Stigmasterol protects human brain microvessel endothelial cells against ischemia-reperfusion injury through suppressing EPHA2 phosphorylation / 中国天然药物

Stigmasterol is a plant sterol with anti-apoptotic, anti-oxidative and anti-inflammatory effect through multiple mechanisms. In this study, we further assessed whether it exerts protective effect on human brain microvessel endothelial cells (HBMECs) against ischemia-reperfusion injury and explored the underlying mechanisms. HBMECs were used to establish an in vitro oxygen and glucose deprivation/reperfusion (OGD/R) model, while a middle cerebral artery occlusion (MCAO) model of rats were constructed. The interaction between stigmasterol and EPHA2 was detected by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). The results showed that 10 μmol·L-1 stigmasterol significantly protected cell viability, alleviated the loss of tight junction proteins and attenuated the blood-brain barrier (BBB) damage induced by OGD/R in thein vitro model. Subsequent molecular docking showed that stigmasterol might interact with EPHA2 at multiple sites, including T692, a critical gatekeep residue of this receptor. Exogenous ephrin-A1 (an EPHA2 ligand) exacerbated OGD/R-induced EPHA2 phosphorylation at S897, facilitated ZO-1/claudin-5 loss, and promoted BBB leakage in vitro, which were significantly attenuated after stigmasterol treatment. The rat MCAO model confirmed these protective effects in vivo. In summary, these findings suggest that stigmasterol protects HBMECs against ischemia-reperfusion injury by maintaining cell viability, reducing the loss of tight junction proteins, and attenuating the BBB damage. These protective effects are at least meditated by its interaction with EPHA2 and inhibitory effect on EPHA2 phosphorylation.

Anti-inflammatory effects of lipoxin A4 in cerebral ischemia / 国际脑血管病杂志

Lipoxin A4 (LXA4) is one of the metabolites of arachidonic acid, and it is an endogenous anti-inflammatory factor that can alleviate the inflammatory reaction through various pathways. Inflammatory response plays an important role in the process of cerebral ischemia. LXA4 can play a protective role on nerve cells by regulating proinflammatory cytokines, protecting blood-brain barrier, inhibiting activation and infiltration of leukocyte, alleviating local microcirculation inflammatory response, regulating inflammatory mediators such as leukotrienes and inflammasome, regulating the metabolism of inflammatory related enzymes, and alleviating oxidative stress injury. This article reviews the anti-inflammatory effects of LXA4 in cerebral ischemia.

Validation Study of the Chinese Version of Addenbrooke's Cognitive Examination III for Diagnosing Mild Cognitive Impairment and Mild Dementia

BACKGROUND AND PURPOSE: There are only a few cognitive screening tests for the Chinese-speaking population, and so this study aimed to validate the Chinese version of Addenbrooke's Cognitive Examination III (ACE-III) for detecting mild cognitive impairment (MCI) and mild dementia. Its diagnostic accuracy was compared with the Chinese versions of the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). METHODS: The 176 included individuals were divided into 3 groups: mild dementia group, MCI group, and normal control group. MMSE, MoCA, and ACE-III were administered to all participants by researchers who were blinded to the clinical grouping. The receiver operating characteristic (ROC) curves were analyzed. RESULTS: ACE-III exhibited good internal consistency and convergent validity. Age and education level significantly influenced the total ACE-III scores. When screening MCI, the area under the ROC curve (AUC) was significantly larger for ACE-III than for MMSE (0.88 vs. 0.72, p<0.05) and MoCA (0.88 vs. 0.76, p<0.05). ACE-III showed higher sensitivity (0.75) and specificity (0.89) than MMSE (0.64 and 0.63, respectively) and MoCA (0.67 and 0.77) at the optimal cutoff score of 88/89. For detecting mild dementia, ACE-III yielded satisfactory sensitivity (0.94) and specificity (0.83) at the optimal cutoff score of 74/75. The AUC of ACE-III was 0.95, which was comparable to those of MMSE (0.95) and MoCA (0.91). In participants with ≥12 years of education, the AUC was significantly larger for ACE-III than for MMSE when detecting MCI (0.90 vs. 0.68, p<0.05) and mild dementia (0.97 vs. 0.90, p<0.05). CONCLUSIONS: The present study has verified that ACE-III is a reliable and accurate tool for screening MCI and mild dementia in the Chinese-speaking population, and is significantly superior to MMSE and MoCA for detecting MCI.

Effect of breviscapine on serum NSE, Ang-2 and IL-6 levels and its efficacy in patients with acute cerebral infarction / 中国生化药物杂志

Objective To observe the efficacy of breviscapine in the treatment of patients with acute cerebral infarction and its effect on serum neuron specific enolase(NSE), angiotensin-2(Ang-2) and interleukin-6(IL-6) levels.Methods 60 cases of acute cerebral infarction(ACI) patients from January 2014 to January 2015 in Sichuan Provincial People's Hospital were selected and randomly divided into two groups, 30 cases in each group.All patients were given conventional western medicine treatment , and the observation group were also treated with breviscapine.After 2 weeks, the degree of neural function defect scores and efficacy were compared and the serum levels of NSE , Ang-2 and IL-6 were detected by enzyme linked immunosorbent assay(ELISA) and compared pre-and post-treatment between two groups.Results The degree of neural function defect score post-treatment in observation group was significantly lower than that in control group ( P<0.05 ).The overall response in observation group was 27 cases (90.00%), which was significantly higher than 20 cases(66.67%) in control group(χ2 =4.81,P<0.05).The serum levels of Ang-2, IL-6 and NSE post-treatment in observation group were significantly lower than those in control group ( P<0.05 ) .Conclusion The curative effect of breviscapine in treatment of acute cerebral infarction is significantly, which could improve the cerebral microcirculation, protect the brain tissue, and its mechanism may be through reducing the serum levels of NSE, IL-6 and Ang-2.