Micronucleus formation induced by biomass burning particles derived from biomass burning induce high micronucleus frequency in Tradescantia pallida assay (TRAD-MN)

Manual harvesting is usually done after to sugar cane burning which is responsible for seasonal emission of air pollutants in Brazil and it is believed to be responsible for deleterious health effects in exposed populations. The mutagenic potential of sugar cane burning harvesting particulate and particle surrogates of residual oil fly ash (ROFA) were evaluated in assays measuring micronuclei (MN) in the pollen mother cells of Tradescantia pallida (TRAD-MN). Micronuclei frequencies in TRAD-MN to sugar cane burning residues (SCBR) at doses 0.3 and 0.03 mg/mL were respectively 2.18 ± 0.35 and 5.53 ± 1.04, whereas to ROFA from incinerator and ROFA from an electrostatic precipitator installed in one of the chimneys of a steel plant, MN frequencies were, respectively, 3.43 ± 0.7 and 4.90 ± 1.07. Significant differences were detected among the groups (p < 0.001), demonstrating that SCBR was at least as genotoxic as the fossil fuel derived particles. The results suggest that the burning process to harvest sugar cane should be better controlled. Keywords: pollution, burning particles, micronuclei, Tradescantia pallida . Partículas derivadas da queima de biomassa induzem alta frequência de micronúcleos no ensaio de Tradescantia pallida (TRAD-MN) Resumo A coleta de cana-de-açúcar manual é geralmente realizada após a queima, a qual é responsável pela emissão sazonal de poluentes atmosféricos no Brasil e acredita-se que este seja responsável pelos efeitos deletérios a saúde da população exposta. O potencial mutagênico da queima de cana-de-açúcar e partículas oriundas de resíduos em cinza de óleo queimado (ROFA) foi avaliado em ensaio que mede a freqüência de micronúcleos (MN) em células mãe de grão de pólen de Tradescantia pallida (TRAD-MN). A freqüência de TRAD-MN em resíduos de queima de cana de açúcar (SCBR) nas doses de 0.3 e 0,03mg/mL foi, respectivamente de 2,18 ± 0,35 e 5,53 ± 1,04, enquanto para ROFA de incinerador e ROFA de um precipitador eletrostático instalado em uma chaminé de uma indústria siderúrgica, a freqüência de MN foi, respectivamente, 3,43 ± 0,7 e 4,90 ± 1,07. Diferença significante foi observada entre os grupos (p<0,001), demonstrando que SCBR foi ao menos tão genotóxico quanto às partículas derivadas de combustíveis fósseis. Os resultados sugerem que o processo de queima de cana-de-açúcar no período da safra deveria ser mais bem controlado. Palavras-Chave: poluição, partículas de queimadas, micronúcleos, Tradescantia pallida

Long-term air pollution exposure, genome-wide DNA methylation and lung function in the lifelines cohort study

BACKGROUND: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not fully clear. Differential DNA methylation may explain this association. OBJECTIVES: Our main aim was to study the association between long-term air pollution exposure and DNA methylation. METHODS: We performed a genome-wide methylation study using robust linear regression models in 1,017 subjects from the LifeLines cohort study to analyze the association between exposure to nitrogen dioxide (NO2) and particulate matter (PM2.5, fine particulate ma

Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity

Epidermal growth factor receptor is a potential target for cancer treatment and new small-molecule tyrosine kinase inhibitor drugs have been designed to inhibit its activity. In this work we identify potential surrogate markers of drug activity using a proteomic analysis. Two-dimensional electrophoresis was optimised to compare expression patterns of proteins secreted from the cancer cell lines A431 and A549 treated with Gefitinib (Iressa) vs untreated or vehicle-only-treated samples. Upregulated or downregulated proteins were detected using Phoretix 2D image analysis software. Several proteins were then identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. In one case, upregulation of Protein Disulphide Isomerase in response to Gefitinib was confirmed by Western blot analysis, and the response was shown to be concentration dependent. The identification of surrogate markers may be of use for the evaluation of new drugs, in preclinical models, in clinical trials and in the therapy of individual patients to give optimal biological drug doses

Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) gene involved in the regulation of cellular ubiquitin levels plays an important role in different cellular processes including cell growth and differentiation. Aberrant expression of UCHL1 has been found in a number of human solid tumors including renal cell carcinoma (RCC). In RCC, UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression.</p> <p>Methods</p> <p>To determine the underlying mechanisms for the heterogeneous UCHL1 expression pattern in RCC the UCHL1 promoter DNA methylation status was determined in 17 RCC cell lines as well as in 32 RCC lesions and corresponding tumor adjacent kidney epithelium using combined bisulfite restriction analysis as well as bisulfite DNA sequencing.</p> <p>Results</p> <p>UCHL1 expression was found in all 32 tumor adjacent kidney epithelium samples. However, the lack of or reduced UCHL1 mRNA and/or protein expression was detected in 13/32 RCC biopsies and 7/17 RCC cell lines and due to either a total or partial methylation of the UCHL1 promoter DNA. Upon 2'-deoxy-5-azacytidine treatment an induction of UCHL1 mRNA and protein expression was found in 9/17 RCC cell lines, which was linked to the demethylation degree of the UCHL1 promoter DNA.</p> <p>Conclusion</p> <p>Promoter hypermethylation represents a mechanism for the silencing of the UCHL1 gene expression in RCC and supports the concept of an epigenetic control for the expression of UCHL1 during disease progression.</p

Proteome Serological Determination of Tumor-Associated Antigens in Melanoma

Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2–6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins

Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

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