Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

In general population, many protective immune responses are impaired in old age, leading to an increased risk of infection. However, recent studies in SENIEUR subjects (healthy centenarians who are examples of successful aging) suggest that complex remodeling and reshaping of the immune system occurs with aging. An appropriate regular regimen of endurance exercise might help elderly to lead a quality of life by preserving immune function. However, very little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many physiological systems which are known to alter the immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. The immune system response to exercise is multifaceted, depending on the nature of exercise. Significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in immune function are known to occur. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system by increasing the production of endocrine hormones which may contribute to less accumulation of autoreactive immune cells by enhancing the programmed cell death. Active elderly subjects demonstrated a significantly greater proliferative response to phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. A moderate training program can enhance the resting natural killer (NK) cell function of healthy elderly people, potentially increasing resistance to both viral infections and preventing the formation of malignant cells. Recent studies have suggested that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine production. It is important that the dose of physical activity needed to optimize immune function be defined more clearly at various points during the aging process both in females and males in order to optimize the immune function and to prevent any rise in adverse effects of exercise on the elderly population.

Response surface methodology (RSM) using a Box-Behnken design (BBD) was applied to optimize the extraction of Paxillus involutus polysaccharides. The optimum conditions included an extraction time of 3h, extraction temperature of 79°C and a ratio of liquid to raw material of 43.1mL/g. Under the optimized conditions, the polysaccharides yield was 12.25%. Then, the polysaccharides were purified with DEAE-Cellulose 52 and Sephadex G-100 gel columns, and the fraction denoted as PIP2-1 with a molecular weight of 32kDa was obtained. PIP2-1 was composed of mannose, glucose, galactose, fucose with the mole percentages of 2.8%, 62.2%, 25.4% and 9.6%. The PIP2-1 possessed typical Fourier Transform infrared spectroscopy (FTIR) characterization of polysaccharides. The methylation analysis showed that the PIP2-1 mainly included 1-linked-fuc, 1,3-linked-man, 1-linked-glc, 1,4-linked-glc, 1,6-linked-glc, 1-linked-gal, 1,6-linked-gal, 1,4,6-linked-gal and 1,2,6-gal glycosidic bonds. Furthermore, PIP2-1 showed significant antioxidant activity against hydroxyl radicals (OH), 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide radicals. Finally, PIP2-1 significantly enhanced the release of TNF-α and IL-6 in RAW264.7 cells. The results indicated that PIP2-1 could be exploited as a natural antioxidant and immunomodulator for functional food and medical applications.

Patients with glioblastoma multiforme (GBM) exhibit a deficient anti-tumor immune response. Both arms of the immune system were shown to be hampered in GBM, namely the local cellular immunity mediated by the Th1 subset of helper T cells and the systemic humoral immunity mediated by the Th2 subset of helper T cells. Immunotherapy is rapidly becoming one of the pillars of anti-cancer therapy. GBM has not received similar clinical successes as of yet, which may be attributed to its relative inaccessibility (the blood-brain barrier (BBB)), its poor immunogenicity, few characterized cancer antigens, or any of the many other immune mechanisms known to be hampered. Focused ultrasound (FUS) is emerging as a promising treatment approach. The effects of FUS on the tissue are not merely thermal. Mounting evidence suggests that in addition to thermal ablation, FUS induces mechanical acoustic cavitation and immunomodulation plays a key role in boosting the host anti-tumor immune responses. We separately discuss the different pertinent immunosuppressive mechanisms harnessed by GBM and the immunomodulatory effects of FUS. The effect of FUS and microbubbles in disrupting the BBB and introducing antigens and drugs to the tumor milieu is discussed. The FUS-induced pro-inflammatory cytokines secretion and stress response, the FUS-induced change in the intra-tumoral immune-cells populations, the FUS-induced augmentation of dendritic cells activity, and the FUS-induced increased cytotoxic cells potency are all discussed. We next attempt at offering a conceptual synopsis of the synergistic treatment of GBM utilizing FUS and immunotherapy. In conclusion, it is increasingly apparent that no single treatment modality will triumph on GBM. The reviewed FUS-induced immunomodulation effects can be harnessed to current and developing immunotherapy approaches. Together, these may overcome GBM-induced immune-evasion and generate a clinically relevant anti-tumor immune response.

