Background and Objectives: MGN-3/Biobran (BRM4, Lentin Plus or Ribraxx) is a natural, rice bran-derived arabinoxylan immunoceutical that modulates the adaptive immune response to viral infections. In response to bacterial infections, basophils act as “first responders” and are also associated with modulation of the adaptive immune response. The maturation of pluripotent CD34+ stem cells into basophils is supported by the cytokine interleukin-3 (IL-3). The aim was to test the hypothesis that modulation of the adaptive immune response in bacterial infection by MGN-3/Biobran entails a basophilic response. The tick-related disorder Lyme borreliosis was chosen as the disease model; tick bites are associated with cutaneous IL-3-mediated basophil recruitment.

Materials and Methods: A three-month randomised double-blind placebo-controlled trial was conducted in patients with a history of borreliosis who were suffering from symptoms attributable to this disorder. The immunoceutical group received oral Biobran; the dosage for both groups was 1 g thrice daily. Both groups were matched for age, sex, and ethnicity. Results: A higher percentage of basophil count occurred in the immunoceutical group (p = 0.038). The final general linear model included the group (immunoceutical/placebo) and change in fatigue assessed by the 11-item Chalder Fatigue Questionnaire (CFQ) (r2 = 0.63; p = 0.0066). The change in basophil count was positively correlated with CFQ change (rs = 0.633; p = 0.020); only the immunoceutical group showed a positive correlation.

Conclusions: These results support the hypothesis being tested. Basophils may modulate the adaptive immune response by acting as immunoregulatory cells. They can regulate the functioning of type 2 T-helper lymphocytes, enhance immunological memory, and present antigens to CD8 T lymphocytes. Further studies are needed to clarify potential mechanistic factors and the timing of this basophilic response

Background: Nanoparticle-enabled targeted drug delivery has proven effective in cancer treatment due to its ability to cross biological barriers, achieve therapeutic concentrations within tumors, and minimize adverse effects on surrounding healthy tissues. MGN-3/Biobran is a widely recognized natural compound known for its anti-inflammatory, antioxidant, and anti-carcinogenic properties. This study examined the effects of natural product MGN-3 nanoparticles on the toxicity to liver, kidney and spleen caused by Ehrlich ascites cancer (EAC) in an in vivo model. Method: In addition to the negative control group, the EAC model was conducted by injecting EAC cells subcutaneously into the female albino mice’s thighs. Free MGN-3 and MGN-3 nanoparticles were injected intraperitoneally every other day into mice with solid Ehrlich carcinoma (SEC) tumors. Body weight (BW) was monitored throughout the study and tumors were collected on day 22 post-inoculation and weighed. Liver, spleen and kidney organs were excised and weight. Lipid profile parameters and indicators for liver and kidney function were determined using serum. Results: The results showed that EAC inoculation caused in addition to subcutaneous solid tumor formation, significant decrease in Body Weight, increase in organ weights, marked rise in serum concentrations of aspartate, alanine aminotransferases and gamma-glutamyl transferase (AST, ALT, GGT), urea, creatinine, uric acid, and Total cholesterol. Also, remarkable elevation in Low Density Lipoprotein / High Density Lipoprotein (LDL/HDL) ratio and triglycerides level was detected. Besides reducing tumor weight, the protective effects on BW and distant organs by MGN-3 were observed by maintaining normal BW, liver, spleen and kidney weights, ameliorating all biochemical parameters within normal values. Such results were more pronounced with Biobran nanoparticles. Conclusion: In conclusion, Nanocapsulation of MGN-3/Biobran appears promising as a chemopreventive agent against tumor progression and EAC-induced toxicity in healthy liver, kidney and spleen organs.

