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Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine
Liang, LN;Zhong, X;Zhou, Y;Hou, ZQ;Hu, HR;Zhu, FF;Chen, JB;Ji, XF;Shang, DY
AMERICAN JOURNAL OF EMERGENCY MEDICINE 2017年 35卷8期 页码:1082-1089
K-ATP CHANNELS; CARDIOPULMONARY-RESUSCITATION; VENTRICULAR-FIBRILLATION; ARTERIAL-HYPOTENSION; DYSFUNCTION; HEART
Introduction: Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia- reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation.;-;Methods: Ventricular fibrillation was induced electrically for 4 min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n = 8) or nicorandil (n = 8) groups. Nicorandil (150 mu g/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3 mu g/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n = 4). Hemodynamic parameters weremonitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360 min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6 h after ROSC. The animals were euthanized 6 h after ROSC, and the cardiac tissue was removed for analysis.;-;Results: 6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P < 0.05) except the maximum rate of left ventricular pressure decline and heart rate (P > 0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P < 0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P < 0.05). Histopathologic injurywas reducedwith nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P < 0.05).;-;Conclusion: Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitationmyocardial dysfunction and energymetabolism, reduction inmyocardial histopathologic injury, and antiapoptotic effects. (C) 2017 Elsevier Inc. All rights reserved.
Sodium Ferulate Protects against Angiotensin II-Induced Cardiac Hypertrophy in Mice by Regulating the MAPK/ERK and JNK Pathways
Hu, B;Song, JT;Ji, XF;Liu, ZQ;Cong, ML;Liu, DX
BIOMED RESEARCH INTERNATIONAL 2017年
INDUCED APOPTOSIS; ANG-II; STRESS; KINASE; BETA; RATS; INHIBITION; EXPRESSION; FIBROSIS; FAILURE
Background and Objective. It has been reported that sodium ferulate (SF) has hematopoietic function against anemia and immune regulation, inflammatory reaction inhibition, inhibition of tumor cell proliferation, cardiovascular and cerebrovascular protection, and other functions. Thus, this study aimed to investigate the effects of SF on angiotensin II- (AngII-) induced cardiac hypertrophy in mice through the MAPK/ERK and JNK signaling pathways. Methods. Seventy-two male C57BL/6J mice were selected and divided into 6 groups: control group, PBS group, model group (AngII), model + low-dose SF group (AngII + 10 mg/kg SF), model + high-dose SF group (AngII + 40 mg/kg SF), and model + high-dose SF + agonist group (AngII + 40 mg/kg SCU + 10 mg/kg TBHQ). After 7 d/14 d/28 days of treatments, the changes of blood pressure and heart rates of mice were compared. The morphology of myocardial tissue and the apoptosis rate of myocardial cells were observed. The mRNA and protein expressions of atrial natriuretic peptide (ANP), transforming growth factor-beta (TGF-beta), collagen III (Col III), and MAPK/ERK and JNK pathway-related proteins were detected after 28 days of treatments. Results. SF improved the mice's cardiac abnormality and decreased the apoptosis rate of myocardial cells in a time-and dose-dependent manner (all p < 0.05). MAPK/ERK pathway activator inhibited the protective effect of SF inmyocardial tissue of mice (p < 0.05). SF could inhibit the expression of p-ERK, p-p38 MAPK, and p-JNK and regulate the expressions of ANP, TGF-beta, and Col III (all Rho < 0.05). Conclusion. Our findings provide evidence that SF could protect against AngII-induced cardiac hypertrophy in mice by downregulating the MAPK/ERK and JNK pathways.
