Involvement of blood mononuclear cells in the infertility, age-associated diseases and cancer treatment
Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu přehledy, časopisecké články
PubMed
28074124
PubMed Central
PMC5183987
DOI
10.4252/wjsc.v8.i12.399
Knihovny.cz E-zdroje
- Klíčová slova
- Age-associated diseases, Blood mononuclear cells, Cancer immunotherapy, Immune system, Infertility treatment, Regenerative medicine, Stem cells, Tissue control system, Tissue morphostasis, Transfusion morphostatic treatment,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage IV ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.
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Bukovsky A. Immune maintenance of self in morphostasis of distinct tissues, tumour growth and regenerative medicine. Scand J Immunol. 2011;73:159–189. PubMed
Conrad FJ, Rice JS, Cambier JC. Multiple paths to loss of anergy and gain of autoimmunity. Autoimmunity. 2007;40:418–424. PubMed
Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol. 2010;11:21–27. PubMed
Carrel A. GROWTH-PROMOTING FUNCTION OF LEUCOCYTES. J Exp Med. 1922;36:385–391. PubMed PMC
Burwell RG. The role of lymphoid tissue in morphostasis. Lancet. 1963;2:69–74. PubMed
Fidler IJ. Lymphocytes are not only immunocytes. Biomedicine. 1980;32:1–3. PubMed
Bukovský A, Presl J, Krabec Z, Bednarík T. Ovarian function in adult rats treated with antithymocyte serum. Experientia. 1977;33:280–281. PubMed
Bukovský A, Michael SD, Presl J. Cell-mediated and neural control of morphostasis. Med Hypotheses. 1991;36:261–268. PubMed
Bukovsky A, Caudle MR, Keenan JA. Regulation of ovarian function by immune system components: the tissue control system (TCS) In: Motta PM, editor. Microscopy of Reproduction and Development: A Dynamic Approach. Roma: Antonio Delfino Editore; 1997. pp. 79–89.
Bukovsky A, Caudle MR. Immunoregulation of follicular renewal, selection, POF, and menopause in vivo, vs. neo-oogenesis in vitro, POF and ovarian infertility treatment, and a clinical trial. Reprod Biol Endocrinol. 2012;10:97. PubMed PMC
Bürkle A, Caselli G, Franceschi C, Mariani E, Sansoni P, Santoni A, Vecchio G, Witkowski JM, Caruso C. Pathophysiology of ageing, longevity and age related diseases. Immun Ageing. 2007;4:4. PubMed PMC
Cuzick J, Glasier A, La Vecchia C, Maraganore DM, Negri E, Rossi M, Spector T, Trichopoulos D, van Baak MA, Zocchetti C, et al. Perimenopausal risk factors and future health. Hum Reprod Update. 2011;17:706–717. PubMed
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. PubMed
Bukovsky A, Caudle MR, Keenan JA, Upadhyaya NB, Van Meter SE, Wimalasena J, Elder RF. Association of mesenchymal cells and immunoglobulins with differentiating epithelial cells. BMC Dev Biol. 2001;1:11. PubMed PMC
Bockman DE, Kirby ML. Dependence of thymus development on derivatives of the neural crest. Science. 1984;223:498–500. PubMed
Bockman DE. Development of the thymus. Microsc Res Tech. 1997;38:209–215. PubMed
Williams AF, Barclay AN. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. PubMed
Bukovský A, Keenan JA, Caudle MR, Wimalasena J, Upadhyaya NB, Van Meter SE. Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis. Am J Reprod Immunol. 1995;33:323–340. PubMed
Forbes MS, Rennels ML, Nelson E. Innervation of myocardial microcirculation; terminal autonomic axons associated with capillaries and postcapillary venules in mouse heart. Am J Anat. 1977;149:71–92. PubMed
Ashraf S, Crowe R, Loizidou MC, Turmaine M, Taylor I, Burnstock G. The absence of autonomic perivascular nerves in human colorectal liver metastases. Br J Cancer. 1996;73:349–359. PubMed PMC
Bukovsky A, Caudle MR, Carson RJ, Gaytán F, Huleihel M, Kruse A, Schatten H, Telleria CM. Immune physiology in tissue regeneration and aging, tumor growth, and regenerative medicine. Aging (Albany NY) 2009;1:157–181. PubMed PMC
Ginhoux F, Lim S, Hoeffel G, Low D, Huber T. Origin and differentiation of microglia. Front Cell Neurosci. 2013;7:45. PubMed PMC
Diaz-Flores L, Gutierrez R, Varela H. Behavior of postcapillary venule pericytes during postnatal angiogenesis. J Morphol. 1992;213:33–45. PubMed
Lambolez F, Mayans S, Cheroutre H. Lymphocytes: Intraepithelial. Chichester e LS: John Wiley & Sons Ltd; 2013. Available from: http://www.els.net.
