start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=20 article-no= start-page=3307 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2022 dt-pub=20221021 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect en-subtitle= kn-subtitle= en-abstract= kn-abstract=BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, "AB-type Lactosome (AB-Lac)" loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the "molecular glue" effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. en-copyright= kn-copyright= en-aut-name=FithroniAbdul Basith en-aut-sei=Fithroni en-aut-mei=Abdul Basith kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=UjiHirotaka en-aut-sei=Uji en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IshimotoManabu en-aut-sei=Ishimoto en-aut-mei=Manabu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=2 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Material Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=4 en-affil=Fukushima SiC Applied Engineering Inc. kn-affil= affil-num=5 en-affil=Collaborative Research Center for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=boron neutron capture therapy (BNCT) kn-keyword=boron neutron capture therapy (BNCT) en-keyword=biologically self-degradable amphipathic polymer (Lactosome) kn-keyword=biologically self-degradable amphipathic polymer (Lactosome) en-keyword=hydrophobic boron cluster kn-keyword=hydrophobic boron cluster en-keyword=carborane isomers or o-carborane alkylated derivatives kn-keyword=carborane isomers or o-carborane alkylated derivatives en-keyword=molecular glue effect kn-keyword=molecular glue effect END start-ver=1.4 cd-journal=joma no-vol=48 cd-vols= no-issue=4 article-no= start-page=768 end-page=781 dt-received= dt-revised= dt-accepted= dt-pub-year=2007 dt-pub=200704 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis en-subtitle= kn-subtitle= en-abstract= kn-abstract=C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta 2-glycoprotein I (beta 2GPI), implicating oxLDL/P2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta 2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/R2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta 2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of adierosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta 2GPI complexes correlated with total cholesterol and hemoglobin Al c. Thus, the generation of CRP/oxLDL/beta 2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/R2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis. en-copyright= kn-copyright= en-aut-name=TabuchiMasako en-aut-sei=Tabuchi en-aut-mei=Masako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=InoueKatsumi en-aut-sei=Inoue en-aut-mei=Katsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=Usui-KataokaHitomi en-aut-sei=Usui-Kataoka en-aut-mei=Hitomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TeramotoMisako en-aut-sei=Teramoto en-aut-mei=Misako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakasugiKoji en-aut-sei=Takasugi en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamamuraMasahiro en-aut-sei=Yamamura en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=AndoKenji en-aut-sei=Ando en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NishidaKeiichiro en-aut-sei=Nishida en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KasaharaJunko en-aut-sei=Kasahara en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KumeNoriaki en-aut-sei=Kume en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=LopezLuis R. en-aut-sei=Lopez en-aut-mei=Luis R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=MitsudoKazuaki en-aut-sei=Mitsudo en-aut-mei=Kazuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=NobuyoshiMasakiyo en-aut-sei=Nobuyoshi en-aut-mei=Masakiyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KitaToru en-aut-sei=Kita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Pathology, Kokura Memorial Hospital kn-affil= affil-num=3 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Pathology, Kokura Memorial Hospital kn-affil= affil-num=6 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Cardiology, Kokura Memorial Hospital kn-affil= affil-num=10 en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Internal Medicine, Okayama Central Hospital kn-affil= affil-num=12 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=13 en-affil=Corgenix, Inc. kn-affil= affil-num=14 en-affil=Department of Cardiovascular Medicine, Kurashiki