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Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
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Objective To investigate the mechanism of increasing of the level of kidney injury molecule-1(KIM-1)in culture supernatant of human kidney cells(HKC)induced by cyclosporine A(CsA),and to clarify the relationships between the expression levels of KIM-1 and p38 MAPK pathway and ERK1/2MAPK pathway in HKC. Methods The HKC at logarithmic growth phase were randomly divided into control group, CsA control group, CsA + p38 kinase inhibitor group, p38 kinase inhibitor group, CsA + ERK1/2 inhibitor group and ERK1/2 kinase inhibitor group.The inhibitory rates of proliferation of HKC in various groups were detected by MTT assay, and the expression levels of KIM-1 in HKC supernatant in various groups were detected by ELISA;the survival rates,apopototic rates and necrotic rates of the HKC in various groups were detected by flow cytometry. Results Compared with control group,the expression level of KIM-1 protein in the supernatant of HKC in CsA control group was significantly increased (P0.05).Compared with CsA control group,the expression levels of KIM-1 protein in CsA+ p38 kinase inhibitor group and CsA+ ERK1/2 kinase inhibitor group were significantly decreased (P<0.05),and the survival rate was significantly increased (P<0.05),while the apoptotic rate and the necrotic rate were significantly decreased (P<0.05).Conclusion p38 MAPK pathway and ERK1/2MAPK pathway are involved in the process of up-regulation of the KIM-1 level in HKC culture supernatant induced by CsA,and the expression of KIM-1 may become the biochemical marker of clinical monitoring of CsA nephrotoxicity.
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Objective To study the protective effects of the polyphenols of vitis amurensis Rupr(PVAR) on rat heart mitochondria injury induced by oxygen radicals.Methods Experiment was designed into 5 groups:normal group,injury group and 25,50,100 mg?L-1PVAR+injury group.In experiment of rat heart mitochondria injury in vitro,vitamin C and FeSO4 played as an injury agent,PVAR played as a protective agent.The cardiolipin and MDA level of the mitochondria were determined.The membrane fluidity,ATPase activity and swelling of the mitochondria were examined.Results Compared with injury group,the cardiolipin was increased(P
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Objective:To study the relationship between human leukocyte antigen(HLA) typing, HLA crossreaction antigen group(CREGs) mismatching and early rejection after cadaver donor kidney transplantation.Methods:Donor and recipient HLA class Ⅰ typing was performed with Paul Terasaki monoclonal antibody tray and HLA class Ⅱ gene typing with Micro-sequence-specific-primers(Micro-SSP). PRA was detected by using Paul Terasaki mixture antigen tray.Results:The cases of 6, 5, 4, 3, 2, 1, 0 HLA mismatching(MM) in 131 recipients with negative PRA were respectively 0, 4, 26, 49, 33, 15, 4. The incidence of early rejection were 0,25%,23.1%,14.3%,12.1%,6.7%,0. No recipient with 5 and 6 CREGs MM. The case of 4,3,2,1,0 CREGs MM, the early rejection were respectively 28.6%,22.9%,9.5%,6.9%,5.5%.Conclusion:HLA typing and HLA crossreactive antigen group(CREGs) matching play an important role in selecting suitable donor, reducing early rejection, improving the effect of kidney transplantation.
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Objective To study the effect of renal ischemic reperfusion injury on intracellular ionized calcium level and apoptosis. Methods The model of rat's acute renal ischemic reperfusion injury was established.A total of 30 Wistar rats were divided into 5 groups:control, 1 h ischemia and 1 h,2 h,24 h reperfusion groups (n=6 for each group).Renal intracellular [Ca 2+]i level was determined by Fura-2/AM fluorescence assay,and renal cell apoptosis rates were measured by flow cytometry. Results The renal intracellular [Ca 2+]i levels at 1h,2h and 24h timepoint of reperfusion were 156.2 nmol/L,181.6 nmol/L and 260.6 nmol/L,respectively,which were significantly higher (P
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Objective: To investigate the mode of cell death caused by NDV strain Changchun and NDV strain Siping. Methods: Plaque formation, cell suppression test, gel electrophoresis, and TUNEL assay were used after the cells were infected by NDV. Results: The apparently pathological changes were observed in chicken embryo fibroblasts, BHK, Hela, Hep 2, HCT and OS 732 tumor cells, but not in Wish cells. The higher suppressed effect on tumor cells was found in the NDV strain Changchun than that in the NDV strain Siping. There was no dose effect relationship between NDV and tumor cell suppression, only optimum dose NDV could cause maximal tumor cells inhibitory effect. Conclusion: The mode of cell death might be different after infection of NDV. The NDV strain Changchun killed tumor cells mainly through apoptosis, while the NDV strain Siping killed tumor cells mainly through necrosis. \[
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Objective:The human heparin-binding growth factor Midkine(hMK) gene was constructed and expressed in E.coli, and the activity of MK protein was tested.Methods:The MK gene was amplificated from the tissue of human embryo kidney by RT-PCR techniques. The MK fragment without signal peptide was inserted into plasmid pET30a. The gene was expressed in E.coli, the protein was purificated by affinity chromatography, and the activity was tested by ~3H-TdR method.Results:The sequence of hMK in our experiment was as same as the sequence published in Genebank. The activity assay was shown high activity of MK protein in our experiment.Conclusion:The expression carrier of hMK was established successful and it can expression high activity hMK protein in E.coli.
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Objective:To study the relationship between expression of p53,nm23 and invasion and metastasis in human colorectal carcinoma,and the correlation between expression of p53 and nm23.Methods:Expression of p53 and nm23 were studied with SABC immunohistochemical technique Results:The positive rate of p53 and nm23 in 41 samples of human colorectal carcinoma was 58 5% and 53 7% respectively p53 over expression and nm23 low expression was significantly correlated with the depth of invasion and lymphatic metastasis The expression of p53 in pooly differentiated carcinoma was obviously higher than that in well differentiated carcinoma(P0 05) p53 over expression was correlated with nm23 low expression Conclusion:Over expression of p53 and low expression of nm23 might play an important role in invasion and metastasis of human colorectal carcinoma p53 over expression was related to the differentiation of colorectal carcinoma tissue
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Abstract Objective:To explore antitumor effect of NDV HN. Methods: pIRHN nucleic acid vaccin was constructed and was transfectedto Hela cells. Westem blot was used to analyssize the expression of pIRHN nucleic acid vaccine in eukarytic cell. The mode of cell death was de-tected by fluorescence microscope, gel electrophoresis and TUNEL assay. The effect of pIRHN nucleic acid vaccine on the contents of siaha acidin the Hela cell was examined. Results: pIRHN nucleic acid vaccine could be expressed in the eukarytic cell. pIRHN could induced apoptosisafter HeLa cells were transfected. The effect of antitumor responses of pIRHN was correlated with the contents of sialic acid in tumor cells. Con-clusion: The reults of our experiment will provide the theory evidence for the anti tumor mechamism of NDV.