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A low intake of whole grains is actually the leading dietary risk factor for death and disease in the USA. Few healthy grains are discussed in this chapter that can help prevent health problems like heart diseases, diabetes, and cancers.
Galactomannan, β-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.
All fungal biomarkers demonstrated highly variable sensitivity, specificity and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85-100% for screening and 70-100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.
Cellular and molecular effects of yeast probiotics on cancer.
This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.
Yeast-Derived β-Glucan in Cancer: Novel Uses of a Traditional Therapeutic.
These new concepts, along with the emerging success of combinatorial approaches to cancer treatment involving β-glucan, suggest that β-glucan may play an essential role in future strategies to prevent and inhibit tumor growth. This review emphasizes the various characteristics of β-glucan, with an emphasis on fungal β-glucan, and highlights novel approaches of β-glucan in cancer therapy.
New bioactive compounds from korean native mushrooms.
Mushrooms are ubiquitous in nature and have high nutritional attributes. They have demonstrated diverse biological effects and therefore have been used in treatments of various diseases, including cancer, diabetes, bacterial and viral infections, and ulcer. In particular, polysaccharides, including β-glucan, are considered as the major constituents responsible for the biological activity of mushrooms. Although an overwhelming number of reports have been published on the importance of polysaccharides as immunomodulating agents, not all of the healing properties found in these mushrooms could be fully accounted for. Recently, many research groups have begun investigations on biologically active small-molecular weight compounds in wild mushrooms. In this mini-review, both structural diversity and biological activities of novel bioactive substances from Korean native mushrooms are described.
Bioactive fungal polysaccharides as potential functional ingredients in food and nutraceuticals.
Fungal bioactive polysaccharides deriving mainly from the Basidiomycetes family (and some from the Ascomycetes) and medicinal mushrooms have been well known and widely used in far Asia as part of traditional diet and medicine, and in the last decades have been the core of intense research for the understanding and the utilization of their medicinal properties in naturally produced pharmaceuticals. In fact, some of these biopolymers (mainly β-glucans or heteropolysaccharides) have already made their way to the market as antitumor, immunostimulating or prophylactic drugs. The fact that many of these biopolymers are produced by edible mushrooms makes them also very good candidates for the formulation of novel functional foods and nutraceuticals without any serious safety concerns, in order to make use of their immunomodulating, anticancer, antimicrobial, hypocholesterolemic, hypoglycemic and health-promoting properties. This article summarizes the most important properties and applications of bioactive fungal polysaccharides and discusses the latest developments on the utilization of these biopolymers in human nutrition.
Preclinical and clinical studies of Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China.
In this article, the results of PSP-related preclinical and clinical studies conducted in China from over 40 independent studies during the past 40 years based on searching the Chinese VIP, CNKI, and Wanfang databases are presented. Its immunomodulatory and anti-tumor molecular mechanisms are also summarized. PSP activates immune cells, increases the expressions of cytokines and chemokines such as tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6), histamine, and prostaglandin E, enhances dendritic and T-cell infiltration into tumors, and ameliorates the adverse events associated with chemotherapy. The clinical studies support PSP being a potential immunotherapeutic. However, the complicated chemical and multiple pharmacological properties of PSP need to be investigated further.
The effects of β-glucans on cancer metastasis.
Beta-glucans (β-glucans), naturally occurring polysaccharides, are present as constituents of the cell wall of cereal grains, mushrooms, algae, or microbes including bacteria, fungi, and yeast. Since Pillemer et al. first prepared and investigated zymosan in the 1940s and others followed with the investigation of β-glucans in the 1960s and 1970s, researchers have well established the significant role of β-glucans on the immune system relative to cancer treatment, infection immunity, and restoration of damaged bone marrow. However, information on their biological role in anti-metastatic activity remains limited. As an immunomodulating agent, β-glucan acts through the activation of innate immune cells such as macrophages, dendritic cells, granulocytes, and natural killer cells. This activation triggers the responses of adaptive immune cells such as CD4(+) or CD8(+) T cells and B cells, resulting in the inhibition of tumor growth and metastasis. Reports have shown that β-glucans exert multiple effects on cancer cells and cancer prevention. However the mechanisms of their actions appear complex due to differences in source, chemical structure, insufficiently defined preparation, and molecular weight, hence the inconsistent and often contradictory results obtained. This review is focused on the potential of β-glucans as anti-metastatic agents and the known mechanisms underlying their biological effects.
New Concepts in Diagnostics for Invasive Mycoses: Non-Culture-Based Methodologies.
The importance of assessing risk and using non-culture-based diagnostics for invasive fungal disease is clear. Several methods have been evaluated and validated for clinical use including galactomannan, beta-d-glucan, lateral flow technology, T2 magnetic resonance, PCR and others. Non-culture-based biomarkers provide more reliable negative than positive predictive values. When the prevalence of disease is higher than 15%, negative test results exclude the diagnosis, while positive test results include the diagnosis. Clinicians and laboratories need to consider when a test is being requested for screening (when a patient is at risk for invasive fungal disease) as opposed to diagnosis (in which there is a high clinical suspicion of an invasive fungal disease), which will have a substantially higher pre-test probability. Finally, combinations of these tests may provide the greatest benefit in establishing a diagnosis of invasive fungal disease.
Effect of processing on barley β-glucan content, its molecular weight and extractability.
β-Glucan is the most unique polysaccharide of barley which is associated with numerous health benefits including reduction of cholesterol, manage post postprandial blood glucose levels and acts as an anti-cancerous agent. Since food grains including barley are consumed after processing and it may alter the solubility, molecular weight and extractability of β-glucan affecting the health benefits. Therefore, it is important to know the processing effects on β-glucan to confirm such health claims for barley. Most of the review papers published are focused on the health benefits of β-glucan. To the best of our knowledge, no comprehensive report is available on the effects of barley processing on β-glucan content, molecular weight and β-glucan extractability. The present article reviews the literature on processing effects on barley β-glucan.
Fungal mediated innate immune memory, what have we learned?
