This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protectin...This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.展开更多
Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as s...Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.展开更多
A new method for the rapid separation of gangliosides(GLS)by capillary electrophoresis(CE)is described which is based on the use of β—cyclodextrin(β—CD)as buffer additive.The effects of β—CD concentration,pH,ele...A new method for the rapid separation of gangliosides(GLS)by capillary electrophoresis(CE)is described which is based on the use of β—cyclodextrin(β—CD)as buffer additive.The effects of β—CD concentration,pH,electrolyte composition were dis- cussed.Under optimum conditions,the complete separation of a mixture of GM1,GD1a, GD1b and GT1b was obtained within 5 min.展开更多
Determination of sialidase activity in hepatocellular carcinoma (HCC) to complete the mechanism study of GD3 change in HCC. A sensitive assay for ganglioside sialidase activity was used based on the specific binding o...Determination of sialidase activity in hepatocellular carcinoma (HCC) to complete the mechanism study of GD3 change in HCC. A sensitive assay for ganglioside sialidase activity was used based on the specific binding of ricinus communis agglutinin Ⅱ (RCAⅡ) to lactose reside. The substrate used for sialidase assay was ganglioside GM3 coated on a 96- well microtiterplate. After removing static acids from the terminal positions of the ganglioside glycans by sialidase, the glycans were subjected to biotin-labeled RCAⅡ. Then, the ABC assay was used to determine the activity of sialidase. The activities of sialidase with both soluble form and membrane-bound form in HCC decreased significantly as compared with those in peritumor tissue. Our results indicated that the increase in ganglioside GD3 in HCC is not only due to the enhancement of GD3 sythase activity but also due to the decrease in the sialidase展开更多
Objective:To study the effects of gangliosides combined with family rehabilitation training on nerve injury, neurodevelopment and oxidative stress in children with HIE.Methods:Children with HIE who were treated in Zig...Objective:To study the effects of gangliosides combined with family rehabilitation training on nerve injury, neurodevelopment and oxidative stress in children with HIE.Methods:Children with HIE who were treated in Zigong Third People's Hospital between March 2015 and October 2017 were selected and randomly divided into two groups, rehabilitation training group received gangliosides combined with family rehabilitation training and negative control group accepted gangliosides combined with conventional rehabilitation intervention. The contents of nerve injury molecules, neurotrophic molecules and oxidative stress molecules in serum were measured before intervention and 3 months after intervention.Results: Compared with those of same group before intervention, serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of both groups of children were significantly lower whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were significantly higher 3 months after intervention, and serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of rehabilitation training group after intervention were lower than those of negative control group whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were higher than those of negative control group.Conclusion: Gangliosides combined with family rehabilitation training can reduce the nerve injury, improve the neurodevelopment and inhibit the oxidative stress in children with HIE.展开更多
Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted ...Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted in the neonatal ward of our hospital from August 2018 to October 2020 were selected as the research objects,and were divided into control group and observation group according to the random number table method,with 50 cases in each group.The control group was treated with gangliosides,and the observation group was treated with simple head cooling combined with gangliosides.Observe and compare the clinical performance improvement time,the level of relevant hematological examination indexes before and after treatment,and the neonatal behavioral neurological assessment(NBNA),clinical efficacy,and adverse reactions.Results The improvement time of convulsions,disturbance of consciousness,pupil changes,hypotonia,and gastrointestinal dysfunction in the observation group was significantly lower than that in the control group(all P<0.001).After treatment,the NSE,IL-6,CK,CK-MB of the two groups of children were significantly lower than before treatment,and the serum calcium and NBNA scores were significantly higher than before treatment,and the decrease or increase in the observation group was significantly higher than that of the control Group(all P<0.001).The total effective rate of treatment of children in the observation group(82.00%)was higher than that of the control group(62.00%)(P<0.05).There were no obvious adverse reactions in both groups.Conclusion The simple head cooling combined with gangliosides in the treatment of HIE can improve the clinical symptoms,blood test index levels,and NBNA scores.The clinical effect is clear and superior to the single use of gangliosides.展开更多
Objective:To explore the effect of gangliosides combined with hyperbaric oxygenation on neural functional recovery and oxidative stress injury after cerebral infarction intervention. Methods:A total of 120 patients wi...Objective:To explore the effect of gangliosides combined with hyperbaric oxygenation on neural functional recovery and oxidative stress injury after cerebral infarction intervention. Methods:A total of 120 patients with cerebral infarction who received interventional therapy in our hospital between August 2013 and February 2016 were collected and divided into control group and observation group, 60 cases in each group. Control group received hyperbaric oxygenation after intervention, and the observation group received gangliosides combined with hyperbaric oxygenation after intervention. The differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were compared between two groups of patients before and after treatment.Results: Before intervention, differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were not statistically significant between two groups of patients. After intervention, serum neurotrophy indexes BDNF and NT-3 levels in observation group were higher than those in control group;serum nerve injury indexes S100B, NGB, NSE and GFAP levels were lower than those in control group;serum oxidative indexes MDA, MPO and LPO levels were lower than those in control group while antioxidant indexes SOD, GSH-Px, CAT and TAC levels were higher than those in control group.Conclusion: Gangliosides combined with hyperbaric oxygenation for patients with cerebral infarction after interventional therapy helps speed up the neural functional recovery and also reduce systemic inflammatory response.展开更多
Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside a...Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.展开更多
文摘This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.
