Article
Biochemistry & Molecular Biology
Linh Nguyen, Kelli A. McCord, Duong T. Bui, Kim M. Bouwman, Elena N. Kitova, Mohamed Elaish, Dhanraj Kumawat, Gour C. Daskhan, Ilhan Tomris, Ling Han, Pradeep Chopra, Tzu-Jing Yang, Steven D. Willows, Andrew L. Mason, Lara K. Mahal, Todd L. Lowary, Lori J. West, Shang-Te Danny Hsu, Tom Hobman, Stephen M. Tompkins, Geert-Jan Boons, Robert P. de Vries, Matthew S. Macauley, John S. Klassen
Summary: Evidence suggests that host glycans, specifically glycolipids containing sialic acid, play a role in facilitating the entry of SARS-CoV-2 virus into host cells by binding to the receptor-binding domain (RBD) of the spike protein. Depletion of cell surface sialic acid levels through various methods decreases RBD binding and infection of the virus, indicating the importance of sialylated glycans in viral entry.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Anna L. Gray, Richard Karlsson, Abigail R. E. Roberts, Amanda J. L. Ridley, Nabina Pun, Bakhtbilland Khan, Craig Lawless, Rafael Luis, Martyna Szpakowska, Andy Chevigne, Catherine E. Hughes, Laura Medina-Ruiz, Holly L. Birchenough, Iashia Z. Mulholland, Catherina L. Salanga, Edwin A. Yates, Jeremy E. Turnbull, Tracy M. Handel, Gerard J. Graham, Thomas A. Jowitt, Ingo Schiessl, Ralf P. Richter, Rebecca L. Miller, Douglas P. Dyer
Summary: Leukocyte recruitment from the vasculature into tissues plays a crucial role in the immune system and inflammatory diseases. However, the mechanisms underlying this process, particularly the function of CXCL4, have not been well understood. In this study, we demonstrate that CXCL4 binds to glycosaminoglycan (GAG) sugars on proteoglycans in the endothelial extracellular matrix, leading to increased leukocyte adhesion, vascular permeability, and non-specific recruitment of various leukocytes. This research provides mechanistic insights into chemokine biology and offers potential therapeutic targets.
Article
Medicine, General & Internal
Hong Du, Haifeng Hu, Jing Li, Xiaoyan Wang, Hong Jiang, Jianqi Lian, Ying Zhang, Pingzhong Wang
Summary: This study investigated the destruction of glycocalyx and its evaluation value for disease severity and prognosis prediction in hemorrhagic fever with renal syndrome (HFRS). The results showed that exfoliated glycocalyx fragments were significantly increased in HFRS patients, and were significantly associated with disease severity and prognosis.
FRONTIERS IN MEDICINE
(2023)
Article
Virology
Ghadah A. Karasneh, Divya Kapoor, Navya Bellamkonda, Chandrashekhar D. Patil, Deepak Shukla
Summary: The increased levels of HPSE can reduce syncytial plaque formation and promote viral egress and release. Transiently enhanced expression of HPSE does not affect HSV-1 entry into cells but facilitates extracellular release of mature virions.
Article
Microbiology
Maitrayee Chatterjee, Liane Z. X. L. Huang, Anna Mykytyn, Chunyan Wang, Mart B. Lamers, Bart Westendorp, Richard B. Wubbolts, Jos P. M. van Putten, Berend-Jan B. Bosch, Bart Haagmans, Karin B. Strijbis
Summary: In this study, the role of host mucins and mucin glycans on SARS-CoV-2 entry into airway epithelial cells was investigated. The removal of mucins from the surface of cells increased the binding of the virus and enhanced infection. This study demonstrates the important role of glycosylated extracellular mucin domains in the entry of SARS-CoV-2.
Article
Medicine, General & Internal
Elisabeth Zechendorf, Katharina Schroeder, Lara Stiehler, Nadine Frank, Christian Beckers, Sandra Kraemer, Michael Dreher, Alexander Kersten, Christoph Thiemermann, Gernot Marx, Tim-Philipp Simon, Lukas Martin
Summary: Heparanase activity and heparan sulfate levels correlate with the severity and outcomes of COVID-19, and may be helpful in predicting clinical progression and outcomes in patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Chemistry, Physical
Haiyi Chen, Yu Kang, Mojie Duan, Tingjun Hou
Summary: The study revealed that the presence of heparan sulfate is crucial for the binding between the spike protein of SARS-CoV-2 and host ACE2, while the stability of the T470-F490 loop and hydrophobic interactions play key roles in the binding process.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Review
Oncology
Yuanyuan Wang, Stefan W. Schneider, Christian Gorzelanny
Summary: Cancer metastasis is a complex process, and the survival and escape of circulating tumor cells (CTCs) from the blood flow are crucial for their ability to metastasize. CTCs sense their environment through surface receptors and can induce intracellular signaling processes for survival. The interaction of CTCs with plasma proteins, such as fibrinogen and tissue factor, may play a role in cancer-associated thrombosis (CAT) outcomes.
