Article
Biochemistry & Molecular Biology
Hyun-Dong Cho, Nguyen Thi Thanh Nhan, Christopher Zhou, Kayeman Tu, Tara Nguyen, Nicolene A. Sarich, Kaori H. Yamada
Summary: Excessive VEGF-A signaling induces vascular leakage and angiogenesis. KIF13B-mediated recycling of internalized VEGFR2 through Rab11-positive recycling vesicle regulates endothelial permeability. Inhibition of KIF13B-mediated VEGFR2 trafficking mitigates vascular leakage in models of blinding eye disease wet AMD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Inorganic & Nuclear
Rong Fan, Jing-chen Wei, Bing-Bing Xu, Nan Jin, Xiao-Yi Gong, Xiu-Ying Qin
Summary: A novel chiral oxazoline copper(ii)-based complex {[Cu(C13H14NO3S)(2)]}(2) (Cu-A) was synthesized and found to have superior cytotoxicity and angiogenesis inhibition compared to cis-dichlorodiammineplatinum (DDP). In vitro and in vivo studies demonstrated its significant anti-ovarian cancer effects by inducing apoptosis, suppressing migration and metastasis, and inhibiting angiogenesis through down-regulating the expression of proteins in the VEGF/VEGFR2 pathway and modulating the expression of apoptotic proteins.
DALTON TRANSACTIONS
(2023)
Article
Cardiac & Cardiovascular Systems
Tao Zhuang, Yu Lei, Jin-Jia Chang, Yan-Ping Zhou, Yan Li, Yan-Xiu Li, Yong-Feng Yang, Mei-Hua Chen, Ting Meng, Shi-Man Fu, Li-Hao Huang, Wai-San Cheang, John P. Cooke, Zhi-Hui Dong, Ying-Nan Bai, Cheng-Chao Ruan
Summary: Excess sodium intake leads to hypertension. The study reveals that A(2A) receptor plays a crucial role in lymphangiogenesis and sodium balance in the skin. Activation of A(2A) receptor promotes lymphatic capillary density and decreases blood pressure.
EUROPEAN HEART JOURNAL
(2023)
Article
Oncology
Roze Isono, Hiroshi Tsubamoto, Tomoko Ueda, Yumi Takimoto, Kayo Inoue, Kazuko Sakata, Hiroaki Shibahara, Shin Nishiumi
Summary: The study investigated the effects of itraconazole on membrane-associated lipids, revealing its inhibition of cholesterol trafficking and alteration of phospholipid composition in cancer cells. These alterations may potentiate the anticancer activity of itraconazole.
ANTICANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Feng Yao, Zhen Jin, Xiaohan Lv, Zihan Zheng, Hongqian Gao, Ying Deng, Yizhen Liu, Lifang Chen, Weirong Wang, Jianyu He, Jianli Gu, Rong Lin
Summary: The study found that HT-AC can alleviate vascular endothelial cell pyroptosis in AS, showing positive effects in animal experiments.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Dinesh Kumar, Saket Awadhesbhai Patel, Rehan Khan, Saurabh Chawla, Nachiketa Mohapatra, Manjusha Dixit
Summary: Anti-angiogenesis cancer therapies are facing challenges, and the discovery of molecules that can regulate multiple cellular processes is crucial for developing more effective treatments. Our study found a correlation between reduced expression of IQGAP2 in breast cancer and poor patient prognosis, and we confirmed the role of IQGAP2 in tumor angiogenesis through cell culture, patient, and animal models.
