LncRNA AC125982.2 regulates apoptosis of cardiomyocytes through mir-450b-3p/ATG4B axis in a rat model with myocardial infarction.

Background: The occurrence and disability of myocardial infarction (MI) are on the rise globally, making it a significant contributor to cardiovascular mortality. Irreversible myocardial apoptosis plays a crucial role in causing MI. Long non-coding RNAs (LncRNAs) are key regulators of the cardiac remodeling process. Therefore, it is necessary to explore the effect of LncRNAs on cardiomyocyte apoptosis in MI. Methods: The rat-MI model was constructed, LncRNA-Seq and qPCR analyses were used to determine differentially expressed genes obtained from heart tissue of rats in the MI and sham groups. The miRanda software was used to predict the binding sites of LncRNA-miRNA and miRNA-mRNA, which were futhrer verified by dual luciferase assay. The LncRNA-miRNA-apoptosis pathway was further validated using hypoxia-exposed primary cardiomyocytes. Results: Compared to the sham group, 412 LncRNAs were upregulated and 501 LncRNAs were downregulated in MI-rat heart tissues. Among them, LncRNA AC125982.2 was most significantly upregulated in MI-rat heart tissues and hypoxic cardiomyocytes. Knockdown of AC125982.2 and ATG4B expression reversed hypoxia-induced apoptosis. In addition, transfection of mir-450b-3p inhibitor attenuated the protective effect of AC125982.2 knockdown. Moreover, we found that AC125982.2 modulated ATG4B expression by acting as a sponge for miR-450b-3p. Conclusion: Upregulated AC125982.2 expression regulates ATG4B by sponging miR-450b-3p, promoting cardiomyocyte apoptosis and contributing to rat MI development.

Yangxinkang tablet protects against cardiac dysfunction and remodelling after myocardial infarction in rats through inhibition of AMPK/mTOR-mediated autophagy.

Context: Acute myocardial infarction (AMI) is defined as myocardial necrosis. Clinicians use the traditional Chinese patent medicine Yangxinkang Tablet (YXK) to treat chronic heart failure.Objective: To explore the effects of YXK on heart injury following AMI and the underlying mechanisms.Materials and methods: The AMI model was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. Rats were divided into the following five groups: Sham (n = 6), MI (Model, n = 10), AICAR (AMPK agonist, 50 mg/kg/d, i.p., n = 10), Compound C (AMPK inhibitor, 10 mg/kg/d, i.p., n = 10), and YXK (0.72 g/kg/d, gavage, n = 10) groups. Cardiac function, cardiac fibrosis, apoptosis, and expression of p-AMPK, p-mTOR, and autophagy-related proteins was measured after 4 weeks of treatment after the successful modelling of the AMI.Results: Compared to MI group, both YXK and AMPK inhibitor improved cardiac dysfunction and reduced cardiac fibrosis (15.6 ± 2.3; 22.6 ± 4.6 vs. 34.6 ± 4.3%) and myocardial cell apoptosis (12 ± 3.67; 25.6 ± 6.8 vs. 54 ± 4.8%). Futhermore, YXK and AMPK inhibitor significantly decreased p-AMPK expression by 11.05% and 14.64%, LC3II/I by 25.08% and 35.28% and Beclin-1 by 66.71% and 33.85%, increased p-mTOR by 22.14% and 47.46% and p62 by 70.83% and 18.58%.Conclusions: The underlying mechanism appears to include suppression of autophagy via inhibiting AMPK/mTOR signalling, suggesting that YXK may serve as a potentially effective Chinese herbal compound for suppressing cardiac fibrosis in heart injury.

Effect of yangxinkang tablets on chronic heart failure: A multi-center randomized double-blind placebo-controlled trial.

OBJECTIVES: To investigate the safety and efficacy of yangxinkang tablets in patients with chronic heart failure (CHF) and syndrome of qi and yin deficiency, blood stasis, and water retention. METHODS: In a double-blinded, randomized, placebo-controlled, multicenter clinical trail, 228 patients with CHF New York Heart Association (NYHA) class II or III in stage C were assigned by randomized block method to two groups in a 1:1 ratio to undergo either conventional Western treatment or conventional treatment plus yangxinkang tablets for 4 weeks. The outcome measure were effect of cardiac function, Chinese medicine (CM) syndromes, scores of symptoms, signs, and quality of life measured by Minnesota Living with heart failure questionnaire (MLHFQ) before and after the treatment. RESULTS: Totally 112 patients were analyzed in the treatment group and 109 in the control group. They were comparable in NYHA functional class, basic parameters and primary diseases before treatment. Cardiac function and CM syndromes were greatly ameliorated in both groups after treatment. Total effective rates of cardiac function and CM syndrome in the treatment group were significantly higher than those in the control group (P<0.05). Total symptom score and sign score in the treatment group decreased significantly after treatment (P<0.01), which were significantly lower than those in the control group (P<0.05). There were statistically significant differences in post-treatment scores of gasp, cough with phlegm, pulmonary rales and jugular vein engorgement between the two groups (P<0.05 or P<0.01). Three MLHFQ scores decreased significantly in both groups after treatment (P<0.01). Post-treatment total scale score and physical subscale score in the treatment group and the reduction of them showed statistically significant differences (P<0.05) as compared with the control group. There was no significant difference between the two groups in emotional subscale score and the reduction after treatment (P>0.05). There was no obvious adverse reaction in either group noted during the study. CONCLUSIONS: Yangxinkang tablets were safe and efficacious in improving cardiac function, CM syndromes, symptoms, signs, and quality of life in patients with CHF class II or III in stage C on the base of conventional treatment.

Diphenylamine end-capped 1,4-diketo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DPP) derivatives with large two-photon absorption cross-sections and strong two-photon excitation red fluorescence.

Novel donor-pi-bridge-acceptor-pi-bridge-donor (D-pi-A-pi-D)-type 1,4-diketo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DPP) derivatives with end-capping diphenylamine groups have been synthesized and shown to exhibit large two-photon absorption cross-sections over a wide range of wavelengths with strong two-photon excitation red fluorescence.