AIM;Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations.Our aim was to assess whether ascorbic acid,an antioxidant,could have a role in preventing ROS(Reactive Oxygen Species)generation ...AIM;Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations.Our aim was to assess whether ascorbic acid,an antioxidant,could have a role in preventing ROS(Reactive Oxygen Species)generation in experimental gastric carcinoma in a rat model. METHODS:Experimental gastric cancer was induced in twelve Wistar male rats(weighting 250-350 g)by profound duodeno-gastric reflux throught split gastrojenunostomy.The rats were allocated to the following groups:Group Ⅰ(n=6) was the control;Group Ⅱ(n=6)which was mantained with daily intake of tape water with Vitamin C(30 mg/Kg).After 6 or 12 months,samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium.The histopathologic confirmation of adenocarcinoma was made by eosin- hemathoxilin method. RESULTS:The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group Ⅰ whereas only 3 rats of group Ⅱ showed an adenocarcinoma without macroscopic evidence of them.The cancers were located in the anastomosis in all cases.Basal luminescence from tumor gastric tissue generated 38.4±6.8 count per minute/mg/×10~6(mean±SD)and 14.9±4.0 count per minute/mg/×10~6,respectively,in group Ⅰ and Ⅱ animals(P <0.05).The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa. CONCLUSION:Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue.The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid.Therefore,it may have a role in the prevention of gastric carcinoma. Oliveira CPMS Kassab P Lopasso FP Souza HP Janiszewski M Laurindo FRM Iriya K Laudanna AA.Protective effect of ascorbic acid in experimental gastric cancer:reduction of oxidative stress.World J Gastroenterol 2003;9(3):446-448 http://www.wjgnet.com/1007-9327/9/446.htm展开更多
River Ghataprabha, during its course through Belgaum district in Karnataka state (India), receives untreated domestic waste from Gokak town and other neighboring villages situated on the bank of the river. The prese...River Ghataprabha, during its course through Belgaum district in Karnataka state (India), receives untreated domestic waste from Gokak town and other neighboring villages situated on the bank of the river. The present study involves the application of water quality model QUAL2K to predict the water quality of this polluted segment of the river. The model was calibrated and validated for biochemical oxygen demand (BOD), dissolved oxygen (DO) and total nitrogen (TN) in pre-monsoon season. Data for calibration and validation were obtained after the field and laboratory measurements. The performance of the model was evaluated using statistics based on standard errors (SE) and mean multiplicative errors (MME). The model represented the field data quite well with some exceptions. In spite of some differences between the measured and simulated data sets at some points, the calibration and validation results are acceptable especially for the developing countries where the financial resources are often limited for frequent monitoring campaigns and higher accuracy data analysis.展开更多
AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant...AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. METHODS: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO2- + NO3-, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, HspT0 expression and apoptosis ratio. RESULTS: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusioninduced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO2^- + NO3^- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion,but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. CONCLUSION: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.展开更多
To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods: Sixty SPF-class male DS rats wer...To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods: Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results: The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion: Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.展开更多
In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue orland dexamethason were investigated. The results revealed that plasma nitric oxide levels were elevated at 6...In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue orland dexamethason were investigated. The results revealed that plasma nitric oxide levels were elevated at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexamethasone was found to blunt hypoglycemia and hyperlacticemia, to reduce the occurrence rate of loss of response to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to decrease the 24 h mortality. The results suggested that nitric oxide play an important role during the course of fatal P. aeruginosa sepsis, but it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.展开更多
