Neuregulin-1 attenuates hemolysis- and ischemia induced-cerebrovascular inflammation associated with sickle cell disease

Chambliss, Christopher; Stiles, Jonathan K.; Gee, Beatrice E.

doi:10.1016/j.jstrokecerebrovasdis.2022.106912

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…NRG1 was transduced through the receptor tyrosine-protein kinase erythroblastic oncogene B (ErbB) family to regulate downstream pathways PI3K–AKT and PI3K–extracellular-signal-regulated kinase signaling pathway. It had been demonstrated NRG1 signaling involved in NPCs activation [ 38 ], neuroprotective effects [ 39 , 40 ], neuroinflammatory modulation [ 41 , 42 ], and angiogenesis [ 43 ]. Through Western blot, the expression of NRG1 and AKT, typically activated in the EBP-bFGF/ECM group, was verified compared with the other 2 groups.…”

Section: Discussionmentioning

confidence: 99%

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Shi,

Liu,

Sun

et al. 2024

Biomater Res

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Cerebral ischemia was one of the leading causes of mortality and disability worldwide. Extracellular matrix (ECM) hydrogel held great potential to replace volumetric brain tissue loss following ischemic injury but with limited regenerative effect for functional restoration when implanted alone. In the present study, an engineered basic fibroblast growth factor (EBP-bFGF) was constructed, which fused a specific ECM-binding peptide (EBP peptide) with bFGF. The recombinant EBP-bFGF showed typical binding capacity with ECM without affecting the bioactivity of bFGF both in vitro and in vivo. Furthermore, the EBP-bFGF was used for bioactive modification of ECM hydrogel to repair cerebral ischemia. The combination of EBP-bFGF and ECM hydrogels could realize the sustained release of bFGF in the ischemic brain and improve the regenerative effect of ECM, which protected the survival of neurons, enhanced angiogenesis, and decreased the permeability of blood–brain barrier, ultimately promoted the recovery of motor function. In addition, transcriptome analysis revealed neuregulin-1/AKT pathway involved in this process. Therefore, EBP-bFGF/ECM hydrogel would be a promising therapeutic strategy for cerebral ischemia.

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Section: Discussionmentioning

confidence: 99%

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Shi,

Liu,

Sun

et al. 2024

Biomater Res

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Anti-inflammatory effects of neuregulin-1 in HaCaT keratinocytes and atopic dermatitis-like mice stimulated with Der p 38

Yun,

Hong,

Hong

et al. 2024

Cytokine

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Circulating biomarkers associated with pediatric sickle cell disease

Lekpor,

Botchway,

Driss

et al. 2024

Front. Mol. Biosci.

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IntroductionSickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), causing red blood cells to deform into a sickle shape. These deformed cells can block blood flow, leading to complications like chronic hemolysis, anemia, severe pain episodes, and organ damage. SCD genotypes include HbSS, HbSC (HbC is an abnormal variant of hemoglobin), and HbS/β-thalassemia. Sickle cell trait (SCT), HbAS, represents the carrier state, while other hemoglobin variants include HbCC, HbAC, and the normal HbAA. Over 7.5 million people worldwide live with SCD, with a high mortality rate in sub-Saharan Africa, including Ghana. Despite its prevalence, SCD is underdiagnosed and poorly managed, especially in children. Characterized by intravascular hemolysis, SCD leads to oxidative stress, endothelial activation, and systemic inflammation. Identifying circulating blood biomarkers indicative of organ damage and systemic processes is vital for understanding SCD and improving patient management. However, research on biomarkers in pediatric SCD is limited and few have been identified and validated. This study explores specific circulating biomarkers in pediatric SCD in Ghana (West Africa), hypothesizing that inflammatory and neuronal injury markers in children with SCD could predict disease outcomes.MethodsClinical data were collected from 377 children aged 3–8 years with various Hb genotypes, including SCD and SCT, at Korle-Bu Teaching Hospital in Accra, Ghana (2021–2022). A total of 80 age- and sex-matched subjects were identified. A cross-sectional study utilized a multiplexed immunoassay procedure to evaluate serum biomarkers, including cytokines, chemokines, vascular injury markers, systemic inflammation markers, cell-free heme scavengers, brain-derived neurotrophic factor (BDNF), and angiogenic factors.ResultsElevated levels of BDNF, Ang-2, CXCL10, CCL11, TNF-α, IL-6, IL-10, IL12p40, ICAM-1, VCAM-1, Tie-2, and VEGFA were observed in HbSS subjects, correlating with hemoglobin level, leukocyte, and erythrocyte counts. Heme scavengers like HO-1, hemopexin, and haptoglobin also correlated with these parameters. ROC and AUC analyses demonstrated the potential of these biomarkers in predicting SCD outcomes.ConclusionThese findings suggest that there are significant differences between biomarker expression among the different genotypes examined. We conclude that a predictive algorithm based on these biomarkers could be developed and validated through longitudinal assessment of within-genotype differences and correlation of the data with disease severity or outcomes. With such a tool one can enhance SCD management and improve patient outcomes. This approach may pave the way for personalized interventions and better clinical care for pediatric SCD patients.

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Neuregulin-1 attenuates hemolysis- and ischemia induced-cerebrovascular inflammation associated with sickle cell disease

Cited by 3 publications

References 53 publications

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Engineered Basic Fibroblast Growth Factor Specifically Bonded with Injectable Extracellular Matrix Hydrogel for the Functional Restoration of Cerebral Ischemia in Rats

Anti-inflammatory effects of neuregulin-1 in HaCaT keratinocytes and atopic dermatitis-like mice stimulated with Der p 38

Circulating biomarkers associated with pediatric sickle cell disease

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