Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking

Xu, Xiaoyu; Luo, Hongyu; Chen, Qian; Wang, Zikang; Chen, Xixuan; Li, Xiaping; Chen, Huan; Wang, Miao; Xu, Yi; Dai, Min; Wang, Jianwei; Huang, Xinghua; Wu, Bin; Li, Yanping

doi:10.3389/fphar.2022.1047061

Cited by 3 publications

(1 citation statement)

References 70 publications

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“…Suggesting that vitamin D3 plays a key role in the prevention of colorectal cancer (CRC) through core targets, the phosphatidylinositol 3-kinase- protein kinase B (PI3K-AKT), hypoxia-inducible factor 1 (HIF-1), and forkhead box protein (FoxO) pathways [ 28 ]. In addition, vitamin D3 plays an important role in the inhibition of the NF-κB pathway; therefore, it has been proposed as a treatment for rheumatoid arthritis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Putative mechanism of a multivitamin treatment against insulin resistance

Palma-Jacinto,

López-López,

Medina-Franco

et al. 2024

Adipocyte

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Section: Introductionmentioning

confidence: 99%

Putative mechanism of a multivitamin treatment against insulin resistance

Palma-Jacinto,

López-López,

Medina-Franco

et al. 2024

Adipocyte

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Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for the treatment of rheumarthritis

Wang,

Mao

2024

Front. Genet.

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Objective: β-Sitosterol, which is derived from Vladimiriae Radix (VR), is used for the treatment of rheumatoid arthritis (RA), but the pharmacological mechanisms through which β-sitosterol affects RA have not been fully elucidated.Methods: Through the Traditional Chinese Medicine Systems Pharmacology and Analysis (TCMSP), PubChem, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases, “β-sitosterol-RA”-related genes were obtained, and a target protein interaction network (protein–protein interaction [PPI]) was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the intersecting genes. Discovery Studio 2019 software was used to perform molecular docking on MMP9, CASP3, HSP90AA1, SRC, EGFR, and ALB genes. β-Sitosterol was co-cultured with MH7A cells in three experimental groups: control group (DMSO), positive drug group (methotrexate, 80 μmol/L), and drug intervention group (10, 20, 40, 80, and 160 μmol/L β-sitosterol). The CCK8 method was used to investigate the inhibitory effect of β-sitosterol on the proliferation of MH7A cells. RT-PCR was used to analyze the mRNA expression of the abovementioned core targets.Results: A total of 41 genes associated with β-sitosterol and RA were obtained, mainly involving the FoxO signaling pathway and PI3K/AKT signaling pathway. The molecular docking results suggested that β-sitosterol could bind effectively to six core targets. The experimental results showed that β-sitosterol could significantly inhibit the excessive proliferation of MH7A cells (p< 0.05). The RT-PCR results showed that the expression of MMP9, HSP90AA1, SRC, EGFR, and ALB core genes in the control group was significantly upregulated, while the CASP3 gene was downregulated. Compared to the control group, the mRNA expression of MMP9, HSP90AA1, SRC, EGFR, and ALB decreased (p< 0.01), while the apoptosis-related gene CASP3 increased in both the drug intervention (80 μmol/L β-sitosterol) and positive drug groups (80 μmol/L methotrexate).Conclusion: Hence, β-sitosterol could contribute to the inhibition of RA by modulating cell proliferation and regulating the aforementioned six core proteins, potentially through the regulation of the FoxO and PI3K/AKT signaling pathways.

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Identiﬁcation and characterization of immunogenic cell death-related molecular clusters in rheumatoid arthritis

2024

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Background: This study is to analyze the potential mechanisms of immunogenic cell death genes (ICDs) in rheumatoid arthritis (RA) using bioinformatics methods and identify potential biomarkers. Method: We utilized the GSE93777 dataset to systematically evaluate the differential expression and immune characteristics of ICDs in RA patients. Thus, molecular clusters related to ICD, immune cell infiltration, and biological characteristics were explored. Weighted gene co-expression network analysis (WGCNA) was then performed to identify cluster-specific differentially expressed genes. Subsequently, we employed a Support Vector Machine (SVM) machine learning model for prediction analysis, with validation conducted using the external dataset GSE15573. Results: A total of 52 differentially expressed ICDs were identified between healthy individuals and RA patients. Compared to healthy individuals, RA patients exhibited high infiltration of T cells CD4 memory activated, T cells gamma delta, Monocytes, and Neutrophils. The ICD subtypes in RA patients displayed significant heterogeneity in terms of immunity. Specifically, Cluster 2 demonstrated elevated immune scores and relatively high levels of immune infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that cluster-specific differentially expressed genes in Cluster 2 were closely associated with amino acid and glucose metabolism and degradation, as well as the biosynthesis of N-glycosylation. For the diagnosis of RA, the SVM machine model demonstrated optimal performance with relatively low residual and high area under the curve (AUC=0.998) and was validated using an external validation dataset (GSE15573, AUC=0.700). Analysis of the column chart model indicated that CKS2, NDUFB1, CHCHD1, MAGOH, and MAP7D1 could be used as diagnostic markers for RA diseases. Conclusion: This study systematically elucidates the complex relationship between ICD and RA disease and establishes a promising predictive model to evaluate the risk of ICD subtypes and pathological outcomes in RA patients.

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Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking

Cited by 3 publications

References 70 publications

Putative mechanism of a multivitamin treatment against insulin resistance

Putative mechanism of a multivitamin treatment against insulin resistance

Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for the treatment of rheumarthritis

Identiﬁcation and characterization of immunogenic cell death-related molecular clusters in rheumatoid arthritis

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