Article
Biochemistry & Molecular Biology
Jan Krijt, Jana Frydlova, Iuliia Gurieva, Petr Prikryl, Martin Bajecny, Andrea U. Steinbicker, Martin Vokurka, Jaroslav Truksa
Summary: The study reveals a complex interaction between Matriptase-2 and Hemojuvelin, where the absence of one protein leads to decreased content of the other. Feeding experimental diets to mice can affect iron metabolism, and feeding iron-deficient diet can trigger stress erythropoiesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Sho Sato, Siyu Liu, Akihiko Goto, Tomoki Yoneyama, Koki Okita, Syunsuke Yamamoto, Hideki Hirabayashi, Shinji Iwasaki, Hiroyuki Kusuhara
Summary: Transferrin receptor (TfR)-mediated transcytosis is a promising drug delivery pathway for treating central nervous system diseases. However, the optimal drug profile for efficient delivery to the brain via TfR has not been fully understood, especially considering species-related differences. To address this, an advanced physiologically based pharmacokinetic (PBPK) model was developed to simulate the trans- and intracellular disposition of anti-TfR antibodies in the brain. The model was successfully calibrated using data from rats, monkeys, and human TfR knock-in (hTfR-KI) mice, and sensitivity analysis revealed important factors for optimal brain delivery.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Chemistry, Multidisciplinary
Rebecca Faresjo, Hanna Lindberg, Stefan Stahl, John Lofblom, Stina Syvanen, Dag Sehlin
Summary: Affibodies targeting amyloid-beta (A beta) show potential as therapeutic and diagnostic agents in Alzheimer's disease. Fusion of Affibodies with the blood-brain barrier shuttle scFv8D3 improves brain delivery and retention. However, the specificity of affibodies for A beta deposits needs further confirmation.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Laura Rue, Tom Jaspers, Isabelle M. S. Degors, Sam Noppen, Dominique Schols, Bart De Strooper, Maarten Dewilde
Summary: The blood-brain barrier poses a challenge for the treatment of neurological diseases. Researchers have discovered two nanobodies that can bind to both human and cynomolgus transferrin receptors, potentially increasing the brain permeability of therapeutic drugs.
Article
Instruments & Instrumentation
Bettina Gabold, Friederike Adams, Sophie Brameyer, Kirsten Jung, Christian L. Ried, Thomas Merdan, Olivia M. Merkel
Summary: Nose-to-brain delivery is a promising alternative for delivering high molecular weight drugs. Transferrin-decorated chitosan nanoparticles can efficiently cross the nasal epithelial barrier and enhance cellular uptake in tumor cells. This approach offers a potential improvement in drug bioavailability through targeted ligand binding.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Renata Ribeiro de Castro, Flavia Almada do Carmo, Claudia Martins, Alice Simon, Valeria Pereira de Sousa, Carlos Rangel Rodrigues, Lucio Mendes Cabral, Bruno Sarmento
Summary: This study developed polymeric nanoparticles loaded with clofazimine and functionalized with a transferrin receptor-binding peptide for efficient drug delivery to the central nervous system for tuberculosis treatment. The functionalized nanoparticles showed superior cell interaction and permeability, indicating the efficacy of the functionalization strategy.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Neurosciences
Veronica T. Cheli, Diara A. Santiago Gonzalez, Rensheng Wan, Shaina L. Rosenblum, Giancarlo E. Denaroso, Christina G. Angeliu, Zachary Smith, Congying Wang, Pablo M. Paez
Summary: By disrupting the expression of the Tf receptor gene in oligodendrocyte progenitor cells, researchers found that the Tf cycle is uniquely important for the development and function of oligodendrocytes. Deleting the Tfr gene resulted in impaired iron absorption and hypomyelination in mice. The Tf cycle plays a crucial role in iron homeostasis and energy production in oligodendrocyte progenitor cells.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Chemistry, Medicinal
William M. Pardridge, Tom Chou
Summary: This study examines the receptor-mediated transcytosis of monoclonal antibodies targeting transferrin receptor or insulin receptor at the blood-brain barrier, using mathematical models to analyze and predict the transport process. The optimal rates of receptor association with the targeted antibodies are highlighted as crucial factors determining the efficiency of transcytosis.
