MRTF-A alleviates myocardial ischemia reperfusion injury by inhibiting the inflammatory response and inducing autophagy.

Myocardin-related transcription factor A (MRTF-A) has an inhibitory effect on myocardial infarction; however, the mechanism is not clear. This study reveals the mechanism by which MRTF-A regulates autophagy to alleviate myocardial infarct-mediated inflammation, and the effect of silent information regulator 1 (SIRT1) on the myocardial protective effect of MRTF-A was also verified. MRTF-A significantly decreased cardiac damage induced by myocardial ischemia. In addition, MRTF-A decreased NLRP3 inflammasome activity, and significantly increased the expression of autophagy protein in myocardial ischemia tissue. Lipopolysaccharide (LPS) and 3-methyladenine (3-MA) eliminated the protective effects of MRTF-A. Furthermore, simultaneous overexpression of MRTF-A and SIRT1 effectively reduced the injury caused by myocardial ischemia; this was associated with downregulation of inflammatory factor proteins and when upregulation of autophagy-related proteins. Inhibition of SIRT1 activity partially suppressed these MRTF-A-induced cardioprotective effects. SIRT1 has a synergistic effect with MRTF-A to inhibit myocardial ischemia injury through reducing the inflammation response and inducing autophagy.

miR-8485 alleviates the injury of cardiomyocytes through TP53INP1.

MicroRNAs (miRNAs) feature prominently in regulating the progression of chronic heart failure (CHF). This study was performed to investigate the role of miR-8485 in the injury of cardiomyocytes and CHF. It was found that miR-8485 level was markedly reduced in the plasma of CHF patients, compared with the healthy controls. H2 O2 treatment increased tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß levels, inhibited the viability of human adult ventricular cardiomyocyte cell line AC16, and increased the apoptosis, while miR-8485 overexpression reversed these effects. Tumor protein p53 inducible nuclear protein 1 (TP53INP1) was identified as a downstream target of miR-8485, and TP53INP1 overexpression weakened the effects of miR-8485 on cell viability, apoptosis, as well as inflammatory responses. Our data suggest that miR-8485 attenuates the injury of cardiomyocytes by targeting TP53INP1, suggesting it is a protective factor against CHF.

Function and Mechanism of Trimetazidine in Myocardial Infarction-Induced Myocardial Energy Metabolism Disorder Through the SIRT1-AMPK Pathway.

Myocardial energy metabolism (MEM) is an important factor of myocardial injury. Trimetazidine (TMZ) provides protection against myocardial ischemia/reperfusion injury. The current study set out to evaluate the effect and mechanism of TMZ on MEM disorder induced by myocardial infarction (MI). Firstly, a MI mouse model was established by coronary artery ligation, which was then treated with different concentrations of TMZ (5, 10, and 20 mg kg-1 day-1). The results suggested that TMZ reduced the heart/weight ratio in a concentration-dependent manner. TMZ also reduced the levels of Bax and cleaved caspase-3 and promoted Bcl-2 expression. In addition, TMZ augmented adenosine triphosphate (ATP) production and superoxide dismutase (SOD) activity induced by MI and decreased the levels of lipid peroxide (LPO), free fatty acids (FFA), and nitric oxide (NO) in a concentration-dependent manner (all P < 0.05). Furthermore, an H2O2-induced cell injury model was established and treated with different concentrations of TMZ (1, 5, and 10 µM). The results showed that SIRT1 overexpression promoted ATP production and reactive oxygen species (ROS) activity and reduced the levels of LPO, FFA, and NO in H9C2 cardiomyocytes treated with H2O2 and TMZ. Silencing SIRT1 suppressed ATP production and ROS activity and increased the levels of LPO, FFA, and NO (all P < 0.05). TMZ activated the SIRT1-AMPK pathway by increasing SIRT1 expression and AMPK phosphorylation. In conclusion, TMZ inhibited MI-induced myocardial apoptosis and MEM disorder by activating the SIRT1-AMPK pathway.

A novel method to simultaneously record spinal cord electrophysiology and electroencephalography signals.

The brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood. This study developed a novel method to simultaneously record spinal cord electrophysiology (SCE) and electroencephalography (EEG) signals and validated its performance using a classical resting-state study design with two experimental conditions: eyes-closed (EC) and eyes-open (EO). We recruited nine postherpetic neuralgia patients implanted with a spinal cord stimulator, which was modified to record SCE signals simultaneously with EEG signals. For both EEG and SCE, similar differences were found in delta- and alpha-band oscillations between the EC and EO conditions, and the spectral power of these frequency bands was able to predict EC/EO behaviors. Moreover, causal connectivity analysis suggested a top-down regulation in delta-band oscillations from the brain to the spinal cord. Altogether, this study demonstrates the validity of simultaneous SCE-EEG recording and shows that the novel method is a valuable tool to investigate the brain-spinal interaction. With this method, we can better unite knowledge about the brain and the spinal cord for a deeper understanding of the functions of the whole CNS.

