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Cancer cells acquire metabolic advantages over their normal counterparts regarding the use of nutrients for sustained cell proliferation and cell survival in the tumor microenvironment. Notable among the metabolic traits in cancer cells is the Warburg effect, which is a reprogrammed form of glycolysis that favors the rapid generation of ATP from glucose and the production of biological macromolecules by diverting glucose into various metabolic intermediates. Meanwhile, mannose, which is the C‐2 epimer of glucose, has the ability to dampen the Warburg effect, resulting in slow‐cycling cancer cells that are highly susceptible to chemotherapy. This anticancer effect of mannose appears when its catabolism is compromised in cancer cells. Moreover, de novo synthesis of mannose within cancer cells has also been identified as a potential target for enhancing chemosensitivity through targeting glycosylation pathways. The underlying mechanisms by which alterations in mannose metabolism induce cancer cell vulnerability are just beginning to emerge. This review summarizes the current state of our knowledge of mannose metabolism and provides insights into its manipulation as a potential anticancer strategy. [ABSTRACT FROM AUTHOR]

In the pursuit of achieving better therapeutic outcomes in the treatment of HIV, innovative drug delivery strategies have been extensively explored. Mannose receptors, which are primarily found on macrophages and dendritic cells, offer promising targets for drug delivery due to their involvement in HIV pathogenesis. This review article comprehensively evaluates recent drug delivery system advancements targeting the mannose receptor. We have systematically described recent developments in creating and utilizing drug delivery platforms, including nanoparticles, liposomes, micelles, noisomes, dendrimers, and other nanocarrier systems targeted at the mannose receptor. These strategies aim to enhance drug delivery specificity, bioavailability, and therapeutic efficacy while decreasing off-target effects and systemic toxicity. Furthermore, the article delves into how mannose receptors and HIV interact, highlighting the potential for exploiting this interaction to enhance drug delivery to infected cells. The review covers essential topics, such as the rational design of nanocarriers for mannose receptor recognition, the impact of physicochemical properties on drug delivery performance, and how targeted delivery affects the pharmacokinetics and pharmacodynamics of anti-HIV agents. The challenges of these novel strategies, including immunogenicity, stability, and scalability, and future research directions in this rapidly growing area are discussed. The knowledge synthesis presented in this review underscores the potential of mannose receptor-based targeted drug delivery as a promising avenue for advancing HIV treatment. By leveraging the unique properties of mannose receptors, researchers can design drug delivery systems that cater to individual needs, overcome existing limitations, and create more effective and patient-friendly treatments in the ongoing fight against HIV/AIDS. [Display omitted] [ABSTRACT FROM AUTHOR]

The isomerization of glucose to fructose is an important process in the conversion of biomass into valuable fuels and chemicals. Development of efficient catalyst for this reaction has attracted much attention. In this study, Sn‐Beta zeolites with rich silanols were synthesized for glucose isomerization by solid‐state ion‐exchange method, where Si‐Beta zeolites with different amounts of silanols were applied as the precursors. It is confirmed that open Sn sites show much higher catalytic performance than closed Sn sites for glucose isomerization (about 2.1 times). The silanol amount in Si‐Beta not only affects the formation of framework Sn sites in Sn‐Beta but also influences the isomerization reaction. More silanols in the catalyst can promote the 1,2‐H shift in isomerization and reduce the side reactions of formation of mannose and C3 products. Over 3Sn‐Beta‐3h with rich silanols, 64 % of fructose yield was obtained. Furthermore, the prepared Sn‐Beta catalyst is stable and recyclable. High fructose yield and facile synthesis method of Sn‐Beta reported in this work will contribute to the development of biomass and sugar industry. [ABSTRACT FROM AUTHOR]

Copyright of Acta Edulis Fungi is the property of Acta Edulis Fungi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The epimerization of glucose into mannose is of great significance for high-value utilization of monosaccharides. Extensive studies on the epimerization of glucose into mannose have been conducted using molybdenum-based catalysts, owing to their good activities for the epimerization reaction. Nonetheless, a great challenge for this reaction is that molybdenum species are prone to leaching into solution, which is a primary reason for catalyst deactivation. Additionally, the reaction usually gives a very low mannose yield and poor selectivity because it is a thermodynamic equilibrium reaction with sugar prone to side reactions at high temperatures. Herein, a metal–organic framework (MOF) material incorporating Keggin-type phosphomolybdate was explored as the catalyst for the epimerization of glucose. Under optimal conditions, an excellent mannose yield of up to 32.5% with an impressive selectivity of 94% was achieved. When other aldoses such as arabinose were used as starting materials, the catalyst also afforded high yield and product selectivity in the epimerization reaction. This novel hybrid material, a polyoxometalate-based metal–organic framework (POMOF), has been introduced to catalyze the conversion of sugars for the first time. Notably, in contrast to most molybdenum-based catalysts, the target hybrid showed good stability after five successive cycles. Furthermore, the reaction mechanism of the glucose-to-mannose epimerization was proposed, confirming the intramolecular carbon-skeleton rearrangement pathway (involving C-1 and C-2 positions) by isotope-labeling trace experiments. [ABSTRACT FROM AUTHOR]

Brucellosis is a dangerous zoonotic disease caused by bacteria of the genus Brucella. Diagnosis of brucellosis is based on the detection in animal and human sera of antibodies to the O-polysaccharide of Brucella lipopolysaccharide. The currently employed serodiagnosis of brucellosis relies on the use of the Brucella O-polysaccharide as a diagnostic antigen. However, the existence of bacterial species, which also express O-polysaccharides structurally similar to that of Brucella, may decrease the specificity of the brucellosis detection due to false-positive test results. It has been shown that the efficiency of the test can be significantly improved by using synthetic oligosaccharides that correspond to the so-called M epitope of the Brucella O-antigen. This epitope is characterized by an a-(1^3)-linkage between D-perosamine units and is unique to Brucella. Here we report on an efficient approach to the synthesis of oligosaccharides that model the M epitope of the Brucella O-polysaccharide. The approach is based on the use of the a-(1^3)-linked disaccharide thioglycoside as the key donor block. Its application allowed the straightforward assembly of a set of four protected oligosaccharides, which includes a disaccharide, two trisaccharides, and a tetrasaccharide, in five glycosylation steps. The synthesized oligosaccharides are planned to be used in the development of diagnostic tools for identifying brucellosis in humans and domestic animals, as well as a potential vaccine against it. [ABSTRACT FROM AUTHOR]

