Naoki Kiyosawa
Daiichi Sankyo
GeneInternal medicineEndocrinologyGene expressionMolecular biologyFetusGene expression profilingChemistryMicroarrayApoptosisOxidative stressPlacentaClofibrateToxicityProgrammed cell deathGlutathioneBiochemistryBioinformaticsMedicineBiomarker (medicine)Microarray analysis techniquesBiologyToxicogenomicsPharmacology
52Publications
17H-index
778Citations
Publications 52
Newest
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Kenji Watanabe (Daiichi Sankyo)H-Index: 3
Last. Shinya Suzuki (Cardiovascular Institute of the South)H-Index: 22
view all 8 authors...
Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also sho...
5 CitationsSource
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Kenji Watanabe (Daiichi Sankyo)H-Index: 3
Last. Hitoshi Ishizuka (Daiichi Sankyo)H-Index: 9
view all 4 authors...
No practical biomarkers currently exist for the prediction of the analgesic efficacy of opioids. Previously, we reported circulating miRNA signatures differentially regulated by µ-opioid receptor (MOR) agonists in healthy subjects. We hypothesized that these miRNAs could be potential pharmacodynamic biomarkers to estimate MOR stimulation, and predict the efficacy of opioids; i.e., patients with low MOR stimulation may be more vulnerable to strengthening of the MOR signal upon hydromorphone treat...
7 CitationsSource
#1Kaoru Toyama (Daiichi Sankyo)H-Index: 4
#2Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
Last. Hitoshi Ishizuka (Daiichi Sankyo)H-Index: 9
view all 4 authors...
Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time afte...
17 CitationsSource
#1Yusuke Yokouchi (Daiichi Sankyo)H-Index: 7
#2Masako Imaoka (Daiichi Sankyo)H-Index: 7
Last. Kiyonori Kai (Daiichi Sankyo)H-Index: 7
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Two-week administration of (+)-usnic acid (UA) induces mitochondrial swelling of cardiomyocytes, and toxicogenomic analysis of the heart revealed upregulation of oxidative stress, amino acid limitation, and endoplasmic reticulum stress–related genes in rats. To analyze the pathogenesis, UA was orally administrated to rats for 1, 4, 7, and 14 days, and sequential histopathological, genomic, and metabolomic analyses were performed on the heart, liver, and plasma. As a result, mitochondrial swellin...
4 CitationsSource
#1Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
#2Sunao Manabe (Daiichi Sankyo)H-Index: 17
Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. RD it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful...
3 CitationsSource
#1Yusuke Yokouchi (Daiichi Sankyo)H-Index: 7
#2Masako Imaoka (Daiichi Sankyo)H-Index: 7
Last. Toshimasa Jindo (Daiichi Sankyo)H-Index: 6
view all 6 authors...
(+)-Usnic acid (UA) has been known to be a strong uncoupler, and mitochondrial and endoplasmic reticulum (ER)–related stresses are suggested to be involved in the mechanism of hepatotoxicity. However, it has not been clarified whether UA causes toxicity in other mitochondria-rich organs such as the heart. We elucidated whether UA induces cardiotoxicity and its mechanism. UA was orally administered to rats for 14 days, and laboratory and histopathological examinations were performed in conjunctio...
9 CitationsSource
#1Susan C. KandarianH-Index: 34
#2Eric J. StevensonH-Index: 7
Last. Evangeline W. CornwellH-Index: 5
view all 13 authors...
#1Takehiro Hirai (Daiichi Sankyo)H-Index: 3
#2Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
: Comprehensive gene expression analysis has been applied to investigate the molecular mechanism of toxicity, which is generally known as toxicogenomics (TGx). When analyzing large-scale gene expression data obtained by microarray analysis, typical multivariate data analysis methods performed with commercial software such as hierarchical clustering or principal component analysis usually do not provide conclusive outputs by themselves. To best utilize the TGx data for toxicity evaluation in the ...
2 CitationsSource
#1Takuya Matsuyama (Daiichi Sankyo)H-Index: 8
#2Noriyo Niino (Daiichi Sankyo)H-Index: 8
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
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Abstract Rats were treated with a single oral dose of 10, 25 and 50 mg/kg of 1,3-dinitrobenzene (DNB), and the testis was subjected to a GeneChip microarray analysis. A total of 186 and 304 gene probe sets were up- and down-regulated, respectively, by the DNB treatment, where spermatocyte death and Sertoli cell vacuolation in testis and increased debris of spermatogenic cell in epididymis were noted. The expression profile for four sets of genes were investigated, whose expressions are reported ...
8 CitationsSource
#1Shusuke Yamauchi (Daiichi Sankyo)H-Index: 2
#2Naoki Kiyosawa (Daiichi Sankyo)H-Index: 17
Last. Atsushi Sanbuissho (Daiichi Sankyo)H-Index: 11
view all 9 authors...
Hepatic transcriptome and proteome responses against glutathione depletion were investigated by Affymetrix GeneChip Microarray and 2-dimensional gel electrophoresis (2D-DIGE), followed by MALDI-TOF–MS analysis and utilizing a glutathione-depleted rat model treated with diethyl maleate (DEM). Hepatic glutathione content decreased to 1.29 μmol/g liver (25.5% compared to control) after DEM treatment, and there were no apparent hepatotoxic signs estimated by blood chemistry examinations. A total of ...
15 CitationsSource