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Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway

Acta Pharmacologica Sinica 2004年第5期25卷 149-156页

作者： Shin-ichi TASHIRO,Satoshi onodera,takashi IKEJIMA Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan Department of Clinical and Biomedical Sciences Showa College of Pharmaceutical Sciences Tokyo 194-8543 Japan China-Japan Research Institute of Medical and Pharmaceutical Sciences Shenyang Pharmaceutical University Shenyang 110016 China prof

AIM: To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability oforidonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualizedby phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel *** activity was assayed using fluorometric protease assay. ICAD, Bcl-2, and Bax proteins expression weredetected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA andincreased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase(ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activationand down-regulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). However, pretreatment with an inhibitor of poly (ADP-ribose) polymerase (PARP), 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. Inaddition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducerBax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION:Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation ofcaspase-3/ICAD pathway.

关键词： oridonin HeLa cells apoptosis caspase 3 caspases bcl-2 genes bax genes Western blotting

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Evodiamine induces tumor cell death through different pathways: apoptosis and necrosis

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Acta Pharmacologica Sinica 2004年第1期 85-91页

作者： Shin-ichi TASHIRO,Satoshi onodera,takashi IKEJIMA Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan China-Japan Research Institute of Medical and Pharmaceutical Sciences Department of Clinical and Biomedical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan

AIM: To study the different death pathways in human cervical cancer HeLa and melanoma A375-S2 cells Initiated by evodiamine. METHODS: Viability of evodiamine-induced HeLa and A375-S2 cells was measured by MTT assay. Apoptotic cells with condensed or fragmented nuclei were visualized by Hoechst 33258 staining. Nucleoso mal DNA fragmentation was assayed by agarose gel electrophoresis. Proportion of cell death through apoptotic and necrotic pathways was determined by LDH activity-based cytotoxicity assays. Cell cycle distribution was observed by flow cytometry. RESULTS: Evodiamine induced HeLa and A375-S2 cell death dose- and time-dependently. Caspase-3 and -8 were activated in apoptosis induced by evodiamine 15μmol/L. However, over 24- h

关键词： evodiamine apoptosis necrosis caspases MAP kinase signaling system

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Diosgenin induces apoptosis in HeLa cells via activation of caspase pathway

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Acta Pharmacologica Sinica 2004年第8期 103-108页

作者： Shin-ichi TASHIRO,Satoshi onodera,takashi IKEJIMA China Department of Clinical and Biomedical Sciences Department of Clinical and Biomedical Sciences China-Japan Research Institute of Medical and Pharmaceutical Sciences Showa Pharmaceutical University Tokyo 194-8543 Japan Showa Pharmaceutical University Tokyo 194-8543 Japan Shenyang Pharmaceutical University

AIM: To investigate the mechanism of diosgenin-induced HeLa cell apoptosis. METHODS: HeLa cell growth was measured by MTT method. Apoptosis was detected by electron microscopy and agarose gel electrophoresis. Ratio of apoptotic cells was measured by APO-BRDU kit. Cell cycle distribution and changes of mitochondrial membrane potential were monitored by flow cytometry. Caspase activities were assayed by caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of mitochondrial Bcl-2 expression. RESULTS: Diosgenin inhibited HeLa cell growth. HeLa cells treated with diosgenin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-9 inhibitor (Ac-AAVALPAVLLALLAPLEHD-CHO), and caspase-3 inhibitor (z-DEVD-fmk) partially prevented diosgenin-induced apoptosis, but not caspase-8 inhibitor (z-IETD-fmk) and caspase-10 inhibitor (z-AEVD-fmk). Diosgenin caused reduction of mitochondrial membrane po

关键词： diosgenin apoptosis caspases mitochondria HeLa cells

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Norcantharidin induces apoptosis in HeLa cells through caspase, MAPK, and mitochondrial pathways

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Acta Pharmacologica Sinica 2004年第11期 118-124页

作者： Shin-ichi TASHIRO,Satoshi onodera,takashi IKEJIMA Department of Pharmacology Department of Pharmacology Department of Clinical and Biomedical Sciences Shenyang Pharmaceutical University Shenyang 110016 China Shenyang Pharmaceutical University Shenyang 110016 China Showa Pharmaceutical University Tokyo 19-8543 Japan