MOLECULAR CANCER RESEARCH
(2022)
Article
Microbiology
Nathan P. Wiederhold, Ilan S. Schwartz, Thomas F. Patterson, George R. Thompson
Summary: The study revealed a significant correlation between ITZ and OH-ITZ levels, with OH-ITZ levels generally higher than ITZ levels, but marked variability was observed throughout the range of ITZ concentrations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Neurosciences
Jissele A. Verdinez, Julien A. Sebag
Summary: This study identified two N-linked glycosylation sites within the N-terminal region of PKR2 and demonstrated that glycosylation at position 27 is crucial for its plasma membrane localization and signaling. Additionally, glycosylation at position 7 was found to decrease PKR2 signaling through G alpha(s) without affecting G alpha(q/)(11) signaling.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Weibin Zhou, Keli Liu, Lei Zeng, Jiaqi He, Xinbo Gao, Xinyu Gu, Xun Chen, Jing Jing Li, Minghui Wang, Duoguang Wu, Zhixiong Cai, Lena Claesson-Welsh, Rong Ju, Jingfeng Wang, Feng Zhang, Yangxin Chen
Summary: This study found that VEGF-A/VEGFR2 Y949-dependent vascular permeability plays a significant role in the pathogenesis of PH and may serve as an attractive therapeutic target pathway for this disease.
Article
Hematology
Chonghe Zhang, Hao He, Jianing Dai, Yunxia Li, Jing He, Wu Yang, Jialin Dai, Feng Han, Wenyan Kong, Xiaohong Wang, Xiangjian Zheng, Jing Zhou, Weijun Pan, Zhongwen Chen, Singhal Mahak, Yaoyang Zhang, Feng Guo, Junhao Hu
Summary: This study reveals a novel role for KANK4 in arteriogenesis in response to ischemia. KANK4 links VEGFR2 to TALIN-1, resulting in enhanced VEGFR2 activation and increased EC proliferation, highlighting that KANK4 is a potential therapeutic target for promoting arteriogenesis for arterial occlusive diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
John-Michael Arpino, Hao Yin, Emma K. Prescott, Sabrina C. R. Staples, Zengxuan Nong, Fuyan Li, Jacqueline Chevalier, Brittany Balint, Caroline O'Neil, Rokhsana Mortuza, Stephanie Milkovich, Jason J. Lee, Daniel Lorusso, Martin Sandig, Douglas W. Hamilton, David W. Holdsworth, Tamie L. Poepping, Christopher G. Ellis, J. Geoffrey Pickering
Summary: Contrary to prevailing beliefs, angiogenesis in ischemic muscle injury is driven by the formation of wide-caliber conduits that rapidly transform into a hierarchical neocirculation. Inhibiting VEGFR2 accelerates this process, and endothelial cells in low-flow lumens display enhanced VEGFR2 mechanosignals.
Article
Biochemistry & Molecular Biology
Sansong Chen, Xuetao Li, Hao Wang, Guangliang Chen, Youxin Zhou
Summary: In this study, researchers investigated the role of VEGFR2 monoclonal antibodies in inhibiting tumorigenicity and VM formation in GBM. They found that VEGFR2 is highly expressed in glioma tissues and is associated with poor prognosis and VM markers. The monoclonal antibodies could inhibit invasion, migration, and VM formation in vitro and also inhibit tumor growth and VM formation in vivo. This suggests that VEGFR2 monoclonal antibodies could be a potential supplementary treatment for GBM.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Peripheral Vascular Disease
Sheela Nagarkoti, Young-Mee Kim, Dipankar Ash, Archita Das, Eric Vitriol, Tracy-Ann Read, Seock-Won Youn, Varadarajan Sudhahar, Malgorzata McMenamin, Yali Hou, Harriet Boatwright, Ruth Caldwell, David W. Essex, Jaehyung Cho, Tohru Fukai, Masuko Ushio-Fukai
Summary: PDIA1 senses the H2O2 signal induced by VEGF to promote VEGFR2 signaling and angiogenesis in endothelial cells, thereby enhancing postnatal angiogenesis.
