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Summary [ABSTRACT FROM AUTHOR]

We have studied the association between M3 muscarinic acetylcholine receptors (M3-mAChR) and protein kinase C-ε (PKC-ε) during ischemic myocardial injury using Western blot analysis and immunoprecipitation technique. Myocardial ischemia (MI) induced PKC-ε translocation from cytosolic to membrane fractions. This translocation participated in the phosphorylation of M3-mAChR in membrane fractions, which could be abolished by the inhibitor of PKC, chelerythrine chloride. On the other hand, M3-mAChR could also regulate the expression of PKC-ε in ischemic myocardium. Choline (choline chloride, an M3 receptor agonist, administered at 15 min before occlusion) strengthened the association between PKC-ε and M3-mAChR. However, blockade of M3-mAChR by 4-diphenylacetoxy- N-methylpiperidine methiodide (an M3 receptor antagonist, administered at 20 min before occlusion) completely inhibited the effect of choline on the expression of PKC-ε. We conclude that the translocation of PKC-ε is required for the phosphorylation of M3-mAChR; moreover, increased PKC-ε activity is associated with M3-mAChR during MI. This reciprocal regulation is likely to play a role in heart signal transduction during ischemia between ventricular myocytes. [ABSTRACT FROM AUTHOR]

We demonstrated here that an initial treatment with aconitine- or barium-chloride-induced arrhythmias and resulted in reduced susceptibility of the heart to the induction of arrhythmias by a repeated drug treatment 24 h after the initial one, a delayed preconditioning cardioprotection. This delayed preconditioning was accompanied by enhanced expression of cardiac muscarinic M3 receptor and abolished by M3-selective antagonist. We conclude that muscarinic M3 receptors might play an important role in conferring the pharmacological preconditioning against arrhythmias. This study thus expands our understanding of the cellular function and pathophysiological roles of muscarinic M3 receptor and reconsolidates our view of cardioprotective effects of muscarinic M3 receptor on myocardium. [ABSTRACT FROM AUTHOR]

It is well known that choline has protective effects on ischemic arrhythmias. We designed the present study to evaluate the antiarrhythmic effects of choline and to detect its related mechanisms in aconitine-induced rat and ouabain-induced guinea pig models of arrhythmia. Laser scanning confocal microscopy and patch-clamp technique were utilized to study the action of choline on intracellular calcium concentration and L-type calcium current (ICa-L) of cardiac myocytes. M3 receptor antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) was applied preliminarily to evaluate the role of the M3 receptor. Choline significantly increased the survival time of arrhythmic rats and guinea pigs, delayed the onset of arrhythmias and ventricular tachycardia, and decreased the arrhythmia score. The overload of intracellular Ca2+ induced by aconitine or ouabain was reduced in isolated myocytes pretreated with choline. Choline reduced the increased density of ICa-L induced by aconitine or ouabain. Moreover, the beneficial effects of choline were reversed by 4-DAMP. Choline produced antiarrhythmic actions on arrhythmia models by stimulating the cardiac M3 receptor. The mechanism may be related to the improvement of Ca2+ handling. Il est bien connu que la choline a des effets protecteurs sur les arythmies ischémiques. Pour examiner si l’effet antiarythmique de la choline sur le myocarde ischémique pourrait être reproduits dans d’autres modèles animaux arythmogènes, nous avons conçu la présente étude pour évaluer les effets antiarythmiques de la choline et identifier ses mécanismes. Nous avons observés les effets de la choline sur des modèles de rats présentant une arythmie induite par la choline et de cobayes présentant une arythmie induite par l’ouabaïne. Nous avons utilisé la microscopie confocale à balayage laser et la technique du patch clamp pour examiner l’action de la choline sur la concentration de calcium intracellulaire et le courant calcique de type L (ICa-L) des myocytes cardiaques. Nous avons d’abord appliqué l’antagoniste du récepteur M3, 4-DAMP (4-diphénylacétoxy-N-méthylpyridine-méthiodide), pour évaluer le rôle du récepteur M3. La choline a augmenté significativement le temps de survie des rats et des cobayes présentant une arythmie, retardé le déclenchement des arythmies et de la tachycardie ventriculaire, et diminué le score d’arythmie. La surcharge de Ca2+ intracellulaire induite par l’aconitine ou l’ouabaïne a été réduite dans les myocytes isolés prétraités à la choline. La choline a diminué l’augmentation de la densité de l’ICa-L induite par l’aconitine ou l’ouabaïne. Le 4-DAMP a renversé les effets bénéfiques de la choline. La choline a eu des actions antiarythmiques sur les modèles d’arythmie en stimulant le récepteur M3 cardiaque. Le mécanisme pourrait être lié à l’amélioration du métabolisme du Ca2+. [ABSTRACT FROM AUTHOR]

A fault detection method using principal component analysis (PCA) integrated with law-based strategy was presented for detecting sensor faults in variable air volume (VAV) air-conditioning system on the base of VAV system simulation. This method, which divides the measure space into two subspaces: principal subspace and residual subspace, can detect sensor faults by PCA-based strategy and reconstruct the faults by law-based strategy. The simulation results show that this method not only can detect and isolate sensor faults, but also can briefly reconstruct the faults. It gave a necessary base for further study on sensor fault detection. [ABSTRACT FROM AUTHOR]

On the basis of dynamic simulation of variable air volume (VAV) air-conditioning systems and controls, this paper analyzed the effect of supply air and water temperature of VAV air conditioning system on indoor humidity control, according to the relative humidity control requirement of ASHRAE Standard 62-2001. Meanwhile, this paper also brought forward and analyzed the optimal control strategy of supply air temperature satisfying the relative humidity control requirement of ASHRAE Standard 62-2001. [ABSTRACT FROM AUTHOR]

To detect and estimate the bias of temperature sensors in chilled systems, according to the systems configuration some control volumes are selected and the energy conservation equations of each control volume are set up, and then the groups of equations for FDD (Fault Detection and Diagnosis) are obtained based on the mathematical character of the residual of the energy conservation equations. It is also presented to solve the problems of steady state detection and the independence problem of the equations for FDD, which would happen during FDD procedure. The FDD method is validated by simulation of chilling water system. The results show that the FDD method could detect and estimate the faults of fixed bias of temperature sensor. [ABSTRACT FROM AUTHOR]

Background: Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure. 7,8-Dihydroxyflavone (7,8-DHF) is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic. The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy., Methods: Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol (ISO) with or without 7,8-DHF, respectively. F-actin staining was performed to calculate the cell area. Transcriptional levels of hypertrophic markers, including ANP, BNP, and β-MHC, were detected. Echocardiography, hematoxylin-eosin staining, and transmission electron microscopy were used to examine the cardiac function, histology, and ultrastructure of ventricles. Protein levels of mitochondria-related factors, such as adenosine monophosphate-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), were detected., Results: 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy, diminished the cross-sectional area, and alleviated the mitochondrial disorders of cardiomyocytes. Meanwhile, 7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes. In addition, 7,8-DHF activated AMPK and PGC-1α signals without affecting the protein levels of mitochondrial dynamics-related molecules. The effects of 7,8-DHF were eliminanted by Compound C, an AMPK inhibitor., Conclusions: These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling, providing a potential agent for the treatment of pathological cardiac hypertrophy., (© 2022 JGC All rights reserved; www.jgc301.com.)

This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice.

Traditional Chinese medicine (TCM) has a good reputation for preventing or healing diseases in clinic due to its higher efficacy, minor toxicity and abundant resources. Screening bioactive components in TCMs is not only crucial for clarifying their action mechanisms, but also the basis of their safety and quality control. TCM is characterized by multiple components, multiple targets and multiple mechanisms, however the complex composition of TCM makes it difficult to study the therapeutic material basis which has become the bottleneck in the process of its modernization and internationalization. Recently, with the rapid development of modern technologies and the unceasing progress of various disciplines, multidisciplinary approach, such as analytical chemistry, chemistry of TCM, pharmacology, cell biology, systems biology and bioinformatics has been successfully applied to the study of TCM. Multidisciplinary approach realizes the communication and interaction of multi-discipline, and accelerates the research and development of TCM. This review summarizes the application of multidisciplinary approach which may have certain potential of bringing new thoughts to TCM research and provide references for screening and identification of therapeutic material basis of TCMs.

Objective: To evaluate the myocardial protection effects of trimetazidine during percutaneous coronary intervention (PCI)., Methods: 101 patients from 5 hospitals with stable or unstable angina pectoris were enrolled in this study. All the patients were randomized into two groups: a trimetazidine group (n=54) and a control group (n=47). The trimetazidine group received oral trimetazidine 20 mg three times a day for (5±2) days before coronary angiography and a loading dose of 60 mg 30 minutes before PCI. The daily routine dosage was continued for 4 weeks after the procedure. The control group received similar treatment except trimetazidine. For each patient, the angina pectoris attacks, CK-MB, electrocardiogram and echocardiogram were noted., Results: Angina did not occur in trimetazidine group during the procedure but occurred in 12 patients (25.5%) in the control group (P<0.001). The changes of ST-segment and T wave during balloon dilatation in PCI procedure were less in the trimetazidine group (60.8% vs 78.3%, P<0.05). Ejection fraction in the trimetazidine group was higher than that in the control group 4 weeks [(66.6±7.1)% vs (63.0±7.7)%, P=0.03] after PCI., Conclusion: Trimetazidine could reduce the frequency of angina pectoris attacks and myocardial damage during PCI. It also improves left ventricular function during follow-up after PCI.

We have studied the association between M(3) muscarinic acetylcholine receptors (M(3)-mAChR) and protein kinase C-epsilon (PKC-epsilon) during ischemic myocardial injury using Western blot analysis and immunoprecipitation technique. Myocardial ischemia (MI) induced PKC-epsilon translocation from cytosolic to membrane fractions. This translocation participated in the phosphorylation of M(3)-mAChR in membrane fractions, which could be abolished by the inhibitor of PKC, chelerythrine chloride. On the other hand, M(3)-mAChR could also regulate the expression of PKC-epsilon in ischemic myocardium. Choline (choline chloride, an M(3) receptor agonist, administered at 15 min before occlusion) strengthened the association between PKC-epsilon and M(3)-mAChR. However, blockade of M(3)-mAChR by 4-diphenylacetoxy-N-methylpiperidine methiodide (an M(3) receptor antagonist, administered at 20 min before occlusion) completely inhibited the effect of choline on the expression of PKC-epsilon. We conclude that the translocation of PKC-epsilon is required for the phosphorylation of M(3)-mAChR; moreover, increased PKC-epsilon activity is associated with M(3)-mAChR during MI. This reciprocal regulation is likely to play a role in heart signal transduction during ischemia between ventricular myocytes.

Objective: To examine the change in nuclear factor-KappaB (NF-KappaB) activity, tumor necrosis factor-alpha (TNF-alpha) and soluble thrombomodulin (sTM) levels at different time following reperfusion in acute myocardial infarction (AMI), and to identify the role of ischemia/reperfusion after ischemia in injury to endothelial cells and its relevant mechanism., Methods: AMI group included 8 randomly selected patients with AMI, and a normal control group (n=8) composing individuals who underwent health check. NF-KappaB activity in monocytes was determined by electrophoretic mobility shift assays (EMSA). The level of TNF-alpha was measured by radio-immunity and sTM was measured by enzyme linked immunosorbent assay (ELISA)., Results: The NF-KappaB activity, TNF-alpha and sTM levels raised dramatically at 0.5 hour after reperfusion, reaching peak at 1 hour and declined gradually at 3, 12 and 24 hours. The levels of all the determined parameters at every time point were significantly higher than that of normal control group, and their levels at 1 hour were significantly higher than that at 24 hours (all P<0.05). There was a positive correlation between the NF-KappaB activity and the levels of TNF-alpha and sTM (all P<0.05)., Conclusion: These results indicate that NF-KappaB is activated and the levels of TNF-alpha and sTM rise significantly after reperfusion in AMI. The activation of NF-KappaB maybe one of the most important pathogenic mechanism of endothelial injury.