AIM: To investigate the mechanism of norcantharidin (NCTD)-induced HeLa cell apoptosis. METHODS: HeLa cell growth inhibition was measured by MTT method. Apoptosis was detected by Hoechst 33258 staining and agarose gel electrophoresis. Caspase activities were assayed using caspase apoptosis detection kit. Western blot analysis was used to evaluate the level of ICAD, ERK/p-ERK, JNK/p-JNK, and Bcl-XL/Bax expression. RESULTS: Norcantharidin inhibited HeLa cell growth in a time- and dose-dependent manner. HeLa cells treated with norcantharidin showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. Caspase family inhibitor (z-VAD-fmk), caspase-8, -9 inhibitor (z-IETD-fmk, Ac-LEHD-CHO, respectively) and caspase-3 inhibitor (z-DEVD-fmk) partially prevent norcantharidin-induced apoptosis, but initiator caspase-1 inhibitor (Ac-YVAD-fmk) did not. The activities of caspase-3, -8, and -9 were up-regulated after norcantharidin treatment. Furthermore, NCTD-induced activat

关键词： norcantharidin HeLa cells apoptosis caspases Bcl-2 family MAP kinase signaling system

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Some Hybrid Systems of Chiral Schiff Base Zn(II) Complexes and Photochromic Spiropyrans for Environmental Ion Sensing

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American Journal of Analytical Chemistry 2014年第12期5卷 751-765页

作者： Takatomo Miura takashi onodera Shinya Endo Atsuo Yamazaki takashiro Akitsu Department of Chemistry Faculty of Science Tokyo University of Science Tokyo Japan

This is a review article including our recent results and some previous photo functional hybrid system having potential applications for environmental ion sensing. We have prepared several new and known chiral Schiff base Zn(II) complexes and measured (and also calculated) absorption and fluorescence spectra for sole complexes. After assembling hybrid systems with 1,3,3-trime- thylindolino-6’-nitrobenzopyrylospiran (SP) in methanol solutions, we measured spectral changes before and after alternate irradiation of UV and visible light. Intensity of fluorescence spectra for pale yellow Zn(II) complexes (λem = 450 nm, λex = 270 and 360 nm) was quenched by colorless SP (λem = 533 nm, λex = 612 nm). After UV light irradiation to form purple merocyanine (MC), photoisomerization resulted in changes of the intensity of absorption spectra as well as fluorescence spectra. Thus the hybrid systems could successfully act as molecular logic circuit by input (excitation by light) and output (intensity of fluorescence peaks). Moreover, we investigated concentration dependence of doped Zn(II) and Cu(II) ions to confirm quenching of intensity of fluorescence peaks by Zn(II) and Cu(II) MC complexes for metal ion sensing in solutions.

关键词： Zinc(II) Complexes Spiropyran Chirality Fluorescence Ion Sensing

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Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3382-3385页

作者： takashi Ono Radiation Oncology Faculty of MedicineYamagata UniversityYamagata 990-9585Japan

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal *** focuses on the importance of early detection of esophageal cancer,including recurrence or secondary malignancy after chemoradiotherapy(CRT).Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane,while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and *** these treatments are potentially curative,they are more invasive than endoscopic ***-stage esophageal cancer is often asymptomatic and difficult to *** periodic endoscopy is *** less burdensome tests exist,including liquid biopsy and urinary biomarkers,these have not yet been widely used in clinical *** detection is important after radical CRT because the local recurrence rate is higher than that after ***,endoscopic resection or photodynamic therapy is indicated if detected in the early stages,and positive results have been *** detection of esophageal cancer is *** is the main diagnostic method;however,new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

关键词： Esophageal neoplasms Screening Endoscopy Prognosis Endoscopic mucosal resection Endoscopic submucosal dissection Photodynamic therapy

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Field induced Chern insulating states in twisted monolayer–bilayer graphene

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Chinese Physics B 2024年第6期33卷 69-73页

作者：王政文韩英卓 Kenji Watanabe takashi Taniguchi 姜宇航毛金海 School of Physical Science and CAS Center for Excellence in Topological Quantum Computation University of Chinese Academy of SciencesBeijing 100049China College of Materials Science and Optoelectronic Technology Center of Materials Science and Optoelectronics EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China Advanced Materials Laboratory National Institute for Materials ScienceTsukuba 305-0044Japan

Unraveling the mechanism underlying topological phases, notably the Chern insulators(Ch Is) in strong correlated systems at the microscopy scale, has captivated significant research interest. Nonetheless, Ch Is harboring topological information have not always manifested themselves, owing to the constraints imposed by displacement fields in certain experimental configurations. In this study, we employ density-tuned scanning tunneling microscopy(DT-STM) to investigate the Ch Is in twisted monolayer–bilayer graphene(t MBG). At zero magnetic field, we observe correlated metallic *** under a magnetic field, a metal–insulator transition happens and an integer Ch I is formed emanating from the filling index s = 3 with a Chern number C = 1. Our results underscore the pivotal role of magnetic fields as a powerful probe for elucidating topological phases in twisted Van der Waals heterostructures.

