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International Journal of Molecular... Jan 2019To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold... (Review)
Review
To date, a number of mannose-binding lectins have been isolated and characterized from plants and fungi. These proteins are composed of different structural scaffold structures which harbor a single or multiple carbohydrate-binding sites involved in the specific recognition of mannose-containing glycans. Generally, the mannose-binding site consists of a small, central, carbohydrate-binding pocket responsible for the "broad sugar-binding specificity" toward a single mannose molecule, surrounded by a more extended binding area responsible for the specific recognition of larger mannose-containing -glycan chains. Accordingly, the mannose-binding specificity of the so-called mannose-binding lectins towards complex mannose-containing -glycans depends largely on the topography of their mannose-binding site(s). This structure⁻function relationship introduces a high degree of specificity in the apparently homogeneous group of mannose-binding lectins, with respect to the specific recognition of high-mannose and complex -glycans. Because of the high specificity towards mannose these lectins are valuable tools for deciphering and characterizing the complex mannose-containing glycans that decorate both normal and transformed cells, e.g., the altered high-mannose -glycans that often occur at the surface of various cancer cells.
Topics: Binding Sites; Fungi; Mannose; Mannose-Binding Lectins; Models, Molecular; Oligosaccharides; Plants; Protein Binding; Protein Conformation; Structure-Activity Relationship
PubMed: 30634645
DOI: 10.3390/ijms20020254 -
JAMA Internal Medicine Jun 2024Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established.
OBJECTIVE
To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI.
DESIGN, SETTING, AND PARTICIPANTS
This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022.
INTERVENTION
Two grams daily of d-mannose powder or matched volume of placebo powder.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions.
RESULTS
Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN13283516.
Topics: Humans; Urinary Tract Infections; Female; Mannose; Double-Blind Method; Middle Aged; Adult; Recurrence; Aged
PubMed: 38587819
DOI: 10.1001/jamainternmed.2024.0264 -
Military Medical Research May 2024Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the...
BACKGROUND
Intervertebral disc degeneration (IVDD) is a multifaceted condition characterized by heterogeneity, wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus (NP) cells plays a central role. Presently, the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes. D-mannose (referred to as mannose) has demonstrated anti-catabolic properties in various diseases. Nevertheless, its therapeutic potential in IVDD has yet to be explored.
METHODS
The study began with optimizing the mannose concentration for restoring NP cells. Transcriptomic analyses were employed to identify the mediators influenced by mannose, with the thioredoxin-interacting protein (Txnip) gene showing the most significant differences. Subsequently, small interfering RNA (siRNA) technology was used to demonstrate that Txnip is the key gene through which mannose exerts its effects. Techniques such as colocalization analysis, molecular docking, and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP. To elucidate the mechanism of action of mannose, metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose. Next, various methods, including integrated omics data and the Gene Expression Omnibus (GEO) database, were used to validate the one-way pathway through which TXNIP regulates glutamine. Finally, the therapeutic effect of mannose on IVDD was validated, elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.
RESULTS
In both in vivo and in vitro experiments, it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism. From a mechanistic standpoint, it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein (MondoA), resulting in the upregulation of TXNIP. This upregulation, in turn, inhibits glutamine metabolism, ultimately accomplishing its anti-catabolic effects by suppressing the mitogen-activated protein kinase (MAPK) pathway. More importantly, in vivo experiments have further demonstrated that compared with intradiscal injections, oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.
CONCLUSIONS
In summary, through integrated multiomics analysis, including both in vivo and in vitro experiments, this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis. These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD. Compared to existing clinically invasive or pain-relieving therapies for IVDD, the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment.
Topics: Intervertebral Disc Degeneration; Mannose; Animals; Rats; Glutamine; Male; Rats, Sprague-Dawley; Humans; Nucleus Pulposus; Cell Cycle Proteins
PubMed: 38711073
DOI: 10.1186/s40779-024-00529-4 -
Frontiers in Immunology 2022D-mannose can be transported into a variety of cells glucose transporter (GLUT), and supraphysiological levels of D-mannose impairs tumor growth and modulates immune...
D-mannose can be transported into a variety of cells glucose transporter (GLUT), and supraphysiological levels of D-mannose impairs tumor growth and modulates immune cell function through mechanisms such as interference with glycolysis and induction of oxidative stress. Blood-stage mainly depends on glycolysis for energy supply and pathological immune response plays a vital role in cerebral malaria. However, it is not clear whether mannose affects malaria blood-stage infection. Here, we fed D-mannose to -infected mice and found weight loss and reduced parasitemia without apparent side effects. Compromised parasitemia in C57BL/6 mice was accompanied by an increase in splenic macrophages compared to an untreated group. When mannose was applied to a rodent experimental cerebral malaria (ECM) model, the incidence of ECM decreased. Expression of activation marker CD69 on T cells in peripheral blood and the brain were reduced, and cerebral migration of activated T cells was prevented by decreased expression of CXCR3. These findings suggest that mannose inhibits infection by regulating multiple host immune responses and could serve as a potential strategy for facilitating malaria treatment.
