21 results on '"Dos Santos EO"'
Search Results
2. A comprehensive epidemiological assessment of female rape in São Paulo State, Brazil: trends, patterns, and implications for public health.
- Author
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Dos Santos EO, Moscardini AW, and Miziara ID
- Abstract
Sexual violence against women remains a global challenge, with Brazil exemplifying persistent issues despite legislative advancements. This study examined sexual violence within São Paulo state, Brazil's largest and economically affluent state, focusing on prevalence, patterns, forensic evidence, and health consequences. We analyzed 40,757 medical reports of alleged cases of rape against women available from the São Paulo Medical Legal Institute from 2014 to 2017. An increase in female rape cases was observed, reflecting broader societal trends, but underreporting, prevalent due to fear and stigma, underscored the need for multifaceted interventions. We also explored correlations between rape prevalence and the Human Development Index, highlighting disparities between urban and rural areas. Additionally, the study revealed concerning proportions of cases involving vulnerable victims, emphasizing the imperative for tailored interventions and legislative reforms. Furthermore, we demonstrated that only a small portion of medicolegal examinations were able to find evidence of sexual violence or recent sexual acts, necessary for conducting the criminal investigation of the alleged act. Therefore, despite challenges in forensic evidence collection, efforts to enhance medical examination protocols and awareness among professionals are crucial. Moreover, findings underscored the significant health consequences of rape, including unwanted pregnancies and sexually transmitted infections, necessitating comprehensive healthcare services for survivors. In conclusion, we reinforced that addressing sexual violence demands coordinated action, including legislative reforms, community engagement, and survivor-centered approaches, to create safer and more resilient communities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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3. Correction: Aurora kinase targeting in lung cancer reduces KRAS-induced transformation.
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Dos Santos EO, Carneiro-Lobo TC, Aoki MN, Levantini E, and Bassères DS
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- 2024
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4. Characterization of male sexual assault in the state of São Paulo, Brazil: an epidemiological study from 2014 to 2017.
- Author
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Dos Santos EO, Moscardini AW, and Miziara ID
- Subjects
- Humans, Male, Female, Brazil epidemiology, Cross-Sectional Studies, Epidemiologic Studies, Crime Victims, Sex Offenses, Rape
- Abstract
Sexual violence is a pervasive global issue that affects individuals of all genders. However, the experiences of male survivors have often been marginalized and inadequately represented. Male rape, which encompasses several forms of sexual violence against men, remains a sensitive and under-discussed topic in academic literature and public discourse. This study presents a descriptive cross-sectional analysis based on data collected from the Legal Medicine Institute (IML-São Paulo, Brazil) between 2014 and 2017. The analysis includes 7386 reports of sexological examinations performed on male victims of alleged rape. The analysis reveals that a significant majority of rape reports involved victims under the age of 12 or 14, which is considered vulnerable rape by the Brazilian legislation. Regarding the examination of reported cases of abuse against men, it was observed that only the minority of these cases exhibited visible injuries consistent with rape or tested positive for the presence of spermatozoa in the perianal region. Since the absence of visible injuries or spermatozoa does not negate the possibility of rape, this work highlights the challenges in obtaining conclusive evidence, necessitating a comprehensive approach to investigate and prosecute these crimes, creating a more inclusive and supportive environment for all survivors of rape, irrespective of their gender., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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5. Calcium anacardate and its association with citric acid in diets for meat-type breeding quails.
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Freitas ER, da Silva CP, Gomes TR, Nepomuceno RC, Dos Santos EO, Silva VS, Rocha LLCV, and Trevisan MTS
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- Animals, Female, Male, Coturnix, Ovum, Calcium, Dietary, Diet veterinary, Meat, Citric Acid, Lipids, Calcium, Quail
- Abstract
The purpose of this study was to evaluate the effects of using calcium anacardate (CaA) as a source of anacardic acid and its association with citric acid (CA) in diets for breeding quails on the performance, the egg quality, incubation parameters, and progeny performance. Were used 540 quails European quails (Coturnix coturnix coturnix) that were 21 weeks old, housed in laying cages based on a completely randomized design, with nine treatments and six replications of 10 quails per parcel, with each experimental unit having eight females and two males. The following additions to the diet were evaluated: 1, no addition (control diet); 2, 0.25% CaA; 3, 0.25% CaA and 0.25% CA; 4, 0.50% CaA; 5, 0.50% CaA and 0.25% CA; 6, 0.50% CaA and 0.50% CA; 7, 0.75% CaA; 8, 0.75% CaA and 0.25% CA; and 9, 0.75% CaA and 0.50% CA. The treatments had no significant effects on the performance of the breeding quails, incubation parameters, and progeny performance. For egg quality, there was only an effect on yolk lipid oxidation, which was lower for eggs from quails fed the diets containing 0.50% CaA and 0.25% CA, 0.50% CaA and 0.50% CA, or 0.75% CaA alone, when compared with the control group. Considering that including CaA with or without CA in diets for breeding quails only affected yolk lipid oxidation, it can be recommend including 0.50% CaA and 0.25% CA or 0.75% CaA alone to mitigate oxidative damage in the yolk of fertile eggs., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2023
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6. Influence of landscape structure on previous exposure to Leptospira spp. and Brucella abortus in free-living neotropical primates from southern Brazil.
