Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

PURPOSE: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. METHODS: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. CONCLUSIONS: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

[Relation of advanced oxidation protein products with VEGF and TGF-ß1 in colon cancer cells exposed to intermittent hypoxia].

OBJECTIVE: To investigate the association of advanced oxidation protein products (AOPP) with oxidative stress in colon cancer cells exposed to intermittent hypoxia (IH). METHODS: Colon cancer SW480 cells were exposed to IH, continuous hypoxia, or normoxia. Enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of AOPP and vascular endothelial growth factor (VEGF), xanthine oxidase assay was used to determine malonaldehyde (MDA) and glutathione peroxidase (GSH-PX), and Western blotting and immunofluorescence assay were performed for detection of transforming growth factor-ß(1) (TGF-ß(1)) expression. RESULTS: Compared with the normoxia group, the two hypoxia groups showed significantly increased AOPP and MDA levels (P<0.05) and lowered SOD and GSH-PX levels (P<0.05). The concentration of AOPP was positively correlated to MDA, VEGF, and TGF-ß(1) levels (P<0.05), but inversely to SOD. No significant correlation was found between AOPP and GSH-PX levels. CONCLUSION: Compared with continuous hypoxia, IH results in more obvious protein oxidation in relation to oxidative stress. The increased expression of VEGF and TGF-ß(1) in the context of hypoxia is closely related to AOPP level.