Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10(-/-) model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10(-/-) mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.     

Effects of Eyjafjallaj?kull Volcanic Ash on Innate Immune System Responses and Bacterial Growth in Vitro

Background: On 20 March 2010, the Icelandic volcano Eyjafjallajökull erupted for the first time in 190 years. Despite many epidemiological reports showing effects of volcanic ash on the respiratory system, there are limited data evaluating cellular mechanisms involved in the response to ash. Epidemiological studies have observed an increase in respiratory infections in subjects and populations exposed to volcanic eruptions.Methods: We physicochemically characterized volcanic ash, finding various sizes of particles, as well as the presence of several transition metals, including iron. We examined the effect of Eyjafjallajökull ash on primary rat alveolar epithelial cells and human airway epithelial cells (20–100 µg/cm²), primary rat and human alveolar macrophages (5–20 µg/cm²), and Pseudomonas aeruginosa (PAO1) growth (3 µg/10⁴ bacteria).Results: Volcanic ash had minimal effect on alveolar and airway epithelial cell integrity. In alveolar macrophages, volcanic ash disrupted pathogen-killing and inflammatory responses. In in vitro bacterial growth models, volcanic ash increased bacterial replication and decreased bacterial killing by antimicrobial peptides.Conclusions: These results provide potential biological plausibility for epidemiological data that show an association between air pollution exposure and the development of respiratory infections. These data suggest that volcanic ash exposure, while not seriously compromising lung cell function, may be able to impair innate immunity responses in exposed individuals.     

New insight into determining indicators of metabolic status in women: Expression of PPARγ and FABP4 in PBMCs

Adiposity and its metabolic disturbances could be regulated by adipocyte-specific peroxisome proliferator-activated receptor gamma and fatty acid-binding protein4. Although these two proteins are mainly expressed in adipose tissues, they can also be expressed in peripheral blood mononuclear cells, which could be useful for predicting body composition and blood parameters. Thus, this cross-sectional study was performed during January 2013–January 2014 with 229 women (age range, 22–52 years) who were classified as obese or nonobese. Serum glucose, insulin, lipids, and body composition were measured in the fasting state. Peripheral blood mononuclear cells were isolated to extract ribonucleic acid (RNA) and to determine gene expression by real time polymerase chain reaction (PCR). All serum parameters and components of body composition were significantly higher in obese than in nonobese women. Gene expression analysis showed that serum levels of glucose and lipids, except high-density lipoprotein (HDL), were higher in the group that expressed high fatty acid-binding protein4. Increased expression of the peroxisome proliferator-activated receptor gamma was associated with a significant reduction of blood sugar and increased HDL and other lipids and visceral fat. Therefore, it seems that the level of expression of these genes in peripheral blood mononuclear cells may indicate metabolic status.     

Effects of Selenium on DNA Binding Activity of Nuclear Factor-κB Induced by Arsenic in Mouse Skin JB6-CI41 Cells in vitro

目的 研究硒对砷诱导小鼠皮肤JB6-CI41细胞核因子κB(nuclear factor κB,NF-κB)的DNA结合活性和细胞凋亡的作用.方法 调整JB6-CI41细胞密度为1×105/孔,分别设立对照(生理盐水)组,不同浓度的亚砷酸(3.125、6.25、12.5 μmol/L)和亚硒酸钠(2.5 μmol/L)单独染毒组,亚硒酸钠(2.5μmol/L)+不同浓度的亚砷酸(3.125、6.25和12.5μmol/L)联合染毒组,NF-κB特异化学抑制剂二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DTYC,100 μmol/L,提前染毒2 h)+亚砷酸(6.25 μmol/L)联合染毒组.采用凝胶阻滞电泳法(electrophoretic mobility shift assay,EMSA)检测NF-κB的DNA结合活性,采用流式细胞术检测细胞凋亡情况.结果 2.5 μmol/L亚硒酸钠对小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性和细胞凋亡无显著影响(P＞0.05).6.25和12.5 μmol/L的亚砷酸能够增强小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性(P＜0.01),具有明显剂量-效应关系(r=0.942 6,P＜0.01).3.125、6.25和12.5 μmol/L亚砷酸诱导小鼠皮肤JB6-CI41细胞凋亡(P＜0.01),呈现显著剂量-反应关系(r=0.991 8,P＜0.01).NF-κB的DNA结合活性与细胞凋亡率呈显著正相关(r=0.977 5,P＜0.01).2.5 μmol/L亚硒酸钠能抑制6.25和12.5 μmol/L亚砷酸作用下的小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性(P＜0.01),对3.125、6.25和12.5 μmol/L的亚砷酸引起的小鼠皮肤JB6-CI41细胞凋亡率也表现出显著抑制作用(P＜0.01).100 μmol/L的DTYC对6.25μmol/L亚砷酸引起的小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性和细胞凋亡率具有显著抑制作用(P＜0.01).结论 在本实验中,一定剂量(6.25～12.5 μmol/L)的砷能够使小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性显著增高并诱导细胞凋亡,2.5 μmol/L的硒能抑制砷引起的NF-κB的活化和细胞凋亡.     

