Silencing of long noncoding RNA XIST attenuated Alzheimer's disease-related BACE1 alteration through miR-124.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. However, its pathogenetic mechanism is still poorly understood. An increasing number of studies have evidenced the important role of long noncoding RNAs (lncRNAs) in AD. The aim of the current study was to investigate the effect and molecular mechanism of the lncRNA X-inactive specific transcript (XIST) in AD. Bilateral common carotid artery occlusion (2VO) was used to induce an AD model in mice. Hydrogen peroxide (H2 O2 ) was used to induce an AD model in N2a cells. The lncRNA XIST, miR-124, and BACE1 messenger RNA expression levels were detected by a real-time polymerase chain reaction. The BACE1 protein expression level was detected by western blot and immunofluorescence assay. The Aß1-42 expression level was detected using an enzyme-linked immunosorbent assay kit. The expression level of lncRNA XIST was significantly upregulated in AD models, both in vivo and in vitro. Silencing of lncRNA XIST negatively regulated miR-124 and positively regulated BACE1 expression in N2a cells, which is attenuated by cotransfection of anti-miR-124 oligodeoxyribonucleotide (AMO-124). Silencing of lncRNA XIST reversed the effect of H2 O2 on miR-124, BACE1, and Aß1-42 expression in N2a cells, which was reversed by cotransfection of AMO-124. Silencing of lncRNA XIST attenuated AD-related BACE1 alteration through miR-124. LncRNA XIST may be a new potential target for the treatment of AD.

Study on the Correlation between apolipoprotein and homocysteine levels with carotid atherosclerotic plaque stability and degree of stenosis / 中国综合临床

Objective To investigate the correlation between apolipoprotein and homocysteine levels with the stability of carotid plaque and the degree of stenosis??Methods One hundred elderly patients with acute cerebral infarction from January 2017 to December 2017 were collected continuously in Harbin Fourth Hospital,All patients underwent color Doppler ultrasound examination of carotid artery??They were divided into stable plaque group and unstable plaque group according to the results of color Doppler ultrasound,then according to the degree of stenosis they were divided into intimal thickening group with 23 cases, mild stenosis (stenosis degree＜50%) with 26 cases,moderate stenosis group (50%≤stenosis degree＜70%) with 28 cases,severe stenosis group (70%≤stenosis degree) with 23 cases??All the patients were selected to collect the blood of the elbow in the early morning to detect the level of apolipoprotein B and Hcy??Results Compared with unstable plaque group, smoking, drinking, hemoglobin A1c ( HbA1c), ApoB and Hcy had significant differences (all P＜0??05)??Gender,history of diabetes mellitus,history of hypertension,systolic pressure,diastolic pressure,low density lipoprotein cholesterol (LDL?C),triglyceride (TG) There was no significant difference in total cholesterol ( TC) and total cholesterol ( all P＞0??05)??Multivariate logistic regression was performed after correcting the related risk factors excluding blood lipids??The results showed that alcohol ( OR＝ 1??247 ( 95%CI: 0??626－1??958), P＝ 0??043), Hcy ( OR＝ 3??163 ( 95%CI: 1??824 －4??772),P＝0??045), bloodpressure ( OR＝1??286 ( 95%CI: 0??688－2??005), P＝0??027), HbA1c ( OR＝3??671(95%CI: 1??904－6??630),P＝0??011),ApoB (OR＝1??717(95%CI: 1??005－2??634),P＝0??036), LDL?C(OR＝1??516(95%CI: 0??968－2??489),P＝0??024),TC( OR＝1??403( 95%CI: 0??801－2??343),P＝0??030) and TG ( OR＝1??342 ( 95%CI: 0??712－2??198), P＝0??019) are independent risk factors for unstablecarotid plaque and severe carotid stenosis??Conclusion Apolipoprotein and homocysteine may be independent predictors of unstable carotid plaque and severity of carotid stenosis??

Effects of Dihuang Yinzi on RAGE/ROS/Apoptosis Pathway in SH-SY5Y Cells Induced by Aβ1-42 / 广州中医药大学学报

