Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

Overweight and Obesity in Young Adulthood and the Risk of Stroke: a Meta-analysis.

BACKGROUND: A systematic review assessing the association between overweight and obesity in young adulthood and stroke risk is lacking. Therefore, we conducted a meta-analysis to evaluate the association between overweight and obesity in young adulthood and stroke risk. METHODS: We systematically searched PubMed and Embase databases for related studies of human subjects in the English language. Two investigators independently selected original studies in a 2-step process. Fixed- and random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Subgroup analyses were also performed. RESULTS: Eight studies met the inclusion criteria. The pooled adjusted RR of stroke was 1.36 (95% CI: 1.28-1.44) for overweight in young adulthood and 1.81 (95% CI: 1.45-2.25) for obesity in young adulthood. In subgroup analyses, overweight and obesity in young adulthood increased the risk of stroke in most groups, except for the group of stroke subtype. For ischemic stroke, the adjusted RR was 1.40 (95% CI: 1.24-1.58) for overweight in young adulthood and 1.78 (95% CI: 1.003-3.16) for obesity in young adulthood, whereas adjusted RR for hemorrhagic stroke was 1.25 (95% CI: .83-1.90) for overweight in young adulthood and 1.80 (95% CI: .97-3.35) for obesity in young adulthood. CONCLUSIONS: Overweight and obesity in young adulthood are associated with an increased risk of stroke, probably, independent of other cardiovascular risk factors. The risk effect gradually increases with increasing body weight.

Effect of Urinary Kallidinogenase on Transforming Growth Factor-ß1 and High-Sensitivity C-Reactive Protein Expression in Rat Focal Cerebral Ischemic Injury.

BACKGROUND In this study we investigated the effect of urinary kallidinogenase (UK) on transforming growth factor beta 1 (TGF-ß1) expression in brain tissue. We also explored the neuroprotective mechanism of UK against ischemic injury by measuring serum high-sensitivity C-reactive protein (hs-CRP) level changes after rat cerebral ischemic injury. MATERIAL AND METHODS The rat middle cerebral artery ischemia/reperfusion model was established using the suture method. Sprague-Dawley rats were randomly divided into 3 groups: treatment, Gegen control, and blank control. Each group was subsequently divided into 5 subgroups according to time (6, 12, 24, 48, and 72 h). Rats in the treatment group were administered UK as treatment. TGF-ß1 expression was observed at each time point using SABC and immunohistochemical staining methods to estimate cerebral infarct volume percentage. Serum hs-CRP levels were also measured. RESULTS TGF-ß1 protein expression in ischemic brain tissues of the treatment group significantly increased at each time point (P<0.01) compared with both control groups. Treatment group serum hs-CRP levels significantly decreased at each time point (P<0.05) compared with both control groups. CONCLUSIONS UK exerts a neuroprotective effect by upregulating TGF-ß1 expression and inhibiting excessive inflammatory responses.

Improvement of the suture-occluded method in rat models of focal cerebral ischemia-reperfusion.

The aim of the present study was to provide a simple method of establishing a rat model for focal cerebral ischemia-reperfusion (FCIR). The suture-occluded method was used to establish FCIR in male Sprague-Dawley rats. An incision was made over the bifurcation of the common carotid artery (CCA), through which a suture was inserted up to the internal carotid artery (ICA). The suture remained in the skin subsequent to model establishment and was withdrawn to the CCA to enable reperfusion. The reliability of the rat model was assessed via analysis of nerve function, tetrazolium (TTC) staining and pathological examination. Following FCIR in rats, the resulting neurological impairments were observed. TTC staining revealed infarcts and pathological examination revealed typical pathological changes. This modified method was simple, reliable and, therefore, may be used to investigate FCIR.

Tissue factor pathway inhibitor-2 silencing promotes hepatocellular carcinoma cell invasion in vitro.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world and metastasis is an essential aspect of HCC progression. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a potential suppressor gene to regulate tumor invasion and metastasis. In this study, we silenced TFPI-2 in the HCC cell line MHCC97-L and evaluated the role of TFPI-2 in cell invasion and its impact on gene expression. We showed in this study that stable TFPI-2 downregulation in MHCC97-L cells resulted in increased cell adhesion and invasion. We also showed that mRNA and protein expression levels of MMP-1/3, CD44, and ICAM-1 were increased, while those of MMP-2/9 were not changed by TFPI-2 silencing. Furthermore, silencing of TFPI-2 caused increased Akt phosphorylation level and NF-κB transcription in MHCC97-L cells. In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumor invasion of HCC cells through alteration in the expression of metastasis-related genes.