Human mesenchymal stem cells prevent neurological complications of radiotherapy
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ABSTRACT:
PROVIDER: PRJNA475889 | ENA |
REPOSITORIES: ENA
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Project description:Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer survivors. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cell (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. The molecular analysis revealed that hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in the irradiated neurogenic niches. Furthermore, hMSC treatment did not compromise survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as an effective and non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor survivors.
2019-06-21 | GSE115735 | GEO
Project description:Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer patients. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cells (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. This intervention confers protection against inflammation, oxidative stress, and neuronal loss. hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in irradiated brains. Furthermore, hMSC treatment did not compromise the survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as a non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor patients.
| S-EPMC6532528 | biostudies-literature
Project description:Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications, e.g., hydrocephalus are observed in up to 50% of patients affected. The study of TBM pathogenesis is hampered, at least partially, by a lack of experimental models that recapitulate all clinical features of the human disease. With single-cell transcriptome of blood in tuberculosis revealed, the single cell transcriptome atlas in TBM brain remains yet to be explored. Here, a TBM model was built and then whole brain was dissected for single cell sequencing. Transcriptional changes were observed in all cell types, suggesting a complex biology in TBM pathogenesis. As a result, pervasive immune response was activated by transcription factors Stat1 and IRF1 in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons links TBM with neurodegenerative diseases. Finally, Ependymal cells show most remarkable transcriptional changes, and decreased Frmd4a may contribute to hydrocephalus and neurodegenerative disorders. We first revealed a comprehensive transcriptome map in TBM mouse model with ScRNA-Seq, and link the cell types, transcriptional genes with regulons and functional processes with neurological complications. These identified cellular and molecular changes offer an unprecedented clue for inspiring the clinical diagnosis and therapeutics of TBM.
2023-08-02 | GSE199649 | GEO
Project description:Single cell analysis reveals transcriptional changes underlying neurological complications in tuberculous meningitis
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Project description:Association of miR-29 with postoperative neurological complications in acute type A aortic dissection patients
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Project description:The study of new biomarkers for early detection of diabetes complications could bring new prevent approaches perspectives.
2023-05-11 | E-MTAB-13000 | biostudies-arrayexpress
Project description:Objectives. Postoperative neurological complications (PONC), associated with substantial morbidity and mortality, represent a prevalent clinical challenge following surgical repair of acute type A aortic dissection (AAD). This study aimed to identify novel biomarkers for early diagnosis of PONC to facilitate timely clinical intervention. Methods. We established deep hypothermic circulatory arrest (DHCA) rat models, extracted total RNA from the hippocampus of rats (DHCA group and control group), performed miRNA sequencing, screened for differentially expressed genes (DEGs) between the two groups, and analyzed their associated biological processes (BP) and pathways. A cohort of 95 patients diagnosed with AAD was enrolled in this study. Comprehensive clinical assessments and a standardized neuropsychological test battery were systematically conducted. Serum miR-29 levels were quantified via reverse transcription quantitative real-time polymerase chain reaction. Results. Transcriptomic profiling of rat hippocampus under deep hypothermic circulatory arrest / cardiopulmonary bypass (DHCA/CPB) identified 37 differentially expressed miRNAs (|log2FC|≥1.3, P<0.05), with miR-29a-5p and miR-29b-3p showing the most significant dysregulation. Functional enrichment implicated MAPK signaling and junctional pathways in blood-brain barrier modulation. In a clinical cohort of 95 aortic dissection patients, the PONC group exhibited prolonged CPB time (164.00 (137.00, 193.00) vs. 140.00 (120.25, 161.00), P=0.012), elevated inflammatory biomarkers (pre-op interleukin-6: 106.60 vs. 47.00, P<0.001), and altered miR-29 expression profiles. Multivariate analysis confirmed preoperative miR-29b-3p (OR=2.53, 95%CI 1.17-5.47) and postoperative miR-29a-5p (OR=0.21, 95%CI 0.05-0.96) as independent PONC predictors. The nomogram demonstrated robust discrimination (AUC=0.867, 95%CI 0.771-0.963) and clinical utility (net benefit=0.23), with 30-day survival analysis revealing miR-29b-3p-associated mortality risk (HR=4.372, 95%CI 0.928-20.596, P=0.041). Conclusions. Dual-phase miR-29 dysregulation predicts PONC post-AAD repair, validated by a nomogram and miR-29b-3p-associated mortality risk, guiding early intervention strategies.
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2026-02-25 | PXD056537 | JPOST Repository
Project description:Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up. miRNA expression analysis in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline. miRNAs with increased expression correlated positively with cardiopulmonary dose-volume histogram metrics, while those with decreased expression exhibited negative correlations.
2023-05-07 | GSE225243 | GEO
Project description:Dog neurological disease-identification of mutation
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