33 resultados para Proteína Adaptadora de Sinalização NOD2


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The present study evaluated the influence of non-surgical periodontal treatment on the levels of C- reactive protein (hsCRP) in patients with chronic renal failure (CRF) in pretransplant. We conducted a controlled and randomized trial to evaluate the periodontal condition and plasma concentrations of hsCRP, albumin and transferrin in 56 dialysis patients divided into two groups: experimental and control. The study was conducted at the dental clinic of Family and Community Health s Unit (USFC), located in Onofre Lopes University Hospital (HUOL), Federal University of Rio Grande do Norte (UFRN), from December 2010 to November 2011. Severe periodontitis was the type of periodontal disease more common, affecting 78.6% of patients. Periodontal conditions, evaluated through the means of probing depth, clinical attachment level, bleeding index and plaque index, proved to be uniform for both groups at the initial examination. There were no differences in levels of inflammatory markers between the two groups. The analysis of the concentrations of hsCRP allowed classifying study participants as at high risk of developing cardiovascular disease. After completion of periodontal treatment in the experimental group, there was a statistically significant reduction of the mean of all periodontal parameters assessed; however this improvement of periodontal health was not accompanied by changes in the levels of hsCRP, albumin and transferrin in the evaluation time. Given this, the periodontal treatment did not promote the reduction of systemic inflammatory burden and risk of cardiovascular complications in patients with CRF

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Oral squamous cell carcinoma (OSCC) is the most common malignancy in oral cavity and human papillomavirus (HPV) may have an important role in its development. The aim of this experiment was to investigate the HPV DNA and viral types in 90 cases of OSCC. Moreover, a comparative analysis between the cases of OSSC with and without HPV DNA was performed by using cell cycle markers p21 and pRb in order to detect a possible correlation of these proteins and HPV infection. DNA was extracted from paraffin embedded tissue and amplified by PCR (polymerase chain reaction) with primers PCO3+ e PCO4+ for a fragment of human β-globin gene. After this procedure, PCR for HPV DNA detection was realized using a pair of generic primers GP5+ e GP6+. Immunohistochemical study was performed by streptoavidin-biotin technique and antibodies against p21 and pRb proteins were employed. Eighty-eight cases were positive for human β-globin gene and HPV DNA was found in 26 (29.5%) of then. It could not be detected significant correlation between HPV and age, sex and anatomical sites of the lesion. The most prevalent viral type was HPV 18 (80.8%). Regarding the immunohistochemical analysis, it was detected significant association between HPV presence and pRb immunoexpression (p=0,044), nevertheless, the same was not observed in relation to p21 protein (p =0,416). It can be concluded that the low detection of HPV DNA in OSCC by the present experiment suggests a possible role of the virus in the development and progression in just a subset of this disease

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Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression

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As social animals, primates use different sensory modalities (acoustic, chemical, tactile and visual) to convey information about social and sexual status to conspecifics. Among these modalities, visual signals are widely used, especially color signals, since primates are the mammalian group that displays the greatest variety of colors in their skin and fur. Studies with Old World primate species suggest that hormonal variations are related to variations in the colors of individual faces and genitals. Therefore, chromatic cues can be used by conspecifics to identify the reproductive condition of an individual. To date, studies with the same approach are unknown for New World species. However, behavioral and physiological studies suggest that different New World primate species seem to perceive reproductive conditions such as the timing of female conception and gestation. Thus, in this study, our aim was to: i) identify whether there are chromatic cues on the skin of female common marmosets, (Callithrix jacchus) that indicate their reproductive condition; ii) define whether this chromatic variation can be perceived by all visual phenotypes known in this species; iii) identify if these chromatic cues can be perceived under different light intensity levels (dim, intermediate and high). For this, we selected 13 female common marmosets in four distinct reproductive conditions: pregnant female preceding parturition, postpartum mothers, noncycling and cycling females. The coloration of the skin in genital and thigh areas in females was measured using a spectrophotometer. Using mathematical models of visual perception, we calculated the values of quantum catch for each photoreceptor type known in this species, the visual opponency channels and color contrast between those body spots. Our results indicate the occurance of chromatic variations in the genital area during the weeks that precede and follow parturition, forming a U-pattern of variation perceptible to males and females in natural conditions of low and high luminosity. Furthermore, we observed distinct color patterns in the genital skin of pregnant and cycling females that indicate their reproductive conditions. Finally, we present evidence of color contrast in noncycling females that is higher than that of pregnant ones. This study suggests that there is a chromatic xii variation in the genital skin of females that can be perceived by conspecifics and that may be related to hormonal changes typical of pregnancy and the ovarian cycle

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Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