Cutolo M, Accardo S, Villaggio B, Clerico P, Bagnasco M, Coviello DA, Carruba G, lo Casto M, Castagnetta L. Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+, CD29+, CD45RO+ T lymphocytes in normal and rheumatoid synovium. Arthritis Rheum. 1993;36:1087–1097. PubMed
Avrameas S. Natural autoantibodies: from ‘horror autotoxicus’ to ‘gnothi seauton’. Immunol Today. 1991;12:154–159. PubMed
Cuk M, Radosević-Stasić B, Milin C, Kirigin M, Rukavina D. Lymphoid system as a regulator of morphostasis and hormonal modulation of these functions. Ann N Y Acad Sci. 1987;496:104–107. PubMed
Itagaki S, McGeer PL, Akiyama H. Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer’s disease brain tissue. Neurosci Lett. 1988;91:259–264. PubMed
Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol Aging. 1988;9:339–349. PubMed
McGeer PL, McGeer EG, Kawamata T, Yamada T, Akiyama H. Reactions of the immune system in chronic degenerative neurological diseases. Can J Neurol Sci. 1991;18:376–379. PubMed
Kumar M, Cohen D, Eisdorfer C. Serum IgG brain reactive antibodies in Alzheimer disease and Down syndrome. Alzheimer Dis Assoc Disord. 1988;2:50–55. PubMed
Blennow K, Wallin A, Davidsson P, Fredman P, Gottfries CG, Svennerholm L. Intra-blood-brain-barrier synthesis of immunoglobulins in patients with dementia of the Alzheimer type. Alzheimer Dis Assoc Disord. 1990;4:79–86. PubMed
Singh VK. Immune-activation model in Alzheimer disease. Mol Chem Neuropathol. 1996;28:105–111. PubMed
Hartwig M. Immune ageing and Alzheimer’s disease. Neuroreport. 1995;6:1274–1276. PubMed
Hong H, Kim BS, Im HI. Pathophysiological Role of Neuroinflammation in Neurodegenerative Diseases and Psychiatric Disorders. Int Neurourol J. 2016;20:S2–S7. PubMed PMC
Bukovsky A, Caudle MR, Keenan JA. Dominant role of monocytes in control of tissue function and aging. Med Hypotheses. 2000;55:337–347. PubMed
Mathé G. Immunity aging. I. The chronic perduration of the thymus acute involution at puberty? Or the participation of the lymphoid organs and cells in fatal physiologic decline? Biomed Pharmacother. 1997;51:49–57. PubMed
Hellström I, Hellström KE, Sjögren HO, Warner GA. Demonstration of cell-mediated immunity to human neoplasms of various histological types. Int J Cancer. 1971;7:1–16. PubMed
Hellström I, Hellström KE, Sjögren HO, Warner GA. Serum factors in tumor-free patients cancelling the blocking of cell-mediated tumor immunity. Int J Cancer. 1971;8:185–191. PubMed
Bukovsky A, Ayala ME, Dominguez R, Keenan JA, Wimalasena J, McKenzie PP, Caudle MR. Postnatal androgenization induces premature aging of rat ovaries. Steroids. 2000;65:190–205. PubMed
Bukovsky A, Ayala ME, Dominguez R, Keenan JA, Wimalasena J, Elder RF, Caudle MR. Changes of ovarian interstitial cell hormone receptors and behavior of resident mesenchymal cells in developing and adult rats with steroid-induced sterility. Steroids. 2002;67:277–289. PubMed
Bukovsky A, Presl J. Ovarian function and the immune system. Med Hypotheses. 1979;5:415–436. PubMed
Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol. 2004;2:20. PubMed PMC
Bukovsky A, Caudle MR, Svetlikova M, Wimalasena J, Ayala ME, Dominguez R. Oogenesis in adult mammals, including humans: a review. Endocrine. 2005;26:301–316. PubMed
Bukovsky A, Ayala ME, Dominguez R, Svetlikova M, Selleck-White R. Bone marrow derived cells and alternative pathways of oogenesis in adult rodents. Cell Cycle. 2007;6:2306–2309. PubMed
Bukovsky A. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases. Reprod Biol Endocrinol. 2015;13:10. PubMed PMC
Bukovsky A, Svetlikova M, Caudle MR. Oogenesis in cultures derived from adult human ovaries. Reprod Biol Endocrinol. 2005;3:17. PubMed PMC
Baas T. Repowering the ovary. SciBX. 2012;5:4–6. Available from: http://www.nature.com/scibx/journal/v5/n10/full/scibx.2012.244.html.
