559 results on '"N. Takagi"'
Search Results
2. Lessons Learned by the Strong Local Earthquake at the Petrochemical Plant
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Y. Wada, M. Wakakura, Y. Hayashi, N. Takagi, H. Oba, M. Kumasaki, A. Miyake, and M. Arai
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Chemical engineering ,TP155-156 ,Computer engineering. Computer hardware ,TK7885-7895 - Abstract
On 11 and 12 April, 2011, unexpected strong local earthquakes stroke petrochemical plants in Fukushima Prefecture. That local earthquake is caused by the old active fault near the plant activated by the Great East Japan Earthquake. The plants were attacked by the Great East Japan Earthquake, and all facilities of the plant had been stopped since 11 March, 2011. In spite of having received twice earthquakes (especially the bigger second local earthquake), damages of main facilities of the plant were little. The investigation team constituted by specialists of material safety, plant engineering and engineers of that petrochemical company, searched the damage of the facilities and emergency response, and recovery efforts. We summarized the lessons learned from the large earthquake of the chemical plant, related with the emergency correspondence and its organization, support for surrounding, recovery and reconstruction program, etc.
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- 2013
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3. Electronic structure of the 4 × 4 silicene monolayer on semi-infinite Ag(111)
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H Ishida, Y Hamamoto, Y Morikawa, E Minamitani, R Arafune, and N Takagi
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silicene ,Ag(111) ,density functional theory ,embedded Green’s function technique ,semi-infinite surface ,Science ,Physics ,QC1-999 - Abstract
The electronic structure of the 4 × 4 silicene monolayer on a semi-infinite Ag(111) substrate is calculated within density functional theory by using the embedded Green’s function technique. The present calculation confirms the conclusion of previous studies that the two-dimensional (2D) Dirac bands do not exist on this surface as a result of the symmetry breaking and strong orbital hybridizations between the Si π and Ag sp states. In addition, by making use of the advantage of the semi-infinite calculation in which the energy continuum of the bulk Ag bands is fully reproduced, we investigate details of the silicene-induced electronic states, including not only their energy dispersion with 2D wave vector ${\bf k}$ but also their spectral shape as a function of energy at each ${\bf k}$ .
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- 2015
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4. <Abstract of published report>Anti-Candida Activity of Synthetic Hydroxychalcones
- Author
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H., TSUCHIYA, M., SATO, M., AKAGIRI, N., TAKAGI, T., TANAKA, and M., IINUMA
- Published
- 1995
5. Design of a reconfigurable data-path prototype in the single-flux-quantum circuit.
- Author
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S Iwasaki, M Tanaka, Y Yamanashi, H Park, H Akaike, A Fujimaki, N Yoshikawa, N Takagi, K Murakami, H Honda, and K Inoue
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ELECTRONIC circuit design ,PROTOTYPES ,NETWORK routers ,COMPUTER networks - Abstract
We have designed a reconfigurable data-path (RDP) prototype based on the single-flux-quantum (SFQ) circuit. The RDP serves as an accelerator for a high performance computer and is composed of many stages of the array of floating point number processing units (FPUs) connected by reconfigurable operand routing networks (ORNs). The FPU array usually includes shift-registers (SRs) in order that the data is forwarded to the next stage without calculation. The data-path is reconfigured so as to reflect a long repeat instruction appearing in large-scale calculations. We can implement parallel and pipelined processing without memory access in such calculations, reducing the required bandwidth between a memory and a microprocessor. The SFQ high speed network switches and bit-serial/slice FPUs realize reduction in the circuit areas and in the power consumption compared to semiconductor devices when we make up the RDP by using the SFQ circuit. As a first step of the development of the SFQ-RDP, we design a 2 × 2 RDP prototype composed of double arrays of dual arithmetic logic units (ALUs). The prototype also has dual SRs in each array and four ORNs. We use bit-serial ALUs designed to operate at 25 GHz. Each ORN behaves like a 4 × 2 crossbar switch. We have demonstrated the reconfiguration in the RDP prototype made up of 15 050 Josephson junctions though only some of the functions of ALUs are available. [ABSTRACT FROM AUTHOR]
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- 2007
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6. High-performance liquid chromatographic analysis of bacterial fatty acid composition for chemotaxonomic characterization of oral streptococci
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H Tsuchiya, I Namikawa, Masaru Sato, T Hayashi, Motohiro Kato, N Takagi, and M Tatsumi
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Microbiology (medical) ,Chromatography ,biology ,Streptococcus ,Cardiolipins ,Fatty Acids ,Phosphatidylglycerols ,biology.organism_classification ,medicine.disease_cause ,Streptococcus mutans ,Lipids ,Streptococcus salivarius ,Biochemistry ,Reagent ,medicine ,Fatty acid composition ,Streptococcus sanguis ,Saponification ,Bacteria ,Chromatography, High Pressure Liquid ,Phospholipids ,Research Article - Abstract
A high-performance liquid chromatographic method was developed to analyze the fatty acid composition of bacterial lipids. After saponification of lipids extracted from bacteria, the liberated fatty acids were labeled with a fluorescence reagent, 4-bromomethyl-7-acetoxycoumarin, followed by reversed-phase high-performance liquid chromatographic separation and fluorescence detection. All bacterial fatty acids were simultaneously separated within 30 min and sensitively determined. This method was applied to the chemotaxonomic characterization of oral streptococci. The fatty acid composition of phospholipids and total lipids distinguished Streptococcus mutans from any other species examined and showed that Streptococcus sanguis had a close taxonomic relationship with Streptococcus salivarius.
- Published
- 1986
7. Electronic structure of the 4 × 4 silicene monolayer on semi-infinite Ag(111).
- Author
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E Minamitani, R Arafune, N Takagi, H Ishida, Y Hamamoto, and Y Morikawa
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MOLECULAR structure of monomolecular films ,SILICON crystallography ,SILVER ,DENSITY functional theory ,GREEN'S functions ,ORBITAL hybridization ,DIRAC equation - Abstract
The electronic structure of the 4 × 4 silicene monolayer on a semi-infinite Ag(111) substrate is calculated within density functional theory by using the embedded Green’s function technique. The present calculation confirms the conclusion of previous studies that the two-dimensional (2D) Dirac bands do not exist on this surface as a result of the symmetry breaking and strong orbital hybridizations between the Si π and Ag sp states. In addition, by making use of the advantage of the semi-infinite calculation in which the energy continuum of the bulk Ag bands is fully reproduced, we investigate details of the silicene-induced electronic states, including not only their energy dispersion with 2D wave vector but also their spectral shape as a function of energy at each . [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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8. Acute lymphocytic leukemia presenting as phlegmone of the cheek
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T., Miyagishima, Y., Sawa, M., Itou, T., Takemoto, and N., Takagi
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- 1997
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9. CARD9-Mediated Macrophage Responses and Collagen Fiber Capsule Formation Caused by Textured Breast Implants.
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Shoji M, Kanno E, Tanno H, Yamaguchi K, Ishi S, Takagi N, Kurosaka S, Sato K, Niiyama M, Ito A, Ishii K, Imai Y, Kawakami K, and Tachi M
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- Animals, Female, Mice, Breast Implantation adverse effects, Implant Capsular Contracture etiology, Implant Capsular Contracture pathology, Mice, Inbred C57BL, Mice, Knockout, Silicone Gels adverse effects, Surface Properties, Transforming Growth Factor beta metabolism, Breast Implants adverse effects, CARD Signaling Adaptor Proteins metabolism, CARD Signaling Adaptor Proteins genetics, Collagen metabolism, Macrophages metabolism, Macrophages immunology
- Abstract
Background: An increasing number of women are undergoing breast implantation for cosmetic purposes or for reconstructive purposes after breast excision. The surface morphology of the breast implant is a key factor associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response after implant insertion remains unclear, however. The authors conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets., Methods: Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9 , Dectin-1 , Dectin-2 , or Mincle . The authors analyzed collagen fiber capsule thickness, histologic findings, and macrophage inflammatory response, including transforming growth factor (TGF)-β synthesis., Results: The authors found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-β-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-β synthesis, although the responsible C-type lectin receptors remain to be clarified., Conclusion: These results suggest that CARD9 may have a strong impact on silicone sheet morphology through the regulation of macrophage responses., Clinical Relevance Statement: Silicone breast implants have been widely used for postmastectomy and cosmetic augmentation mammaplasty breast reconstruction. The authors sought to elucidate the surface morphology of the breast implant as one of the key factors associated with the formation of collagen fiber capsules., Clinical Question/level of Evidence: Therapeutic, V., (Copyright © 2023 by the American Society of Plastic Surgeons.)
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- 2024
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10. Definitive-dose adjuvant radiotherapy following endoscopic submucosal dissection for superficial esophageal cancer.