Topics: Animals; Glucose Transport Proteins, Facilitative; Immunity; Malaria, Cerebral; Mannose; Mice; Mice, Inbred C57BL; Parasitemia; Parasites; Plasmodium berghei
PubMed: 36211381
DOI: 10.3389/fimmu.2022.859228 -
Current Opinion in Structural Biology Jun 2020Mannosidases are a diverse group of enzymes that are important in the biological processing of mannose-containing polysaccharides and complex glycoconjugates. They are... (Review)
Review
Mannosidases are a diverse group of enzymes that are important in the biological processing of mannose-containing polysaccharides and complex glycoconjugates. They are found in 12 of the >160 sequence-based glycosidase families. We discuss evidence that nature has evolved a small set of common mechanisms that unite almost all of these mannosidase families. Broadly, mannosidases (and the closely related rhamnosidases) perform catalysis through just two conformations of the oxocarbenium ion-like transition state: a B (or enantiomeric B) boat and a H half-chair. This extends to a new family (GT108) of GDPMan-dependent β-1,2-mannosyltransferases/phosphorylases that perform mannosyl transfer through a boat conformation as well as some mannosidases that are metalloenzymes and require divalent cations for catalysis. Yet, among this commonality lies diversity. New evidence shows that one unique family (GH99) of mannosidases use an unusual mechanism involving anchimeric assistance via a 1,2-anhydro sugar (epoxide) intermediate.
Topics: Biocatalysis; Mannose; Mannosidases; Molecular Conformation
PubMed: 31891872
DOI: 10.1016/j.sbi.2019.11.008 -
Journal of Dentistry Sep 2023To identify the metabolomic differences in the saliva of healthy children versus children with active carious lesions and to estimate the predictive capacity of a model...
OBJECTIVES
To identify the metabolomic differences in the saliva of healthy children versus children with active carious lesions and to estimate the predictive capacity of a model based on the salivary metabolomic profile.
METHODS
A study of cases (n = 31) and controls (n = 37) was designed for children aged between 6 and 12 (mean age of the cases: 8.9; controls: 8.7). The said children attended public health centers in Valencia, Spain. Intraoral examinations were performed by a single examiner using ICDAS II diagnostic criteria. Unstimulated total saliva samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy.
RESULTS
The dft index for cases was 2.84 while it was 0.19 for the control group, the DMFT index was 1.13 and 0.11, respectively. The predictive model generated by the multivariate PLS-DA analysis projects a separation between the cases and the controls on the score chart with a predictive capacity and generating an area under the curve of 0.71. The metabolites: 3-methyl-2-oxovalerate, 3-hydroxybutyrate, lactate, acetone, citrate, ornithine, ethanolamine, taurine, proline, glycine, mannose, glucose, 1-6-Anhydro-β-d-glucose and citraconate, are those that show greater significance in the model. In the controls, glycine (Cohen's d = 0.430) and glucose (Cohen's d = 0.560) present higher means compared to the cases. On the contrary, taurine (Cohen's d= -0.474) and mannose (Cohen's d= -0.456) show higher means in cases compared to controls.
CONCLUSIONS
Our findings show a difference in the salivary metabolomic profiles, specifically in the groups of saccharides and amino acids, suggesting an association of these with the level of caries risk.
CLINICAL SIGNIFICANCE
The results reported in the present study reinforce the use of salivary metabolomics as a research method for the search for salivary biomarkers that allow the evaluation of caries risk in patients. Furthermore, it brings us closer to a personalized medicine that will help in dental caries prevention strategies.
Topics: Humans; Child; Dental Caries; Mannose; Saliva; Metabolomics; Glucose; Glycine; Taurine
PubMed: 37524196
DOI: 10.1016/j.jdent.2023.104645 -
Marine Drugs Jul 2019To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae. In fact, man-specific seaweed lectins... (Review)
Review
To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae. In fact, man-specific seaweed lectins consist of different structural scaffolds harboring a single or a few carbohydrate-binding sites which specifically recognize mannose-containing glycans. Depending on the structural scaffold, man-specific seaweed lectins belong to five distinct structurally-related lectin families, namely (1) the griffithsin lectin family (β-prism I scaffold); (2) the agglutinin homolog (OAAH) lectin family (β-barrel scaffold); (3) the legume lectin-like lectin family (β-sandwich scaffold); (4) the agglutinin (GNA)-like lectin family (β-prism II scaffold); and, (5) the MFP2-like lectin family (MFP2-like scaffold). Another algal lectin from , has been inferred to the methanol dehydrogenase related lectin family, because it displays a rather different GlcNAc-specificity. In spite of these structural discrepancies, all members from the five lectin families share a common ability to specifically recognize man-containing glycans and, especially, high-mannose type glycans. Because of their mannose-binding specificity, these lectins have been used as valuable tools for deciphering and characterizing the complex mannose-containing glycans from the glycocalyx covering both normal and transformed cells, and as diagnostic tools and therapeutic drugs that specifically recognize the altered high-mannose -glycans occurring at the surface of various cancer cells. In addition to these anti-cancer properties, man-specific seaweed lectins have been widely used as potent human immunodeficiency virus (HIV-1)-inactivating proteins, due to their capacity to specifically interact with the envelope glycoprotein gp120 and prevent the virion infectivity of HIV-1 towards the host CD4+ T-lymphocyte cells in vitro.
Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Humans; Mannose; Mannose-Binding Lectins; Rhodophyta
PubMed: 31357490
DOI: 10.3390/md17080440 -
Bioengineered Dec 2021Raman spectroscopy was applied to an aqueous solution containing D-mannose and D-glucose at a fixed dry matter content. The Raman measurement apparatus was adapted...
Raman spectroscopy was applied to an aqueous solution containing D-mannose and D-glucose at a fixed dry matter content. The Raman measurement apparatus was adapted online at the industrial scale to monitor a bioprocess including an epimerization reaction. Online Raman spectroscopy and deconvolution techniques were successfully applied to monitor in real time the D-mannose and D-glucose concentrations using the Raman shifts at 960 cm and 974 cm respectively. The two anomeric forms, α and β of D-mannose in the pyranose conformation were quantified. In silico analysis of vibrational frequencies and Raman intensities of hydrated structure of D-mannose and D-glucose in the pyranose form for α and β anomers were carried out using a two-step procedure. First molecular dynamics was used to generate the theoretical carbohydrates' structures keeping the experimental dry matter content, then quantum mechanics was used to compute the Raman frequencies and intensities. Computed vibrational frequencies are in satisfactory agreement with the experimental spectra considering a hydration shell approach. Raman intensities are qualitatively in accordance with the experimental data. The interpretation of Raman frequencies and intensities led to acceptable results regarding the current possible structures of D-mannose and D-glucose in aqueous solution. Online Raman spectroscopy coupled with in silico approaches such as quantum mechanics and molecular dynamics methodology is proved to be a valuable tool to quantify the carbohydrates and stereoisomers content in complex aqueous mixtures. This methodology offers a new way to monitor any bioprocesses that encounter aqueous mixtures of D-glucose and D-mannose.
Topics: Glucose; Mannose; Molecular Dynamics Simulation; Spectrum Analysis, Raman; Vibration; Water
PubMed: 34308749
DOI: 10.1080/21655979.2021.1955550 -
Angewandte Chemie (International Ed. in... Jul 2018O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of...
O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of α-dystroglycan, which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 core M1 and core M2 O-mannose glycans. This chemoenzymatic strategy features the gram-scale chemical synthesis of five judiciously designed core structures, and the diversity-oriented modification of the core structures with three enzyme modules to provide 58 complex O-mannose glycans in a linear sequence that does not exceed four steps. The binding profiles of synthetic O-mannose glycans with a panel of lectins, antibodies, and brain proteins were also explored by using a printed O-mannose glycan array.
Topics: Animals; Biocatalysis; Chemistry Techniques, Synthetic; Dystroglycans; Glycosylation; Glycosyltransferases; Humans; Mannose; Polysaccharides
PubMed: 29802667
DOI: 10.1002/anie.201804373 -
The Journal of Nutrition Sep 2009Nonglucose carbohydrates such as mannose and inositol are important in early growth and development, although little is known about their metabolism. Our aim in this...
Nonglucose carbohydrates such as mannose and inositol are important in early growth and development, although little is known about their metabolism. Our aim in this study was to determine the plasma appearance rates (Ra) for mannose and inositol in newborns as an index of utilization and as an improved guide to supplementation practices. We studied late-preterm (n = 9) and term (n = 5) infants (median 34 wk gestation, range 33-41 wk) using a multiple isotope infusion start time protocol to determine Ra for each carbohydrate. The plasma mannose concentration [median (range)] was 69.83 (48.60-111.75) micromol/L and the Ra was 0.59 (0.42-0.98) micromol x kg(-1) x min(-1) (854 micromol x kg(-1) x d(-1)). The plasma inositol concentration was 175.74 (59.71-300.60) micromol/L and Ra was 1.06 (0.33-1.75) micromol x kg(-1).min(-1) (1521 micromol x kg(-1) x d(-1)). The Ra for mannose and inositol are >10-fold higher than the amounts a breast-fed infant typically ingests, which are approximately 6 micromol x kg(-1) x d(-1) mannose and 150 micromol x kg(-1) x d(-1) inositol. Thus, for both mannose and inositol, the newborn infant must produce these compounds from glucose at rates sufficient to meet nutritional requirements.
Topics: Blood Glucose; Breast Feeding; Dietary Carbohydrates; Gestational Age; Humans; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Inositol; Mannose; Milk, Human
PubMed: 19494026
DOI: 10.3945/jn.109.109108