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1.
Nutrients ; 16(14)2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39064683

ABSTRACT

ß-glucans found in cereal grains have been previously demonstrated to improve blood glucose control; however, current understanding points to their high viscosity as the primary mechanism of action. In this work, we present a novel, highly soluble, low-viscosity ß-glucan fiber (HS-BG fiber) and a preclinical dataset that demonstrates its impact on two mechanisms related to the prevention of hyperglycemia. Our results show that HS-BG inhibits the activity of two key proteins involved in glucose metabolism, the α-glucosidase enzyme and the SGLT1 transporter, thereby having the potential to slow starch digestion and subsequent glucose uptake. Furthermore, we demonstrate in a multi-donor fecal fermentation model that HS-BG is metabolized by several different members of the gut microbiome, producing high amounts of short-chain fatty acids (SCFAs), known agonists of GPR43 receptors in the gut related to GLP-1 secretion. The production of SCFAs was verified in the translational gut model, SHIME®. Moreover, HS-BG fiber fermentation produces compounds that restored permeability in disrupted epithelial cells, decreased inflammatory chemokines (CXCL10, MCP-1, and IL-8), and increased anti-inflammatory marker (IL-10), which could improve insulin resistance. Together, these data suggest that the novel HS-BG fiber is a promising new functional ingredient that can be used to modulate postprandial glycemic responses while the high solubility and low viscosity enable easy formulation in both beverage and solid food matrices.


Subject(s)
Blood Glucose , Dietary Fiber , Fatty Acids, Volatile , Gastrointestinal Microbiome , Permeability , Sodium-Glucose Transporter 1 , beta-Glucans , Dietary Fiber/pharmacology , beta-Glucans/pharmacology , Blood Glucose/metabolism , Humans , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/physiology , Fatty Acids, Volatile/metabolism , Sodium-Glucose Transporter 1/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Fermentation , Solubility , Feces/chemistry , Feces/microbiology , Viscosity , Glycoside Hydrolase Inhibitors/pharmacology , Hyperglycemia/prevention & control , Intestinal Barrier Function
2.
Life Sci ; 352: 122894, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38971365

ABSTRACT

This study assessed the therapeutic potential of swimming exercise in the curdlan-injected SKG mouse model and investigated the modulatory effects of irisin on inflammation. Curdlan-injected SKG were randomly assigned to either a home-cage group or a swimming group for 6 weeks. Changes in clinical arthritis scores and ankle thickness were measured weekly. Post-swimming program, mice were anesthetized for collection of vastus lateralis muscle and blood, which was followed by histological analysis, micro-CT imaging of the ankle joints, and the measurement of pro-inflammatory cytokines and irisin levels. Additionally, curdlan-injected SKG mice were intravenously injected with recombinant irisin protein and observed. Finally, serum levels of irisin in healthy control and ankylosing spondylitis (AS) patient groups were measured by ELISA. The swimming group of curdlan-injected SKG mice exhibited significant improvements in arthritis and enthesitis compared to the home-cage group. In particular, micro-CT and histological analyses revealed a notable reduction in pathological bone features in the swimming group compared to the home-cage group. Muscle endurance was also enhanced in the swimming group compared to the home-cage group, as determined by the wire-hanging test. Intriguingly, irisin levels not only were statistically increased in the swimming group but, also, TNF-α, IL-1ß, and IL-6 levels were decreased. Additionally, injection of irisin protein slightly attenuated both arthritis and enthesitis in curdlan-injected SKG mice. Meanwhile, irisin serum levels were declined in AS patients. Overall, we found that swimming exercise attenuated pathological bone features in an AS animal model, potentially mediated by increased irisin serum levels with associated anti-inflammatory effects.


Subject(s)
Fibronectins , Physical Conditioning, Animal , Swimming , beta-Glucans , Animals , Fibronectins/metabolism , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , Swimming/physiology , Mice , Male , Humans , Female , Disease Models, Animal
3.
Carbohydr Polym ; 342: 122401, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39048236

