Targeting S1P in Inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration.

Science.gov (United States)

Danese, Silvio; Furfaro, Federica; Vetrano, Stefania

2017-07-28

Sphingosine 1 phosphate (S1P) is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors (S1PRs). Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, S1P/ S1PR1 axis has been identified as key regulator for the lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocytes migration into the mucosa in inflammatory bowel disease (IBD). This review briefly summarizes the current evidence coming from clinical studies and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Phototherapy with low intensity laser in carrageenan-induced acute inflammatory process in mice paw - dosimetry studies

International Nuclear Information System (INIS)

Meneguzzo, Daiane Thais

2010-01-01

The importance of modulation of inflammation on the treatment of inflammatory diseases and the difficulty in determining the laser irradiation parameters has led us to study the effects of different protocols of phototherapy with low intensity laser (power, energy, time and place of irradiation) in the treatment and prevention of edema in acute inflammatory process using the experimental model of paw edema induced by carrageenan (CGN) in three strains of mice (Balb-c, Swiss and C57BL/6). The first stage of the study evaluated different combinations of energy (1J and 3J) with different powers (30, 60 and 100mW) in Balb-C mice paw irradiated 1 and 2h after injection of CGN. The second stage studied different combinations of location (foot, inguinal lymph nodes and both) and exposure time (2 and 1h before, 1h and immediately before the CGN, 1 and 2h and 3.5 and 4.5h after CGN) using fixed irradiation parameters (1J, 100mW, 35J/cm 2 , spot area of 0.028 cm 2 ). The third stage compared different strains of mice Balb-c and C57BL/6) in the best local and time parameters found in step 2. At all stages, we evaluated the change in paw volume by plethysmography and inflammatory infiltrate by histomorphometry or analysis of myeloperoxidase (MPO). The results showed that laser phototherapy treated and prevented edema and modulated the inflammatory process with paw and inguinal lymph nodes irradiations accordingly with the parameters and mice strain used. (author)

Immuno-modulation and anti-inflammatory benefits of antibiotics: the example of tilmicosin.

Science.gov (United States)

Buret, André G

2010-01-01

Exaggerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects.

Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

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Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

2016-01-08

Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Immuno-modulation and anti-inflammatory benefits of antibiotics: The example of tilmicosin

Science.gov (United States)

Buret, André G.

2010-01-01

Exagerated immune responses, such as those implicated in severe inflammatory reactions, are costly to the metabolism. Inflammation and pro-inflammatory mediators negatively affect production in the food animal industry by reducing growth, feed intake, reproduction, milk production, and metabolic health. An ever-increasing number of findings have established that antibiotics, macrolides in particular, may generate anti-inflammatory effects, including the modulation of pro-inflammatory cytokines and the alteration of neutrophil function. The effects are time- and dose-dependent, and the mechanisms responsible for these phenomena remain incompletely understood. Recent studies, mostly using the veterinary macrolide tilmicosin, may have shed new light on the mode of action of some macrolides and their anti-inflammatory properties. Indeed, research findings demonstrate that this compound, amongst others, induces neutrophil apoptosis, which in turn provides anti-inflammatory benefits. Studies using tilmicosin model systems in vitro and in vivo demonstrate that this antibiotic has potent immunomodulatory effects that may explain why at least parts of its clinical benefits are independent of anti-microbial effects. More research is needed, using this antibiotic and others that may have similar properties, to clarify the biological mechanisms responsible for antibiotic-induced neutrophil apoptosis, and how this, in turn, may provide enhanced clinical benefits. Such studies may help establish a rational basis for the development of novel, efficacious, anti-microbial compounds that generate anti-inflammatory properties in addition to their antibacterial effects. PMID:20357951

Inflammatory Process in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

MARCO ANTONIO eMERAZ RIOS

2013-08-01

Full Text Available Alzheimer Disease (AD is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs and extracellular neuritic plaques (NPs surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ, a small fragment of 40-42 amino acids with a molecular weight of 4kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with nonsteroidal anti-inflammatory drugs (NSAIDs indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients.

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

Energy Technology Data Exchange (ETDEWEB)

Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

2013-10-01

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

International Nuclear Information System (INIS)

Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R.; Delgado-Roche, Liván; Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto; Pardo-Andreu, Gilberto L.; Polentarutti, Nadia; Riva, Federica; Pentón-Arias, Eduardo; Pentón-Rol, Giselle

2013-01-01

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H 2 O 2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H 2 O 2 and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy

Purinergic signaling modulates the cerebral inflammatory response in experimentally infected fish with Streptococcus agalactiae: an attempt to improve the immune response.

Science.gov (United States)

Souza, Carine F; Baldissera, Matheus D; Bottari, Nathiele B; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Santos, Roberto C V; Baldisserotto, Bernardo

2018-06-01

Appropriate control of the immune response is a critical determinant of fish health, and the purinergic cascade has an important role in the immune and inflammatory responses. This cascade regulates the levels of adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate and adenosine (Ado), molecules involved in physiological or pathological events as inflammatory and anti-inflammatory mediators. Thus, the aim of this study was to evaluate whether purinergic signaling, through the activities of nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase, and adenosine deaminase (ADA), is capable of modulating the cerebral immune and inflammatory responses in silver catfish that is experimentally infected with Streptococcus agalactiae. Cerebral NTPDase (with ATP as substrate) and 5'-nucleotidase activities increased, while ADA activity decreased in silver catfish that is experimentally infected with S. agalactiae, compared to the control group. Moreover, the cerebral levels of ATP and Ado increased in infected animals compared to the uninfected control group. Brain histopathology in infected animals revealed inflammatory demyelination (the presence of occasional bubbly collections), increased cellular density in the area near to pia-mater and intercellular edema. Based on this evidence, the modulation of the purinergic cascade by the enzymes NTPDase, 5'-nucleotidase, and ADA exerts an anti-inflammatory profile due to the regulation of ATP and Ado levels. This suggests involvement of purinergic enzymes on streptococcosis pathogenesis, through regulating cerebral ATP and Ado levels, molecules known to participate in physiological or pathological events as inflammatory and anti-inflammatory mediators, respectively. In summary, the modulation of the cerebral purinergic cascade exerts an anti-inflammatory profile in an attempt to reduce inflammatory damage.

Space-time-modulated stochastic processes

Science.gov (United States)

Giona, Massimiliano

2017-10-01

Starting from the physical problem associated with the Lorentzian transformation of a Poisson-Kac process in inertial frames, the concept of space-time-modulated stochastic processes is introduced for processes possessing finite propagation velocity. This class of stochastic processes provides a two-way coupling between the stochastic perturbation acting on a physical observable and the evolution of the physical observable itself, which in turn influences the statistical properties of the stochastic perturbation during its evolution. The definition of space-time-modulated processes requires the introduction of two functions: a nonlinear amplitude modulation, controlling the intensity of the stochastic perturbation, and a time-horizon function, which modulates its statistical properties, providing irreducible feedback between the stochastic perturbation and the physical observable influenced by it. The latter property is the peculiar fingerprint of this class of models that makes them suitable for extension to generic curved-space times. Considering Poisson-Kac processes as prototypical examples of stochastic processes possessing finite propagation velocity, the balance equations for the probability density functions associated with their space-time modulations are derived. Several examples highlighting the peculiarities of space-time-modulated processes are thoroughly analyzed.

Melatonin modulates inflammatory response and suppresses burn-induced apoptotic injury

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Ganka Bekyarova

2017-04-01

Full Text Available Introduction: Melatonin, the principal secretory product of the pineal gland, has antioxidant functions as a potent antioxidant and free radical scavenger. Objectives of the present study were to investigate the effect of melatonin against inflammatory response, burn-induced oxidative damage and apoptotic changes of rat liver. Methods: Melatonin (10 mg /kg, i.p. was applied immediately after 30% of total body surface area (TBSA burns on male Wistar rats. The level of malondialdehyde (MDA as a marker of an oxidative stress was quantified by thiobarbituric method. Hepatic TNFα and IL-10 as inflammatory markers were assayed by ELISA. Using light immunоchistochemistry the expression Ki67 proliferative marker was investigated. Results: Hepatic MDA and TNF-α levels increased significantly following burns without any change in IL-10 level. Intracellular vacuolization, hepatic cell degeneration and apoptosis occurred in rats after burns. The number of apoptotic cells was increased whereas no significant increase in Ki67 proliferative marker. Melatonin decreased the MDA and TNF-α content and increased the IL-10 level. It also limited the degenerative changes and formation of apoptotic cells in rat liver but did not increase expression of the marker of proliferation. In conclusion, our data show that melatonin relieves burn-induced hepatic damage associated with modulation of the proinflammatory/anti-inflammatory balance, mitigation of lipid peroxidation and hepatic apoptosis.

Transintestinal transport of the anti-inflammatory drug 4F and the modulation of transintestinal cholesterol efflux[S

Science.gov (United States)

Meriwether, David; Sulaiman, Dawoud; Wagner, Alan; Grijalva, Victor; Kaji, Izumi; Williams, Kevin J.; Yu, Liqing; Fogelman, Spencer; Volpe, Carmen; Bensinger, Steven J.; Anantharamaiah, G. M.; Shechter, Ishaiahu; Fogelman, Alan M.; Reddy, Srinivasa T.

2016-01-01

The site and mechanism of action of the apoA-I mimetic peptide 4F are incompletely understood. Transintestinal cholesterol efflux (TICE) is a process involved in the clearance of excess cholesterol from the body. While TICE is responsible for at least 30% of the clearance of neutral sterols from the circulation into the intestinal lumen, few pharmacological agents have been identified that modulate this pathway. We show first that circulating 4F selectively targets the small intestine (SI) and that it is predominantly transported into the intestinal lumen. This transport of 4F into the SI lumen is transintestinal in nature, and it is modulated by TICE. We also show that circulating 4F increases reverse cholesterol transport from macrophages and cholesterol efflux from lipoproteins via the TICE pathway. We identify the cause of this modulation of TICE either as 4F being a cholesterol acceptor with respect to enterocytes, from which 4F enhances cholesterol efflux, or as 4F being an intestinal chaperone with respect to TICE. Our results assign a novel role for 4F as a modulator of the TICE pathway and suggest that the anti-inflammatory functions of 4F may be a partial consequence of the codependent intestinal transport of both 4F and cholesterol. PMID:27199144

Curcumin Protects Against the Acute Inflammatory Process in Irradiated Rats

International Nuclear Information System (INIS)

El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

2010-01-01

Nutraceuticals that provide medical or health benefits, including prevention and treatment of disease may be advantageous in inflammation and exposure to radiation. The aim of this study was to investigate the potential of curcumin to modulate, counteract or prevent the inflammatory response induced in irradiated and non-irradiated rats using the carrageenan air-pouch model as an acute model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to a single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-alpha, PGE2 and MDA and was able to restore blood GSH levels. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded after irradiation of animals before induction of inflammation. Curcumin restored the hepatic concentrations of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response while curcumin suppressed the inflammatory response in both irradiated and control animals.

