Kanazawa Medical University

About: Kanazawa Medical University is a education organization based out in Kanazawa, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 3103 authors who have published 6322 publications receiving 144592 citations. The organization is also known as: Kanazawa ika daigaku.

Simvastatin and atorvastatin facilitates amyloid β‐protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways

Abstract: One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid β-protein (Aβ) in the brain. Aβ accumulation seems to arise from an imbalance between Aβ production and clearance. Neprilysin (NEP) and insulin-degrading enzyme (IDE) are the important Aβ-degrading enzymes in the brain, and deficits in their expression may promote Aβ deposition in patients with sporadic late-onset AD. Statins, which are used clinically for reducing cholesterol levels, can exert beneficial effects on AD. Therefore, we examined whether various statins are associated with Aβ degradation by inducing NEP and IDE expression, and then evaluating the relation between activation of intracellular signaling transduction, inhibition of cholesterol production, and morphological changes to astrocytes. Treating cultured rat astrocytes with simvastatin and atorvastatin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner. The decrease in NEP expression was a result of activation of extracellular signal-regulated kinase (ERK) but not the reduction of cholesterol synthesis pathway. This NEP reduction was achieved by the release to the extracellular space of cultured astrocytes. Furthermore, the cultured medium prepared from simvastatin- and atorvastatin-treated astrocytes significantly induced the degradation of exogenous Aβ. These results suggest that simvastatin and atorvastatin induce the increase of Aβ degradation of NEP on the extracellular of astrocytes by inducing ERK-mediated pathway activity and that these reagents regulate the differential mechanisms between the secretion of NEP, the induction of cholesterol reduction, and the morphological changes in the cultured astrocytes.

Microvessel Density: Correlation with 18F-FDG Uptake and Prognostic Impact in Lung Adenocarcinomas

Abstract: Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with 18F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and 18F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas. Methods: Forty-four patients with 45 lung adenocarcinomas underwent 18F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/α-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD. Results: MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to 18F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with 18F-FDG uptake (P

Serum hepcidin-25 levels and anemia in non-dialysis chronic kidney disease patients: a cross-sectional study

Abstract: Background. Hepcidin is a central regulator of iron homeostasis. Increased hepcidin concentrations could cause iron-restricted erythropoiesis in chronic kidney disease (CKD)-associated anemia. This cross-sectional observational study was conducted to evaluate the association between hepcidin and CKD-associated anemia in nondialysis CKD patients. Methods. A total of 505 non-dialysis CKD patients not treated with parenteral iron were recruited, and serum hepcidin-25 levels were measured by liquid chromatography tandem mass spectrometry. Multiple linear regression analysis was used to examine the relationship between hepcidin and glomerular filtration rate (GFR) and the relationship between hemoglobin concentration and predictors including the hepcidin level. Results. The median hepcidin level among the 505 CKD patients was 15.4 ng/mL (interquartile range, 5.5– 33.6 ng/mL). Although hepcidin level significantly increased according to the CKD stage, multivariate analysis did not reveal an association of GFR with the hepcidin level. Hepcidin level was a significant predictor of hemoglobin concentration after the adjustment for confounders, and a significant interaction between hepcidin and ferritin was found. After stratifying at the median ferritin level, 91 ng/mL, we found a negative association between hepcidin level and hemoglobin in the high-ferritin group. A trend toward a negative association between hepcidin level and mean corpuscular volume was observed in the high-ferritin group. Conclusions. Serum hepcidin-25 levels were negatively associated with hemoglobin concentrations in non-dialysis CKD patients with sufficient iron stores. We found that ferritin modified the association between hepcidin level and hemoglobin concentration. In addition, our results confirmed that the serum hepcidin level is not associated with GFR.

Endothelial autophagy deficiency induces IL6 - dependent endothelial mesenchymal transition and organ fibrosis.

Abstract: Macroautophagy/autophagy plays a vital role in the homeostasis of diverse cell types. Vascular endothelial cells contribute to vascular health and play a unique role in vascular biology. He...