ABSTRACT

The regeneration of absorbed alveolar bone and reconstruction of periodontal support tissue are huge challenges in the clinical treatment of periodontitis due to the limited regenerative capacity of alveolar bone. It is essential to regulate inflammatory reaction and periodontal cell differentiation. Based on the anti-inflammatory effect of baker's yeast ß-glucan (BYG) with biosafety by targeting macrophages, the BYG-based nanoparticles loading methotrexate (cBPM) were fabricated from polyethylene glycol-grafted BYG through chemical crosslinking for treatment of periodontitis. In our findings, cBPM promoted osteogenesis of human dental pulp stem cells (hDPSCs) under inflammatory microenvironment, characterized by the enhanced expression of osteogenesis-related Runx2 and activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/Erk) pathway in vitro. Animal experiments further demonstrate that cBPM effectively promoted periodontal bone regeneration and achieved in a better effect of recovery indicated by 19.2 % increase in tissue volume, 7.1 % decrease in trabecular separation, and a significant increase in percent bone volume and trabecular thickness, compared with the model group. Additionally, cBPM inhibited inflammation and repaired alveolar bone by transforming macrophage phenotype from inflammatory M1 to anti-inflammatory M2. This work provides an alternative strategy for the clinical treatment of periodontitis through BYG-based delivery nanoplatform of anti-inflammatory drugs.


Subject(s)
Bone Regeneration , Dental Pulp , Methotrexate , Nanoparticles , Osteogenesis , beta-Glucans , Humans , Osteogenesis/drug effects , Nanoparticles/chemistry , Bone Regeneration/drug effects , beta-Glucans/pharmacology , beta-Glucans/chemistry , Dental Pulp/drug effects , Dental Pulp/cytology , Animals , Methotrexate/pharmacology , Methotrexate/chemistry , Stem Cells/drug effects , Periodontitis/drug therapy , Periodontitis/pathology , Male , Mice , Inflammation/drug therapy , Drug Carriers/chemistry , Cells, Cultured , Cell Differentiation/drug effects
6.
Sci Rep ; 14(1): 16047, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992105

ABSTRACT

ß-glucans are polysaccharides found in the cell walls of various fungi, bacteria and cereals. ß-glucan have been found to show various kinds of anti-inflammatory, antimicrobial, antidiabetic antioxidant and anticancerous activities. In the present study, we have isolated ß-glucan from the baker's yeast Saccharomyces cerevisiae and white button mushroom Agaricus bisporus and tested their antioxidant potential and anticancerous activity against prostate cancer cell line PC3. Particles were characterized with zeta sizer and further with FTIR that confirmed that the isolated particles are ß-glucan and alginate sealing made slow and sustained release of the Quercetin from the ß-glucan particles. Morphological analysis of the hollow and Quercetin loaded ß-glucan was performed with the SEM analysis and stability was analyzed with TGA and DSC analysis that showed the higher stability of the alginate sealed particles. Assessments of the antioxidant potential showed that Quercetin loaded particles were having higher antioxidant activity than hollow ß-glucan particles. Cell viability of the PC3 cells was examined with MTT assay and it was found that Quercetin loaded alginate sealed Agaricus bisporus derived ß-glucan particles were having lowest IC50. Further ROS generation was found to increase in a dose dependent manner. Apoptosis detection was carried out with Propidium iodide and AO/EtBr staining dye which showed significant death in the cells treated with higher concentration of the particles. Study showed that particles derived from both of the sources were having efficient anticancer activity and showing a dose dependent increase in cell death in PC3 cells upon treatment.


Subject(s)
Agaricus , Antineoplastic Agents , Antioxidants , Quercetin , Saccharomyces cerevisiae , beta-Glucans , Quercetin/pharmacology , Quercetin/chemistry , beta-Glucans/pharmacology , beta-Glucans/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Agaricus/chemistry , Saccharomyces cerevisiae/drug effects , Cell Survival/drug effects , PC-3 Cells , Cell Line, Tumor , Reactive Oxygen Species/metabolism
7.
Fish Shellfish Immunol ; 151: 109740, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960104

