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Mucopolysaccharidoses (MPS) are genetic metabolic diseases characterized by defects in the activity of lysosomal hydrolases. In MPS, secondary cell disturbance affects pathways related to cardiovascular disorders. Hence, the study aimed to identify MPS-related drugs targeting cardiovascular disease and select a list of drugs for repositioning. We obtained a list of differentially expressed genes and pathways. To identify drug perturbation-driven gene expression and drug pathways interactions, we used the CMAP and LINCS databases. For molecular docking, we used the DockThor web server. Our results suggest that pirfenidone and colchicine are promising drugs to treat cardiovascular disease in MPS patients. We also provide a brief description of good practices for the repositioning analysis. Furthermore, the list of drugs and related MPS-enriched genes could be helpful to new treatments and considered for pathophysiological studies.
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HIV-1-associated neurocognitive disorders (HAND) are a major concern in HIV-infected individuals despite the currently available antiretroviral therapy regime. Impaired M1 pro-inflammatory microglial activation is considered one of the hallmark features of HAND neuropathogenesis, and it has been suggested that circulant HIV-1 transactivator protein (Tat) can play a critical role in this process. At the same time, endoplasmatic reticulum (ER) stress has also been implicated in neurodegenerative conditions resulting from the accumulation of misfolded proteins and subsequent unfolded protein response (UPR) deflagration. Here, we demonstrate that pharmacological inhibition of UPR-related protein kinase R-like endoplasmic reticulum kinase (PERK) can attenuate HIV-1 Tat-induced M1 inflammatory state in microglia in vitro. Our initial experiments demonstrate that the bystander stimulus of recombinant Tat on BV-2 microglial cells result in the coupled overexpression of central UPR markers and pro-inflammatory mediators such as iNOS, surface CD16/32 and secreted tumour necrosis factor-α (TNF-α), IL-6, monocyte chemoattractant protein (MCP)-1 and NO. We show that blocking PERK-eIF2-α-ATF4 signalling using the PERK inhibitor GSK2606414 leads to reduced inflammatory response in M1-like BV-2 cells activated by recombinant Tat. Taken together, these findings suggest that PERK targeting may provide a therapeutic intervention to mitigate against lasting neuroinflammation and neuronal loss in of HAND.
Assuntos
Microglia , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Microglia/metabolismo , Fenótipo , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismoRESUMO
Quick meals available in markets are popular among consumers. Generally, these products are not recognized as functional foods owing to nutrient-poor composition. In this study, energy snack bars were developed with different formulations, using puffed quinoa, amaranth, cacao liquor, and coconut oil, and the effects of the addition of commercial vegetal mixtures (VM) on nutritional and functional properties were assessed. VM addition showed significant effects on the protein, lipid, and fiber contents, phenolic compounds (PHC) content, and antioxidant activity of the snacks. The control snack showed higher levels of free and bound PHC. The oxygen radical absorbance capacity (ORAC) analyses recorded highest values of free PHC (9392.7 µmol TE/100 g dry weight) in PC65 (concentrate based on a combination of vegetal proteins), whereas the highest bound PHC levels of 47,087 and 46,531 µmol TE/100 g dry weight were observed in PC65 and the control snacks, respectively. Sensorial attributes assessment provided a high score on the hedonic scale, wherein panelists detected no differences among the samples. Altogether, the selection of non-conventional ingredients with high antioxidant activities emerged as a successful strategy to produce sensory acceptable meals.
