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Action Mechanisms of Complementary and Alternative Medicine Therapies for Rheumatoid Arthritis

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Chinese Journal of Integrative Medicine 2011年第10期17卷 723-730页

作者： Imada Keisuke 边宝林李向东 sato takashi Ito Akira Department of Biochemistry and Molecular Biology School of PharmacyTokyo University of Pharmacy and Life Sciences1432-1 HorinouchiHachiojiTokyo(192-0392)Japan China Academy of Chinese Medical Sciences

Rheumatoid arthritis （RA） is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type Ⅱ collagen and aggrecan are enzymatically degraded by matrix metalloproteinases （MMPs） and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor （TNF） α antibodies, soluble TNF receptor, anti-interleukin （IL）-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to anti- inflammatory agents and disease-modifying antirheumatic drugs （DMARDs）, such as methotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of Iow-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternativemedicines including traditional Chinese medicines （TCM） have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis.

关键词： rheumatoid arthritis extracellular matrix aggrecanase matrix metalloproteinase complementary and alternative medicine

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基于DNA甲基化测序技术研究青蒿琥酯干预脑胶质瘤的分子机制

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中草药 2023年第6期54卷 1814-1824页

作者：闫向英毛霞李涛 Koji Mizuno Katsuki Okuyama 林娜张彦琼 takashi sato 中国中医科学院中药研究所北京100700 东京药科大学生物化学系东京192-0392

目的探究青蒿琥酯干预胶质母细胞瘤(glioblastoma,GBM)的药效及其潜在分子机制。方法采用Cell TiterBlue检测青蒿琥酯对U87和U2512种人源胶质母细胞瘤细胞活性和增殖的影响;流式细胞术检测青蒿琥酯对2种细胞周期的调节作用;采用q RT-PCR... 详细信息

目的探究青蒿琥酯干预胶质母细胞瘤(glioblastoma,GBM)的药效及其潜在分子机制。方法采用Cell TiterBlue检测青蒿琥酯对U87和U2512种人源胶质母细胞瘤细胞活性和增殖的影响;流式细胞术检测青蒿琥酯对2种细胞周期的调节作用;采用q RT-PCR和Western blotting检测青蒿琥酯对2种细胞自噬水平的影响。采用DNA甲基化联合网络药理学从表观遗传学层面研究青蒿琥酯干预GBM的靶标基因,并建立蛋白质-蛋白质相互作用网络,通过计算网络中各节点的网络拓扑特征值,筛选出青蒿琥酯干预GBM的核心靶点并进行生物功能富集分析;采用AutoDock v4.2.6和Auto Dock Vina v1.2.0软件开展分子对接虚拟计算,考察青蒿琥酯与其候选关键靶点的结合能力,并采用Western blotting验证青蒿琥酯对2种脑胶质瘤细胞中关键靶点表达的影响。结果青蒿琥酯可显著抑制U87细胞的活性和增殖(P<0.05、0.01、0.001),而对U251细胞的药效不显著;高剂量青蒿琥酯可影响2种细胞周期分布;高剂量青蒿琥酯可显著提高U87细胞中3种自噬标志分子[自噬关键分子酵母Atg6同系物(ATG6 autophagy related 6 homolog,Beclin1)、泛素结合蛋白(ubiquitin-binding protein,p62)、微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)]的m RNA表达水平(P<0.001),而仅高剂量青蒿琥酯升高U251细胞中p62的m RNA表达水平(P<0.05);低、中、高剂量青蒿琥酯可显著提高U87细胞中Beclin1、p62、LC3B蛋白表达水平(P<0.05、0.01),仅中、高剂量青蒿琥酯可以影响U251细胞中Beclin1、p62、LC3B蛋白表达。利用给药前后的U87与U251细胞进行DNA甲基化测序与网络药理学整合分析,在获得青蒿琥酯敏感型和耐药型脑胶质瘤细胞的差异基因集,以及青蒿琥酯干预2种细胞效应基因集的基础上,发现其干预2类脑胶质瘤细胞的关键网络靶标共同参与GBM恶性进展密切相关的血小板衍生生长因子受体α(platelet derived growth factor receptorα,PDGFRA)-大鼠肉瘤基因(rat sarcoma viral oncogene homolog,RAS)-B-Raf原癌基因(B-Raf proto-oncogene,BRAF)-丝裂原活化蛋白激酶激酶(mitogenactivated protein kinase kinase,MEK)-细胞外信号调节激酶(extracellular signal regulated kinase,ERK)通路,且青蒿琥酯与其直接靶标(PDGFRA、BRAF)具有较强的亲和力。Western blotting实验证实青蒿琥酯可以抑制U87和U251细胞中关键靶点PDGFRA和BRAF蛋白的表达(P<0.05、0.01、0.001)。结论青蒿琥酯可能通过靶向调控PDGFRA-RAS-BRAF-MEKERK信号通路,从而抑制GBM细胞的生长和扩散,为青蒿琥酯治疗GBM提供了体外实验依据,也为解决临床抗肿瘤药物的耐药问题提供了新思路和新方法。