- Author
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Dos Santos EO, Klain VF, B Manrique S, Rodrigues RO, Dos Santos HF, Sangioni LA, Dasso MG, de Almeida MAB, Dos Santos E, Born LC, Reck J, and Botton SA
- Subjects
- Animals, Brucella abortus, Brazil epidemiology, Antibodies, Bacterial, Leptospira, Leptospirosis epidemiology, Leptospirosis veterinary, Brucellosis epidemiology, Brucellosis veterinary, Brucellosis microbiology, Alouatta caraya, Cebinae
- Abstract
The environments in which neotropical primates live have been undergoing an intense fragmentation process, constituting a major threat to the species' survival and causing resource scarcity, social isolation, and difficulty in dispersal, leaving populations increasingly vulnerable. Moreover, the proximity of wild environments to anthropized landscapes can change the dynamics of pathogens and the parasite-host-environment relationship, creating conditions that favor exposure to different pathogens. To investigate the previous exposure of free-living primates in Rio Grande do Sul State (RS), southern Brazil, to the bacterial agents Leptospira spp. and Brucella abortus, we investigated agglutinating antibodies against 23 serovars of Leptospira spp. using the microscopic agglutination test and B. abortus acidified antigen test in primate serum samples; 101 samples from primates captured between 2002 and 2016 in different forest fragments were used: 63 Alouatta caraya, 36 Alouatta guariba clamitans, and 02 Sapajus nigritus cucullatus. In addition, the forest remnants where the primates were sampled were characterized in a multiscale approach in radii ranging from 200 to 1400 m to investigate the potential relationship of previous exposure to the agent with the elements that make up the landscape structure. The serological investigation indicated the presence of antibodies for at least one of the 23 serovars of Leptospira spp. in 36.6% (37/101) of the samples analyzed, with titers ranging from 100 to 1600. The most observed serovars were Panama (17.8%), Ballum (5.9%), Butembo (5.9%), Canicola (5.9%), Hardjo (4.9%), and Tarassovi (3.9%); no samples were seropositive for Brucella abortus. Decreased forest cover and edge density were the landscape factors that had a significant relationship with Leptospira spp. exposure, indicating that habitat fragmentation may influence contact with the pathogen. The data generated in this study demonstrate the importance of understanding how changes in landscape structure affect exposure to pathogenic microorganisms of zoonotic relevance. Hence, improving epidemiological research and understanding primates' ecological role in these settings can help improve environmental surveillance and conservation strategies for primate populations in different landscapes., (© 2023 Wiley Periodicals LLC.)
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- 2023
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7. The Influence of Landscape Structure on the Occurrence of Neospora caninum, Toxoplasma gondii, and Sarcocystis spp. in Free-Living Neotropical Primates.
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Dos Santos EO, Klain VF, Manrique SB, Roman IJ, Dos Santos HF, Sangioni LA, Vogel FSF, Reck J, Webster A, Padilha TC, de Almeida MAB, Dos Santos E, Born LC, and Botton SA
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- Animals, Antibodies, Protozoan, Brazil epidemiology, Immunoglobulin G, Seroepidemiologic Studies, Neospora, Sarcocystis, Toxoplasma, Alouatta, Toxoplasmosis, Animal epidemiology, Coccidiosis epidemiology, Coccidiosis veterinary
- Abstract
Purpose: Habitat fragmentation is the main threat to primate survival in the world. Additionally, changes in the environments in which they live can also contribute to exposure to pathogens. To investigate some pathogens that free-living primates may be exposed to in Rio Grande do Sul State (RS; southern Brazil) and characterize the forest remnants in which they live, we investigated anti-Neospora caninum, Toxoplasma gondii, and Sarcocystis spp. antibodies in the serum of the animals., Methods: We analyzed 105 serum samples from 63 black howler monkeys (Alouatta caraya), 39 southern brown howler monkeys (Alouatta guariba clamitans), and 03 capuchin monkeys (Sapajus nigritus cucullatus), which were captured in forest fragments of RS. Indirect fluorescence antibody test (IFAT) and indirect hemagglutination assay (IHA) were used to detect antibodies to the agents. We then characterized the landscapes in a multiscale approach in radii from 200 to 1400 m to investigate the relationship of the presence of the agents with landscape elements., Results: In the IFAT-IgG, 13.3% (14/105) of the samples were seropositive for N. caninum, 4.8% (5/105) for T. gondii, and 5.7% (6/105) for Sarcocystis spp. In the IHA-IgM/IgG, 24.8% (26/105) were seropositive for T. gondii. The metrics that best explained exposure to agents were edge and patch density, forest cover, urban cover, and average Euclidean distance to the nearest patch., Conclusions: This study indicated that the primates were exposed to the agents studied, demonstrating that some landscape features are associated with exposures to the investigated pathogens., (© 2022. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)
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- 2022
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8. Passion fruit seed cake in the feeding of meat quails: effects on performance, carcass characteristics, lipid stability of the meat, litter quality, and economic viability.