基金supported by grants and fellowships from the Departamento de Ciência e Tecnologia(DECIT/MS)do Ministério da Saúde,Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa,Fundação de AmparoàPesquisa do Estado do Rio de Janeiro(FAPERJ)(to RMO).
文摘Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.
文摘A new method for the rapid separation of gangliosides(GLS)by capillary electrophoresis(CE)is described which is based on the use of β—cyclodextrin(β—CD)as buffer additive.The effects of β—CD concentration,pH,electrolyte composition were dis- cussed.Under optimum conditions,the complete separation of a mixture of GM1,GD1a, GD1b and GT1b was obtained within 5 min.
文摘Determination of sialidase activity in hepatocellular carcinoma (HCC) to complete the mechanism study of GD3 change in HCC. A sensitive assay for ganglioside sialidase activity was used based on the specific binding of ricinus communis agglutinin Ⅱ (RCAⅡ) to lactose reside. The substrate used for sialidase assay was ganglioside GM3 coated on a 96- well microtiterplate. After removing static acids from the terminal positions of the ganglioside glycans by sialidase, the glycans were subjected to biotin-labeled RCAⅡ. Then, the ABC assay was used to determine the activity of sialidase. The activities of sialidase with both soluble form and membrane-bound form in HCC decreased significantly as compared with those in peritumor tissue. Our results indicated that the increase in ganglioside GD3 in HCC is not only due to the enhancement of GD3 sythase activity but also due to the decrease in the sialidase
文摘Objective:To study the effects of gangliosides combined with family rehabilitation training on nerve injury, neurodevelopment and oxidative stress in children with HIE.Methods:Children with HIE who were treated in Zigong Third People's Hospital between March 2015 and October 2017 were selected and randomly divided into two groups, rehabilitation training group received gangliosides combined with family rehabilitation training and negative control group accepted gangliosides combined with conventional rehabilitation intervention. The contents of nerve injury molecules, neurotrophic molecules and oxidative stress molecules in serum were measured before intervention and 3 months after intervention.Results: Compared with those of same group before intervention, serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of both groups of children were significantly lower whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were significantly higher 3 months after intervention, and serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of rehabilitation training group after intervention were lower than those of negative control group whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were higher than those of negative control group.Conclusion: Gangliosides combined with family rehabilitation training can reduce the nerve injury, improve the neurodevelopment and inhibit the oxidative stress in children with HIE.
基金Natural Science Foundation of Anhui Province(1808085MH308)School Research Fund Project of Anhui Medical University(2019xkj178)Hefei Science and Technology Research Project(J2018Y06)。
文摘Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted in the neonatal ward of our hospital from August 2018 to October 2020 were selected as the research objects,and were divided into control group and observation group according to the random number table method,with 50 cases in each group.The control group was treated with gangliosides,and the observation group was treated with simple head cooling combined with gangliosides.Observe and compare the clinical performance improvement time,the level of relevant hematological examination indexes before and after treatment,and the neonatal behavioral neurological assessment(NBNA),clinical efficacy,and adverse reactions.Results The improvement time of convulsions,disturbance of consciousness,pupil changes,hypotonia,and gastrointestinal dysfunction in the observation group was significantly lower than that in the control group(all P<0.001).After treatment,the NSE,IL-6,CK,CK-MB of the two groups of children were significantly lower than before treatment,and the serum calcium and NBNA scores were significantly higher than before treatment,and the decrease or increase in the observation group was significantly higher than that of the control Group(all P<0.001).The total effective rate of treatment of children in the observation group(82.00%)was higher than that of the control group(62.00%)(P<0.05).There were no obvious adverse reactions in both groups.Conclusion The simple head cooling combined with gangliosides in the treatment of HIE can improve the clinical symptoms,blood test index levels,and NBNA scores.The clinical effect is clear and superior to the single use of gangliosides.
文摘Objective:To explore the effect of gangliosides combined with hyperbaric oxygenation on neural functional recovery and oxidative stress injury after cerebral infarction intervention. Methods:A total of 120 patients with cerebral infarction who received interventional therapy in our hospital between August 2013 and February 2016 were collected and divided into control group and observation group, 60 cases in each group. Control group received hyperbaric oxygenation after intervention, and the observation group received gangliosides combined with hyperbaric oxygenation after intervention. The differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were compared between two groups of patients before and after treatment.Results: Before intervention, differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were not statistically significant between two groups of patients. After intervention, serum neurotrophy indexes BDNF and NT-3 levels in observation group were higher than those in control group;serum nerve injury indexes S100B, NGB, NSE and GFAP levels were lower than those in control group;serum oxidative indexes MDA, MPO and LPO levels were lower than those in control group while antioxidant indexes SOD, GSH-Px, CAT and TAC levels were higher than those in control group.Conclusion: Gangliosides combined with hyperbaric oxygenation for patients with cerebral infarction after interventional therapy helps speed up the neural functional recovery and also reduce systemic inflammatory response.
基金supported by Fondo para la Investigación Cientifica y Tecnológica(FONCy T),Argentina,grant#PICT 2015-2473(to PHHL)supported by grants from National Institute of Health/National Institute of Neurological Disorders and Stroke(NIH/NINDS,USA)(NS121621)+2 种基金Department of Defense,USA(Do D-CL1)(PR200530)partially financed with a fellowship for Research in Medicine from Fundación Florencio Fiorinisupported with a PhD fellowship from CONICET。
文摘Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.
