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The Quantum Health Human Research Institute is a private non-profit research facility started in 2009 originally named the Pegasus Biochemistry Research Institute. The Institute's mission is to research new science which includes the continued collaboration with other research teams worldwide. A bioinfomatics data base is being developed to provide information on the biological processes compiled from the research for the public and health care community. From this research the institute designs courses of study to educate the health care professional and public. The Institute's research teams continue the research on the most promising chemistry found from published research studies. The Institute has an ongoing exchange of information with other medical and bioinformatics systems and researchers. www.quanthealth.org MUSHROOM CHEMISTRY Numerous studies have demonstrated that certain components present in medicinal mushrooms have been responsible for the modulation of cellular and physiological changes in the host. It is for this reason that mushrooms are often used as cancer therapeutic agents. 45,46,47 These studies used cultivated hybrid strains developed in the research labs with proprietary organic substrates. The hybrid strains and specific substrates used in these studies are not available in the wild or from most commercial mushroom growers. All of the hybrid strains of species used were cultivated in a controlled sterile environment and are not available from most commercial growers for the supplements or neutraceutical industry, and or as a raw food which come from the common strains of species available from commercial mushroom growers. These hybrid strains of medicinal mushrooms in these studies contain valuable unique constituents including polysaccharides, lectins, lipids, hericenone, erinacol, erinacine, and terpenoids. Recently these components, including water-soluble polysaccharides of a specific specie of Cordyceps, were isolated from its fruit bodies and induced intriguing biological activities such as cytotoxicity, synthesis of nerve growth factor, and antimicrobial function. 45 Interleukin (IL) -1 is a pluripotent and proinflammatory cytokine that orchestrates inflammatory and host-defense responses. Biologically active IL-1b is a 17.5-kDa protein resulting from cleavage of an inactive 31_34 kDa pro-IL-1b. IL-1b augments T-cell responses to mitogens, indirectly activates B cells, increases expression of vascular adhesion molecules, and induces other proinflammatory cytokines and chemokines. IL-1 is produced mainly by monocytes and macrophages when stimulated with various antigenic stimulants, including viruses or bacterial components such as lipopolysaccharide (LPS). Numerous studies have demonstrated that Lipopolysaccharide (NF0kB), activator protein 1 (AP-1), nuclear factor interleukin-6 (NF-IL6), and cAMP response element (CRE)/activating transcription factor (ATF) regulate IL-1 transcription in macrophages upon stimulations. 47 Since IL-1 is a proinflammatory cytokine, agents that induce the activity of IL-1 have recently gained particular therapeutic and clinical interest. Mushrooms are known for their nutritional and healthful value and also for the diversity of the bioactive compounds they contain. Protein-bound polysaccharides, designated as PSK and PSP (Polysaccharopeptide) have been isolated from certain mushrooms. PSP is classified as a biological response modifier. It originally induced in experimental animals and now has also in human and other mammals, increased y-interferon production, interleukin-2 production, and T-cell proliferation. It also counteracts the depressive effect of cyclophosphamide on white blood cell count, interleukin-2 production and delayed type hypersensitivity reaction. Its antiproliferative activity against tumor cell lines in vivo antitumor activity has been demonstrated. A small peptide with a molecular weight of 16-18 kDa