Central Hospital kn-affil= affil-num=15 en-affil=Department of Cardiology, Kokura Memorial Hospital kn-affil= affil-num=16 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=17 en-affil=Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine kn-affil= affil-num=18 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=19 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=beta 2-glycoprotein I kn-keyword=beta 2-glycoprotein I en-keyword=oxidized LDL/beta 2-glycoprotein I complexes kn-keyword=oxidized LDL/beta 2-glycoprotein I complexes en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=oxidized LDL kn-keyword=oxidized LDL END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=4 article-no= start-page=716 end-page=726 dt-received= dt-revised= dt-accepted= dt-pub-year=2003 dt-pub=200304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Circulating oxidized LDL forms complexes with β(2)-glycoprotein I: implication as an atherogenic autoantigen en-subtitle= kn-subtitle= en-abstract= kn-abstract=beta(2)-glycoprotein I (beta(2)-GPI) is a major antigen for antiphospholipid antibodies (Abs, aPL) present in patients with antiphospholipid syndrome (APS). We recently reported (I. Lipid Res., 42: 697, 200 1; J Lipid Res., 43: 1486, 2002) that beta(2)-GPI specifically binds to Cu2+-oxidized LDL (oxLDL) and that the beta(2)-GPI ligands are omega-carboxylated 7-ketocholesteryl esters. In the present study, we demonstrate that oxLDL forms stable and nondissociable complexes with beta(2)-GPI in serum, and that high serum levels of the complexes are associated with arterial thrombosis in APS. A conjugated ketone function at the 7-position of cholesterol as well as the omega-carboxyl function of the beta(2)-GPI ligands was necessary for beta(2)-GPI binding. The ligand-mediated noncovalent interaction of beta(2)-GPI and oxLDL undergoes a temperature- and time-dependent conversion to much more stable but readily dissociable complexes in vitro at neutral pH. In contrast, stable and nondissociable beta(2)-GPI-oxLDL complexes were frequently detected in sera from patients with APS and/or systemic lupus erythematodes. Both the presence Of beta(2)-GPI-oxLDL complexes and IgG Abs recognizing these complexes were strongly associated with arterial thrombosis. Further, these same Abs correlated with IgG immune complexes containing beta(2)-GPI or LDL.jlr Thus, the beta(2)-GPI-oxLDL complexes acting as an autoantigen are closely associated with autoimmune-mediated atherogenesis. en-copyright= kn-copyright= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KishiMakoto en-aut-sei=Kishi en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AtsumiTatsuya en-aut-sei=Atsumi en-aut-mei=Tatsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=BertolacciniMaria L. en-aut-sei=Bertolaccini en-aut-mei=Maria L. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SakairiNobuo en-aut-sei=Sakairi en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YamamotoItaru en-aut-sei=Yamamoto en-aut-mei=Itaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KhamashtaMunther A. en-aut-sei=Khamashta en-aut-mei=Munther A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HughesGraham R. V. en-aut-sei=Hughes en-aut-mei=Graham R. V. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KoikeTakao en-aut-sei=Koike en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=VoelkerDennis R. en-aut-sei=Voelker en-aut-mei=Dennis R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=2 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil=Department of Medicine II, Hokkaido University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London kn-affil= affil-num=5 en-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=6 en-affil=Division of Bioscience, Graduate School of Environment Earth Science, Hokkaido University kn-affil= affil-num=7 en-affil=Department of Immunochemistry, Faculty of Pharmaceutical Science, Okayama University kn-affil= affil-num=8 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=9 en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London kn-affil= affil-num=10 en-affil=Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital London kn-affil= affil-num=11 en-affil=Department of Medicine II, Hokkaido University Graduate School of Medicine kn-affil= affil-num=12 en-affil=Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center kn-affil= affil-num=13 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=antiphospholipid