scholarly journals Time-Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor-Induced Myocardial Ischemia Pigs

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Qi Qiu ◽  
Yang Lin ◽  
Cheng Xiao ◽  
Chun Li ◽  
Yong Wang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Time Course ◽  
Caspase 3 ◽  
Heart Function ◽  
Cardiac Injury ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Ang Ii ◽  
Histological Changes ◽  
Active Caspase

We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF-αand active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF-αand active caspase-3 seemed to be the critical potential target of QSYQ.

scholarly journals QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yong Wang ◽  
Chun Li ◽  
Yuli Ouyang ◽  
Tianjiao Shi ◽  
Xiaomin Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Nadph Oxidase ◽  
Caspase 3 ◽  
Ventricular Remodeling ◽  
Cardiac Injury ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Histological Changes ◽  
Nadph Oxidase 4

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.

scholarly journals Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Yuji Haraguchi ◽  
Tatsuya Shimizu ◽  
Masayuki Yamato ◽  
Teruo Okano
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Cardiac Disease ◽  
Heart Function ◽  
Cell Sheet ◽  
Three Dimensional ◽  
Tissue Cell ◽  
Myocardial Tissue ◽  
Therapeutic Effects ◽  
Cardiac Diseases

At present, cardiac diseases are a major cause of morbidity and mortality in the world. Recently, a cell-based regenerative medicine has appeared as one of the most potential and promising therapies for improving cardiac diseases. As a new generational cell-based regenerative therapy, tissue engineering is focused. Our laboratory has originally developed cell sheet-based scaffold-free tissue engineering. Three-dimensional myocardial tissue fabricated by stacking cardiomyocyte sheets, which are tightly interconnected to each other through gap junctions, beats simultaneously and macroscopically and shows the characteristic structures of native heart tissue. Cell sheet-based therapy cures the damaged heart function of animal models and is clinically applied. Cell sheet-based tissue engineering has a promising and enormous potential in myocardial tissue regenerative medicine and will cure many patients suffering from severe cardiac disease. This paper summarizes cell sheet-based tissue engineering and its satisfactory therapeutic effects on cardiac disease.

Pressure-dependent effect of shock waves on rat brain: induction of neuronal apoptosis mediated by a caspase-dependent pathway

2007 ◽  
Vol 106 (4) ◽  
pp. 667-676 ◽  
Author(s):  
Kaoruko Kato ◽  
Miki Fujimura ◽  
Atsuhiro Nakagawa ◽  
Atsushi Saito ◽  
Tomohiro Ohki ◽  
...  
Keyword(s):  
Shock Wave ◽  
Brain Injury ◽  
Shock Waves ◽  
Caspase 3 ◽  
Wave Exposure ◽  
Histological Changes ◽  
Dependent Effect ◽  
Wave Induced ◽  
Dependent Pathway ◽  
Active Caspase

Object Shock waves have been experimentally applied to various neurosurgical treatments including fragmentation of cerebral emboli, perforation of cyst walls or tissue, and delivery of drugs into cells. Nevertheless, the application of shock waves to clinical neurosurgery remains challenging because the threshold for shock wave–induced brain injury has not been determined. The authors investigated the pressure-dependent effect of shock waves on histological changes of rat brain, focusing especially on apoptosis. Methods Adult male rats were exposed to a single shot of shock waves (produced by silver azide explosion) at over-pressures of 1 or 10 MPa after craniotomy. Histological changes were evaluated sequentially by H & E staining and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The expression of active caspase-3 and the effect of the nonselective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were examined to evaluate the contribution of a caspase-dependent pathway to shock wave–induced brain injury. High-overpressure (> 10 MPa) shock wave exposure resulted in contusional hemorrhage associated with a significant increase in TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle-shaped changes in neurons and elongation of nuclei without marked neuronal injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL-positive cells observed 24 hours after high-overpressure shock wave exposure (p < 0.01). A significant increase in the cytosolic expression of active caspase-3 was evident 24 hours after high-overpressure shock wave application; this increase was prevented by Z-VAD-FMK administration. Double immunofluorescence staining showed that TUNEL-positive cells were exclusively neurons. Conclusions The threshold for shock wave–induced brain injury is speculated to be under 1 MPa, a level that is lower than the threshold for other organs. High-overpressure shock wave exposure results in brain injury, including neuronal apoptosis mediated by a caspase-dependent pathway. This is the first report in which the pressure-dependent effect of shock wave on the histological characteristics of brain tissue is demonstrated.

