19 results on '"Nagashima, Y."'
Search Results
2. Eddy, drift wave and zonal flow dynamics in a linear magnetized plasma
- Author
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Arakawa, H., primary, Inagaki, S., additional, Sasaki, M., additional, Kosuga, Y., additional, Kobayashi, T., additional, Kasuya, N., additional, Nagashima, Y., additional, Yamada, T., additional, Lesur, M., additional, Fujisawa, A., additional, Itoh, K., additional, and Itoh, S.-I., additional
- Published
- 2016
- Full Text
- View/download PDF
3. Experimental Identification of Electric Field Excitation Mechanisms in a Structural Transition of Tokamak Plasmas
- Author
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Kobayashi, T., primary, Itoh, K., additional, Ido, T., additional, Kamiya, K., additional, Itoh, S.-I., additional, Miura, Y., additional, Nagashima, Y., additional, Fujisawa, A., additional, Inagaki, S., additional, Ida, K., additional, and Hoshino, K., additional
- Published
- 2016
- Full Text
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4. A Concept of Cross-Ferroic Plasma Turbulence
- Author
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Inagaki, S., primary, Kobayashi, T., additional, Kosuga, Y., additional, Itoh, S.-I., additional, Mitsuzono, T., additional, Nagashima, Y., additional, Arakawa, H., additional, Yamada, T., additional, Miwa, Y., additional, Kasuya, N., additional, Sasaki, M., additional, Lesur, M., additional, Fujisawa, A., additional, and Itoh, K., additional
- Published
- 2016
- Full Text
- View/download PDF
5. Identification of nonlinear effects of background asymmetry on solitary oscillations in a cylindrical plasma.
- Author
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Kobayashi T, Fujisawa A, Nagashima Y, Moon C, Yamasaki K, Nishimura D, Inagaki S, Shimizu A, Tokuzawa T, and Ido T
- Abstract
A symmetry-breaking in rotational spatial pattern of quasi-periodic solitary oscillations is revealed with tomography measurement of plasma emission, simultaneously with background asymmetry in stationary plasma structure. Although the oscillatory pattern deformation is a natural course in the presence of asymmetry, elaborate analyses identify existence unfeatured nonlinear effects of the background asymmetry, i.e., its nonlinear couplings with harmonic modes of rotational symmetry, to produce non-harmonic mode to break the symmetry and cause the oscillatory pattern to be chaotic. The findings suggest the unrecognized fundamental process for plasmas to be turbulent., (© 2024. The Author(s).)
- Published
- 2024
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6. Development of machine learning models for predicting unfavorable functional outcomes from preoperative data in patients with chronic subdural hematomas.
- Author
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Fuse Y, Nagashima Y, Nishiwaki H, Ohka F, Muramatsu Y, Araki Y, Nishimura Y, Ienaga J, Nagatani T, Seki Y, Watanabe K, Ohno K, and Saito R
- Subjects
- Humans, Retrospective Studies, Trephining, Machine Learning, Logistic Models, Hematoma, Subdural, Chronic surgery
- Abstract
Chronic subdural hematoma (CSDH) often causes neurological deterioration and is treated with hematoma evacuation. This study aimed to assess the feasibility of various machine learning models to preoperatively predict the functional outcome of patients with CSDH. Data were retrospectively collected from patients who underwent CSDH surgery at two institutions: one for internal validation and the other for external validation. The poor functional outcome was defined as a modified Rankin scale score of 3-6 upon hospital discharge. The unfavorable outcome was predicted using four machine learning algorithms on an internal held-out cohort (n = 188): logistic regression, support vector machine (SVM), random forest, and light gradient boosting machine. The prediction performance of these models was also validated in an external cohort (n = 99). The area under the curve of the receiver operating characteristic curve (ROC-AUC) of each machine learning-based model was found to be high in both validations (internal: 0.906-0.925, external: 0.833-0.860). In external validation, the SVM model demonstrated the highest ROC-AUC of 0.860 and accuracy of 0.919. This study revealed the potential of machine learning algorithms in predicting unfavorable outcomes at discharge among patients with CSDH undergoing burr hole surgery., (© 2023. Springer Nature Limited.)