Objective To investigate the effects of Dihuang Yinzi (DY) on the receptor for advanced glycation end-products(RAGE)/reactive oxygen species(ROS)/apoptosis pathway in SH-SY5Y cells induced by amyloid-beta1-42 (Aβ1-42) oligomer. Methods Firstly, we adopted methyl thiazolyl tetrazolium(MTT) method to detect the cell vitality in fetal bovine serum (FBS) group, blank serum group, and low-, middle- and high- dose DY-containing serum groups, so as to confirm the optimal concentration and treatment time of DY-containing serum. Secondly, we applied MTT method to detect cell vitality and applied Annexin V/propidium iodide (PI) staining method to observe the apoptosis of SH-SY5Y cells treated with 0~20 μmol/L Aβ1-42 for 24 and 48 h, so as toconfirm the optimal concentration and treatment time of Aβ1-42 for establishing Alzheimer's disease (AD) model in vitro. Thirdly, MTT method was used for the detection of cell vitality, and Annexin V/PI staining method was used for detection of the apoptosis of SH-SY5Y cells in blank serum group, model group, western medicine control group and low-, middle-and high-dose DY-containing serum groups, and Dihydroethidium (DHE) method was used for the assay of ROS contents, so as to observe the effect of DY on the recovery of injured SH-SY5Y cells induced by Aβ1-42. Finally, we applied Western blot method to detect the expression level of RAGE in SH-SY5Y cells of blank group, model group and DY-containing serum group; after Aβ1-42-induced SH-SY5Y cells were transfected with RAGE gene, we adopted DHE staining method and Annexin V/PI staining method to detect ROS content and cell apoptotic rate in all of the above groups, so as to observe the effect of DY on SH-SY5Y cell apoptosis and RAGE expression. Results The cell vitalities were increased in low- and middle-dose DY-containing serum groups at 24 h (P < 0.05 or P < 0.01 compared with that in the blank serum group). The conditions for the establishment of AD model in vitro were as follows: the optimal concentration of Aβ1-42 was 5μmol/L, and the treatment time was 24 h. The cell vitalities were significantly enhanced, the cell apoptotic rate and ROS content were significantly lowered in Aβ1-42-induced SH-SY5Y cells of the medication groups(P <0.05 or P < 0.01 compared with those in the model group) , and the cell vitality was the highest and the cell apoptotic rate was the lowest in the middle-dose DY-containing serum group. The RAGE expression level was decreased in Aβ1-42-induced SH-SY5Y cells of the middle-dose DY-containing serum group(P < 0.05 compared with that in the model group) . ROS content and cell apoptotic rate were decreased in Aβ1-42-induced SH-SY5Y cells transfected with RAGE gene in the middle-dose DY-containing serum group (P<0.01). Conclusion DY may play an anti-oxidative role through inhibiting the production of ROS and cell apoptosis, thus to suppress RAGE protein and to achieve the preventive and therapeutic effect for AD.

Effect of Dihuangyinzi-medicated serum on receptor for advanced glycation end product/p38 miotgen-activated protein kinase/nuclear factor-κB pathway in SH-SY5Y cells induced by Aβ1-42 / 中华神经医学杂志

Objective To investigate the effect ofDihuangyinzi (DHYZ)-medicated serum on receptor for advanced glycation end product (RAGE)/p38 miotgen-activated protein kinase (MAPK) /nuclear factor (NF)-κB pathway in SH-SY5Y cells induced by Aβ1-42.Methods Male SD rats were randomly divided into normal control group and experimental group (n=20);natural sera medium and DHYZ sera medium were prepared.(1) SH-SY5Y cells were divided into control group,model group and DHYZ treatment group;natural sera medium,natural sera medium+Aβ1-42 oligomer,and DHYZ sera medium+Aβ1-42 oligomer were given to the cells,respectively.Westem blotting was used to detect the protein expressions of NF-κB p65,p38 and phosphorylate (p)-p38.(2) SH-SY5Y cells were given DHYZ sera medium+Aβ1-42 oligomer treatment,and at different time points of Aβ1-42 oligomer treatment (15 min,30 min,60 min,12 h,24 h,48 h and 72 h),Western blotting was used to detect the protein expressions of p38 and p-p38.(3) SH-SY5Y cells were divided into 6 groups:mock-transfected RAGE blank group,transfected RAGE blank group,mock-transfected RAGE model group,transfected RAGE model group,mock-transfected RAGE herb group and transfected RAGE herb group;herb groups were given DHYZ-medicated serum;inflammatory factors,interleukin (IL)-1β,IL-6,and tumor necrosis factor (TNF)-a,were measured by ELISA and cytometric bead array.Results (1) As compared with model group,DHYZ treatment group had significantly decreased NF-κB p65 and p-p38/p38 protein expression.(2) The p-p38 protein expression began to increase 30 min after Aβ1-42 treatment,reached to its peak level 24 h after Aβ1-42 treatment,and began to decrease 48 h after Aβ1-42 treatment.(3) The IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE model group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were increased significantly in the transfected RAGE herb group as compared with those in the mock-transfected RAGE herb group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the mock-transfected RAGE herb group as compared with those in the mock-transfected RAGE model group (P＜0.05);the IL-1β,IL-6 and TNF-α levels were decreased significantly in the transfected RAGE herb group as compared with those in the transfected RAGE model group (P＜0.05).Conclusion DHYZ-medicated serum could inhibit the RAGE-p38 pathway and improve the inflammatory reaction in Aβ1-42-induced SH-SY5Ycells transfected with RAGE gene to protect the SH-SY5Y cells.