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Wada Y, Kumagai S, Takagi N, Shinozaki T, Murata T, Sugawara D, Watanabe K, Matsuhashi T, Iijima K, and Mori N
- Abstract
Background: Prophylactic chemoradiation therapy (CRT) using 40-41.4 Gy post-endoscopic submucosal dissection (ESD) for clinical T1N0M0 esophageal cancer reportedly yields favorable outcomes. However, it cannot completely prevent locoregional lymph node (LN) metastases. We retrospectively analyzed outcomes and adverse events associated with our dose-escalated treatment regimen (definitive-dose radiotherapy [RT] of 50-61.2 Gy, with/without chemotherapy) for these patients, and predictors of progression-free survival (PFS) and overall survival (OS)., Methods: Between 2006 and 2018, 44 consecutive patients (42 men and 2 women; median age, 70 years) who underwent definitive-dose RT post-ESD and had a pathological depth of the muscularis mucosa with lymphovascular invasion (LVI) or the upper-middle submucosal third at our institution were included. We excluded patients who could not obtain a margin-free resection by ESD. If feasible, systemic chemotherapy with 5-fluorouracil plus high- or low-dose cisplatin or nedaplatin was administered concurrently., Results: Five-year PFS, OS, and disease-specific survival rates were 78.8%, 88.4%, and 97.7%, respectively. Six metachronous esophagus (14%), two locoregional LN within the irradiated area with a prophylactic dose of 41.4 Gy (5%), and two locoregional LN plus liver (5%) recurrences occurred. No LN recurrence occurred within the definitive dose of ≥ 50 Gy in the irradiated area. Metachronous esophageal recurrence involved areas receiving ≥ 50 Gy. Univariate and multivariate analyses revealed that age was an independent prognostic factor for both PFS and OS., Conclusions: Definitive-dose RT/CRT post-ESD could provide favorable locoregional LN control and PFS/OS regardless of patient characteristics, including pathological findings and chemotherapy regimen/course, except for age. These results need to be interpreted carefully given several limitations, therefore, definitive-dose RT/CRT should be conducted with caution in clinical practice until high-quality prospective clinical trials evaluating the effectiveness and safety., (© 2024. Japanese Society of Gastroenterology.)
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- 2024
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11. Model of driving factors for success in public health project management using structural equation modeling.
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Santos C, Varajão J, Takagi N, and Manuela Gonçalves A
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- Humans, Latent Class Analysis, Models, Theoretical, COVID-19 epidemiology, COVID-19 virology, Public Health methods
- Abstract
In a context where pandemic crises and chronic conditions are a constant and increasing threat, the success of public health projects is absolutely critical. However, little is known about the factors that influence the success of projects that aim to provide conditions for people to be healthy and prolong the life of the population as a whole. A mixed-method study was carried out to fill the literature gap, resulting in a new model of success factors for public health projects. The research work theorizes the success factors that impact public health project success, providing relevant knowledge for project managers and contributing to the successful management of public health projects., (© 2024. The Author(s).)
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- 2024
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12. Possible involvement of NAMPT in neuronal survival in cerebral ischemic injury under high-glucose conditions through the FoxO3a/LC3 pathway.
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Iwatani Y, Hayashi H, Oba H, Oba M, Sawamura A, Moriyama Y, and Takagi N
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- Animals, Male, Mice, Cytokines metabolism, Mice, Inbred C57BL, Infarction, Middle Cerebral Artery pathology, Infarction, Middle Cerebral Artery metabolism, Cell Line, Tumor, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 complications, Nicotinamide Phosphoribosyltransferase metabolism, Forkhead Box Protein O3 metabolism, Glucose metabolism, Glucose deficiency, Neurons metabolism, Neurons pathology, Neurons drug effects, Cell Survival drug effects, Signal Transduction drug effects, Brain Ischemia metabolism, Brain Ischemia pathology
- Abstract
The incidence of cerebral infarction triggered by abnormal glucose tolerance has increased; however, the relationship between glucose concentration in the brain and the detailed mechanism of post ischemic cell death remains unclear. Nicotinamide phosphoribosyltransferase (NAMPT), an adipocytokine, is the rate-limiting enzyme for NAD
+ synthesis in the salvage pathway. Although NAMPT activation prevents neuronal injury, the relationship between NAMPT activity, glucose metabolism disorders, and cerebral ischemia-induced neuronal cell death is unknown. In this study, we determined changes in NAMPT on cerebral ischemic injuries with diabetes using a db/db mouse model of type 2 diabetes and then identified the underlying mechanisms using Neuro2a cells. The expression of inflammatory cytokine mRNAs was increased in db/db and db/+ middle cerebral artery occlusion and reperfusion (MCAO/R) mice. Although NeuN-positive cells were decreased after MCAO/R, the number of NAMPT and NeuN double-positive cells in NeuN-positive neuronal cells increased in db/db MCAO/R mice. Next, the role of NAMPT in Neuro2a cells under conditions of high glucose (HGC) and oxygen-glucose deprivation (OGD), which mimics diabetes-complicated cerebral infarction, was examined. Treatment with P7C3-A20, a NAMPT activator, suppressed the decrease in cell viability caused by HGC/OGD; however, there were no significant differences in the levels of cleaved caspase-3 and Bax proteins. Moreover, increased FoxO3a and LC3-II levels after HGC/OGD were inhibited by P7C3-A20 treatment. Our findings indicate that NAMPT activation is associated with neuronal survival under ischemic conditions with abnormal glucose tolerance through the regulation of FoxO3a/LC3., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)- Published
- 2024
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13. Chiral Honeycomb Lattices of Nonplanar π-Conjugated Supramolecules with Protected Dirac and Flat Bands.
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Nemoto R, Arafune R, Nakano S, Tsuchiizu M, Takagi N, Suizu R, Uchihashi T, and Awaga K
- Abstract
The honeycomb lattice is a fundamental two-dimensional (2D) network that gives rise to surprisingly rich electronic properties. While its expansion to 2D supramolecular assembly is conceptually appealing, its realization is not straightforward because of weak intermolecular coupling and the strong influence of a supporting substrate. Here, we show that the application of a triptycene derivative with phenazine moieties, Trip-Phz, solves this problem due to its strong intermolecular π-π pancake bonding and nonplanar geometry. Our scanning tunneling microscopy (STM) measurements demonstrate that Trip-Phz molecules self-assemble on a Ag(111) surface to form chiral and commensurate honeycomb lattices. Electronically, the network can be viewed as a hybrid of honeycomb and kagome lattices. The Dirac and flat bands predicted by a simple tight-binding model are reproduced by total density functional theory (DFT) calculations, highlighting the protection of the molecular bands from the Ag(111) substrate. The present work offers a rational route for creating chiral 2D supramolecules that can simultaneously accommodate pristine Dirac and flat bands.
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- 2024
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14. Rab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1.
- Author
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Fukatsu S, Sashi H, Shirai R, Takagi N, Oizumi H, Yamamoto M, Ohbuchi K, Miyamoto Y, and Yamauchi J
- Abstract
Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a. However, it remains to be established which Rab protein is related to promoting or sustaining neuronal morphogenesis or homeostasis. In this study, we describe that the knockdown of Rab11a decreases the expression levels of neuronal differentiation marker proteins, as well as the elongation of neurite-like processes, using N1E-115 cells, a well-utilized neuronal differentiation model. Similar results were obtained in primary cortical neurons. In contrast, the knockdown of Rab11b, a Rab11a homolog, did not significantly affect their cell morphological changes. It is of note that treatment with hesperetin, a citrus flavonoid (also known as Vitamin P), recovered the neuronal morphological phenotypes induced by Rab11a knockdown. Also, the knockdown of Rab11a or Rab11b led to a decrease in glial marker expression levels and in morphological changes in FBD-102b cells, which serve as the oligodendroglial differentiation model. Rab11a is specifically involved in the regulation of neuronal morphological differentiation. The knockdown effect mimicking the loss of function of C9orf72 is reversed by treatment with hesperetin. These findings may reveal a clue for identifying one of the potential molecular and cellular phenotypes underlying FTDALS1.
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- 2024
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15. Pathogenic role of NAMPT in the perivascular regions after ischemic stroke in mice with type 2 diabetes mellitus.
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Iwatani Y, Hayashi H, Yamamoto H, Minamikawa H, Ichikawa M, Orikawa H, Masuda A, Tada N, Moriyama Y, and Takagi N
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- Animals, Humans, Mice, Cytokines, Glucose metabolism, Infarction, Middle Cerebral Artery complications, Nicotinamide Phosphoribosyltransferase metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Ischemic Stroke, Stroke complications, Stroke pathology
- Abstract
Ischemic stroke in patients with abnormal glucose tolerance results in poor outcomes. Nicotinamide phosphoribosyltransferase (NAMPT), an adipocytokine, exerts neuroprotective effects. However, the pathophysiological role of NAMPT after ischemic stroke with diabetes and the relationship of NAMPT with cerebrovascular lesions are unclear. The purpose of this study was to clarify the pathophysiological role of NAMPT in cerebral ischemia with diabetes, using db/db mice as a type 2 diabetes animal model. The number of degenerating neurons increased after middle cerebral artery occlusion and reperfusion (MCAO/R) in db/db mice compared with the degenerating neurons in db/+ mice. Extracellular NAMPT (eNAMPT) levels, especially monomeric eNAMPT, increased significantly in db/db MCAO/R mice but not db/+ mice in isolated brain microvessels. The increased eNAMPT levels were associated with increased expression of inflammatory cytokine mRNA. Immunohistochemical analysis demonstrated that NAMPT colocalized with GFAP-positive cells after MCAO/R. In addition, both dimeric and monomeric eNAMPT levels increased in the conditioned medium of primary cortical astrocytes under high glucose conditions subsequent oxygen/glucose deprivation. Our findings are the first to demonstrate the ability of increased monomeric eNAMPT to induce inflammatory responses in brain microvessels, which may be located near astrocyte foot processes., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. No potential conflicts of interest relevant to this article were reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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16. Role of senkyunolide I in the promotion of neural stem/progenitor cell proliferation via the Akt/β-catenin pathway.