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Introdução: A bandagem elástica é uma fita elástica adesiva utilizada na prevenção e reabilitação do complexo do ombro. Entretanto, existem divergências na literatura sobre seus efeitos na atividade eletromiográfica dos músculos periescapulares durante exercícios com carga. Objetivo: Avaliar os efeitos da bandagem elástica na atividade eletromiográfica de músculos periescapulares durante o movimento de flexão do ombro sem carga e com halter em indivíduos saudáveis. Métodos: Vinte e seis indivíduos do sexo masculino realizaram o movimento de flexão do ombro sem carga e com halter com a bandagem elástica sobre o trapézio descendente. Foram avaliadas as atividades eletromiográficas de trapézio descendente, trapézio ascendente e serrátil anterior. São comparados os valores de pico e RMS em percentual da contração isométrica voluntária máxima através da ANOVA One Way. Resultados: Na flexão de ombro com halter ocorreu diminuição do pico da atividade eletromiográfica do trapézio descendente (p = 0,035). Não houve influência sobre os demais músculos periescapulares (p > 0,05). Conclusão: A bandagem elástica diminuiu o pico da atividade eletromiográfica do trapézio descendente durante a flexão do ombro com halter. Pode-se aplicar este resultado na prevenção de indivíduos que podem tender a aumentar a atividade do trapézio descendente. (AU)
Introduction: The kinesio tape is an elastic adhesive tape used in the prevention and rehabilitation of the shoulder complex. However, there are divergences in the literature about its effects on the electromyographic activity of the periescapular muscles during load exercises. Objective: To evaluate the effects of kinesio tape on the electromyographic activity of the periescapular muscles during the flexion of the shoulder without load and with a dumbbell in healthy subjects. Methods: Twenty-six male individuals perform the flexion movement of the shoulder without load and halter with and kinesio tape over the upper trapezius muscle. The electromyographic activities of upper trapezius, lower trapezius and anterior serratus were evaluated. Normalized Peak and RMS through percentage of maximum voluntary isometric contraction were compared using ANOVA One Way. Results: During flexion of the shoulder with a dumbbell, the electromyographic activity of the upper trapezius (p = 0.035) decreased. We did not observe influence on the other periescapular muscles (p > 0.05). Conclusion: The kinesio tape decrease the peak value of the upper trapezius during the flexion of the shoulder with dumbbell. We can apply this result to individuals who may increase the activity of the upper trapezius. (AU)
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Humanos , Masculino , Eletromiografia , Fita Atlética , Ombro , Exercício Físico , Voluntários Saudáveis , MovimentoRESUMO
Scapular dyskinesis is an abnormality in scapula static or dynamic position. There are several techniques for scapular dyskinesis conservative treatment, including Kinesio Tape application, which is used to promote and support scapula joint alignment, decrease pain and improve local muscle control. The study aim to investigate the effect of kinesio tape on scapular kinematics in subjects with scapular dyskinesis. Fourteen subjects with scapular dyskinesis performed flexion and scaption movements in two conditions: (1) without load and (2) holding a dumbbell. A scapular tape was applied over the lower trapezius (Y shaped) muscle with a 20% tension. Kinematic data were captured with 10 infrared cameras and analyzed based on Euler angles, peak values of upward rotation, internal rotation, and posterior tilt angles. To compare the situations with and without kinesio tape the repeated measures two-way ANOVAs (α = 0.05) was performed using SPSS software. Scapular tape increase upward rotation and posterior tilt during flexion of the shoulder. No interaction (Load x KT) was found during flexion, suggesting that KT effect in the peak values is the same, regardless the load condition. Scapular tape decreases internal rotation during scaption and a significant interaction was found between load x KT, suggesting the effect of using KT could depend the load u sed during this movement. The results suggest that kinesio tape may can be use as assistant to increase upward rotation, posterior tilt and decrease internal rotation in scapular dyskinesis subjects. (AU)
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Humanos , Masculino , Feminino , Adulto , Ombro , Anormalidade Torcional , Fenômenos Biomecânicos , Fita Atlética , Anormalidades Musculoesqueléticas , Dor , Escápula , Cinesiologia Aplicada , Músculos Superficiais do Dorso , Escala de Movimento Involuntário Anormal , Articulações , Movimento , MúsculosRESUMO
The aim of the current study was to evaluate the effect of chronic administration of Eugenia uniflora fruit extract on behavioral parameters, oxidative stress markers, and acetylcholinesterase activity in an animal model of depression, which was induced by chronic unpredictable stress (CUS). Mice were divided into six groups as follows: control/vehicle (water), control/fluoxetine (20 mg/kg), control/extract (200 mg/kg), CUS/vehicle, CUS/fluoxetine (20 mg/kg), and CUS/extract (200 mg/kg). Animals of the CUS group were exposed to a series of stressors for a period of 21 days. Vehicle, fluoxetine, and hydroalcoholic extract were administered daily by gavage. Results showed that E. uniflora treatment: (a) prevented the depressant-like effect induced by CUS; (b) regulated the activity of acetylcholinesterase; (c) reduced oxidative damage to lipids and reactive oxygen species production, in the prefrontal cortex and hippocampus; and (d) prevented the reduction of glutathione peroxidase in the hippocampus of animals subjected to CUS protocol. Taken together, our findings suggested that E. uniflora extract exerts a neuroprotective effect by preventing oxidative damage and decreasing CUS-induced acetylcholinesterase activity, thus, ameliorating depressive-type behavior. PRACTICAL APPLICATIONS: E. uniflora fruit extract revealed an antidepressant-like effect and prevented the oxidative damage as well as cholinergic alterations caused by chronic stress in mice. Therefore, we believe that the results obtained in this study can be used to develop an alternative therapy for the management of depressive disorders.