This review aims at presenting the newly described aspect of memory in innate immunity with an emphasis on the historically fungal mediated one, covering the known molecular mechanisms associated with training. In addition, the review uncovers the numerous non-specific effect that β-glucans trigger in the context of infectious diseases and septicaemia, inflammatory diseases and cancer.
Effects of dietary fiber and its components on metabolic health.
Epidemiological and clinical studies demonstrate that intake of dietary fiber and whole grain is inversely related to obesity, type two diabetes, cancer and cardiovascular disease (CVD). Defining dietary fiber is a divergent process and is dependent on both nutrition and analytical concepts. The most common and accepted definition is based on nutritional physiology. Generally speaking, dietary fiber is the edible parts of plants, or similar carbohydrates, that are resistant to digestion and absorption in the small intestine. Dietary fiber can be separated into many different fractions. Recent research has begun to isolate these components and determine if increasing their levels in a diet is beneficial to human health. These fractions include arabinoxylan, inulin, pectin, bran, cellulose, β-glucan and resistant starch. The study of these components may give us a better understanding of how and why dietary fiber may decrease the risk for certain diseases. The mechanisms behind the reported effects of dietary fiber on metabolic health are not well established. It is speculated to be a result of changes in intestinal viscosity, nutrient absorption, rate of passage, production of short chain fatty acids and production of gut hormones. Given the inconsistencies reported between studies this review will examine the most up to date data concerning dietary fiber and its effects on metabolic health.
Diagnostic Accuracy of β-d-Glucan (Fungitell) Testing Among Patients With Hematologic Malignancies or Solid Organ Tumors: A Systematic Review and Meta-Analysis.
We screened 12,426 references and identified 189 studies for full-text review. Nineteen studies were included in the final meta-analysis. There was moderate heterogeneity between studies. Nine studies had a high risk of bias, which significantly elevated the overall specificity estimate. Restricting to only low-bias studies, the sensitivity and specificity were 80% and 63%, respectively. Conclusions: The overall sensitivity and specificity of Fungitell as a diagnostic test for IFI is moderate, and there is substantial heterogeneity between studies. Limiting studies to only low-bias risk reduced heterogeneity but also lowered the overall specificity estimate.
Mycotherapy of cancer: an update on cytotoxic and antitumor activities of mushrooms, bioactive principles and molecular mechanisms of their action.
Mycotherapy is defined as the study of the use of extracts and compounds obtained from mushrooms as medicines or health-promoting agents. The present review updates the recent findings on anticancer/antitumor agents derived from mushroom extracts and their metabolites. The increasing number of studies in the past few years revealed mushroom extracts as potent antitumor agents. Also, numerous studies were conducted on bioactive compounds isolated from mushrooms reporting the heteropolysaccharides, β-glucans, α-glucans, proteins, complexes of polysaccharides with proteins, fatty acids, nucleoside antagonists, terpenoids, sesquiterpenes, lanostanoids, sterols and phenolic acids as promising antitumor agents. Also, molecular mechanisms of cytotoxicity against different cancer cell lines are discussed in this review. Findings with Antrodia camphorata and Ganoderma lucidium extracts and isolated compounds are presented, as being the most deeply studied previously.
Beta-glucan contamination of pharmaceutical products: How much should we accept?
In patients with cancer (the intended patient population for the CRUKD/14/001 trial), possible immunostimulatory and/or direct anti-tumour effects of beta-glucan contaminants would, if anything, be considered desirable from a patient benefit perspective. However, in this first-in man, first-in-class, proof-of-concept trial, it is important to ensure that any anti-tumour efficacy observed is due to therapeutic MOv18 IgE itself. Moreover, for biotherapeutic agents developed for non-oncology indications, immunostimulatory effects would not necessarily be desirable. Based on currently available data, a limit of 10 ng/mg (or 500 ng total dose) of beta-glucans seems unlikely to provoke any clinically significant immunological effects and this level may be acceptable for medicinal agents.
Effects of orally administered yeast-derived beta-glucans: a review.
In human trials, orally administered Y-BG significantly reduced the incidence of upper respiratory tract infections in individuals susceptible to upper respiratory tract infections, whereas significant differences were not seen in healthy individuals. Increased salivary IgA in healthy individuals, increased IL-10 levels in obese subjects, beneficial changes in immunological parameters in allergic patients, and activated monocytes in cancer patients have been reported following Y-BG intake. The studies were conducted with different doses (7.5-1500 mg/day), using different preparations that vary in their primary structure, molecular weight, and solubility. In animal models, oral Y-BG have reduced the incidence of bacterial infections and levels of stress-induced cytokines and enhanced antineoplastic effects of cytotoxic agents. Protective effects toward drug intoxication and ischemia/reperfusion injury have also been reported. In conclusion, additional studies following good clinical practice principles are needed in which well-defined Y-BG preparations are used and immune markers and disease endpoints are assessed. Since optimal dosing may depend on preparation characteristics, dose-response curves might be assessed to find the optimal dose for a specific preparation.
Vaccine adjuvants as potential cancer immunotherapeutics.
Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. From VV (via email w/ AJ) Description of the possible use of glucan as vaccine adjuvant, leading to subsequent use of glucan as vaccine carrier.
Beta-glucans in higher fungi and their health effects.
Together with chitin, the beta-glucans are components of mycetes' cell walls. A high level of biological efficiency has been found in beta-glucans, especially beta-1,3-D-glucans and beta-1,6-D-glucans isolated from some basidiomycetes. (Biological efficiency refers to the relative ability of beta-glucans to promote a desired response, for example to induce leukocyte activation and to produce inflammatory mediators.) These polysaccharides increase the number of Th1 lymphocytes, which help protect organisms against allergic reactions. A number of beta-glucans, for example pleuran from Oyster (Pleurotus spp.) mushrooms or lentinan from Shiitake (Lentinus edodes) mushrooms, have shown marked anticarcinogenic activity. In addition to having an immunity-stimulating effect, beta-glucans may participate in physiological processes related to the metabolism of fats in the human body. Their application results in a decrease in the total cholesterol content in blood and may also contribute to reductions in body weight.
Non-Starch Polysaccharides in Durum Wheat: A Review.
