752 research outputs found

    The Impact of Polyphenols-Based Diet on the Inflammatory Profile in COVID-19 Elderly and Obese Patients

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    The World Health Organization declared the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated disease (coronavirus disease 2019 - COVID-19) as a pandemic in March 2020. COVID-19 is characterized by cytokine storm, acute respiratory distress syndrome (ARDS), and systemic inflammation-related pathology and already kills more than 1.5 million of people worldwide. Since aged and obese COVID-19 patients exhibit an enhanced inflammatory status, they represent a high-risk cluster for rapidly progressive clinical deterioration. These individuals present comorbid disorders and immunosenescence that may promote viral-induced cytokine storm and expression of molecules acting as virus receptor as angiotensin I converting enzyme 2 (ACE2) and CD26 (dipeptidyl-peptidase 4), resulting in respiratory failure and increased morbidity and mortality. A better knowledge of SARS-CoV-2 infection in inflammatory-associated high-risk population is essential in order to develop the therapies needed to combat or prevent severe COVID-19. Here, we review the pathogenesis and clinical implications of inflammatory disorders and disease markers associated to senescence in COVID-19 patients and the emerging evidence to argue that a high intake of polyphenols may have a protective effect on SARS-CoV-2 illness severity

    Pharmacological targeting of BET bromodomain proteins in acute myeloid leukemia and malignant lymphomas: from molecular characterization to clinical applications

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    Bromodomain and extra-terminal domain; BRD2; BRD4Bromodominio y dominio extra terminal; BRD2; BRD4Bromodomini i domini extra terminal; BRD2; BRD4Abstract: Alterations in protein-protein and DNA-protein interactions and abnormal chromatin remodeling are a major cause of uncontrolled gene transcription and constitutive activation of critical signaling pathways in cancer cells. Multiple epigenetic regulators are known to be deregulated in several hematologic neoplasms, by somatic mutation, amplification, or deletion, allowing the identification of specific epigenetic signatures, but at the same time providing new therapeutic opportunities. While these vulnerabilities have been traditionally addressed by hypomethylating agents or histone deacetylase inhibitors, pharmacological targeting of bromodomain-containing proteins has recently emerged as a promising approach in a number of lymphoid and myeloid malignancies. Indeed, preclinical and clinical studies highlight the relevance of targeting the bromodomain and extra-terminal (BET) family as an e_cient strategy of target transcription irrespective of the presence of epigenetic mutations. Here we will summarize the main advances achieved in the last decade regarding the preclinical and clinical evaluation of BET bromodomain inhibitors in hematologic cancers, either as monotherapies or in combinations with standard and/or experimental agents. A mention will finally be given to the new concept of the protein degrader, and the perspective it holds for the design of bromodomain-based therapies.G.R. acknowledges supports from Fondo de Investigación Sanitaria PI15/00102 and PI18/01383, European Regional Development Fund (ERDF) “Una manera de hacer Europa”

    How to distinguish the \u3ci\u3eXestotrachelus\u3c/i\u3e Bruner, 1913 (Orthoptera: Romaleidae: Romaleini) from other Romaleini in South America, with a report of the first record in Minas Gerais, Brazil

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    The present study provides an important contribution to the knowledge of the geographic distribution of Xestotrachelus Bruner, 1913 (Orthoptera: Romaleidae: Romaleini), a monotypic genus comprised of Xestotrachelus robustus (Bruner, 1911) that has a wide geographic distribution in Brazil. Specimens were collected at the Panga Ecological Reserve, Uberlândia, Minas Gerais, in the Brazilian Cerrado. We provide a key to distinguish Xestotrachelus from other genera found in South America

    Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma

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    Background: Gene silencing of the repair genes MLH1 and MGMT was shown to be a mechanism underlying the development of microsatellite instability (MSI), a phenotype frequently associated with various human malignancies. Recently, aberrant methylation of MLH1, MGMT and MSI were shown to be associated with mutations in genes such as BRAF, RAS and IDH1 in colon and brain tumours. Little is known about the methylation status of MLH1 and MGMT in thyroid tumours and its association with MSI and mutational status.Methods: in a series of 96 thyroid tumours whose mutational profiles of BRAF, IDH1 and NRAS mutations and RET/PTC were previously determined, we investigated MLH1 and MGMT expression and methylation status by qPCR and methylation-specific PCR after bisulphite treatment, respectively. MSI was determined by PCR using seven standard microsatellite markers.Results: Samples with point mutations (BRAF, IDH1 and NRAS) show a decrease in MLH1 expression when compared to negative samples. Additionally, malignant lesions show a higher MSI pattern than benign lesions. the MSI phenotype was also associated with down-regulation of MLH1.Conclusions: the results of this study allow us to conclude that low expression of MLH1 is associated with BRAF V600E mutations, RET/PTC rearrangements and transitions (IDH1 and NRAS) in patients with thyroid carcinoma. in addition, a significant relationship between MSI status and histological subtypes was found.Univ Sao Francisco, Unidade Integrada Farmacol & Gastroenterol, BR-12900000 Braganca Paulista, SP, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Lab Bases Genet Tumores Tiroide, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Lab Bases Genet Tumores Tiroide, São Paulo, BrazilWeb of Scienc

    O perfil de clientes de um shopping center: um estudo exploratório com consumidores do interior

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    The study was carried out in a Minas Gerais' inland city, so as to get acquainted with the profile and habits of its clients. This research is innovative as it approaches as customer the citizen of an inland town. The objective of this work was to identify the groups of customers taking into consideration their level of satisfaction as well as their social-economic profile. The collection of data was accomplished through the application of a closed questionnaire to the probabilistic, casual and stratified sample of the population of the city being researched, resulting in 500 questionnaires altogether. Entering and processing of the data were performed through a Statistical Package for the Social Science software (SPSS) v. 10.0. The analyses of data were accomplished through the use of the descriptive and multivaried statistics (cluster and discriminative). Other resources provided by the SPSS software were also used such as crosstabs and frequency. As a result three groups of consumers were formed, so called a) sporadic consumers group formed by people with lower income, not assiduous frequenters of the establishment and displaying difficulties in evaluating the mall; b) regular consumers with higher income capacity who frequent the establishment twice a month and finding themselves able to evaluate the quality of services and products in the mall; and c) assiduous consumers, with higher income and frequenting the establishment more often, being classified as critical and strict. The factors which discriminated the groups were: cinema and recreation facilities, trademarks, security, cleanliness, live music, events, the food area and advertisement of the mall.shopping mall, satisfaction, multivariate research,

    Recent advances in the targeting of epigenetic regulators in b-cell non- Hodgkin lymphoma

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    B-cell lymphoma; DNMT; EZH2Linfoma de células B; DNMT; EZH2Limfoma de cèl·lules B; DNMT; EZH2In the last 10 years, major advances have been made in the diagnosis and development of selective therapies for several blood cancers, including B-cell non-Hodgkin lymphoma (B-NHL), a heterogeneous group of malignancies arising from the mature B lymphocyte compartment. However, most of these entities remain incurable and current treatments are associated with variable efficacy, several adverse events, and frequent relapses. Thus, new diagnostic paradigms and novel therapeutic options are required to improve the prognosis of patients with B-NHL. With the recent deciphering of the mutational landscapes of B-cell disorders by high-throughput sequencing, it came out that different epigenetic deregulations might drive and/or promote B lymphomagenesis. Consistently, over the last decade, numerous epigenetic drugs (or epidrugs) have emerged in the clinical management of B-NHL patients. In this review, we will present an overview of the most relevant epidrugs tested and/or used so far for the treatment of different subtypes of B-NHL, from first-generation epigenetic therapies like histone acetyl transferases (HDACs) or DNA-methyl transferases (DNMTs) inhibitors to new agents showing selectivity for proteins that are mutated, translocated, and/or overexpressed in these diseases, including EZH2, BET, and PRMT. We will dissect the mechanisms of action of these epigenetic inhibitors, as well as the molecular processes underlying their lack of efficacy in refractory patients. This review will also provide a summary of the latest strategies being employed in preclinical and clinical settings, and will point out the most promising lines of investigation in the field.The authors received financial support from Fondo de Investigacion Sanitaria PI15/00102 and PI18/01383, European Regional Development Fund (ERDF) "Una manera de hacer Europa" (to GR). The authors received fundings from TG Therapeutics and Celgene Corp to support researches unrelated to the present work. Funders were involved neither in the design, nor in the writing of this review