ABSTRACT

ß-glucans are carbohydrates present in the cell wall of many fungi, which are often used as immunostimulants in feeds for farmed species. Their capacity to activate innate immune responses directly acting on innate cell populations has been widely documented in fish. However, whether they can affect the functionality of adaptive immune cells has been scarcely explored. In this context, in the current work, we have determined the effects of ß-glucans on rainbow trout blood IgM+ B cells in the presence or absence of 2,4,6-trinitrophenyl hapten conjugated to lipopolysaccharide (TNP-LPS), a model antigen. For this, rainbow trout peripheral blood leukocytes were incubated with different doses of ß-glucans or media alone in the presence or absence of TNP-LPS for 48 h. The size, levels of expression of surface MHC II, antigen processing and phagocytic capacities and proliferation of IgM+ B cells were then studied by flow cytometry. The number of IgM-secreting cells in the cultures was also estimated by ELISpot. ß-glucans significantly decreased the levels of surface MHC II expression and the antigen processing capacities of these cells, especially in the presence of TNP-LPS, while they increased their phagocytic activity. On their own, ß-glucans slightly activated the proliferation of IgM+ B cells but reduced that induced by TNP-LPS. In contrast, ß-glucans significantly increased the number of cells secreting IgM in the cultures. This effect of ß-glucans on the IgM-secreting capacity of B cells was also confirmed through a feeding experiment, in which the IgM-secreting capacity of blood leukocytes obtained from fish fed a ß-glucan-supplemented diet for one month was compared to that of leukocytes obtained from fish fed a control diet. Altogether, these findings contribute to increase our knowledge regarding the effects of ß-glucans on fish adaptive responses.


Subject(s)
B-Lymphocytes , Immunoglobulin M , Oncorhynchus mykiss , beta-Glucans , Animals , Oncorhynchus mykiss/immunology , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , Immunoglobulin M/immunology , B-Lymphocytes/immunology , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/administration & dosage , Lipopolysaccharides/pharmacology , Immunity, Innate/drug effects , Dietary Supplements/analysis
8.
Molecules ; 29(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38930852

ABSTRACT

Nutraceutical immune support offers potential for designing blends with complementary mechanisms of action for robust support of innate immune alertness. We documented enhanced immune activation when bovine colostrum peptides (BC-Pep) were added to an immune blend (IB) containing ß-glucans from yeast, shiitake, maitake, and botanical non-ß-glucan polysaccharides. Human peripheral blood mononuclear cells (PBMCs) were cultured with IB, BC-Pep, and IB + BC-Pep for 20 h, whereafter expression of the activation marker CD69 was evaluated on NK cells, NKT cells, and T cells. Cytokine levels were tested in culture supernatants. PBMCs were co-cultured with K562 target cells to evaluate T cell-mediated cytotoxicity. IB + BC-Pep triggered highly significant increases in IL-1ß, IL-6, and TNF-α, above that of cultures treated with matching doses of either IB or BC-Pep. NK cell and T cell activation was increased by IB + BC-Pep, reaching levels of CD69 expression several fold higher than either BC-Pep or IB alone. IB + BC-Pep significantly increased T cell-mediated cytotoxic killing of K562 target cells. This synergistic effect suggests unique amplification of signal transduction of NK cells and T cells due to modulation of IB-induced signaling pathways by BC-Pep and is of interest for further pre-clinical and clinical testing of immune defense activity against virally infected and transformed cells.


Subject(s)
Colostrum , Immunity, Innate , Peptides , beta-Glucans , Animals , Cattle , Humans , Colostrum/chemistry , Colostrum/immunology , Immunity, Innate/drug effects , beta-Glucans/pharmacology , beta-Glucans/chemistry , Peptides/pharmacology , Peptides/chemistry , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Cytokines/metabolism , Lymphocyte Activation/drug effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Agaricales/chemistry , Antigens, Differentiation, T-Lymphocyte/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , K562 Cells , Antigens, CD/metabolism , Lectins, C-Type
9.
Int J Biol Macromol ; 272(Pt 1): 132736, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830494

ABSTRACT

Fatal massive hemorrhage and diabetic wound healing are world widely challenging in surgical managements, and uncontrolled bleeding, chronic inflammation and damaged remodeling heavily hinder the whole healing processes. Considering hemostasis, inflammation and wound microenvironment cooperatively affect the healing progression, we design all-in-one beta-glucan (BG) hybrid hydrogels reinforced with laponite nanoclay that demonstrate tunable tissue adhesion, resistant vascular burst pressure and cooperative wound microenvironment regulation for arterial hemostasis and diabetic wound prohealing. Those hydrogels had honeycomb-like porous microstructure with average pore size of 7-19 µm, tissue adhesion strength of 18-46 kPa, and vascular burst pressure of 58-174 mmHg to achieve superior hemostasis in rat liver and femoral artery models. They could effectively scavenge reactive oxygen species, transform macrophages from proinflammatory M1 into prohealing M2, and shorten the inflammation duration via synergistic actions of BG and nitric oxide (NO). Single treatment of NO-releasing BG hybrid hydrogels attained complete closure of diabetic wounds within 14 days, orchestrated to accelerate the epithelization and dermis growth, and restored normal vascularization, achieving high performance healing with optimal collagen deposition and hair follicle regeneration. Consequently, this work opens up a new avenue to design all-in-one polysaccharide hydrogels for applications in massive bleeding hemostats and diabetic wound dressings.


