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Background: Beneficial effects of probiotics have been reported for patients with allergic diseases and intestinal disorders. There is increasing interest in studying the role of different strains or combined probiotic administration on immunoregulation. In this study, we investigated whether probiotics modulate the immune response through regulating T cell proliferation and differentiation. Methods: We examined the effect of probiotic I (a combination of Lactobacillus acidophilus and Bifidobacterium bifidus) and probiotic II (a combination of L. acidophilus and B. infantis) on cell survival and proliferation, the progression of the cell cycle, and the production of Th1/Th2 cytokines by mitogen-stimulated murine spleen cells and human peripheral blood mononuclear cells (PBMCs). Results: Our experimental results showed that high concentrations (≧1 × 106 CFU/ml) of probiotic I or II inhibited mitogen-induced cell proliferation and arrested the cell cycle at the G0/G1 stage in both mitogen-stimulated spleen cells and PBMCs. In the results of low concentrations (6 CFU/ml), probiotic I or II enhanced the production of IFN-γ but inhibited the production of IL-4. Our results indicated that high concentrations of probiotic I or II treatment could attenuate mitogen-induced overactive immune responses. On the other hand, low concentrations of probiotic I or II treatment could promote a shift in the Th1/Th2 balance toward Th1-skewed immunity. Conclusion: Dose selection is an important issue for probiotic studies. Our results indicated that probiotics have beneficial effects on regulating T cell-mediated immune responses by attenuating mitogen-induced overactive immune responses and promoting Th1 immune responses.

Polymyositis (PM) and dermatomyositis (DM) are associated with high risk of nasopharyngeal carcinoma (NPC) in Asian countries. Epstein-Barr virus (EBV) might induce autoimmunity and malignancies in susceptible individuals.To investigate the association of EBV with PM/DM and NPC in PM/DM patients.Serum levels of anti-EBV viral capsid antigens (VCA) and anti-EBV-coded nuclear antigens-1 (EBNA-1) antibodies were measured by ELISA, and EBV DNA loads were determined using real-time PCR for 98 PM/DM patients, 94 systemic lupus erythematosus (SLE) patients and 370 healthy controls (HC). Anti-transfer-RNA synthetase antibodies (ASA) were determined by radioimmunoprecipitation for PM/DM patients.Thirteen (13.3%) of PM/DM patients vs. none of SLE patients had detectable NPC. ASA were detectable in 31.7% of PM/DM without malignancy, while lack of ASA in any PM/DM patient with NPC. IgA anti-EBNA-1 were detectable in 30.6% of PM/DM patients and 31.9% of SLE patients, but only in 4.1% of HC (odds ratio [OR] 10.44 and 11.12 respectively, both p0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p0.01), in SLE patients (OR 13.2, p0.05) and in HC (OR 99.4, p0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC.Our results showed a positive association of EBV with PM/DM and NPC. PM/DM patients who have IgA anti-EBNA-1 or increased EBV DNA loads should be highly suspected to have occult NPC.

Aims: To examine the tumor-forming in nude mice of human epithelial cells co-expressed Bcl-2 and EBV LMP-1 ability, the phenotype of tumor cells and their expression of oncogenes and tumor-suppressor genes. Methods: Following an in vivo tumorigenesis test in nude mice, the phenotype and growth properties of tumor cells were observed. Levels of expression of Bcl-2, and EBV LMP-1, and of onco- and tumor-suppressor proteins were detected by Western blot assay. Results: Human epithelial cells co-expressing Bcl-2 and EBV LMP-1 can form tumors in nude mice. Tumors appeared 48–65 days postinoculation in 6 of 10 nude mice tested but not in mice given Bcl-2-positive (0/5), LMP-1-positive (0/5) and RHEK-1 control (0/5) cells. Levels of c-myc protein were upregulated by LMP-1 but were not affected by Bcl-2 in this cell background; screening for other cellular oncogene and tumor suppressor gene products showed no change. Conclusion: The complementary effects of EBV LMP-1 and Bcl-2 in human epithelial cells resulted in tumor formation in nude mice but did not affect the expression of onco- and tumor suppressor proteins except for elevated c-myc. These findings suggest that LMP-1 and Bcl-2 can contribute together to the formation of EBV-associated epithelial cell tumors.

Epstein—Barr virus (EBV) induces human B cell transformation and is closely associated with naso-pharyngeal carcinoma. The expression of an EBV latent membrane protein, LMP-1, protects B cells from apoptosis by up-regulating the expression of a cellular oncogene, bcl-2. LMP-1 also transforms rodent fibroblasts and affects the differentiation, morphology and growth of human and rodent epithelial cells. In this report, we describe a novel finding that high level expression of the LMP-1 gene in a human epithelial cell line (RHEK-1) induces apoptosis, characterized by chromosomal DNA fragmentation in the transfected cells. In particular, such an effect was more apparent under serum starvation. We also found that in the transfected RHEK-1 cells, LMP-1 expression neither affected bcl-2 expression nor led the cells to grow in semisolid soft agar medium. These results indicate that LMP-1 may participate in the development of EBV-associated epithelial malignancy via a mechanism different from that seen in B cell or fibroblast transformation.