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Base excision repair (BER) proteins has been associated with functions beyond DNA repair. Apurynic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein involved in a plethora of cellular activities, such as redox activation of transcription factors, RNA processing and DNA repair. Some studies have described the action of the protein 8-oxoguanine (OGG1) in correcting oxidized lesions in promoters as a step in the transcription of pro-inflammatory cytokines. Despite being especially important in redox activation of transcription factors such as nuclear factor κB (NF-κB) and AP- 1, the repair activity of APE1 has not yet been associated with the inflammatory response. In this study, experimental and bioinformatic analysis approaches have been used to investigate the relationship between inhibition of the repair of abasic sites in DNA by MX, a synthetic molecule designed to inhibt the repair activity of APE1, and the modulation of the inflammatory response. The results showed that treatment of monocytes with lipopolysaccharide (LPS) and MX reduced the expression of cytokines, chemokines and toll-like receptors, and negatively regulated biological immune processes, as macrophages activation, and NF-κB and tumor necrosis factor (TNF-α) and interferon pathways, without inducing cell death. The transcriptomic analysis suggests that LPS/MX treatment induces mitochondrial dysfunction, endoplasmic reticulum stress and activation of autophagy pathways, probably activated by impairment of cellular energy and/or the accumulation of nuclear and mitochondria DNA damage. Additionally, it is proposed that the repair activity of APE1 is required for transcription of inflammatory genes by interaction with abasic sites at specific promoters and recruitment of transcriptional complexes during inflammatory signaling. This work presents a new perspective on the interactions between the BER activity and the modulation of inflammatory response, and suggests a new activity for APE1 protein as modulator of the immune response in a redox-independent manner.

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This work evaluated the fresh, spray dried (with 10 % of Arabic Gum) and freeze dried jambolan pulp (Eugenia jambolana Lam.) in regard to physicochemical (pH, moisture, water activity, average particle diameter, solubility and color), bioactive [total phenolic content (TPC), monomeric anthocyanin, pronathocyanidin (PA), total elagic acid (TEA), myricetin and cyanidin] and in vitro functionality (antioxidant, antienzymatic and antimicrobial activities]. In addition, the in vivo functionality of jambolan pulp was investigated using the Caenorhabditis elegans model for insulin signaling, longevity and induced neurodegeneration (Alzheimer’s disease and Parkinson’s disease related symptoms). The dried jambolan pulp presented TPC retention (50% to 75%), PA (90% to 98%), TEA (31% to 83%), myricetin (40% to 84%), cyanidin (72% to 84%) and antioxidant activity (15%). The fresh jambolan pulp, the freeze dried pulp and the spray dried jambolan pulp presented high enzymatic inhibitory activity against pancreatic lipase (4,4 to 5,8 mg/mL), alpha-glycosidase (10,3 to 13,8 mg/mL) and alpha-amylase (8,9 to 11,2 mg/mL). They also were active inhibitors against the pathogen S. aureus. The dried jambolan experimental samples were able to increase the expression of several genes linked to the insulin signaling pathways (SIR-2.1, PPTR-1, DAF-16, SOD-3, e CTL) and increased the lifespan in C. elegans (18,07 % - 24,34 %), besides decreasing the amyloid AB1-42 aggregation induced paralysis and MPP+ (1-methyl-4-phenylpyridinium) induced neurodegeneration. Based on that, the jambolan pulp and the spray dried jambolan pulp were further selected for the production of caprine frozen yogurt with the addition of Bifidobacterium animalis subsp. lactis BI-07. The final product were evaluated in regard to their physicochemical (pH, acidity, total solids, protein, total reducing sugars, fat, ashes, overrun, melting test), bioactive (TPC and monomeric anthocyanin, antioxidant activity, probiotic viability and sensory analysis (sensory acceptance). The results showed that samples with probiotic had lowest pH and higher acidity, TPC, anthocyanin and antioxidant activity. It was also observed low overrun (14.2% to 22.6%). vi Samples with probiotic had lower flavor scores. Overall, this research presents the jambolan as a highly functional bioactive-rich fruit with the potential to modulate important biological pathways, extend lifespan and retard the development of neurodegenerative diseases. Jambolan is an underexploited exotic fruit with a high colorant potential and this thesis shows for the first time in the literature important technological, biological and scientific data about this fruit that could be used towards the development of health-oriented food products.

