ABSTRACT
BACKGROUND: Studies have shown that mitochondrial function and macrophages may play a role in the development of idiopathic pulmonary fibrosis (IPF). However, the understanding of the interactions and specific mechanisms between mitochondrial function and macrophages in pulmonary fibrosis is still very limited. METHODS: To construct a prognostic model for IPF based on Macrophage- related genes (MaRGs) and Mitochondria-related genes (MitoRGs), differential analysis was performed to achieve differentially expressed genes (DEGs) between IPF and Control groups in the GSE28042 dataset. Then, MitoRGs, MaRGs and DEGs were overlapped to screen out the signature genes. The univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) algorithm were implemented to achieve key genes. Furthermore, the independent prognostic analysis was employed. The ingenuity pathway analysis (IPA) was employed to further understand the molecular mechanisms of key genes.Next, the immune infiltration analysis was implemented to identify differential immune cells between two risk subgroups. RESULTS: There were 4791 DEGs between IPF and Control groups. Furthermore, 26 signature genes were achieved by the intersection processing. Three key genes including ALDH2, MCL1, and BCL2A1 were achieved, and the risk model based on the key genes was created. In addition, a nomogram for survival forecasting of IPF patients was created based on riskScore, Age, and Gender, and we found that key genes were associated with classical pathways including 'Apoptosis Signaling', 'PI3K/AKT Signaling', and so on. Next, two differential immune cells including Monocytes and CD8 T cells were identified between two risk subgroups. Moreover, we found that MIR29B2CHG and hsa-mir-1-3p could regulate the expression of ALDH2. CONCLUSION: We achieved 3 key genes including ALDH2, MCL1,, and BCL2A1 associated with IPF, providing a new theoretical basis for clinical treatment of IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis , Phosphatidylinositol 3-Kinases , Humans , Prognosis , Myeloid Cell Leukemia Sequence 1 Protein , Macrophages , DNA, Mitochondrial , Idiopathic Pulmonary Fibrosis/genetics , Mitochondria/genetics , Aldehyde Dehydrogenase, MitochondrialABSTRACT
Cell growth and flavonoid production in cell suspension cultures of Glycyrrhiza inflata Batal were investigated under various initial inoculum densities, and sucrose and nitrogen concentrations to develop an optimization method for an improved flavonoid production. Both biomass accumulation and flavonoid production exhibited an "S" curve in one culture cycle, with the greatest value obtained on day 21, which showed that cell growth and flavonoid biosynthesis went along isochronously. Moreover, according to the biomass and flavonoid production, the appreciate inoculum density, and the sucrose and nitrogen concentrations were 50 g FW L(-1), 50 g L(-1) and 120 mmol L(-1), respectively. In addition, cell growth and flavonoid production showed a peak of 16.4 g DW L(-1) and 95.7 mg L(-1) on day 21 under the optimizing conditions, respectively. The flavonoid productivity of the cells which were cultured for 3 years is higher than that of the 3-year-old plant, which suggested that flavonoid production by cell cultures of G. inflata is a potentially profitable method. Therefore, this work is considered to be helpful for efficient large-scale bioprocessing of cell cultures in bioreactors.