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Introdução: é inquestionável que o câncer é um problema de saúde pública, especialmente entre os países em desenvolvimento, onde é esperado que, nas próximas décadas, o impacto do câncer na população corresponda a 80% dos mais de 20 milhões de casos novos estimados para 2025. Em relação às doenças malignas hematológicas estima-se para o Brasil, 5.940 casos novos de leucemia em homens e 4.860 em mulheres para cada ano do biênio 2018-2019. Diante disso, a fisioterapia aplicada à oncologia tem o objetivo de preservar, manter e restaurar a integridade cinético-funcional dos órgãos e sistemas do paciente oncológico, bem como de prevenir os distúrbios causados pelo tratamento da doença, conforme esclarece o Instituto Nacional de Câncer. Nesse contexto, o objetivo deste estudo foi descrever o perfil dos pacientes hematológicos avaliados pelo serviço de fisioterapia na unidade de Hematologia e Oncologia do Hospital Nossa Senhora da Conceição (HNSC). Metodologia: é um estudo do tipo retrospectivo transversal e foram utilizados dados do prontuário eletrônico dos pacientes hospitalizados na unidade de Oncologia e Hematologia do HNSC e o registro de dados presente na tabela de controle de avaliações fisioterapêuticas realizadas pelo serviço de fisioterapia. Resultados: foram analisados prontuários de 89 pacientes, com predominância do sexo masculino (56%) e uma média de idade de 57 anos, sendo os principais diagnósticos clínicos encontrados Linfoma não-Hodgkin e Leucemias. Além de apresentarem boa força muscular, boa performance status e nenhuma sensação de dispneia. Conclusão: o estudo possibilitou o conhecimento mesmo que parcial, do provável perfil hematológico dos pacientes que contribui como facilitador da intervenção fisioterapêutica na busca da qualificação do serviço e assistência integral ao paciente hematológico. (AU)
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Humanos , Masculino , Feminino , Serviço Hospitalar de Fisioterapia , Sistema Único de Saúde , Saúde Pública , HematologiaRESUMO
The aim of this study was to investigate the effect of blueberry (Vaccinium virgatum) fruit extract on metabolic, behavioral and oxidative stress parameters in the hippocampus and cerebral cortex of mice submitted to an experimental model of metabolic syndrome induced by a highly palatable diet (HPD). Mice C57BL/6 were divided into 4 experimental groups: (1) received standard chow and saline orally, (2) received standard chow and blueberry hydroalcoholic extract, (3) received HPD and saline orally, (4) received HPD and blueberry hydroalcoholic extract. The animals were treated for 150days. Our results showed that the animals fed with HPD presented insulin resistance, increased body weight, visceral fat, glucose, triglycerides, and total cholesterol when compared to the control group. The blueberry extract prevented the increase of these metabolic parameters. Also, the extract was able to reduce the levels of thiobarbituric acid reactive substances in the cerebral cortex and hippocampus of animals submitted to HPD. In contrast, no differences were observed in the total thiol content, activity of the antioxidant enzymes catalase and superoxide dismutase. In addition, the HPD fed animals showed a significant increase in immobility time in the forced swimming test and blueberry prevented this alteration, although no changes were observed in the ambulatory behavior, as well as in the anxiolytic profile of these animals. Overall, our findings suggest that chronic consumption of blueberry extract exhibits hypoglycemic, hypolipidemic, antidepressant-like and antiperoxidative effects in an animal model of metabolic syndrome.