关键词：青蒿琥酯胶质母细胞瘤 DNA甲基化分析耐药 PDGFRA-RAS-BRAF-MEK-ERK信号通路

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Triptolide,a Novel Diterpenoid Triepoxide From Tripterygium wilfordii Hook.f., Suppresses the Production and Gene Expression of Pro-Matrix Metalloproteinases 1 and 3 and Augments Those of Tissue Inhibitiors of Metalloproteinases 1 and 2 in Human

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中国实验方剂学杂志 2002年第S1期8卷 -页

作者： takashi sato Akira Ito

Ｍｅｔｈｏｄｓ.Ｈｕｍａｎｓｙｎｏｖｉａｌｆｉｂｒｏｂｌａｓｔｓａｎｄｍｏｕｓｅｍａｃｒｏｐｈａｇｅｓｗｅｒｅｃｕｌｔｕｒｅｄｗｉｔｈｉｎｔｅｒｌｅｕｋｉｎ 1α(ＩＬ 1α)ｏｒｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅ(ＬＰＳ...

Ｍｅｔｈｏｄｓ.Ｈｕｍａｎｓｙｎｏｖｉａｌｆｉｂｒｏｂｌａｓｔｓａｎｄｍｏｕｓｅｍａｃｒｏｐｈａｇｅｓｗｅｒｅｃｕｌｔｕｒｅｄｗｉｔｈｉｎｔｅｒｌｅｕｋｉｎ 1α(ＩＬ 1α)ｏｒｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅ(ＬＰＳ)ｉｎｔｈｅｐｒｅｓｅｎｃｅｏｒａｂｓｅｎｃｅｏｆｔｒｉｐｔｏｌｉｄｅ .ＴｈｅｐｒｏｄｕｃｔｉｏｎｏｆｐｒｏＭＭＰｓ 1ａｎｄ 3 ,ＴＩＭＰｓ 1ａｎｄ 2 ,ｃｙｃｌｏｏｘｙｇｅｎａｓｅ 1 (ＣＯＸ 1 )ａｎｄＣＯＸ 2 ,ｐｒｏｓｔａｇｌａｎｄｉｎＥ2 (ＰＧＥ2 ) ,ＩＬ 1 β ,ａｎｄＩＬ 6ｗａｓａｓｓａｙｅｄｂｙＷｅｓｔｅｒｎｂｌｏｔａｎａｌｙｓｉｓａｎｄｅｎｚｙｍｅｌｉｎｋｅｄｉｍｍｕｎｏｓｏｒｂｅｎｔａｓｓａｙ .ＧｅｎｅｅｘｐｒｅｓｓｉｏｎｏｆｐｒｏＭＭＰｓ 1ａｎｄ 3 ,ＴＩＭＰｓ 1ａｎｄ 2 ,ＣＯＸ 1ａｎｄＣＯＸ 2 ,ＩＬ 1α ,ＩＬ 1 β ,ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒα(ＴＮＦα) ,ａｎｄＩＬ 6ｗａｓａｌｓｏｍｏｎｉｔｏｒｅｄｂｙＮｏｒｔｈｅｒｎｂｌｏｔａｎａｌｙｓｉｓａｎｄｒｅｖｅｒｓｅｔｒａｎｓｃｒｉｐｔａｓｅｐ...

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Suppression of Sebum Production and Accumulation by <i>β</i>-Cryptoxanthin Due to the Inhibition of the Expression of Diacylglycerol Acyltransferase-1 and Perilipin in Hamster Sebocytes

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Journal of Cosmetics, Dermatological Sciences and Applications 2013年第1期3卷 99-106页

作者： takashi sato Yoshiyuki Shirakura Katsuyuki Mukai Akira Ito Department of Biochemistry and Molecular Biology School of Pharmacy Tokyo University of Pharmacy and Life Sciences Hachioji Tokyo Japan R & D Center Unitika Ltd. Kyoto Japan

