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Glycosaminoglycans and Disease: Experimental Approaches, Interactions and Mechanisms

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 10207

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Special Issue Editors

Dr. Jill Madine

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Guest Editor

Department of Biochemistry, Institute of Integrative Biology, G09/Biosciences Building, University of Liverpool, Liverpool L69 7ZB, UK
Interests: protein interactions; amyloid; glycosaminoglycans; cardiovascular disease; neurodegenerative disease; protein aggregation; biochemistry; structural biology

Dr. Edwin Yates

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Guest Editor

Department of Biochemistry, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK
Interests: glycosaminoglycan structure and function; protein–polysaccharide interactions; extraction; purification; spectroscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glycosaminoglycans are becoming a defining feature associated with many disease processes. The aim of this Special Issue is to provide an platform for the dissemination of the latest research investigating the role of glycosaminoglycans in human health and disease. We welcome novel practical approaches for their study and the potential for future exploration as therapeutic targets and/or biomarkers. We are keen to probe characterisation of protein–glycosaminoglycan interactions and encourage submissions focussed on the identification of glycosaminoglycans associated with health and disease or that study its changes upon ageing. We invite researchers interested in glycosaminoglycans to join this Special Issue and submit original research articles, short communications, and review articles for consideration.

Dr. Jill Madine
Dr. Edwin Yates
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

glycosaminoglycans
proteoglycans
protein interactions
human disease
ageing and health

Published Papers (4 papers)

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Research

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16 pages, 3395 KiB

Open AccessArticle

Chondroitin Sulfate Protects the Liver in an Experimental Model of Extra-Hepatic Cholestasis Induced by Common Bile Duct Ligation

by Pedro L. R. Guedes, Carolina P. F. Carvalho, Adriana A. F. Carbonel, Manuel J. Simões, Marcelo Y. Icimoto, Jair A. K. Aguiar, Maria Kouyoumdjian, Marcos L. Gazarini and Marcia R. Nagaoka

Molecules 2022, 27(3), 654; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030654 - 20 Jan 2022

Cited by 2 | Viewed by 1731

Abstract

During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Disease: Experimental Approaches, Interactions and Mechanisms)

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16 pages, 804 KiB

Open AccessArticle

Isolation and Characterization of Heparan Sulfate from Human Lung Tissues

by Rupert Derler, Nikola Kitic, Tanja Gerlza and Andreas J. Kungl

Molecules 2021, 26(18), 5512; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26185512 - 10 Sep 2021

Cited by 2 | Viewed by 1591

Abstract

Glycosaminoglycans are a class of linear, highly negatively charged, O-linked polysaccharides that are involved in many (patho)physiological processes. In vitro experimental investigations of such processes typically involve porcine-derived heparan sulfate (HS). Structural information about human, particularly organ-specific heparan sulfate, and how it compares with HS from other organisms, is very limited. In this study, heparan sulfate was isolated from human lung tissues derived from five donors and was characterized for their overall size distribution and disaccharide composition. The expression profiles of proteoglycans and HS-modifying enzymes was quantified in order to identify the major core proteins for HS. In addition, the binding affinities of human HS to two chemokines—CXCL8 and CCL2—were investigated, which represent important inflammatory mediators in lung pathologies. Our data revealed that syndecans are the predominant proteoglycan class in human lungs and that the disaccharide composition varies among individuals according to sex, age, and health stage (one of the donor lungs was accidentally discovered to contain a solid tumor). The compositional difference of the five human lung HS preparations affected chemokine binding affinities to various degrees, indicating selective immune cell responses depending on the relative chemokine–glycan affinities. This represents important new insights that could be translated into novel therapeutic concepts for individually treating lung immunological disorders via HS targets. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Disease: Experimental Approaches, Interactions and Mechanisms)

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13 pages, 978 KiB

Open AccessArticle

Diagnostic Accuracy of Serum Hyaluronan for Detecting HCV Infection and Liver Fibrosis in Asymptomatic Blood Donors

by Itatiana F. Rodart, Madalena M. Pares, Aline Mendes, Camila M. Accardo, João R. M. Martins, Cleidenice B. Silva, Fabrício O. Carvalho, José A. Barreto, Mitermayer G. Reis, Ivarne L. S. Tersariol and Helena B. Nader

Molecules 2021, 26(13), 3892; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26133892 - 25 Jun 2021

Cited by 5 | Viewed by 2025

Abstract

Background: The disease caused by hepatitis C virus (HCV) is asymptomatic, silent, and progressive liver disease. In HCV-infected patients the increase in serum HA is associated with the development of hepatic fibrosis and disease progression. Methods: HCV-RNA detection was performed in all serological samples of blood donors that tested positive using HCV Ultra ELISA. Determination of hyaluronan (HA) was performed in positive HCV samples using ELISA-like fluorometric method. The HA content was compared to HCV viral load, genotype of the virus, liver fibrosis as well as ALT and GGT liver biomarkers. Results: Persistently normal ALT (<40 U/L) and GGT (<50 U/L) serum levels were detected in 75% and 69% of the HCV-Infected blood donors, respectively. Based on ROC analysis, the HA value < 34.2 ng/mL is an optimal cut-off point to exclude HCV viremia (specificity = 91%, NPV = 99%). Applying HA value ≥34.2 ng/mL significant liver fibrosis (≥F2) can be estimated in 46% of the HCV-infected blood donors. HA serum level (≥34.2 ng/mL) associated with a high ALT level (>40 U/mL) can correctly identify HCV infection and probable liver fibrosis (sensitivity = 96% and specificity = 90%) in asymptomatic blood donors. Conclusions: A high level of HA (≥34.2 ng/mL) in association with ALT (≥40 U/L) in serum can provide a good clinical opportunity to detect HCV-infected asymptomatic persons that potentially require a liver biopsy confirmation and antiviral treatment to prevent the development of advanced liver fibrosis or cirrhosis. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Disease: Experimental Approaches, Interactions and Mechanisms)

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Review

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22 pages, 1560 KiB

Open AccessReview

Chemical Modification of Glycosaminoglycan Polysaccharides

by Lais C. G. F. Palhares, James A. London, Aleksandra M. Kozlowski, Emiliano Esposito, Suely F. Chavante, Minghong Ni and Edwin A. Yates

Molecules 2021, 26(17), 5211; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26175211 - 27 Aug 2021

Cited by 16 | Viewed by 4282

Abstract

The linear anionic class of polysaccharides, glycosaminoglycans (GAGs), are critical throughout the animal kingdom for developmental processes and the maintenance of healthy tissues. They are also of interest as a means of influencing biochemical processes. One member of the GAG family, heparin, is exploited globally as a major anticoagulant pharmaceutical and there is a growing interest in the potential of other GAGs for diverse applications ranging from skin care to the treatment of neurodegenerative conditions, and from the treatment and prevention of microbial infection to biotechnology. To realize the potential of GAGs, however, it is necessary to develop effective tools that are able to exploit the chemical manipulations to which GAGs are susceptible. Here, the current knowledge concerning the chemical modification of GAGs, one of the principal approaches for the study of the structure-function relationships in these molecules, is reviewed. Some additional methods that were applied successfully to the analysis and/or processing of other carbohydrates, but which could be suitable in GAG chemistry, are also discussed. Full article

(This article belongs to the Special Issue Glycosaminoglycans and Disease: Experimental Approaches, Interactions and Mechanisms)

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