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
Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its r...Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its research object and systematically analyzes the external treatment methods for abscesses during the Song dynasty reflected in Jiu Ai Tu.By examining the understanding of abscesses during that period,the paper explores the level of development in external medicine techniques.By analyzing the medical awareness and behaviors of patients when facing such severe illnesses,it aims to explore the societal cognition and experiences regarding health and disease.The paper attempts to present the folk medical ecology of the Song dynasty represented by Jiu Ai Tu.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
Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat ...Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results: Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion: TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.展开更多
AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or ...AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.展开更多
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
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
BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a the...BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.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
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 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 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
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.
基金financed from the grant of the National Social Science Foundation General Project(No.23BZS010)。
文摘Jiu Ai Tu(The Moxa Treatment)from the Song dynasty is the earliest surviving painting that focuses on the subject of acupuncture and moxibustion.This paper takes the medical activities depicted in the artwork as its research object and systematically analyzes the external treatment methods for abscesses during the Song dynasty reflected in Jiu Ai Tu.By examining the understanding of abscesses during that period,the paper explores the level of development in external medicine techniques.By analyzing the medical awareness and behaviors of patients when facing such severe illnesses,it aims to explore the societal cognition and experiences regarding health and disease.The paper attempts to present the folk medical ecology of the Song dynasty represented by Jiu Ai Tu.
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.
基金supported by“the Fundamental Research Funds for the Central Universities”(2020-JYB-ZDGG-054)“Beijing university of Chinese medicine XINAO Award Fund”(2019)Beijing University of Chinese Medicine Scientific Research and Development Fund(2170072220002).
文摘Objective:To determine the active components of Eupolyphaga sinensis Walker(Tu Bie Chong)and explore the mechanisms underlying its fracture-healing ability.Methods: A modified Einhorn method was used to develop a rat tibial fracture model.Progression of bone healing was assessed using radiological methods.Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site.Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration.The Transwell assay was used to explore the invasion capacity of the cells.Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells(HUVECs).qRT-PCR was used to evaluate the changes in gene transcription levels.Results: Tu Bie Chong fraction 3(TF3)significantly shortened the fracture healing time in model rats.X-ray results showed that on day 14,fracture healing in the TF3 treatment group was significantly better than that in the control group(P=.0086).Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group.In vitro,TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs(all P<.01).Transwell assays showed that TF3 promoted the migration of HUVECs,but inhibited the migration of MC3T3-E1 cells.Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules.Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA,SPOCD1,NGF,and NGFR in HUVECs.In MC3T3-E1 cells,the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment.Conclusion: TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.
基金Supported by The Natural Sciences and Engineering Research Council of Canada,the Broad Foundation,the Canadian Institutes of Health Research and The Alberta Livestock and Meat Agency
文摘AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
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.
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
基金This study was approved by the Ethic Committee of Basic Medical College of Qingdao University(Approval No.QDWMkj-2020-012).
文摘BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.
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.
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 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.
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.
