Cold stress causes liver damage by inducing ferroptosis through the p38 MAPK/Drp1 pathway.

Acute extreme cold exposure impairs human health and even causes hypothermia which threatens human life. Liver, as a hub in metabolism and thermogenesis, is vital for cold acclimatization. Although accumulating evidence has suggested that cold exposure can cause liver damage, the underlying mechanisms remain poorly understood. This study investigated the role and underlying mechanisms of ferroptosis in cold stress-induced liver damage. To evaluate the role of ferroptosis in cold stress-induced liver damage, rats were pretreated with ferroptosis inhibitor liproxstatin-1 (Lip-1) before exposed to -10 °C for 8 h. Core body temperature was recorded. The levels of ferroptosis-related indicators were examined with the corresponding assay kits or by western blotting. Hepatic pathological changes were analyzed by hematoxylin-eosin staining and ultrastructural observation. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess liver function. Rats were also pretreated with p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or Dynamin-related protein 1 (Drp1) inhibitor Mdivi-1 to determine the underlying mechanisms. We found that Lip-1 inhibited ferroptosis, attenuated hepatic pathological damages and blocked the increased ALT and AST levels in cold-exposed rats. Moreover, Mdivi-1 inhibited mitochondrial fission and suppressed ferroptosis. Furthermore, SB203580 and Mdivi-1 administration alleviated cold stress-induced liver injury. Our results suggested that cold stress caused liver damage partially by inducing ferroptosis through the p38 MAPK/Drp1 pathway. These findings might provide an effective preventive and therapeutic target for cold stress-induced liver injury.

Inhibitory effect of a natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid against the attachment phase of biofilm formation of Staphylococcus aureus through targeting sortase A.

The antibiofilm activity and molecular mechanism of a natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid (CHQA) against Staphylococcus aureus were investigated in this study. Crystal violet staining and XTT reduction assay demonstrated that CHQA could prominently prevent the biofilm formation of S. aureus accompanied with decrease in metabolic activity of biofilm cells. Meanwhile, microscopic observations revealed that CHQA caused a huge collapse on the architecture of S. aureus biofilm. Moreover, CHQA specifically inhibited the initial attachment phase of biofilm development and reduced S. aureus adhesion to fibrinogen. Fluorescence resonance energy transfer assay and molecular simulation showed that CHQA inhibited the activity of S. aureus sortase A (SrtA) through binding to the active region via non-covalent interactions. Additionally, CHQA efficiently reduced S. aureus attachment to stainless steel. Hence, these results suggested CHQA as a potential bacterial biofilm inhibitor which achieved antibiofilm activity through affecting the attachment phase of biofilm formation by targeting SrtA.