ETHNOPHARMACOLOGICAL RELEVANCE:Ganoderma lucidum (G. lucidum) has been broadly used for health endorsement as well as longevity for over 2000 years in Asian countries. It is an example of an ancient remedy and known as immortality mushroom. It has been employed as a health promoting agent owing to its broad pharmacological and therapeutical approaches. It has been confirmed that G. lucidum exhibits significant potency to prevent and treat different types of cancers such as breast, prostate, colon, lung and cervical.

AIM OF THE STUDY:To explore anticancer effects of various pharmacologically active compounds obtained from G. lucidum and their possible mechanism of action.

MATERIALS AND METHODS:A literature search was conducted using PubMed, Goggle Scholar, Saudi Digital Library and Cochrane Library until October 11, 2019. Search was made by using keywords such as anticancer evidence, mechanism of action, pharmacology, antioxidant, toxicity, chemotherapy, triterpenoids and polysaccharides of G. lucidum.

RESULTS:Various chemical compounds from G. lucidum exhibit anticancer properties mainly through diverse mechanism such as cytotoxic properties, host immunomodulators, metabolizing enzymes induction, prohibit the expression of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in cancer cells. Among the various compounds of G. lucidum triterpenoids and polysaccharides are under the major consideration of studies due to their several evidence of preclinical and clinical studies against cancer.

CONCLUSION:Natural alternatives associated with mild side effects are the basic human need of present therapy to eradicate the new emerging disorders. This review is an attempt to compile pharmacologically active compounds of G. lucidum those exhibit anti cancer effects either alone or along with chemotherapy and anticancer mechanisms against various cancer cells, clinical trials, chemotherapy induced toxicity challenges with limitations. It acts as a possible substitute to combat cancer growth with advance and conventional combination therapies as natural alternatives.

Ganoderma sinense is one of well-known herb medicine and has been used for 2000 years in China. G. lucidum and G. sinense are two family members of Ganoderma, a genus of polypore fungi. In Chinese,"Lingzhi"is designated as G. lucidum or red"Lingzhi"whereas"Zizhi"as G. sinense or purple"Lingzhi."The polysaccharides or glycans extracted from both G. lucidum and G. sinense have been developed into clinical drugs and recorded in Chinese Pharmacopeia. G. lucidum polysaccharide (GLPS) is one of a few non-hormonal drugs used for treating neurosis, polymyositis, dermatomyositis, atrophic myotonia and muscular dystrophy in China during the past 40 years. In contrast, G. sinense polysaccharide (GSP) tablet is approved as an adjunctive therapeutic drug in China for treating leukopenia and hematopoietic injury caused by concurrent chemo/radiation therapy during cancer treatment by the State Food and Drug Administration (SFDA) in 2010.β-glucan, an established immunostimulanting polysaccharide, is one of the components in GSP. In this study, we will review the biological activities and preclinical studies of GSP in China based on literatures searches from CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP ChineseScientific Journals Database), Wanfang database, and PubMed database. Both basic and preclinical studies showed that GSP has antitumor, antioxidant, anticytopenia, and unique mushroom-poison detoxification properties that are different from that of GLPS. Our goal is to provide a molecular picture that would allow in-depth evaluation of GSP as one of few glycan-based drugs that has been used as an immunomodulatory adjunctive drug during cancer therapy.

BACKGROUND:Vitamin C (vit C) is an essential dietary nutrient, which is a potent antioxidant, a free radical scavenger and functions as a cofactor in many enzymatic reactions. Vit C is also considered to enhance the immune effector function of macrophages, which are regarded to be the first line of defence in response to any pathogen. The THP-1 cell line is widely used for studying macrophage functions and for analyzing host cell-pathogen interactions.

RESULTS:We performed a genome-wide temporal gene expression and functional enrichment analysis of THP-1 cells treated with 100 μM of vit C, a physiologically relevant concentration of the vitamin. Modulatory effects of vitamin C on THP-1 cells were revealed by differential expression of genes starting from 8 h onwards. The number of differentially expressed genes peaked at the earliest time-point i.e. 8 h followed by temporal decline till 96 h. Further, functional enrichment analysis based on statistically stringent criteria revealed a gamut of functional responses, namely, 'Regulation of gene expression', 'Signal transduction', 'Cell cycle', 'Immune system process', 'cAMP metabolic process', 'Cholesterol transport' and 'Ion homeostasis'. A comparative analysis of vit C-mediated modulation of gene expression data in THP-1cells and human skin fibroblasts disclosed an overlap in certain functional processes such as 'Regulation of transcription', 'Cell cycle' and 'Extracellular matrix organization', and THP-1specific responses, namely, 'Regulation of gene expression' and 'Ion homeostasis'. It was noteworthy that vit C modulated the 'Immune system' process throughout the time-course.