Purpose: Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[18F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer's ability to target the macrophage mannose receptor CD206. Methods: First, the uptake of intravenously (i.v.) administered Al[18F]F-NOTA-D10CM was compared between wild-type (WT) and CD206−/− knockout (KO) mice. C57BL/6N mice were injected with complete Freund's adjuvant (CFA) in the left hind leg and the uptake of Al[18F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14 days after CFA induction of inflammation. Healthy C57BL/6N mice were studied as controls. Mice underwent PET/CT on consecutive days with [18F]FDG, i.v. Al[18F]F-NOTA-D10CM, and i.d. Al[18F]F-NOTA-D10CM. After the last imaging, Al[18F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[18F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining. Results: Compared with WT mice, the uptake of Al[18F]F-NOTA-D10CM was significantly lower in several CD206−/− KO mice tissues, including liver (SUV 8.21 ± 2.51 vs. 1.06 ± 0.16, P < 0.001) and bone marrow (SUV 1.63 ± 0.37 vs. 0.22 ± 0.05, P < 0.0001). The uptake of i.v. injected Al[18F]F-NOTA-D10CM was significantly higher in inflamed ankle joint (SUV 0.48 ± 0.13 vs. 0.18 ± 0.05, P < 0.0001) and inflamed foot pad skin (SUV 0.41 ± 0.10 vs. 0.04 ± 0.01, P < 0.0001) than in the corresponding tissues in healthy mice. The i.d.-injected Al[18F]F-NOTA-D10CM revealed differences between CFA-induced lymph node activation and lymph nodes in healthy mice. Ex vivo γ-counting, autoradiography, and immunohistochemistry supported the results, and a decrease of ~ 80% in the binding of Al[18F]F-NOTA-D10CM in the displacement study with excess NOTA-D10CM confirmed that tracer binding was specific. At 60 min after i.v. injection, an average 96.70% of plasma radioactivity was derived from intact Al[18F]F-NOTA-D10CM, indicating good in vivo stability. The uptake of Al[18F]F-NOTA-D10CM into inflamed tissues was positively associated with the area percentage of CD206-positive staining. Conclusion: The uptake of mannosylated dextran derivative Al[18F]F-NOTA-D10CM correlated with CD206 expression and the tracer appears promising for inflammation imaging. [ABSTRACT FROM AUTHOR]

Wounds are most commonly caused by accidents, surgery and burns, and can be internal or external. Naturally, the wound healing process can take a long time and lead to scarring. In this study we present a technique to shorten wound healing time and prevent or mitigate scarring using D-mannose that is applied directly on the wound. The results showed that the healing time is almost halved compared to treatment with povidone-iodine solution which is an antiseptic widely used in surgery. D-Mannose is neither an antisepsis nor an antibiotic. We propose a posssible mechanism by which D-mannose binds to D-mannose binding lectin and immediately activates the innate immune system that ultimately phagocytizes pathogens and clears the wound of degraded cells and materials, which reduces inflammation and implicitly wound healing time. D-Mannose also intervenes in the coagulation process by binding to fibrinogen, generating a finer and denser fibrin, which visibly reduces collagen scars. Our findings show that applying D-mannose directly on the wound as a powder shortens wound healing time and visibly attenuates scarring. Apart from the unaesthetic appearance, these scars can also cause a certain tissue dysfunction, regardless of the affected organ. [ABSTRACT FROM AUTHOR]

Background: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. Results: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. Conclusions: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii. [ABSTRACT FROM AUTHOR]

This article discusses a new method for efficiently modifying oligonucleotides with multiple sugars in a one-step reaction. The researchers used a bifunctional linker and Cu-catalyzed alkyne-azide click chemistry to achieve this modification. The method is fast, highly selective, and cost-effective, allowing for the synthesis of oligonucleotides with multiple sugar modifications. This research has implications for the development of nucleic acid therapeutics in the pharmaceutical industry. The study was supported by various funding sources and the data is available in the supporting information. [Extracted from the article]

Tenacibaculum discolor develops biofilm in marine aquaculture production tanks and is identified as one of the causative agents of tenacibaculosis, a bacterial disease that causes significant losses in marine aquaculture production. In this study, the biofilm characteristics of T. discolor strain FMCC B487 were evaluated. Cell growth and biofilm formation and development were studied in miniaturized assays to assess the effect of different levels of environmental factors temperature and salinity, as well as the presence of monosaccharides potentially found in aquaculture hatcheries. The ability of the strain to grow and develop strong biofilms in ambient to high temperatures and at salinities above 20 g/L was shown. Mannose was the monosaccharide with the most prominent impact on the T. discolor strain FMCC B487 biofilm. The composition of planktonic cell extract, biofilm extracts, and extracellular polymeric substances (EPS) produced by T. discolor strain FMCC B487 were investigated by means of colorimetric and fluorometric assays as well as analyses by electrophoresis, gas chromatography, and high-performance size-exclusion chromatography coupled with a multiangle light scattering detector, revealing the dominance of proteins and lipids and the absence of high-molecular-weight polysaccharides. This information may serve as a basis for considering anti-biofilm strategies against the pathogen T. discolor. [ABSTRACT FROM AUTHOR]

Proteins containing DM9 motifs, which were originally identified in the Drosophila melanogaster genome, are widely distributed in various organisms and are assumed to be involved in their innate immune response. In this study, we produced a recombinant protein of CG13321 (rCG13321) from D. melanogaster , which consists of four DM9 motifs, in Escherichia coli cells. In affinity chromatography using a mannose-immobilized column, rCG13321 exhibited mannose-binding ability and was separated into high-affinity and low-affinity fractions, named HA and LA, respectively, based on its binding ability to the column. In addition to having a higher affinity for the column, HA exhibited self-oligomerization ability, suggesting slight differences in tertiary structure. Both LA and HA showed hemagglutinating activity and were able to agglutinate an oligomannose-containing dendrimer, indicating that they have multiple carbohydrate-binding sites. Glycan array analysis suggested that rCG13321 primarily recognizes d -mannose and d -rhamnose through hydrogen bonding with the 2-, 3- and 4-hydroxy groups. Isothermal titration calorimetry demonstrated that rCG13321 has a comparable affinity to typical lectins. These findings suggest that CG13321 functions as a carbohydrate-binding protein or lectin that recognizes mannose and related carbohydrate-containing molecules on the surface of foreign organisms as a pattern recognition molecule. [ABSTRACT FROM AUTHOR]

Lipid-laden foam cells within the arterial walls play a key role in the development of atherosclerotic lesions at early disease stages, and they have been recognized as attractive targets for developing targeted therapeutics in atherosclerosis. Herein, we developed mannose-conjugated beta-cyclodextrin (MAN-βCD) and evaluated its targeting ability and intracellular cholesterol efflux toward cholesterol-laden foam cells. The synthesized MAN-βCD showed effective cholesterol extraction ability in aqueous conditions. The nontoxic and cytocompatible MAN-βCD specifically targeted cholesterol-laden foam cells with positive CD206 expressions and was internalized into the cells via receptor-mediated endocytosis. Additionally, the internalized MAN-βCD exhibited effective lipid droplet (LD) reduction within the cholesterol-laden foam cells, leading to remarkable prevention of LD accumulation. Therefore, the specific delivery of MAN-βCD into CD206-expressing lipid-laden foam cells provides a promising prevention strategy in the progression of atherosclerotic plaques. [ABSTRACT FROM AUTHOR]

