Article
Hematology
Yuto Nakajima, Masahiro Takeyama, Akihisa Oda, Naruto Shimonishi, Keiji Nogami
Summary: This study aimed to identify mutated FVIII proteins that increase FVIIIa cofactor activity in the 1811-1818 region. The FVIII-K1813A mutant showed a lower affinity for FIXa binding but a significantly higher speed in FX activation compared to the wild-type. In coagulation assays, the addition of FVIII-K1813A displayed a clotting potential similar to the wild-type.
Article
Hematology
James R. Fuller, Kevin E. Knockenhauer, Nina C. Leksa, Robert T. Peters, Joseph D. Batchelor
Summary: The interaction between FVIII and VWF is crucial for hemostasis, and mutations affecting this interaction can lead to von Willebrand disease type 2N. Understanding the structural basis of this interaction is important for developing therapies for bleeding disorders like hemophilia A. The structure of the bioengineered FVIII molecule BIVV001 provides insights into the FVIII-VWF complex formation and sheds light on mutations associated with hemophilia A and VWD type 2N.
Article
Biology
Jeong Pil Han, Dong Woo Song, Jeong Hyeon Lee, Geon Seong Lee, Su Cheong Yeom
Summary: Innovative gene therapy is advancing towards functional restoration, with hemophilia being a representative genetic disorder. A novel mouse model of hemophilia A has been developed in this study, which could be utilized for future gene correction preclinical trials.
Article
Biochemistry & Molecular Biology
Junzheng Wu, Hang Zhang, Tong Lian, Yaling Ding, Chunlei Song, Dekuan Li, Liheng Wu, Tao Lei, Hong Liang
Summary: A novel B-domain-deleted recombinant FVIII was developed in this study without the use of animal or human serum-derived components. rFVIII promoted the generation of activated factor X and downstream thrombin, and exhibited ideal binding affinity to human von Willebrand factor. In vitro and in vivo experiments demonstrated the satisfactory efficacy and potency of rFVIII, suggesting its potential as an effective treatment strategy for FVIII deficiency.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yung-Tsung Kao, Yen-Ting Chen, Hueng-Chuen Fan, Tung-Chou Tsai, Shin-Nan Cheng, Ping-Shan Lai, Jen-Kun Chen, Chuan-Mu Chen
Summary: A novel nonviral gene therapy strategy utilizing DPPC-Fe3O4 to deliver BDD-FVIII plasmid was developed and successfully improved bleeding disorder in FVIII KO mice. The results suggest the potential of this approach for treating hemophilia A patients in clinical settings, with no observed adverse effects after treatment.
Article
Hematology
Kuniyoshi Mizumachi, Yuto Nakajima, Naruto Shimonishi, Shoko Furukawa, Kenichi Ogiwara, Masahiro Takeyama, Keiji Nogami
Summary: Hybrid FVIII proteins containing porcine FVIII A2 and/or C2 domain(s) can avoid neutralization and may support effective therapy in patients with congenital haemophilia A and inhibitor antibodies.
Article
Multidisciplinary Sciences
Tiago J. S. Lopes, Ricardo Rios, Tatiane Nogueira, Rodrigo F. Mello
Summary: This study investigated the pathogenesis of hemophilia A by creating a residue interaction network, revealing important properties related to disease severity. The properties derived from the network were found to be in close agreement with in vitro and clinical reports, indicating that the detailed map of the FVIII protein accurately captures its biological properties.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Giang N. Nguyen, Jonathan R. Lindgren, Maria C. Seleme, Samita Kafle, Catherine B. Zander, X. Long Zheng, Denise E. Sabatino
Summary: This study investigates the biochemical and functional characteristics of various variants of human factor VIII (hFVIII) in vitro and in vivo after gene therapy using adeno-associated virus (AAV). The results demonstrate that the furin cleavage site and the a3 cleavage site variants significantly improve hFVIII secretion and have comparable specific activity to the existing variants, without inducing immune responses.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
Amber Vander Kooi, Shuaishuai Wang, Meng-Ni Fan, Alex Chen, Junping Zhang, Chun-Yu Chen, Xiaohe Cai, Barbara A. Konkle, Weidong Xiao, Lei Li, Carol H. Miao
Summary: The N-glycosylation of FVIII has a significant impact on its immunogenicity, as shown in this study. Gene mutations were introduced to eliminate glycosylation at potential sites, and it was found that FVIII activity remained stable while immune responses varied. A specific glycopeptide epitope surrounding one of the glycosylation sites was identified and characterized for its activation of T cells.
