Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)
. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the ...mechanisms involved are not completely understood
. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14
cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.
A valorização de alimentos regionais, como o mel e leite caprino, pode acelerar o desenvolvimento social e crescimento econômico de regiões produtoras no Brasil. Objetivou-se com esta pesquisa ...elaborar e avaliar a estabilidade físico-química durante o armazenamento de iogurtes de leite caprino adoçados com méis de diferentes floradas. Os iogurtes de leite de cabra com inulina (5%) como agente prebiótico foram elaborados, sem adição de mel (padrão) e com adição de mel das floradas silvestre (sem florada predominante), marmeleiro (Croton sonderianus) e juazeiro (Zizyphus joazeiro Mart). Os iogurtes foram avaliados em 5 tempos, durante 40 dias de armazenamento (4 °C) quanto aos parâmetros de extrato seco, cinzas, pH e acidez total. O méis atenderam a todos os parâmetros preconizados pela legislação. A adição de mel nos iogurtes caprinos promoveu o aumento dos valores de extrato seco total e redução dos valores de cinzas, pH e acidez. Durante o armazenamento ocorreu redução dos valores de extrato seco total, cinzas e pH e elevação dos valores de acidez. Os iogurtes apresentaram comportamento físico-químico semelhante durante o armazenamento, destacando-se aqueles adicionados com mel de juazeiro e marmeleiro. Infere-se que os produtos sofreram alterações significativas, sendo necessárias análises complementares para atestar a viabilidade mercadológica.
Cell-cell interactions control the physiology and pathology of the central nervous system (CNS). To study astrocyte cell interactions in vivo, we developed rabies barcode interaction detection ...followed by sequencing (RABID-seq), which combines barcoded viral tracing and single-cell RNA sequencing (scRNA-seq). Using RABID-seq, we identified axon guidance molecules as candidate mediators of microglia-astrocyte interactions that promote CNS pathology in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis (MS). In vivo cell-specific genetic perturbation EAE studies, in vitro systems, and the analysis of MS scRNA-seq datasets and CNS tissue established that Sema4D and Ephrin-B3 expressed in microglia control astrocyte responses via PlexinB2 and EphB3, respectively. Furthermore, a CNS-penetrant EphB3 inhibitor suppressed astrocyte and microglia proinflammatory responses and ameliorated EAE. In summary, RABID-seq identified microglia-astrocyte interactions and candidate therapeutic targets.
Recently a textile azo dye processing plant effluent was identified as one of the sources of mutagenic activity detected in the Cristais River, a drinking water source in Brazil G.A. Umbuzeiro, D.A. ...Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton, Investigating the sources of the mutagenic activity found in a river using the
Salmonella assay and different water extraction procedures, Chemosphere 54 (2004) 1589–1597. Besides presenting high mutagenic activity in the
Salmonella/microsome assay, the mutagenic nitro-aminoazobenzenes dyes CI Disperse Blue 373, CI Disperse Violet 93, and CI Disperse Orange 37 G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of the Cristais river, Chemosphere 60 (2005) 55–64 as well as benzidine, a known carcinogenic compound T.M. Mazzo, A.A. Saczk, G.A. Umbuzeiro, M.V.B. Zanoni, Analysis of aromatic amines in surface waters receiving wastewater from textile industry by liquid chromatographic with eletrochemical detection, Anal. Lett., in press were found in this effluent. After ∼6
km from the discharge of this effluent, a drinking water treatment plant treats and distributes the water to a population of approximate 60,000. As shown previously, the mutagens in the DWTP intake water are not completely removed by the treatment. The water used for human consumption presented mutagenic activity related to nitro-aromatics and aromatic amines compounds probably derived from the cited textile processing plant effluent discharge G.A. Umbuzeiro, D.A. Roubicek, C.M. Rech, M.I.Z. Sato, L.D. Claxton, Investigating the sources of the mutagenic activity found in a river using the
Salmonella assay and different water extraction procedures, Chemosphere 54 (2004) 1589–1597; G.A. Umbuzeiro, H.S. Freeman, S.H. Warren, D.P. Oliveira, Y. Terao, T. Watanabe, L.D. Claxton, The contribution of azo dyes in the mutagenic activity of the Cristais river, Chemosphere 60 (2005) 55–64. Therefore, it is important to evaluate the possible risks involved in the human consumption of this contaminated water. With that objective, one sample of the cited industrial effluent was tested for carcinogenicity in the aberrant crypt foci medium-term assay in colon of Wistar rats. The rats received the effluent
in natura through drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity was also confirmed in the
Salmonella/microsome assay with the strains TA98 and YG1041. There was an increased number of preneoplastic lesions in the colon of rats exposed to concentrations of 1% and 10% of the effluent, and a positive response for both
Salmonella strains tested. These results indicate that the discharge of the effluent should be avoided in waters used for human consumption and show the sensitivity of the ACF crypt foci assay as an important tool to evaluate the carcinogenic potential of environmental complex mixtures.
