Effects of Citrus unshiu Powder on the Cytokine Balance in Peripheral Blood Mononuclear Cells of Patients with Seasonal Allergic Rhinitis to Pollen

We evaluated the effects of a 50% methanol extract of Citrus unshiu powder (MEC) on cytokines in peripheral blood mononuclear cells (PBMCs) obtained from patients with seasonal allergic rhinitis to cedar pollen. The levels of cytokines, such as TNF-α, IFN-γ, IL-2, IL-4, IL-5, IL-10, IL-12 (p70), IL-13, and GM-CSF, produced by pollen-stimulated PBMC were measured. We found that MEC suppressed pollen-induced TNF-α release and increased IFN-γ release from PBMCs. The results suggest that Citrus unshiu powder has an immunomodulatory effect in vitro and that its use could improve seasonal allergic rhinitis symptoms.     

A weight of evidence approach for selecting exposure biomarkers for biomonitoring

Context: It is known that there are usually several biomarkers and/or medium combinations that can be applied to answer a specific exposure question. To help determine an appropriate combination for the specific question, we have developed a weight-of-evidence Framework that provides a relative appropriateness score for competing combinations.

Methods: The Framework is based on an expert assessor’s evaluation of the relevance and suitability of the biomarker and medium for the question based on a set of criteria. We provide a computer based modeling tool to guide the researcher through the process.

Results: We present an example with six biomarkers of benzene exposure in one matrix; the six are either the most commonly used biomarkers and/or have recent widespread usage. The example clearly demonstrates the usefulness of the Framework for scoring the choices, as well as the transparency of the method that provides the basis for discussion.

Conclusions: The Framework provides for the first time a method to transparently document the rationale behind selecting, from among a set of alternatives, the most scientifically supportable exposure biomarker to address a specific biomonitoring question, thus providing a reproducible account of expert opinions on the suitability of a biomarker.     

Barley γ3-hordein: Glycosylation at an atypical site,disulfide bridge analysis,and reactivity with IgE from patients allergic to wheat

Post translational modifications of a seed storage protein, barley γ3-hordein, were determined using immunochemical and mass spectrometry methods. IgE reactivity towards this protein was measured using sera from patients diagnosed with allergies to wheat. N-glycosylation was found at an atypical Asn-Leu-Cys site. The observed glycan contains xylose. This indicates that at least some γ3-hordein molecules trafficked through the Golgi apparatus. Disulfide bridges in native γ3-hordein were almost the same as those found in wheat γ46-gliadin, except the bridge involving the cysteine included in the glycosylation site. IgE reacted more strongly towards the recombinant than the natural γ3-hordein protein. IgE binding to γ3-hordein increased when the protein sample was reduced. Glycosylation and disulfide bridges therefore decrease epitope accessibility. Thus the IgE from patients sensitized to wheat cross-react with γ3-hordein due to sequence homology with wheat allergens rather than through shared carbohydrate determinants.     

An Optimized Proteomics Approach Reveals Novel Alternative Proteins in Mouse Liver Development

Alternative ORFs (AltORFs) are unannotated sequences in genome that encode novel peptides or proteins named alternative proteins (AltProts). Although ribosome profiling and bioinformatics predict a large number of AltProts, mass spectrometry as the only direct way of identification is hampered by the short lengths and relative low abundance of AltProts. There is an urgent need for improvement of mass spectrometry methodologies for AltProt identification. Here, we report an approach based on size-exclusion chromatography for simultaneous enrichment and fractionation of AltProts from complex proteome. This method greatly simplifies the variance of AltProts discovery by enriching small proteins smaller than 40 kDa. In a systematic comparison between 10 methods, the approach we reported enabled the discovery of more AltProts with overall higher intensities, with less cost of time and effort compared to other workflows. We applied this approach to identify 89 novel AltProts from mouse liver, 39 of which were differentially expressed between embryonic and adult mice. During embryonic development, the upregulated AltProts were mainly involved in biological pathways on RNA splicing and processing, whereas the AltProts involved in metabolisms were more active in adult livers. Our study not only provides an effective approach for identifying AltProts but also novel AltProts that are potentially important in developmental biology.     

Weight Change in Adult Life and Health Outcomes

Objective: To investigate the relationship between weight change in adult life and subsequent mortality and cancer incidence in women. Research Methods and Procedures: In 1994 to 1995, all women (age range, 42 to 81) still under general practitioner observation in the United Kingdom's Royal College of General Practitioners Oral Contraception Study (n = 12 303) were sent a health survey asking about health and lifestyle issues, including current weight and weight at age 30. The main outcome measures were 6‐year all‐cause mortality and cancer incidence among different weight change deciles. Cox regression was used to calculate hazard ratios that were adjusted for: social class at recruitment, BMI at age 30, and age group, parity, smoking status, and hormone replacement therapy status in 1995. Results: Women who had been obese at age 30 were more likely to die and significantly more likely to develop cancer in the 6 years after the health survey than non‐obese respondents. Women reporting weight gains between age 30 and 1995 were significantly less likely to die during the 6 years after the health survey than those with a stable weight, whereas those with weight loss did not fare any better than those in the stable‐weight group. Discussion: Although obesity at young age was associated with subsequent mortality and cancer incidence, weight gain over a time period of 12 to 51 years appeared to be beneficial when compared with women with stable weight over the same time period. Further research is needed to confirm or refute our findings and to allow detailed examination of potential explanations for them.