Takarazuka University of Medical and Health Care

Takarazuka, Japan

Takarazuka University of Medical and Health Care

Takarazuka, Japan
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Atik N.,Osaka University | Atik N.,Padjadjaran University | Kunii M.,Osaka University | Avriyanti E.,Osaka University | And 7 more authors.
Cell Structure and Function | Year: 2014

Protein Kinase D (PKD) 1, 2, and 3 are members of the PKD family. PKDs influence many cellular processes, including cell polarity, structure of the Golgi, polarized transport from the Golgi to the basolateral plasma membrane, and actin polymerization. However, the role of the PKD family in cell polarity has not yet been elucidated in vivo. Here, we show that KO mice displayed similar localization of the apical and basolateral proteins, transport of VSV-G and a GPI-anchored protein, and similar localization of actin filaments. As DKO mice were embryonic lethal, we generated MEFs that lacked all PKD isoforms from the PKD1 and PKD2 double floxed mice using Cre recombinase and PKD3 siRNA. We observed a similar localization of various organelles, a similar time course in the transport of VSV-G and a GPI-anchored protein, and a similar distribution of F-actin in the PKD-null MEFs. Collectively, our results demonstrate that the complete deletion of PKDs does not affect the transport of VSV-G or a GPI-anchored protein, and the distribution of F-actin. However, simultaneous deletion of PKD1 and PKD2 affect embryonic development, demonstrating their functional redundancy during development. © 2014 by Japan Society for Cell Biology.

PubMed | Shanghai JiaoTong University, The Second Artillery General Hospital PLA, CAS Shanghai Institute of Materia Medica and Takarazuka University of Medical and Health Care
Type: | Journal: Scientific reports | Year: 2017

Aortic dissection (AD), a severe cardiovascular disease with the characteristics of high mortality, is lack of specific clinical biomarkers. In order to facilitate the diagnosis of AD, we investigated plasma amino acid profile through metabolomics approach. Total 33 human subjects were enrolled in the study: 11 coronary heart disease (CHD) patients without aortic lesion and 11 acute AD and 11 chronic AD. Amino acids were identified in plasma using liquid chromatography and mass spectrometry (LC-MS/MS), and were further subjected to multiple logistic regression analysis. The score plots of principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) showed clear discrimination of CHD patients with AD, acute AD or chronic AD patients, respectively. The contents of histidine, glycine, serine, citrate, ornithine, hydroxyproline, proline and sarcosine were significant different in acute AD patients comparing with CHD patients. The levels of citrate, GABA, glutamate and cysteine were significant different in chronic AD patients comparing with CHD patients. The contents of glutamate and phenylalanine were significant changed in acute AD patients comparing with chronic AD patients. Plasma aminograms were significantly altered in patients with AD comparing with CHD, especially in acute AD, suggesting amino acid profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

PubMed | Shenyang Pharmaceutical University, Takarazuka University of Medical and Health Care and CAS Shanghai Institute of Materia Medica
Type: Journal Article | Journal: Journal of the Chinese Medical Association : JCMA | Year: 2015

The herb pair of Salvia miltiorrhiza and Panax notoginseng has widely been used for improving coronary and cerebral circulation in China. However, the exact contribution of the major active components of S. miltiorrhiza and P. notoginseng to cardioprotection is far from clear. In the present study, three representative ingredients, salvianolic acid B (SalB) from S. miltiorrhiza and ginsenoside Rg1 (Rg1) and ginsenoside Rb1 (Rb1) from P. notoginseng, were selected to elucidate the mechanism of the herb pair at the ingredient level.The purity of SalB, Rg1, and Rb1 was >99%, as detected by high-performance liquid chromatography. Acute myocardial infarction was introduced by ligation of the left anterior descending coronary artery near the main pulmonary artery. Cardiac contractility was detected through a Mikro-tipped catheter, and cardiac infarct size was determined using triphenyltetrazolium chloride stain.The combination of SalB and Rg1, and not the combination of SalB and Rb1, improved heart contractility in rats with myocardial infarction. The different contributions of Rg1 and Rb1, in combination with SalB, to cardioprotection provides further direction to optimize and modernize the herbal medicines containing S. miltiorrhiza and P. notoginseng.The combination of SalB and Rg1 may provide potential protection against myocardial infarction.

