Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America. The pro-inflammatory cytokine IL-1β that is mainly derived from the activation of the cytoplasmic multiprotein complex inflammasome is an essential host factor against opportunistic fungal infections; however, its role in infection with a primary fungal pathogen, such as P. brasiliensis, is not well understood. In this study, we found that murine bone marrow-derived dendritic cells responded to P. brasiliensis yeast cells infection by releasing IL-1β in a spleen tyrosine kinase (Syk), caspase-1 and NOD-like receptor (NLR) family member NLRP3 dependent manner. In addition, P. brasiliensis-induced NLRP3 inflammasome activation was dependent on potassium (K+) efflux, reactive oxygen species production, phagolysosomal acidification and cathepsin B release. Finally, using mice lacking the IL-1 receptor, we demonstrated that IL-1β signaling has an important role in killing P. brasiliensis by murine macrophages. Altogether, our results demonstrate that the NLRP3 inflammasome senses and responds to P. brasiliensis yeast cells infection and plays an important role in host defense against this fungus.
Obesity is associated with increased risk and aggressiveness of many types of cancer. Women with obesity and breast cancer are more likely to be diagnosed with larger and higher-grade tumors and have higher incidence of metastases than lean individuals. Increasing evidence indicates that obesity includes systemic, chronic low-grade inflammation, and that adipose tissue can act as an important endocrine site, secreting a variety of substances that may regulate inflammation, immune response, and cancer predisposition. Obesity-associated inflammation appears to be initially mediated by macrophage infiltration into adipose tissue. Macrophages can surround damaged or necrotic adipocytes, forming "crown-like" structures (CLS). CLS are increased in breast adipose tissue from breast cancer patients and are more abundant in patients with obesity conditions. Moreover, the CLS index-ratio from individuals with obesity seems to influence breast cancer recurrence rates and survival. In this review, we discuss the most recent cellular and molecular mechanisms involved in CLS establishment in the white adipose tissue of women with obesity and their implications for breast cancer biology. We also explain how CLS influence the tumor microenvironment and affect breast cancer behavior. Targeting breast adipose tissue CLS can be a crucial therapeutic tool in cancer treatment, especially in patients with obesity.
Foam cells are specialized lipid-loaded macrophages derived from monocytes and are a key pathological feature of atherosclerotic lesions. Lysophosphatidylcholine (LPC) is a major lipid component of the plasma membrane with a broad spectrum of proinflammatory activities and plays a key role in atherosclerosis. However, the role of LPC in lipid droplet (LD) biogenesis and the modulation of inflammasome activation is still poorly understood. In the present study, we investigated whether LPC can induce foam cell formation through an analysis of LD biogenesis and determined whether the cell signaling involved in this process is mediated by the inflammasome activation pathway in human endothelial cells and monocytes. Our results showed that LPC induced foam cell formation in both types of cells by increasing LD biogenesis via a NLRP3 inflammasome-dependent pathway. Furthermore, LPC induced pyroptosis in both cells and the activation of the inflammasome with IL-1β secretion, which was dependent on potassium efflux and lysosomal damage in human monocytes. The present study described the IL-1β secretion and foam cell formation triggered by LPC via an inflammasome-mediated pathway in human monocytes and endothelial cells. Our results will help improve our understanding of the relationships among LPC, LD biogenesis, and NLRP3 inflammasome activation in the pathogenesis of atherosclerosis.
Abstract. Nowadays information technology (IT) is present in all organizations. This pervasive use of technology has created a critical dependency on IT that calls for a specific focus on IT Governance (ITG). Organizations with effective governance have actively adopted a set of ITG mechanisms. However, ITG mechanisms are not well defined among the literature and in some cases there are incongruities in their definition. In this paper we intend to perform a literature review (LR) in order to elicit which are the main ITG mechanisms as well as to describe them and state what they are useful for. We finish our work with conclusion, contributions, limitations and future work.
Hydrological models are becoming more and more widespread, mainly due to their capacity to simulate the impact of environmental changes on water resources. In this way, the aim of this study was to calibrate and validate the SWAT model for the soil and climatic conditions of the Mucuri River Basin, located in the Northeast region of the States of Minas Gerais, Brazil. The SWAT-CUP software module SUFI2 was used to analyze the sensitivity, calibration and validation of the model. The calibration was performed in an intermediate fluviometric station and the validation in five other located: three upstream, one downstream and one independent from the calibration point. It was evidenced for the study area that the parameters referring to the basic flow processes were more sensitive. The model obtained a good adjustment with an overestimate tendency of 15%. In general, the SWAT model, using SWAT-CUP was good and adequate in terms of its calibration performance and validation of the flow simulation in the Mucuri River Basin by the determination coefficients, Nash-Suttclife efficiency and percentage of trend.
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