Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two familie...Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2)with numerous subtypes.In the last few decades,there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions.Mainly,signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies.Thus,interference with P2 receptors may be a promising strategy for the modulation of immune responses.Although only a few clinical studies have been conducted in isolated entities with limited success,preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases.Despite the association of P2 receptors with several disorders from this field,the use of P2 receptor antagonists in clinical therapy is still very scarce.In this narrative review,we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes.We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events.Using suramin,a non-specific purinergic inhibitor,as an example,we further show that off-target effects could be responsible for observed effects in immunological settings,which may have interesting implications.Overall,we believe that it is worthwhile to further investigate this hitherto underexplored area.展开更多
To explore the effect of the extracellular ATP and its receptors on axon regeneration in the sciatic nerve defect in rats, 0.5 cm defect of the sciatic nerve was made and repaired with long arm silicon tube like a ...To explore the effect of the extracellular ATP and its receptors on axon regeneration in the sciatic nerve defect in rats, 0.5 cm defect of the sciatic nerve was made and repaired with long arm silicon tube like a 'Y' type. The single arm of the silicon tube was sutured to proximal of the sciatic nerve. 10 μl 1 mmol/L ATP in physiological saline was injected into the left chamber of the silicon tube (experimental group) and physiological saline injected into another silicon tube as a control group. In another model 1 mmol/L 10 μl ATP and 1 mmol/L 10 μl ATP+0.2 mg/ml suramin were injected respectively into two arms of the silicon tube. After 4 and 8 weeks the specimens were obtained from the silicon tube for examining the axon regeneration histologically and image analysis. All the regeneration axons grew into the silicon tube containing the ATP, but there was no axon regeneration in the silicon tube containing the ATP+Suramin or physiological saline. It was demonstrated that extracellular ATP had a powerful attraction to the regenerated axon of peripheral nerve. The suramin inhibited the axon induction of the extracellular ATP completely via the ATP receptors.展开更多
In this study, the mechanism by which Suramin inhibits the replication of epidemic encephalitis B virus was explored to provide a theoretical basis for its further application in clinical practice. After viral infecti...In this study, the mechanism by which Suramin inhibits the replication of epidemic encephalitis B virus was explored to provide a theoretical basis for its further application in clinical practice. After viral infection of HepG2 and IMR 32 cells, different concentrations of Suramin were added to the culture media, and then the cultural supernatants and infected cells were collected 48 h later. For the evaluation of the curative effect, cytopathic effect (CPE), virus titers, the expression of viral protein and viral RNA were determined by Western blot, RT PCR and in vitro RNA synthesis, respectively. At the concentration of 50 μg/ml of Suramin, HepG2 and IMR 32 infected with epidemic encephalitis B virus decreased by 51.8 % and 0.03 % respectively, as compared with controls. It was suggested that expression of encephalitis B virus proteins NS3 and E was notably reduced by Suramin. This is especially true of E protein. At RNA level, however, no difference in RNA virus was found between Suramin treated virus and non treated cells. Our results suggest that Suramin can inhibit viral replication by blocking the production of viral proteins.展开更多
The aim of the study was to investigate the role of suramin in the proliferation and apoptosis of activated hepatic stellate cells（HSCs）.HSCs were cultured in medium with different doses of suramin.The cell prolifer...The aim of the study was to investigate the role of suramin in the proliferation and apoptosis of activated hepatic stellate cells（HSCs）.HSCs were cultured in medium with different doses of suramin.The cell proliferation rate was determined using methyl thiazolyl tetrazolium（MTT）assay.Both the cell cycle and proliferation index（PRI）were analyzed using flow cytometry.The apoptotic rate of HSCs was measured using TdT-mediated dUTP nick end labeling（TUNEL）method.The conformation of HSCs was observed using microscopy.The results indicated that the HSCs proliferation rate of suramin treated cells was significantly reduced compared to the control cells.After HSCs were treated with suramin for 72 h,the cell proliferation rate reached the lowest value compared to the control cells.Our results indicated that suramin inhibited the proliferation of HSCs in a time-and dose-dependent manner.After HSCs were treated with suramin for 24 h,the percentage of HSCs in the G_1 phase exhibited a significant increase,the PRI showed a remarkable decrease,while the HSCs apoptosis rate did not show any obvious change.In addition,it seemed that suramin failed to affect the conformation of HSCs.Our data suggested that within the dose range used in the present study,suramin inhibited the proliferation of HSCs,but it could not induce HSCs apoptosis.展开更多
