Nutraceutical strategies for alleviation of UVB phototoxicity.

Ultraviolet B exposure to keratinocytes promotes carcinogenesis by inducing pyrimidine dimer lesions in DNA, suppressing the nucleotide excision repair mechanism required to fix them, inhibiting the apoptosis required for the elimination of initiated cells, and driving cellular proliferation. Certain nutraceuticals - most prominently spirulina, soy isoflavones, long-chain omega-3 fatty acids, the green tea catechin epigallocatechin gallate (EGCG) and Polypodium leucotomos extract - have been shown to oppose photocarcinogenesis, as well as sunburn and photoaging, in UVB-exposed hairless mice. It is proposed that spirulina provides protection in this regard via phycocyanobilin-mediated inhibition of Nox1-dependent NADPH oxidase; that soy isoflavones do so by opposing NF-κB transcriptional activity via oestrogen receptor-beta; that the benefit of eicosapentaenoic acid reflects decreased production of prostaglandin E2; and that EGCG counters UVB-mediated phototoxicity via inhibition of the epidermal growth factor receptor. The prospects for practical nutraceutical down-regulation of photocarcinogenesis, sunburn, and photoaging appear favourable.

Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens.

It has been shown that SARS-CoV-2 shares homology and cross-reacts with vaccines, other viruses, common bacteria and many human tissues. We were inspired by these findings, firstly, to investigate the reaction of SARS-CoV-2 monoclonal antibody with different pathogens and vaccines, particularly DTaP. Additionally, since our earlier studies have shown immune reactivity by antibodies made against pathogens and autoantigens towards different food antigens, we also studied cross-reaction between SARS-CoV-2 and common foods. For this, we reacted monoclonal and polyclonal antibodies against SARS-CoV-2 spike protein and nucleoprotein with 15 different bacterial and viral antigens and 2 different vaccines, BCG and DTaP, as well as with 180 different food peptides and proteins. The strongest reaction by SARS-CoV-2 antibodies were with DTaP vaccine antigen, E. faecalis, roasted almond, broccoli, soy, cashew, α+ß casein and milk, pork, rice endochitinase, pineapple bromelain, and lentil lectin. Because the immune system tends to form immune responses towards the original version of an antigen that it has encountered, this cross-reactivity may have its advantages with regards to immunity against SARS-CoV-2, where the SARS-CoV-2 virus may elicit a "remembered" immune response because of its structural similarity to a pathogen or food antigen to which the immune system was previously exposed. Our findings indicate that cross-reactivity elicited by DTaP vaccines in combination with common herpesviruses, bacteria that are part of our normal flora such as E. faecalis, and foods that we consume on a daily basis should be investigated for possible cross-protection against COVID-19. Additional experiments would be needed to clarify whether or not this cross-protection is due to cross-reactive antibodies or long-term memory T and B cells in the blood.

Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson's Disease Synucleinopathy.

INTRODUCTION: Parkinson's disease is characterized by non-motor/motor dysfunction midbrain neuronal death and α-synuclein deposits. The accepted hypothesis is that unknown environmental factors induce α-synuclein accumulation in the brain via the enteric nervous system. MATERIAL AND METHODS: Monoclonal antibodies made against recombinant α-synuclein protein or α-synuclein epitope 118-123 were applied to the antigens of 180 frequently consumed food products. The specificity of those antibody-antigen reactions was confirmed by serial dilution and inhibition studies. The Basic Local Alignment Search Tool sequence matching program was used for sequence homologies. RESULTS: While the antibody made against recombinant α-synuclein reacted significantly with 86/180 specific food antigens, the antibody made against α-synuclein epitope 118-123 reacted with only 32/180 tested food antigens. The food proteins with the greatest number of peptides that matched with α-synuclein were yeast, soybean, latex hevein, wheat germ agglutinin, potato, peanut, bean agglutinin, pea lectin, shrimp, bromelain, and lentil lectin. Conclusions: The cross-reactivity and sequence homology between α-synuclein and frequently consumed foods, reinforces the autoimmune aspect of Parkinson's disease. It is hypothesized that luminal food peptides that share cross-reactive epitopes with human α-synuclein and have molecular similarity with brain antigens are involved in the synucleinopathy. The findings deserve further confirmation by extensive research.

The Gut-Brain Axis: Autoimmune and Neuroimmune Disorders.

No Abstract Available.

The evolution of food immune reactivity testing: why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another.

