Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke

Gao, Juan; Liu, Jifei; Li, Yonghong; Liu, Junxi; Wang, He; Chai, Miao; Dong, Ying; Zhang, Z; Su, Gang; Wang, Manxia

doi:10.1002/jnr.25200

Cited by 10 publications

(5 citation statements)

References 173 publications

(189 reference statements)

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“…Simultaneously, the overlapping mRNAs were enriched in the regulation of myeloid cell differentiation, response to cycloheximide, and cellular response to interleukin-1, which were associated with neuroimmune and neuropathic pain [ 29 , 30 , 31 ]. KEGG pathway analysis also illustrated that overlapping mRNAs were enriched in the p53 signaling pathway, natural killer (NK) cell-mediated cytotoxicity, and TNF signaling pathway, which could modulate the development of pain [ 32 , 33 , 34 ]. Moreover, NK cells, a key component of the innate immune response [ 35 ], regulate chronic pain and chemically induced neuropathies [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

Cao

Wang

et al. 2023

CIMB

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Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and severe side effect of first-line chemotherapeutic agents. The association between circular RNAs (circRNAs) and CIPN remains unclear. In this study, CIPN models were constructed with Taxol, while 134 differentially expressed circRNAs, 353 differentially expressed long non-coding RNAs, and 86 differentially expressed messenger RNAs (mRNAs) were identified utilizing RNA sequencing. CircRNA-targeted microRNAs (miRNAs) were predicted using miRanda, and miRNA-targeted mRNAs were predicted using TargetScan and miRDB. The intersection of sequencing and mRNA prediction results was selected to establish the circRNA–miRNA–mRNA networks, which include 15 circRNAs, 18 miRNAs, and 11 mRNAs. Functional enrichment pathway analyses and immune infiltration analyses revealed that differentially expressed mRNAs were enriched in the immune system, especially in T cells, monocytes, and macrophages. Cdh1, Satb2, Fas, P2ry2, and Zfhx2 were further identified as hub genes and validated by RT-qPCR, correlating with macrophages, plasmacytoid dendritic cells, and central memory CD4 T cells in CIPN. Additionally, we predicted the associated diseases, 36 potential transcription factors (TFs), and 30 putative drugs for hub genes using the DisGeNET, TRRUST, and DGIdb databases, respectively. Our results indicated the crucial role of circRNAs, and the immune microenvironment played in CIPN, providing novel insights for further research.

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Section: Discussionmentioning

confidence: 99%

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

Cao

Wang

et al. 2023

CIMB

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“…β-Sitosterol can also regulate the intestinal flora to inhibit the production of trimethylamine, reduce the levels of translation machinery-associated protein (TMA) and flavin-containing monooxygenase 3 (FMO3), improve cholesterol metabolism and atherosclerotic plaques, and enhance antioxidant capacity [20] . In addition, based on literature supplements, the active ingredients of Angelica sinensis, Ligustilide and Ferulic Acid, also have neuroprotective effects such as inhibiting oxidative stress, inhibiting cell apoptosis, anti-inflammatory, anti-platelet aggregation, and alleviating brain edema [21][22] .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Salvia miltiorrhiza and Angelica sinensis herbal pair in intervening ischemic stroke based on network pharmacology and molecular docking

