Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify...Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.展开更多
The limited treatment options for advanced prostate cancer(PCa)lead to the urgent need to discover new anticancer drugs.Mannose,an isomer of glucose,has been reported to have an anticancer effect on various tumors.How...The limited treatment options for advanced prostate cancer(PCa)lead to the urgent need to discover new anticancer drugs.Mannose,an isomer of glucose,has been reported to have an anticancer effect on various tumors.However,the anticancer effect of mannose in PCa remains unclear.In this study,we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro,and mannose was observed to have an anticancer effect in mice without harming their health.Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential,increased mitochondrial and cellular reactive oxygen species(ROS)levels,and reduced adenosine triphosphate(ATP)production in PCa cells.Mannose treatment of PCa cells induced changes in mitochondrial morphology,caused dysregulated expression of the fission protein,such as fission,mitochondrial 1(FIS1),and enhanced the expression of proapoptotic factors,such as BCL2-associated X(Bax)and BCL2-antagonist/killer 1(Bak).Furthermore,lower expression of mannose phosphate isomerase(MPI),the key enzyme in mannose metabolism,indicated poorer prognosis in PCa patients,and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose.This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.展开更多
[ Objective] The aim was to construct drought and saline-alkaline resistance plant expression vector with mannose as selective agent, and further breed unmarked resilient varieties. [ Method] The plant expression vect...[ Objective] The aim was to construct drought and saline-alkaline resistance plant expression vector with mannose as selective agent, and further breed unmarked resilient varieties. [ Method] The plant expression vector was constructed by using Chimonanthus praecox（ L. ）Link aquapor.in CpTIP cDNA and Escherichia coli pmi gene, combined stress resistance gene with mannose positive selection system. [ Result] The test successfully constructed the plant expression vector pPMI：：CpTIP. [ Conclusion] The constructed vector linked advantages of stress resistance gene and mannose positive selection system.展开更多
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To ...BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.展开更多
Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in mainta...Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.展开更多
Rapid detection and identification of Escherichia coli(E.coli)is essential to prevent its quickly spread.In this study,a novel fluorescence probe based on ZnTe quantum dots(QDs)modified by mannose(MAN)had been prepare...Rapid detection and identification of Escherichia coli(E.coli)is essential to prevent its quickly spread.In this study,a novel fluorescence probe based on ZnTe quantum dots(QDs)modified by mannose(MAN)had been prepared for the determination of E.coli.The results showed that the obtained QDs showed excellent selectivity toward E.coli,and presented a good linearity in range of 1.0×10~5~1.0×10~8 CFU/mL.The optimum fluorescence intensity for detecting E.coli was found to be at pH 7.0 with a temperature of25℃and incubation time of 20 min.Under these optimum conditions,the detection limit of E.coli was4.6×10~4 CFU/mL.The quenching was discussed to be a static quenching procedure,which was proved by the quenching efficiency of QDs decreased with the temperature increasing.展开更多
To investigate the chemical structure of cell wall mannan obtained from pathogenic yeast, Candida tropicalis NBRC 1400 (former antigenic standard strain, IFO 1400). As a result of two-dimensional NMR analysis, it was ...To investigate the chemical structure of cell wall mannan obtained from pathogenic yeast, Candida tropicalis NBRC 1400 (former antigenic standard strain, IFO 1400). As a result of two-dimensional NMR analysis, it was shown that the mannan of this strain is composed of α-1,6-, α-1,3-, α-1,2- and β-1,2-linked mannose residues. In this research, the mannan was subjected to three degradation procedures, acid-treatment, α-mannosidase, and acetolysis under two conditions in order to determine the chemical structure of the antigenic oligomannosyl side chains in this molecule. The 1H-nuclear magnetic resonance spectra of resultant oligosaccharides, pentaose and hexaose, demonstrated the existence of the oligomannosyl side chains corresponding to Manα1-3Manα1-2Manα1-2Manα1-2Man and Manα1-3Manα1-2Manα1-2Manα1-2Manα1-2Man, respectively, which have previously also been found in Candida albicans serotype A strain mannans. These findings indicate that C. tropicalis and C. albicans serotype A have no significant difference in the chemical structure of these cell wall mannans. Therefore, it can be interpreted that it is extremely difficult to distinguish both species by targeting the antigenic group in these mannans.展开更多
[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mic...[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mice were selected and then randomly divided into normal control,model group and positive group( bifendate 120 mg/kg),high-dose arabinose + mannose group( 800 mg/kg),middle-dose arabinose + mannose group( 400 mg/kg) and low-dose arabinose + mannose group( 200 mg/kg),each group had 10 mice,which were fed adaptively for 1 week. Except normal control group and model group,each treatment group was given medicine by gavage once a day and lasted for7 days according to the dosage of 20 ml/kg. After the last drug,except normal control group,the mice of other groups were injected 10 ml/kg0. 12% CC14 peanut oil through enterocoelia,thereby establishing acute liver injury model. The mice were fasted but not water for 24 h,after that,blood was sampled from mice eyes,then dissected rapidly. The activities of ALT and AST in the serum were determined,the expression levels of TNF-α,IL-1β and IL-6 from the hepatic tissues were detected by enzyme-linked immunosorbent assay( ELISA); then after HE dye,the changes of liver histopathology were observed. [Results]Compared with CCl_4 model,the activities of ALT and AST from the serum of mice from high-dose and middle dose groups decreased significantly( P < 0. 01); the contents of TNF-α,IL-1β and IL-6 from the hepatic tissues of mice decreased significantly( P < 0. 01); the pathological section showed that the liver injury of mice from the combined drug groups showed alleviating trend to varying degrees,in which the liver injury of mice from the high-dose group was the best. [Conclusions] Arabinose + mannose has an obvious protective effect on mice with acute liver injury induced by CCl_4,and its mechanism may relate to anti-inflammatory.展开更多