The characterisation of specific plant materials and the release of the durum wheat genome sequences, together with the development of more accurate classes of DNA-based markers and consensus maps, have allowed the identification of important genes involved in the control of (1,3;1,4)-β-glucan and arabinoxylan biosynthesis. Many QTL region have been described to be involved in the control of (1,3;1,4)-β-glucan and arabinoxylan but none of them were associated to one of the cellulose synthase (CslF, CslH and CslJ) and glycosyl transferase genes (GT43, GT47 and GT61), which have been designated as responsible for the regulation and accumulation of (1,3;1,4)-β-glucan and arabinoxylan, respectively, in different tissues types. Nevertheless, the isolation and characterisation of the CslF6 and CslH durum gene sequences have been reported together with the expression pattern in durum endosperm at different developmental stages, increasing the speed of the genetic gains. The control of these traits by several genes makes it interesting to incorporate beneficial alleles, which can contribute to the rise in non-starch polysaccharides content in durum kernels, into introgressed lines to obtain new durum genotypes with higher (1,3;1,4)-β-glucan and arabinoxylan. The additive effects of some designated genes in the QTL regions reported could be used to generate breeding plants though the marker assisted selection (MAS) approach.
Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.
Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties.
Beta-glucans and cancer: The influence of inflammation and gut peptide.
This article reviews the effects of different enriched β-glucan food consumption on immune responses, inflammation, gut hormone and cancer. Gut hormones are influenced by enriched β-glucan food consumption and levels of such peptide as YY, ghrelin, glucagon-like peptide 1 and 2 in humans influence serum glucose concentration as well as innate and adaptive immunity. Cancer cell development is also regulated by obesity and glucose dishomeostasy that are influenced by β-glucan food consumption that in turn regulated gut hormones.
β-glucans as potential immunoadjuvants: A review on the adjuvanticity, structure-activity relationship and receptor recognition properties.
β-glucans, a group of polysaccharides exist in many organism species such as mushrooms, yeasts, oats, barley, seaweed, but not mammalians, have a variety of biological activities and applications in drugs and other healthcare products. In recent years, β-glucans have been studied as adjuvants in anti-infection vaccines as well as immunomodulators in anti-cancer immunotherapy. β-glucans can regulate immune responses when administered alone and can connect innate and adaptive immunity to improve immunogenicity of vaccines. When β-glucans act as immunostimulants or adjuvants, a set of receptors have been revealed to recognize β-glucans, including dectin-1, complement receptor 3 (CR3), CD5, lactosylceramide, and so on. Therefore, this review is mainly focused on the application of β-glucans as immune adjuvants, the receptors of β-glucans, as well as their structure and activity relationship which will benefit future research of β-glucans.
β-Glucans and their applications in cancer therapy: focus on human studies.
β-glucans belong to a group of polysaccharides located in the cell wall of bacteria, fungi including mushrooms, as well as cereals such as barley and oats. All β-glucans are glucose polymers linked together by a (β 1-3) linear β-glycosidic chain core and they differ by their length and branching structures. They are considered biological response modifiers with immunomodulatory and health beneficial effects including anticancer properties. Few studies using purified β- glucans were performed, but their anticancer potential was demonstrated mainly through studies using extracts from mushrooms, yeast or other sources which contain β-glucan as a key component. Their anticancer effects were demonstrated mainly in in vitro and in vivo experimental systems but fewer studies from human populations are available. β-glucans have been used as adjuvant therapy in clinical trials, mainly in the Far East, with a positive effect on patients'survival and quality of life. The mechanism of action is suggested to be through its stimulation of the immune system. This review focuses on human studies; clinical trials and epidemiological data assessing the efficacy and safety of mushroom-derived β- glucans in cancer treatment and prevention. The potential direct effects of β-glucans on cancer cells are also described.
Lung cancer and β-glucans: review of potential therapeutic applications.
The potential of natural substances with immunotherapeutic properties has long been studied. β-glucans, a cell wall component of certain bacteria and fungi, potentiate the immune system against microbes and toxic substances. Moreover, β-glucans are known to exhibit direct anticancer effects and can suppress cancer proliferation through immunomodulatory pathways. Numerous researchers are now dedicated to using β-glucans as a therapy for lung cancer. In the present attempt, we have reviewed the studies addressing therapeutic effects of β-glucans in primary and metastatic lung cancer published in the time period of 1991-2016.
Consumption of β-glucans to spice up T cell treatment of tumors: a review.
This review summarizes timely reports with respect to absorption, trafficking and immune stimulatory effects of β-glucans, particularly in relation to innate immune cells. Furthermore, we list effects toward well-being and immune functions in healthy subjects as well as cancer patients treated with orally administered β-glucans, extended with effects of β-glucan treatments in mouse cancer models. Expert opinion: Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer.
Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3-1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects.
In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (i.v.) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily i.v. infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non-compartmental analyses were performed. Results: Thirty-six subjects (N = 24 Phase 1a; N = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67% of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in ≥10% of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t1/2) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t1/2, and Vss values were larger at steady state on days 6-30 versus day 0. Conclusions: BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg.
Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta-analysis.
This study was sought to evaluate the efficacy of adjuvant lentinan combined with chemotherapy for advanced cancer. A meta-analysis of published prospective controlled trials investigating the effects of lentinan for kinds of advanced cancer was performed. Sensitivity analysis, inverted funnel plots, and trial sequence analysis were conducted to explore the reliability and stability of results. Seventeen clinical studies were identified containing 1423 patients. Twelve trials included gastrointestinal cancer (GIC), three trials included lung cancer (LC), and two trials included the two cancers. There was a increase in survival rate in 1 year (risk ratios [RR], 1.46, P = 0.001) and overall response rate including both complete and partial response (RR, 1.28, P = 0.005). There was also a reduction in progressive disease (RR, 0.57, P = 0.0005), nonsevere adverse events (RR, 0.88, P = 0.004), and severe adverse events (RR, 0.73, P = 0.007). Similar results were shown in the two subgroups of GIC and LC. Limited trials reported the data of median overall survival and time to treatment failure, and the data were insufficient for quantitative analysis, and no significant difference were found in 2-year survival rate. Adjuvant lentinan used with chemotherapy achieved improvements in 1-year survival rate, response rate, and adverse events in advanced cancer. The effect seemed to be similar irrespective of cancer type. However, its sustained efficacy on survival was still unclear.
