ABSTRACT
OBJECTIVE@#To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME).@*METHODS@#CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.@*RESULTS@#The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.@*CONCLUSION@#FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.
Subject(s)
Humans , Actins , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins , Drugs, Chinese Herbal/therapeutic use , Lung Neoplasms/metabolism , Tumor MicroenvironmentABSTRACT
Exosome is a kind of vesicular body which can be secreted by most cells and can communicate information between cells through the transfer of specific signal molecules. More and more studies have shown that exosomes are widely involved in the occurrence and development of cardiovascular diseases, such as hypertension, heart failure and myocardial infarction. In recent years, studies have shown that exercise has a great impact on the biological function of body fluids and blood circulation exosomes. Different exercise modes can promote the release of exosomes and affect the expression of miRNA and proteins. At present, studies have found that exercise promotion of exosome release may be related to the laminar shear force induced by blood flow, the increase of Ca
ABSTRACT
<p><b>OBJECTIVE</b>This study was aimed to investigate the effects of emodin combined with 3'-azido-3'-deoxythymidine (AZT) on proliferation and apoptosis of leukemia cell line KG-1a cells and its mechanism.</p><p><b>METHODS</b>KG-1a cells were transfected with Egr-1 siRNA by electroporation and divided into blank control (KG-1a), nonspecific control (KG-1a/NC) and Egr-1 siRNA (KG-1a/siRNA) groups. Transfection efficiency was tested through fluorescence microscopy and flow cytometry and the transfection effect was detected by using qPCR. The cell proliferation rate was detected with MTT method. After the cells were treated with 10 µmol/L of emodin, 3200 or 1600 µmol/L of AZT and their combinations, the proliferation inhibition rates and the apoptosis rates of cells in 3 groups were detected with MTT method and FCM, respectively.</p><p><b>RESULTS</b>The transfection efficiency of Egr-1 siRNA was found to reach more than 59.21%; as compared with blank control(KG-1a) and nonspectic control(KG-1a/NC), the cell proliferation in Egr-1 siRNA group significantly reduced (P<0.01). The combination of emodin and AZT had considerable synergistic inhibitory effects on proliferation of normal KG-1a cells and nonspecific control(KG-1a NC) cells, but the synergistic effects disappeared after Egr-1 gene silencing.</p><p><b>CONCLUSION</b>The effects of the combination of emodin and AZT on proliferation and apoptosis may be related with Egr-1.</p>
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Early Growth Response Protein 1 , Emodin , Flow Cytometry , Leukemia , RNA, Small Interfering , Transfection , ZidovudineABSTRACT
<p><b>OBJECTIVE</b>To explore the renal protective effect of Tongxinluo (TXL) and its mechanism of action.</p><p><b>METHODS</b>Eight-week old SD rats were divided into the sham-operated group (A), the model group (B) and the TXL group, 6 rats in each group. Angiotensin II (Ang II) was administered slowly (200 ng/kg per min) to rats in group B and C via subcutaneously embedded osmotic pump to make them stimulative model of renal injury, while to rats in group A, pump embedding with saline infusion. After modeling, TXL was given to group C by gastric perfusion in dosage of 0.8 g/kg per day. And the following indexes were observed 14 days later: configuration of renal arterial endothelium by transmission electron microscope; pathologic figure of kidney with HE stain; renal apoptosis by TUNEL; expression of p53 and p22phox by RT-PCR;and level of reactive oxygen species (ROS) in kidney.</p><p><b>RESULTS</b>Different degree of congestion, swelling, denudation of endothelial cell in renal arterial endothelial cell; glomerular matrix proliferation and partial glomerular atrophy with tendency of fibrosis; increased renal parenchymal apoptosis; enhanced expression of p53 and p22phox; and elevated ROS were found in model animals. All the above-mentioned abnormalities, including glomerular injury, renal cell apoptosis, as well as the increased p53, p22phox expressions and ROS production were all alleviated in group C after TXL treatment.</p><p><b>CONCLUSION</b>TXL could protect renal against Ang II injury, and it may be realized by inhibiting NADPH-ROS/p53 pathways and suppressing cell apoptosis in renal parenchyma.</p>