Background： The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus a...Background： The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short （2-wk） and long （8-wk） durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions （1-wk hyperinsulinemic-isoglycemic clamp） to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. Results： A maternal insulin infusion resulted in lower maternal （50%, P 〈 0.01） and fetal （35-45%, P 〈 0.01） mannose concentrations, which were highly correlated （r^2 = 0.69, P 〈 0.01）. A fetal insulin infusion resulted in a 50% reduction of fetal mannose （P 〈 0.05）. Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose （P 〈 0.01）. Conclusions： Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.展开更多
A highly efficient method to get 3-and 6-modified mannose/ahrose derivatives for oligosaccharide synthesis is described. All the compounds were obtained exclusively with the combinations of 3-and/or 6-hydroxyl protect...A highly efficient method to get 3-and 6-modified mannose/ahrose derivatives for oligosaccharide synthesis is described. All the compounds were obtained exclusively with the combinations of 3-and/or 6-hydroxyl protection and/or activation（ including the configuration conversion of 3-carbon atom）.展开更多
Mannose,a different isomer of the hydroxyl group at the C-2 position of glucose,shares the same transport carrier protein with glucose to enter cells and participate in the regulation of glucose metabolism.It affects ...Mannose,a different isomer of the hydroxyl group at the C-2 position of glucose,shares the same transport carrier protein with glucose to enter cells and participate in the regulation of glucose metabolism.It affects cell growth,differentiation,and function and plays an active role in tumor immunity and inflammatory processes.This paper provides theoretical support for expanding the clinical applications of mannose by exploring its constitution,metabolic pathways,and role in regulating immune cell function and treating immunology-related diseases.展开更多
ᴅ-Mannose is a functional monosaccharide that is difficult to prepare on a large scale via chemical or enzymatic synthetic routes due to low conversion rates and complex downstream isolation.In this study,a two-step e...ᴅ-Mannose is a functional monosaccharide that is difficult to prepare on a large scale via chemical or enzymatic synthetic routes due to low conversion rates and complex downstream isolation.In this study,a two-step enzymatic route was established to achieve highly efficient conversion ofᴅ-fructose toᴅ-mannose without the need for a tedious isomer separation process.Firstly,a mannose isomerase from Xanthomonas phaseoli was coupled with a sugar 1-kinase from Bifidobacterium infantis and a polyphosphate kinase to synthesize mannose 1-phosphate(Man-1-P)fromᴅ-fructose and polyphosphate(PolyP),using adenosine 5′-triphosphate or adenosine 5′-monophosphate(AMP)as the regenerating co-factor.The reaction was optimized to achieve 99%conversion ofᴅ-fructose at substrate concentrations of 300 mmol/L forᴅ-fructose,with only 0.5 mmol/L AMP(1/600 equiv.)as the co-factor.The solution from the first-step reaction,containing Man-1-P,was simply clarified by centrifugation and then precipitated with calcium salt.Subsequently,Man-1-P was hydrolyzed by a phosphatase to yieldᴅ-mannose,which was purified by desalting with activated carbon adsorption.As a demonstration of this strategy,11.1 g ofᴅ-mannose was produced with an overall yield of 85.6%.This synthesis strategy is expected to be applicable for large-scale preparation.展开更多
The biosynthesis of Ganoderma lucidum polysaccharides(GLPs)begins with the nucleotide sugar precursor synthesis.Guanosine diphosphate(GDP)-mannose pyrophosphorylase(GMP)specifically catalyzes the conversion of mannose...The biosynthesis of Ganoderma lucidum polysaccharides(GLPs)begins with the nucleotide sugar precursor synthesis.Guanosine diphosphate(GDP)-mannose pyrophosphorylase(GMP)specifically catalyzes the conversion of mannose-1-phosphate to GDP-mannose.However,the specific role of GMP in GLP synthesis remains unclear.Therefore,we investigated the function of the glgmp gene in mycelial growth,polysaccharide production,and the transcriptional regulation of key genes involved in GLP biosynthesis through genetic manipulation.A 2131 bp gene encoding a 50.93 kDa protein was cloned,and the overexpression and silencing transformed strains were constructed.The expression level of the glgmp gene influenced mycelial growth and pellet size.Overexpression of the glgmp gene boosted the production of high-mannose polysaccharides.The monosaccharide composition of polysaccharides changed significantly,with the proportion of mannose reaching a maximum of 13.28% and 11.64%.This was accompanied by a decrease in glucose percentage and an increase in galactose and fucose percentages.At the transcriptional level,overexpressing the glgmp gene upregulated the expression of phosphomannose isomerase and phosphomannomutase genes,which play critical roles in GDP-mannose synthesis.This promoted GDP-mannose supply and subsequently increased the mannose percentage.Upregulation of glgmp also increased the gene expression involved in the synthesis of GDP-fucose and uridine diphosphate(UDP)-galactose,resulting in increased ratios of fucose and galactose.In contrast,the glgmp silencing strains exhibited opposite effects,confirming these findings.This study provides a valuable reference for the efficient production of GLPs,inspiring a comprehensive exploration of the polysaccharide biosynthesis pathway.展开更多
