ABSTRACT
OBJECTIVE@#To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.@*METHODS@#The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP@*RESULTS@#Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP@*CONCLUSION@#Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Subject(s)
Animals , Humans , Mice , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Leukemia , Myeloid-Lymphoid Leukemia Protein/genetics , Telomerase/metabolism , Telomere/metabolismABSTRACT
Objective:In the study of urine metabolomics of rats,necessary antiseptic measures should be taken for collection of urine samples,the effect of several antiseptic measures on the endogenous metabolites in urine was studied. Method:The urine samples of rats were collected on ice,sodium azide was added,and both of them were used together to prevent corrosion.Differences of antiseptic measures were analyzed by nuclear magnetic resonance (NMR) metabolomics. Result:The results of NMR metabolomics showed that sodium azide+ice group and ice group had many overlaps,but they clearly separated with the control group and sodium azide group;sodium azide group and the control group had a small part overlap,but there was a tendency of separation.The antiseptic effect of sodium azide+ice group and ice group was similar;compared with control group,valine,betaine and hippuricacid in these two groups increased,but the alanine and 2-ketoglutaric acid decreased. Conclusion:In the study of rat urine metabolomics,low temperature antiseptic measures must be taken when urine samples are collected,and the addition of sodium azide can improve the antiseptic effect slightly under protective conditions.
ABSTRACT
Objective To explore the inhibitory effect of resveratrol on hypertension-related myocardial fibrosis and the key role of TNF-β/Smads signaling pathway in the anti-fibrosis of resveratrol.Methods The expression of vimentin in the primary rat CFs was evaluated by immunofluorescence to determine the cell type.CFs were treated in different conditions,the mRNA expression levels of type Ⅰ and type Ⅲ collagen and TGF-β1 were detected by Real-time PCR;the protein expression levels of type Ⅰ and type Ⅲ collagen,TGF-β1 ,Smad-3 and P-Smad-3 were detected by Western blot.The secretion levels of type Ⅰ collagen and TGF-β1 in CFs supernatant were measured by ELISA assay.Results Rat CFs were successfully extracted,and vimentin expression was obvious. Real-time PCR results indicated that the gene expression levels of collagen Ⅰ and Ⅲ and TGF-β1 in CFs by exposure to AngⅡ were significantly increased as compared with those in normal group (P＜0.05).However,AngⅡ-induced collagen Ⅰ and Ⅲ and TGF-β1 mRNA upregulation was inhibited by Res treatment (P＜0.05).Western blot analysis showed that the protein expressions of collagen Ⅰ and Ⅲ and TGF-β1 in CFs were also increased after exposed to AngⅡ when compared to the normal controls (P＜0.05).Similarly,AngⅡ-mediated collagen Ⅰ and Ⅲand TGF-β1 upregulation was prevented by Res treatment (P＜0.05).In addition,the phosphorylation level of Smad-3 was enhanced by both interventions (P＜0.05).However,AngⅡ stimulated TGF-β1 upregulation while Smad-3 phosphorylation was suppressed by Res treatment (P＜0.05).The secretion levels of collagen Ⅰ and TGF-β1 in CFs supernatant increased significantly in CFs exposed to AngⅡ condition as compared with those in normal condition (P＜0.05).However,AngⅡ increased collagen Ⅰ and TGF-β1 secretion was prevented by Res intervention (P＜0.05).Conclusion Resveratrol inhibits the expressions of type Ⅰ and type Ⅲ collagen induced by AngⅡ in cardiac fibroblasts through regulating the TGF-β1/Smad3 signaling pathway.