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Frontiers in Immunology 2019Monocytes are subdivided into three subsets, which have different phenotypic and functional characteristics and different roles in inflammation and malignancy. When in... (Review)
Review
Monocytes are subdivided into three subsets, which have different phenotypic and functional characteristics and different roles in inflammation and malignancy. When in man CD14 and CD16 monoclonal antibodies are used to define these subsets, then the distinction of non-classical CD14low and intermediate CD14high monocytes requires setting a gate in what is a gradually changing level of CD14 expression. In the search for an additional marker to better dissect the two subsets we have explored the marker 6-sulfo LacNAc (slan). Slan is a carbohydrate residue originally described to be expressed on the cell surface of a type of dendritic cell in human blood. We elaborate herein that the features of slan+ cells are congruent with the features of CD16+ non-classical monocytes and that slan is a candidate marker for definition of non-classical monocytes. The use of this marker may help in studying the role of non-classical monocytes in health and in diagnosis and monitoring of disease.
Topics: Amino Sugars; Animals; Biomarkers; Dendritic Cells; Humans; Inflammation; Monocytes; Neoplasms; Phenotype
PubMed: 31572354
DOI: 10.3389/fimmu.2019.02052 -
Journal of Pharmaceutical and... Feb 2020Erythropoiesis stimulating agents (ESAs) are a group of therapeutic glycoproteins used to treat anaemia caused by chronic kidney disease or chemotherapy. A variety of...
Erythropoiesis stimulating agents (ESAs) are a group of therapeutic glycoproteins used to treat anaemia caused by chronic kidney disease or chemotherapy. A variety of ESA products are available in the European Union, including innovator, biosimilar and second-generation medicines. Glycosylation is a critical quality attribute of ESA products, as it has a crucial influence upon in vivo biological activity. In this study, a combination of chromatography and mass spectrometry analysis has been used to characterise and compare the glycosylation profiles of five ESA products; Eprex® (epoetin alfa), NeoRecormon® (epoetin beta), Binocrit® (epoetin alfa biosimilar), Silapo (epoetin alfa biosimilar) and Aranesp® (darbepoetin alfa). The methods utilised include mixed-mode anion-exchange/hydrophilic interaction chromatography (AEX/HILIC-MS) for N-glycan identification and quantitation, and HILIC-MS for O-glycan characterisation. The products exhibit notable differences in N- and O-glycosylation, including attributes such as sialic acid occupation, O-acetylation, N-acetyllactosamine extended antennae and sulphated/penta-sialylated N-glycans, which have the potential to cause divergence of therapeutic potencies. The study highlights the need for continued monitoring of ESA product glycosylation, ideally allied to pharmacological data, in order to ensure consistency and therapeutic equivalence between products and enhance our understanding of ESA structure-activity-relationships.
Topics: Acetylation; Amino Sugars; Biosensing Techniques; Chromatography, High Pressure Liquid; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Glycosylation; Hematinics; Molecular Structure; N-Acetylneuraminic Acid; Polysaccharides; Recombinant Proteins; Tandem Mass Spectrometry
PubMed: 31838284
DOI: 10.1016/j.jpba.2019.113031 -
Carbohydrate Research May 2024Sialic acid, the terminal structure of cell surface glycans, has essential functions in regulating immune response, cell-to-cell communication, and cell adhesion. More... (Review)
Review
Sialic acid, the terminal structure of cell surface glycans, has essential functions in regulating immune response, cell-to-cell communication, and cell adhesion. More importantly, an increased level of sialic acid, termed hypersialylation, has emerged as a commonly observed phenotype in cancer. Therefore, targeting sialic acid ligands (sialoglycans) and their receptors (Siglecs) may provide a new therapeutic approach for cancer immunotherapy. We highlight the complexity of the sialic acid metabolism and its involvement in malignant transformation within individual cancer subtypes. In this review, we focus on the dysregulation of sialylation, the intricate nature of sialic acid synthesis, and clinical perspective. We aim to provide a brief insight into the mechanism of hypersialylation and how our understanding of these processes can be leveraged for the development of novel therapeutics.
Topics: Humans; Neoplasms; N-Acetylneuraminic Acid; Animals
PubMed: 38669826
DOI: 10.1016/j.carres.2024.109123 -
The Journal of Biological Chemistry Mar 2023The human gastrointestinal (GI) tract harbors diverse microbial communities collectively known as the gut microbiota that exert a profound impact on human health and... (Review)
Review
The human gastrointestinal (GI) tract harbors diverse microbial communities collectively known as the gut microbiota that exert a profound impact on human health and disease. The repartition and availability of sialic acid derivatives in the gut have a significant impact on the modulation of gut microbes and host susceptibility to infection and inflammation. Although N-acetylneuraminic acid (Neu5Ac) is the main form of sialic acids in humans, the sialic acid family regroups more than 50 structurally and chemically distinct modified derivatives. In the GI tract, sialic acids are found in the terminal location of mucin glycan chains constituting the mucus layer and also come from human milk oligosaccharides in the infant gut or from meat-based foods in adults. The repartition of sialic acid in the GI tract influences the gut microbiota composition and pathogen colonization. In this review, we provide an update on the mechanisms underpinning sialic acid utilization by gut microbes, focusing on sialidases, transporters, and metabolic enzymes.
Topics: Infant; Humans; N-Acetylneuraminic Acid; Gastrointestinal Microbiome; Sialic Acids; Mucins; Polysaccharides
PubMed: 36758803
DOI: 10.1016/j.jbc.2023.102989 -
Nature Chemical Biology Jan 2022The vast array of cell types of multicellular organisms must individually fine-tune their internal metabolism. One important metabolic and stress regulatory mechanism is... (Review)
Review
The vast array of cell types of multicellular organisms must individually fine-tune their internal metabolism. One important metabolic and stress regulatory mechanism is the dynamic attachment/removal of glucose-derived sugar N-acetylglucosamine on proteins (O-GlcNAcylation). The number of proteins modified by O-GlcNAc is bewildering, with at least 7,000 sites in human cells. The outstanding challenge is determining how key O-GlcNAc sites regulate a target pathway amidst thousands of potential global sites. Innovative solutions are required to address this challenge in cell models and disease therapy. This Perspective shares critical suggestions for the O-GlcNAc field gleaned from the international O-GlcNAc community. Further, we summarize critical tools and tactics to enable newcomers to O-GlcNAc biology to drive innovation at the interface of metabolism and disease. The growing pace of O-GlcNAc research makes this a timely juncture to involve a wide array of scientists and new toolmakers to selectively approach the regulatory roles of O-GlcNAc in disease.
Topics: Acetylglucosamine; Disease; Glycosylation; Humans; Protein Processing, Post-Translational; Proteins
PubMed: 34934185
DOI: 10.1038/s41589-021-00903-6 -
International Journal of Molecular... Oct 2022Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its... (Review)
Review
Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems.
Topics: Humans; Hyaluronic Acid; Polyelectrolytes; Acetylglucosamine; Hydrogels; Glycosaminoglycans; Glucuronic Acid; Disaccharides; Nervous System; Tissue Scaffolds; Tissue Engineering
PubMed: 36293030
DOI: 10.3390/ijms232012174 -
Acta Clinica Croatica Nov 2022Osteoarthritis (OA) can be treated using either a pharmacological or non-pharmacological approach, or a combination of both. The purpose of the present study was to...
Osteoarthritis (OA) can be treated using either a pharmacological or non-pharmacological approach, or a combination of both. The purpose of the present study was to investigate the efficacy of crystalline glucosamine sulfate (CGS) in patients with knee OA. This open-label prospective study (with a 12-month follow-up) included 111 patients of both genders suffering from knee OA, who attended the Special Hospital for Rheumatic Diseases in Novi Sad, Serbia during the 2011-2013 period. Patients were divided into the experimental (n=52) and the control (n=59) group. While the former was prescribed CGS 1500 mg/day, the latter was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) according to the standard protocol. The efficacy of both treatment modes was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne index, along with the radiological findings which involved knee joint space width (JSW) measurements. One year following the initial assessment, all patients reported pain intensity reduction; however, those in the CGS group experienced significantly lower pain intensity when compared with controls. At the end of the study, no reduction in the progression of joint structure damage (p>0.5) was noted in either group. Thus, while CGS demonstrated symptomatic efficacy, it failed to delay the progression of knee OA.
Topics: Female; Humans; Male; Follow-Up Studies; Glucosamine; Osteoarthritis, Knee; Prospective Studies; Treatment Outcome
PubMed: 37492361
DOI: 10.20471/acc.2022.61.03.09 -
Molecules (Basel, Switzerland) Jun 2023Amino sugars are a kind of carbohydrates with one or more hydroxyl groups replaced by an amino group. They play crucial roles in a broad range of biological activities.... (Review)
Review
Amino sugars are a kind of carbohydrates with one or more hydroxyl groups replaced by an amino group. They play crucial roles in a broad range of biological activities. Over the past few decades, there have been continuing efforts on the stereoselective glycosylation of amino sugars. However, the introduction of glycoside bearing basic nitrogen is challenging using conventional Lewis acid-promoted pathways owing to competitive coordination of the amine to the Lewis acid promoter. Additionally, diastereomeric mixtures of -glycoside are often produced if aminoglycoside lack a C2 substituent. This review focuses on the updated overview of the way to stereoselective synthesis of 1,2--aminoglycoside. The scope, mechanism, and the applications in the synthesis of complex glycoconjugates for the representative methodologies were also included.
Topics: Amino Sugars; Lewis Acids; Carbohydrates; Glycoconjugates; Aminoglycosides; Cardiac Glycosides; Stereoisomerism
PubMed: 37375279
DOI: 10.3390/molecules28124724 -
The Journal of Organic Chemistry Dec 2021We recently reported the incorporation of diazirine photo-cross-linkers onto the -GlcNAc posttranslational modification in mammalian cells, enabling the identification...
We recently reported the incorporation of diazirine photo-cross-linkers onto the -GlcNAc posttranslational modification in mammalian cells, enabling the identification of binding partners of -GlcNAcylated proteins. Unfortunately, the syntheses of the diazirine-functionalized substrates have exhibited inconsistent yields. We report a robust and stereoselective synthesis of cell-permeable GlcNAc-1-phosphate esters based on the use of commercially available bis(diisopropylamino)chlorophosphine. We demonstrate this approach for two diazirine-containing GlcNAc analogues, and we report the cellular incorporation of these compounds into glycoconjugates to support photo-cross-linking applications.
Topics: Acetylglucosamine; Animals; Diazomethane; Glycoconjugates; Phosphates; Proteins
PubMed: 34618463
DOI: 10.1021/acs.joc.1c01781 -
Journal of Biosciences 2024GNE myopathy is a rare genetic neuromuscular disease that is caused due to mutations in the GNE gene responsible for sialic acid biosynthesis. Foot drop is the most... (Review)
Review
GNE myopathy is a rare genetic neuromuscular disease that is caused due to mutations in the GNE gene responsible for sialic acid biosynthesis. Foot drop is the most common initial symptom observed in GNE myopathy patients. There is slow progressive muscle weakness in the lower and upper extremities while the quadriceps muscles are usually spared. The exact pathophysiology of the disease is unknown. Besides sialic acid biosynthesis, recent studies suggest either direct or indirect involvement of GNE in other cellular functions such as protein aggregation, apoptosis, ER stress, cell migration, HSP70 chaperone activity, autophagy, muscle atrophy, and myogenesis. Both animal and cell-based model systems are generated to elucidate the mechanism of GNE myopathy and evaluate the efficacy of therapies. The many therapeutic avenues explored include supplementation with sialic acid derivatives or precursors and gene therapy. Recent studies suggest other therapeutic options such as modulators of HSP70 chaperone (BGP-15), cofilin activator (CGA), and ligands like IGF-1 that may help to rescue cellular defects due to GNE dysfunction. This review provides an overview of the pathophysiology associated with GNE function in the cell and promising therapeutic leads to be explored for future drug development.
Topics: Animals; Humans; N-Acetylneuraminic Acid; Distal Myopathies; Mutation; Muscle, Skeletal
PubMed: 38383974
DOI: No ID Found