- Author
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Wang M, Hayashi H, Horinokita I, Asada M, Iwatani Y, Ren JG, Liu JX, and Takagi N
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- beta Catenin metabolism, Glycogen Synthase Kinase 3 beta metabolism, Cell Proliferation, Cell Differentiation, Proto-Oncogene Proteins c-akt metabolism, Neural Stem Cells metabolism
- Abstract
Following brain injury, neural stem cells (NSCs) can generate mature neurons and replace damaged cells. However, the capacity of endogenous NSCs to self-repair from injured brain is limited as most NSCs die before becoming mature neurons. Therefore, a boosting endogenous NSCs by pharmacological support offers the potential to repair the damaged brain. Recently, small molecules have hold considerable promise for neuron regeneration and repair as they can penetrate the blood-brain barrier easily. Senkyunolide I (SEI) is a bioactive constituent derived from traditional Chinese medicines Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, and was found to able to prevent ischemic stroke. This study examined the effects of SEI on the proliferation and neuronal lineage differentiation of prepared neural stem/progenitor cells (NS/PCs). The NS/PC proliferation was determined by 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt, and neurosphere formation assays. The NS/PC differentiation was also investigated by immunocytochemistry, and western blotting was employed to measure phosphorylated Akt (pAkt) and GSK-3β (pGSK-3β), and active-β-catenin protein levels. We showed that the NS/PC proliferation was enhanced after SEI exposure. Elevated cell numbers were also observed in neurospheres, which were incubated with SEI for 3 days, whereas the NS/PC differentiation was decreased after SEI exposure for 5 days. Furthermore, SEI upregulated pAkt/Akt and active-β-catenin levels and increased NS/PC proliferation after SEI treatment was reversed by phosphatidylinositol 3-kinase inhibitor LY294002. downregulated differentiated processes. Thus, SEI promoted the NS/PC proliferation and suppressed NS/PC differentiation into neurons and/or astrocytes, therefore SEI could be an interesting and promising candidate for stimulating NSCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2023
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17. Treatment outcomes of radiotherapy for malignant psoas syndrome: A single-center retrospective study.
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Wada Y, Kumagai S, Shinozaki T, Murata T, Okuyama E, Takagi N, and Mori N
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- Humans, Retrospective Studies, Prospective Studies, Radiotherapy Dosage, Treatment Outcome, Bone Neoplasms radiotherapy
- Abstract
Introduction: The efficacy of radiotherapy for symptomatic relief of malignant psoas syndrome (MPS) remains unknown because there are limited publications with high level evidence, including analyses with sufficient number of cases, clinical trials, and systematic reviews about radiotherapy for MPS. We aimed to investigate the characteristics of and symptom relief rates in patients treated with radiotherapy for MPS in palliative intent., Methods: In this single-center retrospective study, we analyzed data of 22 consecutive patients treated with radiotherapy for MPS at our institution in Japan between 2012 and 2022. We recorded patient characteristics, including primary site, invasion pattern, recognition of MPS by the attending physician, radiation regimen, biological effective dose with α/β = 10 Gy (BED
10 ), and adverse events. Since no objective evaluation index for palliative radiotherapy for non-bone metastases has been established, we modified and used an International Consensus on Palliative Radiotherapy Endpoint, which was originally used for bone metastases, to evaluate symptom relief in the present retrospective study. "Response" was defined as symptom relief described in medical records or the use of analgesic medications reduced by ≥25% within 3 months post-initiation of radiotherapy., Results: Genitourinary organs (41%) were the most common primary-tumor sites. MPS was caused by metastasis in the iliopsoas muscle in 14 patients (64%) and by direct invasion of the primary tumor in eight patients (36%). Since the optimal radiation dose for MPS has not been established, the radiation dose varied from low dose, which are used in palliative radiotherapy for painful bone metastases, to high dose with conventional fraction using 1.8 to 2 Gy per fraction, with a median BED10 of 48 Gy (range, 10.6-79.2 Gy). Fifteen patients (68%) achieved a response. No acute nor late adverse events of grade 2 or higher, according to Common Terminology Criteria for Adverse Events version 5.0, were reported during the observation period., Conclusion: Radiotherapy for symptomatic MPS might be an effective treatment option with a high response rate (68%) and minimal adverse events. Since the present study is a retrospective study with small number of cases, a prospective study with a larger sample size is required., (Copyright © 2023. Published by Elsevier Inc.)- Published
- 2023
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18. Usefulness of Alternative Therapy with Hydrocortisone in the Postoperative Management of Severe Primary Aldosteronism.
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Asakawa M, Takagi N, Hamada D, Yamasaki Y, Takaku Y, Kawada M, Murata T, and Katsuta H
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- Male, Humans, Middle Aged, Hydrocortisone therapeutic use, Adrenalectomy, Aldosterone, Hyperkalemia etiology, Hyperaldosteronism drug therapy, Hyperaldosteronism surgery, Hyperaldosteronism complications, Hypertension etiology, Kidney Diseases complications
- Abstract
Mineralocorticoid deficiency (MD) with hyperkalemia is an important complication of adrenalectomy in patients with primary aldosteronism (PA). We herein report a 52-year-old man with refractory hypertension, hypokalemia, and severe renal dysfunction due to PA caused by a right adrenal adenoma. His estimated glomerular filtration rate (eGFR) transiently increased immediately after adrenalectomy but then gradually declined, and he developed hyperkalemia. A postoperative endocrine examination revealed MD. Considering the patient's hypertension and severe renal dysfunction, we administered hydrocortisone instead of fludrocortisone, which improved the hyperkalemia and stopped the decline in the eGFR. Alternative therapy with hydrocortisone may be useful in such patients with MD.
- Published
- 2023
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19. In Regard to Kil et al.
- Author
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Wada Y, Shinozaki T, Murata T, Kumagai S, Takagi N, and Mori N
- Abstract
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2023
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20. Re.: "A Systematic Review of the Safety and Efficacy of Stenting of the Inferior Vena Cava".
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Takagi N, Wada Y, and Mori N
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- Humans, Systematic Reviews as Topic, Vena Cava, Inferior diagnostic imaging, Vena Cava, Inferior surgery
- Published
- 2023
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21. Origin of Silicate Spherules and Geochemistry of Re and Platinum-Group Elements Within Microfossil-Bearing Archean Chert from the 3.4 Ga Strelley Pool Formation, Western Australia.
- Author
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Sugitani K, Mimura K, Senda R, Kouketsu Y, Wallis S, Takagi N, Iizuka T, and Lowe DR
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- Western Australia, Silicates, Platinum, Geologic Sediments chemistry
- Abstract
Silicate spherules have been identified from the ca. 3.4 Ga-old Strelley Pool Formation (SPF) in the Pilbara Craton, Western Australia. Their origins and geochemical characteristics, including the Re and platinum-group elements of their host clastic layer and the overlying and underlying microfossil-bearing finely laminated carbonaceous cherts, were examined. The spherules have various morphologies (completely spherical to angular), sizes (∼20 to >500 μm), textures (layered, non-layered, and fibrous), mineralogy (various proportions of microcrystalline quartz, sericite, anatase and Fe-oxides), and chemistry (enriched in Ni and/or Cr), commonly with thin anatase-rich walls. Their host clastic layer is characterized by rip-up clasts, suggesting a suddenly occurring high-energy depositional environment, such as tsunamis. Although various origins other than asteroid impact were considered, none could unequivocally explain the features of the spherules. In contrast, non-layered spherical spherules that occur as individual framework grains or collectively comprise angular-shaped rock fragments appear to be more consistent with the asteroid impact origin. The calculated Re-Os age of the cherts (3331 ± 220 Ma) was consistent with the established age of the SPF (3426-3350 Ma), suggesting that the Re-Os system was not significantly disturbed by later metamorphic and weathering events.
- Published
- 2023
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22. Decoding cellular deformation from pseudo-simultaneously observed Rho GTPase activities.
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Kunida K, Takagi N, Aoki K, Ikeda K, Nakamura T, and Sakumura Y
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- rhoA GTP-Binding Protein metabolism, cdc42 GTP-Binding Protein metabolism, Cell Movement, rho GTP-Binding Proteins metabolism, rac1 GTP-Binding Protein metabolism
- Abstract
Limitations in simultaneously observing the activity of multiple molecules in live cells prevent researchers from elucidating how these molecules coordinate the dynamic regulation of cellular functions. Here, we propose the motion-triggered average (MTA) algorithm to characterize pseudo-simultaneous dynamic changes in arbitrary cellular deformation and molecular activities. Using MTA, we successfully extract a pseudo-simultaneous time series from individually observed activities of three Rho GTPases: Cdc42, Rac1, and RhoA. To verify that this time series encoded information on cell-edge movement, we use a mathematical regression model to predict the edge velocity from the activities of the three molecules. The model accurately predicts the unknown edge velocity, providing numerical evidence that these Rho GTPases regulate edge movement. Data preprocessing using MTA combined with mathematical regression provides an effective strategy for reusing numerous individual observations of molecular activities., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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23. Crystallization with Nodular Aggregation near the Glass Transition Temperature for Syndiotactic Polypropylene.
