ABSTRACT
Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.
ABSTRACT
Anti-Sj?gren's syndrome type A（SSA) and anti-Sj?gren's syndrome type B（SSB) antibodies both belong to the antinuclear antibody spectrum and are common in patients with systemic lupus erythematosus, Sj?gren's syndrome and undifferentiated connective tissue disease as well as asymptomatic patients. Approximately 1% of pregnant women are positive for anti-SSA and anti-SSB antibodies and only 1%-3% of the fetuses carried by primiparae with anti-SSA and anti-SSB antibodies show immune-mediated cardiac conduction and structural abnormalities. Due to its low incidence and insidious onset, some pregnant women were diagnosed positive for antibodies against SSA and SSB for the first time only due to fetal heart block or structural abnormalities during pregnancy. Domestic and international research on the effects of anti-SSA and anti-SSB antibodies on fetal heart and the prenatal monitoring, diagnosis, intrauterine treatment and prognosis of fetal cardiac abnormalities related to anti-SSA and anti-SSB exposure are reviewed to guide the clinical work of obstetrics.
ABSTRACT
BACKGROUND@#Solitary pulmonary nodule has received increasing attention in recent years. A couple of lung nodules have been recognized as primary malignant tumors, which leads to an urgent need in enhancing the diagnosis of benign/malignant lung nodules at clinical settings. This study aims to explore the value of the combined detection of cytokines and tumor markers in differencing benign and malignant solitary pulmonary nodules in diagnose.@*METHODS@#With 81 solitary pulmonary nodules cases with a clear diagnosis, the general clinical data, nodule imaging features, pathological diagnosis data, serological index cytokine series and tumor marker expression levels were collected in groups. Both single factor and multi-factors analysis were conducted to screen out the serum influence indexes that can predict the malignant probability of lung nodules, and mean while binary logistic regression analysis was used to construct joint indexes; After receiver operating characteristic curve (ROC) was drawn, the area under the curve and the corresponding sensitivity, specificity and positive of each index predicted value, negative predicted value and accuracy could be calculated with a view to determine the statistical significance of area under the curve (AUC).@*RESULTS@#There are differences in the distribution of malignant solitary pulmonary nodules at different locations, with the highest proportion of the right upper lobe (40.4%). The serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), interleukin-6 (IL-6), interleukin-8 (IL-8) in the malignant nodule group were higher than those in the benign nodule group. Logistic regression analysis suggests that CEA, IL-6 and IL-8 are independent risk factors for predicting malignant nodules. ROC curve analysis shows that the areas under the curve of the individual indicators CEA, IL-6 and IL-8 are 0.642, 0.684 and 0.749. The comparison result of the test efficiency of the area under the curve suggests that CEA+IL-6+IL-8 has a larger area under the curve and higher detection efficiency.@*CONCLUSIONS@#CEA, IL-6 and IL-8 are independent risk factors for malignant solitary pulmonary nodules. The combined detection of cytokines and tumor markers has played a role in the differential diagnosis of benign and malignant lung nodules. The diagnostic value of the combined detection of CEA+IL-6+IL-8 is the highest.
ABSTRACT
Objective To investigate G protein-coupled estrogen receptor(GPER)mediated neuroprotective effect and mechanism in an ischemic stroke model. Methods Bilateral ovariectomy (OVX)was used to establish a castrated model of adult SPF grade female SD rats. Enzyme-linked immunosorbent assay was used to detect serum estrogen level at 4 weeks after procedure.Middle cerebral artery occlusion(MCAO)was use to prepare a stroke model.The rats were randomly divided into sham operation(n=6),MCAO(n=7),MCAO+estrogen(MCAO+E2,n=8),MCAO+agonist(MCAO+G1,n=8)and MCAO +antagonist G15(MCAO +G15,n =7)groups. The neurological severity score (NSS),2,3,5-triphenyltetrazolium chloride(TTC)staining were used to measure the volume of cerebral infarction in order to assess the effects of different interventions.Western blot was used to detect the protein expression of hypoxia inducible factor-1α(HIF-1α),c-Jun N-terminal kinase(JNK),and Caspase-3 in the ischemic penumbra. Results (1)Estrogen level:after OVX,The level of serum estrogen in rats was significantly lower than that before castration(20 ± 9 ng/L vs. 73 ± 21 ng/L,P <0. 01).(2)NSS score:the NSS score of MCAO in each group was significant higher than that in the sham operation group (P<0.01);The NSS score of the MCAO+G1 group was significantly lower than that of the MCAO group and the MCAO+G15 group(6.0 ±1.8 vs.11.9 ±2.0 and 10.0 ±2.1).The difference was statistically significant (all P<0.05).(3)Cerebral infarct volume:there was significant difference in infarcted volume between the sham operation group and all other groups(all P<0.01);Compared with the MCAO group and the MCAO+G15 group,the infarct volume of the MCAO+E2 group and MCAO+G1 group was significantly reduced(19.8 ± 4.0%,14.0 ± 2.9%)vs.29.7 ± 5.8% and 27.6 ± 3.6%).The difference was statistically significant (all P<0.05).(4)Results of Western blot:the relative optical density values of HIF-1α,JNK,and Caspase-3 of the MCAO group were higher than those of the MCAO + G1 group(all P <0.01). Conclusions GPER mediates the neuroprotective effect of estrogen in the ischemic stroke model.This protective effect is associated with the regulation of the expression levels of HIF-1α,JNK,and Caspase-3.
ABSTRACT
Bone marrow-derived mesenchymal stem cells (BMSCs) for repairing damaged heart tissue are a new kind of important treatment options because of their potential to differentiate into cardiomyocytes. We in this experiment investigated the effect of different electrical stimulation time on the expression of myocardial specificity gene and protein in rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. The rBMSCs of second or third generation were randomly divided into three groups, i.e, electrical stimulation (ES) group, 5-Azacytidine (5-Aza) group and the control group. The rBMSCs in the ES groups with complete medium were exposed to 2 V, 2 Hz, 5 ms electrical stimulation for 0. 5 h, 2 h, 4 h, and 6 h respectively every day for 10 days. Those in the 5-Aza group were induced by 5-Aza (10 μmol/L) for 24 h, and then cultured with complete medium for 10 days. Those in the control group were only cultured with complete medium, without any treatment, for 10 days. The rBMSCs' morphological feature in each group was observed with inverted phase microscope. The mRNA expression of myocyte-specific enhancer factor 2C (MEF-2C) and connexin 43 (Cx43) were examined with Real-Time quantitative PCR and the protein expression of MEF-2C, Cx43 were detected with Western Blot method. The results showed that the mRNA expression level of the MEF-2C, Cx43 and the protein expression level of MEF-2C, Cx43 were significantly higher in the ES group and 5-Aza group than those in the relative control group (P < 0.05). It suggests that electrical stimulation could play a part of role in the induction of the rBMSCs to differentiate into the cariomyocyte-like cells in vitro and the effectiveness of the electrical stimulation with 2 h/d had the best in our experiment. But the mechanism how electrical stimulation promotes the differentiation of rBMSC into cardiomyocyte is still unclear.