Peripheral blood mononuclear cell low molecular mass protein 7 in acute ischemic stroke: vertical change from admission to discharge and correlation with disability, stroke recurrence, and death
Ontology highlight
ABSTRACT:
SUBMITTER: Hou L
PROVIDER: S-EPMC10885349 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Stroke is the leading cause of severe long-term disability. Cell therapy has recently emerged as an approach to facilitate functional recovery in stroke. Although administration of peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation (OGD-PBMCs) has been shown to be a therapeutic strategy for ischemic stroke, the recovery mechanisms remain largely unknown. We hypothesised that cell-cell communications within PBMCs and between PBMCs and resident cells are necessary for a polarising protective phenotype. Here, we investigated the therapeutic mechanisms underlying the effects of OGD-PBMCs through the secretome. We compared levels of transcriptomes, cytokines, and exosomal microRNA in human PBMCs by RNA sequences, Luminex assay, flow cytometric analysis, and western blotting under normoxic and OGD conditions. We also performed microscopic analyses to assess the identification of remodelling factor-positive cells and evaluate angiogenesis, axonal outgrowth, and functional recovery by blinded examination by administration of OGD-PBMCs after ischemic stroke in Sprague-Dawley rats. We found that the therapeutic potential of OGD-PBMCs was mediated by a polarised protective state through decreased levels of exosomal miR-155-5p, and upregulation of vascular endothelial growth factor and a pluripotent stem cell marker stage-specific embryonic antigen-3 through the hypoxia-inducible factor-1α axis. After administration of OGD-PBMCs, microenvironment changes in resident microglia by the secretome promoted angiogenesis and axonal outgrowth, resulting in functional recovery after cerebral ischemia. Our findings revealed the mechanisms underlying the refinement of the neurovascular unit by secretome-mediated cell-cell communications through reduction of miR-155-5p from OGD-PBMCs, highlighting the therapeutic potential carrier of this approach against ischemic stroke.
| S-EPMC10480381 | biostudies-literature
Project description:Epigenetic modification may play an important role in pathophysiology of ischemic stroke (IS) risk. MicroRNAs (miRNAs), which constitute one of the modes of epigenetic regulation, have been shown to be associated with a number of clinical disorders including IS. The purpose of this study was to investigate the miRNA profile in the peripheral blood mononuclear cells (PBMCs) of IS patients and compare it with stroke-free controls. Blood samples were obtained from 19 healthy age-gender-race matched individuals who served as controls to 20 IS patients. miRNA microarray analysis with RNA from PBMCs was performed and significantly dysregulated miRNAs common among IS patients were identified. We identified 117 miRNAs with linear fold values of at least ±1.5, of which, 29 were significantly altered (p value <0.05). Ingenuity Pathway Analysis (IPA) indicated a role for the dysregulated miRNAs in conditions relevant to IS (e.g., organismal injury and abnormalities, hematological disease and immunological disease). Pro-inflammatory genes like STAT3, interleukin (IL) 12A, and IL12B were some of the highly predicted targets for the dysregulated miRNAs. Notably, we further identified three common and significantly upregulated miRNAs (hsa-miR-4656, -432, -503) and one downregulated miRNA (hsa-miR-874) among all IS patients. Molecular interactive network analysis revealed that the commonly dysregulated miRNAs share several targets with roles relevant to IS. Altogether, we report dysregulation of miRNAs in IS PBMCs and provide evidence for their involvement in the immune system alteration during IS pathophysiology.
| S-EPMC5545163 | biostudies-literature
Project description:Background and purposeAcute stroke presentation and outcome depend on both ischemic infarct volume and location. We aimed to determine the association between acute ischemic infarct topology and lesion volume and stroke severity at presentation and discharge.Materials and methodsPatients with acute ischemic stroke who underwent MR imaging within 24 hours of symptom onset or last seen well were included. Infarcts were segmented and coregistered on the Montreal Neurological Institute-152 brain map. Voxel-based analyses were performed to determine the distribution of infarct lesions associated with larger volumes, higher NIHSS scores at admission and discharge, and greater NIHSS/volume ratios.ResultsA total of 238 patients were included. Ischemic infarcts involving the bilateral lentiform nuclei, insular ribbons, middle corona radiata, and right precentral gyrus were associated with larger infarct volumes (average, 76.7 ± 125.6 mL versus 16.4 ± 24.0 mL, P < .001) and higher admission NIHSS scores. Meanwhile, brain stem and thalami infarctions were associated with higher admission NIHSS/volume ratios. The discharge NIHSS scores were available in 218 patients, in whom voxel-based analysis demonstrated that ischemic infarcts of the bilateral posterior insular ribbons, middle corona radiata, and right precentral gyrus were associated with more severe symptoms at discharge, whereas ischemic lesions of the brain stem, bilateral thalami, and, to a lesser extent, the middle corona radiata were associated with higher ratios of discharge NIHSS score/infarct volume.ConclusionsAcute ischemic infarcts of the insulae, lentiform nuclei, and middle corona radiata tend to have larger volumes, more severe presentations, and worse outcomes, whereas brain stem and thalamic infarcts have greater symptom severity relative to smaller lesion volumes.
