Development of a renal carbon monoxide delivery system for treatment of lethal rhabdomyolysis

• Project/Area Number: 18H02604
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kumamoto University
• Principal Investigator: Maruyama Toru 熊本大学, 大学院生命科学研究部(薬), 教授 (90423657)
• Co-Investigator(Kenkyū-buntansha): 渡邊 博志 熊本大学, 大学院生命科学研究部(薬), 准教授 (70398220) ; 前田 仁志 熊本大学, 大学院生命科学研究部(薬), 助教 (80791483)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 一酸化炭素 / バイオミメティック / 赤血球 / 細胞療法 / 急性腎障害 / COデリバリーシステム / 横紋筋融解症 / アルブミン創薬プラットフォーム / 災害医療 / アルブミン融合技術 / アルブミン / ヘムオキシゲナーセ-1

Outline of Final Research Achievements

Severe rhabdomyolysis, which occurs in disasters and accidents, often complicates with acute kidney injury (AKI), leading to a fatal case of multiple organ failure. Thus, the development of drugs that improve the prognosis is eagerly desired. “Carbon monoxide (CO)” from renal heme oxygenase (HO)-1, which is activated by rhabdomyolysis-induced AKI, plays an important role as a stress response defense mechanism in kidney. In the present study, to develop a new therapeutic agent for rhabdomyolysis-induced AKI, we created a CO-releasing nano-formulation, that can be used in various situations such as disasters, using hemoglobin as a CO-carrier. We further loaded a renal-oriented peptide to the formulation and developed a "renal CO delivery system". Finally, we demonstrated its preventive and therapeutic effect using rhabdomyolysis model animals.

Academic Significance and Societal Importance of the Research Achievements

“クラッシュ症候群”は外傷性横紋筋融解症の一つである。阪神大震災や福知山列車事故など、本邦のように災害や事故が多発する状況下では、横紋筋融解症AKIに対する治療法の開発は重要かつ急務であるが、医療機関だけでなく、災害現場でも使用可能で予後を改善する有効な治療法は存在せず、現行では輸液や頻回な血液透析等の対処療法に留まっている。申請者は、熊本地震に被災した際に、この点を強く実感した。本邦のような災害・事故多発国において、横紋筋融解症の予後改善を企図とした薬剤を開発する意義は高い。

Research Products

• [Journal Article] Effects of Uremic Toxins on the Binding of Aripiprazole to Human Serum Albumin (2021)
  • Author(s): Koji Nishi, Keiki Sakurama, Hiroshi Watanabe, Toru Maruyama, Keishi Yamasaki, Masaki Otagiri
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 44 Issue: 3 Pages: 437-441
  • DOI: 10.1248/bpb.b20-00929
  • NAID: 130007993459
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2021-03-01
  • Peer Reviewed / Open Access
• [Journal Article] Cysteinylated albumin as a potential biomarker for the progression of kidney disease in patients with type 2 diabetes (2021)
  • Author(s): Imafuku T, Watanabe H, Oniki K, Yoshida A, Kato H, Nakano T, Tokumaru K, Fujita I, Arimura N, Maeda H, Sakamoto Y, Kondo N, Morita A, Saruwatari J, Tanaka M, Matsushita K, Wada T, Fukagawa M, Otagiri M, Fitzgerald ML, Jinnouchi H, Maruyama T.