Gougeon A. [Is neo-oogenesis in the adult ovary, a realistic paradigm?] Gynecol Obstet Fertil. 2010;38:398–401. PubMed
Bukovsky A. Ovarian stem cell niche and follicular renewal in mammals. Anat Rec (Hoboken) 2011;294:1284–1306. PubMed
Gupta SK. Role of zona pellucida glycoproteins during fertilization in humans. J Reprod Immunol. 2015;108:90–97. PubMed
Escrich L, Grau N, de los Santos MJ, Romero JL, Pellicer A, Escribá MJ. The dynamics of in vitro maturation of germinal vesicle oocytes. Fertil Steril. 2012;98:1147–1151. PubMed
Yu W, Zheng H, Lin W, Tajima A, Zhang Y, Zhang X, Zhang H, Wu J, Han D, Rahman NA, et al. Estrogen promotes Leydig cell engulfment by macrophages in male infertility. J Clin Invest. 2014;124:2709–2721. PubMed PMC
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433:760–764. PubMed
Conboy MJ, Conboy IM, Rando TA. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 2013;12:525–530. PubMed PMC
Katcher HL. Studies that shed new light on aging. Biochemistry (Mosc) 2013;78:1061–1070. PubMed
Lee TH, Paglieroni T, Ohto H, Holland PV, Busch MP. Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. Blood. 1999;93:3127–3139. PubMed
Smith AD, Tilling K, Lawlor DA, Nelson SM. External validation and calibration of IVF predict: a national prospective cohort study of 130,960 in vitro fertilisation cycles. PLoS One. 2015;10:e0121357. PubMed PMC
Block E. Quantitative morphological investigations of the follicular system in women; variations at different ages. Acta Anat (Basel) 1952;14:108–123. PubMed
Gougeon A, Ecochard R, Thalabard JC. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod. 1994;50:653–663. PubMed
Ingram DL. In The Ovary, S Zuckerman (ed) London, Academic Press: 1962. pp. 247–273.
