Elevated SIRT2 of serum exosomes is positively correlated with diagnosis of acute ischemic stroke patients.

BACKGROUND: Silent Information Regulator 2 (SIRT2) protein inhibition has been shown to play a neuroprotective role in acute ischemic stroke (AIS) in mice. However, its role in AIS patients has not been fully understood. In this study, we aimed to analyze SIRT2 protein expression in serum exosomes of AIS and non-AIS patients, and evaluate its potential role in diagnosis and prognosis of AIS. METHODS: Serum exosomes from 75 non-AIS subjects and 75 AIS patients were isolated. The SIRT2 protein levels in exosomes were analyzed using enzyme linked immunosorbent assay (ELISA). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of the disease. The modified Rankin Scale (mRS) was employed to assess the functional outcomes of the patients at 3-months following stroke onset. RESULTS: The SIRT2 protein concentration of serum exosomes were higher in AIS patients than non-AIS patients (p < 0.001). Furthermore, the receiver operative characteristic curve (ROC) demonstrated that higher serum exosome SIRT2 could differentiate AIS patients from non-AIS patients with a sensitivity of 81.3% and a specificity of 75.3%. The area under the curve was 0.838 (95% CI: 0.775, 0.902). Additionally, higher SIRT2 concentration of serum exosomes were associated with NIHSS ≥ 4 (p < 0.001) and mRS ≥ 3 (p = 0.025) in AIS patients. The ROC analysis showed SIRT2 could discriminate stroke with NIHSS ≥ 4 from mild stroke (NIHSS < 4) with a sensitivity of 75.0% and a specificity of 69.6%. The area under the curve was 0.771 (95% CI: 0.661,0.881). Similarly, the test showed SIRT2 could differentiate between AIS patients with mRS ≥ 3 from those with mRS < 3 with a sensitivity of 78.3% and a specificity of 51.9%. The area under the curve was 0.663 (95% CI: 0.531,0.796). The logistic regression analysis revealed that SIRT2 concentration in serum exosomes can independently predict the diagnosis of AIS (odd ratio = 1.394, 95%CI 1.231-1.577, p < 0.001) and higher NIHSS scores (≥ 4) (odd ratio = 1.258, 95%CI 1.084-1.460, p = 0.002). However, it could not independently predict the prognosis of AIS (odd ratio = 1.065, 95%CI 0.983-1.154, p = 0.125). CONCLUSION: The elevation of SIRT2 in serum exosomes may be a valuable biomarker of AIS, which may be a potential diagnostic tool to facilitate decision making for AIS patients.

SIRT2 plays complex roles in neuroinflammation neuroimmunology-associated disorders.

Neuroinflammation and neuroimmunology-associated disorders, including ischemic stroke and neurodegenerative disease, commonly cause severe neurologic function deficits, including bradypragia, hemiplegia, aphasia, and cognitive impairment, and the pathological mechanism is not completely clear. SIRT2, an NAD+-dependent deacetylase predominantly localized in the cytoplasm, was proven to play an important and paradoxical role in regulating ischemic stroke and neurodegenerative disease. This review summarizes the comprehensive mechanism of the crucial pathological functions of SIRT2 in apoptosis, necroptosis, autophagy, neuroinflammation, and immune response. Elaborating on the mechanism by which SIRT2 participates in neuroinflammation and neuroimmunology-associated disorders is beneficial to discover novel effective drugs for diseases, varying from vascular disorders to neurodegenerative diseases.

24-hour ambulatory blood pressure alterations in patients with Parkinson's disease.

OBJECTS: Abnormal blood pressure (BP) regulation is a feature of autonomic dysfunction in Parkinson's disease (PD) patients. The present study was to analyze the BP alterations by 24-h ambulatory BP monitoring in PD patients with different disease stages and subtypes. METHODS: 32 consecutive patients PD patients and 43 control patients in our hospital from 2017 to 2020 were included. The circadian BP rhythm was divided into three types according to the 24-h ambulatory BP monitoring. Dipping was defined as an average systolic BP (SBP) reduction during night-time of 10%-19%. Reverse dipping was defined as an average increase in night-time SBP values. The differences of the circadian BP rhythm and BP variability (BPV) were analyzed between PD group and the control group, the early PD group and the advanced PD group, as well as the tremor-dominant group and the nontremor-dominant group. RESULTS: There was statistical difference in circadian BP rhythm between PD group and control group (p < .05). There were statistical differences in circadian BP rhythm between the early PD group and the advanced PD group (p < .05). The mean values of night-time SBP and diastolic BP (DBP) in the advanced PD group were higher than those in the control group and the early PD group (p < .05). The DBP CV in the advanced PD group was higher than that in the control group and the early PD group (p < .05). There was no significant difference of circadian BP rhythm, mean BP, and BPV between the tremor-dominant and the nontremor-dominant PD group after matching the disease duration. CONCLUSIONS: Reverse dipping was more common in PD patients in this study, especially in the advanced PD patients. 24-h ambulatory BP monitoring is an important method to evaluate the BP alterations in PD patients. Clinicians should be alert to reverse dipping in PD patients and intervene to prevent serious clinical events.