Mannans,the predominant component in spent coffee grounds,can be transformed into mannose and man-nooligosaccharides.These derivatives serve as valuable prebiotics and bioactive components in the functional food and p...Mannans,the predominant component in spent coffee grounds,can be transformed into mannose and man-nooligosaccharides.These derivatives serve as valuable prebiotics and bioactive components in the functional food and pharmaceutical industries.In this study,two eco-friendly pretreatment techniques were utilized to process spent coffee grounds,enhancing the release of valuable sugars and improvingβ-mannanase accessibility,thereby increasing the yields of mannose and mannooligosaccharides.Following a combined treatment with laccase and cellulase,most soluble sugars were efficiently produced via microwave hydrothermal treatment at 210℃for 30 min.From 1 g of defatted spent coffee grounds,74.2 mg of mannose and 121.1 mg of man-nooligosaccharides were obtained,representing 83%of the total mannose content.This method has proven to be an efficient way to utilize spent coffee grounds,with significant implications for their high-value conversion and utilization.展开更多
Ulcerative colitis(UC)is a public health concern.The quest for drugs characterized by minimal side effects and optimal safety profiles for managing UC has emerged as a primary research topic.Recent evidence suggests t...Ulcerative colitis(UC)is a public health concern.The quest for drugs characterized by minimal side effects and optimal safety profiles for managing UC has emerged as a primary research topic.Recent evidence suggests the efficacy of Lactobacillus-derived exopolysaccharides containing mannose(MnEPSs)in alleviating UC.Lactoba-cillus could not synthesize MnEPSs in the glucose-only MRS medium,but with mannose added to the carbon source,MnEPSs were produced directionally,of which mannose accounts for 5.9-7.8%of the total sugar content.Subsequently,MnEPS-6M3,MnEPS-Q5M22,MnEPS-D4L1,and MnEPS-CCFM 1393 were used to investigate the mechanism of UC relief.The results showed that compared with non-MnEPSs,MnEPSs had the better effect on reliving UC.Phenotypically,four MnEPSs alleviated weight loss,DAI score,crypt disappearance,inflammatory cell infiltration,and mucosal edema of UC in mice.Mechanistically,MnEPSs increased the expression of ZO-1 by 52.38-115.87%to repair intestinal barrier,inhibited inflammatory factors(TNF-α,IL-1β,IL-6,IFN-γand IL-17)and increasd anti-inflammatory cytokines(IL-10)by reducing colonic F4/80^(+)macrophages(decreased 4.34-7.01%)and colonic iNOS^(+)M1 macrophages(decreased 7.3-10.52%),and promoted the production of acetic acid(increased 153.21-226.93%),propionic acid(increased 360.71-528.57%),and butyric acid(increased 127.45-156.86%)in cecal contents.Interestingly,MnEPS-Q5M22 and MnEPS-CCFM 1393 increased the abundance of butyric acid-producing Dunaliella.In summary,this study provides a theoretical basis for the directional synthesis of functional MnEPSs.展开更多
The clinical application of Chuanminshen violaceum polysaccharides(CVP),a natural immunomodulator with intrinsic antioxidant activity,is constrained by rapid systemic clearance,limited tissue specificity,and short-liv...The clinical application of Chuanminshen violaceum polysaccharides(CVP),a natural immunomodulator with intrinsic antioxidant activity,is constrained by rapid systemic clearance,limited tissue specificity,and short-lived bioactivity.To address these limitations,a multifunctional biomimetic nanoplatform incorporating erythrocyte membrane camouflage,mannose-mediated active targeting,and squalene-stabilized Pickering emulsion technology was developed.CVP-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(CVPP)were fabricated via solvent evaporation,coated with erythrocyte membranes,and subsequently functionalized with mannose to obtain CVPP@M-M.This dual modification enabled selective recognition by macrophage and dendritic cell(DC)mannose receptors,while the erythrocyte membrane imparted prolonged systemic circulation.Subsequent emulsification for the first time with squalene yielded CVPP@M-M-PPAS,a Pickering emulsion designed for enhanced lymph node delivery.In vitro,CVPP@M-M-PPAS significantly promoted macrophage activation,as evidenced by elevated CD80+/CD86+expression,compared with free CVP.In vivo,intramuscular co-administration with ovalbumin(OVA)antigen induced pronounced DC maturation and T cell polarization in the spleen.This formulation also elicited robust and sustained production of antigen-specific IgG,accompanied by increased upregulation of pro-inflammatory cytokines interleukin-6(IL-6)and interferon-γ(IFN-γ).In vivo imaging demonstrated prolonged lymph node retention(>336 h)with a near-linear fluorescence decay profile,confirming controlled release kinetics.By integrating stealth properties,receptor-specific targeting,and emulsion-enabled lymphatic trafficking,this nanoplatform effectively circumvents the pharmacokinetic and biodistributional barriers of plant-derived polysaccharides,enabling durable humoral and cellular immune responses.This strategy offers a generalizable framework for translating natural immunomodulators into clinically viable nanotherapeutics.展开更多
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 suppleme...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-αproduction translationally by reducing the glyceraldehyde 3-phosphate level,thus promoting GAPDH binding to TNF-αmRNA.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.展开更多
Previous studies have documented that selective delivery of protein antigens to cells expressing mannose receptor （MR） can lead to enhanced immune responses. We postulated that agents that influenced the MR expressi...Previous studies have documented that selective delivery of protein antigens to cells expressing mannose receptor （MR） can lead to enhanced immune responses. We postulated that agents that influenced the MR expression level, and the activation and migration status of MR-expressing antigen presenting cells, would modulate immune responses to MR-targeted vaccines. To address this question, we investigated the effect of clinically used adjuvants in human MR transgenic （hMR-Tg） mice immunized with an MR-targeting cancer vaccine composed of the human anti-MR monoclonal antibody B 11 fused with the oncofetal protein, human chorionic gonadotropin beta chain （hCGβ）, and referred to as B 11-hCGβ. We found that humoral responses to low doses of B11-hCGβ could be enhanced by prior administration of GM-CSF, which upregulated MR expression in vivo. However, co-administration of the Toll-like receptor （TLR） agonists, poly-ICLC and/or CpG with B11-hCGβ was required to elicit Thl immunity, as measured by antigen-specific T-cell production of IFN-γ. The TLR agonists were shown to increase the number of vaccine-containing cells in the draining lymph nodes of immunized hMR-Tg mice. In particular, with B11-hCGβand poly-ICLC, a dramatic increase in vaccine-positive cells was observed in the T-ceU areas of the lymph nodes, compared to the vaccine alone or combined with GM-CSF. Importantly, the absence of the TLR agonists during the priming immunization led to antigen-specific tolerance. Therefore, this study provides insight into the mechanisms by which adjuvants can augment immune responses to B11-hCGβ and have implications for the rationale design of clinical studies combining MR-targeted vaccination with TLR agonists.展开更多
