Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis

Huang, Jinke; Zhang, Jiaqi; Wang, Fengyun; Zhang, Beihua; Tang, Xudong

doi:10.3389/fimmu.2022.1008146

Cited by 22 publications

(13 citation statements)

References 37 publications

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“…As for immune reaction gene‐sets, we observed a significant negative correlation between the majority of cuproptosis genes and most immune reaction gene‐sets. This aligns with other studies exploring the interplay between cuproptosis and immune responses in other diseases 47,48 . Utilizing these immune characteristics, we categorized the IHF sample expression patterns influenced by cuproptosis into two subtypes.…”

Section: Discussionsupporting

confidence: 73%

“…This aligns with other studies exploring the interplay between cuproptosis and immune responses in other diseases. 47 , 48 Utilizing these immune characteristics, we categorized the IHF sample expression patterns influenced by cuproptosis into two subtypes. From an immune feature perspective, subtype‐1 is predominantly associated with innate immunity and immune regulation, whereas subtype‐2 is primarily associated with adaptive immunity.…”

Section: Discussionmentioning

confidence: 99%

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Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis

Chen,

Zhu,

Chen

et al. 2024

J Cellular Molecular Medi

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Cuproptosis is a recently discovered programmed cell death pattern that affects the tricarboxylic acid (TCA) cycle by disrupting the lipoylation of pyruvate dehydrogenase (PDH) complex components. However, the role of cuproptosis in the progression of ischemic heart failure (IHF) has not been investigated. In this study, we investigated the expression of 10 cuproptosis‐related genes in samples from both healthy individuals and those with IHF. Utilizing these differential gene expressions, we developed a risk prediction model that effectively distinguished healthy and IHF samples. Furthermore, we conducted a comprehensive evaluation of the association between cuproptosis and the immune microenvironment in IHF, encompassing infiltrated immunocytes, immune reaction gene‐sets and human leukocyte antigen (HLA) genes. Moreover, we identified two different cuproptosis‐mediated expression patterns in IHF and explored the immune characteristics associated with each pattern. In conclusion, this study elucidates the significant influence of cuproptosis on the immune microenvironment in ischemic heart failure (IHF), providing valuable insights for future mechanistic research exploring the association between cuproptosis and IHF.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis

Chen,

Zhu,

Chen

et al. 2024

J Cellular Molecular Medi

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“…All procedures involving animal experiments adhered to the ARRIVE guidelines 2.0: Updated guidelines for reporting animal research 23 . To induce UC, the mice were given drinking water containing 3% dextran sulfate sodium (DSS) for 7 days 24 …”

Section: Methodsmentioning

confidence: 99%

“…23 To induce UC, the mice were given drinking water containing 3% dextran sulfate sodium (DSS) for 7 days. 24 Nexrutine (E3306; Selleck Chemicals) was administered to mice at two distinct doses (300 and 600 mg/kg), which were determined to be pharmacologically effective and safe based on a previous study. 25 Mesalazine (S1681; Selleck) served as a positive control regimen.…”

Section: A Mouse Model Of Ucmentioning

confidence: 99%

Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression

Xu,

Wu,

Wang

et al. 2024

Immunity Inflam & Disease

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BackgroundNexrutine is an herbal extract derived from Phellodendron amurense, known for its anti‐inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear.MethodsA mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM‐460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM‐460 cells was determined using the CCK‐8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin‐1, and tight junction protein (ZO‐1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto‐oncogene (RELA) was analyzed using qPCR and western blot assays.ResultsThe Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro‐inflammatory cytokines, enhanced the barrier integrity‐related proteins, and increased NCM‐460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus‐mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC‐related symptoms.ConclusionThis study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.

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“…The GSE57338 dataset (GPL11532 platform) included myocardial tissue samples from 136 healthy controls and 82 DCM samples, and the GSE19303 dataset (GPL570 platform), including myocardial tissue samples from eight healthy controls and 40 DCM samples, and the GSE21610 dataset (GPL570 platform), including myocardial tissue samples from eight healthy controls and 21 DCM samples, were used for validation analyses. 13 genes (FDX1, LIPT1, LIAS, DLD, DBT, GCSH, DLST, DLAT, PDHA1, PDHB, SLC31A1, ATP7A, ATP7B) for CRGs were retrieved from previous publications ( Huang et al, 2022 ; Lai et al, 2022 ) and used for subsequent analyses.…”

Section: Methodsmentioning

confidence: 99%

Identification of cuproptosis-related biomarkers in dilated cardiomyopathy and potential therapeutic prediction of herbal medicines

Bian

Wang

et al. 2023

Front. Mol. Biosci.

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Background: Dilated cardiomyopathy (DCM) is one of the significant causes of heart failure, and the mechanisms of metabolic ventricular remodelling due to disturbances in energy metabolism are still poorly understood in cardiac pathology. Understanding the biological mechanisms of cuproptosis in DCM is critical for drug development.Methods: The DCM datasets were downloaded from Gene Expression Omnibus, their relationships with cuproptosis-related genes (CRGs) and immune signatures were analyzed. LASSO, RF, and SVM-RFE machine learning algorithms were used to identify signature genes and the eXtreme Gradient Boosting (XGBoost) model was used to assess diagnostic efficacy. Molecular clusters of CRGs were identified, and immune Infiltration analysis was performed. The WGCNA algorithm was used to identify specific genes in different clusters. In addition, AUCell was used to analyse the cuproptosis scores of different cell types in the scRNA-seq dataset. Finally, herbal medicines were predicted from an online database, and molecular docking and molecular dynamics simulations were used to support the confirmation of the potential of the selected compounds.Results: We identified dysregulated cuproptosis genes and activated immune responses between DCM and healthy controls. Two signature genes (FDX1, SLC31A1) were identified and performed well in an external validation dataset (AUC = 0.846). Two molecular clusters associated with cuproptosis were further defined in DCM, and immune infiltration analysis showed B-cell naive, Eosinophils, NK cells activated and T-cell CD4 memory resting is significant immune heterogeneity in the two clusters. AUCell analysis showed that cardiomyocytes had a high cuproposis score. In addition, 19 and 3 herbal species were predicted based on FDX1 and SLC31A1. Based on the molecular docking model, the natural compounds Rutin with FDX1 (-9.3 kcal/mol) and Polydatin with SLC31A1 (-5.5 kcal/mol) has high stability and molecular dynamics simulation studies further validated this structural stability.Conclusion: Our study systematically illustrates the complex relationship between cuproptosis and the pathological features of DCM and identifies two signature genes (FDX1 and SLC31A1) and two natural compounds (Rutin and Polydatin). This may enhance our diagnosis of the disease and facilitate the development of clinical treatment strategies for DCM.

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Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis

Cited by 22 publications

References 37 publications

Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis

Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis

Alleviating effect of Nexrutine on mucosal inflammation in mice with ulcerative colitis: Involvement of the RELA suppression

Identification of cuproptosis-related biomarkers in dilated cardiomyopathy and potential therapeutic prediction of herbal medicines

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