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Modifying oxygen tension affects bone marrow stromal cell osteogenesis for regenerative medicine

World Journal of Stem Cells 2017年第7期9卷 98-106页

作者： Yusuke Inagaki Manabu Akahane Takamasa Shimizu Kazuya Inoue Takuya Egawa tsutomu kira Munehiro Ogawa Kenji Kawate Yasuhito Tanaka Department of Orthopedic Surgery Nara Medical University Department of Public Health Health Management and PolicyNara Medical UniversityFaculty of Medicine Departments of Artificial Joint and Regenerative Medicine for Bone and Cartilage Nara Medical University

AIM To establish a hypoxic environment for promoting osteogenesis in rat marrow stromal cells(MSCs) using osteogenic matrix cell sheets(OMCSs).METHODS Rat MSCs were cultured in osteogenic media under one of four varying oxygen conditions: Normoxia(21% O_2) for 14 d(NN), normoxia for 7 d followed by hypoxia(5% O_2) for 7 d(NH), hypoxia for 7 d followed by normoxia for 7 d(HN), or hypoxia for 14 d(HH). Osteogenesis was evaluated by observing changes in cell morphology and calcium deposition, and by measuring osteocalcin secretion(ELISA) and calcium content. In vivo syngeneic transplantation using OMCSs and β-tricalcium phosphate discs, preconditioned under NN or HN conditions, was also evaluated by histology, calcium content measurements,and real-time quantitative *** In the NN and HN groups, differentiated, cuboidal-shaped cells were readily observed, along with calcium deposits. In the HN group, the levels of secreted osteocalcin increased rapidly from day 10 as compared with the other groups, and plateaued at day 12(P < 0.05). At day 14, the HN group showed the highest amount of calcium deposition. In vivo, the HN group showed histologically prominent new bone formation, increased calcium deposition, and higher collagen type Ⅰ?messenger RNA expression as compared with the NN *** The results of this study indicate that modifying oxygen tension is an effective method to enhance the osteogenic ability of MSCs used for OMCSs.

关键词： Hypoxia Osteogenesis Tissue engineering Marrow stromal cells Regenerative medicine

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Bone regeneration with osteogenic matrix cell sheet and tricalcium phosphate:An experimental study in sheep

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World Journal of Orthopedics 2017年第10期8卷 754-760页

作者： tsutomu kira Manabu Akahane Shohei Omokawa Takamasa Shimizu Kenji Kawate Tadanobu Onishi Yasuhito Tanaka Department of Orthopedic Surgery Nara Medical University Department of Public Health Health Management and PolicyNara Medical University School of Medicine Department of Hand Surgery Nara Medical University Department of Artificial Joint and Regenerative Medicine for Bone and Cartilage Nara Medical University

AIM To determine the effects of a cell sheet created from sheep bone marrow and tricalcium phosphate(TCP) on *** Bone marrow cells were harvested from a sheep and cultured in a minimal essential medium(MEM) containing ascorbic acid phosphate(AscP) and dexamethasone(Dex). After 2 wk, the formed osteogenic matrix cell sheet was lifted from the culture dish using a scraper. Additionally, harvested bone marrow cells were cultured in MEM only as a negative control group, and in MEM with AscP, Dex, and β-glycerophosphate as a positive control group. For in vitro evaluation, we measured the alkaline phosphatase(ALP) activity and osteocalcin(OC) content in the media of the cultured cells from each group. For in vivo analysis, a porous TCP ceramic was used as a scaffold. We prepared an experimental group comprising TCP scaffolds wrapped with the osteogenic matrix cell sheets and a control group consisting of the TCP scaffold only. The constructs wereimplanted subcutaneously into athymic rats and the cell donor sheep, and bone formation was confirmed by histology after 4 *** In the in vitro part, the mean ALP activity was 0.39 ± 0.03 mg/well in the negative control group, 0.67 ± 0.04 mg/well in the sheet group, and 0.65 ± 0.07 mg/well in the positive control group. The mean OC levels were 1.46 ± 0.33 ng/well in the negative control group, 3.92 ± 0.16 ng/well in the sheet group, and 4.4 ± 0.47 ng/well in the positive control group, respectively. The ALP activity and OC levels were significantly higher in the cell sheet and positive control groups than in the negative control group(P 0.05). TCP constructs wrapped with cell sheets prior to implantation showed bone formation, in contrast to TCP scaffolds alone, which exhibited poor bone formation when implanted, in the subcutaneous layer both in athymic rats and in the s