Polarization of tumor associated macrophages(TAMs)has been a promising therapeutic paradigm for tumor.However,how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challe...Polarization of tumor associated macrophages(TAMs)has been a promising therapeutic paradigm for tumor.However,how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challenge.Here,we report dicarboxy fullerene modified with mannose(DCFM)as an immunomodulator to selectively polarize TAMs and prominently boost anti-tumor immunity.The dicarboxy fullerene molecule was synthesized through the Prato reaction and further covalently bonded with mannose,obtaining the DCFM with well-defined structure.Due to the exist of mannose in DCFM,it could accurately recognize mannose receptor in TAMs.Our cellular experiment results showed that mannose modification could notably promote the uptake of DCFM by the immunosuppressive M2-type macrophages that effectively reprogrammed M2-type macrophages into anti-tumor M1-type macrophages,leading to enhance the phagocytosis of tumor cells by macrophages and inhibiting tumor cells migration.Subsequently,we observed that DCFM could significantly distribute into tumor tissues by in vivo fluorescence imaging.Importantly,DCFM exhibited a superior anti-tumor efficiency in the subcutaneous colorectal tumor model.In addition,it showed that DCFM precisely polarized TAMs into M1-type macrophages and actively increased the infiltration of cytotoxic T lymphocytes(CTLs),inducing profound tumor growth inhibition.展开更多
High mannose oligosaccharides are characteristic and essential for immune evasion of many viruses and cancer cells.They are potential targets for viral inhibition and cancer diagnosis/therapy.Particularly,high mannose...High mannose oligosaccharides are characteristic and essential for immune evasion of many viruses and cancer cells.They are potential targets for viral inhibition and cancer diagnosis/therapy.Particularly,high mannose-binding reagents may be a unique asset for fighting the ongoing and mutating SARSCoV-2 virus.Lectins are prevailing reagents for saccharide binding but suffer from inadequate specificity and apparent immunogenicity.Meanwhile,other reagents for the same purpose,such as antibodies and aptamers,have rarely been reported.Herein,using molecularly imprinted magnetic nanoparticles as a potent platform,we report a smart selection method for fine screening of high mannose-specific aptamers.Monovalent aptamers were first effectively screened within eight rounds of selection.Multivalent aptamers,in the forms of dendritic polymer or tetrahedral DNA nanostructure(TDN),were further engineered.The aptamers exhibited high affinity toward the spike protein of SARS-CoV-2 and the envelope protein GP120 of HIV.Both the monovalent aptamer and its TDN form exhibited a certain inhibition effect to the SARS-CoV-2 pseudovirus.On the other hand,both the monovalent aptamer and its dendritic form permitted the recognition of cancer cells over normal cells.Therefore,as unprecedented reagents for broad-spectrum viral inhibition and cancer targeting,these aptamers hold great promise for clinical treatment and diagnosis.展开更多
基金the High-level construction discipline of the National Administration of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.
基金supported by grants from the National Natural Science Foundation of China(No.82072813)Natural Science Foundation of Guangdong Province(No.2020A1515010473 and No.2018A030313668)China Postdoctoral Science Foundation(No.2020M682666).
文摘The limited treatment options for advanced prostate cancer(PCa)lead to the urgent need to discover new anticancer drugs.Mannose,an isomer of glucose,has been reported to have an anticancer effect on various tumors.However,the anticancer effect of mannose in PCa remains unclear.In this study,we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro,and mannose was observed to have an anticancer effect in mice without harming their health.Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential,increased mitochondrial and cellular reactive oxygen species(ROS)levels,and reduced adenosine triphosphate(ATP)production in PCa cells.Mannose treatment of PCa cells induced changes in mitochondrial morphology,caused dysregulated expression of the fission protein,such as fission,mitochondrial 1(FIS1),and enhanced the expression of proapoptotic factors,such as BCL2-associated X(Bax)and BCL2-antagonist/killer 1(Bak).Furthermore,lower expression of mannose phosphate isomerase(MPI),the key enzyme in mannose metabolism,indicated poorer prognosis in PCa patients,and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose.This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.
基金Supported by Sub-project of Special Fund in Ministry of Agriculture of Transgenic Plants " Cultivation of New Varieties of Anti-adversity Transgenic Soybeans"(2008ZX08004-2)~~
文摘[ Objective] The aim was to construct drought and saline-alkaline resistance plant expression vector with mannose as selective agent, and further breed unmarked resilient varieties. [ Method] The plant expression vector was constructed by using Chimonanthus praecox（ L. ）Link aquapor.in CpTIP cDNA and Escherichia coli pmi gene, combined stress resistance gene with mannose positive selection system. [ Result] The test successfully constructed the plant expression vector pPMI：：CpTIP. [ Conclusion] The constructed vector linked advantages of stress resistance gene and mannose positive selection system.
