Search

De-Gang Mo,1 Lin Wang,2 Qian-Feng Han,1 Kang Yu,3 Jia-Hui Liu,1 Heng-Chen Yao1 1Department of Cardiology, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of China; 2Cardiologic Color Doppler Room, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of China; 3Department of Laboratory Medicine, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, People’s Republic of ChinaCorrespondence : Heng-Chen YaoDepartment of Cardiology, Liaocheng People’s Hospital Affiliated to Shandong First Medical University, Liaocheng, 252000, People’s Republic of China, Email yaohc66@126.comPurpose: Acute coronary syndrome (ACS) has a high incidence and mortality rate worldwide, which has a considerable negative impact on the global economy. This study aimed to identify a group of ACS patients at a high risk of recurrent adverse cardiac events using the plasma NLRP3 inflammasome.Patients and methods: ACS patients admitted to Liaocheng People’s Hospital between June 2021 and March 2022 were enrolled in this study. Patients were divided into low (levels < 3.84 ng/mL) and high (levels ≥ 3.84 ng/mL) groups based on the median NLRP3 inflammasome levels. The patients were divided into three groups according to the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P): low (scores ≤ 2 points), intermediate (scores = 3 points), and high (score ≥ 4 points) risk. We investigated the relationship between NLRP3 inflammasome and laboratory indicators. Additionally, we examined whether the NLRP3 inflammasome was an independent predictor of high TRS-2P and explored the applicability of the plasma NLRP3 inflammasome for predicting high TRS-2P.Results: Logistic regression analysis revealed that NLRP3 inflammasome was an independent predictor of high TRS-2P (odds ratio [OR]:2.013; 95% confidence interval [CI]: 1.174– 3.452). The area under the receiver operating characteristic curve value of the NLRP3 inflammasome was 0.674 (95% CI: 0.611– 0.737; P < 0.001).Conclusion: NLRP3 inflammasome levels are an independent predictive factor for high TRS-2P levels, which indicates that the NLRP3 inflammasome may help predict the prognosis of ACS patients.Keywords: NLRP3 inflammasome, biomarker, risk stratification, acute coronary syndrome, thrombolysis in myocardial infarction risk score for secondary prevention, TRS-2P

Aims. The prognostic value of plasma D-dimer in patients with coronary artery disease (CAD) remains controversial. The study is aimed at investigating the relationship between plasma D-dimer levels and in-hospital heart failure (HF) in ST-segment elevation myocardial infarction (STEMI) patients who underwent primary percutaneous coronary intervention (pPCI). Methods. STEMI patients who underwent pPCI were enrolled in this study. Venous blood samples were collected from patients on admission before pPCI procedure. The study endpoint was the occurrence of in-hospital HF. The participants were divided into two groups according to plasma D-dimer levels and further compared baseline D-dimer levels between male and female. Logistic regression and receiver operating characteristic (ROC) curves were performed to evaluate the relationship of D-dimer and in-hospital HF. Results. A total of 778 patients were recruited in the study, of which 539 (69.3%) patients had normal D-dimer levels (≤0.5 mg/L) while 239 (30.7%) had increased D-dimer levels (>0.5 mg/L). The female patients have higher D-dimer levels and higher incident rate of in-hospital HF than that in male patients ( p < 0.001 ). The multivariate logistic regression model revealed that D-dimer was an independent predictor for in-hospital HF in overall population (adjusted odds ratio [OR]: 1.197, 95% CI: 1.003-1.429, and p = 0.046 ) and female patients (adjusted OR: 1.429, 95% CI: 1.083-1.885, and p = 0.012 ). Conclusion. Increased plasma D-dimer levels were an independent risk factor for incidence of in-hospital HF in STEMI patients who underwent pPCI, especially in female patients, which provides guidance for clinicians in identifying patients at high risk of developing HF and lowering their risk.

Multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy, and the main cause of MDR has been attributed to overexpression of P-glycoprotein (P-gp). In this present study, four P-gp modulators (E,E)-4,6-bis(styryl)-2-(substituted amino)-pyrimidines were evaluated for their activity in a breast cancer cell line overexpressing P-gp (LCC6MDR). The four modulators displayed significantly better P-gp modulating activity compared with the positive control verapamil (RF = 5.4), with a relative fold (RF) increase in activity ranging from 33.3 to 86.0. In contrast to compounds a and c that exhibited lower cytotoxicity, compounds b and d were nontoxic towards both cancer cells and normal cells, with IC50 values greater than 100 μmol/L. The qRT-PCR results demonstrated that after exposure to 2 μmol/L of compounds a, b, c, and d, the mRNA expression level of MDR1 in LCC6MDR cells decreased to 45%, 50%, 38%, and 51%, respectively. However, the Western-blot results indicated that compound c could reverse P-gp mediated MDR, but not via decreases in protein expression. DOX and Rh123 accumulation and efflux results further confirmed that the reversal of MDR activity happens via inhibition of P-gp efflux and increases in intracellular drug accumulation. These results demonstrated that compound c has low toxicity and is an efficient P-gp modulator, highlighting its potential as a promising candidate for P-gp-mediated reversal of MDR.