Functional activities of beta-glucans in the prevention or treatment of cervical cancer.
Recent studies with focusing on their influence on cytotoxic and helper T cells, APCs, inflammatory pathways, and oxidative burst (by using reactive oxygen species to destroy cells.) have revealed that they can also have some anti-cancer properties. Even so the main mechanisms in which these glucans function are inducing the APCs and T cells and thereby activating the anti-tumor immune system and subverting the suppressors of this immune system by stimulating the differentiation of MDSCs. It is also worth to mention that a study represented an antioxidant effect of oat beta-glucans [160] but further investigations are needed to prove their role in cancer prevention by scavenging free radicals. Likewise, a mAB-based therapy which is a medical progression into a new era of cancer treatment is only effective on tumor cells using adjuvant beta-glucans. The mentioned evidences have shown that sizofiran, zymosan, curdlan, PBG, and other beta-glucans can be employed in the prevention or treatment of cervical cancer. Taken together, it seems that further investigations are needed on beta-glucans to prove their toxicity on cervical cancer cells, non-toxicity on normal cells, and their ability for carrying drugs to the cancer site. We suggest that some beta-glucans such as pleuran, chrysolaminarian, laminarin, and zymosan which are not properly taken into consideration in the cervical cancer therapy field, might be convenient candidates for their characteristics such as anti-inflammatory activities and anti-oxidant impacts (Fig. 1). Moreover, further studies on delivering chemotherapeutic drugs by schizophyllan and curdlan might give new insight into cervical cancer therapy. More explorations on the influence of beta-glucans on the CR3 receptor cervical cancer cells would open new horizons for replacing dangerous common therapies with non-toxic treatments. In the prevention point of view, there is a need for more researches on the mechanisms by which beta-glucans influence HPV infection and also a need for more researches on delivering HPV proteins by beta-glucans as a vaccine.
Immune modulating effects of β-glucan.
β-Glucans have been investigated for their ability to protect against infection and cancer and more recently for their therapeutic potential when combined with cancer therapy. Their immune modulating effects are attributed to the ability to bind to pattern recognition receptors including complement receptor 3, scavenger receptors, lactosylceramide, and dectin-1 that results in activation of different aspects of the immune response depending on the cell types and species involved although there is some controversy about the relative importance of each of these receptors. Most of the available evidence comes from preclinical data and human studies are just now beginning to appear in the literature, therefore firm conclusions on its clinical importance cannot yet be made. Perhaps the most promising evidence to date in human trials has come from recent studies on a benefit of β-glucan on quality of life and survival when given in combination with cancer treatment. We identify the need for future studies that compare purified forms of β-glucans from different sources to further the understanding of the mechanisms of action and aid in the development of clinical studies. Summary: β-Glucans appear to be effective at enhancing immune function and reducing susceptibility to infection and cancer. A better understanding of the mechanisms of β-glucan recognition and subsequent immune activation is necessary for the design of effective treatment approaches in future clinical trials
A critical review on the impacts of β-glucans on gut microbiota and human health.
The review was aimed to accumulate the evidence on types of β-glucans, their functional properties and the mechanism by how the β-glucans regulate the gut microbiota and human health. The various in vitro, in vivo and clinical studies, have been summarized, in particular, the changes happening upon the β-glucans supplementation on the gut microbiota. Overall, this review updates the recent studies on β-glucans and gut microbiota and also inputs the demanding questions to be addressed in β-glucans-microbiota research in the future.
Medicinal mushroom: boon for therapeutic applications.
The present review focuses on the comprehensive account of the medicinal properties of various medicinal mushrooms. This will further help the researchers to understand the metabolites and find other metabolites as well from the mushrooms which can be used for the potential development of the drugs to treat various life-threatening diseases.
Enhanced anti-lung carcinoma and anti-biofilm activity of fungal molecules mediated biogenic zinc oxide nanoparticles conjugated with β-D-glucan from barley.
These results indicated that T-ZnO NPs and T-β-D-glu-ZnO NPs induced the cancer cell death through necrosis and apoptosis pathway, respectively. The antibacterial results indicated that the NPs treatment were significantly inhibited the growth of the Staphylococcus aureus inside of roundworm and enhanced growth of roundworm. Overall, anticancer and in vitro, in vivo antibacterial studies proved the high caliber of T-β-D-glu-ZnO NPs for the further pharmaceutical evaluation.
Natural Macromolecules with Protective and Antitumor Activity.
This review summarizes the literature data regarding plant lectins as novel drug sources in the prevention or treatment of cancer. Moreover, such compounds have been described as natural toxins that possess different biological activities (cytotoxic, antitumor, antimutagenic and anticarcinogenic properties). This activity depends greatly on their structure and affinity. Most of the mushroom heterosides are known as β-glucans with β-(1→3)-glycosidic bonds. It is thought that their conformation, bonds, molecular size can modulate the immune response by triggering different receptors. The mechanism on normal and tumor cells of various plant and mushroom polysaccharides and lectins is briefly presented in this paper.
Agaricus blazei Bioactive Compounds and their Effects on Human Health: Benefits and Controversies.
The amount and quality of the evidence that has been accumulating during the last decade strongly speaks in favor of the health benefits of the ingestion of A.blazei or derived products. However, there are many uncertainties and limitations when attempts are made to extrapolate or to demonstrate their biological effects in the human organism in health or disease. Clearly, more clinical trials, using reliable statistical methods and standardized preparations are needed to establish the efficacy of A. blazei as a therapeutic agent.
Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials.
This paper represents an up-to-date review of glucans (β-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.
Effect of beta glucan on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy: a randomized double-blind placebo-controlled clinical trial.
