The role of lymphocytes in neonatal encephalopathy

Melo, Ashanty M; Taher, Nawal Ab.; Doherty, Derek G.; Molloy, Eleanor J.

doi:10.1016/j.bbih.2021.100380

Cited by 9 publications

(2 citation statements)

References 98 publications

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“…The association between ferroptosis and immune infiltration is extremely complex. It has been confirmed that lymphocytes have a protective role in neonatal encephalopathies, such as decreased T cells increase inflammatory cell infiltration, primarily neutrophils, and inflammatory macrophages, which contribute to increased HI-induced brain damage, indicating that regulatory T cells in the injured brain may be an important mechanism of endogenous neuroprotection [ 50 , 51 ]. Previous studies have shown that the cytotoxicity in neonatal NK cells and low expression levels of L-selectin and CD54 lead to impaired ability to adhere to target cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

Sun³

et al. 2022

Cells

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Background: The mechanisms underlying ferroptosis in neonatal hypoxic-ischemic brain damage (HIBD) remain unclear. Method: Four microarray datasets were collected from the GEO database (three mRNA datasets GSE23317, GSE144456, and GSE112137, and one miRNA microarray dataset GSE184939). Weighted gene co-expression network analysis (WGCNA) was used to identify modules of HIBD-related genes. The ferroptosis-related genes were extracted from FerrDb, of which closely correlated to HIBD were obtained after the intersection with existing HIBD’s DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as protein–protein interaction (PPI) network analysis were subsequently conducted. Cytoscape was used to identify central genes. Immune cell infiltration analysis was performed by the CIBERSORT algorithm. Result: Fifty-six ferroptosis-related differentially expressed genes (FRDEGs) were screened, mainly related to ferroptosis, autophagy, hypoxia response, metabolic pathways, and immune inflammation. The seven optimal hub FRDEGs were obtained by intersecting with key modules of WGCNA. Then, the expression levels of the seven optimal hub FRDEGs were validated in the GSE144456 and GSE112137 datasets, and the ferroptosis-related mRNA-miRNA network was established. In addition, this study revealed immune cell infiltration in the HIBD cerebral cortex and the interaction between immune cells. Moreover, notably, specific FRDEGs were strongly positively correlated with immune function. Conclusions: The mechanism of ferroptosis is intricate and closely related to neonatal HIBD. Therefore, targeting ferroptosis-related gene therapy and immunotherapy may have therapeutic prospects for neonatal HIBD.

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Section: Discussionmentioning

confidence: 99%

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

Sun³

et al. 2022

Cells

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“…Thus far, Zfra1-31 or 4-10, and WWOX7-21 peptides, and antibodies against Hyal-2 or pY216-Hyal-2 are known ligands for activating Z cells [ 68 ]. Inflammatory NK cells kill cancer cells and cause damage to neurons [ 75 , 76 , 77 , 78 ]. In contrast, activated Z cells protect neurons from being damaged [ 71 ].…”

Section: Zfra4-10 Activates Hyal-2/wwox/smad4 Signaling Pathway For R...mentioning

confidence: 99%

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Chen,

Liu,

Wen

et al. 2024

IJMS

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We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer’s disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid β. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells.

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Identification and analysis of oxidative stress‐related genes in hypoxic‐ischemic brain damage using bioinformatics and experimental verification

Jin,

Sha,

Ruan

et al. 2024

Immunity Inflam & Disease

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BackgroundOxidative stress (OS) plays a major role in the progress of hypoxic‐ischemic brain damage (HIBD). This study aimed to investigate OS‐related genes and their underlying molecular mechanisms in neonatal HIBD.MethodsMicroarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS‐related genes were drawn from GeneCards and OS‐DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS‐DEGs in HIBD. Moreover, the hub genes were screened using the protein−protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS‐DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT‐qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS‐DEGs.ResultsIn total, 93 OS‐DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS‐related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS‐related biomarker genes were screened. Eventually, RT‐qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3.ConclusionsFos, Tlr2 and Atf3 are potential OS‐related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD.

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The role of lymphocytes in neonatal encephalopathy

Cited by 9 publications

References 98 publications

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

New Insights into Mechanisms of Ferroptosis Associated with Immune Infiltration in Neonatal Hypoxic-Ischemic Brain Damage

Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration

Identification and analysis of oxidative stress‐related genes in hypoxic‐ischemic brain damage using bioinformatics and experimental verification

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