Review
Cell Biology
Jian Liu, Lars C. Pedersen
Summary: This article summarizes the recent progress in substrate specificity studies of different 3-O-sulfotransferase isoforms and introduces a newly developed method for analyzing the level of 3-O-sulfated heparan sulfate using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lingbo Sun, Andriana Konstantinidi, Zilu Ye, Rebecca Nason, Yuecheng Zhang, Christian Bull, Barbro Kahl-Knutson, Lars Hansen, Hakon Leffler, Sergey Y. Vakhrushev, Zhang Yang, Henrik Clausen, Yoshiki Narimatsu
Summary: Researchers engineered sulfotransferase genes in HEK293 cells to achieve sulfation modification of O-glycans. They used this engineered cell library to study the binding specificity between galectin-4 and sulfated O-glycans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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
Immunology
Maria del Pilar Huby Vidaurre, Baron K. Osborn, Kaylie D. Lowak, Michelle M. McDonald, Yao-Wei W. Wang, Veda Pa, Jillian R. Richter, Yongmei Xu, Katelyn Arnold, Jian Liu, Jessica C. Cardenas
Summary: A synthetic 3-O-sulfated heparan sulfate 12-mer, dekaparin, has been found to have anti-thrombotic and anti-inflammatory properties, which can alleviate organ injury following major trauma and hemorrhagic shock.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Microbiology
Fujun Hou, Zeyu Sun, Yue Deng, Siyu Chen, Xiyuan Yang, Feiyang Ji, Menghao Zhou, Keyi Ren, Dongli Pan
Summary: This study investigates the targets of ICP0 in HSV-1 infection and its roles in neuronal cells. Mass spectrometry analysis identified various proteins interacting with ICP0 in Neuro-2a and 293T cells. Further experiments confirmed that SNX9 and OTUD4 restrict the replication of ICP0-null virus in neuronal cells, and OTUD4 enhances the expression of type I interferon during infection with ICP0-null virus.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Chemistry, Applied
Noemi Veraldi, Isabelle Dentand Quadri, Yohan van de Looij, Laura Malaguti Modernell, Corinne Sinquin, Agata Zykwinska, Benjamin B. Tournier, Fabien Dalonneau, Honglian Li, Jin-Ping Li, Philippe Millet, Romain Vives, Sylvia Colliec-Jouault, Ariane de Agostini, Eduardo Farias Sanches, Stephane V. Sizonenko
Summary: Derivative A5_3, derived from marine polysaccharides, inhibits intracellular HS accumulation and shows protective effects on brain metabolism and microstructure in MPSIIIA mice.
CARBOHYDRATE POLYMERS
(2023)
Review
Cell Biology
Emily Lazarus, Paola Bermudez-Lekerika, Daniel Farchione, Taylor Schofield, Sloan Howard, Iskender Mambetkadyrov, Mikkael Lamoca, Iris V. Rivero, Benjamin Gantenbein, Christopher L. Lewis, Karin Wuertz-Kozak
Summary: Sulfated hydrogels play a crucial role in maintaining the phenotype of chondrocytes and chondrocyte-like cells, as well as in the sustained delivery of growth factors. Current research focuses on identifying and summarizing the knowledge about different sulfated hydrogels, highlighting their benefits in cartilage and disc research, and reviewing the biofabrication processes to ensure quality assurance.
Article
Chemistry, Multidisciplinary
Anil K. Gorle, Thomas Haselhorst, Samantha J. Katner, Arun Everest-Dass, James D. Hampton, Erica J. Peterson, Jennifer E. Koblinski, Eriko Katsuta, Kazuaki Takabe, Mark von Itzstein, Susan J. Berners-Price, Nicholas P. Farrell
Summary: The 1:1 adduct of the pentasaccharide Fondaparinux and the substitution-inert polynuclear platinum complex TriplatinNC was found to modulate the geometry around glycosidic linkages, potentially inhibiting heparan sulfate cleavage in breast cancer cells and metastasis in an animal model. This study provides insights into a novel approach for designing platinum drugs with intrinsic anti-metastatic potential.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Alexandra De Zutter, Luna Dillemans, Nele Berghmans, Sam Noppen, Helena Crijns, Paulien Verscheure, Janne Verhaegen, Erik Martens, Lotte Vanbrabant, Noemie Portner, Dominique Schols, Paul Proost, Sofie Struyf
Summary: Glycosaminoglycans/proteoglycans (GAGs/PGs) play a crucial role in regulating tumor progression and can be potential targets for anti-cancer therapy. A D-amino acid version of CXCL9(74-103), called D-CXCL9(74-103), showed anti-angiogenic properties and inhibited endothelial spheroid sprouting and vessel formation. D-CXCL9(74-103) also exhibited anti-tumoral activity against heparan sulfate high B16-BL6 melanoma cells but had no effect on chondroitin sulfate high HCT116 colon carcinoma cells. These findings highlight the importance of tumor-associated GAGs in adhesion and metastasis and suggest the potential of D-CXCL9(74-103) as a therapeutic agent for heparan sulfate high tumors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Wencheng Zhang, Yongmei Xu, Xicheng Wang, Tsunekazu Oikawa, Guowei Su, Eliane Wauthier, Guoxiu Wu, Praveen Sethupathy, Zhiying He, Jian Liu, Lola M. Reid
Summary: Fibrolamellar carcinomas (FLCs) are lethal tumors that occur in children to young adults, and their genetic signatures suggest that they derive from biliary tree stem cell (BTSC) subpopulations involved in hepatic and pancreatic regeneration. The study has identified a potential new treatment approach for FLCs, which is an exciting prospect for a deadly disease.
Review
Biochemistry & Molecular Biology
James Elste, Angelica Chan, Chandrashekhar Patil, Vinisha Tripathi, Daniel M. Shadrack, Dinesh Jaishankar, Andrew Hawkey, Michelle Swanson Mungerson, Deepak Shukla, Vaibhav Tiwari
Summary: The structural diversity of heparan sulfate (HS) in various vertebrates and invertebrates is remarkably preserved and plays a key role in ligand binding and virus entry. The interaction between glycoprotein D (gD) from herpes simplex virus (HSV) and 3-O sulfated HS leads to virus-cell fusion and HSV entry. HSV-1, which infects a large number of people worldwide, can also cause severe diseases in both primates and non-primates. The enzymatic modification of HS by 3-O sulfotransferase-3 (3-OST-3) enhances HSV-1 infectivity and suggests a possible role of HS in cross-species transmission.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Neurosciences
Susan L. Lindsay, George A. McCanney, Jiangshan Zhan, Miriam Scheld, Rebecca Sherrard Smith, Carl S. Goodyear, Edwin A. Yates, Markus Kipp, Jeremy E. Turnbull, Susan C. Barnett
Summary: There is an urgent need for therapies that target the multicellular pathology of central nervous system (CNS) disease. Modified, nonanticoagulant heparins mimic the heparan sulfate glycan family and are known regulators of multiple cellular processes. In vitro studies demonstrate the potential of low sulfated modified heparin mimetics (LS-mHeps) for repairing CNS demyelination. LS-mHep7, an in vitro lead compound, shows promising results in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination by promoting faster recovery, reducing inflammation, and restoring animal weight. The potential mechanism of action involves sequestering inflammatory cytokines, such as CCL5, which are elevated during immune-mediated inflammatory attacks.
Review
Biochemistry & Molecular Biology
Aikaterini Berdiaki, Monica Neagu, Eirini-Maria Giatagana, Andrey Kuskov, Aristidis M. Tsatsakis, George N. Tzanakakis, Dragana Nikitovic
Summary: The tumor microenvironment (TME) is composed of various cells and extracellular matrix components. Changes in the structure and sulfation pattern of GAGs are associated with cancer progression. GAGs and GAG-based molecules show promise as potential effectors for anticancer therapy due to their unique properties.
Article
Biochemistry & Molecular Biology
Matthew E. Griffin, Alexander W. Sorum, Gregory M. Miller, William A. Goddard, Linda C. Hsieh-Wilson
Summary: Heparan sulfate glycosaminoglycans (HS GAGs) regulate Ang-Tie signaling by interacting directly with Ang ligands and Tie1 receptors, enhancing endothelial survival signaling and maintaining Tie1 stability within the mature vasculature. Loss of HS-Tie1 binding leads to decreased Tie protein levels, pathway suppression, and aberrant retinal vascularization.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Dylan Mah, Yanan Zhu, Guowei Su, Jing Zhao, Ashely Canning, James Gibson, Xuehong Song, Eduardo Stancanelli, Yongmei Xu, Fuming Zhang, Robert J. Linhardt, Jian Liu, Lianchun Wang, Chunyu Wang
Summary: Apolipoprotein E (ApoE)'s epsilon 4 allele is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Heparan sulfate (HS) on the cell surface acts as a cofactor for the interaction between ApoE and LRP1, as well as the prion-like spread of tau pathology between cells. 3-O-sulfated HS has been linked to AD through its interaction with tau, and increased levels of 3-O-sulfated HS and 3-O-sulfotransferases have been observed in the AD brain. This study characterizes the interactions between ApoE and HS in different ApoE isoforms, and suggests that the interplay between 3-O-sulfated HS, tau, and ApoE isoforms may modulate AD risk.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Cell Biology
Chandrashekhar D. Patil, Deepak Shukla
Summary: Very little is known about the mechanisms that restrict neurotropic herpesviruses from infecting the central nervous system and causing neuron death. However, recent research has shown that OPTN-mediated autophagy acts as an intrinsic immune barrier against these viruses and protects the CNS from neurodegenerative stress.
Article
Immunology
Chandrashekhar D. Patil, Rahul Suryawanshi, Joshua Ames, Raghuram Koganti, Alex Agelidis, Divya Kapoor, Tejabhiram Yadavalli, Lulia Koujah, Henry C. Tseng, Deepak Shukla
Summary: This study reveals the key role of optineurin (OPTN) in restricting HSV-2 infection and controlling viral spread. Lack of OPTN leads to enhanced virus production and impaired host autophagy response. The OPTN/CCL5 nexus identified in this study may represent an intrinsic host defense mechanism against herpesviruses.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Ophthalmology
Earon Grinage, Deepak Shukla
Summary: This review summarizes the crucial role of host protein Optineurin during HSV-1 infection of the eye and the nervous system. Recent studies have shown that Optineurin can prevent cell-to-cell spread of the virus and protect the nervous system from damage. Therefore, Optineurin may be a key factor in preventing ocular and neurodegenerative diseases.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Virology
Ilina Bhattacharya, Tejabhiram Yadavalli, David Wu, Deepak Shukla
Summary: This study demonstrates the antiviral activity of plasma membrane-derived liposomes, especially in preventing HSV-1 infection. The research shows that cellular liposomes expressing viral entry-specific cell surface protein receptors exhibit robust antiviral activity, while those lacking the relevant HSV-1 entry receptors do not.
Review
Virology
Pankaj Sharma, Divya Kapoor, Deepak Shukla
Summary: This article discusses the role of HPSE and SDC-1 as newly identified host factors that facilitate HSV-1 release during infection.
Article
Microbiology
Chandrashekhar D. Patil, Rahul K. Suryawanshi, Divya Kapoor, Deepak Shukla
Summary: HSV-1 infection induces significant alterations in host metabolism, limiting the energy and macromolecular precursors required for viral replication. This study is of great importance for understanding the pathogenesis of HSV-1 infection.
Review
Biochemistry & Molecular Biology
Hester van Mourik, Mengying Li, Sabine Baumgartner, Jan Theys, Ronit Shiri-Sverdlov
Summary: Cathepsins are lysosomal proteases that play an essential role in maintaining cellular homeostasis and are involved in various physiological processes. They have been linked to pathologies such as NASH and HCC. Although the information regarding their involvement in NASH-HCC is limited, there is accumulating evidence supporting their role in both NASH and HCC. Given their role in both conditions, it is likely that Cathepsins play a more significant role in the transition from NASH to HCC, compared to HCC derived from other causes. This review provides an overview of the available data on Cathepsins in NASH and HCC, and highlights therapeutic options in this context.
Review
Biochemistry & Molecular Biology
James Elste, Angelica Chan, Chandrashekhar Patil, Vinisha Tripathi, Daniel M. Shadrack, Dinesh Jaishankar, Andrew Hawkey, Michelle Swanson Mungerson, Deepak Shukla, Vaibhav Tiwari
Summary: The structural diversity of heparan sulfate (HS) in various vertebrates and invertebrates is remarkably preserved and plays a key role in ligand binding and virus entry. The interaction between glycoprotein D (gD) from herpes simplex virus (HSV) and 3-O sulfated HS leads to virus-cell fusion and HSV entry. HSV-1, which infects a large number of people worldwide, can also cause severe diseases in both primates and non-primates. The enzymatic modification of HS by 3-O sulfotransferase-3 (3-OST-3) enhances HSV-1 infectivity and suggests a possible role of HS in cross-species transmission.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Microbiology
Divya Kapoor, Deepak Shukla
Summary: Neutrophil extracellular traps (NETs) are net-like structures released from neutrophils mainly containing cell-free DNA decorated with histones and neutrophil granule proteins. NETs can be induced by various stimuli such as pathogens, cytokines, and immune complexes. They have both beneficial and detrimental effects in capturing pathogens and aggravating inflammation. This review focuses on the formation mechanism of NETs in different ocular pathologies, particularly highlighting their potential implications during herpes simplex virus (HSV) ocular infections and as prospective targets for ocular disease treatment.
Review
Biochemistry & Molecular Biology
Annemarie J. F. Westheim, Lara M. Stoffels, Ludwig J. Dubois, Jeroen van Bergenhenegouwen, Ardy van Helvoort, Ramon C. J. Langen, Ronit Shiri-Sverdlov, Jan Theys
Summary: Cancer burden is increasing rapidly globally, with lifestyle factors such as unhealthy diet being major contributors. The specific fatty acids that contribute to a healthy and balanced diet in terms of cancer risk and prognosis are still unclear. This review explores the associations between intake of different fatty acids and cancer risk, as well as the effects of specific fatty acids on tumor cells and inflammation-induced cancer progression, highlighting challenges and opportunities for fatty acid tailored nutritional interventions.
Article
Multidisciplinary Sciences
Rahul K. Suryawanshi, Chandrashekhar D. Patil, Alex Agelidis, Raghuram Koganti, Tejabhiram Yadavalli, Joshua M. Ames, Hemant Borase, Deepak Shukla
Summary: This study found that compared to animals lacking HPSE, wild-type mice exhibit notable pathophysiology during HSV-1 reinfection. HPSE promotes infected cell survival and supports the formation of a pro-disease environment. In contrast, lack of HPSE enhances intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Overall, recent prior infection immunity fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.
Article
Medicine, Research & Experimental
Tejabhiram Yadavalli, Sudhanshu Kumar Singh, Abhijit A. Date, Deepak Shukla
Summary: This study evaluated the acute and short-term toxicity of orally administered BX795 in mice, as well as its pharmacokinetics and tissue distribution. The results showed that orally administered BX795 was well tolerated, had an oral bioavailability of 56%, and reached ocular and genital tissues within the first 15 min of dosing. The study indicated that orally administered BX795 can significantly reduce herpesvirus replication in ocular and genital tissue.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Virology
Hemant Borase, Deepak Shukla
Summary: This review summarizes the pathogenesis of HSV-2 and its cellular interactions, explores new strategies and challenges in regulating HSV-2 replication and influencing the cell cycle through host cellular components, and presents a fresh perspective on the treatment of HSV-2 by targeting cellular proteins and pathways.
Article
Microbiology
Ilina Bhattacharya, Ipsita Volety, Deepak Shukla
Summary: Tank-binding kinase 1 (TBK1) plays a crucial role in defending against herpes simplex virus type 1 (HSV-1), and the interplay between OPTN, TBK1, and autophagy significantly impacts the outcome of HSV-1 infection.