关键词： Cell sheet Osteogenesis Sheep Bone marrow Mesenchymal stromal cell

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Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

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Neural Regeneration Research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya kira M.Holmström Henri J.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

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Localized,non-viral delivery of nucleic acids:Opportunities,challenges and current strategies

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Asian Journal of Pharmaceutical Sciences 2015年第3期10卷 159-175页

作者： Oliver Germershaus kira Nultsch Institute for Pharma Technology School of Life SciencesUniversity of Applied Sciences and Arts Northwestern SwitzerlandGründenstrasse 40CH 4132MuttenzSwitzerland

Localized delivery of drugs is an emerging field both with regards to drug delivery during disease as well as in tissue *** significant achievements made in the last decades,the efficient delivery of proteins and peptides remains challenging,especially in cases requiring long-term release of proteins after *** localized delivery of nucleic acids(NA)represents an interesting alternative due to higher physicochemical stability of NA,increased efficiency by harnessing cells as bioreactors for the production of required proteins and improved versatility with regards to expression of specific proteins through plasmid DNA or repression of gene products through ***,unlike most proteins and peptides,NA must be delivered to the cytoplasm or nucleus to be efficacious,resulting in significant delivery *** herein describe frequently used non-viral vectors for the delivery of NA including polyplexes,lipoplexes and lipopolyplexes and summarize recent developments in the field of nucleic acid delivery systems for local application based on hydrogels,solid scaffolds and physical delivery *** challenges associated with the different approaches are identified and options to address these challenges are discussed.

关键词： Gene delivery Topical application Tissue engineering Controlled release SiRNA DNA

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On 2-Site Voronoi Diagrams Under Geometric Distance Functions

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Journal of Computer Science & Technology 2013年第2期28卷 267-277页

作者： Gill Barequet Matthew Dickerson David Eppstein David Hodorkovsky kira Vyatkina Department of Computer Science Technion-Israel Institute of Technology Department of Mathematics and Computer Science Middlebury College Department of Mathematics and Computer Science University of California Department of Applied Mathematics Technion-Israel Institute of Technology Algorithmic Biology Laboratory St.Petersburg Academic University Russian Academy of Sciences

We revisit a new type of Voronoi diagram, in which distance is measured from a point to a pair of points. We consider a few more such distance functions, based on geometric primitives, namely, circles and triangles, and analyze the structure and complexity of the nearest- and furthest-neighbor 2-site Voronoi diagrams of a point set in the plane with respect to these distance functions. In addition, we bring to notice that 2-point site Voronoi diagrams can be alternatively interpreted as 1-site Voronoi diagrams of segments, and thus, our results also enhance the knowledge on the latter.

关键词： distance function lower envelope Davenport-Schinzel theory crossing-number lemma

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Unveiling T cell evasion mechanisms to immune checkpoint inhibitors in acute myeloid leukemia

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Cancer Drug Resistance 2023年第3期6卷 674-687页

作者： Lindsay Gurska kira Gritsman Department of Cell Biology Albert Einstein College of MedicineBronxNY 10461USA Department of Medical Oncology Montefiore Medical CenterAlbert Einstein College of MedicineBronxNY 10461USA

Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy that is associated with a high relapse rate and poor prognosis. Despite advances in immunotherapies in solid tumors and other hematologic malignancies, AML has been particularly difficult to treat with immunotherapies, as their efficacy is limited by the ability of leukemic cells to evade T cell recognition. In this review, we discuss the common mechanisms of T cell evasion in AML: (1) increased expression of immune checkpoint molecules;(2) downregulation of antigen presentation molecules;(3) induction of T cell exhaustion;and (4) creation of an immunosuppressive environment through the increased frequency of regulatory T cells. We also review the clinical investigation of immune checkpoint inhibitors (ICIs) in AML. We discuss the limitations of ICIs, particularly in the context of T cell evasion mechanisms in AML, and we describe emerging strategies to overcome T cell evasion, including combination therapies. Finally, we provide an outlook on the future directions of immunotherapy research in AML, highlighting the need for a more comprehensive understanding of the complex interplay between AML cells and the immune system.

