3.Research progresses of Mycobacterium tuberculosis cytochrome P450s as a potential drug target.
Yun LU ; Feng QIAO ; Xue-Fu YOU ; Xin-Yi YANG
Acta Pharmaceutica Sinica 2014;49(4):427-434
Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents
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chemistry
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pharmacology
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Azoles
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chemistry
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pharmacology
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Cytochrome P-450 Enzyme Inhibitors
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chemistry
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pharmacology
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Cytochrome P-450 Enzyme System
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genetics
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metabolism
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Drug Delivery Systems
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methods
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Drug Discovery
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Humans
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Mycobacterium tuberculosis
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drug effects
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enzymology
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genetics
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Phylogeny
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Tuberculosis
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drug therapy
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microbiology
5.The relationship between oxidative injury induced by low glucose and mitochondrial membrane potential in HUVEC-12 cells
Wen LU ; Yaoming XUE ; Bo ZHU ; Xin LIAN ; Ning LIU
Chinese Journal of Internal Medicine 2011;50(10):873-876
ObjectiveTo investigate the relationship between the oxidative injury induced by low glucose and mitochondrial membrane potential in HUVEC-12 cells. Methods Human umbilicalvein endothelial cells HUVEC-12 were cultured in low concentration glucose for 4 h.Cell viability of HUVEC-12 cell was assessed with MTT assay.Dihydroethidium (DHE) was used as a reactive oxygen species (ROS)capture, which was detected the mean fluorescence intensity of samples and Rhodamine 123 as a fluorescence detector was to measure the level of mitochondrial membrane potential (MMP) in cells.Results Comparing to HUVEC-12 cells viability in 5.5 mmol/L glucose group (96.80 ±3.20)%, cells exposed to 2.8 mmol/L glucose group (66.40 ± 1.60) % and 0 mmol/L glucose group (58.93 ± 1.67) % were decreased by 32% and 40% respectively (P < 0.01).ROS level of 5.5 mmoL/L glucose group, 2.8 mmol/L glucose group and 0 mmol/L glucose group were 0.59 ± 0.02, 0.74 ± 0.04 and 0.88 ± 0.05,respectivdy, increased by 25% in cells exposed to 2.8 mmol/L glucose and by 48% in cells without glucose exposure comparing to 5.5 mmol/L glucose group (P <0.01) ; MMP levels of 5.5 mmol/L glucose group,2.8 mmoL/L glucose group and 0 mmoL/L glucose group were 148.83 ± 3.51, 271.07 ± 19.54 and357.74 ±51.32 respectively, increased to 1.8 times in cells exposed to 2.8 mmol/L glucose and to 2.4times in cells without glucose exposure comparing to 5.5 mmoL/L glucose group (P < 0.01).Conclusion Low glucose leads to injury in HUVEC-12 cells, which is probably induced by the oxidative stress via the increasing MMP.
6.Fluorimetric method for determination of trace lead in alginate sodium
Weili LU ; Jiachao XU ; Xin GAO ; Changhu XUE
Chinese Journal of Marine Drugs 2001;0(05):-
Objective To establish a method for determination of trace lead in alginate sodium.Method The lead in the samples was determined by fluorescence spectroscopy after been digested by hydrothermal decomposition.Results The detection limit of lead was 2.71?10-2?g?mL-1.The relative standard deviation of the three samples were 4.06%,1.57% and 2.12% respectively,the average recovery was 88.32%~100.8%.Conclusion The method had the advantages of simple operation,higher precision,higher sensitivity and repeatability and was suitable for the determination of trace lead in the alginate sodium
7.Application of transanus ilues tube in the case of left-semicolon cancer with intestinal obstruction
Xiang-Shi LU ; Jin-Xue TONG ; Xin-Shu DONG ;
Chinese Journal of Primary Medicine and Pharmacy 2006;0(07):-
Objective To investigate the case of left-semicolon cancer with intestinal obstruction for the methods of one-stage resection and anastomosis.Methods The clinical data of ten patients with left-semicolon can- cer with intestinal obstruction treated by transanus ilues tube,were restrospectively analyzed from October 2004 to December 2006.Results No postoperative anastormotic leakage was found and the patients were clinically cured. Conclusion The technical problem that left-semicolon cancer with obstruction for one-stage resection and anastomo- sis was resolved by the application of transanus ilues tube.
8.Current situation and prospect of treatment for radiation-induced lung injury.
Xin LI ; Jianxin XUE ; You LU
Journal of Biomedical Engineering 2010;27(4):937-940
Radiation-induced lung injury (RILI) is the most common complication of the radiotherapy for thoracic tumor. It can lower the ratio of local control and seriously affect the patients' quality of life. At present, the clinical management of RILI is not more than the use of glucocorticoid and anti-inflammatory agent for symptomatic treatments. These treatments do not have any preventive effect but cause much side reactions. In this paper, we review the data from the contigency researches on the mechanism of RILI, from the researches on gene therapy and stem cell-therapy, and we dicuss the more safe, more stable and more efficacious treatment of RILI.
