沿岸海洋景観のGISデータベースの構築

<p>Superimposition of the top poses of LASSBio-448 obtained by docking with PDE4A and PDE4C (light purple surface, PDE4A) (A), PDE4B and PDE4D (gold surface, PDE4D) (B). Hydrogen atoms have been omitted for clarity.</p

Gold nanoparticles inhibit steroid-insensitive asthma in mice preserving histone deacetylase 2 and NRF2 pathways

Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GCresistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2

Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis

The Mediterranean diet, rich in olive oil, is beneficial, reducing the risk of cardiovascular diseases and cancer. Olive oil is mostly composed of the monounsaturated fatty acid omega-9. We showed omega-9 protects septic mice modulating lipid metabolism. Sepsis is initiated by the host response to infection with organ damage, increased plasma free fatty acids, high levels of cortisol, massive cytokine production, leukocyte activation, and endothelial dysfunction. We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. We treated mice for 14 days with omega-9 and induced sepsis by cecal ligation and puncture (CLP). We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. We further studied omega-9 effects on leukocyte rolling in mouse cremaster muscle-inflamed postcapillary venules and in the cerebral microcirculation of septic mice. Here, we demonstrate that omega-9 treatment is associated with increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the proinflammatory cytokines TNF-alpha and IL-1 beta in peritoneal lavage fluid of mice with sepsis. Omega-9 treatment also decreased systemic corticosterone levels. Neutrophil migration from circulation to the peritoneal cavity and leukocyte rolling on the endothelium were decreased by omega-9 treatment. Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. The significant reduction of inflammation detected after omega-9 enteral injection can further contribute to the already known beneficial properties facilitated by unsaturated fatty acid-enriched diets

Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions

T cell response plays an essential role in the host resistance to infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. This infection is often associated with multiple manifestations of T cell dysfunction, both during the acute and the chronic phases of disease. Additionally, the normal development of T cells is affected. As seen in animal models of Chagas disease, there is a strong thymic atrophy due to massive death of CD4+CD8+ double-positive cells by apoptosis and an abnormal escape of immature and potentially autoreactive thymocytes from the organ. Furthermore, an increase in the release of corticosterone triggered by T. cruzi-driven systemic inflammation is strongly associated with the alterations seen in the thymus of infected animals. Moreover, changes in the levels of other hormones, including growth hormone, prolactin, and testosterone are also able to contribute to the disruption of thymic homeostasis secondary to T. cruzi infection. In this review, we discuss the role of hormonal circuits involved in the normal T cell development and trafficking, as well as their role on the thymic alterations likely related to the peripheral T cell disturbances largely reported in both chagasic patients and animal models of Chagas disease

Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions

Submitted by Sandra Infurna ([email protected]) on 2018-10-09T12:20:48Z No. of bitstreams: 1 alexandre_Morrot_etal_IOC_2018.pdf: 414698 bytes, checksum: 4a7b03fa9eed4564722701df4f6c87c1 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-10-09T12:56:16Z (GMT) No. of bitstreams: 1 alexandre_Morrot_etal_IOC_2018.pdf: 414698 bytes, checksum: 4a7b03fa9eed4564722701df4f6c87c1 (MD5)Made available in DSpace on 2018-10-09T12:56:16Z (GMT). No. of bitstreams: 1 alexandre_Morrot_etal_IOC_2018.pdf: 414698 bytes, checksum: 4a7b03fa9eed4564722701df4f6c87c1 (MD5) Previous issue date: 2018Institute of Clinical and Experimental Immunology. Rosario, Argentina.Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Centro de Pesquisas em Tuberculose. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.T cell response plays an essential role in the host resistance to infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. This infection is often associated with multiple manifestations of T cell dysfunction, both during the acute and the chronic phases of disease. Additionally, the normal development of T cells is affected. As seen in animal models of Chagas disease, there is a strong thymic atrophy due to massive death of CD4+CD8+ double-positive cells by apoptosis and an abnormal escape of immature and potentially autoreactive thymocytes from the organ. Furthermore, an increase in the release of corticosterone triggered by T. cruzi-driven systemic inflammation is strongly associated with the alterations seen in the thymus of infected animals. Moreover, changes in the levels of other hormones, including growth hormone, prolactin, and testosterone are also able to contribute to the disruption of thymic homeostasis secondary to T. cruzi infection. In this review, we discuss the role of hormonal circuits involved in the normal T cell development and trafficking, as well as their role on the thymic alterations likely related to the peripheral T cell disturbances largely reported in both chagasic patients and animal models of Chagas disease

Alterações histopatológicas em girinos de rã-touro alimentados com rações comerciais de diferentes níveis protéicos Histopathological alterations in bullfrog tadpoles fed commercial diets with three levels of crude protein