- Author
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Konishi T, Taguchi K, Fukao K, Takagi N, and Miyamoto Y
- Abstract
The isothermal crystallization from the melt state of syndiotactic polypropylene (sPP) has been studied by wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS), and optical microscopy. The WAXD and SAXS results show the crystallization mechanism near the glass transition temperature in which the crystalline and mesomorphic nodules cover the entire sample with the formation of aggregation regions. For the SAXS analysis, the scattering function for the three-component system has been suggested. Furthermore, to analyze the growth kinetics of the aggregation region for sPP, the time-dependent structure factor combined with the homogeneous and inhomogeneous nucleation-and-growth kinetics has been suggested. The analysis shows that the growth kinetics of the aggregation region for sPP is the homogeneous nucleation-and-growth. The growth velocity of the aggregation region is a natural extrapolation of that of spherulite to the high supercooling region. These results might indicate that the crystallization with the nodular aggregation is a fundamental crystallization process near the glass transition temperature for polymers.
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- 2023
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24. Efficacy of 3 months of additional pioglitazone treatment in type 2 diabetes patients with alcoholic fatty liver disease.
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Asakawa M, Takagi N, Hamada D, Yamasaki Y, and Katsuta H
- Abstract
Pioglitazone ameliorates liver dysfunction in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD); however, its efficacy in T2D patients with alcoholic fatty liver disease (AFLD) is unclear. Here, we conducted a retrospective single-center trial investigating whether pioglitazone ameliorates liver dysfunction in T2D patients with AFLD. T2D patients ( n = 100) receiving 3 months of additional pioglitazone were divided into those with or without fatty liver (FL), and those with FL were further classified into AFLD ( n = 21) and NAFLD ( n = 57) groups. The effects of pioglitazone were compared across groups using medical record data on body weight changes; HbA1c, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (γ-GTP) levels; and fibrosis-4 (FIB-4) index. The pioglitazone dose (mean dose: 10.6 ± 4.6 mg/day) did not affect weight gain but significantly decreased the HbA1c level in patients with or without FL ( P < 0.01 and P < 0.05, respectively). The decrease in HbA1c level was significantly more pronounced in patients with FL than in those without FL ( P < 0.05). In patients with FL, the HbA1c, AST, ALT, and γ-GTP levels significantly decreased after pioglitazone treatment than before ( P < 0.01). The AST and ALT levels, but not the γ-GTP level, and the FIB-4 index significantly decreased after pioglitazone addition in the AFLD group, similar to that in the NAFLD group ( P < 0.05 and P < 0.01, respectively). Similar effects were observed following low-dose pioglitazone treatment (≤ 7.5 mg/day) ( P < 0.05) in T2D patients with AFLD and NAFLD. These results suggest that pioglitazone may be also an effective treatment option for T2D patients with AFLD., Competing Interests: Conflict of interestThe authors have no funding and conflicts of interest to disclose., (© The Japan Diabetes Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
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- 2023
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25. Cytotoxic Effects of Darinaparsin, a Novel Organic Arsenical, against Human Leukemia Cells.
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Yuan B, Kikuchi H, Li J, Kawabata A, Yao K, Takagi N, and Okazaki M
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- Humans, Tumor Suppressor Protein p53, Apoptosis, Cell Line, Tumor, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Arsenicals pharmacology, Leukemia drug therapy
- Abstract
To explore the molecular mechanisms of action underlying the antileukemia activities of darinaparsin, an organic arsenical approved for the treatment of peripheral T-cell lymphoma in Japan, cytotoxicity of darinaparsin was evaluated in leukemia cell lines NB4, U-937, MOLT-4 and HL-60. Darinaparsin was a more potent cytotoxic than sodium arsenite, and induced apoptosis/necrosis in NB4 and HL-60 cells. In NB4 cells exhibiting the highest susceptibility to darinaparsin, apoptosis induction was accompanied by the activation of caspase-8/-9/-3, a substantial decrease in Bid expression, and was suppressed by Boc-D-FMK, a pancaspase inhibitor, suggesting that darinaparsin triggered a convergence of the extrinsic and intrinsic pathways of apoptosis via Bid truncation. A dramatic increase in the expression level of γH2AX, a DNA damage marker, occurred in parallel with G
2 /M arrest. Activation of p53 and the inhibition of cdc25C/cyclin B1/cdc2 were concomitantly observed in treated cells. Downregulation of c-Myc, along with inactivation of E2F1 associated with the activation of Rb, was observed, suggesting the critical roles of p53 and c-Myc in darinaparsin-mediated G2 /M arrest. Trolox, an antioxidative reagent, suppressed the apoptosis induction but failed to correct G2 /M arrest, suggesting that oxidative stress primarily contributed to apoptosis induction. Suppression of Notch1 signaling was also confirmed. Our findings provide novel insights into molecular mechanisms underlying the cytotoxicity of darinaparsin and strong rationale for its new clinical application for patients with different types of cancer.- Published
- 2023
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26. Nutritional Management in a 101-Year-Old Woman with Physical Inactivity and General Weakness: A Case Report.
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Mineyama R, Tezuka F, Takagi N, Kokabu S, and Okubo M
- Abstract
Japan has the world's highest life longevity, and centenarian patients are no longer rare. However, sufficient information related to centenarians is not available. Herein, we report the case of a 101-year-old centenarian woman who recovered from extreme inactivity and general weakness, mainly through nutritional management at home, to understand instances of nutritional management in centenarians. The patient developed lethargy, with a rapid decline in activity levels and food intake. She was diagnosed with senility by a primary doctor. We concluded that she had no problems with feeding and swallowing and predicted that her motivation to eat had decreased. We planned an intervention that lasted three months. To reduce the risk of aspiration, we paid attention to her posture while eating. To stimulate her appetite, we increased the variety and color of food items. To consider both the texture of food and safety, we changed the form of foods from paste (IDDSI Level 4)-like to solid food of regular size as much as possible. We recommended that the patient consume her favorite sweet between meals to enjoy eating. Two and half months after the initial intervention, the patient's inactivity and general weakness improved dramatically, which was recognized by her willingness to eat, laugh loudly, and hum, although she could not speak clearly. The patient finally was able to have dinner with her family.
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- 2023
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27. Development of an expression-tunable multiple protein synthesis system in cell-free reactions using T7-promoter-variant series.
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Senda N, Enomoto T, Kihara K, Yamashiro N, Takagi N, Kiga D, and Nishida H
- Abstract
New materials with a low environmental load are expected to be generated through synthetic biology. To widely utilize this technology, it is important to create cells with designed biological functions and to control the expression of multiple enzymes. In this study, we constructed a cell-free evaluation system for multiple protein expression, in which synthesis is controlled by T7 promoter variants. The expression of a single protein using the T7 promoter variants showed the expected variety in expression levels, as previously reported. We then examined the expression levels of multiple proteins that are simultaneously produced in a single well to determine whether they can be predicted from the promoter activity values, which were defined from the isolated protein expression levels. When the sum of messenger ribonucleic acid (mRNA) species is small, the experimental protein expression levels can be predicted from the promoter activities (graphical abstract (a)) due to low competition for ribosomes. In other words, by using combinations of T7 promoter variants, we successfully developed a cell-free multiple protein synthesis system with tunable expression. In the presence of large amounts of mRNA, competition for ribosomes becomes an issue (graphical abstract (b)). Accordingly, the translation level of each protein cannot be directly predicted from the promoter activities and is biased by the strength of the ribosome binding site (RBS); a weaker RBS is more affected by competition. Our study provides information regarding the regulated expression of multiple enzymes in synthetic biology., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2022
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28. Anomalous dewetting growth of Si on Ag(111).
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Kawakami N, Arafune R, Minamitani E, Kawahara K, Takagi N, and Lin CL
- Abstract
We demonstrate the novel growth of silicene grown on Ag(111) using STM and reveal the mechanism with KMC simulation. Our STM study shows that after the complete formation of the first layer of silicene, it is transformed into bulk Si with the reappearance of the bare Ag surface. This dewetting (DW) during the epitaxial growth is an exception in the conventional growth behavior. Our KMC simulation reproduces DW by taking into account the differences in the activation energies of Si atoms on Ag, silicene, and bulk Si. The growth modes change depending on the activation energy of the diffusion, temperature, and deposition rate, highlighting the importance of kinetics in growing metastable 2D materials.
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- 2022
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29. Tip-Mediated Bandgap Tuning for Monolayer Transition Metal Dichalcogenides.
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Lin MK, Chen GH, Ho CL, Chueh WC, Hlevyack JA, Kuo CN, Fu TY, Lin JJ, Lue CS, Chang WH, Takagi N, Arafune R, Chiang TC, and Lin CL
- Abstract
Monolayer transition metal dichalcogenides offer an appropriate platform for developing advanced electronics beyond graphene. Similar to two-dimensional molecular frameworks, the electronic properties of such monolayers can be sensitive to perturbations from the surroundings; the implied tunability of electronic structure is of great interest. Using scanning tunneling microscopy/spectroscopy, we demonstrated a bandgap engineering technique in two monolayer materials, MoS
2 and PtTe2 , with the tunneling current as a control parameter. The bandgap of monolayer MoS2 decreases logarithmically by the increasing tunneling current, indicating an electric-field-induced gap renormalization effect. Monolayer PtTe2 , by contrast, exhibits a much stronger gap reduction, and a reversible semiconductor-to-metal transition occurs at a moderate tunneling current. This unusual switching behavior of monolayer PtTe2 , not seen in bulk semimetallic PtTe2 , can be attributed to its surface electronic structure that can readily couple to the tunneling tip, as demonstrated by theoretical calculations.- Published
- 2022
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30. Effect of Progranulin on Proliferation and Differentiation of Neural Stem/Progenitor Cells after Oxygen/Glucose Deprivation.
