epiglucan and Disease-Models--Animal

Understanding the host anti-fungal immunity induced by beta-glucan has been one of the most challenging conundrums in the field of biomedical research. During the last couple of decades, insights on the role of beta-glucan in fungal disease progression, susceptibility, and resistance have been greatly augmented through the utility of various beta-glucan cognate receptor-deficient mouse models. Analysis of dectin-1 knockout mice has clarified the downstream signaling pathways and adaptive effector responses triggered by beta-glucan in anti-fungal immunity. On the other hand, assessment of CR3-deficient mice has elucidated the compelling action of beta-glucans in neutrophil-mediated fungal clearance, and the investigation of EphA2-deficient mice has highlighted its novel involvement in host sensing and defense to oral mucosal fungal infection. Based on these accounts, this review focuses on the recent discoveries made by these gene-targeted mice in beta-glucan research with particular emphasis on the multifaceted aspects of fungal immunity.

Topics: Adaptive Immunity; Animals; beta-Glucans; Disease Models, Animal; Fungi; Gene Deletion; Humans; Immunity; Lectins, C-Type; Macrophage-1 Antigen; Mice; Mice, Knockout; Mycoses; Receptor, EphA2

Poly-β-(1→6)-N-acetylglucosamine (PNAG) was first discovered as a major component of biofilms formed by Staphylococcus aureus and some other staphylococci but later this exopolysaccharide was also found to be produced by pathogens of various nature. This common antigen is considered as a promising target for construction of a broadly protective vaccine. Extensive studies of PNAG, its de-N-acetylated derivative (dPNAG, containing around 15% of residual N-acetates) and their conjugates with Tetanus Toxoid (TT) revealed the crucial role of de-N-acetylated glucosamine units for the induction of protective immunity. Conjugates of synthetic penta- (5GlcNH

Topics: Animals; Bacterial Infections; Bacterial Vaccines; beta-Glucans; Disease Models, Animal; Glycoconjugates; Humans; Immunogenicity, Vaccine; Polysaccharides, Bacterial; Tetanus Toxoid; Vaccines, Synthetic

In our current world, antibiotic resistance among pathogenic microbes keeps getting worse with few new antibiotics being pursued by pharmaceutical companies. Modern-day immunotherapies, reminiscent of the serotherapy approaches used in the early days of antimicrobial treatments, are a potential counter-measure, but are usually limited by the narrow spectrum against target antigens. Surprisingly, many multidrug-resistant (MDR) bacteria share a common surface polysaccharide, poly-β-1,6-N-acetylglucosamine (PNAG). Natural antibodies to PNAG are present in normal human sera, but are not protective. However, human monoclonal antibodies (MAbs) or polyclonal antisera raised to a deacetylated glycoform of PNAG mediate opsonic killing and protect mice against infections due to all PNAG-positive MDR pathogens tested. An MAb is currently in Phase II clinical trials. These discoveries could lead to utilization of antibodies to PNAG for either therapeutic use in patients infected by PNAG-producing MDR bacteria or prophylactic use in patients at risk of developing MDR infections.

Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Bacteria; Bacterial Infections; beta-Glucans; Clinical Trials as Topic; Disease Models, Animal; Humans; Immunotherapy; Treatment Outcome

House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Antigens, Dermatophagoides; Asthma; beta-Glucans; Bronchi; Bronchial Hyperreactivity; Chitin; Cytokines; Dendritic Cells; Disease Models, Animal; Epithelial Cells; Humans; Immunotherapy; Mice; Pyroglyphidae; Respiratory Mucosa; Spores, Fungal; Toll-Like Receptors

Beta-glucan is an immuno-stimulating agent that has been used to treat cancer and infectious disease for many years with varying and unpredictable efficacy. Recent studies have unraveled the action mode of yeast-derived beta-glucan in combination with anti-tumor monoclonal antibodies (mAbs) in cancer therapy. It has demonstrated that particulate or large molecular weight soluble beta-glucans are ingested and processed by macrophages. These macrophages secrete the active moiety that primes neutrophil complement receptor 3 (CR3) to kill iC3b-opsonized tumor cells. In vitro and in vivo data demonstrate that successful combination therapy requires complement activation and deposition on tumors and CR3 expression on granulocytes. Pre-clinical animal studies have demonstrated the efficacy of combined beta-glucan with anti-tumor mAb therapy in terms of tumor regression and long-term survival. Clinical trials are underway using anti-epidermal growth factor receptor mAb (cetuximab) in combination with beta-glucan for metastatic colorectal cancer. This review provides a brief overview of this combination therapy in cancer and describes in detail the beta-glucan composition and structure, mechanism of action, and preclinical studies in human carcinoma xenograft models. It is proposed that the addition of beta-glucan will further improve the therapeutic efficacy of anti-tumor mAbs in cancer patients.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Neoplasm; beta-Glucans; Disease Models, Animal; Humans; Immunotherapy; Models, Immunological; Neoplasm Transplantation; Neoplasms; Neutrophils; Saccharomyces cerevisiae; Solubility; Transplantation, Heterologous

The role played by antibodies (Abs) in the anticandidal defense has long been a matter of controversy, mostly due to the past inability to clearly define antigen specificity, the relationship between the type of immune response within the different settings of experimental and human candidiasis and, last but not least, a misunderstanding about the role of T helper cell in cell-mediated versus the humoral immunity. Contributory was also the lack of precise identification of virulence traits of the fungus which are the best candidates for a protective Ab response. In recent years, an impressive amount of experimental evidence, and also some clinical proof, have been generated which assign to Abs of defined specificity an important role in the anticandidal defense both at systemic and mucosal sites. Paradigmatic among them, Abs against defined virulence factors such as adhesins or aspartyl-proteinase enzymes, or against critical viability molecules such as beta-glucan, have been detected or generated which hold great promise for immunotherapeutic interventions in humans.

Topics: Animals; Antibodies, Fungal; Antibodies, Monoclonal; beta-Glucans; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Disease Models, Animal; Female; Humans; Immunization, Passive

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80(+)CD11c(+) cells in vitro that served as potent APC to induce Ag-specific CD4(+) and CD8(+) T cell responses in a dectin-1-dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c(+) cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non-small cell lung carcinoma that had received WGP treatment for 10-14 d prior to any other treatment had a decreased frequency of CD14(-)HLA-DR(-)CD11b(+)CD33(+) MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antigen-Presenting Cells; Apoptosis; beta-Glucans; Blotting, Western; Carcinoma, Lewis Lung; Carcinoma, Non-Small-Cell Lung; Cell Differentiation; Cell Separation; Disease Models, Animal; Female; Flow Cytometry; Humans; Lectins, C-Type; Lung Neoplasms; Lymphocyte Culture Test, Mixed; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Monocytes; Myeloid Cells; Neutrophils; Real-Time Polymerase Chain Reaction; Yeasts

Food polysaccharide 1,3-β-d-glucan (OBG) has been shown to alleviate ulcerative colitis (UC) in a mouse model, but the underlying mechanisms remain unclear. Here, we aimed to investigate potential mechanisms involving interactions among gut microbiota, microbial metabolites and host metabolic function.. OBG alleviated colonic inflammation, barrier dysfunction and intestinal concentrations of short-chain fatty acids in mice with UC. In addition, the relative abundance of Muribaculaceae, Alistipes, Erysipelatoclostridium and Blautia increased, whereas the abundance of Proteus, Lachnospiraceae and Ruminococcus decreased within the gut microbiota upon OBG treatment. Kyoto Encyclopedia of Genes and Genomes analyses showed that intestinal enzymes altered upon OBG treatment were mainly enriched in sub-pathways of amino acid biosynthesis. Metabolomics analyses showed that l-tryptophan, l-tyrosine, l-phenylalanine and l-alanine increased, which is consistent with the predictive metabolism of gut microbiota. Correlation analysis and interaction networks highlighted gut microbiota (especially Lactobacillus, Parabacteroides, Proteus and Blautia), metabolites (especially l-phenylalanine, l-tryptophan, l-tyrosine and acetic acid) and metabolism (phenylalanine, tyrosine and tryptophan biosynthesis) that may be key targets of OBG.. OBG is beneficial to the gut microecological balance in mice with colitis, mainly becaue of its impact on the interactions between gut microbes and amino acids metabolism (especially tyrosine and tryptophan metabolism). © 2022 Society of Chemical Industry.

Topics: Animals; beta-Glucans; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Tryptophan

The intestinal flora has been shown to be involved in the progression of Alzheimer's disease (AD) and can be improved by β-glucan, a polysaccharide derived from Saccharomyces cerevisiae, which affects cognitive function through the intestinal flora. However, it is not known if this effect of β-glucan is involved in AD.. This study used behavioral testing to measure cognitive function. After that, high-throughput 16 S rRNA gene sequencing and GC-MS were used to analyze the intestinal microbiota and metabolite SCFAs of AD model mice, and further explore the relationship between intestinal flora and neuroinflammation. Finally, the expressions of inflammatory factors in the mouse brain were detected by Western blot and Elisa methods.. We found that appropriate supplementation of β-glucan during the progression of AD can improve cognitive impairment and reduce A β plaque deposition. In addition, supplementation of β-glucan can also promote changes in the composition of the intestinal flora, thereby changing the flora metabolites in the intestinal content and reduce the activation of inflammatory factors and microglia in the cerebral cortex and hippocampus through the brain-gut axis. While reducing the expression of inflammatory factors in the hippocampus and cerebral cortex, thereby controlling neuroinflammation.. The imbalance of the gut microbiota and metabolites plays a role in the progression of AD; β-glucan blocks the development of AD by improving the gut microbiota and its metabolites and reducing neuroinflammation. β-Glucan is a potential strategy for the treatment of AD by reshaping the gut microbiota and improving its metabolites.

Topics: Alzheimer Disease; Animals; beta-Glucans; Cognitive Dysfunction; Disease Models, Animal; Gastrointestinal Microbiome; Mice; Mice, Transgenic; Neuroinflammatory Diseases

Topics: Animals; beta-Glucans; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Dextrans; Disease Models, Animal; Glucans; Inflammation; Interleukin-6; Mesalamine; Mice; Mice, Inbred C57BL; Proto-Oncogene Proteins c-bcl-2

Spondyloarthritis (SpA) is a systemic inflammatory arthritis mediated mainly by interleukin (IL)-17. The vitronectin-derived bioactive peptide, VnP-16, exerts an anti-osteoporotic effect via β1 and αvβ3 integrin signaling. SpA is associated with an increased risk of osteoporosis, and we investigated the effect of VnP-16 in mice with SpA.. SpA was induced by curdlan in SKG ZAP-70W163C mice, which were treated with vehicle, celecoxib, VnP-16, or VnP-16+celecoxib. The clinical score, arthritis score, spondylitis score, and proinflammatory cytokine expression of the spine were evaluated by immunohistochemical staining. Type 17 helper T cell (Th17) and regulatory T cell (Treg) differentiation in the spleen was evaluated by flow cytometry and in the spine by confocal staining. Splenocyte expression of signal transducer and activator of transcription (STAT) 3 and pSTAT3 was evaluated by in vitro Western blotting.. The clinical score was significantly reduced in the VnP16+celecoxib group. The arthritis and spondylitis scores were significantly lower in the VnP-16 and VnP16+celecoxib groups than the vehicle group. In the spine, the levels of IL-1β, IL-6, tumor necrosis factor-α, and IL-17 expression were reduced and Th17/Treg imbalance was regulated in the VnP-16 alone and VnP-16+celecoxib groups. Flow cytometry of splenocytes showed increased polarization of Tregs in the VnP-16+celecoxib group. In vitro, VnP-16 suppressed pSTAT3.. VnP-16 plus celecoxib prevented SpA progression in a mouse model by regulating the Th17/Treg imbalance and suppressing the expression of proinflammatory cytokines.

Topics: Animals; beta-Glucans; Celecoxib; Cytokines; Disease Models, Animal; Disease Progression; Female; Gene Expression Regulation; Humans; Integrin alphaVbeta3; Integrin beta1; Mice; Peptides; Signal Transduction; Spleen; Spondylarthritis; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Th17 Cells; Vitronectin

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and axonal degeneration in the central nervous system (CNS). Bacterial and fungal infections have been associated with the development of MS; microbial components that are present in several microbes could contribute to MS pathogenesis. Among such components, curdlan is a microbial 1,3-β-glucan that can stimulate dendritic cells, and enhances T helper (Th) 17 responses. We determined whether curdlan administration could affect two animal models for MS: an autoimmune model, experimental autoimmune encephalomyelitis (EAE), and a viral model, Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD). We induced relapsing-remitting EAE by sensitizing SJL/J mice with the myelin proteolipid protein (PLP)

Topics: Animals; beta-Glucans; Disease Models, Animal; Mice; Multiple Sclerosis; Theilovirus

Topics: Animals; beta-Glucans; Caco-2 Cells; Candida; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Dysbiosis; Humans; Klebsiella pneumoniae; Mice; Mice, Inbred C57BL; Sepsis; Toll-Like Receptor 2

Chronic Toxoplasma gondii (T. gondii) infection has been revealed to be a risk factor for neuropsychiatric diseases, including anxiety. However, there is no intervention strategy. The present study aimed to investigate the protective effect of β-glucan on T. gondii Wh6 strain-induced anxiety-like behavior in mice. The anxiety mouse model was established by infection with 10 cysts of the T. gondii Wh6 strain. β-Glucan was intraperitoneally administered 2 weeks before infection. Open field and elevated plus maze tests were performed to assess anxiety-like behavior. In the open field test, Wh6-infected mice spent less time in the central zone and had fewer entries into the central zone. In the elevated plus maze test, the infection reduced the frequency and time of head entries in the open arms. These results showed that Wh6 causes anxiety-like behavior in mice. Interestingly, the administration of β-glucan significantly ameliorated anxiety-like behavioral performance. The present study shows that β-glucan can alleviate the anxiety-like behavior induced by chronic T. gondii infection in mice, which indicates that β-glucan may be a potential drug candidate for treating T. gondii-related mental disorders, including anxiety.

Topics: Animals; Anxiety; beta-Glucans; Disease Models, Animal; Mice; Toxoplasma; Toxoplasmosis; Toxoplasmosis, Animal

Ankylosing spondylitis (AS) is a type of rheumatic disease characterized by chronic inflammation and pathological osteogenesis in the entheses. Previously, we demonstrated that enhanced osteogenic differentiation of MSC from AS patients (AS-MSC) resulted in pathological osteogenesis, and that during the enhanced osteogenic differentiation course, AS-MSC induced TNF-α-mediated local inflammation. However, whether TNF-α in turn affects AS-MSC remains unknown. Herein, we further demonstrate that a high-concentration TNF-α treatment triggers enhanced directional migration of AS-MSC in vitro and in vivo, which enforces AS pathogenesis. Mechanistically, TNF-α leads to increased expression of ELMO1 in AS-MSC, which is mediated by a METTL14 dependent m

Topics: Adaptor Proteins, Signal Transducing; Adenosine; Animals; beta-Glucans; Biopsy; Bone Marrow; Case-Control Studies; Cell Differentiation; Cell Movement; Disease Models, Animal; DNA Methylation; Epigenesis, Genetic; Female; Healthy Volunteers; HEK293 Cells; Humans; Male; Mesenchymal Stem Cells; Mice; Osteogenesis; Primary Cell Culture; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha; X-Ray Microtomography

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-wk dietary supplementation in healthy mice to evaluate the effects of different fiber composition (soluble vs. particulate Y-BG) and dose (0.1% vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver

Topics: Animals; beta-Glucans; Bile Acids and Salts; Bilophila; Cholesterol 7-alpha-Hydroxylase; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Gastrointestinal Microbiome; Glucagon-Like Peptide-1 Receptor; Insulin Resistance; Intestine, Small; Inulin; Liver; Male; Mice, Inbred C57BL; Obesity; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Yeasts

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

Topics: Adjuvants, Immunologic; Animals; Aureobasidium; beta-Glucans; Cell Line, Tumor; Dendritic Cells; Disease Models, Animal; Drug Screening Assays, Antitumor; Humans; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Transgenic; Neoplasms; T-Lymphocytes; Tumor Microenvironment

We previously reported medicinal chemistry efforts that identified MK-5204, an orally efficacious β-1,3-glucan synthesis inhibitor derived from the natural product enfumafungin. Further extensive optimization of the C2 triazole substituent identified 4-pyridyl as the preferred replacement for the carboxamide of MK-5204, leading to improvements in antifungal activity in the presence of serum, and increased oral exposure. Reoptimizing the aminoether at C3 in the presence of this newly discovered C2 substituent, confirmed that the (R) t-butyl, methyl aminoether of MK-5204 provided the best balance of these two key parameters, culminating in the discovery of ibrexafungerp, which is currently in phase III clinical trials. Ibrexafungerp displayed significantly improved oral efficacy in murine infection models, making it a superior candidate for clinical development as an oral treatment for Candida and Aspergillus infections.

Topics: Administration, Oral; Animals; Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Candida albicans; Candidiasis; Disease Models, Animal; Glycosides; Half-Life; Mice; Structure-Activity Relationship; Triterpenes

AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS.. Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT.. In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively).. Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.

Topics: Adult; Animals; beta-Glucans; Cell Differentiation; Disease Models, Animal; Female; Humans; Ileitis; Inflammation; Male; Mice; Middle Aged; Osteoblasts; Osteogenesis; Phosphorylation; Positron-Emission Tomography; Spondylitis, Ankylosing; STAT3 Transcription Factor; Stem Cells; Thiophenes; X-Ray Microtomography; Young Adult

Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract with alternating periods of exacerbation and remission. The aim of this study was to determine the time-dependent effects of dietary oat beta-glucans on colon apoptosis and autophagy in the CD rat model.. A total of 150 Sprague-Dawley rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed with feed without beta-glucans (βG-) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. The expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors, in the colon epithelial cells, was determined using immunohistochemistry and Western blot.. The results showed that in rats with colitis, after 3 days of induction of inflammation, the expression of Caspase-3 and LC3B in intestinal epithelial cells did not change, while that of TLR 4 and Dectin-1 decreased. Beta-glucan supplementation caused an increase in the expression of TLR 5 and Dectin-1 with no changes in the expression of Caspase-3 and LC3B. After 7 days, a high expression of Caspase-3 was observed in the colitis-induced animals without any changes in the expression of LC3B and TLRs, and simultaneously, a decrease in Dectin-1 expression was observed. The consumption of feed with βGl or βGh resulted in a decrease in Caspase-3 expression and an increase in TLR 5 expression in the CβGl group, with no change in the expression of LC3B and TLR 4. After 21 days, the expression of Caspase-3 and TLRs was not changed by colitis, while that of LC3B and Dectin-1 was decreased. Feed supplementation with βGh resulted in an increase in the expression of both Caspase-3 and LC3B, while the consumption of feed with βGh and βGl increased Dectin-1 expression. However, regardless of the type of nutritional intervention, the expression of TLRs did not change after 21 days.. Dietary intake of βGl and βGh significantly reduced colitis by time-dependent modification of autophagy and apoptosis, with βGI exhibiting a stronger effect on apoptosis and βGh on autophagy. The mechanism of this action may be based on the activation of TLRs and Dectin-1 receptor and depends on the period of exacerbation or remission of CD.

Topics: Animals; Apoptosis; Autophagy; beta-Glucans; Caspase 3; Colon; Crohn Disease; Cytokines; Dietary Supplements; Disease Models, Animal; Inflammation; Intestinal Mucosa; Lectins, C-Type; Male; Microtubule-Associated Proteins; Rats; Rats, Sprague-Dawley; Signal Transduction; Toll-Like Receptors

This study was aimed to verify the hypothesis that periodontal disease contributes to endothelial dysfunction in the coronary arteries of middle-aged rats. Besides we evaluated the effects of a prebiotic (β-glucan isolated from Saccharomyces cerevisiae) in preventing vascular dysfunction. The sample comprised young (sham and induced to periodontal disease) and middle-aged rats (sham, periodontal disease, sham-treated and periodontal disease-treated), at 12 and 57 weeks, respectively. The treated-groups received daily doses of β-glucan (50 mg/kg) orally (gavage) for 4 weeks, and periodontal disease was induced in the last 2 weeks by ligature. A myograph system assessed vascular reactivity. The expression of endothelial nitric oxide synthase (eNOS), cyclooxygenase 1 (COX-1), COX-2, p47phox, gp91phox, NF-KB p65, p53, p21, and p16 was quantified by western blotting. Serum hydroperoxide production was measured by the ferrous oxidation-xylenol orange (FOX-2) assay method. Interleukin-1 beta (IL-1β), IL-10, and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. Periodontal disease in middle-aged rats was associated with reduced acetylcholine-induced relaxations of coronary artery rings affecting the endothelium-dependent hyperpolarization- and the nitric oxide-mediated relaxations. The endothelial dysfunction was related to eNOS downregulation, pronounced impairment of the EDH-mediated relaxation, increased IL-1β and TNF-α proinflammatory cytokines, and also upregulation of NADPH oxidase and COXs, starting accumulate aging markers such as p53/p21 and the p16. Treatment with β-glucan effectively reduced bone loss in periodontal disease and delayed endothelial dysfunction in the coronary artery. Our data show that yeast β-glucan ingestion prevented oxidative stress and synthesis of proinflammatory marker and prevented eNOS reduction induced by periodontal disease in middle-aged rats. These results suggest that β-glucan has a beneficial effect on the coronary vascular bed.

Topics: Animals; beta-Glucans; Coronary Vessels; Dietary Fiber; Disease Models, Animal; Endothelium, Vascular; NADPH Oxidases; Nitric Oxide Synthase Type III; Oxidative Stress; Periodontal Diseases; Prebiotics; Protective Agents; Rats; Reactive Oxygen Species; Treatment Outcome; Vascular Diseases; Vasodilation

The incidence of Crohn's disease (CD) is increasing worldwide, and it has currently become a serious public health issue in society. The treatment of CD continues throughout a patient's lifetime, and therefore, it is necessary to develop new, effective treatment methods, including dietotherapy. The present study aimed to determine the effects of consumption of oat beta-glucans with different molar mass on colon inflammation (. Sprague-Dawley rats (control and TNBS-induced CD) were divided into three dietary groups and fed for 3 days (reflecting acute inflammation) or 7 days (reflecting remission) with a feed containing 1% low (βGl) or high (βGh) molar mass oat beta-glucan or a feed without this polysaccharide. The level of colon inflammatory markers and the expression of cytokines and their receptor genes were measured by ELISA and RT-PCR methods, respectively.. Acute inflammation or remission (3 or 7 days after TNBS administration, respectively) stages of experimentally induced CD were characterized by an increase in the level of inflammatory markers (IL-1, IL-6, IL-10, IL-12, TNF-α, CRP, MPO, COX, and PGE2) and the disruption of some cytokine signaling pathways as well as macro- and microscopic changes of colon tissue. The consumption of oat beta-glucans reduced the level of inflammatory markers and recovered the signaling pathways and histological changes, with stronger effects of βGl after 7 days of. Dietary oat beta-glucans can reduce

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Avena; beta-Glucans; Biomarkers; Body Weight; Carrier Proteins; Colon; Crohn Disease; Cytokines; Disease Models, Animal; Gene Expression Regulation; Intestinal Mucosa; Male; Rats, Sprague-Dawley

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration. A lack of dystrophin in DMD leads to inflammatory response, autophagic dysregulation, and oxidative stress in skeletal muscle fibers that play a key role in the progression of the pathology. β-glucans can modulate immune function by modifying the phagocytic activity of immunocompetent cells, notably macrophages. Mitochondrial function is also involved in an important mechanism of the innate and adaptive immune responses, owing to high need for energy of immune cells. In the present study, the effects of 1,3-1,6 β-glucans on five-day-old non-dystrophic and dystrophic (

Topics: Animals; beta-Glucans; Dietary Supplements; Disease Models, Animal; Larva; Locomotion; Mitochondria, Muscle; Muscular Dystrophy, Duchenne; Zebrafish

The epithelium-associated cytokine thymic stromal lymphopoietin (TSLP) can induce OX40L and CCL17 expression by myeloid dendritic cells (mDCs), which contributes to aberrant Th2-type immune responses. Herein, we report that such TSLP-induced Th2-type immune response can be effectively controlled by Dectin-1, a C-type lectin receptor expressed by mDCs. Dectin-1 stimulation induced STAT3 activation and decreased the transcriptional activity of p50-RelB, both of which resulted in reduced OX40L expression on TSLP-activated mDCs. Dectin-1 stimulation also suppressed TSLP-induced STAT6 activation, resulting in decreased expression of the Th2 chemoattractant CCL17. We further demonstrated that Dectin-1 activation was capable of suppressing ragweed allergen (Amb a 1)-specific Th2-type T cell response in allergy patients

Topics: Adult; Allergens; Animals; Antigens, Dermatophagoides; Antigens, Plant; beta-Glucans; Case-Control Studies; Cytokines; Dendritic Cells; Dermatophagoides farinae; Disease Models, Animal; Female; HEK293 Cells; Humans; Hypersensitivity; Immunity; Lectins, C-Type; Macaca mulatta; Male; Middle Aged; NF-kappa B p50 Subunit; OX40 Ligand; Plant Proteins; Signal Transduction; STAT3 Transcription Factor; STAT6 Transcription Factor; Th2 Cells; Thymic Stromal Lymphopoietin; Transcription Factor RelB

Nonalcoholic fatty liver disease (NAFLD) is characterized by marked imbalances in lipid storage and metabolism. Because the beneficial health effects of cereal β-glucan (BG) include lowering cholesterol and regulating lipid metabolism, BG may alleviate the imbalances in lipid metabolism observed during NAFLD. The aim of our study was to investigate whether BG from highland barley has an effect on western diet-induced NAFLD in mice. Using lipidomics, we investigated the underlying mechanisms of BG intervention, and identified potential lipid biomarkers. The results reveal that BG (300 mg/kg body weight) significantly alleviated liver steatosis. Lipidomics analysis demonstrated that BG also altered lipid metabolic patterns. We were able to identify 13 differentially regulated lipid species that may be useful as lipid biomarkers. Several genes in the hepatic lipid and cholesterol metabolism pathways were also modulated. These findings provide evidence that BG ameliorates NAFLD by altering liver lipid metabolites and regulating lipid metabolism-related genes.