originating from PSP has been produced with antiproliferative and antitumor activities. PSP administered to patients with esophageal cancer, gastric cancer and lung cancer, and who are undergoing radiotherapy or chemotherapy, helps alleviate symptoms and prevents the decline in immune stress. Aspergillomarasmine A is an polyamino acid found in some of the medicinal mushroom chemistry from the hybrid strains produced in each study. The substance has been reported to inhibit two antibiotic resistance carbapenemase proteins in bacteria, New Delhi metallo-beta-lactamase 1 (NDM-1) and Verona integron-encoded metallo-beta-lactamase (VIM-2), and make those antibiotic resistant bacteria susceptible to antibiotics. Further anecdotal tests show that the Gram-negative bacterias including the new spirochetes strains in Lyme disease are resistant to antibiotics and the immune system. When consuming a dosage of 16 grams a day of these medicinal mushroom strains that have the Aspergillomarasamine A, then the resistance is removed for some. Lyme disease is an infectious disease caused by Borrelia burgdorferi, a bacterium classified as a spirochete. Further tests are being prepared to determine on a larger scale what specific Gram-negative bacterias are affected. Gram-negative bacteria have thin walls with an outer layer composed of proteins and lypopolysacchrides. This outer layer sometimes reacts with the immune system, causing inflamation and infection. In addition to preventing the bacteria from staining the outer membrane of the cell, it also helps the bacteria resist an assortment of drugs, making treatment of infections with Gram-negative bacteria rather challenging. Some examples of Gram-negative bacteria include Legionella, Salmonella, and E. Coli. Numerous other pathogens are also Gram-negative, including some forms of meningitis, a number of bacterial sources of gastrointestinal distress, and spirochetes. Gram-negative bacteria can be stubborn infectious agents, and many sources of lethal infection are Gram-negative, including the bacteria which contribute to secondary infections in hospitals and clinics. 50 By the term mushrooms, we generally mean the definition of Chang and Miles (1992): a macro fungus with a distinctive fruiting body which can be hypogeous or epigeous, large enough to be seen with the naked eye and to be picked by hand. The number of mushroom species on Earth is estimated at 140,000, yet maybe only 10% (approximately 14,000 named species) are known. Mushrooms comprise a vast and yet largely untapped source of powerful new chemical and pharmaceutical products. They represent an unlimited source of polysaccharides with antitumor and immuno-stimulating properties. Data on mushroom polysaccharides have been collected from 651 species and 7 infraspecific taxa from 182 genera if higher Hetero - and Homobasidiomycetes. Mushroom polysaccharides prevent oncogenesis, show direct antitumor activity against various allogeneic and syngenetic tumors, and prevent tumor metastasis. Polysaccharides from mushrooms do not attack cancer cells directly, but produce antitumor effects by activating different immune responses in the host. These substances are regarded as biological response modifiers. This basically means that: (1) they cause no harm and place no additional stress on the body; (2) they help the body adapt to various environmental and biological stresses; and (3) they exert a non-specific action on the body, supporting some or all of the major systems, including nervous, hormonal, and immune systems, as well as regulatory functions. Studies show there is no chronic or acute toxicity. Cell nucleus studies show no detrimental effects and DNA showed no mutations. Pregnant animal studies demonstrated there is no detriment to fetal development, and no LD50, a measure of toxicity that has never been shown. Medicinal mushrooms apparently produce no harmful side effects. ____________________________________________________________________________________________________________________________ BIBLIOGRAPHY ____________________________________________________________________________________________________________________________ 1) Dastrun et al. (2004), Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells, Dept. cell biology, Institute of Biomembranes, Utrecht University, The Netherlands, Online Pub. 2) Kakkura B., (2006), Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle, Dept of Obstetrics and Gynecology, University of Siena, Italy, Online Pub. 3) Jeffery Klein, (2003), Susan Ackerman, Oxidative stress, cell cycle, and neurodegeneration, J. Clin Invest, 111; pp 785-793. 4) Nagy Z, Esiri, M (1998), The Cell Division Cycle and the Pathophysiology of Alzheimer’s disease. 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Exp Biol Med 221; pp 281-293. 12) Fullerton SA, Samadi AA, (2000), Induction of apoptosis in human prostatic cancer cells with beta-glucan from Maitake, Mol Urol 4: pp 7-13. 13) Breene W., Nutritional and Medicinal Value of Specialty Mushrooms (1989), J. of food protection vol 53: No. 10, pp 883-894. 14) Nathon Sharon, Halina Lis (1993), Carbohydrates in Cell Recognition, Scientific America, Jan 1993. 15) So-Young Won and Eun-Hee Park (2005), Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris, College of Pharmacy, Sookmyung Women’s University, Seoul 140-742, South Korea, Journal of Ethnopharmacology, Vol 96, issue 3, 15 Jan 2005 pp 555-561. 16) Chiou et al, 2000, Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps Sinensis, Life Sciences 66 (2000), pp 1369-1376. 17) Ingber et al, 1990 D. Ingber, T. Fujita, Synthetic analogs of fumagillin that inhibit angiogenesis and suppress tumor growth, Nature 348 (1990), pp 555-557. 18) Koh et al, 2003 J.H. Koh, K.M. Kim, Anti fatigue and anti stress effects of the hot water fraction from mycelia of Cordyceps sinesis, Biological and Pharmaceuetin 26 (2003), pp 691-694. 19) Bok et al, 1999 J.W. Bok, L. Lermer, J. Chilton, H.G. Klingerman, Antitumor sterols from the mycelia of Cordyceps sinensis, Phytochemistry 51 (1999), pp 891-898. 20) Bourlon, P. M., Billaudel, B& Faure-Dussert, A. (1999), Influence of vitamin D3 deficiency and 1, 25 dihydroxyvitamin D3 on de novo insulin biosynthesis in the islets of the rat endocrine pancreas, Journal of Endocrinology, 160, pp 87-95. 21) Ohno, R., Imai, K. Yokomaku, S. & Yamada, K. (1975) Antitumor effect of protein bound polysaccharide preparation, PSK against 3-methylcholanthrene induced fibrosarcoma in C57BL/6 mice. Gann 66 pp 697-681. 22) Matsunaga, K., Oguchi, Y, Ando T, (1980) Effect of PSK on intestinal immune system in tumor bearing mice. Proceedings of the Japanese Cancer Association, 29th Annual meeting, p 145. http://www.pskmushroom.info/ 23) Muto, S. Kobayashi, A. (1982) Structure and antitumor effect of PSK (Kreston): mechanistic aspects of the antitumor activity. Proceedings of 2nd International Conference of Immunopharmachology, p 308. 24) Muto, S., Kobayashi, A. (1983) Structural analysis and antitumor effect of PSK, Proceedings of 13th International Congress of Chemoradiotherapy, Vienna: part 287, pp 37-40. 25) Morimasa, K. Yamana, S. Matsueda, H. (1980) Immunostimulent therapy with protein bound polysaccharide preparation in patients with SLE or RA. Clinical Immunology 12: pp 393-398. 26) Aoki T (1984) Fenichei RL, Chirgis MA, Immune modulating agents and their mechanisms, Immunol Stud 25, 62-77.27) Fujimiya Y, Yamamoto H, Noji M (2000) Peroral effect on tumor progression of soluable B-1,6 glucans prepared by acid treatment from Agaricus blazei, Agaricaceae Higher Basidiomycetes, Int. J Med Mushrooms 2: pp 43-49. 27) Che Ys, Lin Lz, Clinical observation of therapeutic effects of JinShuBao on coronary heart disease, hyperlipidemia, and blood rheology. Chinese traditional herbal drugs 1996. 28) Kiho T, Yamane A, Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultured mycelia of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol Pharm Bull (1996); 19(2) pp 294-296. 