OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor po...OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin pathway.Bisulfite amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein expression.RESULTS:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long term.Mechanically,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s FRP5.Furthermore,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin pathway.CONCLUSIONS:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.展开更多
A preliminary clinical study by our group demonstrated Bushen Yisui Capsule （formerly called Er- huang Formula） in combination with conventional therapy is an effective prescription for the treat- ment of multiple s...A preliminary clinical study by our group demonstrated Bushen Yisui Capsule （formerly called Er- huang Formula） in combination with conventional therapy is an effective prescription for the treat- ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re- mains unclear. In this study, a MOG35 55-immunized C57BL/6 mouse model of experimental auto- immune encephalomyelitis was intragastrically administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim- mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of regen- eration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.展开更多
For Alzheimer's disease(AD),the earliest symptom is memory loss,which runs throughout the disease.The mutual growth and decline of long-term potentiation(LTP)and long-term depression(LTD)in synaptic plasticity is ...For Alzheimer's disease(AD),the earliest symptom is memory loss,which runs throughout the disease.The mutual growth and decline of long-term potentiation(LTP)and long-term depression(LTD)in synaptic plasticity is the basic condition of learning and memory.In the early stage of AD,there is no significant change in synaptic plasticity,so the treatment should mainly focus on warming yang and replenishing qi.In the middle stage of AD,LTP is continuously damaged and reduced,and synaptic plasticity is destroyed,such as weakness of the spleen and stomach,causing stagnation of endogenous retention of phlegm in the brain,so the treatment should focus on enriching yin and tonifying yang,resolving phlegm to remove stagnation.In the late stage of AD,due to excessive deposition of amyloid and other metabolites,neurotoxins are produced and brain atrophy is aggravated,such as depression leading to stasis,phlegm and stasis binding together,long term of stasis turning to heat toxin,which invades the brain,excessive heat damages yin,then both yin and yang are damaged,finally,the brain collateral loses nutrition,so the treatment should focus on replenishing essence and reinforcing marrow,detoxifying and resolving stasis.Yisui Fuyong Decoction can replenish essence and reinforce marrow to nourish yin,warm yang and tonify qi to strengthen yang,combine phlegm resolving,stasis elimination and collateral vessels dredging,realizing the treatment effects in all three stages of synaptic plasticity.展开更多
Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： T...Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin （Hb）, red blood cells （RBCs）, and reticulocyte percent （Ret）] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy （TEM）; activities of antioxidant defense enzymes [superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, and catalase （Cat）] and erythrocyte membrane malondialdehyde （MDA） concentrations were determined. Results： In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment （P〈0.01）. Measured values of Ret from the second to the third months aftertreatment were significantly lower than before treatment （P〈0.05 and P〈0.01, respectively）. Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity （P〈0.01）, a decrease in Cat activity （P〈0.01）, and no significant differences in GSH-Px activity （P〉0.05） or MDA concentration （P〉0.05）. However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels （P〈0.01） both before and after treatment. Conclusions： YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of β-globin chains.展开更多
Objective: To examine the clinical effects of Yisui Shengxue Granules(益髓生血颗粒) in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. Methods: A randomized placebo-controlled doub...Objective: To examine the clinical effects of Yisui Shengxue Granules(益髓生血颗粒) in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. Methods: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group(12 g/bag, 3 times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin(Hb), red blood cells(RBCs), reticulocytes(Ret), and fetal hemoglobin(HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0. Results: Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group(P<0.01 or P<0.05). Meanwhile, HbF increased from the 2 nd to the 3 rd month(P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor(IGF1 R) and Janus kinase 3(JAK3) revealed the most relations with other genes(degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2(PLCG2) and mitogen-activated protein kinase 10(MAPK10) showed a stronger intermediary role(betweenness centrality=0.04). Conclusions: JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis.(Registration No. NCT01549080).展开更多