- Published
- 2023
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7. Characterization of human anti-EpCAM antibodies for developing an antibody-drug conjugate.
- Author
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Satofuka H, Wang Y, Yamazaki K, Hamamichi S, Fukuhara T, Rafique A, Osako N, Kanazawa I, Endo T, Miyake N, Honma K, Nagashima Y, Hichiwa G, Shimoya K, Abe S, Moriwaki T, Murakami Y, Gao X, Kugoh H, Oshimura M, Ito Y, and Kazuki Y
- Subjects
- Humans, Mice, Animals, Epithelial Cell Adhesion Molecule, Antigens, Neoplasm, Antibodies, Monoclonal, Immunoconjugates pharmacology, Immunoconjugates therapeutic use, Colonic Neoplasms pathology
- Abstract
We previously generated fully human antibody-producing TC-mAb mice for obtaining potential therapeutic monoclonal antibodies (mAbs). In this study, we investigated 377 clones of fully human mAbs against a tumor antigen, epithelial cell adhesion molecule (EpCAM), to determine their antigen binding properties. We revealed that a wide variety of mAbs against EpCAM can be obtained from TC-mAb mice by the combination of epitope mapping analysis of mAbs to EpCAM and native conformational recognition analysis. Analysis of 72 mAbs reacting with the native form of EpCAM indicated that the EpCL region (amino acids 24-80) is more antigenic than the EpRE region (81-265), consistent with numerous previous studies. To evaluate the potential of mAbs against antibody-drug conjugates, mAbs were directly labeled with DM1, a maytansine derivative, using an affinity peptide-based chemical conjugation (CCAP) method. The cytotoxicity of the conjugates against a human colon cancer cell line could be clearly detected with high-affinity as well as low-affinity mAbs by the CCAP method, suggesting the advantage of this method. Thus, this study demonstrated that TC-mAb mice can provide a wide variety of antibodies and revealed an effective way of identifying candidates for fully human ADC therapeutics., (© 2023. The Author(s).)
- Published
- 2023
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8. Automated fracture screening using an object detection algorithm on whole-body trauma computed tomography.
- Author
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Inoue T, Maki S, Furuya T, Mikami Y, Mizutani M, Takada I, Okimatsu S, Yunde A, Miura M, Shiratani Y, Nagashima Y, Maruyama J, Shiga Y, Inage K, Orita S, Eguchi Y, and Ohtori S
- Subjects
- Algorithms, Humans, Pelvis, Retrospective Studies, Tomography, X-Ray Computed methods, Rib Fractures, Spinal Fractures
- Abstract
The emergency department is an environment with a potential risk for diagnostic errors during trauma care, particularly for fractures. Convolutional neural network (CNN) deep learning methods are now widely used in medicine because they improve diagnostic accuracy, decrease misinterpretation, and improve efficiency. In this study, we investigated whether automatic localization and classification using CNN could be applied to pelvic, rib, and spine fractures. We also examined whether this fracture detection algorithm could help physicians in fracture diagnosis. A total of 7664 whole-body CT axial slices (chest, abdomen, pelvis) from 200 patients were used. Sensitivity, precision, and F1-score were calculated to evaluate the performance of the CNN model. For the grouped mean values for pelvic, spine, or rib fractures, the sensitivity was 0.786, precision was 0.648, and F1-score was 0.711. Moreover, with CNN model assistance, surgeons showed improved sensitivity for detecting fractures and the time of reading and interpreting CT scans was reduced, especially for less experienced orthopedic surgeons. Application of the CNN model may lead to reductions in missed fractures from whole-body CT images and to faster workflows and improved patient care through efficient diagnosis in polytrauma patients., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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9. Coenzyme Q10 in the eye isomerizes by sunlight irradiation.