Oak kombucha protects against oxidative stress and inflammatory processes.

Science.gov (United States)

Vázquez-Cabral, B D; Larrosa-Pérez, M; Gallegos-Infante, J A; Moreno-Jiménez, M R; González-Laredo, R F; Rutiaga-Quiñones, J G; Gamboa-Gómez, C I; Rocha-Guzmán, N E

2017-06-25

Black tea infusion is the common substrate for preparing kombucha; however other sources such as oak leaves infusions can be used for the same purpose. Almost any white oak species have been used for medicinal applications by some ethnic groups in Mexico and could be also suitable for preparing kombucha analogues from oak (KAO). The objective of this research was to investigate the antioxidant activity and anti-inflammatory effects of KAO by examining its modulation ability on macrophage-derived TNF-alpha and IL-6. Herbal infusions from oak and black tea were fermented by kombucha consortium during seven days at 28 °C. Chemical composition was determined by LC-ESI-MS/MS. The antioxidant activity of samples against oxidative damage caused by H 2 O 2 in monocytes activated (macrophages) was explored. Additionally, it was determined the anti-inflammatory activity using lipopolysaccharide (LPS) - stimulated macrophages; in particular, the nitric oxide (NO), TNF-alpha, and IL-6 production was assessed. Levels of pro-inflammatory cytokines IL-6 and TNF-alpha were significantly reduced by the sample treatment. Likewise, NO production was lower in treatment with kombucha and KAO compared with LPS-stimulated macrophages. Fermented beverages of oak effectively down-regulated the production of NO, while pro-inflammatory cytokines (TNF-alpha and IL-6) in macrophages were stimulated with LPS. Additionally, phytochemical compounds present in KAO decrease oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of anti-inflammatory drugs - the research and development process.

Science.gov (United States)

Knowles, Richard Graham

2014-01-01

The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics

Science.gov (United States)

Plaza-Diaz, Julio; Gomez-Llorente, Carolina; Fontana, Luis; Gil, Angel

2014-01-01

The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics" and "gene expression" combined with “intestines", "liver", "enterocytes", "antigen-presenting cells", "dendritic cells", "immune system", and "inflammation". Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and

Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

Science.gov (United States)

Nwachukwu, Jerome C; Srinivasan, Sathish; Bruno, Nelson E; Parent, Alexander A; Hughes, Travis S; Pollock, Julie A; Gjyshi, Olsi; Cavett, Valerie; Nowak, Jason; Garcia-Ordonez, Ruben D; Houtman, René; Griffin, Patrick R; Kojetin, Douglas J; Katzenellenbogen, John A; Conkright, Michael D; Nettles, Kendall W

2014-01-01

Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity. DOI: http://dx.doi.org/10.7554/eLife.02057.001 PMID:24771768

Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

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Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

Neuropsychiatric comorbidity in obesity: role of inflammatory processes

Directory of Open Access Journals (Sweden)

Nathalie eCastanon

2014-05-01

Full Text Available Neuropsychiatric symptoms are frequent in obesity. In addition to their substantial economic and health impact, these symptoms significantly interfere with the quality of life and social function of obese individuals. While the pathophysiological mechanisms underlying obesity-related neuropsychiatric symptoms are still under investigation and remain to be clearly identified, there is increasing evidence for a role of inflammatory processes. Obesity is characterized by a chronic low-grade inflammatory state that is likely to influence neuropsychiatric status given the well-known and highly documented effects of inflammation on brain activity/function and behavior. This hypothesis is supported by recent findings emanating from clinical investigations in obese subjects and from experimentations conducted in animal models of obesity. These studies converge to show that obesity-related inflammatory processes, originating either from the adipose tissue or gut microbiota environment, spread to the brain where they lead to substantial changes in neurocircuitry, neuroendocrine activity, neurotransmitter metabolism and activity, and neurogenesis. Together, these alterations contribute to shape the propitious bases for the development of obesity-related neuropsychiatric comorbidities.

HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

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Osiris Marroquin Belaunzaran

Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats

Science.gov (United States)

Marroquin Belaunzaran, Osiris; Kleber, Sascha; Schauer, Stefan; Hausmann, Martin; Nicholls, Flora; Van den Broek, Maries; Payeli, Sravan; Ciurea, Adrian; Milling, Simon; Stenner, Frank; Shaw, Jackie; Kollnberger, Simon; Bowness, Paul; Petrausch, Ulf; Renner, Christoph

2015-01-01

Objectives HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM). HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules. Conclusion HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders. PMID:26125554

Modulation of intestinal inflammation by yeasts and cell wall extracts: strain dependence and unexpected anti-inflammatory role of glucan fractions.

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Samir Jawhara

Full Text Available Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4, as well as mannoprotein (MP and β-glucan crude fractions prepared from Sc2 and highly purified β-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNFα and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas β-glucan fraction was protective against both. Surprisingly, purified β-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that β-glucan fractions or pure β-glucans from C. albicans displayed the most potent anti-inflammatory effect in the

Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

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Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

2012-04-02

Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

Effects of short-term dietary restriction and glutamine supplementation in vitro on the modulation of inflammatory properties.

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C de Oliveira, Dalila; Santos, Ed Wilson; Nogueira-Pedro, Amanda; Xavier, José Guilherme; Borelli, Primavera; Fock, Ricardo Ambrósio

2018-04-01

Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB. We subjected 3-mo-old male Balb/c mice to DR by reducing their food intake by 30%. DR animals lost weight and showed reduced levels of serum triacylglycerols, glucose, cholesterol, and calcium as well as a reduction in bone density. Additionally, blood, peritoneal, and spleen cellularity were reduced, lowering the number of peritoneal F4/80- and CD86-positive cells and the total number of splenic CD4- and CD8-positive cells. The production of interleukin (IL)-10 and the expression of NF-κB in splenic cells were not affected by DR or by GLN supplementation. However, peritoneal macrophages from DR animals showed reduced IL-12 and tumor necrosis factor-α production and increased IL-10 production with reduced phosphorylation of NF-κB expression. Additionally, GLN was able to modulate cytokine production by peritoneal cells from the control group, although no effects were observed in cells from the DR group. DR induces biochemical and immunologic changes, in particular by reducing IL-12 and tumor necrosis factor-α production by macrophages and clearly upregulating IL-10 production, whereas GLN supplementation did not modify these parameters in cells from DR animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice.

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De Domenico, Ivana; Zhang, Tian Y; Koening, Curry L; Branch, Ryan W; London, Nyall; Lo, Eric; Daynes, Raymond A; Kushner, James P; Li, Dean; Ward, Diane M; Kaplan, Jerry

2010-07-01

Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-alpha transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses.

Rosiglitazone inhibits chlorpyrifos-induced apoptosis via modulation of the oxidative stress and inflammatory response in SH-SY5Y cells

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Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon; Jang, Sea Jeong [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

2014-07-15

Oxidative stress can lead to expression of inflammatory transcription factors, which are important regulatory elements in the induction of inflammatory responses. One of the transcription factors, nuclear transcription factor kappa-B (NF-κB) plays a significant role in the inflammation regulatory process. Inflammatory cell death has been implicated in neuronal cell death in some neurodegenerative disorders such as Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying apoptosis initiated by chlorpyrifos (CPF)-mediated oxidative stress. Based on the cytotoxic mechanism of CPF, we examined the neuroprotective effects of rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, against CPF-induced neuronal cell death. The treatment of SH-SY5Y cells with CPF induced oxidative stress. In addition, CPF activated the p38, JNK and ERK mitogen-activated protein kinases (MAPKs), and induced increases in the inflammatory genes such as COX-2 and TNF-α. CPF also induced nuclear translocation of NF-κB and inhibitors of NF-κB abolished the CPF-induced COX-2 expression. Pretreatment with RGZ significantly reduced ROS generation and enhanced HO-1 expression in CPF-exposed cells. RGZ blocked the activation of both p38 and JNK signaling, while ERK activation was strengthened. RGZ also attenuated CPF-induced cell death through the reduction of NF-κB-mediated proinflammatory factors. Results from this study suggest that RGZ may exert an anti-apoptotic effect against CPF-induced cytotoxicity by attenuation of oxidative stress as well as inhibition of the inflammatory cascade via inactivation of signaling by p38 and JNK, and NF-κB. - Highlights: • CPF induces apoptotic cell death in SH-SY5Y cells • ROS involved in CPF-mediated apoptotic cell death • Inflammation involved in CPF-mediated apoptotic cell death • Rosiglitazone modulates ROS and inflammatory response in CPF-treated cells.