Dyce PW, Li J. From skin cells to ovarian follicles? Cell Cycle. 2006;5:1371–1375. PubMed
Dyce PW. Differentiation of newborn mouse skin derived stem cells into germ-like cells in vitro. J Vis Exp. 2013:e50486. PubMed PMC
Lei L, Spradling AC. Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells. Science. 2016;352:95–99. PubMed PMC
Motta PM, Makabe S, Naguro T, Correr S. Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy. Arch Histol Cytol. 1994;57:369–394. PubMed
Mason C, Dunnill P. A brief definition of regenerative medicine. Regen Med. 2008;3:1–5. PubMed
de Sá Silva F, Almeida PN, Rettore JV, Maranduba CP, de Souza CM, de Souza GT, Zanette Rde S, Miyagi SP, Santos Mde O, Marques MM, et al. Toward personalized cell therapies by using stem cells: seven relevant topics for safety and success in stem cell therapy. J Biomed Biotechnol. 2012;2012:758102. PubMed PMC
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. PubMed
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–872. PubMed
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. PubMed
Gutierrez-Aranda I, Ramos-Mejia V, Bueno C, Munoz-Lopez M, Real PJ, Mácia A, Sanchez L, Ligero G, Garcia-Parez JL, Menendez P. Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection. Stem Cells. 2010;28:1568–1570. PubMed PMC
Lamm N, Ben-David U, Golan-Lev T, Storchová Z, Benvenisty N, Kerem B. Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects. Cell Stem Cell. 2016;18:253–261. PubMed
Diukman R, Golbus MS. In utero stem cell therapy. J Reprod Med. 1992;37:515–520. PubMed
Ankrum J, Karp JM. Mesenchymal stem cell therapy: Two steps forward, one step back. Trends Mol Med. 2010;16:203–209. PubMed PMC
Golpanian S, Schulman IH, Ebert RF, Heldman AW, DiFede DL, Yang PC, Wu JC, Bolli R, Perin EC, Moyé L, et al. Concise Review: Review and Perspective of Cell Dosage and Routes of Administration From Preclinical and Clinical Studies of Stem Cell Therapy for Heart Disease. Stem Cells Transl Med. 2016;5:186–191. PubMed PMC
Broughton KM, Sussman MA. Empowering Adult Stem Cells for Myocardial Regeneration V2.0: Success in Small Steps. Circ Res. 2016;118:867–880. PubMed PMC
Shiota G, Itaba N. Progress in stem cell-based therapy for liver disease. Hepatol Res. 2016 Epub ahead of print. PubMed
Deng P, Torrest A, Pollock K, Dahlenburg H, Annett G, Nolta JA, Fink KD. Clinical trial perspective for adult and juvenile Huntington’s disease using genetically-engineered mesenchymal stem cells. Neural Regen Res. 2016;11:702–705. PubMed PMC
Bukovsky A. From cellular to chemical approach for acute neural and alternative options for age-induced functional diseases. World J Stem Cells. 2015;7:1109–1117. PubMed PMC
Utter GH, Owings JT, Lee TH, Paglieroni TG, Reed WF, Gosselin RC, Holland PV, Busch MP. Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response. J Trauma. 2005;58:925–931; discussion 931-932. PubMed
Bukovsky A. Sex steroid-mediated reprogramming of vascular smooth muscle cells to stem cells and neurons: possible utilization of sex steroid combinations for regenerative treatment without utilization of in vitro developed stem cells. Cell Cycle. 2009;8:4079–4084. PubMed
Bukovsky A, Caudle MR. Sex steroid combinations in regenerative medicine for brain and heart diseases: The vascular stem cell niche and a clinical proposal. In: Schatten H, editor. Cell and Molecular Biology and Imaging of Stem Cells. Hoboken: Wiley; 2014. pp. 193–210.
Chamberlain G, Kitchin Y. Steroids in the assessment of prenatal development. Postgrad Med J. 1976;52:615–619. PubMed PMC
Rogers I. Transdifferentiation of endogenous cells: cell therapy without the cells. Cell Cycle. 2009;8:4027–4028. PubMed
Tesche LJ, Gerber DA. Tissue-derived stem and progenitor cells. Stem Cells Int. 2010;2010:824876. PubMed PMC
Choumerianou DM, Dimitriou H, Kalmanti M. Stem cells: promises versus limitations. Tissue Eng Part B Rev. 2008;14:53–60. PubMed
Bukovsky A, Caudle MR, Svetlikova M. Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro. Cell Cycle. 2008;7:3577–3583. PubMed
Bukovsky A. The role of resident monocytes and vascular pericytes in the stem cell niche and regenerative medicine. Stem Cell Stud. 2011;1:126–147.
