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Articles by Y Naito
Total Records ( 3 ) for Y Naito
  W Aoi , Y Naito , K Mizushima , Y Takanami , Y Kawai , H Ichikawa and T. Yoshikawa

MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional gene regulation that have been shown to be involved in growth, development, function, and stress responses of various organs. The purpose of this study was to identify the miRNA response to physical activity, which was related to functions such as nutrient metabolism, although the miRNAs involved are currently unknown. C57BL/6 mice were divided into exercise and control groups. The exercise group performed running exercise, with a gradual increase of the load over 4 wk. On the other hand, to examine the effect of muscle inactivity, the unilateral hindlimbs of other mice were fixed in a cast for 5 days. Microarray analysis for miRNA in gastrocnemius revealed that miR-696 was markedly affected by both exercise and immobilization, showing opposite responses to these two interventions. Peroxisome proliferator-activated receptor- coactivator-1 (PGC-1), which was increased by exercise and decreased by immobilization in the protein level, was predicted as a target regulated by miR-696. In cultured myocytes, intracellular miR-696 variation led to negative regulation of PGC-1 protein along with the expression of mRNAs for downstream genes. In addition, we found decreases in the biogenesis of mitochondria and fatty acid oxidation in miR-696-overexpressing myocytes compared with normal control myocytes. These observations demonstrate that miR-696 is a physical activity-dependent miRNA involved in the translational regulation of PGC-1 and skeletal muscle metabolism in mice.

  Y Minamiyama , S Takemura , S Kodai , H Shinkawa , T Tsukioka , H Ichikawa , Y Naito , T Yoshikawa and S. Okada

Accumulating evidence suggests that alcohol, hepatitis C virus infection, steatosis with obesity, and insulin resistance are accompanied by iron overload states. Phlebotomy and oral iron chelators are effective treatments for these conditions and for hemochromatosis. However, the mechanisms by which iron depletion improves clinical factors remain unclear. We examined the effect of iron depletion in a model of type 2 diabetes, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Age-matched Long-Evans Tokushima Otsuka (LETO) rats were used as controls for all experiments. Iron restriction was performed by eliminating iron in the diet from 15 wk of age or by phlebotomy. Phlebotomy was commenced at 29 wk of age by removing 4 and 3 ml of blood from the tail vein every week in OLETF and LETO rats, respectively. Rats were euthanized at 43 wk of age, and detailed analyses were performed. The plasma ferritin concentration was markedly higher in OLETF rats and decreased in iron-deficient (ID) diet and phlebotomy rats. Hemoglobin A1c (Hb A1c) was decreased significantly in OLETF rats fed the ID diet and in the phlebotomy group. Increased levels of triglycerides, glucose, free fatty acids, and total cholesterol were found in ID OLETF rats. Plasma, liver, and pancreas lipid peroxidation and hepatic superoxide production decreased in both groups. Pancreatic fibrosis and insulin levels improved in both groups of OLETF rats. Pancreatic levels of peroxisome proliferator-activated receptor-β/ (PPARβ/) ligands and hypoxia-inducible factor (HIF)-1 were decreased significantly in OLETF rats. These factors were normalized in both rats fed ID and phlebotomy groups of OLETF rats. In conclusion, iron depletion improved diabetic complications by inhibition of oxidative stress and TGFβ signal pathways and the maintenance of pancreatic PPARβ/ and HIF-1 pathways.

  Y Naito , H Mukai and S. Nagai

Previous reports have demonstrated that treatment efficacy is not modified by age and that there are no major differences in outcomes among stage-matched patients as their ages increase. However, there seems to be a substantial undertreatment in the elderly.


We reviewed consecutive patients with breast cancer, 60 years old or older, between July 2003 and March 2007. Patient characteristics, clinicopathologic factors and treatment delivery were retrieved from medical records. Patients were subdivided into two groups (mid-elderly, 60–74 years old and high-elderly, 75 years old or older) and compared based on these factors.


A total of 280 patients were included. All were female. Sixteen percent were high-elderly. Most patients had favorable performance status (0/1, 87%), positive estrogen receptor (57%), negative human epidermal growth factor receptor 2 overexpression (65%) and axillary lymph node metastases (57%). The high-elderly group had significantly less human epidermal growth factor receptor 2 overexpression and less axillary lymph node metastasis. Chemotherapy was administered to 180 patients, and among them, those in the high-elderly group underwent significantly less chemotherapy (P < 0.001). Both anthracycline and taxane were significantly less frequently administered in high-elderly (P < 0.001, respectively). An alternative regimen for anthracycline and taxane was mainly a 5-fluorouracil-based single agent. Chemotherapy was omitted in 12 patients (3 mid-elderly and 9 high-elderly) because of age, and in 9 patients, age was the only reason for omitting chemotherapy.


We confirmed that elderly patients were substantially undertreated. The development of a safer and more efficacious treatment strategy is urgently needed.

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