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Estresses ambientais abióticos são fatores que causam respostas ao nível molecular, fisiológico e morfológico em plantas, dependendo também de sua intensidade e duração. É visto que algumas espécies apresentam tolerância a condições estressantes e ao mesmo tempo são fontes naturais de matéria prima para indústria. Nesse contexto encontra-se a mamona (Ricinus comunnis L.), principal fonte de óleo de rícino valorizado por suas aplicações farmacêuticas e principalmente industriais, vem sendo usada como cultura em regiões onde a disponibilidade de água é reduzida, usada como fonte de renda para agricultura da região nordeste brasileira. Visto que pouco se sabe sobre as respostas moleculares que levam essa planta a tolerar regiões secas e como as sementes, principais foco de interesse, respondem a essa escassez, nesse trabalho foram construídas duas bibliotecas de cDNAs, onde a partir de uma abordagem subtrativa, continham RNAs diferencialmente expressos em sementes de plantas mamona submetidas ao estresse hídrico durante 5 dias (biblioteca L7), e a outra RNAs diferencialmente expressos em sementes controle (biblioteca L5). A biblioteca L7 apresentou a maior variedade de transcritos com um total de 182. A maior parte das funções estabelecidas pelo sistema Gene Ontology - GO, foram direcionadas aos “Processos Metabólicos” (526), em segundo “Respostas a estímulos” (57), o terceiro termo mais abundante foram referentes a “Desenvolvimento”(26). Já na biblioteca L5, foram encontrados 91 transcritos, com maior parte de suas funções referentes a “Processos Metabólicos”(413), em segundo “Respostas a estímulos” (8) e em terceiro Regulação (6). Alguns dos transcritos da biblioteca L7 foram escolhidos para análise por repetirem-se mais de 3x e não aparecerem na biblioteca L5, o que indica uma possível regulação positiva sobre estresse. As análises sobre Metalotioneína (4x), mostraram que a sequência de proteica apresentava os domínios conservados que a caracterizava como tipo II, onde são encontrados dois domínios funcionais ricos em cisteína com posições altamente conservadas, desempenhando a função de ligar-se a metais pesados, correlacionadas assim como a atividade de eliminação EROs e defesa contra o estresse oxidativo, além de apresentar homologia com a sequência de Bruguiera gymnorhiza, uma planta de mangue adaptada a ambientes salinos. Analisamos também os transcritos da referente a proteína AUXIN-REPRESSED 12.5 KDA (3x), apontada como sendo reprimida pelo hormônio auxina e associada ao processo de dormência da semente, é descrito em uma família gênica onde vários membros pertencem as vias de resposta ao estresse. Por último, analisamos a proteína GLUTELIN TYPE-A 3 (5x), uma importante proteína de armazenamento com caráter hidrofílico, possivelmente direcionada para o vacúolo. Em nosso trabalho foi possível observar um aumento de transcritos em relação a subtração controle, possivelmente reflexo do aumento do metabolismo da semente, tanto para resposta defensiva ao estresse hídrico quanto para o amadurecimento rápido da semente onde foram observados transcritos referentes a resposta oxidativa, controle hormonal, proteínas de reserva e produção de óleo.

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Introduction: Apurinic/Apyrimidinic Endonuclease 1 (APE-1) is an essential protein for DNA base excision repair (BER) pathway and regulation of redox activities. The ability of malignant cells to recognize and repair DNA damage is an important mechanism for tumor survival, and recent studies suggest that APE-1 overexpression is related to poor prognosis in some tumors. Purpose: To analyze the immunoreactivity of APE-1 in Pleomorphic Adenomas (PA) and Carcinomas Ex Pleomorphic Adenomas (CaExPA) of salivary glands. Materials and Methods: A total of 49 tumors fixed in formalin and embedded in paraffin (33 PA and 16 CaExPA) underwent immunohistochemical study by the immunoperoxidase technique. APE-1 immunoreactivity was evaluated quantitatively by the percentage of immunopositive cells. For statistical analysis a significance level of 5% (p≤ 0.05) was adopted. Results: All cases of PA and CaExPA (n=49) were positive for APE-1, however, there was a higher expression in CaExPA, with statistically significant difference (p<0.001). There was no association between APE-1 expression and tumors of major or minor salivary gland, however, not encapsulated PA (median expression = 54.2%) showed higher expression when compared to encapsulated tumors (p=0.02). APE-1 overexpression was found mainly in cases of CaExAP with lymph node metastasis (median expression = 90.3% - p=0.002) and invasive pattern (median expression = 89.9% - p=0.003), when compared to cases without metastasis and intracapsular pattern. Conclusion: This study suggests that APE-1 is deregulated in the studied tumors. The increased expression of APE-1 is associated with the absence of complete capsule in PA and it is associated with more aggressive behavior in CaExPA.