Although chemotherapy is one of the pillars in cancer treatment, its side effects have extremely harmful impacts on many of the body’s organs. This study investigates the potential protective effect of the natural product, Biobran/MGN-3, against kidney damage and immune modulation caused by the chemotherapeutic agent Etoposide in rats. Etoposide impairs kidney function, demonstrated by high levels of urea, and imbalances in electrolytes Na and K, and low calcium levels. Etoposide also increased parameters reflecting oxidative stress, malondialdehyde (MDA) and nitric oxide (NO), while reduced the enzyme-mediated antioxidant defense activity, Glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Immunostaining of kidney tissues revealed that Etoposide caused inflammation by increasing proinflammatory cytokines IL-1β, TNF-α, and TGF-β expression. In addition, it increased apoptosis by raising levels of Bax, Caspase-3, and Cytochrome C, which was evident by qPCR. Comet assay revealed DNA damage in kidney cells following Etoposide treatment. It was evident by flow cytometry that Etoposide increased CD8, CD4, CD3, and CD19, which indicates lymphocyte infiltration into the kidney. On the other hand, Biobran/MGN-3 helped protect kidney function, lowering oxidative stress, restoring antioxidant enzyme activity, and reducing pro-inflammatory substances. Biobran/MGN-3 also counteracted the Etoposide-induced increase in Bax, Caspase-3, and Cytochrome C, lowering the cell death rate in the kidneys. Additionally, the results showed that Biobran/MGN-3 adjusted immune cell levels by increasing CD8+, CD4+, CD3+, and CD19+ cells, boosting both T-cell and B-cell activity. These findings suggest that Biobran/MGN-3 could be a helpful treatment addition to reduce kidney damage and mitigate immune impairment from Etoposide.

Context: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. Objective: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. Methods: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. Results: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. Conclusion: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Corona Virus Disease 19 (COVID-19) has been a major pandemic impacting a huge population worldwide, and it continues to present serious health threats, necessitating the development of novel protective nutraceuticals. Biobran/MGN-3, an arabinoxylan rice bran, is a potent immunomodulator for both humans and animals that has recently been demonstrated to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We here investigate Biobran/MGN3′ s potential to enhance an antiviral immune response in humans. Peripheral blood mononuclear cells (PBMCs) derived from eight subjects taking Biobran/MGN-3 (age 55–65 years) and eight age-matched control subjects were stimulated with irradiated SARS-CoV-2 virus and then subjected to immuno-phenotyping and multiplex cytokine/chemokine assays. Results showed that PBMCs from subjects supplemented with Biobran/MGN-3 had significantly increased activation of plasmacytoid dendritic cells (pDCs) coupled with increased IFN-α secretion. We also observed higher baseline expression of HLA-DR (human leukocyte antigen-DR isotype) on dendritic cells (DCs) and increased secretion of chemokines and cytokines, as well as a substantial increase in cytotoxic T cell generation for subjects taking Biobran/MGN-3. Our results suggest that Biobran/MGN-3 primes immunity and therefore may be used for boosting immune responses against SARS-CoV-2 infections and other diseases, particularly in high-risk populations such as the elderly.

Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), poses a serious global public health threat for which there is currently no satisfactory treatment. This study examines the efficacy of Biobran/MGN-3 against SARS-CoV-2. Biobran is an arabinoxylan rice bran that has been shown to significantly inhibit the related influenza virus in geriatric subjects. Here, Biobran’s anti-SARS-CoV-2 activity was assessed using MTT and plaque reduction assays, RT-PCR, ELISA techniques, and measurements of SARS-CoV-2-related gene expression and protein levels. For Vero E6 cells infected with SARS-CoV-2, Biobran reduced the viral load by 91.9% at a dose of 100 µg/mL, it reduced viral counts (PFU/mL) by 90.6% at 50 µg/mL, and it exhibited a significant selectivity index (EC50/IC50) of 22.5. In addition, Biobran at 10 µg/mL inhibited papain-like proteinase (PLpro) by 87% and ACE2 SARS-CoV-2 Sprotein RBD by 90.5%, and it significantly suppressed SARS-CoV-2 gene expression, down-regulating E-gene and RdRp gene expression by 93% each at a dose of 50 µg/mL and inhibiting the E-protein by 91.3%. An in silico docking study was also performed to examine the protein–protein interaction (PPI) between SARS-CoV-2 RBD and DC-SIGN as well as between serine carboxypeptidase and papain-like protease PLpro. Serine carboxypeptidase, an active ingredient in Biobran, was found to interfere with the binding of SARS-CoV-2 to its receptor DC-SIGN on Vero cells, thus preventing the cell entry of SARS-CoV-2. In addition, it impairs the viral replication cycle by binding to PLpro. We conclude that Biobran possesses potent antiviral activity against SARS-CoV-2 in vitro and suggest that Biobran may be able to prevent SARS-CoV-2 infection. This warrants further investigation in clinical trials.