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

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Danielle Ingrid Bezerra de Vasconcelos

2011-01-01

Full Text Available Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals

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Gupta, Subash C.; Kim, Ji Hye; Prasad, Sahdeo

2010-01-01

Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed “Let food be thy medicine and medicine be thy food.” Exploring the association between diet and health continues today. For example, we now know that as many as 35% of all cancers can be prevented by dietary changes. Carcinogenesis is a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of the tumor and may take up to 30 years. The pathways associated with this process have been linked to chronic inflammation, a major mediator of tumor progression. The human body consists of about 13 trillion cells, almost all of which are turned over within 100 days, indicating that 70,000 cells undergo apoptosis every minute. Thus, apoptosis/cell death is a normal physiological process, and it is rare that a lack of apoptosis kills the patient. Almost 90% of all deaths due to cancer are linked to metastasis of the tumor. How our diet can prevent cancer is the focus of this review. Specifically, we will discuss how nutraceuticals, such as allicin, apigenin, berberine, butein, caffeic acid, capsaicin, catechin gallate, celastrol, curcumin, epigallocatechin gallate, fisetin, flavopiridol, gambogic acid, genistein, plumbagin, quercetin, resveratrol, sanguinarine, silibinin, sulforaphane, taxol, γ-tocotrienol, and zerumbone, derived from spices, legumes, fruits, nuts, and vegetables, can modulate inflammatory pathways and thus affect the survival, proliferation, invasion, angiogenesis, and metastasis of the tumor. Various cell signaling pathways that are modulated by these agents will also be discussed. PMID:20737283

Potent anti-inflammatory effects of systemically-administered curcumin modulates periodontal disease in vivo

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Guimarães, Morgana R.; Coimbra, Leila S.; de Aquino, Sabrina Garcia; Spolidorio, Luis C.; Kirkwood, Keith L.; Junior, Carlos Rossa

2011-01-01

Background Curcumin is a plant-derived dietary spice with various biological activities, including anti-tumoral and anti-inflammatory. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression; but no studies evaluated the effects of curcumin on periodontal disease in vivo. Methods Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats intragastrically daily in two doses (30 and 100 mg/Kg) during 15 days. Control animals received ligatures but only the corn oil vehicle by gavage and no treatment negative control animals were included. Bone resorption was assessed by microcomputer tomography and the inflammatory status was evaluated by stereometric analysis. RT-qPCR and ELISA were used to determine the expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and prostaglandin E2 (PGE2) synthase on the gingival tissues. Modulation of p38 mitogen-activated protein kinase (MAPK) and NK-kB activation was assessed by western blot. Results Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at mRNA and protein levels and dose-dependently inhibited activation of NF-kB in the gingival tissues. p38 MAPK activation was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction on the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Conclusions Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests it may have a therapeutic potential in periodontal diseases. PMID:21306385

Digital intermediate frequency QAM modulator using parallel processing

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Pao, Hsueh-Yuan [Livermore, CA; Tran, Binh-Nien [San Ramon, CA

2008-05-27

The digital Intermediate Frequency (IF) modulator applies to various modulation types and offers a simple and low cost method to implement a high-speed digital IF modulator using field programmable gate arrays (FPGAs). The architecture eliminates multipliers and sequential processing by storing the pre-computed modulated cosine and sine carriers in ROM look-up-tables (LUTs). The high-speed input data stream is parallel processed using the corresponding LUTs, which reduces the main processing speed, allowing the use of low cost FPGAs.

Rats Born to Mothers Treated with Dexamethasone 15 cH Present Changes in Modulation of Inflammatory Process

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Leoni V. Bonamin

2012-01-01

Full Text Available As little information about the effect of ultra high dilutions of glucocorticoid in reproduction is available in the literature, pregnant female Wistar rats (N=12 were blindly subcutaneously treated during all gestational and lactation period with: dexamethasone 4 mg/kg diluted into dexamethasone 15 cH (mixed; or dexamethasone 4 mg/kg diluted in water; or dexamethasone 15 cH, or vehicle. Parental generation had body weight, food and water consumption monitored. The F1 generation was monitored regarding to newborn development. No birth occurred in both groups treated with dexamethasone 4 mg/kg. After 60 days from birth, 12 male F1 rats were randomly selected from each remaining group and inoculated subcutaneously with 1% carrageenan into the footpad, for evaluation of inflammatory performance. Edema and histopathology of the footpad were evaluated, using specific staining methods, immunohistochemistry and digital histomorphometry. Mothers treated with mixed dexamethasone presented reduced water consumption. F1 rats born to dexamethasone 15 cH treated females presented significant increase in mast cell degranulation, decrease in monocyte percentage, increase in CD18+ PMN cells, and early expression of ED2 protein, in relation to control. The results show that the exposure of parental generation to highly diluted dexamethasone interferes in inflammation modulation in the F1 generation.

Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd Teng

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Yan Zhou

2014-01-01

Full Text Available Glycopeptide from Ganoderma capense (Lloyd Teng (GCGP injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages.

Inflammatory Modulation Effect of Glycopeptide from Ganoderma capense (Lloyd) Teng

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Zhou, Yan; Chen, Song; Yao, Wenbing; Gao, Xiangdong

2014-01-01

Glycopeptide from Ganoderma capense (Lloyd) Teng (GCGP) injection is widely used in kinds of immune disorders, but little is known about the molecular mechanisms of how GCGP could interfere with immune cell function. In the present study, we have found that GCGP had inflammatory modulation effects on macrophage cells to maintain NO production and iNOS expression at the normal level. Furthermore, western blot analysis showed that the underlying mechanism of immunomodulatory effect of GCGP involved NF-κB p65 translation, IκB phosphorylation, and degradation; NF-κB inhibitor assays also confirmed the results. In addition, competition study showed that GCGP could inhibit LPS from binding to macrophage cells. Our data indicates that GCGP, which may share the same receptor(s) expressed by macrophage cells with LPS, exerted immunomodulatory effect in a NF-κB-dependent signaling pathway in macrophages. PMID:24966469

Chitosan drives anti-inflammatory macrophage polarisation and pro-inflammatory dendritic cell stimulation

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MI Oliveira

2012-07-01

Full Text Available Macrophages and dendritic cells (DC share the same precursor and play key roles in immunity. Modulation of their behaviour to achieve an optimal host response towards an implanted device is still a challenge. Here we compare the differentiation process and polarisation of these related cell populations and show that they exhibit different responses to chitosan (Ch, with human monocyte-derived macrophages polarising towards an anti-inflammatory phenotype while their DC counterparts display pro-inflammatory features. Macrophages and DC, whose interactions with biomaterials are frequently analysed using fully differentiated cells, were cultured directly on Ch films, rather than exposed to the polymer after complete differentiation. Ch was the sole stimulating factor and activated both macrophages and DC, without leading to significant T cell proliferation. After 10 d on Ch, macrophages significantly down-regulated expression of pro-inflammatory markers, CD86 and MHCII. Production of pro-inflammatory cytokines, particularly TNF-α, decreased with time for cells cultured on Ch, while anti-inflammatory IL-10 and TGF-β1, significantly increased. Altogether, these results suggest an M2c polarisation. Also, macrophage matrix metalloproteinase activity was augmented and cell motility was stimulated by Ch. Conversely, DC significantly enhanced CD86 expression, reduced IL-10 secretion and increased TNF-α and IL-1β levels. Our findings indicate that cells with a common precursor may display different responses, when challenged by the same biomaterial. Moreover, they help to further comprehend macrophage/DC interactions with Ch and the balance between pro- and anti-inflammatory signals associated with implant biomaterials. We propose that an overall pro-inflammatory reaction may hide the expression of anti-inflammatory cytokines, likely relevant for tissue repair/regeneration.

DEFINITION OF ETIOLOGICAL ANTIBIOTIC SENSITIVITY FACTORS IN PURULENT-INFLAMMATORY PROCESSES.

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Dubovyk, O; Mishyna, М; Malanchuk, S; Kuzmenko, A; Kozlov, O

2017-10-01

The purpose of the study - assessment of purulent-inflammatory processes etiologic factors and determination of microbial agents' in forms of plankton and biofilms sensitivity to antibiotics. Clinical microbial strains isolated from patients with purulent-inflammatory processes were the subject of the study. The study material comprised of wound tissue, pus, bandage and suture, catheters and drainage devices. Sensitivity of isolates to antimicrobial preparations with various mechanism of activity on the microbial cells was studied with the help of micro-test system. Formation of biofilms was studied with the help of definition of bacteria strains ability to adhesion to the surface of polystyrene flatbeds. It was revealed that one of the leading factors of purulent-inflammatory process development is S.aureus, which disseminated in 36,5% of cases; E.coli disseminated in 17,3% of cases. Among the agents of purulent-inflammatory processes the specific gravity attributed to: Proteus spp. - 14,6%, S.рyogenes - 12,8%, P.aeruginosa - 6,9%, K.pneumoniae - 6,7%. It was revealed that all isolates formed dense biofilms. It was demonstrated that most isolates in plankton form were sensitive to Novapime, Cefepime, Gatifloxacin, Imipenem; sensitive strains were registered in a smaller quantity to Gentamicin, Clindamycin and Doxycycline. In terms of sensitivity of isolates in the form of biofilm to antibacterial preparations it was revealed that most isolates were polyresistant to them. Thus, the study of the sensitivity of allotted microbial strains to antimicrobial preparations demonstrated, that there were strains among cultures with multiple resistances which was the consequence of a wide and not always effective use of antimicrobial preparations.

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

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Beatrice Menicacci

2017-10-01

Full Text Available Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP, playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5 and neonatal human dermal (NHDF fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks treatment with 1 μM hydroxytyrosol (HT or 10 μM oleuropein aglycone (OLE on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2 and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols.

Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo.

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Guimarães, M R; Coimbra, L S; de Aquino, S G; Spolidorio, L C; Kirkwood, K L; Rossa, C

2011-04-01

Curcumin is a plant-derived dietary spice with various biological activities, including anticarcinogenic and anti-inflammatory effects. Its therapeutic applications have been studied in a variety of conditions, including rheumatoid arthritis, colon cancer and depression, but no studies have evaluated the effects of curcumin on periodontal disease in vivo. Experimental periodontal disease was induced in rats by placing cotton ligatures around both lower first molars. Curcumin was given to the rats by the intragastric route daily at two dosages (30 and 100 mg/kg) for 15 d. Control animals received ligatures but only the corn oil vehicle by gavage, and no treatment-negative control animals were included. Bone resorption was assessed by micro-computed tomography, and the inflammatory status was evaluated by stereometric analysis. Both RT-qPCR and ELISA were used to determine the expression of interleukin-6, tumor necrosis factor-α and prostaglandin E(2) synthase in the gingival tissues. Modulation of p38 MAPK and nuclear factor-κB activation were assessed by western blotting. Bone resorption was effectively induced in the experimental period, but it was not affected by either dose of curcumin. Curcumin effectively inhibited cytokine gene expression at both the mRNA and the protein level and produced a dose-dependent inhibition of the activation of nuclear factor-κB in the gingival tissues. Activation of p38 MAPK was not inhibited by curcumin. Curcumin-treated animals also presented a marked reduction of the inflammatory cell infiltrate and increased collagen content and fibroblastic cell numbers. Curcumin did not prevent alveolar bone resorption, but its potent anti-inflammatory effect suggests that it may have a therapeutic potential in periodontal diseases. © 2011 John Wiley & Sons A/S.

Metallothionein as an Anti-Inflammatory Mediator

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Ken-ichiro Inoue

2009-01-01

Full Text Available The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions.

Key Inflammatory Processes in Human NASH Are Reflected in Ldlr-/-.Leiden Mice: A Translational Gene Profiling Study.

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Morrison, Martine C; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

2018-01-01

inflammatory processes (e.g., "Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes," "PI3K signaling in B Lymphocytes") and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr -/- .Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators.