This study demonstrates that Lactobacillus can produce exopolysaccharides (EPSs) using alternative carbon sources, such as sugarcane molasses and glycerol. After screening 22 strains of Lactobacillus to determine which achieved the highest production of EPS based on dry weight at 37 °C, the strain Ke8 (L. casei) was selected for new experiments. The EPS obtained using glycerol and glucose as carbon sources was classified as a heteropolysaccharide composed of glucose and mannose, containing 1730 g.mol−1, consisting of 39.4% carbohydrates and 18% proteins. The EPS obtained using molasses as the carbon source was characterized as a heteropolysaccharide composed of glucose, galactose, and arabinose, containing 1182 g.mol−1, consisting of 52.9% carbohydrates and 11.69% proteins. This molecule was characterized using Size Exclusion Chromatography (HPLC), Gas chromatography–mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). The existence of polysaccharides was confirmed via FT-IR and NMR analyses. The results obtained suggest that Lacticaseibacillus casei can grow in media that use alternative carbon sources such as glycerol and molasses. These agro-industry residues are inexpensive, and their use contributes to sustainability. The lack of studies regarding the use of Lacticaseibacillus casei for the production of EPS using renewable carbon sources from agroindustry should be noted. [ABSTRACT FROM AUTHOR]

Biochemical analysis of human normal bronchial cells (BEpiC) and human cancer lung cells (A549) has been performed by using Raman spectroscopy and Raman imaging. Our approach provides a biochemical compositional mapping of the main cell components: nucleus, mitochondria, lipid droplets, endoplasmic reticulum, cytoplasm and cell membrane. We proved that Raman spectroscopy and Raman imaging can distinguish successfully BEpiC and A549 cells. In this study, we have focused on the role of mannose in cancer development. It has been shown that changes in the concentration of mannose can regulate some metabolic processes in cells. Presented results suggest lipids and proteins can be considered as Raman biomarkers during lung cancer progression. Analysis obtained for bands 1444 cm−1, and 2854 cm−1 characteristic for lipids and derivatives proved that the addition of mannose reduced levels of these compounds. Results obtained for protein compounds based on bands 858 cm−1, 1004 cm−1 and 1584 cm−1 proved that the addition of mannose increases the values of protein in BEpiC cells and blocks protein glycolisation in A549 cells. Noticing Raman spectral changes in BEpiC and A549 cells supplemented with mannose can help to understand the mechanism of sugar metabolism during cancer development and could play in the future an important role in clinical treatment. [ABSTRACT FROM AUTHOR]

Astrocyte-derived pyruvate is considered to have neuroprotective functions. In order to investigate the processes that are involved in astrocytic pyruvate release, we used primary rat astrocyte cultures as model system. Depending on the incubation conditions and medium composition, astrocyte cultures established extracellular steady state pyruvate concentrations in the range between 150 µM and 300 µM. During incubations for up to 2 weeks in DMEM culture medium, the extracellular pyruvate concentration remained almost constant for days, while the extracellular lactate concentration increased continuously during the incubation into the millimolar concentration range as long as glucose was present. In an amino acid-free incubation buffer, glucose-fed astrocytes released pyruvate with an initial rate of around 60 nmol/(h × mg) and after around 5 h an almost constant extracellular pyruvate concentration was established that was maintained for several hours. Extracellular pyruvate accumulation was also observed, if glucose had been replaced by mannose, fructose, lactate or alanine. Glucose-fed astrocyte cultures established similar extracellular steady state concentrations of pyruvate by releasing pyruvate into pyruvate-free media or by consuming excess of extracellular pyruvate. Inhibition of the monocarboxylate transporter MCT1 by AR-C155858 lowered extracellular pyruvate accumulation, while inhibition of mitochondrial pyruvate uptake by UK5099 increased the extracellular pyruvate concentration. Finally, the presence of the uncoupler BAM15 or of the respiratory chain inhibitor antimycin A almost completely abolished extracellular pyruvate accumulation. The data presented demonstrate that cultured astrocytes establish a transient extracellular steady state concentration of pyruvate which is strongly affected by modulation of the mitochondrial pyruvate metabolism. [ABSTRACT FROM AUTHOR]

The major challenge in the development of affordable medicines from natural sources is the unavailability of logical protocols to explain their mechanism of action in biological targets. FimH (Type 1 fimbrin with D-mannose specific adhesion property), a lectin on E. coli cell surface is a promising target to combat the urinary tract infection (UTI). The present study aimed at predicting the inhibitory capacity of saccharides on FimH. As mannosides are considered FimH inhibitors, the readily accessible saccharides from the PubChem collection were utilized. The artificial neural networks (ANN)-based machine learning algorithm Self-organizing map (SOM) has been successfully employed in predicting active molecules as they could discover relationships through self-organization for the ligand-based virtual screening. Docking was used for the structure-based virtual screening and molecular dynamic simulation for validation. The result revealed that the predicted molecules malonyl hexose and mannosyl glucosyl glycerate exhibit exactly similar binding interactions and better docking scores as that of the reference bioassay active, heptyl mannose. The pharmacokinetic profile matches that of the selected bioflavonoids (quercetin malonyl hexose, kaempferol malonyl hexose) and has better values than the control drug bioflavonoid, monoxerutin. Thus, these two molecules can effectively inhibit type 1 fimbrial adhesin, as antibiotics against E. coli and can be explored as a prophylactic against UTIs. Moreover, this investigation can pave the way to the exploration of the potential benefits of plant-based treatments. [ABSTRACT FROM AUTHOR]

Two unreported heteropolysaccharides, denoted as YCJP–1 and YCJP–2, were isolated from the herbs of Chloranthus japonicus. YCJP–1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475–228,443 Da range. YCJP–2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP–1 and YCJP–2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP–1, and YCJP–2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP–1, and YCJP–2. Moreover, YCJP–2 demonstrated superior anti-gastric cancer effects compared to YCJP–1. This could potentially be attributed to YCJP–2's higher glucose content and narrower molecular weight distribution. [ABSTRACT FROM AUTHOR]

This Special Issue was assembled to mark the 25th anniversary of the proposal of the d -mannose/ l -galactose (Smirnoff–Wheeler) ascorbate biosynthesis pathway in plants (Wheeler et al. , 1998). The issue aims to assess the current state of knowledge and to identify outstanding questions about ascorbate metabolism and functions in plants. [ABSTRACT FROM AUTHOR]

