Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems. Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of th...Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems. Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatooltes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites; protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.展开更多
At the present time, more than one-half of all cancer patients are treated with radiation therapy. Despite a good therapeutic index, radiotherapy can disable normal tissue injury to normal tissues in long-term cancer ...At the present time, more than one-half of all cancer patients are treated with radiation therapy. Despite a good therapeutic index, radiotherapy can disable normal tissue injury to normal tissues in long-term cancer survivors.Thus, an important challenge to modern radiation therapy is to increase the tolerance of normal tissues,展开更多
Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentra...Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized,placebo-controlled trials,and meta-analyses when available,that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD,modifying the treatment goals. However,the large majority of patients with CD will be managed through conventional therapy,even if they are a prelude to biological therapy.展开更多
In the present study, we aimed to explore the mechanism of Salvia miltiorrhiza in the treatment of pathological scars(PS) by network pharmacology. The active ingredients and drug targets of Salvia miltiorrhiza were sc...In the present study, we aimed to explore the mechanism of Salvia miltiorrhiza in the treatment of pathological scars(PS) by network pharmacology. The active ingredients and drug targets of Salvia miltiorrhiza were screened out through TCMSP database, the disease targets of PS in Gene Cards database were obtained, and Venn diagram analysis on drug targets and disease targets was performed, and the intersection was used as the target of Salvia miltiorrhiza for the treatment of PS. Cytoscape software was used to construct a drug-ingredient-target-disease network diagram. A protein-protein interaction network was constructed through String website, its key protein modules and hub genes were screened with Cytoscape software, and GO and KEGG enrichment analyses were performed in DAVID database. Fifty-nine active ingredients, 138 drug targets, and 90 targets of Salvia miltiorrhiza for the treatment of PS were screened out. Core ingredients, such as luteolin and tanshinone IIA, were obtained. The hub genes, such as VEGFA, TP53, JUN, STAT3, AKT1, MAPK1, and PTGS2, and signaling pathways, such as HIF-1, TNF, MAPK, PI3 K-Akt, and Jak-STAT, were screened out. Salvia miltiorrhiza might improve PS hypoxia, inflammation, and balance of proliferation and apoptosis of fibroblasts by regulating HIF-1, TNF, MAPK, PI3 K-Akt, and Jak-STAT signaling pathways. Moreover, it had the characteristics of multiple centers, multiple targets, and multiple pathways.展开更多
Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with ca...Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.展开更多
Objective: To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits. Methods: Thirty male New Zealand white rabbits were randomly divi...Objective: To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits. Methods: Thirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L 5) were removed immediately for histopathological study. Results: The neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P< 0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P< 0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r= 0.839, P< 0.01). Conclusions: Puerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.展开更多
文摘Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems. Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatooltes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites; protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.
文摘At the present time, more than one-half of all cancer patients are treated with radiation therapy. Despite a good therapeutic index, radiotherapy can disable normal tissue injury to normal tissues in long-term cancer survivors.Thus, an important challenge to modern radiation therapy is to increase the tolerance of normal tissues,
文摘Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD. This review concentrates on the results of randomized,placebo-controlled trials,and meta-analyses when available,that provide the highest degree of evidence. Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase. The advent of biological drugs has opened new therapeutic horizons for treating CD,modifying the treatment goals. However,the large majority of patients with CD will be managed through conventional therapy,even if they are a prelude to biological therapy.
基金The National Key Research and Development Projects(Grant No.2017YFC1307602)the Scientific Research Projects of Tianjin(Grant No.16ZXHLSY00120+2 种基金15ZXLCSY00040)Logistics College of PAP Projects(Grant No.WHJ201729)Logistics Project of PAP(Grant No.CWJ18L004)。
文摘In the present study, we aimed to explore the mechanism of Salvia miltiorrhiza in the treatment of pathological scars(PS) by network pharmacology. The active ingredients and drug targets of Salvia miltiorrhiza were screened out through TCMSP database, the disease targets of PS in Gene Cards database were obtained, and Venn diagram analysis on drug targets and disease targets was performed, and the intersection was used as the target of Salvia miltiorrhiza for the treatment of PS. Cytoscape software was used to construct a drug-ingredient-target-disease network diagram. A protein-protein interaction network was constructed through String website, its key protein modules and hub genes were screened with Cytoscape software, and GO and KEGG enrichment analyses were performed in DAVID database. Fifty-nine active ingredients, 138 drug targets, and 90 targets of Salvia miltiorrhiza for the treatment of PS were screened out. Core ingredients, such as luteolin and tanshinone IIA, were obtained. The hub genes, such as VEGFA, TP53, JUN, STAT3, AKT1, MAPK1, and PTGS2, and signaling pathways, such as HIF-1, TNF, MAPK, PI3 K-Akt, and Jak-STAT, were screened out. Salvia miltiorrhiza might improve PS hypoxia, inflammation, and balance of proliferation and apoptosis of fibroblasts by regulating HIF-1, TNF, MAPK, PI3 K-Akt, and Jak-STAT signaling pathways. Moreover, it had the characteristics of multiple centers, multiple targets, and multiple pathways.
基金supported by the National Natural Science Foundation of China (81530009 to Youyi Zhang, 81670205 to Han Xiao)
文摘Cardiac remodelling is generally accepted as a critical process in the progression of heart failure. Myocyte hypertrophy,inflammatory responses and cardiac fibrosis are the main pathological changes associated with cardiac remodelling.AMP-activated protein kinase(AMPK) is known as an energy sensor and a regulator of cardiac metabolism under normal and ischaemic conditions. Additionally, AMPK has been shown to play roles in cardiac remodelling extending well beyond metabolic regulation. In this review, we discuss the currently defined roles of AMPK in cardiac remodelling and summarize the effects of AMPK on cardiac hypertrophy, inflammatory responses and fibrosis and the molecular mechanisms underlying these effects. In addition, we discuss some pharmacological activators of AMPK that are promising treatments for cardiac remodelling.
基金ThisworkwassupportedbytheNaturalScienceFoundationofShaanxiProvince (No .99SM39)
文摘Objective: To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits. Methods: Thirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L 5) were removed immediately for histopathological study. Results: The neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P< 0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P< 0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r= 0.839, P< 0.01). Conclusions: Puerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.