This randomized double-blind placebo-controlled clinical trial was conducted on 30 women with breast carcinoma aged 28-65 years. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure with matching based on age, course of chemotherapy and menopause status. Patients in the intervention group received two 10-mg capsules of soluble 1-3, 1-6, D-beta glucan daily and the control group receiving placebo during 21 days, the interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts as well as serum levels of IL-4 and IL-12 were measured at baseline and at the end of the study as primary outcomes of the study. Results: In both groups white blood cell counts decreased after 21 days of the intervention, however in the beta glucan group, WBC was less decreased non significantly than the placebo group. At the end of the study, the change in the serum level of IL-4 in the beta glucan group in comparison with the placebo group was statistically significant (p=0.001). The serum level of IL-12 in the beta glucan group statistically increased (p=0.03) and comparison between two groups at the end of the study was significant after adjusting for baseline values and covariates (p=0.007). Conclusions: The findings suggest that beta glucan can be useful as a complementary or adjuvant therapy and immunomodulary agent in breast cancer patients in combination with cancer therapies, but further studies are needed for confirmation.
Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701).
Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. Results: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. Conclusions: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer.
Ganoderma sinense polysaccharide: An adjunctive drug used for cancer treatment.
Both basic and preclinical studies showed that GSP has antitumor, antioxidant, anticytopenia, and unique mushroom-poison detoxification properties that are different from that of GLPS. Our goal is to provide a molecular picture that would allow in-depth evaluation of GSP as one of few glycan-based drugs that has been used as an immunomodulatory adjunctive drug during cancer therapy.
Potential of the beta-glucans to enhance innate resistance to biological agents.
The use of numerous mushroom species in traditional medicine has been widely documented, with their observed immunomodulatory effects now attributed, in part, to bioactive components called beta-glucans. The beta-glucans are of particular interest since they are naturally occurring polymers of glucose, are orally active when taken as food supplements and have a long track record of safe use. Due to their immunomodulatory properties, purified beta-glucans have been used clinically as part of a combination therapy for a variety of cancers and their potential anti-infective properties have received attention. This review relates the structure of beta-glucans to their function, with a particular focus on their documented immunomodulatory effects and the mechanisms by which they affect inter- and intracellular function, resulting in potential antimicrobial benefits. Overall, the benefits of dietary supplementation with beta-glucans in order to enhance innate resistance to biological agents are evaluated.
A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer.
Results: ORR was higher in the BTH1677 vs Control arm but the difference between groups was not statistically significant (60.4% vs 43.5%; P = .2096). All other clinical endpoints also favored the BTH1677 arm but none statistically differed between arms. PK was consistent with previous studies. Although a higher incidence of Grade 3/4 AEs occurred in the BTH1677 vs Control arm (93.2% vs 66.7%), no unexpected AEs were observed. Serious AEs and discontinuations due to AEs were lower in the BTH1677 vs Control arm. Conclusions: Improvements in tumor assessments and survival were observed with BTH1677/bevacizumab/carboplatin/paclitaxel compared with control treatment in patients with advanced NSCLC.
The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System.
Several experimental evidences have demonstrated a crucial role for β-glucan in the host–pathogen interaction during infections. Moreover, considerable efforts have been made to understand the cellular and molecular mechanisms of action of β-glucan in fungal pathogenesis as well as how it promotes a phagocytic-mediated immune response. Similarly, administration of fungal β-glucan is well known to stimulate the immune system and boost resistance to various infectious diseases and cancers, highlighting the multifaceted role of this molecule (Figure ​(Figure1).1). However, although many in vivo studies have shown a beneficial effect of the β-glucans isolated from different sources, a comprehensive investigation of the mechanism of action is still lacking. In addition, the absence of detailed methodology on experimentation, β-glucan molecules source and purity reached render interpretation of the various results very complex. As such, discrepancies observed in the different studies are mainly related to the choice of purified components being used. In addition, unfortunately only few human studies are available and most of them have not been followed up with success. Hence, the possibility for clinical application of β-glucan should be considered with caution and will require further investigation. Future studies need to deeply characterize how β-glucans with different structure and molecular weight interact with each receptor and which specific signaling pathways are triggered. Moreover, providing details on the procedure and composition of the carbohydrate molecule under investigation remains crucial. An understanding should be made in the near future to use a common standardized β-glucan molecule with described biochemical properties. With such a common control, we might endeavor a rational use of this promising molecule in the future as an adjuvant or therapeutic agent.
Biosynthesis of pneumocandin lipopeptides and perspectives for its production and related echinocandins.
Recently, the biosynthetic steps leading to formation of pneumocandin B0 and echinocandin B have been elucidated, and thus, provide a framework and attractive model for further design new antifungal therapeutics around natural variations in echinocandin structural diversities via genetic and chemical tools. In this article, we analyze the biosynthetic pathway of pneumocandins and other echinocandins, provide an update on the array of pneumocandin analogues generated by genetic manipulation, and summarize advances in the enhancement of pneumocandin B0 production by random mutagenesis and fermentation optimization. We also give offer advice on the development of improved pneumocandin drug candidates and more efficient production of pneumocandin B0.
Chemistry, physico-chemistry and applications linked to biological activities of β-glucans.
β-Glucans is the common name given to a group of chemically heterogeneous polysaccharides. They are long- or short-chain polymers of (1-->3)-β-linked glucose moieties which may be branched, with the branching chains linked to the backbone by a (1-->6)-β linkage. β-(1-->3)-Glucans are widely distributed in bacteria, algae, fungi and plants, where they are involved in cell wall structure and other biological function. β-Glucans have been shown to provide a remarkable range of health benefits, and are especially important against the two most common conventional causes of death in industrialized countries, i.e. cardiovascular diseases (where they promote healthy cholesterol and blood glucose levels) and cancer (where they enhance immune system functions). This Highlight provides a comprehensive and up-to-date commentary on β-glucans, their chemistry, physico-chemistry, functional role in immunological responses, and possible applications as therapeutic tools. In addition, we discuss the mechanism behind their health benefits, which are not yet fully understood.
Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans.
Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.
Dietary roles of non-starch polysaccharides in human nutrition: a review.