Purpose: Soluble mannose receptor (sMR) relates to mannose receptor expression on macrophages, and is elevated in inflammatory disorders. Gaucher disease (GD) has altered macrophage function and utilises mannose receptors for enzyme replacement therapy (ERT) endocytosis. sMR has not previously been studied in GD. Methods: sMR was measured by ELISA and correlated with GD clinical features including spleen and liver volume, haemoglobin and platelet count, bone marrow burden (BMB) scores and immunoglobulin levels. sMR was compared with biomarkers of GD: chitotriosidase, lyso‐GL1, PARC, CCL3, CCL4, osteoactivin, serum ACE and ferritin. Results: Median sMR in untreated GD patients was 303.0 ng/mL compared to post‐treatment 190.9 ng/mL (p =.02) and healthy controls 202 ng/mL. Median sMR correlated with median spleen volume 455 mL (r =.70, p =.04), liver volume 2025 mL (r =.64, p =.04), BMB 7 (r =.8, p =.03), IgA 1.9 g/L (r =.54, p =.036), IgG 9.2 g/L (r =.57, p =.027), IgM 1.45 g/L (r =.86, p <.0001), with inverse correlation to median platelet count of 125 × 109/L (r = −.47, p =.08) and haemoglobin of 137 g/L (r = −.77, p =.0008). sMR correlated with established biomarkers: osteoactivin 107.8 ng/mL (r =.58, p =.0006), chitotriosidase 3042 nmol/mL/h (r =.52, p =.0006), PARC 800 ng/mL (r =.67, p =.0068), ferritin 547 μg/L (r =.72, p =.002) and CCL3 50 pg/mL (r =.67, p =.007). Conclusions: sMR correlates with clinical features and biomarkers of GD and reduces following therapy. [ABSTRACT FROM AUTHOR]

Receptor-mediated cellular uptake of specific ligands constitutes an important step in the dynamic regulation of individual protein levels in extracellular fluids. With a focus on the inflammatory lung, we here performed a proteomics-based search for novel ligands regulated by the mannose receptor (MR), a macrophage-expressed endocytic receptor. WT and MR-deficient mice were exposed to lipopolysaccharide, after which the protein content in their lung epithelial lining fluid was compared by tandem mass tag-based mass spectrometry. More than 1200 proteins were identified in the epithelial lining fluid using this unbiased approach, but only six showed a statistically different abundance. Among these, an unexpected potential new ligand, thrombospondin-4 (TSP-4), displayed a striking 17-fold increased abundance in the MR-deficient mice. Experiments using exogenous addition of TSP-4 to MRtransfected CHO cells or MR-positive alveolar macrophages confirmed that TSP-4 is a ligand for MR-dependent endocytosis. Similar studies revealed that the molecular interaction with TSP-4 depends on both the lectin activity and the fibronectin type-II domain of MR and that a closely related member of the TSP family, TSP-5, is also efficiently internalized by the receptor. This was unlike the other members of this protein family, including TSPs −1 and −2, which are ligands for a close MR homologue known as urokinase plasminogen activator receptor-associated protein. Our study shows that MR takes part in the regulation of TSP-4, an important inflammatory component in the injured lung, and that two closely related endocytic receptors, expressed on different cell types, undertake the selective endocytosis of distinct members of the TSP family. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Vaccination is an effective method to prevent viral diseases. However, the biological barrier prevents the immersion vaccine from achieving the best effect without adding adjuvants and carriers. Researches on the targeted presentation technology of vaccines with nanocarriers are helpful to develop immersion vaccines for fish that can break through biological barriers and play an effective role in fish defense. In our study, functionally modified single-walled carbon nanotubes (SWCNTs) were used as carriers to construct a targeted immersion vaccine (SWCNTs-M−MCP) with mannose modified major capsid protein (MCP) to target antigen-presenting cells (APCs), against iridovirus diseases. After bath immunization, our results showed that SWCNTs-M−MCP induced the presentation process and uptake of APCs, triggering a powerful immune response. Moreover, the highest relative percent survival (RPS) was 81.3% in SWCNTs-M−MCP group, which was only 41.5% in SWCNTs-MCP group. Altogether, this study indicates that the SWCNTs-based targeted immersion vaccine induces strong immune response and provided an effective protection against iridovirus diseases. [ABSTRACT FROM AUTHOR]

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-COVID-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up-modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans, as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of the mannose receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of COVID-19 pathology and immunity to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Recombinant Cordyceps militaris lipase (rCML) expressed in Komagataella phaffii is more highly N -mannosylated (Man 8–11 GlcNAc 2) than the native lipase. The lipase activity of rCML was enhanced compared to its deglycosylated form (drCML), but the increases in the V max values of rCML for substrates with chain lengths of C4:0–C14:0 were 1.8 to 2.9-fold greater than those of drCML, whereas the difference was narrower for C16:0–C18:0. Changes in acyl chain length selectivity correlated with the conformational changes rather than hydrophobicity changes induced by N -mannosylation, which may have altered active site accessibility by shifting the favorable binding locations depending on acyl chain length. Nevertheless, high N -mannosylation did not significantly affect the melting temperature of rCML compared to that of drCML (55.5 °C and 57.0 °C, respectively) during thermal unfolding, but alleviated harsh deactivation in the thermal-transition state (60–70 °C). Furthermore, high N -mannosylation enhanced the long-term storage stability at –20 °C, and loss of activity was 5.2 ± 1.1% and 32.8 ± 1.2% for rCML and drCML, respectively. Overall, the introduction of yeast-derived high mannose moieties endowed short- to medium-chain selectivity and improved the biochemical properties of recombinant lipase. [Display omitted] • Recombinant Cordyceps militaris lipase (rCML) from Komagataella phaffii is highly mannosylated. • Lipase activity of rCML was higher than its deglycosylated form, regardless of acyl chain length. • Notable variations in acyl chain length-dependent kinetic parameters were observed. • N -Mannosylation enhanced selectivity for short- to medium-chain fatty acids. • N -Mannosylation enhanced stability during thermal processing and long-term storage. [ABSTRACT FROM AUTHOR]

In this study, a homogeneous polysaccharide, named, DRMP-1 was isolated from the mycelium of Dictyophora rubrovolvata by water extraction and alcohol precipitation, and its structure and activity were studied. The molecular weight of DRMP-1 is 2.33 × 106 Da, and it does not contain protein and nucleic acid. DRMP-1 is composed of mannose, glucose and galactose with a molar ratio of 0.04: 1: 0.04. Through methylation and NMR analysis, DRMP-1 is mainly composed of 1 → 6)-α-Gal p -(1 →, T-α-D-Glc p , →1)-α-D-Man p , → 6)-β-D-Glc p -(1 →, → 4, 6)- α-D-Man p -(1 →, → 4)- α-D-Glc p -(1 →, → 3)-β-D-Glc p -(1 → and → 4, 6)- α-D-Glc p -(1 →. In addition, the immunomodulative activity of DRMP-1 was evaluated by establishing the RAW264.7 cell model. The results showed that DRMP-1 could significantly increase phagocytosis activity and NO production more than twice as much as that of the blank group, and could increase intracellular ACP, LSZ and SOD activities. Therefore, it is concluded that the polysaccharide of Dictyophora rubrovolvata mycelium may be a potential immunomodulator. [Display omitted] • A new polysaccharide DRMP-1 was extracted from Dictyophora rubrodictya mycelia. • The chemical structure of DRMP-1 was characterized. • DRMP-1 has immune activity and can be used as a natural immunomodulator. [ABSTRACT FROM AUTHOR]