Subject(s)
Hemorrhage , Hydrogels , Wound Healing , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Wound Healing/drug effects , Rats , Hemorrhage/drug therapy , Diabetes Mellitus, Experimental/complications , Male , Nitric Oxide/metabolism , beta-Glucans/chemistry , beta-Glucans/pharmacology , Mice , Rats, Sprague-Dawley , Polysaccharides/pharmacology , Polysaccharides/chemistry
10.
Animal ; 18(6): 101185, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843664

ABSTRACT

Although anticoccidials effectively control coccidiosis, a needed reduction in the reliance on antimicrobials in animal production leads to the exploration of alternative compounds. The present study aimed to test five different dietary treatments to counteract the negative impact of coccidiosis on broiler chickens' health and performance. 1-day-old male Ross 308 broilers (n = 960) were randomly assigned to one of eight treatments, with six cages per treatment (20 birds/cage). To the diet of the broiler chickens of treatments (Trt) 1-5, a synbiotic was added from d0-10. From d10-28, birds of Trt1 and Trt2 were fed synbiotics, whereas birds of Trt3 were fed diets with glutamine, and birds of Trt4 and Trt5 were fed diets with a combination of ß-glucans and betaine. From d28-35 onwards, birds of Trt1 were fed a diet with a synbiotic, whereas birds of Trt2-4 received diets with glutamine, and birds of Trt5 were fed a non-supplemented diet. Birds of the positive control group (PC; Trt6) were fed a standard diet supplemented with an anticoccidial (Decoquinate). The challenged negative control (NCchall; Trt7) and non-challenged negative control (NC) Trt8 were fed a standard diet without anticoccidial or other dietary treatment. At 7 days (d) of age, all birds were inoculated with 1 023, 115, and 512 sporulated oocysts of E. acervulina, E. maxima, and E. tenella, respectively, except for Trt8. Body weight gain (BWG), feed intake, and feed conversion ratio were assessed for each feeding phase (d0-10, d10-28 and d28-35) and overall experimental period (d0-35). Oocyst shedding, Eimeria lesion scores, cecal length, and relative weight were assessed at d13, d22, d28 and d35. Additionally, oocyst shedding was determined at d9 and d17. Litter quality was evaluated at d27 and d34, and footpad lesions at d34. During the starter (d0-10) and finisher (d28-35) periods, performance did not differ between the treatments. During the grower period (d10-28), Trt6 (PC) and Trt8 (NC) chickens had the highest BWG of all treatments (P < 0.001). Dietary treatment had no effect on litter quality and severity of footpad lesions. In the PC group (Trt6), low oocyst excretion and lesion scores were found. When comparing Trt1-5 with NCchall (Trt7), none of the treatments significantly reduced oocyst output or lesion scores. In conclusion, in this experiment, none of the dietary treatments performed similar or better compared to the PC group (Trt6) regarding performance or reducing Eimeria oocyst shedding or lesion scores.


Subject(s)
Animal Feed , Chickens , Coccidiosis , Diet , Eimeria , Oocysts , Poultry Diseases , Animals , Coccidiosis/veterinary , Poultry Diseases/parasitology , Poultry Diseases/prevention & control , Poultry Diseases/drug therapy , Male , Animal Feed/analysis , Eimeria/physiology , Diet/veterinary , Dietary Supplements/analysis , Synbiotics/administration & dosage , Random Allocation , Betaine/administration & dosage , Betaine/pharmacology , Glutamine/pharmacology , Glutamine/administration & dosage , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , beta-Glucans/therapeutic use
11.
PLoS One ; 19(6): e0304112, 2024.
Article in English | MEDLINE | ID: mdl-38900829