- Author
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Mamun MA, Nabi MM, Sato T, Aramaki S, Takanashi Y, Sakamoto T, Hizume K, Mori C, Yasue M, Ozaki M, Islam A, Kahyo T, Horikawa M, Takahashi Y, Okazaki S, Ohishi K, Nagashima Y, Seno K, Hotta Y, and Setou M
- Subjects
- Chromatography, Liquid, Lipids, Ubiquinone analogs & derivatives, Sunlight, Ultraviolet Rays
- Abstract
Photoisomerization of lipids has been well studied. As for the eyes, photoisomerization from 11-cis isomer to all-trans-retinal is well-known as the first step of the visual transduction in the photoreceptors. In addition to that, there would be other ocular lipids that undergo photoisomerization, which may be involved in ocular health and function. To explore any photoisomerizable lipids in the eyes, the nonirradiated and sunlight-irradiated eyeball extracts were subjected to liquid chromatography-mass spectrometry analysis, followed by the identification of the decreased lipid species in the irradiated extracts. Surprisingly, more than nine hundred lipid species were decreased in the irradiated extracts. Three lipid species, coenzyme Q10 (CoQ10), triglyceride(58:4), and coenzyme Q9, were decreased both significantly (p < 0.05) and by more than two-fold, where CoQ10 showed the most significant decrease. Later, photoisomerization was identified as the prominent cause underlying the decrease of CoQ10. Interestingly, CoQ10 in the sunlight-irradiated fresh eyeballs was also isomerized. Both the visible light and ultraviolet radiation were capable of producing CoQ10 isomer, while the latter showed rapid action. This study is believed to enhance our understanding of the biochemistry and photodamage of the eye and can potentially contribute to the advancement of opto-lipidomics., (© 2022. The Author(s).)
- Published
- 2022
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10. The first observation of 4D tomography measurement of plasma structures and fluctuations.
- Author
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Moon C, Yamasaki K, Nagashima Y, Inagaki S, Ido T, Yamada T, Kasuya N, Kosuga Y, Sasaki M, Kawachi Y, Nishimura D, Kobayashi T, and Fujisawa A
- Abstract
A tomography system is installed as one of the diagnostics of new age to examine the three-dimensional characteristics of structure and dynamics including fluctuations of a linear magnetized helicon plasma. The system is composed of three sets of tomography components located at different axial positions. Each tomography component can measure the two-dimensional emission profile over the entire cross-section of plasma at different axial positions in a sufficient temporal scale to detect the fluctuations. The four-dimensional measurement including time and space successfully obtains the following three results that have never been found without three-dimensional measurement: (1) in the production phase, the plasma front propagates from the antenna toward the end plate with an ion acoustic velocity. (2) In the steady state, the plasma emission profile is inhomogeneous, and decreases along the axial direction in the presence of the azimuthal asymmetry. Furthermore, (3) in the steady state, the fluctuations should originate from a particular axial position located downward from the helicon antenna.
- Published
- 2021
- Full Text
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11. Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT.
- Author
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Toguchi M, Takagi T, Ogawa Y, Morita S, Yoshida K, Kondo T, Iizuka J, Ishida H, Nagashima Y, and Tanabe K
- Subjects
- Aged, Carcinoma, Renal Cell diagnostic imaging, Female, Humans, Kidney Neoplasms diagnostic imaging, Male, Middle Aged, Tomography, X-Ray Computed, Carcinoma, Renal Cell surgery, Kidney Neoplasms surgery, Nephrectomy methods
- Abstract
To investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.
- Published
- 2021
- Full Text
- View/download PDF
12. Molecular contrast on phase-contrast microscope.
- Author
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Toda K, Tamamitsu M, Nagashima Y, Horisaki R, and Ideguchi T
- Subjects
- HeLa Cells, Humans, Lasers, Semiconductor, Light, Microscopy, Phase-Contrast methods, Microspheres, Polystyrenes chemistry, Silicon Dioxide chemistry, Spectrophotometry, Infrared methods, Molecular Imaging methods
- Abstract
An optical microscope enables image-based findings and diagnosis on microscopic targets, which is indispensable in many scientific, industrial and medical settings. A standard benchtop microscope platform, equipped with e.g., bright-field and phase-contrast modes, is of importance and convenience for various users because the wide-field and label-free properties allow for morphological imaging without the need for specific sample preparation. However, these microscopes never have capability of acquiring molecular contrast in a label-free manner. Here, we develop a simple add-on optical unit, comprising of an amplitude-modulated mid-infrared semiconductor laser, that is attached to a standard microscope platform to deliver the additional molecular contrast of the specimen on top of its conventional microscopic image, based on the principle of photothermal effect. We attach this unit, termed molecular-contrast unit, to a standard phase-contrast microscope, and demonstrate high-speed label-free molecular-contrast phase-contrast imaging of silica-polystyrene microbeads mixture and molecular-vibrational spectroscopic imaging of HeLa cells. Our simple molecular-contrast unit can empower existing standard microscopes and deliver a convenient accessibility to the molecular world.