Dried anaerobic granular sludge (DAGS) for removing phenol (organic) and lead (inorganic) pollutants from synthetic wastewater was examined in a fixed bed system. A general rate multi-component model has been bu...Dried anaerobic granular sludge (DAGS) for removing phenol (organic) and lead (inorganic) pollutants from synthetic wastewater was examined in a fixed bed system. A general rate multi-component model has been built to predict the fixed bed breakthrough curves for single and dual-component system. This model considers both external and internal mass transfer resistances as well as axial dispersion with non-liner multi-component isotherm. The equilibrium isotherm model parameters such as isotherm model constants (qm and b), pore diffusion coefficients (Dp) were obtained from batch experiments, while the external mass transfer coefficients and axial dispersion (kf, Dz) were calculated from empirical correlations. The results show that the general rate multi-component model was found suitable for describing the biosorption process of the dynamic behavior of the DAGS adsorber column and that DAGS can be used efficiently to remove organic and inorganic pollutants.展开更多
We evaluate economic and environmental impacts of climate change mitigation in a country scale considering various time horizons in the analysis applying a single-country dynamic computable general equilibrium model w...We evaluate economic and environmental impacts of climate change mitigation in a country scale considering various time horizons in the analysis applying a single-country dynamic computable general equilibrium model with endogenous technological change. Although there is a possibility that Gross Domestic Product (GDP) becomes larger for the abatement cases than the baseline case in the earlier years, it tends to be lower than that in the later years. The longer the time horizon and/or the more severe the abatement, the larger the negative impacts will be. When subsidizing R&D investment, increase in GDP compared to the baseline case is realized in the middle of the time horizon, and the larger increase tends to be observed for the longer-term cases. These results would be due to technological change induced by the subsidies and emission abatement. Environmental indicators are also improved. We showed that the results were influenced by the target time horizon when using an intertemporal dynamic model.展开更多
Carbonate cement is the most abundant cement type in the Fourth Member of the Xujiahe Formation in the Xiaoquan-Fenggu area of the West Sichuan Depression. Here we use a systematic analysis of carbonate cement petrolo...Carbonate cement is the most abundant cement type in the Fourth Member of the Xujiahe Formation in the Xiaoquan-Fenggu area of the West Sichuan Depression. Here we use a systematic analysis of carbonate cement petrology, mineralogy, carbon and oxygen isotope ratios and enclosure homogenization temperatures to study the precipitation mechanism, pore fluid evolu- tion, and distribution of different types of carbonate cement in reservoir sand in the study area. Crystalline calcite has relatively heavy carbon and oxygen isotope ratios (δ13C = 2.14%o, 8180 = -5.77‰), and was precipitated early. It was precipitated di- rectly from supersaturated alkaline fluid under normal temperature and pressure conditions. At the time of precipitation, the fluid oxygen isotope ratio was very light, mainly showing the characteristics of a mixed meteoric water-seawater fluid( δ180 = -3‰), which shows that the fluid during precipitation was influenced by both meteoric water and seawater. The calcite cement that fills in the secondary pores has relatively lighter carbon and oxygen isotope ratios (δ13C = -2.36%0, 8180 = -15.68‰). This cement was precipitated late, mainly during the Middle and Late Jurassic. An important material source for this carbonate cement was the feldspar corrosion process that involved organic matter. The Ca2+, Fe3+ and Mg2+ ions released by the clay mineral transformation process were also important source materials. Because of water-rock interactions during the buri- al process, the oxygen isotope ratio of the fluid significantly increased during precipitation, by about 3‰. The dolomite ce- ments in calcarenaceous sandstone that was precipitated during the Middle Jurassic have heavier carbon and oxygen isotope ratios, which are similar to those of carbonate debris in the sandstone (δ13C = 1.93%o, δ180 = -6.11‰), demonstrating that the two are from the same source that had a heavier oxygen isotope ratio (δ180 of about 2.2‰). The differences in fluid oxygen isotope ratios during cement precipitation reflect the influences of different water-rock interaction systems or different wa- ter-rock interaction strengths. This is the main reason why the sandstone containing many rigid particles (lithic quartz sand- stone) has a relatively negative carbon isotope ratio and why the precipitation fluid in calcarenaceous sandstone has a relatively heavier oxygen isotope ratio.展开更多