CONCLUSIONS:This study reveals the genome-wide effects of physiological levels of vit C on THP-1 gene expression. The multitude of effects impacted by vit C in macrophages highlights its role in maintaining homeostasis of several cellular functions. This study provides a rational basis for the use of the Vitamin C- THP-1 cell model, to study biochemical and cellular responses to stresses, including infection with M. tuberculosis and other intracellular pathogens.

Wild mushrooms, especially from North America, have not been systematically explored for their medicinal properties. Here we report screening for the growth-inhibitory and immunomodulatory activities of 12 species collected from multiple locations in north-central British Columbia, Canada. Mushrooms were characterized using morphology and DNA sequencing, followed by chemical extraction into 4 fractions using 80% ethanol, 50% methanol, water, and 5% sodium hydroxide. Growth-inhibitory, immunostimulatory, and anti-inflammatory activities of 5 mushrooms (Leucocybe connata, Trichaptum abietinum, Hydnellum sp., Gyromitra esculenta, and Hericium coralloides) are reported here, to our knowledge for the first time. Growth-inhibitory effects were assessed using the cytotoxic MTT assay. Immunostimulatory activity was assessed by tumor necrosis factor-α production in Raw 264.7 macrophages, whereas anti-inflammatory activity was assessed based on the inhibition of lipopolysaccharide-induced tumor necrosis factor-α production. The ethanol and aqueous extracts of Hydnellum sp. were potent growth inhibitors, with a half-maximal inhibitory concentration of 0.6 mg/mL. All 5 fungi displayed strong immunostimulatory activity, whereas only L. connata and T. abietinum showed strong anti-inflammatory activity. For the 7 other fungi investigated, which included well-known medicinal species such as Inonotus obliquus, Phellinus igniarius, and Ganodermaapplanatum, the remarkable similarities in the biological activities reported here, and by others for specimens collected elsewhere, suggest that mushrooms can produce similar metabolites regardless of their habitat or ecosystem. This is to our knowledge the first study to explore wild mushrooms from British Columbia for biological activities that are relevant to cancer, and the results provide an initial framework for the selection of mushroom species with the potential for discovery of novel anticancer compounds.

Vitamin C (VC) is an essential nutrient for humans and certain other animals. It has antioxidant properties and has been reported to ameliorate oxidative damage to lipids, DNA and proteins. However, the effects of VC on immune function are poorly understood, especially the influence of long-term high-dose VC intake on the number and function of immune cells. In the present study, to evaluate the immune effects of VC, VC-deficient senescence marker protein-30 knockout (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg per d; 0·02 % VC) or a high level of VC (200 mg/kg per d; 0·2 % VC) for 1 year. The plasma VC concentration of the 0·02 % group was the same as that of age-matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration and thymus weight were significantly higher in the 0·2 % VC group than in the 0·02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and monocytes in the peripheral blood, as well as the number of splenocytes and thymocytes, were all significantly higher in the 0·2 % VC group than in the 0·02 % VC group. In addition, the number of naive T cellsin peripheral blood lymphocytes, the number of memory T-cell populations in splenocytes, and the number of cluster of differentiation (CD)4⁺CD8⁺ or CD4⁺CD8⁻ or CD4⁻CD8⁺ T cells in thymocytes were all markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment. These results suggest that a long-term high-dose intake of VC is effective in the maintenance of immune cells, partly through the suppression of age-related thymic involution in VC-deficient SMP30KO mice.