Long non-coding RNAs LOC285194, RP11-462C24.1 and Nbla12061 in serum provide a new approach for distinguishing patients with colorectal cancer from healthy controls
Wang, CX;Yu, JY;Han, YP;Li, LP;Li, J;Li, T;Qi, P
ONCOTARGET 2016年 7卷43期 页码:70769-70778 影响因子:5.008
SQUAMOUS-CELL CARCINOMA; POOR-PROGNOSIS; GASTRIC-CANCER; LOW EXPRESSION; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; TUMOR-SUPPRESSOR; BIOMARKERS; LNCRNA; METASTASIS
Colorectal cancer (CRC) is currently the most prevalent malignant cancer worldwide. However, there is a lack of efficient biomarkers for CRC screening. Accumulating evidence reveals that long non-coding RNAs (lncRNAs) detectable in serum are associated with the genesis and development of various types of cancer. Therefore, we examined the diagnostic ability of lncRNAs in blood samples from patients with CRC by evaluating the levels of 17 CRC- or gastrointestinal cancer-related lncRNAs in serum samples from 71 CRC patients and 70 healthy individuals using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We detected 13 lncRNAs in serum, three of which displayed significantly different levels between CRC patients and healthy controls. A three-lncRNA signature (LOC285194, RP11462C24.1 and Nbla12061) identified via stepwise regression analysis showed potential as a diagnostic marker for CRC. The area under the receiver operating characteristic curve of this signature for distinguishing CRC patients from healthy individuals was 0.793 (95% CI: 0.709 to 0.861). The diagnostic ability of this marker was much higher than that of conventional blood biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125) and carbohydrate antigen 724 (CA724). Combining this novel marker with conventional biomarkers produced even greater diagnostic ability. Furthermore, the levels of the three lncRNAs decreased after the patients underwent surgical resection. The results of this study suggest an additional marker for CRC screening and provide new directions for further investigation.
Short-chain C6 ceramide sensitizes AT406-induced anti-pancreatic cancer cell activity
Zhao, XG;Sun, BY;Zhang, JJ;Zhang, RS;Zhang, Q
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2016年 479卷2期 页码:166-172
IN-VITRO; IAP PROTEINS; VIVO; CHEMOTHERAPY; INHIBITOR; APOPTOSIS; FAMILY; INTERVENTION; GEMCITABINE; SURVIVAL
Our previous study has shown that AT406, a first-in-class small molecular antagonist of IAPs (inhibitor of apoptosis proteins), inhibits pancreatic cancer cell proliferation in vitro and in vivo. The aim of this research is to increase AT406's sensitivity by adding short-chain C6 ceramide. We show that co-treatment of C6 ceramide dramatically potentiated AT406-induced caspase/apoptosis activation and cytotoxicity in established (Pant-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells. Reversely, caspase inhibitors largely attenuated C6 ceramide plus AT406-induced above cancer cell death. Molecularly, C6 ceramide downregulated Bcl-2 to increase AT406's sensitivity in pancreatic cancer cells. Intriguingly, C6 ceramide-mediated AT406 sensitization was nullified with Bcl-2 shRNA knockdown or pretreatment of the Bcl-2 inhibitor ABT-737. In vivo, liposomal C6 ceramide plus AT406 co-administration dramatically inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) mice. The combined anti-tumor activity was significantly more potent than either single treatment. Expressions of IAPs (cIAP1/XIAP) and Bcl-2 were downregulated in Panc-1 xenografts with the co-administration. Together, we demonstrate that C6 ceramide sensitizes AT406-mediated anti pancreatic cancer cell activity possibly via downregulating Bcl-2. (C) 2016 The Authors. Published by Elsevier Inc.
The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo
Jiang, YS;Meng, QH;Chen, B;Shen, HY;Yan, B;Sun, BY
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2016年 478卷1期 页码:293-299
INDUCED APOPTOSIS; PROTEINS; FAMILY; INTERVENTION; CHEMOTHERAPY; GEMCITABINE; TARGETS
In the present study, we tested the anti-pancreatic cancer activity by AT406, a small-molecule antagonist of IAP (inhibitor of apoptosis proteins). In established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells, treatment of AT406 significantly inhibited cell survival and proliferation. Yet, same AT406 treatment was non-cytotoxic to pancreatic epithelial HPDE6c7 cells. AT406 increased caspase-3/-9 activity and provoked apoptosis in the pancreatic cancer cells. Reversely, AT406' cytotoxicity in these cells was largely attenuated with pre-treatment of caspase inhibitors. AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreatic cancer cells. Bcl-2 inhibition (by ABT-737) or shRNA knockdown dramatically sensitized Panc-1 cells to AT406. In vivo, oral administration of AT406 at well-tolerated doses down regulated IAPs (cIAP1/XIAP) and inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) nude mice. Together, our preclinical results suggest that AT406 could be further evaluated as a promising anti-pancreatic cancer agent. (C) 2016 Elsevier Inc. All rights reserved.
