Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

Hemostatic effect of collagen sponge on liver trauma / 中国组织工程研究

BACKGROUND: iRegene collagen sponge exhibits stable physical and chemical properties, and has passed the test by the State Food and Drug Administration of China. OBJECTIVE: To study the hemostatic effect and the biocompatibility of the iRegene collagen sponge on a liver wound by means of rat models. METHODS: Liver trauma bleeding models were made in 21 Sprague-Dawley rats. These model rats were randomized into three groups (n=7 per group): experimental group with implantation and external application of iRegene collagen sponge; positive control group with implantation of medical collagen sponge and external application of iRegene collagen sponge; blank control group with external application of medical gauze. The bleeding time and amount on the liver wounds were observed. Histological observation on the liver wound was performed at 7, 14, 28 days after intervention. RESULTS AND CONCLUSION: The bleeding time was shorter in the experimental group than the positive control group (P ≤ 0.05). Beyond that, there was no difference in the bleeding amount and time among the three groups. Histological findings on the liver wound showed that the iRegene collagen sponge in the experimental group was completely wrapped with fibrous connective tissues and began to degrade at 7 days after intervention, the Inflammatory cell infiltration mainly occurred in neutrophils, and new capillaries were observed in peripheral connective tissues; at 14 days after intervention, the fibrous connective tissues became remarkably thickened, the number of neurophils was reduced, and the number of macrophages was increased; at 28 days after intervention, the iRegene collagen sponge degraded completely, most of the liver tissues recovered, and there were macrophages, monocytes, fibroblasts and capillaries in the inflammatory connective tissues adjacent to a part of liver tissues. Similar findings were observed in the positive control group. In the blank control group, there were obvious connective tissues on the wound and red blood cells in the liver sinus, and occasionally liver tissue bleeding and vacuolar degeneration were visible; at 28 days after intervention, there were thickened connective tissues on the wound, red blood cells in the liver sinus and reversed hepatic stellate cells. To conclude, the iRegene collagen sponge possesses effective hemostatic effects on liver wounds and shows good histocompatibility.

Hemostatic effect of collagen sponge on liver trauma / 中国组织工程研究

BACKGROUND: iRegene collagen sponge exhibits stable physical and chemical properties, and has passed the test by the State Food and Drug Administration of China. OBJECTIVE: To study the hemostatic effect and the biocompatibility of the iRegene collagen sponge on a liver wound by means of rat models. METHODS: Liver trauma bleeding models were made in 21 Sprague-Dawley rats. These model rats were randomized into three groups (n=7 per group): experimental group with implantation and external application of iRegene collagen sponge; positive control group with implantation of medical collagen sponge and external application of iRegene collagen sponge; blank control group with external application of medical gauze. The bleeding time and amount on the liver wounds were observed. Histological observation on the liver wound was performed at 7, 14, 28 days after intervention. RESULTS AND CONCLUSION: The bleeding time was shorter in the experimental group than the positive control group (P ≤ 0.05). Beyond that, there was no difference in the bleeding amount and time among the three groups. Histological findings on the liver wound showed that the iRegene collagen sponge in the experimental group was completely wrapped with fibrous connective tissues and began to degrade at 7 days after intervention, the Inflammatory cell infiltration mainly occurred in neutrophils, and new capillaries were observed in peripheral connective tissues; at 14 days after intervention, the fibrous connective tissues became remarkably thickened, the number of neurophils was reduced, and the number of macrophages was increased; at 28 days after intervention, the iRegene collagen sponge degraded completely, most of the liver tissues recovered, and there were macrophages, monocytes, fibroblasts and capillaries in the inflammatory connective tissues adjacent to a part of liver tissues. Similar findings were observed in the positive control group. In the blank control group, there were obvious connective tissues on the wound and red blood cells in the liver sinus, and occasionally liver tissue bleeding and vacuolar degeneration were visible; at 28 days after intervention, there were thickened connective tissues on the wound, red blood cells in the liver sinus and reversed hepatic stellate cells. To conclude, the iRegene collagen sponge possesses effective hemostatic effects on liver wounds and shows good histocompatibility.