  • Journal Title: Diabetes Care Volume: 26 Issue: 6 Pages: e115-e117
  • DOI: 10.2337/dc20-3003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An acute phase protein alfa1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action (2021)
  • Author(s): Hiroshi Watanabe*,#, Rui Fujimura*, Yuto Hiramoto*, Ryota Murata, Kento Nishida, Jing Bi, Tadashi Imafuku, Hisakazu Komori, Hitoshi Maeda, Ayumi Mukunoki, Toru Takeo, Naomi Nakagata, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama# *equal contribution; #equal correspondence
  • Journal Title: Sci Rep. Volume: 12;11(1) Issue: 1 Pages: 7953-7953
  • DOI: 10.1038/s41598-021-87217-8
  • Peer Reviewed / Open Access
• [Journal Article] Reduction-responsive and multi-drug deliverable albumin nanoparticles: an antitumor drug to Abraxane_ against human pancreatic tumor-bearing mice (2021)
  • Author(s): Naoki Hirakawa, Yu Ishima, Ryo Kinoshita, Ryuto Nakano, Victor Tuan Giam Chuang, Hidenori Ando, Taro Shimizu, Keiichiro Okuhira, Toru Maruyama, Masaki Otagiri, Tatsuhiro Ishida
  • Journal Title: ACS Applied Bio Materials Volume: 4,5 Pages: 4302-4309
  • DOI: 10.1016/j.lfs.2020.118991
  • Peer Reviewed / Open Access
• [Journal Article] Sacran, a sulfated polysaccharide, suppresses the absorption of lipids and modulates the intestinal flora in non-alcoholic steatohepatitis model rats (2021)
  • Author(s): Miwa Goto, Kazuo Azuma, Hidetoshi Arima, Shinichiro Kaneko, Taishi Higashi, Keiichi Motoyama, Akihiro Michihara, Takae Shimizu, Daisuke Kadowaki, Toru Maruyama, Masaki Otagiri, Daisuke Iohara, Fumitoshi Hirayama, Makoto Anraku
  • Journal Title: Life Sci Volume: 1;268 Issue: 1 Pages: 118991-118991
  • DOI: 10.1111/1744-9987.13500
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Cinacalcet on the Redox Status of Albumin in Secondary Hyperparathyroidism Patients Receiving Hemodialysis (2020)
  • Author(s): Imafuku Tadashi、Tanaka Motoko、Tokunaga Koki、Miyamura Shigeyuki、Kato Hiromasa、Tanaka Shoma、Nakano Takehiro、Hirata Kenshiro、Kadowaki Daisuke、Maeda Hitoshi、Matsushita Kazutaka、Otagiri Masaki、Komaba Hirotaka、Fukagawa Masafumi、Watanabe Hiroshi、Maruyama Toru
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 43 Issue: 10 Pages: 1583-1590
  • DOI: 10.1248/bpb.b20-00472
  • NAID: 130007920876
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2020-10-01
  • Peer Reviewed / Open Access
• [Journal Article] Drug Delivery System for Refractory Cancer Therapy <i>via</i> an Endogenous Albumin Transport System (2020)
  • Author(s): Ishima Yu、Maruyama Toru、Otagiri Masaki、Ishida Tatsuhiro
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 68 Issue: 7 Pages: 583-588
  • DOI: 10.1248/cpb.c20-00026
  • NAID: 130007867325
  • ISSN: 0009-2363, 1347-5223
  • Year and Date: 2020-07-01
  • Peer Reviewed / Open Access
• [Journal Article] Strategy of Drug Development Based on the Bioactive Gas-carrying Capacity of Hemoglobin (2020)
  • Author(s): Taguchi K, Matsumoto K, Maruyama T, Otagiri M.