The gold standard for identifying food reactions is the elimination-provocation diet. Embarking on this long, tedious journey takes an expert practitioner and a completely dedicated patient, with a whole lot of patience from both. In the contemporary fast lane, microwave, "give me a pill" popping, I-want-satisfaction-now society, many clinicians have turned to laboratory assessments for quick answers to food reactivity. From the introduction of cytotoxic testing for food allergies in 1947 until today, food reactivity testing has evolved and branched; it has been both pseudoimproved and scientifically improved. With multiple available options for methodology, specimen types, and clinical lab, how is a clinician expected to find the one that fits the requirements of a particular practice? How, indeed, when one self-promoting paper supports a particular methodology, while another criticizes it? In this article, with the benefit of his years of training and experience as a research scientist and test development expert, the author, who is trained in both microbiology and immunology, discusses the history of food testing, analyzes the criticisms of it, reviews the scientific literature, and tours the methodologies.

Oral tolerance and its relationship to food immunoreactivities.

A child is born with almost no protective immune system other than passive immunity and maternal transfer of immunoglobulin G (IgG) against various food antigens and infectious agents. This lack provides a window of opportunity for infectious attacks in the first 6 mo of life as the infant's body begins to develop its own immune system. As the maternal IgG is catabolized, the child's mucosal immune system evolves its own immunocytes and starts producing a significant amount of immunoglobulin A (IgA) and immunoglobulin M (IgM) against pathogens and food antigens. This antibody production helps modulate or inhibit colonization by bacteria or yeast and to prevent penetration of the mucosal tissue by a variety of dangerous lumenal antigens. Simultaneously, the body develops its own suppressive mechanism or oral tolerance to avoid local and peripheral immune reactivities to microbial and dietary antigens. In this article, the author describes the (1) importance of oral tolerance in maintaining homeostasis against bacterial toxins and food antigens; (2) way in which antigen-presenting cells (APCs), through their collaboration with effector T (TEFF) cells, T-helper (TH) cells, and regulatory T (TREG) cells, regulate the immune system to induce anergy or immune suppression; (3) the importance of various factors in the induction of oral tolerance and the consequences of its breakdown; and (4) the reasons why a disruption of oral tolerance to food antigens and bacterial toxins can result in autoimmunity.

Molecular mimicry as a mechanism for food immune reactivities and autoimmunity.

The mucosal immune system is constantly exposed to challenges from the antigenic substances found in food and released from the body's own microbial flora. The body's normal tolerance to friendly antigenic substances can be disrupted by a number of factors, such as disease, injury, shock, trauma, surgery, drugs, blood transfusion, environmental triggers, etc. When this disruption happens, the ingestion of foods containing antigenic substances that have compositions similar to those of the body's autoantigens can result in the production of antibodies that react not only against the food antigens but also the body's own tissues. This response is known as food autoimmune reactivity. Between 7% and 10% of the world's population suffers from some form of autoimmune disease. Each patient's antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry. The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross-reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy.

Lectins, agglutinins, and their roles in autoimmune reactivities.

Lectins are carbohydrate-binding proteins present throughout nature that act as agglutinins. Approximately 30% of our food contains lectins, some of which may be resistant enough to digestion to enter the circulation. Because of their binding properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause severe intestinal damage when consumed in excess by an individual with dysfunctional enzymes. These effects are followed by disruption of intestinal barrier integrity, which is the gateway to various autoimmunities. Shared amino acid motifs between dietary lectins, exogenous peptides, and various body tissues may lead to cross-reactivity, resulting in the production of antibodies against lectin and bacterial antigens, followed by autoimmunity. The detection of immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific lectins may serve as a guide for the elimination of these lectins from the diet. It is proposed that this process can reduce the peripheral antigenic stimulus and, thereby, result in a diminution of disease symptoms in some-but not all-patients with autoimmune disorders.

Immune reactivity to food coloring.

Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. They are widely used in the food and pharmaceutical industries to increase the appeal and acceptability of their products. Synthetic food colorants can achieve hues not possible for natural colorants and are cheaper, more easily available, and last longer. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences. This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely unaware of the perilous truth behind the deceptive allure of artificial color.

Immune reactivities to peanut proteins, agglutinins, and oleosins.

