Takashi Onaka

Bio: Takashi Onaka is an academic researcher. The author has contributed to research in topics: Cholesterol & Triglyceride. The author has an hindex of 4, co-authored 6 publications receiving 106 citations.

Immunological Actions of Sophy β-Glucan (β-1,3-1,6 Glucan), Currently Available Commercially as a Health Food Supplement

Abstract: We examined the immunological actions of Sophy β-glucan (Ikewaki N., et al. United States Patent 6956120 and Japan Patent 2004-329077), a type of β-1,3–1,6 glucan produced by the black yeast Aureobasidium pullulans (A. pullulans) strain AFO-202, currently available commercially as a health food supplement, using different human in vitro experimental systems. Sophy β-glucan significantly (P<0.01) stimulated the 3H-thymidine incorporation rates (marker of DNA synthesis) in human peripheral blood mononuclear cells (PBMCs) obtained from normal adult donors, in vitro. Enzyme-linked immunoassays (EIAs) revealed that Sophy β-glucan stimulated the production of interleukin-8 (IL-8) or soluble Fas (sFas), but not that of IL-1β, IL-2, IL-6, IL-12 (p70+40), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) or soluble Fas ligand (sFasL), in either cultured PBMCs or cells of the human monocyte-like cell line, U937. The induction by Sophy β-glucan of DNA synthesis in PBMCs was completely blocked by the addition of monoclonal antibodies (mAbs) to CD11a, CD54, human leukocyte antigen-class II (HLA-class II), Toll-like receptor-2 (TLR-2), and Toll-like receptor-4 (TLR-4). In these blocking experiments using the mAbs, the main differences in the results between PBMCs and U937 cells were that the mAbs against TLR-2 and TLR-4 did not block the Sophy β-glucan -induced production of IL-8 in the U937 cells. Furthermore, a mAb to the β-glucan receptor, Dectin-1, significantly (P<0.05) blocked the Sophy β-glucan-induced DNA synthesis in the PBMCs, and Sophy β-glucan -induced production of IL-8 in the U937 cells. The Sophy β-glucan-induced production of IL-8 in the U937 cells was significantly (P<0.01) blocked by the conventional protein kinase C (PKC) inhibitor Go6976, the novel PKC inhibitor Rottlerin, the protein kinase A (PKA) inhibitor H-89, and the protein tyrosine kinase (PTK) inhibitor herbimycin A. Among these, the blocking effect of the novel PKC (PKC delta isoenzyme) inhibitor Rottlerin was the most pronounced. Studies employing reverse transcriptase-polymerase chain reaction (RT-PCR) showed that Sophy β-glucan stimulated the expression of IL-8 mRNA in the U937 cells, and that this induction was inhibited by Rottlerin. Sophy β-glucan also blocked the stimulator cell induction of DNA synthesis and IFN-γ production in the responder cells in a one-way mixed lymphocyte reaction (MLR) using allogenic PBMCs. Interestingly, immunoglobulin G (IgG), but not IgM to Sophy β-glucan was detected in the sera derived from normal adult donors and from the umbilical cord blood of neonates. Taken together, these findings strongly suggest that the Sophy β-glucan may have unique immune regulatory or enhancing properties that could be exploited by the health food, medical and pharmaceutical industries.

Beta-1.3-1.6 glucan (Aureobasidium medium)

Abstract: Aureobasidium β-1.3-1.6glucans and compositions containing such glucans, as well as methods of their preparation. Aureobasidium medium that contains β-1.3-1.6glucans, particularly medium produced by Aureobasidium strain FERM P-18099. The β-glucans of the present invention have a variety of industrial and commercial uses, including applications in pharmaceutical or medical products or treatments, for the removal or control of environmental or microbiological contaminants, in cosmetics, and in nutritional products and foods.

APPLICATION OF beta-1,3-1,6-GLUCAN (AUREOBASIDIUM CULTURE SOLUTION) IN VARIOUS INDUSTRIAL FIELDS INCLUDING MEDICAL, HEALTH WELFARE AND FOOD INDUSTRIES

Abstract: PROBLEM TO BE SOLVED: To provide applications of β-1,3-1,6-glucan produced by the use of the latest technique for culturing Aureobasidium fungi (Aureobasidium culture solution) in various industrial fields, particularly the medical, health, welfare, environment and food industries. SOLUTION: Aureobasidium culture solutions or supernatants obtained by centrifuging the culture solutions are applied to the medical, health, welfare, environment and food industries, particularly as pharmaceutical preparations for various diseases (for research and therapy), auxiliary reagents for clinical examination systems (clinical examination kits), new materials involved in preventing in-hospital infections and the cleanup of environmental pollutants, sterile foods for patients after subjected to transplantation, and functional supplements involved in the health maintenance of elderly persons and women (pregnant women, women suffered from menopausal disorders).

