Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes
Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level....
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| Veröffentlicht in: | BMC complementary and alternative medicine 2014-01, Vol.14 (1), p.14-14, Article 14 |
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| creator | Song, Kwang Hoon Kim, Yun Hee Kim, Bu-Yeo |
| description | Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level.
By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region.
The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns.
We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST. |
| doi_str_mv | 10.1186/1472-6882-14-14 |
| format | Article |
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By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region.
The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns.
We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.</description><identifier>ISSN: 1472-6882</identifier><identifier>EISSN: 1472-6882</identifier><identifier>DOI: 10.1186/1472-6882-14-14</identifier><identifier>PMID: 24410935</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Animals ; Cell Cycle - drug effects ; Cells, Cultured ; Drugs, Chinese Herbal - pharmacology ; Gene Expression Profiling ; Gene Expression Regulation - drug effects ; Genetic aspects ; Hepatocytes - cytology ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Herbal Medicine ; Instrument industry ; Kinases ; Liver ; Liver - cytology ; Liver - drug effects ; Liver - metabolism ; Male ; Medical research ; Medicine, East Asian Traditional ; Messenger RNA ; Mice ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; Oligonucleotide Array Sequence Analysis ; Phytotherapy ; Plants, Medicinal - genetics ; Promoter Regions, Genetic - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Signal Transduction - drug effects ; Transcription Factors - metabolism</subject><ispartof>BMC complementary and alternative medicine, 2014-01, Vol.14 (1), p.14-14, Article 14</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Song et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Copyright © 2014 Song et al.; licensee BioMed Central Ltd. 2014 Song et al.; licensee BioMed Central Ltd.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b611t-95e4ea1a0c99cd951e3ff9f43c63d5bbbaa82dbe3cb0beac2fdbb46a014107f13</citedby><cites>FETCH-LOGICAL-b611t-95e4ea1a0c99cd951e3ff9f43c63d5bbbaa82dbe3cb0beac2fdbb46a014107f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893506/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893506/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24410935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Kwang Hoon</creatorcontrib><creatorcontrib>Kim, Yun Hee</creatorcontrib><creatorcontrib>Kim, Bu-Yeo</creatorcontrib><title>Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes</title><title>BMC complementary and alternative medicine</title><addtitle>BMC Complement Altern Med</addtitle><description>Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level.
By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region.
The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns.
We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.</description><subject>Analysis</subject><subject>Animals</subject><subject>Cell Cycle - drug effects</subject><subject>Cells, Cultured</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic aspects</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Herbal Medicine</subject><subject>Instrument industry</subject><subject>Kinases</subject><subject>Liver</subject><subject>Liver - cytology</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine, East Asian Traditional</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>MicroRNAs - biosynthesis</subject><subject>MicroRNAs - genetics</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Phytotherapy</subject><subject>Plants, Medicinal - genetics</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><subject>Transcription Factors - metabolism</subject><issn>1472-6882</issn><issn>1472-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kl2L1DAUhoso7rp67Z0EBPFiu5s0_bwRxsUvWBT8uA5JetJmTZOxadX5Ff5lT5lxnJGVBBKS9zw557xJkseMXjBWl5csr7K0rOssZTnOO8np_uTuwf4keRDjDaWsqll-PznJ8pzRhhenya9PfUijtF9DOoVzIsk0ytZONnjpSA-jwmWA1mrr4ZyM0M1OThBJBx4I_FyPECOKifQtUTa40FmNIWb2eoEQtSE_5IYEQwarx_Dx_SoS68l6tIMcN2QIcwR8Zy2noDcIfpjcM9JFeLRbz5Ivr199vnqbXn948-5qdZ2qkrEpbQrIQTJJddPotikYcGMak3Nd8rZQSklZZ60CrhVVIHVmWqXyUlKGhVeG8bPkxZa7nhXWp8Fj4U7s8hJBWnF8420vuvBd8Br7RksEvNwCsOr_AI5vdBjEYohYDMEdToQ832Uxhm8zxEkMNmpwTnrAzghW0ILznDZLwk__kd6EeUSX4kKt6pJVlP5VddKBsN4EfFsvULEqeFM0NaM1qi5uUeFoAV0KHozF86OAZwcBPUg39TG4ebE4Hgsvt0L0OsYRzL4hjIrlx97SgieHRuz1f74o_w0mrOjj</recordid><startdate>20140111</startdate><enddate>20140111</enddate><creator>Song, Kwang Hoon</creator><creator>Kim, Yun Hee</creator><creator>Kim, Bu-Yeo</creator><general>BioMed Central Ltd</general><general>BioMed Central</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>3V.