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European Journal of Clinical... Oct 2019The aim of this study was to investigate the effects that prebiotic and candidates for prebiotics on Clostridium difficile strains to adhere to various human epithelial...
The aim of this study was to investigate the effects that prebiotic and candidates for prebiotics on Clostridium difficile strains to adhere to various human epithelial cell lines and to compare the adhesive properties of specific C. difficile strains. We also sought to examine the effect of different concentrations of fructooligosaccharides and mannose on the formation of biofilms by C. difficile strains. The influence of cellobiose, fructooligosaccharides, inulin, mannose, and raffinose on the adherence properties of various C. difficile strains, including motile 630, non-motile M120, and 10 clinical motile ribotype 027 strains, to non-mucous secreting HT-29, mucous secreting HT-29 MXT, and CCD 841 CoN cells lines. The most effective prebiotics were used in biofilm formation assays. We demonstrated that all C. difficile strains adhered to all cell lines. However, the C. difficile M120 non-motile strain was statistically more likely to adhere to all three cell lines (CFU median, 40) compared to the motile strains (CFU median, 3; p < 0.001). Furthermore, among the carbohydrates examined, only fructooligosaccharides and mannose were found to significantly decrease adhesion (p < 0.001) of C. difficile strains. Alternatively, using a biofilm assay, we observed, via confocal laser scanning microscopy, that sub-inhibitory concentrations (1%) of fructooligosaccharides and mannose functioned to increase biofilm formation by C. difficile. We demonstrated that specific prebiotics and candidate prebiotics exhibit varying anti-adhesive properties towards C. difficile in vitro and that treatment with sub-inhibitory concentrations of prebiotics can cause an increase in biofilm formation by C. difficile.
Topics: Anti-Bacterial Agents; Bacterial Adhesion; Biofilms; Cell Line; Clostridioides difficile; Epithelial Cells; Humans; Locomotion; Mannose; Oligosaccharides; Prebiotics
PubMed: 31363870
DOI: 10.1007/s10096-019-03635-7 -
Critical Reviews in Therapeutic Drug... 2018Dictating the transport of drug carriers and augmenting the drug concentration at the desired anatomical site with high selectivity are worthwhile pursuits of current... (Review)
Review
Dictating the transport of drug carriers and augmenting the drug concentration at the desired anatomical site with high selectivity are worthwhile pursuits of current pharmaceutical research. Such approaches to drug targeting have been classified into passive and active strategies. As discussed in this article, active targeting promises greater selectivity because it exploits the incorporation of appropriate ligands, which are recognized by the target cells. Ligands, such as folate, peptides, transferrin, antibodies and their fragments, sugar, and sugar-mimetics, etc., with affinity to the molecules typical to or enriched in target tissues, have been investigated in this context. Mannose receptors (MRs) are abundantly expressed on a variety of cells, such as antigen-presenting cells, dendritic cells, and macrophages. Mannose receptors have lectin recognition domains that exhibit a high binding affinity for mannose. As a result, specific recognition of mannose-functionalized constructs has extensively been explored in the cell-specific targeting of drugs, vaccines, and other bioactive agents. This review outlines and discusses the key aspects of synthesis of mannosylated constructs, their mode of cellular uptake and application to targeted delivery of bioactive agents.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Humans; Lectins, C-Type; Ligands; Mannose; Mannose Receptor; Mannose-Binding Lectins; Molecular Structure; Receptors, Cell Surface
PubMed: 29717665
DOI: 10.1615/CritRevTherDrugCarrierSyst.2018020313 -
Parasitology Research Jun 2022Naegleria fowleri can cause acute primary amoebic encephalitis. It is known that contact-dependent pathogenicity in free-living amoeba may be mediated through a...
Naegleria fowleri can cause acute primary amoebic encephalitis. It is known that contact-dependent pathogenicity in free-living amoeba may be mediated through a carbohydrate-dependent pathway. In this study, the effect of mannose on the interaction between N. fowleri and pathogenic Escherichia coli O157:H7 and non-pathogenic E. coli DH5α was analyzed. In particular, the changes in proteases expressed by N. fowleri in response to mannose were analyzed. Unlike the conventional method, mannose was treated with N. fowleri for 1 h. The association between N. fowleri and E. coli O157:H7 treated with 50-mM and 100-mM mannose was significantly reduced by approximately 70.9% and 128.5%, respectively. E. coli O157:H7 invasion was reduced by about 10.8% by 100-mM mannose. Moreover, as a result of culturing N. fowleri invaded by E. coli O157:H7 for 24 h, E. coli O157:H7 also grew about 1.2 times in the group not treated with mannose. E. coli DH5α association was reduced by 25.7% by 100-mM mannose. On the other hand, there was almost no inhibitory effect by 100-mM glucose. In the analysis in which mannose bound to either N. fowleri or bacteria and affected the interaction, there was little effect on the interaction between N. fowleri and bacteria. In zymographic analysis, about 135-kDa and 75-kDa bands were observed by 50-mM and 100-mM mannose, and two bands were significantly increased by 100-mM mannose. This study suggests that mannose can be mediated in the contact-dependent pathway of N. fowleri and will serve as a basis for inducing changes in the protease of N. fowleri by other monosaccharides.