Aim: This study aimed to explore leukocyte telomere length (LTL) in the prediction of the severity of coronary artery disease (CAD). Materials & methods: A total of 359 CAD patients who underwent coronary angiography were enrolled in this study. Severity of coronary artery was assessed by Gensini score (GS). Results: LTL is negatively correlated with GS (Spearman's rank correlation coefficient = -0.335; p

Aims. MicroRNAs (miRNAs) are associated with the pathogenesis of coronary artery disease (CAD). The objective of this study is to explore plasma levels of miR-208b and miR-499 in CAD and analyze its association with the severity of CAD. Materials and Methods. 195 consecutive CAD patients who underwent coronary angiography were enrolled in this study. Severity of coronary lesions was evaluated by the synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX) score (SS). Plasma levels of miR-208b and miR-499 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-208b and miR-499 and SS was analyzed. Results. The qRT-PCR results showed that plasma levels of miR-208b and miR-499 in SS>32 (high SS) group was higher than those in low (SS≤22) and intermediate (22

The study aimed to determine whether high sensitivity C-reactive protein to prealbumin (hs-CRP/PAB) ratio could be used to predict in-hospital major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). A total of 659 patients with ACS were included in the study. Patients were divided into two groups: high hs-CRP/PAB ratio group (hs-CRP/PAB ≥0.010) and low hs-CRP/PAB ratio group (hs-CRP/PAB P P = 0.001). Moreover, the area under the curve value of hs-CRP/PAB ratio for predicting MACE was higher than hs-CRP and equal to PAB. High hs-CRP/PAB ratio was considered as a prognostic parameter of MACE in ACS patients, with the predictive power equal to PAB but greater than hs-CRP.

Background: Coronary artery disease(CAD) is a worldwide disease with high morbidity and mortality. There are many risk factors to predict the prognosis of CAD. We aimed to demonstrate the difference of leukocyte telomere length (LTL) between different types of CAD and illustrate the predictive value of LTL on the prognosis in patients with CAD. Methods: 366 patients hospitalized for coronary angiography were divided into three groups according to the CAD criteria and clinical manifestation: 98 stable angina pectoris (SAP), 144 unstable angina pectoris (UAP) and 124 acute myocardial infarction (AMI). Patients with a normal coronary artery diagnosed by coronary computed tomography angiography were chosen as the normal control (NC) group. LTL was measured using quantitative real-time polymerase chain reaction (qRT-PCR). All patients were followed-up for 6 months to analysis major adverse cardiac events (MACEs). Findings: CAD patients had significantly shortened LTL comparing with NC group (p < 0.05). LTL in AMI patients were significantly shorter compared with the SAP and UAP group (p < 0.05). Area under the curve values of LTL for predicting MACEs was 0.769 (p < 0.001). Cox proportional hazards regression analysis revealed shorter LTL was an independent predictor of MACEs. Kaplan-Meier analysis suggested that a trend toward poorer event free survival rate was observed in shorter LTL group (p < 0.001). Interpretations: LTL was independently correlated with short-term MACEs and can be used for risk stratification of CAD patients. Funding Statement: Supported by Traditional Chinese Medicine Science and Technology Development Plan Project of Shandong Province (No. 2019-0891). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study was approved by the Medical Ethics Committee of Liaocheng People's Hospital. All procedures were in accordance with principles of Helsinki Declaration. Informed consent was obtained from all subjects.

Aim: This study aimed to investigate the correlation between the expression of circulating miR-208b and miR-499 and acute coronary syndrome (ACS) patients. Materials & methods: A total of 160 consecutive patients with ACS and 48 healthy control subjects were enrolled for primary analysis. The ACS patients (n = 160) were followed up for 6 months for further analysis regarding major adverse cardiac events. Results: Area under the curve values of miR-208b and miR-499 for predicting ACS were 0.910 and 0.851 (p < 0.001, respectively). Cox proportional hazards regression analysis revealed that miR-208b but not miR-499 was an independent predictor of major adverse cardiac events. Conclusion: Circulating miR-208b and miR-499 could be considered as diagnostic or prognostic biomarkers for patients with ACS.

