Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich enzyme-linked immunosorbent assay (ELISA), and the severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. The results indicated that the median serum TRX levels were significantly (P < 0.0001) higher in stroke patients as compared to normal cases [15.03 ng/mL (interquartile range (IQR), 10.21-32.42) and 8.95 ng/mL (6.79-11.05), respectively]. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r = 0.476, P < 0.0001). After adjusting for all other possible covariates, TRX remained as an independent marker of AIS with an adjusted OR of 1.245 (95 % confidence interval (CI), 1.164-1.352; P < 0.0001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/mL, which yielded a sensitivity of 80.3 % and a specificity of 73.7 %, with the area under the curve at 0.807 (95 % CI, 0.766-0.847). Further, in our study, we found that an increased risk of AIS was associated with serum TRX levels ≥11.0 ng/mL (adjusted OR 6.99; 95 % CI, 2.87-12.87) after adjusting for possible confounders. Our study demonstrated that serum TRX levels at admission were associated with stroke severity and lesion volumes. Elevated levels could be considered as a novel, independent diagnosis marker of AIS in a Chinese sample.

Abstract. The present study aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in drug-induced early cognitive impairment and the underlying mechanism concerning microRNA (miR)-30b. A mouse model of cognitive impairment was established by intraperitoneal injection of scopolamine (2 mg/kg body weight) for 13 days. Behavioral performance was assessed using the Morris water maze (MWM) test. The mRNA expression levels of PAI-1 and miR-30b were detected using quantitative polymerase chain reaction (qPCR). The protein expression levels of PAI-1 in the hippocampus and blood were determined using western blot analysis and enzyme-linked immunosorbent assays. The MWM test demonstrated that, on days 3 and 4, the escape latency was significantly elevated in the model mice in comparison with control group (P<0.05). In addition, the length of swimming path was significantly increased (P<0.05), while the number of times of crossing the platform location was significantly reduced in the model mouse group (P<0.05) in comparison with the control group. qPCR demonstrated that the mRNA expression levels of PAI-1 in the model mice was significantly elevated in the hippocampus and blood in comparison with the control group (P<0.01). Furthermore, western blot analysis and enzyme-linked immunosorbent assay demonstrated that the protein expression levels of PAI-1 were significantly elevated in the hippocampus and blood in the model group, in comparison with the control group (P<0.05). Notably, the levels of miR-30b in the hippocampus and blood were significantly decreased in the model mice in comparison with the control group (P<0.01). To conclude, the expression levels of PAI-1 were significantly elevated in mice with scopolamine-induced cognitive impairment, which may be associated with the downregulation of miR-30b. The findings from the present study suggest that miR-30b may be involved in the regulation of PAI-1, which would contribute to the pathogenesis of cognitive impairment.

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