Topics: Amoeba; Escherichia coli; Mannose; Naegleria fowleri; Peptide Hydrolases
PubMed: 35403922
DOI: 10.1007/s00436-022-07513-8 -
Cancer Biomarkers : Section a of... 2022Although Abelson (ABL) tyrosine kinase inhibitors (TKIs) have demonstrated potency against chronic myeloid leukemia (CML), resistance to ABL TKIs can develop in CML...
BACKGROUND
Although Abelson (ABL) tyrosine kinase inhibitors (TKIs) have demonstrated potency against chronic myeloid leukemia (CML), resistance to ABL TKIs can develop in CML patients after discontinuation of therapy.
OBJECTIVE
Glucose metabolism may be altered in CML cells because glucose is a key metabolite used by tumor cells. We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs.
METHODS
We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs.
RESULTS
Treatment with D-mannose for 72 h inhibited the growth of K562 cells. Combined treatment using ABL TKIs and D-mannose induced a significantly higher level of cytotoxicity in Philadelphia chromosome (Ph)-positive leukemia cells than in control cells. In the mouse model, severe toxicity was observed as evidenced by body weight loss in the ponatinib and D-mannose combination treatment groups.
CONCLUSION
Our results indicate that metabolic reprogramming may be a useful strategy against Ph-positive leukemia cells. However, caution should be exercised during clinical applications.
Topics: Animals; Drug Resistance, Neoplasm; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mannose; Mice; Philadelphia Chromosome; Protein Kinase Inhibitors
PubMed: 35001876
DOI: 10.3233/CBM-210141 -
Proceedings of the National Academy of... Nov 2021Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on...
Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on neuroinflammation and inflammatory cells in the central nervous system have not been studied. We aimed to determine the effects of d-mannose on key macrophage/microglial functions-oxidative stress and phagocytosis. In murine experimental autoimmune encephalomyelitis (EAE), we found d-mannose improved EAE symptoms compared to phosphate-buffered saline (PBS)-control mice, while other monosaccharides did not. Multiagent molecular MRI performed to assess oxidative stress (targeting myeloperoxidase [MPO] using MPO-bis-5-hydroxytryptamide diethylenetriaminepentaacetate gadolinium [Gd]) and phagocytosis (using cross-linked iron oxide [CLIO] nanoparticles) in vivo revealed that d-mannose-treated mice had smaller total MPO-Gd areas than those of PBS-control mice, consistent with decreased MPO-mediated oxidative stress. Interestingly, d-mannose-treated mice exhibited markedly smaller CLIO areas and much less T2 shortening effect in the CLIO lesions compared to PBS-control mice, revealing that d-mannose partially blocked phagocytosis. In vitro experiments with different monosaccharides further confirmed that only d-mannose treatment blocked macrophage phagocytosis in a dose-dependent manner. As phagocytosis of myelin debris has been known to increase inflammation, decreasing phagocytosis could result in decreased activation of proinflammatory macrophages. Indeed, compared to PBS-control EAE mice, d-mannose-treated EAE mice exhibited significantly fewer infiltrating macrophages/activated microglia, among which proinflammatory macrophages/microglia were greatly reduced while antiinflammatory macrophages/microglia increased. By uncovering that d-mannose diminishes the proinflammatory response and boosts the antiinflammatory response, our findings suggest that d-mannose, an over-the-counter supplement with a high safety profile, may be a low-cost treatment option for neuroinflammatory diseases such as multiple sclerosis.
Topics: Animals; Drug Evaluation, Preclinical; Encephalomyelitis, Autoimmune, Experimental; Female; Mannose; Mice, Inbred C57BL; Molecular Imaging; Oxidative Stress; Phagocytosis; Mice
PubMed: 34702739
DOI: 10.1073/pnas.2107663118 -
Biochemical and Biophysical Research... Jun 2024Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural...
Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.
