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Intranasal administration of stem cell-derived exosomes for central nervous system diseases

Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho gotoh Masahito Kawabori Miki Fujimura Department of Neurosurgery Hokkaido University Graduate School of MedicineHokkaidoJapan

Exosomes,lipid bilayer-enclosed small cellular vesicles,are actively secreted by various cells and play crucial roles in intercellular *** nanosized vesicles transport internalized proteins,mRNA,miRNA,and other bioactive *** findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system *** exosomes exhibit multifaceted properties including antiapoptotic,anti-inflammatory,neurogenic,and vasculogenic ***,exosomes offer several advantages over stem cell therapy,such as high preservation capacity,low immunogenicity,the ability to traverse the blood-brain barrier,and the potential for drug ***,researchers have turned their attention to exosomes as a novel therapeutic ***,akin to the limitations of stem cell treatment,the limited accumulation of exosomes in the injured brain poses a challenge to their clinical *** overcome this hurdle,intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous *** exploiting the olfactory and trigeminal nerve axons,this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain ***,exosomes,owing to their small size,can readily access the nerve pathways using this *** a result,intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased *** this comprehensive review,we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system ***,we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

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Non-Obese Type 2 Diabetic Rat Models-GK Rat and SDT Rat

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Open Journal of Animal Sciences 2018年第4期8卷 396-420页

作者： Takeshi Ohta Tomohiko Sasase takayuki gotoh Masami Shinohara Phanthila Sirichaiyakul Suhattaya Furuta Rumpar Techasakulsin Taiichiro Kamiya Chikako Yoshida Takahisa Yamada Biological/Pharmacological Research Laboratories Central Pharmaceutical Research Institute Japan Tobacco Inc. Osaka Japan Technical Service Department CLEA Japan Inc. Shizuoka Japan Tokyo Animal & Diet Department CLEA Japan Inc. Tokyo Japan Nomura Siam International Co. Ltd. Bangkok Thailand Field Center for Sustainable Agriculture and Forestry Faculty of Agriculture Niigata University Niigata Japan Laboratory of Animal Genetics Graduate School of Science and Technology Niigata University Niigata Japan

The number of diabetic patients has recently been increasing all over the world together with lifestyle changes including sedentary life and high-calorie diet intake, and as a result the increase in these suffering from diabetes mellitus has become a global issue. Diabetic animal models play a key role in bettering our understanding of the pathophysiology of diabetes and in developing new therapies for the disease. Diabetes is classified into two types, type 1 and type 2, and type 2 diabetes is chiefly caused by a depletion of insulin secretion in the pancreas and insulin resistance in peripheral tissues. The Goto-Kakizaki (GK) rat and the Spontaneously Diabetic Torii (SDT) rat are genetic non-obese type 2 diabetic models, and the both rats are considered to be suitable models for investigating the etiology of the depletion of insulin secretion and impaired glucose tolerance. In this review, we overviewed the outline of pathophysiological features in GK rats and SDT rats, including biological parameters and pharmacological responses.

关键词： Diabetic Model GK Rat SDT Rat Type 2 Diabetes

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Three-dimensional machining of insulating ceramics materials with electrical discharge machining

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中国有色金属学会会刊：英文版 2009年第B9期19卷 150-156页

作者： Yasushi FUKUZAWA Naotake MOHRI Hiromitsu gotoh takayuki TANI Department of Mechanical Engineering Nagaoka University of Technology Department of Precision Engineering The University of Tokyo Department of Industrial Information Tsuku ba University of Technology

The insulating ceramics were processed with sinking and wire cut electrical discharge machining(EDM). The new technology was named as the assisting electrode method. In the machining, the electrical conductive material was adhered on the surface of insulating workpiece as the starting point of electrical discharge. As the processing operated in oil, the electrical conductive product composed of decomposition carbon element from working oil adhered on the workpiece during discharge. The discharges generated continuously with the formation of the electrical conductive layer. So, the insulating ceramics turn to the machinable material by EDM. We introduced the mechanism and the application of the machining of insulating ceramics such as Si3N4 and ZrO2.