The remarkable properties of dietary NSPs are water dispersibility, viscosity effect, bulk, and fermentibility into short chain fatty acids (SCFAs). These features may lead to diminished risk of serious diet related diseases which are major problems in Western countries and are emerging in developing countries with greater affluence. These conditions include coronary heart disease, colo-rectal cancer, inflammatory bowel disease, breast cancer, tumor formation, mineral related abnormalities, and disordered laxation. Insoluble NSPs (cellulose and hemicellulose) are effective laxatives whereas soluble NSPs (especially mixed-link β-glucans) lower plasma cholesterol levels and help to normalize blood glucose and insulin levels, making these kinds of polysaccharides a part of dietary plans to treat cardiovascular diseases and Type 2 diabetes. Moreover, a major proportion of dietary NSPs escapes the small intestine nearly intact, and is fermented into SCFAs by commensal microflora present in the colon and cecum and promotes normal laxation. Short chain fatty acids have a number of health promoting effects and are particularly effective in promoting large bowel function. Certain NSPs through their fermented products may promote the growth of specific beneficial colonic bacteria which offer a prebiotic effect. Various modes of action of NSPs as therapeutic agent have been proposed in the present review. In addition, NSPs based films and coatings for packaging and wrapping are of commercial interest because they are compatible with several types of food products. However, much of the physiological and nutritional impact of NSPs and the mechanism involved is not fully understood and even the recommendation on the dose of different dietary NSPs intake among different age groups needs to be studied.
Synthesis and Evaluation of 1,5-Dithia-d-laminaribiose, Triose, and Tetraose as Truncated β-(1→3)-Glucan Mimetics.
The preparation and characterization of a series of di-, tri-, and tetrasaccharide analogues of β-(1→3)-glucans is described in which each pyranoside ring is replaced by a 5-thiopyranosyl ring and each glycosidic oxygen by a thioether. These oligomeric 1,5-dithio-d-glucopyranose derivatives were shown to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-Dectin-1 antibodies, respectively.
Cathepsin D--many functions of one aspartic protease.
For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis
Synthesis and Evaluation of Oligomeric Thioether-Linked Carbacyclic β-(1→3)-Glucan Mimetics.
Extrapolating from lessons learnt with previous low-molecular-weight β-(1→3)-glucan mimetics, we designed a series of minimal 2,4-dideoxy-thioether-linked carbacyclic β-(1→3)-glucan mimetics and synthesized di-, tri-, and tetramers in an enantiomerically pure form by an iterative sequence based on a simple building block readily available from commercial ( S)-(-)-3-cyclohexenecarboxylic acid.
Comparison of immunological effects of commercially available beta glucan
In the present paper, fifteen varieties of glucans differing in source and solubility were tested. There was no direct connection between source and immunological effects was found. The conclusion was that the best glucans have pleiotropic effects stimulating all facets of immunological reactions, whereas other glucans have low effects or none at all.
Nanoplatform Constructed from a β-Glucan and Polydeoxyadenylic Acid for Cancer Chemotherapy and Imaging.
A nanoplatform carrying doxorubicin (Dox) for cancer therapy and a dye for imaging was developed based on a natural triple helix β-glucan (t-LNT) and polydeoxyadenylic acid (poly(dA)). The t-LNT-Dox conjugates were prepared through Schiff-base reaction between the aldehyde group in the oxidized t-LNT and the amino group of Dox, the single chains (s-LNT-Dox) of which interacted with the poly(dA)-dye to form a composite s-LNT-Dox/poly(dA)-dye through hydrogen bonding between s-LNT and poly(dA).
Multiphoton fluorescence lifetime imaging microscopy (FLIM) and super-resolution fluorescence imaging with a supramolecular biopolymer for the controlled tagging of polysaccharides.
A new supramolecular polysaccharide complex, comprising a functionalised coumarin tag featuring a boronic acid and β-d-glucan (a natural product extract from barley, Hordeum Vulgare) was assembled based on the ability of the boronate motif to specifically recognise and bind to 1,2- or 1,3-diols in water.
Diagnosis of Fungal Infections. A Systematic Review and Meta-Analysis Supporting American Thoracic Society Practice Guideline.
Rationale: Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings.Objectives: To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis).
Dietary fibre and cardiovascular health: a review of current evidence and policy.
Dietary fibre comprises many different, mainly plant-based, compounds that are not fully digested in the human gut. Insoluble fibres include cellulose, hemi-celluloses and lignin and soluble fibres include pectins, β-glucan and hydro-colloids. In the UK, the daily recommended amount has increased to 30 g but only 13 % of men and 4 % of women meet this recommendation.
Summary for Clinicians: Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice.
Evidence-based guidelines for the use of microbiological laboratory testing for the diagnosis of fungal infections in pulmonary and critical care were recently published by a multidisciplinary committee of experts on behalf of the American Thoracic Society (1). A systematic review of the literature pertaining to the use of microbiological, serological, and molecular tests for the diagnosis of invasive pulmonary aspergillosis (IPA), invasive candidiasis (IC), and the common endemic mycoses was performed.
Alternating consumption of β-glucan and quercetin reduces mortality in mice with colorectal cancer.
The current dietary recommendations for disease prevention and management are scarce and are not well supported. Beta-glucan or quercetin in a diet can alleviate colorectal cancer (CRC) by regulating the gut microbiota and related genes, but the effects of alternating their consumption for routine ingestion during CRC occurrence remain unknown. This study investigated the effects of alternating the consumption of β-glucan and quercetin for routine ingestion on CRC development in mice.
Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway.
Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects.
Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer.
Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage–mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti–PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non–small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound β-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy.
β1,3-glucan anticancer efficacies and synergies: A review
β1,3-glucans from fungi, cereals, seaweeds and bacteria have been shown to possess favourable biological and anti-carcinogenic activities including upregulation of phagocytosis, cytokine production enhancement, superoxide and nitrite production; antibody secretion and stimulation of signalling pathways associated with proto-oncogene expression.
Effect of oyster mushroom (Pleurotus Ostreatus) and its ethanolic extract in diet on absorption and turnover of cholesterol in hypercholesterolemic rat
The effect of the diet containing 5% of powdered oyster mushroom (Pleurotus ostreatus) or an equivalent amount of mushroom ethanolic extract on cholesterol content in serum and liver, on its distribution in lipoproteins, absorption and turnover was studied in male Wistar rats (initial body weight about 70 g) fed a diet with 0.3% cholesterol. 12 weeks of feeding with whole oyster mushroom or mushroom extract reduced cholesterol level in serum by 52 and 33%, respectively.
Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells
The tumor-killing mechanisms available to monoclonal antibodies (mAbs; e.g., antagonism of growth factor receptors, antibody-dependent cell-mediated cytotoxicity) limit efficacy. Previous studies suggested that i.v. beta-glucan might function as an adjuvant for antitumor mAbs. beta- Glucan had been shown to function via the iC3b-receptor complement receptor 3 (CR3; CD11b/CD18) thereby enhancing leukocyte killing of tumor cells coated with iC3b via naturally occurring antitumor antibodies.
Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells
Glucan, a beta-1,3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistently exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.
Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells
When phagocyte CR3 binds to iC3b on bacteria or yeast, phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via a CD11b I-domain binding site and specific microbial polysaccharides via a lectin site located COOH-terminal to the I-domain. By contrast, when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells that lack CR3-binding membrane polysaccharides, neither lysis nor cytotoxicity are stimulated. This investigation showed that soluble CR3-specific polysaccharides such as beta-glucan induced a primed state of CR3 that could trigger killing of iC3b-target cells that were otherwise resistant to cytotoxicity. Anti-CR3 added before sugars prevented priming, whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysaccharide priming required tyrosine kinase(s) and a magnesium-dependent conformational change of the I-domain that exposed the CBRM1/5 activation epitope. Unlike LPS or cytokines, polysaccharides did not up-regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1-binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for immunotherapy. These polysaccharides function through binding to phagocyte or NK cell CR3, priming the receptor for cytotoxicity of neoplastic tissues that are frequently targeted with iC3b and sparing normal tissues that lack iC3b. From VV (via email w/ AJ) First discovery of glucan binding to the CR3 receptors and the mechanisms of priming of this receptor for cytotoxic action. From VV (via email w/ AJ) First discovery of glucan binding to the CR3 receptors and the mechanisms of priming of this receptor for cytotoxic action.
Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury
Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair. We demonstrate here that stroma-iC3b tethers HPCs via the inserted (I) domain of HPC complement receptor 3 (CR3, CD11b/CD18, Mac-1). Following irradiation, stroma-iC3b was observed in the presence of purified IgM and normal mouse serum (NMS), but not serum from Rag-2-/- mice, implicating a role for antibody (Ab) and the classic pathway of C activation. Furthermore, a novel role for soluble yeast β-glucan, a ligand for the CR3 lectin-like domain (LLD), in the priming of CR3+ HPC is suggested. Soluble yeast β-glucan could enhance the proliferation of tethered HPCs, promote leukocyte recovery following sublethal irradiation, and increase the survival of lethally irradiated animals following allogeneic HPC transplantation in a CR3-dependent manner. Taken together, these observations suggest a novel role for C, CR3, and β-glucan in the restoration of hematopoiesis following injury.
Synergism between poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan and cefazolin in prophylaxis of staphylococcal wound infection in a guinea pig model
To determine whether the infection-preventing capability of the neutrophil-activating agent poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan (PGG-glucan) can be enhanced with antibiotic prophylaxis, we administered PGG-glucan and cefazolin, alone and in combination, to guinea pigs inoculated with isolates of staphylococci.
Vitamin D: modulator of the immune system.
This review will discuss the complex immune-regulatory effects of 1,25(OH)(2)D(3) on immune cells as well as its role in infectious and autoimmune diseases, more in particular in tuberculosis and type 1 diabetes (T1D).
Glucan enhances survival in an intraabdominal infection model
We conclude from these results that (i) neither glucan preparation alone effectively enhances survival following CL/P when using the doses and administration schedule employed herein, (ii) both glucan-P and glucan-F do act synergistically with antibiotics to enhance survival in this rat model of polymicrobial sepsis, and (iii) in this particular model, nontoxic glucan-F is as efficacious as glucan-P.
Soluble β-1,3/1,6-glucan from yeast inhibitsexperimental periodontal disease in Wistar rats.
Soluble beta-1,3/1,6-glucan administered by the oral route diminishes ligature-induced periodontal bone loss in this model. This effect may be attributable to the well documented ability of beta-1,3/1,6-glucan to stimulate macrophage phagocytosis and to skew the T helper (Th)1/Th2 balance towards Th1 and T regulatory responses. The HPA axis may play a significant role in beta-1,3/1,6-glucan induced immune modulation.
Effects of beta-glucan on intestinal anastomoses in ratmodel.
Due to significant increases in anastomotic bursting pressures and tissue hydroxyproline levels and considering the inhibitory effect of β-Glucan on epithelial damage, edema, and submucosal-muscular layer damage, β-Glucan was thought to contribute to the healing of the anastomosis.
Direct enhancement of the phagocytic and bactericidalcapability of abdominal macrophage of chicks by β-1,3-1,6-glucan.
Salmonella enterica serovar Enteritidis is the major zoonotic and intracellular pathogen. Different strategies have been developed to prevent the S. Enteritidis infection. The beta-1,3-1,6-glucan of Schizophyllum commune was used as an immunological booster to determine the minimal dietary level of beta-glucan that would restrict S. Enteritidis infection through the effects of beta-glucan on the activity of macrophages and direct physical protection of the intestine.
β-Glucan enhances complement-mediated hematopietic recovery after bone marrow injury.
Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony-stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM stroma (stroma-iC3b). In the present study, we have examined how stroma-iC3b interacts with hematopoietic progenitor cells (HPCs) and the role of complement (C) and complement receptor 3 (CR3) in BM injury/repair.
Antitumor effect of a peptideglucan preparation extracted from Agaricus blazei in a doublegrafted tumor system in mice.
The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (10(6) cells) and left flank (2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5.
Supplemental vitamin C and yeast cell wall β-glucan as growthenhancers in newborn pigs and as immunomodulators after anendotoxin challenge after weaning.
