Review
Cell Biology
Tien K. Nguyen, Stephanie Paone, Enoch Chan, Ivan K. H. Poon, Amy A. Baxter, Shane R. Thomas, Mark D. Hulett
Summary: Cardiovascular disease is the leading cause of death and disability worldwide, and atherosclerosis plays a crucial role in its development. Heparanase, as the only mammalian enzyme known to cleave heparan sulfate, has been found to be involved in various physiological and pathological processes, including inflammation and plaque formation. This review focuses on the emerging role of heparanase in atherosclerosis and provides an up-to-date overview of its functions.
Article
Chemistry, Multidisciplinary
Joseph Wakpal, Vishaka Pathiranage, Alice R. Walker, Hien M. Nguyen
Summary: This article describes a method for synthesizing a library of HS mimetics from natural aminoglycosides, reducing the number of steps compared to traditional methods. Computational modeling was used to identify a new class of trisaccharide compounds derived from tobramycin that mimic natural HS and have a strong binding to heparanase but a low affinity for off-target platelet factor-4 protein.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Zuopeng Wu, Rebecca A. Sweet, Gerard F. Hoyne, Charmaine J. Simeonovic, Christopher R. Parish
Summary: It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, recent studies suggest that there are other mechanisms that allow cell migration through basement membranes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Casper de Boer, Zachary Armstrong, Vincent A. J. Lit, Uri Barash, Gijs Ruijgrok, Ilanit Boyango, Merle M. Weitzenberg, Sybrin P. Schroder, Alexi J. C. Sarris, Nico J. Meeuwenoord, Pedro Bule, Yasmine Kayal, Neta Ilan, Jeroen D. C. Codee, Israel Vlodavsky, Herman S. Overkleeft, Gideon J. Davies, Liang Wu
Summary: Research has shown that by developing effective HPSE inhibitors, extracellular HPSE activity can be reduced, thereby reducing the aggressiveness of cancer and potentially controlling pathological HPSE-driven malignancies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Miriam Gross-Cohen, Sari Feld, Gil Arvatz, Neta Ilan, Israel Vlodavsky
Summary: Hpa2, a close homolog of heparanase, plays a role in a rare genetic disease called urofacial syndrome, indicating its importance in protein coding; despite lacking HS-degrading activity, it shows a high affinity to HS; experimental evidence shows that Hpa2 affects cell adhesion, migration, and colony morphology.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aurelien Kerever, Fumina Nagahara, Kazuko Keino-Masu, Masayuki Masu, Toin H. van Kuppevelt, Romain R. Vives, Eri Arikawa-Hirasawa
Summary: The study reveals that inhibiting 6-O-sulfation in fractones by endosulfatases suppresses neurogenesis in the SVZ, and a higher number of neuroblasts are found in the SVZ of young and aged Sulf1/2 DKO mice.
Review
Biochemistry & Molecular Biology
Tonia L. Vincent, Oliver McClurg, Linda Troeberg
Summary: The extracellular matrix (ECM) plays a crucial role in tissue homeostasis and disease, acting as a mechano-sensor and mechano-effector in cartilage. It is involved in perceiving and responding to mechanical load, releasing growth factors for cartilage repair and protection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Raghuram Koganti, Abdullah Memon, Deepak Shukla
Summary: Heparan sulfate is a glycosaminoglycan found in mammalian tissues that contributes to the structural integrity of the extracellular matrix and cell signaling, but is also exploited by viruses during infection. Loss or inhibition of heparan sulfate proteoglycans during infection can lead to significant decreases in viral entry and infectivity, affecting multiple viruses such as herpesviruses, HIV, dengue virus, HPV, and coronaviruses.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Article
Cell Biology
Alyce J. Mayfosh, Katharine J. Goodall, Tien Nguyen, Nikola Baschuk, Mark D. Hulett
Summary: Heparanase is an important enzyme in NK cell cytotoxicity and activation, and its inhibition in clinical trials for metastatic cancer may impact NK cell immunsurveillance.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Cell Biology
Hind Al Khashali, Jadziah Wareham, Ravel Ray, Ben Haddad, Kai-Ling Coleman, Robert Ranzenberger, Patrick McCombs, Jeffrey Guthrie, Deborah Heyl, Hedeel Guy Evans
Summary: This study investigates the roles of heparanase and IGFBP-3 in regulating the survival of non-small-cell lung cancer cells. The results suggest that inhibiting heparanase activity or expression decreases the levels of soluble HS fragments and reduces interactions between IGFBP-3 and HS. Additionally, blocking HA-CD44 signaling increases p53 activity and the levels of IGFBP-3. Silencing p53 leads to increased heparanase levels, while silencing IGFBP-3 blocks p53 activity and increases heparanase levels.
