ObjectiveTo investigate the protective effect of ellagic acid （EA） against bleomycin （BLM）-induced pulmonary fibrosis and associated pulmonary function impairment in mice， and to elucidate its relationship with the regulation of the interleukin（IL）-17/ nuclear factor （NF）-κB/ matrix metalloproteinase （MMP）9 signaling axis. MethodsA pulmonary fibrosis model was established in male C57BL/6J mice via intratracheal BLM injection. Interventions included IL-17 neutralizing antibody， Ixekizumab， SB-3CT， PDTC， or EA were used to modulate the IL-17/NF-κB/MMP9 signaling axis. Pathological changes in lung tissue were observed via HE， Masson， and Sirius red staining. Pulmonary function was assessed using a pulmonary function test （PFT）. Western blot and qRT-PCR were employed to detect related protein and gene expression. Network pharmacology was utilized to predict the potential targets of EA. A protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape. Molecular docking was performed to validate the binding capability of EA to core targets. ResultsBLM successfully induced obvious pulmonary fibrosis and lung dysfunction in mice， significantly elevating the level of the pro-inflammatory cytokine IL-17. This was associated with the activation of the transcription factor NF-κB p65， leading to the upregulation of the pro-fibrotic factor MMP9. Inhibition of the IL-17/NF-κB/MMP9 signaling axis markedly alleviated the degree of pulmonary fibrosis. EA intervention significantly suppressed the BLM-induced increase in IL-17， blocked the activation of the NF-κB/MMP9 pathway， and consequently reduced lung fibrotic lesions and improved pulmonary function. ConclusionEA may effectively ameliorate BLM-induced pulmonary fibrosis and lung dysfunction in mice， likely by inhibiting the inflammatory and fibrotic responses mediated through the IL-17/NF-κB/MMP9 signaling pathway.

OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (P<0.05), and its high expression was positively correlated with cancer progression (P<0.001) and a lowered postoperative 5-year survival rate of the patients (P<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
Humans ; Stomach Neoplasms/metabolism* ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Gene Expression Regulation, Neoplastic