PubMed | Fudan University, Hong Kong Baptist University, Shenyang Pharmaceutical University, Takarazuka University of Medical and Health Care and CAS Shanghai Institute of Materia Medica
Type: Journal Article | Journal: PloS one | Year: 2015

Lack of pharmacological strategies in clinics restricts the patient prognosis with myocardial ischemia/reperfusion (I/R) injury. The aim of this study was to evaluate the cardioprotection of combined salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) against myocardial I/R injury and further investigate the underlying mechanism. I/R injury was induced by coronary artery ligation for Wistar male rats and hypoxia/reoxygenation injury was induced on H9c2 cells. Firstly, the best ratio between SalB and Rg1was set as 2:5 based on their effects on heart function detected by hemodynamic measurement. Then SalB-Rg1 (2:5) was found to maintain mitochondrial membrane potential and resist apoptosis and necrosis in H9c2 cell with hypoxia/reoxygenation injury. Companying with same dose of SalB or Rg1 only, SalB-Rg1 showed more significant effects on down-regulation of myocardial infarct size, maintenance of myocardium structure, improvement on cardiac function, decrease of cytokine secretion including TNF-, IL-1, RANTES and sVCAM-1. Finally, the SalB-Rg1 improved the viability of cardiac myocytes other than cardiac fibroblasts in rats with I/R injury using flow cytometry. Our results revealed that SalB-Rg1 was a promising strategy to prevent myocardial I/R injury.

PubMed | East China University of Science and Technology, Shenyang Pharmaceutical University, Takarazuka University of Medical and Health Care and CAS Shanghai Institute of Materia Medica
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2015

Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination.

PubMed | Fudan University, Kumamoto University, Shenyang Pharmaceutical University, Takarazuka University of Medical and Health Care and CAS Shanghai Institute of Materia Medica
Type: | Journal: Life sciences | Year: 2016

Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm.Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoEFirstly, SalC showed significant inhibition on the activity of MMP-2 and MMP-9. Aortic aneurysm was defined as >50% increase in maximum diameter of aorta, and the down-regulated tendency of 20mg/kg SalC against formation of aortic aneurysm was detected. Also, 22.2% rupture was detected in ApoESalC significantly ameliorated the progression of aortic aneurysm in ApoE

Sato M.,Gunma University | Yoshimura S.,Osaka University | Hirai R.,Gunma University | Goto A.,Osaka University | And 12 more authors.
Traffic | Year: 2011

VAMP7 or tetanus neurotoxin-insensitive vesicle- associated membrane protein (TI-VAMP) has been proposed to regulate apical transport in polarized epithelial cells, axonal transport in neurons and lysosomal exocytosis. To investigate the function of VAMP7 in vivo, we generated VAMP7 knockout mice. Here, we show that VAMP7 knockout mice are indistinguishable from control mice and display a similar localization of apical proteins in the kidney and small intestine and a similar localization of axonal proteins in the nervous system. Neurite outgrowth of cultured mutant hippocampal neurons was reduced in mutant neurons. However, lysosomal exocytosis was not affected in mutant fibroblasts. Our results show that VAMP7 is required in neurons to extend axons to the full extent. However, VAMP7 does not seem to be required for epithelial cell polarity and lysosomal exocytosis. © 2011 John Wiley & Sons A/S.

Sakai K.,Takarazuka University of Medical and Health Care | Yamane Y.,Ibogawa Hospital | Yamamoto Y.,Kobe University | Maeda K.,Kobe Gakuin University
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica | Year: 2013

Depression is a risk factor for dementia in general, including Alzheimer's disease (AD), its premorbid signs are commonly observed, and the morbidity of depression is higher in dementia patients. Dementia with Lewy bodies (DLB) is considered to have an even higher depression prevalence and premorbid depression rate than other dementias such as AD. This led to depression being listed as a supportive feature in the 2005 criteria for the clinical diagnosis of DLB. However, studies investigating the difference in depression between AD and DLB failed to show consistent results. We examined the Geriatric Depression Scale score, which is designed specifically to rate depression in the elderly, for DLB and AD patients. The scores for DLB patients were twice as high as those for AD patients. There was no correlation between the GDS score and age, sex, or Mini-Mental Sate Examination scores. Depression-specific symptoms were more frequent in the DLB group than non-specific symptoms, while less than one third of DLB patients with very high GDS scores were diagnosed with depression or prescribed antidepressants for depressive symptoms. Other researchers reported that depression of DLB was associated with a higher prevalence of psychiatric symptoms other than major depression, and suggested that depression of DLB might be a part of psychiatric syndrome. There has been no systematic study on the validity or risk of pharmacological therapy, as well as the necessity of intervention, for depression or a high GDS score in DLB. Therefore, intervention must rely on the clinical decision of each doctor. In spite of the paucity of current findings, studies on depression of DLB may play a key role in the elucidation of its neuropathology and psychopathology and offer a new view point on understanding depression itself.

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