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Introduction: Apurinic/Apyrimidinic Endonuclease 1 (APE-1) is an essential protein for DNA base excision repair (BER) pathway and regulation of redox activities. The ability of malignant cells to recognize and repair DNA damage is an important mechanism for tumor survival, and recent studies suggest that APE-1 overexpression is related to poor prognosis in some tumors. Purpose: To analyze the immunoreactivity of APE-1 in Pleomorphic Adenomas (PA) and Carcinomas Ex Pleomorphic Adenomas (CaExPA) of salivary glands. Materials and Methods: A total of 49 tumors fixed in formalin and embedded in paraffin (33 PA and 16 CaExPA) underwent immunohistochemical study by the immunoperoxidase technique. APE-1 immunoreactivity was evaluated quantitatively by the percentage of immunopositive cells. For statistical analysis a significance level of 5% (p≤ 0.05) was adopted. Results: All cases of PA and CaExPA (n=49) were positive for APE-1, however, there was a higher expression in CaExPA, with statistically significant difference (p<0.001). There was no association between APE-1 expression and tumors of major or minor salivary gland, however, not encapsulated PA (median expression = 54.2%) showed higher expression when compared to encapsulated tumors (p=0.02). APE-1 overexpression was found mainly in cases of CaExAP with lymph node metastasis (median expression = 90.3% - p=0.002) and invasive pattern (median expression = 89.9% - p=0.003), when compared to cases without metastasis and intracapsular pattern. Conclusion: This study suggests that APE-1 is deregulated in the studied tumors. The increased expression of APE-1 is associated with the absence of complete capsule in PA and it is associated with more aggressive behavior in CaExPA.

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This study reports recommendations for a tactile and graphic wayfinding system aiming to offer more orientability and mobility for visually impaired people (blindness and low vision) at Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte (IFRN), Parnamirim Campus. It was necessary to focus on visual impaired people and approach concepts like orientation and accessibility at the built environment. In order to provide the comprehension of a complex social phenomenon and preserve the meaningful characteristics of the events, this research has developed a single case study in which elements of Post Occupation Evaluation have been used. Its purpose was to allow not only a technical analysis, but also the user perception about the space in use. The chosen tool to collect the user’s opinions and considerations was the Walk Together Method. The collected and analyzed information has demonstrated that, although Parnamirim Campus has implemented some interventions in relation to the spatial accessibility, they are still not enough to create an environment which arranges safety and autonomy for the visual impaired people and the other ones who attend there. This study suggests that it happened because the engineering interventions at the Campus have been based on Brazilian technical standards NBR 9050:2004, which is proper for the physical impaired people, but it does not offer enough information to respond to all the specific needs demanded by all the classifications of visual impairment.

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This study reports recommendations for a tactile and graphic wayfinding system aiming to offer more orientability and mobility for visually impaired people (blindness and low vision) at Instituto Federal de Educação, Ciência e Tecnologia do Rio Grande do Norte (IFRN), Parnamirim Campus. It was necessary to focus on visual impaired people and approach concepts like orientation and accessibility at the built environment. In order to provide the comprehension of a complex social phenomenon and preserve the meaningful characteristics of the events, this research has developed a single case study in which elements of Post Occupation Evaluation have been used. Its purpose was to allow not only a technical analysis, but also the user perception about the space in use. The chosen tool to collect the user’s opinions and considerations was the Walk Together Method. The collected and analyzed information has demonstrated that, although Parnamirim Campus has implemented some interventions in relation to the spatial accessibility, they are still not enough to create an environment which arranges safety and autonomy for the visual impaired people and the other ones who attend there. This study suggests that it happened because the engineering interventions at the Campus have been based on Brazilian technical standards NBR 9050:2004, which is proper for the physical impaired people, but it does not offer enough information to respond to all the specific needs demanded by all the classifications of visual impairment.

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Reactive oxygen species (ROS) are produced by aerobic metabolism and react with biomolecules, such as lipids, proteins and DNA. In high concentration, they lead to oxidative stress. Among ROS, singlet oxygen (1O2) is one of the main ROS involved in oxidative stress and is one of the most reactive forms of molecular oxygen. The exposure of some dyes, such as methylene blue (MB) to light (MB+VL), is able to generate 1O2 and it is the principle involved in photodynamic therapy (PDT). 1O2 e other ROS have caused toxic and carcinogenic effects and have been associated with ageing, neurodegenerative diseases and cancer. Oxidative DNA damage is mainly repaired by base excision repair (BER) pathway. However, recent studies have observed the involvement of nucleotide excision repair (NER) factors in the repair of this type of injury. One of these factors is the Xeroderma Pigmentosum Complementation Group A (XPA) protein, which acts with other proteins in DNA damage recognition and in the recruitment of other repair factors. Moreover, oxidative agents such as 1O2 can induce gene expression. In this context, this study aimed at evaluating the response of XPA-deficient cells after treatment with photosensitized MB. For this purpose, we analyzed the cell viability and occurrence of oxidative DNA damage in cells lines proficient and deficient in XPA after treatment with MB+VL, and evaluated the expression of this enzyme in proficient and complemented cells. Our results indicate an increased resistance to treatment of complemented cells and a higher level of oxidative damage in the deficient cell lines. Furthermore, the treatment was able to modulate the XPA expression up to 24 hours later. These results indicate a direct evidence for the involvement of NER enzymes in the repair of oxidative damage. Besides, a better understanding of the effects of PDT on the induction of gene expression could be provided

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studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins