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Action Mechanisms of Complementary and Alternative Medicine Therapies for Rheumatoid Arthritis

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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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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Inertial mixing of acoustically levitated droplets for time-lapse protein crystallography

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Droplet 2024年第3期3卷 91-101页

作者： Soichiro Tsujino Yohei sato Shichao Jia Michal W.Kepa Sofia Trampari takashi Tomizaki Division of Biology and Chemistry Paul Scherrer InstitutVilligenSwitzerland Swiss Nanoscience Institute University of BaselBaselSwitzerland Division Scientific Computing Theory and DataPaul Scherrer InstitutVilligenSwitzerland Biozentrum University of BaselBaselSwitzerland Photon Science Division Paul Scherrer InstitutVilligenSwitzerland

Varying the chemical consistency of acoustically levitated droplets opens up an in situ study of chemical and biochemical reactions in small ***,the opti-mization of the mixing time and the minimization of the positional instability induced by solution dispensing are necessary for practical applications such as the study of the transient state of macromolecules crystallography during the ligand binding *** this purpose,we study the inertial mixing in a configuration compatible with the room-temperature crystallography using the acoustic levitation diffractometer,therein solution drops ejected at high velocity collide and coalesce with droplets dis-pensed on acoustically levitated and rotating polymer thin-film sample *** the proposed method,we are able to achieve the mixing time of∼0.1 s for sub-micro and a few microliter *** observed short mixing time is ascribed to the rapid penetration of the solution into the droplets and confirmed by a computational fluid dynamic *** demonstrated accelerated solution mixing is tested in a pilot time-lapse protein crystallography experiment using the acoustic levitation *** results indicate the detection of transient ligand binding state within 2 s after the solution dispensing,suggesting the feasibility of the proposed method for studying slow biochemical processes.

关键词： mixing droplets transient

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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

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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

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

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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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基于转录组测序和网络药理学探究青蒿琥酯干预U87和U251脑胶质瘤细胞的药效差异机制

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药学学报 2023年第6期58卷 1475-1483页

作者：李涛毛霞张彦琼林娜 sato takashi MIZUNO Koji OKUYAMA Katsuki 黄丰云南中医药大学中药学院云南昆明650500 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都八王子市192-0392

青蒿琥酯具有干预脑胶质瘤的潜能,但其药理作用机制尚不明确。本研究首先基于U87和U251两种人源脑胶质瘤细胞,探究青蒿琥酯对细胞活性、增殖和凋亡的影响,发现青蒿琥酯对U87细胞活性和增殖能力的抑制作用强于对U251细胞;Hoechst和TUNEL... 详细信息

青蒿琥酯具有干预脑胶质瘤的潜能,但其药理作用机制尚不明确。本研究首先基于U87和U251两种人源脑胶质瘤细胞,探究青蒿琥酯对细胞活性、增殖和凋亡的影响,发现青蒿琥酯对U87细胞活性和增殖能力的抑制作用强于对U251细胞;Hoechst和TUNEL细胞凋亡染色实验也发现,青蒿琥酯可以显著促进U87细胞的凋亡(P <0.05),而仅大剂量的青蒿琥酯可促进U251细胞的凋亡(P <0.01)。接着,利用青蒿琥酯处理前后的U87和U251细胞裂解液,通过转录组测序检测和差异数据分析,分别获得青蒿琥酯敏感性和非敏感性细胞株的差异基因集以及青蒿琥酯效应相关基因集,旨在挖掘青蒿琥酯对两类细胞敏感性不一的分子机制。通过构建上述各对比组差异基因互作网络和计算网络拓扑特征值,筛选药效相关的关键网络靶标;生物功能富集分析结果表明,上述关键网络靶标显著富集于多条与脑胶质瘤病理环节相关的信号通路,其中,与细胞凋亡相关的转录激活因子4 (ATF4)-DNA损伤诱导转录因子3 (DDIT3)-聚腺苷二磷酸核糖聚合酶1 (PARP1)信号轴的富集显著性最高。分子对接结果也表明,青蒿琥酯与ATF4和DDIT3均具有较好的结合能力。本研究初步揭示了青蒿琥酯干预U87脑胶质瘤细胞的潜能与其抑制肿瘤细胞内异常活化的ATF4-DDIT3-PARP1信号轴,进而诱导细胞凋亡有关;同时也表明了PARP1可能是U251细胞对青蒿琥酯产生耐药的重要靶标。相关结果为青蒿琥酯治疗脑胶质瘤,以及解决脑胶质瘤治疗药物耐药的现状提供了新的实验依据。

关键词：青蒿琥酯脑胶质瘤转录组测序网络药理学药理机制

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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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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)

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...

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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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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

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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

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