A mangaba apresenta grande potencial para elaboração de fermentados alcoólicos, sendo de extrema importância o acompanhamento do processo fermentativo para obtenção dessa bebida, assim como de ...outras. Assim, objetivou-se acompanhar e avaliar o processo cinético de fermentação e os parâmetros fermentativos de bebidas fermentadas de mangaba. Foram elaboradas quatro formulações de fermentados com variação do teor de sólidos solúveis inicial e concentração de leveduras conforme etapas e concentrações descritas no processo de pedido de patente BR 10 2018 075834 9. Durante a fermentação, retirou-se alíquotas para o acompanhamento da cinética de fermentação e parâmetros fermentativos. Verificou-se que o comportamento cinético, com exceção do tempo de fermentação, não sofreu interferência pelas variáveis estudadas, e que a formulação 3 (maior teor de sólidos solúveis e menos concentração de levedura) e formulação 4 (maior teor de sólidos solúveis e maior concentração de levedura) apresentaram melhores resultados principalmente no tocante a teor alcoólico, concentração de etanol experimental e teórico, rendimento do processo e em produto. Conclui-se que não houve diferença no comportamento cinético, mas existiu nos parâmetros fermentativos das bebidas de mangaba.
To evaluate the chronic effects of a static stretching program on the muscle architecture of biceps femoris (BF) and vastus lateralis (VL) muscles in ultrasound (US) images.
Randomized controlled ...longitudinal trial.
Biomechanics Laboratory of Physical Education School of the Army, Rio de Janeiro, Brazil.
The study included 24 healthy and physically active male volunteers (19.05 ± 1.40 years, 1.73 ± 0.07 m, and 73.15 ± 8.33 kg), randomly allocated to 1 of 2 groups: stretching group (SG, n = 12) and control group (n = 12).
The SG was submitted to 3 sets of 30 seconds of static stretching 3 times a week during 8 weeks.
Ultrasound equipment (7.5 MHz) was used for the evaluation of BF and VL muscle architecture variables (pennation angle, fiber length, muscle thickness, and fascicle displacement) before and after training. Knee range of motion (ROM) and isometric flexion and extension torque (TQ) were also measured.
There were no significant changes in muscle architecture, TQ, and maximum knee flexion angle (P > 0.05). However, maximum knee extension angle (MEA) increased significantly in the SG (pretraining: 159.37 ± 7.27 degrees and posttraining: 168.9 ± 3.7 degrees; P < 0.05).
Volume or intensity (or both) of the stretching protocol was insufficient to cause structural changes in the VL and BF muscles. The increase in MEA could not be explained by muscle architecture changes.
To describe changes in the VL and BF muscle tendon unit using US after a long-term stretching program to identify which structures are responsible for ROM increase.
Schistosoma mansoni is one of the major parasites causing human schistosomiasis, recognized as a major global health problem with over 200 million people afflicted worldwide (Moraes et al., 2012). ...Schistosomiasis is a chronic and debilitating disease that continues to threaten millions of people, particularly the rural poor in the developing world (WHO, 2011). The reference drug for treatment of schistosomiasis is praziquantel (PZQ), but this drug is ineffective against immature forms and recent reports of resistance in some strains have worried the world's public health organizations. Therefore many studies have been testing the effectiveness of new drugs against many schistosomiasis strains. The determination of cytotoxicity Peripheral blood mononuclear cells were obtained from heparinized blood from healthy, nonsmoking donors who had not taken any medication for at least 15 days prior to the sample collection (10 volunteers), and cells were isolated via a standard method of density-gradient centrifugation using a Ficoll Hypaque solution (GE Healthcare).
Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth ...microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.
Cardiotonic steroids, such as ouabain and digoxin, are known to bind to Na+/K+-ATPase and to promote several biological activities, including anti-inflammatory activity. However, there are still no ...reports in the literature about inflammation and marinobufagenin, a cardiotonic steroid from the bufadienolide family endogenously found in mammals. Therefore, the aim of this work was to analyze, in vivo and in vitro, the role of marinobufagenin in acute inflammation. Swiss mice were treated with 0.56 mg/kg of marinobufagenin intraperitoneally (i.p.) and zymosan (2 mg/mL, i.p.) was used to induce peritoneal inflammation. Peritoneal fluid was collected and used for counting cells by optical microscopy and proinflammatory cytokine quantification (IL-1β, IL-6, and TNF-α) by immunoenzymatic assay (ELISA). Zymosan stimulation, as expected, induced increased cell migration and proinflammatory cytokine levels in the peritoneum. Marinobufagenin treatment reduced polymorphonuclear cell migration and IL-1β and IL-6 levels in the peritoneal cavity, without interfering in TNF-α levels. In addition, the effect of marinobufagenin was evaluated using peritoneal macrophages stimulated by zymosan (0.2 mg/mL) in vitro. Marinobufagenin treatment at different concentrations (10, 100, 1000, and 10000 nM) showed no cytotoxic effect on peritoneal macrophages. Interestingly, the lowest concentration, which did not inhibit Na+/K+-ATPase activity, attenuated proinflammatory cytokines IL-1β, IL-6, and TNF-α levels. To investigate the putative mechanism of action of marinobufagenin, the expression of surface molecules (TLR2 and CD69) and P-p38 MAPK were also evaluated, but no significant effect was observed. Thus, our results suggest that marinobufagenin has an anti-inflammatory role in vivo and in vitro and reveals a novel possible endogenous function of this steroid in mammals.
É normal que educandos apresentem dificuldade na assimilação do conhecimento teórico da entomologia, já que exige alto grau de abstração. As atividades de campo são métodos utilizados para a redução ...deste impedimento, norteando uma aprendizagem significativa e amplificando o trabalho grupal. Sendo assim, este trabalho objetivou desenvolver a prática de coleta e catalogação de insetos para a confecção de coleções entomológicas nas Escolas Estaduais de Ensino Profissionalizante dos municípios de Guaiúba e Viçosa do Ceará. Para o desenvolvimento desse trabalho, os alunos coletaram insetos nas escolas e suas periferias, os exemplares capturados eram catalogados e inseridos em caixas entomológicas. Na execução das atividades pôde-se observar um grande comprometimento e interesse dos educandos, principalmente por se tratar de uma atividade diferenciada (fora da sala de aula); também, nas diversas fases da atividade, foi observado nitidamente o intercâmbio de conhecimentos, configurando-se assim, uma aprendizagem cooperativa, constatada por observações in loco. Ao final da disciplina foi constatado que nenhum educando necessitou de processo de intervenção educacional, uma vez que a análise das avaliações escritas e não escritas apresentou uma real assimilação do conhecimento. Nesse sentido, a confecção de coleção entomológica mostrou-se um recurso significativamente eficiente no ensino da disciplina de Entomologia Agrícola e Combate a Pragas e Doenças.
PDF