This research identified four amino acid residues (Leu174, Asn297, Tyr301, and Gln291) that contribute to substrate recognition by the high-affinity glucose transporter Xltr1p from Trichoderma reesei. Potential hotspots affecting substrate specificity were selected through homology modeling, evolutionary conservation analyses, and substrate-docking modeling of Xltr1p. Variants carrying mutations at these hotspots were subsequently obtained via in silico screening. Replacement of Leu174 or Asn297 in Xltr1p with alanine resulted in loss of hexose transport activity, indicating that Leu174 and Asn297 play essential roles in hexose transport. The Y301W variant exhibited accelerated mannose transport, but lost galactose transport capacity, and mutation of Gln291 to alanine greatly accelerated mannose transport. These results suggest that amino acids located in transmembrane α-helix 7 (Asn297, Tyr301, and Gln291) play critical roles in substrate recognition by the hexose transporter Xltr1p. Our results will help expand the potential applications of this transporter and provide insights into the mechanisms underlying its function and specificity.

Inducing the degradation of pathological soluble antigens could be the key to greatly enhancing the efficacy of therapeutic monoclonal antibodies (mAbs), extensively used in the treatment of autoimmune and inflammatory disorders or cancer. Lysosomal targeting has gained increasing interest in recent years due to its pharmaceutical applications far beyond the treatment of lysosomal diseases, as a way to address proteins to the lysosome for eventual degradation. Mannose 6-phosphonate derivatives (M6Pn), called AMFA, are unique glycovectors that can significantly enhance the cellular internalization of the proteins conjugated to AMFA via the cation-independent mannose 6-phosphate receptor (M6PR) pathway. AMFA engineering of mAbs results in the generation of a bifunctional antibody that is designed to bind both the antigen and the M6PR. The improvement of the therapeutic potential by AMFA engineering was investigated using two antibodies directed against soluble antigens: infliximab (IFX), directed against tumor necrosis factor α (TNF-α), and bevacizumab (BVZ), directed against the vascular endothelial growth factor (VEGF). AMFA conjugations to the antibodies were performed either on the oligosaccharidic chains of the antibodies or on the lysine residues. Both conjugations were controlled and reproducible and provided a novel affinity for the M6PR without altering the affinity for the antigen. The grafting of AMFA to mAb increased their cellular uptake through an M6PR-dependent mechanism. The antigens were also 2.6 to 5.7 times more internalized by mAb-AMFA and rapidly degraded in the cells. Additional cell culture studies also proved the significantly higher efficacy of IFX-AMFA and BVZ-AMFA compared to their unconjugated counterparts in inhibiting TNF-α and VEGF activities. Finally, studies in a zebrafish embryo model of angiogenesis and in xenografted chick embryos showed that BVZ-AMFA was more effective than BVZ in reducing angiogenesis. These results demonstrate that AMFA grafting induces the degradation of soluble antigens and a significant increase in the therapeutic efficacy. Engineering with mannose 6-phosphate analogues has the potential to develop a new class of antibodies for autoimmune and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) greatly affects human quality of life. Mannose has been reported to be used to treat IBD, but the mechanism is currently unknown. Methods: C57/BL mice were used as research subjects, and the mouse acute colitis model was induced using dextran sulfate sodium salt (DSS). After oral administration of mannose, the body weights and disease activity index (DAI) scores of the mice were observed. The colon lengths, histopathological sections, fecal content microbial sequencing, colon epithelial inflammatory genes, and tight junction protein Occludin-1 expression levels were measured. We further used the feces of mice that had been orally administered mannose to perform fecal bacterial transplantation on the mice with DSS-induced colitis and detected the colitis-related indicators. Results: Oral administration of mannose increased body weights and colon lengths and reduced DAI scores in mice with DSS-induced colitis. In addition, it reduced the expression of colon inflammatory genes and the levels of serum inflammatory factors (TNF-α, IL-6, and IL-1β), further enhancing the expression level of the colonic Occludin-1 protein and alleviating the toxic response of DSS to the intestinal epithelium of the mice. In addition, gut microbial sequencing revealed that mannose increased the abundance and diversity of intestinal flora. Additionally, after using the feces of the mannose-treated mice to perform fecal bacterial transplantation on the mice with DSS-induced colitis, they showed the same phenotype as the mannose-treated mice, and both of them alleviated the intestinal toxic reaction induced by the DSS. It also reduced the expression of intestinal inflammatory genes (TNF-α, IL-6, and IL-1β) and enhanced the expression level of the colonic Occludin-1 protein. Conclusion: Mannose can treat DSS-induced colitis in mice, possibly by regulating intestinal microorganisms to enhance the intestinal immune barrier function and reduce the intestinal inflammatory response. [ABSTRACT FROM AUTHOR]

Polysaccharides extracted from Taxus media hrough an aqueous method were further refined by removing proteins via the Sevag technique and purified by dialysis. The separation of these polysaccharides was accomplished using a DEAE-cellulose chromatog-raphy column, yielding two distinct fractions, named CPTM-P1 and CPTM-P2. Notably, CPTM-P1 emerged as the primary polysaccharide component within Taxus media. Consequently, a comprehensive analysis focusing exclusively on CPTM-P1 was undertaken. The molecular weight of CPTM-P1 was established through gel permeation chromatography (GPC), and its monosaccharide composition was deciphered using HPLC-MS. The structure was further elucidated through nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of CPTM-P1 was determined to be 968.7 kDa. The monosaccharide composition consisted of galactose (Gal), arabinose (Ara), galacturonic acid (Gal-UA), glucose (Glc), rhamnose (Rha), xylose (Xyl), mannose (Man), fucose (Fuc), glucuronic acid (Glc-UA), and ribose (Rib). The proportional distribution of these components was 30.53%, 22.00%, 5.63%, 11.67%, 11.93%, 1.69%, 8.50%, 1.23%, 5.63%, and 1.17%, respectively. This confirmed CPTM-P1 as an acidic heteropolysaccharide with a glycuronic acid backbone. Moreover, CPTM-P1 showed immunoenhancing properties, effectively augmenting the secretion of nitric oxide and cytokines (TNF-α, IL-1β, and IL-6). Additionally, it significantly enhances the phagocytic capacity of RAW264.7 cells. These findings underscore the potential application of these polysaccharides in functional foods and pharmaceuticals, providing a solid scientific basis for further exploration and utilization of Taxus media polysaccharides. [ABSTRACT FROM AUTHOR]

