AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with n...AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.展开更多
AIM: To examine the effects of Helicobacter pylori ( Hpylort)infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.METHODS: Gastric carcinoma cells, MKN-45, were incubatedwith CagA-posi...AIM: To examine the effects of Helicobacter pylori ( Hpylort)infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.METHODS: Gastric carcinoma cells, MKN-45, were incubatedwith CagA-positive H pylori, and cell invasion was determined by Matrigel analysis. The expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly, the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay.RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC, a nuclear factor κB (NF-κB) inhibitor; (2) the induction of MKN-45 cells invasion by H pyloriis associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects; (3) H pylori infectiontransactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter.CONCLUSION: Our data demonstrate that H pylori infectionpromotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway,as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.展开更多
A series of ethylene oxide(EO)-propylene oxide (PO) random co-polymers (EOPO) were used to form aqueous two-phase systems (ATPS) with ammonium sulfate.Effects of EOPO′s properties on the phase separation behaviors an...A series of ethylene oxide(EO)-propylene oxide (PO) random co-polymers (EOPO) were used to form aqueous two-phase systems (ATPS) with ammonium sulfate.Effects of EOPO′s properties on the phase separation behaviors and on the partition of cephalexin and 7-aminodesacetoxicephalosporanic acid(7-ADCA) in ATPS were investigated.Both the molar mass and molar ratio of EO to PO of EOPO could greatly influence partition behaviors of cephalexin and 7-ADCA as well as the binodal curve of ATPS. With the increase of molar mass of co-polymer or the decrease of molar ratio of EO to PO,the critical point of ATPS decreased,the binodal curve became more asymmetry,and both cephalexin and 7-ADCA followed the same tendency to partition into the polymer-poor bottom phase.The experimental results shows that it is feasible to partition cephalexin and 7-ADCA in either the polymer-rich top phase or the polymer-poor bottom phase by choosing a specific phase-forming EOPO.展开更多
Enzymatic synthesis of cefaclor from 7-aminodesacetoxymethyl-3-chlorocephalosporainc acid(6-ACCA) and phenylglycine derivatives using penicillin G acylase was studied .Many factors that affect the conversion of 7-ACCA...Enzymatic synthesis of cefaclor from 7-aminodesacetoxymethyl-3-chlorocephalosporainc acid(6-ACCA) and phenylglycine derivatives using penicillin G acylase was studied .Many factors that affect the conversion of 7-ACCA to cefaclor were examined.The immobilized enzyme from Bacillis megaterium gave a better catalytic properties and the higher conversion was obtained using phenylglycine methyl ester(PGME) as acyl donor.And the external mass transfer limitation could be eliminated when the stirring rate was more than 150r/min.Low temperature was beneficial for the synthesis and the results showed that the synthetase activity was hardly influenced by temperature while the amidase activity was affected greatly by temperature.The optimum reaction conditions were determined at pH 6.5 and 10℃,respectively.The best 7-ACCA conversion of 56% was achieved when the intial concentration of 7-ACCA and PGME was at 50 mM and 150mM,respectively.展开更多
文摘AIM: Several epidemiological studies have demonstrated a dose association between Helicobacter pylori (H Pylon) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences,leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pyloriinfection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due tooxidative DNA damage.METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB),MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2),inhibitor of apoptosis protein (IAP) and myeloid cellleukemia-1 (Mcl-1)] by Western-blot assay.RFSULTS: The concentrations of 8-OHdG, iNOS, NFx3, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFxB, Mcl-1 and lAP were detected in patients infected with H pyloricompared with patients who were not infected with HpylorL Furthermore,8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage1 and 2 patients.CONCLUSION: Chronic Hpylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the rihypothesis that oxygen-free radical-mediated damage due to Hpyloriplays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.
基金Supported by the Taichung Veterans General Hospital Research Grant: TCVGH-933308C
文摘AIM: To examine the effects of Helicobacter pylori ( Hpylort)infection on the invasiveness of gastric cancer cells, and to elucidate its mechanism.METHODS: Gastric carcinoma cells, MKN-45, were incubatedwith CagA-positive H pylori, and cell invasion was determined by Matrigel analysis. The expression of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) were assessed by Western-blot analysis, and transcriptional activation of the COX-2 promoter was examined by measuring luciferase and β-galactosidase activities. Lastly, the proteinDNA interaction was confirmed by an electrophoretic mobility shift assay.RESULTS: The current studies showed that: (1) incubation of CagA-positive H pylori with MKN-45 cells significantly promotes gastric cancer cells invasion, and this effect is attenuated by pre-treatment with NS-398, a COX-2 inhibitor, or PDTC, a nuclear factor κB (NF-κB) inhibitor; (2) the induction of MKN-45 cells invasion by H pyloriis associated with increases in COX-2, MMP-9, and VEGF protein expression, and co-incubation of NS-398 or PDTC significantly reduces these effects; (3) H pylori infectiontransactivates COX-2 promoter activity and increases the binding of NF-κB to this promoter.CONCLUSION: Our data demonstrate that H pylori infectionpromotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-κB and COX-2 mediated pathway,as COX-2 or NF-κB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.
基金Supported by the National Natural Science Foundation of China (No. 29873014) and the Key Disciplinary Foundation of Shanghai.
文摘A series of ethylene oxide(EO)-propylene oxide (PO) random co-polymers (EOPO) were used to form aqueous two-phase systems (ATPS) with ammonium sulfate.Effects of EOPO′s properties on the phase separation behaviors and on the partition of cephalexin and 7-aminodesacetoxicephalosporanic acid(7-ADCA) in ATPS were investigated.Both the molar mass and molar ratio of EO to PO of EOPO could greatly influence partition behaviors of cephalexin and 7-ADCA as well as the binodal curve of ATPS. With the increase of molar mass of co-polymer or the decrease of molar ratio of EO to PO,the critical point of ATPS decreased,the binodal curve became more asymmetry,and both cephalexin and 7-ADCA followed the same tendency to partition into the polymer-poor bottom phase.The experimental results shows that it is feasible to partition cephalexin and 7-ADCA in either the polymer-rich top phase or the polymer-poor bottom phase by choosing a specific phase-forming EOPO.
文摘Enzymatic synthesis of cefaclor from 7-aminodesacetoxymethyl-3-chlorocephalosporainc acid(6-ACCA) and phenylglycine derivatives using penicillin G acylase was studied .Many factors that affect the conversion of 7-ACCA to cefaclor were examined.The immobilized enzyme from Bacillis megaterium gave a better catalytic properties and the higher conversion was obtained using phenylglycine methyl ester(PGME) as acyl donor.And the external mass transfer limitation could be eliminated when the stirring rate was more than 150r/min.Low temperature was beneficial for the synthesis and the results showed that the synthetase activity was hardly influenced by temperature while the amidase activity was affected greatly by temperature.The optimum reaction conditions were determined at pH 6.5 and 10℃,respectively.The best 7-ACCA conversion of 56% was achieved when the intial concentration of 7-ACCA and PGME was at 50 mM and 150mM,respectively.