Article
Chemistry, Medicinal
Yang Wang, Zheng Wang, Xiao Wu, Song Zhu, Qiru Guo, Zhong Jin, Zixian Chen, Delai Zhang, Wangming Hu, Huan Xu, Liangqin Shi, Lan Yang, Yong Wang
Summary: This study investigates the role of Paeonol in regulating reendothelialization after vascular injury. The results demonstrate that Paeonol promotes the proliferation and migration of endothelial cells, leading to enhanced vascular regeneration. This finding suggests that Paeonol could be used as a therapeutic option for treating pathological vascular diseases.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Engineering, Biomedical
Mouhita Humayun, Jose M. Ayuso, Raven A. Brenneke, Maria Virumbrales-Munoz, Karina Lugo-Cintron, Sheena Kerr, Suzanne M. Ponik, David J. Beebe
Summary: In cancer metastasis, tumor cells exit the bloodstream by crossing the endothelium and engaging in crosstalk with other active players, leading to changes in functional behavior. Upregulated secretion of factors from cancer-vascular interactions affects the invasive/metastatic potential of breast cancer cells. Therapeutic inhibitors were used to assess the independent and combined role of multiple signaling factors on promoting extravasation in cancer metastasis.
Article
Genetics & Heredity
Bobby G. Ng, Paulina Sosicka, Francois Fenaille, Annie Harroche, Sandrine Vuillaumier-Barrot, Mindy Porterfield, Zhi-Jie Xia, Shannon Wagner, Michael J. Bamshad, Marie-Christine Vergnes-Boiteux, Sophie Cholet, Stephen Dalton, Anne Dell, Thierry Dupre, Mathieu Fiore, Stuart M. Haslam, Yohann Huguenin, Tadahiro Kumagai, Michael Kulik, Katherine McGoogan, Caroline Michot, Deborah A. Nickerson, Tiffany Pascreau, Delphine Borgel, Kimiyo Raymond, Deepti Warad, Heather Flanagan-Steet, Richard Steet, Michael Tiemeyer, Nathalie Seta, Arnaud Bruneel, Hudson H. Freeze
Summary: The study identified a recurrent mutation in SLC37A4 causing a dominantly inherited congenital disorder of glycosylation characterized by coagulopathy and liver dysfunction with abnormal serum N-glycans. Liver-specific abnormalities in glycosylation were replicated in a CRISPR base-edited hepatoma cell line carrying the mutation. The mutant protein showed relocation to a non-Golgi compartment and altered Golgi morphology and reduced intraluminal pH, potentially explaining the glycosylation alterations.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Immunology
Christine Baksmeier, Pat Blundell, Julia Steckel, Verena Schultz, Quan Gu, Ana Da Silva Filipe, Alain Kohl, Chris Linnington, Dongli Lu, Anne Dell, Stuart Haslam, Jiabin Wang, Dan Czajkowsky, Norbert Goebels, Richard J. Pleass
Summary: IVIG is an established treatment for autoimmune conditions, but mechanisms of action remain unclear. This study used adapted Fc fragments to dissect IVIG effector mechanisms in an ex vivo model of demyelination. The protective effects of the adapted Fc fragments were dose-dependent and attributed to interference with complement-mediated damage to oligodendrocytes. Overall, findings suggest that recombinant biomimetics may be more effective than IVIG in controlling demyelination.
Article
Multidisciplinary Sciences
Huan Cao, Aristotelis Antonopoulos, Sadie Henderson, Heather Wassall, John Brewin, Alanna Masson, Jenna Shepherd, Gabriela Konieczny, Bhinal Patel, Maria-Louise Williams, Adam Davie, Megan A. Forrester, Lindsay Hall, Beverley Minter, Dimitris Tampakis, Michael Moss, Charlotte Lennon, Wendy Pickford, Lars Erwig, Beverley Robertson, Anne Dell, Gordon D. Brown, Heather M. Wilson, David C. Rees, Stuart M. Haslam, J. Alexandra Rowe, Robert N. Barker, Mark A. Vickers
Summary: The surface-exposed high mannose N-glycans on diseased or oxidized red blood cells bind to mannose receptor CD206 on phagocytes, mediating phagocytosis in sickle cell disease and malaria. This recognition of surface N-linked high mannose glycans as a response to cellular stress is a common molecular mechanism in the pathogenesis of sickle cell disease and resistance to severe malaria in individuals with sickle cell trait.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yilin Wang, Aneesah Khan, Aristotelis Antonopoulos, Laura Bouche, Christopher D. Buckley, Andrew Filer, Karim Raza, Kun-Ping Li, Barbara Tolusso, Elisa Gremese, Mariola Kurowska-Stolarska, Stefano Alivernini, Anne Dell, Stuart M. Haslam, Miguel A. Pineda
Summary: Research reveals that in rheumatoid arthritis, pro-inflammatory cytokines reshape the glycome of synovial fibroblasts, converting the synovium into a highly pro-inflammatory microenvironment.