To test possible dietary immune modulators, 32 crossbred male pigs were given 1 of 4 dietary treatments (8 pigs/treatment): control, Saccharomyces cerevisiae with beta-glucan (Energy Plus, Natural Chem Industries LTD, Houston, TX; 0.312 g/kg of BW, 2.5% of diet), vitamin C (Stay C 35, DSM Nutritional Products Inc., Prisippany, NJ; 75 ppm), or beta-glucan plus vitamin C together (combination; 0.312 g/kg of BW and 75 ppm, respectively).
Barley-derived β-glucans increased gut permeability, ex vivo epithelial cell binding to E. coli, and naïve T-cellproportions in weaning pigs.
Weaning in young animals is associated with an increased incidence of gastrointestinal infections. β-glucans exert numerous physiological effects, including altering immune function. The objective of this study was to determine the effects of feeding barley (Hordeum vulgare L.)-derived β-glucans on immune and intestinal function in weanling pigs (Sus scrofa).
Structure of a β-glucan from Grifola frondosa and its antitumoreffects by activating Dectin-1/Syk/NF-kB signaling.
A soluble homogeneous β-glucan, GFPBW1, with a molecular mass of 300 kDa was purified from the fraction of the fruit bodies of Grifola frondosa extracted with 5% NaOH. Using various methods, such as infrared spectroscopy, NMR, methylation and monosaccharide composition analysis, its structure was determined to be a β-D-(1-3)-linked glucan backbone with a single β-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue.
Glucan improves impaired wound healing in diabeticrats.
Diabetes mellitus (DM) is a contributing factor to impaired wound healing in humans. A large body of evidence indicates that the diabetic state is associated with delayed or reduced wound repair capacity. The present study was designed to evaluate the efficacy of glucan on improving abdominal wall wound healing in rats with DM.
Evaluation of genotoxic and cytotoxic effects of H2O2 and DMNQ on freshly isolated rat hepatocytes; protective effects of carbohymethyl chitin-glucan.
Utilizing primary rat hepatocytes we investigated the potential antimutagenic and anti-cytotoxic effects of carboxymethyl chitin-glucan (CM-CG) with respect to oxidative stress induced by the model free-radical-generating compounds hydrogen peroxide (H2O2) or 2,3-dimethoxy-1,4-naphthoquinone (DMNQ). Different kinds of CM-CG action were studied by two different treatment protocols: a. pre-incubation of freshly isolated hepatocytes with the potential anti-mutagen followed by exposure to the oxidant or b. simultaneous treatment of hepatocytes with the potential anti-mutagen and the oxidant.
Modulation of intestinal inflammation by yeasts and cell wall extracts: strain dependence and unexpected antiinflammatoryrole of glucan fractions.
Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation.
Fungal b-glucan, a Dectin-a ligand, promotes protectionfrom Type 1 diabetes by inducting regulatory innate immune response.
β-Glucans are naturally occurring polysaccharides in cereal grains, mushrooms, algae, or microbes, including bacteria, fungi, and yeast. Immune cells recognize these β-glucans through a cell surface pathogen recognition receptor called Dectin-1. Studies using β-glucans and other Dectin-1 binding components have demonstrated the potential of these agents in activating the immune cells for cancer treatment and controlling infections.
Prophylactic anti-infective activity of poly-[1-6]-β-D-glucopyranosyl-[1-3]-β-Dglucopyranose glucan in guinea pig model of staphylococcal would infection.
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.
Dietary patterns and stroke: A systematic review and re-meta-analysis.
The effect of diet on the development of stroke has recently achieved much interest by various research groups, but with inconclusive results. The aim of the present review was to systematically present and discuss the up to date available research regarding the relationship between adherence to dietary patterns and stroke.
Normal human fibroblasts express pattern recognition receptors for fungal (1-3)-β-D-glucans.
Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF).
Mushrooms, tumors, and immunity
In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects.
Conformation-dependent change in antitumor activity of linear and branched (1----3)-beta-D-glucans on the basis of conformational elucidation by carbon-13 nuclear magnetic resonance spectroscopy
The antitumor activity of (1----3)-beta-D-glucans was tested in order to clarify its conformation-dependent response together with conformational elucidation by carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. It was shown that the following three conformations, single chain, single helix and triple helix, are readily distinguished by the high-resolution solid-state 13C-NMR method.
Relationship between conformation and biological response for (1----3)-beta-D-glucans in the activation of coagulation factor G from limulus amebocyte lysate and host-mediated antitumor activity. Demonstration of single-helix conformation as a stimulant
The relationship between the conformation of (1----3)-beta-D-glucans in gel or hydrated form and the stimulation of two types of biological responses, namely, activation of coagulation Factor G from limulus amebocyte lysate (LAL) and host-mediated antitumor activity was examined.
Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides
Heparanase activity correlates with the metastatic potential of tumor cells. Moreover, the anti-metastatic effect of non-anti-coagulant species of heparin and certain sulfated polysaccharides was attributed to their heparanase-inhibiting activity. We investigated the effect of a chemically sulfated polysaccharide (laminarin), consisting primarily of beta-1,3 glucan (sodium laminarin), and of synthetic phosphorothioate oligodeoxynucleotides, primarily phosphorothioate homopolymer of cytidine (SdC28), on heparanase activity and tumor metastasis.
Modulation of the antitumor effect and tissue distribution of highly branched (1-->3)-beta-D-glucan, SSG, by carrageenan
The action of carrageenan (CAR), a representative blocking reagent for phagocytes, on the antitumor effect and tissue distribution of highly branched (1-->3-beta-D-glucan, SSG, was examined. CAR inhibited the antitumor effect of intraperitoneally administered SSG only when applied before inoculation of the tumor, and had little effect when applied after tumor inoculation.
β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects - Implications for coronavirus disease (COVID-19) immunotherapies
Coronavirus pneumonia is accompanied by rapid virus replication, where a large number of inflammatory cell infiltration and cytokine storm may lead to acute lung injury, acute respiratory distress syndrome (ARDS) and death. The uncontrolled release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, is associated with ARDS. This constituted the first study to report on the variability in physicochemical properties of β-glucans extracts from the same edible mushroom Lentinus edodes on the reduction of these pro-inflammatory cytokines and oxidative stress.