The purpose of the present study was to investigate the anti-inflammatory effect of hepatocyte growth factor (HGF) on pulmonary artery hypertension (PAH) in a rat model and underlying mechanisms. Wistar rats were treated with monocrotaline intravenously to induce PAH and then treated with vehicle or HGF for 2 weeks, respectively. The mean pulmonary artery pressure (mPAP), the index of right heart ventricular hypertrophy (RHVI), pathological changes, and inflammation in the lungs of individual rats were measured. The levels of serum inflammatory interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and high mobility group protein B1 (HMGB1) and the relative levels of IκBα and NF-κB p65 expression in the lungs of individual rats were determined by methods of enzyme-linked immunosorbent assay (ELISA) and Western blot. The levels of mPAP and RVHI in the HGF group were significantly lower than that in the PAH group (P

Aim: The present study aimed to examine the correlation between high-sensitivity CRP to albumin ratio (CAR) and in-hospital and short-term major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). Materials & methods: We analyzed 652 consecutive patients who had been hospitalized for ACS. The MACEs were defined as cardiogenic shock, reinfarction, acute heart failure and all-cause death. Results: The incidence rate of MACEs was significantly higher in the high CAR (≥0.114) group than in the low CAR (

Exogenous high mobility group box 1 (HMGB1) may exert beneficial effect on myocardial ischemia reperfusion (I/R) injury. It was previously proven that myocardial expression of vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) are related to the cardioprotective effects of basic fibroblast growth factor. So, we hypothesized that intravenous HMGB1 may protect myocardium from I/R injury via increases the myocardial expression of VEGF through the activation of PI3K/Akt pathway. Thus, the purpose of the present study was to investigate the effects of intravenous HMGB1 on the myocardial expression of VEGF, myocardial fibrosis and cardiac function in rats following acute myocardial ischemia. Myocardial ischemia was induced by temporary (30 min) ligation of the left anterior descending coronary artery in sham or HMGB1 treated rats, followed by a 3-h reperfusion. Myocardial MDA content, Infarct size and myocardial CVF decreased while the SOD activity, expression of VEGF and p-Akt protein were significantly increased in HMGB1 treated group than in the I/R group (all P

The effects of intravenous high mobility group box 1 (HMGB1) on myocardial ischemia/reperfusion (I/R) injury remains to be elucidated. The purpose of the present study was to investigate the effects of intravenous HMGB1 on the expression of hypoxia inducible factor-1α (HIF-1α) in the myocardium of rats following acute myocardial ischemia, and to examine the effects of intravenous HMGB1 on myocardial I/R injury. Male Wistar rats were divided into the following groups: Sham operation group (n=10), a group exposed to ischemia for 30 min and reperfusion for 4 h (I/R group) as a control (n=10), an HMGB group, in which 100 ng/kg HMGB was administered intravenously 30 min prior to ischemia (n=10), an LY group, in which LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), was administered intravenously (0.3 mg/kg) 40 min prior to ischemia (n=10), and the HMGB1+LY group, in which HMGB1 (100 ng/kg) and LY294002 (0.3 mg/kg) were administered intravenously 30 min and 40 min prior to ischemia, respectively (n=10). The serum levels of cardiac troponin I (cTnI) and tumor necrosis factor-α (TNF-α), and myocardial infarct size were measured. The expression levels of phosphorylated Akt and HIF-1α were investigated using western blot analyses. The results showed that pre-treatment with HMGB1 significantly decreased serum levels of cTnI, and TNF-α, and reduced myocardial infarct size following 4 h reperfusion (all P

The aim of this study is to evaluate if low prealbumin levels on admission predict subsequent adverse cardiac events in patients hospitalized with acute coronary syndrome (ACS). We designed a cohort study and enrolled 610 consecutive patients with ACS from whom venous blood for serum prealbumin measurement was drawn immediately upon hospital admission. Patients were classified in two groups according to prealbumin level: “normal” prealbumin levels (≥17 mg/dL, n=413) and “low” prealbumin (

The aim of the present study was to investigate whether postconditioning with simvastatin attenuated myocardial ischemia reperfusion injury by inhibiting the expression of high mobility group box 1 (HMGB1) in rat myocardium following acute myocardial ischemia. In total, 30 male Sprague-Dawley rats were divided into sham operation (sham; n=10), acute myocardial infarction (AMI; n=10) and simvastatin (sim; n=10) groups. The AMI and sim groups were subjected to ischemia for 30 min, followed by reperfusion for 180 min. The rats in the sim group were administered 20 mg/kg simvastatin intravenously 5 min prior to reperfusion. Subsequently, the infarct size, serum cardiac troponin (c-TnI), tumor necrosis factor (TNF)-α and myocardial malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Western blot analysis was used to detect the protein expression of HMGB1. Postconditioning with simvastatin was shown to decrease the infarct size and HMGB1 expression levels in the myocardium following AMI (P