- Author
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Silva TF, Freitas ER, Gomes TR, Nepomuceno RC, de Souza OF, Dos Santos EO, de Melo MCA, and de Oliveira Lima PJD
- Subjects
- Animals, Diet veterinary, Fruit, Lipids, Meat analysis, Animal Feed analysis, Quail
- Abstract
The objective of this study was to determine the chemical composition and energy value of passion fruit seed cake (PFSC) and to evaluate the inclusion of different levels of PFSC in the diets for quails on growth performance, carcass quality, litter quality, lipid stability of the meat, and economic viability. In the metabolism assay, 108 European quails of 21 days of age were used, being distributed in a completely randomized design with 3 treatments (one reference ration and two test rations with substitution of 20% and 40% of the reference ration by PFSC) and 6 replications of 6 birds each. It was observed that the apparent metabolizable energy corrected by the nitrogen balance (AMEn) determined in the ration with 20% PFSC (3876.17 kcal/kg DM) was higher than in the 40% (3469.00 kcal/kg DM). In the performance assay, 432 European quails from 7 to 42 days of age were used, being distributed in a completely randomized design with 6 treatments, consisting of a control diet and the others with increasing levels of inclusion of passion fruit seed (5, 10, 15, 20, and 25%), and 6 replications of 12 birds. It was observed that the inclusion of PFSC starting from 10% promoted increase FI and FC values, and increasing linear effect of these variables starting from 5% of inclusion. The PFSC did not affect the carcass characteristics and lipid oxidation of the meat. Regarding the litter quality, there was a linear increase in the pH values and worse economic indexes starting from the inclusion of 10% of PFSC. In conclusion, PFSC can be used up to the level of 5% in diets for meat quails from 7 to 42 days of age., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2021
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9. Organic zinc and manganese and 25-hydroxycholecalciferol improves eggshell thickness in late-phase laying hens.
- Author
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Dos Santos EO, Freitas ER, Nepomuceno RC, Watanabe PH, Souza DH, Fernandes DR, de Abreu Freitas C, do Nascimento GAJ, Aguiar GC, and de Melo MCA
- Subjects
- Animal Feed analysis, Animals, Calcifediol pharmacology, Chickens, Diet veterinary, Dietary Supplements, Eggs, Female, Ovum, Zinc, Egg Shell, Manganese
- Abstract
The aim of this study was to evaluate the effects of organic micromineral zinc (Zn) and manganese (Mn) and 25-hydroxycholecalciferol supplementation in late-phase laying hens' diets on performance, egg quality, lipid stability of fresh and stored eggs, and bone quality. The treatments were a basal diet and diets supplemented with 32 mg Zn-Met/kg diet; 26 mg Mn-Met/kg diet; 32 mg Zn-Met/kg diet and 26 mg Mn-Met/kg diet; 1500 IU 25-hydroxycholecalciferol/kg diet; 32 mg Zn-Met/kg diet; 26 mg Mn-Met/kg diet; and 1500 IU 25-hydroxycholecalciferol/kg diet. On performance, the birds supplemented with organic manganese had the lowest feed intake. Regarding egg quality, the birds supplemented with Zn-Met and Mn-Met, with 25-hydroxycholecalciferol alone, and with Zn-Met, Mn-Met and 25-hydroxycholecalciferol presented a greater eggshell thickness than those receiving the basal diet. Lipid stability of the yolk varied only according to storage time. No effect of supplementation was observed on bone quality. Supplementation with Zn-Met and Mn-Met, or associated with 25-hydroxycholecalciferol, or 25-hydroxycholecalciferol alone, improved eggshell thickness in aged white layers. However, the associated or isolated supplementation with these nutrients did not influence performance, lipid stability of fresh and stored egg yolk or bone quality., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2021
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10. Aurora A kinase and its activator TPX2 are potential therapeutic targets in KRAS-induced pancreatic cancer.