</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20140111</creationdate><title>Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes</title><author>Song, Kwang Hoon ; Kim, Yun Hee ; Kim, Bu-Yeo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b611t-95e4ea1a0c99cd951e3ff9f43c63d5bbbaa82dbe3cb0beac2fdbb46a014107f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Cell Cycle - drug effects</topic><topic>Cells, Cultured</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genetic aspects</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Herbal Medicine</topic><topic>Instrument industry</topic><topic>Kinases</topic><topic>Liver</topic><topic>Liver - cytology</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine, East Asian Traditional</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>MicroRNAs - biosynthesis</topic><topic>MicroRNAs - genetics</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Phytotherapy</topic><topic>Plants, Medicinal - genetics</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction - drug effects</topic><topic>Transcription Factors - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Song, Kwang Hoon</creatorcontrib><creatorcontrib>Kim, Yun Hee</creatorcontrib><creatorcontrib>Kim, Bu-Yeo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMC complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Kwang Hoon</au><au>Kim, Yun Hee</au><au>Kim, Bu-Yeo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes</atitle><jtitle>BMC complementary and alternative medicine</jtitle><addtitle>BMC Complement Altern Med</addtitle><date>2014-01-11</date><risdate>2014</risdate><volume>14</volume><issue>1</issue><spage>14</spage><epage>14</epage><pages>14-14</pages><artnum>14</artnum><issn>1472-6882</issn><eissn>1472-6882</eissn><abstract>Sho-saiko-to (SST) (also known as so-shi-ho-tang or xiao-chai-hu-tang) has been widely prescribed for chronic liver diseases in traditional Oriental medicine. Despite the substantial amount of clinical evidence for SST, its molecular mechanism has not been clearly identified at a genome-wide level.
By using a microarray, we analyzed the temporal changes of messenger RNA (mRNA) and microRNA expression in primary mouse hepatocytes after SST treatment. The pattern of genes regulated by SST was identified by using time-series microarray analysis. The biological function of genes was measured by pathway analysis. For the identification of the exact targets of the microRNAs, a permutation-based correlation method was implemented in which the temporal expression of mRNAs and microRNAs were integrated. The similarity of the promoter structure between temporally regulated genes was measured by analyzing the transcription factor binding sites in the promoter region.
The SST-regulated gene expression had two major patterns: (1) a temporally up-regulated pattern (463 genes) and (2) a temporally down-regulated pattern (177 genes). The integration of the genes and microRNA demonstrated that 155 genes could be the targets of microRNAs from the temporally up-regulated pattern and 19 genes could be the targets of microRNAs from the temporally down-regulated pattern. The temporally up-regulated pattern by SST was associated with signaling pathways such as the cell cycle pathway, whereas the temporally down-regulated pattern included drug metabolism-related pathways and immune-related pathways. All these pathways could be possibly associated with liver regenerative activity of SST. Genes targeted by microRNA were moreover associated with different biological pathways from the genes not targeted by microRNA. An analysis of promoter similarity indicated that co-expressed genes after SST treatment were clustered into subgroups, depending on the temporal expression patterns.
We are the first to identify that SST regulates temporal gene expression by way of microRNA. MicroRNA targets and non-microRNA targets moreover have different biological roles. This functional segregation by microRNA would be critical for the elucidation of the molecular activities of SST.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24410935</pmid><doi>10.1186/1472-6882-14-14</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Animals Cell Cycle - drug effects Cells, Cultured Drugs, Chinese Herbal - pharmacology Gene Expression Profiling Gene Expression Regulation - drug effects Genetic aspects Hepatocytes - cytology Hepatocytes - drug effects Hepatocytes - metabolism Herbal Medicine Instrument industry Kinases Liver Liver - cytology Liver - drug effects Liver - metabolism Male Medical research Medicine, East Asian Traditional Messenger RNA Mice MicroRNAs - biosynthesis MicroRNAs - genetics Oligonucleotide Array Sequence Analysis Phytotherapy Plants, Medicinal - genetics Promoter Regions, Genetic - genetics RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Signal Transduction - drug effects Transcription Factors - metabolism |
| title | Sho-saiko-to, a traditional herbal medicine, regulates gene expression and biological function by way of microRNAs in primary mouse hepatocytes |
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