syndrome kn-keyword=antiphospholipid syndrome en-keyword=arterial thrombosis kn-keyword=arterial thrombosis en-keyword=autoantibody kn-keyword=autoantibody END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=9 article-no= start-page=1486 end-page=1495 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=200209 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=ω-Carboxyl variants of 7-ketocholesteryl esters are ligands for β2-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=beta(2)-Glycoprotein I (beta(2)-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that beta(2)-GPI specifically binds to oxidized LDL (oxLDL) and that the beta(2)-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K, E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Welker, and T. Koike. 2001. A specific ligand for beta(2)-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J Lipid Res. 42: 697-709). In the present study, we demonstrate that omega-carboxylated 7-ketocholesteryl esters are critical for beta(2)-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by beta(2)-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of beta(2)-GPI and an anti-beta(2)-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytxidecanoate (13-COOH-7KC), also showed a significant interaction with beta(2)-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with beta(2)-GPI. Thus, omega-carboxyl variants of 7-ketocholesteryl esters can mediate anti-beta(2)-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to beta(2)-GPI interaction with oxLDL. en-copyright= kn-copyright= en-aut-name=LiuQingping en-aut-sei=Liu en-aut-mei=Qingping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=FurukawaJun-ichi en-aut-sei=Furukawa en-aut-mei=Jun-ichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InagakiJunko en-aut-sei=Inagaki en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakairiNobuo en-aut-sei=Sakairi en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=IwadoAkimasa en-aut-sei=Iwado en-aut-mei=Akimasa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=KoikeTakao en-aut-sei=Koike en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=VoelkerDennis R. en-aut-sei=Voelker en-aut-mei=Dennis R. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=2 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil=Division of Bioscience, Graduate School of Environment Earth Science, Hokkaido University kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=5 en-affil=Division of Bioscience, Graduate School of Environment Earth Science, Hokkaido University kn-affil= affil-num=6 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=8 en-affil=Department of Medicine II, Hokkaido University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center kn-affil= affil-num=10 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=antiphospholipid syndrome kn-keyword=antiphospholipid syndrome en-keyword=atherosclerosis kn-keyword=atherosclerosis en-keyword=autoantibody kn-keyword=autoantibody en-keyword=beta(2)-glycoprotein I kn-keyword=beta(2)-glycoprotein I en-keyword=oxidized LDL kn-keyword=oxidized LDL en-keyword=omega-oxidation kn-keyword=omega-oxidation END start-ver=1.4 cd-journal=joma no-vol=110 cd-vols= no-issue= article-no= start-page=1788 end-page=1798 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210430 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Lactosome-Conjugated siRNA Nanoparticles for Photo-Enhanced Gene Silencing in Cancer Cells en-subtitle= kn-subtitle= en-abstract= kn-abstract=The A3B-type Lactosome comprised of poly(sarcosine)3-block-poly(l-lactic acid), a biocompatible and biodegradable polymeric nanomicelle, was reported to accumulate in tumors in?vivo via the enhanced permeability and retention (EPR) effect. Recently, the cellular uptake of Lactosome particles was enhanced through the incorporation of a cell-penetrating peptide (CPP), L7EB1. However, the ability of Lactosome as a drug delivery carrier has not been established. Herein, we have developed a method to conjugate the A3B-type Lactosome with ATP-binding cassette transporter G2 (ABCG2) siRNA for inducing in?vitro apoptosis in the cancer cell lines PANC-1 and NCI-H226. The L7EB1 peptide facilitates the cellular uptake efficiency of Lactosome but does not deliver siRNA into cytosol. To establish the photoinduced cytosolic dispersion of siRNA, a photosensitizer loaded L7EB1-Lactosome was prepared, and