Topics: Animals; beta-Glucans; Diet, High-Fat; Diet, Western; Disease Models, Animal; Hordeum; Lipid Metabolism; Lipidomics; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease

Ulcerative colitis (UC) is one of the most prevalent inflammatory bowel diseases (IBD) worldwide, while oat β-glucan has been shown to suppress the progress of colitis in UC mice. However, the underlying mechanism of oat β-glucan in ameliorating colitis is unclear and the role of gut microbiota in the protective effect of oat β-glucan against colitis remains unknown. In the present study, we aim to investigate the effect of oat β-glucan on gut microbiota in colitis mice and explore the health effect related mechanism. Dextran sulfate sodium (DSS) was used to induce the colitis model in mice. The results showed that β-glucan treatment attenuated hematochezia, splenomegaly and colon shortening in colitis mice. Histological evaluation of H&E and TUNEL staining showed that β-glucan treatment suppressed DSS-induced colonic inflammatory infiltration and reduced cell apoptosis levels of colon tissues. mRNA expression levels of the pro-inflammatory factors were also significantly reduced in the β-glucan group. Moreover, β-glucan treatment increased the protein and mRNA expression levels of tight junction proteins. Analysis of gut microbiota community showed that β-glucan treatment modulated gut microbial composition and structure at the OTU level in colitis mice. Further analysis of gut microbial metabolism revealed that β-glucan treatment significantly increased acetate, propionate and butyrate concentrations, and affected microbial metabolome in colitis mice. Notably, the increased acetate and propionate concentrations could directly affect pro-inflammatory factor expression levels and tight junction protein levels. In contrast, the changes in metabolic profiles affected pro-inflammatory factor levels and thus affected tight junction protein levels. Overall, our study revealed that oat β-glucan ameliorated DSS-induced colitis in mice simultaneously through regulating gut-derived short-chain fatty acids (SCFAs) and microbial metabolic biomarkers. Our study demonstrated that oat β-glucan could be an effective nutritional intervention strategy towards targeting gut microbiota metabolism for ameliorating colitis.

Topics: Animals; Avena; beta-Glucans; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Functional Food; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL

The influence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mouse models. Pristane, administered in 4-wk-old wild-type (WT) female mice, induced lupus characteristics at 24-wk-old similar to the lupus-onset in FcGRIIb-/- mice. Gut-microbiota alteration was induced by co-housing together with the gavage of feces from 40-wk-old FcGRIIb-/- mice (symptomatic lupus). On the other hand,  gut-leakage was induced  by dextran sulfate solution (DSS). DSS and gut-microbiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days post-DSS only in FcGRIIb-/- mice. DSS, but not gut-microbiota alteration, enhanced lupus characteristics (serum creatinine and proteinuria) in both lupus models (but not in WT) at 60 days post-DSS. Indeed, DSS induced the translocation of molecular components of gut-pathogens as determined by bacterial burdens in mesenteric lymph node (MLN), endotoxemia (gut-bacterial molecule) and serum (1→3)-β-D-glucan (BG) (gut-fungal molecule) as early as 15 days post-DSS together with enhanced MLN apoptosis in both WT and lupus mice. However, DSS induced spleen apoptosis in FcGRIIb-/- and WT mice at 30 and 60 days post-DSS, respectively, suggesting the higher impact of gut-leakage against spleen of lupus mice. In addition, macrophages preconditioning with LPS plus BG were susceptible to starvation-induced apoptosis, predominantly in FcGRIIb-/- cell, implying the influence of gut-leakage upon cell stress. In summary, gut-leakage induced gut-translocation of organismal-molecules then enhanced the susceptibility of stress-induced apoptosis, predominantly in lupus. Subsequently, the higher burdens of apoptosis in lupus mice increased anti-dsDNA Ig and worsen lupus severity through immune complex deposition. Hence, therapeutic strategies addressing gut-leakage in lupus are interesting.

Topics: Animals; beta-Glucans; Cytokines; Dextran Sulfate; Disease Models, Animal; Disease Progression; Feces; Female; Lupus Erythematosus, Systemic; Mice; Receptors, IgG; Terpenes

Vulvovaginal candidiasis (VVC) is one of the most common infections in women. The purpose of this study was to evaluate the ability of a water-soluble β-glucan salecan to protect against Candida albicans (C. albicans) vaginal infection. The model was reproduced with intravaginal inoculation of yeast blastoconidia in pseudoestrus mice. We found that mice that received salecan (0.5 mg per mouse) after infection had 85% fewer CFU than infected mice given saline. Compared with the C.albicans group, salecan reduced the migration of polymorphonuclear neutrophils (PMNs) in the vagina, decreased mRNA levels of cytokines IL23, IL22, IL17a, and IL17f, anti-candidal genes S100a8 and S100a9 and C.albicans pattern recognition receptor Dectin1. The analysis for vaginal microbial community composition at different taxa levels revealed that the bacterial flora composition in the vagina of the salecan-treated mice was similar to that of the uninfected mice, and distinguished from the infected mice. The vaginal lavages from the salecan treated group had more Enterococcus and its metabolite lactate. Our results suggest salecan might be a potential therapeutic agent for vaginal infection of C.albicans.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis, Vulvovaginal; Colony Count, Microbial; Cytokines; Disease Models, Animal; Female; Gene Expression Regulation, Fungal; Lactic Acid; Mice; Neutrophils; Receptors, Pattern Recognition; RNA, Messenger; Vagina

Topics: Animals; beta-Glucans; Cell Physiological Phenomena; Cells, Cultured; Disease Models, Animal; Drug Delivery Systems; Gene Knockdown Techniques; Infarction, Middle Cerebral Artery; Mice; Microglia; Nanoparticles; Neuroprotective Agents; RNA Interference; RNA, Small Interfering; Transcription Factor RelA

Alzheimer's disease (AD) is a neurodegenerative disease that remarkably imposes a huge global public health burden. Yeast β-glucans have been incorporated in functional foods and used in prophylactic applications owing to their biological effects. However, few studies had investigated the effects of yeast β-glucans on neurodegenerative diseases. Here, gut microbiota and metabolites SCFAs were analyzed through high-throughput 16S rRNA gene sequencing and GC-MS, respectively. Results indicated that yeast β-glucans could prominently shape the intestinal flora and produce SCFAs. Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; beta-Glucans; Biomarkers; Cognition; Disease Models, Animal; Fungal Polysaccharides; Gastrointestinal Microbiome; Hippocampus; Insulin; Male; Metagenome; Metagenomics; Mice; Peptide Fragments; Prebiotics; RNA, Ribosomal, 16S

Our previously reported efforts to produce an orally active β-1,3-glucan synthesis inhibitor through the semi-synthetic modification of enfumafungin focused on replacing the C2 acetoxy moiety with an aminotetrazole and the C3 glycoside with a N,N-dimethylaminoether moiety. This work details further optimization of the C2 heterocyclic substituent, which identified 3-carboxamide-1,2,4-triazole as a replacement for the aminotetrazole with comparable antifungal activity. Alkylation of either the carboxamidetriazole at C2 or the aminoether at C3 failed to significantly improve oral efficacy. However, replacement of the isopropyl alpha amino substituent with a t-butyl, improved oral exposure while maintaining antifungal activity. These two structural modifications produced MK-5204, which demonstrated broad spectrum activity against Candida species and robust oral efficacy in a murine model of disseminated Candidiasis without the N-dealkylation liability observed for the previous lead.

Topics: Administration, Oral; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Disease Models, Animal; Glucosyltransferases; Glycosides; Half-Life; Mice; Microbial Sensitivity Tests; Stereoisomerism; Structure-Activity Relationship; Triazoles; Triterpenes

Chronic stress elevates the cortisol beyond normal levels, which affects cognition including learning & memory. This injurious effect is primarily mediated via over excitation of metabotropic glucocorticoid receptors (mGR).. The present study was aimed to appraise the neuroprotective effects of naturally occurring molecule β-1,3-glucan by interfering with stress-cortisol-mGR axis. Our data of virtual screening (in silico) exhibited the promising interactions of β-glucan with the mGR. Therefore, the study was extended to evaluate its efficacy (2.5, 5 and 10 mg/kg/ i.p) in an animal model of chronic unpredictable mild stress (CUMS, 28 days) induced memory impairment.. Results of the current study revealed the β-glucan provided dose dependent protection against deleterious effects of stress on learning and memory associated parameters observed in Morris water maze (MWM) task. At higher tested doses, it has also significantly antagonized the stress induced weight loss and corticosterone elevation.

Topics: Animals; beta-Glucans; Cognitive Dysfunction; Corticosterone; Disease Models, Animal; Glucans; Hippocampus; Maze Learning; Rodentia; Stress, Psychological

Very high mortality rate in sepsis may be related to oxidative stress. This study was conducted on the rats to investigate the presence of oxidative stress and also the potential protective effects of the ß-glucan in the intra-abdominal sepsis model formed by cecal ligation-perforation (CLP).. In this study, 30 Male rats were equally divided into three groups as 'Sham', 'Sepsis' and 'ß-Glucan'. Only laparotomy was performed in the Sham group, and sepsis was induced by CLP in Sepsis and ß-Glucan groups. Following CLP, a single dose of 4 mg ß-glucan/kg was also intraperitoneally administered to the β-Glucan group. Blood and tissue (liver, lung and kidney) samples were taken from Sepsis and ß-Glucan groups after sepsis development determined at the end of the 48th hour, also from the Sham group. The levels of myeloperoxidase (MPO) and advanced oxidation protein products (AOPP) were determined in plasma samples, and the malondialdehyde (MDA) was measured in plasma and tissues.. MPO and AOPP were higher in both the Sepsis and ß-Glucan groups; however, plasma and tissue MDA levels were higher only in the Sepsis group than the Sham group (p<0.05). However, when compared to the Sepsis group, all parameters measured, except kidney MDA, were significantly lower in the ß-Glucan group (p<0.05).. To our knowledge, this is the first study to investigate the AOPP levels in the CLP sepsis model, ROS produced by the reaction of MPO derived from neutrophils may form oxidative damage to the proteins, compared to the lipids, and ß-glucan may be used as an alternative agent for sepsis treatment.

Topics: Advanced Oxidation Protein Products; Animals; beta-Glucans; Disease Models, Animal; Male; Malondialdehyde; Oxidative Stress; Protective Agents; Rats; Sepsis

We evaluated whether intake of β-glucan-rich barley flour affects expression levels of genes related to glucose and lipid metabolism in the ileum, liver, and adipose tissues of mice fed a high-fat diet. C57BL/6J male mice were fed a high-fat diet supplemented with high β-glucan barley, for 92 days. We measured the expression levels of genes involved in glucose and lipid metabolism in the ileum, liver, and adipose tissues using DNA microarray and q-PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. The metabolic syndrome indices were improved by barley flour intake. Microarray analysis showed that the expression of genes related to steroid synthesis was consistently decreased in the liver and adipose tissues. The expression of genes involved in glucose metabolism did not change in these organs. In liver, a negative correlation was showed between some SCFAs and the expression levels of mRNA related to lipid synthesis and degradation. Barley flour affects lipid metabolism at the gene expression levels in both liver and adipose tissues. We suggest that SCFAs are associated with changes in the expression levels of genes related to lipid metabolism in the liver and adipose tissues, which affect lipid accumulation.

Topics: Adipose Tissue; Animals; beta-Glucans; Diet, High-Fat; Disease Models, Animal; Flour; Glucose; Hordeum; Ileum; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Oligonucleotide Array Sequence Analysis

Chronic obstructive pulmonary disease (COPD), a lung disease caused by chronic exposure to cigarette smoke, increases the number of inflammatory cells such as macrophages and neutrophils and emphysema. Isoflavone is a polyphenolic compound that exists in soybeans. Daidzein and genistein, two types of isoflavones, have been reported to have anti-inflammatory effects in various organs. We hypothesized that the daidzein-rich soy isoflavone aglycones (DRIAs) attenuate cigarette smoke-induced emphysema in mice. Mice were divided into four groups: the (i) control group, (ii) isoflavone group, (iii) smoking group, and (iv) isoflavone + smoking group. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and the airspace enlargement using the mean linear intercept (MLI) were determined 12 weeks after smoking exposure. Expressions of neutrophilic inflammatory cytokines and chemokines were also examined. In the isoflavone + smoking group, the number of neutrophils in BALF and MLI was significantly less than that in the smoking group. Furthermore, the gene-expressions of TNF-α and CXCL2 (MIP-2) in the isoflavone + smoking group were significantly less than those in the smoking group. Supplementation of the COPD murine model with DRIAs significantly attenuates pathological changes of COPD via suppression of neutrophilic inflammation.

Topics: Animals; Anti-Inflammatory Agents; beta-Glucans; Cytokines; Disease Models, Animal; Inflammation Mediators; Isoflavones; Lung; Male; Mice, Inbred C57BL; Neutrophil Infiltration; Neutrophils; Pneumonia; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Signal Transduction; Smoke; Tobacco Products

Inflammatory bowel diseases are an important health problem. Therefore, the aim of the present study was to compare the impact of isolated oat beta-glucan fractions of low and high molecular weight, taken as dietary supplementation, on inflammatory markers in the colitis model.. Two groups of Sprague-Dawley rats-control and with experimentally induced colitis-were subsequently divided into three subgroups and fed over 21 days feed supplemented with 1% of low (βGl) or high (βGh) molecular weight oat beta-glucan fraction or feed without supplementation. The level of colon inflammatory markers, cytokines, and their receptors' genes expressions and immune cells numbers were measured by ELISA, RT-PCR, and by flow cytometry methods, respectively.. The results showed moderate inflammation affecting the colon mucosa and submucosa, with significant changes in the number of lymphocytes in the colon tissue, elevated cytokines and eicosanoid levels, as well as disruption of the main cytokine and chemokine cell signaling pathways in colitis rats. Beta-glucans supplementation caused a reverse in the percentage of lymphocytes with stronger effects of βGh and reduction of the levels of the inflammatory markers, and improvement of cytokine and chemokine signaling pathways with stronger effects of βGl supplementation.. The results indicate the therapeutic effect of dietary oat beta-glucan supplementation in the colitis in evident relation to the molecular weight of polymer.

Topics: Animals; Anti-Inflammatory Agents; Avena; beta-Glucans; Colitis; Cytokines; Dietary Supplements; Disease Models, Animal; Gene Expression Regulation; Lymphocyte Count; Male; Molecular Weight; Rats; Rats, Sprague-Dawley; Trinitrobenzenesulfonic Acid

Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (β-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of β-glucan against Leptospira infection in hamsters. First, β-glucan was administered 24 h prior to, during and after infection. The results showed that β-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of β-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1β and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1β and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, β-glucan was administered 5 days prior to infection. β-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that β-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1β and IL-6) in vitro, indicating that β-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of β-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Cricetinae; Cytokines; Disease Models, Animal; Immunity, Innate; Interleukin-1beta; Leptospira; Leptospira interrogans; Leptospirosis; Macrophages; Nitric Oxide Synthase Type II; Toll-Like Receptor 2

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD.

Topics: ADAM17 Protein; Adult; Animals; beta-Glucans; Disease Models, Animal; Female; Healthy Volunteers; Hordeum; Humans; Inflammation; Male; Mice; Middle Aged; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Renal Insufficiency, Chronic; Sphingomyelin Phosphodiesterase; Vascular Calcification; Young Adult

Beta-glucans are biologically active polysaccharides having antioxidant, immunomodulatory, and antiinflammatory properties. This study investigated the transcriptomic profile in peripheral blood of rats with LPS-induced enteritis, which were fed a diet supplemented with high- (G1) and low- (G2) molecular-weight oat beta-glucans.. Two-color rat gene expression microarrays were applied and the analysis was performed using a common reference design to provide easy means of comparing samples from various experimental conditions against one another. Common reference sample was labeled with cyanine 3 (Cy3) and investigated samples from each experimental group: C-G0 (control group fed semi-synthetic diet), LPS-G0 (LPS-challenged group fed semi-synthetic diet), LPS-G1 (LPS-challenged group fed G1 beta-glucan enriched diet), and LPS-G2 (LPS-challenged group fed G2 beta-glucan enriched diet) were labeled with cyanine 5 (Cy5). Each microarray was performed in quadruplicate. Statistical analysis was performed using one-way ANOVA and Tukey's HSD post-hoc test (p < 0.05). A multiple testing correction was performed using Benjamini and Hochberg False Discovery Rate < 5%. A quantitative real-time RT-PCR was performed to verify the expression of chosen transcripts.. The microarray analyses revealed differentially expressed transcripts between: the LPS-G0 and the control groups: C-G0 (138 genes), the LPS-G1 and LPS-G0 groups (533 genes), and the LPS-G2 and LPS-G0 groups (97 genes). Several differentially expressed genes in the beta-glucan-supplemented groups encoded proteins belonging to TLR and NLR signaling pathways, as well as prostaglandin synthesis and regulation pathways. Both beta-glucans up-regulated the expression of Atg10, which belongs to the family of autophagy-related genes, suggesting a possible link between autophagy induction and beta-glucan supplementation.. The changes in gene expression observed in the peripheral blood indicate that oat beta-glucans exerted a protective effect in rats with an induced inflammatory state caused by LPS challenge. The greater number of differentially expressed genes was observed in group supplemented with G1 beta-glucan, pointing at the differences in the mode of action of high- and low-molecular-weight beta-glucans in the organism.

Topics: Administration, Oral; Animal Feed; Animals; Avena; beta-Glucans; Disease Models, Animal; Enteritis; Gene Expression Regulation; Immunity; Lipopolysaccharides; Male; Molecular Weight; Rats; Rats, Sprague-Dawley

Pro‑inflammatory (M1) macrophages have key roles in atherogenesis. As β‑glucan has been demonstrated to exert pro‑inflammatory effects, the present study examined whether β‑glucan exerts atherogenic effects via converting macrophages into M1 phenotype. The results from reverse transcription‑quantitative polymerase chain reaction, flow cytometry, western blotting and transmission electron microscope indicated that M1 macrophage markers inducible nitric oxide synthase and cluster of differentiation 80 were upregulated, dectin‑1 (a receptor for β‑glucan) expression and nuclear factor (NF)‑κB nuclear translocation were promoted, and autophagy level was inhibited following β‑glucan treatment of macrophages. Additionally, dectin‑1 small interfering RNA (siRNA), autophagy inducer rapamycin and NF‑κB inhibitor SN50 reversed the effects of β‑glucan on autophagy level and macrophage M1 polarization, suggesting that dectin‑1 and NF‑κB are upstream of autophagy in β‑glucan‑induced macrophage M1 polarization. Notably, simultaneous treatment with dectin‑1 siRNA and SN50 exhibited similar effects on β‑glucan‑reduced autophagy compared with dectin‑1 siRNA treatment alone. These findings demonstrate that dectin‑1 may mediate β‑glucan‑reduced autophagy through NF‑κB in macrophages. Accordingly, results from hematoxylin and eosin staining, western blotting and immunofluorescence staining demonstrated that β‑glucan accelerated the progress of atherosclerosis in apolipoprotein E‑deficient mice and modulated expression of dectin‑1, beclin‑1 and light chain 3II/I in aortas similarly to that observed in macrophages. These results indicate that dectin‑1 activation by β‑glucan exerts atherogenic effects via converting macrophages into M1 phenotype in an NF‑κB‑autophagy‑dependent pathway.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Autophagy; B7-1 Antigen; beta-Glucans; Cell Polarity; Disease Models, Animal; Lectins, C-Type; Macrophages; Male; Mice; Microscopy, Electron, Transmission; NF-kappa B; Nitric Oxide Synthase; RAW 264.7 Cells; Signal Transduction

β-1,6-glucan is an important component of the fungal cell wall. The β-1,6-glucan synthase gene KRE6 was thought to be essential in the fungal pathogen Candida albicans because it could not be deleted in previous efforts. Also, the role of its homolog SKN1 was unclear because its deletion caused no defects. Here, we report the construction and characterization of kre6Δ/Δ, skn1Δ/Δ and kre6Δ/Δ skn1Δ/Δ mutants in C. albicans. While deleting KRE6 or SKN1 had no obvious phenotypic consequence, deleting both caused slow growth, cell separation failure, cell wall abnormalities, diminished hyphal growth, poor biofilm formation and loss of virulence in mice. Furthermore, the GPI-linked cell surface proteins Hwp1 and the invasin Als3 or Ssa1 were not detected in kre6Δ/Δ skn1Δ/Δ mutant. In GMM medium, RT-qPCR and western blotting revealed a constitutive expression of KRE6 and growth conditions-associated activation of SKN1. Like many hypha-specific genes, SKN1 is repressed by Nrg1, but its activation does not involve the transcription factor Efg1. Dysregulation of SKN1 reduces C. albicans ability to damage epithelial and endothelial cells and attenuates its virulence. Given the vital role of β-1,6-glucan synthesis in C. albicans physiology and virulence, Kre6 and Skn1 are worthy targets for developing antifungal agents.

Topics: Animals; beta-Glucans; Candida albicans; Candidiasis; Disease Models, Animal; Gene Deletion; Glucosyltransferases; Mice; Virulence; Virulence Factors

Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models.. Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day).. Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group.. The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Topics: Animals; beta-Glucans; Candida albicans; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Wall; Ciprofloxacin; Disease Models, Animal; Immunity, Cellular; Immunoglobulin A, Secretory; Intestines; Liver; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Salmonella typhimurium; Typhoid Fever

β-(1→3)-D-Glucan is an essential component of the fungal cell wall. Mouse monoclonal antibodies (mAbs) against synthetic nona-β-(1→3)-D-glucoside conjugated with bovine serum albumin (BSA) were generated using hybridoma technology. The affinity constants of two selected mAbs, 3G11 and 5H5, measured by a surface plasmon resonance biosensor assay using biotinylated nona-β-(1→3)-D-glucan as the ligand, were approximately 11 nM and 1.9 nM, respectively. The glycoarray, which included a series of synthetic oligosaccharide derivatives representing β-glucans with different lengths of oligo-β-(1→3)-D-glucoside chains, demonstrated that linear tri-, penta- and nonaglucoside, as well as a β-(1→6)-branched octasaccharide, were recognized by mAb 5H5. By contrast, only linear oligo-β-(1→3)-D-glucoside chains that were not shorter than pentaglucosides (but not the branched octaglucoside) were ligands for mAb 3G11. Immunolabelling indicated that 3G11 and 5H5 interact with both yeasts and filamentous fungi, including species from Aspergillus, Candida, Penicillium genera and Saccharomyces cerevisiae, but not bacteria. Both mAbs could inhibit the germination of Aspergillus fumigatus conidia during the initial hours and demonstrated synergy with the antifungal fluconazole in killing C. albicans in vitro. In addition, mAbs 3G11 and 5H5 demonstrated protective activity in in vivo experiments, suggesting that these β-glucan-specific mAbs could be useful in combinatorial antifungal therapy.

Topics: Animals; Antibodies, Monoclonal; Antifungal Agents; Antigens, Fungal; Aspergillus fumigatus; beta-Glucans; Candida albicans; Candidiasis; Cell Wall; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Fluconazole; Humans; Mice; Microbial Sensitivity Tests; Treatment Outcome

Methotrexate (MTX) is a widely used cancer chemotherapy agent. The efficacy of MTX is often limited by serious side effects, such as intestinal mucositis. The aim of this study was to evaluate the protective effect of water-soluble β-glucan salecan on MTX-induced intestinal toxicity in mice.. Intestinal mucositis was induced in C57BL/6 mice by intraperitoneal injection of MTX for two consecutive days. Mice were orally administrated with saline or salecan for 6 days before MTX injection and continued to the end of the study. Several histological and biochemical parameters were measured in the jejunum.. Orally administration of salecan improved the severity of intestinal mucositis in a dose-dependent manner, as evidenced by the well-maintained mucosal architecture and body weight in salecan-treated groups. Salecan treatment inhibited MTX-induced oxidative stress and effectively scavenged free radicals both in vitro and in vivo. Metabolomics analysis revealed that salecan treatment reversed the intestinal metabolic profiling changes in mice with MTX-induced mucositis. Salecan treatment modulated the innate immunity through the regulation of TLR and Dectin1 expression in the jejunum, thus protecting mice from MTX-induced intestinal damage.. Salecan has potential advantages in the treatment of MTX-induced intestinal mucositis, and its protective effect is mainly attributed to its antioxidant and immunomodulatory properties.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antioxidants; beta-Glucans; Disease Models, Animal; Free Radical Scavengers; Immunity, Innate; Intestinal Mucosa; Male; Metabolomics; Methotrexate; Mice; Mice, Inbred C57BL; Mucositis; Oxidative Stress

The aim of this study was to investigate the potential beneficial effects of β-glucan treatment against oxidative, histological and spermatological damage caused by cisplatin on the male reproductive system. Twenty-eight Sprague Dawley male rats were used in the study. The rats were randomly divided into four equal-sized groups: a control group, cisplatin group (7 mg/kg in a single-dose cisplatin administered intraperitoneally), β-glucan group (β-glucan given at a dose of 50 mg kg

Topics: Animals; Antineoplastic Agents; Antioxidants; beta-Glucans; Cisplatin; Disease Models, Animal; Epididymis; Humans; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sperm Count; Sperm Motility; Testicular Diseases; Testis; Thiobarbituric Acid Reactive Substances

Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 and mitogen-activated protein kinase signalling in an inoculum-dependent manner, and is required for induction of a proinflammatory and antifungal response. EphA2

Topics: Animals; beta-Glucans; Candida albicans; Candidiasis, Oral; Cell Line; Cytokines; Disease Models, Animal; Endocytosis; Epithelial Cells; ErbB Receptors; Inflammation Mediators; Male; Mice; Mice, Inbred C57BL; Mouth Mucosa; Phosphorylation; Receptor, EphA2; Receptors, Pattern Recognition; Signal Transduction; STAT3 Transcription Factor

Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse.. Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions.. Zymosan-induced SKG mice developed articular and extra-articular features as well as molecular changes that resembled those of human SpA. These findings suggest that the zymosan-induced SKG mouse is a good animal model to reflect the complex features of human SpA.