- Author
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Gomes-Filho SM, Dos Santos EO, Bertoldi ERM, Scalabrini LC, Heidrich V, Dazzani B, Levantini E, Reis EM, and Bassères DS
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- Adenocarcinoma genetics, Adenocarcinoma pathology, Aurora Kinase A antagonists & inhibitors, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Humans, Kaplan-Meier Estimate, Mutation genetics, Oncogenes, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Phenotype, Prognosis, Protein Kinase Inhibitors pharmacology, RNA, Small Interfering metabolism, Aurora Kinase A metabolism, Cell Cycle Proteins metabolism, Microtubule-Associated Proteins metabolism, Molecular Targeted Therapy, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms metabolism, Proto-Oncogene Proteins p21(ras) metabolism
- Abstract
Purpose: Oncogenic KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDACs). As yet, however, no effective therapies are available for KRAS-induced malignancies. Therefore, research aimed at the identification of KRAS targets with therapeutic potential is warranted. Our goal was to investigate Aurora A (AURKA) and targeting protein for Xklp2 (TPX2) as potential therapeutic targets in PDAC., Methods: AURKA and TPX2 expression was assessed using RNAseq and qRT-PCR in PDAC patient samples and matched non-tumor pancreatic tissues. Publicly available PDAC datasets were used to investigate associations of AURKA and TPX2 expression levels with patient survival and the presence of KRAS mutations. Next, we used an Aurora kinase inhibitor, or KRAS, AURKA and TPX2 targeting using RNA interference in KRAS-mutant PDAC cells and, subsequently, analyzed their clonogenic and anchorage-independent growth and migration., Results: We found that relative to matched non-tumor tissues, PDAC tumors displayed significantly higher expression levels of AURKA and TPX2. In addition, we found that AURKA and TPX2 were co-expressed in PDAC datasets, and that high expression levels of AURKA and TPX2 were associated with a shorter patient survival and with the presence of oncogenic KRAS mutations. In addition, we found that siRNA-mediated KRAS targeting in KRAS-mutant PDAC cells reduced AURKA and TPX2 expression. Furthermore, targeting AURKA or TPX2 in KRAS-mutant PDAC cells reduced their clonogenic and anchorage-independent growth, as well their migration., Conclusions: From our data we conclude that AURKA and TPX2 may act as KRAS biomarkers in PDAC that can predict a worse prognosis, and that AURKA or TPX2 targeting in PDAC cells may reduce their transformed phenotype. These results indicate that AURKA and TPX2 may serve as promising targets to be explored for KRAS-mutant PDAC therapy.
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- 2020
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11. Sand as a solid support in ultrasound-assisted MSPD: A simple, green and low-cost method for multiresidue pesticide determination in fruits and vegetables.
- Author
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Dos Santos EO, Gonzales JO, Ores JC, Marube LC, Caldas SS, Furlong EB, and Primel EG
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- Chromatography, High Pressure Liquid, Dimethoate chemistry, Fruit chemistry, Fruit metabolism, Limit of Detection, Pesticide Residues isolation & purification, Pyrethrins chemistry, Sonication, Tandem Mass Spectrometry, Triazoles chemistry, Vegetables metabolism, Gas Chromatography-Mass Spectrometry, Pesticide Residues analysis, Solid Phase Extraction methods, Vegetables chemistry
- Abstract
Sand was studied as a solid support in ultrasound-assisted matrix solid-phase dispersion (UA-MSPD) for the extraction of different pesticide classes, including organophosphates, carbamates, triazoles and pyrethroids from fruits and vegetables, with determination by GC-MS and LC-MS/MS. The performance of sand was compared with that of different types of classic solid supports and alternative natural materials from renewable sources. The best results were obtained using 0.5 g sample, 1 g sand as a solid support, 20 mg activated charcoal and 5 mL ethyl acetate as elution solvent. Recoveries ranged from 55 to 140% with an RSD ≤ 20%. LOQs varied from 0.005 to 0.5 mg kg
-1 for all analytes. Thiamethoxam, captan, chlorpyrifos, dimethoate and pyrimethanil were found in strawberry samples at concentrations from 0.01 to 0.06 mg kg-1 . Acephate and tebuconazole were found in a tomato sample at concentrations of 0.45 and 0.30 mg kg-1 , respectively. The method developed was efficient, simple, cheap, robust, and environmentally friendly., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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12. The influence that different urban development models has on PM 2.5 elemental and bioaccessible profiles.
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Polezer G, Oliveira A, Potgieter-Vermaak S, Godoi AFL, de Souza RAF, Yamamoto CI, Andreoli RV, Medeiros AS, Machado CMD, Dos Santos EO, de André PA, Pauliquevis T, Saldiva PHN, Martin ST, and Godoi RHM
- Subjects
- Brazil, Cities, Industrial Development, Inhalation Exposure, Risk Assessment, Air Pollutants analysis, Air Pollution analysis, Environmental Monitoring, Metals, Heavy analysis, Particulate Matter analysis, Urban Renewal
- Abstract
Limited studies have reported on in-vitro analysis of PM
2.5 but as far as the authors are aware, bioaccessibility of PM2.5 in artificial lysosomal fluid (ALF) has not been linked to urban development models before. The Brazilian cities Manaus (Amazon) and Curitiba (South region) have different geographical locations, climates, and urban development strategies. Manaus drives its industrialization using the free trade zone policy and Curitiba adopted a services centered economy driven by sustainability. Therefore, these two cities were used to illustrate the influence that these different models have on PM2.5 in vitro profile. We compared PM2.5 mass concentrations and the average total elemental and bioaccessible profiles for Cu, Cr, Mn, and Pb. The total average elemental concentrations followed Mn > Pb > Cu > Cr in Manaus and Pb > Mn > Cu > Cr in Curitiba. Mn had the lowest solubility while Cu showed the highest bioaccessibility (100%) and was significantly higher in Curitiba than Manaus. Cr and Pb had higher bioaccessibility in Manaus than Curitiba. Despite similar mass concentrations, the public health risk in Manaus was higher than in Curitiba indicating that the free trade zone had a profound effect on the emission levels and sources of airborne PM. These findings illustrate the importance of adopting sustainable air quality strategies in urban planning.- Published
- 2019
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13. Increasing Isoprene Epoxydiol-to-Inorganic Sulfate Aerosol Ratio Results in Extensive Conversion of Inorganic Sulfate to Organosulfur Forms: Implications for Aerosol Physicochemical Properties.
