Background and Purpose-Ischemic postconditioning has been found to decrease brain infarct area and spinal cord ischemic injury. In this study, we tested the hypothesis that ischemic postconditioning reduces global cerebral ischemia/reperfusion-induced structural and functional injury in rats. Methods-Ten-minute global ischemia was induced by 4-vessel occlusion in male Sprague-Dawley rats.
BackgroundNeuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R) injury. The P2X7 receptor (P2X7R) has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury.MethodsImmediately after infusion with the P2X7R antagonists Brilliant blue G (BBG), adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP) or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL). In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes.ResultsThe P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg) and A-0438079 (3 μg), and a low dosage of OxATP (1 μg) significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus.ConclusionsOur study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.
This study identifies several novel susceptibility genes for MMD. The association with homocysteine metabolism and the immune system enrichment of susceptibility gene expression suggest that therapeutic interventions targeting these pathways may be effective approaches for MMD treatment.
Clinical prediction of advanced hepatic fibrosis (HF) and cirrhosis has long been challenging due to the gold standard, liver biopsy, being an invasive approach with certain limitations. Less invasive blood test tandem with a cutting-edge machine learning algorithm shows promising diagnostic potential.
In this study, we constructed and compared machine learning methods with the FIB-4 score in a discovery dataset (
n
= 490) of hepatitis B virus (HBV) patients. Models were validated in an independent HBV dataset (
n
= 86). We further employed these models on two independent hepatitis C virus (HCV) datasets (
n
= 254 and 230) to examine their applicability.
In the discovery data, gradient boosting (GB) stably outperformed other methods as well as FIB-4 scores (
p
< .001) in the prediction of advanced HF and cirrhosis. In the HBV validation dataset, for classification between early and advanced HF, the area under receiver operating characteristic curves (AUROC) of GB model was 0.918, while FIB-4 was 0.841; for classification between non-cirrhosis and cirrhosis, GB showed AUROC of 0.871, while FIB-4 was 0.830. Additionally, GB-based prediction demonstrated good classification capacity on two HCV datasets while higher cutoffs for both GB and FIB-4 scores were required to achieve comparable specificity and sensitivity.
Using the same parameters as FIB-4, the GB-based prediction system demonstrated steady improvements relative to FIB-4 in HBV and HCV cohorts with different cutoff values required in different etiological groups. A user-friendly web tool, LiveBoost, makes our prediction models freely accessible for further clinical studies and applications.
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