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Horinokita I, Hayashi H, Nagatomo T, Fushiki Y, Iwatani Y, and Takagi N
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- Animals, Astrocytes drug effects, Astrocytes metabolism, Brain Ischemia drug therapy, Brain Ischemia metabolism, Glycogen Synthase Kinase 3 beta metabolism, Male, Neural Stem Cells metabolism, Neurons drug effects, Neurons metabolism, Phosphorylation drug effects, Rats, Rats, Wistar, Cell Differentiation drug effects, Cell Proliferation drug effects, Glucose metabolism, Neural Stem Cells drug effects, Oxygen metabolism, Progranulins pharmacology
- Abstract
We previously demonstrated that sivelestat, a selective neutrophil elastase inhibitor, attenuates the cleavage of progranulin (PGRN) and ischemia-induced cell injury in the brain. To obtain further insight into the role of PGRN, in the present study we evaluated the direct effects of sivelestat and recombinant PGRN (rPGRN) on the proliferation and differentiation of neural stem cells in cultures of neural stem/progenitor cells (NS/PC) under the ischemic condition in vitro. We demonstrated that oxygen/glucose deprivation (OGD)-induced cell proliferation of NS/PC was increased by rPGRN treatment. In addition, this increase was accompanied by increased phosphorylation of Akt and GSK-3β (Ser9) after OGD. But none of these responses occurred by treatment with sivelestat. Therefore, activation of the Akt/GSK-3β pathway could well be involved in this proliferative effect of rPGRN. Although OGD and reoxygenation-induced changes in the differentiation of NS/PC into neurons or astrocytes was not affected by treatment with rPGRN or sivelestat, it is noteworthy that rPGRN enhanced neurite outgrowth of β3-tubulin-positive neurons that had differentiated from the NS/PC. These findings suggest that enhancement of proliferation of endogenous NS/PC and neurite outgrowth of differentiated neurons from NS/PC by PGRN could be useful for a new therapeutic approach for cerebral ischemia.
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- 2022
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31. Characterization, pharmacokinetics, and pharmacodynamics of anti-Siglec-15 antibody and its potency for treating osteoporosis and as follow-up treatment after parathyroid hormone use.
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Tsuda E, Fukuda C, Okada A, Karibe T, Hiruma Y, Takagi N, Isumi Y, Yamamoto T, Hasegawa T, Uehara S, Koide M, Udagawa N, Amizuka N, and Kumakura S
- Subjects
- Alendronate pharmacology, Animals, Bone Density, Female, Follow-Up Studies, Humans, Immunoglobulins pharmacology, Membrane Proteins, Mice, Ovariectomy, Parathyroid Hormone pharmacology, Parathyroid Hormone therapeutic use, Rats, Sialic Acid Binding Immunoglobulin-like Lectins pharmacology, Bone Resorption drug therapy, Osteoporosis drug therapy
- Abstract
Recent studies have established the idea that Siglec-15 is involved in osteoclast differentiation and/or function, and it is anticipated that therapies suppressing Siglec-15 function can be used to treat bone diseases such as osteoporosis. We have produced rat monoclonal anti-Siglec-15 antibody (32A1) and successively generated humanized monoclonal anti-Siglec-15 antibody (DS-1501a) from 32A1. Studies on the biological properties of DS-1501a showed its specific binding affinity to Siglec-15 and strong activity to inhibit osteoclastogenesis. 32A1 inhibited multinucleation of osteoclasts and bone resorption (pit formation) in cultured mouse bone marrow cells. 32A1 also inhibited pit formation in cultured human osteoclast precursor cells. Maximum serum concentration and serum exposure of DS-1501a in rats were increased in a dose-dependent manner after single subcutaneous or intravenous administration. Furthermore, single administration of DS-1501a significantly suppressed bone resorption markers with minimal effects on bone formation markers and suppressed the decrease in bone mineral density (BMD) of the lumbar vertebrae in ovariectomized (OVX) rats. In histological analysis, the osteoclasts distant from the chondro-osseous junction of the tibia tended to be flattened, shrunken, and functionally impaired in 32A1-treated rats, while alkaline phosphatase-positive osteoblasts were observed throughout the metaphyseal trabeculae. In addition, we compared the efficacy of 32A1 with that of alendronate (ALN) as follow-up medicine after treatment with parathyroid hormone (PTH) using mature established osteoporosis rats. The beneficial effect of PTH on bone turnover disappeared 8 weeks after discontinuing the treatment. The administration of 32A1 once every 4 weeks for 8 weeks suppressed bone resorption and bone formation when the treatment was switched from PTH to 32A1, leading to the maintenance of BMD and bone strength. Unlike with ALN, the onset of suppression of bone resorption with 32A1 was rapid, while the suppression of bone formation was mild. The improvement of bone mass, beneficial bone turnover balance, and suppression of osteoclast differentiation/multinucleation achieved by 32A1 were supported by histomorphometry. Notably, the effects of 32A1 on bone strength, not only structural (extrinsic) but also material (intrinsic) properties, were significantly greater than those of ALN. Since the effect of 32A1 on BMD was moderate, its effect on bone strength could not be fully explained by the increase in BMD. The beneficial balance of bone turnover caused by 32A1 might, at least in part, be responsible for the improvement in bone quality. This is the first report describing the effects of anti-Siglec-15 antibody in OVX rats; the findings suggest that this antibody could be an excellent candidate for treating osteoporosis, especially in continuation therapy after PTH treatment, due to its rapid action and unprecedented beneficial effects on bone quality., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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32. Possible Involvement of DNA Methylation and Protective Effect of Zebularine on Neuronal Cell Death after Glutamate Excitotoxity.
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Asada M, Hayashi H, and Takagi N
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- Cell Death, Cytidine analogs & derivatives, DNA Methylation, Humans, RNA, Small Interfering genetics, Receptors, N-Methyl-D-Aspartate metabolism, Brain Ischemia, Glutamic Acid metabolism, Glutamic Acid toxicity
- Abstract
Neuronal cell death after cerebral ischemia consists various steps including glutamate excitotoxity. Excessive Ca
2+ influx through the N-methyl-D-aspartate (NMDA) receptor, which is one of the ionotropic glutamate receptors, plays a central role in neuronal cell death after cerebral ischemia. We previously reported that DNA methylation is transiently increased in neurons during ischemic injury and that this aberrant DNA methylation is accompanied by neuronal cell death. Therefore, we performed the present experiments on glutamate excitotoxicity to gain further insight into DNA methylation involvement in the neuronal cell death. We demonstrated that knockdown of DNA methyltransferase (DNMT)1, DNMT3a, or DNMT3b gene in Neuro2a cells was performed to examine which DNMTs were more important for neuronal cell death after glutamate excitotoxicity. Although we confirmed a decrease in the levels of the target DNMT protein after small interfering RNA (siRNA) transfection, the Neuro2a cells were not protected from injury by transfection with siRNA for each DNMT. We next revealed that the pharmacological inhibitor of DNMTs protected against glutamate excitotoxicity in Neuro2a cells and also in primary cultured cortical neurons. This protective effect was associated with a decrease in the number of 5-methylcytosine (5 mC)-positive cells under glutamate excitotoxicity. In addition, the increased level of cleaved caspase-3 was also reduced by a DNMT inhibitor. Our results suggest the possibility that at least 2 or all DNMTs functionally would cooperate to activate DNA methylation after glutamate excitotoxicity and that inhibition of DNA methylation in neurons after cerebral ischemia might become a strategy to reduce the neuronal injury.- Published
- 2022
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33. Interferon-γ downregulates tight junction function, which is rescued by interleukin-17A.
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Mizutani Y, Takagi N, Nagata H, and Inoue S
- Subjects
- Claudin-1 metabolism, Down-Regulation, Humans, Cytokines metabolism, Dermatitis, Atopic physiopathology, Interferon-gamma metabolism, Interleukin-17 metabolism, Tight Junctions metabolism
- Abstract
Although atopic dermatitis (AD) has been reported to be a typical type 2 immune response disease, it is also an inflammatory skin disease that involves cytokines, such as Th1, Th17 and Th22. However, little is known about the mechanism by which the candidate cytokines, alone or in combination, are involved in AD pathology. Differences in cytokine balance, which contribute to the complexity of AD pathology, may influence the stratum corneum barrier function through tight junction (TJ) functional stability and contribute to disease severity. To confirm the regulatory mechanism of TJ protein expression in AD, we investigated the Th1 and Th17 pathways, which are the initiation factors of chronic AD pathology. We examined the effects of these cytokines on TJ protein expression in normal human epidermal keratinocytes in vitro, and also examined their function in a human skin equivalent model. We observed a time- and dose-dependent inhibitory effect of IFN-γ on claudin-1 expression via the IFN-γ receptor/JAK/STAT signalling pathway. IFN-γ impaired TJ function in a human skin equivalent model. Moreover, we investigated co-stimulation with IL-17A, which is highly expressed in AD skin lesions and found that IL-17A restores IFN-γ-induced TJ dysfunction. This restoration of TJ function was mediated by atypical protein kinase C zeta activation without recovery of TJ protein expression. These results are informative for personalized AD treatment via systemic therapies using anti-cytokine antibodies and/or JAK inhibitors., (© 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)
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- 2021
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34. Topical Administration of Heat-Killed Enterococcus faecalis Strain KH2 Promotes Re-Epithelialization and Granulation Tissue Formation during Skin Wound-Healing.