Effects of ω3- and ω6-Polyunsaturated Fatty Acids on RANKL-Induced Osteoclast Differentiation of RAW264.7 Cells: A Comparative in Vitro Study

Polyunsaturated fatty acids (PUFAs) have been reported to have an anabolic effect on bone in vivo, but comparative studies to identify inhibitors of osteoclast formation amongst ω3- and ω6-PUFAs are still lacking. Here we assessed the effects of the ω3-PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the ω6-PUFAs, arachidonic acid (AA) and γ-linolenic acid (GLA) on a RAW264.7 osteoclast differentiation model. The effects of PUFAs on RANKL-induced osteoclast formation were evaluated by counting tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells. PUFAs significantly inhibited RANKL-induced osteoclast formation in a dose-dependent manner with AA- and DHA-mediated inhibition being the strongest. Furthermore, RANKL-induced mRNA- and protein expression of the key osteoclastogenic genes cathepsin K and TRAP were inhibited by AA and more potently by DHA. Owing to the attenuated osteoclastogenesis by DHA and AA, actin ring formation and bone resorptive activity of these cells as evaluated on bone-mimetic plates were severely compromised. Hence, of the tested PUFAs, AA and DHA were found to be the most effective in inhibiting RANKL-induced osteoclast formation with the latter providing the strongest inhibitory effects. Collectively, the data indicates that these PUFAs may play an important role in regulating bone diseases characterized by excessive osteoclast activity.     

Is beauty in the eye of the beholder? Effects of weight and shape on attractiveness ratings of female line drawings by restrained and nonrestrained eaters

This study tested the differences between restrained and nonrestrained eaters' attractiveness perceptions of female line drawings, of their own figures, and the ideal female figure. Female line drawings varied systematically in body weight and in waist and hip circumference. Forty-six female undergraduate students, 23 nonrestrainers and 23 restrainers, rated stimuli in attractiveness, identified the figure which best represented their own body type (PAF), and the ideal body figure (IF) according to the Restraint Scale [RS; Herman, C. P., & Polivy, J. (1980). Restrained eating. In: A. Stunkard (Ed.), Obesity (pp. 208-225). Philadelphia, PA: Saunders]. Restrainers did not generally differ from nonrestrainers in attractiveness ratings or in their choice of IF. However, differences between IF and PAF were larger in restrainers than in nonrestrainers because restrainers chose PAFs with larger hips than nonrestrainers did. This difference between the restraint groups was independent of between-group differences in hip size. This discrepancy between IF and PAF may contribute to the restrainers' motivation to diet.     

Effects of Dietary Fat and Endurance Exercise on Plasma Cortisol,Prostaglandin E2, Interferon-γ and Lipid Peroxides in Runners

Objective: Exercise and the neuroendocrine and oxidative stress it elicits on immune function is modulated by dietary fat intake. The effects of increasing dietary fat on endurance exercise-induced alterations (80% of V?O_2max for 2 hours) in the plasma levels of cortisol and prostaglandin E₂ (PGE₂), interferon-γ (IFN-γ) and lipid peroxides were investigated. As higher levels of cortisol, PGE₂ and lipid peroxides could be immunosuppressive, the effects of different levels of dietary fat on these measures in runners were determined.

Methods: Healthy trained runners (males and females) consumed serially 15% fat diet (of daily energy), 30% fat diet and 40% fat diets for four weeks each. In the last week of each diet period the subjects ran to exhaustion at 80% of their V?O_2max and blood was drawn pre- and post-run. Cortisol, IFN-γ, PGE₂ and lipid peroxides were determined using standard techniques.

Results: Pre-exercise levels of plasma cortisol were elevated, IFN-γ was unchanged and PGE₂ and lipid peroxides decreased on the 40%F diet compared to 30%F and 15%F. Post-exercise levels of plasma cortisol (p < 0.004), PGE₂ (p < 0.0057) and lipid peroxide levels increased (p < 0.0001) after endurance exercise on all diets. The rates of increase of plasma cortisol levels during exercise were similar on all three diets. Although absolute cortisol levels were higher in the high fat group, the rate of increase of plasma cortisol level during exercise was similar on each diet. The dietary fat levels did not affect IFN-γ, however, PGE₂ and lipid peroxides decreased with increasing fat at baseline at 40%F level (p < 0.01; 30%F vs. 40%F: p < 0.002; 15%F vs. 40%F: p < 0.007).