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Riva M, Chen Y, Zhang Y, Lei Z, Olson NE, Boyer HC, Narayan S, Yee LD, Green HS, Cui T, Zhang Z, Baumann K, Fort M, Edgerton E, Budisulistiorini SH, Rose CA, Ribeiro IO, E Oliveira RL, Dos Santos EO, Machado CMD, Szopa S, Zhao Y, Alves EG, de Sá SS, Hu W, Knipping EM, Shaw SL, Duvoisin Junior S, de Souza RAF, Palm BB, Jimenez JL, Glasius M, Goldstein AH, Pye HOT, Gold A, Turpin BJ, Vizuete W, Martin ST, Thornton JA, Dutcher CS, Ault AP, and Surratt JD
- Subjects
- Aerosols, Butadienes, Hemiterpenes, Sulfates, Tennessee, Atmosphere, Pentanes
- Abstract
Acid-driven multiphase chemistry of isoprene epoxydiols (IEPOX), key isoprene oxidation products, with inorganic sulfate aerosol yields substantial amounts of secondary organic aerosol (SOA) through the formation of organosulfur compounds. The extent and implications of inorganic-to-organic sulfate conversion, however, are unknown. In this article, we demonstrate that extensive consumption of inorganic sulfate occurs, which increases with the IEPOX-to-inorganic sulfate concentration ratio (IEPOX/Sulf
inorg ), as determined by laboratory measurements. Characterization of the total sulfur aerosol observed at Look Rock, Tennessee, from 2007 to 2016 shows that organosulfur mass fractions will likely continue to increase with ongoing declines in anthropogenic Sulfinorg , consistent with our laboratory findings. We further demonstrate that organosulfur compounds greatly modify critical aerosol properties, such as acidity, morphology, viscosity, and phase state. These new mechanistic insights demonstrate that changes in SO2 emissions, especially in isoprene-dominated environments, will significantly alter biogenic SOA physicochemical properties. Consequently, IEPOX/Sulfinorg will play an important role in understanding the historical climate and determining future impacts of biogenic SOA on the global climate and air quality.- Published
- 2019
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14. IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target.
- Author
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Carneiro-Lobo TC, Scalabrini LC, Magalhães LDS, Cardeal LB, Rodrigues FS, Dos Santos EO, Baldwin AS, Levantini E, Giordano RJ, and Bassères DS
- Subjects
- Animals, Cell Line, Tumor, Cell Movement, Humans, I-kappa B Kinase antagonists & inhibitors, I-kappa B Kinase genetics, Interleukin-8 genetics, Interleukin-8 metabolism, Lung Neoplasms genetics, Male, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mutation genetics, NF-kappa B genetics, NF-kappa B metabolism, Neovascularization, Pathologic, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins p21(ras) genetics, RNA, Small Interfering genetics, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Xenograft Model Antitumor Assays, Endothelial Cells physiology, I-kappa B Kinase metabolism, Lung Neoplasms blood supply, Oxazines pharmacology, Piperidines pharmacology, Pyridines pharmacology
- Abstract
Objectives: The ability of tumor cells to drive angiogenesis is an important cancer hallmark that positively correlates with metastatic potential and poor prognosis. Therefore, targeting angiogenesis is a rational therapeutic approach and dissecting proangiogenic pathways is important, particularly for malignancies driven by oncogenic KRAS, which are widespread and lack effective targeted therapies. Based on published studies showing that oncogenic RAS promotes angiogenesis by upregulating the proangiogenic NF-κB target genes IL-8 and VEGF, that NF-κB activation by KRAS requires the IKKβ kinase, and that targeting IKKβ reduces KRAS-induced lung tumor growth in vivo, but has limited effects on cell growth in vitro, we hypothesized that IKKβ targeting would reduce lung tumor growth by inhibiting KRAS-induced angiogenesis., Materials and Methods: To test this hypothesis, we targeted IKKβ in KRAS-mutant lung cancer cell lines either by siRNA-mediated transfection or by treatment with Compound A (CmpdA), a highly specific IKKβ inhibitor, and used in vitro and in vivo assays to evaluate angiogenesis., Results and Conclusions: Both pharmacological and siRNA-mediated IKKβ targeting in lung cells reduced expression and secretion of NF-κB-regulated proangiogenic factors IL-8 and VEGF. Moreover, conditioned media from IKKβ-targeted lung cells reduced human umbilical vein endothelial cell (HUVEC) migration, invasion and tube formation in vitro. Furthermore, siRNA-mediated IKKβ inhibition reduced xenograft tumor growth and vascularity in vivo. Finally, IKKβ inhibition also affects endothelial cell function in a cancer-independent manner, as IKKβ inhibition reduced pathological retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Taken together, these results provide a novel mechanistic understanding of how the IKKβ pathway affects human lung tumorigenesis, indicating that IKKβ promotes KRAS-induced angiogenesis both by cancer cell-intrinsic and cancer cell-independent mechanisms, which strongly suggests IKKβ inhibition as a promising antiangiogenic approach to be explored for KRAS-induced lung cancer therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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15. Fibroblast Growth Factor 2 lethally sensitizes cancer cells to stress-targeted therapeutic inhibitors.