Topics: Animals; Arthritis, Experimental; beta-Glucans; Biopsy, Needle; Cytokines; Disease Models, Animal; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Injections, Intraperitoneal; Interleukin-17; Interleukin-6; Mice; Mice, Inbred Strains; Positron Emission Tomography Computed Tomography; Random Allocation; Sensitivity and Specificity; Spondylarthritis; Zymosan

We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. Spontaneous gut leakage, determined by (i) the presence of FITC-dextran, (ii) elevated serum endotoxin, and (iii) elevated serum (1→3)-β-D-glucan (BG), was demonstrated in symptomatic lupus but not in the asymptomatic group. In parallel, spontaneous gut leakage, detected by elevated serum BG without fungal infection, was demonstrated in patients with active lupus nephritis. Gut leakage induced by dextran sulfate solution (DSS) or endotoxin administration together with BG or endotoxin alone, but not BG alone, enhanced the severity of cecal ligation and puncture (CLP) sepsis more prominently in 8-week-old FcGRIIb-/- mice. Additionally, the bone marrow-derived macrophages of FcGRIIb-/- mice produced higher cytokine levels when coexposed to endotoxin and BG, when compared to wild-type mice. In summary, spontaneous gut leakage was demonstrated in symptomatic FcGRIIb-/- mice and the induction of gut permeability worsened sepsis severity. Gut translocation of endotoxin and BG had a minor effect on wild-type mice, but the synergistic effect of BG and endotoxin was prominent in FcGRIIb-/- mice. The data suggest that therapeutic strategies addressing gut leakage may be of interest in sepsis conditions in patients with lupus.

Topics: Adult; Animals; beta-Glucans; Cytokines; Dextran Sulfate; Disease Models, Animal; Endotoxins; Female; Gastrointestinal Tract; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Macrophages; Mice; Permeability; Proteoglycans; Receptors, IgG; Sepsis; Survival Analysis

β-Glucans are well-established immunomodulators with strong effects across all immune reactions. Due to the extensive amount of studies, glucans are steadily progressing from a non-specific immunomodulator to a licensed drug. However, direct comparisons of higher numbers of different glucans are rare.. In this study, we used 16 different glucans isolated from yeasts, mushroom, algae, and oat and compared their effects on phagocytosis, IL-2 production, antibody secretion, and inhibition of three experimental cancer models.. Our results showed significant differences among tested glucans, showing that despite the fact that glucans in general have strong stimulating effects on most aspects of the immune system, it is necessary to choose the right glucan.. Based on our studies, we can conclude that highly purified and active glucans have significant pleiotropic effects.

Topics: Agaricales; Animals; Antibody Formation; Avena; beta-Glucans; Carcinoma, Lewis Lung; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Interleukin-2; Mammary Neoplasms, Experimental; Mice, Inbred BALB C; Phagocytosis; Spleen; Yeasts

Topics: Animals; beta-Glucans; Biomarkers; Blood Glucose; Dietary Supplements; Disease Models, Animal; Energy Metabolism; Exercise Tolerance; Fatigue; Gene Expression Regulation; Glycogen; Liver; Male; Mice, Inbred ICR; Muscle Fatigue; Muscle, Skeletal; Oxidative Stress; Swimming; Time Factors

Arthritis in a genetically susceptible SKG strain of mice models a theoretical paradigm wherein autoimmune arthritis arises because of interplay between preexisting autoreactive T cells and environmental stimuli. SKG mice have a point mutation in ZAP-70 that results in attenuated TCR signaling, altered thymic selection, and spontaneous production of autoreactive T cells that cause arthritis following exposure to microbial β-glucans. In this study, we identify Nod2, an innate immune receptor, as a critical suppressor of arthritis in SKG mice. SKG mice deficient in Nod2 (Nod2

Topics: Animals; Arthritis; Autoimmune Diseases; beta-Glucans; Cells, Cultured; Cytokines; Disease Models, Animal; Humans; Immune Tolerance; Immunity, Innate; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Mutant Strains; Mutation; Nod2 Signaling Adaptor Protein; Th17 Cells; ZAP-70 Protein-Tyrosine Kinase

Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity.. We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1.. α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal levels of sensitivity. Administration of cecal mycobiomes from rats that had been separated from their mothers (but not non-handled mycobiome) restored hypersensitivity to distension. Administration of soluble β-glucans or a SYK inhibitor reduced visceral hypersensitivity, compared with controls. Particulate β-glucan (a DECTIN-1 agonist) induced mast cell degranulation in mesenteric windows and HMC-1 cells responded to fungal antigens by release of histamine.. In an analysis of patients with IBS and controls, we associated fungal dysbiosis with IBS. In studies of rats, we found fungi to promote visceral hypersensitivity, which could be reduced by administration of fungicides, soluble β-glucans, or a SYK inhibitor. The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity.

Topics: Abdominal Pain; Adult; Animals; Antifungal Agents; Anxiety, Separation; Behavior, Animal; beta-Glucans; Case-Control Studies; Cell Degranulation; Cell Line; Disease Models, Animal; Dysbiosis; Fecal Microbiota Transplantation; Feces; Female; Fungi; Gastrointestinal Microbiome; Humans; Hyperalgesia; Intestinal Mucosa; Intestines; Irritable Bowel Syndrome; Male; Mast Cells; Maternal Deprivation; Middle Aged; Pain Measurement; Pain Perception; Pain Threshold; Protein Kinase Inhibitors; Rats, Long-Evans; Syk Kinase

Chronic wounds represent a significant health problem worldwide. There is a need for advanced- and cost-efficient wound healing products able to increase patient comfort and reduce the healing time. The aim of this study was to develop a sprayable hydrogel dressing with beta-glucan (βG) as the active ingredient, targeting future application in the treatment of both chronic and burn wounds. The βG was chosen as an active ingredient because of its promising wound healing capabilities, whereas Carbopol 971P NF (Carbopol) was chosen as the thickening agent in the formulation due to several attractive characteristics such as its low viscosity, low toxicity, high transparency and good ion tolerance. Four different hydrogel formulations were prepared with varying Carbopol concentrations. The higher Carbopol concentration, 0.5% (w/w), was used to prepare three formulations comprising the HighCP:NoβG, HighCP:LowβG and the HighCP:MediumβG formulation, respectively. Lower Carbopol concentration, 0.25% (w/w), was used to prepare the LowCP:HighβG formulation. The content of βG varied from 0.25% in the HighCP:LowβG, 0.5% in the HighCP:MediumβG and 1.0% (w/w) in the LowCP:HighβG formulation, respectively. The first part of the study focused on the rheological characterization of the hydrogels and the fluid affinity testing. All formulations were confirmed to be stable gels; the βG was shown to augment the gel strength by increasing the yield strength of the gel in a dose dependent manner. The stability of the formulations containing either Carbopol alone or in a combination with βG did not deteriorate over 26weeks, and the fluid donation and absorption study indicated a fluid donation profile, which favors healing of dry wounds. The in vivo efficacy of the formulations, evaluated in the modified diabetic male mice (db/db mice), showed that Carbopol alone was unable to induce improved healing and caused adverse reactions in some wounds. The inclusion of βG increased the epithelialization and wound contraction in the db/db mice when given at high βG:Carbopol ratio. The positive effect of βG was, however, not sufficient to counteract the adverse effect of Carbopol, thus a more suitable thickening agent should be investigated for further development of a sprayable wound care product.

Topics: Acrylates; Animals; beta-Glucans; Diabetes Mellitus; Disease Models, Animal; Hydrogels; Male; Mice; Rheology; Viscosity; Wound Healing

Candida albicans is the most common fungus in the human intestinal microbiota but not in mice. To make a murine sepsis model more closely resemble human sepsis and to explore the role of intestinal C. albicans, in the absence of candidemia, in bacterial sepsis, live- or heat-killed C. albicans was orally administered to mice at 3h prior to cecal ligation and puncture (CLP). A higher mortality rate of CLP was demonstrated with Candida-administration (live- or heat-killed) prior to CLP. Fecal Candida presented only in experiments with live-Candida administration. Despite the absence of candidemia, serum (1→3)-β-D-glucan (BG) was higher in CLP with Candida-administration than CLP-controls (normal saline administration) at 6h and/or 18h post-CLP. Interestingly, fluconazole attenuated the fecal Candida burden and improved survival in mice with live-Candida administration, but not CLP-control. Microbiota analysis revealed increased Bacteroides spp. and reduced Lactobacillus spp. in feces after Candida administration. Additionally, synergy in the elicitation of cytokine production from bone marrow-derived macrophages, in vitro, was demonstrated by co-exposure to heat-killed E. coli and BG. In conclusion, intestinal abundance of fungi and/or fungal-molecules was associated with increased bacterial sepsis-severity, perhaps through enhanced cytokine elicitation induced by synergistic responses to molecules from gut-derived bacteria and fungi. Conversely, reducing intestinal fungal burdens decreased serum BG and attenuated sepsis in our model.

Topics: Administration, Oral; Animals; beta-Glucans; Blood Bactericidal Activity; Candida albicans; Cecum; Cytokines; Disease Models, Animal; Escherichia coli; Feces; Gastrointestinal Microbiome; Ligation; Macrophages; Male; Mice, Inbred ICR; Punctures; Sepsis; Survival Analysis; Time Factors

β-glucans are one of the most abundant forms of polysaccharides known as biological response modifiers which influence host's biological response and stimulate immune system. Accordingly, this study was initiated to evaluate irradiated β-glucan as a modulator for cellular signaling growth factors involved in the pathogenesis of hepatocellular carcinoma in rats. Hepatocellular carcinoma was induced with 20 mg diethylnitrosamine/kg BW. Rats received daily by gastric gavage 65 mg irradiated β-glucan/kg BW. It was found that treatment of rats with diethylnitrosamine induced hepatic injury and caused significant increase in liver injury markers with a concomitant significant increase in both hepatic oxidative and inflammatory indices: alpha-fetoprotein, interferon gamma, and interleukin 6 in comparison with normal and irradiated β-glucan-treated groups. Western immunoblotting showed a significant increase in the signaling growth factors: extracellular signal-regulated kinase 1 and phosphoinositide 3-kinase proteins in a diethylnitrosamine-treated group while both preventive and therapeutic irradiated β-glucan treatments recorded significant improvement versus diethylnitrosamine group via the modulation of growth factors that encounters hepatic toxicity. The transcript levels of vascular endothelial growth factor A and inducible nitric oxide synthase genes were significantly higher in the diethylnitrosamine-treated group in comparison with controls. Preventive and therapeutic treatments with irradiated β-glucan demonstrated that the transcript level of these genes was significantly decreased which demonstrates the protective effect of β-glucan. Histological investigations revealed that diethylnitrosamine treatment affects the hepatic architecture throughout the significant severe appearance of inflammatory cell infiltration in the portal area and congestion in the portal vein in association with severe degeneration and dysplasia in hepatocytes all over hepatic parenchyma. The severity of hepatic architecture changes was significantly decreased with both β-glucan therapeutic and preventive treatments. In conclusion, irradiated β-glucan modulated signal growth factors, vascular endothelial growth factor A, extracellular signal-regulated kinase 1, and phosphatidylinositol-3-kinase, which contributed to experimental hepatocarcinogenesis.

Topics: Animals; beta-Glucans; Carcinoma, Hepatocellular; Diethylnitrosamine; Disease Models, Animal; Gamma Rays; Humans; Liver; Liver Neoplasms; Mitogen-Activated Protein Kinase 3; Phosphatidylinositol 3-Kinases; Rats; Signal Transduction; Vascular Endothelial Growth Factor A

β-glucan (BG) and mulberry have received increasing attention for their benefits as natural sources of metabolic health. In the current study, we investigated the synergetic beneficial effects of BG and mulberry leaf extract (MLE) in mice fed a high-fat diet (HFD). Male C57BL6 mice were fed a HFD for twelve weeks to induce significant obesity and insulin resistance. BG and MLE were administrated orally throughout the feeding period. The administration of BG resulted in a significant reduction in body weight gain, perirenal fat mass, fasting insulin, serum lipids, serum inflammation markers, and fatty liver, showing systemic health improvement. Likewise, the administration of MLE showed benefits similar to BG, with the exception of body weight gain. In addition to the systemic benefits, the combination of BG and MLE resulted in a synergetic improvement in insulin sensitivity. Meanwhile, only the combination of BG and MLE significantly enhanced liver GST (Glutathione S-Transferase) activity and CuZn-SOD (Superoxide dismutase (Cu-Zn)) activity, resulting in a significant reduction in GSH/GSSG (Glutathione disulfide) and reactive oxygen species (ROS) levels in the liver. These results further confirm the beneficial effects of BG and MLE on metabolic disorders and show that the combination of BG and MLE has synergetic effects.

Topics: Adiposity; Animals; Anti-Inflammatory Agents; Antioxidants; beta-Glucans; Biomarkers; Diet, High-Fat; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Hypoglycemic Agents; Hypolipidemic Agents; Inflammation Mediators; Insulin; Insulin Resistance; Lipids; Liver; Male; Mice, Inbred C57BL; Morus; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Plant Extracts; Plant Leaves; Time Factors; Weight Gain

Baker's yeast glucan (BYG) has been reported to be an anti-diabetic agent. In the work described herein, further study on the effect of orally administered BYG on glucose and lipid homeostasis in the livers of ob/ob mice was performed. It was found that BYG decreased the blood glucose and the hepatic glucose and lipid disorders. Western blotting analysis revealed that BYG up-regulated p-AKT and p-AMPK, and down-regulated p-Acc in the liver. Furthermore, RNA-Seq analysis indicated that BYG down-regulated genes responsible for gluconeogenesis (G6pase and Got1), fatty acid biosynthesis (Acly, Acc, Fas, etc.), glycerolipid synthesis (Gpam and Lipin1/2), and cholesterol synthesis (Hmgcr, Fdps, etc.). Additionally, BYG decreased glucose transporters SGLT1 and GLUT2, fat emulsification, and adipogenic genes/proteins in the intestine to decrease glucose and lipid absorption. All these findings demonstrated that BYG is beneficial for regulating glucose and lipid homeostasis in diabetic mice, and thus has potential applications in anti-diabetic foods or drugs.

Topics: Animals; beta-Glucans; Blood Glucose; Cholesterol; Diabetes Mellitus; Disease Models, Animal; Gluconeogenesis; Glucose; Glucose Transporter Type 2; Humans; Hypoglycemic Agents; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Saccharomyces cerevisiae; Sodium-Glucose Transporter 1

Acid nucleic aptamers are RNA or DNA oligonucleotides capable of binding to a target molecule with high affinity and selectivity. These molecules are promising tools in nuclear medicine. Many aptamers have been used as targeting molecule of radiopharmaceuticals in preclinical studies. (1→3)-β-D-glucans are the main structural cell wall components of fungi and some bacteria. In the present study two radiolabeled (1→3)-β-D-glucan aptamers (seq6 and seq30) were evaluated to identity infectious foci caused by fungal or bacterial cells.. Aptamer labeling with. Seq6 and seq30 aptamers proved to be inefficient for diagnosis of C. albicans infection. Nevertheless, their applicability for diagnosis of S. aureus and other bacterial infections by scintigraphy should be further explored.

Topics: Animals; Aptamers, Nucleotide; beta-Glucans; Candida albicans; Disease Models, Animal; Drug Stability; Isotope Labeling; Mice; Mycoses; Proteoglycans; Staphylococcal Infections; Staphylococcus aureus; Technetium; Tissue Distribution

The in vitro activity of posaconazole (PSC) and voriconazole (VRC) was tested by using time-kill studies against 3 strains of Candida lusitaniae. Both drugs showed fungistatic activity against all strains. The efficacy of those compounds was evaluated by reducing kidney fungal burden and by determining (1→3)-β-d-glucan serum levels in a murine model of invasive infection of C. lusitaniae. The therapies tested were VRC at 10, 25, or 40 mg/kg/day and PSC at 5, 12.5, or 20 mg/kg/twice a day. All the dosages showed efficacy in a dose-dependant manner being high doses of both antifungals able to sterilize some kidneys after 10 days. With the exception of the strain FMR 9474, against which PSC was more effective than VRC, no differences in reducing tissue burden were found between the treatments. All doses of both antifungals were able to significantly reduce (1→3)-β-d-glucan serum levels with no significant differences between treatments and between the same doses of both drugs.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Kidney; Male; Mice; Proteoglycans; Treatment Outcome; Triazoles; Voriconazole

The EuropeanAspergillusPCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and β-d-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and β-d-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and β-d-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and β-d-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.

Topics: Animals; beta-Glucans; Blood; Diagnostic Tests, Routine; Disease Models, Animal; Galactose; Guinea Pigs; Invasive Pulmonary Aspergillosis; Male; Mannans; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Proteoglycans; Sensitivity and Specificity; Time Factors

Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 μg ml

Topics: Amphotericin B; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis, Invasive; Caspofungin; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Fluconazole; Kidney; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Microbial Viability; Proteoglycans; Survival Analysis; Treatment Outcome

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 μL/rat) was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1β and TNF-α. The activities of inducible nitric oxide synthase (iNOS) and lipid peroxidation (MDA) were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

Topics: Administration, Topical; Alveolar Bone Loss; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antioxidants; Bacteria; beta-Glucans; Calcium Gluconate; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Interleukin-1beta; Lipid Peroxidation; Male; Oxidative Stress; Periodontitis; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Gastrointestinal (GI) leakage is believed to exacerbate sepsis and new, validated markers of GI barrier performance might benefit clinical decision-making. Serum (1→3)-β-D-glucan (BG) was evaluated as a potential GI leakage marker. Serum BG was tested in several mouse models of GI leakage, including dextran sulfate solution (DSS) administration, endotoxin (LPS) injection, and cecal ligation and puncture sepsis (CLP). Serum BG titer was also evaluated in patients with sepsis and septic shock, for comparison.With 0.75% DSS administration, BG increased only after oral administration of heat-killed C. albicans, but increased spontaneously with 1.5% DSS. In the LPS and CLP models, BG increased as early as 1 h and at 12 h after LPS administration and surgery, respectively. GI leakage was confirmed by orthogonal validation methods including FITC-dextran oral administration in the DSS, LPS, and CLP models and, in the DSS model, with urine sucralose after oral administration and serum endotoxemia. IL-6 increased in parallel with serum BG. Serum BG or IL-6, at 18 h, anticipated sepsis mortality in the CLP model.Analysis of serum BG from patients with febrile neutropenic sepsis (N = 49) and febrile non-neutropenic sepsis (N = 39) demonstrated BG elevation. Patients with bacterial septic shock had serum BG titers similar to levels observed in invasive fungal disease, regardless of febrile neutropenia. Serum BG was lower in less severe cases of bacterial sepsis. Elevated serum IL-6 was associated with GI leakage and elevated serum BG.Serum BG may have potential as a sepsis/septic shock biomarker and further study in this context is warranted.

Topics: Animals; beta-Glucans; Candida albicans; Disease Models, Animal; Feces; Gastrointestinal Tract; Humans; Male; Mice; Pilot Projects; Proteoglycans; Sepsis; Shock, Septic

The Cek1 MAP kinase (MAPK) mediates vegetative growth and cell wall biogenesis in the fungal pathogen Candida albicans. Alterations in the fungal cell wall caused by a defective Cek1‑mediated signaling pathway leads to increased β‑1,3‑glucan exposure influencing dectin‑1 fungal recognition by immune cells. We show here that cek1 cells also display an increased exposure of α‑1,2 and β‑1,2‑mannosides (α‑M and β‑M), a phenotype shared by strains defective in the activating MAPKK Hst7, suggesting a general defect in cell wall assembly. cek1 cells display walls with loosely bound material as revealed by transmission electron microscopy and are sensitive to tunicamycin, an inhibitor of N‑glycosylation. Transcriptomal analysis of tunicamycin treated cells revealed a differential pattern between cek1 and wild type cells which involved mainly cell wall and stress related genes. Mapping α‑M and β‑M epitopes in the mannoproteins of different cell wall fractions (CWMP) revealed an important shift in the molecular weight of the mannan derived from mutants defective in this MAPK pathway. We have also assessed the role of galectin‑3, a member of a β‑galactoside‑binding protein family shown to bind to and kill C. albicans through β‑M recognition, in the infection caused by cek1 mutants. Increased binding of cek1 to murine macrophages was shown to be partially blocked by lactose. Galectin-3(-/-) mice showed increased resistance to fungal infection, although galectin-3 did not account for the reduced virulence of cek1 mutants in a mouse model of systemic infection. All these data support a role for the Cek1‑mediated pathway in fungal cell wall maintenance, virulence and antifungal discovery.

Topics: Animals; beta-Glucans; Candida albicans; Candidiasis; Cell Wall; Disease Models, Animal; Fungal Proteins; Galectin 3; Gene Expression Profiling; Gene Expression Regulation, Fungal; Mannosides; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Mutation; Tunicamycin; Virulence

Pathogens hide immunogenic epitopes from the host to evade immunity, persist and cause infection. The opportunistic human fungal pathogen Candida albicans, which can cause fatal disease in immunocompromised patient populations, offers a good example as it masks the inflammatory epitope β-glucan in its cell wall from host recognition. It has been demonstrated previously that β-glucan becomes exposed during infection in vivo but the mechanism behind this exposure was unknown. Here, we show that this unmasking involves neutrophil extracellular trap (NET) mediated attack, which triggers changes in fungal cell wall architecture that enhance immune recognition by the Dectin-1 β-glucan receptor in vitro. Furthermore, using a mouse model of disseminated candidiasis, we demonstrate the requirement for neutrophils in triggering these fungal cell wall changes in vivo. Importantly, we found that fungal epitope unmasking requires an active fungal response in addition to the stimulus provided by neutrophil attack. NET-mediated damage initiates fungal MAP kinase-driven responses, particularly by Hog1, that dynamically relocalize cell wall remodeling machinery including Chs3, Phr1 and Sur7. Neutrophil-initiated cell wall disruptions augment some macrophage cytokine responses to attacked fungi. This work provides insight into host-pathogen interactions during disseminated candidiasis, including valuable information about how the C. albicans cell wall responds to the biotic stress of immune attack. Our results highlight the important but underappreciated concept that pattern recognition during infection is dynamic and depends on the host-pathogen dialog.

Topics: Animals; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; Cell Wall; Disease Models, Animal; Extracellular Traps; Female; HEK293 Cells; Host-Pathogen Interactions; Humans; Image Processing, Computer-Assisted; Immune Evasion; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Fluorescence; Neutrophils

β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.

Topics: Animals; Antifungal Agents; beta-Glucans; Caspofungin; Cytokines; Disease Models, Animal; Echinocandins; Lipopeptides; Mice, Knockout; Microarray Analysis; Pneumocystis; Pneumonia; Pneumonia, Pneumocystis; Real-Time Polymerase Chain Reaction

Proteo-β-glucan from Maitake (PGM) is a strong immune regulator, and its receptor is called Dectin-1. Cumulative evidence suggests that AMPA receptors are important for the treatment of depression. Here, we report that PGM treatment leads to a significant antidepressant effect in the tail suspension test and forced swim test after sixty minutes of treatment in mice. After five consecutive days of PGM treatment, this antidepressant effect remained. PGM treatment did not show a hyperactive effect in the open field test. PGM significantly enhanced the expression of its receptor Dectin-1, as well as p-GluA1(S845) and GluA1, but not GluA2 or GluA3 in the prefrontal cortex (PFC) after five days of treatment. The Dectin-1 inhibitor Laminarin was able to block the antidepressant effect of PGM. At the synapses of PFC, PGM treatment significantly up-regulated the p-GluA1(S845), GluA1, GluA2, and GluA3 levels. Moreover, PGM's antidepressant effects and the increase of p-GluA1(S845)/GluA1 lasted for 3 days after stopping treatment. The AMPA-specific antagonist GYKI 52466 was able to block the antidepressant effect of PGM. This study identified PGM as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signalling.

Topics: Animals; Antidepressive Agents; Benzodiazepines; beta-Glucans; Depression; Disease Models, Animal; Gene Expression Regulation; Grifola; Lectins, C-Type; Male; Mice; Plant Proteins; Prefrontal Cortex; Receptors, AMPA; Signal Transduction

Gastrointestinal (GI) leakage in Clostridium difficile-associated diarrhea (CDAD) is well known but is not routinely assessed in clinical practice. Serum (1→3)-β-D-glucan (BG), a fungal cell wall component used as a biomarker for invasive fungal disease, was tested in a CDAD mouse model with and without probiotics. Higher serum fluorescein isothiocyanate-dextran (FITC-dextran) and spontaneous gram-negative bacteremia, GI leakage indicators, were frequently found in CDAD mice, which died compared with those which survived. BG, serum macrophage inflammatory protein-2 and FITC-dextran but not quantitative blood bacterial count differentiated the clinical severity. Interestingly, a specific dose of Lactobacillus rhamnosus L34 attenuated CDAD and decreased serum BG and FITC-dextran, but not other parameters. BG also showed a higher area under the receiver operating characteristic curve for 7-day mortality than FITC-dextran. Fifty-five percent of CDAD mice with BG ≥ 60 pg/ml (the human negative cut-off value for invasive fungal disease) at 1 day after C. difficile gavage died within 7 days. In conclusion, S: erum BG was elevated in mice with severe CDAD, an established model of GI leakage with a strong association with mortality rate. BG monitoring in patients with CDAD is of interest as both a potential prognostic tool and a therapeutic efficacy indicator.

