Background Immunoglobulin E (IgE) is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino individuals have not been well represented in genetic studies of total IgE. Objective To identify the genetic predictors of serum total IgE levels. Methods We used genome wide association (GWA) data from 4,292 individuals (2,469 African Americans, 1,564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (i.e., African American, Latino, and European American) and asthma status. The resulting p-values were meta-analyzed accounting for sample size and direction of effect. Top single nucleotide polymorphism (SNP) associations from the meta-analysis were reassessed in six additional cohorts comprising 5,767 individuals. Results We identified 10 unique regions where the combined association statistic was associated with total serum IgE levels (P-value <5.0×10−6) and the minor allele frequency was ≥5% in two or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the most significantly associated SNP with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P-value = 0.007 and 2.45×10−7, respectively). In addition, findings from earlier GWA studies were also validated in the current meta-analysis. Conclusion This meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE in multiple race-ethnic groups. This study also extends and confirms the findings of earlier GWA analyses in African American and Latino individuals.

We have concluded that TNF-alpha-308 may be a risk factor for atopic asthma, whereas the LT-alpha-NcoI polymorphism may modify risk to atopic asthma with TNF-alpha-308.

The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

The importance of miRNAs in the progression of prostate cancer (PCa) has further been supported by the finding that miRNAs have been identified as potential oncogenes or tumor suppressors in PCa. Indeed, in eukaryotes, miRNAs have been found to regulate and control gene expression by degrading mRNA at the post-transcriptional level. In this study, we investigated the expression of miR-34 family members, miR-34b and miR-34c, in different PCa cell lines, and discussed the molecular mechanism of miR-34b in the invasion and migration of PCa cells in vitro. The difference analyses of the transcriptome between the DU145 and PC3 cell lines demonstrated that both miR-34b and -34c target critical pathways that are involved in metabolism, such as proliferation, and migration, and invasion. The molecular expression of miR-34b/c were lower in PC3 cells. Moreover, over-expression of miR-34b/c in PC3 cells caused profound phenotypic changes, including decreased cell proliferation, migration and invasion. Moreover, the players that regulate expression levels of transforming growth factor-β (TGF-β), TGF-β receptor 1 (TGF-βR1), and p53 or phosphorylation levels of mothers against decapentaplegic 3 (SMAD3) in the TGF-β/Smad3 signaling pathway have yet to be elucidated, and will provide novel tools for diagnosis and treatment of metastatic PCa.

No abstract

To investigate the effects of dietary manganese (Mn) supplementation on iron (Fe) metabolism, a total of 480 50-week-old hens were fed the basal diet (control, 24.35 mg Mn/kg) without Mn supplementation for 6 weeks to reduce Mn storage in the body. Hens were then randomly assigned to one of three treatments, which included the control and control added with 60 or 300 mg Mn/kg diet (M-Mn or H-Mn). Duodenum, heart, liver, and tibia were collected in hens after 12-week feeding period. No significant differences were observed in egg production, feed/egg ratio, shell breaking strength, and shell thickness among different treatments. Compared with control or M-Mn, H-Mn decreased (P < 0.05) serum Fe concentration, while increased (P < 0.05) total Fe-binding capacity (TIBC). The Fe concentration decreased (P < 0.05) in duodenum, and tended to reduce (P < 0.10) in liver from control to M-Mn and to H-Mn; whereas, dietary Mn supplementation did not influence (P > 0.10) Fe concentration in the heart and tibia. In conjunction with reduced Fe retention, DMT1 mRNA expression decreased (P < 0.05) with dietary Mn concentration increasing in the duodenum and liver. Duodenal FPN1 mRNA level was higher (P < 0.05) in H-Mn group than that in control or M-Mn group, while hepatic FPN1 mRNA expression was lower (P < 0.05) in M-Mn or H-Mn group when compared with control. The results demonstrated that dietary Mn supplementation decreased Fe concentration in duodenum and liver of hens, which may be related to the alteration of DMT1 and FPN1 expression in these tissues.

In order to determine whether exercise-induced profuse sweating could reduce urinary uric acid excretion, we simulated badminton players training and measured their uric acid in urine, sweat and blood during the training period. Thirteen male volunteers who were well-trained badminton players were recruited in this study. On the first 2 days and the last 2 days of the study period none of the subjects engaged in any intense exercise-or activity-inducing profuse sweat, but they accepted routine training 2 h per day during the middle 3 days. The results show that mean serum urate levels of thirteen volunteers rose significantly on day 4, when the concentrations increased by 18.2% over day 2 (P < 0.05). The mean ten-hour urinary uric acid excretion of seven volunteers on the 3 training days was significantly less at 178.5 µmol/day and 118.3 µmol/day than those on the preceding and subsequent days of the training days, respectively (P < 0.05). Furthermore, for six volunteers, the mean ratio of clearance of uric acid to creatinine was 6.6% on day 2, which significantly decreased to 5.4% on day 4 (P < 0.05). It is concluded profuse sweating exercise results in a decrease of urinary uric acid excretion amounts and leads to increased serum uric acid after the exercise. We suggest that persons who take vigorous exercise or are exposed to hot environments need drinking enough fluids to prevent dehydration and maintain adequate urinary output. People with profuse sweat after rigorous exercise are recommended taking sports drinks containing abundant sodium in order to decrease serum uric acid.

Esophageal cancer is one of the fatal cancers around the world. Dexmedetomidine (DEX) is widely used during anesthesia of esophageal cancer surgery. Nevertheless, the role of DEX in the progression of esophageal cancer remains barely known. The proliferation, apoptosis and metastasis of esophageal cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, transwell migration and invasion assays and Western blot assay. The expression of miR-143-3p was measured by quantitative real-time PCR in esophageal cancer tissues and cells. The binding sites between miR-143-3p and epidermal growth factor receptor pathway substrate 8 (EPS8) were predicted by Starbase online software, and the combination was verified by dual-luciferase reporter assay. The murine xenograft model was established using KYSE150 cells to verify the function of DEX in vivo . DEX inhibited the proliferation and metastasis while accelerated the apoptosis of esophageal cancer cells. The abundance of miR-143-3p was lower in esophageal cancer tissues and cells than that in paring normal tissues and normal esophageal mucosal cells Het-1A. MiR-143-3p could be induced by DEX treatment in esophageal cancer cells, and miR-143-3p also suppressed the development of esophageal cancer. EPS8 was a functional target of miR-143-3p, and it played an oncogenic role in esophageal cancer. DEX inhibited the growth of tumor via miR-143-3p/EPS8 in vivo . DEX suppressed the growth and metastasis while facilitated the apoptosis of esophageal cancer cells through upregulating the abundance of miR-143-3p and reducing the level of EPS8 in vivo and in vitro , providing promising target for the treatment of esophageal cancer.