Honey is a natural substance formed primarily of carbohydrates (~80%) which also contains a number of other compounds purported to confer health benefits when consumed. Due to its carbohydrate composition (low glycaemic index, mostly fructose and glucose), honey may theoretically exert positive effects when consumed before, during or after exercise. This review therefore appraised research examining the effects of honey consumption in combination with exercise in humans. Online database (PubMed, MEDLINE, SPORTDiscus) searches were performed, yielding 273 results. Following duplicate removal and application of exclusion criteria, nine articles were reviewed. Large methodological differences existed in terms of exercise stimulus, population, and the nutritional interventions examined. All nine studies reported biochemical variables, with four examining the effects of honey on exercise performance, whilst five described perceptual responses. Acute supplementation around a single exercise session appeared to elicit similar performance, perceptual, and immunological responses compared with other carbohydrate sources, although some performance benefit has been observed relative to carbohydrate-free comparators. When consumed over a number of weeks, honey may dampen immunological perturbations arising from exercise and possibly improve markers of bone formation. More well-controlled research is required to better understand the role for honey in a food-first approach to exercise nutrition.

How might contact with nature promote human health? Myriad studies have linked the two; at this time the task of identifying the mechanisms underlying this link is paramount. This article offers: (1) a compilation of plausible pathways between nature and health; (2) criteria for identifying a possible central pathway; and (3) one promising candidate for a central pathway. The 21 pathways identified here include environmental factors, physiological and psychological states, and behaviors or conditions, each of which has been empirically tied to nature and has implications for specific physical and mental health outcomes. While each is likely to contribute to nature's impacts on health to some degree and under some circumstances, this paper explores the possibility of a central pathway by proposing criteria for identifying such a pathway and illustrating their use. A particular pathway is more likely to be central if it can account for the size of nature's impacts on health, account for nature's specific health outcomes, and subsume other pathways. By these criteria, enhanced immune functioning emerges as one promising candidate for a central pathway between nature and health. There may be others.

A total of 260 patients aged 15 to 57 years with virus hepatitis A were examined over time for some indicators of humoral and cellular immunity (serum IgA, IgM, IgG, the phagocytic number and indicator of the completeness of neutrophil phagocytosis, cytochemical content of ribonucleic and deoxyribonucleic acids in blood leukocytes). The immunological indicators were determined in two patients' groups after intake per os of 300 mg/day of ascorbic acid for 2-3 weeks and without its administration. It has been established that in virus hepatitis A, vitamin C exerts a remarkable immunomodulating action. In view of this fact, it should be necessarily included into multimodality treatment of patients suffering from pathology under consideration.

Background: Cutaneous warts are small skin lesions formed as a result of infection by the human papilloma virus (HPV). In the lesion, viral manipulation creates a microenvironment that favors virus survival and reproduction. Most lesions eventually regress, probably as a result of a Th1-mediated immune response. However, some warts fail to regress and become persistent. Objective: The efficacy of treatment of persistent HPV-caused warts with Energetics of Living Systems acupuncture and monitored immune system involvement was tested. Methods: Eighteen patients with persistent warts were recruited for the study; 9 received acupuncture treatment and 9 received placebo. Each patient was treated 4 times. Results: Clinical success was defined as total clearance of all lesions with no recurrence for 3 months. In the treatment group, clinical success was 36.6% versus 0% in the placebo group. In the treatment group, the level of interleukin (IL)-10 decreased. In a comparison of patients with cleared warts and overall patients with nonresponding warts, different expression levels of IL-8, IL-10, tumor necrosis factor-α, IL-6, and interferon-γ were found, although these differences were not always statistically significant. Trends of differences (not significant) were observed in leukocyte levels. Acupuncture eliminated persistent warts in some of the patients, along with inducing changes in immunologic parameters. Conclusions: Taking the clinical and immunologic outcomes together, clearance of persistent warts following acupuncture might be due to a shift toward a Th1 immune response, or an anti-inflammatory effect against the lesion-induced microenvironment.

Physical exercise has been described as an important tool in the prevention and treatment of numerous diseases as it promotes a range of responses and adaptations in several biological systems, including the immune system. Studies on the effect of exercise on the immune system could play a critical role in improving public health. Current literature suggests that moderate intensity exercise can modulate the Th1/Th2 dichotomy directing the immune system to a Th1 cellular immune response, which favors the resolution of infections caused by intracellular microorganisms. Leishmaniasis is a group of diseases presenting a wide spectrum of clinical manifestations that range from self-limiting lesions to visceral injuries whose severity can lead to death. The etiological agents responsible for this group of diseases are protozoa of the genus Leishmania. Infections by the parasitein mice (Balb/c) provide a prototype model for the polarization of CD4+ T cell responses of both Th1 (resistance) or Th2 (susceptibility), which determines the progression of infections. The aim of this study was to evaluate the effect of exercise on the development ofexperimental infections by scanning the pattern of immune response caused by exercise. Groups of Balb/c mice infected withwere divided into groups that preformed a physical exercise of swimming three times a week or were sedentary along with treatment or not with the reference drug, meglumine antimoniate. Animals in groups submitted to physical exercise did not appear to develop lesions and presented a significantly lower parasite load independent of drug treatment. They also showed a positive delayed hypersensitivity response to a specificantigen compared to control animals. The IFN-γ/IL-4 and IFN-γ/IL10 ratios in trained animals were clearly tilted to a Th1 response in lymph node cells. These data suggest that moderate intensity exercise is able to modulate the Th1 response that provides a protective effect against the development of leishmanial lesions.

Multiple Sclerosis (MS) is a demyelinating and neurodegenerative disease. Though a specific antigen has not been identified, it is widely accepted that MS is an autoimmune disorder characterized by myelin-directed immune attack. Pharmacological treatments for MS are based on immunomodulatory or immunosuppressant drugs, designed to attenuate or dampen the immune reaction, to improve neurological functions. Recently, rehabilitation has gained increasing attention in the scientific community dealing with MS. Engagement of people with MS in exercise programs has been associated with a number of functional improvements in mobility, balance, and motor coordination. Moreover, several studies indicate the effectiveness of exercise against fatigue and mood disorders that are frequently associated with the disease. However, whether exercise acts like an immunomodulatory therapy is still an unresolved question. A good tool to address this issue is provided by the study of the immunomodulatory effects of exercise in an animal model of MS, including the experimental autoimmune encephalomyelitis (EAE), the Theiler's virus induced-demyelinating disease (TMEV-IDD) and toxic-demyelinating models, cuprizone (CPZ), and lysolecithin (LPC). So far, despite the availability of different animal models, most of the pre-clinical data have been gained in EAE and to a lesser extent in CPZ and LPC. These studies have highlighted beneficial effects of exercise, suggesting the modulation of both the innate and the adaptive immune response in the peripheral blood as well as in the brain. In the present paper, starting from the biological differences among MS animal models in terms of immune system involvement, we revise the literature regarding the effects of exercise in EAE, CPZ, and LPC, and critically highlight the advantages of either model, including the so-far unexplored TMEV-IDD, to address the immune effects of exercise in MS.

This study was aimed at investigating the immunomodulating activity of Hericium erinaceus polysaccharide (HEP) in mice, by assessing splenic lymphocyte proliferation (cell-mediated immunity), serum hemolysin levels (humoral immunity), phagocytic capacity of peritoneal cavity phagocytes (macrophage phagocytosis), and NK cell activity. ELISA of immunoglobulin A (SIgA) in the lamina propria, and western blotting of small intestinal proteins were also performed to gain insight into the mechanism by which HEP affects the intestinal immune system. Here, we report that HEP improves immune function by functionally enhancing cell-mediated and humoral immunity, macrophage phagocytosis, and NK cell activity. In addition, HEP was found to upregulate the secretion of SIgA and activate the MAPK and AKT cellular signaling pathways in the intestine. In conclusion, all these results allow us to postulate that the immunomodulatory effects of HEP are most likely attributed to the effective regulation of intestinal mucosal immune activity.

Hericium erinaceus polysaccharide (HEP) has been shown to possess a variety of biological activities. In present study, HEP was successfully modified to obtain its hydroxyethylated derivative hHEP. Its potential immunomodulatory activities on RAW264.7 macrophages were investigated. Results showed that the hHEP were significantly stronger than that of the corresponding unmodified polysaccharide, HEP. Meanwhile, the NO, IL-6 and TNF-α production activities of macrophages were enhanced in the RAW264.7 macrophages by stimulation of hHEP. In addition, the hHEP increase significantly higher iNOS expression than HEP. These results indicated that the hydroxyethylated derivative hHEP could enhance the activation of peritoneal macrophages, and hydroxyethylation modification can enhance the immunomodulation function of HEP.