基金Supported by the Class A Project of the Key Research and Development Programs of the Science and Technology Department of Anhui Province,No.1804h08020236the Key Project of the Natural Science Foundation of Anhui Province,No.KJ2018A0206
文摘BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a syndrome with a high short-term mortality rate,and it is crucial to identify those patients at a high mortality risk clinically.AIM To investigate the clinical value of soluble mannose receptor(sMR)in predicting the 90-day mortality of HBV-ACLF patients.METHODS A total of 43 patients were diagnosed with HBV-ACLF between October 2017 and October 2018 at the Second Hospital of Anhui Medical University,and all of them were enrolled in this retrospective study.Their serum sMR levels were determined using an enzyme-linked immunosorbent assay.Demographic and clinical data,including gender,age,albumin level,total bilirubin(TBIL)level,international normalized ratio,HBV-DNA level,HBV serological markers,procalcitonin level,interleukin-6 level,and model for end-stage liver disease(MELD)score were accessed at the time of diagnosis of HBV-ACLF.A multivariate logistic regression analysis was used to analyze the independent risk factors for mortality.RESULTS Serum sMR level was significantly increased in HBV-ACLF patients compared with chronic hepatitis B patients and healthy controls(P<0.01).When compared with surviving patients,it was higher in those patients who succumbed to HBVACLF(P<0.05).Serum sMR level was positively correlated with MELD score(rs=0.533,P=0.001),HBV-DNA level(rs=0.497,P=0.022),and TBIL level(rs=0.894,P<0.001).Serum sMR level(odds ratio=1.007,95%confidence interval:1.004–1.012,P=0.001)was an independent risk factor for the 90-day mortality in the HBV-ACLF cases.The patients with HBV-ACLF were stratified into two groups in accordance with their serum sMR levels at the baseline(low risk:<99.84 pg/mL and high risk:≥99.84 pg/mL).The 90-day mortality rates were 27.3%in the low-risk group and 87.5%in the high-risk group.Furthermore,sMR level apparently improved the performance of MELD score for predicting the prognosis of patients with HBV-ACLF.CONCLUSION Serum sMR level may be a predictor of the prognosis of HBV-ACLF patients.
基金the Macao Science and Technology Development Fund(No.0086/2021/A2)Shenzhen Fundamental Research Program(No.SGDX20210823103804030)+1 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012416).
文摘Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.
基金the grants from National Natural Science Foundation of Guangdong Province(Nos.2017A030310666 and 2018A030307003)Guangdong Medical University Nanhai Marine Biomedical Resources R&D Public Service Platform Open Fund Project(Nos.2HC18013 and 2HC18016)+4 种基金"Group-type"Special Support Project for Education Talents in Universities(No.4SG19045G)Foundation of Young Innovative Talents in Guangdong Province Colleges(No.2018KQNCX091)Undergraduate Science&Technology Innovation Foundation of Guangdong Province(Nos.201810571046 and 201810571073)Medical Science and Technology Development Foundation of Guangdong Province(No.A2016355)The Opening Project of State Key Laboratory of Polymer Materials Engineering of Sichuan University(No.sklpme2018-4-23)。
文摘Rapid detection and identification of Escherichia coli(E.coli)is essential to prevent its quickly spread.In this study,a novel fluorescence probe based on ZnTe quantum dots(QDs)modified by mannose(MAN)had been prepared for the determination of E.coli.The results showed that the obtained QDs showed excellent selectivity toward E.coli,and presented a good linearity in range of 1.0×10~5~1.0×10~8 CFU/mL.The optimum fluorescence intensity for detecting E.coli was found to be at pH 7.0 with a temperature of25℃and incubation time of 20 min.Under these optimum conditions,the detection limit of E.coli was4.6×10~4 CFU/mL.The quenching was discussed to be a static quenching procedure,which was proved by the quenching efficiency of QDs decreased with the temperature increasing.
文摘To investigate the chemical structure of cell wall mannan obtained from pathogenic yeast, Candida tropicalis NBRC 1400 (former antigenic standard strain, IFO 1400). As a result of two-dimensional NMR analysis, it was shown that the mannan of this strain is composed of α-1,6-, α-1,3-, α-1,2- and β-1,2-linked mannose residues. In this research, the mannan was subjected to three degradation procedures, acid-treatment, α-mannosidase, and acetolysis under two conditions in order to determine the chemical structure of the antigenic oligomannosyl side chains in this molecule. The 1H-nuclear magnetic resonance spectra of resultant oligosaccharides, pentaose and hexaose, demonstrated the existence of the oligomannosyl side chains corresponding to Manα1-3Manα1-2Manα1-2Manα1-2Man and Manα1-3Manα1-2Manα1-2Manα1-2Manα1-2Man, respectively, which have previously also been found in Candida albicans serotype A strain mannans. These findings indicate that C. tropicalis and C. albicans serotype A have no significant difference in the chemical structure of these cell wall mannans. Therefore, it can be interpreted that it is extremely difficult to distinguish both species by targeting the antigenic group in these mannans.
