The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive ...The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.展开更多
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause o...The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.展开更多
Objective: To study the adverse effects of advanced glycation end products(AGEs) on chondrocytes and the role of autophagy in this process. Methods: Chondrocytes were harvested from the human articular cartilage tissu...Objective: To study the adverse effects of advanced glycation end products(AGEs) on chondrocytes and the role of autophagy in this process. Methods: Chondrocytes were harvested from the human articular cartilage tissues in surgery. AGEs were administered during chondrocytes culture. The rapamycin was used to induce autophagy. The cell viability was determined by 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT) assay.The expression of tumor necrosis factor-α(TNF-α) and nuclear factor-κ B(NF-κ B) was detected by quantitative real-time polymerase chain reaction. The reactive oxygen species(ROS) production and apoptosis of the chondrocytes were determined by fluorescent probe and flow cytometer, respectively. Results: The chondrocytes viability was significantly reduced after 12 h incubation with AGEs(P<0.01)). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF-α and NF-κ B mRNA expression of chondrocytes and autophagy receded or proceeded the change. AGEs increased intracellular ROS accumulation and autophagy reversed the change. AGEs accelerated chondrocytes apoptosis and autophagy suspended apoptosis. Conclusions: Accumulation of AGEs may have an adverse role for chondrocytes by increasing TNF-α and NF-κB expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEsinduced adverse effects.展开更多
Introduction: Extracorporeal Membrane Oxygenation (ECMO) is used in selected patient with cardiogenic and/or re- spiratory shock. We report our experience with standardized management protocols and the application of ...Introduction: Extracorporeal Membrane Oxygenation (ECMO) is used in selected patient with cardiogenic and/or re- spiratory shock. We report our experience with standardized management protocols and the application of the Qua- droxD oxygenator with a centrifugal pump to maximize end-organ recovery and improve survival. Methods: This is an Internal Review Board (IRB) approved, single institution retrospective study of end-organ recovery and survival in pa- tients who required ECMO for cardiogenic and/or respiratory shock between July 2010 and June 2011. Results: Sixteen patients (median age: 46 years) were initiated on either Veno-Arterial (VA) or Veno-Venous (VV) ECMO. Cardiogenic shock, acute respiratory distress syndrome (ARDS) and a combined respiratory and cardiogenic compromise were the primary indications for ECMO in 8 (50%), 5 (31%) and 3 (19%) patients respectively. The median time on ECMO was 8 days (range: 4 - 26 days). Twelve patients (75%) were successfully weaned off ECMO, of which four (25%) were bridged to a ventricular assist device (VAD) and eight (50%) were weaned to recovery. All eight patients (100%) that were weaned to recovery and two patients (50%) that were bridged to a VAD were successfully discharged from the hospital, resulting in a discharge rate of 63%. There was an improvement in pre- vs. post-ECMO AST (449 IU/L vs. 63 IU/L, p Conclusion: ECMO using the QuadroxD oxygenator and a centrifugal pump, coupled with standardized management protocols is beneficial in carefully selected patients. Improvement or main- tenance of end-organ function is associated with successful bridge to device therapy and/or increased survival.展开更多
Artificial intelligence techniques have been used to predict basic oxygen furnace(BOF) end-points. However,the main challenge is to effectively reduce the input nodes as too many input nodes in neural network increase...Artificial intelligence techniques have been used to predict basic oxygen furnace(BOF) end-points. However,the main challenge is to effectively reduce the input nodes as too many input nodes in neural network increase complexity,decrease accuracy and slow down the training speed of the network.Simply picking-up variables as input usually influence validity of model.It is quite necessary to develop an effective method to reduce the number of input nodes whereby to simplify the network and improve model performance.In this study,a variable-filtrating technique combining both metallurgical mechanism model and partial least-squares(PLS ) regression method has been proposed by taking the advantages of both of them,i.e.qualitive and quantative relationships between variables respectively.Accordingly,a fuzzy-reasoning neural network(FNN) prediction model for basic oxygen furnace(BOF) end-point carbon content based on this technique has been developed.The prediction results showed that this model can effectively improve the hit rate of end-point carbon content and increase network training speed.The successful hit rate of the model can reach up to 94.12%with about 0.02% error range.展开更多