- Author
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Tanno H, Kanno E, Kurosaka S, Oikawa Y, Watanabe T, Sato K, Kasamatsu J, Miyasaka T, Ishi S, Shoji M, Takagi N, Imai Y, Ishii K, Tachi M, and Kawakami K
- Abstract
Lactic acid bacteria (LAB) are known to have beneficial effects on immune responses when they are orally administered as bacterial products. Although the beneficial effects of LAB have been reported for the genera Lactobacillus and Lactococcus , little has been uncovered on the effects of the genus Enterococcus on skin wound-healing. In this study, we aimed to clarify the effect of heat-killed Enterococcus faecalis KH2 (heat-killed KH2) strain on the wound-healing process and to evaluate the therapeutic potential in chronic skin wounds. We analyzed percent wound closure, re-epithelialization, and granulation area, and cytokine and growth factor production. We found that heat-killed KH2 contributed to the acceleration of re-epithelialization and the formation of granulation tissue by inducing tumor necrosis factor-α, interleukin-6, basic fibroblast growth factor, transforming growth factor (TGF)-β1, and vascular endothelial growth factor production. In addition, heat-killed KH2 also improved wound closure, which was accompanied by the increased production of TGF-β1 in diabetic mice. Topical administration of heat-killed KH2 might have therapeutic potential for the treatment of chronic skin wounds in diabetes mellitus. In the present study, we concluded that heat-killed KH2 promoted skin wound-healing through the formation of granulation tissues and the production of inflammatory cytokines and growth factors.
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- 2021
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35. Corrigendum: Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines.
- Author
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Yuan B, Xu K, Shimada R, Li J, Hayashi H, Okazaki M, and Takagi N
- Abstract
[This corrects the article DOI: 10.3389/fonc.2021.628914.]., (Copyright © 2021 Yuan, Xu, Shimada, Li, Hayashi, Okazaki and Takagi.)
- Published
- 2021
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36. Apolipoprotein E-Containing Lipoproteins and LRP1 Protect From NMDA-Induced Excitotoxicity Associated With Reducing α2-Macroglobulin in Müller Glia.
- Author
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Hayashi H, Mori M, Harashima M, Hashizume T, Furiya M, Mukaigaito C, Takemura E, Yamada M, Mise K, Yuan B, and Takagi N
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Ependymoglial Cells drug effects, Ependymoglial Cells pathology, Female, Male, Mice, Mice, Inbred C57BL, N-Methylaspartate toxicity, Neuroprotective Agents pharmacology, Pregnancy-Associated alpha 2-Macroglobulins biosynthesis, RNA genetics, Rats, Rats, Sprague-Dawley, Retinal Degeneration drug therapy, Retinal Degeneration metabolism, Retinal Ganglion Cells drug effects, Retinal Ganglion Cells metabolism, Apolipoproteins E metabolism, Ependymoglial Cells metabolism, Gene Expression Regulation, Low Density Lipoprotein Receptor-Related Protein-1 metabolism, Pregnancy-Associated alpha 2-Macroglobulins genetics, Retinal Degeneration genetics, Retinal Ganglion Cells pathology
- Abstract
Purpose: Optic nerve damage leads to impairment of visual functions. We previously demonstrated that apolipoprotein E-containing lipoproteins (E-LPs) protect retinal ganglion cells (RGCs) from degeneration in a glaucoma model of glutamate/aspartate transporter-deficient mice. This study aimed to determine whether E-LPs protect RGCs from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, and to investigate the details of an indirect neuroprotective mechanism of E-LPs by reducing α2-macroglobulin, which interferes with the neuroprotective effect of E-LPs, in Müller glia., Methods: Excitotoxicity was caused by intravitreal injection of NMDA, and then retinae were subjected to immunoblotting or quantitative reverse transcription-PCR. Primary cultures of mouse mixed retinal cells and mouse Müller glia were used for evaluating the effects of E-LPs on the expression of α2-macroglobulin., Results: Intravitreal injection of E-LPs protected the optic nerve from degeneration and attenuated the increase in α2-macroglobulin in aqueous humor and retina of rats. E-LPs directly decreased the expression and secretion of α2-macroglobulin in primary cultures of Müller glia; this decrease in production of α2-macroglobulin was blocked by knockdown of the low-density lipoprotein receptor-related protein 1 (LRP1) with small interfering RNA. E-LPs promoted the phosphorylation of STAT3, whereas Stattic, an inhibitor of STAT3, restored the expression of α2-macroglobulin decreased by E-LPs., Conclusions: In addition to our previous findings of the protection of RGCs by E-LPs, the new observations in Müller glia indicate that a reduction of the intraocular α2-macroglobulin, regulated by the E-LP-LRP1-STAT3 pathway, might be an additional protective mechanism against excitotoxicity in the retina.
- Published
- 2021
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37. Renadirsen, a Novel 2'OMeRNA/ENA ® Chimera Antisense Oligonucleotide, Induces Robust Exon 45 Skipping for Dystrophin In Vivo.
- Author
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Ito K, Takakusa H, Kakuta M, Kanda A, Takagi N, Nagase H, Watanabe N, Asano D, Goda R, Masuda T, Nakamura A, Onishi Y, Onoda T, Koizumi M, Takeshima Y, Matsuo M, and Takaishi K
- Subjects
- Animals, Chromatography, Liquid, Male, Mice, Mice, Inbred mdx, Molecular Structure, Muscle, Skeletal metabolism, Myocardium metabolism, Oligodeoxyribonucleotides chemistry, Oligonucleotides, Antisense administration & dosage, Oligonucleotides, Antisense chemical synthesis, Oligonucleotides, Antisense chemistry, Oligoribonucleotides chemistry, Tandem Mass Spectrometry, Tissue Distribution, Alternative Splicing, Dystrophin genetics, Oligonucleotides, Antisense genetics
- Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by out-of-frame or nonsense mutation in the dystrophin gene. It begins with a loss of ambulation between 9 and 14 years of age, followed by various other symptoms including cardiac dysfunction. Exon skipping of patients' DMD pre-mRNA induced by antisense oligonucleotides (AOs) is expected to produce shorter but partly functional dystrophin proteins, such as those possessed by patients with the less severe Becker muscular dystrophy. We are working on developing modified nucleotides, such as 2'- O ,4'- C -ethylene-bridged nucleic acids (ENAs), possessing high nuclease resistance and high affinity for complementary RNA strands. Here, we demonstrate the preclinical characteristics (exon-skipping activity in vivo, stability in blood, pharmacokinetics, and tissue distribution) of renadirsen, a novel AO modified with 2'- O -methyl RNA/ENA chimera phosphorothioate designed for dystrophin exon 45 skipping and currently under clinical trials. Notably, systemic delivery of renadirsen sodium promoted dystrophin exon skipping in cardiac muscle, skeletal muscle, and diaphragm, compared with AOs with the same sequence as renadirsen but conventionally modified by PMO and 2'OMePS. These findings suggest the promise of renadirsen sodium as a therapeutic agent that improves not only skeletal muscle symptoms but also other symptoms in DMD patients, such as cardiac dysfunction.
- Published
- 2021
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38. Nicotine affects tight junction barriers via alpha7 nicotine-like acetylcholine receptor in keratinocytes.
- Author
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Nagata H, Takagi N, Inoue S, and Mizutani Y
- Subjects
- Benzamides pharmacology, Bridged Bicyclo Compounds pharmacology, Cell Culture Techniques, Three Dimensional, Cell Line, Cell Survival, Down-Regulation drug effects, Humans, Keratinocytes cytology, Signal Transduction drug effects, Tight Junctions drug effects, Tight Junctions metabolism, Zonula Occludens-1 Protein analysis, Zonula Occludens-1 Protein metabolism, alpha7 Nicotinic Acetylcholine Receptor agonists, Keratinocytes pathology, Nicotine adverse effects, Smoking adverse effects, Tight Junctions pathology, alpha7 Nicotinic Acetylcholine Receptor metabolism
- Abstract
Competing Interests: Declaration of Competing Interest Department of Cosmetic Health Science of Gifu Pharmaceutical University is financially supported by a grant from Gifu City Hall, which, in turn, is financially supported by donations from Ichimaru Pharcos Co. Ltd., Gifu, Japan. The authors have no conflict of interest to declare.
- Published
- 2021
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39. Cytotoxic Effects of Hellebrigenin and Arenobufagin Against Human Breast Cancer Cells.
- Author
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Zhang Y, Yuan B, Bian B, Zhao H, Kiyomi A, Hayashi H, Iwatani Y, Sugiura M, and Takagi N
- Abstract
Development of new therapeutic strategies for breast cancer is urgently needed due to the sustained emergence of drug resistance, tumor recurrence and metastasis. To gain a novel insight into therapeutic approaches to fight against breast cancer, the cytocidal effects of hellebrigenin (Helle) and arenobufagin (Areno) were investigated in human estrogen receptor (ER)-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. Helle exhibited more potent cytotoxicity than Areno in both cancer cells, and MCF-7 cells were more susceptible to both drugs in comparison with MDA-MB-231 cells. Apoptotic-like morphological characteristics, along with the downregulation of the expression level of Bcl-2 and Bcl-xL and the upregulation of the expression level of Bad, were observed in Helle-treated MCF-7 cells. Helle also caused the activation of caspase-8, caspase-9, along with the cleavage of poly(ADP-ribose) polymerase in MCF-7 cells. Helle-mediated necrosis-like phenotype, as evidenced by the increased propidium iodide (PI)-positive cells was further observed. G
2 /M cell cycle arrest was also induced by Helle in the cells. Upregulation of the expression level of p21 and downregulation of the expression level of cyclin D1, cyclin E1, cdc25C and survivin were observed in MCF-7 cells treated with Helle and occurred in parallel with G2 /M arrest. Autophagy was triggered in MCF-7 cells and the addition of wortmannin or 3-MA, two well-known autophagy inhibitors, slightly but significantly rescued the cells. Furthermore, similar alterations of some key molecules associated with the aforementioned biological phenomena were observed in MDA-MB-231 cells. Intriguingly, the numbers of PI-positive cells in Helle-treated MCF-7 cells were significantly reduced by wortmannin and 3-MA, respectively. In addition, Helle-triggered G2 /M arrest was significantly corrected by wortmannin, suggesting autophagy induction contributed to Helle-induced cytotoxicity of breast cancer cells by modulating necrosis and cell cycle arrest. Collectively, our results suggested potential usefulness of both Helle and Areno in developing therapeutic strategies to treat patients with different types of breast cancer, especially ER-positive breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Yuan, Bian, Zhao, Kiyomi, Hayashi, Iwatani, Sugiura and Takagi.)- Published
- 2021
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40. Neuroprotective effects of Senkyunolide I against glutamate-induced cells death by attenuating JNK/caspase-3 activation and apoptosis.