29) Shao G. You Zj, Treatment of hyperlipidemia with Cordyceps sinensis; a double blind placebo control trial. Int j oriental Med 1990;15(2);77-80.31) Mizuno T. et al Antitumor active polysaccharides isolated from the fruiting body of Hericium erinaceum, an edible and medicinal mushroom called yamabushitake Biosci, Biotech, Biochem 56 (2), pp 347-348 (1992). 30) S. Konno, H Tazaki et al, A possible hypoglycemic effect of Maitake mushroom on type 2 diabetic patients, Diabetic Medicine, Vol 18 Issue 12 p 1010 Issue 12 Dec 2001. 31) Kaoru Nagai, Akiko Chiba et al, Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress dependent Neuro2a cel. 32) Jia-Shi Shu, M.D., Ph.D., George M. Halpern, M.D. Ph. D., and Kenneth Jones, The Scientific Rediscovery of an Ancient Chinese Herbal-Medicine: Cordyceps-sinensis. Department of Pediatrics, Stanford University School of Medicine, Stanford, California, Zhi Dao Tower, 12th Floor, Shanghai Medical University, Shanghai, China., Emeritus, University of California, Davis, California., Armana Research, Inc., Gibsons, British Columbia, Canada. [The Journal of Alternative and Complementary Medicine, Volume 4, Number 3, 1998, pp 289-303]. 33) Tsukagoshi, S., *Hashimoto, Y., ** Fujii, G., † Kobayashi, H., ‡ Nomoto, K. § and Orita, K. ll, Krestin (PSK) Cancer Chemotheraphy Center, The Japanese Foundation for Cancer Research, Tokyo, ** Department of Hygienic Chemistry, Pharmaceutical Institute, Tahoku University, Sendai, †Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, Tokyo, ‡Laboratory of Pathology, Cancer Institute, Hokkaido University, School of Medicine, Sapporo, § Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuokam, and ll The First Department of Surgery, Okayama University, Medical School, Okayama, Japan. [Cancer Treatment Reviews (1984) 11, pp 131-155]. 34) T.B.Ng*, A Review of Research on the Protein-Bound Polysaccharide (Polysaccharopeptide, PSP) from the Mushroom Coriolus versicolor (Basidiomycetes: Polyporaceae), Department of Biochemistry, Faculty of Medicien, Chinese University of Hong Kong, Shatin, N.T. Hong Kong. [Gen. Pharmac. Vol. 30, no. 1, pp 1-4, 1998]. 35) Sean A. Fullerton, M.D., Albert A. Samadi, M.D., Dean G. Tortorelis, M.D., Muhammad S. Choudhury, M.D., Camille Mallouh, M.D. Hiroshi Tazaki, M.D. ph. D., and Sensuke Konno, Ph. D. Induction of Apoptosis in Human Prostatic Cancer Cells with β-Glucan (Maitake Mushroom Polysaccharide) Department of Urology, New York Medical College, Valhalla, New York, [Molecular Urology, Volume 4, Number 1, 2000]. 36) S.P.Wasser, Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides, Institute of Evolution, University of Haifa, Mt. Carmel, Haifa 31905, Israel, N.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine, [Applied Microbiology biotechnology (2002) 60, pp 258-274]. 37) You-Cheng Hseu ª, Ssu-Ching Chen, Pei-Chuan Tsai, Chee-Shan Chen, Fung-Jou Lu, Nai-Wen Chang, Hsin-Ling Yang, Inhibition of cyclooxygenase-2 and induction of apoptosis in estrogen-nonresponsive breast cancer cells by Antrodia Camphorata, Department of Cosmeceutics, China Medical University, Taichung, Taiwan, Department of Biotechnology, National Kaohsiung Normal University, Kaohsiung, Taiwan [Food and Chemical Toxicology 45 (2007) pp 1107-1115]. 38) Wikipedia, 2006, Mushroom 39) Jim Kling, Medicinal Mushroom Research to be Presented at ACS (American Chemical Society) NationalMeeting. www.chemistry.org/portal/a/c/s/1/feature_pro.html?id=c373e905cd8d4dfc8f6a17245 (2006). 40) Beinfield, H., 1997. Medicinal mushrooms: help yourself to a serving of health, Nature's Impact, December. 41) Chang R., 1996. Functional properties of edible mushrooms. Nutr Rev 54(11), S91-S93. 42) Salvucci O, 1996. Differential regulation of interleukin-12- and interleukin -15- induced natural killer cell activation by interleikin-4. Eur J. Immunol 26(11), pp 2736-2741. 43) Ukai S, 1972. Antitumor activity on sarcoma 180 of the polysaccharides from Tremella fuciformis Berk. Chem Phara Bull (Tokyo) 20(10), pp 2293-2294. 