Expressão da progranulina durante os primeiros estágios de desenvolvimento hepático em ratos Fischer 344

Transplants are the only effective therapy for the treatment of advanced liver diseases such as cirrhosis. Given the limited number of organ donors, regenerative medicine has sought for sources of cells and tissues for replacement therapy. Embryonic stem cells are a promising source of material for transplantation because of their exclusive property of being expanded indefinitely in culture, thus, they are a source of replacement tissue. Moreover, they are capable of differentiating into practically all cell types, and may be utilized in replacement therapy in various diseases. The liver bud has bipotent stem cells that have not yet differentiated into hepatocytes or biliary duct cells; however, they have great potential of proliferation and differentiation. Thus, the challenge is to identify methods that promote their differentiation in specific and functional strains. This study aimed to evaluate the role of the progranulin growth factor PGRN during the liver development of rats F344, since this growth factor could be utilized in protocols of differentiation of stem cells of the liver bud in functional hepatocytes. The results showed that PGRN is present during different periods of hepatogenesis in F344 rats, and that this growth factor should be involved in the process of differentiation of hepatoblasts into hepatocytes after activation by HNF4α , however, PGRN seems not to exert a cellular proliferation function during the hepatogenesis. Thus, PGRN can be used in future protocols of liver cell differentiation directed toward cellular therapy in Regenerative Medicine.Os transplantes são a única terapia eficaz para o tratamento de doenças hepáticas avançadas, como a cirrose. Dado o número limitado de doadores de órgãos, a medicina regenerativa tem procurado fontes de células para a terapia de substituição. As células embrionárias são uma fonte promissora de material para o transplante devido à sua propriedade exclusiva de ser expandida indefinidamente em cultura, assim, elas são uma fonte de tecido de substituição. Além disso, são capazes de se diferenciar em praticamente todos os tipos celulares, e podem ser utilizadas na terapia de substituição em várias doenças. O broto hepático tem células-tronco (CT) bipotenciais que ainda não se diferenciam em hepatócitos ou células do ducto biliar, contudo, elas têm um grande potencial de proliferação e de diferenciação. Desse modo, o desafio é identificar métodos que promovam sua diferenciação em linhagens específicas e funcionais. Este estudo teve como objetivo avaliar o papel do fator de crescimento progranulina (PGRN) durante o desenvolvimento hepático em ratos F344, uma vez que a PGRN poderia ser utilizada em protocolos de diferenciação de CT do broto hepático em hepatócitos funcionais. Os resultados mostraram que PGRN está presente durante diferentes períodos da hepatogênese em ratos F344, e que a mesma deve estar envolvida no processo de diferenciação de hepatoblastos em hepatócitos após ativação por HNF4α, no entanto, a PGRN parece não desempenhar uma função de proliferação celular durante a hepatogênese. Assim, a PGRN pode ser usada em futuros protocolos de diferenciação de células hepáticas voltadas para a terapia celular na medicina regenerativa

A single bout of exercise with a flexible pole induces significant cardiac autonomic responses in healthy men

OBJECTIVES: Flexible poles can provide rapid eccentric and concentric muscle contractions. Muscle vibration is associated with a "tonic vibration reflex” that is stimulated by a sequence of rapid muscle stretching, activation of the muscle spindles and stimulation of a response that is similar to the myotatic reflex. Literature studies analyzing the acute cardiovascular responses to different exercises performed with this instrument are lacking. We investigated the acute effects of exercise with flexible poles on the heart period in healthy men. METHOD: The study was performed on ten young adult males between 18 and 25 years old. We evaluated the heart rate variability in the time and frequency domains. The subjects remained at rest for 10 min. After the rest period, the volunteers performed the exercises with the flexible poles. Immediately after the exercise protocol, the volunteers remained seated at rest for 30 min and their heart rate variability was analyzed. RESULTS: The pNN50 was reduced at 5-10 and 15-20 min after exercise compared to 25-30 min after exercise (p = 0.0019), the SDNN was increased at 25-30 min after exercise compared to at rest and 0-10 min after exercise (p = 0.0073) and the RMSSD was increased at 25-30 min after exercise compared to 5-15 min after exercise (p = 0.0043). The LF in absolute units was increased at 25-30 min after exercise compared to 5-20 min after exercise (p = 0.0184). CONCLUSION: A single bout of exercise with a flexible pole reduced the heart rate variability and parasympathetic recovery was observed approximately 30 min after exercise

A single bout of exercise with a flexible pole induces significant cardiac autonomic responses in healthy men