scholarly journals Role of PTEN-less in cardiac injury, hypertrophy and regeneration

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Tian Liang ◽  
Feng Gao ◽  
Jinghai Chen
Keyword(s):  
Stress Responses ◽  
Cardiac Fibrosis ◽  
Cardiac Development ◽  
Heart Function ◽  
Cardiac Injury ◽  
Therapeutic Effects ◽  
Hypertrophic Growth ◽  
Dual Specificity ◽  
Cellular Factors ◽  
Physiological Homeostasis

AbstractCardiovascular diseases are the leading cause of death worldwide. Cardiomyocytes are capable of coordinated contractions, which are mainly responsible for pumping blood. When cardiac stress occurs, cardiomyocytes undergo transition from physiological homeostasis to hypertrophic growth, proliferation, or apoptosis. During these processes, many cellular factors and signaling pathways participate. PTEN is a ubiquitous dual-specificity phosphatase and functions by dephosphorylating target proteins or lipids, such as PIP3, a second messenger in the PI3K/AKT signaling pathway. Downregulation of PTEN expression or inhibiting its biologic activity improves heart function, promotes cardiomyocytes proliferation, reduces cardiac fibrosis as well as dilation, and inhibits apoptosis following ischemic stress such as myocardial infarction. Inactivation of PTEN exhibits a potentially beneficial therapeutic effects against cardiac diseases. In this review, we summarize various strategies for PTEN inactivation and highlight the roles of PTEN-less in regulating cardiomyocytes during cardiac development and stress responses.

scholarly journals Catheter-Free Arrhythmia Ablation Using Scanned Proton Beams

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Atsushi Suzuki ◽  
Amanda J. Deisher ◽  
Maryam E. Rettmann ◽  
H. Immo Lehmann ◽  
Stephan Hohmann ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Proton Beam ◽  
Time Course ◽  
Caspase 3 ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Proton Beams ◽  
Atrioventricular Junction ◽  
Active Caspase

Background: Proton beam therapy offers radiophysical properties that are appealing for noninvasive arrhythmia elimination. This study was conducted to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Methods: Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography scans were acquired at end-expiration breath hold. Structures (atrioventricular junction or left ventricular myocardium) and organs at risk were contoured. Doses of 30, 40, and 55 Gy were delivered during expiration to the atrioventricular junction (n=5) and left ventricular myocardium (n=20) of intact animals. Results: In this study, procedural success was tracked by pacemaker interrogation in the atrioventricular junction group, time-course magnetic resonance imaging in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 Gy caused slowing and interruption of cardiac impulse propagation at the atrioventricular junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. Conclusions: Scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

scholarly journals LuQi Formula Regulates NLRP3 Inflammasome to Relieve Myocardial-Infarction-Induced Cardiac Remodeling in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xiaoqing Zhang ◽  
Dandan Zhao ◽  
Jiling Feng ◽  
Xiaoli Yang ◽  
Zhenzhen Lan ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Caspase 3 ◽  
Sham Group ◽  
Ventricular Remodeling ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Internal Diameter ◽  
Model Group ◽  
Caspase 1

Background. Excessive activation of the nod-like receptor family pyrin domain containing 3(NLRP3) inflammasome plays a significant role in the progression of cardiac injury. In China, it has been well recognized that Chinese herbal medicine is markedly effective in treating cardiovascular diseases (CVDs). LuQi Formula (LQF) has been used clinically for more than 10 years and confirmed to be effective in improving cardiac function and inhibiting apoptosis. However, the specific mechanisms underlying its efficacy are mostly unknown. This study aimed to evaluate whether LQF could alleviate cardiac injury and apoptosis by regulating the NLRP3 inflammasome and the caspase-3/Bax pathway. Purpose. In this study, we investigated the effects of LQF on cardiac remodeling in a mouse model of myocardial infarction (MI) in vivo. Methods. Forty male C57BL/6 mice were randomly divided into four groups: the sham group, the model group, the LQF group, and the perindopril group, with a sample size (n) of 10 mice in each group. Except the sham group, the other groups received left anterior descending (LAD) coronary artery ligation to induce MI and then treated with LQF, perindopril, or saline. Six weeks after MI, echocardiography was used to evaluate cardiac structure and function. Myocardial tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson’s trichrome to analyse myocardial fibrosis. Myocardial hypertrophy was observed by fluorescent wheat germ agglutinin (WGA) staining. The expressions of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, Bcl-2, and Bax in heart tissues were assessed by western blot analysis. mRNA expressions of ANP and BNP in heart tissues were measured by RT-PCR. The expression of reactive oxygen species in myocardial tissue was detected by using a DCFH-DA probe. Results. Echocardiographic analysis showed that compared with the model group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the LQF and perindopril group were increased ( P < 0.05 ), left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end-systole (LVIDs) were reduced ( P < 0.05 ), and H&E and Masson’s trichrome staining of cardiac tissues showed that LQF and perindopril could partially reverse ventricular remodeling and alleviate myocardial fibrosis ( P < 0.05 ). WGA fluorescence results showed that compared with the model group, myocardial hypertrophy was significantly reduced in the LQF and perindopril group. We also found that LQF and perindopril reduce the oxidative stress response in the heart of MI mice. The protein expression of NLRP3, ASC, Cle-caspase-1, IL-1β, TXNIP, Cle-caspase-3, and Bax was downregulated in the LHF and perindopril treatment group, and Bcl-2 expression was upregulated. Conclusion. LQF and perindopril significantly attenuated cardiac injury and apoptosis in the MI model. In addition, we found that LQF effectively inhibited the activation of the NLRP3/ASC/caspase-1/IL-1β cascade, decreased inflammatory infiltration, delayed ventricular remodeling, and downregulated caspase-3/Bax signaling, which can effectively reduce the apoptosis of cardiomyocytes. Perindopril showed the same mechanism.

