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Background: Intracranial aneurysms (IA) frequently cause subarachnoid hemorrhage (SAH) and have poor prognosis. However, the molecular mechanisms and diagnostic biomarkers associated with IA and ruptured IA (rIA) remain poorly understood.
Methods: In this study, single-cell and transcriptome datasets were obtained from the GEO database. The cell populations were annotated to identify potential pathogenic subpopulations, followed by intercellular communication, pseudotime, and SCENIC analyses. Proteome-wide and transcriptome-wide Mendelian randomization (MR) analyses were conducted to identify risk factors for IA and SAH. The major pathological changes and diagnostic biomarkers of IA and SAH were identified based on the transcriptome datasets. A clinical cohort was established to identify the diagnostic biomarkers and validate the results.
Results: Macrophages and neutrophils were predominantly increased in IA and rIA tissues, and neutrophils were markedly upregulated in the blood of SAH patients. SPP1 Macrophage was progressively elevated in aneurysms, promoting vascular smooth muscle cell (VSMC) phenotypic transformation and collagen matrix remodeling through the SPP1 and TGF-β pathways. Furthermore, HIF1α regulon was enriched in SPP1 Macrophage, mediating inflammation and metabolic reprogramming, which contributed to IA progression. Integrated MR analysis identified CD36 as a risk factor for both IA and SAH, and it has been recognized as an effective blood biomarker for SAH. Neutrophils and their related indicators have emerged as excellent biomarkers of SAH in clinical cohorts.
Conclusion: This study highlighted the detrimental role of SPP1 Macrophage in IA and SAH using single-cell sequencing and MR analyses. CD36 was identified as a risk factor for IA and SAH and was also an efficient blood biomarker for SAH. In a clinical cohort, neutrophils and related indicators were valuable for the early diagnosis of SAH.
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http://dx.doi.org/10.2147/JIR.S493828 | DOI Listing |
3 Biotech
October 2025
Department of Oncology, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, China.
Unlabelled: By integrating single-cell and bulk RNA-sequencing data for esophageal cancer (ESCA), we developed and validated a seven-macrophage-gene prognostic signature (FCN1, SCARB2, ATF5, PHLDA2, GLIPR1, CHORDC1, and BCKDK). This signature effectively stratified patients into high- and low-risk groups with significantly different overall survival, achieving area under the curve (AUC) values greater than 0.7 for 1-, 2-, and 3-year survival prediction.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
July 2025
Department of Geriatrics, Hospital of Chengdu University of Traditional Chinese Medicine Chengdu 610072, China.
Idiopathic pulmonary fibrosis(IPF) is a chronic progressive interstitial lung disease characterized by a complex pathogenesis and limited treatment options. Although studies have indicated that lipid metabolism dysregulation is associated with the progression of IPF, the core regulatory mechanisms remain unclear. By integrating RNA sequencing data from the GEO database, we identified four key genes related to lipid metabolism: peroxisome proliferator-activated receptor gamma(PPARG), secreted phosphoprotein 1(SPP1), caspase 3(CASP3), and platelet endothelial cell adhesion molecule 1(PECAM1).
View Article and Find Full Text PDFFront Cell Dev Biol
August 2025
School of Life Sciences, Central South University, Changsha, China.
Introduction: Cardiac arrhythmia frequently co-presents with structural abnormalities such as cardiomyopathy and myocardial fibrosis, creating a bidirectional relationship where electrical disturbances and structural remodeling exacerbate each other. Current genetic studies focus on ion channel variants, which explain part of the etiology. Molecular mechanisms underlying arrhythmias pathogenesis and its progression warrant further investigation.
View Article and Find Full Text PDFCancer Res
September 2025
Guangzhou Medical University, Guangzhou, China.
Hypoxia, immune evasion, and metabolic reprogramming are key features of hepatocellular carcinoma (HCC) that limit the efficacy of therapies. Members of the solute carrier (SLC) family regulate metabolite homeostasis within tumor cells to maintain tumor survival under stressed conditions like hypoxia. Investigating the SLC family members could offer insights into the hypoxic microenvironment of HCC and potentially help identify improved therapeutic strategies.
View Article and Find Full Text PDFJ Exp Med
November 2025
Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Monocytes and macrophages in patients with lupus nephritis exhibit altered behavior compared with healthy kidneys. How to optimally use mouse models to develop treatments targeting these cells is poorly understood. This study compared intrarenal myeloid cells in four mouse models and 155 lupus nephritis patients using single-cell profiling, spatial transcriptomics, and functional studies.
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