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Adjuvantes Farmacêuticos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Mirtilos Azuis (Planta)/química , Frutas/química , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Extratos Vegetais/uso terapêutico , Adjuvantes Farmacêuticos/farmacologia , Animais , Antocianinas/análise , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Catalase/metabolismo , Dieta , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Síndrome Metabólica/enzimologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Different concentrations of essential oil obtained from Acantholippia deserticola (Phil.ex F. Phil.) Moldenke were assessed against Chilean agricultural pests like Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker, and Tetranychus urticae Koch. Thebioassays were carried out under laboratory conditions and both direct and residual applications were done through Potter precision spraytower test. The oil was obtained by steam distillation containing a rich fraction of alpha and beta-thujones (88.4 percent) and it shows marked toxic effects against pests. Indeed, a mortality of 82 percent and 89 percent was observed in both B. chilensis and T. urticae after 48 h whereas in A. floccosus over 97 percent of mortality was seen after 7 days. These results open the possibility to use essential oil from Acantholippia deserticola as natural pesticide.
Se evaluó el efecto a diferentes concentraciones de una solución de aceite esencial de Acantholippia deserticola sobre plagas agrícolas en Chile, tales como Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker y Tetranychus urticae Koch. Los bioensayos fueron realizados mediante una torre de Potter en condiciones de laboratorio y las aplicaciones fueron directas y residuales. El aceite se obtuvo por hidrodestilación, el cual contenía una gran cantidad de alfa and beta-tuyonas (88.4 por ciento), mostrando marcados efectos tóxicos para A. floccosus, con un 97 por ciento de mortalidad después de 7 d y, para B. chilensis, y T. urticae, con una mortalidad de 82 por ciento y 89 por ciento respectivamente, después de 48 h. Estos resultados abren la posibilidad de usar aceite esencial de Acantholippia deserticola como pesticida natural.
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Ácaros , Óleos Voláteis/farmacologia , Hemípteros , Praguicidas/farmacologia , Verbenaceae/química , Agricultura , Bioensaio , Monoterpenos/farmacologia , Controle Biológico de Vetores , Testes de ToxicidadeRESUMO
It has been shown that elevation of plasma methionine (Met) and its metabolites may occur in several genetic abnormalities. In this study we investigated the in vitro and in vivo effects of the Met and methionine sulfoxide (MetO) on oxidative stress parameters in the liver of rats. For in vitro studies, liver homogenates were incubated with Met, MetO, and Mix (Met + MetO). For in vivo studies, the animals were divided into groups: saline, Met 0.4 g/kg, MetO 0.1 g/kg, and Met 0.4 g/kg + MetO 0.1 g/kg. The animals were euthanized 1 and 3 h after injection. In vitro results showed that Met 1 and 2 mM and Mix increased catalase (CAT) activity. Superoxide dismutase (SOD) was enhanced by Met 1 and 2 mM, MetO 0.5 mM, and Mix. Dichlorofluorescein oxidation was increased by Met 1 mM and Mix. In vivo results showed that Met, MetO, and Mix decreased TBARS levels at 1 h. Total thiol content decreased 1 h after and increased 3 h after MetO and Met plus MetO administrations. Carbonyl content was enhanced by Met and was reduced by MetO 1 h after administration. Met, MetO and Met plus MetO decreased CAT activity 1 and 3 h after administration. Furthermore, only MetO increased SOD activity. In addition, Met, MetO, and Mix decreased dichlorofluorescein oxidation at 1 and 3 h. Our data indicate that Met/MetO in vivo and in vitro modify liver homeostasis by altering the redox cellular state. However, the hepatic changes caused by these compounds suggest a short-time adaptation of this tissue.