Naringenin ameliorates vascular senescence and atherosclerosis involving SIRT1 activation.

Objectives: This study was to explore the potential effects and mechanism of naringenin against vascular senescence in atherosclerosis focusing on the SIRT1-mediated signalling pathway.

Methods: Aged apoE-/- mice were administrated with naringenin continuously for three months. Lipid parameters in serum and pathological changes and associated protein expression in aorta were examined.

MDM2-Mediated Ubiquitination of RXRβ Contributes to Mitochondrial Damage and Related Inflammation in Atherosclerosis.

A novel function of retinoid X receptor beta (RXRβ) in endothelial cells has been reported by us during the formation of atherosclerosis. Here, we extended the study to explore the cellular mechanisms of RXRβ protein stability regulation. In this study, we discovered that murine double minute-2 (MDM2) acts as an E3 ubiquitin ligase to target RXRβ for degradation.

Roles of necroptosis in alcoholic liver disease and hepatic pathogenesis.

Chronic alcohol consumption can cause alcoholic liver disease (ALD), leading to morbidity and mortality worldwide. Complex disease progression of ALD varies from alcoholic fatty liver to alcoholic steatohepatitis, eventually contributing to fibrosis and cirrhosis. Accumulating evidence revealed that necroptosis, a way of programmed cell death different from apoptosis and traditional necrosis, is involved in the underlying pathogenic molecular mechanism of ALD.

Activation of UQCRC2-dependent mitophagy by tetramethylpyrazine inhibits MLKL-mediated hepatocyte necroptosis in alcoholic liver disease.

Hepatocyte necroptosis is a core pathogenetic event during alcoholic liver disease. This study was aimed to explore the potential of tetramethylpyrazine (TMP), an active hepatoprotective ingredient extracted from Ligusticum Wallichii Franch, in limiting alcohol-triggered hepatocyte necroptosis and further specify the molecular mechanism. Results revealed that TMP reduced activation of receptor-interacting protein kinase 1 (RIPK1)/RIPK3 necrosome in ethanol-exposed hepatocytes and phosphorylation of mixed-lineage kinase domain-like protein (MLKL), which thereby diminished necroptosis and leakage of damage-associated molecular patterns.

Pterostilbene attenuates RIPK3-dependent hepatocyte necroptosis in alcoholic liver disease via SIRT2-mediated NFATc4 deacetylation.

Receptor-interacting protein kinase (RIPK) 3-dependent necroptosis plays a critical role in alcoholic liver disease. RIPK3 also facilitates steatosis, oxidative stress, and inflammation. Pterostilbene (PTS) has favorable hepatoprotective activities.

NFATc4 mediates ethanol-triggered hepatocyte senescence.

Background: Hepatocyte senescence is a core event that mediates the occurrence and development of alcoholic liver disease. Nuclear factor of activated T-cells 4 (NFATc4) is a key driver of nonalcoholic steatohepatitis. However, little was known about the implication of NFATc4 for alcoholic liver disease.