ABSTRACT

The development and application of functional feed ingredients represents a great opportunity to advance fish growth and health, boost the immune system, and induce physiological benefits beyond those provided by traditional feeds. In the present study, we looked at the feasibility of in vitro methods for screening the qualities of functional feed ingredients using the fish cell line RTgill-W1, which has never been used in fish nutrition, and the culture of Paramoeba perurans. Five functional feed ingredients (arginine, ß-glucan, vitamin C, and two phytogenic feed additives) were selected to investigate their effects on cell viability and reactive oxygen species production. Three of the selected ingredients (arginine and two phytogenic feed additives) were additionally tested to assess their potential amoebicidal activity. As these functional ingredients are the core of a commercially available feed (Protec Gill, Skretting AS), their beneficial effects were further assessed in a field trial in fish affected by complex gill disease. Here, the analyzed parameters included the evaluation of macroscopic and histopathological gill conditions, pathogen detections, and analyses of plasma parameters. RTgill-W1 cell line assays were a good tool for screening functional ingredients and provided information about the optimal ingredient concentration ranges, which can be helpful for adjusting the concentrations in future feed diets. Through the culture of P. perurans, the tested ingredients showed a clear amoebicidal activity, suggesting that their inclusions in dietary supplements could be a viable way to prevent microbial infections. A three-week period of feeding Protec Gill slowed the disease progression, by reducing the pathogen load and significantly improving gill tissue conditions, as revealed by histological evaluation. The use of diets containing selected functional ingredients may be a feasible strategy for preventing or mitigating the increasingly common gill diseases, particularly in cases of complex gill disease, as documented in this study.


Subject(s)
Animal Feed , Fish Diseases , Gills , Salmo salar , Animals , Animal Feed/analysis , Fish Diseases/prevention & control , Gills/pathology , Gills/parasitology , Gills/drug effects , Cell Line , beta-Glucans/pharmacology , Arginine/pharmacology , Ascorbic Acid/pharmacology , Reactive Oxygen Species/metabolism , Dietary Supplements , Amebiasis/parasitology , Cell Survival/drug effects
12.
Cell Rep ; 43(6): 114324, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38850536

ABSTRACT

Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo ß-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named DrDectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.


Subject(s)
Hepatocytes , Pyroptosis , Sepsis , Zebrafish Proteins , Zebrafish , Animals , Hepatocytes/metabolism , Hepatocytes/immunology , Sepsis/immunology , Zebrafish Proteins/metabolism , Zebrafish Proteins/genetics , Lipopolysaccharides , Liver/pathology , Liver/metabolism , Liver/immunology , Mitophagy , Lectins, C-Type/metabolism , Immunity, Innate , Histones/metabolism , beta-Glucans/pharmacology , Trained Immunity
13.
Physiol Rep ; 12(12): e16115, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923221

ABSTRACT

Pro-inflammatory fungal ß-d-glucan (BDG) polysaccharides cause respiratory pathology. However, specific immunological effects of unique BDG structures on pulmonary inflammation are understudied. We characterized the effect of four unique fungal BDGs with unique branching patterns, solubility, and molecular weights in murine airways. Scleroglucan (1 → 3)(1 → 6)-highly branched BDG, laminarin (1 → 3)(1 → 6)-branched BDG, curdlan (1 → 3)-linear BDG, and pustulan (1 → 6)-linear BDG were assessed by nuclear magnetic resonance spectroscopy. Each BDG was tested by inhalation model with C3HeB/FeJ mice and compared to saline-exposed control mice and unexposed sentinels (n = 3-19). Studies were performed ±heat-inactivation (1 h autoclave) to increase BDG solubility. Outcomes included bronchoalveolar lavage (BAL) differential cell counts (macrophages, neutrophils, lymphocytes, eosinophils), cytokines, serum IgE, and IgG2a (multiplex and ELISA). Ex vivo primary cells removed from lungs and plated at monolayer were stimulated (BDG, lipopolysaccharide (LPS), anti-CD3), and cytokines compared to unstimulated cells. Right lung histology was performed. Inhalation of BDGs with distinct branching patterns exhibited varying inflammatory potency and immunogenicity. Lichen-derived (1 → 6)-linear pustulan was the most pro-inflammatory BDG, increasing inflammatory infiltrate (BAL), serum IgE and IgG2a, and cytokine production. Primed lung cells responded to secondary LPS stimulation with a T-cell-specific response to pustulan. Glucan source and solubility should be considered in exposure and toxicological studies.