MiR-130b inhibits proliferation and induces apoptosis of gastric cancer cells via CYLD
Sun, BY;Li, L;Ma, WD;Wang, SK;Huang, CJ
TUMOR BIOLOGY 2016年 37卷6期 页码:7981-7987
DOWN-REGULATION; DEUBIQUITINASE CYLD; BREAST-CANCER; METASTASIS; GROWTH; OSTEOSARCOMA; MMP7; PHOSPHORYLATION; INFLAMMATION; ACTIVATION
A role of microRNA-130b (miR-130b) in the carcinogenesis of gastric cancer remains undetermined. In this study, we studied the effects and mechanism of miR-130b to the gastric cell proliferation and apoptosis. We found that the levels of miR-130b significantly up-regulated in gastric cancer tissue, compared to the paired adjacent non-tumor gastric tissue. The miR-130b levels in gastric cancer cell lines were significantly higher than those in control normal gastric tissues. Transfection with the miR-130b mimic enhanced the cell proliferation and suppressed cell apoptosis in gastric cancer cells, while transfection with the anti-sense of miR-130b (anti-miR-130b) suppressed cell proliferation and induced cell apoptosis in gastric cancer cells. Bioinformatics analyses showed that cylindromatosis gene (CYLD) was a potential target gene of miR-130b. The luciferase activity assay and western blot verified that miR-130b targeted CYLD messenger RNA (mRNA) to modulate its protein levels. Together, our study suggests that aberrantly expressed miR-130b may regulate cell apoptosis and proliferation of human gastric cancer cells via CYLD, which appears to be a promising therapeutic target for gastric cancer.
Association of Genetic Polymorphisms on VEGFA and VEGFR2 With Risk of Coronary Heart Disease
Liu, DX;Song, JT;Ji, XF;Liu, ZQ;Cong, ML;Hu, B
MEDICINE 2016年 95卷19期
ENDOTHELIAL GROWTH-FACTOR; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY; HYPERTENSION; POPULATION; STROKE; METAANALYSIS; ANGIOGENESIS; EXPRESSION
Coronary heart disease (CHD) is a cardiovascular disease which is contributed by abnormal neovascularization. VEGFA (vascular endothelial growth factor A) and VEGFR2 (vascular endothelial growth factor receptor 2) have been revealed to be involved in the pathological angiogenesis. This study was intended to confirm whether single nucleotide polymorphisms (SNPs) of VEGFA and VEGFR2 were associated with CHD in a Chinese population, considering pathological features and living habits of CHD patients.Peripheral blood samples were collected from 810 CHD patients and 805 healthy individuals. Six tag SNPs within VEGFA and VEGFR2 were obtained from HapMap Database. Genotyping of SNPs was performed using SNapShot method (Applied Biosystems, Foster, CA). Odd ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the association between SNPs and CHD risk.Under the allelic model, 6 SNPs of VEGFA and VEGFR2 were remarkably associated with the susceptibility to CHD. Genotype CT of rs3025039, TT of rs2305948, and AA of rs1873077 were associated with a reduced risk of CHD when smoking, alcohol intake and diabetes were considered, while homozygote GG of rs1570360 might elevate the susceptibility to CHD (all P<0.05) for patients who were addicted to smoking or those with hypertension. All of the combined effects of rs699947 (CC/CA) and rs2305948 (TT), rs3025039 (TT) and rs2305948 (TT), rs3025039 (CT) and rs1870377 (AA) had positive effects on the risk of CHD, respectively (all P<0.05). By contrast, the synthetic effects of rs69947 (CA/AA) and rs1870377 (TA), rs699947 (CA) and rs7667298 (GG), rs699947 (AA) and rs7667298 (GG), rs1570360 (GG) and rs2305948 (TT), as well as rs1570360 (GG) and rs1870377 (AA) all exhibited adverse effects on the risk of CHD, respectively (all P<0.05).Six polymorphisms in VEGFA and VEGFR2 may have substantial influence on the susceptibility to CHD in a Han Chinese population. Prospective cohort studies should be further designed to confirm the above conclusions.