Article
Respiratory System
Yanlin Zhang, Fei Xu, Li Guan, Ming Chen, Yiran Zhao, Lixia Guo, Xiao Li, Yimu Zheng, Ai Gao, Shuqiang Li
Summary: In chlorine gas-induced ARDS, histone H4 activates HPSE to induce HS degradation, leading to lung injury. Inhibitors of HPSE and RNA interference targeting HPSE can attenuate lung injury and HS degradation. Histone H4 promotes HPSE expression through TLRs and NF-kappa B pathways.
RESPIRATORY RESEARCH
(2022)
Article
Hematology
Yona Nadir
Summary: Heparanase, the only known mammalian enzyme to degrade heparan sulfate chains, affects the hemostatic system through various mechanisms, including degrading effect, release of Syndecan-1, and enhancing tissue factor activity. In clinical settings such as cancer and pregnancy, elevated levels of Heparanase and heparan sulfate chains may increase the risk of thrombosis.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2021)
Review
Biochemistry & Molecular Biology
Harkanwalpreet Sodhi, Alyssa Panitch
Summary: Glycosaminoglycans play a crucial role in tissue engineering by driving stem cell fate and promoting cell proliferation, and recent studies have explored their use in tissue constructs. The research trends in this area are evaluated, providing insights into future directions.
Review
Biochemistry & Molecular Biology
Anastasia V. Strokotova, Elvira V. Grigorieva
Summary: Glucocorticoids are commonly used to treat various diseases but can cause side effects. Recent studies suggest that the toxic effects of glucocorticoids on key extracellular components in the brain may be an underlying mechanism for these side effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Mohit Chhabra, Gareth G. Doherty, Nicholas W. See, Neha S. Gandhi, Vito Ferro
Summary: Heparan sulfate is a complex polysaccharide widely expressed on cell surfaces and in the extracellular matrix, interacting with numerous proteins to mediate various biological and pathological processes. Developing synthetically tractable HS mimetics with fewer side effects has become an attractive approach for treating cancer and infectious diseases.
Review
Biochemistry & Molecular Biology
Matthew J. A. Hein, Marc Kvansakul, Fung T. Lay, Thanh Kha Phan, Mark D. Hulett
Summary: Defensins, as a class of host defence peptides, have attracted attention as novel therapeutics due to their antimicrobial and anticancer activities. They uniquely target specific membrane lipids, offering increased selectivity and reduced susceptibility to resistance mechanisms in tumour cells and infectious pathogens.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Cell Biology
Alyce J. Mayfosh, Katharine J. Goodall, Tien Nguyen, Nikola Baschuk, Mark D. Hulett
Summary: Heparanase is an important enzyme in NK cell cytotoxicity and activation, and its inhibition in clinical trials for metastatic cancer may impact NK cell immunsurveillance.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guneet K. Bindra, Scott A. Williams, Fung T. Lay, Amy A. Baxter, Ivan K. H. Poon, Mark D. Hulett, Thanh Kha Phan
Summary: Defensins are a crucial component of the cationic host defence peptide (HDP) family and have antimicrobial and immunomodulatory activities. This study reveals that human beta-defensin 2 (HBD-2) can kill tumor cells through acute lytic cell death and does not affect tumor cell migration.
Article
Chemistry, Multidisciplinary
Sourabh Mehta, Viktoria Bongcaron, Tien K. Nguyen, Yugandhara Jirwanka, Ana Maluenda, Aidan P. G. Walsh, Jathushan Palasubramaniam, Mark D. Hulett, Rohit Srivastava, Alex Bobik, Xiaowei Wang, Karlheinz Peter
Summary: Atherosclerosis is a major cause of death and illness worldwide. This study reports a method of delivering 2-Hydroxypropyl-beta-cyclodextrin (CD) using nanoparticles, which improves the anti-atherosclerotic efficacy of CD and can be used for ultrasound imaging.
Article
Multidisciplinary Sciences
Saba Islam, Mirren Charnley, Guneet Bindra, Julian Ratcliffe, Jiangtao Zhou, Raffaele Mezzenga, Mark Hulett, Kyunghoon Han, Joshua T. Berryman, Nicholas P. Reynolds, Jeremy Engwirda
Summary: The authors report the presence of toxic clumps of protein in the COVID-19 virus that resemble amyloid assemblies found in Alzheimer's disease. They suggest that these clumps may play a role in the neurological symptoms observed in long-COVID.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Tien K. Nguyen, Stephanie Paone, Enoch Chan, Ivan K. H. Poon, Amy A. Baxter, Shane R. Thomas, Mark D. Hulett
Summary: Cardiovascular disease is the leading cause of death and disability worldwide, and atherosclerosis plays a crucial role in its development. Heparanase, as the only mammalian enzyme known to cleave heparan sulfate, has been found to be involved in various physiological and pathological processes, including inflammation and plaque formation. This review focuses on the emerging role of heparanase in atherosclerosis and provides an up-to-date overview of its functions.
Article
Biochemistry & Molecular Biology
Alyce J. Mayfosh, Zoe Day, Nathan B. Unsworth, Chun-Qiang Liu, Ruchi Gupta, Soraya Haynes, Rebecca Abraham, Sam Abraham, Zo L. Shaw, Sumeet Walia, Aaron Elbourne, Mark D. Hulett, Thomas F. Rau
Summary: GS-2 is a novel water-soluble antimicrobial agent that demonstrates activity against bacteria, fungi, and viruses, and performs more effectively in surface testing. Its ingredients are non-toxic to humans and animals, and when mixed with thymol, it can generate a bactericidal effect in a short period of time.
Article
Biochemistry & Molecular Biology
Zoe Day, Alyce J. Mayfosh, Marie-Claire Giel, Yuning Hong, Scott A. Williams, Jascinta P. Santavanond, Thomas F. Rau, Ivan K. Poon, Mark D. Hulett
Summary: This study presents a novel platform for solubilizing fatty acids using amino acids and investigates the tumoricidal activity and mechanism of undecylenic acid. The results demonstrate that the GS-1 formulation, a combination of undecylenic acid and L-Arginine, induces concentration-dependent tumor cell death through a pro-apoptotic mechanism. GS-1 localizes to lipid droplets intracellularly and is taken up by cells via Fatty Acid Transport Protein 2 (FATP2). These findings contribute to the emerging field of fatty acids as potential anti-cancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Scott A. Williams, Fung T. Lay, Guneet K. Bindra, Suresh Banjara, Ivan K. H. Poon, Thanh Kha Phan, Marc Kvansakul, Mark D. Hulett
Summary: The authors report the structure of saltwater crocodile defensin CpoBD13 and its pH-dependent antifungal activity.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Krishnath M. Jayatilleke, Hendrika M. Duivenvoorden, Gemma F. Ryan, Belinda S. Parker, Mark D. Hulett
Summary: Breast cancer ranks as the second most prevalent malignancy globally and poses a significant health burden. The involvement of Heparanase (HPSE) in the development and progression of solid tumors, including breast cancer, has been well established. Using a murine model, this study investigated the role of HPSE in breast cancer establishment, progression, and metastasis. The findings indicate that HPSE may not play a significant role in the development of mammary tumors in the model used, which has implications for breast cancer treatment using HPSE inhibitors.
Article
Biology
Emily R. R. Mackie, Andrew S. S. Barrow, Marie-Claire Giel, Mark D. D. Hulett, Anthony R. R. Gendall, Santosh Panjikar, Tatiana P. Soares P. da Costa
Summary: Herbicide resistance is a major concern in the natural environment and agricultural sector. In this study, a 'failed' antibiotic was repurposed into a herbicidal compound that effectively targets weed species. The compound inhibits the enzyme involved in lysine biosynthesis in plants and bacteria, without toxic effects on human cells. This research demonstrates the potential of repurposing antibiotics for the development of new herbicides.
COMMUNICATIONS BIOLOGY
(2023)