The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.
Background:
Cell death is a fundamental biological phenomenon that contributes to the pathogenesis of various
diseases. Regulation of iron and iron metabolism has received considerable research interests especially concerning the progression of metabolic diseases.
Discussion:
Emerging evidence shows that ferroptosis, a non-apoptotic programmed cell death induced by iron-dependent
lipid peroxidation, contributes to the development of complex diseases such as non-alcoholic steatohepatitis, cardiomyopathy, renal ischemia-reperfusion, and neurodegenerative diseases. Therefore, inhibiting ferroptosis can improve the pathophysiology of associated metabolic diseases. This review describes the vital role of ferroptosis in mediating the development
of certain metabolic diseases. Besides, the potential risk of iron and ferroptosis in atherosclerosis and cardiovascular diseases is also described. Iron overload and ferroptosis are potential secondary causes of death in metabolic diseases. Moreover,
this review also provides potential novel approaches against ferroptosis based on recent research advances.
Conclusion:
Several controversies exist concerning mechanisms underlying ferroptotic cell death in metabolic diseases, particularly in atherosclerosis. Since ferroptosis participates in the progression of metabolic diseases such as non-alcoholic steatohepatitis (NASH), there is a need to develop new drugs targeting ferroptosis to alleviate such diseases.
This study aims to investigate the role of Toll-like receptors (TLRs) on fine particulate matter (PM2.5)-induced inflammatory responses of vascular endothelial cells. Inflammatory factors and TLRs were examined in the aorta of mice after nonsurgical intratracheal instillation of PM2.5 as well as in the human umbilical vein endothelial cells (HUVECs) treated with PM2.5. In addition, the effects of TLR2 and TLR4 inhibitors in the secretion of interleukin 6 (IL-6) and IL-1β and the expression of TLRs were determined in the HUVECs. The results showed that PM2.5 could increase the expression of IL-1β, IL-6, TLR2, and TLR4 in vitro and in vivo. Anti-TLR2 IgG or TAK242, an inhibitor of TLR4, decreased the secretion of IL-1β and IL-6 by HUVECs and reduced the expression of corresponding TLRs. In conclusion, we demonstrate that both TLR2 and TLR4 are involved in PM2.5-induced inflammatory responses of vascular endothelial cells. Inhibition of TLR2 and TLR4 expression has the potential to prevent PM2.5-induced cardiovascular diseases.
Carpesium abrotanoides L. (CA) is widely used as a medicinal plant in Asia. The biological activities of the extract from the roots of Carpesium abrotanoides L. (PCA) and its major components were analyzed in this study. PCA was separated and identified with mass spectrometry. Furthermore, we sought to elucidate the anticancer activity of PCA and its mechanisms. PCA exerted its anti-breast cancer activity through inhibiting the expression of glycolysis-related genes, such as glucose transporter 1, lactate dehydrogenase A, and hexokinase 2. Moreover, PCA downregulated the expression of pyruvate kinase M2 and altered its cellular translocation. We also demonstrated PCA is an inhibitor of the PKM2/hypoxia-inducible factor-1α axis, indicating that PCA is potentially useful as an anti-breast cancer agent.Practical Application: In this study, the extract from roots of Carpesium abrotanoides Linn. (PCA) was shown to have a noticeable anticancer effect against breast cancer in vitro, and PCA exerts the anticancer activity by regulating glucose metabolism and PKM2 expression. These findings indicate that PCA is a promising agent with practical applications in the development of functional food containing Carpesium abrotanoides L. root extracts.
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