An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning

Turhon, Mirzat; Maimaiti, Aierpati; Gheyret, Dilmurat; Axier, Aximujiang; Rexiati, Nizamidingjiang; Kadeer, Kaheerman; Su, Riqing; Wang, Zengliang; Chen, Xiaohong; Cheng, Xiaojiang; Zhang, Yisen; Aisha, Maimaitili

doi:10.3389/fimmu.2022.1001320

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…The cancer cells undergoing ICD could expel HMGB1 from nucleus outside the cells (Gao et al., 2022 ; Turhon et al., 2022 ). The expression level of HMGB1 on MCF-7/ADR cells was conducted by immunofluorescence assay.…”

Section: Resultsmentioning

confidence: 99%

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Zhang

Wang

et al. 2023

Drug Delivery

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Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

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Section: Resultsmentioning

confidence: 99%

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Zhang

Wang

et al. 2023

Drug Delivery

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“…Previously, the mechanisms of m6A methylation [49] and immunogenic cell death [50] in IAs were also investigated. In the future, further investigation should be conducted on the mechanism of its role in IAs in DNA methylation and more epigenetic regulation.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation-estimated Phenotypes, Telomere length, Aging and Risk of Intracranial Aneurysms: Evidence from genetic studies

Maimaiti,

Turhon,

Abulaiti

et al. 2023

Preprint

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Background The risk of intracranial aneurysm (IA) is increased in older population, suggesting a role for aging. To evaluate the association of genetic variants linked to DNA methylation-estimated phenotypes, telomere length, and aging, with the risk of IA by employing two-sample Mendelian randomization. Methods Sex-specific summary-level outcome data were extracted from the GWAS of IA, including 23 cohorts with a total of 5140 cases and 71934 controls. All the study participants were of European ancestry. To improve validity, five varying Mendelian randomization techniques were used in the analysis (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode). Results There was a negative causal relationship between Intrinsic epigenetic age acceleration and unruptured IA (P = 0.022272, OR = 0.9059 [95% CI, 0.83–0.99]). No causal effect existed between any other estimated methylation phenotype and aneurysmal subarachnoid hemorrhage (aSAH) (P > 0.05). There was a causal relationship between longevity and risk of developing aSAH (P = 0.020289, OR = 1.099528 [1.01–1.19]), with a 9.95% increase in the risk of disease for every 1-SD increase in age. In addition, each 1-SD rise in telomere length caused a 0.9% increase in the estimated proportion of granulocytes with DNA methylation (P = 0.002518, OR = 1.009041[1.003166,1.01495]) and a 55% increase in the intrinsic epigenetic age acceleration (P = 0.017597, OR = 1.55152[ 1.079562,1.551152]). Conclusion A negative causal relationship between intrinsic epigenetic age acceleration and IA suggests that an increase in intrinsic apparent age acceleration reduces the risk of IA. The underlying mechanisms and their potential to lower the prevalence of IA as an intervention target require further research.

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“…In recent years, advancements in genetic technologies and bioinformatics, including gene expression profiling and protein–protein interaction analyses, 5,6 have been supplemented by robust machine learning techniques to identify key gene expressions in intracranial aneurysms 7,8 . A recent study by Alejandra et al reported a comprehensive analysis of gene heterogeneity by single‐cell RNA sequencing in healthy as well as atheromatous mice 9 .…”

Section: Introductionmentioning

confidence: 99%

Elucidating key immunological biomarkers and immune microenvironment dynamics in aging‐related intracranial aneurysm through integrated multi‐omics analysis

Wang,

Xiao,

Zhang

et al. 2024

Environmental Toxicology

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BackgroundThe exact cause of intracranial aneurysms (IA) is still unclear. However, pro‐inflammatory factors are known to contribute to IA progression. The specific changes in the immune microenvironment of IAs remain largely unexplored.MethodsThis study analyzed single‐cell sequencing data from a male mouse model of brain aneurysm, focusing on samples before and after elastase‐induced Willis aneurysms. The data helped identify eight distinct cell subpopulations: fibroblasts, macrophages, NK cells, endothelial cells, B cells, granulocytes, and monocytes. The study also involved bulk RNA sequencing of 97 IA samples, utilizing ssGSEA and CIBERSORT algorithms for analysis. Intercellular communication among these cells was inferred to understand the immune dynamics in IA.ResultsThe study found that fibroblasts and macrophages are predominant in various disease states of IA. Notably, the onset of IA was marked by a significant increase in fibroblasts and a decrease in macrophages. There was a marked increase in cellular interactions, especially involving macrophages, at the onset of the disease. Through enrichment analysis, 12 potential immunogenic biomarkers were identified. Of these, Rgs1 emerged as a critical molecule in IA formation, confirmed through secondary validation in a single‐cell sequencing dataset.ConclusionThis comprehensive analysis of immune cell composition and intercellular communication in IA tissues highlights the significant roles of macrophages and the molecule Rgs1. These findings shed light on the physiological and pathological conditions of IA, offering new insights into its immune microenvironment.

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An immunogenic cell death-related regulators classification patterns and immune microenvironment infiltration characterization in intracranial aneurysm based on machine learning

Cited by 16 publications

References 39 publications

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity

DNA Methylation-estimated Phenotypes, Telomere length, Aging and Risk of Intracranial Aneurysms: Evidence from genetic studies

Elucidating key immunological biomarkers and immune microenvironment dynamics in aging‐related intracranial aneurysm through integrated multi‐omics analysis

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