关键词：绝缘陶瓷放电加工三维加工陶瓷材料工件表面导电材料机械加工分解过程

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On systematic development of FSI solvers in the context of particle methods

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Journal of Hydrodynamics 2022年第3期34卷 395-407页

作者： Abbas Khayyer Hitoshi gotoh Yuma Shimizu Department of Civil and Earth Resources Engineering Kyoto UniversityKyotoJapan

This paper presents a review on state-of-the-art of developments corresponding to fluid-structure interaction(FSI)solvers developed within the context of particle *** paper reviews and highlights the potential robustness of entirely Lagrangian meshfree FSI solvers in reproducing FSI corresponding to extreme events and portrays the future perspectives for systematic developments towards reliable engineering applications with respect to rapid advances in technology and emergence of so-called advanced materials that can result in complex and highly non-linear structural ***,the paper highlights the necessity for reproduction of comprehensive structural responses,including viscoelastic,elastoplastic and progressive damages/failures,by the advanced FSI solvers developed within the context of particle *** this regard,extensions of the structure model are suggested to be conducted in a variationally consistent framework to ensure stability,accuracy and physical reliability including thermodynamic *** paper reviews basics of mathematical and numerical modelling for entirely Lagrangian meshfree hydroelastic FSI solvers and presents a brief background on extensions of such solvers towards reproducing viscoelastic structural *** preliminary numerical results on structural viscoelasticity achieved by an extended Hamiltonian SPH(HSPH)model are *** vision paper also concisely portrays the future perspectives for systematic development of particle-based FSI solvers.

关键词： Fluid-structure interaction(FSI) entirely Lagrangian meshfree smoothed particle hydrodynamics(SPH) Hamiltonian SPH(HSPH) viscoelasticity

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Towards development of enhanced fully-Lagrangian mesh-free computational methods for fluid-structure interaction

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Journal of Hydrodynamics 2018年第1期30卷 49-61页

作者： Abbas Khayyer Hitoshi gotoh Hosein Falahaty Yuma Shimizu Department of Civil and Earth Resources Engineering Kyoto UniversityKatsura Campus

Simulation of incompressible fluid flow-elastic structure interactions is targeted by using fully-Lagrangian mesh-free computational methods. A projection-based fluid model（moving particle semi-implicit（MPS）） is coupled with either a Newtonian or a Hamiltonian Lagrangian structure model（MPS or HMPS） in a mathematically-physically consistent manner. The fluid model is founded on the solution of Navier-Stokes and continuity equations. The structure models are configured either in the framework of Newtonian mechanics on the basis of conservation of linear and angular momenta, or Hamiltonian mechanics on the basis of variational principle for incompressible elastodynamics. A set of enhanced schemes are incorporated for projection-based fluid model（Enhanced MPS）, thus, the developed coupled solvers for fluid structure interaction（FSI） are referred to as Enhanced MPS-MPS and Enhanced MPS-HMPS. Besides, two smoothed particle hydrodynamics（SPH）-based FSI solvers, being developed by the authors, are considered and their potential applicability and comparable performance are briefly discussed in comparison with MPS-based FSI solvers. The SPH-based FSI solvers are established through coupling of projection-based incompressible SPH（ISPH） fluid model and SPH-based Newtonian/Hamiltonian structure models, leading to Enhanced ISPH-SPH and Enhanced ISPH-HSPH. A comparative study is carried out on the performances of the FSI solvers through a set of benchmark tests, including hydrostatic water column on an elastic plate,high speed impact of an elastic aluminum beam, hydroelastic slamming of a marine panel and dam break with elastic gate.

关键词： Fluid structure interaction(FSI) projection-based method moving particle semi-implicit incompressible smoothed particle hydrodynamics(ISPH) Hamiltonian MPS(HMPS) Hamiltonian SPH(HSPH)

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Incompressible SPH simulation of solitary wave propagation on permeable beaches

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Journal of Hydrodynamics 2020年第4期32卷 664-671页

作者： Chiaki Tsurudome Dongfang Liang Yuma Shimizu Abbas Khayyer Hitoshi gotoh Department of Engineering University of CambridgeTrumpington StreetCambridgeUK Graduate School of Engineering Kyoto UniversityKyotoJapan

Wave propagation on uniformly sloped beaches is a canonical coastal engineering topic that has been studied extensively in the past few ***,most of these studies treat beaches as solid boundaries even though they are often made of porous materials,such as sediment and *** beaches struck by tsunami-like waves have not been adequately *** is expected that the degree of penneability plays a crucial role in mitigating the impact of the *** study examines solitary wave run-ups on sandy beaches using an incompressible smoothed particle hydrodynamics(ISPH)*** permeability of the beach is considered to be directly related to the diameter of its constituent sand *** obtain a satisfactory pressure field,which cannot be achieved using the original ISPH algorithm,the source term of the pressure Poisson equation has been modified based on a higher-order source-term *** within the porous medium are computed in the same framework as those outside the porous *** the current model,no transition zone is needed at the boundary of the porous *** wave-attenuation effect of the porous medium is discussed,with a particular focus on the relationship between the mn-up height and grainsize.

