Beta Glucan MH3 - Immune System Video

Beta-glucans are known as "biological response modifiers" because of their ability to activate the immune system.Immunologists at the University of Louisville, discovered that a receptor on the surface of innate immune cells called Complement Receptor 3 (CR3 or CD11b/CD18) is responsible for binding to beta-glucans, allowing the immune cells to recognize them as "non-self." However, it should be noted that the activity of beta-glucans is different from some pharmaceutical drugs which have the ability to over-stimulate the immune system. Pharmaceutical drugs have the potential to push the immune system to over-stimulation, and hence are contraindicated in individuals with autoimmune diseases, allergies, or yeast infections. Beta-glucans seem to make the immune system work better without becoming overactive. In addition to enhancing the activity of the immune system, beta-glucans also reportedly lower elevated levels of LDL cholesterol, aid in wound healing, help prevent infections, and have potential as an adjuvant in the treatment of cancer.

Beta-glucans, like lentinan (derived from the Shiitake mushroom) and Polysaccharide-K, have been used as an immunoadjuvant therapy for cancer since 1980, primarily in Japan. There is a large collection of research which demonstrates beta-glucans have anti-tumor and anti-cancer activity. In a mouse model study, beta 1,3 glucan in conjunction with interferon gamma inhibited tumors and liver metastasis.[10] In some studies, beta-1,3 glucans enhanced the effects of chemotherapy. In a cancer experiment, using a mouse model, administration of cyclophosphamide, in conjunction with beta-1,3 glucans derived from yeast resulted in reduced mortality. In human patients with advanced gastric or colorectal cancer, the administration of beta-1,3 glucans derived from shiitake mushrooms, in conjunction with chemotherapy resulted in prolonged survival times.

Preclinical studies have shown that a soluble yeast β-glucan product, Imprime PGG, when used in combination with certain monoclonal antibodies or cancer vaccines, offers significant improvements in long-term survival versus monoclonal antibodies alone.This benefit, however, does not result from Betafectin enhancing the specific killing action of the antibody. The anti-tumor activity is caused by a unique killing mechanism that involves neutrophils that are primed with Betafectin and which are not normally involved in the fight against cancer. Recent research by Hong et al., demonstrates that this mechanism of action is effective against a broad range of cancers when used in combination with specific monoclonal antibodies that activate or cause complement to be bound to the tumor.The complement enables these primed neutrophils to find and bind to the tumor, which facilitates killing. Innate immune cells are the body’s first line of defense and circulate throughout the body engaging in an immune response against “foreign” challenges (bacteria, fungus, parasites). Typically, neutrophils are not involved in the destruction of cancerous tissue because these immune cells view cancer as "self" rather than foreign or "non-self." Current cancer immunotherapies involve monoclonal antibodies and vaccines, which stimulate the acquired immune response, but do nothing to change the innate immune system's view of cancer as "self." As a result the monoclonal antibodies alone do not engage or initiate the potential killing ability of the innate immune system, which is our primary mechanism of defense against bacteria and yeast (fungal) infections.

Dr. Gordon Ross and Dr. Vaclav Vetvicka, respected immunologists and cancer researchers at the University of Louisville, discovered that a receptor on the surface of these innate immune cells called Complement Receptor 3 (CR3 or CD11b/CD18) was responsible for binding to fungi or yeast, allowing the immune cells to recognize them as "non-self." This receptor is a dual occupancy receptor in that it has two binding sites. The first site is responsible for binding to a type of complement, a soluble blood protein, known as C3 (or iC3b). C3 becomes attached to pathogens that specific antibodies have targeted and opsonized. The second site of this receptor binds to a carbohydrate on yeast or fungal cells that allows the innate immune cell to recognize yeast and fungi as being "non-self ”.Both of these receptor sites must be simultaneously occupied to trigger the innate immune cell to destroy the yeast or fungi. Two obstacles prevent neutrophils from using this mechanism of action against cancer. First, the body usually does not generate enough natural antibodies to bind to the tumor, and this prevents the activation and attachment of (or “fixing”) complement to the surface of the cancer cell. Therefore, neutrophils don’t bind to cancer via the first receptor site of CR3. The second obstacle is that even when the natural antibody response is supplemented with monoclonal antibodies that fix complement and binding occurs at the first site, tumors do not contain a foreign carbohydrate serving as “second signal” on their surface that allows neutrophils to recognize the cancer as "non-self “.[13][16] Other human receptors have been identified as being able to receive signals from beta-glucans such as Dectin-1, lactosylceramide, and scavenger receptors.