CONTEXT: Certain individuals are sensitive enough to react to peanuts and peanut oil, sometimes with deadly effect. It is thus crucial to have an accurate testing methodology for the assessment of allergies and immune reactivities to peanuts and their components, such as agglutinins and oleosins. Currently, skin-prick testing is performed only with the water-soluble components of peanut proteins and can produce false negatives. Testing with all possible food antigens and with both immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies may offer a more accurate alternative. OBJECTIVE: The research team intended to measure IgG and IgE antibodies against peanut proteins, agglutinins, and oleosins to identify variations in IgG and IgE immune reactivities to these antigens among the general population. DESIGN: Sera from 288 healthy individuals-144 males of different ethnicities, aged 18-65 y with a median age of 35.5 y, and 144 females of different ethnicities, aged 18-65 y with a median age of 36.2 y-were obtained from Innovative Research, Inc. Four sera from patients with a known allergy to peanuts and 4 sera from individuals with no known allergy to peanuts were used as positive and negative controls. Several wells in the microtiter plate were coated with unrelated proteins, such as human serum albumin, rabbit serum albumin, and bovine serum albumin and used only for the determination of any background in the enzyme-linked immunosorbent assay (ELISA). SETTING: Immunosciences Lab, Inc, Los Angeles, CA, USA. OUTCOME MEASURES: The sera were screened for peanut-specific IgG and IgE antibodies against water-soluble proteins of peanut, peanut agglutinins, and peanut oleosins, using the ELISA. Color development was measured at 405 nM. For demonstration of the specificity of the antibodies, inhibition ELISA was performed with 4 sera that had very high levels of IgG and IgE antibodies. RESULTS: Using mean values as the cutoff, 19%, 17%, and 22% of the specimens tested for IgG antibodies and 14%, 11%, and 14% of the specimens tested for IgE antibodies produced high levels of antibodies against peanut proteins, agglutinins, and oleosins, respectively. CONCLUSIONS: The study's findings support the proposition that IgE sensitization to foods may not necessarily coincide with positive prick tests to commercial extracts. Falsely negative skin testing or IgG, IgA, or IgE antibody testing is often linked to the nature of the preparation of the food antigens and their use in in-vivo and in-vitro testing. The study's results support the need to improve the quality of food extracts used in the diagnosis of allergies and immune reactivity to nuts and seeds. Testing should use all possible food antigens and measure both IgG and IgE antibodies.

Immune reactivities against gums.

CONTEXT: Different kinds of gums from various sources enjoy an extremely broad range of commercial and industrial use, from food and pharmaceuticals to printing and adhesives. Although generally recognized as safe by the US Food and Drug Administration (FDA), gums have a history of association with sensitive or allergic reactions. In addition, studies have shown that gums have a structural, molecular similarity to a number of common foods. A possibility exists for cross-reactivity. OBJECTIVE: Due to the widespread use of gums in almost every aspect of modern life, the overall goal of the current investigation was to determine the degree of immune reactivity to various gum antigens in the sera of individuals representing the general population. DESIGN: The study was a randomized, controlled trial. PARTICIPANTS: 288 sera purchased from a commercial source. OUTCOME MEASURES: The sera was screened for immunoglobulin G (IgG) and immunoglobulin E (IgE) antibodies against extracts of mastic gum, carrageenan, xantham gum, guar gum, gum tragacanth, locust bean gum, and ß-glucan, using indirect enzyme-linked immunosorbent assay (ELISA) testing. For each gum antigen, inhibition testing was performed on the 4 sera that showed the highest IgG and IgE immune reactivity against the different gums used in the study. Inhibition testing on these same sera for sesame albumin, lentil, corn, rice, pineapple, peanut, pea protein, shrimp, or kidney bean was used to determine the cross-reactivity of these foods with the gum. RESULTS: Of the 288 samples, 4.2%-27% of the specimens showed a significant elevation in IgG antibodies against various gums. Only 4 of 288, or 1.4%, showed a simultaneous elevation of the IgG antibody against all 7 gum extracts. For the IgE antibody, 15.6%-29.1% of the specimens showed an elevation against the various gums. A significant percentage of the specimens, 12.8%, simultaneously produced IgE antibodies against all 7 tested extracts. CONCLUSIONS: Overall, the percentage of elevation in IgE antibodies against different gum extracts, with the exception of carrageenan, was much higher than for the IgG antibody. The results of the current study showed that a subgroup of healthy individuals who produced not only IgG but also IgE antibodies against various gums may suffer from hidden food immune reactivities and sensitivities. Further study is needed to examine the clinical importance of gums and cross-reactive food antibodies in symptomatic individuals.

For the assessment of intestinal permeability, size matters.

