Honokiol Provides Cardioprotection from Myocardial Ischemia/Reperfusion Injury (MI/RI) by Inhibiting Mitochondrial Apoptosis via the PI3K/AKT Signaling Pathway.

Background: Myocardial injury refers to a major complication that occurs in myocardial ischemia/reperfusion injury (MI/RI). Honokiol is a well-recognized active compound extracted from the traditional Chinese herb known as Magnolia officinalis and is utilized in treating different vascular diseases. This research is aimed at examining whether Honokiol might alleviate myocardial injury in an MI/RI model. Methods: Seventy-eight male C57BL/6 mice were categorized randomly into three cohorts including the Sham operation (Sham) cohort, the MI/RI cohort (Con), and the Honokiol cohort (n = 26 for each cohort). The mice in the Honokiol cohort were treated with Honokiol before MI/RI surgery (0.2 mg/kg/day for 14 days, intraperitoneal), while the mice in the Con cohort were given an intraperitoneal injection with an equivalent volume of vehicle (DMSO) daily in 14 days prior to exposure to MI/RI. After the surgery, creatine kinase- (CK-) MB and cardiac troponin T (cTnT) levels, as well as the infarct area, were measured to assess the degree of myocardial damage. Apoptotic levels were detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Electron microscopy was utilized to identify mitochondrial damage. Lastly, the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cleaved caspase-9, cytochrome C (Cyt-C), B cell lymphoma/leukemia-2 (Bcl-2), B cell lymphoma/leukemia-2 associated X (Bax), AKT, p-AKT, PI3K, and p-PI3K were analyzed utilizing western blotting. Results: Honokiol can reduce the MI/RI-induced cTnT and CK-MB levels, apoptosis index, and mitochondrial swelling in cardiomyocytes via activating the PI3K/AKT signaling pathway. Conclusion: Honokiol provides cardiac protection from MI/RI by suppressing mitochondrial apoptosis through the PI3K/AKT signaling pathway.

Preoperative Liver Function Test Abnormalities Were Associated With Short-Term and Long-Term Prognosis in Cardiac Surgery Patients Without Liver Disease.

Aims: To explore the value of preoperative liver function tests (LFTs) for the prognosis of cardiac surgery patients without liver disease. Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to extract the clinical data. Adult cardiac patients (≥18 years) without liver disease in the database were enrolled. The association of LFTs with the time of hospital stay and ICU stay was analyzed with the Spearman correlation. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariable logistic regression was used to identify LFTs that were independent prognostic factors of mortality. Results: A total of 2,565 patients were enrolled in this study. Albumin (ALB) was negatively associated with the time of hospital stay and ICU stay, while alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin were positively associated with the time of hospital stay and ICU stay (all p < 0.001). Abnormal ALB, ALT, AST, and total bilirubin were associated with lower 90-day and 4-year survival (all p < 0.001) and could be used as independent risk factors for hospital mortality and 90-day mortality. However, only ALB and total bilirubin were independent risk factors for 4-year mortality. Conclusion: Preoperative LFT abnormalities were associated with short-term and long-term prognosis of cardiac surgery patients without liver disease.

Association of Post-operative Systolic Blood Pressure Variability With Mortality After Coronary Artery Bypass Grafting.

Background: Blood pressure variability (BPV) has long been considered a risk factor for cardiovascular events. We aimed to investigate whether post-operative systolic BPV was associated with early and late all-cause mortality in patients undergoing coronary artery bypass grafting (CABG). Methods: Clinical variables and blood pressure records within the first 24 h in the post-operative intensive care unit stay from 4,509 patients operated on between 2001 and 2012 were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. BPV was measured as the coefficient of the variability of systolic blood pressure, and we compared patients in the highest quartile with patients in the other three quartiles. Results: After full adjustment, patients in the highest quartile of BPV were at a higher risk of intensive care unit mortality (OR = 2.02, 95% CI: 1.11-3.69), 30-day mortality (OR = 1.92, 95% CI: 1.22-3.02), and 90-day mortality (HR = 1.64, 95% CI: 1.19-2.27). For 2,892 patients with a 4-year follow-up, the association between a higher post-operative BPV and the risk of 4-year mortality was not significant (HR = 1.17, 95% CI: 0.96-1.42). The results were supported by the comparison of survival curves and remained generally consistent in the subgroup analyses and sensitivity analyses. Conclusions: Our findings demonstrated that in patients undergoing CABG, a higher post-operative BPV was associated with a higher risk of early mortality while the association was not significant for late mortality. Post-operative BPV can support doctors in identifying patients with potential hemodynamic instability and making timely clinical decisions.

Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? - A Case-Control Study.

INTRODUCTION: Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. METHODS: Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases' autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson's trichrome staining. RESULTS: SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group (P=0.023). SNX10 expression was negatively associated with the degree of fibrosis (P=0.017, Spearman rho=-0.447), the New York Heart Association degree (P=0.003, Spearman rho=-0.545), left atrial diameter (P=0.038, Spearman rho=-0.393), right atrial diameter (P=0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery (P=0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. CONCLUSION: Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

Does decreased snx10 serve as a novel risk factor in atrial fibrillation of the valvular heart disease? - a case-control study

Abstract Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. Methods: Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases' autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson's trichrome staining. Results: SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group (P=0.023). SNX10 expression was negatively associated with the degree of fibrosis (P=0.017, Spearman rho=-0.447), the New York Heart Association degree (P=0.003, Spearman rho=-0.545), left atrial diameter (P=0.038, Spearman rho=-0.393), right atrial diameter (P=0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery (P=0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. Conclusion: Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

Respiratory nursing care with Angong Niuhuang pill for patients with chronic obstructive pulmonary disease following cardiac surgery.

AIM: Angong Niuhuang pill (ANP) is a traditional Chinese medicine (TCM) drug widely used for treating stroke. This study aimed to investigate the effect of ANP on respiratory nursing outcomes in chronic obstructive pulmonary disease (COPD) patients following cardiac surgery. METHODS: A total of 80 COPD patients following cardiac surgery were enrolled and randomized into the control group receiving routine postoperative nursing and ANP group additionally receiving ANP treatment for 3 days (n = 40 for both group). The frequency of back percussion, time of back percussion, amount of expectoration, arterial blood gas levels were compared between groups. RESULTS: Compared to the control group, the ANP group had a significantly shorter daily mean time of back percussion at day 3 (p = .036) and day 7 (p = .014). The daily mean amount of expectoration was higher at day3 (p = .018) but lower at day 7 (p = .043) in the ANP group than in the control group. In addition, the ANP group had significantly higher hemoglobin saturation (SpO2 ) and partial pressure of oxygen (PaO2 ) but lower partial pressure of carbon dioxide (PaCO2 ) at both day 3 and day 7 than the control group (all p < .05). Furthermore, the time of postoperative aerosol inhalations (p = .041), pulmonary infection rate (p = .025) and postoperative hospital stay (p = .036) were significantly reduced in the ANP group. The ANP group had significantly lower TCM symptom scores at day 3 and day 7 after surgery. CONCLUSION: These results suggested that ANP treatment can effectively promote the postoperative recovery and respiratory nursing outcomes in COPD patients following cardiac surgery.

M2b macrophages protect against myocardial remodeling after ischemia/reperfusion injury by regulating kinase activation of platelet-derived growth factor receptor of cardiac fibroblast.