  • Journal Title: YAKUGAKU ZASSHI Volume: 140 Issue: 2 Pages: 141-146
  • DOI: 10.1248/yakushi.19-00187-1
  • NAID: 130007793385
  • ISSN: 0031-6903, 1347-5231
  • Year and Date: 2020-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Repeated Administration of Kupffer Cells-Targeting Nanoantioxidant Ameliorates Liver Fibrosis in an Experimental Mouse Model (2020)
  • Author(s): Maeda H, Minayoshi Y, Ichimizu S, Mizuta Y, Nagasaki T, Matsusaka K, Oshiro S, Oniki K, Saruwatari J, Ishima Y, Watanabe H, Otagiri M, Maruyama T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 43 Issue: 1 Pages: 93-101
  • DOI: 10.1248/bpb.b19-00599
  • NAID: 130007779193
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2020-01-01
  • Peer Reviewed / Open Access
• [Journal Article] Effects of surface-deacetylated chitin nanofibers on non-alcoholic steatohepatitis model rats and their gut microbiota (2020)
  • Author(s): Goto Miwa、Iohara Daisuke、Michihara Akihiro、Ifuku Shinsuke、Azuma Kazuo、Kadowaki Daisuke、Maruyama Toru、Otagiri Masaki、Hirayama Fumitoshi、Anraku Makoto
  • Journal Title: International Journal of Biological Macromolecules Volume: 164 Pages: 659-666
  • DOI: 10.1016/j.ijbiomac.2020.07.184
  • Peer Reviewed / Open Access
• [Journal Article] Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice (2020)
  • Author(s): Kento Nishida*, Hiroshi Watanabe*,#, Masako Miyahisa, Yuto Hiramoto, Hiroto Nosaki, Rui Fujimura, Hitoshi Maeda, Masaki Otagiri, Toru Maruyama# *equal contribution; #equal correspondence
  • Journal Title: Sci Rep Volume: 26;10(1): Issue: 1 Pages: 20635-20635
  • DOI: 10.1038/s41598-020-75025-5
  • Peer Reviewed / Open Access
• [Journal Article] The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models (2020)
  • Author(s): Abdullah-Al-Shoeb Mohammad、Sasaki Kenta、Kikutani Saori、Namba Nanami、Ueno Keiichi、Kondo Yuki、Maeda Hitoshi、Maruyama Toru、Irie Tetsumi、Ishitsuka Yoichi
  • Journal Title: Antioxidants Volume: 9 Issue: 10 Pages: 965-965
  • DOI: 10.3390/antiox9100965
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of the Interaction of Daptomycin With Site II on Human Serum Albumin (2020)
  • Author(s): Yamasaki Keishi、Sakurama Keiki、Nishi Koji、Watanabe Hiroshi、Maruyama Toru、Seo Hakaru、Otagiri Masaki、Taguchi Kazuaki
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 109 Issue: 9 Pages: 2919-2924
  • DOI: 10.1016/j.xphs.2020.06.011
  • Peer Reviewed / Open Access
• [Journal Article] Indoxyl sulfate contributes to adipose tissue inflammation through the activation of NADPH oxidase (2020)
  • Author(s): Shoma Tanaka*, Hiroshi Watanabe*,#, Takehiro Nakano, Tadashi Imafuku, Hiromasa Kato, Kai Tokumaru, Nanaka Arimura, Yuki Enoki, Hitoshi Maeda, Motoko Tanaka, Kazutaka Matsushita, Masafumi Fukagawa, Toru Maruyama# *equal contribution; #equal correspondence
  • Journal Title: Toxins (Basel) Volume: 5;12(8): Issue: 8 Pages: 502-502
  • DOI: 10.3390/toxins12080502
  • Peer Reviewed / Open Access
• [Journal Article] Development of a long acting FGF21 analogue-albumin fusion protein and its anti-diabetic effects (2020)
  • Author(s): Hiroshi Watanabe*,#, Masako Miyahisa*, Mayuko Chikamatsu*, Kento Nishida, Yuki Minayoshi, Mei Takano, Shota Ichimizu, Yoshihiro Kobashigawa, Hiroshi Morioka, Hitoshi Maeda, Toru Maruyama# *equal contribution; #equal correspondence
  • Journal Title: J Control Release Volume: 10;324: Pages: 522-531
  • DOI: 10.1016/j.jconrel.2020.05.036
  • Peer Reviewed / Open Access
• [Journal Article] A synthetic retinoic acid receptor agonist Am80 ameliorates renal fibrosis via inducing the production of alpha-1-acid glycoprotein (2020)
  • Author(s): Watanabe Hiroshi、Bi Jing、Murata Ryota、Fujimura Rui、Nishida Kento、Imafuku Tadashi、Nakamura Yuka、Maeda Hitoshi、Mukunoki Ayumi、Takeo Toru、Nakagata Naomi、Kurauchi Yuki、Katsuki Hiroshi、Tanaka Motoko、Matsushita Kazutaka、Fukagawa Masafumi、Maruyama Toru
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 11424-11424
  • DOI: 10.1038/s41598-020-68337-z
  • Peer Reviewed / Open Access
• [Journal Article] Advanced oxidation protein products contribute to renal tubulopathy via perturbation of renal fatty acids (2020)
  • Author(s): Imafuku, T., Watanabe, H., Satoh, T., Matsuzaka, T., Inazumi, T., Kato, H., Tanaka, S., Nakamura, Y., Nakano, T., Tokumaru, K., Maeda, H., Tanaka, M., Matsushita, K., Tsuchiya, S., Sugimoto, Y., Shimano, H., Fukagawa, M., and Maruyama, T.