NATURE COMMUNICATIONS
(2021)
Review
Biotechnology & Applied Microbiology
Elizabeth Edwards, Maria Livanos, Anja Krueger, Anne Dell, Stuart M. Haslam, C. Mark Smales, Daniel G. Bracewell
Summary: Glycosylation plays a critical role in the quality and characteristics of therapeutic monoclonal antibodies in biologic manufacturing. Advances have been made in upstream processing, such as mammalian cell line engineering, to improve the predictability of glycosylation. Downstream processing strategies, including the use of novel technologies, are also being explored to control glycosylation. However, more research is needed to establish holistic and consistent manufacturing processes for antibody therapies.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Amber R. Peswani, Jaraspim Narkpuk, Anja Krueger, Daniel G. Bracewell, Porntippa Lekcharoensuk, Stuart M. Haslam, Anne Dell, Peera Jaru-Ampornpan, Colin Robinson
Summary: This study presents a new production workflow for an updated and cost-effective PCV2d vaccine candidate, showing high yields of purified PCV2d-based antigen from E. coli fermentation systems and a chimeric PCV2d-PCV3 capsid construct. The recombinant protein effectively induced capsid-specific and PCV2d-neutralizing antibodies in immunized animals, suggesting significant potential as a new vaccine candidate that can be easily manufactured at commercial scale.
FOOD AND BIOPRODUCTS PROCESSING
(2022)
Article
Microbiology
Lucy Duncombe, Laurence Howells, Anna Haughey, Andrew Taylor, Daryan Kaveh, Sevil Erdenlig Gurbilek, Anne Dell, Paul G. Hitchen, Stuart M. Haslam, Satadru Sekhar Mandal, N. Vijaya Ganesh, David R. Bundle, John McGiven
Summary: This study reveals the limitations of serological tests for brucellosis and demonstrates that adding chemical features to synthetic antigens can improve their specificity by blocking antibody binding to the tip of the OPS. This finding suggests the possibility of developing improved serological tests for brucellosis.
Article
Multidisciplinary Sciences
Gang Wu, Paola Grassi, David A. MacIntyre, Belen Gimeno Molina, Lynne Sykes, Samit Kundu, Cheng-Te Hsiao, Kay-Hooi Khoo, Phillip R. Bennett, Anne Dell, Stuart M. Haslam
Summary: This study used a comprehensive glycomic strategy to reveal the complex and abundant N-glycome in cervicovaginal fluid (CVF) of pregnant and non-pregnant women. The N-glycosylation profiles were found to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Additionally, lower sialylation and higher fucosylation were observed in CVF from women who subsequently experienced preterm birth, indicating their potential roles in the mechanism of microbial driven preterm birth.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Zhengyuan Huang, Pei F. Lai, Alexander T. H. Cocker, Stuart M. Haslam, Anne Dell, Hugh J. M. Brady, Mark R. Johnson
Summary: Protein N-linked glycosylation is a diverse post-translational modification that stores biological information in a larger magnitude than other modifications. It impacts trophoblast functions and their interactions with decidual cells. Understanding N-glycosylation can improve approaches to predicting and diagnosing pregnancy complications related to placental dysfunction.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Meeting Abstract
Immunology
Belen Gimeno-Molina, Erna Bayar, Katherine Mountain, Ryan Love, Yun Lee, Ingrid Muller, Anne Dell, Stuart Haslam, Paola Grassi, Gang Wu, David MacIntyre, Phillip Bennett, Pascale Kropf, Lynne Sykes