Previous studies have shown that soybean fermentation products can act as cancer chemoprevention or therapeutic agents. In this study, the anticancer activities of a fermentation product of soybean, black bean, and green bean mixture (BN999) were investigated. We found that BN999 inhibited the growth of human breast cancer AU565 cells and prostate adenocarcinoma PC-3 cells but not that of normal human cells. BN999 induced apoptosis in various human cancer cells but not in normal human cells. BN999 treatment of AU565 cancer cells resulted in activation of calpain and caspase-8, -9, and -3, suggesting that BN999 induces apoptosis via receptor-, mitochondria-, and endoplasmic reticulum–mediated pathways. Finally, we showed that BN999 inhibited the growth of mouse CT-26 colon cancer xenografts in syngenic BALB/c mice without causing obvious side effects. Together, these data suggest that BN999 has potential to be used as a cancer chemoprevention or therapeutic agent.

Beneficial effects of probiotics have been reported for patients with allergic diseases and intestinal disorders. There is increasing interest in studying the role of different strains or combined probiotic administration on immunoregulation. In this study, we investigated whether probiotics modulate the immune response through regulating T cell proliferation and differentiation.We examined the effect of probiotic I (a combination of Lactobacillus acidophilus and Bifidobacterium bifidus) and probiotic II (a combination of L. acidophilus and B. infantis) on cell survival and proliferation, the progression of the cell cycle, and the production of Th1/Th2 cytokines by mitogen-stimulated murine spleen cells and human peripheral blood mononuclear cells (PBMCs).Our experimental results showed that high concentrations (≥ 1 × 10(6) CFU/ml) of probiotic I or II inhibited mitogen-induced cell proliferation and arrested the cell cycle at the G0/G1 stage in both mitogen-stimulated spleen cells and PBMCs. In the results of low concentrations (1 × 10(6) CFU/ml), probiotic I or II enhanced the production of IFN-γ but inhibited the production of IL-4. Our results indicated that high concentrations of probiotic I or II treatment could attenuate mitogen-induced overactive immune responses. On the other hand, low concentrations of probiotic I or II treatment could promote a shift in the Th1/Th2 balance toward Th1-skewed immunity.Dose selection is an important issue for probiotic studies. Our results indicated that probiotics have beneficial effects on regulating T cell-mediated immune responses by attenuating mitogen-induced overactive immune responses and promoting Th1 immune responses.

The first universal hepatitis B vaccination program for newborns in the world was launched in Taiwan in July 1984. Most studies on the effectiveness of hepatitis B vaccination focused on the seroprevalence of HBs Ag among children under 14 years old. Only few studies focused on the seropositivity of anti-HBs among adolescents aged 15-18 years old. The present study aimed to evaluate the impact of the nationwide hepatitis B vaccination program on the immunity to HBV infection and the necessity of boost among adolescents. In this study including eight annual seroprevalence surveys from 2000 to 2007, 2342 college entrants (1589 15-year-olds in group I and 753 18-year-olds in group II) and 1851 university freshmen (18-year-olds in group III) participated. Subjects identified anti-HBs, HBs Ag and anti-HBc negative were given boost three doses of HBV vaccine. The HBs Ag seroprevalence was 11.6%, 3.5% and 1.0% for participants who were born before 1984, 1984-1986 and after 1986. The anti-HBs-seropositive rates were significantly higher in group II (83.1%) than in group I (53.0%) and group III (53.5%). All 572 participants who were seronegative for anti-HBs, HBs Ag and anti-HBc became anti-HBs-seropositive after catch-up vaccination. It is concluded that the anti-HBs-seropositive rate decreased to 50% in 15 years after vaccination, and boost vaccination was 100% effective. The necessity and age for boost among anti-HBs negative adolescents and the timing of the first immunization should be further evaluated.

Co-expression of B-cell leukemia-lymphoma 2 gene (Bcl-2) and Epstein-Barr virus latent membrane protein 1 (LMP-1) in nasopharyngeal carcinoma tissues were tested using immunohistochemical methods. Results showed that there were 32% (14/44) and 68% (30/44) LMP-1 and Bcl-2-positive cases, respectively. Among the LMP-1-positive tissues, 8 (57%) of 14 specimens were also Bcl-2-positive. The level of LMP-1 and Bcl-2 expression was associated with the clinical stages of nasopharyngeal carcinoma. Furthermore, when LMP-1- and Bcl-2-positive cases were combined, the highest positive score was found in clinical stage II as well as in the early stage (stages I and II) of nasopharyngeal carcinoma. While further studies with more cases are needed, this study suggests that co-expression of Bcl-2 and LMP-1 may be involved in the process of nasopharyngeal carcinoma aggravation.