Article
Biophysics
Tianzhi Yang, Skye Curtis, Albert Bai, Abby Young, Derek Derosier, Shannon Ripley, Shuhua Bai
Summary: This study aimed to knock down P-glycoprotein (P-gp) expression through CRISPR-Cas9 gene-editing and establish a viable cell line for evaluating the pharmacoresistance of therapeutic agents mediated by efflux. A cationic liposome was prepared as a smart bomb by conjugating with a peptide-based targeting ligand that specifically bound to transferrin receptors at the blood-brain barrier (BBB), and then formed a nanocomplex with the P-gp knockdown CRISPR/Cas9 plasmid. The cell-friendly CRISPR/Cas9 targeted liposomes successfully knocked down the P-gp transporters and increased P-gp associated ATP activities in the transfected cells. Functional studies of the knocked down cells showed enhanced accumulation of rhodamine 123 and increased cytotoxic sensitivity to doxorubicin.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Engineering, Biomedical
Marie Piantino, Fiona Louis, Yukari Shigemoto-Mogami, Kimiko Kitamura, Kaoru Sato, Tomoko Yamaguchi, Kenji Kawabata, Syunsuke Yamamoto, Shinji Iwasaki, Hideki Hirabayashi, Michiya Matsusaki
Summary: This study compared HBEC and hiPS-BMEC and found that hiPS-BMEC had higher expressions of transporters and tight junction proteins, resembling the BBB more accurately. Additionally, it confirmed the presence of transferrin receptor in hiPS-BMEC and its functionality in the RMT pathway.
MATERIALS TODAY BIO
(2022)
Article
Neurosciences
Rebecca Faresjo, Gillian Bonvicini, Xiaotian T. Fang, Ximena Aguilar, Dag Sehlin, Stina Syvanen
Summary: This study compared the brain pharmacokinetics of two BBB-penetrating bispecific antibodies of different sizes and found that the smaller non-IgG antibody di-scFv3D6-8D3 exhibited faster elimination from blood, lower brain C-max, higher parenchymal-to-capillary concentration ratio, and earlier brain elimination compared to the larger IgG-based bispecific antibody mAb3D6-scFv8D3. The study also indicated that di-scFv3D6-8D3 had lower avidity towards TfR1, potentially contributing to its faster brain delivery.
FLUIDS AND BARRIERS OF THE CNS
(2021)
Article
Chemistry, Medicinal
William M. Pardridge
Summary: Biologic drugs are large molecule pharmaceuticals that cannot cross the blood-brain barrier. They can be re-engineered for BBB transport as IgG fusion proteins. The kinetics of BBB transport can be quantified with mathematical models.
Article
Endocrinology & Metabolism
Yanqi Ma, Qikai Zhou, Pingping Zhao, Xiaoyu Lv, Caixia Gong, Jie Gao, Jingfang Liu
Summary: This study observed the glycation degree and sites of transferrin induced by different concentrations of high glucose, and investigated the effects of high glucose on human renal tubular epithelial cells. The results showed that the glycation degree of transferrin increased with high glucose stimulation, but the binding capacity with iron decreased. Additionally, in vitro stimulation of HK-2 cells with AGE-Tf led to increased cell apoptosis, decreased antioxidant capacity, and downregulated TfR expression levels.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Hematology
O. Yaw Addo, Zuguo Mei, Eldad A. Hod, Maria Elena Jefferds, Andrea J. Sharma, Rafael C. Flores-Ayala, Steven L. Spitalnik, Gary M. Brittenham
Summary: The study aimed to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals, specifically focusing on women aged 20 to 49 years. Results indicated that serum ferritin levels below a certain threshold were associated with iron-deficient erythropoiesis, as seen through the levels of soluble transferrin receptor and hemoglobin.
Article
Biochemistry & Molecular Biology
Jenny Jin, Kenji Schorpp, Daniel Samaga, Kristian Unger, Kamyar Hadian, Brent R. Stockwell
Summary: A machine learning approach combined with staining techniques was developed to unbiasedly classify different cell death mechanisms based on specific cell features, providing a novel analytic framework.