Background:Human African trypanosomiasis(HAT)is one of the most complex parasitic diseases known to humankind.It usually occurs in endemic areas in Africa,but is occasionally detected in returning travelers and migran...Background:Human African trypanosomiasis(HAT)is one of the most complex parasitic diseases known to humankind.It usually occurs in endemic areas in Africa,but is occasionally detected in returning travelers and migrants in non-endemic countries.Case presentation:In August 2017,a case of HAT was diagnosed in China in a traveler returning from the Masai Mara area in Kenya and the Serengeti area in Tanzania.The traveler visited Africa from 23 July to 5 August,2017.Upon return to China,she developed a fever(on 8 August),and Trypanosoma brucei rhodesiense infection was confirmed by laboratory tests(on 14 August)including observation of parasites in blood films and by polymerase chain reaction.She was treated with pentamidine followed by suramin,and recovered 1 month later.Conclusions:This is the first imported rhodesiense HAT case reported in China.This case alerts clinical and public health workers to be aware of HAT in travelers,and expatriates and migrants who have visited at-risk areas in Africa.展开更多
I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of M...I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated展开更多
Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of compleme...Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of complement inhibitors against the overall function of the complement system. The main objective of our study was to develop a specific enzyme-linked immunosoihent assay (ELISA) as an alternative method to assess the anti-complement activity, particularly against the lectin pathway. By using respective coating substrates against different activation pathways, followed by capturing the stable C3c fragments, our ELBA method can be used to screen complement inhibitors against the classical pathway and the lectin pathway. The inhibitory effect of sununin on the classical pathway, as measured by our hemolytic assay is consistent with previous reports. Further assessment of suramin and Bupleurum polysaccharides against the lectin pathway showed a good reproducibility of the method. Comparison of the lectin pathway IC5is between Ruplearum.smithii var, purviPliam polysaccharides (1.055 ingtmE) and Buplcurann chinense polysaccharides (0.98 ing/mL) showed that similar to the classical and alterative pathway, these two Bupleurum polysaccharides had comparable anti complementary properties against the lectin pathway. The results demonstrate that the described EIASA assay can compensate for he shortcomings of the hemolytic assay in lectin pathway. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).展开更多
基金supported by the UZH Postdoc grant(to MH)the Foundation for Research in Science at the University of Zurich(to MTW)。
文摘Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis.This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2)with numerous subtypes.In the last few decades,there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions.Mainly,signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies.Thus,interference with P2 receptors may be a promising strategy for the modulation of immune responses.Although only a few clinical studies have been conducted in isolated entities with limited success,preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases.Despite the association of P2 receptors with several disorders from this field,the use of P2 receptor antagonists in clinical therapy is still very scarce.In this narrative review,we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes.We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events.Using suramin,a non-specific purinergic inhibitor,as an example,we further show that off-target effects could be responsible for observed effects in immunological settings,which may have interesting implications.Overall,we believe that it is worthwhile to further investigate this hitherto underexplored area.
文摘To explore the effect of the extracellular ATP and its receptors on axon regeneration in the sciatic nerve defect in rats, 0.5 cm defect of the sciatic nerve was made and repaired with long arm silicon tube like a 'Y' type. The single arm of the silicon tube was sutured to proximal of the sciatic nerve. 10 μl 1 mmol/L ATP in physiological saline was injected into the left chamber of the silicon tube (experimental group) and physiological saline injected into another silicon tube as a control group. In another model 1 mmol/L 10 μl ATP and 1 mmol/L 10 μl ATP+0.2 mg/ml suramin were injected respectively into two arms of the silicon tube. After 4 and 8 weeks the specimens were obtained from the silicon tube for examining the axon regeneration histologically and image analysis. All the regeneration axons grew into the silicon tube containing the ATP, but there was no axon regeneration in the silicon tube containing the ATP+Suramin or physiological saline. It was demonstrated that extracellular ATP had a powerful attraction to the regenerated axon of peripheral nerve. The suramin inhibited the axon induction of the extracellular ATP completely via the ATP receptors.