Background: There are conflicting data about the relationship between diabetes mellitus and cancer risk in that growing evidence suggest a possible role of endogenous elevated insulin level which is often found in Non-Insulin-Dependent-Diabetes-Mellitus or an exogenous hyperinsulinemia observed often in Insulin-Dependent-Diabetes-Mellitus. In the last years higher attention focused on the role of immunoregulation both in the insulin production by β-cell of Langerhans-islets and in the insulin sensitivity (resistance) of insulin receptors. Interestingly, cytokines from type-2 innate immune cells, such as M2 macrophages or D2 dendritic cells exhibit a protective effect on both types of diabetes. However, the effect of insulin on the balance between type-1 and type-2 natural immune mechanisms, which is important for the tumor defense, was poorly investigated. Material and methods: Streptozotocin (STX)-treated Wister rats was treated per oral with a non-optimal single dose of an evidence based and standardized plant immunomodulator, namely Rice Bran Arabinoxylan Concentrate (RBAC) which has been shown to activate type-1 innate immune cells (such as M1, D1 and NK cells). 24h after a single dose of RBAC (45mg/kg) four parameters of NK cells were determined with flow cytometry using stained CD161-APC and CD314-PE monoclonal antibodies and by hematological examinations. The results were compared with negative controls (without STX or RBAC treatment). Results: Since STX caused a significantly reduced lymphocyte production in bone marrow, only the RBAC-induced relative increases in number of NKR-P1+ and LGL cells among the all lymphocyte population parallel with the frequency and intensity of the most important Killing Activator Receptor, namely NKG2D among the total NK cell population were determined. In the STX-untreated group RBAC induced only not significant increases compared with negative control values. However, in STX-treated groups all four NK parameters revealed RBAC-induced significant increases (p<0.05) compared to the negative controls. Conclusion: These results suggest the hypothesis that insulin deficit can increase the immunomodulator-induced activation of type-1 innate immune cells indicating that insulin takes part on regulation of the natural immune balance inhibiting the type-1 innate antitumor defense.

Abstract: Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.

This clinical cancer strategy incorporates advancements in cancer treatment based on a multi-approach to the disease that includes targeting apoptosis, immune cell activation, angiogenesis, restoration of cellular respiration, inhibition of inflammatory mediators, not mentioning some secondary factors such as intoxication, disturbed microbiome, and nervous disorders. I believe that a real breakthrough in cancer needs to promote immune system enhancement and activate apoptosis. These two important mechanisms of approaching cancer, principally through the clinical application of the P53 tumor suppressor gene and other apoptotic players that for the past 15 years have been included in my cancer strategy as a diagnostic, prognosis, and follow up treatment. P53 mutation or mutated P53 protein remains the essential factor when it comes to treating cancer either from conventional therapy or an alternative approach or in combination.

Introduction : Rice bran arabinoxylan com pound (RBAC) is a nutraceutical for enhancing a depleted immune system during and after cancer treatment. This pilot feasibility trial aims to evaluate the effects of RBAC on cancer patients’ quality of life during active treatment, compared to placebo, using a validated questionnaire. Other outcome measures include changes in inflammatory and nutritional status, cytokine pro file, and gut mi – crobiota. Methods/ Design : The study will recruit 50 participants from a regional cancer center in Australia. Patients aged 18 –70, diagnosed with solid or an cancers stage II and above, and currently undergoing active systemic thera – pies, are eligible. Random allocation of participants into two groups is stratified based on metastatic status and treatment type. The dosage is either 3 g/ day of RBAC or placebo in identical packaging. The participants, study coordinator, and treating oncologists are blinded to the interventions. Data collections are at base line and at four follow – up sessions, which are six weeks apart (24 weeks). Statistical analysis will in volve a pro – tected p – value with multiple dependent values and analyzed by ANOVA with repeated measures on the occa – sion of testing and with both a full Bonferroni or Sidak corrections applied to protect against Type I errors. Any observed significance war rants further analysis with pair wise comparisons. Analysis of covariance will also be performed to assess any in fluence of the demographic data, cancer diagnosis, as well as changes in physical activity, dietary habits, and complementary medicine usage. Comparisons of gut microbiota will be based on the analysis of the fecal microbiome using 16S ribosomal ribonucleic acid amplicon sequencing. The proposed research time line is from October 2018 to May 2022. Trial registration : ANZCTR. Reg No: AC TRN12619000562178p.