the photosensitizer 5,10,15,20-tetra-kis(pentafluorophenyl)porphyrin (TPFPP) showed superiority in photoinduced cytosolic dispersion. We exploited the combined effects of enhanced cellular uptake by L7EB1 and photoinduced endosomal escape by TPFPP to efficiently deliver ABCG2 siRNA into the cytosol for gene silencing. Moreover, the silencing of ABCG2, a protoporphyrin IX (PpIX) transporter, also mediated photoinduced cell death via 5-aminolevulinic acid (ALA)-mediated PpIX accumulated photodynamic therapy (PDT). The synergistic capability of the L7EB1/TPFPP/siRNA-Lactosome complex enabled both gene silencing and PDT. en-copyright= kn-copyright= en-aut-name=LimMelissa Siaw Han en-aut-sei=Lim en-aut-mei=Melissa Siaw Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=NishiyamaYuki en-aut-sei=Nishiyama en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WatanabeKazunori en-aut-sei=Watanabe en-aut-mei=Kazunori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil= kn-affil= affil-num=3 en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Natural Science and Technology, Okayama University kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil= kn-affil= en-keyword=Lactosome kn-keyword=Lactosome en-keyword=ABCG2 kn-keyword=ABCG2 en-keyword=siRNA kn-keyword=siRNA en-keyword=Cancer kn-keyword=Cancer en-keyword=siRNA delivery kn-keyword=siRNA delivery en-keyword=Photodynamic therapy kn-keyword=Photodynamic therapy en-keyword=Polymeric micelle kn-keyword=Polymeric micelle en-keyword=Photosensitizer kn-keyword=Photosensitizer en-keyword=Photochemical internalization kn-keyword=Photochemical internalization END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=2 article-no= start-page=158 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210218 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Novel 89Zr-labeled DDS Device Utilizing Human IgG Variant (scFv): “Lactosome” Nanoparticle-Based Theranostics for PET Imaging and Targeted Therapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=“Theranostics,” a new concept of medical advances featuring a fusion of therapeutic and diagnostic systems, provides promising prospects in personalized medicine, especially cancer. The theranostics system comprises a novel 89Zr-labeled drug delivery system (DDS), derived from the novel biodegradable polymeric micelle, “Lactosome” nanoparticles conjugated with specific shortened IgG variant, and aims to successfully deliver therapeutically effective molecules, such as the apoptosis-inducing small interfering RNA (siRNA) intracellularly while offering simultaneous tumor visualization via PET imaging. A 27 kDa-human single chain variable fragment (scFv) of IgG to establish clinically applicable PET imaging and theranostics in cancer medicine was fabricated to target mesothelin (MSLN), a 40 kDa-differentiation-related cell surface glycoprotein antigen, which is frequently and highly expressed by malignant tumors. This system coupled with the cell penetrating peptide (CPP)-modified and photosensitizer (e.g., 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TPP))-loaded Lactosome particles for photochemical internalized (PCI) driven intracellular siRNA delivery and the combination of 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) offers a promising nano-theranostic-based cancer therapy via its targeted apoptosis-inducing feature. This review focuses on the combined advances in nanotechnology and material sciences utilizing the “89Zr-labeled CPP and TPP-loaded Lactosome particles” and future directions based on important milestones and recent developments in this platform. en-copyright= kn-copyright= en-aut-name=LimMelissa Siaw Han en-aut-sei=Lim en-aut-mei=Melissa Siaw Han kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtsukiTakashi en-aut-sei=Ohtsuki en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakenakaFumiaki en-aut-sei=Takenaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=UjiHirotaka en-aut-sei=Uji en-aut-mei=Hirotaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KobuchiHirotsugu en-aut-sei=Kobuchi en-aut-mei=Hirotsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzekiEiichi en-aut-sei=Ozeki en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University kn-affil= affil-num=3 en-affil=Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Material Chemistry, Graduate School of Engineering, Kyoto University kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Collaborative