关键词： Chern insulators strong correlation effects two-dimensional van der Waals heterostructure density-tuned scanning tunneling microscopy(DT-STM)

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New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

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World Journal of Orthopedics 2024年第3期15卷 302-309页

作者： takashi Noguchi Akio Sakamoto Kensaku Kakehi Shuichi Matsuda Department of Orthopaedic Surgery Graduate School of MedicineKyoto UniversityKyoto 606-8507Japan

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis *** phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection *** adjuvant method to remove or resolve the residual crystals during the operation is *** SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the *** resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was *** the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot *** resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s *** The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

关键词： Tumoral calcinosis Adjuvant therapy Bicarbonate Ringer’s solution Surgery Case report

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α,β-Dehydroamino Acid Synthesis through Proline-Catalyzed Aldol Condensation with a Glycine Schiff Base

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Precision Chemistry 2024年第1期2卷 14-20页

作者： Jun Sawamura Daikan Ieiri Ryo Yazaki takashi Ohshima Graduate School of Pharmaceutical Sciences Kyushu UniversityFukuoka 812-8582Japan

A general protocol for the synthesis ofα,β-dehydroamino acids and their peptides was *** efficiently catalyzed an aldol condensation reaction of a glycine Schiff base with a variety of *** hydroxy group on the benzophenone imine was crucial for high Z/E selectivity and further transimination for protecting group-freeα,β-dehydroamino *** elongation of both the C-and N-terminals highlighted the usefulness of our present protocol.

关键词： α β-dehydroamino acid peptide proline aldol condensation glycine Schiff base transimination

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CHARACTERISTICS OF PRION,BOVINE SPONGIFORM ENCEPHALOPATHY PATHOGEN,GENE KNOCKOUT COWS

CHARACTERISTICS OF PRION,BOVINE SPONGIFORM ENCEPHALOPATHY PA...

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中国畜牧兽医学会动物繁殖学分会第十五届学术研讨会

作者： Noboru MANABE Ichiro ONOYAMA Yasufumi GOTO takashi onodera Yasuhiro YOSHIKAWA Yutaka SENDAI Yoshito AOYAGI Animal Resource Science Center and Research Center for Food Safety The University of Tokyo

Prion(Pr) protein plays a pivotal role in the infection of bovine spongiform encephalopathy(BSE). The aim of the present research was to make Pr gene knockout(KO) cows,which lack Pr mRNA or protein,and to reveal their characteristics for estimating the *** were successful in production of Pr gene homo KO Japanese Black cows using leading-edge genetic engineering techniques,cell culture techniques and animal reproductive techniques(somatic cell nuclear transfer:SCNT and so on) as follows:Firstly,hetero Pr gene was knockouted in fibroblastic cells derived from bovine *** somatic cell nucleus with hetero Pr gene KO was transferred into oocyte without germinal vesicle(GV).After activation and in vitro culture,somatic cell nucleus of the somatic cell nuclear cloning embryo at blastocyst stage was pulled out and transferred into oocyte without GV to make homo Pr gene KO *** homo Pr gene KO embryos were transferred in to the uterus. In the present meeting,we would like to show and discuss the procedure to make Pr gene homo KO cows and their usefulness,and to propose the importance of animal biotechnological techniques on food safety and public ***,detailed data of Pr distribution in organs of somatic cell nuclear cloning Japanese Black cows (used as controls) will be demonstrated as follows:A sandwich enzyme linked immunosorbent assay(ELISA) revealed that high levels of Pr proteinrotein(9.0-11.0μg/g wet tissue) was demonstrated in brain of somatic cell nuclear transfer-cows(wild-type control animals).Lower levels of Pr proteinrotein were shown in other organs as follows in decreasing order:skeletal muscles(longissimus,iliocostalis thoracis,splenius,femoris biceps,triceps brachii,longissimus thoracis and omotransversarius muscles),intestinal tracts(ileum,jejunum,duodenum,colon and cecum) and tongue(apex,posterior,anterior and radix areas)(approx.5.0-to 31.0-fold less Pr proteinrotein than the brain).Immunohistochemical analyses showed t

关键词： Bovine spongiform encephalopathy(BSE) Japanese black cow Prion(Pr) protein Pr gene homo knockout(KO)

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