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Dias MH, Fonseca CS, Zeidler JD, Albuquerque LL, da Silva MS, Cararo-Lopes E, Reis MS, Noël V, Dos Santos EO, Prior IA, and Armelin HA
- Subjects
- Animals, Bortezomib pharmacology, Cell Cycle drug effects, Cell Death drug effects, Cell Line, Tumor, Extracellular Signal-Regulated MAP Kinases metabolism, Mice, Proteasome Inhibitors pharmacology, Proto-Oncogene Proteins p21(ras) metabolism, Antineoplastic Agents pharmacology, Fibroblast Growth Factor 2 pharmacology, Stress, Physiological
- Abstract
In malignant transformation, cellular stress-response pathways are dynamically mobilized to counterbalance oncogenic activity, keeping cancer cells viable. Therapeutic disruption of this vulnerable homeostasis might change the outcome of many human cancers, particularly those for which no effective therapy is available. Here, we report the use of fibroblast growth factor 2 (FGF2) to demonstrate that further mitogenic activation disrupts cellular homeostasis and strongly sensitizes cancer cells to stress-targeted therapeutic inhibitors. We show that FGF2 enhanced replication and proteotoxic stresses in a K-Ras-driven murine cancer cell model, and combinations of FGF2 and proteasome or DNA damage response-checkpoint inhibitors triggered cell death. CRISPR/Cas9-mediated K-Ras depletion suppressed the malignant phenotype and prevented these synergic toxicities in these murine cells. Moreover, in a panel of human Ewing's sarcoma family tumor cells, sublethal concentrations of bortezomib (proteasome inhibitor) or VE-821 (ATR inhibitor) induced cell death when combined with FGF2. Sustained MAPK-ERK1/2 overactivation induced by FGF2 appears to underlie these synthetic lethalities, as late pharmacological inhibition of this pathway restored cell homeostasis and prevented these described synergies. Our results highlight how mitotic signaling pathways which are frequently overridden in malignant transformation might be exploited to disrupt the robustness of cancer cells, ultimately sensitizing them to stress-targeted therapies. This approach provides a new therapeutic rationale for human cancers, with important implications for tumors still lacking effective treatment, and for those that frequently relapse after treatment with available therapies., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
- Published
- 2019
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16. Development of a hydrophilic interaction liquid chromatography (HILIC) method for the chemical characterization of water-soluble isoprene epoxydiol (IEPOX)-derived secondary organic aerosol.
- Author
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Cui T, Zeng Z, Dos Santos EO, Zhang Z, Chen Y, Zhang Y, Rose CA, Budisulistiorini SH, Collins LB, Bodnar WM, de Souza RAF, Martin ST, Machado CMD, Turpin BJ, Gold A, Ault AP, and Surratt JD
- Subjects
- Catalysis, Hydrophobic and Hydrophilic Interactions, Isomerism, Particulate Matter chemistry, Sulfates chemistry, Aerosols chemistry, Butadienes chemistry, Chromatography, Liquid methods, Epoxy Compounds chemistry, Hemiterpenes chemistry
- Abstract
Acid-catalyzed multiphase chemistry of isoprene epoxydiols (IEPOX) on sulfate aerosol produces substantial amounts of water-soluble secondary organic aerosol (SOA) constituents, including 2-methyltetrols, methyltetrol sulfates, and oligomers thereof in atmospheric fine particulate matter (PM2.5). These constituents have commonly been measured by gas chromatography interfaced to electron ionization mass spectrometry (GC/EI-MS) with prior derivatization or by reverse-phase liquid chromatography interfaced to electrospray ionization high-resolution mass spectrometry (RPLC/ESI-HR-MS). However, both techniques have limitations in explicitly resolving and quantifying polar SOA constituents due either to thermal degradation or poor separation. With authentic 2-methyltetrol and methyltetrol sulfate standards synthesized in-house, we developed a hydrophilic interaction liquid chromatography (HILIC)/ESI-HR-quadrupole time-of-flight mass spectrometry (QTOFMS) protocol that can chromatographically resolve and accurately measure the major IEPOX-derived SOA constituents in both laboratory-generated SOA and atmospheric PM2.5. 2-Methyltetrols were simultaneously resolved along with 4-6 diastereomers of methyltetrol sulfate, allowing efficient quantification of both major classes of SOA constituents by a single non-thermal analytical method. The sum of 2-methyltetrols and methyltetrol sulfates accounted for approximately 92%, 62%, and 21% of the laboratory-generated β-IEPOX aerosol mass, laboratory-generated δ-IEPOX aerosol mass, and organic aerosol mass in the southeastern U.S., respectively, where the mass concentration of methyltetrol sulfates was 171-271% the mass concentration of methyltetrol. Mass concentrations of methyltetrol sulfates were 0.39 and 2.33 μg m-3 in a PM2.5 sample collected from central Amazonia and the southeastern U.S., respectively. The improved resolution clearly reveals isomeric patterns specific to methyltetrol sulfates from acid-catalyzed multiphase chemistry of β- and δ-IEPOX. We also demonstrate that conventional GC/EI-MS analyses overestimate 2-methyltetrols by up to 188%, resulting (in part) from the thermal degradation of methyltetrol sulfates. Lastly, C5-alkene triols and 3-methyltetrahydrofuran-3,4-diols are found to be largely GC/EI-MS artifacts formed from thermal degradation of 2-methyltetrol sulfates and 3-methyletrol sulfates, respectively, and are not detected with HILIC/ESI-HR-QTOFMS.
