OBJECTIVE: To explore the effect and the mechanism of Chaiqinchengqi decoction(CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis(ANP) in rats.METHODS: Sixty Sprague-D...OBJECTIVE: To explore the effect and the mechanism of Chaiqinchengqi decoction(CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis(ANP) in rats.METHODS: Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis(AP)model was induced by intraperitoneal injections of4 g/kg 8% L-Arginine(PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD(20 mL/kg every 2 h, 3 times,then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP.The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria.RESULTS: CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group(0.67±0.13 vs 1.54±0.03 vs 0.81±0.09; 0.71±0.08 vs 1.55±0.09 vs 0.89±0.16, P<0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group(1.36±0.15 vs 0.67±0.04, 1.46±0.08 vs 0.59±0.09, P<0.01), or the ANP group(0.96±0.13, P>0.05;0.97±0.09, P<0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h.CONCLUSION: CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.展开更多
Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical tri...Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains unclear.Here,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP.We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models.We also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points.Moreover,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity.Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-lactate.Lastly,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP patients.These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.展开更多
Tourism destination branding is an important goal in the development of tourism industry,and brand image and brand loyalty are important components of destination brand equity.Based on analyzing the framework of influ...Tourism destination branding is an important goal in the development of tourism industry,and brand image and brand loyalty are important components of destination brand equity.Based on analyzing the framework of influencing factors of brand image and brand loyalty in tourism destinations,this paper takes Xinjiang Production and Construction Corps of China as an example,and conducts an empirical study on the influencing mechanism of brand awareness,brand association,brand trust and perceived quality on brand image and brand loyalty in tourism destinations by constructing a structural equation model.We find that brand awareness,brand association,and perceived quality have positive effects on brand image and brand loyalty,and some of these effects are mediated by brand trust.In addition,we find that tourists’subjective experience,as reflected by tourists’age and frequency of travel,moderates each of the influences on brand image and brand loyalty differently.This study enriches the theory of tourism destination research and provides a basis for the improvement of tourism destination brand.展开更多
基金Supported by National Natural Science Foundation of China (No.81072910)Science and Technology Support Program of Sichuan (No.2011SZ0291)
文摘OBJECTIVE: To explore the effect and the mechanism of Chaiqinchengqi decoction(CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis(ANP) in rats.METHODS: Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis(AP)model was induced by intraperitoneal injections of4 g/kg 8% L-Arginine(PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD(20 mL/kg every 2 h, 3 times,then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP.The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria.RESULTS: CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group(0.67±0.13 vs 1.54±0.03 vs 0.81±0.09; 0.71±0.08 vs 1.55±0.09 vs 0.89±0.16, P<0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group(1.36±0.15 vs 0.67±0.04, 1.46±0.08 vs 0.59±0.09, P<0.01), or the ANP group(0.96±0.13, P>0.05;0.97±0.09, P<0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h.CONCLUSION: CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.
基金supported by the National Natural Science Foundation of China(Dan Du,82170905)the Program of Science and Technology Department of Sichuan Province(Dan Du,2023NSFSC1755,China)+2 种基金the State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College(Dan Du,GTZK202107,China)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Qing Xia,ZYJC18005,China)the West China,Nursing Discipline Development Special Fund Project,Sichuan University(Xia Li,HXHL21060,China).
文摘Acute pancreatitis(AP)is a potentially fatal condition with no targeted treatment options.Although inhibiting xanthine oxidase(XO)in the treatment of AP has been studied in several experimental models and clinical trials,whether XO is a target of AP and what its the main mechanism of action is remains unclear.Here,we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP.We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models.We also found that allopurinol and febuxostat,as purine-like and non-purine XO inhibitors,respectively,exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points.Moreover,we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity.Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha(HIF-1α)-regulated lactate dehydrogenase A(LDHA)and NOD-like receptor family pyrin domain containing 3(NLRP3)signaling pathways and reduced the enrichment of^(13)C_(6)-glucose to^(13)C_(3)-lactate.Lastly,we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels,while pancreatic XO and urate were also increased in severe AP patients.These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.
文摘Tourism destination branding is an important goal in the development of tourism industry,and brand image and brand loyalty are important components of destination brand equity.Based on analyzing the framework of influencing factors of brand image and brand loyalty in tourism destinations,this paper takes Xinjiang Production and Construction Corps of China as an example,and conducts an empirical study on the influencing mechanism of brand awareness,brand association,brand trust and perceived quality on brand image and brand loyalty in tourism destinations by constructing a structural equation model.We find that brand awareness,brand association,and perceived quality have positive effects on brand image and brand loyalty,and some of these effects are mediated by brand trust.In addition,we find that tourists’subjective experience,as reflected by tourists’age and frequency of travel,moderates each of the influences on brand image and brand loyalty differently.This study enriches the theory of tourism destination research and provides a basis for the improvement of tourism destination brand.
