Quantitative Microscopy of Hepatic Changes Induced by Phenethyl Isothiocyanate in Fischer-344 Rats Fed Either a Cereal-Based Diet or a Purified Diet

Hepatic changes induced by phenethyl isothiocyanate (PEITC) in the liver of rats were determined by quantitative microscopy. Groups of male Fischer-344 rats were fed either a standard, cereal-based diet (Wayne rodent meal) or a purified diet (AIN-76A) containing PEITC at concentrations of 0.75 and 6.0 mmol/kg for 13 wk. Severe hepatic lipidosis was observed in control rats fed the purified diet. Addition of PEITC to the purified diet significantly reduced lipid content in hepatocytes. In contrast, lipid content in the liver of the rats fed the cereal-based diet containing PEITC was greater than in control rats maintained on the same diet. In addition, dose-related reductions in hepatocyte, lipid droplet, peroxisome, and mitochondrial volumes were observed in PEITC-treated rats fed the cereal-based diet. These results indicate that PEITC exerts differential effects on the liver of rats fed either the cereal-based or purified diet.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68493/2/10.1177_019262339502300602.pd

Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model

A Fluorescent Probe for Diacetyl Detection

A water-soluble fluorescent probe, rhodamine B hydrazide (RBH), was prepared and its properties for recognition of diacetyl were studied. The method employs the reaction of diacetyl with RBH, a colorless and non-fluorescent rhodamine B spiro form derivative to give a pink-colored fluorescent substance. In weakly acidic media, RBH reacts more selectively with diacetyl than with other carbonyls, causing a large increase in fluorescence intensity and thereby providing an easy assay for the determination of diacetyl

Inter-rater reliability of categorical versus continuous scoring of fish vitality: does it affect the utility of the reflex action mortality predictor (RAMP) approach?

Scoring reflex responsiveness and injury of aquatic organisms has gained popularity as predictors of discard survival. Given this method relies upon the individual interpretation of scoring criteria, an evaluation of its robustness is done here to test whether protocol-instructed, multiple raters with diverse backgrounds (research scientist, technician, and student) are able to produce similar or the same reflex and injury score for one of the same flatfish (European plaice, Pleuronectes platessa) after experiencing commercial fishing stressors. Inter-rater reliability for three raters was assessed by using a 3-point categorical scale (‘absent’, ‘weak’, ‘strong’) and a tagged visual analogue continuous scale (tVAS, a 10 cm bar split in three labelled sections: 0 for ‘absent’, ‘weak’, ‘moderate’, and ‘strong’) for six reflex responses, and a 4-point scale for four injury types. Plaice (n = 304) were sampled from 17 research beam-trawl deployments during four trips. Fleiss kappa (categorical scores) and intra-class correlation coefficients (ICC, continuous scores) indicated variable inter-rater agreement by reflex type (ranging between 0.55 and 0.88, and 67% and 91% for Fleiss kappa and ICC, respectively), with least agreement among raters on extent of injury (Fleiss kappa between 0.08 and 0.27). Despite differences among raters, which did not significantly influence the relationship between impairment and predicted survival, combining categorical reflex and injury scores always produced a close relationship of such vitality indices and observed delayed mortality. The use of the continuous scale did not improve fit of these models compared with using the reflex impairment index based on categorical scores. Given these findings, we recommend using a 3-point categorical over a continuous scale. We also determined that training rather than experience of raters minimised inter-rater differences. Our results suggest that cost-efficient reflex impairment and injury scoring may be considered a robust technique to evaluate lethal stress and damage of this flatfish species on-board commercial beam-trawl vessels

Impact of gastro-oesophageal reflux on microRNA expression, location and function

We have shown that miRNA expression is altered in the oesophageal squamous mucosa from individuals with gastro-oesophageal reflux and ulcerative oesophagitis. These changes in miR-143, miR-145 and miR-205 expression appear to be most pronounced in the basal layer of the oesophageal epithelium. In the context of gastro-oesophageal reflux these expression changes might influence proliferation and apoptosis and thereby regulate epithelial restoration. It is reasonable to hypothesise that they could represent early molecular events preceding the development of Barrett’s oesophagus, although proving this will require further studies as described above. Future detailed analyses of the role of these miRNAs in progression from gastro-oesophageal reflux to Barrett’s oesophagus, and then to oesophageal adenocarcinoma will be valuable, and may help in efforts to control and treat these diseases.This study was funded by a Competing Project Grant from the National Health and Medical Research Council of Australia. Cameron Smith was supported by a PROBE-NET PhD scholarship funded by a Strategic research Partnerships Grant from the Cancer Council of New South Wales

Supplementation of a western diet with golden kiwifruits (Actinidia chinensis var.'Hort 16A':) effects on biomarkers of oxidation damage and antioxidant protection