The general strategy and method of constructing universal calibration model for levofioxacin injections by near-infrared spectroscopy have been investigated and discussed. Firstly, a constant-temperature homogeneous l...The general strategy and method of constructing universal calibration model for levofioxacin injections by near-infrared spectroscopy have been investigated and discussed. Firstly, a constant-temperature homogeneous liquid calibration model for levofloxacin hydrochloride injections with the same composition but different active principal ingredient (API) content was established as the basic unit for universal model. Then, samples of levofloxacin hydrochloride injections containing propylene glycol or levofloxacin lactate injections were added to develop a primary constant-temperature liquid universal model. Temperature- amended final universal model was established to apply to samples under different temperatures. The final model was built from 61 calibration samples and 77 validation samples. The value of the root mean square error of cross validation (RMSECV) and coefficient of determination (r2) of leave-one-out cross-validation (LOOCV) were 0.792 and 0.9993, respectively, the root mean square error of prediction (RMSEP) of test set validation (TSV) was 0.87, and the average relative deviation was 1.44%. According to the ICH guidelines, the universal calibration model was evaluated. Based on the experimental statistical results, the recommended number of calibration samples for a constant-temperature homogeneous liquid quantitative model was no less than 15.展开更多
Herein, new poly(ortho ester disulfide urethanes) (POEDU) and poly(ortho ester urethanes) (POEU) were successfully syn- thesized via polycondensation between active esters of 1,6-hexandiol (HD) and dual-stim...Herein, new poly(ortho ester disulfide urethanes) (POEDU) and poly(ortho ester urethanes) (POEU) were successfully syn- thesized via polycondensation between active esters of 1,6-hexandiol (HD) and dual-stimuli-sensitive ortho ester disulfide diamine or pH-senstive ortho ester diamine. The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique. In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments. Doxorubicin (DOX) as a model antitumor drug was suc- cessfully incorporated into these nanospheres to give DOX-loaded nanoparticles (POEDU-DOX and POEU-DOX). In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol (DTT) and mildly acidic conditions. In addition, in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitnmor effect than POEU-DOX did against both two- dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS). Finally, in a mice H22 tumor model, POEDU-DOX exhibited preferable antitumor capability. In conclusion, the pH and redox dual-stimuli-sensitive POEDU na- nospheres can be superior drug carriers for cancer treatment.展开更多
文摘AIM;Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations.Our aim was to assess whether ascorbic acid,an antioxidant,could have a role in preventing ROS(Reactive Oxygen Species)generation in experimental gastric carcinoma in a rat model. METHODS:Experimental gastric cancer was induced in twelve Wistar male rats(weighting 250-350 g)by profound duodeno-gastric reflux throught split gastrojenunostomy.The rats were allocated to the following groups:Group Ⅰ(n=6) was the control;Group Ⅱ(n=6)which was mantained with daily intake of tape water with Vitamin C(30 mg/Kg).After 6 or 12 months,samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium.The histopathologic confirmation of adenocarcinoma was made by eosin- hemathoxilin method. RESULTS:The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group Ⅰ whereas only 3 rats of group Ⅱ showed an adenocarcinoma without macroscopic evidence of them.The cancers were located in the anastomosis in all cases.Basal luminescence from tumor gastric tissue generated 38.4±6.8 count per minute/mg/×10~6(mean±SD)and 14.9±4.0 count per minute/mg/×10~6,respectively,in group Ⅰ and Ⅱ animals(P <0.05).The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa. CONCLUSION:Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue.The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid.Therefore,it may have a role in the prevention of gastric carcinoma. Oliveira CPMS Kassab P Lopasso FP Souza HP Janiszewski M Laurindo FRM Iriya K Laudanna AA.Protective effect of ascorbic acid in experimental gastric cancer:reduction of oxidative stress.World J Gastroenterol 2003;9(3):446-448 http://www.wjgnet.com/1007-9327/9/446.htm
文摘River Ghataprabha, during its course through Belgaum district in Karnataka state (India), receives untreated domestic waste from Gokak town and other neighboring villages situated on the bank of the river. The present study involves the application of water quality model QUAL2K to predict the water quality of this polluted segment of the river. The model was calibrated and validated for biochemical oxygen demand (BOD), dissolved oxygen (DO) and total nitrogen (TN) in pre-monsoon season. Data for calibration and validation were obtained after the field and laboratory measurements. The performance of the model was evaluated using statistics based on standard errors (SE) and mean multiplicative errors (MME). The model represented the field data quite well with some exceptions. In spite of some differences between the measured and simulated data sets at some points, the calibration and validation results are acceptable especially for the developing countries where the financial resources are often limited for frequent monitoring campaigns and higher accuracy data analysis.