Article
Biochemistry & Molecular Biology
Elena Carava, Paola Moretto, Ilaria Caon, Arianna Parnigoni, Alberto Passi, Evgenia Karousou, Davide Vigetti, Jessica Canino, Ilaria Canobbio, Manuela Viola
Summary: Cardiovascular diseases result from various risk factors, and inflammation induced by cytokines like TNF-alpha may lead to changes in vessel matrix composition without affecting cell proliferation or migration.
Article
Biochemistry & Molecular Biology
Yuanyuan Wang, Xiaobo Liu, Tobias Obser, Alexander T. Bauer, Martin Heyes, Sarah Starzonek, Mina Zulal, Karena Opitz, Leonie Ott, Sabine Riethdorf, Tobias Lange, Klaus Pantel, Gerd Bendas, Stefan W. Schneider, Marion Kusche-Gullberg, Christian Gorzelanny
Summary: In this study, it was found that the exposure of HS on the surface of blood circulating melanoma cells recruited a significant amount of plasmatic vWF, forming a tight molecular complex. The length of HS chains or the absence of HS was associated with reduced vWF encapsulation. The vWF-HS complex prevented vascular adhesion and promoted the repulsion of circulating cancer cells from the blood vessel wall. Cancer cells with low HS levels evaded recognition by vWF and were prone to form metastases.
Article
Biochemistry & Molecular Biology
Dmitry K. Sokolov, Oleg B. Shevelev, Anna S. Khotskina, Alexandra Y. Tsidulko, Anastasia V. Strokotova, Galina M. Kazanskaya, Alexander M. Volkov, Evgenii E. Kliver, Svetlana V. Aidagulova, Evgenii L. Zavjalov, Elvira V. Grigorieva
Summary: Glioblastoma (GB) is an aggressive cancer with a high chance of recurrence, and the effects of chemotherapy drugs on heparan sulfate (HS) in brain tissue are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anthony J. J. Hayes, James Melrose
Summary: Heparan sulfate is a complex glycosaminoglycan that plays important roles in various biological processes through interactions with extracellular ligands and cellular receptors. Its chain lengths and sequences can vary, providing structural diversity. Heparan sulfate has regulatory properties in tissue development, wound healing, immune regulation, inflammation, and tumor development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Prashant Jain, Chethan D. Shanthamurthy, Shani Leviatan Ben-Arye, Robert J. Woods, Raghavendra Kikkeri, Vered Padler-Karavani
Summary: Selective inhibition of chemokines using structurally defined heparan sulfate oligosaccharides can provide insights into cancer cell migration and metastasis. Rational design and synthesis of N-unsubstituted and N-acetylated heparan sulfate tetrasaccharides have shown selective inhibition of structurally homologous chemokines.
Article
Medicine, Research & Experimental
Kimberly A. Queisser, Rebecca A. Mellema, Elizabeth A. Middleton, Irina Portier, Bhanu Kanth Manne, Frederik Denorme, Ellen J. Beswick, Matthew T. Rondina, Robert A. Campbell, Aaron C. Petrey
Summary: Vascular injury in COVID-19 patients is linked to increased levels of glycosaminoglycans, particularly hyaluronan fragments and hyaluronidase activity. This damage to the glycocalyx is associated with disease severity and elevated levels of inflammatory cytokines. Pulmonary microvascular endothelial cells exposed to the COVID-19 milieu exhibit dysregulated HA biosynthesis and degradation, leading to the release of pathological HA fragments into circulation.
Article
Biochemistry & Molecular Biology
Sohyun Moon, Ying-Tao Zhao
Summary: The study systematically analyzed the spatial, temporal, and cell-type-specific expression of genes encoding HS biosynthesis enzymes and HSPG core proteins, providing a valuable resource for the research community in the field of heparan sulfate.