基金Supported by Natural Science Foundation of China(81360685)
文摘[Objectives] Taking mice with acute liver injury induced by CCl_4 as the model,the effect of arabinose + mannose( w/w = 1∶ 1) on mice with acute liver injury induced by CCl_4 was studied. [Methods]60 experimental mice were selected and then randomly divided into normal control,model group and positive group( bifendate 120 mg/kg),high-dose arabinose + mannose group( 800 mg/kg),middle-dose arabinose + mannose group( 400 mg/kg) and low-dose arabinose + mannose group( 200 mg/kg),each group had 10 mice,which were fed adaptively for 1 week. Except normal control group and model group,each treatment group was given medicine by gavage once a day and lasted for7 days according to the dosage of 20 ml/kg. After the last drug,except normal control group,the mice of other groups were injected 10 ml/kg0. 12% CC14 peanut oil through enterocoelia,thereby establishing acute liver injury model. The mice were fasted but not water for 24 h,after that,blood was sampled from mice eyes,then dissected rapidly. The activities of ALT and AST in the serum were determined,the expression levels of TNF-α,IL-1β and IL-6 from the hepatic tissues were detected by enzyme-linked immunosorbent assay( ELISA); then after HE dye,the changes of liver histopathology were observed. [Results]Compared with CCl_4 model,the activities of ALT and AST from the serum of mice from high-dose and middle dose groups decreased significantly( P < 0. 01); the contents of TNF-α,IL-1β and IL-6 from the hepatic tissues of mice decreased significantly( P < 0. 01); the pathological section showed that the liver injury of mice from the combined drug groups showed alleviating trend to varying degrees,in which the liver injury of mice from the high-dose group was the best. [Conclusions] Arabinose + mannose has an obvious protective effect on mice with acute liver injury induced by CCl_4,and its mechanism may relate to anti-inflammatory.
基金supported by National Institutes of Health training grant T32 HD007186-32 (W Hay, PI and PD)supported by NIH Grants R01DK088139 and K08HD060688+5 种基金American Diabetes Association Junior Faculty Award 7-08-JF-51(PJR, PI)provided by the UC Denver DERC (P30DK57516 J. Hutton, PI)supported as a Scholar by NIH Building Interdisciplinary Careers in Women ’ s Health Scholar Award K12HD057022 (J. Regensteiner, PI)a Children ’ s Hospital Colorado Research Institute Research Scholar Award (PI)supported by NIH K01DK090199 (PI) and as a trainee on NIH training grant T32 HD007186-32 (W Hay, PI and PD)
文摘Background： The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short （2-wk） and long （8-wk） durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions （1-wk hyperinsulinemic-isoglycemic clamp） to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. Results： A maternal insulin infusion resulted in lower maternal （50%, P 〈 0.01） and fetal （35-45%, P 〈 0.01） mannose concentrations, which were highly correlated （r^2 = 0.69, P 〈 0.01）. A fetal insulin infusion resulted in a 50% reduction of fetal mannose （P 〈 0.05）. Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose （P 〈 0.01）. Conclusions： Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted.
文摘A highly efficient method to get 3-and 6-modified mannose/ahrose derivatives for oligosaccharide synthesis is described. All the compounds were obtained exclusively with the combinations of 3-and/or 6-hydroxyl protection and/or activation（ including the configuration conversion of 3-carbon atom）.
基金supported by Natural Science Foundation Project of Jilin Provincial Department of Science and Technology(YDZJ202301ZYTS348)。
文摘Mannose,a different isomer of the hydroxyl group at the C-2 position of glucose,shares the same transport carrier protein with glucose to enter cells and participate in the regulation of glucose metabolism.It affects cell growth,differentiation,and function and plays an active role in tumor immunity and inflammatory processes.This paper provides theoretical support for expanding the clinical applications of mannose by exploring its constitution,metabolic pathways,and role in regulating immune cell function and treating immunology-related diseases.
基金supported by National Key Research and Development Program of China(2018YFA0902000)National Natural Science Foundation of China(21778035)Shandong Provincial Key Research and Development Program(2019GSF107032).
文摘ᴅ-Mannose is a functional monosaccharide that is difficult to prepare on a large scale via chemical or enzymatic synthetic routes due to low conversion rates and complex downstream isolation.In this study,a two-step enzymatic route was established to achieve highly efficient conversion ofᴅ-fructose toᴅ-mannose without the need for a tedious isomer separation process.Firstly,a mannose isomerase from Xanthomonas phaseoli was coupled with a sugar 1-kinase from Bifidobacterium infantis and a polyphosphate kinase to synthesize mannose 1-phosphate(Man-1-P)fromᴅ-fructose and polyphosphate(PolyP),using adenosine 5′-triphosphate or adenosine 5′-monophosphate(AMP)as the regenerating co-factor.The reaction was optimized to achieve 99%conversion ofᴅ-fructose at substrate concentrations of 300 mmol/L forᴅ-fructose,with only 0.5 mmol/L AMP(1/600 equiv.)as the co-factor.The solution from the first-step reaction,containing Man-1-P,was simply clarified by centrifugation and then precipitated with calcium salt.Subsequently,Man-1-P was hydrolyzed by a phosphatase to yieldᴅ-mannose,which was purified by desalting with activated carbon adsorption.As a demonstration of this strategy,11.1 g ofᴅ-mannose was produced with an overall yield of 85.6%.This synthesis strategy is expected to be applicable for large-scale preparation.
基金funded by the Postdoctoral Fellowship Program of CPSF(GZC20230988)China Postdoctoral Science Foundation(Certificate Number:2024M751158).