Realizaram-se necropsia e exame histopatológico de girinos de rã-touro (Rana catesbeiana) alimentados com rações comerciais formuladas com 32, 36, 45 ou 55% de proteína bruta (PB) visando estabelecer a relação entre o nível de proteína bruta da ração e a sanidade do animal. Na necropsia, os girinos não apresentaram externamente nenhuma alteração aparente, no entanto, o fígado dos animais, em todos os níveis de proteína bruta, apresentou-se de cor palha e manchado. Na análise histopatológica, observaram-se fígados com rarefação e degeneração celular protéica, intestinos com colite e achatamento das microvilosidades; baço com hiperplasia linfocitária; coração sem nenhuma alteração; rins com glomerulonefrite e áreas de tubulonefroses; gastrite mononuclear e hiperplasia e hipertrofia dos linfonodos regionais. Em todos os órgãos, verificou-se depósito de hemossiderina. Essas lesões sugerem quadro degenerativo nutricional, com desenvolvimento de processos inflamatórios, se difundindo para todos os órgãos. Os resultados sugerem que os animais foram alimentados com rações com proteínas de baixo valor biológico, portanto, de má qualidade, o que comprometeu a sanidade e o desempenho dos animais. Estudos complementares são necessários para compreensão do comportamento bioquímico de rãs-touro na fase de girino visando à nutrição adequada desses animais.<br>Necropsy and histological examination were made on bullfrog (Rana catesbeiana) tadpoles fed commercial rations with 32, 36, 45 or 55% crude protein (CP) to establish the relationship between dietary crude protein and health of the animal. In the necropsy, the tadpoles did not show externally any changes, however, the liver of animals at all crude protein levels, presented a straw color and stained. Histological analysis showed livers with rarefaction and degeneration of cell protein, intestines, with colitis and flattening of microvilli, spleen with lymphocyte hyperplasia, heart, without alterations, kidneys with glomerulonephritis and areas of tubulonefroses; mononuclear gastritis and hyperplasia and hypertrophy of regional lymph nodes. In all organs, there was hemossiderin deposit. These injuries suggest degenerative nutritional condition, with development of inflammatory processes, spreading to all organs. The results suggest that the animals were fed diets with low biological value proteins, therefore, poor quality, which affects health and performance of the animals. Further studies are necessary to understanding the biochemical behavior of bullfrogs in the tadpole stage, aiming to adequate nutrition of these animals

Proteomic profiling of splenic interstitial fluid of malnourished mice infected with Leishmania infantum reveals defects on cell proliferation and pro-inflammatory response

Protein malnutrition is a risk factor for developing visceral leishmaniasis. Because we previously demonstrated that protein malnutrition and infection with Leishmania infantum disrupts the splenic microarchitecture in BALB/c mice, alters T cell-subsets and increases splenic parasite load, we hypothesize that splenic microenvironment is precociously compromised in infected animals that suffered a preceding malnutrition. To evaluate this, we characterized the abundance of proteins secreted in the splenic interstitial fluid (IF) using an iTRAQ-based quantitative proteomics approach. In addition, local levels of pro-inflammatory and proliferation molecules were analyzed. Whereas well-nourished infected animals showed increased IL-1β and IL-2 levels, malnourished-infected mice displayed significant reduction of these cytokines. Remarkably, a two-weeks infection with L. infantum already modified protein abundance in the splenic IF of well-nourished mice, but malnourished animals failed to respond to infection in the same fashion. Malnutrition induced significant reduction of chemotactic and pro-inflammatory molecules as well as of proteins involved in nucleic acid and amino acid metabolism, indicating an impaired proliferative microenvironment. Accordingly, a significant decrease in Ki67 expression was observed, suggesting that splenocyte proliferation is compromised in malnourished animals. Together, our results show that malnutrition compromises the splenic microenvironment and alters the immune response to the parasite in malnourished individuals. Significance: Protein malnutrition is recognized as an important epidemiological risk factor for developing visceral leishmaniasis (VL). Locally secreted factors present in the interstitial fluid have important roles in initiating immune responses and in regulating fluid volume during inflammation. However, the regulation of secreted factors under pathological conditions such as malnutrition and infection are widely unknown. To analyze how protein malnutrition alters secreted proteins involved in the immune response to L. infantum infection we evaluated the proteomic profile of the interstitial fluid of the spleen in malnourished BALB/c mice infected with L. infantum. Our work revealed new elements that contribute to the understanding of the immunopathological events in the spleen of malnourished animals infected with L. infantum and opens new pathways for consideration of other aspects that could improve VL treatment in malnourished individuals

Symbols, GenBank accession numbers and descriptions of the genes mentioned in the text.

<p>Symbols, GenBank accession numbers and descriptions of the genes mentioned in the text.</p

Metaclopramide diminishes the abnormal appearance of CD4⁺CD8⁺ cells in subcutaneous lymph nodes from <i>T. cruzi</i> infected mice.

<p>The figure shows that in mice treated with the vehicle alone, acute <i>T. cruzi</i> infection did induce the abnormal appearance of CD4⁺CD8⁺ cells in subcutaneous lymph nodes (SCLN). Although such cells were also detected after <i>in vivo</i> treatment metoclopramide (MET, which promotes an increase in circulating PRL levels) their absolute numbers were significantly lower than those recorded in infected counterparts treated with the vehicle alone. Uninfected and infected mice received daily s.c. MET from 10 to 14 dpi or PBS as vehicle. At 15 dpi they were killed and their SCLN removed, homogenized and counted using Neubauer chamber. One million viable cells were immunostained with anti-CD4, anti-CD8 and anti-TCRβ antibodies, and CD4⁺CD8⁺ T cells were thus characterized. Absolute numbers of these CD4⁺CD8⁺ T cells were expressed as mean ± SE. These data are representative of two independent experiments using three mice per group in each experiment. Statistically significant differences (p<0.05) between uninfected versus infected (<b>*</b>) or between 8 and 15 dpi (<b>#</b>) mice. ***p<0.001.</p