To investigate the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholinesterase (AchE) fibers in rats. According to random digits table, 60 SD rats were divided into two groups, marrow stromal cells (MSCs) intracranial transplantation group and MSCs intracranial transplantation + ultrasonic microbubbles group. Marrow stromal cells were cultivated and isolated in vitro; 12 weeks after transplantation, spatial learning and memorizing abilities of rats were assessed by Morris water maze; AchE staining method was used to observe changes in density and appearance of AchE staining positive fibers in hippocampal CA1 region. There was asignificant increase in spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group. Hippocampal AchE staining suggested an increase in the density of AchE staining positive fibers in MSCs intracranial transplantation group; the fibers were regular, intact and dense. Density of hippocampal AchE positive fibers was negatively correlated with the escape latent period and was positively correlated with percentage of the time needed to cross each platform quadrant. Better promotion of spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group may be related with the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholine fibers.
Abstract Objectives Our study investigated left ventricular dyssynchrony (LVD) in coronary artery disease (CAD) patients without regional wall‐motion abnormality (RWMA) by three‐dimensional echocardiography (3‐DE) and explored the relationship between LVD and severity of CAD as assessed by the Gensini score (GS). Methods Sixty‐one patients with a confirmed diagnosis of CAD by coronary angiography (CAG) were enrolled. We quantified LVD parameters, including the left ventricular segments (16, 12, and 6) standard deviation of the time to minimum systolic volume (TmsvSD‐16, TmsvSD‐12, and TmsvSD‐6) and the systolic dyssynchrony index in regions 16, 12, and 6 (16R‐SDI, 12R‐SDI, 6R‐SDI) using 3‐DE. The severity of coronary atherosclerotic lesions was evaluated by the GS system on the basis of CAG findings. We further divided all patients into three groups according to the tertiles of GS: low‐GS ≤20, mid‐GS >20 and ≤48, and high‐GS >48. The differences of LVD values among the three groups were compared, and the associations between LVD parameters and GS were analyzed. Results Coronary artery disease patients demonstrated increased LVD parameters compared with healthy controls. TmsvSD12, 16R‐SDI, and 6R‐SDI were prolonged in the high‐GS group compared with the low‐ and mid‐GS groups. 16R‐SDI was positively correlated with the GS, and multivariate regression analysis showed that 16R‐SDI was an independent predictor of the GS. 16R‐SDI above 10.7% had a sensitivity of 84.21% and a specificity of 92.86% for identifying high‐GS. Conclusion Three‐dimensional echocardiography is a noninvasive technique to detect LVD in non‐RWMA CAD patients, and the parameter 16R‐SDI was significantly correlated with CAD severity.
Objective To study on evaluation of cardiac resynchronization therapy(CRT) in clinical by threedimensional speckle tracking imaging.Methods Two-dimensional echocardiography and three-dimensional speckle tracking imaging examination were performed on 20 normal subjects and 18 congestive heart failure patients,who received the CRT,before implantation,one week,one month and three months after operation respectively.The left ventricular end-diastolic volume(LVEDV),left ventricular contraction to the end of the volume(LVESV) and left ventricular ejection fraction(LVEF) were measured.And then,left ventricular function and myocardial movement synchronization were evaluated by three-dimensional speckle tracking imaging with ultrasonic parameters including left ventricular overall global longitudinal strain(GLS),the left ventricle as a whole ring to the global circumferential strain(GCS),left ventricular overall global radial strain(GRS),the area of the 16 segments of the left ventricular response time to peak maximum differential(A-Max-Ts) and standard deviation(A-Ts-SD).Results In contrast to those in the normal,preoperative LVEDV and LVESV increased while LVEF,GLS,GCS and GRS decreased,A-Max-Ts and A-Ts-SD extended.Compared with those before CRT in the patients,GRS during postoperative one week slightly improved(P 0.05) though there wasn’t any significant difference in the rest parameters(P 0.05).At the end of the first month after CRT,LVEDV,LVESV were significantly reduced(P 0.05),LVEF,GLS,GCS,GRS significantly increased(P 0.05),A-Max-Ts,A-Ts-SD were shortened significantly(P 0.05).There was no significant difference in all ultrasonic parameters between one and three months after CRT.Conclusion It’s seemed to be certain that CRT could significantly improve cardiac function soon in patients with heart failure.Threedimensional speckle tracking imaging could be used to detect left ventricular function and myocardial movement synchronization changes effectively and could be used to evaluate the short-term efficacy of CRT therapy.
