Calycosin improves cognitive function in a transgenic mouse model of Alzheimer's disease by activating the protein kinase C pathway

The major pathological changes in Alzheimer＇s disease are beta amyloid deposits and cognitive impairment. Calycosin is a typical phy- toestrogen derived from radix astragali that binds to estrogen receptors to produce estrogen-like effects. Radix astragali Calycosin has been shown to relieve cognitive impairment induced by diabetes mellitus, suggesting calycosin may improve the cognitive function of Alzhei- mer＇s disease patients. The protein kinase C pathway is upstream of the mitogen-activated protein kinase pathway and exerts a neuropro- tective effect by regulating Alzheimer＇s disease-related beta amyloid degradation. We hypothesized that calycosin improves the cognitive function of a transgenic mouse model of Alzheimer＇s disease by activating the protein kinase C pathway. Various doses of calycosin （10, 20 and 40 mg/kg） were intraperitoneally injected into APP/PS1 transgenic mice that model Alzheimer＇s disease. Calycosin diminished hippocampal beta amyloid, Tau protein, interleukin-lbeta, tumor necrosis factor-alpha, acetylcholinesterase and malondialdehyde levels in a dose-dependent manner, and increased acetylcholine and glutathione activities. The administration of a protein kinase C inhibitor, cal- phostin C, abolished the neuroprotective effects of calycosin including improving cognitive ability, and anti-oxidative and anti-inflammato- ry effects. Our data demonstrated that calycosin mitigated oxidative stress and inflammatory responses in the hippocampus of Alzheimer＇s disease model mice by activating the protein kinase C pathway, and thereby improving cognitive function.

Mitogen-activated protein kinase phosphatase 1 protects PC12 cells from amyloid beta-induced neurotoxicity

The mitogen-activated protein kinase（MAPK） signaling pathway plays an important role in the regulation of cell growth, proliferation, differentiation, transformation and death. Mitogen-activated protein kinase phosphatase 1（MKP1） has an inhibitory effect on the p38 MAPK and JNK pathways, but it is unknown whether it plays a role in Aβ-induced oxidative stress and neuronal inflammation. In this study, PC12 cells were infected with MKP1 sh RNA, MKP1 lentivirus or control lentivirus for 12 hours, and then treated with 0.1, 1, 10 or 100 μM amyloid beta 42（Aβ42）. The cell survival rate was measured using the cell counting kit-8 assay. MKP1, tumor necrosis factor-alpha（TNF-α） and interleukin-1β（IL-1β） m RNA expression levels were analyzed using quantitative real time-polymerase chain reaction. MKP1 and phospho-c-Jun N-terminal kinase（JNK） expression levels were assessed using western blot assay. Reactive oxygen species（ROS） levels were detected using 2′,7′-dichlorofluorescein diacetate. Mitochondrial membrane potential was measured using flow cytometry. Superoxide dismutase activity and malondialdehyde levels were evaluated using the colorimetric method. Lactate dehydrogenase activity was measured using a microplate reader. Caspase-3 expression levels were assessed by enzyme-linked immunosorbent assay. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase d UTP nick end labeling method. MKP1 overexpression inhibited Aβ-induced JNK phosphorylation and the increase in ROS levels. It also suppressed the Aβ-induced increase in TNF-α and IL-1β levels as well as apoptosis in PC12 cells. In contrast, MKP1 knockdown by RNA interference aggravated Aβ-induced oxidative stress, inflammation and cell damage in PC12 cells. Furthermore, the JNK-specific inhibitor SP600125 abolished this effect of MKP1 knockdown on Aβ-induced neurotoxicity. Collectively, these results show that MKP1 mitigates Aβ-induced apoptosis, oxidative stress and neuroinflammation by inhibiting the JNK signaling pathway, thereby playing a neuroprotective role.

PEEK modified PLA shape memory blends:towards enhanced mechanical and deformation properties

Polylactic acid(PLA)is one of the most promising shape memory polymers with outstanding biocompatibility,while poly(ether ether ketone)(PEEK)is a special engineering plastic with excellent mechanical performance.In this work,PEEK was selected to modify PLA,and a series of PLA blended with different PEEK contents(PLA/PEEK blends)were obtained.The effects of PEEK on thermodynamic,mechanical and shape memory properties of PLA/PEEK blends were investigated.The results showed that the thermal stabillity of the PL A/PEEK blend was improved with the PEEK content increase.The tensile strength reached the highest value of 20.6 MPa when the PEEK content was 10%.While the best shape memory performance occurred with the PEEK content of 15%,the shape recovery time was less than 2 s,and the shape fixation/recovery ratio was more than 99%.Furthermore,the programmable mimetic flower opening process was achieved by using PLA/PEEK blends with different PEEK content ratios.The above results indicated that the blend of an appropriate proportion of PEEK had positive effects on mechanical and deformation performances of PLA.