    Amphibia, Anura, Centrolenidae, Hyalinobatrachium crurifasciatum Myers and Donnelly, 1997: first record from Brazil and geographic distribution map

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    The current note reports the presence of Hyalinobatrachium crurifasciatum at municipality of Cotriguaçu, state of Mato Grosso, Central Brazil. This is the first occurrence of this species in Brazil

    EPIDEMIOLOGICAL INVESTIGATION OF SCHISTOSOMIASIS MANSONI IN MUNICIPALITIES IN THE MARANHÃO STATE, BRAZIL

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    Schistosomiasis is a serious parasitic infectious disease, one of the most important waterborne diseases, which is closely related to poverty, lack of health education and basic sanitation. It is a public health problem in Brazil, presenting endemic in some municipalities in the Maranhão State. In this way, this study aimed to evaluate the research profile of schistosomiasis mansoni in some endemic municipalities in the Maranhão State. A descriptive, retrospective and quantitative study was carried out with data obtained in “Programa de Controle da Esquistossomose (PCE) – MA” (Program for Schistosomiasis Control) between 2005 and 2015. We evaluated 42, 40 and 25 municipalities in the years 2005, 2010 and 2015, respectively. In 2005 the population evaluated was 184787, in 2010 162220 and in 2015 they were only 48484. The highest number of people evaluated in the year 2015 was in São Luís (8068) and the lowest was in Tutoia (83). The municipalities of Bacurituba, Guimarães, Guimaraes, Mirinzal, Paulino Neves and São João Batista presented a survey coverage of schistosomiasis major in the year 2015, compared to 2005 and 2010. Schistosomiasis remains a public health problem in the Maranhão State, however, its scope of research is still low, taking into account the number of endemic municipalities, sites susceptible to infection and the number of people examined.Key words: Schistosomiasis; Schistosoma mansoni; Maranhão

    Hidrolisado proteico de carne mecanicamente separada de tilápia-do-nilo

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    The objective of this work was to enzymatically obtain hydrolysate tilapia protein powder by two drying methods, and to perform a physicochemical characterization of the final products, as well as to evaluate their thermal stability. Proximal composition, aminogram, fatty acid profile, pH, color, water activity, and microbiological analyses were performed. Crude protein was the prominent component, with 87% in the spray-dried powder and 89% in the lyophilized powder, showing no statistical difference. The samples showed no bacterial growth, which may be associated with the low water activity in the products. Dry samples had b* positive, and the freeze-dried ones were more yellowish than the spray-dried ones. Both drying methods promoted similar luminosity near the white color. In the thermal analysis, samples showed 26% mass loss at 200°C, and degradation started at 290°C. Enzymatic hydrolysis is efficient, and the hydrolysate tilapia protein powder contains all essential amino acids. The hydrolysate shows similar protein content for both spray-dried and freeze-dried samples, and the final products are stable at high temperatures.O objetivo deste trabalho foi obter, por via enzimática, um hidrolisado proteico de tilápia em pó, por dois métodos de secagem, e realizar uma caracterização físico-química dos produtos finais, bem como avaliar sua estabilidade térmica. Foram realizadas análises de composição proximal, aminograma, perfil de ácidos graxos, pH, cor, atividade da água e análises microbiológicas. A proteína bruta foi o componente proeminente, com 87% no pó obtido por secagem por aspersão e 89% no pó liofilizado, e não apresentou diferença estatística. As amostras não apresentaram crescimento bacteriano, o que pode estar associado à baixa atividade de água dos produtos. As amostras secas tiveram b* positivo, e as amostras secas por liofilização mostraram-se mais amareladas do que as obtidas por aspersão. A secagem em ambos os métodos promoveu luminosidades semelhantes, próximas à cor branca. Na análise térmica, as amostras apresentaram perda de massa de 26% a 200°C, e a degradação foi observada a temperaturas a partir de 290°C. A hidrólise enzimática é eficiente, e os hidrolisados proteicos de tilápia em pó contém todos os aminoácidos essenciais. O hidrolisado apresenta teor de proteína semelhante em amostras secas por aspersão e liofilizadas, e os produtos finais são estáveis em altas temperaturas
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