Integrated Clinical, Imaging, and Proteomic Profiling Reveals Molecular Pathways and Predictive Signatures of Acute Ischemic Stroke Recurrence
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ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Chen Ding
PROVIDER: PXD079739 | iProX | Mon Jun 15 00:00:00 BST 2026
REPOSITORIES: iProX
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Project description:Acute ischemic stroke (AIS) is a major cause of disability and mortality worldwide, typically resulting from a thrombus that blocks cerebral blood flow and often leading to severe neurological impairment and irreversible brain damage. Current treatments focus on thrombolysis and neuroprotection, with recombinant tissue plasminogen activator (rt-PA) and edaravone (Eda) as key drugs. However, their therapeutic efficacy is constrained by poor targeting, leading to suboptimal drug delivery to the brain. Herein, we develop a biomimetic delivery system (PLEA) by hybridizing platelet membranes with liposomes, leveraging natural thrombus-targeting ability of platelet membrane to enhance drug delivery efficiency. Eda was encapsulated in the lipid bilayer of PLEA, while rt-PA was loaded into the core. PLEA (platelet membrane-liposome hybrid delivery system encapsulating Eda and rt-PA) effectively targeted thrombus sites, enabling localized drug delivery, synchronously enhancing thrombolysis and providing neuroprotection in a mouse model of AIS. Photoacoustic (PA) imaging was used to monitor clot formation and assess changes in intracranial blood flow and oxygen levels, highlighting its potential for evaluating therapeutic efficacy. These findings indicate that PA imaging-guided PLEA treatment represents a promising approach for precise stroke treatment.
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Project description:Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circRNA expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-contained circRNAs after AIS is still unknown. Plasma exosomes from ten AIS patients and ten controls were isolated, and through microarray and bioinformatics analysis, profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 FoldChange|≥1.00, P<0.05) between AIS patients and controls.The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion and leukocyte transendothelial migration, were associated with the development of AIS. As miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2- two RNA binding proteins (RBPs)- and play a role in AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls, and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.
2022-01-28 | GSE195442 | GEO
Project description:To understand the role of exosome miRNAs in AIS disease and to explore the miRNAs and the potential mechanisms related to the occurrence and development of the disease. This research collected serum samples from AIS patients and healthy volunteers and extracted exosome miRNA. The exosome miRNA associated with AIS was screened by illumina high-throughput sequencing . The differentially expressed target genes related to miRNAs were analyzed using bioinformatics analysis including GO functional enrichment analysis, KEGG pathway enrichment analysis, and the screening of key genes via PPI diagram. These differentially expressed mRNAs were indicated an important role in a variety of biological processes and multiple pathways of AIS disease.
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Project description:This project presents large-scale plasma proteomic profiling of 367 acute ischemic stroke (AIS) patients and 200 healthy controls. The dataset was generated to investigate molecular signatures associated with AIS diagnosis, lesion location, and clinical prognosis. Comprehensive bioinformatic and machine-learning analyses were performed to identify disease-related proteins and predictive biomarkers. This resource provides a valuable proteomic dataset for studying the molecular mechanisms of AIS and for developing diagnostic and prognostic biomarkers.
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Project description:Background: Long noncoding RNAs (lncRNAs) have been confirmed to be associated with ischemic stroke (IS); however, their involvement still needs to be extensively explored. Therefore, we aimed to study the expression profile of lncRNAs and the potential roles and mechanisms of lncRNAs in the pathogenesis of acute ischemic stroke (AIS) in the Southern Chinese Han population. Methods: lncRNA and mRNA expression profiles in AIS were analyzed using high-throughput RNA sequencing (RNA-Seq) and validated using quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses were performed to predict the functions and interactions of the aberrantly expressed genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of lncRNAs in AIS. Results: RNA-Seq analysis showed that 428 lncRNAs and 957 mRNAs were significantly upregulated, while 791 lncRNAs and 4263 mRNAs were downregulated in patients with AIS when compared with healthy controls. GO enrichment and KEGG pathway analyses of differentially expressed genes showed that the apoptosis, inflammatory, oxidative and calcium signaling pathways were potentially implicated in AIS pathology. The PCR results showed that the selected lncRNA-C14orf64 and lncRNA-AC136007.2 were significantly downregulated in AIS. ROC curve analysis showed that the area under the ROC curve (AUC) values of lncRNA-C14orf64 and lncRNA-AC136007.2 between AIS and healthy controls were 0.74 and 0.94, respectively. Conclusion: This study provides evidence of altered expression of lncRNAs and their potential functions in AIS. Our findings may facilitate pathological mechanistic studies of lncRNAs in AIS and provide potential diagnostic biomarkers and therapeutic targets for AIS.
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Project description:Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs can be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke. We profiled the blood circRNA expression in mice subjected to experimental focal cerebral ischemia, and validated the selected circRNAs in AIS patients. We demonstrated that 128, 198 and 789 circRNAs were significantly altered at 5 min, 3 h and 24 h after ischemic stroke, respectively.
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