- Published
- 2018
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17. Aurora kinase targeting in lung cancer reduces KRAS-induced transformation.
- Author
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Dos Santos EO, Carneiro-Lobo TC, Aoki MN, Levantini E, and Bassères DS
- Subjects
- Animals, Aurora Kinase A antagonists & inhibitors, Aurora Kinase B antagonists & inhibitors, Cell Line, Tumor, Cell Proliferation drug effects, Cell Transformation, Neoplastic drug effects, Gene Knockdown Techniques, Male, Mice, Inbred BALB C, Mice, Nude, Phenotype, Protein Kinase Inhibitors pharmacology, RNA, Small Interfering metabolism, Xenograft Model Antitumor Assays, Aurora Kinase A metabolism, Aurora Kinase B metabolism, Cell Transformation, Neoplastic pathology, Lung Neoplasms enzymology, Molecular Targeted Therapy, Proto-Oncogene Proteins p21(ras) metabolism
- Abstract
Background: Activating mutations in KRAS are prevalent in lung cancer and have been causally linked to the oncogenic process. However, therapies targeted to oncogenic RAS have been ineffective to date and identification of KRAS targets that impinge on the oncogenic phenotype is warranted. Based on published studies showing that mitotic kinases Aurora A (AURKA) and B (AURKB) cooperate with oncogenic RAS to promote malignant transformation and that AURKA phosphorylates RAS effector pathway components, the aim of this study was to investigate whether AURKA and AURKB are KRAS targets in lung cancer and whether targeting these kinases might be therapeutically beneficial., Methods: In order to determine whether oncogenic KRAS induces Aurora kinase expression, we used qPCR and western blotting in three different lung cell-based models of gain- or loss-of-function of KRAS. In order to determine the functional role of these kinases in KRAS-induced transformation, we generated KRAS-positive A549 and H358 cells with stable and inducible shRNA-mediated knockdown of AURKA or AURKB and evaluated transformation in vitro and tumor growth in vivo. In order to validate AURKA and/or AURKB as therapeutically relevant KRAS targets in lung cancer, we treated A549 and H358 cells, as well as two different lung cell based models of gain-of-function of KRAS with a dual Aurora kinase inhibitor and performed functional in vitro assays., Results: We determined that KRAS positively regulates AURKA and AURKB expression. Furthermore, in KRAS-positive H358 and A549 cell lines, inducible knockdown of AURKA or AURKB, as well as treatment with a dual AURKA/AURKB inhibitor, decreased growth, viability, proliferation, transformation, and induced apoptosis in vitro. In addition, inducible shRNA-mediated knockdown of AURKA in A549 cells decreased tumor growth in vivo. More importantly, dual pharmacological inhibiton of AURKA and AURKB reduced growth, viability, transformation, and induced apoptosis in vitro in an oncogenic KRAS-dependent manner, indicating that Aurora kinase inhibition therapy can specifically target KRAS-transformed cells., Conclusions: Our results support our hypothesis that Aurora kinases are important KRAS targets in lung cancer and suggest Aurora kinase inhibition as a novel approach for KRAS-induced lung cancer therapy.
- Published
- 2016
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18. Physiologic and metagenomic attributes of the rhodoliths forming the largest CaCO3 bed in the South Atlantic Ocean.
