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Application of Glycobiology in the Treatment of Diseases
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Application of Glycobiology in the Treatment of Diseases

A special issue of Medicines (ISSN 2305-6320).

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 28009

Special Issue Editor

Prof. Dr. Vitor H. Pomin

E-Mail Website
Guest Editor
Department of BioMolecular Sciences, Pharmacognosy Division, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA
Interests: biological chemistry; structural biology; glycobiology; NMR spectrocopy; sulfated glycans; glycosaminoglycans; marine medicinal glycomics; interactomics; glycosaminoglycan–protein interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glycobiology is a branch of science aimed at understanding the structure and function of carbohydrates and/or glycosylated compounds. It was previously believed that carbohydrates were biomolecules mainly responsible for storing energy, like glycogen and starch in animals and plants, or to serve as structural components, like chitin on the exoskeleton of insects and mollusks, and cellulose on the cell walls of plants and algae. This limited conception has been considerably enlarged over the last decades as the number of glycans and glycoconjugate structures have been revealed and associated with their various functions in biology and with their potential uses in medicine. Today, a series of functional glycans and glycoconjugates are widely studied in many scientific laboratories around the world. The research not only concerns the structural variations of carbohydrates, but also the functional roles and/or the beneficial effects of these molecules in various human diseases, such as inflammation, coagulation, thrombosis, cancer, microbial infections and neuronal disorders. Examples of carbohydrates under intense investigation today are the N- or O-linked glycoproteins, glycolipids, glycosaminoglycans, proteoglycans and marine glycans like chitosan and sulfated polysaccharides. The impact of glycobiology on medicine has grown so intensively lately that even certain academic courses such as medicine, pharmacy, biology, biochemistry and chemistry, are now incorporating glycobiology as a separate subject in their curricula. Besides this, new international research programs related to this science have been developed. Examples of these projects include glycomics, medicinal glycomics, glycosaminoglycanomics, glycoproteomics and others. In this Special Issue, research and review papers are presented to enlighten the discussion about the potential therapeutic applications of carbohydrates.

Prof. Dr. Vitor H. Pomin
Guest Editor

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Keywords

  • N-linked glycans
  • O-linked glycans
  • glycolipids
  • proteoglycans
  • glycosaminoglycans
  • chitosan
  • sulfated fucans
  • sulfated galactans

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Published Papers (5 papers)

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Research

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15 pages, 1917 KiB  
Article
Glucosamine Enhances TRAIL-Induced Apoptosis in the Prostate Cancer Cell Line DU145
by Chao Sun, Viktor Chesnokov, Garrett Larson and Keiichi Itakura
Medicines 2019, 6(4), 104; https://doi.org/10.3390/medicines6040104 - 15 Oct 2019
Cited by 3 | Viewed by 4137
Abstract
Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells in cancer patients. However, patients often develop TRAIL resistance; thus, agents that can sensitize cells to TRAIL therapy would be beneficial clinically. Methods: Immunoblotting, flow cytometry, confocal microscopy, qPCR [...] Read more.
Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells in cancer patients. However, patients often develop TRAIL resistance; thus, agents that can sensitize cells to TRAIL therapy would be beneficial clinically. Methods: Immunoblotting, flow cytometry, confocal microscopy, qPCR and caspase 8 activity assays were used to investigate whether glucosamine (GlcN) can sensitize cancer cells to TRAIL thereby enhancing apoptosis and potentially improving clinical response. Results: GlcN sensitized DU145 cells to TRAIL-induced apoptosis but did not increase death receptor 5 (DR5) cell surface expression. Once treated, these cells responded to TRAIL-induced apoptosis through both extrinsic and intrinsic apoptotic pathways as evidenced by the cleavage of both caspases 8 and 9. The combination of GlcN and TRAIL suppressed the expression of key anti-apoptotic factors cFLIP, BCL-XL, MCL-1 and XIAP and translocated BAK to the mitochondrial outer membrane thereby facilitating cytochrome C and SMAC release. In addition to the activation of apoptotic pathways, TRAIL-mediated inflammatory responses were attenuated by GlcN pretreatment reducing nuclear NF-kB levels and the expression of downstream target genes IL-6 and IL-8. Conclusions: GlcN/TRAIL combination could be a promising strategy for treating cancers by overcoming TRAIL resistance and abrogating TRAIL-induced inflammation. Full article
(This article belongs to the Special Issue Application of Glycobiology in the Treatment of Diseases)
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10 pages, 645 KiB  
Communication
Targeting Aberrant Sialylation to Treat Cancer
by Jennifer Munkley and Emma Scott
Medicines 2019, 6(4), 102; https://doi.org/10.3390/medicines6040102 - 13 Oct 2019
Cited by 47 | Viewed by 8174
Abstract
Cell surface carbohydrates (known as glycans) are often aberrantly expressed or found at atypical levels in cancer. Glycans can impact all steps in tumour progression, from malignant transformation to metastasis, and have roles in all the cancer hallmarks. An increased understanding of glycans [...] Read more.
Cell surface carbohydrates (known as glycans) are often aberrantly expressed or found at atypical levels in cancer. Glycans can impact all steps in tumour progression, from malignant transformation to metastasis, and have roles in all the cancer hallmarks. An increased understanding of glycans in the metastatic cascade offers exciting new therapeutic opportunities. Glycan-based targeting strategies are currently being tested in clinical trials and are a rich and untapped frontier for development. As we learn more about cancer glycobiology, new targets will continue to emerge for drug design. One key change in tumour glycosylation is the upregulation of cancer-associated sialylated glycans. Abnormal sialylation is integral to tumour growth, metastasis and immune evasion; therefore, targeting sialic acid moieties in cancer could be of high therapeutic value. Here, we summarise the changes to sialic acid biology in cancer and discuss recent advances and technologies bringing sialic-acid targeting treatments to the forefront of cancer therapeutics. Full article
(This article belongs to the Special Issue Application of Glycobiology in the Treatment of Diseases)
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10 pages, 309 KiB  
Article
Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults
by Kenny Mendoza-Herrera, Celia Aradillas-García, Miguel A. Mejía-Diaz, Jorge A. Alegría-Torres, Ma. Eugenia Garay-Sevilla and Claudia Luevano-Contreras
Medicines 2018, 5(4), 128; https://doi.org/10.3390/medicines5040128 - 1 Dec 2018
Cited by 10 | Viewed by 3960
Abstract
Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 [...] Read more.
Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18–35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (≥10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29–18.60, p < 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96–7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake. Full article
(This article belongs to the Special Issue Application of Glycobiology in the Treatment of Diseases)

Review

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21 pages, 1163 KiB  
Review
Early Stage Glycosylation Biomarkers in Alzheimer’s Disease
by Patricia Regan, Paula L. McClean, Thomas Smyth and Margaret Doherty
Medicines 2019, 6(3), 92; https://doi.org/10.3390/medicines6030092 - 3 Sep 2019
Cited by 19 | Viewed by 5836
Abstract
Alzheimer’s disease (AD) is of great cause for concern in our ageing population, which currently lacks diagnostic tools to permit accurate and timely diagnosis for affected individuals. The development of such tools could enable therapeutic interventions earlier in the disease course and thus [...] Read more.
Alzheimer’s disease (AD) is of great cause for concern in our ageing population, which currently lacks diagnostic tools to permit accurate and timely diagnosis for affected individuals. The development of such tools could enable therapeutic interventions earlier in the disease course and thus potentially reducing the debilitating effects of AD. Glycosylation is a common, and important, post translational modification of proteins implicated in a host of disease states resulting in a complex array of glycans being incorporated into biomolecules. Recent investigations of glycan profiles, in a wide range of conditions, has been made possible due to technological advances in the field enabling accurate glycoanalyses. Amyloid beta (Aβ) peptides, tau protein, and other important proteins involved in AD pathogenesis, have altered glycosylation profiles. Crucially, these abnormalities present early in the disease state, are present in the peripheral blood, and help to distinguish AD from other dementias. This review describes the aberrant glycome in AD, focusing on proteins implicated in development and progression, and elucidates the potential of glycome aberrations as early stage biomarkers of AD. Full article
(This article belongs to the Special Issue Application of Glycobiology in the Treatment of Diseases)
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26 pages, 2043 KiB  
Review
Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends
by Giancarlo Ghiselli
Medicines 2019, 6(3), 80; https://doi.org/10.3390/medicines6030080 - 29 Jul 2019
Cited by 15 | Viewed by 4955
Abstract
The polyanionic nature and the ability to interact with proteins with different affinities are properties of sulfated glycosaminoglycans (GAGs) that determine their biological function. In designing drugs affecting the interaction of proteins with GAGs the challenge has been to generate agents with high [...] Read more.
The polyanionic nature and the ability to interact with proteins with different affinities are properties of sulfated glycosaminoglycans (GAGs) that determine their biological function. In designing drugs affecting the interaction of proteins with GAGs the challenge has been to generate agents with high binding specificity. The example to emulated has been a heparin-derived pentasaccharide that binds to antithrombin-III with high affinity. However, the portability of this model to other biological situations is questioned on several accounts. Because of their structural flexibility, oligosaccharides with different sulfation and uronic acid conformation can display the same binding proficiency to different proteins and produce comparable biological effects. This circumstance represents a formidable obstacle to the design of drugs based on the heparin scaffold. The conceptual framework discussed in this article is that through a direct intervention on the heparin-binding functionality of proteins is possible to achieve a high degree of action specificity. This objective is currently pursued through two strategies. The first makes use of small molecules for which in the text we provide examples from past and present literature concerning angiogenic factors and enzymes. The second approach entails the mutagenesis of the GAG-binding site of proteins as a means to generate a new class of biologics of therapeutic interest. Full article
(This article belongs to the Special Issue Application of Glycobiology in the Treatment of Diseases)
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