Antioxidants
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therapeutic use
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Genetic Therapy
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methods
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Humans
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Lung
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pathology
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radiation effects
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Lung Neoplasms
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radiotherapy
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Mesenchymal Stem Cell Transplantation
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methods
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Radiation Injuries
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etiology
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therapy
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Radiation Pneumonitis
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etiology
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therapy
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Radiation-Protective Agents
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therapeutic use
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Radiotherapy, Conformal
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adverse effects
9.Preparation, characterization and Calu-3 cellular uptake of three kinds of poly(b-benzyl-L-amino)block-poly(ethylene glycol) nanoparticles.
Yin ZHOU ; Lina LU ; Xue XIN ; Dongfeng HUO ; Hongbing WU ; Mingfeng QIU
Acta Pharmaceutica Sinica 2013;48(4):560-5
The aim of this paper is to compare the cytotoxicity and cellular uptake efficiency of three kinds of poly(b-benzyl-L-amino) block-poly(ethylene glycol) nanoparticles (PXA-PEG-NPs) using Calu-3 cells, and select one as a nasal drug delivery vector for curcumin (Cur). Poly(gamma-benzyl-L-glutamate) block-poly(ethylene glycol) nanoparticles (PBLG-PEG-NPs), poly(gamma-benzyl-L-lysine) block-poly(ethyleneglycol) nanoparticles (PZLL-PEG-NPs) and poly(gamma-benzyl-L-aspartate) block-poly(ethylene glycol) nanoparticles (PBLA-PEG-NPs) were prepared by emulsion-solvent evaporation method. MTT assays were used to evaluate the cytotoxicity of PXA-PEG-NPs against Calu-3 cells. The cellular uptake of nanoparticles was visualized by an inverted fluorescence microscope and quantified by a flow cytometer. The results indicated that even at high concentration of 2 mg x mL(-1) the three nanoparticles had no cytotoxicity on Calu-3 cells. Compared to the curcumin solution, the three curcumin-loaded PXA-PEG-NPs showed significantly higher cellular uptake efficiency on Calu-3 cells (at equal concentration of curcumin with 5 microg x mL(-1) Cur solution), PBLG-PEG-NPs group was the highest. The cellular uptake increased with incubation time, and has positive correlation with nanoparticle concentration. In brief, PXA-PEG-NPs are conducive to delivery Cur into cells, and PBLG-PEG-NPs might be provided as a good nasal drug delivery carrier.
10.11 β-hydroxysteriod dehydrogenase and S100A16 co-regulate differentiation of 3T3-L1 adipocytes
Lu LI ; Jing XIN ; Yi XUE ; Xinli DU ; Rihua ZHANG ; Yun LIU
Chinese Journal of Endocrinology and Metabolism 2014;30(9):779-785
Objective To investigate the synergistic effect of 11 β-hydroxysteriod dehydrogenase (11 β-HSD1) and S100A16 on the differentiation of3T3-L1 preadipocytes and its mechanism.Methods Lentiviral vectors PLJM1-11β-HSD1 and PLJM1-S100A16-GFP were respectively constructed and co-transfected into 3T3-L1 preadipocytes.The cell strains expressing 11 β-HSD1/S100A16 were screened with 2.5 μg/ml puromycin for two weeks.Western blot was employed to verify the lentiviral carrier transfection effects.The expressions of marker genes related to the adipocyte differentiation were detected by mean of realtime PCR.Oil red O staining was used to observe the lipid droplet accumulation and the content of triglyceride was measured after differentiation of preadipocytes.The effect of 11β-HSD1 and S100A16 on PPARγ promoter activity was detected by luciferase reporter gene.Results Compared with the empty vector group,the expressions of 11β-HSD1 and S100A16 protein in the lentivirus cotransfected 3T3-L1 cell strain were significantly higher.After 3T3-L1 cell strain co-expressing 1 1β-HSD1 and S100A16 was induced to differentiate for 8 days,the lipid droplets accumulation and triglyceride content were siginificantly increased,along with increased expressions of adipocyte differentiation marker genes such as PPARγ,CCAAT/enhancer binding protein α,lipoprotein lipase,fatty acid synthase,and adipocyte fatty acid-binding protein,in comparison with 11 β-HSD1 or S100A16 overexpression.The result of reporter gene indicated that 11 β-HSD1/ S100A16 enhanced PPARγ promoter activity.Conclusions 11β-HSD1 and S100A16 may jointly promote the differentiation of 3T3-L1 preadipocytes through a synergistic effect on PPARγexpression and play a critical role in the development of obesity.