文摘The biosynthesis of Ganoderma lucidum polysaccharides(GLPs)begins with the nucleotide sugar precursor synthesis.Guanosine diphosphate(GDP)-mannose pyrophosphorylase(GMP)specifically catalyzes the conversion of mannose-1-phosphate to GDP-mannose.However,the specific role of GMP in GLP synthesis remains unclear.Therefore,we investigated the function of the glgmp gene in mycelial growth,polysaccharide production,and the transcriptional regulation of key genes involved in GLP biosynthesis through genetic manipulation.A 2131 bp gene encoding a 50.93 kDa protein was cloned,and the overexpression and silencing transformed strains were constructed.The expression level of the glgmp gene influenced mycelial growth and pellet size.Overexpression of the glgmp gene boosted the production of high-mannose polysaccharides.The monosaccharide composition of polysaccharides changed significantly,with the proportion of mannose reaching a maximum of 13.28% and 11.64%.This was accompanied by a decrease in glucose percentage and an increase in galactose and fucose percentages.At the transcriptional level,overexpressing the glgmp gene upregulated the expression of phosphomannose isomerase and phosphomannomutase genes,which play critical roles in GDP-mannose synthesis.This promoted GDP-mannose supply and subsequently increased the mannose percentage.Upregulation of glgmp also increased the gene expression involved in the synthesis of GDP-fucose and uridine diphosphate(UDP)-galactose,resulting in increased ratios of fucose and galactose.In contrast,the glgmp silencing strains exhibited opposite effects,confirming these findings.This study provides a valuable reference for the efficient production of GLPs,inspiring a comprehensive exploration of the polysaccharide biosynthesis pathway.
基金supported by the Shuangcheng cooperative agreement research grant of Yibin,China(XNDX2022020012)National Natural Science Foundation of China(no.32172158)+1 种基金Chongqing Municipal College Student Innovation and Entrepreneurship Training Program(S202210635020)Postgraduate mentor team-building program of Southwest University(XYDS201905).
文摘Mannans,the predominant component in spent coffee grounds,can be transformed into mannose and man-nooligosaccharides.These derivatives serve as valuable prebiotics and bioactive components in the functional food and pharmaceutical industries.In this study,two eco-friendly pretreatment techniques were utilized to process spent coffee grounds,enhancing the release of valuable sugars and improvingβ-mannanase accessibility,thereby increasing the yields of mannose and mannooligosaccharides.Following a combined treatment with laccase and cellulase,most soluble sugars were efficiently produced via microwave hydrothermal treatment at 210℃for 30 min.From 1 g of defatted spent coffee grounds,74.2 mg of mannose and 121.1 mg of man-nooligosaccharides were obtained,representing 83%of the total mannose content.This method has proven to be an efficient way to utilize spent coffee grounds,with significant implications for their high-value conversion and utilization.
基金supported by the National Key Research and Development Program of China(NO.2022YFF1100203).
文摘Ulcerative colitis(UC)is a public health concern.The quest for drugs characterized by minimal side effects and optimal safety profiles for managing UC has emerged as a primary research topic.Recent evidence suggests the efficacy of Lactobacillus-derived exopolysaccharides containing mannose(MnEPSs)in alleviating UC.Lactoba-cillus could not synthesize MnEPSs in the glucose-only MRS medium,but with mannose added to the carbon source,MnEPSs were produced directionally,of which mannose accounts for 5.9-7.8%of the total sugar content.Subsequently,MnEPS-6M3,MnEPS-Q5M22,MnEPS-D4L1,and MnEPS-CCFM 1393 were used to investigate the mechanism of UC relief.The results showed that compared with non-MnEPSs,MnEPSs had the better effect on reliving UC.Phenotypically,four MnEPSs alleviated weight loss,DAI score,crypt disappearance,inflammatory cell infiltration,and mucosal edema of UC in mice.Mechanistically,MnEPSs increased the expression of ZO-1 by 52.38-115.87%to repair intestinal barrier,inhibited inflammatory factors(TNF-α,IL-1β,IL-6,IFN-γand IL-17)and increasd anti-inflammatory cytokines(IL-10)by reducing colonic F4/80^(+)macrophages(decreased 4.34-7.01%)and colonic iNOS^(+)M1 macrophages(decreased 7.3-10.52%),and promoted the production of acetic acid(increased 153.21-226.93%),propionic acid(increased 360.71-528.57%),and butyric acid(increased 127.45-156.86%)in cecal contents.Interestingly,MnEPS-Q5M22 and MnEPS-CCFM 1393 increased the abundance of butyric acid-producing Dunaliella.In summary,this study provides a theoretical basis for the directional synthesis of functional MnEPSs.
基金supported by the Natural Science Foundation of Sichuan(No.2024NSFJQ0005)in part by the Scientific and Technological Innovation Team for Qinghai-Tibetan Plateau Research in Southwest Minzu University(No.2024CXTD15).
文摘The clinical application of Chuanminshen violaceum polysaccharides(CVP),a natural immunomodulator with intrinsic antioxidant activity,is constrained by rapid systemic clearance,limited tissue specificity,and short-lived bioactivity.To address these limitations,a multifunctional biomimetic nanoplatform incorporating erythrocyte membrane camouflage,mannose-mediated active targeting,and squalene-stabilized Pickering emulsion technology was developed.CVP-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(CVPP)were fabricated via solvent evaporation,coated with erythrocyte membranes,and subsequently functionalized with mannose to obtain CVPP@M-M.This dual modification enabled selective recognition by macrophage and dendritic cell(DC)mannose receptors,while the erythrocyte membrane imparted prolonged systemic circulation.Subsequent emulsification for the first time with squalene yielded CVPP@M-M-PPAS,a Pickering emulsion designed for enhanced lymph node delivery.In vitro,CVPP@M-M-PPAS significantly promoted macrophage activation,as evidenced by elevated CD80+/CD86+expression,compared with free CVP.In vivo,intramuscular co-administration with ovalbumin(OVA)antigen induced pronounced DC maturation and T cell polarization in the spleen.This formulation also elicited robust and sustained production of antigen-specific IgG,accompanied by increased upregulation of pro-inflammatory cytokines interleukin-6(IL-6)and interferon-γ(IFN-γ).In vivo imaging demonstrated prolonged lymph node retention(>336 h)with a near-linear fluorescence decay profile,confirming controlled release kinetics.By integrating stealth properties,receptor-specific targeting,and emulsion-enabled lymphatic trafficking,this nanoplatform effectively circumvents the pharmacokinetic and biodistributional barriers of plant-derived polysaccharides,enabling durable humoral and cellular immune responses.This strategy offers a generalizable framework for translating natural immunomodulators into clinically viable nanotherapeutics.