  • Journal Title: Kidney360 Volume: 1 Issue: 8 Pages: 781-796
  • DOI: 10.34067/kid.0000772019
  • Peer Reviewed / Open Access
• [Journal Article] Changes in redox state of albumin before and after kidney transplantation in patients with end-stage renal disease (2020)
  • Author(s): Ryota Tanaka, Tadashi Imafuku, Yosuke Suzuki, Kento Nishida, Kotaro Matsusaka, Toshitaka Shin, Yuhki Sato, Yu Ishima, Hiroshi Watanabe, Hiromitsu Mimata, Toru Maruyama, Hiroki Itoh
  • Journal Title: Clin Biochem Volume: 81 Pages: 20-26
  • DOI: 10.1016/j.clinbiochem.2020.04.010
  • Peer Reviewed / Open Access
• [Journal Article] In vivo evaluation of drug dialyzability in a rat model of hemodialysis. (2020)
  • Author(s): Fukunaga M, Kadowaki D, Mori M, Hagiwara S, Narita Y, Saruwatari J, Tanaka R, Watanabe H, Yamasaki K, Taguchi K, Ito H, Maruyama T, Otagiri M, Hirata S.
  • Journal Title: PLoS One Volume: 15 Issue: 6 Pages: 20-26
  • DOI: 10.1371/journal.pone.0233925
  • Peer Reviewed / Open Access
• [Journal Article] Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor Against Pathophysiological Decline of Lung Function (2020)
  • Author(s): Fujikawa H, Sakamoto Y, Masuda N, Oniki K, Kamei S, Nohara H, Nakashima R, Maruta K, Kawakami T, Eto Y, Takahashi N, Takeo T, Nakagata N, Watanabe H, Otake K, Ogata Y, Tomioka NH, Hosoyamada M, Takada T, Ueno-Shuto K , Suico MA, Kai H, Saruwatari J, Shuto T.