Role of apolipoprotein E in the pathogenesis of Alzheimer's disease and molecular mechanisms
Song, ZH;Xu, S;Song, B;Zhang, QH
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2016年 9卷4期 页码:4615-4621
AMYLOID-BETA-PEPTIDE; RECEPTOR-RELATED PROTEIN; NEURONAL CELL-DEATH; TRANSGENIC MICE; APOPTOSIS; AGE; NEUROGENESIS; INJURY; DOMAIN; MODEL
Alzheimer's disease (AD), as one severe neurodegenerative disorder, severely threatens public health under the current aging of population. Some studies have speculated the presence of apolipoprotein E (apoE) in the occurrence and progression of AD. This study thus investigated the role of apoE in AD pathogenesis and related molecular mechanisms. Neural tissue samples from both AD model rats and normal rats were collected for quantifying apoE expression levels using RT- PCR and Western blotting. Cultured neural cells D283 were then transfected to over- express apoE or to down- regulate apoE using RNA interference approach. MTT assay and flow cytometry were applied to describe the growth and apoptosis of D283 cells. Clonal formation assay was then used to measure the ability of cell proliferation. AD rats had elevated apoE protein and mRNA levels compared to normal animals. Anti- sense siRNA of apoE inhibited the growth of D283 cells and induce their apoptosis, accompanied with lower clonal formation ability. The over- expression of apoE, on the contrary, facilitated cell growth, inhibited apoptosis, and potentiated clonal formation. ApoE expression level is closely correlated with AD. The lowering of apoE level inhibits neural cell D283 growth and clonal formation while induces cell apoptosis. Over- expression of apoE can facilitate cell growth and proliferation while inhibit apoptosis.
Complete mitochondrial genome sequence of the heart failure model of cardiomyopathic Syrian hamster (Mesocricetus auratus)
Hu, B;Liu, DX;Zhang, YQ;Song, JT;Ji, XF;Hou, ZQ;Zhang, ZH
MITOCHONDRIAL DNA PART A 2016年 27卷3期 页码:2182-2183
MYOCARDIAL-CONTRACTILITY
In this study we sequenced the complete mitochondrial genome sequencing of a heart failure model of cardiomyopathic Syrian hamster (Mesocricetus auratus) for the first time. The total length of the mitogenome was 16,267 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region.
Association of AT1R polymorphism with hypertension risk: An update meta-analysis based on 28,952 subjects
Liu, DX;Zhang, YQ;Hu, B;Zhang, JF;Zhao, Q
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM 2015年 16卷4期 页码:898-909
II TYPE-1 RECEPTOR; RENIN-ANGIOTENSIN SYSTEM; GENE POLYMORPHISMS; ALDOSTERONE SYSTEM; A1166C POLYMORPHISM; HAN CHINESE; POPULATION; HAPLOTYPE; JAPANESE
Background: Previous studies have shown that angiotensin II AT1 receptor gene (AT1R) polymorphisms are associated with the risk for hypertension. However, the results remain controversial. In the present study, we performed a meta-analysis to systematically summarize the association between AT1R genetic polymorphisms and the risk for hypertension.;-;Methods: We searched the literature in PubMed, EMBASE, ISI Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases (CNKI) to find case-control studies on the associations of AT1R genetic polymorphisms with the risk for hypertension. The meta-analysis was performed by using RevMan 5.0 software. The association of hypertension risk with AT1R genetic polymorphism was estimated by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs).;-;Results: Fifty-six studies involving 28,952 subjects were included in the present meta-analysis. Our results suggest that the polymorphism (A1166C) of AT1R gene is associated with a statistically increased hypertension risk, not only in Asian populations but also in Caucasian populations. We did not find any association in African populations.;-;Conclusions: This meta-analysis suggests that A1166C polymorphism in the AT1R gene is associated with the risk of hypertension in Asian and Caucasian populations.
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