In this study, for the first time, polyphenols are extracted using microwave-assisted deep eutectic solvents (MW-DES) from supercritical CO2 defatted date seeds under variable operating conditions. The best conditions consisted of choline chloride: formic acid (1:2 molar ratio), a solid to solvent ratio of 1/20 (g/mL) (0.75 g of dry biomass in 15 mL solvent), an extraction time of 50 s, and a microwave power of 400 W. The maximum polyphenols extraction yield was 128 g gallic acid equivalent/kg dry biomass (g GAE/kg) (which is the highest value ever reported in literature for date seeds extracts). The antioxidant activity of the optimum extracts was assessed with the DPPH and ABTS quenching capacities being equal to 27 and 145 mg trolox equivalent/g dry biomass, respectively. Mainly mannose and manno-oligosaccharides were solubilized during extraction. The highest yields were (obtained at 200 W, 120 s) 35.07 and 32.18 mg/g of dry biomass for mannose and manno-oligosaccharides, respectively. It was also observed that the total mannose (monomer and oligomer) release during the extraction increased linearly (r2 = 0.9951) with respect to microwave energy applied per gram of date seeds (J/g). [ABSTRACT FROM AUTHOR]

Acidovorax sp. KKS102 is a beta-proteobacterium capable of degrading polychlorinated biphenyls (PCBs). In this study, we examined its growth in liquid nutrient broth supplemented with different carbon sources. KKS102 had at least 3 distinct metabolic phases designated as metabolic phases 1-3, with phase 2 having 2 sub-phases. For example, succinate, fumarate, and glutamate, known to repress the PCB/biphenyl catabolic operon in KKS102, were utilized in phase 1, while acetate, arabinose, and glycerol in phase 2, and glucose and mannose in phase 3. We also showed that the BphQ response regulator mediating catabolite control in KKS102, whose expression level increased moderately through the growth, plays important roles in carbon metabolism in phases 2 and 3. Our study elucidates the hierarchical growth of KKS102 in nutrient-rich media. This insight is crucial for studies exploiting microbial biodegradation capabilities and advancing studies for catabolite regulation mechanisms. [ABSTRACT FROM AUTHOR]

Alveolar macrophages play a vital role in a variety of lung diseases, including tuberculosis. Thus, alveolar macrophage targeted anti-tubercular drug delivery through nanocarriers could improve its therapeutic response against tuberculosis. The current study aimed at exploring the efficacy of glyceryl monostearate (GMS)-based solid-lipid nanoparticles (SLNs) and their mannose functionalized forms on the alveolar macrophage targeting ability of an anti-tubercular model drug, rifampicin (Rif). Rif-loaded SLNs were accomplished by the solvent diffusion method. These carriers with unimodal particle size distribution (~170 nm) were further surface-modified with mannose via Schiff-base reaction, leading to slight enhancement of particle diameter and a decline of drug loading capacity. The encapsulated Rif, which was molecularly dispersed within the matrices as indicated by their XRD patterns, was eluted in a sustained manner with an initial burst release effect. The uptake efficiency of mannose-modified SLNs was remarkably higher than that of corresponding native forms on murine macrophage Raw 264.7 cells and human lung adenocarcinoma A549 cells. Eventually, the mannose-modified SLNs showed a greater cytotoxicity on Raw 264.7 and A549 cells relative to their unmodified forms. Overall, our study demonstrated that mannose modification of SLNs had an influence on their uptake by alveolar macrophages, which could provide guidance for the future development of alveolar macrophage targeted nanoformulations. [ABSTRACT FROM AUTHOR]

In this study, three homogeneous fractions, PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1, were obtained from an aqueous extract of Polygonatum using DEAE cellulose column chromatography, CL-6B agarose gel chromatography, and Sephadex G100 chromatography. Their monosaccharide compositions and molecular weights were analyzed. The results revealed that PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1 are primarily composed of six monosaccharides: Man (mannose), GlcA (glucuronic acid), Rha (rhamnose), GalA (galacturonic acid), Glc (glucose), and Ara (arabinose), with molecular weights of 6.3 KDa, 5.78 KDa, and 3.45 KDa, respectively. Furthermore, we observed that Polygonatum polysaccharides exhibited protective effects against CCL4-induced liver damage in HepG2 cells in vitro, operating through both anti-oxidant and anti-inflammatory mechanisms. Our research findings suggest that Polygonatum polysaccharides may emerge as a promising option in the development of hepatoprotective drugs or functional foods with anti-inflammatory and antioxidant properties. [ABSTRACT FROM AUTHOR]

This article explores the role of innate IgM antibodies to mannose in patients with gastric cancer. It emphasizes the significance of mannose in the progression of gastric cancer and its potential as a target for therapy. The article presents studies that demonstrate the inhibitory effects of mannose on tumor cell growth and the correlation between high levels of mannose in the blood and improved survival rates in patients with esophageal adenocarcinoma. It also discusses the expression of mannose receptors in gastric tumors and their association with tumor size, stage, and metastases. Additionally, the article examines the genetic variations of mannose-binding lectin and their potential impact on the risk of gastric cancer. The authors propose that specific innate immunoglobulins could potentially address the deficiency in anti-glycan antibodies observed in patients with gastric cancer, leading to improved elimination of cancer cells. [Extracted from the article]

Many lysosomal enzymes contain N-glycans carrying mannose 6-phosphate (M6P) residues. Modifying lysosomal enzymes by M6P residues requires a two-step process in the Golgi apparatus. Then the lysosomal enzymes with M6P residues are transported from the trans -Golgi network to endosomes and lysosomes by M6P receptors. In insect cells, M6P residues are not added to N-glycans. Therefore, many insect lysosomal enzymes are transported to lysosomes by the M6P-independent pathway. The expression and subcellular distribution of M6P-modifying enzymes were examined by amplifying DNA fragments of M6P-modifying enzymes, generating the corresponding plasmid constructs, and transfection each construct into Sf9 cells, an insect cell line. The human GlcNac-1-phosphotransferase α/β subunit, one of the M6P-modifying enzymes, was found to differ in maturation and localization between mammalian and insect cells. In mammalian cells, newly biosynthesized α/β subunit localized in the cis -Golgi. In Sf9 cells, most of the α/β subunit was localized in the endoplasmic reticulum, and few mature forms of α/β subunit were observed. However, by the co-expression of the human site-1 protease, the mature forms were observed significantly and co-localization with each protein. Our study indicates new insights into regulating the intracellular distribution of the human GlcNac-1-phosphotransferase α/β subunit in insect cells. [ABSTRACT FROM AUTHOR]