Article
Biology
Aditi Gupta, Sadna Budhu, Kelly Fitzgerald, Rachel Giese, Adam O. Michel, Aliya Holland, Luis Felipe Campesato, Jacques van Snick, Catherine Uyttenhove, Gerd Ritter, Jedd D. Wolchok, Taha Merghoub
Summary: The study highlights the potential of TGF beta as a target in cancer treatment, showing that myeloid/dendritic cells are main sources of TGF beta 1 and TGF beta 3 in stroma-poor tumors. Targeting isoform-specific TGF beta leads to enhanced CD8 T cell function and improved tumor control when compared to pan-TGF beta inhibition. Combining TGF beta inhibition with immune checkpoint blockade results in a more effective tumor control by shifting the local immune environment to favor tumor suppression.
COMMUNICATIONS BIOLOGY
(2021)
Article
Optics
Ying Liu, Qiushi Wang, Yidi Liu, Ying Wang, Haixia Qiu, Dan Zhu, Ying Gu, Defu Chen
Summary: This study investigated the therapeutic enhancement of vascular-targeted photodynamic therapy (V-PDT) in combination with an optical clearing agent (OCA) for port wine stain (PWS) treatment. The effects of V-PDT with OCA on blood flow and vessel size of skin microvasculature were quantitatively demonstrated in a rodent model. The combination of OCA and V-PDT resulted in significant vascular damage and shows promising potential for treating vascular-related diseases, including PWS.
JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES
(2023)
Article
Hematology
Joseph S. Gish, Lexi Jarvis, Kenneth C. Childers, Shaun C. Peters, Connor S. Garrels, Ian W. Smith, H. Trent Spencer, Christopher B. Doering, Pete Lollar, P. Clint Spiegel
Summary: The study reveals the structure of a therapeutically active fVIII construct complexed with an anti-C1 domain inhibitor, shedding light on the interaction between the antibody and fVIII, which may lead to the development of more effective and safe fVIII replacement therapies.
Article
Biochemistry & Molecular Biology
Yulia Solomonov, Nurit Hadad, Rachel Levy
Summary: The present study aimed to determine whether there is a binding between cPLA(2)alpha-C2 domain and p47(Phox)-PX in mouse macrophages, to further support the role of cPLA(2)alpha in oxidase regulation also in mouse phagocytes.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Chemistry, Applied
Qian Wang, Hao Jiang, Hongli Zhang, Weiqiao Lu, Xiao Wang, Wenfeng Xu, Jia Li, Youjing Lv, Guoyun Li, Chao Cai, Guangli Yu
Summary: This study proposes a novel strategy of antibody-beta-glucan conjugates (AGC) to enhance the antitumor immune response to immune checkpoint blockade (ICB) therapy. AGC demonstrated powerful tumor suppression and promoted interaction between tumor cells and dendritic cells (DCs), thereby enhancing immunotherapeutic benefits.
CARBOHYDRATE POLYMERS
(2024)
Article
Oncology
Yuedi Wang, Yiyuan Gao, Congyi Niu, Bo Wang, Shushu Zhao, Gils Roex, Jiawen Qian, Jingbo Qie, Lin Chen, Chenhe Yi, Sebastien Anguille, Jie Liu, Feifei Luo, Yiwei Chu
Summary: Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in hematological malignancies. This study introduces a novel strategy of promoting CAR clustering to enhance the antitumor activity of CAR-T cells. By using a hinge region containing cysteine residues, CAR-T cells exhibited larger diameter of CAR clusters and improved antigen-specific tumor lysis.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Hematology
N. Church, L. Leong, Y. Katterle, H. -F. Ulbrich, I. Noerenberg, S. Kitchen, L. A. Michaels
Article
Hematology
L. Tang, L. Leong, D. Sim, E. Ho, J. -M. Gu, D. Schneider, R. I. Feldman, F. Monteclaro, H. Jiang, J. E. Murphy
Article
Hematology
J-M. Gu, P. Ramsey, V. Evans, L. Tang, H. Apeler, L. Leong, J. E. Murphy, V. Laux, T. Myles
Article
Hematology
Lilley Leong, Irina N. Chernysh, Yifan Xu, Derek Sim, Chandrasekaran Nagaswami, Zelda de Lange, Sofia Kosolapova, Adam Cuker, Katalin Kauser, John W. Weisel
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2017)
Article
Ophthalmology
L Leong, AS Menko, GB Grunwald
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2000)