Rheumatoid arthritis (RA) is a systemic autoimmune disease that results in a chronic and inflammatory disorder. Dynamic balance of helper T cells (Th) 1 and 17 and regulatory T cells (Treg) is broken in RA. Since there is no cure for RA at present, it is necessary to find a truly effective and convenient treatment. Several studies have intended to induce ergotopic regulation to treat autoimmune diseases. This study was undertaken to find potential ergotope peptides and investigate their effects in treating the animal model of RA and their underlying regulatory mechanisms. First, we selected functional ergotope peptides from 25 overlapping peptides derived from the interleukin 2 receptor (IL-2R) α chain, and then used these peptides to treat collagen-induced arthritis (CIA). We showed ergotope peptides as immunomodulatory factors with great benefits at the clinical and pathologic levels. This effect was associated with inhibition of type II collagen (CII)-specific proliferation and autoantibody production as well as induction of antiergotypic immune response, downregulation of both Th1 and Th17 cells and their related components, and emergence of Treg cells that had suppressive action on autoreactive T cells. We also proved that cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and IL-10 are two important mediators that are critical to Treg suppressive function. Inhibition of Th1 and Th17 in established CIA could be attributed to ergotope-induced Treg cells. Our findings reveal that ergotope peptides induce regulatory immune responses and restore immune tolerance, suggesting that treatment with ergotope peptides may be a novel approach to therapy for RA patients and has good application prospects, with cheap, effective, convenient, wide-spectrum features.

BackgroundWithin a population, the differences of pharmacogenomic variant frequencies may produce diversities in drug efficacy, safety, and the risk associated with adverse drug reactions. With the development of pharmacogenomics, widespread genetic research on drug metabolism has been conducted on major populations, but less is known about minorities.ResultsIn this study, we recruited 100 unrelated, healthy Mongol adults from Xinjiang and genotyped 85 VIP variants from the PharmGKB database. We compared our data with eleven populations listed in 1000 genomes project and HapMap database. We used χ2 tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations.ConclusionsOur results demonstrated that different polymorphic allele frequencies exist between different nationalities,and indicated Mongol is most similar to Chinese populations, followed by JPT. This information on the Mongol population complements the existing pharmacogenomic data and provides a theoretical basis for screening and therapy in the different ethnic groups within Xinjiang.

BackgroundSeveral genome-wide association studies revealed that several variants of UMOD gene were related to the estimated glomerular filtration rate (eGFR), CKD or hypertension. In this study, we investigated the association between a common variant rs13333226 in the promoter region of UMOD gene and end stage renal disease (ESRD).MethodsVariant rs13333226 of UMOD gene was genotyped by using the ABI Real time TaqMan allelic discrimination assay in a case-control study including 638 unrelated patients with ESRD and 366 controls.ResultsThe frequency of UMOD SNP rs13333226 GG/GA genotype was significantly higher (36.83% vs. 20.22%, P = 4.02 × 10-8) and the frequency of G allele was much higher (19.04% vs. 11.20%, P = 4.00 × 10−6) in the patients with ESRD than in the controls. The G allele was associated with an increased risk of ESRD (odds ratio 2.30, 95% confidence interval 1.70–3.11, P = 6.10 × 10−8). And G allele (odds ratio 2.33, 95% confidence interval 1.32–4.13, P = 3.65 × 10−3) was associated independently with ESRD.ConclusionsA common variation rs13333226 in the promoter region of UMOD gene was independently associated with ESRD in Han Chinese.

BackgroundSeedlessness in grape (Vitis vinifera) is of considerable commercial importance for both the table grape and processing industries. Studies to date of grape seed development have been made certain progress, but many key genes have yet to be identified and characterized.ResultsIn this study we analyzed the seed transcriptomes of progeny derived from the V. vinifera seeded maternal parent ‘Red Globe’ and the seedless paternal parent ‘Centennial seedless’ to identify genes associated with seedlessness. A total of 6,607 differentially expressed genes (DEGs) were identified and examined from multiple perspectives, including expression patterns, Gene Ontology (GO) annotations, pathway enrichment, inferred hormone influence and epigenetic regulation. The expression data of hormone-related genes and hormone level measurement reveals the differences during seed development between seedless and seeded progeny. Based on both our results and previous studies of A. thaliana seed development, we generated network maps of grape seed-related DEGs, with particular reference to hormone balance, seed coat and endosperm development, and seed identity complexes.ConclusionIn summary, the major differences identified during seed development of seedless and seeded progeny were associated with hormone and epigenetic regulation, the development of the seed coat and endosperm, and the formation of seed identity complexes. Overall the data provides insights into the possible molecular mechanism controlling grape seed size, which is of great importance for both basic research and future translation applications in the grape industry.

BackgroundAnnual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia.MethodsHyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period).ResultsMyocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4–6.2 days and $25,666–$30,321, respectively. Acute-phase incremental costs accounted for 61–75 % of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE.ConclusionsAmong hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.

BackgroundMost studies on air pollution exposure and its associations with human health in China have focused on the heavily polluted industrial areas and/or mega-cities, and studies on cities with comparatively low air pollutant concentrations are still rare. Only a few studies have attempted to analyse particulate matter (PM) for the vibrant economic centre Shenzhen in the Pearl River Delta. So far no systematic investigation of PM spatiotemporal patterns in Shenzhen has been undertaken and the understanding of pollution exposure in urban agglomerations with comparatively low pollution is still limited.MethodsWe analyze daily and hourly particulate matter concentrations and all-cause mortality during 2013 in Shenzhen, China. Temporal patterns of PM (PM2.5 and PM10) with aerodynamic diameters of 2.5 (10) μm or less (or less (including particles with a diameter that equals to 2.5 (10) μm) are studied, along with the ratio of PM2.5 to PM10. Spatial distributions of PM10 and PM2.5 are addressed and associations of PM10 or PM2.5 and all-cause mortality are analyzed.ResultsAnnual average PM10 and PM2.5 concentrations were 61.3 and 39.6 μg/m3 in 2013. PM2.5 failed to meet the Class 2 annual limit of the National Ambient Air Quality Standard. PM2.5 was the primary air pollutant, with 8.8 % of days having heavy PM2.5 pollution. The daily PM2.5/PM10 ratios were high. Hourly PM2.5 concentrations in the tourist area were lower than downtown throughout the day. PM10 and PM2.5 concentrations were higher in western parts of Shenzhen than in eastern parts. Excess risks in the number of all-cause mortality with a 10 μg/m3 increase of PM were 0.61 % (95 % confidence interval [CI]: 0.50–0.72) for PM10, and 0.69 % (95 % CI: 0.55–0.83) for PM2.5, respectively. The greatest ERs of PM10 and PM2.5 were in 2-day cumulative measures for the all-cause mortality, 2-day lag for females and the young (0–65 years), and L02 for males and the elder (>65 years). PM2.5 had higher risks on all-cause mortality than PM10. Effects of high PM pollution on mortality were stronger in the elder and male.ConclusionsOur findings provide additional relevant information on air quality monitoring and associations of PM and human health, valuable data for further scientific research in Shenzhen and for the on-going discourse on improving environmental policies.