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Molecules (Basel, Switzerland) Mar 2020Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this... (Review)
Review
Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this set of engineered polysaccharides finds application in different sectors, spanning from food to the biomedical field. Overcoming chitosan (physical) limitations or grafting biological relevant molecules, to mention a few, represent two cardinal strategies to modify parent biopolymer; thereby, synthetizing high added value polysaccharides. The present review is focused on the introduction of oligosaccharide side chains on the backbone of chitosan. The synthetic aspects and the effect on physical-chemical properties of such modifications are discussed. Finally, examples of potential applications in biomaterials design and drug delivery of these novel modified chitosans are disclosed.
Topics: Animals; Biocompatible Materials; Chitosan; Drug Delivery Systems; Glycosylation; Humans; Molecular Dynamics Simulation; Nanoparticles; Oligosaccharides; Tissue Engineering
PubMed: 32230971
DOI: 10.3390/molecules25071534 -
Cells Feb 2020Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is...
Glycosylation is the most commonly occurring post-translational modifications, and is believed to modify over 50% of all proteins. The process of glycan modification is directed by different glycosyltransferases, depending on the cell in which it is expressed. These small carbohydrate molecules consist of multiple glycan families that facilitate cell-cell interactions, protein interactions, and downstream signaling. An alteration of several types of O-glycan core structures have been implicated in multiple cancers, largely due to differential glycosyltransferase expression or activity. Consequently, aberrant O-linked glycosylation has been extensively demonstrated to affect biological function and protein integrity that directly result in cancer growth and progression of several diseases. Herein, we provide a comprehensive review of several initiating enzymes involved in the synthesis of O-linked glycosylation that significantly contribute to a number of different cancers.
Topics: Animals; Disease Progression; Glycosylation; Humans; Neoplasm Metastasis; Neoplasms; Polysaccharides; Protein Processing, Post-Translational
PubMed: 32075174
DOI: 10.3390/cells9020446 -
Arteriosclerosis, Thrombosis, and... Mar 2020Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current...
OBJECTIVE
Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but fibrinolysis was found to be decreased, as a consequence of increased density and decreased permeability of clots. Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis. Other modifications were studied less or contrasting results were found. Therefore, substantial gaps in the knowledge about the effect of post-translational modifications remain.
CONCLUSIONS
Overall, post-translational modifications do affect clot formation and characteristics. More studies need to be performed to reveal the effects of all post-translational modifications and the effects on thrombotic diseases. Expanding the knowledge about modifications of fibrinogen can ultimately contribute to optimizing treatments for thrombotic diseases.
Topics: Acetylation; Animals; Fibrinogen; Fibrinolysis; Glycosylation; Humans; Oxidation-Reduction; Polymerization; Protein Processing, Post-Translational; Thrombosis
PubMed: 31914791
DOI: 10.1161/ATVBAHA.119.313626 -
Journal of Inherited Metabolic Disease May 2020Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an...
Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an inborn error of carbohydrate metabolism caused by deficient activity of any of the galactose metabolising enzymes. The current standard of care, a galactose-restricted diet, fails to prevent long-term complications. Studies in cellular and animal models in the past decades have led to an enormous progress and advancement of knowledge. Summarising current evidence in the pathophysiology underlying hereditary galactosemia may contribute to the identification of treatment targets for alternative therapies that may successfully prevent long-term complications. A systematic review of cellular and animal studies reporting on disease complications (clinical signs and/or biochemical findings) and/or treatment targets in hereditary galactosemia was performed. PubMed/MEDLINE, EMBASE, and Web of Science were searched, 46 original articles were included. Results revealed that Gal-1-P is not the sole pathophysiological agent responsible for the phenotype observed in galactosemia. Other currently described contributing factors include accumulation of galactose metabolites, uridine diphosphate (UDP)-hexose alterations and subsequent impaired glycosylation, endoplasmic reticulum (ER) stress, altered signalling pathways, and oxidative stress. galactokinase (GALK) inhibitors, UDP-glucose pyrophosphorylase (UGP) up-regulation, uridine supplementation, ER stress reducers, antioxidants and pharmacological chaperones have been studied, showing rescue of biochemical and/or clinical symptoms in galactosemia. Promising co-adjuvant therapies include antioxidant therapy and UGP up-regulation. This systematic review provides an overview of the scattered information resulting from animal and cellular studies performed in the past decades, summarising the complex pathophysiological mechanisms underlying hereditary galactosemia and providing insights on potential treatment targets.
Topics: Animals; Disease Models, Animal; Galactokinase; Galactose; Galactosemias; Genotype; Humans; Oxidative Stress; Phenotype; UDPglucose 4-Epimerase; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 31808946
DOI: 10.1002/jimd.12202 -
World Journal of Gastroenterology Jun 2019Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core...
BACKGROUND
Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels.
AIM
To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma.
METHODS
The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal.
RESULTS
A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples.
CONCLUSION
Amplification of genes involved in the pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.
Topics: Carbohydrate Epimerases; Carcinoma, Hepatocellular; DNA Copy Number Variations; DNA Methylation; Gene Expression Regulation, Neoplastic; Glycoproteins; Glycosylation; Guanosine Diphosphate Fucose; Humans; Hydro-Lyases; Ketone Oxidoreductases; Liver Neoplasms; Metabolic Networks and Pathways; Mutation
PubMed: 31249452
DOI: 10.3748/wjg.v25.i23.2947 -
Cancer Management and Research 2019Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools... (Review)
Review
INTRODUCTION
Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.
METHODS
This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.
RESULTS
A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.
CONCLUSION
Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite.
PubMed: 30881111
DOI: 10.2147/CMAR.S188661 -
PloS One 2018Diabetes mellitus (DM) is associated with hyperglycaemia and advanced glycosylation end-products. In the foot, the consequences of chronic or uncontrolled diabetes are...
INTRODUCTION
Diabetes mellitus (DM) is associated with hyperglycaemia and advanced glycosylation end-products. In the foot, the consequences of chronic or uncontrolled diabetes are micro and macrovascular disease, neuropathy, reduced joint mobility and structural and soft tissue changes that increase the risk of ulcer development and amputation. Diabetes foot assessment currently includes a comprehensive history, neurological and vascular assessments and examination focussed on dermatological and musculoskeletal abnormalities. Whilst these assessments are helpful for predicting ulceration risk, direct identifiers that enable early therapeutic intervention are lacking. The intention of this review was to ascertain if B-mode ultrasound could be clinically applied to identify structural change in the diabetic foot and be utilised as an early predictor of ulceration risk.
METHODS
Primary databases and grey literature sources were systematically searched. Selection criteria were that the study included a diabetic sample and used B-mode ultrasound to assess soft tissue structures of the foot (plantar skin, plantar fat pad or intrinsic muscles).
RESULTS
Fifteen studies were identified for inclusion (combined diabetic sample of 773). Ultrasound demonstrated reductions in tissue thickness in diabetics compared to non-diabetics under first (p = 0.01) and second (p = 0.03) metatarsal heads, but not the third (p = 0.24). Statistical heterogeneity was high for ultrasound thickness measures under metatarsal heads four/five (I2 65%, 81%) and very high for plantar skin (I2 98%), heel pad (I2 76%) and intrinsic muscles (I2 91%, 81%). Extensor digitorum brevis (EDB) ultrasound measures were significantly thinner in diabetics for all dimension measures compared to healthy controls except one study, which reported no significant differences in EDB thickness.
CONCLUSIONS
No direct evidence was found to indicate B-mode ultrasound measures can predict soft tissue changes in the plantar foot in diabetes, although low level studies indicate ultrasound has the potential to identify structural change. Clinical, methodological and statistical heterogeneity limit result applicability. This review highlights the need for robust prospective longitudinal research to examine the predictive validity of this method.
Topics: Adipose Tissue; Diabetic Foot; Feasibility Studies; Foot; Humans; Muscle, Skeletal; Predictive Value of Tests; Prognosis; Skin; Ultrasonography
PubMed: 29906277
DOI: 10.1371/journal.pone.0199055 -
Epidemiology and Infection Jul 2018Almost the full range of 16 haemagglutinin (HA) and nine neuraminidase subtypes of avian influenza viruses (AIVs) has been detected either in waterfowl, land-based...
Almost the full range of 16 haemagglutinin (HA) and nine neuraminidase subtypes of avian influenza viruses (AIVs) has been detected either in waterfowl, land-based poultry or in the environment in Bangladesh. AIV infections in Bangladesh affected a wide range of host species of terrestrial poultry. The highly pathogenic avian influenza (AI) H5N1 and low pathogenic AI H9N2 were found to co-circulate and be well entrenched in the poultry population, which has caused serious damage to the poultry industry since 2007. By reviewing the available scientific literature, the overall situation of AIVs in Bangladesh is discussed. All Bangladeshi (BD) H5N1 and H9N2 AIV sequences available at GenBank were downloaded along with other representative sequences to analyse the genetic diversity among the circulating AIVs in Bangladesh and to compare with the global situation. Three different H5N1 clades, 2.2.2, 2.3.2.1 and 2.3.4.2, have been detected in Bangladesh. Only 2.3.2.1a is still present. The BD LP H9N2 viruses mostly belonged to the H9 G1 lineage but segregated into many branches, and some of these shared internal genes with HP viruses of subtypes H7N3 and H5N1. However, these reassortment events might have taken place before introduction to Bangladesh. Currently, H9N2 viruses continue to evolve their HA cleavage, receptor binding and glycosylation sites. Multiple mutations in the HA gene associated with adaptation to mammalian hosts were also observed. Strict biosecurity at farms and gradual phasing out of live-bird markets could be the key measures to better control AIVs, whereas stamping out is not a practicable option in Bangladesh. Vaccination also could be an additional tool, which however, requires careful planning. Continuous monitoring of AIVs through systematic surveillance and genetic characterisation of the viruses remains a hallmark of AI control.
Topics: Animals; Bangladesh; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H9N2 Subtype; Influenza in Birds; Mutation; Poultry; Poultry Diseases; Risk Factors
PubMed: 29781424
DOI: 10.1017/S0950268818001292 -
PloS One 2017Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.
METHODS
Serum samples from patients with MS (n = 108) and controls (n = 77) were tested for the presence of anti-KIR4.1 antibodies using three methods: 1) by ELISA with the low-glycosylated fraction of recombinant KIR4.1 purified from transfected HEK293 cells according to original protocols; 2) by immunocytochemistry using KIR4.1-transfected HEK293 cells; and 3) by immunocytochemistry using the KIR4.1.-transfected MO3.13 oligodendrocyte cell line. We developed a systematic review and meta-analysis of the association of anti-KIR4.1 antibodies with MS according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
We did not detect anti-KIR4.1 antibodies in the MS patients or in controls using ELISA. Neither did we detect any significant reactivity against the antigen on the cell surface using the KIR4.1-transfected HEK293 cells or the KIR4.1-transfected MO3.13 cells. We included 13 prospective controlled studies in the systematic review. Only three studies showed a positive association between anti-KIR4.1 and MS. Clinical and statistical heterogeneity between studies precluded meta-analysis of their results.
CONCLUSION
We found no association between anti-KIR4.1 antibody positivity and MS. Although this lack of replication may be due to technical limitations, evidence from our study and others is mounting against the role of KIR4.1 as a relevant MS autoantigen.
Topics: Adult; Aged; Aged, 80 and over; Antibodies; Autoantigens; Cell Line; Female; Glycosylation; HEK293 Cells; Humans; Male; Middle Aged; Multiple Sclerosis; Potassium Channels, Inwardly Rectifying; Prospective Studies; Young Adult
PubMed: 28414733
DOI: 10.1371/journal.pone.0175538 -
Medicine Dec 2016The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and ischemic stroke (IS) remain controversial. The Gly82Ser polymorphism is located in the ligand-binding V domain of RAGE, suggesting a possible influence of this variant on RAGE function. The aim of the present study is to clarify the association between the RAGE Gly82Ser polymorphism and susceptibility to CAD and IS.
METHODS
Eligible studies were identified through a comprehensive literature search. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association of Gly82Ser polymorphism with CAD and IS risk. Fixed- or random-effects model was used depending on the heterogeneity between studies. A funnel plot and Egger linear regression test were applied to assess publication bias. We also performed subgroup analyses to investigate potential sources of heterogeneity.
RESULTS
A total of 16 eligible articles containing 18 studies were analyzed. The pooled analysis indicated that the Gly82Ser polymorphism significantly increased CAD risk in recessive and homozygous genetic models (SS vs GS + GG: OR = 1.34, 95% CI = 1.09-1.64; SS vs GG: OR = 1.38, 95% CI = 1.12-1.71). A significant association between the Gly82Ser polymorphism and IS risk was observed in all tested models except the heterozygous genetic model (GS + SS vs GG: OR = 1.20, 95% CI = 1.04-1.38; SS vs GS + GG: OR = 2.20, 95% CI = 1.74-2.78; SS vs GG: OR = 2.23, 95% CI = 1.72-2.91; S vs G: OR = 1.32, 95% CI = 1.05-1.65). Subgroup analysis suggested an association between CAD and IS risk and the Gly82Ser polymorphism in the Chinese population, but not in the non-Chinese population.
CONCLUSIONS
The current meta-analysis suggests that the RAGE Gly82Ser polymorphism is associated with an increased risk of CAD and IS, especially in the Chinese population. However, better-designed studies with larger sample sizes are needed to validate the results.
Topics: Antigens, Neoplasm; Brain Ischemia; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; Incidence; Male; Mitogen-Activated Protein Kinases; Polymorphism, Genetic; Risk Assessment; Sensitivity and Specificity; Stroke
PubMed: 27930580
DOI: 10.1097/MD.0000000000005593