Top 72 Articles About All Cancers

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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.