Conclusions: Data from the present study suggest that higher levels of fat in the diet, up to 40%, increase endurance running time without adverse effects on plasma cortisol, IFN-γ, and lipid peroxide levels.     

Experimental Study on Differentiation of Human Hepatocarcinoma Cells Induced by Zhengganfang Drug Serum in Vitro

Objective To study the effect of Zhengganfang （ZGF） drug serum in inducing differentiation of BEL - 7402 human hepatocarcinoma cell （ HHC ） and its influence of the telomerase activity. Methods Rats were fed with ZGF decoction to prepare the drug - serum of ZGF, and the drug - serum was used for Bel - 7402 HHC culture. Serum of normal rat was taken as negative control and retinoic acid （RA） as the positive control, cell proliferation was detected by MTr colorimetric assy, nucleocytoplasm ratio by image assay, a - fetoprotein （ AFP） by RIA alkaline phosphatase （ ALP） activity and T - glutamy transpeptidase （γ- GT） by dynamic colorimetric assy, and telomerase activity of Bel- 7402 cell by PCR - ELISA. Results Drug - serum of ZGF could inhibit the prohferation of Bel - 7402 cell, markedly reduce the nucleocytoplasm ratio and the secretion of AFP, decrease γ - GT activity, increase ALP activity, and suppress the telomerase activity of Bel - 7402 cell. Conclusion ZGF can induce the differentiation of Bel - 7402 HHC, the main mechanism maybe through the supression of the telomerase activity.     

Characterizing the Peroxisome Proliferator-Activated Receptor (PPARγ) Ligand Binding Potential of Several Major Flame Retardants,Their Metabolites,and Chemical Mixtures in House Dust

Background: Accumulating evidence has shown that some environmental contaminants can alter adipogenesis and act as obesogens. Many of these contaminants act via the activation of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor.Objectives: Our goal was to determine the PPARγ ligand binding potency of several major flame retardants, including polybrominated diphenyl ethers (PBDEs), halogenated phenols and bisphenols, and their metabolites. Ligand binding activity of indoor dust and its bioactivated extracts were also investigated.Methods: We used a commercially available fluorescence polarization ligand binding assay to investigate the binding potency of flame retardants and dust extracts to human PPARγ ligand-binding domain. Rosiglitazone was used as a positive control.Results: Most of the tested compounds exhibited dose-dependent binding to PPARγ. Mono(2-ethylhexyl) tetrabromophthalate, halogenated bisphenols and phenols, and hydroxylated PBDEs were found to be potent PPARγ ligands. The most potent compound was 3-OH-BDE-47, with an IC₅₀ (concentration required to reduce effect by 50%) of 0.24 μM. The extent of halogenation and the position of the hydroxyl group strongly affected binding. In the dust samples, 21 of the 24 samples tested showed significant binding potency at a concentration of 3 mg dust equivalent (DEQ)/mL. A 3–16% increase in PPARγ binding potency was observed following bioactivation of the dust using rat hepatic S9 fractions.Conclusion: Our results suggest that several flame retardants are potential PPARγ ligands and that metabolism may lead to increased binding affinity. The PPARγ binding activity of house dust extracts at levels comparable to human exposure warrants further studies into agonistic or antagonistic activities and their potential health effects.Citation: Fang M, Webster TF, Ferguson PL, Stapleton HM. 2015. Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust. Environ Health Perspect 123:166–172; http://dx.doi.org/10.1289/ehp.1408522     

Evaluation of the Antiproliferative Effects of Essiac™ on In Vitro and In Vivo Models of Prostate Cancer Compared to Paclitaxel

Essiac?, a widely consumed, sparsely tested herbal tea, was evaluated for preparation consistency and antiproliferative effects on prostate cancer cells and xenografts. High performance liquid chromatography (HPLC) was used to compare different lots of Essiac and evaluate extraction consistency by comparing peak areas in concentrated preparations. Repeated analysis of one lot showed < 2% RSD between corresponding peaks. Absolute peak areas varied widely between lots, but similarity in relative size of corresponding peaks was observed. Cytotoxic effects of Essiac were tested in vitro by crystal violet assay and analysis of cell cycle distribution by flow cytometry, but no differences between control and treatment groups was observed. Paclitaxel was used as a positive control in cell cycle analysis and was the only treatment which showed significant effects on cell cycle distribution. Toxicity in nude mice was tested, and efficacy in inhibiting PC-3 xenograft growth. No toxicity or tumour size difference was observed dosing up to 240 mg/kg QD, over 28 days, excepting the positive control group treated with paclitaxel. Ki-67 and PCNA expression was analyzed in treated tumors, but no difference in expression of either marker was observed. These evaluations suggest Essiac has no marked antiproliferative effect on the models tested.     