Djebaili M, Guo Q, Pettus EH, Hoffman SW, Stein DG. The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats. J Neurotrauma. 2005;22:106–118. PubMed
Check JH, Levin E, Bollendorf A, Locuniak J. Miscarriage in the first trimester according to the presence or absence of the progesterone-induced blocking factor at three to five weeks from conception in progesterone supplemented women. Clin Exp Obstet Gynecol. 2005;32:13–14. PubMed
Borna S, Sahabi N. Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2008;48:58–63. PubMed
Gray PB, Singh AB, Woodhouse LJ, Storer TW, Casaburi R, Dzekov J, Dzekov C, Sinha-Hikim I, Bhasin S. Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. J Clin Endocrinol Metab. 2005;90:3838–3846. PubMed
Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93:914–919. PubMed PMC
Dohmann HF, Perin EC, Takiya CM, Silva GV, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Pascarelli BM, Assis IM, et al. Transendocardial autologous bone marrow mononuclear cell injection in ischemic heart failure: postmortem anatomicopathologic and immunohistochemical findings. Circulation. 2005;112:521–526. PubMed
Schram JH, Boerrigter PJ, The TY. Influence of two hormone replacement therapy regimens, oral oestradiol valerate and cyproterone acetate versus transdermal oestradiol and oral dydrogesterone, on lipid metabolism. Maturitas. 1995;22:121–130. PubMed
Thomas WE. Brain macrophages: on the role of pericytes and perivascular cells. Brain Res Brain Res Rev. 1999;31:42–57. PubMed
Gui J, Mustachio LM, Su DM, Craig RW. Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma. Aging Dis. 2012;3:280–290. PubMed PMC
de Groot AC. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects. Dermatitis. 2013;24:263–282. PubMed
Fan Y, Ma L, Zhang W, Wang J, Chen Y, Gao Y, Feng W, Zhong L, Song X. The design of propolis flavone microemulsion and its effect on enhancing the immunity and antioxidant activity in mice. Int J Biol Macromol. 2014;65:200–207. PubMed
Missima F, Sforcin JM. Green brazilian propolis action on macrophages and lymphoid organs of chronically stressed mice. Evid Based Complement Alternat Med. 2008;5:71–75. PubMed PMC
Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007;113:1–14. PubMed
Pagliarone AC, Orsatti CL, Búfalo MC, Missima F, Bachiega TF, Júnior JP, Sforcin JM. Propolis effects on pro-inflammatory cytokine production and Toll-like receptor 2 and 4 expression in stressed mice. Int Immunopharmacol. 2009;9:1352–1356. PubMed
Petersen HO, Afzelius H. [Maximization test with propolis on albino guinea pigs] Ugeskr Laeger. 1977;139:2329–2331. PubMed
Gambichler T, Boms S, Freitag M. Contact dermatitis and other skin conditions in instrumental musicians. BMC Dermatol. 2004;4:3. PubMed PMC
Kubota Y, Umegaki K, Kobayashi K, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Shinozuka K. Anti-hypertensive effects of Brazilian propolis in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol. 2004;31 Suppl 2:S29–S30. PubMed
Kitamura H, Naoe Y, Kimura S, Miyamoto T, Okamoto S, Toda C, Shimamoto Y, Iwanaga T, Miyoshi I. Beneficial effects of Brazilian propolis on type 2 diabetes in ob/ob mice: Possible involvement of immune cells in mesenteric adipose tissue. Adipocyte. 2013;2:227–236. PubMed PMC
Tao Y, Wang D, Hu Y, Huang Y, Yu Y, Wang D. The immunological enhancement activity of propolis flavonoids liposome in vitro and in vivo. Evid Based Complement Alternat Med. 2014;2014:483513. PubMed PMC
Magnusson NE, Dyrskjøt L, Grimm D, Wehland M, Pietsch J, Rungby J. Gene networks modified by sulphonylureas in beta cells: a pathway-based analysis of insulin secretion and cell death. Basic Clin Pharmacol Toxicol. 2012;111:254–261. PubMed
Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K. Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res. 2013;303:30–38. PubMed PMC