Subject(s)
Lung , beta-Glucans , Animals , Male , Mice , beta-Glucans/pharmacology , Lung/drug effects , Lung/pathology , Lung/immunology , Lung/metabolism , Pneumonia/immunology , Pneumonia/pathology , Pneumonia/metabolism , Pneumonia/chemically induced , Cytokines/metabolism , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/chemistry , Mice, Inbred C3H , Glucans/pharmacology
14.
Vet Microbiol ; 295: 110107, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38838382

ABSTRACT

Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of ß-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity. Here, we found that BG pretreatment improved the survival rate, weight loss outcomes, alleviated histological injury and decreased PRV copy number of tissues in PRV-infected mice. Type I interferons (IFNs) including IFN-α/ß levels in serum were significantly increased by BG. However, these effects were abrogated in the presence of Dectin-1 antagonist. Dectin-1-mediated effect of BG was also confirmed in porcine and murine macrophages. These results suggested that BG have effects on type I IFNs with antiviral property involved in Dectin-1. In piglets, oral or injected immunization with BG and PRV vaccine could significantly elevated the level of PRV-specific IgG and type I IFNs. And it also increased the antibody levels of porcine reproductive and respiratory syndrome virus vaccine and classical swine fever vaccine that were later immunized, indicating a broad-spectrum effect on improving vaccine immunity. On the premise that the cost was greatly reducing, the immunological effect of oral was better than injection administration. Our findings highlighted that BG induced type I IFNs related antiviral effect against PRV involved in Dectin-1 and potential application value as a feed additive to help control the spread of PRV and future emerging viruses.


Subject(s)
Herpesvirus 1, Suid , Interferon Type I , Lectins, C-Type , Pseudorabies , beta-Glucans , Animals , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , Mice , Swine , Lectins, C-Type/immunology , Pseudorabies/immunology , Pseudorabies/prevention & control , Interferon Type I/immunology , Herpesvirus 1, Suid/immunology , Herpesvirus 1, Suid/drug effects , Macrophages/immunology , Macrophages/drug effects , Antiviral Agents/pharmacology , Viral Vaccines/immunology , Female
15.
Cell Mol Immunol ; 21(7): 770-786, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38839914

ABSTRACT

The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.


Subject(s)
Chondrogenesis , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit , Macrophage Migration-Inhibitory Factors , Neutrophils , Animals , Macrophage Migration-Inhibitory Factors/metabolism , Macrophage Migration-Inhibitory Factors/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neutrophils/immunology , Neutrophils/metabolism , Humans , Mice , Spondylarthritis/immunology , Spondylarthritis/pathology , Intramolecular Oxidoreductases/metabolism , Intramolecular Oxidoreductases/genetics , Interleukin-23/metabolism , beta-Glucans/pharmacology , Mice, Inbred C57BL , Male , Female , Immunity
16.
Inflamm Res ; 73(8): 1283-1297, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38850343

ABSTRACT

OBJECTIVE P. AERUGINOSA: (PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with ß-glucan might improve their response to P. aeruginosa infections. METHODS: To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae ß-glucan and exposed to PA57, the strong biofilm-forming bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of macrophage phenotypic markers were measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. The effect of in vivo ß-glucan-trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained and naïve macrophages was compared. RESULTS: Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Most importantly, transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. PA57 bacterial growth and formation of biofilm were significantly suppressed. The level of serum amyloid A (SAA), a systemic inflammation biomarker, was reduced. CONCLUSIONS: Training of murine macrophages with S. cerevisiae ß-glucan improved macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such ß-glucans might be a new therapeutic strategy in P. aeruginosa biofilm infections, including CF, to promote eradication of pathogens and resolution of inflammation.


Subject(s)
Biofilms , Cytokines , Mice, Inbred C57BL , Pseudomonas Infections , Pseudomonas aeruginosa , Saccharomyces cerevisiae , beta-Glucans , Animals , beta-Glucans/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/immunology , Cytokines/metabolism , Biofilms/drug effects , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Female , Mice , Serum Amyloid A Protein , Macrophages/drug effects , Macrophages/immunology , Cells, Cultured
17.
Int J Biol Macromol ; 273(Pt 1): 133032, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862053

ABSTRACT

Collagen's unique properties promise hemostatic potential, but its sponge form's stability and mechanics need improvement. In this study, we developed a series of homeostatic sponges by co-assembling collagen and curdlan at different ratios into hydrogels, followed by freeze-drying treatment. The incorporation of curdlan into collagen sponges has been found to significantly enhance the sponge's properties, including increased porosity, elevated water uptake, improved elasticity, and enhanced resistance to degradation. In vitro cytotoxicity and hemolysis assays have demonstrated the biocompatibility and nontoxicity of composite sponges. In mouse liver perforation and incision models, the composite sponges achieved rapid coagulation within 67 s and 75 s, respectively, outperforming gauze and gelatin sponge in reducing blood loss. Furthermore, composite sponges demonstrated superior wound healing potential in mice full-thickness skin defects model, with accelerated healing rates observed at days 3, 7, and 14 compared to the control group. Overall, collagen/curdlan composite sponge show promise for hemostasis and wound healing applications.