To investigate the effect of basic fibroblast growth factor (bFGF) on myocardial expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) following acute myocardial infarction (AMI) in rats.Eighty male Sprague-Dawley rats were divided into sham operation (n=20), AMI control (n=20), bFGF50 (intravenous bFGF 50 μg/kg/d, n=20) and bFGF200 (intravenous bFGF 200 μg/kg/d, n=20) groups. The left ventricular ejection fraction (LVEF) was measured by echocardiography. The expression of HIF-1α mRNA and VEGF mRNA in the ischaemic tissues was analysed by reverse transcription-polymerase chain reaction.The LVEF in the bFGF50 and bFGF200 group was higher than in the AMI control group (p0.05) seven and 14 days after the treatment. There was no difference in HIF-1α mRNA expression between the bFGF50 and AMI control group (p0.05). However, the HIF-1α mRNA expression in the bFGF200 group was higher than in the AMI control group seven days (1.13 ± 0.18 vs 0.90 ± 0.14, p0.01) and 14 days (1.31 ± 0.18 vs 0.93 ± 0.09, p0.01) after the treatment. The VEGF mRNA expression in the bFGF200 group was also higher than in the AMI control group seven days (1.10 ± 0.17 vs 0.86 ± 0.14, p0.01) and 14 days after the AMI (1.28 ± 0.19 vs 0.89 ± 0.14, p0.01).bFGF therapy was associated with an improvement in left ventricular function and an increase in myocardial expression of HIF-1α mRNA and VEGF mRNA following AMI. bFGF may exert its cardioprotective effect through upregulating HIF-1α mRNA and VEGF mRNA in the ischaemic myocardium.

Insulin-like growth factor 1 (IGF-1) is a molecule with strong proliferative effects, and statins have been reported to exhibit antitumor effects based on clinical and experimental studies. However, their effects on cardiac myxoma (CM) cells and the underlying signaling mechanism(s) are largely unknown. Therefore, we investigated whether the protein/lipid phosphatases and tensin homolog deleted on chromosome ten (PTEN) and pleckstrin homology domain leucine-rich repeat phosphatase 1 and 2 (PHLPP1 and 2) are involved in the proliferative effect of IGF-1 on CM cells and the pharmacological impact of atorvastatin. The activity of PTEN and PHLPPs was determined using specific substrate diC16PIP3 and pNPP. We found that IGF-1 enhanced CM cell proliferation and inhibited both PTEN and PHLPP2 activity in a concentration- and time-dependent manner. Atorvastatin acted counter to IGF-1 and reversed the above effects mediated by IGF-1. Both IGF-1 and atorvastatin did not affect the activity of PHLPP1 and the protein expression of the three phosphatases. The results suggest that IGF-1 may exert its proliferative effects by negatively regulating the PTEN/PHLPP2 signaling pathway in CM cells, and atorvastatin may be a potential drug for the treatment of CM by enhancing the activity of PTEN and PHLPP2.

The aim of this study was to evaluate the prognostic values of serum tenascin-C in patients with heart failure and ischaemic heart disease.Serum tenascin-C levels were assessed in 83 patients with heart failure and in 30 healthy subjects. The correlations between serum tenascin-C levels and left ventricular ejection fraction, serum B-type natriuretic peptide and procollagen III were analysed. Patients were followed up for 12 months, and the relations between the serum levels of tenascin-C and cardiac events (re-hospitalisation for worsening heart failure and mortality) were analysed.Serum tenascin-C levels in patients with heart failure were higher than in healthy volunteers (72.24 ± 11.02 vs. 22.78 ± 2.51 μg/L, p0.01). Serum tenascin-C levels in patients of NYHA class IV were higher than in patients with NYHA class II (88.56 ± 3.73 vs. 64.88 ± 3.15 μg/L, p0.01). The levels of tenascin-C were negatively correlated with the left ventricular ejection fraction (r=-0.636, p0.01), but were positively correlated with serum B-type natriuretic peptide (r=0.553, p0.01) or procollagen III levels (r=0.665, p0.01). An increased level of tenascin-C was an independent predictor for combined re-hospitalisation and mortality (OR 1.22, 95% CI: 0.86-2.14).Serum tenascin-C levels were elevated in patients with heart failure. The levels of tenascin-C were associated with the severity of left ventricular dysfunction and 12-month major adverse cardiac events.

