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Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)
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 distri...
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| Published in: | Chinese journal of integrative medicine 2019-07, Vol.25 (7), p.490-496 |
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| container_end_page | 496 |
| container_issue | 7 |
| container_start_page | 490 |
| container_title | Chinese journal of integrative medicine |
| container_volume | 25 |
| creator | Cheng, Yan-ling Zhang, Xin-hua Sun, Yu-wen Wang, Wen-juan Huang, Jie Chu, Na-li Fang, Su-ping Wu, Zhi-kui |
| description | 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 three 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 |
| doi_str_mv | 10.1007/s11655-018-2777-9 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2039294265</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2039294265</sourcerecordid><originalsourceid>FETCH-LOGICAL-c344t-e49d9ecb2c8ca3130805add5d960b23969814046fc7ffc4780e68c3c660b6c03</originalsourceid><addsrcrecordid>eNp9kL9uFDEQxi1ERELgAWiQy1BssL279rqMAhyRwh_BNVSWzzubc7TrPTy7CmkQNSUgUaSIQkuXB-E1jrwFjjZQUs1ovm8-zfwIecDZLmdMPUbOZVlmjFeZUEpl-hbZ4lrnGSuYuJ16qUTqeblJ7iIeM1Yqyco7ZFNoJXnO8y3ycQah7-DE10CfvNyjL2BYnrZ28H2gbwBXfUBA6gN9nWYQBqQnfljSX5fZfGlbiwidt3QewQ5QT9o7j6Onb5cQjj6MQGfRhrFNITvrs89XP7-uv53_vvh09eP7-vLLo3tko7Etwv2buk3mz57O959nh69mB_t7h5nLi2LIoNC1BrcQrnI23c0qVtq6Lmst2ULkWuqKF6yQjVNN4wpVMZCVy51MsnQs3yY7U-wq9u9HwMF0Hh20rQ3Qj2gEy7XQhZBlsvLJ6mKPGKExq-g7G08NZ-aaupmom0TdXFM3Ou08vIkfFx3U_zb-Yk4GMRkwSeEIojnuxxjSx_9J_QOhk5Ss</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2039294265</pqid></control><display><type>article</type><title>Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)</title><source>Springer Nature</source><creator>Cheng, Yan-ling ; Zhang, Xin-hua ; Sun, Yu-wen ; Wang, Wen-juan ; Huang, Jie ; Chu, Na-li ; Fang, Su-ping ; Wu, Zhi-kui</creator><creatorcontrib>Cheng, Yan-ling ; Zhang, Xin-hua ; Sun, Yu-wen ; Wang, Wen-juan ; Huang, Jie ; Chu, Na-li ; Fang, Su-ping ; Wu, Zhi-kui</creatorcontrib><description>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 three 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 2nd to the 3rd 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 (IGF1R) 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)</description><identifier>ISSN: 1672-0415</identifier><identifier>EISSN: 1993-0402</identifier><identifier>DOI: 10.1007/s11655-018-2777-9</identifier><identifier>PMID: 29761313</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adolescent ; beta-Thalassemia - drug therapy ; beta-Thalassemia - genetics ; DNA Methylation - genetics ; Drugs, Chinese Herbal - pharmacology ; Drugs, Chinese Herbal - therapeutic use ; Erythrocytes - drug effects ; Female ; Genome, Human ; Hemoglobins - metabolism ; Humans ; Male ; Medicine ; Medicine & Public Health ; Original Article ; Signal Transduction</subject><ispartof>Chinese journal of integrative medicine, 2019-07, Vol.25 (7), p.490-496</ispartof><rights>The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-e49d9ecb2c8ca3130805add5d960b23969814046fc7ffc4780e68c3c660b6c03</citedby><cites>FETCH-LOGICAL-c344t-e49d9ecb2c8ca3130805add5d960b23969814046fc7ffc4780e68c3c660b6c03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29761313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cheng, Yan-ling</creatorcontrib><creatorcontrib>Zhang, Xin-hua</creatorcontrib><creatorcontrib>Sun, Yu-wen</creatorcontrib><creatorcontrib>Wang, Wen-juan</creatorcontrib><creatorcontrib>Huang, Jie</creatorcontrib><creatorcontrib>Chu, Na-li</creatorcontrib><creatorcontrib>Fang, Su-ping</creatorcontrib><creatorcontrib>Wu, Zhi-kui</creatorcontrib><title>Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)</title><title>Chinese journal of integrative medicine</title><addtitle>Chin. J. Integr. Med</addtitle><addtitle>Chin J Integr Med</addtitle><description>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 three 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 2nd to the 3rd 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 (IGF1R) 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)</description><subject>Adolescent</subject><subject>beta-Thalassemia - drug therapy</subject><subject>beta-Thalassemia - genetics</subject><subject>DNA Methylation - genetics</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Drugs, Chinese Herbal - therapeutic use</subject><subject>Erythrocytes - drug effects</subject><subject>Female</subject><subject>Genome, Human</subject><subject>Hemoglobins - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Original Article</subject><subject>Signal Transduction</subject><issn>1672-0415</issn><issn>1993-0402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kL9uFDEQxi1ERELgAWiQy1BssL279rqMAhyRwh_BNVSWzzubc7TrPTy7CmkQNSUgUaSIQkuXB-E1jrwFjjZQUs1ovm8-zfwIecDZLmdMPUbOZVlmjFeZUEpl-hbZ4lrnGSuYuJ16qUTqeblJ7iIeM1Yqyco7ZFNoJXnO8y3ycQah7-DE10CfvNyjL2BYnrZ28H2gbwBXfUBA6gN9nWYQBqQnfljSX5fZfGlbiwidt3QewQ5QT9o7j6Onb5cQjj6MQGfRhrFNITvrs89XP7-uv53_vvh09eP7-vLLo3tko7Etwv2buk3mz57O959nh69mB_t7h5nLi2LIoNC1BrcQrnI23c0qVtq6Lmst2ULkWuqKF6yQjVNN4wpVMZCVy51MsnQs3yY7U-wq9u9HwMF0Hh20rQ3Qj2gEy7XQhZBlsvLJ6mKPGKExq-g7G08NZ-aaupmom0TdXFM3Ou08vIkfFx3U_zb-Yk4GMRkwSeEIojnuxxjSx_9J_QOhk5Ss</recordid><startdate>20190701</startdate><enddate>20190701</enddate><creator>Cheng, Yan-ling</creator><creator>Zhang, Xin-hua</creator><creator>Sun, Yu-wen</creator><creator>Wang, Wen-juan</creator><creator>Huang, Jie</creator><creator>Chu, Na-li</creator><creator>Fang, Su-ping</creator><creator>Wu, Zhi-kui</creator><general>Springer Berlin Heidelberg</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20190701</creationdate><title>Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)</title><author>Cheng, Yan-ling ; Zhang, Xin-hua ; Sun, Yu-wen ; Wang, Wen-juan ; Huang, Jie ; Chu, Na-li ; Fang, Su-ping ; Wu, Zhi-kui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-e49d9ecb2c8ca3130805add5d960b23969814046fc7ffc4780e68c3c660b6c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>beta-Thalassemia - drug therapy</topic><topic>beta-Thalassemia - genetics</topic><topic>DNA Methylation - genetics</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Drugs, Chinese Herbal - therapeutic use</topic><topic>Erythrocytes - drug effects</topic><topic>Female</topic><topic>Genome, Human</topic><topic>Hemoglobins - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Original Article</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cheng, Yan-ling</creatorcontrib><creatorcontrib>Zhang, Xin-hua</creatorcontrib><creatorcontrib>Sun, Yu-wen</creatorcontrib><creatorcontrib>Wang, Wen-juan</creatorcontrib><creatorcontrib>Huang, Jie</creatorcontrib><creatorcontrib>Chu, Na-li</creatorcontrib><creatorcontrib>Fang, Su-ping</creatorcontrib><creatorcontrib>Wu, Zhi-kui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chinese journal of integrative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cheng, Yan-ling</au><au>Zhang, Xin-hua</au><au>Sun, Yu-wen</au><au>Wang, Wen-juan</au><au>Huang, Jie</au><au>Chu, Na-li</au><au>Fang, Su-ping</au><au>Wu, Zhi-kui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒)</atitle><jtitle>Chinese journal of integrative medicine</jtitle><stitle>Chin. J. Integr. Med</stitle><addtitle>Chin J Integr Med</addtitle><date>2019-07-01</date><risdate>2019</risdate><volume>25</volume><issue>7</issue><spage>490</spage><epage>496</epage><pages>490-496</pages><issn>1672-0415</issn><eissn>1993-0402</eissn><abstract>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 three 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 2nd to the 3rd 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 (IGF1R) 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)</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>29761313</pmid><doi>10.1007/s11655-018-2777-9</doi><tpages>7</tpages></addata></record> |
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| issn | 1672-0415 1993-0402 |
| language | eng |
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| source | Springer Nature |
| subjects | Adolescent beta-Thalassemia - drug therapy beta-Thalassemia - genetics DNA Methylation - genetics Drugs, Chinese Herbal - pharmacology Drugs, Chinese Herbal - therapeutic use Erythrocytes - drug effects Female Genome, Human Hemoglobins - metabolism Humans Male Medicine Medicine & Public Health Original Article Signal Transduction |
| title | Genomewide DNA Methylation Responses in Patients with β-Thalassemia Treated with Yisui Shengxue Granules (益髓生血颗粒) |
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