基金ThisprojectwassupportedbythefundofChineseServiceCenterforScholarlyExchange (No .1999- 36 3)
文摘In this study, the mechanism by which Suramin inhibits the replication of epidemic encephalitis B virus was explored to provide a theoretical basis for its further application in clinical practice. After viral infection of HepG2 and IMR 32 cells, different concentrations of Suramin were added to the culture media, and then the cultural supernatants and infected cells were collected 48 h later. For the evaluation of the curative effect, cytopathic effect (CPE), virus titers, the expression of viral protein and viral RNA were determined by Western blot, RT PCR and in vitro RNA synthesis, respectively. At the concentration of 50 μg/ml of Suramin, HepG2 and IMR 32 infected with epidemic encephalitis B virus decreased by 51.8 % and 0.03 % respectively, as compared with controls. It was suggested that expression of encephalitis B virus proteins NS3 and E was notably reduced by Suramin. This is especially true of E protein. At RNA level, however, no difference in RNA virus was found between Suramin treated virus and non treated cells. Our results suggest that Suramin can inhibit viral replication by blocking the production of viral proteins.
文摘The aim of the study was to investigate the role of suramin in the proliferation and apoptosis of activated hepatic stellate cells（HSCs）.HSCs were cultured in medium with different doses of suramin.The cell proliferation rate was determined using methyl thiazolyl tetrazolium（MTT）assay.Both the cell cycle and proliferation index（PRI）were analyzed using flow cytometry.The apoptotic rate of HSCs was measured using TdT-mediated dUTP nick end labeling（TUNEL）method.The conformation of HSCs was observed using microscopy.The results indicated that the HSCs proliferation rate of suramin treated cells was significantly reduced compared to the control cells.After HSCs were treated with suramin for 72 h,the cell proliferation rate reached the lowest value compared to the control cells.Our results indicated that suramin inhibited the proliferation of HSCs in a time-and dose-dependent manner.After HSCs were treated with suramin for 24 h,the percentage of HSCs in the G_1 phase exhibited a significant increase,the PRI showed a remarkable decrease,while the HSCs apoptosis rate did not show any obvious change.In addition,it seemed that suramin failed to affect the conformation of HSCs.Our data suggested that within the dose range used in the present study,suramin inhibited the proliferation of HSCs,but it could not induce HSCs apoptosis.
基金This work was supported by the National Key Research and Development Program of China(Grant Nos.2016YFC1202000,2016YFC1202002)by the International Development Research Center(IDRC),Canada(grant No.108100–001).
文摘Background:Human African trypanosomiasis(HAT)is one of the most complex parasitic diseases known to humankind.It usually occurs in endemic areas in Africa,but is occasionally detected in returning travelers and migrants in non-endemic countries.Case presentation:In August 2017,a case of HAT was diagnosed in China in a traveler returning from the Masai Mara area in Kenya and the Serengeti area in Tanzania.The traveler visited Africa from 23 July to 5 August,2017.Upon return to China,she developed a fever(on 8 August),and Trypanosoma brucei rhodesiense infection was confirmed by laboratory tests(on 14 August)including observation of parasites in blood films and by polymerase chain reaction.She was treated with pentamidine followed by suramin,and recovered 1 month later.Conclusions:This is the first imported rhodesiense HAT case reported in China.This case alerts clinical and public health workers to be aware of HAT in travelers,and expatriates and migrants who have visited at-risk areas in Africa.
文摘I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated
基金supported by grants from the National Natural Science Foundation of China (Nos. 81274165, 81330089 and 30925042)the State Key Program for Innovative Drugs from the Ministry of Science and Technology of the people’s Republic of China (No. 2012ZX09301001-003)+1 种基金the Science and Technology Commission of Shanghai Municipality (Nos. 12JC1400800 and 10XD1405900)Fudan's Undergraduate Research Opportunities Program (Xiyuan, No. 102305)
文摘Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of complement inhibitors against the overall function of the complement system. The main objective of our study was to develop a specific enzyme-linked immunosoihent assay (ELISA) as an alternative method to assess the anti-complement activity, particularly against the lectin pathway. By using respective coating substrates against different activation pathways, followed by capturing the stable C3c fragments, our ELBA method can be used to screen complement inhibitors against the classical pathway and the lectin pathway. The inhibitory effect of sununin on the classical pathway, as measured by our hemolytic assay is consistent with previous reports. Further assessment of suramin and Bupleurum polysaccharides against the lectin pathway showed a good reproducibility of the method. Comparison of the lectin pathway IC5is between Ruplearum.smithii var, purviPliam polysaccharides (1.055 ingtmE) and Buplcurann chinense polysaccharides (0.98 ing/mL) showed that similar to the classical and alterative pathway, these two Bupleurum polysaccharides had comparable anti complementary properties against the lectin pathway. The results demonstrate that the described EIASA assay can compensate for he shortcomings of the hemolytic assay in lectin pathway. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