The science that underpins our knowledge and understanding of Isotope-Based Hydrograph separation (IHS) has gained grounds, over the last few decades, in the identification of streamflow sources. However, challenges s...The science that underpins our knowledge and understanding of Isotope-Based Hydrograph separation (IHS) has gained grounds, over the last few decades, in the identification of streamflow sources. However, challenges still exist in identifying appropriate tracers and the right combination of end-members for the IHS process. In a two-component IHS analysis, the application of the dual isotopes tracers, δ18O and (or) δ2H, is regarded as the simplest method. We undertook an IHS study within a nested system of eight Prairie watersheds located in South central Manitoba, Canada. The work evaluated about 17,000 results emanating from the application of a combination of two potential tracers (δ18O and δ2H) and eight each of potential “old” and “new” water end-members in a two-component IHS process. The outcome showed occurrences of many mathematically possible but hydrologically unacceptable IHS results. The observation was particularly predominant within relatively larger perennial sub-catchments of the watershed. It is also shown that inter-site sub-catchment isotopic end-member transferability is possible within watersheds of similar physio-hydrographic characteristics. We suggest that a careful evaluation of the physio-hydrographic characteristics of catchments be considered in IHS studies in addition to the recommended guidelines in the selection of tracers and end-members.展开更多
晚期糖基化终末产物受体(receptor for advanced glycation end product,RAGE)是免疫球蛋白受体,能够与多种配体结合,研究发现RAGE参与了非专职吞噬细胞对组蛋白修饰的微米颗粒的吞噬过程,但目前没有研究证明组蛋白是RAGE的配体。该研...晚期糖基化终末产物受体(receptor for advanced glycation end product,RAGE)是免疫球蛋白受体,能够与多种配体结合,研究发现RAGE参与了非专职吞噬细胞对组蛋白修饰的微米颗粒的吞噬过程,但目前没有研究证明组蛋白是RAGE的配体。该研究对组蛋白分子能否直接激活RAGE及其下游信号通路进行探究。使用共聚焦显微镜和流式细胞仪检测哺乳动物细胞对可溶性组蛋白分子的内化;采用钙黄绿素乙酰氧基甲酯/碘化丙啶染色法检测细胞活性;通过荧光探针2′,7′-二氯二氢荧光素二乙酸酯检测胞内活性氧水平;利用酶联免疫吸附剂测定法(enzyme-linked immunosorbent assay,ELISA)测定炎症因子的释放。结果表明,组蛋白分子能够被野生型HEK293T细胞内化并于胞内溶酶体中聚集,RAGE-敲除细胞则无法内化组蛋白;培养基组蛋白质量浓度在100μg/mL时对细胞无明显毒性,细胞活性正常;组蛋白能够通过RAGE刺激细胞活性氧水平升高,并释放炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6);组蛋白与DNA结合能够增强对RAGE的刺激。以上结果表明,组蛋白能够激活RAGE及其下游炎症通路。展开更多
文摘The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.
文摘The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
文摘Objective: To study the adverse effects of advanced glycation end products(AGEs) on chondrocytes and the role of autophagy in this process. Methods: Chondrocytes were harvested from the human articular cartilage tissues in surgery. AGEs were administered during chondrocytes culture. The rapamycin was used to induce autophagy. The cell viability was determined by 3-[4,5-dimethylthiazol2-yl]-2,5-diphenyl tetrazolium bromide(MTT) assay.The expression of tumor necrosis factor-α(TNF-α) and nuclear factor-κ B(NF-κ B) was detected by quantitative real-time polymerase chain reaction. The reactive oxygen species(ROS) production and apoptosis of the chondrocytes were determined by fluorescent probe and flow cytometer, respectively. Results: The chondrocytes viability was significantly reduced after 12 h incubation with AGEs(P<0.01)). In contrast, rapamycin pretreatment increased the chondrocytes viability through autophagy. AGEs increased TNF-α and NF-κ B mRNA expression of chondrocytes and autophagy receded or proceeded the change. AGEs increased intracellular ROS accumulation and autophagy reversed the change. AGEs accelerated chondrocytes apoptosis and autophagy suspended apoptosis. Conclusions: Accumulation of AGEs may have an adverse role for chondrocytes by increasing TNF-α and NF-κB expression, ROS accumulation and apoptosis; meanwhile, autophagy ameliorates the AGEsinduced adverse effects.
