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Cellular & Molecular Immunology Feb 2023Mannose is a naturally occurring sugar widely consumed in the daily diet; however, mechanistic insights into how mannose metabolism affects intestinal inflammation...
Mannose is a naturally occurring sugar widely consumed in the daily diet; however, mechanistic insights into how mannose metabolism affects intestinal inflammation remain lacking. Herein, we reported that mannose supplementation ameliorated colitis development and promoted colitis recovery. Macrophage-secreted inflammatory cytokines, particularly TNF-α, induced pathological endoplasmic reticulum stress (ERS) in intestinal epithelial cells (IECs), which was prevented by mannose via normalization of protein N-glycosylation. By preserving epithelial integrity, mannose reduced the inflammatory activation of colonic macrophages. On the other hand, mannose directly suppressed macrophage TNF-α production translationally by reducing the glyceraldehyde 3-phosphate level, thus promoting GAPDH binding to TNF-α mRNA. Additionally, we found dysregulated mannose metabolism in the colonic mucosa of patients with inflammatory bowel disease. Finally, we revealed that activating PMM2 activity with epalrestat, a clinically approved drug for the treatment of diabetic neuropathy, elicited further sensitization to the therapeutic effect of mannose. Therefore, mannose metabolism prevents TNF-α-mediated pathogenic crosstalk between IECs and intestinal macrophages, thereby normalizing aberrant immunometabolism in the gut.
Topics: Humans; Animals; Mice; Tumor Necrosis Factor-alpha; Mannose; Colitis; Inflammatory Bowel Diseases; Intestinal Mucosa; Homeostasis; Mice, Inbred C57BL
PubMed: 36471112
DOI: 10.1038/s41423-022-00955-1 -
European Urology Focus Sep 2021The inexorable rise of antimicrobial resistance reinforces the need for alternative approaches to both treat and prevent urinary tract infections (UTIs). A potential... (Review)
Review
The inexorable rise of antimicrobial resistance reinforces the need for alternative approaches to both treat and prevent urinary tract infections (UTIs). A potential approach is administration of D-mannose, an inert monosaccharide that is metabolised and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium. We performed a systematic review to assess the effect of D-mannose in the prevention of recurrent UTIs. Of the eight studies reporting on D-mannose in this context, six were clinical and included 695 individuals. Three studies reported that time to UTI recurrence was longer with D-mannose. D-Mannose improved quality of life and significantly reduced recurrent UTIs in both catheter and non-catheter users. D-Mannose was effective in reducing the incidence of recurrent UTIs and prolonging UTI-free periods, which consequently increased quality of life. PATIENT SUMMARY: D-Mannose is a sugar that seems to reduce the incidence of recurrent urinary tract infections and associated bothersome symptoms. It also leads to a longer duration between episodes of recurrences and consequently improves patient quality of life. D-Mannose can be used as a supplementary or alternate treatment for recurrent urinary tract infections.
Topics: Anti-Bacterial Agents; Humans; Mannose; Quality of Life; Urinary Tract Infections
PubMed: 32972899
DOI: 10.1016/j.euf.2020.09.004 -
Biomedicine & Pharmacotherapy =... Sep 2020Mannose is a monosaccharide widely distributed in body fluids and tissues, especially in the nerve, skin, testicles, retina, liver and intestines. It is used to... (Review)
Review
Mannose is a monosaccharide widely distributed in body fluids and tissues, especially in the nerve, skin, testicles, retina, liver and intestines. It is used to synthesize glycoproteins and participate in immune regulation. In recent years, mannose has been applied more and more widely in the biomedical context as people have a deeper understanding of its biological effects. This review introduces the use of mannose in treating various diseases (including cancer, urinary tract infections, type 1 diabetes, and diabetic wounds), preventing pancreatic fistula, and improving magnetic resonance imaging for acute pancreatitis. We also demonstrate that mannose has the potential for clinical applications.
Topics: Animals; Anti-Obesity Agents; Antineoplastic Agents; Contrast Media; Drug Carriers; Humans; Hypoglycemic Agents; Magnetic Resonance Imaging; Mannose; Pancreatic Fistula; Pancreatitis; Wound Healing
PubMed: 32563989
DOI: 10.1016/j.biopha.2020.110420 -
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 -
Journal of Translational Medicine Jan 2023Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term...
BACKGROUND
Astronauts undergo significant microgravity-induced bone loss during space missions, which has become one of the three major medical problems hindering human's long-term space flight. A risk-free and antiresorptive drug is urgently needed to prevent bone loss during space missions. D-mannose is a natural C-2 epimer of D-glucose and is abundant in cranberries. This study aimed to investigate the protective effects and potential mechanisms of D-mannose against bone loss under weightlessness.
METHODS
The hind legs of tail-suspended (TS) rats were used to mimic weightlessness on Earth. Rats were administered D-mannose intragastrically. The osteoclastogenic and osteogenic capacity of D-mannose in vitro and in vivo was analyzed by micro-computed tomography, biomechanical assessment, bone histology, serum markers of bone metabolism, cell proliferation assay, quantitative polymerase chain reaction, and western blotting. RNA-seq transcriptomic analysis was performed to detect the underlying mechanisms of D-mannose in bone protection.