| S-EPMC7963653 | biostudies-literature
Project description:PurposeThis study aimed to investigate the value of a machine learning-based magnetic resonance imaging (MRI) radiomics model in predicting the risk of recurrence within 1 year following an acute ischemic stroke (AIS).MethodsThe MRI and clinical data of 612 patients diagnosed with AIS at the Second Affiliated Hospital of Nanchang University from March 1, 2019, to March 5, 2021, were obtained. The patients were divided into recurrence and non-recurrence groups according to whether they had a recurrent stroke within 1 year after discharge. Randomized splitting was used to divide the data into training and validation sets using a ratio of 7:3. Two radiologists used the 3D-slicer software to label the lesions on brain diffusion-weighted (DWI) MRI sequences. Radiomics features were extracted from the annotated images using the pyradiomics software package, and the features were filtered using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Four machine learning algorithms, logistic regression (LR), Support Vector Classification (SVC), LightGBM, and Random forest (RF), were used to construct a recurrence prediction model. For each algorithm, three models were constructed based on the MRI radiomics features, clinical features, and combined MRI radiomics and clinical features. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) were used to compare the predictive efficacy of the models.ResultsTwenty features were selected from 1,037 radiomics features extracted from DWI images. The LightGBM model based on data with three different features achieved the best prediction accuracy from all 4 models in the validation set. The LightGBM model based solely on radiomics features achieved a sensitivity, specificity, and AUC of 0.65, 0.671, and 0.647, respectively, and the model based on clinical data achieved a sensitivity, specificity, and AUC of 0.7, 0.799, 0.735, respectively. The sensitivity, specificity, and AUC of the LightGBM model base on both radiomics and clinical features achieved the best performance with a sensitivity, specificity, and AUC of 0.85, 0.805, 0.789, respectively.ConclusionThe ischemic stroke recurrence prediction model based on LightGBM achieved the best prediction of recurrence within 1 year following an AIS. The combination of MRI radiomics features and clinical data improved the prediction performance of the model.
| S-EPMC10192708 | biostudies-literature
Project description:The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients.This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC) stem cell transplantation in patients with chronic ischemic stroke (CIS) using clinical scores and functional imaging (fMRI and DTI).Non randomised controlled observational study Study: Twenty four (n=24) CIS patients were recruited with the inclusion criteria as: 3 months-2years of stroke onset, hand muscle power (MRC grade) at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI) and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks.The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05) whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.
| S-EPMC3908296 | biostudies-other
Project description:IntroductionWe aimed to develop and validate a prognostic score for disability at discharge and functional outcome at three months in patients with acute ischemic stroke based on clinical information available on admission.Patients and methodsThe Dutch Stroke Score (DSS) was developed in 1227 patients with ischemic stroke included in the Paracetamol (Acetaminophen) In Stroke study. Predictors for Barthel Index (BI) at discharge ('DSS-discharge') and modified Rankin Scale (mRS) at three months ('DSS-3 months') were identified in multivariable ordinal regression. The models were internally validated with bootstrapping techniques. The DSS-3 months was externally validated in the PRomoting ACute Thrombolysis in Ischemic StrokE study (1589 patients) and the Preventive Antibiotics in Stroke Study (2107 patients). Model performance was assessed in terms of discrimination, expressed by the area under the receiver operating characteristic curve (AUC), and calibration.ResultsAt model development, the strongest predictors of Barthel Index at discharge were age per decade over 60 (odds ratio = 1.55, 95% confidence interval (CI) 1.41-1.68), National Institutes of Health Stroke Scale (odds ratio = 1.24 per point, 95% CI 1.22-1.26) and diabetes (odds ratio = 1.62, 95% CI 1.32-1.91). The internally validated AUC was 0.76 (95% CI 0.75-0.79). The DSS-3 months, additionally consisting of previous stroke and atrial fibrillation, performed similarly at internal (AUC 0.75, 95% CI 0.74-0.77) and external validation (AUC 0.74 in PRomoting ACute Thrombolysis in Ischemic StrokE (95% CI 0.72-0.76) and 0.69 in Preventive Antibiotics in Stroke Study (95% CI 0.69-0.72)). Observed outcome was slightly better than predicted.Discussion: The DSS had satisfactory performance in predicting BI at discharge and mRS at three months in ischemic stroke patients.ConclusionIf further validated, the DSS may contribute to efficient stroke unit discharge planning alongside patients' contextual factors and therapeutic needs.