Years off Your Life? The Effects of Homicide on Life Expectancy by Neighborhood and Race/Ethnicity in Los Angeles County

Homicide is one of the leading causes of death in Los Angeles County and is known to be elevated in low-income urban neighborhoods and in black males. However, because homicide occurs primarily among young adults, mortality rate statistics may underrepresent its importance. We estimated the impact of homicide on life expectancy by demographic group and geographic area in Los Angeles County, 2001–2006. Life expectancy estimates were calculated using mortality records and population estimates for Los Angeles County. Cause elimination techniques were used to estimate the impact of homicide on life expectancy. Homicide was estimated to reduce life expectancy by 0.4 years for Los Angeles County residents and by 2.1 years for black males. The impact of homicide on life expectancy was higher in low-income neighborhoods. In some low-income urban neighborhoods, homicide was estimated to decrease life expectancy in black males by nearly 5 years. Homicide causes substantial reductions in life expectancy in Los Angeles County. Its impact is magnified among black males and in low-income urban areas, underscoring the need for homicide reduction in urban centers.     

Effects of item and rater characteristics on checklist recording: what should we look for?

OBJECTIVE: Examinations based on using standardised patients (SPs) commonly use checklist recordings to evaluate students' clinical performance. This paper examines whether and to what extent item and rater characteristics affect the reliability of history checklist recording in an SP-based assessment. METHODS: Checklist items were reviewed for the presence or absence of 5 item characteristics and a 2-point versus 3-point scoring scale. Agreement between checklist recordings obtained from SPs and clinician-examiners (CEs) were compared by item characteristics, scoring scale and CEs' level of involvement in the assessment. RESULTS: Based on 3179 pairs of recordings, the overall percentage of agreement between SPs and CEs was 83% (kappa = 0.64). Agreement was significantly higher for items scored on a 2-point than on a 3-point scale, and when the CE was also the author and the trainer of the station. After controlling for other factors, item characteristics were only marginally associated with level of interrater agreement. CONCLUSIONS: This study suggests that attention should be paid to specific aspects of checklist development and checklist recording training when an SP or CE is used as recorder.     

Stability of Intimate Partner Violence by Men across 12?Years in Young Adulthood: Effects of Relationship Transitions

The present study examined the stability of young men??s intimate partner violence (IPV) over a 12-year period as a function of relationship continuity or discontinuity. Multiwave measures of IPV (physical and psychological aggression) were obtained from 184 men at risk for delinquency and their women partners. The effects of relationship continuity versus transitions on change in IPV were examined using multilevel analyses. In general, men??s IPV decreased over time. Men??s physical aggression in their early 20s predicted levels of physical aggression about 7?years later, and men??s psychological aggression in their early 20s predicted levels of psychological aggression about 10?C12?years later. As hypothesized, higher stability in IPV was found for men who stayed with the same partners, whereas men experiencing relationship transitions showed greater change. The IPV of new partners was linked to the changes in men??s IPV that occurred with repartnering. There was less change in men??s IPV over time as men changed partners less frequently.     

Do Tobacco and Alcohol Modify Protective Effects of Diet on Oral Carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27–0.78) and heavy (OR = 0.30; 95% CI = 0.14–0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22–1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31–0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30–0.87) and 0.18 for fruits (95% CI = 0.07–0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.     

Acute Effects of Different Multivitamin Mineral Preparations with and without Guaraná on Mood,Cognitive Performance and Functional Brain Activation

Previous work has identified the positive effects of the acute administration of a multivitamin-guaraná preparation during an effortful executive/working memory task. Here, we aimed to differentiate the effects of multivitamins with and without guaraná and to examine the neural substrates of such effects using functional magnetic resonance imaging (fMRI). Following a double-blind, placebo-controlled, randomised, balanced crossover design, 20 participants (mean age 29 ± 5.54 years) consumed multivitamin preparations with or without guaraná (Berocca^® Performance and Boost, respectively) and a placebo. Thirty minutes post-treatment, they underwent neurocognitive assessment, consisting of a 10 min Cognitive Demand Battery, with mood ratings taken immediately before and after the battery. Five additional participants underwent post-treatment fMRI scanning during Rapid Visual Information Processing and Inspection Time activation tasks. The multivitamin with guaraná treatment was associated with significantly enhanced Serial Threes performance and self-rated contentment. fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and attentional processing, with the effect being greater in the multivitamin with guaraná condition. These data confirm the acute benefits of multivitamins with guaraná on mood and cognitive performance. Furthermore, they demonstrate for the first time increased brain activation from multivitamin preparations both with and without guaraná, as measured using fMRI.