Topics: Animals; Anti-Bacterial Agents; beta-Glucans; Biomarkers; Chemokine CXCL2; Clostridioides difficile; Diarrhea; Disease Models, Animal; Enterocolitis, Pseudomembranous; Gastrointestinal Tract; Lacticaseibacillus rhamnosus; Male; Mice; Mice, Inbred ICR; Permeability; Probiotics; ROC Curve

With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

Topics: Animals; Antibody Formation; beta-Glucans; Candida albicans; Candidiasis; Disease Models, Animal; Drug Discovery; Female; Fungal Vaccines; Immunoglobulin G; Mice; Mice, Inbred C57BL; Oligosaccharides; Vaccines, Conjugate

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) β-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; beta-Glucans; Biological Transport; Disease Models, Animal; Down-Regulation; Glucans; Ileum; Indomethacin; Inflammation; Intestinal Absorption; Jejunum; Male; Proteoglycans; Rats, Wistar; RNA, Messenger; Time Factors

Benign prostatic hyperplasia (BPH), one of the most common disease usually occurring in men in their 50s, has now become an atypical direct cause of mortality. Currently, phytotherapeutic agents are emerging and are frequently used as a complementary alternative treatment of BPH. β-glucan has shown a diversity of bioactivities involving anticancer, immunomodulatory and anti-inflammatory effects. Antrodia cinnamomea exhibits a diversity of biological activities. Only a few literature references have cited the biomedicinal effects of antrodan, which is a unique β-glucan present in A. cinnamomea mycelia. We hypothesized that antrodan could be beneficial to BPH. Using the Sprague-Dawley rat model, we performed this present experiment. Results indicated that antrodan alleviated most of the pathophysiological manifestations that can be elicited by BPH, by alleviating the prostatic epithelial hyperplasia and collagen deposition, increasing the total cholesterol biosynthesis and conversion into HDL, and suppressing the production of LDL and ROS and the upregulation of IL-1, COX-2 and CD68. Antrodan also effectively suppressed the serum level testosterone and DHT and downregulated aromatase, estradiol and the expression of the androgen receptor. More importantly, antrodan downregulated N-cadherin and vimentin and upregulated E-cadherin, underlying the effective inhibition on the epithelial-mesenchymal transition (EMT). Conclusively, the β-glucan antrodan present in the A. cinamomea mycelia is beneficial to the BPH therapy.

Topics: Animals; Anti-Inflammatory Agents; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antrodia; Aromatase; beta-Glucans; Cadherins; Cholesterol, HDL; Cholesterol, LDL; Cyclooxygenase 2; Dihydrotestosterone; Disease Models, Animal; Down-Regulation; Epithelial-Mesenchymal Transition; Estradiol; Humans; Interleukin-1; Male; Middle Aged; Plant Extracts; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Receptors, Androgen; Testosterone; Up-Regulation; Vimentin

Aspergillus fumigatus is a fungal pathogen that is capable of adapting to different host niches and to avoid host defenses. An enhanced understanding of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes is essential for the development of improved disease control strategies. Protein phosphatases are central to numerous signal transduction pathways. To comprehend the functions of protein phosphatases in A. fumigatus, 32 phosphatase catalytic subunit encoding genes were identified. We have recognized PtcB as one of the phosphatases involved in the high osmolarity glycerol response (HOG) pathway. The ΔptcB mutant has both increased phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. The ΔptcB strain was more sensitive to cell wall damaging agents, had increased chitin and β-1,3-glucan, and impaired biofilm formation. The ΔptcB strain was avirulent in a murine model of invasive pulmonary aspergillosis. These results stress the importance of the HOG pathway in the regulation of pathogenicity determinants and virulence in A. fumigatus.

Topics: Animals; Aspergillus fumigatus; beta-Glucans; Biofilms; Cell Wall; Chitin; Computational Biology; Disease Models, Animal; Fungal Proteins; Gene Expression Regulation, Fungal; Glycerol; Mice; Mutation; Osmolar Concentration; Phosphoric Monoester Hydrolases; Signal Transduction

Topical antifungal agents which have anti-inflammatory effects have the potential to provide additional clinical benefits. Therefore, an anti-inflammatory activity of lanoconazole (LCZ), a topical antifungal agent, was investigated against in vitro and in vivo models of inflammation. The release of interleukin-8 (IL-8) from human epidermal keratinocytes stimulated by the addition of 100 μg ml(-1) β-glucan of Saccharomyces cerevisiae was significantly inhibited by LCZ at the concentration of 10(-5) mol l(-1). The release of interferon-γ and IL-2 from human peripheral blood mononuclear cells stimulated by the addition of 30 and 100 μg ml(-1) phytohemagglutinin was significantly inhibited by LCZ at the concentrations of 10(-7) and 10(-6) mol l(-1), respectively. The increase in the ear thickness induced by topical application of 0.01% 12-O-tetradecanoyl phorbol-13-acetate and 1% 2,4,6-trinitrochlorobenzene (TNCB) after sensitisation with 3% TNCB were established as the mouse models of irritant and contact dermatitis, respectively. Application of 1% and 3% LCZ showed a significant anti-inflammatory activity against both the irritant and contact dermatitis models. These findings suggest that LCZ possesses an anti-inflammatory activity, which may be partially helpful in the treatment of dermatomycoses.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Glucans; Cells, Cultured; Dermatitis, Contact; Disease Models, Animal; Female; Humans; Imidazoles; Interferon-gamma; Interleukin-2; Interleukin-8; Keratinocytes; Leukocytes, Mononuclear; Mice; Phytohemagglutinins; Saccharomyces cerevisiae

Staphylococcus aureus is an important pathogen that forms biofilms on the surfaces of medical implants. Biofilm formation by S. aureus is associated with the production of poly N-acetylglucosamine (PNAG), also referred to as polysaccharide intercellular adhesin (PIA), which mediates bacterial adhesion, leading to the accumulation of bacteria on solid surfaces. This study shows that the ability of S. aureus SA113 to adhere to nasal epithelial cells is reduced after the deletion of the ica operon, which contains genes encoding PIA/PNAG synthesis. However, this ability is restored after a plasmid carrying the entire ica operon is transformed into the mutant strain, S. aureus SA113Δica, showing that the synthesis of PIA/PNAG is important for adhesion to epithelial cells. Additionally, S. carnosus TM300, which does not produce PIA/PNAG, forms a biofilm and adheres to epithelial cells after the bacteria are transformed with a PIA/PNAG-expressing plasmid, pTXicaADBC. The adhesion of S. carnosus TM300 to epithelial cells is also demonstrated by adding purified exopolysaccharide (EPS), which contains PIA/PNAG, to the bacteria. In addition, using a mouse model, we find that the abscess lesions and bacterial burden in lung tissues is higher in mice infected with S. aureus SA113 than in those infected with the mutant strain, S. aureus SA113Δica. The results indicate that PIA/PNAG promotes the adhesion of S. aureus to human nasal epithelial cells and lung infections in a mouse model. This study elucidates a mechanism that is important to the pathogenesis of S. aureus infections.

Topics: Animals; Bacterial Adhesion; Bacterial Load; Bacterial Proteins; Base Sequence; beta-Glucans; Biofilms; Cell Line, Tumor; Disease Models, Animal; Epithelial Cells; Gene Expression Regulation, Bacterial; Genetic Complementation Test; Humans; Lung; Mice; Molecular Sequence Data; Operon; Plasmids; Polysaccharides, Bacterial; Sequence Deletion; Staphylococcal Infections; Staphylococcus aureus; Transformation, Bacterial

Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

Topics: Acute Disease; Animals; beta-Glucans; Colitis; Colon; Cytokines; Dextran Sulfate; Discriminant Analysis; Disease Models, Animal; Fluconazole; Fungi; Inflammation; Intestinal Mucosa; Least-Squares Analysis; Lymph Nodes; Mice; Mice, Inbred C57BL; Occludin; Proteoglycans; Real-Time Polymerase Chain Reaction; RNA, Ribosomal, 16S; RNA, Ribosomal, 18S; Spleen; Zonula Occludens-1 Protein

Galactomannan and (1→3)-β-D-glucan are useful biomarkers of invasive pulmonary aspergillosis (IPA). However, the effects of immunosuppression on levels of galactomannan or (1→3)-β-D-glucan in IPA are not well understood or quantified. We therefore studied the simultaneous levels of galactomannan and (1→3)-β-D-glucan in two rabbit models of experimental IPA: (1) AraC-induced neutropenia in untreated (UC-AraC) and liposomal amphotericin B-treated (LAMB-AraC) rabbits; and (2) nonneutropenic cyclosporine-methylprednisolone immunosuppression in untreated (UC-CsA+M) and LAMB-treated (LAMB-CsA+M) rabbits. Simultaneous levels of galactomannan and (1→3)-β-D-glucan were determined in bronchoalveolar lavage (BAL) fluid and serial serum specimens and correlated with pulmonary host response. Serum galactomannan index (GMI) and (1→3)-β-D-glucan concentration-time-curves were higher in UC-AraC vs. UC-CsA+M (Mann-Whitney U-test, P < .05). Serum galactomannan and (1→3)-β-D-glucan in treatment groups demonstrated therapeutic responses with similarly lower levels in comparison to UC (P < .01) in both models. Host differences did not affect BAL fluid GMI or (1→3)-β-D-glucan but did affect galactomannan and (1→3)-β-D-glucan levels in serum. The higher serum GMI and (1→3)-β-D-glucan concentration-time-curves in UC-AraC correlated with extensive pulmonary infiltration by angioinvasive hyphae and minimal inflammation, while the lower concentration-time-curves in UC-CsA+M were associated with shorter and fewer hyphae in lung tissue and an intensive neutrophil response to Aspergillus hyphae. Thus, serum levels of galactomannan and (1→3)-β-D-glucan in IPA depended upon immunosuppression, which also affected severity of infection and hyphal morphology, while BAL fluid galactomannan and (1→3)-β-D-glucan were sensitive biomarkers not affected by host response.

Topics: Animals; Antifungal Agents; beta-Glucans; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Galactose; Host-Pathogen Interactions; Invasive Pulmonary Aspergillosis; Lung; Mannans; Proteoglycans; Rabbits

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these microbial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.

Topics: Animals; Asthma; beta-Glucans; Disease Models, Animal; Drug Resistance; Inflammation; Lipopolysaccharides; Mice, Knockout; Neutrophil Infiltration; Neutrophils; Pyroglyphidae; Steroids; Th17 Cells; Th2 Cells

Systemic rheumatic conditions are often accompanied by intraocular inflammatory disease (termed uveitis). Despite the frequent manifestation of uveitis with arthritis, very little is understood of the underlying mechanisms that mediate the eye's susceptibility to disease. The genetically susceptible SKG mouse strain develops arthritis that arises from an inherent mutation that disrupts T-cell antigen receptor signal transduction and thymic selection. The ensuing T-cell-mediated disease is further modulated through exposure to microbial triggers. The purpose of this study was to elucidate how a genetically determined shift in the T-cell repertoire toward self-reactive T cells that drive arthritis influences uveitis in SKG mice.. SKG mice (BALB/c mice that harbor the W163C point mutation in zeta-chain-associated protein kinase 70 [i.e., ZAP-70]) were housed under arthritis-resistant, specific pathogen-free conditions. Arthritis was induced by intraperitoneal injection with fungal glucans (zymosan or curdlan). Arthritis onset and severity were evaluated by clinical scoring, histopathology and infrared imaging within the joints. Periocular traits involving blepharoconjunctivitis were evaluated by clinical scoring and histology. Eyes were evaluated for signs of anterior uveitis using intravital videomicroscopy to document cell-trafficking responses within the iris vasculature and stroma and by histology to detect inflammatory infiltrate and tissue damage within the anterior and posterior eye segments.. Exposure to zymosan resulted in the predicted arthritic, sexually dimorphic phenotype in SKG mice. The eyes of SKG mice exhibited episodic intravascular cellular responses to zymosan or curdlan as indicated by significant increases in leukocyte-endothelium interactions akin to ocular vasculitis. However, despite the significant increase in early cell-trafficking responses, cellular infiltration into the iris stroma was not observed and histopathological signs indicative of a sustained uveitis were absent. Instead, eyes of SKG mice developed blepharoconjunctivitis that coincided with arthritis and exhibited sexual dimorphism.. This study underscores the complexity surrounding the pathogenesis of uveitis and its relationship with arthritis. The findings suggest that distinct mechanisms exist by which pathogenic autoimmune T cells target the eyes versus joints, which likely involves the environmental context but nonetheless should be taken into account in the identification and development of effective therapies for each organ.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; beta-Glucans; Disease Models, Animal; Disease Progression; Genetic Predisposition to Disease; Humans; Mice, Inbred BALB C; Mice, Knockout; Mutation, Missense; Severity of Illness Index; T-Lymphocytes; Time Factors; Uveitis; ZAP-70 Protein-Tyrosine Kinase; Zymosan

The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with β-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease.

Topics: Alveolar Bone Loss; Animals; beta-Glucans; Blood Glucose; Cholesterol; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Disease Models, Animal; Gingiva; Male; Osteoprotegerin; Periodontal Diseases; RANK Ligand; Rats; Rats, Wistar; Saccharomyces cerevisiae; Streptozocin; Triglycerides

Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. However, the role of IDO in immune responses against fungal corneal infection has not been investigated. To evaluate the regulatory mechanisms of IDO in fungal inflammation, we resorted to human corneal epithelial cells (HCECs), known as the first barrier of cornea against pathogenic microorganisms. We found that IDO was significantly up-regulated in corneal epithelium infected with Aspergillus fumigatus (A. fumigatus) and HCECs incubated with spores of A. fumigatus. Furthermore, IDO inhibitor (1-methyltryptophan, 1-MT) enhanced inflammatory cytokines IL-1β and IL-6 expression which were up-regulated by A. fumigatus spores infection. Dectin-1, as one of the important C-type lectin receptors, can identify β-glucan, and mediate fungal innate immune responses. In the present study, pre-treatment with curdlan, a Dectin-1 agonist, further enhanced IDO expression compared with A. fumigatus stimulation. While laminarin, the Dectin-1 specific inhibitor, partially inhibited IDO expression stimulated by A. fumigatus. Further studies demonstrated inhibition of IDO activity amplified the expressions of inflammatory cytokines IL-1β and IL-6 induced by activation of Dectin-1. These results suggested that IDO was involved in the immune responses of fungal keratitis. The activation of Dectin-1 may contribute to A. fumigatus spores-induced up-regulation of IDO.

Topics: Animals; Aspergillus fumigatus; beta-Glucans; Cytokines; Disease Models, Animal; Epithelium, Corneal; Female; Gene Expression; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Inflammation Mediators; Keratitis; Lectins, C-Type; Mice; RNA, Messenger

The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-β-D-glucan levels in serum, tissue burden reduction, and histopathology.

Topics: Animals; Antifungal Agents; Basidiomycota; beta-Glucans; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Immunocompromised Host; Kidney; Male; Mice, Inbred Strains; Microbial Sensitivity Tests; Mycoses; Neutropenia; Proteoglycans; Triazoles

The current standard of treatment of invasive candidiasis with echinocandins requires once-daily therapy. To improve quality of life, reduce costs, and improve outcome, we studied the pharmacokinetics (PK), efficacy, and safety of alternate dosing regimens of micafungin (MFG) for the treatment of experimental subacute disseminated candidiasis.. MFG was administered for 12 days starting 24 hours after intravenous inoculation of 1 × 10(3) Candida albicans blastoconidia. Study groups consisted of MFG at 1 mg/kg every 24 hours (MFG1), 2 mg/kg every 48 hours (MFG2), and 3 mg/kg every 72 hours (MFG3), and untreated controls. PK of MFG were determined on day 7 by high-performance liquid chromatography and modeled using nonparametric adaptive grid program. A 2-compartment PK model with volume of the central compartment (Vc), clearance (SCL), and the intercompartmental rate constants Kcp and Kpc was used. The fungal burden in 7 tissues was determined 312 hours after the initiation of therapy.. PK of MFG were linear and the parameter means ± SD were Vc = 0.41 ± 0.18 L, Kcp = 2.80 ± 1.55/hour, Kpc = 1.71 ± 0.93/hour, and SCL = 0.16 ± 0.003 L/hour (r(2) = 0.99). The area under the plasma drug concentration - time curve for MFG1, MFG2, and MFG3 was 198.7 ± 19.8, 166.3 ± 36.7, and 192.8 ± 46.2 mg × hour/L, respectively (P = .24). All treatment groups showed significant and comparable resolution of (1→3)-β-D-glucan levels and clearance of C. albicans from liver, spleen, kidney, brain, lung, vitreous humor, and vena cava in comparison to untreated controls (P ≤ .05). There were no differences in hepatic or renal function among study groups.. Less fractionated MFG regimens of every 48 and 72 hours are safe and as effective in experimental disseminated candidiasis as once-daily therapy in neutropenic hosts.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis; Candidiasis, Invasive; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Echinocandins; Female; Lipopeptides; Micafungin; Neutropenia; Proteoglycans; Rabbits

As a water-soluble extracellular β-glucan produced by Agrobacterium sp. ZX09, Salecan has an excellent toxicological profile and exerts multiple physiological effects. The aims of the present study were to investigate the protective effects of a Salecan diet in the well-defined dextran sulphate sodium (DSS) model of experimental murine colitis and to elucidate the mechanism involved in its effects with special attention being paid to its effect on the production of TNF-α, a primary mediator involved in the inflammatory response. Male C57BL/6J mice were fed a diet supplemented with either 4 or 8 % Salecan for 26 d and DSS was administered to induce acute colitis during the last 5 d of the experimental period. Several clinical and inflammatory parameters as well as mRNA expression of TNF-α and Dectin-1 were evaluated. The results indicated that the dietary incorporation of Salecan attenuated the severity of DSS colitis as evidenced by the decreased disease activity index, reduced severity of anaemia, attenuated changes in colon architecture and reduced colonic myeloperoxidase activity. This protection was associated with the down-regulation of TNF-α mRNA levels, which might derive from its ability to increase Dectin-1 mRNA levels. In conclusion, the present study suggests that Salecan contributes to the reduction of colonic damage and inflammation in mice with DSS-induced colitis and holds promise as a new, effective nutritional supplement in the management of inflammatory bowel disease.

Topics: Analysis of Variance; Animals; beta-Glucans; Colitis; Colon; Dextran Sulfate; Dietary Supplements; Disease Models, Animal; Down-Regulation; Inflammation; Intestinal Mucosa; Lectins, C-Type; Male; Mice; Mice, Inbred C57BL; Peroxidase; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha

Beta-glucans are naturally occurring polysaccharides that exert important immunostimulatory activities. In the present study, we evaluated whether beta-glucans could modulate the development and the course of systemic lupus erythematosus (SLE). To this aim, we employed the classical model of SLE represented by the F1 hybrid between the NZB and NZW mouse strains which develop severe lupus-like phenotypes comparable to that of SLE patients. The administration of beta-glucan was associated to a more aggressive development of the disease and a worse prognosis, as observed from the clinical, biochemical and histopathological data. This finding implies that restraint should be practised in the possible use of beta-glucans as immunomodulators in human therapy in the context of SLE.

Topics: Animals; beta-Glucans; Disease Models, Animal; Female; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; Prognosis; Severity of Illness Index; Species Specificity

Acremonium is an emerging fungal pathogen causing severe infections. We evaluated the virulence of three clinically relevant species within the genus, i.e., Acremonium kiliense (currently Sarocladium kiliense), Acremonium sclerotigenum-A. egyptiacum complex and Acremonium implicatum in a murine model of disseminated infection. Both immunocompetent and immunosuppresssed mice were infected with two inocula concentrations (2 × 10(6) and 2 × 10(8) conidia/animal) of two strains of each species. Tissue burden, mortality rate, histopathology and levels of (1→3)-β-D-glucan were used as virulence markers. None of the species of Acremonium tested was able to cause infection in immunocompetent mice. Conversely, severe infections were produced in immunocompromised mice, the spleen being the most affected organ. In general, the virulence of the Acremonium species tested was low, S. kiliense being the most virulent species.

Topics: Acremonium; Animal Structures; Animals; beta-Glucans; Colony Count, Microbial; Communicable Diseases, Emerging; Disease Models, Animal; Histocytochemistry; Humans; Male; Mice; Microscopy; Mycoses; Opportunistic Infections; Proteoglycans; Survival Analysis; Virulence

Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70(W163C)-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan).. Eight weeks after curdlan injection in wild-type or IL-17A(-/-) SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs.. In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22.. In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

Topics: Animals; Antibodies; beta-Glucans; Disease Models, Animal; Endoplasmic Reticulum Stress; Female; Ileitis; Immune Tolerance; Interleukin-17; Interleukin-22; Interleukin-23 Subunit p19; Interleukins; Intestinal Mucosa; Intestines; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Receptors, Interleukin; Spondylarthritis

Many pathogens produce the β-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from di

Topics: Animals; Animals, Newborn; Antibodies, Bacterial; Antibodies, Neutralizing; Antitoxins; beta-Glucans; Disease Models, Animal; Escherichia coli Infections; Escherichia coli Vaccines; Mice; Microbial Viability; Opsonin Proteins; Rabbits; Shiga Toxin; Shiga-Toxigenic Escherichia coli; Vaccines, Conjugate

Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly I:C, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1-dependent fashion. These CD103+ CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+ CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection.

Topics: Animals; beta-Glucans; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Dendritic Cells; Disease Models, Animal; Female; Humans; Lectins, C-Type; Mice; Mucous Membrane; Signal Transduction; T-Lymphocyte Subsets; Th2 Cells; Transforming Growth Factor beta

The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Cell Wall; Chitin; Colony Count, Microbial; Disease Models, Animal; Humans; Mice, Inbred BALB C; Neutropenia; Pneumonia; Virulence

Aspergillus fumigatus, a thermotolerant fungus, is the main causative agent of invasive pulmonary aspergillosis (IPA) in immunocompromised patients that is associated with high mortality rates. Early diagnosis of IPA is crucial for mortality reduction and improved prognosis. An experimental inhalational model of IPA was developed in rats and the efficacy of three biomarkers, namely β-D-glucan (BDG), a panfungal marker, galactomannan (GM), a genus-specific marker, and A. fumigatus DNA, a species-specific marker was evaluated in serum and bronchoalveolar lavage (BAL) specimens at different time points postinfection for early diagnosis of IPA. BDG and GM were detected by using commercial Fungitell and Platelia Aspergillus EIA kits, respectively. A. fumigatus DNA was detected by developing a sensitive, single-step PCR assay. IPA was successfully developed in immunosuppressed rats and all animals until 5 days post-infection were positive for A. fumigatus by culture and KOH-calcofluor microscopy also showed A. fumigatus in 19 of 24 (79%) lung tissue samples. Fourteen of 30 (47%) and 27 of 30 (90%) serum and BAL specimens, respectively, were positive for all three biomarkers with 100% specificity (none of sera or BAL specimens of 12 control rats was positive for biomarkers). Our data show that BAL is a superior specimen than serum and combined detection of BDG, GM and A. fumigatus DNA provide a sensitive diagnosis of IPA in an experimental animal model. Moreover, combined detection of GM and DNA in BAL and detection of either GM or DNA in serum was also positive in 27 of 30 (90%) animals. For economic reasons and considering that the positive predictive value of BDG is low, the detection of GM and/or DNA in serum and BAL samples has the potential to serve as an integral component of the diagnostic-driven strategy in high-risk patients suspected for IPA.

Topics: Animals; Aspergillus fumigatus; beta-Glucans; Biological Assay; Biomarkers; Bronchoalveolar Lavage; Disease Models, Animal; Female; Galactose; Immunocompromised Host; Inhalation; Invasive Pulmonary Aspergillosis; Lung; Mannans; Polymerase Chain Reaction; Rats; Rats, Wistar

Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.