Article
Biochemical Research Methods
Feng Xiao, Jiazhang Lian, Shuai Tu, Linlin Xie, Jun Li, Fuming Zhang, Robert J. Linhardt, Haichan Huang, Weihong Zhong
Summary: This study demonstrates the efficient microbial production of chlorogenic acid (CGA) by engineering Saccharomyces cerevisiae on a simple mineral medium. The optimized biosynthetic pathway and multimodule engineering strategy lead to a significant increase in CGA titer, reaching up to 806.8 +/- 1.7 mg/L in a 1 L fed-batch fermenter. This provides a new approach for large-scale production of CGA and its derivatives.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yi-En Liao, Yongmei Xu, Katelyn Arnold, Fuming Zhang, Jine Li, Rani Sellers, Chaoyin Yin, Vijayakanth Pagadala, Anna Marie Inman, Robert J. Linhardt, Ding Xu, Rafal Pawlinski, Jian Liu
Summary: This study discovered that a synthetic heparan sulfate octadecasaccharide (18-mer) can effectively prevent sepsis and reduce related injuries and inflammation. The 18-mer inhibits the pro-inflammatory activity of histone H3 and HMGB1, while eliciting the anti-inflammatory effect of ApoA-I. By directly interacting with proteins, the 18-mer neutralizes cytotoxic histone H3 and separates HMGB1 and lipopolysaccharide complex, thereby reducing cell death and tissue damage in sepsis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Food Science & Technology
Jingjing Tai, Dan Qiao, Xue Huang, Huang Hu, Wanzheng Li, Xinle Liang, Fuming Zhang, Yanbin Lu, Hong Zhang
Summary: This study aimed to investigate the structural and immunological properties of parvalbumin from mandarin fish during the Maillard reaction. The microwave-assisted Maillard reaction was optimized using orthogonal designed experiments, and the results showed that the type of sugar and heating time had a significant effect on the reaction. SDS-PAGE analysis revealed changes in the molecular weight of the glycated parvalbumin, and Nano-LC-MS/MS identified glycation sites and groups. The study also found that microwave heating reduced the immunoreactivity of parvalbumin and improved its ease of digestion compared to induction cookers.
Article
Nanoscience & Nanotechnology
Jie Zheng, Han Xu, Bingzhi Li, Muhammad Sohail, Jingjing Bi, Fuming Zhang, Robert J. Linhardt, He Huang, Xing Zhang
Summary: Based on the Modular-Enzymes Assembly by Spatial Segregation (MASS) strategy, a universal immobilization platform was developed to assemble multiple glycoenzymes in compartmentalized MOF particles, reducing interference and cross-inhibitions. Different glycans, including glycosyl donor, disaccharides, oligosaccharides, and polysaccharides with cofactor regeneration, were efficiently prepared. This robust multienzyme immobilization platform has industrial potential for enzymatic synthesis of more complex glycans.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Deena Al Mahbuba, Sayaka Masuko, Shiwei Wang, Deepsing Syangtan, Jeong Seuk Kang, Yuefan Song, Tay Won Shin, Ke Xia, Fuming Zhang, Robert J. Linhardt, Edward S. Boyden, Laura L. Kiessling
Summary: Using expansion microscopy, researchers found that the nanotopography of heparan sulfate (HS) changes significantly during human pluripotent stem cell differentiation, and these changes are correlated with growth factor signaling. In undifferentiated cells, HS is densely distributed as hair-like protrusions, which can recruit fibroblast growth factor for signaling. However, during differentiation into ectodermal lineage, HS becomes localized into dispersed puncta, leading to a decrease in fibroblast growth factor binding to neural cells. This study highlights the importance of HS nanotopography in growth factor binding.