关键词： Solitary wave porosity incompressible smoothed particle hydrodynamics(ISPH) run-up

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Effect of Microstructure of Cementite on Interphase Stress State in Carbon Steel

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Journal of Iron and Steel Research International 2007年第4期14卷 31-38页

作者： CHE Lei gotoh Masahide HORIMOTO Yoshiaki HIROSE Yukio Graduate School Kanazawa University Kanazawa 920-1192 Japan Department of Materials Science and Engineering Kanazawa University Kanazawa 920-1192 Japan

The experiments related to stress states of ferrite and cementite in carbon steels were carried out including in situ four-point bending and tensile test by X-ray diffraction technique. Stresses in the cementite phase can be measured by conventional X-ray diffraction instrument after a specific treatment on the specimen surface. In order to estimate the stress states in two phases, the X-ray elastic constants of two phases in single-phase state （PXEC） are determined by the experimental X-ray elastic constants of them in composite state （CXEC）. The effects of volume fraction and particle size of spheroidal cementite on the interphase stress state are estimated. The experimental results are in good agreement with the theoretical relationships reported in the previous studies.

关键词： multi-phase material surface treatment plastic deformation residual stress X-ray diffraction

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Drug resistance mechanisms of cancer stem-like cells and their therapeutic potential as drug targets

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Cancer Drug Resistance 2019年第3期2卷 457-470页

作者： Takahiko Murayama Noriko gotoh Division of Cancer Cell Biology Cancer Research InstituteKanazawa UniversityKanazawa 920-1192Japan.

Despite of recent advances in cancer research and development of new anti-cancer drugs,tumor patients’prognoses have not yet been improved well *** failure of tumors is highly attributed to the drug resistance of a small population of cancer cell known as cancer stem-like cells(CSCs).CSCs also have the self-renewal activity and differentiation potency,conferring strong tumorigenicity on ***,development of CSC targeting therapy is urgently needed in order to overcome possible recurrence and metastasis by them after *** show some characteristic features that are not observed in other differentiated cancer cells,which give them higher resistance against conventional chemotherapy or *** such specific features could be useful for CSC *** review will summarize the recent advances in the study of CSC characteristics along with the promising therapeutic strategies targeting them.

关键词： Cancer stem-like cell drug resistance epithelial-to-mesenchymal transition hypoxia quiescence

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Recurrence of unilateral angioedema of the tongue:A case report

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世界临床病例杂志 2023年第27期11卷 6603-6612页

作者： Yuki Matsuhisa Tsuneaki Kenzaka Hironori Shimizu Hideo Hirose Tadao gotoh Department of General Medicine Center for Community Medicine in North-Western Gifu Prefecture National Health Insurance Shirotori HospitalGujo 501-5122Japan Department of Pediatrics Center for Community Medicine in North-Western Gifu Prefecture National Health Insurance Shirotori HospitalGujo 501-5122Japan Department of Internal Medicine Hyogo Prefectural Tamba Medical CenterTamba 669-3495Japan Division of Community Medicine and Career Development Kobe University Graduate School of MedicineKobe 652-0032Japan

BACKGROUND Angioedema is a disorder characterized by edema of the face,lips,tongue,and extremities due to increased vascular *** of the tongue usually occurs bilaterally,and the incidence of unilateral angioedema of the tongue is *** study reports a rare case of unilateral angioedema of the tongue with no identifiable cause and repeated recurrence even after discontinuation of an angiotensin-converting enzyme *** SUMMARY The patient was a 65-year-old woman with pre-existing hypertension and hyperlipidemia and had been receiving 20 mg/d of *** was diagnosed with angioedema due to unilateral swelling of the *** airway obstruction was observed,and the symptoms improved following the administration of 0.3 mg of epinephrine intramuscularly and 125 mg of methylprednisolone *** lisinopril was discontinued,unilateral angioedema of the tongue continued to recur every 2-5 mo,with the symptoms improving following the administration of prednisolone and an *** oral administration of 500 mg of tranexamic acid after dinner prevented the recurrence of *** Careful monitoring and identification of the underlying mechanism play a crucial role in the treatment of angioedema.

关键词： Angioedema Tongue Unilateral Bradykinin Tranexamic acid Case report

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Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

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International Journal of Oral Science 2013年第1期5卷 14-20页

作者： Hiroshi Kobayashi Kenichi Kumagai Akito gotoh Takanori Eguchi Hiroyuki Yamada Yoshiki Hamada Satsuki Suzuki Ryuji Suzuki Department of Oral and Maxillofacial Surgery Tsurumi University Department of Rheumatology and Clinical Immunology Clinical Research Center for Rheumatology and AllergySagamihara National HospitalNational Hospital Organization Section of Biological Science Research Center for Odontology Nippon Dental University School of Dentistry

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and *** mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP *** of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM *** were strongly expressed by epithelial keratinocytes in LP lesions,as shown by *** the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM ***,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

关键词： epidermal growth factor receptor immunohistochemistry oral leukoplakia quantitative real-time polymerase chain reaction

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