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

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Gottesman Irving I

2005-02-01

Full Text Available Abstract Background Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. Discussion A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular

Morita-Baylis-Hillman Adducts Display Anti-Inflammatory Effects by Modulating Inflammatory Mediator Expression in RAW264.7 Cells

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Glaucia V. Faheina-Martins

2017-01-01

Full Text Available Inflammatory response plays an important role not only in the normal physiology but also in pathologies such as cancers. The Morita-Baylis-Hillman adducts (MBHA are a novel group of synthetic molecules that have demonstrated many biological activities against some parasitic cells such as Plasmodium falciparum, Leishmania amazonensis, and Leishmania chagasi, and antimitotic activity against sea urchin embryonic cells was also related. However, little is known about the mechanisms induced by MBHA in inflammatory process and its relation with anticancer activity. The present work investigated the cytotoxicity of three MBHA derivatives (A2CN, A3CN, and A4CN, on human colorectal adenocarcinoma, HT-29 cells, and their anti-inflammatory activities were examined in lipopolysaccharide- (LPS- stimulated RAW264.7 macrophage cells, being these derivatives potentially cytotoxic to HT-29 cells. Coincubation with A2CN, A3CN, or A4CN and LPS in RAW264.7 cells inhibited NO production, as well as the production of reactive oxygen species (ROS was also repressed. The mRNA expressions of IL-1β and IL-6 were significantly downregulated by such MBHA compounds in RAW264.7 cells, but only A2CN was able to inhibit the COX-2 gene expression. We also showed that MBHA compounds decreased almost to zero the production of IL-1β and IL-6. These findings display that such MBHA compounds exhibit anticancer and anti-inflammatory activities.

Inflammatory Breast Diseases during Lactation: Health Effects on the Newborn—A Literature Review

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Achim Wöckel

2008-01-01

Full Text Available Breastfeeding-associated inflammatory breast diseases appear especially during the first twelve weeks postpartum and are the most common reason for early cessation of breastfeeding. It also becomes increasingly evident that these inflammatory mammary diseases are triggered or perpetuated in a large part by psychosocial stress. Immunological processes taking place during this cascade in the mammary gland and consequences for the breastfeed newborn are mostly yet unknown. This review summarizes insights from studies on modulation of cytokine levels in breast milk during inflammatory processes like milk stasis and mastitis systematically. It also gives an overview on possible pathological effects, which these cytokine changes in the breast milk might have on the newborn.

Diminazene aceturate (Berenil modulates the host cellular and inflammatory responses to Trypanosoma congolense infection.

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Shiby Kuriakose

Full Text Available BACKGROUND: Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense. METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b⁺ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25⁺ cells, a concomitant reduction in the percentage of regulatory (CD4⁺Foxp3⁺ T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm. CONCLUSIONS/SIGNIFICANCE: Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology

Systemic Inflammatory Load in Young and Old Ringdoves Is Modulated by Consumption of a Jerte Valley Cherry-Based Product

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Delgado, Jonathan; Terrón, María del Pilar; Garrido, María; Barriga, Carmen; Paredes, Sergio Damián; Espino, Javier

2012-01-01

Abstract A chronic subclinical inflammatory status that coexists with immune dysfunction is commonly found in the elderly population. Consumption of foods rich in antioxidants (e.g., cherries) is an attractive strategy to reduce risk from chronic diseases. Based on previous studies showing the antioxidant effect of a Jerte Valley cherry derivative product in humans, the objective of this work was to evaluate the effect of the intake of a Jerte Valley cherry-based beverage on inflammatory load in both young and old ringdoves (Streptopelia risoria). To this purpose, circulating levels of pro-inflammatory and anti-inflammatory cytokines as well as serum levels of different acute-phase proteins were measured before and after a 10-day treatment with the Jerte Valley cherry-based beverage. Thus, the 10-day treatment with the cherry-based beverage modulated the balance of pro- and anti-inflammatory cytokines in both young and old ringdoves by down-regulating the levels of pro-inflammatory cytokines (interleukin [IL]-1β, tumor necrosis factor-α, and interferon-γ) and up-regulating the levels of anti-inflammatory cytokines (IL-4, IL-2, and IL-10). Moreover, the 10-day treatment with the Jerte Valley cherry-based product reduced the levels of several proteins involved in acute-phase responses, such as C-reactive protein, haptoglobin, α2-macroglobulin, and serum amyloid P component. On the other hand, old birds showed imbalanced levels of inflammatory markers toward a pro-inflammatory status, thereby underlining the fact that aging is usually accompanied by systemic inflammation and inflammation-related chronic diseases. To sum up, the data suggest a potential health benefit by consuming the cherry-based beverage, especially in aged populations, through their anti-inflammatory properties. PMID:22846077

Angiotensin II modulates interleukin-1β-induced inflammatory gene expression in vascular smooth muscle cells via interfering with ERK-NF-κB crosstalk

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Xu, Shanqin; Zhi, Hui; Hou, Xiuyun; Jiang, Bingbing

2011-01-01

Highlights: → We examine how angiotensin II modulates ERK-NF-κB crosstalk and gene expression. → Angiotensin II suppresses IL-1β-induced prolonged ERK and NF-κB activation. → ERK-RSK1 signaling is required for IL-1β-induced prolonged NF-κB activation. → Angiotensin II modulates NF-κB responsive genes via regulating ERK-NF-κB crosstalk. → ERK-NF-κB crosstalk is a novel mechanism regulating inflammatory gene expression. -- Abstract: Angiotensin II is implicated in cardiovascular diseases, which is associated with a role in increasing vascular inflammation. The present study investigated how angiotensin II modulates vascular inflammatory signaling and expression of inducible nitric oxide synthase (iNOS) and vascular cell adhesion molecule (VCAM)-1. In cultured rat aortic vascular smooth muscle cells (VSMCs), angiotensin II suppressed interleukin-1β-induced prolonged phosphorylation of extracellular signal-regulated kinase (ERK) and ribosomal S6 kinase (RSK)-1, and nuclear translocation of nuclear factor (NF)-κB, leading to decreased iNOS but enhanced VCAM-1 expression, associated with an up-regulation of mitogen-activated protein kinase phosphatase-1 expression. Knock-down of RSK1 selectively down regulated interleukin-1β-induced iNOS expression without influencing VCAM-1 expression. In vivo experiments showed that interleukin-1β, iNOS, and VCAM-1 expression were detectable in the aortic arches of both wild-type and apolipoprotein E-deficient (ApoE -/- ) mice. VCAM-1 and iNOS expression were higher in ApoE -/- than in wild type mouse aortic arches. Angiotensin II infusion (3.2 mg/kg/day, for 6 days, via subcutaneous osmotic pump) in ApoE -/- mice enhanced endothelial and adventitial VCAM-1 and iNOS expression, but reduced medial smooth muscle iNOS expression associated with reduced phosphorylation of ERK and RSK-1. These results indicate that angiotensin II can differentially modulate inflammatory gene expression in aortic smooth muscle cells

Key Inflammatory Processes in Human NASH Are Reflected in Ldlr−/−.Leiden Mice: A Translational Gene Profiling Study

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Morrison, Martine C.; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

2018-01-01

inflammatory processes (e.g., “Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes,” “PI3K signaling in B Lymphocytes”) and master regulators (e.g., TNF, CSF2, TGFB1). The majority of these processes and regulators are modulated in the same direction in Ldlr−/−.Leiden mice fed HFD with a human-like macronutrient composition, thus demonstrating that specific experimental conditions recapitulate human disease on the molecular level of disease pathways and upstream/master regulators. PMID:29527177

Modulation of PPAR-γ by Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases

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D. Ortuño Sahagún

2012-01-01

Full Text Available A direct correlation between adequate nutrition and health is a universally accepted truth. The Western lifestyle, with a high intake of simple sugars, saturated fat, and physical inactivity, promotes pathologic conditions. The main adverse consequences range from cardiovascular disease, type 2 diabetes, and metabolic syndrome to several cancers. Dietary components influence tissue homeostasis in multiple ways and many different functional foods have been associated with various health benefits when consumed. Natural products are an important and promising source for drug discovery. Many anti-inflammatory natural products activate peroxisome proliferator-activated receptors (PPAR; therefore, compounds that activate or modulate PPAR-gamma (PPAR-γ may help to fight all of these pathological conditions. Consequently, the discovery and optimization of novel PPAR-γ agonists and modulators that would display reduced side effects is of great interest. In this paper, we present some of the main naturally derived products studied that exert an influence on metabolism through the activation or modulation of PPAR-γ, and we also present PPAR-γ-related diseases that can be complementarily treated with nutraceutics from functional foods.

Cyanidin-3-O-Glucoside Modulates the In Vitro Inflammatory Crosstalk between Intestinal Epithelial and Endothelial Cells

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Daniela Ferrari

2017-01-01

Full Text Available Intestinal epithelium represents a protective physical barrier and actively contributes to the mucosal immune system. Polarized basolateral intestinal secretion of inflammatory mediators, followed by activation of NF-κB signaling and inflammatory pathways in endothelial cells, efficiently triggers extravasation of neutrophils from the vasculature, therefore contributing to the development and maintenance of intestinal inflammation. Proper regulation of NF-κB activation at the epithelial interface is crucial for the maintenance of physiological tissue homeostasis. Many papers reported that anthocyanins, a group of compounds belonging to flavonoids, possess anti-inflammatory effects and modulate NF-κB activity. In this study, by using a coculture in vitro system, we aimed to evaluate the effects of TNF-α-stimulated intestinal cells on endothelial cells activation, as well as the protective effects of cyanidin-3-glucoside (C3G. In this model, TNF-α induced nuclear translocation of NF-κB and TNF-α and IL-8 gene expression in Caco-2 cells, whereas C3G pretreatment dose-dependently reduced these effects. Furthermore, TNF-α-stimulated Caco-2 cells induced endothelial cells activation with increased E-selectin and VCAM-1 mRNA, leukocyte adhesion, and NF-κB levels in HUVECs, which were inhibited by C3G. We demonstrated that selective inhibition of the NF-κB pathway in epithelial cells represents the main mechanism by which C3G exerts these protective effects. Thus, anthocyanins could contribute to the management of chronic gut inflammatory diseases.

Aerobic Exercise Modulates the Free Fatty Acids and Inflammatory Response During Obesity and Cancer Cachexia.