OBJECTIVES: Flexible poles can provide rapid eccentric and concentric muscle contractions. Muscle vibration is associated with a "tonic vibration reflex” that is stimulated by a sequence of rapid muscle stretching, activation of the muscle spindles and stimulation of a response that is similar to the myotatic reflex. Literature studies analyzing the acute cardiovascular responses to different exercises performed with this instrument are lacking. We investigated the acute effects of exercise with flexible poles on the heart period in healthy men. METHOD: The study was performed on ten young adult males between 18 and 25 years old. We evaluated the heart rate variability in the time and frequency domains. The subjects remained at rest for 10 min. After the rest period, the volunteers performed the exercises with the flexible poles. Immediately after the exercise protocol, the volunteers remained seated at rest for 30 min and their heart rate variability was analyzed. RESULTS: The pNN50 was reduced at 5-10 and 15-20 min after exercise compared to 25-30 min after exercise (p = 0.0019), the SDNN was increased at 25-30 min after exercise compared to at rest and 0-10 min after exercise (p = 0.0073) and the RMSSD was increased at 25-30 min after exercise compared to 5-15 min after exercise (p = 0.0043). The LF in absolute units was increased at 25-30 min after exercise compared to 5-20 min after exercise (p = 0.0184). CONCLUSION: A single bout of exercise with a flexible pole reduced the heart rate variability and parasympathetic recovery was observed approximately 30 min after exercise

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.Universidade Estadual Paulista (UNESP) Botucatu School of MedicineUniversidade Federal do Rio de JaneiroUniversidade Estadual de CampinasUniversidade Federal de São Paulo (UNIFESP)Pontificia Universidade Catolica de São PauloUNIFESPSciEL

Desafios para bibliotecas volantes frente à pandemia: relato de experiência do carro-biblioteca da UFOP / Tchallenges for mobile library in front of the pandemic: experience report of carro-biblioteca da UFOP

O Sistema de Bibliotecas e Informação (SISBIN) é o órgão da Universidade Federal de Ouro Preto (UFOP) responsável pela gestão de 12 bibliotecas setoriais e uma biblioteca itinerante. As bibliotecas itinerantes buscam democratizar o acesso ao livro e incentivar a leitura, e o Carro Biblioteca da Universidade Federal de Ouro Preto é um projeto de extensão criado com esse propósito. A leitura é um direito humano universal, contudo as desigualdades sociais no Brasil comprometem o seu acesso. O advento da Covid-19 impediu as atividades presenciais desenvolvidas pela universidade, assim como, as atividades de extensão desenvolvidas por ela junto à comunidade, criando o desafio de se manter a continuidade das ações de acesso e incentivo à leitura por meios virtuais. Esse relato de experiência busca conhecer os desafios encontrados pelo projeto e os caminhos desenvolvidos para superá-los, seja criando perfis em mídias sociais ou dialogando com um novo público diferente do usuário real do projeto. Para embasar esse artigo foram pesquisados e analisados relatórios anuais de atividades desenvolvidas apresentadas ao SISBIN e também à Pró-reitoria de Extensão e Cultura (PROEX), e por fim, houve o acompanhamento das mídias do projeto

Bioactive evaluation and application of different formulations of the natural colorant curcumin (E100) in a hydrophilic matrix (yogurt)

Curcumin (E100) is a natural colorant that, besides conferring color, has bioactivity, serving as an alternative to some artificial colorants. As a hydrophobic colorant, its modification/compatibilization with the aqueous medium is required to improve stability and enable its application in hydrophilic food matrices. Herein, different formulations of curcumin (curcumin powder: PC, water-dispersible curcumin: DC: and nanoencapsulated curcumin: NC) were evaluated as yogurt colorants. PC showed the strongest bioactivity in all assays (EC50 values: 63±2 to 7.9±0.1 μg.mL-1; GI50 values: 48±1 to 17±1 μg.mL-1 and MIC values: 0.0625 to 0.5 mg.mL-1), which might indicate that DC and NC reduce the short-term accessibility to curcumin. The tested curcumin formulations produced yogurts with different appearance, specifically associated with their color parameters, besides presenting slight changes in nutritional composition and free sugars and fatty acids profiles. The water compatible formulations (DC and NC) showed advantages over hydrophobic (PC) having a wider industrial utilization.info:eu-repo/semantics/publishedVersio

Mineração de dados na predição do tempo de imobilidade de camundongos no teste de nado forçado.

Este trabalho tem como objetivo colher informações sobre camundongos, expostos a um fármaco na sua forma livre e nanoencapsulado avaliados no teste do nado forçado. Os resultados foram aplicados em um algoritmo de mineração de dados que pode identificar padrões que permitem a predição do tempo, por grupo de avaliação, com acertividade de 78,19 %

Interação do NLRP3-Inflamassoma com doenças autoimunes: uma revisão de literatura