Background: Acne vulgaris is characterized by the enhancement of sebaceous lipogenesis and sebum secretion, and apart from retinoids and some natural products there are few effective antiacne agents that directly suppress sebum production and accumulation in sebaceous glands. Objective: We examined the effects of β-cryptoxanthin (β-CRX), which is a carotenoid pigment most abundant in Citrus unshiu Marcovich (Satsuma mandarin orange) and plays a role as a vitamin A precursor on sebum production and accumulation in hamster sebaceous gland cells (sebocytes). Materials and methods: The regulation of sebum production was examined by the measurement of triacylglycerols (TGs), the major sebum component, and oil red O staining in insulindifferentiated hamster sebocytes. The expression of diacylglycerol acyltransferase-1 (DGAT-1), a rate-limiting enzyme of TG biosynthesis, and perilipin 1 (PLIN1), a lipid storage droplet protein, was analyzed using real-time PCR and Western blotting. Results: Hamster sebocytes constitutively produced TGs during cultivation and the production of TGs was enhanced by insulin treatment. Both constitutive and insulin-enhanced TG productions were dose- and time-dependently inhibited by β-CRX as well as 13-cis retinoic acid. In addition, the gene expression of DGAT-1 was suppressed by β-CRX in the sebocytes. Furthermore, the insulin-en- hanced sebum accumulation as lipid droplets was reduced in the β-CRX-treated cells. Moreover, β-CRX was found to suppress the gene expression and production of PLIN1 in insulin-differentiated hamster sebocytes. Conclusions: These results provide novel evidence that β-CRX is an effective candidate for acne therapy by its ability to exert dual inhibitory actions against DGAT-1-dependent TG production and PLIN1-mediated lipiddroplet formation in hamster sebocytes.

关键词： β-Cryptoxanthin Sebocytes Triacylglycerol Biosynthesis Diacyglycerol Acyltransferase Perilipin Lipid-Droplet Formation Sebum

Correlation between dose-volume parameters and rectal bleeding after 12 fractions of carbon ion radiotherapy for prostate cancer

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World Journal of Radiology 2024年第7期16卷 256-264页

作者： takashi Ono Hiraku sato Yuya Miyasaka Yasuhito Hagiwara Natsuko Yano Hiroko Akamatsu Mayumi Harada Mayumi Ichikawa Department of Radiation Oncology Faculty of MedicineYamagata UniversityYamagata 990-9585Japan Department of Heavy Particle Medical Science Yamagata University Graduate School of Medical ScienceYamagata 990-9585Japan

BACKGROUND Carbon ion radiotherapy(CIRT)is currently used to treat prostate *** bleeding is a major cause of toxicity even with ***,to date,a correlation between the dose and volume parameters of the 12 fractions of CIRT for prostate cancer and rectal bleeding has not been ***,the clinical risk factors for rectal bleeding were absent after 12 fractions of *** To identify the risk factors for rectal bleeding in 12 fractions of CIRT for prostate *** Among 259 patients who received 51.6 Gy[relative biological effectiveness(RBE)],in 12 fractions of CIRT,15 had grade 1(5.8%)and nine had grade 2 rectal bleeding(3.5%).The dose-volume parameters included the volume(cc)of the rectum irradiated with at least x Gy(RBE)(Vx)and the minimum dose in the most irradiated x cc normal rectal volume(Dx).RESULTS The mean values of D6cc,D2cc,V10 Gy(RBE),V20 Gy(RBE),V30 Gy(RBE),and V40 Gy(RBE)were significantly higher in the patients with rectal bleeding than in those *** cutoff values were D6cc=34.34 Gy(RBE),D2cc=46.46 Gy(RBE),V10 Gy(RBE)=9.85 cc,V20 Gy(RBE)=7.00 cc,V30 Gy(RBE)=6.91 cc,and V40 Gy(RBE)=4.26 *** D2cc,V10 Gy(RBE),and V20 Gy(RBE)cutoff values were significant predictors of grade 2 rectal *** The above dose-volume parameters may serve as guidelines for preventing rectal bleeding after 12 fractions of CIRT for prostate cancer.

关键词： Carbon ion radiotherapy Prostate cancer Rectal bleeding Dose volume parameters Prevention

雷公藤甲素抑制人体滑膜成纤维细胞基质金属蛋白酶并提高组织抑制因子的产物和基因表达(英文)

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雷公藤甲素抑制人体滑膜成纤维细胞基质金属蛋白酶并提高组织抑制...