- Published
- 2019
- Full Text
- View/download PDF
13. Chloramphenicol inhibits eukaryotic Ser/Thr phosphatase and infection-specific cell differentiation in the rice blast fungus.
- Author
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Nozaka A, Nishiwaki A, Nagashima Y, Endo S, Kuroki M, Nakajima M, Narukawa M, Kamisuki S, Arazoe T, Taguchi H, Sugawara F, and Kamakura T
- Subjects
- Antifungal Agents pharmacology, Bacteriophage T7, Cell Differentiation, DNA, Fungal, Gene Deletion, Genetic Complementation Test, Humans, Magnaporthe enzymology, Mutation, Peptide Library, Phosphoprotein Phosphatases chemistry, Phosphoprotein Phosphatases metabolism, Plant Diseases microbiology, Plasmids genetics, RNA, Fungal, Chloramphenicol pharmacology, Magnaporthe drug effects, Oryza microbiology, Phosphoprotein Phosphatases antagonists & inhibitors
- Abstract
Chloramphenicol (Cm) is a broad-spectrum classic antibiotic active against prokaryotic organisms. However, Cm has severe side effects in eukaryotes of which the cause remains unknown. The plant pathogenic fungus Magnaporthe oryzae, which causes rice blast, forms an appressorium to infect the host cell via single-cell differentiation. Chloramphenicol specifically inhibits appressorium formation, which indicates that Cm has a novel molecular target (or targets) in the rice blast fungus. Application of the T7 phage display method inferred that MoDullard, a Ser/Thr-protein phosphatase, may be a target of Cm. In animals Dullard functions in cell differentiation and protein synthesis, but in fungi its role is poorly understood. In vivo and in vitro analyses showed that MoDullard is required for appressorium formation, and that Cm can bind to and inhibit MoDullard function. Given that human phosphatase CTDSP1 complemented the MoDullard function during appressorium formation by M. oryzae, CTDSP1 may be a novel molecular target of Cm in eukaryotes.
- Published
- 2019
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14. A Rho-based reaction-diffusion system governs cell wall patterning in metaxylem vessels.
- Author
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Nagashima Y, Tsugawa S, Mochizuki A, Sasaki T, Fukuda H, and Oda Y
- Subjects
- Cell Membrane enzymology, Models, Theoretical, Plant Cells enzymology, Protein Binding, Arabidopsis cytology, Arabidopsis Proteins metabolism, Cell Membrane metabolism, Cell Wall metabolism, Guanine Nucleotide Exchange Factors metabolism, Plant Cells metabolism, Xylem cytology, rho GTP-Binding Proteins metabolism
- Abstract
Rho GTPases play crucial roles in cell polarity and pattern formation. ROPs, Rho of plant GTPases, are widely involved in cell wall patterning in plants, yet the molecular mechanism underlying their action remains unknown. Arabidopsis ROP11 is locally activated to form plasma membrane domains, which direct formation of cell wall pits in metaxylem vessel cells through interaction with cortical microtubules. Here, we show that the pattern formation of cell wall pits is governed by ROP activation via a reaction-diffusion mechanism. Genetic analysis and reconstructive assays revealed that ROPGEF4/7 and ROPGAP3/4, which encode ROP activators and inactivators, respectively, regulated the formation of ROP-activated domains; these in turn determined the pattern of cell wall pits. Mathematical modelling showed that ROP-activation cycle generated ROP domains by reaction-diffusion mechanism. The model predicted that a positive feedback and slow diffusion of ROP11-ROPGEF4 complex were required to generate ROP-activated domains. ROPGEF4 formed a dimer that interacted with activated ROP11 in vivo, which could provide positive feedback for ROP activation. ROPGEF4 was highly stable on the plasma membrane and inhibited ROP11 diffusion. Our study indicated that ROP-based reaction-diffusion system self-organizes ROP-activated domains, thereby determines the pit pattern of metaxylem vessels.