文摘AIM: To investigate the hypothesis that the protective effects of curcumin in hepatic warm ischemia/reperfusion (I/R) injury are associated with increasing heat shock protein 70 (Hsp70) expression and antioxidant enzyme activity. METHODS: Sixty Sprague-Dawley male rats were randomly divided into sham, I/R, C + I/R groups. The model of reduced-size liver warm ischemia and reperfusion was used. Curcumin (50 mg/kg) was administered by injection through a branch of superior mesenteric vein at 30 min before ischemia in C + I/R group. Five rats were used to investigate the survival during 1 wk after operation in each group. Blood samples and liver tissues were obtained in the remaining animals after 3, 12, and 24 h of reperfusion to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver tissue NO2- + NO3-, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT), nitricoxide synthase (NOS) and myeloperoxidase (MPO) activity, HspT0 expression and apoptosis ratio. RESULTS: Compared with I/R group, curcumin pretreatment group showed less ischemia/reperfusioninduced injury. CAT and SOD activity and Hsp70 expression increased significantly. A higher rate of apoptosis was observed in I/R group than in C + I/R group, and a significant increase of MDA, NO2^- + NO3^- and MPO level in liver tissues and serum transaminase concentration was also observed in I/R group compared to C + I/R group. Curcumin also decreased the activity of inducible NO synthase (iNOS) in liver after reperfusion,but had no effect on the level of endothelial NO synthase (eNOS) after reperfusion in liver. The 7 d survival rate was significantly higher in C + I/R group than in I/R group. CONCLUSION: Curcumin has protective effects against hepatic I/R injury. Its mechanism might be related to the overexpression of Hsp70 and antioxidant enzymes.
文摘To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods: Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results: The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion: Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.
文摘In a newborn rat model of sepsis, the changes of nitric oxide and the protective effects of methylene blue orland dexamethason were investigated. The results revealed that plasma nitric oxide levels were elevated at 6 h and peaked at 12 h after bacterial challenge. The treatment with methylene or/and dexamethasone was found to blunt hypoglycemia and hyperlacticemia, to reduce the occurrence rate of loss of response to pain, and to prolong the survival time. Moreover, therapy by dexamethasone was shown to decrease the 24 h mortality. The results suggested that nitric oxide play an important role during the course of fatal P. aeruginosa sepsis, but it is clear that the clinical value of nitric oxide and its inhibitors need to be further studied.
文摘Dried anaerobic granular sludge (DAGS) for removing phenol (organic) and lead (inorganic) pollutants from synthetic wastewater was examined in a fixed bed system. A general rate multi-component model has been built to predict the fixed bed breakthrough curves for single and dual-component system. This model considers both external and internal mass transfer resistances as well as axial dispersion with non-liner multi-component isotherm. The equilibrium isotherm model parameters such as isotherm model constants (qm and b), pore diffusion coefficients (Dp) were obtained from batch experiments, while the external mass transfer coefficients and axial dispersion (kf, Dz) were calculated from empirical correlations. The results show that the general rate multi-component model was found suitable for describing the biosorption process of the dynamic behavior of the DAGS adsorber column and that DAGS can be used efficiently to remove organic and inorganic pollutants.
文摘We evaluate economic and environmental impacts of climate change mitigation in a country scale considering various time horizons in the analysis applying a single-country dynamic computable general equilibrium model with endogenous technological change. Although there is a possibility that Gross Domestic Product (GDP) becomes larger for the abatement cases than the baseline case in the earlier years, it tends to be lower than that in the later years. The longer the time horizon and/or the more severe the abatement, the larger the negative impacts will be. When subsidizing R&D investment, increase in GDP compared to the baseline case is realized in the middle of the time horizon, and the larger increase tends to be observed for the longer-term cases. These results would be due to technological change induced by the subsidies and emission abatement. Environmental indicators are also improved. We showed that the results were influenced by the target time horizon when using an intertemporal dynamic model.