Introduction: Among the protection mechanisms of the immune system, there is the protein-inflammasome complex. This intracellular complex acts as a sensor and mediator of danger signals, being formed by three basic structures: NOD-type receptor, ASC adapter protein and pro-caspase1. Once activated, it is able to induce interleukin maturation and secretion, mainly IL-1β and IL-18. However, the deregulation of this molecular platform has been associated with the development and progression of many inflammatory and autoimmune diseases. Methods: Bibliographic review using the academic Google, Medline, as databases. Center for Biotechnology Information (PubMed) and the Scientific Electronic Electronic Library Online (SciELO) electronic library. The search was carried out in articles published from 2000 to 2020, in Portuguese and /or English, with the keywords inflammasome, autoimmune disease, rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus and multiple sclerosis. Development: An etiological relationship between autoimmune diseases and inflammasome activation has been shown. Studies have demonstrated the importance of the protein complex in the regulation of innate immunity and its significance in autoimmune diseases. Conclusion: This analysis demonstrated that the loss of self-tolerance involved in autoimmune diseases is substantially related to the exacerbated production of cytokines IL-1β and IL-18 due to the altered genes resulting from the activation of the NLR-Inflamasome complex.Introdução: Dentre os mecanismos de proteção do sistema imunológico, está o complexo proteico-inflamassoma. Este complexo intracelular atua como sensor e mediador de sinais de perigo, sendo formado por três estruturas básicas: receptor do tipo NOD, proteína adaptadora ASC e pró-caspase1. Uma vez ativado, é capaz de induzir a maturação e a secreção de interleucinas, principalmente, IL-1β e IL-18. No entanto, a desregulação dessa plataforma molecular tem sido associada ao desenvolvimento e progressão de muitas doenças inflamatórias e autoimunes. Métodos: Revisão bibliográfica utilizando como bases de dados o Google acadêmico, Medline, Center for Biotechnology Information (PubMed) e a biblioteca eletrônica Scientific Eletronic Library Online (SciELO). A busca foi realizada em artigos publicados no período de 2000 a 2020, em português e/ou inglês, com as palavras-chaves inflamassoma, doença autoimune, artrite reumatoide, diabetes melittus tipo I, lúpus eritematoso sistêmico e esclerose múltipla. Desenvolvimento: Foi evidenciado uma relação etiológica das doenças autoimunes com a ativação do inflamassoma. Estudos demonstraram a importância do complexo proteico na regulação da imunidade inata e seu significado nas doenças autoimunes. Conclusão: Esta análise demonstrou que a perda da autotolerância envolvidas nas doenças autoimunes está substancialmente relacionada a produção exacerbada de citocinas IL-1β e IL-18 devido aos genes alterados decorrentes à ativação do complexo-NLR-Inflamassoma

Prolonged caffeine intake decreases alveolar bone damage induced by bingelike ethanol consumption in adolescent female rats

Ethanol consumption has been reported to negatively impact on periodontal disease. In particular, oral cavity disorders occur upon ethanol exposure during adolescence, a life period associated with particular patterns of short and intense (‘binge-like’) ethanol consumption that is most deleterious to oral health. The hazardous central effects of ethanol have been linked to the overfunction of adenosine receptors, which are antagonized by caffeine, a bioactive substance present in numerous natural nutrients, which can also modify bone metabolism. The aim of this study was to investigate the effects of caffeine on alveolar bone damage induced by an ethanol binge drinking paradigm during adolescence. Female Wistar rats (35 days old; n = 30) were allocated to six groups: control (vehicle), ethanol (3 g/kg/day; 3 days On-4 days Off challenge), caffeine (10 mg/kg/day), caffeine plus ethanol, SCH58261 (0.1 mg/kg/day, an antagonist of A2A receptors), and SCH58261 plus ethanol. Bone micromorphology and vertical bone loss were analyzed by computed microtomography. Our data showed that ethanol binge drinking reduced alveolar bone quality, with repercussion on alveolar bone size. This ethanolinduced alveolar bone deterioration was abrogated upon treatment with caffeine, but not with SCH58261. This shows that caffeine prevented the periodontal disorder caused by ethanol binge drinking during adolescence, an effect that was not mediated by adenosine A2A receptor blockad

Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine

Butyrylcholinesterase (BChE) is a plasma enzyme that catalyzes the hydrolysis of choline esters, including the muscle-relaxant succinylcholine and mivacurium. Patients who present sustained neuromuscular blockade after using succinylcholine usually carry BChE variants with reduced enzyme activity or an acquired BChE deficiency. We report here the molecular basis of the BCHE gene underlying the slow catabolism of succinylcholine in a patient who underwent endoscopic nasal surgery. We measured the enzyme activity of BChE and extracted genomic DNA in order to study the promoter region and all exons of the BCHE gene of the patient, her parents and siblings. PCR products were sequenced and compared with reference sequences from GenBank. We detected that the patient and one of her brothers have two homozygous mutations: nt1615 GCA > ACA (Ala539Thr), responsible for the K variant, and nt209 GAT > GGT (Asp70Gly), which produces the atypical variant A. Her parents and two of her brothers were found to be heterozygous for the AK allele, and another brother is homozygous for the normal allele. Sequence analysis of exon 1 including 5′UTR showed that the proband and her brother are homozygous for –116GG. The AK/AK genotype is considered the most frequent in hereditary hypocholinesterasemia (44%). This work demonstrates the importance of defining the phenotype and genotype of the BCHE gene in patients who are subjected to neuromuscular block by succinylcholine, because of the risk of prolonged neuromuscular paralysis