Curcumin Improves Diabetic Cardiomyopathy by Inhibiting Pyroptosis through AKT/Nrf2/ARE Pathway.

This study is aimed at exploring whether curcumin can regulate the AKT pathway, promote the transfer of Nrf2 into the nucleus, and inhibit cell pyroptosis in diabetic cardiomyopathy. Diabetic rats and cardiomyocytes were treated with curcumin to study its effect on myocardial pyroptosis. Whether curcumin can promote the transfer of Nrf2 into the nucleus through AKT pathway regulation was assessed by western blotting and immunofluorescence. The Nrf2 knockout vector and ml385 were used to block the Nrf2 pathway, and the differences between the different groups in the expression of pyroptosis protein, cell activity, and incidence of apoptosis were evaluated to verify the relationship between the effect of curcumin on pyroptosis inhibition and the Nrf2 pathway. Curcumin promoted the transfer of Nrf2 into the nucleus through the AKT pathway and increased the expression of the antioxidant factors HO-1 and GCLC. These effects reduced reactive oxygen species accumulation and mitochondrial damage in diabetic myocardium and inhibited diabetes-induced pyroptosis. However, in cardiomyocytes with a blocked Nrf2 pathway, the ability of curcumin to inhibit pyroptosis was significantly reduced, and the protective effect on the cells was lost. Curcumin can reduce the accumulation of superoxide in the myocardium through AKT/Nrf2/ARE pathway activation and inhibit pyroptosis. It also has a role in diabetic cardiomyopathy treatment. This study provides new directions for evaluating the mechanism of diabetic cardiomyopathy and treating diabetic myocardium.

Refined metabolite profiling in the collateral circulation of chronic total occlusion of coronary arteries: Insights from a metabolomics investigation.

Background and aims: To investigate the disparities in coronary collateral circulation (CCC) and peripheral serum metabolites among patients presenting with chronic total occlusion (CTO) of the coronary arteries, a non-targeted metabolic approach was employed. Methods: A cohort of 22 patients diagnosed with CTO of coronary arteries in the context of coronary heart disease (CHD) was selected for blood sample collection from CCC and peripheral arteries. The patients were categorized into two groups, namely CTO-C and CTO-P. The Waters UPLC I-Class Plus is combined with the Q Exactive high-resolution mass spectrometer for metabolite separation and detection. The acquired raw data from mass spectrometry is subsequently imported into Compound Discoverer 3.2 software for comprehensive analysis, which seamlessly integrates the BGI Metabolome Database (BMDB), mzCloud database, and ChemSpider online database. Subsequently, the identified differential metabolites were subjected to a metabolic pathway enrichment analysis, as documented in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: A total of 403 differential metabolites were identified in CCC and peripheral serum samples from patients with CTO of coronary arteries in CHD. Compared to the CTO-P group, the CTO-C group exhibited decreased levels of metabolites such as Testosterone, dehydroepiandrosterone (DHA), deoxyacetone, while demonstrating increased levels of metabolites including Progesterone, androstanone, l-threonine. The biosynthesis pathway of steroid hormones emerges as the key metabolic pathway significantly associated with differential metabolites. Conclusions: Through metabolomics analysis, distinct differences in the CCC and peripheral serum metabolites have been identified among patients with CTO of coronary artery. Notably, a significant association between the steroid hormone biosynthesis pathway and CCC has been observed.

Curcumin Attenuates Ferroptosis-Induced Myocardial Injury in Diabetic Cardiomyopathy through the Nrf2 Pathway.