The dietary pattern can influence the immune system directly, but may also modulate it indirectly by regulating the gut microbiota. Here, we investigated the effect of a 3-months lacto-ovo-vegetarian diet on the diversity of gut microbiota and the immune system in healthy omnivorous volunteers, using high-throughput sequencing technologies. The short-term vegetarian diet did not have any major effect on the diversity of the immune system and the overall composition of the metagenome. The prevalence of bacterial genera/species with known beneficial effects on the intestine, including butyrate-producers and probiotic species and the balance of autoimmune-related variable genes/families were, however, altered in the short-term vegetarians. A number of bacterial species that are associated with the expression level of IgA, a key immunoglobulin class that protects the gastrointestinal mucosal system, were also identified. Furthermore, a lower diversity of T-cell repertoire and expression level of IgE, as well as a reduced abundance of inflammation-related genes in the gut microbiota were potentially associated with a control group with long-term vegetarians. Thus, the composition and duration of the diet may have an impact on the balance of pro-/anti-inflammatory factors in the gut microbiota and immune system.

Lentinula edodes, known as "shiitake" is one of the widely used medicinal mushrooms in the Orient. Antitumour activity of extracts of this mushroom has been widely demonstrated in animals and humans. However, this activity was shown to be host mediated and not by direct cytotoxic activity to cancer cells. This study demonstrates cytotoxic and cell growth inhibitory (cytostatic) effect of aqueous extracts of the mushroom on MCF-7 human breast adenocarcinoma cell line using an MTT cytotoxicity assay. Such effect was demonstrated with fruit body and mycelial extracts, the difference being that there was no significant suppression on normal cells with the latter. Furthermore mycelial extracts did not induce any cytostatic effect in both cancer and normal cell lines based on a DNA synthesis assay. The significant suppression of the proliferation of cancer cells was reflected by the comparatively low IC(50) values and the simultaneous higher respective values on normal fibroblast cells. The immunostimulatory activity of both fruit body and mycelial extracts was tested by the lymphocyte transformation test (LTT), which is based on the capacity of active immunomodulators to augment the proliferative response of rat thymocytes to T mitogens in vitro. Both fruit body and mycelial preparations were able to enhance the proliferation of rat thymocytes directly and act as co-stimulators in the presence of the T-mitogen PHA. Interestingly both extracts, similarly to zymosan showed SI(comit)/SI(mit) ratios of about 2, indicating adjuvant properties. Overall L. edodes aqueous extracts have demonstrated direct inhibition of the proliferation of human breast cancer cells in vitro and immunostimulatory properties in terms of mitogenic and co-mitogenic activity in vitro.

OBJECTIVE: To observe the influence of electroacupuncture (EA) on T cell immunologic function in the aged rats so as to reveal its underlying mechanism in anti-aging effect. METHODS: Fifty SD rats (half male and half female) were randomly divided into normal control (young rats), aging model (model), EA group, immunosuppression (IS), and EA+ IS groups. Aging model (in the late 4 groups) was duplicated by subcutaneous injection of D-galactose for 40 days. Guanyuan (CV 4) and bilateral Zusanli (ST 36) were punctured and stimulated electrically (2 Hz, 1 mA), 15 min every time, six times a week and for four weeks. IS model was induced by i. p. i. of cytoxan (60 mg/kg) after 26 and 27 days' EA treatment. Splenetic T lymphocyte proliferation index was assayed by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) chromatometry. IL-2/IL-2 receptor (R) expression level of T cells was measured by enzyme linked immunosorbent assay (ELISA). CD8+ CD28(+) -T cell subset fluorescence intensity was detected by flow cytometry. RESULTS: Compared with normal control group, the splenetic T lymphocyte proliferation index, IL-2 and IL-2R expression levels, and CD8+ CD28(+) -T cell density in model and IS groups decreased significantly (P<0.01). In comparison with model group, the abovementioned indexes in EA and EA + IS groups increased significantly (P<0.01), and those indexes levels of EA + IS group were also significantly higher than those in IS group ( P<0.05, P<0.01). Comparison between EA and EA+ IS groups showed that CD8+ CD2+ T cell expression of the later group was significantly lower than that in EA group (P<0 05). No significant differences were found between EA and EA + IS groups in T cell proliferation rate and IL-2 and IL-2R expression levels (P>0.05) CONCLUSION: EA of CV 4 and ST 36 induced upregulation of T cell proliferation and IL-2/IL-2R, and CD8+ CD(+)28 -T cell may contribute to its antiaging and immuno-enhancement effects in the aged rats.