Novel Anti-tumor Metastatic Actions of Shikonin,a Pigment from Lithospermum Erythrorhizon,and p-cymene,a Monoterpenoid from Angelica Acutiloba,in Human Fibrosarcoma HT-1080 cells

作者：林娜 takashi sato Akira Ito Tokyo University of Pharmacy and life Science Tokyo Japan Department of Biochemistry and Molecular Biology School of Pharmacy Tokyo University of Pharmacy and Life ScienceHorinouchiHachiojiTokyo 192-0392Japan

*** extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f.(TWHF) have been reported to be therapeutically efficacious in rheumatoid arthritis(RA) in China,but their mechanism of action remains *** investigated the effect of triptolide,a diterpenoid triepoxide from TWHF,on the production of pro-matrix metalloproteinase 1 (proMMP- 1;or procollagenase 1 or pro-interstitial collagenase 1 ),proMMP-3(or prostromelysin 1),tissue inhibitors of metalloproteinases(TIMPs),and proinflammatory cytokines in human synovial fibroblasts and J774A.1 mouse macrophages.

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Novel Anti-tumor Metastatic Actions of Shikonin,a Pigment fr...

重型车辆涡轮增压柴油机的研制——为获得良好的燃油经济性

第十四届全国中药和天然药物学术研讨会

作者： takashi sato JingZhe Li Akira Ito School of Pharmacy Tokyo University of Pharmacy and Life Sciences China Academy of Chinese Medical Sciences The Institute for Social Medicine at Tokyo University of Pharmacy and Life Sciences

＜正＞Shikonin,a pigment from Lithospermum erythrorhizon,and p-cymene,a monoterpenoid from Angelica acutiloba,exert anti-angiogenic and immunomodulating activities,respectively,those of which are therapeutically efficient for the prevention of cancer ***,whether Shikonin and p-cymene exhibit anti-tumor invasive actions

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车用发动机 1983年第5期 13-29页

作者： takashi Suzuki,Akihiko sato,尼鲜利日野发动机有限公司日野发动机有限公司日本日本

本文介绍了在载重卡车的增压柴油机上既要获得良好的燃油经济性,又要具有极好的驱动能力的一些技术解决方法和研制过程。为获得良好的燃油经济性,首先要考虑怎样减少发动机本身的摩擦损失,同时又要保持所要求的马力和扭矩特性。高增压... 详细信息

本文介绍了在载重卡车的增压柴油机上既要获得良好的燃油经济性,又要具有极好的驱动能力的一些技术解决方法和研制过程。为获得良好的燃油经济性,首先要考虑怎样减少发动机本身的摩擦损失,同时又要保持所要求的马力和扭矩特性。高增压的小型发动机具有这种可能性,但它又有一些严重的缺点。最近研制了一台新型的较高增压、中冷柴油机。在这台发动机上采用了许多新技术,如发动机工作客积的最佳化;可变控制的惯性进气系统,带有超后弯叶轮增压器;电子控制的燃油喷射定时器(电子定时控制)以及闸门式排气制动系统等等。新近研制的卡车安装了这种发动机,该发动机的燃油经济性比原来发动机提高20～30％。为获得柴油机良好的燃油经济性,新研制的较高增压小型涡轮增压发动机带有一个空气——空气式中冷器和一个电子定时控制的燃油喷射装置。它主要是通过减少自身摩擦损失来获得良好的燃油经济性。这种发动机的燃烧系统是以日野微混合系统(HMMS)为基础的,这种系统的燃烧周期非常短,这是由于气缸内空气的高紊流能量促进了燃油微粒与空气的混合。同时,在这台发动机上还采用了可变控制的惯性进气系统,带有超后弯叶轮的涡轮增压器以及闸门式排气制动系统等等。本论文阐述了这个基本设计方案及其细节。

关键词：发动机高增压工作容积卡车后弯叶轮涡轮增压器摩擦损失摩阻损失重型车辆燃油经济性

Execution System for User Programs in Kernel Mode

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通讯和计算机（中英文版） 2013年第10期10卷 1307-1311页

作者： takashi sato Yoshikatsu Tada Department of Information System Fundamentals Graduate School of Information Systems The University of Electro-Communications Tokyo 182-8585 Japan

We developed a system that allows user programs to run in kernel mode. In our proposed system, source codes of the user programs require no modifications to be executed in kernel mode. Furthermore, developers can improve user programs in kernel mode to access kernel resources directly. Developers can therefore focus on such improvements, because other parts of the source code can be left untouched. In this paper, we present a design and implementation of our system and show how the cp command was accelerated with our system. We modified the cp command to call a function that copies buffer caches directly between files. This modification requires only a few lines, and the experimental results show that the new cp reduces the time required to copy files on the memory file system by about 26%.

关键词：内核模式用户程序执行系统文件复制直接访问高速缓存文件系统源代码