Integrated proteomics identified up-regulated focal adhesion-mediated proteins in human squamous cell carcinoma in an orthotopic murine model

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by co95e98208FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2009/54067-3; 2010/19278-0; 2011/22421-2; 2009/53839-2; 2011/02267-9470567/2009-0; 470549/2011-4; 301702/2011-0; 470268/2013-1; 505413/2013-

Concentrações sangüíneas de metais pesados e praguicidas organoclorados em crianças de 1 a 10 anos

Foi realizado estudo em 6 bairros do Município de Cubatão, SP, Brasil, situados às margens dos principais rios do município, com uma amostragem de 251 crianças de 1 a 10 anos de idade. Foram verificadas as concentrações sangüíneas de praguicidas organoclorados em 242 crianças, sendo que 73 crianças (30%) apresentaram concentrações de p-p'DDE (média = 0,85 ± 2,13 µg/l.), e em 47 crianças (19%) foi encontrado HCH total (média = 0,28 ± 0,79 µg/l.). Verificou-se também a concentração sangüínea de chumbo e mercúrio, sendo que se obteve a plumbemia média de 17,8 ± 5,8 µg/dl. e concentração média de mercúrio de 9,1 ± 6,4 µg/l. Crianças consumidoras de organismos aquáticos de origem exclusiva dos rios de Cubatão apresentaram teores médios de mercúrio (média = 14,7 ±7,1 µg/l.) significativamente maiores (p < 0,04) em comparação às crianças não consumidoras de organismos aquáticos de qualquer origem (média = 10,0 ± 6,5 µg/l.).A study of a sample of 251 children aged between 1 and 10 was carried out in 6 districts of Cubatão county, S. Paulo State, Brazil. This study showed the presence of organochlorine pesticides in the blood serum of 242 children, p-p' DDE was detected in 73 of the samples (30%) and HCH in 47 them (19%). The mean value of p-p' DDE was 0.85 ± 2.13 µg/l. and that of HCH was 0.28 ± 0.79 µg/l. Lead and mercury were also detected in the blood serum. The mean value for lead was 17.8 ± 5.8 µg/l. and for mercury was 9.1 ± 0.79 µg/l. The levels found in consumers of aquatic organisms taken from the rivers of Cubatão showed a mean mercury level (mean = 14.7 ± 7.1 µg/l.) higher than (p < 0.04) that of those who did not consume any aquatic organisms at all (mean = 10.0 ± 6.5 µg/l.)

Assessment of the risk of burnout and its associated factors in healthcare professionals during the COVID-19 pandemic: A prospective cohort study

IntroductionThe COVID-19 pandemic resulted in tremendous physical and psychological pressure on healthcare professionals, especially on those working in intensive care units (ICUs) and Emergency Departments (EDs). The present study intended to characterize the profile of these professionals which is associated with burnout and determine the potential predictors of such condition.MethodsA Prospective cohort study was carried out in a tertiary hospital between March 2020 and March 2021, in Salvador, Brazil. A standardized and validated version of the Oldenburg Burnout inventory (OLBI) was applied to assess risk of burnout together with data forms designed to collect information on sociodemographic characteristics and religious beliefs. ICU and ED healthcare professionals were evaluated during off-hours at two distinct periods of the COVID-19 pandemic, in 2020 and in 2021. Differences in the results obtained from each study participant between the timepoints were compared. A binary logistic regression analysis was performed to identify the predictors of burnout development independent of other confounding factors.ResultsSeventy-seven healthcare professionals with a median age of 33 (interquartile range [IQR]: 31–37.5) years and predominantly female (72.7%; n = 56) were enrolled. There were 62 professionals at risk of developing burnout through the OLBI. Those had a median age of 33 (IQR: 31–37) and female predominance (71%, n = 44). Disengagement and burnout were the only features which frequencies significantly changed over time, with increasing detection at the latest timepoint. Alcohol consumption was found to be an important risk factor for burnout development [adjusted odds ratio (aOR): 10.8 (95% CI: 1.8–64.2)]. Importantly, working in the ICU [aOR: 0.04 (95%CI: 0.01–0.32)] and the habit of praying daily [aOR: 0.07 (95%CI: 0.01–0.41)] were characteristics linked to reduced odds of burnout.DiscussionDisengagement substantially increased during the COVID-19 pandemic in healthcare professionals. Alcohol consumption favors the onset of burnout whereas habit of praying daily and working in the ICU are protective against such outcome. Institutional policies aimed at minimizing etilism may positively impact mental health of these professionals

Levels of exposure to organochlorine pesticides in open-air dump dwellers

OBJECTIVE: To estimate the degree of internal exposure to organochlorine pesticides (persistent organic pollutants, POP) among inhabitants of an open-air dump. METHODS: This was an observational study with simultaneous measurement and control, in which the criterion for subjects was that they dwelled in an area contaminated by POP and the effect of such contamination was the concentration of such substances into the blood. The study population consisted of 238 people living on an open-air dump in Pilões, in the municipality of Cubatão, SP, Brazil, and the control population was formed by 258 people, also resident in that municipality, in the Cota 200 district. The following pesticides were analysed: hexachlorobenzene (HCB), p-p'DDT, p-p'DDE, p-p'DDD, o-p'DDT, a HCH (hexachlorocyclohexane); b HCH; g HCH; aldrin; dieldrin; endrin; heptachlor; heptachlor-epoxy and mirex. RESULTS: The average blood level of HCB in Pilões was 4.66 µg/l, which was 155 times higher than the average for Cota 200 (0.03 µg/l). In Pilões the average blood concentration of total DDT was 3.71 µg/l, which was twice the level found in Cota 200 (1.85 µg/l). Total HCH presented blood concentrations that were six times greater in Pilões (0.84 µg/l versus 0.13 µg/l). CONCLUSIONS: A positive association was shown between dwelling in Pilões and the presence of POP in the blood, with much higher risks than in localities without the presence of these contaminants.OBJETIVO: Estimar o grau de exposição interna aos praguicidas organoclorados (POP) dos moradores de um atêrro a céu aberto. MÉTODOS: Estudo observacional, de aferição simultânea e controlado, cujo fator de estudo foi residir em área contaminada por POP e o efeito foi a concentração sanguínea dessas substâncias. A população de estudo foi de 238 pessoas residentes em um aterro a céu aberto (Pilões), no município de Cubatão, SP; e a população de controle ficou dimensionada em 258 pessoas, também residentes no mesmo município (Cota 200). Foram analisados os praguicidas HCB, p-p'DDT, p-p'DDE, p-p'DDD, o-p'DDT, a HCH; b HCH; g HCH; Aldrin; Dieldrin; Endrin; Heptaclor; Heptaclor-epoxi e Mirex. RESULTADOS: Os teores médios sangüíneos de HCB em Pilões foram de 4,66 µg/L, 155 vezes maior que a média na Cota 200 (0,03 µg/L). Em Pilões, os teores médios de DDT total foram de 3,71 µg/L, duas vezes maior do que na Cota 200 (1,85 µg/L) e o HCH total apresentou concentrações sangüíneas seis vezes maiores em Pilões, 0,84 µg/L, contra 0,13 µg/L. CONCLUSÕES: Evidenciou-se associação positiva entre residir em Pilões e apresentar teores sangüíneos de POP, com risco muitas vezes maior quando comparado a localidades sem a presença desses contaminantes

Integrative analysis to select cancer candidate biomarkers to targeted validation

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOTargeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS.Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS6414363543652FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2009/54067-3; 2010/19278-0; 2011/22421-2; 2009/53839-2470567/2009-0; 470549/2011-4; 301702/2011-0; 470268/2013-

Use of Opuntia ficus-indica (L.) Mill extracts from Brazilian Caatinga as an alternative of natural moisturizer in cosmetic formulations

ABSTRACT The aim of this work was the obtainment of Opuntia fícus-indica (L.) Mill extract for the development of cosmetic formulations and in vivo evaluation of its moisturizing effects. The formulations were tested for preliminary and accelerated stability. Organoleptic characteristics, pH values and rheological behavior were assessed. The evaluation of moisturizing efficacy of the emulsions formulated with 3.0% of Polyacrylamide (and) C13-14 Isoparaffin (and) Laureth-7 containing 1.0 and 3.0% of O. ficus-indica hydroglycolic extract (EHG001) was performed using the capacitance method (Corneometer(r)) and the transepidermal water loss - TEWL evaluation (Tewameter(r)). The emulsions formulated were stable, exhibiting pseudoplastic and thixotropic behavior. The results of evaluation of moisturizing efficacy showed increased skin hydration after five hours by mainly increasing the skin barrier effect. The formulations containing 1.0 and 3.0% of EHG001 enhanced the skin barrier effect by reducing TEWL up to four hours after application. The results observed suggest that O. ficus-indica hydroglycolic extract may act through a humectant and occlusion mechanism