Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury

Yang, Wei; Ding, Ning; Luo, Rong; Zhang, Qian; Li, Zhenhua; Zhao, Fang; Zhang, Shuixian; Zhang, Xuyang; Zhou, Tengyuan; Wang, Haomiao; Wang, Long; Hu, S. Jack; Wang, Guixue; Feng, Hua; Hu, Rong

doi:10.1016/j.bioactmat.2023.03.007

Cited by 43 publications

(12 citation statements)

References 63 publications

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“…Multiple behavioral tests were performed to assess the overall behavioral performance of mice in the groups. As previously reported, motor function was assessed using the open field test on day 7 after IVH 43 (Figure 5 E). On day 7 after IVH, mice in the IVH group exhibited notable deficits in motor function, including decreases in total movement and average speed, in comparison to mice in the Sham group (Figure 5 F, G).…”

Section: Resultsmentioning

confidence: 91%

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Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Zhang,

Chen,

et al. 2024

Theranostics

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Rationale: Hydrocephalus is a substantial complication after intracerebral hemorrhage (ICH) or intraventricular hemorrhage (IVH) that leads to impaired cerebrospinal fluid (CSF) circulation. Recently, brain meningeal lymphatic vessels (mLVs) were shown to serve as critical drainage pathways for CSF. Our previous studies indicated that the degradation of neutrophil extracellular traps (NETs) after ICH/IVH alleviates hydrocephalus. However, the mechanisms by which NET degradation exerts beneficial effects in hydrocephalus remain unclear. Methods: A mouse model of hydrocephalus following IVH was established by infusing autologous blood into both wildtype and Cx3cr1 -/- mice. By studying the features and processes of the model, we investigated the contribution of mLVs and NETs to the development and progression of hydrocephalus following secondary IVH. Results: This study observed the widespread presence of neutrophils, fibrin and NETs in mLVs following IVH, and the degradation of NETs alleviated hydrocephalus and brain injury. Importantly, the degradation of NETs improved CSF drainage by enhancing the recovery of lymphatic endothelial cells (LECs). Furthermore, our study showed that NETs activated the membrane protein CX3CR1 on LECs after IVH. In contrast, the repair of mLVs was promoted and the effects of hydrocephalus were ameliorated after CX3CR1 knockdown and in Cx3cr1 -/- mice. Conclusion: Our findings indicated that mLVs participate in the development of brain injury and secondary hydrocephalus after IVH and that NETs contribute to acute LEC injury and lymphatic thrombosis. CX3CR1 is a key molecule in NET-induced LEC damage and meningeal lymphatic thrombosis, which leads to mLV dysfunction and exacerbates hydrocephalus and brain injury. NETs may be a critical target for preventing the obstruction of meningeal lymphatic drainage after IVH.

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Section: Resultsmentioning

confidence: 91%

“…The open field test was performed to measure the overall locomotion behavior of mice 43 . The testing instrument was 50 cm × 50 cm × 50 cm in size.…”

Section: Methodsmentioning

confidence: 99%

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Zhang,

Chen,

et al. 2024

Theranostics

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“…Proteins (30 ug) were extracted from whole cell lysates and separated on 10% SDS-PAGE gels as described previously [ 20 ]. The protein ribbons were then transferred to the PVDF membrane and closed with a PBS containing 5% BSA for 1 h. After incubation with CXCR4 antibody (1:2000, Abcam, Waltham, MA, USA) overnight at 4 °C, the protein band was incubated for 1 h with the corresponding secondary antibody (CST, 6883, Danvers, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

et al. 2023

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Glioblastoma (GBM) is a highly malignant and aggressive tumor with poor prognosis. Therefore, the discovery of new prognostic molecular markers is of great significance for clinical prognosis. The CXC chemokine receptor (CXCR) members play a key regulatory role in many cancers. In this study, we explore the clinical value and application of the CXCR members in primary glioblastoma. Two GBM datasets from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases were used to explore the relationship between differential expression of CXCRs and GBM subtypes as well as immune infiltration. C-X-C motif chemokine receptor 4 (CXCR4) was screened as an independent prognostic factor, and a nomogram and risk prediction model were developed and tested in the CGGA database using the TCGA database. Receiver operating curve (ROC) and decision curve analysis (DCA) found good accuracy and net benefit of the models. The correlation of CXCR4 with immune infiltration and tumor was analyzed using CancerSEA and TIMER. In in vitro experiments, we found that CXCR4 was significantly overexpressed in glioblastoma and was closely related to the inflammatory response of U251/U87 cells. CXCR4 is an excellent independent prognostic factor for glioblastoma and positively correlates with tumor inflammation.

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“…Three studies [ 74 , 77 , 78 ] explored ferroptosis-related lncRNAs in CRC patients from the TCGA dataset. Ferroptosis is an iron-dependent programmed cell death that is different from other types of cell death, such as apoptosis or necrosis [ 79 ]. They incorporated the risk score with clinicopathological variables, of which age, sex, and tumor staging were the most relevant variables, and a clinical nomogram was developed.…”

Section: Elfn1-as1 Clinical Implicationmentioning

confidence: 99%

Role of long non-coding RNA ELFN1-AS1 in carcinogenesis

HajiEsmailpoor,

Fayazi,

Teymouri

et al. 2024

Discov Onc

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As one of the leading causes of death worldwide, cancer significantly burdens patients and the healthcare system. The role of long non-protein coding RNAs (lncRNAs) in carcinogenesis has been extensively studied. The lncRNA ELFN1-AS1 was discovered recently, and subsequent studies have revealed its aberrantly high expression in various cancer tissues. In vitro and in vivo experiments have consistently demonstrated the close association between increased ELFN1-AS1 expression and malignant tumor characteristics, particularly in gastrointestinal malignancies. Functional assays have further revealed the mechanistic role of ELFN1-AS1 as a competitive endogenous RNA for microRNAs, inducing tumor growth, invasive features, and drug resistance. Additionally, the investigation into the clinical implication of ELFN1-AS1 has demonstrated its potential as a diagnostic, therapeutic, and, notably, prognostic marker. This review provides a comprehensive summary of evidence regarding the involvement of ELFN1-AS1 in cancer initiation and development, highlighting its clinical significance.

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Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury

Cited by 43 publications

References 63 publications

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

Role of long non-coding RNA ELFN1-AS1 in carcinogenesis

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