Research Centre for OMIC, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=10 en-affil=Department of Cell Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=theranostics kn-keyword=theranostics en-keyword=single chain variable fragment of IgG (scFv) kn-keyword=single chain variable fragment of IgG (scFv) en-keyword=drug delivery system (DDS) kn-keyword=drug delivery system (DDS) en-keyword=photodynamic therapy (PDT) kn-keyword=photodynamic therapy (PDT) en-keyword=PET imaging kn-keyword=PET imaging en-keyword=accelerated blood clearance (ABC) kn-keyword=accelerated blood clearance (ABC) en-keyword=cell penetrating peptide (CPP) kn-keyword=cell penetrating peptide (CPP) en-keyword=siRNA kn-keyword=siRNA en-keyword=ATP-binding cassette subfamily G member 2 (ABCG2) kn-keyword=ATP-binding cassette subfamily G member 2 (ABCG2) END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=12 article-no= start-page=e05743 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202012 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Antioxidative attributes of rice bran extracts in ameliorative effects of atherosclerosis-associated risk factors en-subtitle= kn-subtitle= en-abstract= kn-abstract=Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr?/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis. en-copyright= kn-copyright= en-aut-name=XianWen Tan en-aut-sei=Xian en-aut-mei=Wen Tan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LianhuaShen en-aut-sei=Lianhua en-aut-mei=Shen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InagakiJunko en-aut-sei=Inagaki en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=IdeMasahiro en-aut-sei=Ide en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HwangSiaw San en-aut-sei=Hwang en-aut-mei=Siaw San kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Collaborative Research Center for OMIC, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Pathophysiology, Zunyi Medical University kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=School of Chemical Engineering and Science, Faculty of Engineering, Computing and Science, Swinburne University of Technology Sarawak Campus kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Food science kn-keyword=Food science en-keyword=Food analysis kn-keyword=Food analysis en-keyword=Rice bran extract (RBE) kn-keyword=Rice bran extract (RBE) en-keyword=Functional food kn-keyword=Functional food en-keyword=Phytochemicals kn-keyword=Phytochemicals en-keyword=Atherosclerosis kn-keyword=Atherosclerosis en-keyword=Oxidative stress kn-keyword=Oxidative stress en-keyword=Inflammation kn-keyword=Inflammation en-keyword=Antioxidant kn-keyword=Antioxidant en-keyword=Anti-inflammation kn-keyword=Anti-inflammation en-keyword=Oxidized lipoprotein (oxLDL) kn-keyword=Oxidized lipoprotein (oxLDL) END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=6 article-no= start-page=e04114 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200608 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Rapid and specific detection of oxidized LDL/β2GPI complexes via facile lateral flow immunoassay en-subtitle= kn-subtitle= en-abstract= kn-abstract=β2-Glycoprotein I (β2GPI) forms indissociable complex with oxidized LDL (oxLDL) into proatherogenic oxLDL/β2GPI complex through a specific ligand known as 7-ketocholesteryl-9-carboxynonanoate (oxLig-1). Recent discoveries have demonstrated the atherogenicity of these complexes in patients of both systemic and non-systemic autoimmune diseases. Hence, serological level of oxLDL/β2GPI complexes may represent one crucial clinical parameter for disease prognosis of atherosclerosis-related diseases. Herein, we established a simple, specific and rapid gold nanoparticle (GNP) based lateral flow immunoassay (LFIA) to quantify oxLDL/β2GPI complexes from test samples. Specificities of hybridoma cell-derived monoclonal antibodies against antigen, optimal conditions for conjugation of antibody with GNP, and sensitivity of oxLDL/β2GPI LFIA in comparison to an ELISA-based detection method were assessed accordingly. The established oxLDL/β2GPI LFIA was capable of detecting oxLDL/β2GPI specifically without interference from autoantibodies and solitary components of oxLDL/β2GPI present in test samples. A significant correlation (R2 > 0.8) was also obtained with the oxLDL/β2GPI LFIA when compared to the ELISA-based detection. On the whole, the oxLDL/β2GPI LFIA remains