- Published
- 2018
- Full Text
- View/download PDF
15. Efficient and surface site-selective ion desorption by positron annihilation.
- Author
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Tachibana T, Yamashita T, Nagira M, Yabuki H, and Nagashima Y
- Abstract
We compared positron- and electron-stimulated desorption (e
+ SD and ESD) of positive ions from a TiO2 (110) surface. Although desorption of O+ ions was observed in both experiments, the desorption efficiency caused by positron bombardment was larger by one order of magnitude than that caused by electron bombardment at an incident energy of 500 eV. e+ SD of O+ ions remained highly efficient with incident positron energies between 10 eV and 600 eV. The results indicate that e+ SD of O+ ions is predominantly caused by pair annihilation of surface-trapped positrons with inner-shell electrons. We also tested e+ SD from water chemisorbed on the TiO2 surface and found that the desorption of specific ions was enhanced by positron annihilation, above the ion yield with electron bombardment. This finding corroborates our conclusion that annihilation-site selectivity of positrons results in site-selective ion desorption from a bombarded surface.- Published
- 2018
- Full Text
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16. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis.
- Author
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Honda Y, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Fujita K, Yoneda M, Takizawa T, Saito S, Nagashima Y, and Nakajima A
- Subjects
- Animals, Biomarkers, Biopsy, Disease Models, Animal, Female, Gene Expression Regulation, Lipid Metabolism, Liver drug effects, Liver metabolism, Liver pathology, Male, Mice, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease pathology, Rodentia, Severity of Illness Index, Uncoupling Protein 3 genetics, Uncoupling Protein 3 metabolism, Benzoxazoles pharmacology, Butyrates pharmacology, Non-alcoholic Fatty Liver Disease etiology, Non-alcoholic Fatty Liver Disease metabolism, PPAR alpha antagonists & inhibitors, PPAR alpha metabolism
- Abstract
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH. Pemafibrate efficacy was assessed in a diet-induced rodent model of NASH compared with fenofibrate. Pemafibrate and fenofibrate improved obesity, dyslipidaemia, liver dysfunction, and the pathological condition of NASH. Pemafibrate improved insulin resistance and increased energy expenditure significantly. To investigate the effects of pemafibrate, we analysed the gene expressions and protein levels involved in lipid metabolism. We also analysed uncoupling protein 3 (UCP3) expression. Pemafibrate stimulated lipid turnover and upregulated UCP3 expression in the liver. Levels of acyl-CoA oxidase 1 and UCP3 protein were increased by pemafibrate significantly. Pemafibrate can improve the pathogenesis of NASH by modulation of lipid turnover and energy metabolism in the liver. Pemafibrate is a promising therapeutic agent for NAFLD/NASH., Competing Interests: The authors declare no competing financial interests.
- Published
- 2017
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17. Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis.
- Author
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Kessoku T, Imajo K, Honda Y, Kato T, Ogawa Y, Tomeno W, Kato S, Mawatari H, Fujita K, Yoneda M, Nagashima Y, Saito S, Wada K, and Nakajima A
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cell Line, Fibrosis genetics, Fibrosis metabolism, Fibrosis prevention & control, Fluorescent Antibody Technique, Gene Expression drug effects, Humans, Immunoblotting, Inflammation genetics, Inflammation metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Lipopolysaccharide Receptors genetics, Lipopolysaccharide Receptors metabolism, Lipopolysaccharides, Male, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease chemically induced, Non-alcoholic Fatty Liver Disease genetics, Resveratrol, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor metabolism, Signal Transduction drug effects, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Disease Models, Animal, Inflammation prevention & control, Non-alcoholic Fatty Liver Disease prevention & control, Stilbenes pharmacology
- Abstract
The natural polyphenol compound resveratrol (RSV) is considered to have a broad spectrum of beneficial biological activities upon human health. However, the exact effect of RSV on steatosis (a phenotype of non-alcoholic fatty liver [NAFL]) or fibrosis and inflammation (major phenotypes of non-alcoholic steatohepatitis [NASH]) is not known. Our data showed that administration of RSV (2 or 20 mg/kg/day) did not suppress steatosis in a high-fat diet-induced model of NAFL in mice. In contrast, identical concentrations of RSV dramatically inhibited inflammation and fibrosis in a low-dose lipopolysaccharide-induced model of NASH. These data suggested that RSV administration-mediated improvement of inflammation and fibrosis was due to the inhibition of LPS reactivity controlled by CD14 expression in Kupffer cells. These findings suggest that RSV could be a candidate agent for the treatment of NASH.