  • Journal Title: Antioxidants Volume: 9 Issue: 5 Pages: 387-387
  • DOI: 10.3390/antiox9050387
  • Peer Reviewed / Open Access
• [Journal Article] α1-acid glycoprotein attenuates adriamycin-induced nephropathy via CD163 expressing macrophages induction (2020)
  • Author(s): Fujimura Rui、Watanabe Hiroshi、Nishida Kento、Fujiwara Yukio、Koga Tomoaki、Bi Jing、Imafuku Tadashi、Kobayashi Kazuki、Komori Hisakazu、Miyahisa Masako、Maeda Hitoshi、Tanaka Motoko、Matsushita Kazutaka、Wada Takashi、Fukagawa Masafumi、Maruyama Toru
  • Journal Title: Kidney360 Volume: ー Issue: 5 Pages: 343-353
  • DOI: 10.34067/kid.0000782019
  • Peer Reviewed / Open Access
• [Journal Article] α1-acid glycoprotein attenuates adriamycin-induced nephropathy via CD163 expressing macrophages induction (2020)
  • Author(s): Fujimura, Watanabe H, Nishida K, Fujiwara Y, Koga T, Bi J, Imafuku T, Kobayashi K, Komori H, Miyahisa M, Maeda H, Tanaka M, Matsushita K, Wada T, Fukagawa M, Maruyama T
  • Journal Title: Kidney360 Volume: －
  • Peer Reviewed / Open Access
• [Journal Article] Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice (2020)
  • Author(s): Nishida K, Watanabe H, Miyahisa M, Hiramoto Y, Nosaki H, Fujimura R, Maeda H, Otagiri M, and Maruyama M
  • Journal Title: Sci Rep Volume: －
  • Peer Reviewed / Open Access
• [Journal Article] The DsbA-L gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties (2020)
  • Author(s): Oniki K, Nohara H, Nakashima R, Obata Y, Muto N, Sakamoto Y, Ueno-Shuto K, Imafuku T, Ishima Y, Watanabe H, Maruyama T, Otake K, Ogata Y, Suico MA, Kai H, Shuto T, and Saruwatari J
  • Journal Title: Sci Rep Volume: －
  • NAID: 120007146111
  • Peer Reviewed / Open Access
• [Journal Article] Evasion of the accelerated blood clearance phenomenon by polysarcosine coating of liposomes (2020)
  • Author(s): Son K, Ueda M, Taguchi K, Maruyama T, Takeoka S, Ito Y.
  • Journal Title: J Control Release Volume: －
  • Peer Reviewed / Open Access
• [Journal Article] Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions (2020)
  • Author(s): Oniki K, Kawakami T, Nakashima A, Miyata K, Watanabe T, Fujikawa H, Nakashima R, Nasu A, Eto Y, Takahashi N, Nohara H, Suico MA, Kotani S, Obata Y, Sakamoto Y, Seguchi Y, Saruwatari J, Imafuku T, Watanabe H, Maruyama T, Kai H, Shuto T
  • Journal Title: Sci Rep Volume: －
  • Peer Reviewed / Open Access
• [Journal Article] Carbon monoxide rescues the developmental lethality of experimental rat models of rhabdomyolysis-induced acute kidney injury (2020)
  • Author(s): Taguchi K, Ogaki S, Nagasaki T, Yanagisawa H, Nishida K, Maeda H, Enoki Y, Matsumoto K, Sekijima H, Ooi K, Ishima Y, Watanabe H, Fukagawa M, Otagiri M, Maruyama T
  • Journal Title: J Pharmacol Exp Ther Volume: 372(3) Issue: 3 Pages: 355-365
  • DOI: 10.1124/jpet.119.262485
  • Peer Reviewed / Open Access
• [Journal Article] Effect of Serum Parathyroid Hormone on Tacrolimus Therapy in Kidney Transplant Patients: A Possible Biomarker for a Tacrolimus Dosage Schedule (2019)
  • Author(s): Hirata K, Watanabe H, Toyoda M, Sugimoto R, Ikegami K, Imafuku T, Matsuzaka K, Ichimizu S, Maeda H, Uekihara S, Jingami S, Maruyama T.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 42 Issue: 5 Pages: 786-791
  • DOI: 10.1248/bpb.b18-00976
  • NAID: 130007641447
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2019-05-01
  • Peer Reviewed / Open Access
• [Journal Article] S-Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics (2019)
  • Author(s): Ishima Yu、Watanabe Kaori、Chuang Victor T. G.、Takeda Iyo、Kuroda Teruo、Ogawa Wakano、Watanabe Hiroshi、Iwao Yasunori、Ishida Tatsuhiro、Otagiri Masaki、Maruyama Toru
  • Journal Title: FASEB BioAdvances Volume: 1 Issue: 3 Pages: 137-150
  • DOI: 10.1096/fba.1018
  • NAID: 120007153321
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Albumin domain mutants with enhanced Aβ binding capacity identified by phage display analysis for application in various peripheral Aβ elimination approaches of Alzheimer's disease treatment (2019)
  • Author(s): Ishima Yu、Mimono Ai、Tuan Giam Chuang Victor、Fukuda Tetsuya、Kusumoto Kohshi、Okuhira Keiichiro、Suwa Yoshiaki、Watanabe Hiroshi、Ishida Tatsuhiro、Morioka Hiroshi、Maruyama Toru、Otagiri Masaki
  • Journal Title: IUBMB Life Volume: 72 Issue: 4 Pages: 641-651
  • DOI: 10.1002/iub.2203
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Unique Hydrolysis of an Ester-Type Prodrug of Levodopa in Human Plasma: Relay-Type Role Sharing between Alpha-1 Acid Glycoprotein and Human Serum Albumin (2019)
  • Author(s): Kono K, Fukuchi Y, Okawa H, Nunoya KI, Imawaka H, Watanabe H, Maruyama T.