Dr. Ross discovered that a bio-processed fragment of Imprime PGG specifically binds to the second CR3 receptor site on neutrophils. When neutrophils bind to tumors, the Betafectin allows them to “see” cancer as if it were a yeast or fungal pathogen and provide the “second signal” to trigger killing. In summary, Betafectin engages neutrophils in the fight against cancer, dramatically and synergistically enhancing the effectiveness of complement activating monoclonal antibodies and vaccines through a different killing mechanism.

Multinational research has successfully demonstrated that the oral form of yeast Beta 1,3-D glucan has similar protective effects as the injected version, including defense against infectious diseases and cancer.Recently, orally-delivered glucan was found to significantly increase proliferation and activation of monocytes in peripheral blood of patients with advanced breast cancer.

The technology has wide applicability for cancer therapy. Each form of cancerous tumor cell has specific antigens on the cell surface, some of which are common to other types of cancer. (Example: Mucin 1 is present on about 70% of all types of cancer cells) Different immunotherapies target different antigens for binding monoclonal antibodies to tumor cells. This has resulted in the development of hundreds of monoclonal antibodies, many targeting a different specific antigen on cancer cells. In research studies, Betafectin has improved the effectiveness of all complement-activating monoclonal antibodies tested including breast, liver and lung cancer (company data). The magnitude of success varies based on the specific monoclonal antibody used and the type of cancer.

Prevention of infection

To date there have been numerous studies and clinical trials conducted with the soluble yeast β-glucan and the whole glucan particulate. These studies have ranged from the impact of β-glucan on post-surgical nosocomial infections to the role of yeast β-glucans in treating anthrax infections.

Post-surgical infections are a serious challenge following major surgery with estimates of 25-27% infection rates post-surgery.Alpha-Beta Technologies conducted a series of human clinical trials in the 1990’s to evaluate the impact of β-glucan therapy for controlling infections in high-risk surgical patients. In the initial trial 34 patients were randomly (double-blind, placebo-controlled) assigned to treatment or placebo groups. Patients that received the PGG-glucan had significantly fewer infectious complications than the placebo group (1.4 infections per infected patient for PGG-glucan group vs. 3.4 infections per infected patient for the placebo group). Additional data from the clinical trial revealed that there was decreased use of intravenous antibiotics and shorter stays in the intensive care unit for the patients receiving PGG-glucan vs. patients receiving the placebo.

A subsequent human clinical trial further studied the impact of β-glucan for reducing the incidence of infection with high-risk surgical patients. The authors found a similar result with a dose-response trend (higher dose provided greater reduction in infectious occurrences than low doses). In the human clinical trial 67 patients were randomized and received either a placebo or a dose of 0.1, 0.5, 1.0 or 2.0 mg PGG-Glucan per kilogram of body weight. Serious infections occurred in four patients that received the placebo, three patients that received the low dose (0.1 mg/kg) of PGG-Glucan and only one infection was observed at the highest dose of 2.0 mg/kg of PGG-Glucan.

The results of a phase III human clinical trial showed that PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations. This study was conducted in patients that were already as high-risk because of the type of surgery and were more susceptible to infections and other complications.

At this point in the development of an injectable form of b-glucan (Betafectin PGG-glucan) most scientists already concluded that yeast-derived b-glucan promoted phagocytosis and subsequent killing of pathogenic bacteria. A phase III clinical trial was proposed and conducted at thirty-nine medical centers in the U.S. involving 1,249 subjects stratified according to colorectal or non-colorectal surgical patients. The PGG-glucan was given once pre-operatively and three times post-operative at 0, 0.5 or 1.0 mg/kg body weight. The measured outcome was serious infection or death of the subjects within 30 days post-surgery. The results of the phase III human clinical trial showed that injectable PGG-Glucan therapy reduced serious post-operative infections by 39% after high-risk noncolorectal operations.

There have been studies with humans and animal models that further support the efficacy of β-glucan in combating various infectious diseases. One human study demonstrated that consumption of oral whole glucan particles increased the ability of immune cells to consume a bacterial challenge (phagocytosis). The total number of phagocytic cells and the efficiency of phagocytosis in healthy human study participants increased while consuming a commercial particulate yeast β-glucan. This study demonstrated the potential for yeast β-glucan to increase the reaction rate of the immune system to infectious challenges. The study concluded that oral consumption of whole glucan particles represented a good enhancer of natural immunity.