The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were subsequently measured. Myocardial levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were also determined. Myocardial infarction size (IS) was determined by 2,3,5-triphenyltetrazolium chloride staining. Myocardial expression of hypoxia inducible factor (HIF)-1α and phosphorylated p38 mitogen-activated protein kinase (P-p38 MAPK) protein was measured using western blotting. The results demonstrated that HMGB1 significantly decreased serum levels of cTnI, IL-6 and TNF-α and myocardial IS in I/R rats compared with the sham group (all P

Our objective was to investigate the effect of interleukin-2 (IL-2) on the cytotoxic activity of natural killer (NK) cells in patients with chronic heart failure (CHF). Natural killer cells were isolated from 48 patients with CHF and 30 healthy subjects. The cytotoxic activities of the NK cells were assessed with the thiazolyl blue tetrazolium bromide (MTT) approach. Interleukin-2 (20 ng/ml) was added to the cell culture to stimulate the cytotoxicity of the NK cells. The cell number in the New York Heart Association (NYHA) class II, III, and IV was 27.9 +/- 2.5, 21.2 +/- 2.7, and 16.8 +/- 2.6 cells/microl, respectively, which was significantly lower than in the control group (31.2 +/- 3.6 cells/microl, all P0.01). The cytotoxic activities in NYHA II, III, and IV groups were 28.6% +/- 3.2%, 16.0% +/- 2.2%, and 12.1% +/- 2.9%, respectively, which was lower than in the control group (41.0% +/- 4.0%, all P0.01). Univariate analysis showed a close correlation between the NK cell cytotoxicity and the left ventricular ejection fraction (r = 0.949, P0.001). After in vitro treatment with IL-2, there was a significant increase in the cytotoxic activity of the NK cells in the control and the three heart failure groups (all P0.01). There is a significant reduction in the number and the cytotoxic activity of circulating NK cells in patients with CHF. The degree of NK cell deficiency is closely related to the severity of left ventricular dysfunction. In vitro treatment with IL-2 improves the cytotoxic activity of NK cell from the CHF patients.

a Department of Cardiology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Shandong Province, Liaocheng 252000, PR China b Department of Echocardiography, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Shandong Province, Liaocheng 252000, PR China c Department of Andrology, Liaocheng People's Hospital and Clinical School of Taishan Medical University, Liaocheng 252000, PR China

[1] Ribeiro AL, Nunes MP, Teixeira MM, Rocha MO. Diagnosis and management of Chagas disease and cardiomyopathy. Nat Rev Cardiol Oct 2012;9(10):576–89. [2] Piepoli MF, Conraads V, Corra U, et al. Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation. Eur J Heart Fail Apr 2011;13(4):347–57. [3] Sousa L, Botoni FA, Britto RR, et al. Six-minute walk test in Chagas cardiomyopathy. Int J Cardiol Mar 28 2008;125(1):139–41. [4] Neder JA, Andreone S, Leratio MC, et al. Reference values for lung function test. II. Maximal respiratory pressures and voluntary ventilation. Braz J Biol Res 1999;32(6):719–27. [5] ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 2002;166(4):518–624. [6] Oca M, Torres SH, Loyo JG, et al. Exercise performance and skeletal muscles in patients with advanced Chagas disease. Chest 2004;125(4):1306–14. [7] ChuaTP, Anker SD, HarringtonD, et al. Inspiratorymuscle strength is a determinant of maximum oxygen consumption in chronic heart failure. Br Heart J 1995;74:381–5. [8] Lima MM, Rocha MO, Nunes MC, et al. A randomized trial of the effects of exercise training in Chagas cardiomyopathy. Eur J Heart Fail Aug 2010;12(8):866–73. [9] Dall'Ago P, Chiappa GR, Guths H, Stein R, Ribeiro JP. Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J Am Coll Cardiol Feb 21 2006;47(4):757–63. [10] Lima MM, Nunes MC, Rocha MO, et al. Left ventricular diastolic function and exercise capacity in patients with Chagas cardiomyopathy. Echocardiography May 2010;27(5):519–24.

The aim of this study was to evaluate the correlation between levels of serum high-mobility group box-1 (HMGB1) and high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin I in patients with coronary artery disease. The levels of serum HMGB1, hs-CRP and cardiac troponin I were measured in 98 patients with coronary artery disease and in 30 healthy subjects. The correlation between serum HMGB1 levels and hs-CRP and cardiac troponin I levels was analyzed. Serum HMGB1 levels in patients with coronary artery disease were higher compared with those in healthy volunteers (63.5±15.29 vs. 21.98±4.33 μg/l; P