  • Journal Title: Mol Pharm. Volume: 16(10) Issue: 10 Pages: 4131-4138
  • DOI: 10.1021/acs.molpharmaceut.9b00435
  • Peer Reviewed / Open Access
• [Journal Article] α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents. (2019)
  • Author(s): Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, Giam Chuang VT, Nishi K, Yamasaki K, Otagiri M, Watanabe H, Maruyama T
  • Journal Title: J Pharm Sci. Volume: 108(11) Issue: 11 Pages: 3592-3598
  • DOI: 10.1016/j.xphs.2019.07.002
  • Peer Reviewed
• [Journal Article] Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape (2019)
  • Author(s): Ichimizu Shota、Watanabe Hiroshi、Maeda Hitoshi、Hamasaki Keisuke、Ikegami Komei、Chuang Victor Tuan Giam、Kinoshita Ryo、Nishida Kento、Shimizu Taro、Ishima Yu、Ishida Tatsuhiro、Seki Takahiro、Katsuki Hiroshi、Futaki Shiroh、Otagiri Masaki、Maruyama Toru
  • Journal Title: Journal of Controlled Release Volume: 304 Pages: 156-163
  • DOI: 10.1016/j.jconrel.2019.05.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distribution of Polysulfide in Human Biological Fluids and Their Association with Amylase and Sperm Activities (2019)
  • Author(s): Ikeda Mayumi、Ishima Yu、Chuang Victor T. G.、Sakai Maki、Osafune Hiroki、Ando Hidenori、Shimizu Taro、Okuhira Keiichiro、Watanabe Hiroshi、Maruyama Toru、Otagiri Masaki、Akaike Takaaki、Ishida Tatsuhiro
  • Journal Title: Molecules Volume: 24 Issue: 9 Pages: 1689-1689
  • DOI: 10.3390/molecules24091689
  • NAID: 120006995454
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A downstream molecule of 1,25-dihydroxyvitamin D3, alpha-1-acid glycoprotein, protects against mouse model of renal fibrosis (2018)
  • Author(s): Bi J, Watanabe H, Fujimura R, Nishida K, Nakamura R, Oshiro S, Imafuku T, Komori H, Miyahisa M, Tanaka M, Matsushita K, Maruyama T
  • Journal Title: Sci Rep Volume: 26 Issue: 1 Pages: 17329-17329
  • DOI: 10.1038/s41598-018-35339-x
  • Peer Reviewed / Open Access
• [Journal Article] Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity. (2018)
  • Author(s): Taguchi K, Nagao S, Maeda H, Yanagisawa H, Sakai H, Yamasaki K, Wakayama T, Watanabe H, Otagiri M, Maruyama T
  • Journal Title: Drug Deliv Volume: 25 Issue: 1 Pages: 1266-1274
  • DOI: 10.1080/10717544.2018.1477860
  • Peer Reviewed / Open Access
• [Journal Article] Dual therapeutic effects of an albumin-based nitric oxide donor on two experimental models of chronic kidney disease (2018)