scholarly journals Tetrandrine inhibits colon carcinoma HT-29 cells growth via the Bcl-2/Caspase 3/PARP pathway and G1/S phase

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
JiaNan Li ◽  
QiuHong Wang ◽  
ZhiBin Wang ◽  
Na Cui ◽  
BingYou Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Molecular Docking ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Ht 29 ◽  
Active Caspase

Abstract Tetrandrine (Tet) bisbenzylisoquinoline alkaloids isolated from Stephania tetrandra and other related species of Menispermaceae. It has been demonstrated to have positive therapeutic effects on cardiovascular disease, hypertension, silicosis, autoimmune diseases. In recent years, some reports have shown that Tet has anticancer activity in human cancers. To explore the pharmacological activity and mechanism of Tet on colon cancer and its unique advantages as a natural product. In the present study, analyses of the cell cycle, apoptosis, targets prediction, molecular docking, and alterations in protein levels were performed to elucidate how Tet functions in colon cancer. We found that Tet robustly induced arrest at the G1 phase in colon cancer cell line HT-29. It induced HT-29 cell apoptosis in a dose-dependent manner. Similarly, analysis of protein expression levels in HT-29 cells showed down-regulation of Bcl-2, pro-caspase 3, pro-caspase 8, PARP, cyclin D1 (CCND1), cyclin-dependent kinase 4 (CDK 4), and up-regulation of Bax, active caspase 3, and active caspase 8. These results indicate that Tet induces apoptosis of colon cancer cells through the mitochondrial pathway and caspase family pathway. Molecular docking showed interaction effects and binding energy. Comparing with the CDK4 inhibitors ribociclib and palbociclib, the docking energy is similar to the docked amino acid residues. Therefore, we conclude that Tet and the CCND1/CDK4 compound could form hydrogen bonds and a stable compound structure, which can inhibit colon cancer cells proliferation by regulating CCND1/CDK4 compound and its downstream proteins phosphorylated Rb (p-Rb). In summary, Tet may be a potential drug for colon cancer therapy.

Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade

2014 ◽  
Vol 307 (7) ◽  
pp. R879-R887 ◽  
Author(s):  
Naimeh Rafatian ◽  
Katherine V. Westcott ◽  
Roselyn A. White ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Time Course ◽  
Caspase 3 ◽  
Macrophage Infiltration ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Intracerebroventricular Infusion ◽  
Apoptosis And Inflammation ◽  
A Minor ◽  
The Brain ◽  
Active Caspase

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and β-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone. In the present study, we assessed the time course of macrophage infiltration and apoptosis in the heart as detected by both terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and active caspase-3 immunostaining in both myocytes and nonmyocytes, as well as the effects of central MR blockade by intracerebroventricular infusion of eplerenone at 5 μg/day on peak changes in macrophage infiltration and apoptosis post-MI. Macrophage numbers were markedly increased in the infarct and peri-infarct zones and to a minor extent in the noninfarct part of the left ventricle at 10 days post-MI and decreased over the 3-mo study period. Apoptosis of both myocytes and nonmyocytes was clearly apparent in the infarct and peri-infarct areas at 10 days post-MI. For TUNEL, the increases persisted at 4 and 12 wk, but the number of active caspase-3-positive cells markedly decreased. Central MR blockade significantly decreased CD80-positive proinflammatory M1 macrophages and increased CD163-positive anti-inflammatory M2 macrophages in the infarct. Central MR blockade also reduced apoptosis of myocytes by 40–50% in the peri-infarct and to a lesser extent of nonmyocytes in the peri-infarct and infarct zones. These findings indicate that MR activation in the brain enhances apoptosis both in myocytes and nonmyocytes in the peri-infarct and infarct area post-MI and contributes to the inflammatory response.