Contrera KJ, Wallhagen MI, Mamo SK, Oh ES, Lin FR. Hearing Loss Health Care for Older Adults. J Am Board Fam Med. 2016;29:394–403. PubMed
Rifa’i M, Widodo N. Significance of propolis administration for homeostasis of CD4(+)CD25(+) immunoregulatory T cells controlling hyperglycemia. Springerplus. 2014;3:526. PubMed PMC
Aral CA, Kesim S, Greenwell H, Kara M, Çetin A, Yakan B. Alveolar bone protective and hypoglycemic effects of systemic propolis treatment in experimental periodontitis and diabetes mellitus. J Med Food. 2015;18:195–201. PubMed PMC
El-Sharkawy EE, Kames AO, Sayed SM, Nisr NA, Wahba NM, Elsherif WM, Nafady AM, Abdel-Hafeez MM, Aamer AA. The ameliorative effect of propolis against methoxychlor induced ovarian toxicity in rat. Exp Toxicol Pathol. 2014;66:415–421. PubMed
Russo A, Troncoso N, Sanchez F, Garbarino JA, Vanella A. Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species. Life Sci. 2006;78:1401–1406. PubMed
Yousef MI, Kamel KI, Hassan MS, El-Morsy AM. Protective role of propolis against reproductive toxicity of triphenyltin in male rabbits. Food Chem Toxicol. 2010;48:1846–1852. PubMed
Capucho C, Sette R, de Souza Predes F, de Castro Monteiro J, Pigoso AA, Barbieri R, Dolder MA, Severi-Aguiar GD. Green Brazilian propolis effects on sperm count and epididymis morphology and oxidative stress. Food Chem Toxicol. 2012;50:3956–3962. PubMed
Collodel G, Moretti E, Del Vecchio MT, Biagi M, Cardinali R, Mazzi L, Brecchia G, Maranesi M, Manca D, Castellini C. Effect of chocolate and Propolfenol on rabbit spermatogenesis and sperm quality following bacterial lipopolysaccharide treatment. Syst Biol Reprod Med. 2014;60:217–226. PubMed
Cedikova M, Miklikova M, Stachova L, Grundmanova M, Tuma Z, Vetvicka V, Zech N, Kralickova M, Kuncova J. Effects of the czech propolis on sperm mitochondrial function. Evid Based Complement Alternat Med. 2014;2014:248768. PubMed PMC
Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol. 2014;67:176–186. PubMed
Reyes-Escogido Mde L, Gonzalez-Mondragon EG, Vazquez-Tzompantzi E. Chemical and pharmacological aspects of capsaicin. Molecules. 2011;16:1253–1270. PubMed PMC
Ware M. Cayenne Pepper: Health Benefits, Nutritional Information. Medical News Today, 2016. Available from: http://www.medicalnewstoday.com/articles/267248.php.
Christopher JR. Herbal Legacy - Dr. John R. Christopher, 2016. Available from: http://www.herballegacy.com/
Feyh A, Bracero L, Lakhani HV, Santhanam P, Shapiro JI, Khitan Z, Sodhi K. Role of Dietary Components in Modulating Hypertension. J Clin Exp Cardiolog. 2016;7 PubMed PMC
Dougnon TJ, Gbeassor M. Evaluation of the effects of the powder of Capsicum frutescens on glycemia in growing rabbits. Vet World. 2016;9:281–286. PubMed PMC
Tolan I, Ragoobirsingh D, Morrison EY. Isolation and purification of the hypoglycaemic principle present in Capsicum frutescens. Phytother Res. 2004;18:95–96. PubMed
The Promise Pyramid Healing Systems. The Promise Revealed, 2016. Available from: http://thepromiserevealed.com/the-promise-pyramid-systems/
Bhat S, Rao G, Murthy KD, Bhat PG. Effect of housing rats within a pyramid on stress parameters. Indian J Exp Biol. 2003;41:1289–1293. PubMed
Bhat MS, Rao G, Murthy KD, Bhat PG. Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats. Evid Based Complement Alternat Med. 2007;4:35–42. PubMed PMC
Bhat S, Rao G, Murthy KD, Bhat PG. Influence of alignment of the pyramid on its beneficial effects. Indian J Exp Biol. 2007;45:455–458. PubMed
Murthy KD, George MC, Ramasamy P, Mustapha ZA. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring. Indian J Exp Biol. 2013;51:1070–1078. PubMed
Bhat S, Rao G, Murthy KD, Bhat PG. Effect of varying durations of pyramid exposure - an indication towards a possibility of overexposure. Indian J Clin Biochem. 2009;24:430–432. PubMed PMC
Harris H. Unfinished business. In: Gordon S, editor. The Legacy of Cell Fusion. Oxford: Oxford University Press; 1994. pp. 286–295.