Review
Cell Biology
Alicia N. Rizzo, Eric P. Schmidt
Summary: The alveolar epithelial glycocalyx is a layer of glycosaminoglycans (GAGs) and proteoglycans on the surface of alveolar epithelial cells. Recent studies have shown that the degradation of the glycocalyx is associated with acute respiratory distress syndrome (ARDS) in mice models and respiratory failure patients. This suggests that the alveolar epithelial glycocalyx plays a crucial role in the pathogenesis of ARDS.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Physiology
Christina Sul, Caitlin Lewis, Nathan Dee, Nana Burns, Kaori Oshima, Eric Schmidt, Christine Vohwinkel, Eva Nozik
Summary: Acute respiratory distress syndrome (ARDS) is a significant cause of morbidity and mortality in critically ill patients. This study investigates the protective effects of the R213G variant of extracellular superoxide dismutase (EC-SOD) in a methicillin-resistant S. aureus (MRSA) pneumonia model. The results suggest that the R213G EC-SOD variant preserves the integrity of the alveolar-capillary interface, attenuates proinflammatory cytokine levels, reduces neutrophil recruitment and neutrophil extracellular trap (NET) generation, and prevents extrapulmonary dissemination of bacteria.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Article
Chemistry, Physical
Feng Wang, Chao Li, Haohao Wang, Lu Yu, Fuming Zhang, Robert J. Linhardt
Summary: In this study, amphiphilic O(Phe-r-Glu) nanoparticles were synthesized using choline as a catalyst and were used to stabilize squalene/water emulsions. The investigation found that the stability of emulsions was maintained through different mechanisms under different pH conditions. The enzymatically synthesized amphiphilic peptides have potential applications in fields such as pharmaceuticals, food, and cosmetics.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2023)
Article
Plant Sciences
Rohini Dwivedi, Marwa Farrag, Poonam Sharma, Deling Shi, Anter A. Shami, Sandeep K. Misra, Priya Ray, Jayanti Shukla, Fuming Zhang, Robert J. Linhardt, Joshua S. Sharp, Ritesh Tandon, Vitor H. Pomin
Summary: Two new sulfated glycans, TgFucCS and TgSF, were isolated from the sea cucumber Thyonella gemmata. NMR results revealed the structures and compositions of TgFucCS and TgSF. The inhibitory properties of these sulfated glycans against SARS-CoV-2 were investigated, and TgSF showed significant antiviral activity and low anticoagulant properties, making it a potential candidate for drug development.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Peng He, Deling Shi, Yunran Li, Ke Xia, Seon Beom Kim, Rohini Dwivedi, Marwa Farrag, Vitor H. H. Pomin, Robert J. J. Linhardt, Jonathan S. S. Dordick, Fuming Zhang
Summary: Sulfated glycans from marine organisms have therapeutic activities and can inhibit the interactions between monkeypox virus proteins and heparin. This is important for developing broad-spectrum antiviral therapeutics for monkeypox.
Article
Multidisciplinary Sciences
Zhangjie Wang, Vaishali N. Patel, Xuehong Song, Yongmei Xu, Andrea M. Kaminski, Vivien Uyen Doan, Guowei Su, Yien Liao, Dylan Mah, Fuming Zhang, Vijayakanth Pagadala, Chunyu Wang, Lars C. Pedersen, Lianchun Wang, Matthew P. Hoffman, Marla Gearing, Jian Liu
Summary: Through analysis of brain heparan sulfate, it was found that the genetic risk gene HS3ST1, associated with Alzheimer's disease and other tauopathies, is overexpressed in patients. A specific 3-O-sulfated heparan sulfate was significantly increased in Alzheimer's disease patients, and it was confirmed that this sulfated heparan sulfate is produced by the 3-O-sulfotransferase isoform 1 encoded by the HS3ST1 gene. The synthetic 14-mer with the specific 3-O-sulfated domain showed stronger inhibitory effects on tau internalization, suggesting the important role of 3-O-sulfated heparan sulfate in tau cellular uptake. These findings uncover a previously unidentified therapeutic target for Alzheimer's disease.
Article
Food Science & Technology
Lijuan Hou, Laiming Zhang, Chengxiao Yu, Jianle Chen, Xingqian Ye, Fuming Zhang, Robert J. Linhardt, Shiguo Chen, Haibo Pan
Summary: In this study, a novel one-pot coaxial electrospinning method was used to encapsulate curcumin in zein and Eudragit S100 fibers, forming zein-curcumin core-shell nanoparticles. The resulting structure provided double protection for curcumin and exhibited pH responsiveness and sustained release performance, making it suitable for sustainable and controllable intestine-targeted drug delivery.
Article
Biology
Paul S. S. Kwon, Shirley Xu, Hanseul Oh, Seok-Joon Kwon, Andre L. Rodrigues, Maisha Feroz, Keith Fraser, Peng He, Fuming Zhang, Jung Joo Hong, Robert J. J. Linhardt, Jonathan S. S. Dordick
Summary: A polysulfated synthetic drug called suramin binds to the ACE2 receptor and heparan sulfate binding sites on SARS-CoV-2 receptor binding domains (RBDs), with preferential binding for the Omicron RBD and inhibition of infection by the Omicron variant in vitro. These findings suggest that suramin and other polysulfated molecules could be potential therapeutic and prophylactic options against COVID-19.
COMMUNICATIONS BIOLOGY
(2023)
Letter
Medicine, General & Internal
Samuel A. Hofacker, Eric P. Schmidt
NEW ENGLAND JOURNAL OF MEDICINE
(2023)