Effects of miR-26a-5p and PTEN on Myocardium of Myocardial Ischemia-reperfusion Mice

2021 ◽  
Vol 7 (5) ◽  
pp. 4057-4065
Author(s):  
Lifei Yu ◽  
Shiwen Lu
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Tissue ◽  
Model Group ◽  
Caspase 9 ◽  
Blank Group ◽  
Myocardial Ischemia Reperfusion

This study aimed to investigate the effects of miR-26a-5p and PTEN on myocardium of myocardial ischemia-reperfusion mice. Twelve C57/B6 male mice were randomly selected and divided into control group and mouse model group with 6 mice in each group, in which no surgical modeling was normally performed. Mice were killed 2 hours after operation to collect myocardial tissue. H9C2 was transfected with miR-26a-5p-mimic and blank vector to overexpress miR-26a-5p, and then normal group, hypoxia/reoxygenation group (cell model group), blank group and overexpression group were established respectively. Protein expressions of PTEN, Caspase-3, Caspase-9, P13K and p-Akt in tissues and cells of mice were detected. Expressions of miR-26a-5p and PTEN in myocardial tissue and cells of mice were detected. Apoptosis was detected. The relationship between miR-26a-5p and PTEN was determined. Expressions of miR-26a-5p in tissues of mouse model group were lower than those of normal group, while PTEN expressions were opposite (p<0.05). Expressions of miR-126 in overexpression group were increased compared with those of cell model group and blank group, and decreased compared with those of control group (P<0.05). Expressions of PTEN in overexpression group were lower than those in cell model group and blank group, and higher than those in control group (p<0.05). Compared with control group, miR-26a-5p was decreased and PTEN was increased in cell model group (P<0.05). Compared with blank group and cell model group, expressions of PTEN, Caspase-3 and Caspase-9 proteins in overexpression group were significantly decreased, while expressions of P13K and p-Akt proteins were significantly increased (p<0.05). Apoptosis rate in overexpression group was significantly lower than that in cell model group and blank group (p<0.05). Dual-luciferase reporter proved that there was a targeted regulatory relationship between miR-26a-5p and PTEN. In conclusion, up-regulation of miR-26a-5p regulates PTEN/PI3K/p-Akt signaling pathway and reduces myocardial cell apoptosis, thus improving ischemia-reperfusion injury.

scholarly journals The cardioprotective potential of Tadalafil in myocardial ischemia/reperfusion

2020 ◽  
Vol 8 (2) ◽  
pp. 87-100
Author(s):  
Najah R. Hadi ◽  
Fadhil G. Al-Amran
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Male Rats ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

The objective of this study is to assess the potential protective effect of Tadalafil on myocardial ischemia reperfusion injury induced by LAD ligation, 28 male rats were randomized into 4 groups (7 rats per group); Sham, rats underwent the same anesthetic and surgical procedure except for LAD ligation; control, rats underwent LAD ligation for 30 minutes and reperfusion for 2 hours; vehicle, rats treated with 10% DMSO, the Tadalafil solvent 30 minutes before the ligation; Tadalafil group, rats pretreated with Tadalafil1mg/kg i.p 30 minutes before ligation. In control group, as compared with sham, tissue TNF-α, IL-6, IL-10, caspase-3 and BAX, plasma cTn-T and serum MDA significantly increased (P<0.05), while serum GSH significantly decreased (P<0.05). Histopathologically, control group showed a significant cardiac injury (P<0.05) compared with sham group. Tadalafil significantly counteracted (P<0.05) the increase of TNF-α, IL-6, caspase-3 and BAX and counteracted the increase in plasma cTn-T and serum MDA. Tadalafil produces a significant elevation (P<0.05) in cardiac IL-10 and serum GSH with significant reduction in (P<0.05) cardiac injury. In We concluded that Tadalafil attenuates myocardial I/R injury in male rats through interfering with inflammatory reactions and apoptosis .

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