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PURPOSE: Ubiquitin ligase genes can act as oncogenes or tumor suppressor genes. They play a role in various diseases, including development and progression of breast cancer; the objective of this study was to evaluate the association of common variants in the ductal-epithelium-associated RING chromosome 1 (DEAR1) gene with breast cancer risk in a sample of Colombian population. METHODS: We carried out a case-control study to investigate associations of variants in DEAR1 with breast cancer in women from Colombia. Single nucleotide polymorphisms (SNPs) rs584298, rs2927970, rs59983645, and rs599167 were genotyped in 1022 breast cancer cases and 1023 healthy controls using the iPLEX® and Kompetitive Allele Specific PCR (polymerase chain reaction) (KASP) method. The associations between SNPs and breast cancer were examined by conditional logistic regression. The associations between SNPs and epidemiological/histopathological variables were examined by multinomial logistic regression. RESULTS: Associations were found between tag SNPs and breast cancer adjusted for the epidemiological risk factors rs584298 genotypes AG and GG (P = .048 and P = .004, respectively). The analysis of the disease characteristics showed that SNP rs584298 (genotype AG) (P = .015) shows association with progesterone receptor (PR) status and (genotype AA) (P = .048) shows association with human epidermal growth factor receptor 2 (HER2) status. CONCLUSIONS: The SNP rs584298 in DEAR1 showed associations with breast cancer and the expression of HER2 receptor; when this receptor is amplified, the result is aggressive tumoral subtype and expression of PR receptor that is associated with high-proliferative tumor grade. Validation of this SNP is important to establish whether this variant or the tagged variant is the cause for the risk association showed.
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Streptococcus pneumoniae is a causal agent of otitis media, pneumonia, meningitis and severe cases of septicemia. This human pathogen infects elderly people and children with a high mortality rate of approximately one million deaths per year worldwide. Antibiotic-resistance of S. pneumoniae strains is an increasingly serious health problem; therefore, new therapies capable of combating pneumococcal infections are indispensable. The application of gold nanoparticles has emerged as an option in the control of bacterial infections; however, the mechanism responsible for bacterial cell lysis remains unclear. Specifically, it has been observed that gold nanoparticles are capable of crossing different structures of the S. pneumoniae cells, reaching the cytosol where inclusion bodies of gold nanoparticles are noticed. In this work, a novel process for the separation of such inclusion bodies that allowed the analysis of the biomolecules such as carbohydrates, lipids and proteins associated with the gold nanoparticles was developed. Then, it was possible to separate and identify proteins associated with the gold nanoparticles, which were suggested as possible candidates that facilitate the interaction and entry of gold nanoparticles into S. pneumoniae cells.
Assuntos
Antibacterianos/farmacologia , Ouro/farmacologia , Nanopartículas Metálicas , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Metabolismo dos Carboidratos/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Ouro/química , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Viabilidade Microbiana/efeitos dos fármacos , Streptococcus pneumoniae/fisiologiaRESUMO
The anatomical location of adipose tissue might have direct implications for its functionality and risk of cardiovascular disease. Adipose tissue surrounding blood vessels may be thermogenically more active in specific areas of the body, releasing substances that regulate vascular metabolism. In humans, the phenotypic characteristics of adipose tissue surrounding the aorta and the cardiovascular disease risk that it might entail remain largely unknown. Here, we compared thermogenesis-related molecular features of human periaortic adipose tissue samples with those of subcutaneous adipose tissue, obtained by sternotomy from 42 patients undergoing cardiovascular surgery. To determine the expression of genes related to energy expenditure and the levels of some adipokines, histological examinations, quantitative PCR, and protein expression measurements in adipocyte precursor cells were performed. Periaortic adipocytes were smaller than those from subcutaneous tissue. Moreover, weight gain induced periaortic adipocyte hypertrophy (r = -0.91, p<0.01). Compared to subcutaneous tissue, adiponectin, FABP4, IL-4 and IL-6 was decreased in periaortic adipocytes, whereas FGF21, UCP-1, PGC-1a, CITED1, Omentin and TFAM (Mitochondrial protein) increased. Upon analyzing patients' clinical conditions, it emerged that the levels of PGC-1a both in male (r = -0.48 p<0.04) and female (r = -0.61, p<0.05) and TFAM in male (r = -0.72, p<0.0008) and female (r = -0.86, p<0.002) decreased significantly with progressive weight gain. However, no differences were observed in patients with diabetes mellitus 2 or Hyperlipidemia. Adipocytes surrounding the ascending aorta present markers of major thermogenic activity than those in subcutaneous tissue. Nevertheless, this characteristic might change, due to unfavorable metabolic conditions such as obesity, which is a risk factor for cardiovascular disease.