The novel echocardiographic parameter of myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. We sought to investigate the diagnostic value of myocardial work to identify different grades of stenosis severity in coronary heart disease (CHD) patients with preserved left ventricular ejection fraction and without regional wall motion abnormalities.One hundred and seventeen consecutive subjects with preserved ejection fraction referred for coronary angiography were randomized and prospectively included in this study. Forty-six in the control group, and 25, 24, and 22 in each of the grade-1, grade-2, and grade-3 CHD groups as classified by the Gensini score. The following indices of myocardial work were assessed with a Vivid E95 Version 203 instrument: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE).Both GWI (P<0.001) and GCW (P<0.001) decreased significantly in CHD grade-1, increased slightly in CHD grade-2 compared with CHD grade-1, and decreased significantly in CHD grade-3. GWW (P<0.001) increased significantly from CHD grade-1 to CHD grade-3, while GWE (P<0.001) decreased significantly from CHD grade-1 to CHD grade-3. Receiver operating characteristic curves analysis revealed good discrimination between the control group and CHD grade-3 for GWI [area under the curve (AUC): 0.810; 95% confidence interval (CI): 0.691-0.930], GCW (AUC: 0.758; 95% CI: 0.631-0.885), GWW (AUC: 0.754; 95% CI: 0.624-0.885) and GWE (AUC: 0.817; 95% CI: 0.709-0.926). The assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85).Myocardial work incorporates left ventricular pressure into the assessment of left ventricular systolic function and thereby corrects for afterload. It identifies patients with incipient left ventricular dysfunction caused by chronic ischemia due to CHD. A gradual worsening of myocardial work parameters was observed when comparing patients with higher degrees of stenosis severity. Therefore, adding myocardial work when evaluating patients with suspected CHD may help increase diagnostic accuracy.
Objective To identify the proteins related to ischemia in the mitochondia of cerebral cortex.Methods Totally 7 adult male SD rats were inflicted by middle cerebral artery occlusion(MCAO)for 6 h with nylon monofilament.Another 7 rats served as normal control.Then cerebral cortex were collected and mitochondria were extracted and purified.After 2-dimensional electrophoresis and PDQuest for gel image analysis,the MS/MS of the peptides from the differential proteins digested by tripsin were analyzed by HPLC-Chip/MS and the original data were pre-processed by Spectrum Mill then searched in NCBInr database.Results Specific protein spots were identified as TUC-4b,CKB,HS1 binding protein,mitochondrial ribosomal protein S27,dihydrolipoamide dehydrogenase,malate dehydrogenase,isocitrate dehydrogenase(NAD+)alpha,dihydrolipoamide S-acetyltransferase,cytochrome c oxidase subunit Vla,succinate-coenzyme A ligase,ubiquinol-cytochrome c reductase core protein,ATP synthase beta subunit,heat shock 70×103 protein,heat shock 60×103 protein,acyl-coenzyme A dehydrogenase family.Conclusion Cerebebral ischemia affects the proteins related to cerebral cortex mitochondria,which suggests that these proteins may be correlated with the energy metabolism and apoptosis of mitochondria.
To evaluate whether myocardial strain under adenosine stress calculated from two-dimensional echocardiography by automatic frame-by-frame tracking of natural acoustic markers enables objective description of myocardial viability in clinic.Two-dimensional echocardiography and two-dimensional speckle tracking imaging (2D STI) at rest were performed first and once again after adenosine was infused at 140 ug/kg/min over a period of 6 minutes in 36 stable patients with previous myocardial infarction. Then radionuclide myocardial perfusion/metabolic imaging served as the "gold standard" to define myocardial viability was given in all patients within 1 day. Two-dimensional speckle tracking images were acquired at rest and after adenosine administration. An automatic frame-by-frame tracking system of natural acoustic echocardiographic markers was used to calculate 2D strain variables including peak-systolic circumferential strain (CS(peak-sys)), radial strain (RS(peak-sys)), and longitudinal strain (LS(peak-sys)). Those segments with abnormal motion from visual assessment of two-dimensional echocardiography were selected for further study. As a result, 126 regions were viable whereas 194 were nonviable among 320 abnormal motion segments in 36 patients according to radionuclide imaging. At rest, there were no significant changes of 2D strain between the viable and nonviable myocardium. After adenosine administration (140 ug/kg/min), CS(peak-sys) had a little change of the viable myocardium while RS(peak-sys) and LS(peak-sys) increased significantly compared with those at rest. In nonviable group, CS(peak-sys), RS(peak-sys), and LS(peak-sys) had no significant changes during adenosine administration. After adenosine administration, RS(peak-sys) and LS(peak-sys) in viable group increased significantly compared with nonviable group. Obtained strain data were highly reproducible and affected in small intraobserver and interobserver variabilities. A change of radial strain more than 9.5% has a sensitivity of 83.9% and a specificity of 81.4% for viable whereas a change of longitudinal strain more than 14.6% allowed a sensitivity of 86.7% and a specificity of 90.2%.2D STI combined with adenosine stress echocardiography could provide a new and reliable method to identify myocardium viability.