基金supported by the National Natural Science Foundation of China(82271862 and 81873418 to YK,82171730 to PX,81970484 to QC)the Zhejiang Provincial Ten Thousand Program for Leading Talents of Science and Technology Innovation(2021R52015 to YK)the Natural Science Foundation of Zhejiang Province(LY20H160032 to PX,LQ21H090064 to TP).
文摘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-αproduction translationally by reducing the glyceraldehyde 3-phosphate level,thus promoting GAPDH binding to TNF-αmRNA.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.
文摘Previous studies have documented that selective delivery of protein antigens to cells expressing mannose receptor （MR） can lead to enhanced immune responses. We postulated that agents that influenced the MR expression level, and the activation and migration status of MR-expressing antigen presenting cells, would modulate immune responses to MR-targeted vaccines. To address this question, we investigated the effect of clinically used adjuvants in human MR transgenic （hMR-Tg） mice immunized with an MR-targeting cancer vaccine composed of the human anti-MR monoclonal antibody B 11 fused with the oncofetal protein, human chorionic gonadotropin beta chain （hCGβ）, and referred to as B 11-hCGβ. We found that humoral responses to low doses of B11-hCGβ could be enhanced by prior administration of GM-CSF, which upregulated MR expression in vivo. However, co-administration of the Toll-like receptor （TLR） agonists, poly-ICLC and/or CpG with B11-hCGβ was required to elicit Thl immunity, as measured by antigen-specific T-cell production of IFN-γ. The TLR agonists were shown to increase the number of vaccine-containing cells in the draining lymph nodes of immunized hMR-Tg mice. In particular, with B11-hCGβand poly-ICLC, a dramatic increase in vaccine-positive cells was observed in the T-ceU areas of the lymph nodes, compared to the vaccine alone or combined with GM-CSF. Importantly, the absence of the TLR agonists during the priming immunization led to antigen-specific tolerance. Therefore, this study provides insight into the mechanisms by which adjuvants can augment immune responses to B11-hCGβ and have implications for the rationale design of clinical studies combining MR-targeted vaccination with TLR agonists.
基金supported by the National Natural Science Foundation of China(No.92061123).M.M.Z.particularly thanks the Youth Innovation Promotion Association of CAS(No.2022036).
文摘Polarization of tumor associated macrophages(TAMs)has been a promising therapeutic paradigm for tumor.However,how to achieve precise regulation of TAMs and high efficiency of tumor immunotherapy is still a huge challenge.Here,we report dicarboxy fullerene modified with mannose(DCFM)as an immunomodulator to selectively polarize TAMs and prominently boost anti-tumor immunity.The dicarboxy fullerene molecule was synthesized through the Prato reaction and further covalently bonded with mannose,obtaining the DCFM with well-defined structure.Due to the exist of mannose in DCFM,it could accurately recognize mannose receptor in TAMs.Our cellular experiment results showed that mannose modification could notably promote the uptake of DCFM by the immunosuppressive M2-type macrophages that effectively reprogrammed M2-type macrophages into anti-tumor M1-type macrophages,leading to enhance the phagocytosis of tumor cells by macrophages and inhibiting tumor cells migration.Subsequently,we observed that DCFM could significantly distribute into tumor tissues by in vivo fluorescence imaging.Importantly,DCFM exhibited a superior anti-tumor efficiency in the subcutaneous colorectal tumor model.In addition,it showed that DCFM precisely polarized TAMs into M1-type macrophages and actively increased the infiltration of cytotoxic T lymphocytes(CTLs),inducing profound tumor growth inhibition.
基金supported by the National Key Research and Development Program of China(grant no.2018YFC0910301)from the Ministry of Science and Technology of China,the Key Grant(grant no.21834003)from the National Natural Science Foundation of China,and the Excellent Research Program of Nanjing University(grant no.ZYJH004)to Z.L.
文摘High mannose oligosaccharides are characteristic and essential for immune evasion of many viruses and cancer cells.They are potential targets for viral inhibition and cancer diagnosis/therapy.Particularly,high mannose-binding reagents may be a unique asset for fighting the ongoing and mutating SARSCoV-2 virus.Lectins are prevailing reagents for saccharide binding but suffer from inadequate specificity and apparent immunogenicity.Meanwhile,other reagents for the same purpose,such as antibodies and aptamers,have rarely been reported.Herein,using molecularly imprinted magnetic nanoparticles as a potent platform,we report a smart selection method for fine screening of high mannose-specific aptamers.Monovalent aptamers were first effectively screened within eight rounds of selection.Multivalent aptamers,in the forms of dendritic polymer or tetrahedral DNA nanostructure(TDN),were further engineered.The aptamers exhibited high affinity toward the spike protein of SARS-CoV-2 and the envelope protein GP120 of HIV.Both the monovalent aptamer and its TDN form exhibited a certain inhibition effect to the SARS-CoV-2 pseudovirus.On the other hand,both the monovalent aptamer and its dendritic form permitted the recognition of cancer cells over normal cells.Therefore,as unprecedented reagents for broad-spectrum viral inhibition and cancer targeting,these aptamers hold great promise for clinical treatment and diagnosis.