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Tecido Adiposo/metabolismo , Aorta , Peso Corporal , Termogênese , Adipócitos/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Idoso , Índice de Massa Corporal , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Termogênese/genéticaRESUMO
Streptococcus pneumoniae is a human pathogen whose principal virulence factor is its capsule. This structure allows the bacterium to evade the human immune system. Treatment of infections caused by this bacterium is based on antibiotics; however, the emergence of antibiotic-resistant strains makes this task increasingly difficult. Therefore, it is necessary to investigate new therapies, such as those based on gold nanoparticles, for which unfortunately the mechanisms involved have not yet been investigated. As far as we know, this study is the first that attempts to explain how gold nanoparticles destroy the bacterium Streptococcus pneumoniae. We found that the mean particle size was an important issue, and that the effect on the bacterium was dose-dependent. Cellular growth was inhibited by the presence of the nanoparticles, as was cell viability. The pH of the bacterial growth media was acidified, but interestingly the reactive species were not affected. A transmission electron microscopy analysis revealed the presence of inclusion bodies of gold nanoparticles within the bacterium. We present the first findings that attempt to explain how gold nanoparticles lyse Gram-positive bacteria.
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Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Streptococcus pneumoniae/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/citologia , Streptococcus pneumoniae/crescimento & desenvolvimentoRESUMO
INTRODUCTION: Metabolic syndrome is characterized by the simultaneous or sequential appearance of various metabolic and inflammatory changes at molecular, cellular or hemodynamic level associated with the presence of insulin resistance and dominant visceral adiposity. Different expert groups, including the International Diabetes Federation and the National Cholesterol Education Program, have tried to develop criteria for its diagnosis. OBJECTIVE: To establish diagnostic criteria concordance levels for metabolic syndrome. MATERIALS AND METHODS: A total of 357 people were part of the study. We performed a descriptive analysis of qualitative variables, and laboratory and anthropometric measurement results to determine the prevalence of metabolic syndrome according to the International Diabetes Federation and National Cholesterol Education Program - ATP III definitions. We used kappa concordance and logistic regression for the comparison of methodologies. RESULTS: The prevalence of metabolic syndrome was 19.9% according to the International Diabetes Federation, and 10.4% using the National Cholesterol Education Program - ATP III. The estimate of agreement between the two diagnostic criteria of the International Diabetes Federation and the National Cholesterol Education Program - ATP III was fair (low) (κ=0.3997, CI 95% 0.28-0.52). CONCLUSIONS: In the working population who participated in this study, the obtained prevalence of metabolic syndrome occurred at a higher rate using the International Diabetes Federation definition, being higher in men than in women. The use of diagnostic criteria for metabolic syndrome must take into account the study population as well as sex and age.
Assuntos
Síndrome Metabólica/diagnóstico , Adulto , Estudos Transversais , Técnicas e Procedimentos Diagnósticos , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Adulto JovemRESUMO
Debido al incremento del estudio de la justicia como un fenómeno social de interés para la psicología,se hace una revisión que precisa los antecedentes de la psicología social en el estudio de las distribuciones materiales individuales en diversas situaciones, y las limitaciones de los análisis derivados de dichos estudios. Además, se presentan las posibilidades de indagación de las decisiones distributivas en al menos tres tipos de estudios que se reseñan en amplias revisiones y finaliza con la presentación de una reflexión sobre un "contexto" experimental como nueva perspectiva para el estudio de la justicia distributiva. Desde ese contexto, se describe el término "decisiones distributivas", y se propone como alternativa metodológica la consideración de variables habitualmente utilizadas en el análisis de algunos procesos cognitivos de interés para la economía experimental y comportamental.
Due to the increased study of justice as a social phenomenon of interest to psychology, a revision is carried out to specify the social psychology background in the study of individual material distributions in various situations and the constraints derived from such studies. In addition, the possibilities of inquiry into allocation decisions in at least three types of studies summarized in extensive reviews are presented, and finally, there is a reflection about an experimental "context" as a new perspective for the study of distributive justice. From this context, the term "distributive decisions" is described and, as a methodological alternative, the consideration of variables commonly used for the analysis of cognitive processes of interest for experimental and behavioral economics is proposed.
Devido ao aumento do estudo da justiça como um fenômeno social de interesse para a psicologia se faz uma revisão que especifica os antecedentes da psicologia social no estudo das distribuições materiais individuais em diversas situações, e as limitações das análises derivadas desses estudos. Além disso, apresentam-se as possibilidades de indagação das decisões distributivas em pelo menos três tipos de estudos que são resenhados em amplas revisões e finaliza com a apresentação de uma reflexão sobre um "contexto" experimental como nova perspectiva para o estudo da justiça distributiva. Desde esse contexto, descreve-se o termo "decisões distributivas", e propõe-se como alternativa metodológica a consideração de variáveis habitualmente utilizadas na análise de alguns processos cognitivos de interesse para a economia experimental e comportamental.