<p>Abstract</p> <p>Background</p> <p>The health positive effects of diets high in fruits and vegetables are generally not replicated in supplementation trials with isolated antioxidants and vitamins, and as a consequence the emphasis of chronic disease prevention has shifted to whole foods and whole food products.</p> <p>Methods</p> <p>We carried out a human intervention trial with the golden kiwifruit, Actinidia chinensis, measuring markers of antioxidant status, DNA stability, plasma lipids, and platelet aggregation. Our hypothesis was that supplementation of a normal diet with kiwifruits would have an effect on biomarkers of oxidative status. Healthy volunteers supplemented a normal diet with either one or two golden kiwifruits per day in a cross-over study lasting 2 × 4 weeks. Plasma levels of vitamin C, and carotenoids, and the ferric reducing activity of plasma (FRAP) were measured. Malondialdehyde was assessed as a biomarker of lipid oxidation. Effects on DNA damage in circulating lymphocytes were estimated using the comet assay with enzyme modification to measure specific lesions; another modification allowed estimation of DNA repair.</p> <p>Results</p> <p>Plasma vitamin C increased after supplementation as did resistance towards H₂O₂-induced DNA damage. Purine oxidation in lymphocyte DNA decreased significantly after one kiwifruit per day, pyrimidine oxidation decreased after two fruits per day. Neither DNA base excision nor nucleotide excision repair was influenced by kiwifruit consumption. Malondialdehyde was not affected, but plasma triglycerides decreased. Whole blood platelet aggregation was decreased by kiwifruit supplementation.</p> <p>Conclusion</p> <p>Golden kiwifruit consumption strengthens resistance towards endogenous oxidative damage.</p

Thermal conductivity and thermal boundary resistance of nanostructures

International audienceWe present a fabrication process of low-cost superlattices and simulations related with the heat dissipation on them. The influence of the interfacial roughness on the thermal conductivity of semiconductor/semiconductor superlattices was studied by equilibrium and non-equilibrium molecular dynamics and on the Kapitza resistance of superlattice's interfaces by equilibrium molecular dynamics. The non-equilibrium method was the tool used for the prediction of the Kapitza resistance for a binary semiconductor/metal system. Physical explanations are provided for rationalizing the simulation results

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

BACKGROUND: Continuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China. METHODS: A population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China

Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon

<p>Abstract</p> <p>Background</p> <p>Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of BB on colon tumors and in both genders are unknown.</p> <p>Methods</p> <p>We examined efficacy of BB in inhibition of azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults.</p> <p>Results</p> <p>Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (<it>P </it>< 0.05) ACF numbers within the distal colon of female but not male rats. There was a significant (<it>P </it>< 0.05) diet by gender interaction with respect to total colon ACF number. Colon and duodenum tumor incidences were less in females than males at 17 weeks after AOM. BB tended (0.1 > <it>P </it>> 0.05) to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (<it>P </it>> 0.1) by BB. There was a tendency (0.1 > <it>P </it>> 0.05) for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas) in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (<it>P </it>< 0.05). BB favored (<it>P </it>< 0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total tumor number) in female rat small intestine.</p> <p>Conclusion</p> <p>Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma) by BB.</p

EGCG Enhances the Therapeutic Potential of Gemcitabine and CP690550 by Inhibiting STAT3 Signaling Pathway in Human Pancreatic Cancer

Background: Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogene, which promotes cell survival, proliferation, motility and progression in cancer cells. Targeting STAT3 signaling may lead to the development of novel therapeutic approaches for human cancers. Here, we examined the effects of epigallocathechin gallate (EGCG) on STAT3 signaling in pancreatic cancer cells, and assessed the therapeutic potential of EGCG with gemcitabine or JAK3 inhibitor CP690550 (Tasocitinib) for the treatment and/or prevention of pancreatic cancer. Methodology/Principal Findings: Cell viability and apoptosis were measured by XTT assay and TUNEL staining, respectively. Gene and protein expressions were measured by qRT-PCR and Western blot analysis, respectively. The results revealed that EGCG inhibited the expression of phospho and total JAK3 and STAT3, STAT3 transcription and activation, and the expression of STAT3-regulated genes, resulting in the inhibition of cell motility, migration and invasion, and the induction of caspase-3 and PARP cleavage. The inhibition of STAT3 enhanced the inhibitory effects of EGCG on cell motility and viability. Additionally, gemcitabine and CP690550 alone inhibited STAT3 target genes and synergized with EGCG to inhibit cell viability and induce apoptosis in pancreatic cancer cells. Conclusions/Significance: Overall, these results suggest that EGCG suppresses the growth, invasion and migration of pancreatic cancer cells, and induces apoptosis by interfering with the STAT3 signaling pathway. Moreover, EGCG furthe