- Published
- 2016
- Full Text
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18. Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice.
- Author
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Hata R, Izukuri K, Kato Y, Sasaki S, Mukaida N, Maehata Y, Miyamoto C, Akasaka T, Yang X, Nagashima Y, Takeda K, Kiyono T, and Taniguchi M
- Subjects
- Animals, Antigens, Ly immunology, Autoantibodies immunology, Cell Transformation, Neoplastic immunology, Cell Transformation, Neoplastic metabolism, Chemokines, CXC metabolism, Chronic Disease, Colitis complications, Colitis genetics, Colitis immunology, Disease Models, Animal, Female, G(M1) Ganglioside immunology, Galactosylceramides metabolism, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Lymphocyte Depletion, Melanoma, Experimental, Mice, Mice, Transgenic, NK Cell Lectin-Like Receptor Subfamily B immunology, Neoplasms mortality, Tumor Burden, Cell Transformation, Neoplastic genetics, Chemokines, CXC genetics, Lung Neoplasms secondary, Neoplasms genetics, Neoplasms pathology
- Abstract
Cancer progression involves carcinogenesis, an increase in tumour size, and metastasis. Here, we investigated the effect of overexpressed CXC chemokine ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice was significantly lower compared with that for isogenic wild type C57BL/6 (Wt) mice. When tumour cells were injected into these mice, the size of the tumours that developed and the number of metastatic nodules in the lungs of the animals were always significantly lower in the Tg mice than in the Wt ones. Injection of anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis, suggesting that NK cell activity played an important role during CXCL14-mediated suppression of tumour growth and metastasis. The importance of NK cells on the metastasis was also supported when CXCL14 was expressed in B16 melanoma cells. Further, the survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention.
- Published
- 2015
- Full Text
- View/download PDF
19. Arabidopsis IRE1 catalyses unconventional splicing of bZIP60 mRNA to produce the active transcription factor.
- Author
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Nagashima Y, Mishiba K, Suzuki E, Shimada Y, Iwata Y, and Koizumi N
- Subjects
- Arabidopsis genetics, Polymerase Chain Reaction, Transcriptome, Tunicamycin pharmacology, Arabidopsis metabolism, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism, Basic-Leucine Zipper Transcription Factors genetics, Biocatalysis, Protein Kinases metabolism, RNA Splicing, RNA, Messenger genetics, Transcription Factors metabolism
- Abstract
IRE1 plays an essential role in the endoplasmic reticulum (ER) stress response in yeast and mammals. We found that a double mutant of Arabidopsis IRE1A and IRE1B (ire1a/ire1b) is more sensitive to the ER stress inducer tunicamycin than the wild-type. Transcriptome analysis revealed that genes whose induction was reduced in ire1a/ire1b largely overlapped those in the bzip60 mutant. We observed that the active form of bZIP60 protein detected in the wild-type was missing in ire1a/ire1b. We further demonstrated that bZIP60 mRNA is spliced by ER stress, removing 23 ribonucleotides and therefore causing a frameshift that replaces the C-terminal region of bZIP60 including the transmembrane domain (TMD) with a shorter region without a TMD. This splicing was detected in ire1a and ire1b single mutants, but not in the ire1a/ire1b double mutant. We conclude that IRE1A and IRE1B catalyse unconventional splicing of bZIP60 mRNA to produce the active transcription factor.
- Published
- 2011
- Full Text
- View/download PDF
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