| S-EPMC5992735 | biostudies-literature
Project description:ObjectiveTo discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones.MethodsMetabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort.ResultsMetabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described.ConclusionsThe use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.
| S-EPMC4336096 | biostudies-literature
Project description:BackgroundSkeletal muscle dysfunction occurring as a result of ICU admission associates with higher mortality. Although preadmission higher BMI correlates with better outcomes, the impact of baseline muscle and fat mass has not been defined. We therefore investigated the association of skeletal muscle and fat mass at ICU admission with survival and disability at hospital discharge.MethodsThis single-center, prospective, observational cohort study included medical ICU (MICU) patients from an academic institution in the Unites States. A total of 401 patients were evaluated with pectoralis muscle area (PMA) and subcutaneous adipose tissue (SAT) determinations conducted by CT scanning at the time of ICU admission, which were later correlated with clinical outcomes accounting for potential confounders.ResultsLarger admission PMA was associated with better outcomes, including higher 6-month survival (OR, 1.03; 95% CI, 1.01-1.04; P < .001), lower hospital mortality (OR, 0.96; 95% CI, 0.93-0.98; P < .001), and more ICU-free days (slope, 0.044 ± 0.019; P = .021). SAT was not significantly associated with any of the measured outcomes. In multivariable analyses, PMA association persisted with 6 months and hospital survival and ICU-free days, whereas SAT remained unassociated with survival or other outcomes. PMA was not associated with regaining of independence at the time of hospital discharge (OR, 0.99; 95% CI, 0.98-1.01; P = .56).ConclusionsIn this study cohort, ICU admission PMA was associated with survival during and following critical illness; it was unable to predict regaining an independent lifestyle following discharge. ICU admission SAT mass was not associated with survival or other measured outcomes.
| S-EPMC6363817 | biostudies-literature
Project description:BackgroundWe aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), platelet-to-white blood cell ratio (PWR) and 90-day mortality in patients with acute ischemic stroke (AIS).MethodsWe retrospectively included 633 patients with AIS from January 2017 to May 2018. The correlation between each indicator and the degree of neurologic deficit was assessed. Kaplan-Meier survival curves based on blood cell ratios were used to analyze the 90-day survival rate of patients with AIS.ResultsA total of 663 patients with AIS were enrolled, of which 24 (3.6%) experienced recurrence and 13 (2.0%) died. NLR>3.23 (odds ratio; OR = 2.236; 95% confidence interval [CI], 1.472-3.397; P<0.001), PNR<31.14 (OR = 0.471; 95% CI, 0.297-0.749; P = 0.001), and PWR<20.62 (OR = 0.498; 95% CI, 0.309-0.800; P = 0.004) were associated with an unfavorable 90-day prognosis. NLR>3.23, PWR<20.62, and PNR<31.14 were associated with an increased risk of 90-day mortality.ConclusionPNR, PWR, and NLR were associated with the 90-day mortality of patients with AIS. Patients with high NLRs or low PWRs and PNRs may have a greater risk of mortality than other patients. These clinical indicators may help clinicians judge unfavorable prognosis early and implement the appropriate interventions.
| S-EPMC7454963 | biostudies-literature
Project description:Background and purposeThis study aimed to explore the association between triglyceride-glucose (TyG) index and stroke recurrence in elderly patients with ischemic stroke in China.MethodsWe enrolled ischemic stroke patients aged ≥ 65 years from the Nanjing Stroke Registry Program. The primary endpoint was defined as recurrent stroke within one year after the index stroke. We used multivariable Cox proportional hazards regression models to investigate the association between TyG index and stroke recurrence. We assessed the discriminative ability of TyG index with the receiver operative characteristic and the area under the curve.ResultsA total of 955 patients (median age, 70.0 [67.0, 75.0]; male sex, 67.2%) from the Nanjing Stroke Registry Program were enrolled. During one year follow-up, 97 (10.2%) elderly patients experienced stroke recurrence. In multivariable analyses, the association between TyG index and stroke recurrence remained significant after adjusting for confounders (quartile 4 versus quartile 1; hazard ratio, 2.073, 95% confidence interval, 1.158-3.711; P = 0.014). The restricted cubic spline showed an increasing trend for TyG index and stroke recurrence (P for non-linearity = 0.072). The area under the curve to predict stroke recurrence with TyG index was 0.719 (95% confidence interval, 0.666-0.772). Besides, TyG index slightly improved the prediction for stroke recurrence.ConclusionElevated TyG index was associated with stroke recurrence in elderly patients with ischemic stroke. Further studies are warranted to assess the role of TyG index in the development of stroke recurrence in the elderly.
| S-EPMC9467280 | biostudies-literature