The purpose of this review is to demonstrate that an intestine leaky to small molecules can be impermeable to large antigenic molecules. The author proposes that the permeability of the epithelium to very small sugar molecules such as lactulose/mannitol-used for the past 50 years to gauge intestinal permeability-does not necessarily correlate with epithelial permeability to macromolecules. This article begins with the history and science behind the use of small sugars to measure permeability, a method developed in 1899. The lactulose/mannitol test may give useful information regarding the overall condition of the digestive tract; however, the author suggests that the test is not indicative of the transport of macromolecules such as bacterial toxins and food antigens, which have the capacity to damage the structure of the intestinal barrier and/or challenge the immune system. This article describes the various mechanisms and physiological transport pathways through which increased antigen uptake may result in immunological reactions to food antigens and bacterial lipopolysaccharides, resulting in the pathogenesis of disease. Finally, the article presents evidence indicating that increased intestinal, antigenic permeability plays a key role in the development of various inflammatory and autoimmune disorders. Therefore, more knowledge about the epithelium's permeability to large molecules undoubtedly contributes not only to early detection but also to secondary prevention of many inflammatory autoimmune, neuroimmune, and neurodegenerative disorders.

The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II.

Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17), which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.

The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part I.

CD4(+) effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-ß, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-ß and IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.

The Role of Th17 in Neuroimmune Disorders: A Target for CAM Therapy. Part III.

Abundant research has mapped the inflammatory pathways leading to autoimmunity and neuroinflammatory disorders. The latest T helper to be identified, Th17, through its proinflammatory cytokine IL-17, plays a pathogenic role in many inflammatory conditions. Today, healthcare providers have a wealth of anti-inflammatory agents from which to choose. On one hand, pharmaceutical companies market brand-name drugs direct to the public and physicians. Medical botanical knowledge, on the other hand, has been passed down from generation to generation. The demands for natural healing therapies have brought corresponding clinical and laboratory research studies to elucidate the medicinal properties of alternative practices. With a variety of options, it can be difficult to pinpoint the proper anti-inflammatory agent for each case presented. In this review, the authors highlight a vast array of anti-inflammatory medicaments ranging from drugs to vitamins and from botanicals to innate molecules. This compilation may serve as a guide for complimentary and alternative healthcare providers who need to target neuroinflammation driven by Th17 and its inflammatory cytokine IL-17. By understanding the mechanisms of anti-inflammatory agents, CAM practitioners can tailor therapeutic interventions to fit the needs of the patient, thereby providing faster relief from inflammatory complaints.

Novel Diagnosis of Lyme Disease: Potential for CAM Intervention.

Lyme disease (LD) is the most common tick-borne disease in the northern hemisphere, producing a wide range of disabling effects on multiple human targets, including the skin, the nervous system, the joints and the heart. Insufficient clinical diagnostic methods, the necessity for prompt antibiotic treatment along with the pervasive nature of infection impel the development and establishment of new clinical diagnostic tools with increased accuracy, sensitivity and specificity. The goal of this article is 4-fold: (i) to detail LD infection and pathology, (ii) to review prevalent diagnostic methods, emphasizing inherent problems, (iii) to introduce the usage of in vivo induced antigen technology (IVIAT) in clinical diagnostics and (iv) to underscore the relevance of a novel comprehensive LD diagnostic approach to practitioners of Complementary and Alternative Medicine (CAM). Utilization of this analytical method will increase the accuracy of the diagnostic process and abridge the time to treatment, with antibiotics, herbal medicines and nutritional supplements, resulting in improved quality of care and disease prognosis.

Regulatory T cells, a potent immunoregulatory target for CAM researchers: modulating tumor immunity, autoimmunity and alloreactive immunity (III).

Regulatory T (T(reg)) cells are the major arbiter of immune responses, mediating actions through the suppression of inflammatory and destructive immune reactions. Inappropriate T(reg) cell frequency or functionality potentiates the pathogenesis of myriad diseases with ranging magnitudes of severity. Lack of suppressive capability hinders restraint on immune responses involved in autoimmunity and alloreactivity, while excessive suppressive capacity effectively blocks processes necessary for tumor destruction. Although the etiology of dysfunctional T(reg) cell populations is under debate, the ramifications, and their mechanisms, are increasingly brought to light in the medical community. Methods that compensate for aberrant immune regulation may not address the underlying complications; however, they hold promise for the alleviation of debilitating immune system-related disorders. The dominant immunoregulatory nature of T(reg) cells, coupled with recent mechanistic knowledge of natural immunomodulatory compounds, highlights the importance of T(reg) cells to practitioners and researchers of complementary and alternative medicine (CAM).

Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: Modulating Allergic and Infectious Disease Pathology (II).

Regulatory T (T(reg)) cells maintain dominant control of immune responses to foreign materials and microbes. Appropriate T(reg) cell suppression of immune responses is essential for the maintenance of efficacious defensive responses and the limitation of collateral tissue damage due to excess inflammation. Allergy and infection are well studied and frequent afflictions in which T(reg) cells play an essential role. As such, they provide excellent models to communicate the significance and relevance of T(reg) cells to complementary and alternative medicine (CAM).