Relationship between serum homocysteine levels and long-term outcomes in patients with ST-segment elevation myocardial infarction

Background:The mortality of cardiovascular disease is constantly rising,and novel biomarkers help us predict residual risk.This study aimed to evaluate the predictive value of serum homocysteine (HCY) levels on prognosis in patients with ST-segment elevation myocardial infarction (STEMI).Methods:The 419 consecutive patients with STEMI,treated at one medical center,from March 2010 to December 2015 were retrospectively investigated.Peripheral blood samples were obtained within 24 h of admission and HCY concentrations were measured using an enzymatic cycling assay.The patients were divided into high HCY level (H-HCY) and low HCY level (L-HCY) groups.Short- and long-term outcomes were compared,as were age-based subgroups (patients aged 60 years and younger vs.those older than 60 years).Statistical analyses were mainly conducted by Student t-test,Chi-squared test,logistic regression,and Cox proportional-hazards regression.Results:The H-HCY group had more males (84.6% vs.75.4%,P=0.018),and a lower prevalence of diabetes (20.2% vs.35.5%,P<0.001),compared with the L-HCY group.During hospitalization,there were seven mortalities in the L-HCY group and 10 in the H-HCY group (3.3% vs.4.8%,P= 0.440).During the median follow-up period of 35.8 (26.9–46.1) months,33 (16.2%) patients in the L-HCY group and 48 (24.2%) in the H-HCY group experienced major adverse cardiovascular and cerebrovascular events (MACCE)(P=0.120).History of hypertension (hazard ratio [HR]:1.881,95% confidence interval [CI]:1.178–3.005,P=0.008) and higher Killip class (HR:1.923,95% CI:1.419–2.607,P<0.001),but not HCY levels (HR:1.007,95% CI:0.987–1.027,P=0.507),were significantly associated with long-term outcomes.However,the subgroup analysis indicated that in older patients,HCY levels were significantly associated with long-term outcomes (HR:1.036,95% CI:1.011–1.062,P=0.005).Conclusion:Serum HCY levels did not independently predict in-hospital or long-term outcomes in patients with STEMI;however,among elderly patients with STEMI,this study revealed a risk profile for late outcomes that incorporated HCY level.

A Prospective Randomized Multicenter Controlled Trial on Salvianolate for Treatment of Unstable Angina Pectoris in A Chinese Elderly Population

Objective: To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris(UAP). Methods: A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group(160 patients) and a control group(158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein(hs-CRP) and N-terminal pro-B-type natriuretic peptide(NT-proBNP), as well as major adverse cardiovascular events(MACEs). Safety was assessed according to adverse events and serious adverse events. Results: Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angi na attacks(2.92 vs. 4.08, P =0.025), th e biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks(P <0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group(P <0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated. Conclusions: Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP.

Changes of dipalmitoyl phosphatidyl choline after mechanical ventilation in patients with acute cerebral injury

客观：没有主要肺的损害，在机械通风治疗以后与尖锐服的损害在病人的唾沫检测 dipalmitoyl phosphatidyl 胆碱(DPPC ) 的层次。方法：在有尖锐服的损害，但是没有肺的损害的 35 个病人的唾沫的 DPPC 层次在通风和 16-20 的开始与高效液体层析被检测在通风以后的天， 21-40 天，和 41-60 天分别地。结果：没有在在通风以后的 16-20 天之间的 DPPC 层次的重要差别(3.36 ± 0.49 ) 并且在通风(3.37 ± 0 .58 ) 的开始(P 】 0.05 ) 。DPPC 的 Themean 层次在 21-40 天显著地减少了(2.87 mg/ml ± 0 .26 nig/ml， P 【 0.05 ) and41-60 天(1.93 mg/ml ± 0 .21 mg/ml， P 【 0.01 ) 在通风以后与那相比在通风的开始。在一样的时期，吸入的压力和平均数航线迫使的山峰显著地增加了，而静态的依从和在动脉的氧的部分压力显著地减少了。在收到了通风超过 20 天的 25 个病人之中，(32%) 8 在通风的开始与那相比在动脉有氧的稍微减少的部分压力。结论：DPPC 铺平的机械通风罐头减少，减少肺依从和增加航线压力，甚至与尖锐服的损害损害氧化功能住院病人。反常 DPPC 是主要原因之一联系 ofventilator 的肺损害。