Topics: Aerobiosis; Animals; beta-Glucans; Candida albicans; Candidiasis; Disease Models, Animal; Epigenesis, Genetic; Female; Glucose; Glycolysis; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunity, Innate; Immunologic Memory; Male; Mice; Mice, Inbred C57BL; Monocytes; Sepsis; Staphylococcal Infections; Staphylococcus aureus; TOR Serine-Threonine Kinases; Transcriptome

Probiotic bacteria have been associated with a reduction in cardiovascular disease risk, a leading cause of death and disability.. The aim of this study was to assess the impact of dietary administration of exopolysaccharide-producing probiotic Lactobacillus cultures on lipid metabolism and gut microbiota in apolipoprotein E (apoE)-deficient mice.. First, we examined lipid metabolism in response to dietary supplementation with recombinant β-glucan-producing Lactobacillus paracasei National Food Biotechnology Centre (NFBC) 338 expressing the glycosyltransferase (Gtf) gene from Pediococcus parvulus 2.6 (GTF), and naturally exopolysaccharide-producing Lactobacillus mucosae Dairy Product Culture Collection (DPC) 6426 (DPC 6426) compared with the non-β-glucan-producing isogenic control strain Lactobacillus paracasei NFBC 338 (PNZ) and placebo (15% wt:vol trehalose). Second, we examined the effects on the gut microbiota of dietary administration of DPC 6426 compared with placebo. Probiotic Lactobacillus strains at 1 × 10(9) colony-forming units/d per animal were administered to apoE(-/-) mice fed a high-fat (60% fat)/high-cholesterol (2% wt:wt) diet for 12 wk. At the end of the study, aortic plaque development and serum, liver, and fecal variables involved in lipid metabolism were analyzed, and culture-independent microbial analyses of cecal content were performed.. Total cholesterol was reduced in serum (P < 0.001; ∼33-50%) and liver (P < 0.05; ∼30%) and serum triglyceride concentrations were reduced (P < 0.05; ∼15-25%) in mice supplemented with GTF or DPC 6426 compared with the PNZ or placebo group, respectively. In addition, dietary intervention with GTF led to increased amounts of fecal cholesterol excretion (P < 0.05) compared with all other groups. Compositional sequencing of the gut microbiota revealed a greater prevalence of Porphyromonadaceae (P = 0.001) and Prevotellaceae (P = 0.001) in the DPC 6426 group and lower proportions of Clostridiaceae (P < 0.05), Peptococcaceae (P < 0.001), and Staphylococcaceae (P < 0.01) compared with the placebo group.. Ingestion of exopolysaccharide-producing lactobacilli resulted in seemingly favorable improvements in lipid metabolism, which were associated with changes in the gut microbiota of mice.

Topics: Animals; Apolipoproteins E; Atherosclerosis; beta-Glucans; Cholesterol; Diet; Dietary Supplements; Disease Models, Animal; Feces; Gastrointestinal Tract; Gene Expression Regulation, Enzymologic; Glycosyltransferases; Lactobacillus; Lipid Metabolism; Liver; Mice; Mice, Knockout; Microbiota; Pediococcus; Probiotics; Triglycerides; Vascular Cell Adhesion Molecule-1

Ischemia/reperfusion (IR) injury (IRI) in liver transplant patients may negatively affect graft function. Although β-glucan protects kidneys against IRI, its effect on the liver is unknown. This study sought to investigate β-glucan effects on oxidative damage to the liver after IRI in rats.. Thirty-two rats were randomly divided into 4 experimental groups n = 8 in each group: sham, IR, β-glucan and IR + β-glucan. β-Glucan (50 mg.kg(-1) . day(-1)) was orally administered for 10 days to rats in the β-glucan and IR + β-glucan groups. The rats in the IR and IR + β-glucan groups were subjected to ischemia and reperfusion (IR) for 60 minutes each. All rats were killed on day 11 to evaluate histological changes as well as tissue levels of oxidants and antioxidants.. Malondialdehyde (MDA) levels were significantly higher in the IR than the sham group (P = .001). MDA level was significantly higher in the IR group than in the IR + β-glucan group (P = .001). The levels of tissue antioxidant markers (superoxide dismutase [SOD], glutathione-peroxidase [GPx], and catalase [CAT]) were significantly lower in the IR group than in the sham group (P < .05). SOD and GPx levels did not differ significantly between the IR and IR + β-glucan groups. CAT activity was significantly higher in the IR than the IR + β-glucan group (P = .001). Histological tissue damage was reduced in the IR + β-glucan than the IR group.. Liver IRI is an inevitable problem during liver surgery. Our results suggested that β-glucan pretreatment suppressed oxidative stress and increased antioxidant levels in an rat model of liver IRI.

Topics: Administration, Oral; Animals; Antioxidants; beta-Glucans; Catalase; Disease Models, Animal; Glutathione Peroxidase; Liver; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase

Constipation is one of the most common gastrointestinal complaints with a highly prevalent and often chronic functional gastrointestinal disorder affecting health-related quality of life. The aim of the present study was to evaluate the effects of Salecan on fecal output and small intestinal transit in normal and two models of drug-induced constipation mice.. ICR mice were administrated intragastrically (i.g.) by gavage with 100, 200 and 300 mg/kg body weight (BW) of Salecan while the control mice were received saline. The constipated mice were induced by two types of drugs, loperamide (5 mg/kg BW, i.g.) and clonidine (200 μg/kg BW, i.g.), after Salecan treatment while the control mice were received saline. Number, weight and water content of feces were subsequently measured. Small intestinal transit was monitored by phenol red marker meal.. Salecan (300 mg/kg BW) significantly increased the number and weight of feces in normal mice. In two models of drug-induced constipation, Salecan dose-dependently restored the fecal number and fecal weight. The water content of feces was markedly affected by loperamide, but not by clonidine. Treatment with Salecan significantly raised the fecal water content in loperamide-induced constipation mice. Moreover, Salecan markedly stimulated the small intestinal transit in both loperamide- and clonidine-induced constipation model mice.. These results suggest that Salecan has a potential to be used as a hydrophilic laxative for constipation.

Topics: Animals; beta-Glucans; Clonidine; Constipation; Defecation; Disease Models, Animal; Dose-Response Relationship, Drug; Gastrointestinal Transit; Laxatives; Loperamide; Male; Mice; Mice, Inbred ICR; Treatment Outcome

RNA interference therapy utilizes physiological gene silencing that is originally found as a defense function against foreign RNAs. To silence the target gene, short double stranded RNA has to be delivered to cytosol. However, lack of a suitable delivering carrier is the major obstacle to practical usage. In this study, we present a novel complex consisting of β-1,3-glucan and short interference RNA (siRNA) as a solution for the problem. We used a β-1,3-glucan schizophyllan (SPG) and a siRNA (dA-siTNFα) that is designed to suppress tumor necrosis factor alpha (TNF-α), where the sense strand of siRNA has (dA(40)) tail to induce complexation with SPG. The dA-siTNFα/SPG complex showed higher affinity to recombinant dectin-1 than SPG itself, where dectin-1 is a β-1,3-glucan receptor expressed on antigen presenting cells and can be a target for specific delivery. The complex suppressed lipopolysaccharide (LPS)-induced TNF-α secretion by peritoneal macrophages in vitro. When the complex was intravenously injected, the oligonucleotide accumulated in liver; especially distributed into Kupffer cells. The complex significantly decreased the serum TNF-α level for the mouse model of LPS-induced acute hepatitis. This new siRNA delivery system may overcome the problem for RNA interference therapy because of its non-toxicity and high target specificity.

Topics: Acute Disease; Animals; beta-Glucans; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Hepatitis; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; RNA, Small Interfering; Structure-Activity Relationship; Tissue Distribution; Tumor Necrosis Factor-alpha

Cachexia, a negative prognostic factor, worsens a patient's quality of life. We established 2 novel cachexia models with the human stomach cancer cell line MKN-45, which was subcloned to produce potent cachexia-inducing cells by repeating the xenografts in immune-deficient mice. After subsequent xenografts, we isolated potent cachexia-inducing cells (MKN45cl85 and 85As2mLuc). Xenografts of MKN45cl85 cells in mice led to substantial weight loss and reduced adipose tissue and musculature volumes, whereas xenografts of 85As2mLuc cells resulted in highly metastatic and cachectic mice. Surgical removal of tumor tissues helped the mice regain body-weight in both mouse models. In vitro studies using these cells showed that isoflavones reduced their proliferation, implying that the isoflavones possess antiproliferative effects of these cancer cell lines. Isoflavone treatment on the models induced tumor cytostasis, attenuation of cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive tumor growth and weight loss. The inhibitory effects of tumor growth and weight loss by isoflavones were graded as soy isoflavone aglycone AglyMax > daidzein > genistein. These results demonstrated that the 2 novel cachectic mouse models appear useful for analyzing the mechanism of cancer cachexia and monitoring the efficacy of anticachectic agents.

Topics: Animals; beta-Glucans; Cachexia; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Female; Genistein; Humans; Isoflavones; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Stomach Neoplasms; Xenograft Model Antitumor Assays

We have evaluated the in vitro activity of caspofungin against 36 wild-type strains of Candida parapsilosis sensu stricto using 3 techniques: broth microdilution, disk diffusion, and the determination of minimal fungicidal concentration (MFC). The first 2 methods showed a good in vitro activity of caspofungin, but the MFCs were ≥2 dilutions above their corresponding MICs. In a murine model of disseminated infection, we evaluated the efficacy of caspofungin at 5 mg/kg against 8 strains of C. parapsilosis representing different degrees of in vitro susceptibility (0.12-1 μg/mL). All the isolates responded to treatment and (1→3)-β-D-glucan levels were reduced in all the cases; however, the study revealed differences among isolates, since caspofungin reduced the tissue burden of mice infected with isolates with MICs ≤0.5 μg/mL but was less effective against those with MICs of 1 μg/mL.

Topics: Animals; beta-Glucans; Candida; Candidiasis; Caspofungin; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Proteoglycans; Treatment Outcome

To determine the impact of β-1,3-glucan isolated from Euglena gracilis on corneal epithelial cell migration and on wound healing in a rat alkali burn model.. Immortalized human corneal epithelial cells (HCECs) were cultured in media with 50, 100 and 200 μg/mL laminarin (β-1,3- and β-1,6-glucans), β-1,3-glucan and hyaluronic acid (HA)-conjugated β-1,3-glucan; Dulbecco's modified Eagle's medium (DMEM)/nutrient mixture F-12 (negative control) and serum containing DMEM/nutrient mixture F-12 (positive control). Migration assays were conducted via the manual scraping of HCECs. Next, alkali injuries were induced using 1 N NaOH in 40 eyes of 40 Sprague-Dawley male rats. The injury-only group (n = 10) received topical phosphate-buffered saline four times a day for 2 d. The study groups received 200 μg/mL topical laminarin (n = 10), β-1,3-glucan (n = 10) and β-1,3-glucan HA (n = 10). Using slit-lamp biomicroscopy, injured corneas were evaluated in terms of re-epithelialization and opacity, and tissue sections were histologically analyzed.. Migration assay rates were enhanced as laminarin and β-1,3-glucan increased, compared to negative control cells (all p < 0.05). In the comparison between β-1,3-glucan and its HA conjugate form, β-1,3-glucan-HA showed more enhanced migration rate than β-1,3-glucan (p < 0.05). In rat alkali burn model, wound-healing ratio was greatest in β-1,3-glucan-HA groups (96.0 ± 4.1%), followed by β-1,3-glucan (86.0 ± 6.5%), laminarin (67.0 ± 7.5%) and injury-only group (54.0 ± 6.5%) (p < 0.0001; ANOVA). The opacity score was also lowest in β-1,3-glucan-HA groups (3.0 ± 0.75), followed by β-1,3-glucan (3.4 ± 0.5), laminarin (3.7 ± 0.8) and injury-only group (4.7 ± 0.46) (p < 0.0001; ANOVA) Histologically, relatively fewer polymorphonuclear leukocytes infiltrated the corneal stroma in the β-1,3-glucan and β-1,3-glucan-HA groups, compared to the injury-only group.. β-1,3-Glucan, particularly when conjugated with HA, promoted epithelial wound healing in vitro and suppressed the acute inflammatory reaction in corneal alkali burns.

Topics: Adjuvants, Immunologic; Alkalies; Animals; beta-Glucans; Burns, Chemical; Cell Line, Transformed; Cell Movement; Corneal Opacity; Disease Models, Animal; Epithelium, Corneal; Euglena gracilis; Eye Burns; Humans; Male; Rats; Rats, Sprague-Dawley; Wound Healing

Nonalcoholic steatohepatitis (NASH) is part of the spectrum of nonalcoholic fatty liver disease. However, there are few suitable animal models to study the pathogenesis of NASH or very limited advances in the prevention. Our aims were to establish a mouse model of NASH by intraperitoneally injecting lipopolysaccharide (LPS) at a dose of 1.5 mg per kg body weight per day for 6 weeks and to investigate the potential inhibitory effects of oat β-glucan (1%, 5%, or 10%) added to a specific pathogen-free diet. Intraperitoneal injection of LPS for 6 weeks increased serum LPS levels; decreased serum glucagon-like peptide-2 levels; triggered abnormal aminotransferase activity, glucose intolerance, and insulin resistance; and increased hepatic proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-1β), triglyceride, and malonyl dialdehyde levels; but reduced hepatic superoxide dismutase activity. Histologic evaluation revealed evidence of hepatic steatosis, inflammation, and mild necrosis in LPS-treated mice. Dietary supplementation of oat β-glucan prevented most of the LPS-induced metabolic disorders, and improved hepatic steatosis and inflammation, although a dose-dependent effect was not observed. In conclusion, oat β-glucan could inhibit LPS-induced NASH in mice.

Topics: Animals; Avena; beta-Glucans; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxemia; Fatty Liver; Glucagon-Like Peptide 2; Glucose Intolerance; Inflammation; Insulin Resistance; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Liver; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Superoxide Dismutase; Transaminases; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

Aspergillus fumigatus is the most common cause of invasive mold disease in humans. The mechanisms underlying the adherence of this mold to host cells and macromolecules have remained elusive. Using mutants with different adhesive properties and comparative transcriptomics, we discovered that the gene uge3, encoding a fungal epimerase, is required for adherence through mediating the synthesis of galactosaminogalactan. Galactosaminogalactan functions as the dominant adhesin of A. fumigatus and mediates adherence to plastic, fibronectin, and epithelial cells. In addition, galactosaminogalactan suppresses host inflammatory responses in vitro and in vivo, in part through masking cell wall β-glucans from recognition by dectin-1. Finally, galactosaminogalactan is essential for full virulence in two murine models of invasive aspergillosis. Collectively these data establish a role for galactosaminogalactan as a pivotal bifunctional virulence factor in the pathogenesis of invasive aspergillosis.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Carbohydrate Epimerases; Cell Line; Disease Models, Animal; Fungal Polysaccharides; Fungal Proteins; Humans; Hyphae; Lectins, C-Type; Mice; Polysaccharides; Virulence Factors

Saving the zone of stasis is one of the major goals of burn specialists. Increasing the tissue tolerance to ischaemia and inhibiting inflammation have been proposed to enable salvage of this zone. After a burn, excessive inflammation, including increased vascular permeability, local tissue oedema and neutrophil activation, causes local tissue damage by triggering vascular thrombosis and blocking capillaries, resulting in tissue ischaemia and necrosis. Oxygen radicals also contribute to tissue damage after a burn. However, macrophages play a pivotal role in the response to burn. We studied β-glucan because of its many positive systemic effects that are beneficial to burn healing, including immunomodulatory effects, antioxidant effects (free-radical scavenging activity) and effects associated with the reduction of the inflammatory response. There were four test groups in this study with eight rats in each group. Group 1 was the control group, group 2 was administered a local pomade (bacitracin+neomycin sulphate), group 3 received β-glucan (50 mg kg(-1), orally) + the local pomade and group 4 received β-glucan. Burns were created using a brass comb model. Macroscopic, histopathological and statistical assessments were performed. Samples were harvested on the 3rd, 7th and 21 days for analysis. The neutrophilic infiltration into the zone of stasis was analysed on day 3. Macrophage infiltration, fibroblast proliferation, angiogenesis and re-epithelialisation ratios in the zone of stasis were analysed on days 7 and 21. The β-glucan groups (groups 3 and 4) exhibited lower neutrophil counts on the 3rd day, and macrophage infiltration, fibroblast proliferation, angiogenesis and re-epithelialisation were very high in these groups on the 7th day. In particular, re-epithelialisation on the 21st day was significantly better in the β-glucan groups. This study demonstrated that β-glucan may prevent neutrophil-dependent tissue damage and burn-induced oxidative injury through its anti-inflammatory and antioxidant properties. We speculate that the inhibition of neutrophil activation preserves vascular patency by preventing capillary blockage. β-Glucan is also a powerful macrophage stimulator, and is therefore very effective in saving the zone of stasis.

Topics: Analysis of Variance; Animals; Antioxidants; beta-Glucans; Burns; Disease Models, Animal; Ischemia; Male; Neutrophils; Rats; Rats, Sprague-Dawley; Skin

Infection by the human fungal pathogen Aspergillus fumigatus induces hypoxic microenvironments within the lung that can alter the course of fungal pathogenesis. How hypoxic microenvironments shape the composition and immune activating potential of the fungal cell wall remains undefined. Herein we demonstrate that hypoxic conditions increase the hyphal cell wall thickness and alter its composition particularly by augmenting total and surface-exposed β-glucan content. In addition, hypoxia-induced cell wall alterations increase macrophage and neutrophil responsiveness and antifungal activity as judged by inflammatory cytokine production and ability to induce hyphal damage. We observe that these effects are largely dependent on the mammalian β-glucan receptor dectin-1. In a corticosteroid model of invasive pulmonary aspergillosis, A. fumigatus β-glucan exposure correlates with the presence of hypoxia in situ. Our data suggest that hypoxia-induced fungal cell wall changes influence the activation of innate effector cells at sites of hyphal tissue invasion, which has potential implications for therapeutic outcomes of invasive pulmonary aspergillosis.

Topics: Anaerobiosis; Animals; Aspergillus fumigatus; beta-Glucans; Cell Wall; Cytokines; Disease Models, Animal; Hyphae; Immunity, Innate; Lectins, C-Type; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Pulmonary Aspergillosis

The soluble fiber β-glucan, a natural component of barley, has been shown to lower the postprandial glucose response and is thought to improve insulin resistance.. This study examined the effect of chronic consumption of the high β-glucan barley flour on glucose control, liver lipids and markers of muscle fatty acid oxidation in the Zucker diabetic fatty (ZDF) rat. Two groups of ZDF rats were fed diets containing either 6% β-glucan in the form of barley flour or cellulose as a control for 6 weeks. A group of Zucker lean rats served as a negative control.. The barley flour group had an increased small intestinal contents viscosity compared to the obese control group. After 6 weeks, the barley flour group had reduced glycated hemoglobin, lower relative kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Fasting plasma adiponectin levels increased in the barley flour group and were not different than the lean control group. ZDF rats on the barley flour diet had lower relative epididymal fat pad weights than the obese control and a greater food efficiency ratio. The barley flour group also had reduced liver weights and a decreased concentration of liver lipids. The barley flour group had significantly higher concentrations of muscle acylcarnitines, a metabolite generated during fatty acid oxidation.. These results show that chronic consumption of β-glucans can improve glucose control and decrease fatty liver in a model of diabetes with obesity.

Topics: Adiponectin; Animals; beta-Glucans; Blood Glucose; Body Weight; Carnitine; Cholesterol; Diabetes Mellitus, Type 2; Dietary Fiber; Disease Models, Animal; Fatty Acids, Nonesterified; Fatty Liver; Flour; Glucose Tolerance Test; Hordeum; Insulin; Insulin Resistance; Intestine, Small; Ketones; Liver; Obesity; Organ Size; Postprandial Period; Rats; Rats, Zucker; Thiobarbituric Acid Reactive Substances; Triglycerides

The aim of this study was to evaluate and characterize the therapeutic potential of curdlan, a naturally occurring β-glucan immunomodulator, against visceral leishmaniasis, a fatal parasitic disease. Curdlan eliminated the liver and spleen parasite burden in a 45-day BALB/c mouse model of visceral leishmaniasis at a dosage of 10 mg/kg/day as determined by Giemsa-stained organ impression smears. Curdlan was associated with production of the disease-resolving T-helper (Th) 1 and Th17-inducing cytokines interleukin (IL)-6, IL-1β, and IL-23, as well as with production of Th17 cytokines IL-17 and IL-22, as determined by enzyme-linked immunosorbent assay (ELISA) and real time polymerase chain reaction (RT-PCR). Reversal of curdlan-mediated protection by anti-IL-17 and anti-IL-23 monoclonal antibodies showed the importance of Th17 cytokines. Significantly decreased production of both IL-17 and IL-22 by mice that received anti-IL-23 antibody suggested the essential role of IL-23 in Th17 differentiation. Although administration of recombinant IL-17 or IL-23 caused significant suppression of the organ parasite burden, with marked generation of interferon γ and nitric oxide (NO), effects were much faster for IL-17. These results documented that although both IL-23 and IL-17 play major roles in the antileishmanial effect of curdlan, the effect of IL-23 may occur indirectly, through the induction of IL-17 production.

Topics: Animals; Antibodies, Monoclonal; beta-Glucans; Disease Models, Animal; Immunologic Factors; Interferon-gamma; Interleukin-1; Interleukin-17; Interleukin-1beta; Interleukin-22; Interleukin-23; Interleukins; Leishmania donovani; Leishmaniasis, Visceral; Macrophages; Mice; Mice, Inbred BALB C; Nitric Oxide; Th1 Cells; Th17 Cells

Mastitis, caused by mammary pathogenic bacteria which are frequent implications of Escherichia coli, is an important disease affecting women and dairy animals worldwide. The β-glucan binding of dectin-1 can induce its own intracellular signaling and can mediate a variety of cellular responses. This work was to investigate the effect of β-glucan on the lipopolysaccharide (LPS)-induced inflammatory response and related innate immune signaling in primary rat mammary epithelial cells. Cells were treated with serum-free medium added with a DMSO solution containing β-glucans at concentrations of 0, 1, 5, 25 μmol/L for 12h, and then exposed to 10 μg/mL LPS for 40 min. Moreover, cells were pretreated with BAY 11-7082 to inhibit NF-κB and then successively exposed to 5 μmol/L β-glucan, 10 μg/mL LPS, 5 μmol/L β-glucan and 10 μg/mL LPS, according to the specific experimental design. Normal control cultures contained an equal volume of DMSO, which was collected at the same time. After incubating rat mammary epithelial cells for 40 min with 10 μg/mL LPS, TLR4, MyD88 and NF-κB expression all increased (P<0.05), as did the secretion of TNF-α and IL-1β (P<0.05), but IκB and β-casein expression both decreased (P<0.05). Treatment with different concentrations of β-glucan for 12h activated Dectin1/Syk, which subsequently suppressed TLR4, MyD88 and NF-κB expression and TNF-α and IL-1β secretion. However, it restored the IκB and β-casein expression that had been induced by the 40 min incubation with 10 μg/mL LPS. Pretreatment with BAY 11-7082 at 10 µmol/L for 2h partially prevented NF-κB induction by LPS, but the presence of β-glucan prevented this inactivation. BAY 11-7082 could not simultaneously inhibit LPS induction of TLR4, MyD88 and β-glucan activation of Dectin1/Syk in rat mammary epithelial cells. These findings demonstrated that β-glucan activation of Dectin1/Syk attenuated LPS induction of TLR4/MyD88/NF-κB and inhibited the LPS-induced inflammation factors in mammary epithelial cells, thereby providing a possibly protective effect of β-glucan in the prevention of LPS-induced dysfunction in mammary epithelial cells.

Topics: Animals; Anti-Inflammatory Agents; beta-Glucans; Cells, Cultured; Disease Models, Animal; Epithelial Cells; Female; Immunity, Innate; Interleukin-1beta; Lectins, C-Type; Lipopolysaccharides; Mammary Glands, Animal; Mastitis; Myeloid Differentiation Factor 88; NF-kappa B; Nitriles; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Signal Transduction; Sulfones; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

We compared the rate and extent of anidulafungin's and fluconazole's activity in neutropenic and non-neutropenic mice with Candida albicans invasive candidiasis. In immunocompetent mice, anidulafungin significantly improved survival vs. controls and fluconazole, and significant reductions in (1→3)-β-D-glucan and fungal burden were observed. In neutropenic animals, the highest doses of anidulafungin (5 mg/kg) and fluconazole (10 mg/kg) also improved survival and reduced fungal burden. However, there were no differences in survival between these antifungals as anidulafungin's activity was attenuated in this model. These results demonstrate that the extent of anidulafungin in vivo efficacy may be dependent on host immune status.

Topics: Anidulafungin; Animals; Antifungal Agents; beta-Glucans; Blood; Blood Chemical Analysis; Candida albicans; Candidiasis, Invasive; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Fluconazole; Mice; Mice, Inbred ICR; Neutropenia; Proteoglycans; Survival Analysis; Treatment Outcome

We developed and assessed the diagnostic value of a novel quantitative nested real-time (QNRT) PCR assay targeting the internal transcribed spacer region of ribosomal DNA (rDNA) in a guinea pig model of invasive pulmonary aspergillosis. Groups of 5 immunosuppressed animals that were infected using an aerosol chamber with Aspergillus fumigatus conidia were humanely terminated 1 h postinoculation and at days 3, 5, 7, and 11 postchallenge, and lung tissue, bronchoalveolar lavage (BAL) fluid, whole blood, and serum samples were collected. The QNRT PCR results obtained with the serum and BAL fluid were compared to those achieved with galactomannan and (1→3)-β-d-glucan assays. High fungal burden levels were detected by QNRT PCR in both lung tissue and BAL fluid in all infected animals at each time point, and the sensitivity of each assay in BAL fluid was 100% by day 3 and remained so through the remainder of the study. The sensitivity of detection of fungi in whole blood and serum samples was significantly lower, and some samples remained negative by all three assays despite the advanced stage of the infection. From these data, we can conclude that this novel QNRT PCR method was highly sensitive for the detection of A. fumigatus from different types of samples in this model. In addition, BAL fluid samples appeared to be the most suitable for the early diagnosis of invasive pulmonary aspergillosis. When testing serum, the use of a combination of available assays may increase the possibility of early detection of this opportunistic mycosis.