文摘Introduction: Extracorporeal Membrane Oxygenation (ECMO) is used in selected patient with cardiogenic and/or re- spiratory shock. We report our experience with standardized management protocols and the application of the Qua- droxD oxygenator with a centrifugal pump to maximize end-organ recovery and improve survival. Methods: This is an Internal Review Board (IRB) approved, single institution retrospective study of end-organ recovery and survival in pa- tients who required ECMO for cardiogenic and/or respiratory shock between July 2010 and June 2011. Results: Sixteen patients (median age: 46 years) were initiated on either Veno-Arterial (VA) or Veno-Venous (VV) ECMO. Cardiogenic shock, acute respiratory distress syndrome (ARDS) and a combined respiratory and cardiogenic compromise were the primary indications for ECMO in 8 (50%), 5 (31%) and 3 (19%) patients respectively. The median time on ECMO was 8 days (range: 4 - 26 days). Twelve patients (75%) were successfully weaned off ECMO, of which four (25%) were bridged to a ventricular assist device (VAD) and eight (50%) were weaned to recovery. All eight patients (100%) that were weaned to recovery and two patients (50%) that were bridged to a VAD were successfully discharged from the hospital, resulting in a discharge rate of 63%. There was an improvement in pre- vs. post-ECMO AST (449 IU/L vs. 63 IU/L, p Conclusion: ECMO using the QuadroxD oxygenator and a centrifugal pump, coupled with standardized management protocols is beneficial in carefully selected patients. Improvement or main- tenance of end-organ function is associated with successful bridge to device therapy and/or increased survival.
文摘Artificial intelligence techniques have been used to predict basic oxygen furnace(BOF) end-points. However,the main challenge is to effectively reduce the input nodes as too many input nodes in neural network increase complexity,decrease accuracy and slow down the training speed of the network.Simply picking-up variables as input usually influence validity of model.It is quite necessary to develop an effective method to reduce the number of input nodes whereby to simplify the network and improve model performance.In this study,a variable-filtrating technique combining both metallurgical mechanism model and partial least-squares(PLS ) regression method has been proposed by taking the advantages of both of them,i.e.qualitive and quantative relationships between variables respectively.Accordingly,a fuzzy-reasoning neural network(FNN) prediction model for basic oxygen furnace(BOF) end-point carbon content based on this technique has been developed.The prediction results showed that this model can effectively improve the hit rate of end-point carbon content and increase network training speed.The successful hit rate of the model can reach up to 94.12%with about 0.02% error range.
文摘The science that underpins our knowledge and understanding of Isotope-Based Hydrograph separation (IHS) has gained grounds, over the last few decades, in the identification of streamflow sources. However, challenges still exist in identifying appropriate tracers and the right combination of end-members for the IHS process. In a two-component IHS analysis, the application of the dual isotopes tracers, δ18O and (or) δ2H, is regarded as the simplest method. We undertook an IHS study within a nested system of eight Prairie watersheds located in South central Manitoba, Canada. The work evaluated about 17,000 results emanating from the application of a combination of two potential tracers (δ18O and δ2H) and eight each of potential “old” and “new” water end-members in a two-component IHS process. The outcome showed occurrences of many mathematically possible but hydrologically unacceptable IHS results. The observation was particularly predominant within relatively larger perennial sub-catchments of the watershed. It is also shown that inter-site sub-catchment isotopic end-member transferability is possible within watersheds of similar physio-hydrographic characteristics. We suggest that a careful evaluation of the physio-hydrographic characteristics of catchments be considered in IHS studies in addition to the recommended guidelines in the selection of tracers and end-members.
文摘晚期糖基化终末产物受体(receptor for advanced glycation end product,RAGE)是免疫球蛋白受体,能够与多种配体结合,研究发现RAGE参与了非专职吞噬细胞对组蛋白修饰的微米颗粒的吞噬过程,但目前没有研究证明组蛋白是RAGE的配体。该研究对组蛋白分子能否直接激活RAGE及其下游信号通路进行探究。使用共聚焦显微镜和流式细胞仪检测哺乳动物细胞对可溶性组蛋白分子的内化;采用钙黄绿素乙酰氧基甲酯/碘化丙啶染色法检测细胞活性;通过荧光探针2′,7′-二氯二氢荧光素二乙酸酯检测胞内活性氧水平;利用酶联免疫吸附剂测定法(enzyme-linked immunosorbent assay,ELISA)测定炎症因子的释放。结果表明,组蛋白分子能够被野生型HEK293T细胞内化并于胞内溶酶体中聚集,RAGE-敲除细胞则无法内化组蛋白;培养基组蛋白质量浓度在100μg/mL时对细胞无明显毒性,细胞活性正常;组蛋白能够通过RAGE刺激细胞活性氧水平升高,并释放炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6);组蛋白与DNA结合能够增强对RAGE的刺激。以上结果表明,组蛋白能够激活RAGE及其下游炎症通路。
