Mammals have several different sirtuins, and SIRT1 can be found in both the cytoplasm and nucleus of cells

Mammals have several different sirtuins, and SIRT1 can be found in both the cytoplasm and nucleus of cells. be used to diagnose AIS using receiver-operating characteristic (ROC) curves, and calculated the area under the curve (AUC) to assess the statistical significance of the test. 3.?Results Table ?Table11 presents the clinical characteristics of subjects. There were no significant differences in age or sex between the AIS group (60 males and 41 females, mean 73.83??9.52 years) and control group (16 males and 22 females, mean age 71.16??7.99 years). Serum SIRT1 levels were significantly higher ( em P /em ??.05) in the AIS group compared with controls (0.63??0.75 vs 0.48??0.80?ng/mL). cis-Urocanic acid SIRT1 levels in stroke patients were not significantly correlated with NIHSS scores at the time of admission ( em r /em ?=??0.01, em P /em ?=?.920; Fig. ?Fig.1).1). The ROC curve of serum SIRT1 activity for AIS patients is shown in Fig. ?Fig.2,2, and the AUC for AIS patients was 0.752. Based cis-Urocanic acid on the ROC, the maximum sensitivity and specificity of serum SIRT1 activity for diagnosing AIS were 47.5% and 76.3%, respectively, with the AUC at 0.615 (95% CI 0.511C0.719), when choosing the optimal cut-off point (0.45?ng/mL). Table 1 Clinical characteristics of stroke patients and healthy controls. Open in a separate window Open in a separate window Figure 1 Linear correlation between serum SIRT1 concentration and NIHSS score. Serum SIRT1 concentration not significantly correlated with NIHSS score ( em r /em ?=??0.01, em P /em ?=?.920). NIHSS?=?National Institutes of Health Stroke Scale, SIRT1?=?Sirtuin1. Open in a separate window Figure 2 ROC curve of serum SIRT1 activities for diagnosing ischemic stroke patients. ROC?=?receiver-operating characteristic, SIRT1?=?Sirtuin1. In the 41 patients with an unfavorable functional outcome, serum SIRT1 levels were higher than those with a favorable outcome (0.58??0.70 vs 0.66??0.79?ng/mL; em P /em ?=?.224). The clinical characteristics of AIS patients with different functional outcomes are shown in Table ?Table2.2. Table ?Table33 shows the results from binary logistic regression analyses, which calculated the correlations between SIRT1 levels and NIHSS score, hs-CRP, age, and other risk factors. With an unadjusted OR of 0.862 (95% CI 0.495C1.502), SIRT1 was not significantly correlated with a favorable functional outcome. In contrast, age, NIHSS score, smoking history, and hs-CRP were all significant predictors of outcome (Table ?(Table33). Table 2 Clinical characteristics of stroke patients with favorable and unfavorable functional outcome. Open in a separate window Table 3 Univariate and cis-Urocanic acid multivariate logistic regression analysis for functional outcome. Open in a separate window 4.?Discussion Sirtuins play an important protective role by resisting cellular stress and regulating metabolism in ischemiaCreperfusion injury processes. Mammals have several different sirtuins, and SIRT1 can be found in both the cytoplasm and nucleus of cells. It is the most widely studied mammalian sirtuin, is expressed at high levels in the brain, and is required for the extended life-span associated with caloric restriction.[7] SIRT1 regulates cell metabolism by regulating multiple downstream genes in response to cis-Urocanic acid cellular stress.[8] For example, in the inflammatory response to ischemiaCreperfusion injury, SIRT1 plays an important neuroprotective role by deacetylating several apoptosis-related proteins, such as Smad7, FOXO3, and FOXO4, thus protecting cells against damage-induced apoptosis. [9C11] SIRT1 also deacetylates p53, which destabilizes it and reduces its Rabbit Polyclonal to XRCC2 transcriptional activity, resulting in decreased apoptosis.[12C14] Moreover, previous studies have shown that SIRT1 can mediate the neuroprotective effect of a rate-limiting enzyme of nicotinamide phosphoribosyl transferase (Nampt) in synthetic neuronal cells in the salvage pathway.[15] cis-Urocanic acid SIRT1 can also increase mitochondrial oxidative phosphorylation by reducing uncoupling protein 2 transcription.[16,17] Furthermore, SIRT1 eliminates the decrease in Bcl-2 expression.