Objective： To study the effects of Bushen Yisui Capsule（补肾益髓胶囊, BSYSC） on the oligodendrocyte lineage genes（Olig） 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis（EAE） in order t...Objective： To study the effects of Bushen Yisui Capsule（补肾益髓胶囊, BSYSC） on the oligodendrocyte lineage genes（Olig） 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis（EAE） in order to explore the remyelination effect of BSYSC. Methods： The mice were randomly divided into normal control（NC）, EAE model（EAE-M）, prednisone acetate（PA, 6 mg/kg）, BSYSC high-dose（3.02 g/kg） and BSYSC low-dose（1.51 g/kg） groups. The mice were induced by immunization with myelin oligodendrocyte glycoprotein（MOG） 35-55. The neurological function scores were assessed once daily. The pathological changes in mice brains were observed with hematoxylin-eosin（HE） staining and transmission electron microscope（TEM）. The protein expressions of myelin basic protein（MBP）, Olig1 and Olig2 in brains were measured by immunohistochemistry. The m RNA expressions of Olig1 and Olig 2 was also determined by quantitative real-time polymerase chain reaction. Results： Compared with the EAE-M mice,（1） the neurological function scores were significantly decreased in BSYSC-treated mice on days 22 to 40（P〈0.01）;（2） the inflammatory cells and demyelination in brains were reduced in BSYSC-treated EAE mice;（3） the protein expression of MBP was markedly increased in BSYSC-treated groups on day 18 and 40 respectively（P〈0.05 or P〈0.01）;（4） the protein expression of Olig1 was increased in BSYSC（3.02 g/kg）-treated EAE mice on day 40（P〈0.01）. Protein and m RNA expression of Olig2 was increased in BSYSC-treated EAE mice on day 18 and 40（P〈0.01）. Conclusion： The effects of BSYSC on reducing demyelination and promoting remyelination might be associated with the increase of Olig1 and Olig2.展开更多
Objective: To find the effective method in treating infantile chronic aplastic anemia (ICAA) by using traditional Chinese medicine (TCM). Methods: Seventy-eight cases of ICAA were observed, 48 in the treated group wer...Objective: To find the effective method in treating infantile chronic aplastic anemia (ICAA) by using traditional Chinese medicine (TCM). Methods: Seventy-eight cases of ICAA were observed, 48 in the treated group were treated with Tiaoxue Yisui recipe, and 30 cases in the control group with SSL regimen. Results: The remission rate and total effective rate in the treated group were 52. 08% and 81. 25% respectively,which were higher than those in the control group (P < 0. 05). After one year's treatment the ratio of hemopoietic and non-hemopoietic cells in the treated group was higher than that in the control group (P< 0. 05). Conclusion: Tiaoxue Yisui recipe could improve the living quality of ICAA patients. The therapeutical mechanism of the recipe might be related to its promoting the proliferation of hemopoietic stem cells and regulating the immune function.展开更多
基金Clinical Translational Research of Beijing Municipal Science and Technology Commission,Administrative Commission of Zhongguancun Science Park-funded Project:Study on Mechanisms and Efficacy of Yisui granule Treating Low and Intermediate Risk of Myelodysplastic Syndromes via DNA Demethylation(No.Z211100002921018)National Natural Science Foundation of Chinafunded Projects:Study on Molecular Mechanisms of Yisui granule Treating Myelodysplastic Syndromes via Regulating DNA Methylation(No.81503575)+1 种基金Mechanism Study of Tea Polyphenols activating c GAS-STING Pathway to Inhibit Lung Adenocarcinoma Immune Escape based on Redox Balance(No.82172760)the Golden Bridge Project of Beijing Association for Science and Technology-funded Project:Study on Mechanisms of Yisui granule Treating Low and Intermediate Risk of Myelodysplastic Syndromes via DNA Demethylation(No.ZZ20059)。
文摘OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin pathway.Bisulfite amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein expression.RESULTS:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long term.Mechanically,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s FRP5.Furthermore,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin pathway.CONCLUSIONS:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.