- Author
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Cavalcanti GS, Gregoracci GB, dos Santos EO, Silveira CB, Meirelles PM, Longo L, Gotoh K, Nakamura S, Iida T, Sawabe T, Rezende CE, Francini-Filho RB, Moura RL, Amado-Filho GM, and Thompson FL
- Subjects
- Animals, Archaea classification, Archaea genetics, Archaea metabolism, Atlantic Ocean, Bacteria classification, Bacteria genetics, Bacteria metabolism, Brazil, Carbon metabolism, Invertebrates physiology, Photosynthesis genetics, Archaea physiology, Bacterial Physiological Phenomena, Biodiversity, Calcium Carbonate metabolism, Ecosystem, Metagenome genetics, Rhodophyta microbiology
- Abstract
Rhodoliths are free-living coralline algae (Rhodophyta, Corallinales) that are ecologically important for the functioning of marine environments. They form extensive beds distributed worldwide, providing a habitat and nursery for benthic organisms and space for fisheries, and are an important source of calcium carbonate. The Abrolhos Bank, off eastern Brazil, harbors the world's largest continuous rhodolith bed (of ∼21,000 km(2)) and has one of the largest marine CaCO3 deposits (producing 25 megatons of CaCO3 per year). Nevertheless, there is a lack of information about the microbial diversity, photosynthetic potential and ecological interactions within the rhodolith holobiont. Herein, we performed an ecophysiologic and metagenomic analysis of the Abrolhos rhodoliths to understand their microbial composition and functional components. Rhodoliths contained a specific microbiome that displayed a significant enrichment in aerobic ammonia-oxidizing betaproteobacteria and dissimilative sulfate-reducing deltaproteobacteria. We also observed a significant contribution of bacterial guilds (that is, photolithoautotrophs, anaerobic heterotrophs, sulfide oxidizers, anoxygenic phototrophs and methanogens) in the rhodolith metagenome, suggested to have important roles in biomineralization. The increased hits in aromatic compounds, fatty acid and secondary metabolism subsystems hint at an important chemically mediated interaction in which a functional job partition among eukaryal, archaeal and bacterial groups allows the rhodolith holobiont to thrive in the global ocean. High rates of photosynthesis were measured for Abrolhos rhodoliths (52.16 μmol carbon m(-2 )s(-1)), allowing the entire Abrolhos rhodolith bed to produce 5.65 × 10(5) tons C per day. This estimate illustrates the great importance of the Abrolhos rhodolith beds for dissolved carbon production in the South Atlantic Ocean.
- Published
- 2014
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19. Isolation and characterization of new ceramides from aerial parts of Lepidaploa cotoneaster.
- Author
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dos Santos EO, Meira M, do Vale AE, David JM, de Queiróz LP, and David JP
- Subjects
- Magnetic Resonance Spectroscopy, Molecular Structure, Ceramides chemistry, Plant Components, Aerial chemistry, Rosaceae chemistry
- Abstract
Two new ceramides were isolated from the bulbs of Lepidaploa cotoneaster (Willd. ex Spreng.) H. Rob. [Vernonia cotoneaster (Willd. ex Spreng.) Less.)], in addition to germanicol, beta-sitosterol, stigmasterol, 3-beta-O-beta-D-glucopyranosyl-sitosterol, lupeol, lupeoyl acetate and tiliroside. The structures of the new compounds were elucidated by spectral techniques (MS, 1H NMR, 13C NMR, HSQC, HMBC, DEPT, and TOCSY) and were compared with data reported in literature, and were established as 2S*,2'R*,3S*,4R*,11E)-N-[2'-hydroxyhenicosanoyl]-2-amino-nonadec-11-ene-1,3,4-triol (1) and (2S*,2'R*,3S*,4R*,8E)-N-[2'-hydroxytricosanoyl]-2-amino-nonadec-8-ene-1,3,4-triol (2). To establish the structure and to locate the double bond, the methyl ester of the fatty acid and dimethyl disulfide (DMDS) derivatives were prepared for both ceramides.
- Published
- 2012
20. An unusual caffeic acid derived bicyclic [2.2.2] octane lignan and other constituents from Cordia rufescens.
- Author
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do Vale AE, David JM, dos Santos EO, David JP, e Silva LC, Bahia MV, and Brandão HN
- Subjects
- Bridged Bicyclo Compounds chemistry, Hydroxybenzoates chemistry, Lignans isolation & purification, Magnetic Resonance Spectroscopy, Molecular Structure, Octanes isolation & purification, Plant Stems chemistry, Sitosterols chemistry, Sitosterols isolation & purification, Stigmasterol chemistry, Stigmasterol isolation & purification, Bridged Bicyclo Compounds isolation & purification, Caffeic Acids chemistry, Cordia chemistry, Lignans chemistry, Octanes chemistry
- Abstract
This work reports isolation of an unusual lignan with a bicyclic [2.2.2] octene skeleton, named rufescenolide (1), from stems of Cordia rufescens, along with β-sitosterol, stigmasterol, syringaldehyde, 3-β-O-D-glucopyranosyl-sitosterol, methyl caffeate, 4-methoxy-protocatechuic acid and methyl rosmarinate. Structural characterizations employed IR spectroscopic, ESIHRMS and mono and dimensional NMR spectroscopy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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21. Evaluation of the composition of culture medium for yeast biomass production using raw glycerol from biodiesel synthesis.
- Author
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Dos Santos EO, Michelon M, Furlong EB, Burkert JF, Kalil SJ, and Burkert CA
- Abstract
The work herewith investigated the production of yeast biomass as a source of protein, using Yarrowia lipolytica NRRL YB-423 and raw glycerol from biodiesel synthesis as the main carbon source. A significant influence of glycerol concentration, initial pH and yeast extract concentration on biomass and protein content was observed according to the 2v (5-1) fractional design. These factors were further evaluated using a central composite design and response surface methodology, and an empirical model for protein content was established and validated. The biomass of Yarrowia lipolytica NRRL YB-423 reached 19.5 ± 1.0 g/L in shaken flasks cultivation, with a protein content of 20.1 ± 0.6% (w/w).
- Published
- 2012
- Full Text
- View/download PDF
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