Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways

Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation end-products(AGEs),an important pathogenic factor of DCM,were found to induce ferroptosis in engineered cardiac tissues(ECTs),as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7 A11 levels.Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy.Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction.Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM.Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes.Nuclear factor erythroid 2-related factor 2(NRF2)activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7 A11 levels.The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase(AMPK)-dependent.These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM;sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

Effects of Chromium on the Microstructures and Mechanical Properties of AlCoCrxFeNi2.1 Eutectic High Entropy Alloys

In the present study,a series of AlCoCrxFeNi2.1(x=0,0.25,0.5,0.75,1.0)eutectic high entropy alloys(EHEAs)have been designed and prepared.And the effect of Cr content on the microstructures and mechanical properties of the AlCoCrxFeNi2.1 alloys was systematically investigated.The results indicate that the AlCoCrxFeNi2.1(x>0)alloys exhibit almost complete lamellar eutectic microstructures with a mixture structure of FCC and B2 phases.And the AlCoFeNi2.1 alloy without Cr element exhibited a hypoeutectic microstructure with a primary B2 phase.In addition,the eutectic microstructures for AlCoCrxFeNi2.1 eutectic alloys do not change significantly.The room temperature compressive tests results show that with an increase in Cr content(from x=0 to x=1.0),the yield strength will first decrease,and thereafter increase.The trend is the opposite with the fracture strength and plastic strain.They show an increase trend at first,and then decrease.The AlCoCr0.5 FeNi2.1(Cr0.5)alloy shows the best comprehensive mechanical properties.The tensile yield strength,fracture strength,and elongation are 536.5 MPa,1062 MPa,and 13.8%,respectively.Furthermore,the Cr0.5 alloy also displays a high strength with a yield strength of 362 MPa at 700℃.In summary,by changing the Cr content,AlCoCrxFeNi2.1 eutectic high entropy alloys with excellent comprehensive mechanical properties were obtained and prepared.