Search

Acute myocardial infarction is regarded as myocardial necrosis resulting from myocardial ischemia/reperfusion (I/R) damage and retains a major cause of mortality. Neferine, which was extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., has been reported to possess a broad range of biological activities. However, its underlying mechanism on the protective effect of I/R has not been fully clarified. A hypoxia/reoxygenation (H/R) model with H9c2 cells closely simulating myocardial I/R injury was used as a cellular model. This study intended to research the effects and mechanism underlying neferine on H9c2 cells in response to H/R stimulation. Cell Counting Kit‐8 and lactate dehydrogenase (LDH) release assays were employed to measure cell viability and LDH, respectively. Apoptosis and reactive oxygen species (ROS) were determined by flow cytometry analysis. Oxidative stress was evaluated by detecting malondialdehyde, superoxide dismutase, and catalase. Mitochondrial function was assessed by mitochondrial membrane potential, ATP content, and mitochondrial ROS. Western blot analysis was performed to examine the expression of related proteins. The results showed that hypoxia/reoxygenation (H/R)‐induced cell damage, all of which were distinctly reversed by neferine. Moreover, we observed that neferine inhibited oxidative stress and mitochondrial dysfunction induced by H/R in H9c2 that were concomitant with increased sirtuin‐1 (SITR1), nuclear factor erythroid 2‐related factor 2 (Nrf2), and heme oxygenase‐1 expression. On the contrary, silencing the SIRT1 gene with its small interferingRNA eliminated the beneficial effects of neferine. It is concluded that neferine preconditioning attenuated H/R‐induced cardiac damage via suppressing apoptosis, oxidative stress, and mitochondrial dysfunction, which may be partially ascribed to the activation of SIRT1/Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: We aim to evaluate the association between CORIN and heart failure. Methods: This study used PubMed, EMBASE, Cochrane database, and China National Knowledge Database (CNKI) to search for CORIN-related full-text articles with heart failure patients. We drew forest plots, performed sensitivity and bias analyses based on the included data. Next, we used Review Manager 5.2 software to assess the heterogeneity among selected articles. Results: Our meta-analysis results showed there was significant relationship between CORIN and heart failure (HF). There was significant difference of CORIN between heart failure group and control group (MD = −293.88, 95% confidence interval [-380.26, −207.49], p <.00001; heterogeneity p <.0001, I2= 97%) and there was significant difference in CORIN between ischemic group and non-ischemic group (MD = 88.79, 95% confidence interval [70.46107.12], heterogeneity p <.000, p = 0.94, l2= 0%). In subgroup analysis, there were significant differences in three different HF levels. Limited publication bias was observed, and this study was robust. Conclusion: In short, the results showed that CORIN was closely related with heart failure and might be helpful in the diagnosis of heart failure. [ABSTRACT FROM AUTHOR]

Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4. In vitro and in vivo, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF. [ABSTRACT FROM AUTHOR]

TUG1 has been reported to play an important role in various cancer types. However, the study about the function of lncRNA TUG1 in myocardial infarction is limited. This study was aimed to investigate the role of TUG1 in H9c2 cell injury induced by hypoxia and explore its possible molecular mechanism. The proliferation assay, migration assay, invasion assay, and apoptosis assay were performed. RT-PCR was used to determine the relative RNA expression of TUG1, miR-124 and Hic-5. Western blotting was used to detect the expression levels of apoptotic proteins, Hic-5, Sp1, and Survivin. Hypoxia could significantly decrease cell proliferation, migration and invasion and increase H9c2 cell apoptosis. Knock-down of TUG1 promoted the cell damage induced by hypoxia. miR-124 was the direct target of TUG1 and down-regulated by TUG1. TUG1 silence aggravated hypoxia injury by up-regulating miR-124. In addition, Hic-5 was the target of miR-124 and negatively regulated by miR-124. Our findings showed that Hic-5 over-expression could significantly induce increases in cell viability, migration and invasion, and induce decrease in cell apoptosis after hypoxia damage. Over-expression of Hic-5 could increase the expression of Sp1 and Survivin, which inhibited the cell apoptosis, thereby reducing the cell damage induced by hypoxia. [ABSTRACT FROM AUTHOR]

Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea , which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe 2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4 . In vitro and in vivo , ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ma et al.)