ACS CHEMICAL BIOLOGY
(2022)
Letter
Allergy
W. Fukushima, A. Honda, R. Murayama, Y. Matsuda, K. Tsuji, T. Hayashi, T. Sawahara, S. Ozawa, Y. Okamot, H. Takano
ALLERGOLOGIA ET IMMUNOPATHOLOGIA
(2015)
Article
Pharmacology & Pharmacy
Akiko Honda, Kenshi Tsuji, Yugo Matsuda, Tomohiro Hayashi, Wataru Fukushima, Takahiro Sawahara, Hitomi Kudo, Rumiko Murayama, Hirohisa Takano
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2015)
Article
Toxicology
Akiko Honda, Takahiro Sawahara, Tomohiro Hayashi, Kenshi Tsuji, Wataru Fukushima, Mizuki Oishi, Gaku Kitamura, Hitomi Kudo, Sho Ito, Seiichi Yoshida, Takamichi Ichinose, Kayo Ueda, Hirohisa Takano
JOURNAL OF APPLIED TOXICOLOGY
(2017)
Article
Environmental Sciences
Pratiti H. Chowdhury, Gaku Kitamura, Akiko Honda, Takahiro Sawahara, Tomohiro Hayashi, Wataru Fukushima, Hitomi Kudo, Sho Ito, Seiichi Yoshida, Takamichi Ichinose, Kayo Ueda, Hirohisa Takano
ENVIRONMENTAL TOXICOLOGY
(2017)
Article
Environmental Sciences
Akiko Honda, Pratiti Home Chowdhury, Sho Ito, Hitoshi Okano, Toshinori Onishi, Yusuke Kawaryu, Kayo Ueda, Hirohisa Takano
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2017)
Article
Pharmacology & Pharmacy
Akiko Honda, Wataru Fukushima, Mizuki Oishi, Kenshi Tsuji, Takahiro Sawahara, Tomohiro Hayashi, Hitomi Kudo, Yuji Kashima, Katsuyuki Takahashi, Hideki Sasaki, Kayo Ueda, Hirohisa Takano
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2017)
Article
Environmental Sciences
Pratiti Home Chowdhury, Hitoshi Okano, Akiko Honda, Hitomi Kudou, Gaku Kitamura, Sho Ito, Kayo Ueda, Hirohisa Takano
ENVIRONMENTAL POLLUTION
(2018)
Article
Environmental Sciences
Toshinori Onishi, Akiko Honda, Michitaka Tanaka, Pratiti H. Chowdhury, Hitoshi Okano, Tomoaki Okuda, Daiki Shishido, Yoshihiro Terui, Shuichi Hasegawa, Takayuki Kameda, Susumu Tohno, Masahiko Hayashi, Chiharu Nishita-Hara, Keiichiro Hara, Kozo Inoue, Makoto Yasuda, Shigeru Hirano, Hirohisa Takano
ENVIRONMENTAL POLLUTION
(2018)
Article
Ophthalmology
Shinsuke Nakamura, Masamitsu Shimazawa, Yuki Inoue, Shinsuke Takata, Yasushi Ito, Kazuhiro Tsuruma, Tsunehiko Ikeda, Akiko Honda, Masahiko Satoh, Hideaki Hara
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2014)
Article
Toxicology
Akiko Honda, Yugo Matsuda, Rumiko Murayama, Kenshi Tsuji, Masataka Nishikawa, Eiko Koike, Seiichi Yoshida, Takamichi Ichinose, Hirohisa Takano
JOURNAL OF APPLIED TOXICOLOGY
(2014)
Article
Toxicology
Shunji Imai, Maki Tokumoto, Yasuyuki Fujiwara, Akiko Honda, Tatsuya Hasegawa, Yoshiyuki Seko, Jin-Yong Lee, Hisamitsu Nagase, Masahiko Satoh
JOURNAL OF TOXICOLOGICAL SCIENCES
(2014)
Article
Toxicology
Minoru Yoshida, Akiko Honda, Chiho Watanabe, Masahiko Satoh, Akira Yasutake
JOURNAL OF TOXICOLOGICAL SCIENCES
(2014)
Article
Toxicology
Akiko Honda, Rumiko Murayama, Yugo Matsuda, Kenshi Tsuji, Takahiro Sawahara, Wataru Fukushima, Tomohiro Hayashi, Akinori Shimada, Hirohisa Takano
TOXICOLOGY MECHANISMS AND METHODS
(2014)
Article
Environmental Sciences
Tomoya Sagawa, Takahiro Tsujikawa, Akiko Honda, Natsuko Miyasaka, Michitaka Tanaka, Takashi Kida, Koichi Hasegawa, Tomoaki Okuda, Yutaka Kawahito, Hirohisa Takano
Summary: The study used a mouse model exposed to particulate matter to evaluate the increased expression of ACE2 and TMPRSS2 in the lungs, which are required for the entry of SARS-CoV-2. The findings suggest that particulate matter may enhance the expression of these proteins in alveolar type 2 cells and macrophages, potentially making them targets for SARS-CoV-2. This research provides insight into how air pollution could influence the severity of COVID-19 infection.
ENVIRONMENTAL RESEARCH
(2021)
Article
Environmental Sciences
Akiko Honda, Tomoaki Okuda, Megumi Nagao, Natsuko Miyasaka, Michitaka Tanaka, Hirohisa Takano
Summary: PM2.5 collected through cyclonic separation induces stronger biological responses and higher levels of inflammatory reactions compared to PM2.5 collected through traditional filtration methods. This suggests that cyclonic separation can provide a more reliable evaluation of the health effects of ambient PM2.5.
ENVIRONMENTAL RESEARCH
(2021)