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Teixeira, Alexandre Abilio de Souza; Lira, Fábio Santos; Pimentel, Gustavo D; Oliveira de Souza, Camila; Batatinha, Helena; Biondo, Luana A; Yamashita, Alex S; Junior, Edson A Lima; Neto, José Cesar Rosa

2016-01-01

White adipose tissue (WAT) is no longer considered a tissue whose main function is the storage of TAG. Since the discovery of leptin in 1994, several studies have elucidated the important role of WAT as an endocrine organ, the source of the adipokines. The low-grade inflammation observed in obese and cancer cachexia patients is explained, at least partially, by the exacerbated release of proinflammatory adipokines. Despite of the recent progress in the characterization of the various adipokines and lipokines produced by WAT, little is known about the mechanisms regulating the secretion of these molecules in different physiological and pathological circumstances. Chronic exercise is a nonpharmacological therapy employed in several chronic diseases and shows an anti-inflammatory effect through the regulation of the cytokine network. In this review, we address the potential mechanisms by which the aerobic physical exercise modulate the production and release of inflammatory adipokines, as well as the inflammation-lipolysis axis in WAT, with special focus in the therapeutic role of exercise in obesity-associated insulin resistance and cancer cachexia.

Kaempferol modulates pro-inflammatory NF-κB activation by suppressing advanced glycation endproducts-induced NADPH oxidase

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Kim, Ji Min; Lee, Eun Kyeong; Kim, Dae Hyun; Yu, Byung Pal

2010-01-01

Advanced glycation endproducts (AGE) are oxidative products formed from the reaction between carbohydrates and a free amino group of proteins that are provoked by reactive species (RS). It is also known that AGE enhance the generation of RS and that the binding of AGE to a specific AGE receptor (RAGE) induces the activation of the redox-sensitive, pro-inflammatory transcription factor, nuclear factor-kappa B (NF-ĸB). In this current study, we investigated the anti-oxidative effects of short-term kaempferol supplementation on the age-related formation of AGE and the binding activity of RAGE in aged rat kidney. We further investigated the suppressive action of kaempferol against AGE's ability to stimulate activation of pro-inflammatory NF-ĸB and its molecular mechanisms. For this study, we utilized young (6 months old), old (24 months old), and kaempferol-fed (2 and 4 mg/kg/day for 10 days) old rats. In addition, for the molecular work, the rat endothelial cell line, YPEN-1 was used. The results show that AGE and RAGE were increased during aging and that these increases were blunted by kaempferol. In addition, dietary kaempferol reduced age-related increases in NF-κB activity and NF-ĸB-dependant pro-inflammatory gene activity. The most significant new finding from this study is that kaempferol supplementation prevented age-related NF-κB activation by suppressing AGE-induced nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Taken together, our results demonstrated that dietary kaempferol exerts its anti-oxidative and anti-inflammatory actions by modulating the age-related NF-κB signaling cascade and its pro-inflammatory genes by suppressing AGE-induced NADPH oxidase activation. Based on these data, dietary kaempferol is proposed as a possible anti-AGE agent that may have the potential for use in anti-inflammation therapies. PMID:20431987

Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

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Yao Wang

Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

Omega-3 fatty acids and inflammatory processes: from molecules to man.

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Calder, Philip C

2017-10-15

Inappropriate, excessive or uncontrolled inflammation contributes to a range of human diseases. Inflammation involves a multitude of cell types, chemical mediators and interactions. The present article will describe nutritional and metabolic aspects of omega-6 (n-6) and omega-3 (n-3) fatty acids and explain the roles of bioactive members of those fatty acid families in inflammatory processes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are capable of partly inhibiting many aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid and production of pro-inflammatory cytokines. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid, and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB so reducing expression of inflammatory genes and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ. Animal experiments demonstrate benefit from EPA and DHA in a range of models of inflammatory conditions. Human trials demonstrate benefit of oral n-3 fatty acids in rheumatoid arthritis and in stabilizing advanced atherosclerotic plaques. Intravenous n-3 fatty acids may have benefits in critically ill patients through reduced inflammation. The anti-inflammatory and inflammation resolving actions of EPA, DHA and their derivatives are of clinical relevance. © 2017 The Author

Alginate micro-encapsulation of mesenchymal stromal cells enhances modulation of the neuro-inflammatory response.

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Stucky, Elizabeth C; Schloss, Rene S; Yarmush, Martin L; Shreiber, David I

2015-10-01

Modulation of inflammation after brain trauma is a key therapeutic goal aimed at limiting the consequences of the subsequent injury cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically regulate the inflammatory environment in several tissue systems, including the central nervous system. There has been limited success, however, with the use of direct implantation of cells in the brain caused by low viability and engraftment at the injury site. To circumvent this, we encapsulated MSCs in alginate microspheres and evaluated the ability of these encapsulated MSCs to attenuate inflammation in rat organotypic hippocampal slice cultures (OHSC). OHSC were administered lipopolysaccharide to induce inflammation and immediately co-cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) produced by OHSC, as well as MSC-produced trophic mediators. Encapsulated MSCs reduced TNF-α more effectively than did monolayer MSCs. Additionally, there was a strong correlation between increased prostaglandin E2 (PGE2) and reduction of TNF-α. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors, from which additional mediators with strong correlations to TNF-α levels were identified. These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for treating neuro-inflammation. Copyright © 2015. Published by Elsevier Inc.

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

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Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

2018-01-01

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function

Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

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Giovanna Trinchese

2018-01-01

Full Text Available Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM and donkey milk (DM are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM, DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA, a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

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Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

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Hele David J

2001-07-01

Full Text Available Abstract The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo® to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

Non-Steroidal Anti-Inflammatory Drugs, Variation in Inflammatory Genes, and Aggressive Prostate Cancer

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John S. Witte

2010-10-01

Full Text Available Increasing evidence suggests that prostatic inflammation plays a key role in the development of prostate cancer. It remains controversial whether non-steroidal anti-inflammatory drugs (NSAIDs reduce the risk of prostate cancer. Here, we investigate how a previously reported inverse association between NSAID use and the risk of aggressive prostate cancer is modulated by variants in several inflammatory genes. We found that NSAIDs may have differential effects on prostate cancer development, depending on one’s genetic makeup. Further study of these inflammatory pathways may clarify the mechanisms through which NSAIDs impact prostate cancer risk.

Optical modulation techniques for analog signal processing and CMOS compatible electro-optic modulation

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Gill, Douglas M.; Rasras, Mahmoud; Tu, Kun-Yii; Chen, Young-Kai; White, Alice E.; Patel, Sanjay S.; Carothers, Daniel; Pomerene, Andrew; Kamocsai, Robert; Beattie, James; Kopa, Anthony; Apsel, Alyssa; Beals, Mark; Mitchel, Jurgen; Liu, Jifeng; Kimerling, Lionel C.

2008-02-01

Integrating electronic and photonic functions onto a single silicon-based chip using techniques compatible with mass-production CMOS electronics will enable new design paradigms for existing system architectures and open new opportunities for electro-optic applications with the potential to dramatically change the management, cost, footprint, weight, and power consumption of today's communication systems. While broadband analog system applications represent a smaller volume market than that for digital data transmission, there are significant deployments of analog electro-optic systems for commercial and military applications. Broadband linear modulation is a critical building block in optical analog signal processing and also could have significant applications in digital communication systems. Recently, broadband electro-optic modulators on a silicon platform have been demonstrated based on the plasma dispersion effect. The use of the plasma dispersion effect within a CMOS compatible waveguide creates new challenges and opportunities for analog signal processing since the index and propagation loss change within the waveguide during modulation. We will review the current status of silicon-based electrooptic modulators and also linearization techniques for optical modulation.

Inflammatory modulation of exercise salience: using hormesis to return to a healthy lifestyle

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Bell Jimmy D

2010-12-01

Full Text Available Abstract Most of the human population in the western world has access to unlimited calories and leads an increasingly sedentary lifestyle. The propensity to undertake voluntary exercise or indulge in spontaneous physical exercise, which might be termed "exercise salience", is drawing increased scientific attention. Despite its genetic aspects, this complex behaviour is clearly modulated by the environment and influenced by physiological states. Inflammation is often overlooked as one of these conditions even though it is known to induce a state of reduced mobility. Chronic subclinical inflammation is associated with the metabolic syndrome; a largely lifestyle-induced disease which can lead to decreased exercise salience. The result is a vicious cycle that increases oxidative stress and reduces metabolic flexibility and perpetuates the disease state. In contrast, hormetic stimuli can induce an anti-inflammatory phenotype, thereby enhancing exercise salience, leading to greater biological fitness and improved functional longevity. One general consequence of hormesis is upregulation of mitochondrial function and resistance to oxidative stress. Examples of hormetic factors include calorie restriction, extreme environmental temperatures, physical activity and polyphenols. The hormetic modulation of inflammation, and thus, exercise salience, may help to explain the highly heterogeneous expression of voluntary exercise behaviour and therefore body composition phenotypes of humans living in similar obesogenic environments.

Language and culture modulate online semantic processing.

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Ellis, Ceri; Kuipers, Jan R; Thierry, Guillaume; Lovett, Victoria; Turnbull, Oliver; Jones, Manon W

2015-10-01

Language has been shown to influence non-linguistic cognitive operations such as colour perception, object categorization and motion event perception. Here, we show that language also modulates higher level processing, such as semantic knowledge. Using event-related brain potentials, we show that highly fluent Welsh-English bilinguals require significantly less processing effort when reading sentences in Welsh which contain factually correct information about Wales, than when reading sentences containing the same information presented in English. Crucially, culturally irrelevant information was processed similarly in both Welsh and English. Our findings show that even in highly proficient bilinguals, language interacts with factors associated with personal identity, such as culture, to modulate online semantic processing. © The Author (2015). Published by Oxford University Press.

The Role of Dietary Inflammatory Index in Cardiovascular Disease, Metabolic Syndrome and Mortality

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Miguel Ruiz-Canela

2016-08-01

Full Text Available Inflammation is an underlying pathophysiological process in chronic diseases, such as obesity, type 2 diabetes mellitus and cardiovascular disease. In fact, a number of systematic reviews have shown the association between inflammatory biomarkers, such as CRP, IL-1β, IL-6, TNF-α, IL-4, or IL-10, and cardio-metabolic diseases. Diet is one of the main lifestyle-related factors which modulates the inflammatory process. Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties. The dietary inflammatory index (DII was recently developed to estimate the inflammatory potential of overall diet. The aim of this review is to examine the findings of recent papers that have investigated the association between the DII, cardio-metabolic risk factors and cardiovascular disease. The relevance of the DII score in the association between inflammation and cardio-metabolic diseases is critically appraised, as well as its role in the context of healthy dietary patterns. We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better understand the relationships between diet, inflammation, and cardio-metabolic diseases.

Biochemical alterations in inflammatory reactive chondrocytes: evidence for intercellular network communication

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Eva Skiöldebrand

2018-01-01

Full Text Available Chondrocytes are effectively involved in the pathophysiological processes of inflammation in joints. They form cellular processes in the superficial layer of the articular cartilage and form gap junction coupled syncytium to facilitate cell-to-cell communication. However, very little is known about their physiological cellular identity and communication. The aim with the present work is to evaluate the physiological behavior after stimulation with the inflammatory inducers interleukin-1β and lipopolysaccharide. The cytoskeleton integrity and intracellular Ca2+ release were assessed as indicators of inflammatory state. Cytoskeleton integrity was analyzed through cartilage oligomeric matrix protein and actin labeling with an Alexa 488-conjugated phalloidin probe. Ca2+ responses were assessed through the Ca2+ sensitive fluorophore Fura-2/AM. Western blot analyses of several inflammatory markers were performed. The results show reorganization of the actin filaments. Glutamate, 5-hydoxytryptamine, and ATP evoked intracellular Ca2+ release changed from single peaks to oscillations after inflammatory induction in the chondrocytes. The expression of toll-like receptor 4, the glutamate transporters GLAST and GLT-1, and the matrix metalloproteinase-13 increased. This work demonstrates that chondrocytes are a key part in conditions that lead to inflammation in the cartilage. The inflammatory inducers modulate the cytoskeleton, the Ca2+ signaling, and several inflammatory parameters. In conclusion, our data show that the cellular responses to inflammatory insults from healthy and inflammatory chondrocytes resemble those previously observed in astrocyte and cardiac fibroblasts networks.

Information processing systems, reasoning modules, and reasoning system design methods

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Hohimer, Ryan E; Greitzer, Frank L; Hampton, Shawn D

2014-03-04

Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

Information processing systems, reasoning modules, and reasoning system design methods

Energy Technology Data Exchange (ETDEWEB)

Hohimer, Ryan E.; Greitzer, Frank L.; Hampton, Shawn D.

2016-08-23

Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

Information processing systems, reasoning modules, and reasoning system design methods

Energy Technology Data Exchange (ETDEWEB)

Hohimer, Ryan E.; Greitzer, Frank L.; Hampton, Shawn D.

2015-08-18

Information processing systems, reasoning modules, and reasoning system design methods are described. According to one aspect, an information processing system includes working memory comprising a semantic graph which comprises a plurality of abstractions, wherein the abstractions individually include an individual which is defined according to an ontology and a reasoning system comprising a plurality of reasoning modules which are configured to process different abstractions of the semantic graph, wherein a first of the reasoning modules is configured to process a plurality of abstractions which include individuals of a first classification type of the ontology and a second of the reasoning modules is configured to process a plurality of abstractions which include individuals of a second classification type of the ontology, wherein the first and second classification types are different.

Pacific ciguatoxin 1B-induced modulation of inflammatory mediators in a murine macrophage cell line.

Science.gov (United States)

Matsui, Mariko; Kumar-Roine, Shilpa; Darius, H Taiana; Chinain, Mireille; Laurent, Dominique; Pauillac, Serge

2010-10-01

Ciguatoxins, potent marine neurotoxins responsible for ciguatera, exert their numerous damaging effects through primary binding to the voltage-sensitive sodium channels of excitable cells. Using RAW 264.7 murine macrophages, we report the first experimental study presenting evidence that P-CTX-1B (the most potent congener from the Pacific) could modulate mRNA expression of pro- and anti-inflammatory cytokines as well as of inducible nitric oxide synthase (iNOS). P-CTX-1B, unlike other less potent marine polyether toxins, P-CTX-3C and PbTx-3, induced the overexpression of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor-alpha and iNOS with different magnitude and kinetic profiles, as compared to bacterial lipopolysaccharide (LPS). Unlike LPS, P-CTX-1B did not modulate IL-11 expression. In this report, we provide new evidence of the P-CTX-1B iNOS- and cytokines-inducing ability and shed new light on host response to potent neurotoxins. Copyright 2009 Elsevier Ltd. All rights reserved.

The gut microbiota and inflammatory noncommunicable diseases

DEFF Research Database (Denmark)

West, Christina E; Renz, Harald; Jenmalm, Maria C

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity...... for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti....... In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention....

Cerium dioxide nanoparticles do not modulate the lipopolysaccharide-induced inflammatory response in human monocytes

Directory of Open Access Journals (Sweden)

Hussain S

2012-03-01

Full Text Available Salik Hussain1,*, Faris Al-Nsour1,*, Annette B Rice1, Jamie Marshburn1, Zhaoxia Ji2, Jeffery I Zink2, Brenda Yingling1, Nigel J Walker3, Stavros Garantziotis11Clinical Research Unit, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, 2UC Center for Environmental Implications of Nanotechnology University of California, Los Angeles, CA, 3Division of National Toxicology Program, National Institute of Environmental Health Sciences/National Institute of Health, Research Triangle Park, NC, USA*Both are principal authorsBackground: Cerium dioxide (CeO2 nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO2 nanoparticles. We investigated the inflammation-modulating effects of CeO2 nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes.Methods: CD14+ cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO2 nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10.Results: CeO2 nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter, zeta potential analysis (-14 mV, and transmission electron microscopy (irregular-shaped particles. Transmission electron microscopy of CD14+ cells exposed to CeO2 nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and

A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

Science.gov (United States)

Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana Del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

2016-03-16

Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Steroid Hormones on the Modulation of Neuroinflammation by Dietary Interventions

Directory of Open Access Journals (Sweden)

Andrea Rodrigues Vasconcelos

2016-02-01

Full Text Available Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain.The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer´s and Parkinson´s diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, whilst metabolic syndromes, like diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact on the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, like calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

Science.gov (United States)

Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

2012-09-21

The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

Roles of inflammatory caspases during processing of zebrafish interleukin-1β in Francisella noatunensis infection

Science.gov (United States)

Vojtech, Lucia N.; Scharping, Nichole; Woodson, James C.; Hansen, John D.

2012-01-01

The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.                   

Stress modulation of cognitive and affective processes

Science.gov (United States)

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Optogenetic exploration and modulation of pain processing.

Science.gov (United States)

Xie, Yu-Feng; Wang, Jing; Bonin, Robert P

2018-08-01

Intractable pain is the single most common cause of disability, affecting more than 20% of the population world-wide. There is accordingly a global effort to decipher how changes in nociceptive processing in the peripheral and central nervous systems contribute to the onset and maintenance of chronic pain. The past several years have brought rapid progress in the adaptation of optogenetic approaches to study and manipulate the activity of sensory afferents and spinal cord neurons in freely behaving animals, and to investigate cortical processing and modulation of pain responses. This review discusses methodological advances that underlie this recent progress, and discusses practical considerations for the optogenetic modulation of nociceptive sensory processing. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

Science.gov (United States)

Rao, Sadia Saleem; Najam, Rahila

2016-01-01

Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

Inhibitory Effects of North American Wild Rice on Monocyte Adhesion and Inflammatory Modulators in Low-Density Lipoprotein Receptor-Knockout Mice.

Science.gov (United States)

Moghadasian, Mohammed H; Zhao, Ruozhi; Ghazawwi, Nora; Le, Khuong; Apea-Bah, Franklin B; Beta, Trust; Shen, Garry X

2017-10-18

The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received a cholesterol (0.06%, w/w)-supplemented diet with or without white or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion and abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to the control diet. Wild rice inhibited monocyte adhesion to the aorta, atherosclerosis, and abundances of the inflammatory and fibrinolytic regulators in the cardiovascular tissue of LDLr-KO mice compared to white rice. White or wild rice did not significantly alter the levels of cholesterol, triglycerides, or antioxidant enzymes in plasma. The anti-atherosclerotic effect of wild rice may result from its inhibition on monocyte adhesion and inflammatory modulators in LDLr-KO mice.

Inflammatory cytokines and immune system modulation by aerobic ...

African Journals Online (AJOL)

Keywords: Immune function, inflammatory cytokines, aerobic exercise, resistance exercise, aging. ... Physical exercise is effective in reducing (or ameliorate) the ..... moderate resistance training program increases muscle .... Nutrition Metabo-.

Physical exercise, inflammatory process and adaptive condition: an overview

OpenAIRE

Silva, Fernando Oliveira Catanho da; Macedo, Denise Vaz

2011-01-01

Physical exercise induces inflammation, a physiological response that is part of immune system activity and promotes tissue remodeling after exercise overload. The activation of the inflammatory process is local and systemic and is mediated by different cells and secreted compounds. The objective is to reestablish organ homeostasis after a single bout of exercise or after several exercise sessions. The acute-phase response involves the combined actions of activated leukocytes, cytokines, acut...

279 Watt Metal-Wrap-Through module using industrial processes

Energy Technology Data Exchange (ETDEWEB)

Guillevin, N.; Heurtault, B.; Geerligs, L.J.; Anker, J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Berkeveld, L.D.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, PO Box 1, 1755 ZG Petten (Netherlands); Wenchao, Zhao; Jianming, Wang; Ziqian, Wang; Yingle, Chen; Yanlong, Shen; Zhiyan, Hu; Gaofei, Li; Jianhui, Chen; Bo, Yu; Shuquan, Tian; Jingfeng, Xiong [Yingli Solar, 3399 Chaoyang North Street, Baoding (China)

2012-09-15

This paper describes results of metal wrap through (MWT) cells produced from n-type Czochralski silicon wafers, and modules produced from those cells. The use of n-type silicon as base material allows for high efficiencies: for front emitter contacted industrial cells, efficiencies up to 20% have been reported. MWT cells allow even higher cell efficiency due to reduced front metal coverage, and additionally full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. MWT cells were produced by industrial process technologies. The efficiency of the MWT cells reproducibly exceeds the efficiency of front contact cells based on the same technology by about 0.2-0.3%, and routes for further improvement are analyzed. 60-cell modules were produced from both types of cells (MWT and H-pattern front emitter). In a direct module performance comparison, the MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter contact module. CTM current differences arise from the higher packing density, and in this experiment from a lower reflectance of the backfoil, in MWT modules. CTM FF differences are related to resistive losses in copper circuitry on the backfoil versus tabs. The CTM FF loss of the MWT module was reduced by 2.2%abs compared to the tabbed front emitter contact module. Finally, simple process optimizations were tested to improve the n-type MWT cell and module efficiency. A module made using MWT cells of 19.6% average efficiency resulted in a power output of 279W. The cell and module results are analyzed and routes for improvements are discussed.

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

Science.gov (United States)

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

GanedenBC^30™ cell wall and metabolites: anti-inflammatory and immune modulating effects in vitro

OpenAIRE

Carter Steve G; Benson Kathleen F; Jensen Gitte S; Endres John R

2010-01-01

Abstract Background This study was performed to evaluate anti-inflammatory and immune modulating properties of the probiotic, spore-forming bacterial strain: Bacillus coagulans: GBI-30, (PTA-6086, GanedenBC30TM). In addition, cell wall and metabolite fractions were assayed separately to address whether biological effects were due to cell wall components only, or whether secreted compounds from live bacteria had additional biological properties. The spores were heat-activated, and bacterial cu...

Malignant transformation of oral lichen planus by a chronic inflammatory process. Use of topical corticosteroids to prevent this progression?

Science.gov (United States)

Otero-Rey, Eva Maria; Suarez-Alen, Fatima; Peñamaria-Mallon, Manuel; Lopez-Lopez, Jose; Blanco-Carrion, Andres

2014-11-01

Oral lichen planus is a potentially malignant disorder with a capacity, although low, for malignant transformation. Of all the factors related to the process of malignant transformation, it is believed that the chronic inflammatory process plays a key role in the development of oral cancer. This inflammatory process is capable of providing a microenvironment based on different inflammatory cells and molecules that affect cellular growth, proliferation and differentiation. The objectives of our study are: to review the available evidence about the possible relationship between the chronic inflammatory process present in oral lichen planus and its malignant transformation, to discuss the potential therapeutic implications derived from this relationship and to study the role that topical corticosteroids play in the control of oral lichen planus inflammation and its possible progression to malignant transformation. The maintenance of a minimum dose of topical corticosteroids could prevent the inflammatory progression of oral lichen planus to oral cancer.

Binaural processing of modulated interaural level differences

DEFF Research Database (Denmark)

Thompson, Eric Robert; Dau, Torsten

2008-01-01

Two experiments are presented that measure the acuity of binaural processing of modulated interaural level differences ILDs using psychoacoustic methods. In both experiments, dynamic ILDs were created by imposing an interaurally antiphasic sinusoidal amplitude modulation AM signal on high...... frequency, broadly tuned, bandpass-shaped patterns were obtained. Simulations with an existing binaural model show that a low-pass filter to limit the binaural temporal resolution is not sufficient to predict the results of the experiments....

Diagnosis of intra abdominal inflammatory processes with 111In-labelled leucocytes

International Nuclear Information System (INIS)

Roevekamp, M.H.; Brummelkamp, W.H.; Schoot, J.B. van der; Reinders Folmer, S.Chr.C.; Royen, E.A. van

1982-01-01

Over a two and a half year period, 225 scintigrams with indium-111 oxinate labelled leukocytes were performed in 184 patients suspected of an intra-abdominal, retroperitoneal or pelvic inflammatory process. In patients suspected of an upper abdominal process, an indium-111 leukocyte-99Tc-Sn colloid subtraction was performed, in order to eliminate the normal liver and spleen uptake. 123 Scintigrams were considered true positive and 73 true negative. A diagnostic accuracy of 87% was calculated. With 18 false-positive scans an 80%-specificity and with 11 false-negative a 92%-sensitivity were obtained. False-positive results in the majority of the scintigrams were based on leukocyte accumulations, due to aspecific cellular inflammatory reactions. False-negative results were mainly related to intra-hepatic, intra-splenic or older lesions. In 150 patients, ultrasonography and/or computed tomography was also performed. A higher diagnostic accuracy was observed with leukocyte scintigraphy compared to ultrasonography. (Auth.)

Low cost solar array project production process and equipment task. A Module Experimental Process System Development Unit (MEPSDU)

Science.gov (United States)

1981-01-01

Technical readiness for the production of photovoltaic modules using single crystal silicon dendritic web sheet material is demonstrated by: (1) selection, design and implementation of solar cell and photovoltaic module process sequence in a Module Experimental Process System Development Unit; (2) demonstration runs; (3) passing of acceptance and qualification tests; and (4) achievement of a cost effective module.

[The contribution of inflammatory process in pathogenesis and natural history of atrial fibrillation].

Science.gov (United States)

Zyśko, Dorota; Gajek, Jacek; Mazurek, Walentyna

2005-02-01

The inflammatory process plays important role in pathogenesis of some cardiovascular diseases. Atrial fibrillation is atrial arrhythmia with rapid, asynchronous activation of atrial myocytes. The inflammatory process can be responsible for atrial electrical and anatomical remodeling and therefore shifts towards arrhythmia persistence. The presence of systemic inflammation may be assessed by means of C-reactive protein (CRP) measurement. Maximal concentration of CRP coincidences with the peak of paroxysmal atrial fibrillation occurrence in patients after cardiac surgery. In patients with sinus rhythm the concentration of CRP is a risk factor for this arrhythmia in long-term follow-up. In patients with atrial fibrillation mean CRP concentration is 2-fold higher comparing to control group. CRP concentration is higher in patients with chronic than paroxysmal form of this arrhythmia. High CRP level predicts worse results of direct current cardioversion and more frequent paroxysms of atrial fibrillation during follow-up. Besides of, the patients with echocardiographic signs of thromboembolic risk have higher CRP levels than control subjects. There is no data about the influence of anti-inflammatory therapy on atrial fibrillation or its recurrences.

Optical metrology for advanced process control: full module metrology solutions

Science.gov (United States)

Bozdog, Cornel; Turovets, Igor

2016-03-01

Optical metrology is the workhorse metrology in manufacturing and key enabler to patterning process control. Recent advances in device architecture are gradually shifting the need for process control from the lithography module to other patterning processes (etch, trim, clean, LER/LWR treatments, etc..). Complex multi-patterning integration solutions, where the final pattern is the result of multiple process steps require a step-by-step holistic process control and a uniformly accurate holistic metrology solution for pattern transfer for the entire module. For effective process control, more process "knobs" are needed, and a tighter integration of metrology with process architecture.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis.

Directory of Open Access Journals (Sweden)

Johannes J Kovarik

Full Text Available A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR, is responsible for controlling the balance between pro-inflammatory interleukin (IL-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP-activated protein kinase (AMPK activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.

Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis

Science.gov (United States)

Kernbauer, Elisabeth; Hölzl, Markus A.; Hofer, Johannes; Gualdoni, Guido A.; Schmetterer, Klaus G.; Miftari, Fitore; Sobanov, Yury; Meshcheryakova, Anastasia; Mechtcheriakova, Diana; Witzeneder, Nadine; Greiner, Georg; Ohradanova-Repic, Anna; Waidhofer-Söllner, Petra; Säemann, Marcus D.; Decker, Thomas

2017-01-01

A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation. PMID:28742108

Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

Directory of Open Access Journals (Sweden)

Humberto Nicastro

2012-01-01

Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

[TLR2 modulates Staphylococcus aureus-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway].

Science.gov (United States)

Li, Shuai; Fang, Lei; Wang, Jiong; Liu, Rongyu

2017-09-01

Objective To investigate the molecular mechanisms of Toll-like receptor 2 (TLR2) taking part in inflammatory response in Staphylococcus aureus (SA)-induced asthma. Methods We established the cell inflammatory response model through stimulating mouse RAW264.7 macrophages with SA. The TLR2, myeloid differentiation factor 88 (MyD88), phosphoinositide-3 kinase (PI3K), nuclear factor κBp65 (NF-κBp65), phospho-NF-κBp65, beclin-1 and microtubule-associated protein 1 light chain 3B (LC3B) were detected by Western blot analysis after treatment with TLR2 small interfering RNA (siRNA) and 3-methyladenine (3-MA), and the tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were determined by ELISA. In addition, the number of autolysosomes was observed by the laser scanning confocal microscope. Results SA-stimulated macrophages activated various signaling pathways including TLR2. TLR2 siRNA markedly repressed the expressions of PI3K, phospho-NF-κBp65, the autophagy protein beclin-1 and LC3B as well as the number of autolysosomes and the production of TNF- and IL-6. We also demonstrated that 3-MA had the same effect on autophagy and inflammation as TLR2 siRNA did. Conclusion TLR2 modulates SA-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway.

Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

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Marcelo Franchin

2013-01-01

Full Text Available The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1 was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway.

Science.gov (United States)

Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

2013-01-01

The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

Odontogenic Inflammatory Processes of Head and Neck in Computed Tomography Examinations

International Nuclear Information System (INIS)

Wabik, Aleksandra; Hendrich, Barbara K.; Nienartowicz, Jan; Guziński, Maciej; Sąsiadek, Marek J.

2014-01-01

Infections of odontogenic origin are the most common cause of inflammatory disease of head and neck region. Computed tomography allows for defining localization and extent of inflammatory lesions, visualizes soft tissue involvement, presence of an abscess or an osteolytic lesion around causative tooth. The aim of this study was to assess pathways, by which odontogenic infections spread into respective deep head and neck structures in computed tomography examination, taking into account the following criteria: frequency of involvement of respective deep cervical spaces, possibility to determine a probable causative tooth and concordance with the results of clinical examination. Thirty-eight patients cervicofacial inflammatory disease had undergone CT examination of head and neck region with a 64-slice CT scanner after intravenous contrast administration. Abscess was reported in 30 (79%) cases, while inflammatory infiltration was diagnosed in remaining 8 (21%) patients. There was full concordance between radiological report and intraoperative report In 33 cases (87%). The most commonly involved cervical space was masticator space – 31 patients (82%), followed by submandibular space – 27 patients (71%). Dental examination was impossible in 29 patient because of trismus. During analysis of CT studies we evaluated maxillary and mandibular alveolar processes for presence of osteolytic bone lesions around causative teeth roots and we found them in 30 cases (79%). In 32 cases (84%) cervicofacial infection were of mandibular odontogenic origin. In most cases CT study in patients suspected of odontogenic craniofacial infection revealed presence of an abscess, needing urgent surgery. Inflammatory infiltration of dental origin most frequently involves masticator space, followed by submandibular space. In most cases CT scanning allows for identification of causative teeth, especially when trismus makes detailed clinical examination impossible

Safety analysis of SISL process module

International Nuclear Information System (INIS)

1983-05-01

This report provides an assessment of various postulated accidental occurrences within an experimental process module which is part of a Special Isotope Separation Laboratory (SISL) currently under construction at the Lawrence Livermore National Laboratory (LLNL). The process module will contain large amounts of molten uranium and various water-cooled structures within a vacuum vessel. Special emphasis is therefore given to potential accidental interactions of molten uranium with water leading to explosive and/or rapid steam formation, as well as uranium oxidation and the potential for combustion. Considerations are also given to the potential for vessel melt-through. Evaluations include mechanical and thermal interactions and design implications both in terms of design basis as well as once-in-a-lifetime accident scenarios. These scenarios include both single- and multiple-failure modes leading to various contact modes and locations within the process module for possible thermal interactions. The evaluations show that a vacuum vessel design based upon nominal operating conditions would appear sufficient to meet safety requirements in connection with both design basis as well as once-in-a-lifetime accidents. Controlled venting requirements for removal of steam and hydrogen in order to avoid possible long-term pressurization events are recommended. Depending upon the resulting accident conditions, the vacuum system (i.e., the roughing system) could also serve this purpose. Finally, based upon accident evaluations of this study, immediate shut-off of all coolant water following an incident leak is not recommended, as such action may have adverse effects in terms of cool-down requirements for the melt crucibles etc. These requirements have not been assessed as part of this study

A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

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Yang Qi

2009-12-01

Full Text Available Abstract The midbrain periaqueductal grey (PAG is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp, one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity.

