Fig 2: Schematic diagram of miR-92b action mechanism. LPS activates IRAKs and TRAF6 through binding to TLR4, leading to NF-?B entering the nucleus and inducing inflammation and cell apoptosis. miR-92b activates the PI3K/AKT/ß-catenin pathway by directly targeting PTEN, thereby blocking TLR4/NF-?B-mediated inflammation and apoptosis and then alleviating the inflammatory injury.

Fig 3: PDCC4 reverses the dysregulation of the PI3K/mTOR/HIF1a pathway in response to TNF-a treatment. (A) HUVECs in the TNF-a group and TNF-a + PDCC4 group were sent for RNA-sequencing analysis. Differentially expressed genes were identified with cut-off values of P<0.05 and |logFC|>1. (B) A heat map of the differentially expressed genes is presented, in which red represents high expression and blue represents low expression. (C) Gene Ontology and (D) Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed with the differentially expressed genes. (E) Immune blotting indicated that the dysregulation of the PI3K/mTOR/HIF1a pathway induced by TNF-a was reversed by PDCC4 treatment (n=3 per group). *P<0.05 vs. negative control group; #P<0.05 and ##P<0.01 vs. TNF-a (+) group. HUVEC, human umbilical vein endothelial cells; PDCC4, peptide derived from complement C4 A chain; HIF1a, hypoxia inducible factor-1a; p-, phosphorylated.

Fig 4: OMT protects H9c2 cardiomyocytes exposed to H/R by activating the Akt/GSK3ß/Nrf2/HO-1 pathway. (A) After H/R injury and treatment with different concentrations of OMT, the levels of proteins involved in the PI3K/Akt/GSK3ß pathway were detected using western blotting. (B) The expression of (a) PI3K, (b) Akt and (c) GSK3ß mRNAs measured using RT-qPCR. (C) In addition, the levels of Nrf2 and HO-1 proteins, which are downstream targets of the PI3K/Akt/GSK3ß pathway, were detected using western blotting and (D) the expression of (a) Nrf2 and (b) HO-1 mRNAs were measured using RT-qPCR. *P<0.05 compared with the control group; #P<0.05 compared with the model group. OMT, oxymatrine; H/R, hypoxia/reoxygenation; GSK3ß, glycogen synthase kinase-3ß; Nrf2, nuclear factor erythroid-2-related factor 2; HO-1, heme oxygenase-1; PI3K, phosphatidylinositol 3-kinase; RT-qPCR, reverse transcription-quantitative PCR.

Fig 5: PDCC4 attenuates the endothelial dysfunction induced by TNF-a via the PI3K/mTOR/HIF1a pathway. (A) Proliferative HUVECs were treated with EdU, representative fluorescent images were captured, and the rate of EdU labelling calculated. PDCC4 attenuated the antiproliferative effect of TNF-a, which was inhibited by LY294002 (n=3 per group). Scale bar, 50 µm. (B) Representative images of wound healing were captured at 0 and 24 h after scratching, and the wound healing rate was calculated. PDCC4 attenuated the antimigration effect of TNF-a, which was inhibited by LY294002 (n=3 per group). Scale bar, 100 µm. (C) Representative fluorescent images of HUVECs after staining with JC-1 are illustrated, and the mitochondrial membrane potential is presented as the ratio of red to green fluorescent density. LY294002 inhibited PDCC4's ability to increase the mitochondrial membrane potential of HUVECs exposed to TNF-a (n=3 per group). Scale bar, 50 µm. (D) Representative images of the tube formation assay indicated that PDCC4 prevented HUVEC tube formation from being impaired by TNF-a, which was inhibited by LY294002 (n=3 per group). Scale bar, 100 µm. **P<0.01 vs. negative control group; #P<0.05 and ##P<0.01 vs. TNF-a (+) group; &P<0.05 vs. TNF-a (+) + PDCC4 group. HUVEC, human umbilical vein endothelial cells; PDCC4, peptide derived from complement C4 A chain; EdU, 5-ethynyl-2'-deoxyuridine.