44) Jia-Shi Shu, M.D., Ph.D., George M. Halpern, M.D. Ph. D., and Kenneth Jones, The Scientific Rediscovery of an Ancient Chinese Herbal-Medicine: Cordyceps-sinensis PART II. Department of Pediatrics, Stanford University School of Medicine, Stanford, California, Zhi Dao Tower, 12th Floor, Shanghai Medical University, Shanghai, China., Emeritus, University of California, Davis, California., Armana Research, Inc., Gibsons, British Columbia, Canada. [The Journal of Alternative and Complementary Medicine, Volume 4, Number 3, 1998, pp 429-457]. 45) Chang-gue SON, juang-woo SHIN, Jung-hyp CHO, Chong-kwan CHO, Cheol-heui YUN, Seung-hyun HAN, Induction of murin interleukin-1 beta expression by water-soluble components from Hericium erinaceum. East-West Cancer Center, Dunsan Oriental Hospital of Daejon University, Daejon, 301-724, Republic of Korea; School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea; Department of Oromaxillofacial Infection and Immunity and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea; Laboratory Sciences Division, International Vaccine Institute, Seuol pp 151-818, Korea. 46) Deng-Bo Ji, Jia Ye, Chang-Ling Li, Yu-Hua Wang, Jiong Zhao, Shao-Quing Cai, Antiaging effect of Cordyceps sinensis extract. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, R.P. China, Department of Nature Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, 100083, P.R. China. 47) Reay J, Kim SH, Lockhart E., Kolls J, Robbins PD, Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response, Department of Microbiology and Molecular Genetics, University of Pittsburg School of Medicine, Pittsburgh, PA, USA. Interleukin 23 (IL-23) is a member of the IL-12 family of heterodimeric cytokines, composed of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent antitumor activities in several establishment models of cancer and a few therapeutic models, but the efficacy of local, adenoviral-mediated expression of IL-23 in established tumors has yet to be investigated. Here we have examined the antitumor activity of adenovirally delivered IL-23 in a day-7 MCA205 murine fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete rejection of 40% of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T lymphocytes. In addition, we have shown that the antitumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on interferon-gamma, CD4(+) and CD8(+) T cells. These results demonstrate that direct intratumoral injection of adenovirus expressing IL-23 results in enhanced survival, tumor eradication and generation of protective immunity by generation of a Th1-type immune response. Cancer Gene Therapy advance online publication, 24 April 2009; doi:10.1038/cgt.2009.27. PMID: 19390568 [PubMed - as supplied by publisher]. 48) Species of Cordyceps studied by the science team at Quantum Health Human Research: H. coralloides, H. americanum, H. erinaceus, and H. erinaceum. 49) Ben-Zion Zaidman, Majed Yassin, Jamal Mahajna, Solomon P. Wasser. Medicinal mushroom modulators of molecular targets as cancer therapeutics, Biodiversity and Biotechnology Center of Cryptogamic Plants and Fungi, The Institute of Evolution, University of Haifa, Mount Carmel, Haifa, Mount Carmet, Haifa, Mount Carmel, Haifa, 1905, Israel. February 23, 2005 "Over the past two to three decades, scientist and medical studies in Japan, China, Europe, Korea and the United States have increasingly demonstrated the potent and unique properties of mushrooms by using mushroom-extracted compounds clinical tests using whole mushrooms for the prevention and treatment of cancer." 50) King, Andrew M.;
Sarah A. Reid-Yu; Wenliang Wang;
Dustin T. King; Gianfranco De Pascale;
Natalie C. Strynadka; Timothy R. Walsh; Brian K. Coombes; Gerard D. Wright (2014)."Aspergillomarasmine
A overcomes metallo-β-lactamase antibiotic resistance". Nature 510 (7506): 503-506. doi: 10.1038/nature13445. ISSN
0028-0836
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