Topics: Animals; Aspergillus fumigatus; beta-Glucans; Bronchoalveolar Lavage Fluid; Colony Count, Microbial; Disease Models, Animal; DNA, Fungal; DNA, Ribosomal Spacer; Galactose; Guinea Pigs; Invasive Pulmonary Aspergillosis; Lung; Male; Mannans; Mycology; Polymerase Chain Reaction; Proteoglycans; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

We previously reported a cardioprotective effect of oral β-glucan in patients who underwent coronary artery bypass grafting. The present study was conducted to determine whether oral β-glucan could reduce myocardial infarction size and whether these changes would be reflected by better preservation of contractile indices measured by speckle tracking echocardiography (STE).. Fourteen pigs were randomized to receive oral β-glucan 50 mg/kg (n = 7) or placebo (control, n = 7) 10 days before they were anaesthetized and subjected to 1 h clamping of the left anterior descending coronary artery followed by reperfusion for 3 h. Longitudinal strain, circumferential strain and radial strain were assessed by STE after 3 h of reperfusion. Infarction size and area at risk were determined by Evans blue and 2,3,5-triphenyltetrazolium chloride staining.. Pretreatment with β-glucan reduced the infarct area/area at risk ratio by 36% (P < 0.05) and the total necrotic area of the left ventricle by 37% (P < 0.05) compared with controls. Viable myocardium at risk was 30% higher in the β-glucan vs. control group (P < 0.05). Anterior apical strain values for β-glucan vs. control were -4.7 ± 9.4 vs. 5.9 ± 6.1% (P < 0.05) for longitudinal strain, -14.7 ± 6.6 vs. -7.7 ± 4.3 (P < 0.05) for circumferential strain, 15.1 ± 7.7 vs. 7.1 ± 11.8 (ns) for radial strain.. Oral β-glucan pretreatment reduces infarction size and improves regional contractile function in a porcine ischaemia/reperfusion model.

Topics: Administration, Oral; Animals; beta-Glucans; Body Temperature; Disease Models, Animal; Drug Evaluation, Preclinical; Feasibility Studies; Hemodynamics; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Sus scrofa; Ultrasonography

The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407-treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL(1-3)-C subfractions) and very low-density lipoprotein-C (VLDL-C) (VLDL(1-2)-C and VLDL(3-5)-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL(2)-C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL(1-3)-C subfraction), and the LDL(1-3)-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P-407.

Topics: Animals; Atorvastatin; beta-Glucans; Biomarkers; Cholesterol, LDL; Disease Models, Animal; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Lipoproteins; Lipoproteins, LDL; Liver; Male; Matrix Metalloproteinases; Mice; Mice, Inbred ICR; Poloxamer; Pyrroles; Scattering, Small Angle; Time Factors; Triglycerides; X-Ray Diffraction

The object of this study was to assess the efficacy of Polycan from Aureobasidium pullulans SM-2001, which is composed mostly of beta-1,3-1,6-glucan, on osteoarthritis (OA)-induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT&PMM). Three different dosages of Polycan (85, 42.5, and 21.25 mg/kg) were orally administered once a day for 84 days to male rats a week after ACLT&PMM surgery. Changes in the circumference and maximum extension angle of each knee, and in cartilage histopathology were assessed using Mankin scores 12 weeks after Polycan administration. In addition, cartilage proliferation was evaluated using bromodeoxyuridine (BrdU). As the result of ACLT&PMM, classic OA was induced with increases in maximum extension angles, edematous knees changes, and capsule thickness, as well as decreases in chondrocyte proliferation, cartilages degenerative changes, and loss of articular cartilage. However, these changes (except for capsule thickness) were markedly inhibited in all Polycan- and diclofenac sodium-treated groups compared with OA control. Although diclofenac sodium did not influence BrdU uptake, BrdU-immunoreactive cells were increased with all dosages of Polycan, which means that Polycan treatment induced proliferation of chondrocytes in the surface articular cartilage of the tibia and femur. The results obtained in this study suggest that 84 days of continuous oral treatment of three different dosages of Polycan led to lesser degrees of articular stiffness and histological cartilage damage compared with OA controls 91 days after OA inducement, suggesting that the optimal Polycan dosage to treat OA is 42.5 mg/kg based on the present study.

Topics: Administration, Oral; Animals; Anterior Cruciate Ligament; Anti-Inflammatory Agents, Non-Steroidal; Ascomycota; beta-Glucans; Cartilage; Diclofenac; Disease Models, Animal; Histocytochemistry; Menisci, Tibial; Microscopy; Osteoarthritis; Rats; Treatment Outcome

Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain associated with altered bowel habits. Since the prevalence of IBS is very high and thus, involves elevated health-care costs, treatment of this condition by methods other than prescribed medicines could be beneficial. β-(1,3)-D-glucan with β-(1,6) branches (β-glucan) has been used as a nutritional supplement for many years. In this study, we examined the effect of β-glucan on fecal pellet output and visceral pain response in animal models of IBS. Oral administration of β-glucan suppressed the restraint stress- or drug-induced fecal pellet output. β-Glucan also suppressed the visceral pain response to colorectal distension. These results suggest that β-glucan could be beneficial for the treatment and prevention of IBS.

Topics: Administration, Oral; Animals; Colon; Disease Models, Animal; Glucans; Irritable Bowel Syndrome; Mice; Mice, Inbred C57BL

The objective of this study is to detect the effect of beta-glucan derived from Aureobasidium pullulans SM-2001, a UV induced mutant of A. pullulans on the ovalbumin (OVA) induced allergic asthma. The test articles were orally administered to OVA-inducing asthmatic mice 4 days after sensitization for 13 days at 31.25, 62.5 or 125 mg/kg levels. Three days after the OVA sensitization, ten mice were selected per group based on body weight and were sacrificed three days after the OVA aerosol challenge. The changes on the body weight, lung weight, total leukocytes in peripheral blood and total cells in bronchoalveolar lavage fluid (BALF) were observed with changes on the lung histopathology and histomorphometry. The results were compared with dexamethasone (DEXA) 3 mg/kg intraperitoneally treated mice. The results showed increases of body weight after the OVA aerosol challenge, lung weight, total leukocytes and eosinophils in peripheral blood, total cell numbers, neutrophil and eosinophils in BALF were detected in the OVA control compared to sham control (non-OVA). However, these changes from asthmatic responses were significantly or dose-dependently decreased in the beta-glucan-dosing groups compared to those of the OVA control. Therefore, it is concluded that beta-glucan has favorable effects on asthmatic response induced by OVA. It was found that beta-glucan 125 mg/kg showed similar or slightly lower efficacy compared with DEXA 3 mg/kg.

Topics: Animals; Anti-Asthmatic Agents; Ascomycota; Asthma; beta-Glucans; Body Weight; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glucocorticoids; Leukocyte Count; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

Zymosan was hydrolysed with HCl and fractionated by ultrafiltration and dialysis to obtain water-soluble fragments A, B and C. Physical and chemical analyses showed that these fractions are composed primarily of glucose and have molecular weights of 8 kDa, 5 kDa and 2 kDa, respectively. A glycosidic linkage analysis indicated that they are mainly composed of β-1,3-glucans. Fragment A, which has the highest molecular weight, contains approximately 30% β-1,6-linked glucans, but fragment C is almost entirely composed of linear β-1,3-glucan chains. The anti-chronic atrophic gastritis activity experiments showed that fragment A has significant activity, the activity of zymosan is quite low and the activities of fragments B and C are in between those of fragment A and zymosan.

Topics: Animals; beta-Glucans; Bile; Chromatography, Gel; Chronic Disease; Disease Models, Animal; Gastric Mucosa; Gastritis, Atrophic; Immunization; Inflammation; Molecular Weight; Rats; Rats, Wistar; Swine; Zymosan

No one single pathogen has been identified as the causative agent of multiple sclerosis (MS). Alternately, the likelihood of an autoimmune event may be nonspecifically enhanced by different infectious agents. In a novel animal model of MS, SJL/J mice primed through infection with a recombinant vaccinia virus (VV) encoding myelin proteolipid protein (PLP) (VV(PLP)) were susceptible to a central nervous system (CNS) inflammatory disease following administration of a nonspecific immunostimulant [complete Freund's adjuvant (CFA) plus Bordetella pertussis (BP)]. Mononuclear cells isolated from the brains, but not the spleens, of VV(PLP)-primed CFA/BP challenged mice produced interleukin (IL)-17 and interferon-γ and transferred a CNS inflammatory disease to naïve SJL/J mice. Administration of curdlan, a T helper 17 cell inducer, unexpectedly resulted in less severe clinical and histological signs of disease, compared to CFA/BP challenged mice, despite the induction of IL-17 in the periphery. Further examination of the VV(PLP)-prime CFA/BP challenge model may suggest new mechanisms for how different pathogens associated with MS can protect or enhance disease.

Topics: Adjuvants, Immunologic; Animals; beta-Glucans; Brain; Disease Models, Animal; Female; Genetic Vectors; Immunomodulation; Interferon-gamma; Interleukin-17; Leukocytes, Mononuclear; Mice; Multiple Sclerosis; Myelin Proteolipid Protein; Organ Specificity; Polysaccharides, Bacterial; Rats; Recombinant Proteins; Severity of Illness Index; Spleen; Vaccinia virus

Pretreatment with β-glucan has been shown to protect against regional ischemia-reperfusion injury, through inhibition of myocardial NF-κB activation. The aim was to examine whether β-glucan pretreatment could protect against the global ischemia-reperfusion injury, which is encountered in the clinical setting during open heart surgery.. Twenty-one pigs were randomized to pretreatment with oral β-glucan (SBGo, n = 7), pretreatment with i.p. β-glucan (SBGip, n = 7), and untreated controls (n = 7). The pigs were subjected to cardiopulmonary bypass (CPB) with 1 h of global cardioplegic ischemia followed by wean from CPB and reperfusion for 4 h. Cardiac function was determined by a conductance catheter, and troponin T was sampled from the coronary sinus. Atrial biopsies obtained at baseline, following 30 min, and 3 h of reperfusion were analyzed for phosphorylated NF-κB by Western blot.. Following reperfusion, phosphorylated NF-κB increased by 210% in the control group, 197% in the SBGo group, but was reduced by 5% in the SBGip group (P < 0.01 versus control). After 4 h of reperfusion, preload recruitable stroke work dropped by 19% in the control group and 25% in the SBGo group compared with 60% in the SBGip group (P < 0.01 versus control). The area under the curve for troponin T was larger in the SBGip group compared with the control group (P < 0.05) and the SBGo group (P < 0.01).. Inhibition of NF-κB activation by i.p. β-glucan does not protect against ischemia-reperfusion injury in pigs subjected to global ischemia and reperfusion, and may be associated with aggravation of ischemia-reperfusion injury.

Topics: Animals; beta-Glucans; Cardiopulmonary Bypass; Coronary Sinus; Disease Models, Animal; Heart Arrest, Induced; Myocardial Reperfusion Injury; NF-kappa B; Phosphorylation; Proto-Oncogene Proteins c-akt; Sus scrofa; Treatment Failure; Troponin T; Ventricular Function, Left

Activation of pattern recognition receptors (PRR) may contribute to arthritis. Here, we elucidated the role of NOD2, a genetic cause of inflammatory arthritis, and several other PRR in a murine model of inflammatory arthritis.. The roles of CR3, TLR2, MyD88, NOD1, NOD2, Dectin-1 and Dectin-2 were tested in vivo in arthritis elicited by intra-articular injections of zymosan, the fungal cell wall components curdlan, laminarin and mannan, and the bacterial cell wall peptidoglycan.. Dectin-1, and to a lesser extent Dectin-2, contributed to arthritis. TLR2, MyD88 and CR3 played non-essential roles. Observations based on injection of curdlan, laminarin or mannan supported the dominant role of the Dectin-1 pathway in the joint. We demonstrated differential roles for NOD1 and NOD2 and identified NOD2 as a novel and essential mediator of zymosan-induced arthritis.. Together, Dectin-1 and NOD2 are critical, sentinel receptors in the arthritogenic effects of zymosan. Our data identify a novel role for NOD2 during inflammatory responses within joints.

Topics: Animals; Arthritis, Experimental; beta-Glucans; Cathepsins; Disease Models, Animal; Immunity, Innate; Joints; Lectins, C-Type; Membrane Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Nod2 Signaling Adaptor Protein; Signal Transduction; Toll-Like Receptors; Zymosan

β-Glucan is known to have anti-inflammatory properties, and several studies have demonstrated the beneficial effects of dietary β-glucan on inflammatory bowel disease (IBD). However, it is unknown how β-glucan mediates its protective effects on IBD. Therefore, we used a well-established mouse model for IBD, interleukin (IL)-10(-/-) mice, to explore the protective effects of β-glucan on IBD-like symptoms caused by IL-10 deficiency. The mice were divided into two groups: IL-10(-/-) and IL-10(-/-) + β-glucan treatment groups. IL-10(-/-) mice treated with dietary β-glucan exhibited less inflammation within the colon. The levels of immunoglobulins A and E were lower in the serum, spleen, mesenteric lymph nodes, and Peyer's patches in the IL-10(-/-) mice compared with the IL-10(-/-) + β-glucan mice. Also, the expression of pro-inflammatory cytokines was lower in the IL-10(-/-) + β-glucan mice compared with the IL-10(-/-) mice. Histological analysis also revealed that administration of dietary β-glucan in IL-10(-/-) mice reduced colonic tissue damage. Finally, the expression of the pro-inflammatory cytokine tissue necrosis factor-α was significantly lower with dietary β-glucan treatment in IL-10(-/-) mice. In conclusion, dietary β-glucan reduces the inflammation associated with IBD caused by IL-10 deficiency.

Topics: Animals; beta-Glucans; Blotting, Western; Colon; Diet; Disease Models, Animal; Immunoglobulin A; Immunoglobulin E; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Male; Mice; Mice, Knockout; Peyer's Patches

In this study, the effects of melatonin or beta-glucan treatments on tumor growth, pro-oxidant, and antioxidant status in tumor tissue were investigated in Dunning 3327 MatLyLu prostatic adenocarcinoma model. Prostate cancer (PCa) was induced by single intradermal injection of 2 x 10(4) MatLyLu cells into the right hind leg of Copenhagen rats. Melatonin (10 mg/kg/daily; IP) or beta-glucan (50 mg/kg/daily; orally) treatments applied alone and together continued for 39 days. Melatonin or beta-glucan treatments alone or together inhibited tumor growth and decreased malondialdehyde (MDA) levels in tumor tissues of Dunning rats. However, there were no significant differences in tumor volumes and MDA levels among treatment groups. Melatonin and melatonin + beta-glucan treatments elevated glutathione (GSH) levels and superoxide dismutase, glutathione peroxidase, and glutathione transferase activities in tumor tissues. However, beta-glucan treatment did not influence GSH levels and antioxidant enzyme activities in tumor tissue of Dunning rats. These results indicate that melatonin and beta-glucan treatments alone or together inhibit tumor progression and oxidative stress in tumor tissues of rats with Dunning PCa.

Topics: Adenocarcinoma; Animals; Antioxidants; beta-Glucans; Blotting, Western; Disease Models, Animal; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Lipid Peroxidation; Male; Malondialdehyde; Melatonin; Oxidative Stress; Prostatic Neoplasms; Rats; Superoxide Dismutase; Tumor Cells, Cultured

Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express beta -1,3-D-glucan synthetase and contain abundant beta -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of beta -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased beta -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens.

Topics: Animals; beta-Glucans; Disease Models, Animal; Echinocandins; Fluorescent Dyes; Lung; Mice; Pneumonia, Pneumocystis; Proteoglycans; Rats

The polysaccharide beta-1,6-glucan is a major component of the cell wall of Cryptococcus neoformans, but its function has not been investigated in this fungal pathogen. We have identified and characterized seven genes, belonging to the KRE family, which are putatively involved in beta-1,6-glucan synthesis. The H99 deletion mutants kre5Delta and kre6Deltaskn1Delta contained less cell wall beta-1,6-glucan, grew slowly with an aberrant morphology, were highly sensitive to environmental and chemical stress and were avirulent in a mouse inhalation model of infection. These two mutants displayed alterations in cell wall chitosan and the exopolysaccharide capsule, a primary cryptococcal virulence determinant. The cell wall content of the GPI-anchored phospholipase B1 (Plb1) enzyme, which is required for cryptococcal cell wall integrity and virulence, was reduced in kre5Delta and kre6Deltaskn1Delta. Our results indicate that KRE5, KRE6 and SKN1 are involved in beta-1,6-glucan synthesis, maintenance of cell wall integrity and retention of mannoproteins and known cryptococcal virulence factors in the cell wall of C. neoformans. This study sets the stage for future investigations into the function of this abundant cell wall polymer.

Topics: Animals; Architecture; beta-Glucans; Cell Wall; Cryptococcosis; Cryptococcus neoformans; Disease Models, Animal; Fungal Proteins; Gene Deletion; Maintenance; Mice; Polysaccharides; Protein Binding; Survival Analysis; Virulence

The present study evaluated the antinociceptive effect of (1→3),(1→6)-linked β-glucan (GL) isolated from Pleurotus pulmonarius (Fr.) Quel. in mice and its possible mechanism of action. Intraperitoneal administration of GL inhibited glutamate-induced licking with an ID(50) of 0.34 mg/kg and inhibition of 96% ± 3%. The treatment of animals with GL (1 mg/kg i.p.) inhibited nociception induced by intrathecal injection of N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate and interleukin -1β in 67% ± 13%, 89% ± 11%, 74% ± 9%, and 75% ± 7%, respectively, but not the nociceptive response induced by (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P, and tumor necrosis factor-α. Moreover, GL (30 mg/kg i.p.) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 2 hours, with inhibition of 47% ± 10% observed 0.5 hours after treatment. When given chronically (twice a day) over 7 days, GL reversed the mechanical allodynia caused by partial sciatic nerve ligation (inhibition of 45% ± 13% to 60% ± 8%). Interestingly, GL did not affect the locomotor activity of mice in an open field test with doses that produce antinociceptive effects. Our findings show that GL inhibits acute and neuropathic pain in mice through mechanisms that involve the inhibition of ionotropic glutamate receptors and the interleukin -1β pathway.. This article presents the antinociceptive activity of GL in acute and neuropathic pain with participation of ionotropic glutamate receptors and pro-inflammatory cytokines (interleukin-1β). After further experiments, this compound may represent a new pharmacological agent for the treatment of clinical pain.

Topics: Acute Disease; Analgesics; Animals; Cytokines; Disease Models, Animal; Female; Glucans; Injections, Intraperitoneal; Interleukin-1beta; Male; Mice; Neuralgia; Pleurotus; Receptors, Glutamate; Signal Transduction

In this study we demonstrated that the oral administration of β-1,3-glucan (Imunoglucan®) protects mice from a lethal dose of Listeria monocytogenes (LM) when administered prophylactically for 10 days at the doses of 150 and 300 mg/kg, with survival rates up to 40%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with LM, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Investigation of the production of colony-stimulating factors revealed an increased colony-stimulating activity (CSA) in the serum of infected mice pre-treated with Imunoglucan®. The treatment also restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures (LTBMC) and up-regulated IL-6 and IL-1α production by these cells in the infected mice, which was consistent with higher number of non-adherent cells. Additional studies to investigate the levels of interferon-gamma (INF-γ) in the supernatant of splenocyte cultures demonstrated a further increase in the level of this cytokine in infected-treated mice, compared to infected controls. In all cases, no differences were observed between the responses of the two optimal biologically effective doses. In contrast, no significant changes were produced by the treatment with the 50mg/kg dose. In addition, no changes were observed in normal mice treated with the three doses used. All together our results suggest that orally given Imunoglucan® indirectly modulates immune activity and probably disengages Listeria induced suppression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1α, IL-6, and INF-γ).

Topics: Adjuvants, Immunologic; Administration, Oral; Animals; beta-Glucans; Bone Marrow Cells; Cell Culture Techniques; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocyte-Macrophage Progenitor Cells; Hematopoiesis; Hematopoietic Stem Cells; Interferon-gamma; Interleukin-1alpha; Interleukin-6; Listeria monocytogenes; Listeriosis; Male; Mice; Mice, Inbred BALB C; Splenomegaly

The incidence of aspergillosis which has high mortality rates, has increased gradually. Since invasive aspergillosis (IA) is one of the leading causes of death in immunocompromized and neutropenic patients, early and accurate diagnosis of IA is of crucial importance. The aims of this study were to compare the results of culture, real-time polymerase chain reaction (RtPCR), galactomannan (GM) antigen and glucan (GC) antigen detection tests and to evaluate their performances in view of rapid and accurate diagnosis of IA in neutropenic rat model. Female Wistar albino rats were included in the study with the consent of Animal Searching Ethical Committee and classified into three groups as healthy controls (n= 6), neutropenic controls (n= 10) and pulmonary aspergillosis (n= 35) groups. Rats were immunosuppressed with 5-flourourasil and then Aspergillus fumigatus conidia were inoculated intranasally. On the seventh day of the infection, blood, bronchoalveolar lavage (BAL) and lung tissue samples were collected from the animals, and control and aspergillosis groups were compared in terms of infection markers. All of the tests (culture, RtPCR, GM and BG tests) were found to be negative in controls. At the end of the study 22 rats in aspergillosis group survived. Lung tissue samples from those 22 animals were all positive for the presence of hypha on pathological preparations, while 20 (91%) yielded Aspergillus colonies on the cultures. Aspergillus DNA was detected in 7 of the 12 BAL samples (58.3%), 7 of 19 blood samples (36.8%) and 4 of 22 lung tissue samples (18%) using RtPCR method. GM antigen was detected in 7 of 20 serum samples (35%) with a commercial kit (Platelia® Aspergillus ELISA, BioRad, France). Quantitative detection of betalucan levels were investigated by using a commercial kit (Fungitell™, Cape Cod, USA) in serum and BAL samples and positive results were obtained in 11 of 22 serum (50%) and 9 of 17 BAL (52.9%) samples. In this study it was demonstrated that PCR performed in BAL samples is the most sensitive method compared to the others, for the diagnosis of IA in the rat model. The sensitivity rates were as follows when culture method accepted as the gold standard: 58.3% for BAL-PCR, 41.2% for blood-PCR, 20% for tissue-PCR, 38.9% for serum GM, 55% for serum GC and 52.9% for BAL-GC. It was also concluded that detection of GC activity in serum was more sensitive than GM detection in serum (sensitivity of GM was %38.9, sensitivity of GC was %55, whi

Topics: Animals; Antigens, Fungal; Aspergillus fumigatus; beta-Glucans; Bronchoalveolar Lavage Fluid; Disease Models, Animal; DNA, Fungal; Enzyme-Linked Immunosorbent Assay; Female; Fluorouracil; Galactose; Immunosuppression Therapy; Immunosuppressive Agents; Invasive Pulmonary Aspergillosis; Lung; Mannans; Neutropenia; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

The impaired wound healing in diabetes mellitus is a major clinical problem. Sparassis crispa (SC) is a medicinal mushroom and its beta-glucan content is more than 40%. This study investigated whether oral administration of SC could improve the impaired wound healing in diabetic rats.. Full-thickness skin wounds were created on the backs of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were then divided into 2 groups: SC-treated group that was orally administered doses of 1,000 mg/kg body weight per day of SC for 4 weeks and a control group without SC administration. Moreover, collagen synthesis of purified beta-glucan from SC was estimated in vitro.. Wound closure was significantly accelerated by oral administration of SC. Furthermore, in SC-treated wounds there were significant increases in macrophage and fibroblast migration, collagen regeneration, and epithelialization compared with the control group. The levels of type I collagen synthesized by cultured human dermal fibroblasts for the SC group were significantly higher than those for the control group.. SC can improve the impaired healing of diabetic wounds. This effect might involve an increase in the migration of macrophages and fibroblasts, and beta-glucan from SC directly increases the synthesis of type I collagen. Therefore, the use of SC may be extended to the clinical setting and prove an effective promoter of wound healing in patients with diabetes.

Topics: Agaricales; Animals; beta-Glucans; Collagen; Diabetes Mellitus, Experimental; Disease Models, Animal; Male; Phytotherapy; Rats; Rats, Sprague-Dawley; Wound Healing

Leukocyte extravasation is initiated by an interaction of selectin adhesion molecules and appropriate carbohydrate ligands. Targeting those interactions seems a promising approach to treat chronic inflammation. We developed a beta-1, 3-glucan sulfate (PS3) with inhibitory activity toward L and P-selectins under static conditions. Here, detailed investigation showed inhibition of P- and L-selectins, but not E-selectin under flow conditions (relative reduction of interaction with appropriate ligands to 34.4+/-16.6, 8.5+/-3.6, or 99.5+/-9.9%, respectively, by PS3 for P-, L- or E-selectin). Intravital microscopy revealed reduction of leukocyte rolling in skin microvasculature from 22.7+/-5.0 to 12.6+/-4.0% after injection of PS3. In the next experiments, mice were sensitized with 2,4,-dinitrofluorobenzene (DNFB), and lymphocytes were transferred into syngeneic recipients, which were challenged by DNFB. Inflammatory responses were reduced when immunity was generated in mice treated with PS3 or in L-selectin-deficient mice. No effect was observed when L-selectin-deficient donor mice were treated with PS3, further suggesting that PS3 acted primarily through inhibition of L-selectin. Elicitation of a contact hypersensitivity response was reduced in P-selectin-deficient and in PS3-treated mice. Again, PS3 had no effect in P-selectin-deficient mice. PS3 is a potent P- and L-selectin inhibitor that may add to the therapy of inflammatory diseases.

Topics: Adoptive Transfer; Allergens; Animals; beta-Glucans; Cell Communication; Cells, Cultured; Dermatitis, Contact; Dinitrofluorobenzene; Disease Models, Animal; Endothelium, Vascular; Glucans; Humans; L-Selectin; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred C57BL; P-Selectin

Experience with anidulafungin against Candida krusei is limited. Immunosuppressed mice were injected with 1.3 x 10(7) to 1.5 x 10(7) CFU of C. krusei. Animals were treated with saline, 40 mg/kg fluconazole, 1 mg/kg amphotericin B, or 10 and 20 mg/kg anidulafungin for 5 days. Anidulafungin improved survival and significantly reduced the number of CFU/g in kidneys and serum beta-glucan levels.