基金supported by the National Natural Science Foundation of China,No.81072765,81173237,81273742Scientific Research Key Project of Beijing Municipal Commission of Education,No.KZ201310025023Special Fund for Capital Traditional Chinese Medicine and Nursing Research,No.12ZYH01
文摘A preliminary clinical study by our group demonstrated Bushen Yisui Capsule （formerly called Er- huang Formula） in combination with conventional therapy is an effective prescription for the treat- ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re- mains unclear. In this study, a MOG35 55-immunized C57BL/6 mouse model of experimental auto- immune encephalomyelitis was intragastrically administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim- mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of regen- eration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.
基金General Program of Chongqing Municipal Natural Science Foundation(cstc2020jcyj-msxmX0011)Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau,2020ZY023596)the First Batch of Young Outstanding Talent Project of Chongqing Traditional Chinese Medicine Hospital(Yu Zhong Yi Yuan Dang[2020]No.20).
文摘For Alzheimer's disease(AD),the earliest symptom is memory loss,which runs throughout the disease.The mutual growth and decline of long-term potentiation(LTP)and long-term depression(LTD)in synaptic plasticity is the basic condition of learning and memory.In the early stage of AD,there is no significant change in synaptic plasticity,so the treatment should mainly focus on warming yang and replenishing qi.In the middle stage of AD,LTP is continuously damaged and reduced,and synaptic plasticity is destroyed,such as weakness of the spleen and stomach,causing stagnation of endogenous retention of phlegm in the brain,so the treatment should focus on enriching yin and tonifying yang,resolving phlegm to remove stagnation.In the late stage of AD,due to excessive deposition of amyloid and other metabolites,neurotoxins are produced and brain atrophy is aggravated,such as depression leading to stasis,phlegm and stasis binding together,long term of stasis turning to heat toxin,which invades the brain,excessive heat damages yin,then both yin and yang are damaged,finally,the brain collateral loses nutrition,so the treatment should focus on replenishing essence and reinforcing marrow,detoxifying and resolving stasis.Yisui Fuyong Decoction can replenish essence and reinforce marrow to nourish yin,warm yang and tonify qi to strengthen yang,combine phlegm resolving,stasis elimination and collateral vessels dredging,realizing the treatment effects in all three stages of synaptic plasticity.
基金Supported by the National Natural Science Foundation of China (No.90409003)the National Basic Research Program(973 Program.No.2010CB530406)
文摘Objective： To investigate the effect of Yisui Shengxue Granule （益髓生血颗粒, YSSXG）, a complex Chinese medicine, on the oxidative damage of erythrocytes from patients with hemoglobin H （HbH） disease. Methods： Twenty-two patients with HbH disease and 22 healthy volunteers were observed. YSSXG was given to patients with HbH disease for 3 months. Before and after the 3-month treatment, blood parameters [hemoglobin （Hb）, red blood cells （RBCs）, and reticulocyte percent （Ret）] were examined; inclusion bodies in erythrocytes were observed by transmission electron microscopy （TEM）; activities of antioxidant defense enzymes [superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, and catalase （Cat）] and erythrocyte membrane malondialdehyde （MDA） concentrations were determined. Results： In patients with HbH disease, measured values of RBC and Hb obtained from the first to the third months after treatment with YSSXG were significantly higher than before treatment （P〈0.01）. Measured values of Ret from the second to the third months aftertreatment were significantly lower than before treatment （P〈0.05 and P〈0.01, respectively）. Prior to treatment with YSSXG, TEM images of RBCs showed the presence of numerous inclusion bodies. After treatment with YSSXG, the amount and volume of inclusion bodies decreased. Treatment with YSSXG also led to a significant increase in SOD activity （P〈0.01）, a decrease in Cat activity （P〈0.01）, and no significant differences in GSH-Px activity （P〉0.05） or MDA concentration （P〉0.05）. However, compared with the healthy counterparts, SOD, GSH-Px, and Cat activities presented at high levels （P〈0.01） both before and after treatment. Conclusions： YSSXG could improve the degree of hemolysis and anemia in patients with HbH disease. The mechanism may be related to its antioxidative effects, which could elevate the activity of total SOD in erythrocytes and efficiently inhibit the oxidative precipitation of β-globin chains.