advantageous over the oxLDL/β2GPI ELISA. The unnecessary washing step, short developmental and analytical time support facile and rapid detection of oxLDL/β2GPI as opposed to the laborious ELISA system. en-copyright= kn-copyright= en-aut-name=TanXian Wen en-aut-sei=Tan en-aut-mei=Xian Wen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TakenakaFumiaki en-aut-sei=Takenaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakekawaHironori en-aut-sei=Takekawa en-aut-mei=Hironori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Faculty of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=Biological sciences kn-keyword=Biological sciences en-keyword=Antibody kn-keyword=Antibody en-keyword=Biochemistry kn-keyword=Biochemistry en-keyword=Lipid peroxidation kn-keyword=Lipid peroxidation en-keyword=Health sciences kn-keyword=Health sciences en-keyword=Oxidized LDL (oxLDL) kn-keyword=Oxidized LDL (oxLDL) en-keyword=β2-glycoprotein I (β2GPI) kn-keyword=β2-glycoprotein I (β2GPI) en-keyword=OxLDL-β2GPI kn-keyword=OxLDL-β2GPI en-keyword=Lateral flow immunoassay (LFIA) kn-keyword=Lateral flow immunoassay (LFIA) en-keyword=Enzyme-linked immunosorbent assay (ELISA) kn-keyword=Enzyme-linked immunosorbent assay (ELISA) en-keyword=Point-of-care kn-keyword=Point-of-care END start-ver=1.4 cd-journal=joma no-vol=311 cd-vols= no-issue= article-no= start-page=1 end-page=12 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Identification and visualization of oxidized lipids in atherosclerotic plaques by microscopic imaging mass spectrometry-based metabolomics en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and aimsDysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. MethodsWe attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. ResultsBased on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M+H-H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cell, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. ConclusionsTaken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis. en-copyright= kn-copyright= en-aut-name=ShenLianhua en-aut-sei=Shen en-aut-mei=Lianhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoTakushi en-aut-sei=Yamamoto en-aut-mei=Takushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TanXian Wen en-aut-sei=Tan en-aut-mei=Xian Wen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgataKoretsugu en-aut-sei=Ogata en-aut-mei=Koretsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=AndoEiji en-aut-sei=Ando en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OzekiEiichi en-aut-sei=Ozeki en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil=Collaborative Research Center (OMIC) kn-affil= affil-num=2 en-affil=Analytical & Measuring Instruments Division, Shimadzu Corporation kn-affil= affil-num=3 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= affil-num=4 en-affil=Analytical & Measuring Instruments Division, Shimadzu Corporation kn-affil= affil-num=5 en-affil=Analytical & Measuring Instruments Division, Shimadzu Corporation kn-affil= affil-num=6 en-affil=Technology Research Laboratory, Shimadzu Corporation kn-affil= affil-num=7 en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences kn-affil= en-keyword=Atherosclerosis kn-keyword=Atherosclerosis en-keyword=Low-density lipoprotein (LDL) kn-keyword=Low-density lipoprotein (LDL) en-keyword=Oxidized LDL (oxLDL) kn-keyword=Oxidized LDL (oxLDL) en-keyword=Oxidized lipids; kn-keyword=Oxidized lipids; en-keyword=Imaging mass microscopy (iMScope) kn-keyword=Imaging mass microscopy (iMScope) en-keyword=Mass spectroscopy (MS) kn-keyword=Mass spectroscopy (MS) END start-ver=1.4 cd-journal=joma no-vol=70 cd-vols= no-issue=1 article-no= start-page=13 end-page=24 dt-received= dt-revised= dt-accepted= dt-pub-year=2016 dt-pub=201602 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=The Function of β2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts en-subtitle= kn-subtitle= en-abstract= kn-abstract=Intact β2-glycoprotein I (iβ2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked β2GPI (nβ2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of βi 2GPI and nβ2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the in vivo distribution of intravenously injected β2GPI variants in tumor lesions in mice. iβ2GPI was incubated with plasmin to obtain nβ2GPI, and its N-terminal sequence was analyzed. nβ2GPI had at least one other cleavage site upstream of the β2GPI?s domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked β2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested β2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that β2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis. en-copyright= kn-copyright= en-aut-name=Arum Tri Wahyuningsih en-aut-sei=Arum Tri Wahyuningsih en-aut-mei= kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShenLianhua en-aut-sei=Shen en-aut-mei=Lianhua kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KobayashiKazuko en-aut-sei=Kobayashi en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakenakaFumiaki en-aut-sei=Takenaka en-aut-mei=Fumiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HanadaTakahisa en-aut-sei=Hanada en-aut-mei=Takahisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkehiMasaru en-aut-sei=Akehi en-aut-mei=Masaru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AkahoshiAkiya en-aut-sei=Akahoshi en-aut-mei=Akiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OzekiEiichi en-aut-sei=Ozeki en-aut-mei=Eiichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=AndoEiji en-aut-sei=Ando en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Department of Cell Chemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Collaborative Research Center (OMIC), Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Technology Research Laboratory, Shimadzu Corporation affil-num=10 en-affil= kn-affil=Life Science Business Department, Shimadzu Corporation affil-num=11 en-affil= kn-affil=Department of Cell Chemistry , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences en-keyword=β2-glycoprotein I (β2GPI) kn-keyword=β2-glycoprotein I (β2GPI) en-keyword=angiogenesis kn-keyword=angiogenesis en-keyword=vascular endothelial growth factor-A (VEGF-A) kn-keyword=vascular endothelial growth factor-A (VEGF-A) en-keyword=positron emission tomography (PET) imaging kn-keyword=positron emission tomography (PET) imaging END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=1 article-no= start-page=19 end-page=28 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Immunity/inflammation-mediated pathophysiological mechanisms of atherosclerosis and clinical applications of antibody technology kn-title=免疫・炎症が関与する動脈硬化の病態生理学的機序と抗体工学の臨床応用 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name=松浦栄次 kn-aut-sei=松浦 kn-aut-mei=栄次 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　産学官連携センター en-keyword=動脈硬化 kn-keyword=動脈硬化 en-keyword=自己免疫 kn-keyword=自己免疫 en-keyword=感染免疫 kn-keyword=感染免疫 en-keyword=インフラマソーム kn-keyword=インフラマソーム en-keyword=PET イメージング kn-keyword=PET イメージング END start-ver=1.4 cd-journal=joma no-vol=179 cd-vols= no-issue=2 article-no= start-page=457 end-page=462 dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=19940201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anticardiolipin Antibodies Recognize β(2)-Glycoprotein I Structure Altered by Interacting with an Oxygen Modified Solid Phase Surface en-subtitle= kn-subtitle= en-abstract= kn-abstract=Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting the antiphospholipid syndrome (APS) directly bind to beta(2)-glycoprotein I (beta(2)-GPI), which is adsorbed to an oxidized polystyrene surface. Oxygen atoms were introduced on a polystyrene surface by irradiation with electron or gamma-ray radiation. X-ray photoelectron spectroscopy revealed the irradiated surfaces were oxidized to generate C-O and C=O moieties. aCL derived from either APS patients or (NZW x BXSB)F-1 mice bound to beta(2)-GPI coated on the irradiated plates, depending on the radiation dose. Antibody binding to beta(2)-GPI on the irradiated plates was competitively inhibited by simultaneous addition of cardiolipin (CL)-coated latex beads mixed together with beta(2)-GPI but were unaffected by addition of excess beta(2)-GPI, CL micelles, or CL-coated latex beads alone. There was a high correlation between binding values of aCL in sera from 40 APS patients obtained by the anti-beta(2)-GPI enzyme-linked immunosorbent assay (ELISA) using the irradiated plates and those by the beta(2)-GPI-dependent aCL ELISA. Therefore, aCL have specificity for an epitope on beta(2)-GPI. This epitope is expressed by a conformational change occurring when beta(2)-GPI interacts with an oxygen-substituted solid phase surface. en-copyright= kn-copyright= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IgarashiYoshiko en-aut-sei=Igarashi en-aut-mei=Yoshiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YasudaTatsuji