gene expression well number biological In addition, m6A affects stability, export, splicing translation transcripts involved autophagic process. Although it been suggested regulates metabolic more frequently seen progression pathogenesis, underlying molecular mechanisms m6A-modified have not thoroughly elucidated. present article fills this gap providing an review its potential role development novel therapeutics.

Language: Английский

Citations

0