Miyazaki Prefectural Industrial Support Foundation
Miyazaki Prefectural Industrial Support Foundation
Yuji K.,Miyazaki Prefectural Industrial Support Foundation |
Yuji K.,University of Miyazaki |
Sakaida H.,Unkai Shuzo Co. |
Kai T.,Unkai Shuzo Co. |
And 5 more authors.
Journal of Oleo Science | Year: 2013
The serum and liver lipid-lowering effects of dietary freeze-dried blueberry leaf powder (BL) and its hydrothermal extract (BLHE) were examined in rats fed diets with or without cholesterol supplementation. Administration of 1% and 3% BL had no adverse effects on food intake or growth; however, relative liver weights were reduced in rats fed diets with and without dietary cholesterol. In the absence of dietary cholesterol, a dose-dependent reduction was evident. The effects of dietary BL on the concentration of serum lipids were marginal; however, the effects on liver triacylglycerol (TG) and cholesterol levels were apparently dose-dependent when the animals were fed diets free of cholesterol. Further, BL significantly attenuated dietary cholesterol-dependent accumulation of hepatic cholesterol, but not of TG. Hydrothermal treatment studies suggested that the active component of BL in terms of its liver lipid-lowering activity is relatively stable at high temperatures. Histopathological analysis of hepatic tissues revealed that BL administration suppresses fatty infiltrations induced by an AIN 76-based high-sucrose diet. The results of this study suggest that some of the active components of BL extracts, which are incorporated into the liver, prevent fatty liver in rats. These results provide further support for the investigation of dietary BL and derivatives thereof as functional human foods. © 2013 by Japan Oil Chemists' Society.
Miyazaki Prefectural Industrial Support Foundation, Kagoshima University and Chugai Seiyaku Kabushiki Kaisha | Date: 2010-08-11
Disclosed are: a marker for the diagnosis of a liver disease, which can determine the disease in a simple manner; an antibody directed agaist the marker; a diagnostic agent; a diagnosis method; and a method for marker detection in blood or serum. Proteome analysis revealed that quantities of the full-length kininogen and three partial peptides therof (sequence A: postion-440 to position-456, sequence B: postion-439 to postion-456, and sequence C: position-43 to position-456) in sera of patients with non-alcoholic fatty liver disease are significantly different from those in sera of healthy individuals; and a diagnostic agent and a detecting method for the non-alcoholic fatty liver disease that can be conveniently used for medical examination are established. The use of a combination of a kininogen-based marker and a C4-based marker (the full length sequence or partial peptides thereof) enables identification of chronic hepatitis and an asymptomatic virus carrier, as well as non-alcoholic fatty liver disease.
Baba T.,University of Miyazaki |
Kawaguchi M.,University of Miyazaki |
Fukushima T.,University of Miyazaki |
Sato Y.,Miyazaki Prefectural Industrial Support Foundation |
And 6 more authors.
Journal of Pathology | Year: 2012
A loss of balance between cell membrane-associated proteases and their inhibitors may underlie cancer invasion and metastasis. We analysed the roles of a membrane- associated serine protease inhibitor, HAI-1, in oral squamous cell carcinoma (OSCC). While membranous HAI-1 was widely observed in cancer cells of human OSCC tissues, this was significantly reduced at the infiltrative invasion front. In vitro, HAI-1 was detected in all eight OSCC cell lines examined, in which its cognate membrane protease, matriptase was also expressed. HAI-1 expression knock-down (KD) in OSCC lines, SAS and HSC-3, reduced the growth of both lines in vitro but significantly enhanced SAS tumourigenicity in vivo, which was accompanied by histological changes suggestive of the epithelial-mesenchymal transition. Both HAI-1-KD lines also exhibited significantly enhanced migratory capability, and membrane-associated but not truncated HAI-1 was required to rescue this phenotype. Other OSCC lines (HSC-2, Sa3, Ca9-22) also showed enhanced migration in response to HAI-1 KD. The enhanced migration is partly attributed to dysregulation of matriptase, as simultaneous matriptase KD alleviated the migration of HAI-1-KD cells. HAI-1 deficiency also altered the expression of CD24, S100A4, CCND2 and DUSP6, all of which are involved in tumour progression. While matriptase was involved in the increased CD24 expression associated with HAI-1 deficiency, the protease appeared to be not responsible for the altered expression of other genes. Therefore, a matriptase-independent mechanism for the invasiveness associated with HAI-1 KD is also present. Together, these observations suggest that HAI-1 has a crucial suppressive role in OSCC cell invasiveness. Copyright © 2012 Pathological Society of Great Britain and Ireland.