RESULTS
The TS rats showed lower bone mineral density (BMD) and poorer bone morphological indices. D-mannose could improve BMD in TS rats. D-mannose inhibited osteoclast proliferation and fusion in vitro, without apparent effects on osteoblasts. RNA-seq transcriptomic analysis showed that D-mannose administration significantly inhibited the cell fusion molecule dendritic cell-specific transmembrane protein (DC-STAMP) and two indispensable transcription factors for osteoclast fusion (c-Fos and nuclear factor of activated T cells 1 [NFATc1]). Finally, TS rats tended to experience dysuria-related urinary tract infections (UTIs), which were suppressed by treatment with D-mannose.
CONCLUSION
D-mannose protected against bone loss and UTIs in rats under weightlessness. The bone protective effects of D-mannose were mediated by inhibiting osteoclast cell fusion. Our findings provide a potential strategy to protect against bone loss and UTIs during space missions.
Topics: Rats; Humans; Animals; Weightlessness; Mannose; X-Ray Microtomography; Osteoclasts; Bone Density; Bone Diseases, Metabolic; Bone Resorption
PubMed: 36617569
DOI: 10.1186/s12967-022-03870-1 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of... (Review)
Review
Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment.
Topics: Humans; Mannose; Neoplasms; Antineoplastic Agents; Glucose; Drug Delivery Systems
PubMed: 37657682
DOI: 10.1016/j.bbcan.2023.188970 -
Proceedings of the Japan Academy.... 2022Pradimicins (PRMs) are an exceptional family of natural products that specifically bind d-mannose (Man). In the past decade, their scientific significance has increased...
Pradimicins (PRMs) are an exceptional family of natural products that specifically bind d-mannose (Man). In the past decade, their scientific significance has increased greatly, with the emergence of biological roles of Man-containing glycans. However, research into the use of PRMs has been severely limited by their inherent tendency to form water-insoluble aggregates. Recently, we have established a derivatization strategy to suppress PRM aggregation, providing an opportunity for practical application of PRMs in glycobiological research. This article first outlines the challenges in studying Man-binding mechanisms and structural modifications of PRMs, and then describes our approach to address them. We also present our recent attempts toward the development of PRM-based research tools.
Topics: Anthracyclines; Biological Products; Humans; Mannose
PubMed: 35013028
DOI: 10.2183/pjab.98.002 -
Chemical Record (New York, N.Y.) Feb 2016Asparagine-linked (N-linked) sugar chains are widely found in the rough endoplasmic reticulum (ER), which has attracted renewed attention because of its participation in... (Review)
Review
Asparagine-linked (N-linked) sugar chains are widely found in the rough endoplasmic reticulum (ER), which has attracted renewed attention because of its participation in the glycoprotein quality control process. In the ER, newly formed glycoproteins are properly folded to higher-order structures by the action of a variety of lectin chaperones and processing enzymes and are transported into the Golgi, while terminally misfolded glycoproteins are carried into the cytosol for degradation. A group of proteins related to this system are known to recognize subtle differences in the high-mannose-type oligosaccharide structures of glycoproteins; however, their molecular foundations are still unclear. In order to gain a more precise understanding, our group has established a strategy for the systematic synthesis of high-mannose-type glycans. More recently, we have developed "top-down" chemoenzymatic approaches that allow expeditious access to theoretically all types of high-mannose glycans. This strategy comprehensively delivered 37 high-mannose-type glycans, including G1M9-M3 glycans, and opened up the possibility of the elucidation of structure-function relationships with a series of high-mannose-type glycans.
Topics: Carbohydrate Conformation; Mannose; Polysaccharides
PubMed: 26493153
DOI: 10.1002/tcr.201500222 -
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 -
Microbial Pathogenesis Dec 2023Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the... (Review)
Review
Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the relevant human antibodies. The peritrichous P. aeruginosa strain with MSHA fimbriae (PA-MSHA strain) has been found to be effective in the inhibition of growth and proliferation of different types of cancer cells. Furthermore, it has been revealed that PA-MSHA exhibits cytotoxicity because of the presence of MSHA and therefore it possesses anti-carcinogenic ability against different types of human cancer cell lines including, gastric, breast, hepatocarcinoma and nasopharyngeal cells. Studies have revealed that PA-MSHA exhibits therapeutic potential against cancer growth by induction of apoptosis, arrest of cell cycle, activating NF-κB/TLR5 pathway, etc. In China, PA-MSHA injections have been approved for the treatment of malignant tumor patients from very long back. The present review article demonstrates the therapeutic potential of PA-MSHA against various types of human cancers and explains the underlying mechanism.
Topics: Humans; Signal Transduction; Pseudomonas aeruginosa; Hemagglutinins; Mannose; Cell Proliferation; Liver Neoplasms
PubMed: 37871855
DOI: 10.1016/j.micpath.2023.106422