2023

FMSR

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This study aims to explore the molecular mechanism of Salvia miltiorrhiza and Angelica sinensis (Salvia-Angelica) herbal pair in intervening ischemic stroke by network pharmacology method. The active ingredients and action targets of the Salvia-Angelica herbal pair were selected through TCMSP. Ischemic stroke disease targets were searched using the GeneCards, DisGeNET, and TTD databases. The Venny platform was used to intersect drug action targets with disease targets, obtaining potential action targets of Salvia-Angelica herbal pair for intervening ischemic stroke. The intersected targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. Using the Cytoscape software, the visual graph of "Drug-Component-Target-Disease" and key targets PPI network were constructed. The DAVID database was used for GO enrichment and KEGG pathway enrichment analysis. Target-ingredient docking was verified and evaluated using CB-Dock2 platform. A total of 63 active ingredients of the Salvia-Angelica herbal pair were obtained, and 93 intersection targets of drugs and diseases were identified. Key active ingredients include luteolin, tanshinone IIA, dihydrotanshinlactone, β-sitosterol, etc. Core targets acting on the disease include AKT1, TNF, IL6, PTGS2, CASP3, EGFR, etc. GO enrichment resulted in 836 entries, suggesting that the Salvia-Angelica herbal pair functions in biological processes such as positive regulation of transcription from RNA polymerase II promoter, positive regulation of cell proliferation, and signal transduction. KEGG pathway enrichment resulted in 170 signal pathways, mainly involving Pathways in cancer, Lipid and atherosclerosis pathways, PI3K-AKT signaling pathways, and AGE-RAGE signaling pathway in diabetes complications, etc. Molecular docking showed that the active components from the Salvia-Angelica herbal pair exhibited better affinity with key targets. This study suggest that the Salvia-Angelica herbal pair exert its therapeutic effect on ischemic stroke through multiple components, multiple targets, and multiple pathways, including anti-inflammatory, antioxidant, anticoagulant effects, inhibiting cell apoptosis, promoting cell proliferation, and improving vascular endothelium.

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“…If for some reason the inflammatory response goes excessively uncontrolled or persists over time, it causes pathological neuroinflammation, which increases blood-cerebrospinal fluid barrier permeability and peripheral immune cell infiltration, and elevated levels of classical inflammatory cytokines, leading to cell death and histopathological damage [ 1 , 4 ]. Neuroinflammation plays a central role in many complex health problems, such as neurodegenerative diseases [ 5 , 6 ], autoimmune diseases (e.g., multiple sclerosis [ 7 ]), infections [ 8 ], strokes [ 9 ], traumatic injuries [ 10 ], inflammatory pain [ 11 ], postoperative cognitive impairment [ 12 ], epilepsy [ 13 ], and depression [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments

Liu

Zhao

et al. 2023

Aging

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Neuroinflammation plays an important role in the pathogenesis of neurological disorders, and despite intensive research, treatment of neuroinflammation remains limited. BaiXiangDan capsule (BXD) is widely used in clinical practice. However, systematic studies on the direct role and mechanisms of BXD in neuroinflammation are still lacking. We systematically evaluated the potential pharmacological mechanisms of BXD on neuroinflammation using network pharmacological analysis combined with experimental validation. Multiple databases are used to mine potential targets for bioactive ingredients, drug targets and neuroinflammation. GO and KEGG pathway analysis was also performed. Interactions between active ingredients and pivotal targets were confirmed by molecular docking. An experimental model of neuroinflammation was used to evaluate possible therapeutic mechanisms for BXD. Network pharmacological analysis revealed that Chrysoeriol, Kaempferol and Luteolin in BXD exerted their anti-neuroinflammatory effects mainly by acting on targets such as NCOA2, PIK3CA and PTGS2. Molecular docking results showed that their average affinity was less than −5 kcal/mol, with an average affinity of −8.286 kcal/mol. Pathways in cancer was found to be a potentially important pathway, with involvement of PI3K/AKT signaling pathways. In addition, in vivo experiments showed that BXD treatment ameliorated neural damage and reduced neuronal cell death. Western blotting, RT-qPCR and ELISA analysis showed that BXD inhibited not only the expression of IL-1β, TNF-α and NO, but also NF-κB, MMP9 and PI3K/AKT signaling pathways. This study applied network pharmacology and in vivo experiments to explore the possible mechanisms of BXD against neuroinflammation, providing insight into the treatment of neuroinflammation.

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Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke

Cited by 10 publications

References 173 publications

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

Identifying circRNA–miRNA–mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy

Mechanisms of Salvia miltiorrhiza and Angelica sinensis herbal pair in intervening ischemic stroke based on network pharmacology and molecular docking

Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments

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