Anthrax is a disease that cannot be tested in human studies for obvious reasons. In a study conducted by the Canadian Department of Defense, Dr. Kournikakis showed that orally administered yeast β-glucan given with or without antibiotics protected mice against anthrax infection. A dose of antibiotics along with oral whole glucan particles (2 mg/KG body weight or 20 mg/KG body weight) for eight days prior to infection with Bacillus anthracis protected mice against anthrax infection over the 10-day post-exposure test period. Mice treated with antibiotic alone did not survive.

A second experiment was conducted to investigate the effect of yeast β-glucan orally consumed after exposure of mice to B. anthracis. The results were similar to the previous experiment with an 80-90% survival rate for mice treated with β-glucan, but only 30% for the control group after 10-days of exposure. The hopeful inference is that similar results would be observed with humans.

Action of glucocorticoids Video

Glucocorticoids (GC) are a class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate animal cell. The name glucocorticoid (glucose + cortex + steroid) derives from their role in the regulation of the metabolism of glucose, their synthesis in the adrenal cortex, and their steroidal structure.

Mechanism of action

Glucocorticoids bind to the cytosolic glucocorticoid receptor (GR). This type of receptor is activated by ligand binding. After a hormone binds to the corresponding receptor, the newly-formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to glucocorticoid response elements (GRE) in the promoter region of the target genes resulting in the regulation of gene expression. This process is commonly referred to as transactivation.

The proteins encoded by these upregulated genes have a wide range of effects including for example:[5]

* anti-inflammatory – lipocortin I and p11/calpactin binding protein
* increased gluconeogenesis – glucose-6-phosphatase and tyrosine aminotransferase


The opposite mechanism is called transrepression. The activated hormone receptor interacts with specific transcription factors (such as AP-1 and NF-κB) and prevents the transcription of targeted genes. Glucocorticoids are able to prevent the transcription of pro-inflammatory  genes, including interleukins IL-1B, IL-4, IL-5, and IL-8, chemokines, cytokines, GM-CSF, and TNFA genes.


The ordinary glucocorticoids do not distinguish among transactivation and transrepression and influence both the "wanted" immune and "unwanted" genes regulating the metabolic and cardiovascular functions. Intensive research is aimed at discovering selectively acting glucocorticoids that will be able to repress only the immune system.

Genetically modified mice which express a modified GR which is incapable of DNA binding are still responsive to the antiinflammatory effects of glucocorticoids while the stimulation of gluconeogenesis by glucocorticoids is blocked. This result strongly suggests that most of the desirable antiinflammatory effects are due to transrepression while the undesirable metabolic effects arise from transactivation, a hypothesis also underlying the development of selective glucocorticoid receptor agonists.


Glucocorticoids have been shown to exert a number of rapid actions that are independent of the regulations of gene transcription.

Binding of corticosteroids to the glucocorticoid receptor (GR) stimulates phosphatidylinositol 3-kinase and protein kinase AKT, leading to endothelial nitric oxide synthase (eNOS) activation and nitric oxide dependent vasorelaxation.Membrane associated GR has been shown to mediate lymphocytolysis.Finally some glucocorticoids have been shown to rapidly inhibit the release of the inflammatory prostaglandin PGE2 and this effect is blocked by the glucocorticoid receptor antagonist RU-486 and this effect is not affected by protein synthesis inhibitors. This data together suggests a non-genomic mechanism of action.

Glucocorticoid. (2010, February 11). In Wikipedia, The Free Encyclopedia. Retrieved 17:23, February 27, 2010, from

Animation about diabetes and the body

Beta Glucan Video

β-Glucans (beta-glucans) are polysaccharides of D-glucose monomers linked by glycosidic bonds. Beta-glucans are a diverse group of molecules which can vary with respect to molecular mass, solubility, viscosity, and three-dimensional configuration. They occur most commonly as cellulose in plants, the bran of cereal grains, the cell wall of bakers' yeast, certain fungi, mushrooms and bacteria. Some forms of beta glucans are useful in human nutrition as texturing agents and as soluble fiber supplements, but can be problematic in the process of brewing.

