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Nature Communications Mar 2024Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered...
Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.
Topics: Animals; Mice; Mannose-6-Phosphate Isomerase; Glycosylation; Mannose; Glucose; Antiviral Agents
PubMed: 38459021
DOI: 10.1038/s41467-024-46415-4 -
International Journal of Molecular... Jan 2024The mannose receptor (MR, CD 206) is an endocytic receptor primarily expressed by macrophages and dendritic cells, which plays a critical role in both endocytosis and... (Review)
Review
The mannose receptor (MR, CD 206) is an endocytic receptor primarily expressed by macrophages and dendritic cells, which plays a critical role in both endocytosis and antigen processing and presentation. MR carbohydrate recognition domains (CRDs) exhibit a high binding affinity for branched and linear oligosaccharides. Furthermore, multivalent mannose presentation on the various templates like peptides, proteins, polymers, micelles, and dendrimers was proven to be a valuable approach for the selective and efficient delivery of various therapeutically active agents to MR. This review provides a detailed account of the most relevant and recent aspects of the synthesis and application of mannosylated bioactive formulations for MR-mediated delivery in treatments of cancer and other infectious diseases. It further highlights recent findings related to the necessary structural features of the mannose-containing ligands for successful binding to the MR.
Topics: Mannose Receptor; Mannose; Receptors, Cell Surface; Mannose-Binding Lectins; Lectins, C-Type; Ligands
PubMed: 38338648
DOI: 10.3390/ijms25031370 -
Current Opinion in Structural Biology Aug 2022A unique glycan-binding protein expressed in macrophages and some types of other immune cells is the mannose receptor (MR, CD206). It is an endocytic, transmembrane... (Review)
Review
A unique glycan-binding protein expressed in macrophages and some types of other immune cells is the mannose receptor (MR, CD206). It is an endocytic, transmembrane protein with multiple glycan-binding domains and different specificities in binding glycans. The mannose receptor is important as it has major roles in diverse biological processes, including regulation of circulating levels of reproductive hormones, homeostasis, innate immunity, and infections. These different functions involve the recognition of a wide range of glycans, and their nature is currently under intense study. But the mannose receptor is just one of many glycan-binding proteins expressed in macrophages, leading to an interest in the potential relationship between the macrophage glycome and how it may regulate cognate glycan-binding protein activities. This review focuses primarily on the mannose receptor and its carbohydrate ligands, as well as macrophages and their glycomes.
Topics: Lectins, C-Type; Ligands; Macrophages; Mannose; Mannose Receptor; Mannose-Binding Lectins; Polysaccharides; Receptors, Cell Surface
PubMed: 35617912
DOI: 10.1016/j.sbi.2022.102394 -
Methods in Molecular Biology (Clifton,... 2020A novel mannose-specific lectin, named CGL1 (15.5 kDa), was isolated from the oyster Crassostrea gigas. Characterization of CGL1 revealed that it has strict specificity...
A novel mannose-specific lectin, named CGL1 (15.5 kDa), was isolated from the oyster Crassostrea gigas. Characterization of CGL1 revealed that it has strict specificity for the mannose monomer and for high mannose-type N-glycans (HMTGs). The primary and crystal structure of CGL1 did not show any homology with known lectins. These characteristics of CGL1 may be helpful as a research tool and for clinical applications. We show a purification protocol of CGL1 from the Pacific oyster.
Topics: Animals; Crassostrea; Crystallography, X-Ray; Mannose; Mannose-Binding Lectins; Models, Molecular; Molecular Weight; Protein Conformation; Substrate Specificity
PubMed: 32306361
DOI: 10.1007/978-1-0716-0430-4_53 -
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 -
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 -
Biochemical and Biophysical Research... Oct 2014Mannose is a simple sugar with a complex life. It is a welcome therapy for genetic and acquired human diseases, but it kills honeybees and blinds baby mice. It could... (Review)
Review
Mannose is a simple sugar with a complex life. It is a welcome therapy for genetic and acquired human diseases, but it kills honeybees and blinds baby mice. It could cause diabetic complications. Mannose chemistry, metabolism, and metabolomics in cells, tissues and mammals can help explain these multiple systemic effects. Mannose has good, bad or ugly outcomes depending on its steady state levels and metabolic flux. This review describes the role of mannose at cellular level and its impact on organisms.
Topics: Animals; Congenital Disorders of Glycosylation; Dietary Carbohydrates; Disease Models, Animal; Female; Gene Knockdown Techniques; Humans; Mannose; Mannose-6-Phosphate Isomerase; Metabolic Flux Analysis; Metabolic Networks and Pathways; Metabolomics; Mice; Phosphotransferases (Phosphomutases); Polysaccharides; Pregnancy; Zebrafish
PubMed: 24931670
DOI: 10.1016/j.bbrc.2014.06.021 -
MBio Jan 2024messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the...
messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the nonspecificity of lipid nanoparticle-encapsulated (LNP) delivery systems result in the need for cold storage and a relatively short-duration immune response to mRNA vaccines. Herein, we develop a novel vaccine in the form of circRNAs encapsulated in LNPs, and the circular structure of the circRNAs enhances their stability. Lyophilization is considered the most effective method for the long-term preservation of RNA vaccines. However, this process may result in irreversible damage to the nanoparticles, particularly the potential disruption of targeting modifications on LNPs. During the selection of lymph node-targeting ligands, we found that LNPs modified with mannose maintained their physical properties almost unchanged after lyophilization. Additionally, the targeting specificity and immunogenicity remained unaffected. In contrast, even with the addition of cryoprotectants such as sucrose, the physical properties of LNPs were impaired, leading to an obvious decrease in immunogenicity. This may be attributed to the protective role of mannose on the surface of LNPs during lyophilization. Freshly prepared and lyophilized mLNP-circRNA vaccines elicited comparable immune responses in both the rabies virus model and the SARS-CoV-2 model. Our data demonstrated that mLNP-circRNA vaccines elicit robust immune responses while improving stability after lyophilization, with no compromise in tissue targeting specificity. Therefore, mannose-modified LNP-circRNA vaccines represent a promising vaccine design strategy.
Topics: RNA, Circular; Mannose; Vaccines; Immunity; Freeze Drying; RNA, Messenger
PubMed: 38078742
DOI: 10.1128/mbio.01775-23 -
Current Opinion in Structural Biology Jun 2019Protein O-mannosylation (O-Man), originally discovered in yeast five decades ago, is an important post-translational modification (PTM) conserved from bacteria to... (Review)
Review
Protein O-mannosylation (O-Man), originally discovered in yeast five decades ago, is an important post-translational modification (PTM) conserved from bacteria to humans, but not found in plants or nematodes. Until recently, the homologous family of ER-located protein O-mannosyl transferases (PMT1-7 in yeast; POMT1/POMT2 in humans), were the only known enzymes involved in directing O-Man biosynthesis in eukaryotes. However, recent studies demonstrate the existence of multiple distinct O-Man glycosylation pathways indicating that the genetic and biosynthetic regulation of O-Man in eukaryotes is more complex than previously envisioned. Introduction of sensitive glycoproteomics strategies provided an expansion of O-Man glycoproteomes in eukaryotes (yeast and mammalian cell lines) leading to the discovery of O-Man glycosylation on important mammalian cell adhesion (cadherin superfamily) and signaling (plexin family) macromolecules, and to the discovery of unique nucleocytoplasmic O-Man glycosylation in yeast. It is now evident that eukaryotes have multiple distinct O-Man glycosylation pathways including: i) the classical PMT1-7 and POMT1/POMT2 pathway conserved in all eukaryotes apart from plants; ii) a yet uncharacterized nucleocytoplasmic pathway only found in yeast; iii) an ER-located pathway directed by the TMTC1-4 genes found in metazoans and protists and primarily dedicated to the cadherin superfamily; and iv) a yet uncharacterized pathway found in metazoans primarily dedicated to plexins. O-Man glycosylation is thus emerging as a much more widespread and evolutionary diverse PTM with complex genetic and biosynthetic regulation. While deficiencies in the POMT1/POMT2 O-Man pathway underlie muscular dystrophies, the TMTC1-4 pathway appear to be involved in distinct congenital disorders with neurodevelopmental phenotypes. Here, we review and discuss the recent discoveries of the new non-classical O-Man glycosylation pathways, their substrates, functions and roles in disease.
Topics: Eukaryota; Glycoproteins; Glycosylation; Mannose; Oxygen; Protein Domains
PubMed: 30999272
DOI: 10.1016/j.sbi.2019.03.003 -
The Senior Care Pharmacist Aug 2023Urinary tract infections (UTIs) are the most prevalent infections in older patients with the potential for morbidity and mortality. Antibiotics are not generally... (Review)
Review
Urinary tract infections (UTIs) are the most prevalent infections in older patients with the potential for morbidity and mortality. Antibiotics are not generally recommended for UTI prophylaxis in this population. There is interest among the public and health providers to try over-the-counter products, such as cranberry, D-mannose, and vitamin C. The objective of this analysis was to review the literature for the efficacy and tolerability of these supplements in older individuals. A literature review was conducted on PubMed using the search terms urinary tract infection or UTI, prevention/prophylaxis, cranberry, D-mannose, vitamin C/ascorbic acid. Few studies were conducted among older people; therefore, the authors included studies of all adults who had recurrent UTIs or were at increased risk of UTIs. Level (quality) of evidence were determined using the ACC/AHA Clinical Practice Guideline Recommendation Classification System. A total of 24 studies were included. This review captured all studies in previous reviews as well as recent publications. The authors determined that there were limited data for D-mannose and vitamin C, and randomized data for cranberry as defined by the classification system. The three supplements reviewed appear not to be strongly supported by clinical data. For those who are interested in trying these products despite the lack of robust evidence for clinical efficacy, it may be helpful to know that the studies included in this review did not identify any clinically important signs of harm, to the extent that safety data were documented and reported.
Topics: Humans; Aged; Vaccinium macrocarpon; Mannose; Ascorbic Acid; Urinary Tract Infections; Anti-Bacterial Agents
PubMed: 37496168
DOI: 10.4140/TCP.n.2023.315