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Objective To investigate the protective effect and underlying mechanism of the superoxide dismutase mimic, manganese (Ⅲ) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP), on paraquat (PQ) -induced lung epithelial-like cell injury. Methods Alveolar epithelial-like cells (A549) were pretreated with 10 μmol/L of MnTMPyP for 1.5 h and then cultured with or without PQ (750 μmol/L) for 24 h. Cell survival was determined using the MTT assay. Reactive oxygen species (ROS) production and Ca2+ levels were measured using flow cytometry. Glutathione reductase (GR) activity was determined using spectrophotometry. Expressions of the endoplasmic reticulum (ER) stress proteins, glucose regulatory protein 78 (Grp78) and C/EBP homologous protein (CHOP), were measured using Western blotting. Results Cell viability and GR activity were decreased, but ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all increased in the PQ group compared to those in the control group. There were no statistically significant changes in the MnTMPyP group. Cell viability and GR activity were increased, while ROS production, cytoplasmic Ca2+ levels, and expressions of Grp78 and CHOP were all significantly reduced in the MnTMPyP group compared to those in the PQ group. Conclusion MnTMPyP effectively reduced PQ-induced lung epithelial-like cell injury, and the underlying mechanism is related to antagonism of PQ-induced ER stress and oxidative stress.
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Objective To investigate the apoptosis mechanism induced by paraquat (PQ) in human type Ⅱ alveolar epithelial-like A549 cells.Methods A549 cells were cultured in vitro.The cells in the experimental group were exposed to various concentrations of PQ (50,100,150,and 200 μmol/L),while those in the control group were cultured in RPMI1640 medium.After treatment for 24 and 48 h,the cell survival rate was assessed by MTT assay.Morphological changes in the nuclei were observed by Hoechst 33258 fluorescence staining.Cellular apoptosis and mitochondrial transmembrane potential were assayed by flow cytometry.The activities of caspase-3 and caspase-9 were assayed by spectrophotometry.Western blotting was used to analyze the expression of proteins in the Bcl-2 family,such as Bcl-2,Bcl-xL,Bax,and Bak.Results PQ exhibited significant anti-proliferative activity in A549 cells.PQ-treated A549 cells were subjected to Hoechst 33258 staining.The hallmarks of apoptosis were detected,and the degree of apoptosis increased.Mitochondrial membrane potential was decreased,the levels of active caspase-3 and caspase-9 increased,the expression of Bcl-2 and Bcl-xL was decreased,and the expression of Bax and Bak was increased.These effects occurred in concentration-and time-dependent manners.Conclusion PQ efficiently induced intracellular apoptosis through the mitochondrial pathway in A549 cells.
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Objects To evaluate the immune protective effect of dexmedetomidine on breast cancer dur-ing perioperative radical mastectomy via sevoflurane inhalation general anesthesia. To explore reasonable anesthet-ic strategyfor breast cancer radical mastectomy. Methods Patients were divided into two groups. Patients in ex-perimental group receivedgeneral anesthesia with dexmedetomidine and sevoflurane. Control group means general anesthesia with sevoflurane only. In both groups, the level of cortisol, IL-6, IL-8 and of TNF-αin serum were measured at 5 time points , 30 minutes before anesthesia , after cutting skin , after surgery , 24 h after surgery and 72 h after surgery. Results The amount of anesthetic used to induce general anesthesia in the experimen-talgroup were lower than that of the control group.There is no obvious difference of cortisol , IL-6, IL-8 and of TNF-αin serumat the time of 30 min before anesthesia between two groups.Concentrations ofseveral markersin-creasedafter anesthesia, of which experimentalgroup were lower than that of the control group. Conclusions Dexmedetomidine could be immunoprotective for patient with breast cancer during perioperative radical mastecto-my via sevoflurane inhalationgeneralanesthesia. This study recommends usingmultiple anestheticdrugs to anes-thetize patients of breast cancer when performing radical mastectomy.
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<p><b>OBJECTIVE</b>To investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.</p><p><b>METHODS</b>Eleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.</p><p><b>RESULTS</b>A total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.</p><p><b>CONCLUSION</b>Due to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.</p>