Subject(s)
Collagen , Hemostasis , Wound Healing , beta-Glucans , Animals , Wound Healing/drug effects , Collagen/chemistry , Collagen/pharmacology , beta-Glucans/pharmacology , beta-Glucans/chemistry , Mice , Hemostasis/drug effects , Skin/drug effects , Skin/injuries , Hydrogels/chemistry , Hydrogels/pharmacology , Hemolysis/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Porosity , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Humans , Male
18.
Immun Inflamm Dis ; 12(6): e1333, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38934407

ABSTRACT

BACKGROUND: Particulate ß-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. CONCLUSION: These results highlight OAW's robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.


Subject(s)
Asthma , Disease Models, Animal , Mast Cells , Mice, Inbred C57BL , beta-Glucans , Animals , Asthma/immunology , Asthma/drug therapy , Asthma/pathology , Mast Cells/immunology , Mast Cells/drug effects , Mast Cells/metabolism , Mice , Administration, Oral , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , Cytokines/metabolism , Inflammation/drug therapy , Inflammation/immunology , Ovalbumin/immunology , Respiratory Hypersensitivity/drug therapy , Respiratory Hypersensitivity/immunology , Bronchoalveolar Lavage Fluid/immunology , Lung/immunology , Lung/pathology , Lung/drug effects
19.
Molecules ; 29(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731488

ABSTRACT

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.


Subject(s)
Chromium , Hypoglycemic Agents , alpha-Glucosidases , beta-Glucans , Humans , Chromium/chemistry , Chromium/pharmacology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/chemical synthesis , beta-Glucans/chemistry , beta-Glucans/pharmacology , Hep G2 Cells , alpha-Glucosidases/metabolism , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Insulin Resistance , Glucose/metabolism , Signal Transduction/drug effects , Glucose Transporter Type 4/metabolism , Avena/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis
20.
Int J Mol Sci ; 25(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731838

ABSTRACT

The effect of dietary supplementation with sodium butyrate, ß-glucan and vitamins (A, D3, E, K, C) on breeding indicators and immune parameters of juvenile African catfish was examined. The fish were fed with unenriched (group C) and enriched feed with a variable proportion of sodium butyrate/ß-glucan, and constant content of vitamins (W1-W3). After the experiment, blood and the middle gut were collected. The microbiome of the gut was determined using Next Generation Sequencing (NGS). Liver tissue was collected for determination of expression of immune-related genes (HSP70, IL-1ß, TNFα). W2 and W3 were characterized by the most favorable values of breeding indicators (p < 0.05). The highest blood cortisol concentration was in group C (71.25 ± 10.45 ng/mL), and significantly the lowest in W1 (46.03 ± 7.01 ng/ mL) (p < 0.05). The dominance of Cetobacterium was observed in all study groups, with the largest share in W3 (65.25%) and W1 (61.44%). Gene expression showed an increased number of HSP70 genes in W1. IL-1ß and TNFα genes peaked at W3. The W3 variant turns out to be the most beneficial supplementation, due to the improvement of breeding and immunological parameters. The data obtained can be used to create a preparation for commercial use in the breeding of this species.


Subject(s)
Butyric Acid , Catfishes , Dietary Supplements , Gastrointestinal Microbiome , Hydrocortisone , Vitamins , beta-Glucans , Animals , beta-Glucans/pharmacology , beta-Glucans/administration & dosage , Gastrointestinal Microbiome/drug effects , Butyric Acid/pharmacology , Catfishes/immunology , Catfishes/genetics , Catfishes/microbiology , Hydrocortisone/blood , Vitamins/pharmacology , Vitamins/administration & dosage , Animal Feed , HSP70 Heat-Shock Proteins/genetics , Interleukin-1beta/genetics , Interleukin-1beta/metabolism
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