关键词： Acute myeloid leukemia T cells immune checkpoint immune evasion

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New g-2 experiment at J-PARC

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Chinese Physics C 2010年第6期34卷 745-748页

作者： tsutomu Mibe KEK High Energy Accelerator Research Organization

A new measurement of the anomalous magnetic moment of the positive muon αμ is proposed with a novel technique utilizing an ultra-cold muon beam accelerated to 300 MeV/c and a 66 cm-diameter muon storage ring without focusing-electric field. This measurement will be complimentary to the previous measurement that achieved 0.54 ppm accuracy with the magic energy of 3.1 GeV in a 14 m diameter storage ring. The proposed experiment aims to achieve the sensitivity down to 0.1 ppm.

关键词： muon anomarous magnetic moment J-PARC

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Enhancing diabetic retinopathy screening:Non-mydriatic fundus photography-assisted telemedicine for improved clinical management

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World Journal of Diabetes 2024年第8期15卷 1820-1823页

作者： kira J Szulborski David J Ramsey Department of Ophthalmology Tufts University School of MedicineBostonMA 02111United States Lahey Department of Surgery Division of OphthalmologyUMass Chan Medical SchoolUniversity of MassachusettsBurlingtonMA 01805United States Graduate Faculty New England College of OptometryBostonMA 02115United States

The utilization of non-mydriatic fundus photography-assisted telemedicine to screen patients with diabetes mellitus for diabetic retinopathy provides an accurate,efficient,and cost-effective method to improve early detection of *** has also been shown to correlate with increased participation of patients in other aspects of diabetes *** particular,patients who undergo teleretinal imaging are more likely to meet Comprehensive Diabetes Care Healthcare Effectiveness Data and Information Set metrics,which are linked to preservation of quality-adjusted life years and additional downstream healthcare savings.

关键词： Diabetes Diabetic retinopathy Telemedicine Tele-ophthalmology Nonmydriatic fundus photography-assisted telemedicine Vision screening Preventative health services Health policy

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A new algorithm based on metaheuristics for data clustering

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2010年第12期11卷 921-926页

作者： tsutomu SHOHDOHJI Fumihiko YANO Yoshiaki TOYODA Department of Computer and Information Engineering Faculty of EngineeringNippon Institute of Technology Division of Integrated Sciences J.F.Oberlin University Aoyama Gakuin University

This paper presents a new algorithm for clustering a large amount of *** improved the ant colony clustering algorithm that uses an ant’s swarm intelligence,and tried to overcome the weakness of the classical cluster analysis *** our proposed algorithm,improvements in the efficiency of an agent operation were achieved,and a new function "cluster condensation" was *** proposed algorithm is a processing method by which a cluster size is reduced by uniting similar objects and incorporating them into the cluster *** with classical cluster analysis methods,the number of steps required to complete the clustering can be suppressed to 1% or less by performing this procedure,and the dispersion of the result can also be ***,our clustering algorithm has the advantage of being possible even in a small-field cluster *** addition,the number of objects that exist in the field decreases because the cluster condenses;therefore,it becomes possible to add an object to a space that has become *** other words,first,the majority of data is put on *** are then clustered,gradually adding parts of the standby data to the clustering *** method can be adopted for a large amount of *** experiments confirmed that our proposed algorithm can theoretically applied to an unrestricted volume of data.

关键词： Metaheuristics Ant colony clustering Data clustering Swarm intelligence

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Electroweak Axion in Light of GRB221009A

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Chinese Physics Letters 2023年第6期40卷 109-110页

作者： Weikang Lin tsutomu T.Yanagida South-Western Institute for Astronomy Research Yunnan UniversityKunming 650500China Tsung-Dao Lee Institute(TDLI)&School of Physics and Astronomy Shanghai Jiao Tong UniversityShanghai 201210China Kavli IPMU(WPI) The University of TokyoKashiwaChiba 277-8583Japan

Very high energy(VHE)photons may have a higher survival rate than that expected in standard-model physics,as suggested by the recently reported gamma ray burst *** a photon-axion like particle(ALP)oscillation can boost the survival rate of the VHE photons,current works have not been based on concrete particle models,leaving the identity of the corresponding ALP ***,we show that the required ALP scenario is consistent with the electroweak axion with an anomaly free Z_(10)Froggatt–Nielsen symmetry.

关键词： symmetry weak oscillation

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