DEC205 (CD205) is one of the major endocytic receptors on dendritic cells and has been widely used as a receptor target in immune therapies. It has been shown that DEC205 can recognize dead cells through keratins in a pH-dependent manner. However, the mechanism underlying the interaction between DEC205 and keratins remains unclear. Here we determine the crystal structures of an N-terminal fragment of human DEC205 (CysR~CTLD3). The structural data show that DEC205 shares similar overall features with the other mannose receptor family members such as the mannose receptor and Endo180, but the individual domains of DEC205 in the crystal structure exhibit distinct structural features that may lead to specific ligand binding properties of the molecule. Among them, CTLD3 of DEC205 adopts a unique fold of CTLD, which may correlate with the binding of keratins. Furthermore, we examine the interaction of DEC205 with keratins by mutagenesis and biochemical assays based on the structural information and identify an XGGGX motif on keratins that can be recognized by DEC205, thereby providing insights into the interaction between DEC205 and keratins. Overall, these findings not only improve the understanding of the diverse ligand specificities of the mannose receptor family members at the molecular level but may also give clues for the interactions of keratins with their binding partners in the corresponding pathways. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD) represents a global health challenge, with its etiology and underlying mechanisms yet to be fully elucidated. Integrating genomics with metabolomics can offer insights into the putatively causal relationships between serum metabolites and CKD. Methods: Utilizing bidirectional Mendelian Randomization (MR), we assessed the putatively causal associations between 486 serum metabolites and CKD. Genetic data for these metabolites were sourced from comprehensive genome-wide association studies, and CKD data were obtained from the CKDGen Consortium. Results: Our analysis identified four metabolites with a robust association with CKD risk, of which mannose and glycine showed the most reliable causal relationships. Pathway analysis spotlighted five significant metabolic pathways, notably including "Methionine Metabolism" and "Arginine and Proline Metabolism", as key contributors to CKD pathogenesis. Conclusion: This study underscores the potential of certain serum metabolites as biomarkers for CKD and illuminates pivotal metabolic pathways in CKD's pathogenesis. Our findings lay the groundwork for potential therapeutic interventions and warrant further research for validation. [ABSTRACT FROM AUTHOR]

The synthesis of glycosides generally requires the use of building blocks that need to be readily prepared, avoiding tricky reaction steps and boring purifications. Thioglycosides represent key donor intermediates for their activation in glycosylation reactions and for their great stability. Moreover, the presence of a benzylidene moiety confers to the molecule a double advantage: it can influence the stereochemistry of the glycosylation reaction and can be selectively opened to generate different species having a free secondary hydroxyl group. Here, the preparation of p‐Tolyl 1‐thio‐4,6‐O‐benzylidene‐2,3‐di‐O‐benzyl‐β‐d‐pyranoses of glucose, galactose, and mannose are described. The global procedure involved the exploitation of simple reactions and crystallization techniques, having a chromatographic purification for the last step only. [ABSTRACT FROM AUTHOR]

Therapy with clinical nerve guidance conduits often causes functional incompleteness in patients. With the aim of better therapeutic efficacy, nerve regeneration and gait function were investigated in this study using a novel nerve guidance conduit consisting of glucose/mannose. The glucose/mannose nerve guidance conduits were prepared by filling the conduits with the glucose/mannose aqueous solutions for different kinematic viscosity, which were applied to sciatic nerve defects (6 mm gap) in a rat model. The nerve regeneration effect and the gait function recovery with the fabricated nerve guidance conduits were examined. From the results of the XRD measurement, the glucose/mannose conduits were identified as crystal structures of cellulose type II. Young's modulus and the maximum tensile strength of the crystalline glucose/mannose conduits demonstrated good strength and softness for the human nerve. Above 4 weeks postoperative, macroscopic observation revealed that the nerve was regenerated in the defective area. In various staining results of the nerve tissue removed at 4 weeks postoperative, myelinated nerves contributing to gait function could not be observed in the proximal and distal sites to the central nerve. At 8–12 weeks postoperative, myelinated nerves were found at the proximal and distal sites in hematoxylin/eosin staining. Glia cells were confirmed by phosphotungstic acid–hematoxylin staining. Continuous nerve fibers were observed clearly in the sections of the regenerated nerves towards the longitudinal direction at 12 weeks postoperative. The angle between the metatarsophalangeal joint and the ground plane was approximately 93° in intact rats. At 4 weeks postoperative, walking was not possible, but at 8 weeks postoperative, the rats were able to walk, with an angle of 53°. At 12 weeks postoperative, the angle increased further, reaching 65°, confirming that the rats were able to walk more quickly than at 8 weeks postoperative. These results demonstrated that gait function in rats treated with glucose/mannose nerve guidance conduits was rapidly recovered after 8 weeks postoperative. The glucose/mannose nerve guidance conduit could be applied as a new promising candidate material for peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS: Mannose was independently associated with IR indexes (all P ≤ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07–2.20) in the overall population. CONCLUSIONS: Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) can kill the tumor in situ, but fail to trigger strong antitumor immune response against its recurrence and metastasis. Herein, mannose-grafting Fe-doped carbon dots (M/Fe-CDs) were prepared via hydrothermal carbonization and chemical modification. The prepared M/Fe-CDs had characteristics of excellent optical qualities, good water solubility, and outstanding biocompatibility. Compared with pure CDs, the doping of Fe atom endowed the M/Fe-CDs with a high photothermal conversion efficiency (from 12.1 up to 30.1%). Under 808-nm NIR irradiation, the M/Fe-CDs could lead to local hyperthermia to kill tumor cells. Importantly, the M/Fe-CDs were capable of loading CpG-ODNs via electrostatic absorption and delivering them into the cytoplasm of dendritic cells (DCs). Finally, the CpG-ODNs-loading M/Fe-CDs could significantly increase the CD80/86 expression on the DCs surface. These results demonstrated that the M/Fe-CDs could be used as a versatile nanoplatform to combine the PTT and immune activation for tumor treatment. [ABSTRACT FROM AUTHOR]

Phosphatidyl-myo-inositol mannosides (PIMs), Lipomannan (LM), and Lipoarabinomannan (LAM) are essential components of the cell envelopes of mycobacteria. At the beginning of the biosynthesis of these compounds, phosphatidylinositol (PI) is mannosylated and acylated by various enzymes to produce Ac1/2PIM4, which is used to synthesize either Ac1/2PIM6 or LM/LAM. The protein PimE, a membrane-bound glycosyltransferase (GT-C), catalyzes the addition of a mannose group to Ac1PIM4 to produce Ac1PIM5, using polyprenolphosphate mannose (PPM) as the mannose donor. PimE-deleted Mycobacterium smegmatis (Msmeg) showed structural deformity and increased antibiotic and copper sensitivity. Despite knowing that the mutation D58A caused inactivity in Msmeg, how PimE catalyzes the transfer of mannose from PPM to Ac1/2PIM4 remains unknown. In this study, analyzing the AlphaFold structure of PimE revealed the presence of a tunnel through the D58 residue with two differently charged gates. Molecular docking suggested PPM binds to the hydrophobic tunnel gate, whereas Ac1PIM4 binds to the positively charged tunnel gate. Molecular dynamics (MD) simulations further demonstrated the critical roles of the residues N55, F87, L89, Y163, Q165, K197, L198, R251, F277, W324, H326, and I375 in binding PPM and Ac1PIM4. The mutation D58A caused a faster release of PPM from the catalytic tunnel, explaining the loss of PimE activity. Along with a hypothetical mechanism of mannose transfer by PimE, we also observe the presence of tunnels through a negatively charged aspartate or glutamate with two differently-charged gates among most GT-C enzymes. Common hydrophobic gates of GT-C enzymes probably harbor sugar donors, whereas, differently-charged tunnel gates accommodate various sugar-acceptors. [ABSTRACT FROM AUTHOR]