- Author
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Wang M, Hayashi H, Horinokita I, Asada M, Iwatani Y, Liu JX, and Takagi N
- Subjects
- Animals, Brain Ischemia drug therapy, Brain Ischemia metabolism, Cell Survival drug effects, Cells, Cultured, Mice, Neuroblastoma drug therapy, Neuroblastoma metabolism, Neuroprotection drug effects, Reperfusion Injury drug therapy, Reperfusion Injury metabolism, Signal Transduction drug effects, Apoptosis drug effects, Benzofurans pharmacology, Caspase 3 metabolism, Cell Death drug effects, Glutamic Acid metabolism, MAP Kinase Signaling System drug effects, Neuroprotective Agents pharmacology
- Abstract
Glutamate-induced neurotoxicity is one of the most important pathogenic mechanisms in neurological diseases and is widely used as an in vitro model for ischemic stroke. Senkyunolide I (SEI), an active constituent derived from traditional Chinese medicine Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, has been shown to have beneficial effects against focal cerebral ischemia-reperfusion in rats. However, the mechanisms underlying SEI-mediated neuroprotection remain not well understood. Thus, we explored the influence of SEI in glutamate-mediated injury to mouse neuroblastoma (Neuro2a) cells and determined the mechanisms involved. Neuro2a cells were treated with SEI under exposure to glutamate for 24 h. Cell viability was assessed by using WST-1 reagents, and apoptosis was evaluated using Annexin V-FITC and a PI double staining kit. The protein expression levels of p-AKT, AKT, p-GSK3β, GSK3β, p-p38, p38, p-ERK, ERK, p-JNK, JNK, Bcl-2, Bax, Bcl-xl, p-Bad, Bad, p53, and cleaved caspase-3 were determined by Western blot analysis. Glutamate significantly decreased cell viability and elevated the level of apoptosis. Treatment with SEI reversed those effects. Furthermore, the expression of p-JNK/JNK and cleaved caspase-3 were also reduced after treatment with SEI. Our findings demonstrate that SEI protected Neuro2a cells against glutamate toxicity by regulating JNK/caspase-3 pathway and apoptosis. Thus, SEI maybe a promising candidate for neuroprotection., (Copyright © 2021. Published by Elsevier Masson SAS.)
- Published
- 2021
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41. Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice.
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Uchida A, Yasuma T, Takeshita A, Toda M, Okano Y, Nishihama K, D'Alessandro-Gabazza CN, Fridman D'Alessandro V, Inoue C, Takagi T, Mukaiyama H, Takagi N, Shimizu K, Yano Y, and Gabazza EC
- Abstract
Introduction: Diabetes mellitus is a serious threat to public health worldwide. It causes a substantial economic burden, mental and physical disabilities, poor quality of life, and high mortality. Limonite is formed when iron-rich materials from the underground emerge and oxidized on the ground surface. It is currently used to purify contaminated water, absorption of irritant gases, and improve livestock breeding. Limonite can change the composition of environmental microbial communities. In the present study, we evaluated whether limonite can ameliorate glucose metabolism abnormalities by remodeling the gut microbiome., Methods: The investigation was performed using mouse models of streptozotocin-induced diabetes mellitus and high-calorie diet-induced metabolic syndrome., Results: Oral limonite supplement was associated with significant body weight recovery, reduced glycemia with improved insulin secretion, increased number of regulatory T cells, and abundant beneficial gut microbial populations in mice with diabetes mellitus compared to control. Similarly, mice with obesity fed with limonite supplements had significantly reduced body weight, insulin resistance, steatohepatitis, and systemic inflammatory response with significant gut microbiome remodeling., Conclusion: This study demonstrates that limonite supplement ameliorates abnormal glucose metabolism in diabetes mellitus and obesity. Gut microbiome remodeling, inhibition of inflammatory cytokines, and the host immune response regulation may explain the limonite's beneficial activity under pathological conditions in vivo., Competing Interests: Hiroyuki Mukaiyama, Norio Takagi, Katsumi Shimizu are employees of Tanisake Corporation, which is the company that funded in part the present study. Takehiro Takagi is a relative of one of the employees of Tanisake Corporation. Hiroyuki Mukaiyama, Esteban C Gabazza, Nario Takagi, and Katsumi Shimizu have a patent JP2020-075683 pending to Tanisake co., Ltd. Esteban C Gabazza was the recipient of a grant from Tanisake Corporation to support the present investigation. Esteban C Gabazza received a grant from the Japan Society for the Promotion of Science to support this study in part. Taro Yasuma reports grants from the Japan Society for the Promotion of Science, outside the submitted work. The other authors declared no conflicts of interest regarding data reported in this work., (© 2021 Uchida et al.)
- Published
- 2021
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42. Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound.
- Author
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Endo-Takahashi Y, Kurokawa R, Sato K, Takizawa N, Katagiri F, Hamano N, Suzuki R, Maruyama K, Nomizu M, Takagi N, and Negishi Y
- Abstract
In brain-targeted delivery, the transport of drugs or genes across the blood-brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB.
- Published
- 2021
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43. Possible involvement of progranulin in the protective effect of elastase inhibitor on cerebral ischemic injuries of neuronal and glial cells.
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Horinokita I, Hayashi H, Yoshizawa R, Ichiyanagi M, Imamura Y, Iwatani Y, and Takagi N
- Subjects
- Animals, Cell Hypoxia, Cells, Cultured, Cytokines metabolism, Glycine pharmacology, Male, Neuroglia metabolism, Neurons metabolism, Pancreatic Elastase antagonists & inhibitors, Rats, Rats, Wistar, Recombinant Proteins pharmacology, Anti-Inflammatory Agents pharmacology, Brain Ischemia metabolism, Glycine analogs & derivatives, Neuroglia drug effects, Neurons drug effects, Progranulins pharmacology, Serine Proteinase Inhibitors pharmacology, Sulfonamides pharmacology
- Abstract
In a previous study, we demonstrated that neutrophil elastase is activated in the brain parenchyma after cerebral ischemia, which enzyme cleaves progranulin (PGRN), an anti-inflammatory factor. In that study, we also found that sivelestat, a selective neutrophil elastase inhibitor, attenuates ischemia-induced inflammatory responses. However, it was not clear whether this anti-inflammatory effect was due to the direct effect of sivelestat. In this study, we evaluated the effects of sivelestat or recombinant PGRN (rPGRN) on cell injuries in cultured neurons, astrocytes, and microglia under oxygen/glucose deprivation (OGD) conditions. We demonstrated that OGD-induced neuronal cell injury, astrocyte activation, and increased proinflammatory cytokines caused by microglial activation, were suppressed by rPGRN treatment, whereas sivelestat had no effect on any of these events. These results indicate that the anti-inflammatory responses after in vivo cerebral ischemia were not due to the direct action of sivelestat but due to the suppression of PGRN cleavage by inhibition of elastase activity. It was also suggested that the pleiotropic effect of rPGRN could be attributed to the differentiation of M1 microglia into anti-inflammatory type M2 microglia. Therefore, the inhibition of PGRN cleavage by sivelestat could contribute to the establishment of a new therapeutic approach for cerebral ischemia., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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44. Cytotoxic Effects of Arsenite in Combination With Gamabufotalin Against Human Glioblastoma Cell Lines.
