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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.
Rho-kinase signaling pathway promotes the expression of PARP to accelerate cardiomyocyte apoptosis in ischemia/reperfusion
Bian, HJ;Zhou, Y;Yu, B;Shang, DY;Liu, FL;Li, B;Qi, JN
MOLECULAR MEDICINE REPORTS 2017年 16卷2期 页码:2002-2008
MEDIATED AIF TRANSLOCATION; POLY(ADP-RIBOSE) POLYMERASE-1; REPERFUSION; INHIBITION; INJURY; CELLS; RAT
It has been previously reported that Rho-kinase (ROCK) and poly ADP-ribose polymerase (PARP) serve critical roles in myocardial ischemia/reperfusion (I/R) injury. Studies have additionally demonstrated that the activation of ROCK and the expression of PARP are increased in I/R. However, the effect and mechanism of the two proteins remains to be fully elucidated in I/R. In addition, whether they can be influenced by each other is unclear. In the present study, it was demonstrated that ischemia followed by reperfusion resulted in a significant increase in ROCK and PARP. In addition, Y-27632 (ROCK inhibitor) and 3-aminobenzamide (3-AB; PARP inhibitor) pretreatment rescued myocardial infarction size and cardiomyocyte apoptosis. The inhibitory role of Y-27632 was observed to be superior to that of the 3-AB group. In addition, Y-27632 and 3-AB diminished extracellular signal-related kinase (ERK) phosphorylation and the production of tumor necrosis factor a and interleukin 6. Overall, the results of the present study suggested that the inhibition of ROCK leads to reduced myocardial infarction size and cardiomyocyte apoptosis via the PARP/ERK signaling pathway.
Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells
Zhang, HY;Zhong, X;Zhang, X;Shang, DY;Zhou, Y;Zhang, CQ
EXPERIMENTAL AND THERAPEUTIC MEDICINE 2016年 11卷2期 页码:669-673
BH3 MIMETIC ABT-737; CARCINOMA CELLS; DOWN-REGULATION; APOPTOSIS; FLAVONOIDS; AKT; CARCINOGENESIS; MECHANISMS; SURVIVAL; LEUKEMIA
Gastric cancer is the second leading cause of cancer-associated mortality and is a frequently occurring cancer worldwide. Multiple drug resistance of gastric cancer cells leads to the poor prognosis. In addition, overexpression of anti-apoptotic protein B-cell lymphoma (Bcl)-2 have been demonstrated in various cancer cells and is closely associated with drug resistance and poor prognosis. Naringenin is a flavonoid that has antimutagenic and anticarcinogenic activities in numerous cancer types. In the present study, naringenin and a Bcl-2 inhibitor, ABT-737, were used to investigate their combinative anticancer effect in the SGC7901 gastric cancer cell line. The results revealed that naringenin and ABT-737 were able to inhibit SGC7901 cell growth and colony formation, alone or in combination. Furthermore, the combination of these drugs was found to further increase the cleavage of caspase-3 and poly ADP-ribose polymerase. Naringenin and ABT-737 also decreased Akt activation and increased p53 expression, suggesting the involvement of these pathways in the inhibition of gastric cell growth.
MUC5AC Upstream Complex Repetitive Region Length Polymorphisms Are Associated with Susceptibility and Clinical Stage of Gastric Cancer
Wang, CH;Wang, JS;Liu, YQ;Guo, XL;Zhang, CQ
PLOS ONE 2014年 9卷6期 影响因子:3.057
TANDEM REPEATS POLYMORPHISM; VARIABLE NUMBER; MICROSATELLITE INSTABILITY; PROGNOSTIC INDICATORS; INSULIN GENE; LUNG-CANCER; MINISATELLITE; CELLS; RISK; EXPRESSION
MUC5AC was deemed to be involved in gastric carcinogenesis since aberrant MUC5AC expression has been repeatedly detected in patients with gastric cancer (GC). In this study, length polymorphisms in a complicated repetitive region adjacent to MUC5AC promoter were assessed in 230 patients with GC and 328 cancer-free controls. Alleles of 1.4 and 1.8 kb were significantly more prevalent in GC group than in controls. In contrast, 2.3 and 2.8 kb alleles occurred at significantly lower frequencies in patients than in controls. Alleles were then classified into susceptible (S; 1.4 and 1.8 kb), protective (P; 2.3 and 2.8 kb) and null (N; all other alleles) categories with respect to their linkage with the susceptibility to GC. Individuals with genotype SS had a 2.7-fold increased risk of GC occurrence, but PN genotype was associated with a significantly reduced risk of this cancer. Moreover, homozygous or heterozygous individuals with one or two copies of 1.4 kb allele showed an earlier age of onset and more advanced metastasis stage compared with patients without this allele (Bonferroni corrected p = 1.35 x 10(-4) and 6.60 x 10(-4) accordingly), whereas homozygous patients with two copies of 1.8 kb allele were linked to less advanced GC TNM stage. Our results suggest that certain genetic variations in MUC5AC upstream repetitive region are associated with the susceptibility and progression of GC.