Beneficial effects of novel strains of Aureobasidium pullulans produced 1,3-1,6 β-glucans on non-esterified fatty acid levels in diabetic KKAy mice

Abstract: Obesity, metabolic syndrome, associated lipotoxicity and its cascade of events contribute to the majority of the burden related to non-communicable diseases globally. Preventive lifestyle changes aside, several beneficial effects have been reported in type II diabetes mellitus and dyslipidaemia patients with biological response modifier glucans (BRMG) produced as an exopolysaccharide by Aureobasidium pullulans. In this study, we compared two strains (AFO 202 and N 163) that produce beta glucans in alleviating lipotoxicity. This study was performed in obese diabetic mice model of KKAy mice, in four groups with six subjects in each group Group 1: sacrificed on Day 0 for baseline values; Group 2: control (drinking water); Group 3: AFO 202 beta glucan 200 mg/kg/day; Group 4: N 163 beta glucan 300 mg/kg/day. The animals in groups 2 to 4 had the test solutions administered by gavage once daily for 28 consecutive days. Biochemical analyses were conducted of blood glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and non-esterified fatty acids (NEFA). Group 4 (N 163) had the lowest NEFA levels, as compared to the other groups, and marginally decreased triglyceride levels. The groups had no significant differences in blood glucose, HbA1c, triglycerides, or LDL and HDL cholesterol. N-163 produced by A. pullulans decreased NEFA in a diabetic mice model in 28 days. These results, although modest, warrant further in-depth research into lipotoxicity and associated inflammatory cascades in both healthy and disease affected subjects to develop novel strategies for prevention and management.

Beneficial effects of the AFO-202 and N-163 strains of Aureobasidium pullulans produced 1,3-1,6 beta glucans on non-esterified fatty acid levels in obese diabetic KKAy mice: A comparative study

Abstract: Background Obesity, metabolic syndrome, associated lipotoxicity and its cascade of events contribute to the majority of the burden related to non-communicable diseases globally. Preventive lifestyle changes aside, several beneficial effects have been reported in type II diabetes mellitus and dyslipidaemia patients with biological response modifier glucans (BRMG) produced as an exopolysaccharide by Aureobasidium pullulans. In this study, we compared two strains (AFO-202 and N-163) that produce beta glucans to differentiate their efficacy in alleviating lipotoxicity. Methods This study was performed in obese diabetic mice model of KK-Ay mice, in four groups with six subjects in each group - Group 1: sacrificed on Day 0 for baseline values; Group 2: control (drinking water); Group 3: AFO-202 beta glucan—200 mg/kg/day; Group 4: N-163 beta glucan—300 mg/kg/day. The animals in groups 2–4 had the test solutions forcibly administered orally into the stomach using a gastric tube once daily for 28 consecutive days. Biochemical analyses were conducted of blood glucose, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol and non-esterified fatty acids (NEFA). Results Group 4 (N-163) had the lowest NEFA levels, as compared to the other groups, and marginally decreased triglyceride levels. The groups had no significant differences in blood glucose, HbA1c, triglycerides, or LDL and HDL cholesterol. Conclusion N-163 produced by A. pullulans decreased NEFA in a diabetic mice model in 28 days. These results, although modest, warrant further in-depth research into lipotoxicity and associated inflammatory cascades in both healthy and disease affected subjects to develop novel strategies for prevention and management.

Protein kinase C and toll-like receptor signaling.

Abstract: Protein kinase C (PKC) is a family of kinases that are implicated in a plethora of diseases, including cancer and cardiovascular disease. PKC isoforms can have different, and sometimes opposing, effects in these disease states. Toll-like receptors (TLRs) are a family of pattern recognition receptors that bind pathogens and stimulate the secretion of cytokines. It has long been known that PKC inhibitors reduce LPS-stimulated cytokine secretion by macrophages, linking PKC activation to TLR signaling. Recent studies have shown that PKC-α, -δ, -e, and -ζ are directly involved in multiple steps in TLR pathways. They associate with the TLR or proximal components of the receptor complex. These isoforms are also involved in the downstream activation of MAPK, RhoA, TAK1, and NF-κB. Thus, PKC activation is intimately involved in TLR signaling and the innate immune response.

Regulation and Function of Protein Kinases and Phosphatases

Abstract: 1Department of Biochemistry &Molecular Biology, Bio21Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia 2Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China 3Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, QC, Canada H3T 1E2 4The Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada H3T 1E2 5Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia

Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes

Abstract: This was a placebo-controlled, double-blind study designed to evaluate the effect of a commercially available dietary supplement on upper-respiratory tract symptoms (URTI) and mood state. Seventy-five marathon runners (35 men, 40 women) ranging in age from 18–53 years, mean age: 36 ± 9, selfadministered placebo, 250 mg or 500 mg of BETA 1,3/1,6 GLUCAN (commercial name Wellmune WGP ® ) daily during the 4 week post-marathon trial period following the 2007 Carlsbad Marathon. Subjects filled out the profile of mood state (POMS) assessment and a questionnaire style health log measuring health status and URTI symptoms after 2- and 4-week treatment administrations. During the course of the 4-week study, subjects in the treatment groups (250 mg and 500 mg BETA-GLUCAN per day) reported significantly fewer URTI symptoms, better overall health and decreased confusion, fatigue, tension, and anger, and increased vigor based on the POMS survey compared to placebo. BETA-GLUCAN may prevent URTI symptoms, and improve overall health and mood following a competitive marathon.