Effect of Yifei Qinghua Granule on the Tumor Microenvironment in Lung Cancer by Regulating the Inflammatory Pathway.

To investigate the mechanism of action of inflammatory molecules regulating the tumor microenvironment and anti-tumor through Yifei Qinghua granules and phloroglucinol-containing serum intervening in the changes of tumor microenvironment in vitro in the co-culture of lung cancer cells and bone marrow cells.  A549 lung adenocarcinoma cell line and ST2 bone marrow stromal cell line were selected and a transwell chamber was used to establish the co-culture system of the two kinds of cells. They were divided into normal saline, phloroglucinol, Qifei Qinghua granule, and phloroglucinol + Yifei Qinghua granule groups. They were given drug-containing serum interventions respectively. A549 cells and ST2 cells cultured separately were used as control. Flow cytometry was used to detect the proportions of MDSCs and Tregs in bone marrow cells of ST2 cells. ELISA was used to detect the levels of inflammatory factors in the culture supernatant. Western blot was used to detect the expressions of inflammatory pathways in A549 and ST2 cells. ST2 cells and A549 cells were co-cultured. The ratio of MDSCs and Treg in ST2 cells was increased. The levels of some inflammatory factors in the culture supernatant were increased. The expression level of the inflammatory pathway in ST2 cells was increased. However, the expression level of the inflammatory pathway in A549 cells had no obvious change. While Yifei Qinghua granule and phloroglucinol could partially reverse these changes. The combination of the two was more effective than a single drug. The conversion of cells to MDSCs and Treg was accelerated after the co-culture of ST2 cells and A549 cells. The combination of Yifei Qinghua granules with phloroglucinol can reshape the tumor microenvironment, prevent this phenomenon from occurring, reduce inflammatory secretion and inhibit tumor cell growth. This may be related to the inhibition of the expressions of TNF-α/IL-1- and NF-κB/STAT3 inflammatory pathways.

SNHG14 Upregulation Was a Molecular Mechanism Underlying MPP+ Neurotoxicity in Dopaminergic SK-N-SH Cells via SNHG14-miR-519a-3p-ATG10 ceRNA Pathway.

Long non-coding RNA small nuclear RNA host gene 14 (SNHG14) is a novel contributor of dopaminergic neuronal injury in Parkinson's disease. We further explored its role in 1-methyl-4-phenylpyridinium (MPP+)-damaged dopaminergic neurons (DAn) and the possible mechanism involving SNHG14, microRNA (miR)-519a-3p, and autophagy-related 10 (ATG10). MPP+ cytotoxicity was measured by MTS cell viability assay, flow cytometry, and a series of assay kits for detecting apoptosis and oxidative stress. Molecule expression was examined by qPCR and Western blotting, and RNA interaction was predicted by starBase2.0 of ENCORI platform and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. SNHG14 and ATG10 expression was increased, and miR-519a-3p was decreased in MPP+-treated SK-N-SH cells, and SNHG14 knockdown alleviated MPP+-induced SK-N-SH cell damage by regulating cell viability, cell cycle arrest, apoptosis, and oxidative stress. Additionally, antisense RNA of miR-519a-3p abated the suppressive role of SNHG14 knockdown, and ectopic expression of ATG10 counteracted the protective role of miR-519a-3p against MPP+ neurotoxicity. Mechanistically, SNHG14 and ATG10 were competitive endogenous RNAs (ceRNAs) for miR-519a-3p, and ATG10 expression could be positively modulated by SNHG14 via sponging miR-519a-3p. Target silencing SNHG14 and restoring miR-519a-3p could prevent DAn from MPP+ toxicity via regulation of ATG10.