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OBJECTIVE@#To investigate the role of human host heme-oxygenase-1 (HO-1) in pathogenesis of cerebral malaria in the in vitro model.@*METHODS@#The effect of human host HO-1 [human brain microvascular endothelial cell (HBMEC)] on hemoglobin degradation in the co-culture model of HBMEC and ITG Plasmodium falciparum-infected red cells (iRBC) through measurement of the enzymatic products iron and bilirubin.@*RESULTS@#Following exposure to the HO-1 inducer CoPPIX at all concentrations, the HBMEC cells apoptosis occurred, which could be prominently observed at 15 μM of 3 h exposure. In contrast, there was no significant change in the morphology in the non-exposed iRBC at all concentrations and exposure time. This observation was in agreement with the levels of the enzymatic degradation products iron and bilirubin, of which the highest levels (106.03 and 1753.54% of baseline level, respectively) were observed at 15 μM vs. 20 μM at 3 h vs. 24 h exposure. For the effect of the HO-1 inhibitor ZnPPIX, HBMEC cell morphology was mostly unchanged, but significant inhibitory effect on cell apoptosis was seen at 10 μM for the exposure period of 3 h (37.17% of baseline level). The degree of the inhibitory effect as reflected by the level of iron produced was not clearly observed (highest effect at 10 μM and 3 h exposure).@*CONCLUSIONS@#Results provide at least in part, insight into the contribution of HO-1 on CM pathogenesis and need to be confirmed in animal model.
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Objective:To explore the effects of protoporphyrin Ⅸ (PpⅨ)-mediated photodynamic therapy (PDT) on induction of apoptosis and death in colon cancer cell and the underlying mechanisms.Methods:The cell killing effect of PDT on HCT116 cell was determined by cell counting kit (CCK).The cells were divided into a control group,a single light group,a single PpⅨ group,and a PDT group.Hoechst 33342 and flow cytometry was used to assess the cell apoptosis.Western blot was employed to analyze the expressions ofbd-2,bax,and caspase-3.Reactive oxygen species (ROS) was detected by flow cytometry.Results:The viability of HCT116 cell was decreased gradually with the increase of irradiation dose (P<0.05).Compared to the other 3 groups,ROS production,the number of apoptotic cells and the protein expressions ofbax and caspase-3 in PDT group increased,while bcl-2 expression was decreased (P<0.05).Conclusion:PpⅨ-mediated PDT can enhance the apoptosis in HCT116 cell,which may be related to mitochondrial apoptosis pathway.
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Objective To determine the concentration difference in protoporphyrin in cancerous intestine and to discuss its application in laser-induced autofluorescence diagnosis for colorectal cancer at early stage.Methods We detected the concentration of protoporphyrin Ⅸ in 30 patients with colorectal cancer and 30 control patients, as well as that in 60 cases of intestinal tissues (30 control tissues and 30 cancer tissues).Results The concentration of blood protoporphyrin Ⅸ in patients with colorectal cancer was significantly higher than that in the controls (P<0.05). Protoporphyrin Ⅸ concentration in the cancer tissue was significantly higher than that in the control tissues (P<0.05).Conclusion That the concentration of protoporphyrin in cancerous intestine becomes abnormally high may be the material basis for spectrum intensity peak of (644.3±5.7)nm in laser-induced autofluorescence diagnosis for colorectal cancer at early stage.
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Objective To study the cell killing effect on isolated sarcoma 180 cells by ultrasound activating Protoporphyrin IX and to explore its biological mechanism.Methods The sonodynamical effect was investigated on S180 tumor cells exposed to the combination of 120 mol/L protoporphyrin Ⅸ (PPⅨ) and focused ultrasound at the frequency of 2.2 MHz and an intensity of 3W/cm2. The livability of cells was evaluated by trypan blue staining. Scanning electron microscope (SEM) observation of the surface of cells was performed to evaluate the morphological changes induced by ultrasonic irradiation. The generation of oxygen free radicals in cell suspensions was immediately detected after treatment by the active oxygen detection kit. Oxidative stress was assessed by measuring the activities of key antioxidant enzymes (ie, Superoxide dismutase[SOD], Glutathione peroxidase [GSH-PX], Catalase [CAT]) in S180 cells after SDT.Results The cell damage rate of ultrasound combined with PPIX was significantly higher than that treated with ultrasound alone only, and PPIX alone had no killing effect on S180 cells. Enzymatic chemical methods showed the content of MDA significantly increased after treatment, while the activities of key antioxidant enzymes in tumor cells all decreased at different levels, and was associated to the generation of oxygen free radicals in cell suspension after treatment. Conclusion Oxygen free radical may play an important role inimproving the membrane lipid peroxidation, decreasing the activities of key antioxidant enzymes in cells, and the biological mechanism might be involved in mediating the killing effect of S180 cells in SDT.
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Objective To explore the effect of protoporphyrin Ⅸ zinc(Znpp) on hyperoxic lung injury in preterm rats.Methods Three-day-old preterm SD rats were randomly assigned to room air control group(group Ⅰ)hyperoxia control group(oxygen≥900 mL/L)(group Ⅱ),room air plus Znpp group(group Ⅲ),hyperoxia plus Znpp group(group Ⅳ).Group Ⅲ and group Ⅳ were injected intraperitoneally with ZnPP 45 ?mol/kg each day.After the third day and the 7th day of exposure,the activity of heme oxygenase-1(HO-1) and the percent of carboxyhemoglobin(HbCO) in the lungs,the lung wet weight /dry weight ratio(W/D),tumor necrosis factor-?(TNF-?),total protein and malondialdehyde(MDA) in bronchoalveolar lavage fluid were determined and lung histophathological changes were examined in all groups.Results On the third day,compared with group Ⅰ the activity of HO-1 and the percent of HbCO in the lungs,W/D,TNF-?,total protein and MDA,all greatly rised in group Ⅱ(Pa
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To evaluate the practical photodynamic therapy (PTD) efficiency on tumor of en-dogenous ALA-induced PP Ⅸ. Methods: Morphoraglcal alterations were observed after PDT 0f protopor-phyrin Ⅸ (PP Ⅸ) by application of endogenous 6-aminolaevulinic acid(ALA) in Kunming mice bearing H22hepatic carcinoma. Results: After PDT, the tumor cells showed degeneration, deformation and nuclearnecrosis and the tumor tissues were defused with hemorrhage and necrosis. The ultrastructural pathologyindicated that mitochondria in tumor cells were injured and destroyed. C0nclusi0n: The pathological alter-ations suggest that PDT of ALA on H22 hepatic carcinoma was conducted by the destruction of mitochon-dria.