Effect of lipo-prostaglandin E1 on cystatin C, beta 2-microglobulin, and estimated glomerular filtration rate in patients with decompensated heart failure and renal dysfunction: a single-center, nonrandomized controlled study
Hou, ZQ;Sun, ZX;Su, CY;Tan, H;Zhong, X;Hu, B;Zhou, Y;Shang, DY
HEART AND VESSELS 2013年 28卷5期 页码:589-595
CARDIORENAL SYNDROMES; KIDNEY INJURY; OUTCOMES; IMPACT; NEPHROPATHY; COMBINATION; PREVALENCE; THERAPY; DISEASE; ANEMIA
A nonrandomized controlled study was conducted to evaluate the effect of lipo-prostaglandin E1 (lipo-PGE1) on cystatin C (CysC), beta 2-microglobulin (B2MG), and estimated glomerular filtration rate (eGFR) in patients with decompensated heart failure (DHF) and renal dysfunction. A total of 286 enrolled patients with DHF and renal dysfunction were nonrandomly assigned a 7-day standard treatment without (n = 146) or with (n = 140) lipo-PGE1 intervention. According to the baseline eGFR, patients were further classified into mild, moderate, and severe renal dysfunction subgroups. By the end of study period, there was no evidence of an immense improvement in B2MG, CysC, and eGFR in response to standard treatment (all P > 0.05). On the contrary, a noticeable decrease of B2MG and CysC was observed in patients receiving lipo-PGE1 intervention, as well as an increase in eGFR (all P < 0.05). Moreover, lipo-PGE1 intervention led to greater changes in renal function variables from baseline than with standard management (all P < 0.05). Most important, the favorable renal protective effects of lipo-PGE1 were maintained in three subgroups. Lipo-PGE1 intervention brought a substantial renoprotective benefit to hospitalized DHF patients as compared with standard therapy, suggesting it might offer a promising therapeutic option for the management of renal dysfunction associated with DHF.
Effect of Levosimendan on Estimated Glomerular Filtration Rate in Hospitalized Patients with Decompensated Heart Failure and Renal Dysfunction
Hou, ZQ;Sun, ZX;Su, CY;Tan, H;Zhong, X;Hu, B;Zhou, Y;Shang, DY
CARDIOVASCULAR THERAPEUTICS 2013年 31卷2期 页码:108-114
DOBUTAMINE; DURATION; SURVIVE; INDEXES; TRIAL
Background Only limited data of the long-term effect of levosimendan on renal dysfunction in patients with decompensated heart failure (DHF) have been published previously. To date, there has been no similar study carried out in a Chinese population. Design and Methods A prospective, randomized, placebo-controlled, and double-blind study was performed to investigate the effect of levosimendan on estimated glomerular filtration rate (eGFR) in DHF patients with renal dysfunction during a 30-day period. Sixty-six patients with left ventricular ejection fraction (LVEF) 40% and eGFR 1589mL/min/1.73m2 were randomized in a 1:1 ratio to receive a 24-h infusion with levosimendan or placebo. The B-type natriuretic peptide (BNP) and eGFR were determined at baseline and day 1, 3, 7, 14, 30 after the start of treatment. Results The eGFR levels were obviously enhanced following levosimendan, peaked at 3days, sustained for at least 14days, and returned to baseline by day 30 after starting infusion. In contrast, placebo did not induce any significant changes in eGFR levels during the follow-up. In addition, levosimendan resulted in a distinct decrease in BNP levels in comparison with placebo, and the beneficial effect returned to baseline by day 14 and remained so at day 30 postinfusion. Conclusions A 24-h infusion with levosimendan transiently improved the renal dysfunction compared with placebo in patients with DHF, and its beneficial effects persisted for at least 14days after the initiation of treatment.
Association of serum omentin-1 levels with coronary artery disease
Zhong, X;Zhang, HY;Tan, H;Zhou, Y;Liu, FL;Chen, FQ;Shang, DY
ACTA PHARMACOLOGICA SINICA 2011年 32卷7期 页码:873-878
INSULIN-RESISTANCE; GENE-EXPRESSION; DIABETES-MELLITUS; 3T3-L1 ADIPOCYTES; ADIPOSE-TISSUE; ADIPONECTIN; INFLAMMATION; INTERLEUKIN-6; VISFATIN; ATHEROSCLEROSIS
Aim: Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD.;-;Methods: One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated.;-;Results: Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08 +/- 61.43 ng/mL; SAP, 155.41 +/- 66.89 ng/mL; control, 254.00 +/- 72.9 ng/mL; P < 0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P < 0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=-0.17, P < 0.05) and serum IL-6 concentration (r=-0.19, P < 0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD.;-;Conclusion: The findings suggest that serum concentrations of omentin-1 are related to CAD.
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