  • Author(s): Oshiro S, Ishima Y, Maeda H, Honda N, Bi J, Kinoshita R, Ikeda M, Iwao Y, Imafuku T, Nishida K, Miyamura S, Watanabe H, Otagiri M, Maruyama T
  • Journal Title: J Pharm Sci Volume: 107 Issue: 3 Pages: 848-855
  • DOI: 10.1016/j.xphs.2017.10.023
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Co-treatment of EPR enhancer increases the anti-tumor effect of nab-paclitaxel against pancreatic cancer；EPR増強剤の併用は膵臓癌に対するnab-パクリタキセルの治療効果を増強する (2019)
  • Author(s): 丸山 徹、木下 遼、前田 仁志、渡邊 博志、小田切 優樹、異島 優
  • Organizer: 第30回 日本消化器癌発生学会総会
  • Int'l Joint Research / Invited
• [Presentation] Albumin fusion protein: next generation of albumin preparation (2019)
  • Author(s): Toru Maruyama, Masaki Otagiri
  • Organizer: The 17th International Symposium on Blood Substitutes & Oxygen Therapeutics (XVII-ISBS-2019)
  • Int'l Joint Research
• [Presentation] 腎線維化病態に対するバイオミメティックな一酸化窒素デリバリーシステム の有用性評価 (2018)
  • Author(s): 大城 俊、異島 優、渡邊 博志、前田 仁志、深川 雅史、 小田切 優樹、丸山 徹
  • Organizer: 日本薬剤学会 第33年会
• [Presentation] クラッシュ症候群誘発急性腎障害に対する一酸化炭素デリバリーの有用性評価 (2018)
  • Author(s): 永崎 太清、柳澤 洋輝、大柿 滋、渡邊 博志、深川 雅史、丸山 徹
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] 急性腎障害に対する一酸化炭素デリバリーシステムの有用性評価 (2018)
  • Author(s): 永崎 太清、柳澤 洋輝、田口 和明、西田 健人、前田 仁志、酒井 宏水、渡邊 博志、深川 雅史、小田切 優樹、丸山 徹
  • Organizer: 第25回日本血液代替物学会
• [Presentation] バイオミメティックな一酸化炭素デリバリーは脂肪肝の再生不全を改善する (2018)
  • Author(s): 和田 直樹、柳澤 洋輝、田口 和明、前田 仁志、木下 学、酒井 宏水、渡邊 博志、小田切 優樹、丸山 徹
  • Organizer: 第25回日本血液代替物学会
• [Presentation] Albumin based nitric oxide delivery system ameliorates the kidney fibrosis in unilateral ureteral obstruction-treated mice (2018)
  • Author(s): Shun Oshiro, Yu Ishima, Hitoshi Maeda, Hiroshi Watanabe , Masaki Otagiri, Toru Maruyama
  • Organizer: 米国薬学会 American Association of Pharmaceutical Scientists (AAPS)
  • Int'l Joint Research
• [Book] Molecular mechanism of muscle wasting in CKD. Recent advances of sarcopenia and frailty in CKD (2020)
  • Author(s): Watanabe H, Enoki Y, Maruyama T
  • Publisher: Springer
  • ISBN: 9789811523656
• [Patent(Industrial Property Rights)] 効率的な抗原の細胞内送達とアジュバント活性を有する化合物を有効成分とする薬剤 (2020)
  • Inventor(s): 2020
  • Industrial Property Rights Holder: 2020
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-020192
  • Filing Date: 2020
• [Patent(Industrial Property Rights)] 薬物送達用担体 (2018)
  • Inventor(s): 丸山徹
  • Industrial Property Rights Holder: 丸山徹
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas