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251.
Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non‐tumour‐bearing rats
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Barbara M. M. Antunes Fabio Santos Lira Gustavo Duarte Pimentel José Cesar Rosa Neto Andrea Maculano Esteves Lila Missae Oyama Cláudio Teodoro de Souza Cinara Ludvig Gonçalves Emilio Luiz Streck Bruno Rodrigues Ronaldo Vagner dos Santos Marco Túlio de Mello 《Cell biochemistry and function》2015,33(6):393-397
We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)‐1β, IL‐6, IL‐10, TNF‐α and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p < 0.01). Hypothalamic malate dehydrogenase activity was reduced when compared with control (p < 0.05). In addition, pro‐inflammatory cytokine levels were unchanged. Therefore, our results demonstrate that doxorubicin leads to an impairment of \hypothalamic energy metabolism, but do not affect the inflammatory pathway. Copyright © 2015 John Wiley & Sons, Ltd.
- Introduction
- Material and Methods
- Results
- Discussion
- Conflict of Interest
252.
At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis
(MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques
for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was
shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated
that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology
in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques.
However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage
in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage.
In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief
perspective with regards to future developments in this field. 相似文献
253.
Renato Almeida Sarmento Diego Macedo Rodrigues Farid Faraji Eduardo A. L. Erasmo Felipe Lemos Adenir V. Teodoro Wagner Toshihiro Kikuchi Gil Rodrigues dos Santos Angelo Pallini 《Experimental & applied acarology》2011,53(3):203-214
One of the most promising plant species for biofuel production in Brazil is the physic nut Jatropha curcas. Major phytosanitary problems include the attack of two pest mite species, the broad mite Polyphagotarsonemus latus and the spider mite Tetranychus bastosi. Owing to pesticide-related problems, there is an increasing demand for sustainable environmental-friendly control methods
such as biological control. In this study we evaluated the suitability of the predatory mite species Iphiseiodes zuluagai and Euseius concordis in controlling P. latus and T. bastosi on J. curcas. The number of T. bastosi killed by I. zuluagai was lower than the number of P. latus consumed.
Euseius concordis preyed upon both T. bastosi and P. latus but the number of prey killed was always lower in comparison with I. zuluagai. However, P. latus and T. bastosi are suitable for the development of I. zuluagai and E. concordis as oviposition of both predators did not differ in relation to prey species. The preference of I. zuluagai for leaves of plants infested by either P. latus or T. bastosi, combined with the higher values for predation obtained by this predatory mite when fed on P. latus, compared to those values obtained by E. concordis, suggests that I. zuluagai can be more efficient than E. concordis in reducing populations of P. latus and T. bastosi under field conditions. Furthermore, we report here on the first record of predatory mites associated with P. latus and T. bastosi on native J. curcas plants in Brazil. In conclusion, we emphasize the crucial importance of predatory mites as agents of natural biological control
of mite pests on J. curcas in small farms. 相似文献
254.
255.
Castoldi A Braga TT Correa-Costa M Aguiar CF Bassi ÊJ Correa-Silva R Elias RM Salvador F Moraes-Vieira PM Cenedeze MA Reis MA Hiyane MI Pacheco-Silva Á Gonçalves GM Saraiva Câmara NO 《PloS one》2012,7(5):e37584
The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2(-/-), TLR4(-/-) and MyD88(-/-) male mice were subjected to sepsis by cecal ligation and puncture (CLP). Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2(-/-), TLR4(-/-) and MyD88(-/-) mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT). MyD88(-/-) mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1(+low) cells migration compared with the knockout mice and decreased in GR1(+high) cells migration into the peritoneal cavity. The TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells. 相似文献
256.
257.
The worldwide rising prevalence of obesity and insulin resistance is associated with a parallel increase in nonalcoholic fatty liver disease (NAFLD). NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to increased inflow of free fatty acids and/or de novo lipogenesis caused by various drugs and multiple defects in energy metabolism. Accumulation of lipids in the hepatocyte impairs the oxidative capacity of the mitochondria, increasing the reduced state of the electron transport chain (ETC) complexes and stimulating peroxisomal and microsomal pathways of fat oxidation. The consequent increased generation of reactive oxygen species (ROS) and reactive aldehydic derivatives causes oxidative stress and cell death, via ATP, NAD, and glutathione depletion and DNA, lipid, and protein damage. Oxidative stress also triggers production of inflammatory cytokines, causing inflammation and a fibrogenic response. This ultimately results in the development of nonalcoholic steatohepatitis (NASH), which can result in end-stage liver disease. The current therapeutic strategies for NASH treatment are mostly directed toward correction of the risk factors. Stimulation of mitochondrial function may also prevent NASH development, protecting the cell against the increased flux of reduced substrates to the ETC and ROS generation. 相似文献
258.
In the past decades, the progress made in plant biotechnology has made possible the use of plants as a novel production platform for a wide range of molecules. In this context, the transformation of the plastid genome has given a huge boost to prove that plants are a promising system to produce recombinant proteins. In this review, we provide a background on plastid genetics and on the principles of this technology in higher plants. Further, we discuss the most recent biotechnological applications of plastid transformation for the production of enzymes, therapeutic proteins, antibiotics, and proteins with immunological properties. We also discuss the potential of plastid biotechnology and the novel tools developed to overcome some limitations of chloroplast transformation. 相似文献
259.
The KDEL receptor couples to Gαq/11 to activate Src kinases and regulate transport through the Golgi
Giannotta M Ruggiero C Grossi M Cancino J Capitani M Pulvirenti T Consoli GM Geraci C Fanelli F Luini A Sallese M 《The EMBO journal》2012,31(13):2869-2881
Membrane trafficking involves large fluxes of cargo and membrane across separate compartments. These fluxes must be regulated by control systems to maintain homoeostasis. While control systems for other key functions such as protein folding or the cell cycle are well known, the mechanisms that control secretory transport are poorly understood. We have previously described a signalling circuit operating at the Golgi complex that regulates intra-Golgi trafficking and is initiated by the KDEL receptor (KDEL-R), a protein previously known to mediate protein recycling from the Golgi to the endoplasmic reticulum (ER). Here, we investigated the KDEL-R signalling mechanism. We show that the KDEL-R is predicted to fold like a G-protein-coupled receptor (GPCR), and that it binds and activates the heterotrimeric signalling G-protein Gα(q/11) which, in turn, regulates transport through the Golgi complex. These findings reveal an unexpected GPCR-like mode of action of the KDEL-R and shed light on a core molecular control mechanism of intra-Golgi traffic. 相似文献
260.
Fabricia Petronilho Francieli Vuolo Letícia Selinger Galant Larissa Constantino Cristiane Damiani Tomasi Vinicius Renne Giombelli Cláudio Teodoro de Souza Sabrina da Silva Denise Frediani Barbeiro Francisco Garcia Soriano Emílio Luiz Streck Cristiane Ritter Alfeu Zanotto-Filho Matheus Augusto Pasquali Daniel Pens Gelain José Luiz Rybarczyk-Filho José Cláudio Fonseca Moreira Norman L Block Rafael Roesler Gilberto Schwartsmann Andrew V Schally Felipe Dal-Pizzol 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1209-1219
In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α and RC-3095 (10 ng/mL). Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal–related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-κB and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling. 相似文献