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International Journal of Molecular... May 2023Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by... (Review)
Review
Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications.
Topics: Humans; Cardiomyopathies; Metabolic Diseases; Heart Defects, Congenital; Glycosylation; Carbohydrates; Sugars; Chondroitinsulfatases; Pentosyltransferases; Mannosyltransferases; Acetyltransferases
PubMed: 37239976
DOI: 10.3390/ijms24108632 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
International Journal of Molecular... Aug 2022Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid... (Review)
Review
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.
Topics: Artificial Intelligence; Biomarkers; Congenital Disorders of Glycosylation; Drug Repositioning; Humans; Rare Diseases
PubMed: 35955863
DOI: 10.3390/ijms23158725 -
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 -
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 -
Frontiers in Immunology 2023Galactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Galactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment options. This updated systematic review aimed to determine the diagnostic and prognostic value of Gd-IgA1 assessment in biological fluids in patients with IgAN.
METHODS
PRISMA guidelines were followed in this review. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Information/China Science and Technology Journal Database, and WANFANG for studies published between database inception and January 31, 2023. Eligible studies that evaluated aberrant IgA1 glycosylation in IgAN patients relative to controls were identified, and random effects meta-analyses were used to compare Gd-IgA1 levels in different groups. The quality of the evidence was assessed using the Newcastle-Ottawa Scale. This study was registered on PROSPERO (CRD42022375246).
FINDINGS
Of the 2727 records identified, 50 were eligible and had available data. The mean Newcastle-Ottawa Scale score was 7.1 (range, 6-8). Data synthesis suggested that IgAN patients had higher levels of blood and/or urine Gd-IgA1 compared with healthy controls (standard mean difference [SMD]=1.43, 95% confidence interval [CI]=1.19-1.68, P<0.00001), IgA vasculitis patients (SMD=0.58, 95% CI=0.22-0.94, P=0.002), and other kidney disease patients (SMD=1.06, 95% CI=0.79-1.33, P<0.00001). Moreover, patients with IgAN had similar levels of serum Gd-IgA1 compared to first-degree relatives (SMD=0.38, 95% CI= -0.04-0.81, P=0.08) and IgA vasculitis with nephritis patients (SMD=0.12, 95% CI= -0.04-0.29, P=0.14). In addition, ten studies demonstrated significant differences in serum Gd-IgA1 levels in patients with mild and severe IgAN (SMD= -0.37, 95% CI= -0.64--0.09, P=0.009).
CONCLUSIONS
High serum and urine Gd-IgA1 levels suggest a diagnosis of IgAN and a poor prognosis for patients with this immunological disorder. Future studies should use more reliable and reproducible methods to determine Gd-IgA1 levels.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375246, identifier CRD42022375246.
Topics: Humans; Glomerulonephritis, IGA; Prognosis; IgA Vasculitis; Immunoglobulin A
PubMed: 37671165
DOI: 10.3389/fimmu.2023.1209394 -
Neurobiology of Disease Jun 2024Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has... (Meta-Analysis)
Meta-Analysis Review
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Topics: Humans; Diabetes Mellitus, Type 2; Alzheimer Disease; Animals; Epigenesis, Genetic
PubMed: 38643861
DOI: 10.1016/j.nbd.2024.106485 -
Cellular Physiology and Biochemistry :... Mar 2023Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of...
BACKGROUND/AIMS
Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systematic review and assess antiglycoxidative properties of trazodone in in vitro models.
METHODS
Trazodone's scavenging and chelating properties were measured with spectrophotometric method. The impact of the drug on carbonyl/oxidative stress was marked in the bovine serum albumin (BSA) model where sugars (glucose, fructose, galactose, ribose) and aldehydes (glyoxal and methylglyoxal) were used as glycation agents. Aminoguanidine and N-acetylcysteine (NAC) were applied as reference glycation/free radical inhibitors. Glycation biomarkers (kynurenine, N-formylkynurenine, dityrosine as well as advanced glycation end products contents) were assessed spectrofluorometrically. Concentrations of oxidation parameters (total thiols (TTs), protein carbonyls (PCs) and also advanced oxidation protein products (AOPPs) levels) were determined spectrophotometrically.
RESULTS
We demonstrated that trazodone poorly scavenged radicals (hydroxyl radical, nitric oxide, hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl radical) and showed low ferrous ion chelating, unlike aminoguanidine and NAC. Sugars/aldehydes caused enhancement of glycation parameters, as well as a decrease of TTs and an increase of PCs and AOPPs levels compared to BSA incubated alone. Trazodone did not reduce oxidation parameters to the baseline (BSA) and significantly exacerbated glycation markers in comparison with both BSA and BSA+glycators. The content of glycation products was markedly lower in aminoguanidine and NAC than in trazodone. The molecular docking of trazodone to BSA revealed its very low affinity, which may indicate non-specific binding of trazodone, facilitating the attachment of glycation factors.
CONCLUSION
According to our findings, it may be concluded that trazodone poorly counteracts oxidation and intensifies glycation in vitro. A possible mechanism for antiglycoxidative effect of trazodone in vivo may be the enhancement of the body's adaptive response, as indicated by the results of our systematic review.
Topics: Antioxidants; Trazodone; Glycosylation; Advanced Oxidation Protein Products; Molecular Docking Simulation; Glycation End Products, Advanced; Serum Albumin, Bovine; Glyoxal; Glucose
PubMed: 36988041
DOI: 10.33594/000000617 -
Journal of Global Health Nov 2022To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In...
BACKGROUND
To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In low-income countries, however, HBV-infected people have limited access to liver histopathology, a reference test. Recently, Asian studies have suggested the usefulness of an inexpensive serum biomarker called Mac-2 binding protein glycosylation isomer (M2BPGi) in staging liver fibrosis and predicting HCC in HBV-infected patients.
METHODS
We systematically searched PubMed for studies examining the performance of M2BPGi in staging liver fibrosis in HBV-infected people, published up to September 21, 2021, to elucidate the knowledge gap. We then conducted a cross-sectional study of 339 HBV-infected patients in The Gambia (cirrhosis = 65, HCC = 73, non-cirrhosis non-HCC = 201). We evaluated the association of M2BPGi with cirrhosis and HCC by computing odds ratios (ORs) derived from logistic regression. We also assessed the performance of M2BPGi to stage liver fibrosis in 49 patients who underwent liver biopsy (derivation set) and 217 patients with transient elastography (validation set). Using the derivation set we drew the receiver operating characteristics (ROC) curves to identify optimal M2BPGi thresholds to indicate significant fibrosis and cirrhosis using biopsy as a reference. We then applied these cut-offs to the validation set to obtain its sensitivity and specificity for indicating significant fibrosis and cirrhosis using transient elastography as a reference.
RESULTS
The systematic review identified 13 studies, all of which were conducted in East Asia and none in Africa. In The Gambia, positive M2BPGi was significantly associated with both cirrhosis (adjusted OR = 7.8, 95% CI = 3.1-19.7) and HCC (adjusted OR = 10.1, 2.6-40.2). The areas under the ROC curve (AUROC) in the derivation and validation set were 0.62 and 0.78, respectively, to diagnose significant fibrosis, and 0.80 and 0.89, respectively, to diagnose cirrhosis. By applying the optimal cut-offs, the sensitivity and specificity in the validation set were 61.5% and 93.4%, respectively, to diagnose significant fibrosis, and 72.5% and 92.2%, respectively, for cirrhosis.
CONCLUSIONS
To the best of our knowledge, this is the first evaluation of M2BPGi in HBV-infected African population. The findings supported its accuracy in the diagnosis of cirrhosis in HBV-infected patients in West Africa.
Topics: Humans; Hepatitis B virus; Glycosylation; Cross-Sectional Studies; Liver Cirrhosis; Carcinoma, Hepatocellular; Hepatitis B; Liver Neoplasms
PubMed: 36370422
DOI: 10.7189/jogh.12.04076 -
Frontiers in Aging Neuroscience 2022D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the...
BACKGROUND
D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents.
METHODS
The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed.
RESULTS
A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: -0.80; 95% CI: -1.14, -0.46; < 0.00001), percentage of distance traversed in the target quadrant (SMD: -1.20; 95% CI: -1.47, -0.92; < 0.00001), percentage of time spent in the target quadrant (SMD: -0.93; 95% CI: -1.18, -0.68; < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; = 0.02). Subsequently, subgroup analysis for the dose of D-ribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses.
CONCLUSION
D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment.
PubMed: 36438006
DOI: 10.3389/fnagi.2022.1036315