Changes of the electrocardiograms and the cardiac markers in patients with acute insular infarction / 中国医师进修杂志

Objective To investigate the changes of the electrocardiograms (ECG) and the cardiac markers in patients with acute insular infarction,and analyze the relationship between them and the prognosis.Methods A total of 202 patients with acute middle cerebral artery territory infarction (patients group) and 150 control subjects (control group) was selected in this study.Patients included insular infarction (insular infarction group,136 cases),non-insular infarction (non-insular infarction group,66 cases),left-side insular infarction(71 cases) and right-side insular infarction(65 cases).ECG recordings and plasma cardiac troponin I (cTnI),creatine kinase-MB (CK-MB) were measured and compared.Death in 6 months was followed-up.Results There was significant difference in the incidence of abnormal changes of ECG and plasma cTnI,CK-MB increasing between patients group and control group (P ＜0.01).The incidence of abnormal changes of ECG and fatality rate were higher in insular infarction group than those in non-insular infarction group [80.88％(110/136) vs.46.97％(31/66) and 11.76％ (16/136) vs.3.03％ (2/66),P ＜ 0.05 or ＜ 0.01].The incidences of ectopy and prolonged QT were higher in right-side insular infarction patients than those in left-side insular infarction patients [44.62％(29/65) vs.11.27％ (8/71),P ＜0.01 ; 55.38％ (36/65) vs.35.21％ (25/71),P ＜ 0.05].The incidences of sinus bradycardia and ST segment deviation were higher in left-side insular infarction patients than those in right-side insular infarction patients [22.54％(16/71) vs.7.69％(5/65),P ＜ 0.05 ;47.89％(34/71) vs.13.85％ (9/65),P ＜ 0.05].The increased rates plasma cTnI and CK-MB level were mainly seen in insular infarction [insular infarction group:47.79％ (65/136),34.56％ (47/136); non-insular infarction group:4.55％ (3/66),1.52％ (1/66),P ＜ 0.01].The incidence of plasma cTnI increasing in right-side insular infarction patients was higher than that in left-side insular infarction patients [67.69％(44/65) vs.29.58％(21/71),P＜ 0.05].There was no significant difference in the incidence of plasma CK-MB increasing between left-side insular infarction patients and right-side insular infarction patients(P ＞ 0.05).The fatality rates in plasma cTnI,CK-MB increasing patients were higher than those in normal plasma cTnI,CK-MB patients [16.18％ (11/68) vs.5.22％ (7/134),P ＜0.05;29.17％ (14/48) vs.2.60％ (4/154),P ＜0.01].Conclusions The effects of acute hemispheric cerebral infarction on heart are mainly associated with destruction of insula.Patients with insular infarction have more abnormal changes of cardiac markers and ECG,which is correlated with poor prognosis.

The study of early recurrence factors of cerebral watershed infarction / 中国综合临床

Objective To investigate clinical features and the early recurrence factors of watershed infarction(WSI).Methods Two hundred and eighty-three patients with acute anterior circulation vascular infraction confirmed by CT or MRI were collected in Heilongjiang Province Hospital from January 2010 to December 2012.Patients' information including gender,sex,risk factors for stroke and vascular stenosis was colleced.Patients were divided into the lacunar infarction group (n =83),large infarction group(n =60) and the WSI group (n =140).All patients were followed up for 6 months to observe cerebral infarction recurrence status.The national institutes of health stroke scale(NIHSS) test of all patients was performed.Meanwhile the information including disease stage was collected and analysed.Results (1) The recurrent rate in WSI group,large infarction group and lacunar infarction group were 40.0％ (56/140),30.0％ (18/60),9.6％ (8/83)respectively.The difference between recurrent rate and lacunar infarction group was statistically significant(x2 =23.5,x2 =9.7,P ＜ 0.05),and the recurrent rate of WSI was highest.(2)The symptoms of patients with WSI were relatively mild in most patients after the initial stroke.75.7％ (106/140)WSI patients were 0-4 points regarding of NIHSS score,22.9％ (32/140) for 5-9 points and only 1.4％ (2/140) for more than 10 points.The clinical symptoms aggravated obviously in recurrent WSI patients.Of recurrent patients,28.6％ (16/56) were with high NIHSS score (score ≥ 10 points).(3)The difference between recurrent group and unrecurrent group in terms of unstable plaque,baseline systolic blood pressure,degree of stenosis ≥ 70％ was statistically significant(P ＜ 0.05).Conclusion The recurrent rate is higher in WSI group than other infarction type.The clinical symptoms are relatively mild in most of the WSI patients after the initial stroke,but the symptoms turn serious when stoke recurrent and the prognosis is poor.The unstable plaque,baseline systolic blood pressure,degree of stenosis ≥ 70％ may be the risk factors of stroke recurrence.