Topics: Animals; Mice; Liver; Mannose; Mice, Inbred C57BL; Molecular Docking Simulation; Network Pharmacology; Non-alcoholic Fatty Liver Disease; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 38678787
DOI: 10.1016/j.bbrc.2024.149999 -
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 -
Acta Tropica May 2023Trichinellosis is a major zoonotic parasitosis which is a vital risk to meat food safety. It is requisite to exploit new strategy to interdict food animal Trichinella...
Trichinellosis is a major zoonotic parasitosis which is a vital risk to meat food safety. It is requisite to exploit new strategy to interdict food animal Trichinella infection and to obliterate Trichinella from food animals to ensure meat safety. Mannose is an oligosaccharide that specifically binds to the carbohydrate-recognition domain of C-type lectin; it has many physiological functions including reliving inflammation and regulating immune reaction. The purpose of this study was to investigate the suppressive role of mannose on T. spiralis larval invasion and infection, its effect on intestinal and muscle inflammation, and immune responses after challenge. The results showed that compared to the saline-treated infected mice, the mannose-treated infected mice had less intestinal adult and muscle worm burdens, mild inflammation of intestine and muscle of infected mice. The levels of specific anti-Trichinella IgG (IgG1/IgG2a), IgA and sIgA in mannose-treated infected mice were obviously inferior to saline-treated infected mice (P < 0.01). Furthermore, the levels of two cytokines (IFN-γ and IL-4) in mannose-treated infected mice were also significantly lower than the saline-treated infected mice (P < 0.01). The protective effect of the mannose against Trichinella infection might be not related to specific antibody and cellular immune responses. The above results demonstrated that mannose could be considered as a novel adjuvant therapeutic agent for anti-Trichinella drugs to block larval invasion at early stage of Trichinella infection.
Topics: Mice; Animals; Trichinella spiralis; Mannose; Trichinellosis; Muscles; Immunoglobulin G; Inflammation; Intestines; Mice, Inbred BALB C
PubMed: 36931335
DOI: 10.1016/j.actatropica.2023.106897 -
Hepatology (Baltimore, Md.) Dec 2019The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of...
The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of hepatic fibrosis. A rare, monogenic disorder in which children with mutations in mannose phosphate isomerase (MPI) develop liver fibrosis led us to explore the function of MPI and mannose metabolism in liver development and adult liver diseases. Herein, analyses of transcriptomic data from three human liver cohorts demonstrate that MPI gene expression is down-regulated proportionate to fibrosis in chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis B virus. Depletion of MPI in zebrafish liver in vivo and in human hepatic stellate cell (HSC) lines in culture activates fibrotic responses, indicating that loss of MPI promotes HSC activation. We further demonstrate that mannose supplementation can attenuate HSC activation, leading to reduced fibrogenic activation in zebrafish, culture-activated HSCs, and in ethanol-activated HSCs. Conclusion: These data indicate the prospect that modulation of mannose metabolism pathways could reduce HSC activation and improve hepatic fibrosis.
Topics: Animals; Cells, Cultured; Glycosylation; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Male; Mannose; Mannose-6-Phosphate Isomerase; Platelet-Derived Growth Factor; Signal Transduction; Zebrafish
PubMed: 31016744
DOI: 10.1002/hep.30677 -
Journal of Natural Products Sep 2021Pradimicin A (PRM-A) and related compounds constitute an exceptional family of natural pigments that show Ca-dependent recognition of d-mannose (Man). Although these...
Pradimicin A (PRM-A) and related compounds constitute an exceptional family of natural pigments that show Ca-dependent recognition of d-mannose (Man). Although these compounds hold great promise as research tools in glycobiology, their practical application has been severely limited by their inherent tendency to form water-insoluble aggregates. Here, we demonstrate that the 2-hydroxyethylamide derivative (PRM-EA) of PRM-A shows little aggregation in neutral aqueous media and retains binding specificity for Man. We also show that PRM-EA stains glycoproteins in dot blot assays, whereas PRM-A fails to do so, owing to severe aggregation. Significantly, PRM-EA is sensitive to glycoproteins carrying high mannose-type and hybrid-type N-linked glycans, but not to those carrying complex-type N-linked glycans. Such staining selectivity has never been observed in conventional dyes, suggesting that PRM-EA could serve as a unique staining agent for the selective detection of glycoproteins with terminal Man residues.
Topics: Anthracyclines; Coloring Agents; Glycoproteins; Mannose; Molecular Structure; Staining and Labeling
PubMed: 34524799
DOI: 10.1021/acs.jnatprod.1c00506