Topics: Anidulafungin; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Disease Models, Animal; Echinocandins; Kidney; Male; Mice

Oat beta-glucan can counteract the exercise-induced increased risk for upper respiratory tract infection (URTI) in mice, which is at least partly mediated by its effects on lung macrophages. Substantial evidence in humans indicates that carbohydrate-containing sports drinks can offset the decreased immune function associated with stressful exercise. However, no studies in animals or humans have directly examined their effects on URTI using a controlled virus-challenge model. We examined the effects of sucrose feedings alone and in combination with oat beta-glucan on susceptibility to infection and on macrophage antiviral resistance in mice following stressful exercise. These effects were also examined in rested, nonimmunocompromised control mice. Mice were assigned to one of four groups: H(2)O (water), sucrose (S), oat beta-glucan (ObetaG), and sucrose + oat beta-glucan (S+ObetaG). ObetaG and S treatments consisted of a solution of 50% ObetaG and 6% sucrose, respectively, and were administered in drinking water for 10 consecutive days. Exercise consisted of a treadmill run to fatigue performed on three consecutive days. Mice were then intranasally inoculated with a standardized dose of herpes simplex virus 1 (HSV-1) and monitored for morbidity and mortality for 21 days. Additional mice were used to determine macrophage antiviral resistance. In the exercise experiment, S, ObetaG, and S+ObetaG all reduced morbidity (P < 0.05), while only S+ObetaG reduced mortality (P < 0.05). Macrophage antiviral resistance was also increased in S, ObetaG, and S+ObetaG treatments (P < 0.05). In resting controls, S and S+ObetaG reduced morbidity and mortality (P < 0.05) and showed a trend toward increased macrophage antiviral resistance. There was no significant additive effect of S and ObetaG in either control or exercised animals. These data extend our previous work on the benefits of oat beta-glucan to show that sucrose feedings have similar effects on susceptibility to respiratory infection and macrophage antiviral resistance in both resting controls and following exercise stress.

Topics: Animal Nutritional Physiological Phenomena; Animals; Avena; beta-Glucans; Blood Glucose; Body Weight; Dietary Sucrose; Disease Models, Animal; Herpes Simplex; Herpesvirus 1, Human; Macrophages; Male; Mice; Muscle Fatigue; Physical Exertion; Respiratory Tract Infections; Stress, Physiological; Time Factors

The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1-->3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously obtained CSF (P < 0.05). CSF beta-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r = 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF beta-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.

Topics: Amphotericin B; Animals; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Monitoring; Echinocandins; Female; Lipopeptides; Meningitis, Fungal; Meningoencephalitis; Micafungin; Rabbits

A glucan was extracted with hot water from the basidiomycete Pleurotus pulmonarius and shown to have a (1-->3)-linked beta-D-glucopyranosyl main-chain substituted at O-6 of every third unit by single beta-D-glucopyranosyl non-reducing end units. This was shown by mono- and bidimensional nuclear magnetic resonance (NMR) spectroscopy, methylation analysis, and a controlled Smith degradation. The glucan was tested for its effects on the acetic acid-induced writhing reaction in mice, a typical model for quantifying inflammatory pain. It caused a marked and dose-dependent anti-inflammatory response, demonstrated by the inhibition of leukocyte migration to injured tissues (82 +/- 6%) with an ID50 of 1.19 (0.74-1.92) mg/kg. Furthermore, animals previously treated with the glucan (3 mg/kg i.p.), showed a reduction of 85 +/- 5% of writhes, after receiving the acetic acid injection. Furthermore, in the formalin test, the glucan (3-30 mg/kg, i.p.) also caused significant inhibition of both the early (neurogenic pain) and the late phases (inflammatory pain) of formalin-induced licking. However, it was more potent and effective in relation to the late phase of the formalin test, with mean ID(50) values for the neurogenic and the inflammatory phases of > 30 and 12.9 (6.7-24.6) mg/kg and the inhibitions observed were 43 +/- 5% and 96 +/- 4%, respectively. These data showed that the glucan had potent anti-inflammatory and analgesic (antinociceptive) activities, possibly by the inhibition of pro-inflammatory cytokines.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Capillary Permeability; Cell Movement; Disease Models, Animal; Dose-Response Relationship, Drug; Formaldehyde; Glucans; Inflammation; Leukocytes; Male; Mice; Molecular Structure; Pain; Pain Measurement; Pleurotus

A study to evaluate the mechanisms of tumoricidal activity resulting from orally administered extract of Agaricus blazei Murill (A. blazei) was performed in mice bearing syngeneic and xenogeneic tumors. Tumor regression was comparably seen in both syngeneic and xenogeneic tumor-bearing mice when administered oral extract preparations. In addition, in a murine syngeneic tumor model, oral administration of water-soluble extracts of A. blazei resulted in significant production of cytokines such as IFN-gamma, and TNF-alpha in peritoneal exudate cells, in parallel with the marked regression of tumor development. The water-soluble extracts also induced pronounced antioxidant activity in in vitro and in vivo assays using two different methods. These results indicate the A. blazei extract may enhance not only the immnunomodulatory effects that promote activity of peritoneal exudate cells for tumor regression but also potentially result in the direct destruction of tumor cells through its antioxidant activity.

Topics: Adjuvants, Immunologic; Agaricus; Animals; Antineoplastic Agents; Antioxidants; beta-Glucans; Cytokines; Cytotoxicity, Immunologic; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Mice; Mice, Inbred ICR; Time Factors

Candida albicans, a clinically important dimorphic fungal pathogen that can evade immune attack by masking its cell wall beta-glucan from immune recognition, mutes protective host responses mediated by the Dectin-1 beta-glucan receptor on innate immune cells. Although the ability of C. albicans to switch between a yeast- or hyphal-form is a key virulence determinant, the role of each morphotype in beta-glucan masking during infection and treatment has not been addressed. Here, we show that during infection of mice, the C. albicans beta-glucan is masked initially but becomes exposed later in several organs. At all measured stages of infection, there is no difference in beta-glucan exposure between yeast-form and hyphal cells. We have previously shown that sub-inhibitory doses of the anti-fungal drug caspofungin can expose beta-glucan in vitro, suggesting that the drug may enhance immune activity during therapy. This report shows that caspofungin also mediates beta-glucan unmasking in vivo. Surprisingly, caspofungin preferentially unmasks filamentous cells, as opposed to yeast form cells, both in vivo and in vitro. The fungicidal activity of caspofungin in vitro is also filament-biased, as corroborated using yeast-locked and hyphal-locked mutants. The uncloaking of filaments is not a general effect of anti-fungal drugs, as another anti-fungal agent does not have this effect. These results highlight the advantage of studying host-pathogen interaction in vivo and suggest new avenues for drug development.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis; Caspofungin; Cell Wall; Disease Models, Animal; Echinocandins; Epitopes; Female; Fluconazole; Host-Pathogen Interactions; Hyphae; Lectins, C-Type; Lipopeptides; Membrane Proteins; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; Mutation; Nerve Tissue Proteins; Receptors, Immunologic

Chronic granulomatous disease (CGD), a genetic disorder characterized by the absence of a functional phagocyte NADPH oxidase, is a severe immune deficiency. However, non-infectious hyperinflammation is a second hallmark of the disease. In CGD mouse models, sterile hyperinflammation can be induced by A. fumigatus cell wall preparations. In this study, we used subcutaneous injection of microbial cell walls and cell wall components to identify causes of CGD hyperinflammation and to characterize its histological features. Sterile cell wall preparations from fungi (A. fumigatus, C. albicans, S. cerevisiae), but not from bacteria (S. aureus, P. aeruginosa, E. coli), caused prolonged and severe skin inflammation in CGD mice. To identify fungal cell wall elements responsible for this process, we investigated microbial cell wall-derived monosubstances. Injection of beta(1-3)(1-6)-glucan induced severe hyperinflammation in CGD mice, while other fungal cell components [mannan, (1-3) beta-glucan] or bacterial cell wall components (lipopolysaccharide, lipoteichoic acid) caused no or only moderate inflammation. beta-glucan-induced hyperinflammation was predominantly due to a defect in termination of inflammation, as in the initial stage (2 days), the severity of inflammation and the extent of cell death were comparable in wild-type and CGD mice. At later stages (7 days), beta(1-3)(1-6)-glucan-induced inflammation had subsided in wild-type mice. In contrast, CGD mice showed persistent severe inflammation with central necrosis, containing abundant apoptotic and necrotic cells. In summary, branched fungal beta-glucan induces a severe inflammatory reaction in the absence of phagocyte NADPH oxidase. As opposed to the commonly perceived notion that reactive oxygen species are the cause of cell death, our results demonstrate that tissue necrosis can be caused by the absence of a superoxide-producing enzyme.

Topics: Animals; Bacteria; beta-Glucans; Cell Death; Cell Wall; Dermatitis; Disease Models, Animal; Fungi; Granulomatous Disease, Chronic; Injections, Intradermal; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NADPH Oxidases; Necrosis; Phagocytes; Skin

Serum (1-->3)-beta-D-glucan concentrations were serially measured in the presence and absence of antifungal therapy in a murine model of invasive pulmonary aspergillosis. Serum (1-->3)-beta-D-glucan was detected early during the course of infection, and reductions in this biomarker were associated with improved survival in animals treated with antifungal agents.

Topics: Animals; Animals, Outbred Strains; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Biomarkers; Disease Models, Animal; Humans; Lung; Lung Diseases, Fungal; Mice; Mice, Inbred ICR; Proteoglycans; Treatment Outcome

We have established a mouse model which shows the symptoms of coronary arteritis after consecutive injections of CAWS, which is released from Candida albicans. In this study, we examined neutrophil activation in the initial period after CAWS injection intraperitoneally. During 10 min to 16 h after the injection, blood profiles and neutrophil functions were determined. At the same time, levels of inflammatory cytokines and chemokines in plasma were measured. Furthermore, level of ICAM-1 as a marker of lesion in arterial endothelial cells was measured. Counts of the peripheral leukocytes increased immediately after CAWS injection, especially involving neutrophil. In vitro sensitivity of neutrophils to stimuli was enhanced. Moreover, proinflammatory cytokines (IL-1beta, IL-12 and IL-6) increased in plasma initially followed by an increase in IL-10, G-CSF, MIP-2 and soluble ICAM-1. Locally, ICAM-1 message in arterial walls was significantly increased 16 h after CAWS injection. A decrease in C3 levels was observed in plasma, suggesting complement activation and consumption. In summary, neutrophil activation occurred after CAWS injection, followed by complement activation, and production of proinflammatory cytokines chemokines and G-CSF which may be involved in development of coronary arteritis.

Topics: Animals; Arteritis; beta-Glucans; Candida albicans; Complement C3; Coronary Vessels; Cytokines; Disease Models, Animal; Granulocyte Colony-Stimulating Factor; Intercellular Adhesion Molecule-1; Male; Membrane Glycoproteins; Mice; Neutrophil Activation; Solubility; Water

Yeast cell walls are critical for maintaining cell integrity, particularly in the face of challenges such as growth in mammalian hosts. The pathogenic fungus Cryptococcus neoformans additionally anchors its polysaccharide capsule to the cell surface via alpha(1-3) glucan in the wall. Cryptococcal cells disrupted in their alpha glucan synthase gene were sensitive to stresses, including temperature, and showed difficulty dividing. These cells lacked surface capsule, although they continued to shed capsule material into the environment. Electron microscopy showed that the alpha glucan that is usually localized to the outer portion of the cell wall was absent, the outer region of the wall was highly disorganized, and the inner region was hypertrophic. Analysis of cell wall composition demonstrated complete loss of alpha glucan accompanied by a compensatory increase in chitin/chitosan and a redistribution of beta glucan between cell wall fractions. The mutants were unable to grow ina mouse model of infection, but caused death in nematodes. These studies integrate morphological and biochemical investigations of the role of alpha glucan in the cryptococcal cell wall.

Topics: Animals; beta-Glucans; Caenorhabditis elegans; Cell Wall; Chitin; Chitosan; Cryptococcus neoformans; Disease Models, Animal; Gene Deletion; Glucans; Glucosyltransferases; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mutagenesis, Insertional; Virulence

Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia (PCP) in immunocompromised individuals. Recent studies have demonstrated that the host's immune response is clearly responsible for the majority of the pathophysiological changes associated with PCP. P. carinii interacts closely with alveolar epithelial cells (AECs); however, the nature and pathological consequences of the epithelial response remain poorly defined. Monocyte chemotactic protein-1 (MCP-1) is involved in lung inflammation, immunity, and epithelial repair and is upregulated during PCP. To determine whether AECs are an important source of MCP-1 in the P. carinii-infected lung, in vivo and in vitro studies were performed. In situ hybridization showed that MCP-1 mRNA was localized to cells with morphological characteristics of AECs in the lungs of infected mice. In vitro studies demonstrated that P. carinii stimulated a time- and dose-dependent MCP-1 response in primary murine type II cells that was preceded by JNK activation. Pharmacological inhibition of JNK nearly abolished P. carinii-stimulated MCP-1 production, while ERK, p38 MAPK, and TNF receptor signaling were not required. Furthermore, delivery of a JNK inhibitory peptide specifically to pulmonary epithelial cells using a recombinant adenovirus vector blocked the early lung MCP-1 response following intratracheal instillation of infectious P. carinii. JNK inhibition did not affect P. carinii-stimulated production of macrophage inflammatory protein-2 in vitro or in vivo, indicating that multiple signaling pathways are activated in P. carinii-stimulated AECs. These data demonstrate that AECs respond to P. carinii in a proinflammatory manner that may contribute to the generation of immune-mediated lung injury.

Topics: Animals; beta-Glucans; Cells, Cultured; Chemokine CCL2; Chemokine CXCL2; Chemokines; Disease Models, Animal; Epithelial Cells; Gene Expression; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, SCID; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Pneumocystis Infections; Pulmonary Alveoli; Respiratory Mucosa

Pneumocystis carinii (PC) pneumonia is a leading opportunistic infection found among HIV-infected individuals worldwide. Although CD4(+) T cell deficiency clearly correlates with susceptibility to PC pneumonia, murine models of disease indicate that PC-directed Abs may prevent infection and/or inhibit growth of existing PC within the lungs. Recognition of PC by alveolar macrophages involves the beta-glucan receptor Dectin-1 and macrophage effector function against PC is enhanced by Abs derived from PC-vaccinated hosts. We developed a fusion protein consisting of the extracellular domain of Dectin-1 linked to the Fc portion of murine IgG1, which we hypothesized would enhance host recognition and opsonic phagocytosis of PC. The recombinant protein, Dectin-Fc, is dimeric and the Ag recognition site identifies beta-1,3 glucan linkages specifically and with high affinity (K(D) = 2.03 x 10(-7) M). Dectin-Fc enhances RAW264.7 macrophage recognition of the beta-glucan containing particulate zymosan in an FcgammaRII- and FcgammaRIII-dependent manner and preopsonization of PC organisms with Dectin-Fc increased alveolar and peritoneal macrophage-dependent killing of PC. SCID mice treated with a replication incompetent adenoviral vector expressing Dectin-Fc had attenuated growth of PC within the lungs, overall decreased PC lung burden, and diminished correlates of PC-related lung damage relative to SCID mice receiving a control vector. These findings demonstrate that targeting PC beta-glucan with Dectin-Fc enhances host recognition and clearance of PC in the absence of B and T cells, and suggest that FcgammaR-based targeting of PC, via cell wall carbohydrate recognition, may promote resistance against PC pneumonia in the immunodeficient host.

Topics: Adenoviridae; AIDS-Related Opportunistic Infections; Animals; Antibody-Dependent Cell Cytotoxicity; beta-Glucans; Disease Models, Animal; Humans; Immunocompromised Host; Immunoglobulin Constant Regions; Lectins, C-Type; Lung; Macrophages, Alveolar; Male; Membrane Proteins; Mice; Mice, SCID; Nerve Tissue Proteins; Pneumocystis carinii; Pneumonia, Pneumocystis; Receptors, IgG; Recombinant Fusion Proteins

Sepsis is one of the most important risk factors in acute respiratory distress syndrome (ARDS). beta-Glucan is a potent reticuloendothelial modulating agent, the immunobiological activity of which is mediated in part by an increase in the number and function of macrophages. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced lung injury. Sepsis was induced by cecal ligation and puncture (CLP) in Wistar rats. The control group received saline, and the treatment groups received beta-glucan or beta-glucan + beta-1,3-D-glucanase. Five hours thereafter, plasma tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and IL-6 levels were determined. Presence of lung injury was determined via lung tissue myeloperoxidase (MPO) activity, intercellular adhesion molecule (ICAM) 1 levels, and histopathological examination at 18 h after CLP. In a separate set of experiments, survival was monitored for 7 days after CLP. beta-Glucan treatment led to a significant increase in survival rate (63% in glucan-treated rats vs 38% in saline-treated rats). Administration of the beta-glucan inhibitor abrogated beta-glucan's survival benefit (50%). After CLP, plasma TNF-alpha, IL-1beta, and IL-6 concentrations were increased in control animals. When beta-glucan was administered, it completely blocked the elevation of TNF-alpha, IL-1beta, and IL-6. Administration of beta-1,3-D-glucanase suppressed glucan-induced decrease in cytokines. Animals treated with beta-glucan showed a significant reduction in lung injury score, a marked decrease in ICAM-1 expression, and a significant decrease in MPO levels. In contrast, beta-1,3-D-glucanase caused a significantly increased MPO and ICAM-1 levels in the lung. These data reveal that beta-glucan treatment improved the course of CLP-induced peritonitis and attenuated the lung injury. Administration of beta-glucanase inhibited the beta-glucan activity and resulted in enhanced lung injury.

Topics: Animals; beta-Glucans; Cytokines; Disease Models, Animal; Inflammation Mediators; Male; Random Allocation; Rats; Rats, Wistar; Respiratory Distress Syndrome; Sepsis

Biofilms are microbial communities that are associated with solid surfaces such as intravascular catheters. Candida species are a major cause of medical device-associated infections. Twenty percent to 70% of all candidemias are associated with this biofilm process. Diagnosis and effective treatment of Candida device-associated infections requires removal of the involved device. The ability to identify a biofilm device infection before catheter removal may obviate removal of a substantial number of devices. Prior studies in our laboratory identified cell wall changes (specifically, increased beta -1,3 glucan) associated with biofilm, compared with planktonic C. albicans. Both in vitro and in vivo (catheter) biofilm models were used to determine whether biofilm cells secreted more beta -1,3 glucan and whether these differences could be used to discern the presence of a Candida biofilm infection with 3 species (C. albicans, C. glabrata, and C. parapsilosis). A limulus lysate assay was used to quantify beta -1,3 glucan in supernatants from planktonic or biofilm cultures and in the serum of rats with an intravascular catheter biofilm infection or disseminated candidiasis. beta -1,3 glucan was detected from both in vitro and in vivo models from each condition. However, the concentrations of beta -1,3 glucan from the biofilm conditions were 4-10-fold greater in vitro (P<.001) and were 10-fold greater in vivo (P<.001), despite equal or fewer numbers of cells in the biofilm conditions. These results suggest the secreted polysaccharide beta -1,3 glucan may serve as a useful tool for the diagnosis of Candida biofilm and device-associated infections.

Topics: Animals; beta-Glucans; Biofilms; Candida; Candida albicans; Candida glabrata; Candidiasis; Catheterization, Central Venous; Disease Models, Animal; Humans; Limulus Test; Microscopy, Confocal; Rats

N-acetylcysteine, beta-glucan, and coenzyme Q10 have been shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on myocardial ischemia-reperfusion injury.. Forty-four New Zealand white rabbits, all female, weighing 2.4 to 4.1 kg (mean, 3.6 kg) were used in the study. Four study groups of 11 animals were arranged by randomization. The groups were the control group (group C), a group premedicated with coenzyme Q10 (group Q), a group premedicated with beta-glucan (group betaT), and a group premedicated with N-acetylcysteine (group N). After exploration of the heart, a basal myocardial biopsy was taken from the anteroapical left ventricle, and the first blood sampling was done before ischemia. For the ischemia-reperfusion experiments, the major left anterior descending artery was occluded after baseline measurements. After a 45-minute transient ischemic period, the heart was perfused for 120 minutes. After perfusion, the second myocardial biopsy was taken from the anteroapical left ventricle, and the second blood sampling was done. Blood and tissue analysis were performed and evaluated statistically.. Baseline and reperfusion levels of glutathione peroxidase, superoxide dismutase, malonyldialdehyde, and nitric oxide changed significantly. While malonyldialdehyde levels increased in group C, they decreased in the other study groups (P =.001). The increases in glutathione peroxidase and superoxide dismutase levels were significant in all groups except group C (P =.0001 and P <.05, respectively). Levels of nitric oxide were found to be decreased in group C, whereas they increased in the other groups (P =.001).. Antioxidant medication may help in lowering the risk of myocardial ischemia-reperfusion injury. All the medications in our study are shown to have effective roles in preventing ischemia-reperfusion injury to some extent through their antioxidant properties.

Topics: Acetylcysteine; Animals; Antioxidants; beta-Glucans; Coenzymes; Disease Models, Animal; Female; Myocardial Reperfusion Injury; Rabbits; Ubiquinone

For the rapid diagnosis of systemic Candida infection, we compared the performance of an established seminested polymerase chain reaction (snPCR), serological tests for (1 --> 3)-beta-D-glucan assay and Candida mannan antigen assay, and blood culture in our murine model for Candida albicans translocation. In this mouse model, C. albicans disseminated to the liver from the intestine after day 6.5; the snPCR and blood culture results became positive from days 8 to 8.5 in about 60% of infected mice with culture-proven translocation, and in 100% on day 9. Both (1 --> 3)-beta-D-glucan and Candida mannan antigen were elevated in the serum as early as day 6.5 of infection, though they did not identify Candida species. Because the established snPCR can differentiate four clinically important Candida species and conventional microbiological methods require at least 48 h to identify Candida species in blood samples, the snPCR assay is advantageous for rapidly identifying Candida species in the blood. Therefore, the combination of the serological assays and the snPCR seems to be valuable for the early diagnosis of systemic C. albicans infection.

Topics: Animals; Bacterial Translocation; beta-Glucans; Blood; Candida albicans; Candidiasis; Disease Models, Animal; DNA, Bacterial; Feces; Fungemia; Liver; Mannans; Mice; Polymerase Chain Reaction; Proteoglycans; Sensitivity and Specificity; Serologic Tests

We have developed an animal model of sepsis in mice by repeatedly administering beta-glucan, a biological response modifier, and indomethacin (IND), a nonsteroidal anti-inflammatory drug. The combination of these drugs induced bacteremia by translocation of the enterobacterial flora, resulting in increasing the number of activated leukocytes, and inducing hyper cytokinemia. In the present study, we examined the effect of antibiotics on beta-glucan and IND-induced septic shock. Treatment with antibiotics inhibited microbial translocation, inhibited contraction of the colon, reduced lipopolysaccharides (LPS)-elicited production of TNF-alpha and IL-6, and finally prolonged survival. However, the efficacy of antibiotics treatment was limited in mice administered IND orally. These findings strongly suggested that the antibiotics controlled the gut-associated action of IND and reduced various symptoms accompanying sepsis.

Topics: Animals; Anti-Bacterial Agents; Bacterial Translocation; beta-Glucans; Body Weight; Colon; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Indomethacin; Liver; Male; Mice; Shock, Septic

Beta-1,3-glucans enhance immune reactions such as antitumor, antibacterial, antiviral, anticoagulatory, and wound healing activities. beta-1,3-Glucans have various functions depending on the molecular weight, degree of branching, conformation, water solubility, and intermolecular association. The molecular weight of the soluble glucan was about 15,000 as determined by a high-performance size exclusion chromatography. From the infrared (IR) and 13C NMR analytical data, the purified soluble glucan was found to exclusively consist of beta-D-glucopyranose with 1,3 linkage. We tested the immunestimulating activities of the soluble beta-1,3-glucan extracted from Agrobacterium sp. R259 KCTC 1019 and confirmed the following activities. IFN-gamma and each cytokines were induced in the spleens and thymus of mice treated with soluble beta-1,3-glucan. Adjuvant effect was observed on antibody production. Nitric oxide was synthesized in monocytic cell lines treated with beta-1,3-glucan. The cytotoxic and antitumor effects were observed on various cancer cell lines and ICR mice. These results strongly suggested that this soluble beta-1,3-glucan could be a good candidate for an immune-modulating agent.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred ICR; Neoplasm Metastasis; Rhizobium; Solubility; Water

The beta-glucans are long-chain polymers of glucose in beta-(1,3)(1,6) linkages, which comprise the fungal cell wall and stimulate cells of the innate immune system. Previous in vitro studies have shown the ability of beta-glucan to increase the chemotactic capacity of human neutrophils. The current study examined an in vivo correlate of that observation by testing the hypothesis that systemic beta-glucan treatment would result in enhanced migration of neutrophils into a site of inflammation and improve antimicrobial function. A model of acute inflammation was used in which polyvinyl alcohol sponges were implanted subcutaneously into the dorsum of rats. Animals treated with beta-glucan showed a 66 +/- 6% and 186 +/- 42% increase in wound cell number recovered 6 and 18 h postwounding, respectively. Increased migration did not correlate with increased chemoattractant content of wound fluid, alterations in neutrophil-induced loss of endothelial barrier function, or changes in neutrophil adhesion to endothelial cells. Systemic administration of SB203580 abrogated the enhanced migration by beta-glucan without altering normal cellular entry into the wound. Studies also showed a priming effect for chemotaxis and respiratory burst in circulating neutrophils isolated from beta-glucan-treated animals. Heightened neutrophil function took place without cytokine elicitation. Furthermore, beta-glucan treatment resulted in a 169 +/- 28% increase in neutrophil number and a 60 +/- 9% decrease in bacterial load in the bronchoalveolar lavage fluid of Escherichia coli pneumonic animals. Taken together, these findings demonstrate that beta-glucan directly affects the chemotactic capacity of circulating neutrophils through a p38 mitogen-activated protein kinase-dependent mechanism and potentiates antimicrobial host defense.