A critical environmental problem in the Brazilian Amazon-rainforest region is the annual generation of 1.4 million tons of açaí seeds as a waste from açaí-pulp production. This work evaluates the techno-economic viability and environmental impacts of four alternatives to avail açaí seeds: complete combustion for power generation, integrated production of polyphenols and electricity, and co-production of mannose, polyphenols, and electricity by two different routes. Incineration is the least profitable alternative and requires long-term payback for the considered capacity of 6000 kg/h of seeds. The alternative that prescribes co-production of polyphenols and electricity has sound economic and environmental performances but misses the opportunity to avail the mannan content of açaí seeds to produce mannose. The comparison of mannose-producing processes unveiled lower capital and operational costs in the single-step oxalic acid hydrolysis than the sequential sulfuric acid and enzymatic hydrolysis, resulting in a payback time of 2.7 years and an internal rate of return of 34.8%. It further evinces lower aquatic toxicity and acidification potentials, but greenhouse gas emissions are slightly higher than in the sulfuric acid case. The biorefinery is shown as a viable and sustainable waste valorization pathway for açaí seeds, which could help develop a circular bioeconomy in the Amazon region. [ABSTRACT FROM AUTHOR]

Microglia are important cells that act on regulating neuroinflammation and neurofunction after the induction of ischemic stroke (IS). Consequently, the efficient accumulation of drugs within ischemic regions, particularly in microglia, serves as a valuable approach for achieving effective therapy by attenuating microglia-mediated cerebral ischemic injury. In this study, we designed mannose (man)-conjugated luteolin (lut)-loaded platelet-derived exosomes (lut/man-pEXO) as surface engineered multifunctional cascade-delivery drug carriers to target ischemic blood vessels and subsequent microglia to enhance drug accumulation and induce neuroprotection of neurovascular unit (NVU) against IS. The results revealed that as platelets naturally gathered in pathological ischemic cerebral vessels, lut/man-pEXO could bind to platelets and efficiently target ischemic injury sites. Moreover, owing to the selective binding affinity of mannose present in lut/man-pEXO towards the mannose receptor expressed on microglia, lut/man-pEXO exhibited superior microglia-targeting properties, inducing the increased uptake of lut by microglia. As a result, lut/man-pEXO regulated microglia by inhibiting the activation of detrimental M1 and promoting the transition towards the anti-inflammatory type (M2), thus attenuating ischemic damage of NVU by reducing the infarct area, rescuing the damage of blood–brain barrier (BBB) and preventing inflammatory transformation of astrocytes. [ABSTRACT FROM AUTHOR]

The fructose-to-furfural transformation is facing major challenges in the selectivity and high efficiency. Herein, we have developed a simple and effective approach for the selective conversion of fructose to furfural using Hβ zeolite modified by organic acids for dealuminization to regulate its textural and acidic properties. It was found that citric acid-dealuminized Hβ zeolite possessed high specific surface areas, wide channels and high Brønsted acid amount, which facilitated the selective conversion of fructose to furfural with a maximum yield of 76.2% at 433 K for 1 h in the g-butyrolactone (GBL)-H2O system, as well as the concomitant formation of 83.0% formic acid. The 13C-isotope labelling experiments and the mechanism revealed that the selective cleavage of C1--C2 or C5--C6 bond on fructose was firstly occurred to form pentose or C5 intermediate by weak Brønsted acid, which was then dehydrated to furfural by strong Brønsted acid. Also this dealuminized Hβ catalyst showed the great recycling performance and was active for the conversion of glucose and mannose. [ABSTRACT FROM AUTHOR]

In recent years, the biological activity of plant polysaccharides has received increasing attention. Polysaccharides, as one of the main components of lilies, have pharmacological effects in regulating immunity, anti-tumor, antioxidant, antibacterial, and hypoglycemic effects. To systematically analyze the structural characteristics of the polysaccharide, the polysaccharide LP-1 was prepared from Lilium lancifolium bulbs by water extraction and ethanol precipitation, ion exchange chromatography and gel filtration chromatography. Structural characterizations show that the weight-average relative molecular weight of LP-1 is 5.3 kDa. LP-1 consists of mannose and glucose at a molar ratio of 1.4:1. Its primary structure is Glcp-α-D-(1 → {4)-β-D-Glcp-(1 → 4)-β-D-2-O-acetyl-Manp-(1 → [4)-β-D-Glcp-(1 → 4)-β-D-Glcp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-Manp-(1 → 4)-β-D-Manp-(1]2}2 → 4)-α-D-Glcp. Acetylation occurs at the O-2 site of mannose. Acetyl substitution degree is 8.21%. The results of structure elucidation showed that LP-1 was a low-molecular weight linear O-acetylated glucomannan. The results of oxidative stress experiments indicate that LP-1 exerts antioxidant effects on HUVEC by activating the Nrf2/HO-1 signaling pathway, thereby improving endothelial cell damage induced by H2O2, and has the potential to be developed as an antioxidant drug. [ABSTRACT FROM AUTHOR]

Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs. COL1, mainly secreted by cancer‐associated fibroblasts, is a niche component for GSCs. COL1 enhances the interaction between CD133 and p85 and activates Akt phosphorylation. Activation of Akt pathway increases transcription factor ATF4 protein level, subsequently enhances SLC1A5‐dependent glutamine uptake and glutathione synthesis. The inhibition of CD133‐COL1 interaction or down‐regulation of SLC1A5 reduces COL1‐accelerated GSCs self‐renewal and tumorigenesis. Analysis of glioma samples reveals that the level of COL1 is correlated with histopathological grade of glioma and the expression of SLC1A5. Collectively, COL1, a niche component for GSCs, enhances the tumorigenesis of GSCs partially through CD133‐Akt‐SLC1A5 signaling axis, providing a new mechanism underlying the cross‐talk between GSCs and extracellular matrix (ECM) microenvironment. [ABSTRACT FROM AUTHOR]

Concanavalin A (ConA) has an intrinsic binding affinity to carbohydrates. Here, we obtained Co2+–Ca2+–ConA (2.83 Å, PDB: 8I7Q) via X-ray crystallography by substituting native ConA (Mn2+–Ca2+); it has binding selectivity for high-mannose N-glycan similar to native ConA. Our findings may thus inform antiviral reagent design. [ABSTRACT FROM AUTHOR]