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Candida albicans Beta-Glucan Induce Anti- Cancer Activity of Mesenchymal Stem Cells against Lung Cancer Cell Line: An In-Vitro Experimental Study.
Peymaeei, F, Sadeghi, F, Safari, E, Khorrami, S, Falahati, M, Roudbar Mohammadi, S, Roudbary, M
Asian Pacific journal of cancer prevention : APJCP. 2020;(3):837-843
Abstract
OBJECTIVE β-glucan, glucopyranosyl polymers of fungi cell wall, represent an immune stimulating effects with potential anti-cancer activity. Mesenchymal stem cells (MSC) have immunomodulating properties in cancer microenvironment. The aim of this study was to investigate the anti-cancer effect of Candida albicans (C. albicans) beta-glucan on MSCs supernatant for apoptosis assay of lung cancer cells in vitro. METHODS Beta-glucan was extracted from cell wall of C.albicans. MSC isolated from adipose tissue of patients and confirmed using specific surface markers expression which examined by flow cytometry. MSCs treated with various concentrations of β-glucans for 48 hours. Cytotoxic effect of β-glucans was evaluated using MTT assay. MSC and lung cancer line cocultured and treated with β-glucans and apoptosis assay was done by flow cytometry. RESULTS Cytotoxicity findings showed a significant decrease in MSC viability during 48h, however it was dose-dependent (P<0.05). According to the obtained findings, supernatant of mesenchymal stem cells treated with β-glucans increased cancer cells apoptosis (P<0.05). CONCLUSION Beta glucan may highlight a potential and novel promising candidate in future strategies to cause apoptosis of cancer cells and consider as therapeutic agent against tumor growth as well. Definitely, more in vitro and in vivo studies are required to understand its functions.
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Detection of Beta-Glucan Contamination in Nanotechnology-Based Formulations.
Neun, BW, Cedrone, E, Potter, TM, Crist, RM, Dobrovolskaia, MA
Molecules (Basel, Switzerland). 2020;(15)
Abstract
Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. Pyrogenicity (the ability to induce fever) and activation of innate immune responses underlying both acute toxicities (e.g., anaphylactoid reactions or pseudoallergy, cytokine storm) and long-term effects (e.g., immunogenicity) are among the IMAE commonly related to IIMI contamination. Endotoxins of gram-negative bacteria are the best-studied IIMIs in that both methodologies for and pitfalls in their detection and quantification are well established. Additionally, regulatory guidance documents and research papers from laboratories worldwide are available on endotoxins. However, less information is currently known about other IIMIs. Herein, we focus on one such IIMI, namely, beta-glucans, and review literature and discuss the experience of the Nanotechnology Characterization Lab (NCL) with the detection of beta-glucans in nanotechnology-based drug products.
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Nutraceutical functions of beta-glucans in human nutrition.
Ciecierska, A, Drywień, ME, Hamulka, J, Sadkowski, T
Roczniki Panstwowego Zakladu Higieny. 2019;(4):315-324
Abstract
Recent studies have shown that naturally occurring substances found in the food of the daily human diet are important for preventing chronic non-communicable diseases. One of them is beta-glucan, which is a natural polysaccharide, occurring in plant cell walls, mainly oats, barley and wheat. It is also present in baker’s yeast cells, fungal cell walls, and some microorganisms. Beta-glucan belongs to one of the dietary fiber fractions, which are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. This compound has biological activity that depends on the size, molecular weight, conformation, frequency of bonds, solubility and changes in structure. Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. In addition to its effects on lipid levels and glucose metabolism, beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. The immunostimulatory activity of beta-glucan occurs as a result of its attachment to specific receptors present on the immune cell surface. Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. It plays an important role in the proper functioning of the gastrointestinal tract and preventing inflammation as well as colon cancer. Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.
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Infectious Agents as Stimuli of Trained Innate Immunity.
Rusek, P, Wala, M, Druszczyńska, M, Fol, M
International journal of molecular sciences. 2018;(2)
Abstract
The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells) after their stimulation with various infectious or non-infectious agents. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin) as well as viruses or even parasites are considered potent inducers of innate immune memory. Epigenetic cell reprogramming occurring at the heart of the phenomenon may provide a useful basis for designing novel prophylactic and therapeutic strategies to prevent and protect against multiple diseases. In this article, we present the current state of art on trained innate immunity occurring as a result of infectious agent induction. Additionally, we discuss the mechanisms of cell reprogramming and the implications for immune response stimulation/manipulation.
