ox-LDL induces autophagy-mediated apoptosis by suppressing secretagogin-regulated autophagic flux in pancreatic ß-cells.

Lipotoxicity has been shown to induce the loss of functional ß-cell mass and lead to type 2 diabetes, but the mechanism remains unknown. In this study, we aim to explore the role of secretagogin (SCGN) in lipotoxicity-induced ß-cell injury. Our results indicate that ox-LDL treatment leads to autophagic cell death, as evidenced by decreased cell viability, aggravated cell apoptosis, and the accumulation of the p62 protein in MIN6 cells. LysoTracker Red staining, TEM and mRFP-GFP-LC3 assays demonstrate that autophagic flux is blocked in ox-LDL-treated MIN6 cells. Intriguingly, SCGN is significantly decreased in MIN6 cells under lipotoxic conditions. Additionally, siRNA-guided SCGN knockdown blocks autophagic flux triggered by rapamycin, while SCGN restoration alleviates autophagic flux retardation and mitigates cell apoptosis. The physical interaction between SCGN and SNAP29 is validated by bioinformatics analysis, coimmunoprecipitation assay and SCGN knockdown test. Downregulation of SCGN expression reduces the interaction of these two proteins. Taken together, our results indicate that ox-LDL treatment induces apoptotic ß-cell death by blocking autophagic flux dependent on SCGN downregulation. SCGN administration prevents lipotoxic ß-cell injury and may be a potential therapeutic strategy to promote ß-cell expansion in type 2 diabetes.

Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Mechanisms of ferroptosis regulating oxidative stress and energy metabolism in myocardial ischemia-reperfusion injury and a novel perspective of natural plant active ingredients for its treatment.

Acute myocardial infarction remains the leading cause of death in humans. Timely restoration of blood perfusion to ischemic myocardium remains the most effective strategy in the treatment of acute myocardial infarction, which can significantly reduce morbidity and mortality. However, after restoration of blood flow and reperfusion, myocardial injury will aggravate and induce apoptosis of cardiomyocytes, a process called myocardial ischemia-reperfusion injury. Studies have shown that the loss and death of cardiomyocytes caused by oxidative stress, iron load, increased lipid peroxidation, inflammation and mitochondrial dysfunction, etc., are involved in myocardial ischemia-reperfusion injury. In recent years, with the in-depth research on the pathology of myocardial ischemia-reperfusion injury, people have gradually realized that there is a new form of cell death in the pathological process of myocardial ischemia-reperfusion injury, namely ferroptosis. A number of studies have found that in the myocardial tissue of patients with acute myocardial infarction, there are pathological changes closely related to ferroptosis, such as iron metabolism disorder, lipid peroxidation, and increased reactive oxygen species free radicals. Natural plant products such as resveratrol, baicalin, cyanidin-3-O-glucoside, naringenin, and astragaloside IV can also exert therapeutic effects by correcting the imbalance of these ferroptosis-related factors and expression levels. Combining with our previous studies, this review summarizes the regulatory mechanism of natural plant products intervening ferroptosis in myocardial ischemia-reperfusion injury in recent years, in order to provide reference information for the development of targeted ferroptosis inhibitor drugs for the treatment of cardiovascular diseases.