Yeast and medicinal mushroom derived beta glucans are notable for their ability to modulate the immune system. Research has shown that insoluble (1,3/1,6) beta glucan, has greater biological activity than that of its soluble (1,3/1,4) beta glucan counterparts. The differences between beta glucan linkages and chemical structure, are significant in regards to solubility, mode of action, and overall biological activity.

Glucans are polysaccharides that only contain glucose as structural components, and are linked with β-glycosidic bonds.

In general, one distinguishes between α- and β-glycosidic bonds, depending on whether the substituent groups on the carbons flanking the ring oxygen are pointing in the same or opposite directions in the standard way of drawing sugars. An α-glycosidic bond for a D-sugar emanates below the plane of the sugar, whereas the hydroxyl (or other substituent group) on the other carbon points above the plane (opposite configuration), while a β-glycosidic bond emanates above that plane.

Lysozyme Reaction

Lysozyme belongs to the hydrolases (EC 3.-.-.-) enzymatic class. The hydrolases catalyze the hydrolysis or hydrolytic cleavage of a chemical bond by reaction: A – B + H2O → A – OH + B – H. This class of enzymes is usually classified by nature of the hydrolysed bond, then by chemical nature of the substrate, and finally by the enzyme. Despite systematic name for hydrolases always include hydrolase, the recommended name is formed by the name of the substrate with the suffix -ase.

Within the class of hydrolases, Lysozyme belongs to the Glycosylases family (EC 3.2.-.-). Lysozyme reaction is the hydrolysis of the beta (1-4) glycosidic bond between N-acetylglucosamine sugar (NAG) and N-acetylmuramic acid sugar (NAM) and therefore it is possible classify it as Glycosidases, i.e. enzymes hydrolyzing O- and S-glycosyl (EC 3.2.1.-) with number 17 (EC in this group.

Lysozyme reaction is hydrolysis of the beta (1-4) glycosidic bond between N-acetylglucosamine sugar (NAG) and N-acetylmuramic acid sugar (NAM). These bonds are circled on the following figure. This reaction is take place in a long deep cleft, which contains the active site of Lysozyme (residues Glu35 and Asp52 for chicken egg white Lysozyme enzyme). This cleft is a very specific active site, which can bind only six sugar rings from a polysaccharide chain and hydrolyze them into a disaccharide and a tetrasaccharide subunit.

ReoVirus in Cancer Therapy

Reovirus (Respiratory Enteric Orphan Virus) is a common virus that most people (70% to 100%) have been exposed to in their lifetime. The virus is considered asymptomatic, meaning that there are no particular symptoms associated with it. Unlike other viruses that continue to reside in the body after infection, the body will eliminate reovirus within two weeks. Because it is considered such a "safe" virus, it has been used for decades by research institutions and individuals studying viral replication structure. In 1998, graduate students working in a laboratory at the University of Calgary discovered that this particular virus seemed to be able to replicate itself in cancer cells that have what is called an activated Ras pathway, one of the most common family of genetic defects leading to cancer. Up to two-thirds of all human cancers, including many brain cancers, are Ras-activated, and are therefore a target for reovirus therapy.

Here's how it works: Viruses on their own cannot replicate. They need to borrow a host cell's manufacturing equipment. A virus particle will enter a cell, borrow the manufacturing equipment, and replicate itself within the cell until the cell dies, or the body's natural defenses kill the virus particles. If the virus is successful in killing the cell, the progeny virus are then free to infect and kill surrounding cells.

When the reovirus enters a normal cell and attempts to borrow the cell's manufacturing equipment to replicate itself, an anti-viral protein called PKR is able to quickly neutralize the virus. In a Ras-activated cancer cell, however, this anti-viral response is turned off. The reovirus is able to replicate itself within the cancer cell, resulting in that cancer cell's death. The cycle of infection, replication and cell death will be repeated until there are no longer any cancer cells available.

Open Reading Frames Animation

An open reading frame (ORF) is a portion of an organism's genome which contains a sequence of bases that could potentially encode a protein. The start-points and end-points of a given ORF are not equivalent to the ends of the messenger RNA (mRNA), but the ends of the ORF are usually contained within the mRNA's sequence. In a gene, ORFs are located between the start-code sequence (initiation codon) and the stop-code sequence (termination codon). ORFs are usually encountered when sifting through pieces of DNA while trying to locate a gene. Since there exist variations in the start-code sequence of organisms with altered genetic code, the ORF will be identified differently. A typical ORF finder will employ algorithms based on existing genetic codes (including the altered ones) and all possible reading frames.