基金Supported by the National Basic Research Program of China(No.2010CB530406)National Natural Science Foundation of China(No.81173167)the Natural Science Foundation of Guangxi(No.2012GXNSFAA053156)
文摘Objective: To examine the clinical effects of Yisui Shengxue Granules(益髓生血颗粒) in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. Methods: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group(12 g/bag, 3 times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin(Hb), red blood cells(RBCs), reticulocytes(Ret), and fetal hemoglobin(HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0. Results: Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group(P<0.01 or P<0.05). Meanwhile, HbF increased from the 2 nd to the 3 rd month(P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor(IGF1 R) and Janus kinase 3(JAK3) revealed the most relations with other genes(degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2(PLCG2) and mitogen-activated protein kinase 10(MAPK10) showed a stronger intermediary role(betweenness centrality=0.04). Conclusions: JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis.(Registration No. NCT01549080).
基金Supported by the National Natural Science Foundation(Nos.81072765,81173237 and 81273742)Beijing Natural Science Foundation(No.7142053)+2 种基金Scientific Research Key Program of Beijing Municipal Commission of Education(No.KZ201310025023)Program for Changcheng Scholars of the ImportationDevelopment of High-Caliber Talents Project of Beijing Municipal Institutions(No.CIT&TCD20140329)
文摘Objective： To study the effects of Bushen Yisui Capsule（补肾益髓胶囊, BSYSC） on the oligodendrocyte lineage genes（Olig） 1 and Olig2 in C57BL/6 mice with experimental autoimmune encephalomyelitis（EAE） in order to explore the remyelination effect of BSYSC. Methods： The mice were randomly divided into normal control（NC）, EAE model（EAE-M）, prednisone acetate（PA, 6 mg/kg）, BSYSC high-dose（3.02 g/kg） and BSYSC low-dose（1.51 g/kg） groups. The mice were induced by immunization with myelin oligodendrocyte glycoprotein（MOG） 35-55. The neurological function scores were assessed once daily. The pathological changes in mice brains were observed with hematoxylin-eosin（HE） staining and transmission electron microscope（TEM）. The protein expressions of myelin basic protein（MBP）, Olig1 and Olig2 in brains were measured by immunohistochemistry. The m RNA expressions of Olig1 and Olig 2 was also determined by quantitative real-time polymerase chain reaction. Results： Compared with the EAE-M mice,（1） the neurological function scores were significantly decreased in BSYSC-treated mice on days 22 to 40（P〈0.01）;（2） the inflammatory cells and demyelination in brains were reduced in BSYSC-treated EAE mice;（3） the protein expression of MBP was markedly increased in BSYSC-treated groups on day 18 and 40 respectively（P〈0.05 or P〈0.01）;（4） the protein expression of Olig1 was increased in BSYSC（3.02 g/kg）-treated EAE mice on day 40（P〈0.01）. Protein and m RNA expression of Olig2 was increased in BSYSC-treated EAE mice on day 18 and 40（P〈0.01）. Conclusion： The effects of BSYSC on reducing demyelination and promoting remyelination might be associated with the increase of Olig1 and Olig2.
文摘Objective: To find the effective method in treating infantile chronic aplastic anemia (ICAA) by using traditional Chinese medicine (TCM). Methods: Seventy-eight cases of ICAA were observed, 48 in the treated group were treated with Tiaoxue Yisui recipe, and 30 cases in the control group with SSL regimen. Results: The remission rate and total effective rate in the treated group were 52. 08% and 81. 25% respectively,which were higher than those in the control group (P < 0. 05). After one year's treatment the ratio of hemopoietic and non-hemopoietic cells in the treated group was higher than that in the control group (P< 0. 05). Conclusion: Tiaoxue Yisui recipe could improve the living quality of ICAA patients. The therapeutical mechanism of the recipe might be related to its promoting the proliferation of hemopoietic stem cells and regulating the immune function.