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
Katherine Mountain, David MacIntyre, Denise Chan, Alice Hyde, James Pasint-Magyar, Yun Lee, Richard Brown, Anna David, Anne Dell, Ten Feizi, Stuart Haslam, Yan Liu, Holly Lewis, Jane Norman, Sarah Stock, Tiong Teoh, Vasso Terzidou, Samit Kundu, Phillip Bennett, Lynne Sykes
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Chika Kikuchi, Aristotelis Antonopoulos, Shengyang Wang, Tadashi Maemura, Rositsa Karamanska, Chiara Lee, Andrew J. Thompson, Anne Dell, Yoshihiro Kawaoka, Stuart M. Haslam, James C. Paulson
Summary: The evolution of human H3N2 influenza viruses has led to a limited specificity of the hemagglutinin to a subset of glycan receptors, presenting challenges for virus recognition and vaccine production. By studying glyco-engineered cell lines, the authors demonstrate the importance of extended glycan receptors for the growth of recent H3N2 viruses and their relevance to vaccine production.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yiran Xie, Fangqi Zhao, Nancy Freitag, Sophia Borowski, Yiru Wang, Charlotte Harms, Poh-Choo Pang, Juliette Desforges, Tianyu Wen, Edzard Schwedhelm, Manvendra Singh, Ralf Dechend, Anne Dell, Stuart M. Haslam, Gabriela Dveksler, Mariana G. Garcia, Sandra M. Blois
Summary: Placental abnormalities can lead to impaired fetal growth and poor pregnancy outcomes, such as preeclampsia (PE), with long-term consequences for both mother and offspring. Galectin-1 (gal-1), a glycan-binding protein expressed at the maternal-fetal interface, plays a critical role in maternal adaptation to pregnancy and placenta development. Deficiency of gal-1 during pregnancy is associated with the development of PE, but the specific contributions of maternal- and placental-derived gal-1 to the disease onset are not well understood. This study demonstrates that the lack of gal-1 increases the risk of PE development in a niche-specific manner, and this is accompanied by placental dysfunction primarily influenced by the absence of maternal-derived gal-1. Notably, differential placental glycosylation through Sda-capped N-glycans plays a dominant role in the invasive capacity of trophoblasts triggered by maternal-derived gal-1. These findings highlight the essential role of maternal-derived gal-1 in healthy placenta development and suggest that impairment of the gal-1 signaling pathway within the maternal niche may be a molecular cause of maternal cardiovascular maladaptation during pregnancy.
Meeting Abstract
Obstetrics & Gynecology
Katherine Mountain, David MacIntyre, Denise Chan, Alice Hyde, Yun Lee, Richard Brown, Anna David, Anne Dell, Ten Feizi, Stuart Haslam, Yan Liu, Holly Lewis, Jane Norman, Sarah Stock, T. G. Teoh, Vasso Terzidou, Samit Kundu, Phillip Bennett, Lynne Sykes
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shuen-Shiuan Wang, Virginia del Solar, Xinheng Yu, Aristotelis Antonopoulos, Alan E. Friedman, Kavita Agarwal, Monika Garg, Syed Meheboob Ahmed, Ahana Addhya, Mehrab Nasirikenari, Joseph T. Lau, Anne Dell, Stuart M. Haslam, Srinivasa-Gopalan Sampathkumar, Sriram Neelamegham
Summary: Ac(5)GalNTGc is an effective inhibitor of O-glycosylation, truncating O-glycan biosynthesis in leukocytes and cells. It mainly affects O-glycans, with minimal impact on N-glycans and glycosphingolipids. In mouse experiments, Ac(5)GalNTGc showed potential in reducing leukocyte infiltration to sites of inflammation.
CELL CHEMICAL BIOLOGY
(2021)