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Use of (1→3)-β-d-glucan for diagnosis and management of invasive mycoses in HIV-infected patients.
Farhour, Z, Mehraj, V, Chen, J, Ramendra, R, Lu, H, Routy, JP
Mycoses. 2018;(10):718-722
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Abstract
People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures. Hence, identification of surrogate markers for the early diagnosis and therapeutic monitoring of IFIs is required. Recent studies have shown that (1→3)-β-d-glucan (BDG), a major fungal cell wall antigen, represents a promising soluble marker for the presumptive diagnosis and therapeutic monitoring of IFIs in HIV-infected patients. Herein, we review findings on the merits of BDG assays in the diagnosis of IFIs and monitoring of antifungal therapies for PLHIV. Conversely to other types of immunocompromised patients, HIV infection is associated with gut damage and subsequent bacterial and fungal translocation leading to elevated BDG plasma levels.
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Respiratory Tract Infections and the Role of Biologically Active Polysaccharides in Their Management and Prevention.
Jesenak, M, Urbancikova, I, Banovcin, P
Nutrients. 2017;(7)
Abstract
Respiratory tract infections (RTIs) are the most common form of infections in every age category. Recurrent respiratory tract infections (RRTIs), a specific form of RTIs, represent a typical and common problem associated with early childhood, causing high indirect and direct costs on the healthcare system. They are usually the consequence of immature immunity in children and high exposure to various respiratory pathogens. Their rational management should aim at excluding other severe chronic diseases associated with increased morbidity (e.g., primary immunodeficiency syndromes, cystic fibrosis, and ciliary dyskinesia) and at supporting maturity of the mucosal immune system. However, RRTIs can also be observed in adults (e.g., during exhausting and stressful periods, chronic inflammatory diseases, secondary immunodeficiencies, or in elite athletes) and require greater attention. Biologically active polysaccharides (e.g., β-glucans) are one of the most studied natural immunomodulators with a pluripotent mode of action and biological activity. According to many studies, they possess immunomodulatory, anti-inflammatory, and anti-infectious activities and therefore could be suggested as an effective part of treating and preventing RTIs. Based on published studies, the application of β-glucans was proven as a possible therapeutic and preventive approach in managing and preventing recurrent respiratory tract infections in children (especially β-glucans from Pleurotus ostreatus), adults (mostly the studies with yeast-derived β-glucans), and in elite athletes (studies with β-glucans from Pleurotus ostreatus or yeast).
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A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects.
Ganda Mall, JP, Casado-Bedmar, M, Winberg, ME, Brummer, RJ, Schoultz, I, Keita, ÅV
Inflammatory bowel diseases. 2017;(1):166-178
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Abstract
BACKGROUND Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro. METHODS Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs. RESULTS β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls. CONCLUSIONS We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.
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A computational model for regulation of nanoscale glucan exposure in Candida albicans.
Wester, MJ, Lin, J, Neumann, AK
PloS one. 2017;(12):e0188599
Abstract
Candida albicans is a virulent human opportunistic pathogen. It evades innate immune surveillance by masking an immunogenic cell wall polysaccharide, β-glucan, from recognition by the immunoreceptor Dectin-1. Glucan unmasking by the antifungal drug caspofungin leads to changes in the nanostructure of glucan exposure accessible to Dectin-1. The physical mechanism that regulates glucan exposure is poorly understood, but it controls the nanobiology of fungal pathogen recognition. We created computational models to simulate hypothetical physical processes of unmasking glucan in a biologically realistic distribution of cell wall glucan fibrils. We tested the predicted glucan exposure nanostructural features arising from these models against experimentally measured values. A completely spatially random unmasking process, reflective of random environmental damage to the cell wall, cannot account for experimental observations of glucan unmasking. However, the introduction of partially edge biased unmasking processes, consistent with an unmasking contribution from active, local remodeling at glucan exposure sites, produces markedly more accurate predictions of experimentally observed glucan nanoexposures in untreated and caspofungin-treated yeast. These findings suggest a model of glucan unmasking wherein cell wall remodeling processes in the local nanoscale neighborhood of glucan exposure sites are an important contributor to the physical process of drug-induced glucan unmasking in C. albicans.