Synergistic Myoelectrical Activities of Forearm Muscles Improving Robust Recognition of Multi-Fingered Gestures.

Currently, surface electromyography (sEMG) features of the forearm multi-tendon muscles are widely used in gesture recognition, however, there are few investigations on the inherent physiological mechanism of muscle synergies. We aimed to study whether the muscle synergies could be used for gesture recognition. Five healthy participants executed five gestures of daily life (pinch, fist, open hand, grip, and extension) and the sEMG activity was acquired from six forearm muscles. A non-negative matrix factorization (NMF) algorithm was employed to decompose the pre-treated six-channel sEMG data to obtain the muscle synergy matrixes, in which the weights of each muscle channel determined the feature set for hand gesture classification. The results showed that the synergistic features of forearm muscles could be successfully clustered in the feature space, which enabled hand gestures to be recognized with high efficiency. By augmenting the number of participants, the mean recognition rate remained at more than 96% and reflected high robustness. We showed that muscle synergies can be well applied to gesture recognition.

[Impact of mesenchymal stem cells transplantation on myocardial myocardin-related transcription factor-A and bcl-2 expression in rats with experimental myocardial infarction].

OBJECTIVE: To observe the impact of mesenchymal stem cells (BMSCs) transplantation on myocardial myocardin-related transcription factor-A (MRTF-A) and bcl-2 expression in rats with experimental myocardial infarction (MI). METHODS: Thirty rats were randomly divided into sham, MI and MI + BMSCs (1 × 10(6) injected into 4 infarct points immediately post coronary artery ligation) groups (n = 10 each).One week later, TUNEL was used to detect cardiomyocyte apoptosis, the myocardial expression of MRTF-A and bcl-2 was detected by laser scanning confocal microscope and Western blot. In vitro plasmid of MRTF-A and co-transfection with plasmids of MRTF-A and bcl-2 or mutated bcl-2 transfection into cardiomyocyte was applied to evaluate the relationship between MRTF-A and bcl-2. RESULTS: The number of apoptotic cardiomyocytes in the sham group, MI group and MI + BMSCs group were (4.05 ± 1.56)%, (62.38 ± 8.41)% and (22.36 ± 6.17)%, respectively (P < 0.05). The protein expression of MRTF-A and bcl-2 in the MI group were significantly lower than those in sham group, while significantly upregulated in MI + BMSCs group (P < 0.05 vs. MI). In cultured neonatal rat cardiomyocyte, the expression of bcl-2 protein was significantly upregulated after transfection with MRTF-A plasmid, and bcl-2-luciferase activity significantly increased after co-transfection with plasmids of MRTF-A and bcl-2-luciferase, however, the positive regulatory effect of MRTF-A was abolished after transfection with mutated bcl-2. CONCLUSION: Mesenchymal stem cells transplantation can effectively reduce cardiomyocyte apoptosis in this rat MI model, and upregulate the expression of MRTF-A. Consequent up-regulated bcl-2 expression might be involved in the beneficial effects of BMSCs transplantation in this model.

Extraction, chemical analysis of Angelica sinensis polysaccharides and antioxidant activity of the polysaccharides in ischemia-reperfusion rats.

Angelica sinensis polysaccharides were analyzed using high performance liquid chromatography (HPLC) and Fourier Transform Infrared (FT-IR). The major sugar of the polysaccharide was saccharose (18.55%); and the sugar constituted about 83% of the monomer content. Glucose and fructose were found as minor components of the polysaccharides. The FT-IR spectra of A. sinensis polysaccharides are used for determination of their structural features. The FT-IR spectrum of A. sinensis polysaccharides showed bands at 1641 cm(-1), 1415 cm(-1), 1050 cm(-1) and 926 cm(-1) characteristic for the carboxylic group. Absorptions at 2920-2930 cm(-1) are attributed to asymmetrical stretching vibration of CH(2)-group. Medium stretch observed in the range 1650-1400 cm(-1) is assigned to C-C stretching of polysaccharides. Cardioprotective effects of A. sinensis polysaccharides were evaluated by using myocardial ischemia/reperfusion (IR) rats. A. sinensis polysaccharides treatment significantly reduced myocardial infarction size, enhanced CT-1 and antioxidant enzymes activity, downregulated caspase-12 mRNA expression in rats. The study strongly suggests the cardioprotective activity of A. sinensis polysaccharides in limiting ischemia-reperfusion induced myocardial injury.