BACKGROUND: Myocardial injury is a major cause of myocardial remodeling. Macrophages are important in cardiac repair as a result of their interactions with fibroblasts. As regulatory macrophages, M2b macrophages modulate inflammatory immune responses without participating in wound healing and could have enhanced protective effects on myocardial remodeling. Therefore, we tested the hypothesis that M2b macrophages could improve cardiac function and ameliorate myocardial fibrosis after the myocardial ischemia/reperfusion injury (MI/RI). METHODS: In vivo, MI/RI models were established with Sprague-Dawley (SD) rats and either M2b macrophages (MT group) or the same volume of vehicle (CK group) was injected into the ischemic zone. Two weeks after the operation, cardiac function and diameters were determined by echocardiography examination. Level of myocardial fibrosis was measured by Sirius red staining and the expression of fibrosis-related factors. In vitro, cardiac fibroblasts (CFs) were co-cultured with M2b macrophages or cultured with M2b macrophage supernatant. Expression of α-smooth muscle actin (α-SMA) and connective tissue growth factor (CCN2/CTGF) in the CFs were measured by western blotting and immunofluorescence staining. In addition, the expression of platelet-derived growth factors (PDGFs), the expression of platelet-derived growth factor receptors (PDGFRs) and the phosphorylation of PDGFRs was detected by western blotting. RESULTS: A significantly higher rat survival rate, improved left ventricular (LV) systolic function, decreased diameter of the LV and alleviated myocardial fibrosis were observed in the MT group than in the CK group. In vitro, the activation of CFs was significantly reduced by the M2b macrophages treatments, relative to the blank control. In addition, the kinase activation of PDGFRs was decreased by M2b macrophage treatments both in vivo and in vitro. CONCLUSIONS: Our study demonstrated that the administration of M2b macrophages could attenuate myocardial remodeling after MI/RI. The regulation of the activation of PDGFRs in CFs is an important part of the protective mechanism.

M2b Macrophages Regulate Cardiac Fibroblast Activation and Alleviate Cardiac Fibrosis After Reperfusion Injury.

BACKGROUND: Macrophages play an important role in the development of cardiac fibrosis. However, the roles of different macrophage subtypes in cardiac fibroblast (CF) activation and cardiac fibrosis are unknown.Methods and Results:Bone marrow-derived macrophages (BMDMs) were treated with different stimuli to induce differentiation into M1, M2a, M2b, and M2c macrophage subtypes. CFs were co-cultured with different subtypes of macrophages or cultured with macrophage supernatants. Results revealed that M2b macrophages significantly suppressed the proliferation and migration of CFs, the expression of fibrosis-related proteins (collagen I [COL-1] and α-smooth muscle actin [α-SMA]), and differentiation into cardiac myofibroblasts (MFs). The opposite effects were observed with M2a macrophages. A rat model of cardiac ischemia/reperfusion (I/R) injury was used to determine the effect of M2b macrophages transplantation. After cardiac I/R injury, transplantation of M2b macrophages improved cardiac function and reduced cardiac fibrosis. The effect of macrophage subtypes on p-ERK, ERK, p-p38, and p38 phosphorylation was examined by Western blotting. The results showed that M2b macrophages significantly inhibited the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: These study results demonstrate for the first time that different subtypes of macrophages have different roles in regulating CF activation. M2b macrophages inhibit CF activation, and thus can be considered anti-fibrotic macrophages. M2a macrophages promote CF activation, and thus are pro-fibrotic macrophages.

Dact1 involvement in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation by regulating cx43

Abstract Objective: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). Methods: The DACT1 expression and its associations with the degree of fibrosis and β-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson's staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of β-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. Results: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and β-catenin expression in clinical samples (P=0.028, Spearman's rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in β-catenin and subsequent partial colocalization of DACT1 and β-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman's rho=0.370) and changed the Cx43 distribution in cardiac cell lines. Conclusion: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF.

DACT1 Involvement in the Cytoskeletal Arrangement of Cardiomyocytes in Atrial Fibrillation by Regulating Cx43.