Holland JF, Frei EI, Bast RC Jr, Morton DL, Weichselbaum RR. Cancer Medicine. Baltimore: Williams & Wilkins; 1997.
Ringetz NR, Savage RE. Cell Hybrids. New York: Academic Press; 1976.
Pawelek JM, Chakraborty AK. Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer. 2008;8:377–386. PubMed
Dittmar T, Nagler C, Schwitalla S, Reith G, Niggemann B, Zänker KS. Recurrence cancer stem cells--made by cell fusion? Med Hypotheses. 2009;73:542–547. PubMed
Ganem NJ, Pellman D. Linking abnormal mitosis to the acquisition of DNA damage. J Cell Biol. 2012;199:871–881. PubMed PMC
Lindahl KF. Anomalous H-2 antigens on tumour cells. Nature. 1979;280:105–106. PubMed
Ferrone S, Pellegrino MA, Callahan GN. Human and murine tumours: changes in cell surface structures coded by the major histocompatibility complex region. J Immunogenet. 1980;7:71–79. PubMed
Bukovsky A, Caudle MR, Wimalasena J, Keenan JA, Elder RF. The role of the host-tumor interface and cell hybridization in invasive cancer. Med Hypotheses. 2001;57:729–735. PubMed
Larsen JF. Electron microscopy of nidation in the rabbit and observations on the human trophoblastic invasion. In: Hubinnot PO, Leroy F, Robyn C, Leleux P, editors. Ovo-implantation, Human Gonadotropins and Prolactin. Basel: S. Karger; 1970. pp. 38–51.
Enders AC, Schlafke S. Penetration of the uterine epithelium during implantation in the rabbit. Am J Anat. 1971;132:219–230. PubMed
Wooding FB. Current topic: the synepitheliochorial placenta of ruminants: binucleate cell fusions and hormone production. Placenta. 1992;13:101–113. PubMed
Buse E, Häeger JD, Svensson-Arvelund J, Markert UR, Faas MM, Ernerudh J, Dixon D, Cline JM, Pfarrer C. The placenta in toxicology. Part I: Animal models in toxicology: placental morphology and tolerance molecules in the cynomolgus monkey (Macaca fascicularis) Toxicol Pathol. 2014;42:314–326. PubMed
Bukovský A, Presl J, Zidovský J. Association of some cell surface antigens of lymphoid cells and cell surface differentiation antigens with early rat pregnancy. Immunology. 1984;52:631–640. PubMed PMC
Bukovsky A, Presl J. The occurrence of host phenotype-related Ia antigens on tumour cells and auto-aggressive phenomena in the host-tumour interface. IRCS Med Sci. 1984;12:915–916.