Diabetes causes lipid peroxide to accumulate within cardiomyocytes. Furthermore, lipid peroxide buildup is a risk factor for ferroptosis. This study is aimed at examining whether curcumin can ameliorate ferroptosis in the treatment of diabetic cardiomyopathy. Hematoxylin and eosin and Masson sections were used to examine the morphology, arrangement, and degree of fibrosis of the myocardium of diabetic rabbit models. The expression levels of nuclear Nrf2, Gpx4, Cox1, and Acsl4 in diabetic animal and cell models were quantitatively analyzed using immunofluorescence and western blotting. Nrf2-overexpression lentivirus vectors were transfected into cardiomyocytes, and the protective effects of curcumin and Nrf2 on cardiomyocytes under high glucose stimulation were assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling and reactive oxygen species probes. Diabetes was found to disorder myocardial cell arrangement and significantly increase the degree of myocardial fibrosis and collagen expression in myocardial cells. Curcumin treatment can increase nuclear transfer of Nrf2 and the expression of Gpx4 and HO-1, reduce glucose induced myocardial cell damage, and reverse myocardial cell damage caused by the ferroptosis inducer erastin. This study confirmed that curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.

Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway.

The present study investigated whether quercetin promotes the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) to inhibit pyroptosis progression and ameliorate diabetic cardiomyopathy. We evaluated the protective effects of quercetin against diabetic cardiomyopathy by analyzing the expression of pyroptosis pathway proteins, myocardial cell apoptosis rate, degree of myocardial fibrosis, and serum inflammatory indices in the hearts of model rats with diabetes. We evaluated the expression of Nrf2 in the nucleus of cardiomyocytes and H9C2 cells to clarify the role of quercetin in promoting the nuclear translocation of Nrf2. In addition, we coincubated cardiomyocytes with the Nrf2 inhibitor ML385 to confirm that quercetin inhibits the diabetes-induced cardiomyocyte pyroptosis via the Nrf2 pathway. We found that quercetin promoted the nuclear translocation of Nrf2 in cardiac cells of diabetic rats, increased the expression of the antioxidant proteins HO-1, GCLC, and SOD, reduced the accumulation of ROS and the degree of cardiomyocyte apoptosis, and alleviated diabetes-induced cardiac fibrosis. The therapeutic effects of quercetin were further validated in H9C2 cardiomyocytes. Interestingly, ML385 prevented the beneficial effects of quercetin on diabetic cardiomyopathy, further indicating that the quercetin-mediated inhibition of pyroptosis requires the participation of the Nrf2 pathway. In conclusion, quercetin promoted the nuclear translocation of Nrf2, increased the expression of antioxidant factors in cells, and inhibited the progression of cell pyroptosis, thereby alleviating diabetic cardiomyopathy.

Expression of miRNAs in plasma exosomes derived from patients with atrial fibrillation.

BACKGROUND: Studies have revealed the association between exosomes and cardiovascular diseases. However, the typical changes of plasma miRNAs in patients with atrial fibrillation (AF) are still controversial, the use of exosomal miRNAs to diagnose and predict the prognosis of AF has not been described. HYPOTHESIS: We hypothesized that there were differences in the exosomal miRNAs between AF and normal sinus rhythm (SR) patients, which might be used as the novel biomarkers to reflect the progression of AF. METHODS: miRNAs were isolated from the plasma of patients, and the target genes of differential miRNAs via enrichment analysis to discover potential pathogenesis related to AF. Combined with high-throughput sequencing results, real-time PCR was used to verify the relative expression of target miRNAs in patients. RESULTS: This study confirmed that the expression of plasma-derived exosomal miRNAs between patients with AF and SR were different. Target gene enrichment analysis suggested that the target genes of 20 miRNAs, which were significantly upregulated were mainly enriched in biological processes such as gene expression process, inflammation response, enzyme modification, etc. Meanwhile, mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and other pathways were highly enriched. The expressions of miR-92b-3p, miR-1306-5p, and miR-let-7b-3p had differences between patients with AF and SR. CONCLUSION: These miRNAs and target genes were involved in the process of AF through affecting biological processes such as energy metabolism, lipid metabolism, inflammation, and enzyme activity. It suggested that the exosomal miRNAs might be used as the novel biomarkers to reflect the progression of AF.