Myocardial infarction (MI) is one of the leading causes of death. Wilms' tumor 1-associating protein (WTAP), one of the components of the m 6 A methyltransferase complex, has been shown to affect gene expression via regulating mRNA modification. Although WTAP has been implicated in various diseases, its role in MI is unclear. In this study, we found that hypoxia/reoxygenation (H/R) time-dependently increased WTAP expression, which in turn promoted endoplasmic reticulum (ER) stress and apoptosis, in human cardiomyocytes (AC16). H/R effects on ER stress and apoptosis were all blocked by silencing of WTAP, promoted by WTAP overexpression, and ameliorated by administration of ER stress inhibitor, 4-PBA. We then investigated the underlying molecular mechanism and found that WTAP affected m 6 A methylation of ATF4 mRNA to regulate its expression, and that the inhibitory effects of WTAP on ER stress and apoptosis were ATF4 dependent. Finally, WTAP's effects on myocardial I/R injury were confirmed in vivo . WTAP promoted myocardial I/R injury through promoting ER stress and cell apoptosis by regulating m 6 A modification of ATF4 mRNA. These findings highlight the importance of WTAP in I/R injury and provide new insights into therapeutic strategies for MI.

Background: Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in heart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells., Methods: THRIL, miR-99a and Brahma-related gene 1 (Brg1) expressions in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated. Cell viability, migration and invasion, and apoptotic cells were respectively measured by trypan blue exclusion assay, transwell migration assay and flow cytometry assay. Dual luciferase reporter assay was conducted to verify the interaction between miR-99a and THRIL. Furthermore, levels of apoptosis-, PI3K/AKT and mTOR pathways-related factors were measured by western blotting., Results: Hypoxia induced an increase of THRIL but a reduction of miR-99a and Brg1. THRIL inhibition significantly attenuated hypoxia-induced cell injuries, as increased cell viability, migration and invasion, and decreased cell apoptosis. THRIL negatively regulated miR-99a expression through sponging with miR-99a binding site, and miR-99a inhibition abolished the protective effects of THRIL knockdown against hypoxia-induced injury in H9C2 cells. Furthermore, miR-99a positively regulated the expression of Brg1. Brg1 inhibition promoted hypoxia-induced cell injuries, while Brg1 overexpression alleviated hypoxia-induced cell injuries. Moreover, Brg1 overexpression activated PI3K/AKT and mTOR pathways., Conclusions: This study demonstrated that THRIL inhibition represented a protective effect against hypoxia-induced injuries in H9C2 cells by up-regulating miR-99a expression.

Ovarian cancer causes more deaths than any other gynecological disorder. Perturbed glycosylation is one of the hallmarks of this malignancy. Kallikrein 6 (KLK6) elevation in serum is a diagnostic and prognostic indicator in ovarian cancer. The majority of ovarian carcinomas express high levels of KLK6, which diffuses into the circulation. Under physiological conditions, KLK6 is expressed highly in the central nervous system and found at high levels in cerebrospinal fluid from where it enters the circulation. Our aim was to characterize and compare the N-glycosylation status of this protein in ovarian cancer ascites fluid and cerebrospinal fluid. Anion-exchange chromatography was used to reveal different post-translational modifications on the two isoforms. Mobility gel shift Western blot analysis coupled with glycosidase digestion showed that the molecular weight difference between the two isoforms was because of differential glycosylation patterns. The presence of a single N-glycosylation site on KLK6 was confirmed by site-directed mutagenesis. Using a Sambucus nigra agglutinin-monoclonal antibody sandwich enzyme-linked immunosorbent assay approach, it was shown that ovarian cancer-derived KLK6 was modified with alpha2-6-linked sialic acid. The structure and composition of glycans of both KLK6 isoforms was elucidated by glycopeptide monitoring with electrospray ionization-Orbitrap tandem mass spectrometry. Therefore, the extensive and almost exclusive sialylation of KLK6 from ovarian cancer cells could lead to the development of an improved biomarker for the early diagnosis of ovarian carcinoma.