en-aut-sei=Yasuda en-aut-mei=Tatsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TriplettDouglas A. en-aut-sei=Triplett en-aut-mei=Douglas A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoikeTakao en-aut-sei=Koike en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil= kn-affil=Department of Cell Chemistry, Institute of Molecular and Cellular Biology, Okayama University School of Medicine affil-num=2 en-affil= kn-affil=Immunology Laboratory, Diagnostics Division, Yamasa Corporation affil-num=3 en-affil= kn-affil=Department of Cell Chemistry, Institute of Molecular and Cellular Biology, Okayama University School of Medicine affil-num=4 en-affil= kn-affil=Department of Pathology, Ball Memorial Hospital affil-num=5 en-affil= kn-affil=Department of Medicine II, Hokkaido University School of Medicine END start-ver=1.4 cd-journal=joma no-vol=64 cd-vols= no-issue=2 article-no= start-page=85 end-page=93 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=201004 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=7-Ketocholesterol Induces Cell Apoptosis by Activation of Nuclear Factor kappa B in Mouse Macrophages en-subtitle= kn-subtitle= en-abstract= kn-abstract=

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC). Cell apoptosis was detected by Annexin V-propidium iodide (PI) staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.

en-copyright= kn-copyright= en-aut-name=HuangZhenyu en-aut-sei=Huang en-aut-mei=Zhenyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=LiuQingping en-aut-sei=Liu en-aut-mei=Qingping kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiWenzhe en-aut-sei=Li en-aut-mei=Wenzhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=WangRenjun en-aut-sei=Wang en-aut-mei=Renjun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=WangDan en-aut-sei=Wang en-aut-mei=Dan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ZhangYingbiao en-aut-sei=Zhang en-aut-mei=Yingbiao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangFan en-aut-sei=Zhang en-aut-mei=Fan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ChiYan en-aut-sei=Chi en-aut-mei=Yan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=LiuZhe en-aut-sei=Liu en-aut-mei=Zhe kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=LiuZibo en-aut-sei=Liu en-aut-mei=Zibo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ZhangQiming en-aut-sei=Zhang en-aut-mei=Qiming kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=2 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=3 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=4 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=5 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=6 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=7 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=8 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=9 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University affil-num=10 en-affil= kn-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=11 en-affil= kn-affil=The No. 10 Senior High School of Dalian Economical and Technological Development Area affil-num=12 en-affil= kn-affil=College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University en-keyword=7-KC kn-keyword=7-KC en-keyword=NF-?B kn-keyword=NF-?B en-keyword=apoptosis kn-keyword=apoptosis en-keyword=atherosclerosis kn-keyword=atherosclerosis END start-ver=1.4 cd-journal=joma no-vol=114 cd-vols= no-issue=1 article-no= start-page=19 end-page=26 dt-received= dt-revised= dt-accepted= dt-pub-year=2002 dt-pub=20020530 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=抗リン脂質抗体症候群 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=松浦栄次 kn-aut-sei=松浦 kn-aut-mei=栄次 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯学総合研究科病態制御科学専攻病態機構学講座（細胞化学分野） en-keyword=抗リン脂質抗体 kn-keyword=抗リン脂質抗体 en-keyword=抗リン脂質抗体症候群 (APS) kn-keyword=抗リン脂質抗体症候群 (APS) en-keyword=β2-グリコプロテインI (β2-GPI) kn-keyword=β2-グリコプロテインI (β2-GPI) en-keyword=動脈血栓 kn-keyword=動脈血栓 en-keyword=酸化LDL kn-keyword=酸化LDL END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=1994 dt-pub=19940325 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=抗カルジオリピン抗体は,酸素原子により修飾された固相表面と相互作用することで変化したβ2-グリコプロテインT構造を認識する kn-title=Anticardiolipin antibodies recognize β(2)-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsuuraEiji en-aut-sei=Matsuura en-aut-mei=Eiji kn-aut-name=松浦栄次 kn-aut-sei=松浦 kn-aut-mei=栄次 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END