基金supported by the State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Foundation (Grant No. PLC201101)the National Natural Science Foundation of China (Grant Nos. 41172119 and 41272130)
文摘Carbonate cement is the most abundant cement type in the Fourth Member of the Xujiahe Formation in the Xiaoquan-Fenggu area of the West Sichuan Depression. Here we use a systematic analysis of carbonate cement petrology, mineralogy, carbon and oxygen isotope ratios and enclosure homogenization temperatures to study the precipitation mechanism, pore fluid evolu- tion, and distribution of different types of carbonate cement in reservoir sand in the study area. Crystalline calcite has relatively heavy carbon and oxygen isotope ratios (δ13C = 2.14%o, 8180 = -5.77‰), and was precipitated early. It was precipitated di- rectly from supersaturated alkaline fluid under normal temperature and pressure conditions. At the time of precipitation, the fluid oxygen isotope ratio was very light, mainly showing the characteristics of a mixed meteoric water-seawater fluid( δ180 = -3‰), which shows that the fluid during precipitation was influenced by both meteoric water and seawater. The calcite cement that fills in the secondary pores has relatively lighter carbon and oxygen isotope ratios (δ13C = -2.36%0, 8180 = -15.68‰). This cement was precipitated late, mainly during the Middle and Late Jurassic. An important material source for this carbonate cement was the feldspar corrosion process that involved organic matter. The Ca2+, Fe3+ and Mg2+ ions released by the clay mineral transformation process were also important source materials. Because of water-rock interactions during the buri- al process, the oxygen isotope ratio of the fluid significantly increased during precipitation, by about 3‰. The dolomite ce- ments in calcarenaceous sandstone that was precipitated during the Middle Jurassic have heavier carbon and oxygen isotope ratios, which are similar to those of carbonate debris in the sandstone (δ13C = 1.93%o, δ180 = -6.11‰), demonstrating that the two are from the same source that had a heavier oxygen isotope ratio (δ180 of about 2.2‰). The differences in fluid oxygen isotope ratios during cement precipitation reflect the influences of different water-rock interaction systems or different wa- ter-rock interaction strengths. This is the main reason why the sandstone containing many rigid particles (lithic quartz sand- stone) has a relatively negative carbon isotope ratio and why the precipitation fluid in calcarenaceous sandstone has a relatively heavier oxygen isotope ratio.
基金National Science and Technology Major Project of the Ministry of Science and Technology of China(Grant No. 2010ZX09401-403)
文摘The general strategy and method of constructing universal calibration model for levofioxacin injections by near-infrared spectroscopy have been investigated and discussed. Firstly, a constant-temperature homogeneous liquid calibration model for levofloxacin hydrochloride injections with the same composition but different active principal ingredient (API) content was established as the basic unit for universal model. Then, samples of levofloxacin hydrochloride injections containing propylene glycol or levofloxacin lactate injections were added to develop a primary constant-temperature liquid universal model. Temperature- amended final universal model was established to apply to samples under different temperatures. The final model was built from 61 calibration samples and 77 validation samples. The value of the root mean square error of cross validation (RMSECV) and coefficient of determination (r2) of leave-one-out cross-validation (LOOCV) were 0.792 and 0.9993, respectively, the root mean square error of prediction (RMSEP) of test set validation (TSV) was 0.87, and the average relative deviation was 1.44%. According to the ICH guidelines, the universal calibration model was evaluated. Based on the experimental statistical results, the recommended number of calibration samples for a constant-temperature homogeneous liquid quantitative model was no less than 15.
基金supported by the National Natural Science Foundation of China (51503001, 51603001)the Research Foundation for Key Program of Education Department of Anhui Province of China (KJ2016A030)+1 种基金the Doctor Research Foundation of Anhui University (J10113190075)the Academic and Technology Introduction Project of Anhui University (AU02303203)
文摘Herein, new poly(ortho ester disulfide urethanes) (POEDU) and poly(ortho ester urethanes) (POEU) were successfully syn- thesized via polycondensation between active esters of 1,6-hexandiol (HD) and dual-stimuli-sensitive ortho ester disulfide diamine or pH-senstive ortho ester diamine. The corresponding POEDU and POEU nanospheres were easily fabricated using an oil-in-water emulsion technique. In vitro degradation experiments indicated that POEDU nanospheres degraded faster than POEU nanospheres in mildly acidic and reductive environments. Doxorubicin (DOX) as a model antitumor drug was suc- cessfully incorporated into these nanospheres to give DOX-loaded nanoparticles (POEDU-DOX and POEU-DOX). In vitro drug release studies showed that release of DOX from dual-stimuli-sensitive POEDU-DOX was accelerated compared with release from the pH-sensitive POEU-DOX under DL-dithiothreitol (DTT) and mildly acidic conditions. In addition, in vitro uptake and cytotoxicity assays revealed that POEDU-DOX exhibited more efficient antitnmor effect than POEU-DOX did against both two- dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS). Finally, in a mice H22 tumor model, POEDU-DOX exhibited preferable antitumor capability. In conclusion, the pH and redox dual-stimuli-sensitive POEDU na- nospheres can be superior drug carriers for cancer treatment.