Topics: Animals; beta-Glucans; Cell Movement; Chemotaxis, Leukocyte; Disease Models, Animal; Endothelial Cells; Imidazoles; Leukocytes; Male; Neutrophils; p38 Mitogen-Activated Protein Kinases; Prostaglandins G; Pyridines; Rats; Rats, Inbred F344; Time Factors; Wound Healing

The aim of this study was to present the preliminary results of a technique of abdominal aortic aneurysm (AAA) sac filling in an attempt to obliterate the sac in a swine AAA model, using deacetylated-poly-N-acetyl glucosamine (DEAC-poly-N-acetyl glucosamine).. Eleven Yucatan pigs, 6 months of age, 40 kg -60 kg, were used to create an AAA with a Dacron pouch implanted surgically and left to mature for 2 weeks. One animal was used to establish the AAA creation procedures. Eight animals were used for AAA sac filling; of the 8 subjects 2 were used for acute studies, and 6 for longer-term studies. Two additional animals were used as controls without polymer sac filling. Two weeks after the AAA creation, a 13 mmx5.5 cm straight tube AneuRx stent-graft was placed to exclude the aneurysm. The aneurysmal sac was filled with a polymer, DEAC-poly-N-acetyl glucosamine at 1.5%, 70% deacetylated, mixed with iohexol. There was filling of a lumbar artery by the polymer in 2 animals. Endpoints were at 1, 2, 4, 6, 12 and 24 weeks, in the chronic study animals and 6 and 12 weeks in the control subjects, procedures consisting of aortography followed by necropsy and pathologic examination.. The AAA creation and aneurysm sac filling was successful in all animals. An organized thrombus layer of about 2 mm in thickness was observed in all subjects along the Dacron aneurysm wall. All aneurysms were angiographically patent at the time of treatment, but fresher thrombus within the sac was seen in 4 subjects before the polymer injection. The stent-graft placement excluded the AAA sac and the polymer injection filled all AAA sacs. The AAA sac had acquired a firm rubbery consistency at the time of necropsy. There was mild inflammatory reaction to the Dacron material in the surrounding tissues and within the sac, to a lesser extent. Two animals developed paralysis of the hind limbs following treatment, most likely related to spinal ischemia, and were used as acute subjects. There was no recanalization of the aneurysm sac, during the follow-up time, ranging from 1 to 24 weeks in the treatment or control subjects. There was a 25% shrinkage of the AAA sac at 6th, 40% at 12th week and 75% by the 24th week. The 2 control subjects showed shrinkage of less than 25% at 6 and 12 weeks. There was replacement of the polymer/thrombus complex by connective tissue, fat tissue with capillary neovascularization in the treated subjects. Fibrosis and calcifications were also detected within the sac, mostly around the stent-graft and in contact with the aortic wall starting at 4 weeks. Control subjects did not show replacement of the thrombus by connective tissue or neovascularization.. The results of this preliminary study support the aneurysm sac filling as a potential tool to exclude the aneurismal sac, promoting shrinkage of the AAA. DEAC -poly-N-acetyl glucosamine promotes clotting within the AAA sac with progressive replacement by connective tissue and neovascularization and may have a potential to prevent endoleaks. The polymer is easy to use, and it seems to have adequate gradual long-term replacement properties, preventing aneurysm sac recanalization.

Topics: Angiography; Animals; Aortic Aneurysm, Abdominal; beta-Glucans; Blood Vessel Prosthesis Implantation; Disease Models, Animal; Embolization, Therapeutic; Follow-Up Studies; Injections, Intralesional; Postoperative Period; Stents; Swine; Treatment Outcome

To investigate the role of beta-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury.. Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2 mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFalpha, IL-1beta, IL-6, IL-10 were measured by ELISA.. CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFalpha, IL-1beta and, IL-6, compared to I/R untreated animals.. The beta-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria.

Topics: Animals; Bacterial Translocation; beta-Glucans; Colony Count, Microbial; Cytokines; Disease Models, Animal; Escherichia coli; Inflammation Mediators; Intestinal Mucosa; Intestine, Small; Male; Proteoglycans; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha

Sepsis leads to various organ damage and dysfunction. One of the underlying mechanisms is thought to be the oxidative damage due to the generation of free radicals. In this study, we investigated the putative protective role of beta-glucan against sepsis-induced oxidative organ damage. Sepsis was induced by caecal ligation and puncture (CLP) in Wistar albino rats. Sham operated (control) and sepsis groups received saline or beta-glucan (50 mg/kg, po) once daily for 10 days and 30 min prior to and 6 h after the CLP. Sixteen hours after the surgery, rats were decapitated and the biochemical changes were determined in the brain, diaphragm, kidney, heart, liver and lung tissues using malondialdehyde (MDA) content - an index of lipid peroxidation - glutathione (GSH) levels - a key antioxidant - and myeloperoxidase (MPO) activity - an index of neutrophil infiltration. Serum TNF-alpha levels were assessed by RIA method. Tissues were also examined under light microscope to evaluate the degree of sepsis-induced damage. The results demonstrate that sepsis significantly decreased GSH levels and increased the MDA levels and MPO activity (p<0.05-p<0.001) causing oxidative damage. Elevated plasma TNF-alpha levels in septic rats significantly reduced to control levels in beta-glucan treated rats. Since beta-glucan administration reversed these oxidant responses, it seems likely that beta-glucan protects against sepsis-induced oxidative organ injury.

Topics: Animals; Antioxidants; beta-Glucans; Disease Models, Animal; Female; Glutathione; Male; Malondialdehyde; Peroxidase; Rats; Rats, Wistar; Sepsis; Tumor Necrosis Factor-alpha

The contribution of the Staphylococcus aureus surface polysaccharide poly-N-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (ica) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA-deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.

Topics: Adhesins, Bacterial; Animals; Bacteremia; Bacterial Proteins; beta-Glucans; Disease Models, Animal; Gene Deletion; Immunity, Innate; Mice; Phagocytosis; Staphylococcal Infections; Staphylococcus aureus; Virulence

Soy isoflavone aglycones (IFAs) have a wide range of biological actions that suggest they may be of use in cancer prevention. On the other hand, a branched beta-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-beta-D-glucan in an edible/medicinal mushroom: Sparassis crispa showing antitumor activity. We have previously reported that both oral and intraperitoneal administration of SCG enhanced the hematopoietic response in cyclophosphamide (CY)-induced leukopenic mice. In this study, we investigated the hematopoietic response due to IFA in combination with SCG in CY-induced leukopenic mice. The oral administration of IFA in combination with SCG synergistically enhanced the number of white blood cells, and increased spleen weight. Analyzing the leukocyte population by flow cytometry, the combination of IFA and SCG increased the number of monocytes and granulocytes in the spleen. Taken together, the combination of IFA and SCG synergistically provides the hematopoietic responses that are enhanced over IFA or SCG alone.

Topics: Administration, Oral; Agaricales; Animals; beta-Glucans; Cell Proliferation; Disease Models, Animal; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Flow Cytometry; Glycine max; Hematopoiesis; Hematopoietic System; Injections, Intraperitoneal; Isoflavones; Leukocyte Count; Leukopenia; Male; Mice; Mice, Inbred ICR; Plant Extracts; Solubility; Soybean Proteins; Spleen; Time Factors

This research intends to clarify the protective effect of barley and its hydrolysates with respect to a water immersion stress-induced ulcer in the rat model. The beta-(1-->3)-glucan content of barley, and specifically beta-(1-->4),(1-->3)-glucan content was determined and then gastric stress ulcerogenesis induced by water immersion was conducted using five-week-old male Sprague-Dawley rats (7 rats in one group). The barley diet group was fed 10% barley flour that was substituted with sucrose in the control diet. For the 3 groups fed on soluble dietary fiber (SDF), the diets were supplemented with 0.46 g of SDF, equivalent to 100 g of the control diet; 0.46 g of SDF is equivalent to 10 g of barley flour. The rats were housed in a stress-cage and immersed in a water bath (23 degrees C) up to their necks for 21 h. The content of SDF and beta-(1-->3)-glucan content in barley flour were 4.6% and 3.4%, respectively. Although strongly anti-ulcer activities were observed in the barley (10%), SDF isolated and beta-(1-->3)-glucan fraction (Hydrolysate I) prepared from barley flour after treatment with lichenase, in other words, beta-(1-->4),(1-->3)-glucan itself, its hydrolysate (Hydrolysate II) with beta-(1-->3)-glucosidase did not display any anti-ulcer activity. This finding suggests that the beta-(1-->3)-glucosyl-linkage on beta-(1-->3)-glucan is an important part of the active principle for anti-ulcerogenesis.

Topics: Animals; beta-Glucans; Dietary Fiber; Disease Models, Animal; Food Analysis; Glucans; Hordeum; Immersion; Male; Rats; Rats, Sprague-Dawley; Solubility; Stomach Ulcer; Stress, Physiological

Intraperitoneal administration of CAWS (water-soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans) to mice induces coronary arteritis similar to Kawasaki disease. We analyzed differences in the production of cytokines involved in the occurrence of coronary arteritis among mouse strains, C3H/HeN, C57BL/6, DBA/2 and CBA/J. The incidence of arteritis was 100% in C57BL/6, C3H/HeN and DBA/2 mice, but only 10% in CBA/J mice. The coronary arteritis observed in DBA/2 mice was the most serious, with several mice expiring during the observation period. The CAWS-sensitive strains revealed increased levels of IL-6 and IFN-gamma during the course of a specific response to CAWS by spleen cells. In contrast, IL-10 levels were observed to increase markedly in CAWS-resistant CBA/J mice, but not the CAWS-sensitive strains. However, TNF-alpha levels were more elevated only in DBA/2 mice. The difference in disease development and cytokine production strongly suggests that the genetic background of the immune response to CAWS contributes to the occurrence of coronary arteritis.

Topics: Animals; beta-Glucans; Candida albicans; Disease Models, Animal; Fungal Proteins; Membrane Glycoproteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mucocutaneous Lymph Node Syndrome

The recent events increasing the threat of bioterrorism have prompted a widespread search for defenses against this peril.. To evaluate the anthrax-protective effect of beta1,3-glucan immune modulators (PGG-glucan and WGP beta glucan) in an experimental animal model.. Beta1,3-glucan immune modulators were administered by subcutaneous injection to Balb/c mice 2 days prior to anthrax challenge. WGP beta glucan was administered by daily oral gavage for 7 days prior to challenge, or in drinking water for 10 days postchallenge with a lethal dose of Bacillus anthracis spores. Survival, survival time, and microbial bioburden relative to an infected, untreated control group were assessed.. A single injected dose of PGG-glucan or WGP beta glucan immune modulators given 2 days before challenge significantly: (a) increased the survival rate of infected mice (2.5-fold), (b) diminished the bacterial load in the lungs of infected mice (4-8-fold), and (c) increased the proportion of bacteria-free animals 10 days after challenge (2-fold). In mice prophylactically administered oral WGP beta glucan for 1 week prior to infection, survival increased from 50% to 100%; therapeutic administration of oral WGP beta glucan for 10 days postinfection increased survival from 30% up to 90% in treatment groups.. These results demonstrate the potential for beta1,3-glucan immune modulators to provide a significant degree of protection against anthrax, a potential biological warfare (BW) agent in a mouse model of anthrax infection. Further studies are needed to optimize protection, evaluate activity in combination with other treatment options, demonstrate activity in a validated primate model of infection, and determine if protection is effective against other potential BW agents.

Topics: Adjuvants, Immunologic; Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Ascomycota; Bacillus anthracis; beta-Glucans; Biological Warfare; Bioterrorism; Disease Models, Animal; Female; Glucans; Lung; Mice; Mice, Inbred BALB C; Survival Rate

Sparassis crispa Fr. is an edible mushroom recently cultivable in Japan. It contains a remarkably high content of 6-branched 1,3-beta-D-glucan showing antitumor activity. Using ion-exchange chromatography, a purified beta-glucan preparation, SCG, was prepared. In this study, we examined the hematopoietic response by SCG in cyclophosphamide (CY)-induced leukopenic mice. SCG enhanced the hematopoietic response in CY induced leukopenic mice by intraperitoneal routes over a wide range of concentrations. SCG enhanced the hematopoietic response in CY-treated mice by prior or post administration. Analyzing the leukocyte population by flow cytometry, monocytes and granulocytes in the peritoneal cavity, liver, spleen and bone marrow (BM) recovered faster than in the control group. The ratio of natural killer cells and gammadelta T cells in the liver, spleen and peritoneal cavity was also increased. In contrast, CD4+ CD8+ cells in the thymus were temporarily significantly decreased by the administration of SCG. Interleukin-6 (IL-6) production of CY+SCG-treated peritoneal exdated cells (PECs), spleen cells and bone marrow cells (BMCs) were higher than that of the CY-treated group. By in vitro culture of CY-treated PEC and spleen cells, IL-6 production was enhanced by the addition of SCG. These facts suggested the possibility that IL-6 might be a key cytokine for the enhanced hematopoietic response by SCG.

Topics: Animals; beta-Glucans; Cell Count; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Drug; Glucans; Injections, Intraperitoneal; Interleukin-6; Leukocytes; Leukopenia; Male; Mice; Mice, Inbred ICR; Organ Specificity; Polyporales

There is an increasing demand from both patients and practicing oncologists for orally formulated chemotherapy. The present study focused on the oral formulation for natural products that may be effectively used in oncologic treatment regimens. Tumor-bearing mice treated with intratumoral administration of aqueous ammonium oxalate-soluble and ethanol-insoluble derivatives of Agaricus blazei showed marked tumor regression at doses ranging from 0.1 to 2.5 mg (p < 0.05 vs. saline control; n = 7). However, oral administration of this same fraction, either prior to, simultaneously with, or after, tumor cell inoculation did not result in tumor regression (p > 0.05 vs. control). When this fraction was treated with hydrochloric acid (acid-treated fraction; ATF), intratumoral administration resulted in a marked regression of tumor growth comparable to that of the acid-untreated fraction. More importantly, parenteral administration of ATF resulted in a significantly greater regression of tumor growth than that produced by the untreated fraction (p < 0.05 vs. untreated; n = 7). When a total of 4.5 mg of ATF was given orally at varying schedules prior to, simultaneously with, or after, tumor inoculation, a significant regression was seen using a schedule starting 4 days prior to inoculation (p < 0.05 vs. all other treatments; n = 7). NMR and molecular analyses showed that the ATF fraction had a molecular weight of approximately 10 kDa and consisted mainly of only (1,6)-beta- D-polyglucose. These results suggest that the oral administration of simple acid-treated ATF results in a remarkable tumor regression. Thus, simple acid hydrolysis of natural products may not only bring measurable benefits in oncological practice, but may also be a useful general formulation for natural products for oral chemotherapy.

Topics: Administration, Oral; Agaricus; Animals; Antineoplastic Agents; beta-Glucans; Disease Models, Animal; Drug Screening Assays, Antitumor; Glucans; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental; Plant Extracts; Xenograft Model Antitumor Assays

Paracoccidioidomycosis (PCM) is a deep mycosis caused by the thermo-dependent dimorphic fungus Paracoccidioides brasiliensis and is prevalent in Latin American countries. Diagnosis of PCM is sometimes difficult outside the endemic countries, thus a rapid and conclusive method for diagnosis of PCM has been anticipated. We compared the sensitivities of a nested PCR method for detecting the gp43 gene and a commercial kit for detecting (1-3)-beta-D-glucan in the blood of experimentally infected mice. Blood samples were collected from mice at 0 (soon after inoculation), 6, 12, 24, 48, and 72 hours and 5, 7, 10, 14, 17, 21, 24, 28 and 56 days after the intravenous inoculation of 10(6) yeast cells of P. brasiliensis, and were separated into clots and plasma. The (1-3)-beta-D-glucan detection kit in the plasma showed positive reactions in some samples within 7 days and 28 and 56 days after infections. In contrast, the PCR method was more sensitive than the (1-3)-beta-D-glucan detection kit throughout the observation period. The clot samples yielded more sensitive PCR-results than did the plasma samples. Although 24 hours is required for the PCR detection, it was confirmed to provide an accurate diagnosis of PCM.

Topics: Adult; Aged; Animals; Antigens, Fungal; beta-Glucans; Biomarkers; Child; Diphosphates; Disease Models, Animal; Drug Combinations; Female; Fungal Proteins; Genes, Fungal; Glucans; Glycoproteins; Humans; Male; Mice; Mice, Inbred Strains; Middle Aged; Nitrates; Paracoccidioides; Paracoccidioidomycosis; Polyethylenes; Polymerase Chain Reaction; Sodium Fluoride

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Disease Models, Animal; Drug Screening Assays, Antitumor; Glucans; Leukocyte Count; Leukopenia; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Polyporales; Polysaccharides; Sarcoma 180; Structure-Activity Relationship

The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system. To test this hypothesis, we administered poly-[1-6]-beta-D-glucopyranosyl- [1-3] -beta-D-glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of body weight on the day before, on the day of, and on the day after intermuscular inoculation with methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis. Abscesses were identified at 72 h, and median infective doses (ID50) and statistical significance were determined by logistic regression. Guinea pigs receiving PGG glucan and inoculated with methicillin-resistant S. aureus and S. epidermidis exhibited ID50 of as much as 2.5- and 60-fold higher, respectively, than those of control guinea pigs not receiving PGG glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg, and efficacy was reduced at higher as well as at lower PGG glucan doses. Furthermore, a single dose of PGG glucan given 24 h following bacterial inoculation was found to be effective in preventing infection. We conclude that PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; beta-Glucans; Disease Models, Animal; Female; Glucans; Guinea Pigs; Male; Staphylococcal Infections; Staphylococcus aureus; Time Factors

Topics: Adjuvants, Immunologic; Amino Acid Sequence; Animals; Blood Glucose; Diabetes Mellitus, Type 1; Disease Models, Animal; Female; Glucans; Insulin; Insulin-Like Growth Factor I; Mice; Mice, Inbred NOD; Molecular Sequence Data; Peptide Fragments; Random Allocation; Recombinant Proteins; Spleen; Statistics as Topic; T-Lymphocytes

Two immunomodulating polysaccharides, poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose (PGG)-glucan and Bacteroides fragilis polysaccharide A (PS A), were evaluated for the prevention of mortality and abscess formation associated with experimental intraabdominal sepsis. Prophylactic treatment with a combination of these compounds significantly reduced mortality (8% vs. 44% in the saline-treated control group) and the incidence of abscesses (30% vs. 100% in the saline-treated control group) after challenge with rat cecal contents. These compounds were also effective when administered therapeutically after bacterial contamination of the peritoneal cavity. PS A treatment conferred long-term protection against abscess formation and resulted in significantly fewer total aerobes and anaerobes in the peritoneal fluid of animals challenged with cecal contents. These data demonstrate the usefulness of two immunomodulatory polysaccharides in preventing experimental intraabdominal sepsis in the absence of antimicrobial therapy and may represent a new adjunct to antibiotic regimens currently used to prevent clinical cases of this disease.

Topics: Abdominal Abscess; Adjuvants, Immunologic; Animals; Bacteroides fragilis; Bacteroides Infections; beta-Glucans; Disease Models, Animal; Glucans; Male; Peritoneal Cavity; Polysaccharides, Bacterial; Rats; Rats, Wistar; Sepsis

Beta-1,3-glucan is a potent stimulator of macrophage functions and has a protective effect against a range of infections in rodent models. We examined whether the agent could also protect against the intracellular Mycobacterium bovis, bacillus Calmette-Guérin (BCG) infection in mice. BCG-susceptible BALB/c mice were injected intravenously (i.v.) with beta-glucan or vehicle 3 days before, or with beta-glucan 7 days after i.v. challenge with live BCG bacilli. The animals were killed 4 or 8 weeks later, their organs were homogenized and applied to object slides and stained with auramin for counting of bacilli, or seeded onto agar in Petri dishes. Mice treated with beta-glucan both pre- and postchallenge had significantly lower numbers of BCG bacilli and BCG colony-forming units in spleen homogenates compared with controls 4 weeks after challenge. A similar, but not statistically significant, tendency was observed in spleen homogenates from mice killed 8 weeks after challenge. In homogenates of liver and lungs there were similar findings, but less pronounced. There was a dose-dependent effect of beta-glucan injected before BCG challenge on the number of BCG bacilli found in spleen and liver homogenates. In addition, antibody cross-reactivity was demonstrated between M. tuberculosis cell wall and beta-glucan. The results suggest that beta-glucan has a protective effect against M. bovis, BCG infection in susceptible mice.

Topics: Animals; Antigens, Bacterial; Antitubercular Agents; beta-Glucans; Cell Wall; Colony Count, Microbial; Cross Reactions; Disease Models, Animal; Female; Glucans; Injections, Intravenous; Liver; Lung; Mice; Mice, Inbred BALB C; Mycobacterium bovis; Spleen; Tuberculosis

Topics: Animals; Antiprotozoal Agents; Babesia; Babesiosis; beta-Glucans; Cattle; Cattle Diseases; Cells, Cultured; Disease Models, Animal; Erythrocytes; Female; Glucans; Mice; Mice, SCID; Parasitemia

The G test containing factor G, fractioned from the Limulus lysate, was used to detect (1-3)-beta-D-glucan in a rat model of aspergillosis. Aspergillus fumigatus strain MF-13, 1 x 10(4) conidia, were inoculated transtracheally into rats treated with cortisone acetate (100 mg/kg) and fed a low-protein (8%) diet. Increased serum (1-3)-beta-D-glucan was found on the sixth day after inoculation in concentrations of 370 +/- 178 pg/ml (mean +/- SD) in untreated controls, and 154 +/- 43 pg/ml in rats treated with 0.5 mg/kg of amphotericin B. On day 11 (1-3)-beta-D-glucan concentrations were 2,590 +/- 2,940 pg/ml and 448 +/- 442 pg/ml, respectively. The elevation in levels of (1-3)-beta-D-glucan increased in correlation with the elevation of galactomannan antigen titers; (1-3)-beta-D-glucan is thus measurable during experimental aspergillosis in rats.

Topics: Amphotericin B; Animals; Aspergillosis; Aspergillus fumigatus; beta-Glucans; Disease Models, Animal; Galactose; Glucans; Horseshoe Crabs; Lung; Male; Mannans; Rats; Rats, Sprague-Dawley

An indirect method to measure beta-glucan, a major structural component of yeast cell walls, is available, but has the disadvantage of requiring the combined use of two assays. Recent reports describe the fungal index, which measures the difference between the conventional limulus test, in which factors C and G react with endotoxin and beta-glucan, and a new endotoxin-specific test, in which only factor C reacts with endotoxin. The G test was developed as a direct method to measure beta-glucan, and contains only factor G reacting with beta-glucan alone. In this study, the G test was examined in sera of rabbits with experimental systemic candidiasis, and compared with the fungal index and mannan assay. The G test showed positive in all rabbits with systemic candidiasis faster and with higher titers than with the fungal index. Three rabbits with fulminant systemic candidiasis showed higher levels of reactivity with the G test and the fungal index than two rabbits with mild reactions. Mannan was positive by at least one serum in four of five rabbits by the latex agglutination test, and there was a good correlation between these assays. The G test is a good serodiagnostic method for the detection of candidiasis.

Topics: Animals; Antigens, Fungal; beta-Glucans; Candidiasis; Disease Models, Animal; Evaluation Studies as Topic; Glucans; Limulus Test; Mannans; Mycology; Rabbits; Sensitivity and Specificity

A series of lipopeptide compounds co-produced during the fermentation of pneumocandin A0 (L-671,329) and related semisynthetic compounds were evaluated in vivo against Pneumocystis carinii pneumonia and systemic candidiasis. In addition, they were tested in vitro against a panel of pathogenic Candida species and in a Candida membrane 1,3-beta-D-glucan synthesis assay. The results of these studies demonstrate that pneumocandin A0 and pneumocandin B0 (L-688,786) are the most potent compounds when considering both antipneumocystis and anticandida activity. Other compounds in the series are selectively more potent against P. carinii or Candida albicans suggesting a diverging structure-activity relationship. Evaluation of these compounds for their ability to inhibit C. albicans 1,3-beta-D-glucan synthesis in vitro demonstrates that they inhibit this process. A positive correlation between 1,3-beta-D-glucan synthesis inhibition and in vitro antifungal activity was also demonstrated for some of the pneumocandins.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; beta-Glucans; Candida albicans; Cell Membrane; Disease Models, Animal; Echinocandins; Erythrocytes; Glucans; Hemolysis; Humans; Mice; Microbial Sensitivity Tests; Mitosporic Fungi; Peptides; Peptides, Cyclic; Pneumocystis; Structure-Activity Relationship

A new beta-1,3-D-glucan synthesis inhibitor, L-687,781 is produced by the cultivation of Dictyochaeta simplex ATCC 20960. L-687,781 exhibits potent in vitro antifungal activity as well as anti-Pneumocystis activity in a rat model.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Cryptococcus neoformans; Disease Models, Animal; Fermentation; Fungi; Glucans; Male; Mice; Mitosporic Fungi; Pneumonia, Pneumocystis; Pyrans; Rats; Rats, Inbred Strains