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BACKGROUND: Leishmania tarentolae is a non-pathogenic species found in lizards representing an important model for Leishmania biology. However, several aspects of this Sauroleishmania remain unknown to explain its low level of virulence. OBJECTIVES: We reported several aspects of L. tarentolae biology including glycoconjugates, proteolytic activities and metabolome composition in comparison to pathogenic species (Leishmania amazonensis, Leishmania braziliensis, Leishmania infantum and Leishmania major). METHODS: Parasites were cultured for extraction and purification of lipophosphoglycan (LPG), immunofluorescence probing with anti-gp63 and resistance against complement. Parasite extracts were also tested for proteases activity and metabolome composition. FINDINGS: Leishmania tarentolae does not express LPG on its surface. It expresses gp63 at lower levels compared to pathogenic species and, is highly sensitive to complement-mediated lysis. This species also lacks intracellular/extracellular activities of proteolytic enzymes. It has metabolic differences with pathogenic species, exhibiting a lower abundance of metabolites including ABC transporters, biosynthesis of unsaturated fatty acids and steroids, TCA cycle, glycine/serine/threonine metabolism, glyoxylate/dicarboxylate metabolism and pentose-phosphate pathways. MAIN CONCLUSIONS: The non-pathogenic phenotype of L. tarentolae is associated with alterations in several biochemical and molecular features. This reinforces the need of comparative studies between pathogenic and non-pathogenic species to elucidate the molecular mechanisms of virulence during host-parasite interactions.

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BACKGROUND Leishmania tarentolae is a non-pathogenic species found in lizards representing an important model for Leishmania biology. However, several aspects of this Sauroleishmania remain unknown to explain its low level of virulence. OBJECTIVES We reported several aspects of L. tarentolae biology including glycoconjugates, proteolytic activities and metabolome composition in comparison to pathogenic species (Leishmania amazonensis, Leishmania braziliensis, Leishmania infantum and Leishmania major). METHODS Parasites were cultured for extraction and purification of lipophosphoglycan (LPG), immunofluorescence probing with anti-gp63 and resistance against complement. Parasite extracts were also tested for proteases activity and metabolome composition. FINDINGS Leishmania tarentolae does not express LPG on its surface. It expresses gp63 at lower levels compared to pathogenic species and, is highly sensitive to complement-mediated lysis. This species also lacks intracellular/extracellular activities of proteolytic enzymes. It has metabolic differences with pathogenic species, exhibiting a lower abundance of metabolites including ABC transporters, biosynthesis of unsaturated fatty acids and steroids, TCA cycle, glycine/serine/threonine metabolism, glyoxylate/dicarboxylate metabolism and pentose-phosphate pathways. MAIN CONCLUSIONS The non-pathogenic phenotype of L. tarentolae is associated with alterations in several biochemical and molecular features. This reinforces the need of comparative studies between pathogenic and non-pathogenic species to elucidate the molecular mechanisms of virulence during host-parasite interactions.

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OBJECTIVE: This study aimed to analyze the urinary concentrations of As, Cd, Pb, Hg, and Mn in children living in areas directly affected by the tailings of the Brumadinho disaster. METHODS: We performed a cross-sectional descriptive study on a population of 217 children aged 0 to 6 years, living in Córrego do Feijão (CF), Parque da Cachoeira (PC), Aranha (AR), and Tejuco (TJ), enrolled in the Longitudinal Study of Child Health in Brumadinho (Minas Gerais) - Projeto Bruminha. Socioeconomic data and urine samples were collected to determine the concentration of selected metals. RESULTS: Children living in locations not directly affected by the disaster (AR and TJ) had higher concentrations of As and Mn than those in directly affected areas (CF and PC). Additionally, children living in locations not potentially exposed to dust from tailings mud or mining activity (AR) showed higher urinary As concentrations than those potentially exposed (CF, PC, and TJ). CONCLUSION: Our results suggest the need to investigate possible sources of As exposure in children living in areas not directly affected by the disaster and not potentially exposed to dust.

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ABSTRACT Objective: This study aimed to analyze the urinary concentrations of As, Cd, Pb, Hg, and Mn in children living in areas directly affected by the tailings of the Brumadinho disaster. Methods: We performed a cross-sectional descriptive study on a population of 217 children aged 0 to 6 years, living in Córrego do Feijão (CF), Parque da Cachoeira (PC), Aranha (AR), and Tejuco (TJ), enrolled in the Longitudinal Study of Child Health in Brumadinho (Minas Gerais) — Projeto Bruminha. Socioeconomic data and urine samples were collected to determine the concentration of selected metals. Results: Children living in locations not directly affected by the disaster (AR and TJ) had higher concentrations of As and Mn than those in directly affected areas (CF and PC). Additionally, children living in locations not potentially exposed to dust from tailings mud or mining activity (AR) showed higher urinary As concentrations than those potentially exposed (CF, PC, and TJ). Conclusion: Our results suggest the need to investigate possible sources of As exposure in children living in areas not directly affected by the disaster and not potentially exposed to dust.

RESUMO Objetivo: Este estudo teve como objetivo analisar as concentrações urinárias de As, Cd, Pb, Hg e Mn em crianças residentes em localidades diretamente atingidas pelos rejeitos do desastre em Brumadinho. Métodos: Foi realizado um estudo descritivo transversal de uma população de 217 crianças de 0 a 6 anos, residentes no Córrego do Feijão (CF), Parque da Cachoeira (PC), Aranha (AR), e Tejuco (TJ) e inscritas no Estudo Longitudinal da Saúde Infantil em Brumadinho (MG) — Projeto Bruminha. Dados socioeconômicos e amostras de urina foram coletados para determinar a concentração dos metais selecionados. Resultados: Crianças residentes em localidades não diretamente atingidas pelo desastre (AR e TJ) apresentaram maiores concentrações de As e Mn do que aquelas em localidades diretamente atingidas (CF e PC). Adicionalmente, crianças residentes em localidades não potencialmente expostas à poeira da lama de rejeito ou da atividade de mineração (AR) apresentaram maiores concentrações urinárias de As do que aquelas potencialmente expostas (CF, PC e TJ). Conclusão: Nossos resultados sugerem a necessidade de se investigar possíveis fontes de exposição ao As em crianças residentes em localidades não diretamente atingidas pelo desastre e não potencialmente expostas à poeira.

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OBJECTIVE: To describe the prevalence of levels of arsenic, cadmium, mercury, lead and manganese above the reference values (RV) in the population of Brumadinho, after the rupture of the mining tailings dam and to verify the factors associated with these levels. METHODS: Baseline study of a prospective cohort, in a representative sample of 3,080 residents (aged 12 and over) in Brumadinho, Minas Gerais. Exploratory variables (age, sex, skin color, household income, smoking and place of residence) were collected using a questionnaire and the levels of As, Cd and Hg in urine and Pb and Mn in blood were evaluated using the technique of inductively coupled plasma mass spectrometry. The distribution of prevalence of levels above the reference for metals was made, according to the exploratory variables. Multiple logistic regression analyzes were used to investigate the association between altered levels of metals and characteristics evaluated. RESULTS: Concentrations above RV were found in 38.08% of the population for Mn, 33.37% for As, 5.04% for Pb, 0.76% for Hg and 0.17% for Cd. There was a significant association between age group and levels of Mn and Pb; and between place of residence and As level. CONCLUSION: The results show a high prevalence of levels above the reference for Mn, As and Pb, with small differences in relation to the other variables, suggesting that it is an exposure distributed throughout the municipality.

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ABSTRACT Objective: To describe the prevalence of levels of arsenic, cadmium, mercury, lead and manganese above the reference values (RV) in the population of Brumadinho, after the rupture of the mining tailings dam and to verify the factors associated with these levels. Methods: Baseline study of a prospective cohort, in a representative sample of 3,080 residents (aged 12 and over) in Brumadinho, Minas Gerais. Exploratory variables (age, sex, skin color, household income, smoking and place of residence) were collected using a questionnaire and the levels of As, Cd and Hg in urine and Pb and Mn in blood were evaluated using the technique of inductively coupled plasma mass spectrometry. The distribution of prevalence of levels above the reference for metals was made, according to the exploratory variables. Multiple logistic regression analyzes were used to investigate the association between altered levels of metals and characteristics evaluated. Results: Concentrations above RV were found in 38.08% of the population for Mn, 33.37% for As, 5.04% for Pb, 0.76% for Hg and 0.17% for Cd. There was a significant association between age group and levels of Mn and Pb; and between place of residence and As level. Conclusion: The results show a high prevalence of levels above the reference for Mn, As and Pb, with small differences in relation to the other variables, suggesting that it is an exposure distributed throughout the municipality.

RESUMO Objetivo: Descrever a prevalência dos níveis dos metais arsênio, cádmio, mercúrio, chumbo e manganês acima dos valores de referência (VR) na população de Brumadinho, após o rompimento da barragem de rejeitos de mineração, e verificar os fatores associados a esses níveis. Métodos: Estudo da linha de base de uma coorte prospectiva, em amostra representativa de 3.080 residentes (12 anos ou mais de idade) de Brumadinho, Minas Gerais. As variáveis exploratórias (idade, sexo, cor de pele, renda domiciliar, tabagismo e local de residência) foram coletadas por questionário, e os níveis de As, Cd e Hg na urina e de Pb e Mn no sangue foram avaliados pela técnica de espectrometria de massa com plasma indutivamente acoplado. Fez-se a distribuição das prevalências de níveis acima da referência para os metais, segundo as variáveis exploratórias. Análises de regressão logística múltipla foram utilizadas para averiguar associação entre os níveis alterados de metais e as características avaliadas. Resultados: Encontraram-se concentrações acima do VR em 38,08% da população para Mn, 33,37% para As, 5,04% para Pb, 0,76% para Hg e 0,17% para Cd. Houve associação significativa entre a faixa etária e os níveis de Mn e Pb; e entre o local de residência e o nível de As. Conclusão: Os resultados demonstram elevada prevalência de níveis acima da referência para Mn, As e Pb, com pequenas diferenças em relação às demais variáveis, sugerindo se tratar de uma exposição distribuída em todo o município.

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Endocrine disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) are substances that may interfere with the actions of endogenous hormones and may be associated with estrogen-related diseases such as endometriosis. This paper describes a case-control study to evaluate the relationship between endometriosis and phthalates and BPA exposure, through biomarkers analysis in urine. The biomarkers of exposure analyzed were metabolites mono-methyl phthalate, mono-isobutyl phthalate (MiBP), mono-butyl phthalate, mono-cyclohexyl phthalate, mono-(ethylhexyl) phthalate, mono-isononyl phthalate, mono-octyl phthalate (MOP), mono-benzyl phthalate and BPA. Urine samples were collected from women aged 18-45 years old. The Study group (n = 30) and Control group (n = 22) were composed of women using as criteria confirmation of endometriosis by videolaparoscopy surgery with histological diagnosis and the absence of the disease, respectively. The analytical method used liquid phase microextraction with determination by gas chromatography coupled to mass spectrometry. The concentrations of biomarkers were adjusted by the creatinine concentration in urine samples of the two groups. The values obtained for the Study Group were compared with the values obtained for the Control Group. The chi-square test and Odds Ratio were used to compare dichotomized phthalate metabolites and BPA metabolite by endometriosis. All nine metabolites were found in different concentrations in the urine samples in both groups The phthalate metabolites that had the highest concentrations, were MOP and MiBP, in which the values of 670 µg g-1 and 560 µg g-1, respectively. The relationship between endometriosis and the all grouped metabolites was evaluated, but was not statistically significant with a 95% CI [X2 (df = 1) = 1.471; p = 0.225]. However, odds ratio (95% confidence interval - CI) for MiBP, which was found at relatively high concentrations in the samples, by endometriosis was 1.929 (0.507-7.332). The food habits and gynecologic history were evaluated and no difference was found between groups. Although no evidences of causal link was found, this study contributes to show that other analysis must be done for evaluating the association between endometriosis and compounds suspected of being EDC.

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BACKGROUND: Oral Lichen Planus is a chronic inflammatory disorder that affects the oral mucosa, with the reticular and erosive forms representing the primary clinical variants of the disease. Previous studies have shown that metabolic alterations may well be involved in the pathogenesis of the disease; however, the molecular mechanisms related to the clinicopathological differences between erosive and reticular forms remain unknown. METHODS: A comparative metabolomic analysis was performed on formalin-fixed and paraffin-embedded tissue samples of erosive (n = 6) and reticular (n = 10) oral lichen planus using gas chromatography-mass spectrometry. RESULTS: The metabolomic analysis showed a distinct profile between the two clinical variants. Five metabolites (cyclohexanamine, glycine, mannitol/sorbitol, methyl palmitate and trehalose) were significantly diminished in erosive oral lichen planus as compared to the reticular form. CONCLUSIONS: Reticular and erosive forms of oral lichen planus have a distinct metabolic profile. However, further studies using a large number of fresh tissue samples are necessary to confirm this data.

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BACKGROUND: Ameloblastoma is a locally infiltrative, aggressive epithelial odontogenic neoplasm. BRAF-V600E mutation is frequently found in this tumor and has a pivotal role in its pathogenesis, but the consequences of this alteration need to be addressed. An untargeted metabolomics approach was applied to verify whether metabolic disturbances are related to tumor biology and whether BRAF-V600E mutation contributes to these alterations. METHODS: Formalin-fixed and paraffin-embedded tissue specimens from thirteen ameloblastoma and six dental follicles were included in this study. BRAF mutational status was determined by competitive allele-specific real-time PCR. Metabolite extracts were analyzed using gas chromatography coupled to mass spectrometry. Univariate and multivariate statistical methods were employed to compare the metabolic profiles of the samples. RESULTS: The abundance of eleven metabolites was significantly higher in ameloblastoma in relation to dental follicles, including amino acids, fatty acids, carbohydrates, inorganic acids, and organoheterocyclic compounds. The presence of BRAF-V600E mutations in ameloblastoma was related to decreased levels of glycerol in comparison with tumors carrying only wild-type alleles of this gene. No metabolic differences were observed between recurrent and primary manifestations of ameloblastoma. CONCLUSIONS: Ameloblastoma exhibits a distinct metabolic profile from normal odontogenic epithelium. BRAF-V600E may contribute to metabolic alterations in ameloblastoma. Collectively, our findings suggest that metabolic alterations might play a role in tumor pathogenesis.

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Phthalates and bisphenol A are important environmental pollutants due to their toxicity for humans and animals, including actions in the endocrine system. Their metabolites in urine can be used as biomarkers to assess human exposure. This paper describes the development of a new method to determine bisphenol A and eight phthalate metabolites in urine samples using hollow fiber liquid phase microextraction (HF-LPME) and gas chromatography-mass spectrometry (GC-MS). This method showed linearity, precision, limits of detection, and quantification suitable to analyze these compounds at low concentration levels in urine. Limits of detection ranged from 0.777 to 23.3µgL-1, showing sensitivity for evaluating environmental exposure. Relative standard deviation (RSD) ranged from 11.7 to 19.7%. The developed method presented a good biomarker alternative for evaluating environmental exposure to bisphenol A and phthalates.

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