The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD.

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden. Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model. Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [ß = -7.31; 95% confidence interval (CI) (-9.40, -4.93); p<0.01; ß = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(ß = -9.22; 95% CI (-11.37, -7.06); p<0.01); ß = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(ß = -2.3; 95% CI (-4.95, 0.05); p = 0.22); ß = 0.02; 95% confidence interval (-0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking. Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders.

As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) is predominantly found in the cytoplasm of cells in the central nervous system (CNS), suggesting its potential role in neurological disorders. Though SIRT2 is generally acknowledged to accelerate the development of neurological pathologies, it protects the brain from deterioration in certain circumstances. This review summarized the complex roles SIRT2 plays in the pathophysiology of diverse neurological disorders, compared and analyzed the discrete roles of SIRT2 in different conditions, and provided possible explanations for its paradoxical functions. In the future, the rapid growth in SIRT2 research may clarify its impacts on neurological disorders and develop therapeutic strategies targeting this protein.

SUMOylation is essential for Sirt2 tumor-suppressor function in neuroblastoma.

SUMOylation is an important post-translational modification that participates in a variety of cellular physiological and pathological processes in eukaryotic cells. Sirt2, a NAD+-dependent deacetylase, usually exerts a tumor-suppressor function. However, the role of SUMOylation in cancer cells is not fully known. In this study, we found that SUMOylation can occur in the Sirt2 protein at both lysine 183 and lysine 340 sites. SUMOylation did not affect Sirt2 localization or stability but was involved in P38-mTORC2-AKT cellular signal transduction via direct deacetylation on a new substrate MAPK/P38. SUMOylation-deficient Sirt2 lost the capability of suppressing tumor processes and showed resistance to the Sirt2-specific inhibitor AK-7 in neuroblastoma cells. Here, we revealed the important function of Sirt2-SUMOylation, which is closely associated with cellular signal transduction and is essential for suppressing tumorigenesis in neuroblastoma.

Neuroprotective Effect of Sirt2-specific Inhibitor AK-7 Against Acute Cerebral Ischemia is P38 Activation-dependent in Mice.

Cerebral ischemia is the most common cause of stroke with high morbidity, disability and mortality. Sirtuin-2 (Sirt2), a vitally important NAD+-dependent deacetylase which has been widely researched in central nervous system diseases, has also been identified as a promising treatment target using its specific inhibitors such as AK-7. In this study, we found that P38 was specifically activated after focal cerebral ischemic injury, and it was also significantly activated after AK-7 administration in a concentration-dependent manner in vitro and in vivo. AK-7 decreased the infarction volume remarkably and promoted the recovery of neurological function efficiently in the mice evaluated by behavior tests. In contrast, pP38 inhibition increased the infarct volume and exacerbated the symptoms of paralysis. Herein, we suggest AK-7 improves the outcome of brain ischemia in dependence on the P38 activation in mice, which may serve as a strategy for the treatment of stroke.

Common carotid artery dissection caused by radiotherapy: A case report.

In the present study, a case of acute cerebral infarction with radiation-induced carotid artery dissection is reported. Carotid artery dissection is generally asymptomatic at the early stages. Due to the non-specific clinical manifestations of carotid artery dissection, a detailed inquiry of the past history of a patient has a critical role in making a diagnosis of radiation-induced common carotid artery dissection. Onset of acute ischemic stroke is the predominant manifestation, and for patients with a history of head-and-neck radiotherapy, dissection should be considered. The condition may progress rapidly, and result in a poor prognosis. Therefore, a correct early diagnosis and initiation of appropriate therapy may lead to rapid recovery, and influence the overall prognosis.