Eapen M, O’Donnell P, Brunstein CG, Wu J, Barowski K, Mendizabal A, Fuchs EJ. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2014;20:1485–1492. PubMed PMC
Pandey MK, Saxena V, Agrawal S. Characterization of mixed lymphocyte reaction blocking antibodies (MLR-Bf) in human pregnancy. BMC Pregnancy Childbirth. 2003;3:2. PubMed PMC
Prather SO, Lausch RN. Kinetics of serum factors mediating blocking, unblocking and antibody-dependent cellular cytotoxicity in hamsters given isografts of para-7 tumor cells. Int J Cancer. 1976;17:380–388. PubMed
Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science. 2013;339:286–291. PubMed PMC
Shabo I, Svanvik J. Expression of macrophage antigens by tumor cells. Adv Exp Med Biol. 2011;714:141–150. PubMed
Prehn RT. The immune reaction as a stimulator of tumor growth. Science. 1972;176:170–171. PubMed
Bukovský A. [Immunological aspects of neoplasia] Cesk Gynekol. 1975;40:464–466. PubMed
Sinkovics JG, DiSaia PJ, Rutledge FN. Tumour immunology and evolution of the placenta. Lancet. 1970;2:1190–1191. PubMed
Hellström I, Hellström KE. Some aspects of the immune defense against cancer. II. In vitro studies on human tumors. Cancer. 1971;28:1269–1271. PubMed
Hellström KE, Hellström I. Some aspects of the immune defense against cancer. I. In vitro studies on animal tumors. Cancer. 1971;28:1266–1268. PubMed
Símová J, Bubeník J. Effect of prophylactic and therapeutic administration of BCG vaccine on growth of experimental sarcoma. Folia Biol (Praha) 1975;21:329–333. PubMed
Currie GA. Active immunotherapy with Corynebacterium parvum and chemotherapy in murine fibrosarcomas. Br Med J. 1970;1:541–544. PubMed PMC
Steele G, Sjögren HO, Ankerst J. The effects of cyclophosphamide on in vitro correlates of tumor immunity. Int J Cancer. 1974;14:743–752. PubMed
Cohen IR, Globerson A, Feldman M. Rejection of tumor allografts by mouse spleen cells sensitized in vitro. J Exp Med. 1971;133:821–833. PubMed PMC
Bukovsky A. Novel immunological aspects for the treatment of age-induced ovarian and testicular infertility, other functional diseases, and early and advanced cancer immunotherapy. Human reproduction: Updates and new horizons. In: Schatten H, editor. Hoboken: Wiley; 2017.
ADNEXBA. 2014-01-01. Available from: http://drug-info.in/adnexba-enterococci-sevapharma.
Schwemmer B, Lehmer A, Hofmann R, Braun J. Natural killer cell activity in patients with prostatic carcinoma and its in vivo boosting with bacillus Calmette-Guérin. Urol Int. 1984;39:321–326. PubMed
de Boer NK, de Meij TG, Oort FA, Ben Larbi I, Mulder CJ, van Bodegraven AA, van der Schee MP. The scent of colorectal cancer: detection by volatile organic compound analysis. Clin Gastroenterol Hepatol. 2014;12:1085–1089. PubMed
de Meij TG, Larbi IB, van der Schee MP, Lentferink YE, Paff T, Terhaar Sive Droste JS, Mulder CJ, van Bodegraven AA, de Boer NK. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study. Int J Cancer. 2014;134:1132–1138. PubMed
Vetvicka V, Vetvickova J. Immune-enhancing effects of Maitake (Grifola frondosa) and Shiitake (Lentinula edodes) extracts. Ann Transl Med. 2014;2:14. PubMed PMC
Dai X, Stanilka JM, Rowe CA, Esteves EA, Nieves C, Spaiser SJ, Christman MC, Langkamp-Henken B, Percival SS. Consuming Lentinula edodes (Shiitake) Mushrooms Daily Improves Human Immunity: A Randomized Dietary Intervention in Healthy Young Adults. J Am Coll Nutr. 2015;34:478–487. PubMed
Mendonça CN, Silva PM, Avelleira JC, Nishimori FS, Cassia Fde F. Shiitake dermatitis. An Bras Dermatol. 2015;90:276–278. PubMed PMC
Boels D, Landreau A, Bruneau C, Garnier R, Pulce C, Labadie M, de Haro L, Harry P. Shiitake dermatitis recorded by French Poison Control Centers - new case series with clinical observations. Clin Toxicol (Phila) 2014;52:625–628. PubMed
Chan GC, Cheung KW, Sze DM. The immunomodulatory and anticancer properties of propolis. Clin Rev Allergy Immunol. 2013;44:262–273. PubMed
Bukovsky A. Immune system involvement in the regulation of ovarian function and augmentation of cancer. Microsc Res Tech. 2006;69:482–500. PubMed
Bukovsky A, Gupta SK, Bansal P, Chakravarty S, Chaudhary M, Svetlikova M, White RS, Copas P, Upadhyaya NB, Van Meter SE, et al. Production of monoclonal antibodies against recombinant human zona pellucida glycoproteins: utility in immunolocalization of respective zona proteins in ovarian follicles. J Reprod Immunol. 2008;78:102–114. PubMed