Xinfuli Granule improves post-myocardial infarction ventricular remodelingand myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway

Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI).MethodsSprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot.ResultsThe LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression.ConclusionXG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.

Qishen capsule safely boosts cardiac function and angiogenesis via the MEK/ERK pathway in a rat myocardial infarction model

Background Qishen(QS) capsules, a Traditional Chinese Medicine, has been widely used to treat coronary heart disease in China. However, evidence of its effectiveness remains unclear. Methods To explore whether QS has cardioprotective efficacy and/or promotes angiogenesis after myocardial infarction (MI), we performed experiments in a preclinical rat MI model. One month after left anterior descending coronary artery ligation, the rats received either QS solution (0.4 g/kg/day) or the same volume of saline by intragastric injection for four weeks. Results Echocardiographic and hemodynamic analyses demonstrated relatively preserved cardiac function in MI rats administered QS. Indeed, QS treatment was associated with reduced infarct scar size and heart weight index, and these beneficial effects were responsible for enhancing angiogenesis. Mechanistically, QS treatment increased phosphorylation of protein kinase B (Akt) and downregulated phosphorylation of mitogen-activated protein kinase/extracellular-regulated kinase (MEK/ERK). Conclusions QS therapy can improve the cardiac function of rats after MI by an underlying mechanism involving increased angiogenesis, at least partially via activation of the Akt signaling pathway and inhibition of MEK/ERK phosphorylation.

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

Background Xinfuli Granule （XG）, a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with dox- orubicin-induced cardiotoxicity. Methods Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin （DOX, 2.5 mg/kg per week） for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline （control group） or different dosage of XG （0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively） for six weeks. Transtho- racic echocardiography was performed to evaluate the left ventricular fractional shortening （LVFS） and left ventricular ejection fraction （LVEF） before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

Essen score in the prediction of cerebrovascular events compared with cardiovascular events after ischaemic stroke or transient ischaemic attack:a nationwide registry analysis

BACKGROUND The Essen risk score improves stratification of patients with acute ischemic stroke by early stroke recurrence.Recent study showed it could also predict myocardial infarction(MI).This study aimed to compare the Essen score’s ability to predict cerebrovascular events with compared cardiovascular events.METHODS We included patients with acute ischaemic stroke or transient ischaemic attack within seven days from the Third China National Stroke Registry.One-year cumulative event rates of combined vascular events(a composite of MI,stroke recurrence or vascular death)and cardiac events(a composite of MI,heart failure or cardiac death)was estimated using the Kaplan-Meier met-hod.The predictive value of the Essen score was assessed with C-statistics.In multivariate Cox regression analyses,we assessed whether Essen score,etiological subtype and imaging parameters were associated with outcomes.RESULTS Of 13,012 patients were included,the cumulative one-year event rates were 10.03%for combined vascular events and 0.77%for cardiac events,respectively.Compared with those with an Essen score<3,patients with an Essen score≥3 were more likely to have a subsequent combined vascular event[hazard ratio(HR)=1.39,95%CI:1.24−1.55]and cardiac events(HR=2.30,95%CI:1.53−3.44).The score tended to be more predictive of the risk of MI(C-statistic=0.63,95%CI:0.55−0.71)and cardiac events(C-statistic=0.62,95%CI:0.56−0.67)than stroke recurrence(C-statistic=0.55,95%CI:0.54−0.57)and combined vascular events(C-statistic=0.56,95%CI:0.54−0.57).In multivariable analysis after adjusted Essen score,patients with multiple acute in-farctions or single acute infarctions and large artery atherosclerosis subtype were independently associated with an increased risk of combined vascular events.While the cardioembolism subtype was associated with an increased risk of cardiac events.CONCLUSIONS The Essen score is potentially more suitable for risk stratification of cardiovascular events than cerebrovascular events.Moreover,future predictive tools should take brain imaging findings and cause of stroke into consideration.

Influence on radiosensitivity of lung glandular cancer cells when ERCC1 gene silenced by targeted siRNA

Objective:To identify the influence on radiosensitivity of lung glandular cancer cells when excisions repair cross-complementing group1(ERCC1) gene was silenced by targeted siR NA.Methods:siR NA which targeting to ERCC1 and control siR NA was designed and synthesized.The human lung glandular cancer SPC-A-1 cells was transfected.A total of 56 nude mice were divided into two groups,and two kinds of SPC-A-1 cells were transplanted to armpit of right forelimb,to establish the nude mice subcutaneous xenotransplanted tumor model of human lung glandular cancer cells.After the tumor was developed,the nude mice were randomly divided into four groups and accepted different doses of X-Ray radiation,then the change of tumor volume,survival time of mice in every group were recorded and the average lifetime was calculated.Twenty-one days later of X-ray experiment,two mice were taken and sacrificed in each group and the tumors organizations were stripped.The cell apoptosis rate and cell cycle distributions were obtained by FCM(flow cytometry).Results:The volume of tumor which ERCC1 gene was silenced was less than single irradiation group after X-ray irradiation,and the growth speed was slower and the lifetime of mice was lengthened as well(P<0.05).The cells apoptosis rate and the rate of G2/M cells which ERCC1 gene was silenced were higher than the same dose control group and the rate of G_1 cells were lower,which indicated that the cells could be stopped at G_2/M point,the cell proliferation was inhibited,the cell apoptosis was promoted and the radiation sensitivity was improved after the ERCC1 was silenced.Conclusions:The radiation sensitivity of lung glandular tumor could be improved after the ERCC1 gene was silenced by siR NA.

Complement use of Chinese herbal medicine after percutaneous coronary intervention: a prospective observational study

BACKGROUND Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease(CAD)patients after percutaneous coronary intervention(PCI)in China.We compared the incidence of the major adverse cardi-ovascular event(MACE)of CAD patients with or without the complement use of Chinese herbal medicine after PCI.METHODS In this prospective,observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital(China),we followed up consecutive patients who received PCI treatment for two years.MACE was defined as the composite all-cause mortality,revascularization,and myocardial infarction(MI)and was compared between those using(integrative medicine group)or those not using Chinese herbal medicine as an additional treatment to standard Western medicine,with unadjusted(Kaplan-Meier curves)and risk-adjusted(multivariable Cox regression)analyses.RESULTS A total of 5942 patients after PCI were enrolled in this study,and 5453 patients were included in the final analysis(4189[76.8%]male;mean age:61.9±9.9%years).During the follow-ups,2932(53.8%)patients used only Western medicine while 2521(46.2%)patients had used Chinese herbal medicine as an additional treatment to standard Western medicine.Patients in the integrative medicine group(IM group)were older than the Western medicine group(WM group),had more females and less pre-vious MI.The incidence of MACE was 15.3%(449/2932)in WM group and 11.54%(291/2521)in IM group.Cox regression ana-lysis showed that cumulative incidence of MACE was 27%lower in patients of the IM group than those in WM group(hazard ra-tio=0.73;95%CI:0.63-0.85;P<0.0001).CONCLUSIONS For CAD patients after PCI treatment,complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence.Randomized prospective studies are warranted to provide higher levels of benefit evidence in these pa-tients.