In fact, the existence of an ORF, especially a long one, is usually a good indication of the presence of a gene in the surrounding sequence. In this case, the ORF is part of the sequence that will be translated by the ribosomes, it will be long, and if the DNA is eukaryotic, the ORF may continue over gaps called introns. However, short ORFs can also occur by chance outside of genes. Usually ORFs outside genes are not very long and terminate after a few codons.

Once a gene has been sequenced it is important to determine the correct open reading frame (ORF). Theoretically, the DNA sequence can be read in six reading frames in organisms with double-stranded DNA; three on each strand. The longest sequence without a stop codon usually determines the open reading frame. That is the case with prokaryotes. Eukaryotic mRNA is typically monocistronic and therefore only contains a single ORF. A problem arises when working with eukaryotic pre-mRNA: long parts of the DNA within an ORF are not translated (introns). When the aim is to find eukaryotic open reading frames it is necessary to have a look at the spliced mRNA.

For example, if a portion of a genome has been sequenced (e.g. 5'-UCUAAAAUGGGUGAC-3'), and it is known to contain a gene, ORFs can be located by examining each of the three possible ORFs (or six in double-stranded DNA). In this sequence two out of three possible reading frames are "open". This is one of the two possible mRNA sequences of the transcript, and we see that it can be read in three different ways:

The last reading frame contains a stop codon (UAA), unlike the first two. Thus, only two of the three reading frames are open. Since there is a start codon (AUG) in the first open reading frame, it is very likely that the first ORF is the correct one.


Nutrigenomics is the study of the effects of foods and food constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins and provides a basis for understanding the biological activity of food components. Nutrigenomics has also been described by the influence of genetic variation on nutrition by correlating gene expression or single-nucleotide polymorphisms with a nutrient's absorption, metabolism, elimination or biological effects. By doing so, Nutrigenomics aims to develop rational means to optimise nutrition, with respect to the subject's genotype. By determining the mechanism of the effects of nutrients or the effects of a nutritional regime, Nutrigenomics tries to define the causality|relationship between these specific nutrients and specific nutrient regimes (diets) on human health. Nutrigenomics has been associated with the idea of personalized nutrition based on genotype. While there is hope that nutrigenomics will ultimately enable such personalised dietary advice, it is a science still in its infancy and its contribution to public health over the next decade is thought to be major.

Reovirus Lifecycle Animation

Respiratory Enteric Orphan viruses, i.e. infect the human respiratory and intestinal tracts, usually without disease symptoms. First recognised in 1959 - and previously (wrongly) classified as echoviruses (Picornaviridae). There are >150 species in the family Reoviridae. They are a diverse group, infecting invertebrates, vertebrates and plants, but are unified by their most unique feature - the composition of their genome

The receptor(s) are known to contain sialic acid (haemagglutination, broad cell tropism), but most have not been definitively identified.Particles are internalized and partially uncoated in endolysosomes in the cytoplasm (resistant to protease digestion- if completely uncoated, virus would be destroyed).
Early transcription of the d/s RNA genome by viral polymerase occurs inside this sub-viral particle. The various genome segments are transcribed/translated at different frequencies - the main advantage of a segmented genome? (reassortment?)
RNA is transcribed conservatively - only (-)sense strands are used, resulting in synthesis of (+)sense mRNAs, which are capped inside the core - all this occurs without de novo protein synthesis.
mRNAs leave core and are translated in the cytoplasm.

Acetylcholine Binding Protein

Acetylcholine-binding protein (AChBP) is a water-soluble protein released from molluscan glial cells and modulates ACh-mediated synaptic transmission. Acetylcholine-binding protein (AChBP) is a water-soluble homolog of the ligand-binding domain of nicotinic receptors and other members of the pharmaceutically important family of pentameric ligand-gated ion channels (LGICs), GABAA, GABAC, 5-HT3 serotonin, and glycine receptors. The crystal structure of AChBP from Lymnaea stagnalis has become an established model for the extracellular domain of the pentameric LGICs, and homology models have been generated to analyze receptorligand interactions. AChBP has pharmacological properties similar to the homomeric alpha7 subtype of nicotinic ACh receptors (nAChRs), with relatively weak affinity for ACh and a 10-fold higher affinity for nicotine.