Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol ( -T), and deltatocotrienol ( -T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented ( < 0.05) in mice that were fed with -T3 or TRF compared to controls. The production of IFN-and IL-4 by splenocytes from the vitamin E treated mice was significantly ( < 0.05) higher than that from controls. The IFN-production was the highest in animals supplemented with -T3 followed by TRF and finally -T. Production of TNF-was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with -T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response

Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers

Background/Objectives: Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems. The objective of this study was to assess the effects of tocotrienol-rich fraction (TRF) supplementation on immune response following tetanus toxoid (TT) vaccine challenge in healthy female volunteers. Subjects/Methods: In this double-blinded, placebo-controlled clinical trial, participants were randomly assigned to receive either placebo (control group) or 400 mg of TRF (study group) supplementation daily. Over the 2-month period of the study, volunteers were asked to attend three clinical sessions (that is, on days 0, 28 and 56) and blood samples were obtained from the volunteers during the follow-up. On day 28, all volunteers were also vaccinated with the TT vaccine (20 Lf) intramuscularly. Results: The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group, indicating overall compliance. Volunteers supplemented with TRF showed a significantly (P0.05) enhanced production of interferon-γ and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group. Volunteers from the TRF group produced significantly (P < 0.05) lower amounts of IL-6 compared with the placebo group. Anti-TT IgG production was also significantly (P < 0.05) augmented in the TRF-supplemented group compared with the placebo group. Conclusions: We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines

Elite Model for the Generation of Induced Pluripotent Cancer Cells (iPCs)

<div><p>The inefficiency of generating induced pluripotent somatic cells (iPS) engendered two contending models, namely the Stochastic model and Elite model. Although the former is more favorable to explain the inherent inefficiencies, it may be fallible to extrapolate the same working model to reprogramming of cancer cells. Indeed, tumor cells are known to be inherently heterogeneous with respect to distinctive characteristics thus providing a suitable platform to test whether the reprogramming process of cancer cells is biased. Here, we report our observations that all randomly picked induced pluripotent cancer cells (iPCs) established previously do not possess mutations known in the parental population. This unanticipated observation is most parsimoniously explained by the Elite model, whereby putative early tumor progenies were selected during induction to pluripotency.</p> </div

Evidence rejecting the Stochastic model for generating iPCs.

<p>(A) Serial dilution assay showing that at 10^3.7 times dilution, <i>CDKN2B</i> in IMR90 is detectable at basal levels. Therefore, at most 1 in 5000 H460 cells are ‘mutation-free’. (B) The probability model to test the null hypothesis: “Generation of iPCs follows the Stochastic model”. Subsequent input of the parameters determined in (A) suggests the rejection of the Stochastic model in the reprogramming of H358 and H460.</p

Unexpected expression of wild-type <i>TP53</i> in iPCH358 but not in H358.

<p>(A) log-transformed intensity readouts from Illumina HumanHT-12 indicating a significant (FDR-adjusted P<0.05) upregulation of <i>TP53</i> transcript in iPCH358 compared to H358. This is unexpected since H358 is known to be <i>TP53</i>−/−. (B) PCR (upper panel) and Western Blot (lower panel) assays confirming expression of <i>TP53</i> in several randomly picked colonies of iPCH358. The coding region of <i>TP53</i> in Col#1, Col#3 and Col#11 are wild-type (GenBank accession: JQ694049–JQ694051). (C) PCR (left panel) and Western Blot (right panel) assays on iPCH358 colonies of >20 passages revealed that passage number is uninformative to the outcome of these assays. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056702#s3" target="_blank">Results</a> from experiments conducted on separate occasions or cropped from the same image are marked by a broken line; original images can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056702#pone.0056702.s005" target="_blank">Presentation S1</a> which includes detailed documentation of passage number.</p

<i>CDKN2A</i> and <i>CDKN2B</i> are not mutated in iPCH460 colonies.

<p>(A) Heat map indicating methylation array probes (rows) failing to hybridize to <i>CDKN2A</i> and <i>CDKN2B</i> promoters in H460 (empty bars), but not so in iPCH460. (B) PCR (upper panel) assay showing <i>CDKN2A</i> and <i>CDKN2B</i> are detectable in iPCH460 while Western Blot (lower panel) assay showing <i>CDKN2A</i>, which is homozygous deleted in H460, is detectable in iPCH460. (C) PCR (upper panel) and Western Blot (lower panel) assays on iPCH460 colonies of >20 passages revealed that passage number is uninformative to the outcome of these assays. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056702#s3" target="_blank">Results</a> from experiments conducted on separate occasions or cropped from the same image are marked by a broken line; original images can be found in Presentation S1 which includes detailed documentation of passage number.</p

Single explant tumor of H358 enriches ‘mutation-free’ subpopulation.

<p>(A) One out of four H358 explant tumor generated show presence of <i>TP53</i> in the genome, indicating enrichment of the elusive ‘mutation-free’ subpopulation. (B) None of the H460 explant tumors were observed to be enriched for ‘mutation-free’ subpopulation. Genomic DNA of SCID mice tail was used to control for mice DNA contamination in explant tumors. Information of explant tumors can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0056702#pone.0056702.s007" target="_blank">Table S2</a>.</p