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Yuan B, Xu K, Shimada R, Li J, Hayashi H, Okazaki M, and Takagi N
- Abstract
Glioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains <5%. Considering the sustained development of metastasis, tumor recurrence, and drug resistance, there is an urgent need for the novel therapeutic approaches to combat glioblastoma. Trivalent arsenic derivative (arsenite, As
III ) with remarkable clinical efficacy in leukemia has been shown to exert cytocidal effect against glioblastoma cells. Gamabufotalin, an active bufadienolide compound, also shows selective cytocidal effect against glioblastoma cells, and has been suggested to serve as a promising adjuvant therapeutic agent to potentiate therapeutic effect of conventional anticancer drugs. In order to gain novel insight into therapeutic approaches against glioblastoma, the cytotoxicity of AsIII and gamabufotalin was explored in the human glioblastoma cell lines U-87 and U-251. In comparison with U-251 cells, U-87 cells were highly susceptible to the two drugs, alone or in combination. More importantly, clinically achieved concentrations of AsIII combined with gamabufotalin exhibited synergistic cytotoxicity against U-87 cells, whereas showed much less cytotoxicity to human normal peripheral blood mononuclear cells. G2 /M cell cycle arrest was induced by each single drug, and further augmented by their combination in U-87 cells. Downregulation of the expression levels of cdc25C, Cyclin B1, cdc2, and survivin was observed in U-87 cells treated with the combined regimen and occurred in parallel with G2 /M arrest. Concomitantly, lactate dehydrogenase leakage was also observed. Intriguingly, SB203580, a specific inhibitor of p38 MAPK, intensified the cytotoxicity of the combined regimen in U-87 cells, whereas wortmannin, a potent autophagy inhibitor, significantly rescued the cells. Collectively, G2 /M arrest, necrosis and autophagy appeared to cooperatively contribute to the synergistic cytotoxicity of AsIII and gamabufotalin. Given that p38 MAPK serves an essential role in promoting glioblastoma cell survival, developing a possible strategy composed of AsIII , gamabufotalin, and a p38 MAPK inhibitor may provide novel insight into approaches designed to combat glioblastoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yuan, Xu, Shimada, Li, Hayashi, Okazaki and Takagi.)- Published
- 2021
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45. Effects of laminin-111 peptide coatings on rat neural stem/progenitor cell culture.
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Hayashi H, Horinokita I, Yamada Y, Hamada K, Takagi N, and Nomizu M
- Subjects
- Animals, Biocompatible Materials chemistry, Chitosan chemistry, Mice, Neural Stem Cells cytology, Neural Stem Cells metabolism, Neuroblastoma metabolism, Neuroblastoma pathology, Rats, Rats, Wistar, Tumor Cells, Cultured, Laminin chemistry, Neural Stem Cells drug effects, Neuroblastoma drug therapy, Neurogenesis, Peptide Fragments pharmacology
- Abstract
Neurons require adhesive scaffolds for their growth and differentiation. Laminins are a major cell adhesive component of basement membranes and have various biological activities in the peripheral and central nervous systems. Here, we evaluated the biological activities of 5 peptides derived from laminin-111 as a scaffold for mouse neuroblastoma Neuro2a cells and rat neural stem/progenitor cells (NPCs). The 5 peptides showed Neuro2a cell attachment activity similar to that of poly-d-lysine. However, when NPCs were cultured on the peptides, 2 syndecan-binding peptides, AG73 (RKRLQVQLSIRT, mouse laminin α1 chain 2719-2730) and C16 (KAFDITYVRLKF, laminin γ1 chain 139-150), demonstrated significantly higher cell attachment and neurite extension activities than other peptides including integrin-binding ones. Long-term cell culture experiments showed that both AG73 and C16 supported the growth of neurons and astrocytes that had differentiated from NPCs. Furthermore, C16 markedly promoted the expression of neuronal markers such as synaptosomal-associated protein-25 and syntaxin 1A. These results indicate that AG73 and C16 are useful for NPC cultures and that C16 can be applied to specialized research on synapses in differentiated neurons. These peptides have the potential for use as valuable biomaterials for NPC research., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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46. Syngenetic rapid growth of ellipsoidal silica concretions with bitumen cores.
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Yoshida H, Kuma R, Hasegawa H, Katsuta N, Sirono SI, Minami M, Nishimoto S, Takagi N, Kadowaki S, and Metcalfe R
- Abstract
Isolated silica concretions in calcareous sediments have unique shapes and distinct sharp boundaries and are considered to form by diagenesis of biogenic siliceous grains. However, the details and rates of syngenetic formation of these spherical concretions are still not fully clear. Here we present a model for concretion growth by diffusion, with chemical buffering involving decomposition of organic matter leading to a pH change in the pore-water and preservation of residual bitumen cores in the concretions. The model is compatible with some pervasive silica precipitation. Based on the observed elemental distributions, C, N, S, bulk carbon isotope and carbon preference index (CPI) measurements of the silica-enriched concretions, bitumen cores and surrounding calcareous rocks, the rate of diffusive concretion growth during early diagenesis is shown using a diffusion-growth diagram. This approach reveals that ellipsoidal SiO
2 concretions with a diameter of a few cm formed rapidly and the precipitated silica preserved the bitumen cores. Our work provides a generalized chemical buffering model involving organic matter that can explain the rapid syngenetic growth of other types of silica accumulation in calcareous sediments.- Published
- 2021
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47. Theoretical Study of NO Dissociative Adsorption onto 3d Metal Particles M 55 (M = Fe, Co, Ni, and Cu): Relation between the Reactivity and Position of the Metal Element in the Periodic Table.
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Takagi N, Ehara M, and Sakaki S
- Abstract
NO dissociative adsorption onto 3d metal particles M
55 (M = Fe, Co, Ni, and Cu) was investigated theoretically using density functional theory computations. A transition state exists at higher energy in the Cu case but at lower energy in the Fe, Co, and Ni cases than the reactant (sum of M55 and NO), indicating that Cu55 is not reactive for NO dissociative adsorption because NO desorption occurs more easily than the N-O bond cleavage in this case, but Fe55 , Co55 , and Ni55 are reactive because NO desorption needs a larger destabilization energy than the N-O bond cleavage. This result agrees with the experimental findings. The energy of transition state E (TS) becomes higher in the order of Fe < Co < Ni ≪ Cu. Exothermicity Eexo (relative energy to the reactant) decreases in the order of Fe > Co > Ni ≫ Cu. These results indicate that the reactivity for NO dissociative adsorption decreases kinetically and thermodynamically in this order. In addition, the E values show that 3d metal particles are more reactive than 4d metal particles when a comparison is made in the same group of the periodic table. Charge transfer (CT) from the metal particle to NO increases as the reaction proceeds. The CT quantity to NO at the TS increases in the order of Cu < Ni < Co < Fe, identical to the increasing order of reactivity. The negative charges of the N and O atoms of the product (N and O adsorbed M Eexo values show that 3d metal particles are more reactive than 4d metal particles when a comparison is made in the same group of the periodic table. Charge transfer (CT) from the metal particle to NO increases as the reaction proceeds. The CT quantity to NO at the TS increases in the order of Cu < Ni < Co < Fe, identical to the increasing order of reactivity. The negative charges of the N and O atoms of the product (N and O adsorbed M55 and those of the N and O negative charges arises from the presence of valence 4s electron of Cu because it suppresses the CT from N and O to Cu Eexo except for the Cu case; in the Cu case, the discrepancy between the order of Eexo and those of the N and O negative charges arises from the presence of valence 4s electron of Cu because it suppresses the CT from N and O to Cu55 . From these results, one can infer that the d-valence band-top energy of M55 plays an important role in determining the reactivity for NO dissociative adsorption. Truly, the d valence orbital energy decreases in the order of Fe > Co > Ni ≫ Cu and the 3d metal > 4d metal in the same group of the periodic table, which reflects the dependence of reactivity on the metal element position in the periodic table., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)- Published
- 2021
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48. Sandwich-type detection of nucleic acids by bioorthogonal SERS probes.
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Ota R, Takagi N, Imaizumi Y, Waku T, and Kobori A
- Subjects
- DNA chemistry, Gold chemistry, Microspheres, Nanotubes chemistry, Nucleic Acid Hybridization, Sepharose chemistry, Surface Properties, DNA analysis, Spectrum Analysis, Raman methods
- Abstract
Nucleic acids in body fluids, such as circulating cell-free nucleic acids, viral DNA, and RNA have received much attention for their great potential as biomarkers in liquid biopsies of serious diseases. Although quantitative polymerase chain reaction (qPCR) has been traditionally used as a laboratory-based assay for measuring nucleic acids, there is a strong demand for techniques to qualitatively, rapidly, and simply measure the extremely low-abundance nucleic acids in order to realize the nucleic acid-based liquid biopsies. With this aim in mind, we developed a simple and highly sensitive sandwich-type assay for nucleic acids using a combination of surface-enhanced Raman scattering (SERS), which enhances Raman scattering by 10
8 - to 1010 -fold, and bioorthogonal Raman tags, which generate signals in the biologically silent region (1800-2800 cm-1 ). Using gold nanorods having approximately 240 strands of oligonucleotides and 4-cyano- N -(2-mercaptoethyl)benzamide (4CMB) as the bioorthogonal Raman tag, we successfully detected target nucleic acids in a sequence-selective manner.- Published
- 2021
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49. Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses.
- Author
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Yamaguchi K, Kanno E, Tanno H, Sasaki A, Kitai Y, Miura T, Takagi N, Shoji M, Kasamatsu J, Sato K, Sato Y, Niiyama M, Goto Y, Ishii K, Imai Y, Saijo S, Iwakura Y, Tachi M, and Kawakami K
- Subjects
- Animals, Disease Models, Animal, Inflammation pathology, Male, Mice, Mice, Inbred C57BL, Neutrophils pathology, Inflammation metabolism, Lectins, C-Type metabolism, Neutrophils metabolism, Wound Healing physiology
- Abstract
C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by β-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these C-type lectin receptors in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of β-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation at the wound sites. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. Dectin-2 deficiency also improved collagen deposition and TGF-β1 expression. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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50. Outcomes of Definitive Chemoradiotherapy for Stage IVa (T4b vs. N4) Esophageal Squamous Cell Carcinoma Based on the Japanese Classification System: A Retrospective Single-Center Study.
- Author
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Wada Y, Anbai A, Takagi N, Kumagai S, Okuyama E, Nanjo H, Sato Y, Motoyama S, and Hashimoto M
- Abstract
The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37-87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6-94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors.
- Published
- 2020
- Full Text
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