Mera K.,Kagoshima University |
Uto H.,Kagoshima University |
Mawatari S.,Kagoshima University |
Ido A.,Kagoshima University |
And 12 more authors.
BMC Gastroenterology | Year: 2014
Background: Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.Methods: Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.Results: A serum AIM level of ≥1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ≥8.6 ng/ml was independently associated with the presence of hepatic steatosis (≥5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.Conclusion: High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism. © 2014 Mera et al.; licensee BioMed Central Ltd.
Ishida Y.-I.,Meiji Pharmaceutical University |
Ishida Y.-I.,Miyazaki Prefectural Industrial Support Foundation |
Yamasaki M.,University of Miyazaki |
Yukizaki C.,Miyazaki Prefecture Food Research and Development Center |
And 5 more authors.
Human Cell | Year: 2014
Adult T-cell leukemia/lymphoma (ATL) is a fatal malignancy caused by infection with human T-lymphotropic virus type-1 and there is no accepted curative therapy for ATL. We searched for biological active substances for the prevention and treatment of ATL from several species of herbs. The ATL cell growth-inhibitory activity and apoptosis assay showed that carnosol, which is an ingredient contained in rosemary (Rosmarinus officinalis), induced apoptosis in ATL cells. Next, to investigate the apoptosis-inducing mechanism of carnosol, we applied proteomic analysis using fluorescent two-dimensional differential gel electrophoresis and mass spectrometry. The proteomic analysis showed that the expression of reductases, enzymes in glycolytic pathway, and enzymes in pentose phosphate pathway was increased in carnosol-treated cells, compared with untreated cells. These results suggested that carnosol affected the redox status in the cells. Further, the quantitative analysis of glutathione, which plays the central role for the maintenance of intracellular redox status, indicated that carnosol caused the decrease of glutathione in the cells. Further, N-acetyl-l-cystein, which is precursor of glutathione, canceled the efficiency of carnosol. From these results, it was suggested that the apoptosis-inducing activity of carnosol in ATL cells was caused by the depletion of glutathione. © 2013 Japan Human Cell Society and Springer Japan.
PubMed | Hamamatsu University School of Medicine, Kagoshima University, Chugai Pharmaceutical Co., Kobe University and Miyazaki Prefectural Industrial Support Foundation
Type: Journal Article | Journal: PloS one | Year: 2013
It has been hypothesized that persistent hepatitis C virus (HCV) infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4), composed of subunits C4, C4, and C4, and the role of HCV proteins in complement activation.Human C4 was incubated with HCV nonstructural (NS) 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined.HCV NS3/4A protease cleaved C4 in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4 cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4 fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4, was also observed in HCV-infected cells expressing C4.C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection.
Tsuruda T.,University of Miyazaki |
Hatakeyama K.,University of Miyazaki |
Nagamachi S.,University of Miyazaki |
Sekita Y.,University of Miyazaki |
And 10 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012
Objective-The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. Methods and Results-Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and-3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl 2 in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. Conclusion-This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder. © 2012 American Heart Association, Inc.
Miyazaki Prefectural Industrial Support Foundation and University of Miyazaki | Date: 2010-03-26
Provided is a preventive, progression inhibitor or remedy for a disease one of the causes of which is the activation of the P13K/AKT signaling pathway or vice versa. A phosphorylation-inhibiting and/or dephosphorylating agent, which has an effect of inhibiting the phosphorylation at least at one of the phosphorylation sites of PTEN protein selected from the group consisting of T382, T383 and S380 and/or an effect of dephosphorylating the same, is prepared. Alternatively, a phosphorylation-inhibiting or dephosphorylating agent for PTEN is screened by a method comprising a step for confirming an ability of a test substance to inhibit the phosphorylation at least at one of the phosphorylation sites of PTEN protein selected from the group consisting of T382, T383 and S380 or a dephosphorylation ability thereof. Then, a substance having an effect opposite to the inhibition of PTEN phosphorylation or dephosphorylation thereof, e.g., an antibody against the phosphorylation-inhibiting or dephosphorylating agent for PTEN obtained above, is also obtained.