Summary Background The accuracy of ultrasound signs as predictors for the presence of coronary artery disease (CAD) has been evaluated extensively in the 1990s and 2000s. Imaging quality has improved tremendously over the last decades. Hypothesis High-end ultrasound systems allow for accurate prediction of the presence or absence of CAD. Methods All patients who underwent a transesophageal echocardiography examination (TEE) between 2007 and 2016 and who had coronary angiography within 24 months before or after the TEE were retrospectively evaluated. Results A total of 242 patients fulfilled the inclusion criteria, 60% were male. Mean age was 70 years (SD ± 13 years). In multivariate regression analysis, plaque in the ascending aorta (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.18–5.32, p = 0.017), plaque in at least one of the thoracic aortic segments (OR 2.07, 95% CI 1.02–4.22, p = 0.045), and the presence of mitral annular calcification (MAC, OR 1.84, 95% CI 1.01–3.36, p = 0.046) were predictors of significant CAD. The isolated finding of aortic stenosis (AS) (OR 2.53, 95%CI 1.23–5.21, p = 0.012) was a significant predictor for the absence of normal coronary arteries. Conclusion With an negative predictive value (NPV) of 80%, the absence of MAC, AS, and aortic plaque makes the presence of significant CAD unlikely. If at least mild AS is present, normal coronary arteries are improbable.
Abstract Background Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) engraftment is a promising therapy for acute ischemic stroke (AIS). However, the harsh ischemic microenvironment limits the therapeutic efficacy of hUC-MSC therapy. Curcumin is an anti-inflammatory agent that could improve inflammatory microenvironment. However, whether it enhances the neuroprotective efficacy of hUC-MSC transplantation is still unknown. In the present study, we investigated the therapeutic efficacy and the possible mechanism of combined curcumin and hUC-MSC treatment in AIS. Methods Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD) microglia were administrated hUC-MSCs with or without curcumin. Neurological deficits assessment, brain water content and TTC were used to assess the therapeutic effects of combined treatment. To elucidate the mechanism, MCAO mice and OGD microglia were treated with AKT inhibitor MK2206, GSK3β activator sodium nitroprusside (SNP), GSK3β inhibitor TDZD-8 and Nrf2 gene knockout were used. Immunofluorescence, flow cytometric analysis, WB and RT-PCR were used to evaluate the microglia polarization and the expression of typical oxidative mediators, inflammatory cytokines and the AKT/GSK-3β/β-TrCP/Nrf2 pathway protein. Results Compared with the solo hUC-MSC-grafted or curcumin groups, combined curcumin-hUC-MSC therapy significantly improved the functional performance outcomes, diminished the infarct volumes and the cerebral edema. The combined treatment promoted anti-inflammatory microglia polarization via Nrf2 pathway and decreased the expression of ROS, oxidative mediators and pro-inflammatory cytokines, while elevating the expression of the anti-inflammatory cytokines. Nrf2 knockout abolished the antioxidant stress and anti-inflammation effects mediated with combined treatment. Moreover, the combined treatment enhanced the phosphorylation of AKT and GSK3β, inhibited the β-TrCP nucleus translocation, accompanied with Nrf2 activation in the nucleus. AKT inhibitor MK2206 activated GSK3β and β-TrCP and suppressed Nrf2 phosphorylation in nucleus, whereas MK2206 with the GSK3β inhibitor TDZD-8 reversed these phenomena. Furthermore, combined treatment followed by GSK3β inhibition with TDZD-8 restricted β-TrCP nucleus accumulation, which facilitated Nrf2 expression. Conclusions We have demonstrated that combined curcumin-hUC-MSC therapy exerts anti-inflammation and antioxidant stress efficacy mediated by anti-inflammatory microglia polarization via AKT/GSK-3β/β-TrCP/Nrf2 axis and an improved neurological function after AIS.
The aim of the present work was to examine the effect of polyethylene glycol (PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles carrying Pik3cb short hairpin RNA (shRNA) in the prevention of restenosis with the aid of ultrasound and a magnetic field. SPIO is a type of contrast agent used in medical imaging to enhance the visibility of specific tissues or organs. It consists of tiny iron oxide nanoparticles that can be targeted to specific areas of interest in the body. PEG-coated SPIO nanoparticles carrying Pik3cb shRNA (SPIO-shPik3cb) were prepared, and the particle size and zeta potential of PEG-coated SPIO nanoparticles with and without Pik3cb shRNA were examined. After a right common artery balloon-injured rat model was established, the rats were randomly divided into four groups, and the injured arteries were transfected with SPIO-shPik3cb, saline, SPIO-shcontrol and naked shRNA Pik3cb. During the treatment, each group was placed under a magnetic field and was transfected with the aid of ultrasound. Rats were sacrificed, and the tissue was harvested for analysis after 14 days. The results suggested that the mean particle size and zeta potential of SPIO-shPik3cbs were 151.45 ± 11 nm and 10 mV, respectively. SPIO-shPik3cb showed higher transfection efficiency and significantly inhibited the intimal thickening compared with naked Pik3cb shRNA in vascular smooth muscle cells (VSMCs) (*P < 0.05). Moreover, SPIO-shPik3cb could also significantly downregulate the expression of pAkt protein compared with naked Pik3cb shRNA. According to the results, SPIO-shPik3cb can remarkably inhibit the intimal thickening under a combination of magnetic field exposure and ultrasound.
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