Objective: To assess the values of endoscopy, 24-hour esophageal pH monitoring, symptom index, 24-hour esophageal bile monitoring, and proton pump inhibitor (PPI) trail in the diagnosis of gastroesophageal reflux disease (GERD)-related noncardiac chest pain (NCCP)., Methods: 27 NCCP patients, selected from a consecutive sample of 255 patients who had received coronary angiography owing to chest pain, underwent upper endoscopy, and 24-hour esophageal pH and bile monitoring, then they took esomeprazole 20 mg orally twice daily for 14 days. Symptom score (SI) was used to measure the severity and frequency of chest pain before and after treatment. The patients also underwent an initial questionnaire survey including the general personal data and symptom characters, reflux diagnostic questionnaire (RDQ), self-rating anxiety scale (SAS) survey, and self-rating depression scale (SDS) survey., Results: If only based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, 9 of the 27 patients (33%) were classified as GERD-related NCCP. Otherwise, 74% (20 of the 27 patients were classified as GERD-related NCCP based on erosive esophagitis and/or abnormal 24-hour esophageal pH monitoring, or positive SI or abnormal bile monitoring. 15 of the 20 GERD patients (75%) had a significant symptom improvement on PPI compared with 14% (1/7) of non-GERD patients (P = 0. 009). The calculated sensitivity and specificity of the PPI trail was 75% and 86% respectively. The typical reflux symptoms presented more frequently among GERD patients than non-GERD patients [65% (13/20) vs 29% (2/7), P = 0.185]. There was no significant RDQ score difference between the 2 groups (10 +/- 4 vs 8 +/- 4, P = 0.411). The sensitivity and specificity of RDQ to GERD-related NCCP were 35% and 86% respectively. The SAS scores of GERD and non-GERD-related NCCP patients were both significantly higher than that of the normal controls (P = 0.008 and P = 0.011), while the SDS scores of the GERD and non-GERD-related NCCP patients were both similar to that of the normal controls (P = 0.090 and P = 0.113)., Conclusion: Combination of endoscopy, 24-hour esophageal pH monitoring, SI, and 24-hour esophageal bile monitoring helped to improve the diagnosis of GERD-related NCCP. PPI trail is the first clinical diagnostic tool in the evaluation of GERD-related NCCP.

Objective: Human umbilical cord blood contains abundant immature stem/progenitor cells, which may contribute to the repair of infarcted myocardium. Present study aimed to explore the feasibility and effects of human umbilical cord blood mononuclear cells (HUCBC) transplantation for the treatment of myocardial infarction., Methods: Forty-five male Wistar rats were randomly divided into three groups: (1) Myocardial infarction (MI plus vehicle, n = 15), (2) MI plus cell transplantation (HUCBC were implanted into the peri-infarct area immediately after MI, n = 15), (3) Normal control group (n = 15). After echocardiography and hemodynamic measurements, the rats were sacrificed for histological and immunochemical examinations one month post MI., Results: The transplanted HUCBC survived and participated the repair process in host heart. Significantly improved left ventricular function was evidenced by echocardiography in cell transplantation group compared to the MI control group. Left ventricular end-diastolic pressure was significantly reduced LVEDP (21.08 +/- 8.10) vs (30.82 +/- 9.59) mm Hg, P < 0.05], +dp/dt(max) [(4.29 +/- 1.27) vs (3.24 +/- 0.75) mm Hg/ms, P < 0.05] and -dp/dt(max) increased [(3.71 +/- 0.79) vs (3.00 +/- 0.49) mm Hg/ms, P < 0.05] in cell transplantation rats compared with MI control rats. vWF immunostaining examination showed significantly increased microvessels within the boundary of infarcted myocardium in cell transplantation group compared to the MI control group (P < 0.01)., Conclusions: HUCBC transplantation may improve cardiac function in MI rats by promoting microvessel formation.