OBJECTIVE: To determine the role of the dishevelled binding antagonist of beta catenin 1 (DACT1) in the cytoskeletal arrangement of cardiomyocytes in atrial fibrillation (AF). METHODS: The DACT1 expression and its associations with the degree of fibrosis and ß-catenin in valvular disease patients were analyzed by immunohistochemistry and Masson's staining. DACT1 was overexpressed in the atrial myocyte cell line (HL-1) and the cardiac cell line (H9C2) by adenoviral vectors. Alterations in the fibrous actin (F-actin) content and organization and the expression of ß-catenin were detected by flow cytometry, immunofluorescence, and Western blotting. Additionally, the association of DACT1 with gap junctions connexin 43 (Cx43) was detected by immunohistochemistry, immunofluorescence, and Western blotting. RESULTS: Decreased cytoplasmic DACT1 expression in the myocardium was associated with AF (P=0.037) and a high degree of fibrosis (weak vs. strong, P=0.028; weak vs. very strong, P=0.029). A positive association was observed between DACT1 and ß-catenin expression in clinical samples (P=0.028, Spearman's rho=0.408). Furthermore, overexpression of DACT1 in HL-1 and H9C2 cells induced an increase in ß-catenin and subsequent partial colocalization of DACT1 and ß-catenin. In addition, F-actin content and organization were enhanced. Interestingly, DACT1 was positively correlated with the Cx43 expression in clinical samples (P=0.048, Spearman's rho=0.370) and changed the Cx43 distribution in cardiac cell lines. CONCLUSION: DACT1 proved to be a novel AF-related gene by regulating Cx43 via cytoskeletal organization induced by ß-catenin accumulation in cardiomyocytes. DACT1 could thus serve as a potential therapeutic marker for AF.

The application of nursing-sensitive quality indicators in evaluating nursing efficacy.

OBJECTIVE: To investigate the application of nursing-sensitive quality indicators in evaluating nursing efficacy. MATERIALS AND METHODS: The study involved the 97 nursing units of four general hospitals, where quality-improvement projects were implemented. The efficacy of the projects was measured through the use of nursing-sensitive quality indicators followed by a Plan-Do-Study-Act cycle. Nursing efficacy was observed before and after the implementation. RESULTS: Indicators revealed that patient satisfaction with basic nursing care, professional skills, and service attitude increased significantly after implementation of the quality-improvement projects (p<0.05). The incidence of nursing adverse events, including deficient care and accidents, also decreased significantly (p<0.01). However, patient satisfaction with the medical environment did not increase. CONCLUSIONS: Nursing-sensitive quality indicators are a valid and reliable way to determine if nursing quality-improvement projects are efficacious. They also promote continual improvement in nursing quality and provide a scientific evidence for setting implementation plan and detecting the implementation efficacy in nursing care, and possess certain promoting effects on the continual improvement of nursing quality.

Luteolin prevents LPS-induced TNF-α expression in cardiac myocytes through inhibiting NF-κB signaling pathway.

Luteolin, a plant flavonoid, has been shown to suppress inflammatory responses; however, the mechanism of luteolin on cardiac myocyte inflammation is still unknown. Because tumor necrosis factor-α (TNF-α), an inflammatory cytokine, is elevated in the failing heart and exerts multiple potentially harmful effects on cardiac myocytes, we therefore sought to examine the effects of luteolin on the expression of TNF-α in neonatal rat cardiac myocytes. In the present study, enzyme-linked immunosorbent assay (ELISA), real-time PCR, immunoblot, immunochemistry staining, and electrophoretic mobility shift assays (EMSA) were performed. ELISA assay showed that luteolin decreased lipopolysaccharide (LPS)-induced production of TNF-α in the medium. Real-time PCR assay confirmed that luteolin also inhibited LPS-induced increase in TNF-α mRNA in myocytes. Furthermore, immunoblot and immunochemistry staining assays represented that luteolin blocked LPS-induced IκB-ß degradation and NF-κB p65 subunit nuclear translocation. In addition, EMSA demonstrated that luteolin reduced LPS-induced NF-κB DNA binding activity. Luteolin protects against LPS-induced TNF-α expression via inhibition of the NF-κB signaling pathway, suggesting that luteolin may be a potential therapeutic agent for the treatment of inflammation-related myocardial diseases.