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Emília R Vaz

Full Text Available The transforming growth factor beta 1 (TGF-β1 is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-β1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-β-targeted pathways, the inducible regulatory T cells (iTreg to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD technology that could mimic TGF-β1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-β1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-α and IL-10 cytokines. The synthetic pm26TGF-β1 peptide tested in PBMC significantly down-modulated TNF-α and up-regulated IL-10 responses, leading to regulatory T cells (Treg phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils' chemoattraction.

Development of coincidence processing module for PEM

International Nuclear Information System (INIS)

Feng Baotong; Shuai Lei; Li Ke

2011-01-01

For the breast cancer diagnosis and therapy, a prototype of positron emission mammography (PEM) was developed in Institute of High Energy Physics, Chinese Academy of Sciences. In this paper, the design of coincidence processing module (CPM) for this PEM was presented. Both the hardware architecture and the software logic were introduced. In this design, the CPM used the Rocket IO fast interface in FPGA and fiber technology to acquire the preprocessed data from the continuous sampling module (CSM) and then selected the valid event with the coincidence timing window method, which was performed in the FPGA on the daughter board. The CPM transmits the processed data to host computer via gigabit Ethernet. The whole system was controlled by CAN bus. The primary tests indicate that the performance of this design is good. (authors)

IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer

DEFF Research Database (Denmark)

Gyrd-Hansen, Mads; Meier, Pascal

2010-01-01

. The development of such inhibitors has radically changed our knowledge of the signalling processes that are regulated by IAPs. Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation and mitosis...

Cocoa Polyphenols and Inflammatory Markers of Cardiovascular Disease

Science.gov (United States)

Khan, Nasiruddin; Khymenets, Olha; Urpí-Sardà, Mireia; Tulipani, Sara; Garcia-Aloy, Mar; Monagas, María; Mora-Cubillos, Ximena; Llorach, Rafael; Andres-Lacueva, Cristina

2014-01-01

Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review. PMID:24566441

Spectrotemporal processing in spectral tuning modules of cat primary auditory cortex.

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Craig A Atencio

Full Text Available Spectral integration properties show topographical order in cat primary auditory cortex (AI. Along the iso-frequency domain, regions with predominantly narrowly tuned (NT neurons are segregated from regions with more broadly tuned (BT neurons, forming distinct processing modules. Despite their prominent spatial segregation, spectrotemporal processing has not been compared for these regions. We identified these NT and BT regions with broad-band ripple stimuli and characterized processing differences between them using both spectrotemporal receptive fields (STRFs and nonlinear stimulus/firing rate transformations. The durations of STRF excitatory and inhibitory subfields were shorter and the best temporal modulation frequencies were higher for BT neurons than for NT neurons. For NT neurons, the bandwidth of excitatory and inhibitory subfields was matched, whereas for BT neurons it was not. Phase locking and feature selectivity were higher for NT neurons. Properties of the nonlinearities showed only slight differences across the bandwidth modules. These results indicate fundamental differences in spectrotemporal preferences--and thus distinct physiological functions--for neurons in BT and NT spectral integration modules. However, some global processing aspects, such as spectrotemporal interactions and nonlinear input/output behavior, appear to be similar for both neuronal subgroups. The findings suggest that spectral integration modules in AI differ in what specific stimulus aspects are processed, but they are similar in the manner in which stimulus information is processed.

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

Science.gov (United States)

Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

2018-05-01

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

All-optical microwave signal processing based on optical phase modulation

Science.gov (United States)

Zeng, Fei

This thesis presents a theoretical and experimental study of optical phase modulation and its applications in all-optical microwave signal processing, which include all-optical microwave filtering, all-optical microwave mixing, optical code-division multiple-access (CDMA) coding, and ultrawideband (UWB) signal generation. All-optical microwave signal processing can be considered as the use of opto-electronic devices and systems to process microwave signals in the optical domain, which provides several significant advantages such as low loss, low dispersion, light weight, high time bandwidth products, and immunity to electromagnetic interference. In conventional approaches, the intensity of an optical carrier is modulated by a microwave signal based on direct modulation or external modulation. The intensity-modulated optical signal is then fed to a photonic circuit or system to achieve specific signal processing functionalities. The microwave signal being processed is usually obtained based on direct detection, i.e., an opto-electronic conversion by use of a photodiode. In this thesis, the research efforts are focused on the optical phase modulation and its applications in all-optical microwave signal processing. To avoid using coherent detection which is complicated and costly, simple and effective phase modulation to intensity modulation (PM-IM) conversion schemes are pursued. Based on a theoretical study of optical phase modulation, two approaches to achieving PM-IM conversions are proposed. In the first approach, the use of chromatic dispersion induced by a dispersive device to alter the phase relationships among the sidebands and the optical carrier of a phase-modulated optical signal to realize PM-IM conversion is investigated. In the second approach, instead of using a dispersive device, the PM-IM conversion is realized based on optical frequency discrimination implemented using an optical filter. We show that the proposed PM-IM conversion schemes can be

Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens.

Science.gov (United States)

Cortés-Vieyra, Ricarda; Bravo-Patiño, Alejandro; Valdez-Alarcón, Juan J; Juárez, Marcos Cajero; Finlay, B Brett; Baizabal-Aguirre, Víctor M

2012-06-12

Glycogen synthase kinase 3β (GSK3β) plays a fundamental role during the inflammatory response induced by bacteria. Depending on the pathogen and its virulence factors, the type of cell and probably the context in which the interaction between host cells and bacteria takes place, GSK3β may promote or inhibit inflammation. The goal of this review is to discuss recent findings on the role of the inhibition or activation of GSK3β and its modulation of the inflammatory signaling in monocytes/macrophages and epithelial cells at the transcriptional level, mainly through the regulation of nuclear factor-kappaB (NF-κB) activity. Also included is a brief overview on the importance of GSK3 in non-inflammatory processes during bacterial infection.

Effect of exposure to radiation on the inflammatory process and its influence by diclofenac

International Nuclear Information System (INIS)

El-Ghazaly, M.; Kenawy, S.; Khayyal, M.T.; Roushdy, H.; Saleh, S.

1985-01-01

The effect of radiation exposure on the inflammatory process was studied in rats using the carrageenan-induced paw oedema and adjuvant-induced arthritis tests. Irradiation (0.5,1 and 2 Grays) resulted in a significant augmentation of the tissue response to carrageenan and the early phase of adjuvant-induced arthritis, but suppressed the late phase. Diclofenac(1-5 mg kg -1 ) effectively reduced the exaggerated inflammatory response in irradiated animals in both the carrageenan paw oedema and adjuvant-induced arthritis tests. The drug also had a prophylactic value in guarding against the induction of radiation damage. The inflammatory responses produced by irradiation and the benefits obtained by drug treatment may be related to changes in tissue prostaglandin levels and/or changes in the immune system. (author)

Immune and inflammatory responses in the CNS : Modulation by astrocytes

DEFF Research Database (Denmark)

Penkowa, Milena; aschner, michael; hidalgo, juan

2008-01-01

Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in the Mouse Air Pouch

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Rita Brines

2018-01-01

Full Text Available Heme oxygenase-1 (HO-1 is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3 was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.

Effective Thermal Analysis of Using Peltier Module for Desalination Process

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Hayder Al-Madhhachi

2018-01-01

Full Text Available The key objective of this study is to analyse the heat transfer processes involved in the evaporation and condensation of water in a water distillation system employing a thermoelectric module. This analysis can help to increase the water production and to enhance the system performance. For the analysis, a water distillation unit prototype integrated with a thermoelectric module was designed and fabricated. A theoretical model is developed to study the effect of the heat added, transferred and removed, in forced convection and laminar flow, during the evaporation and condensation processes. The thermoelectric module is used to convert electricity into heat under Peltier effect and control precisely the absorbed and released heat at the cold and hot sides of the module, respectively. Temperatures of water, vapour, condenser, cold and hot sides of the thermoelectric module and water production have been measured experimentally under steady state operation. The theoretical and experimental water production were found to be in agreement. The amount of heat that needs to be evaporated from water-vapour interface and transferred through the condenser surface to the thermoelectric module is crucial for the design and optimization of distillation systems.

Comprehensive two-dimensional gas chromatography: A perspective on processes of modulation.

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Tranchida, Peter Q

2018-02-09

The first comprehensive two-dimensional gas chromatography (GC×GC) experiment was reported about 25 years ago [J. Chromatogr. Sci. 29 (1991) 227-231]; the GC×GC process was made possible by the development of a transfer device, defined as modulator. The process of modulation enables the isolation of effluent segments from the first column, and their re-injection onto the second column, in a continuous and sequential manner throughout the analysis. Over the years, many types of modulation systems have been introduced, each with specific advantages and disadvantages. Cryogenic systems are, at present, the most popular devices and represent the most effective form of modulation. The present contribution is focused on possible future scenarios, with respect to modulation, and as a consequence related to comprehensive GC, in general. The development of new forms of modulation may open the road to a more widespread use of GC×GC technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

Science.gov (United States)

Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

2016-01-04

The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

Visible light communications modulation and signal processing

CERN Document Server

Wang, Zhaocheng; Huang, Wei; Xu, Zhengyuan

2018-01-01

This informative new book on state-of-the-art visible light communication (VLC) provides, for the first time, a systematical and advanced treatment of modulation and signal processing for VLC. Visible Light Communications: Modulation and Signal Processing offers a practical guide to designing VLC, linking academic research with commercial applications. In recent years, VLC has attracted attention from academia and industry since it has many advantages over the traditional radio frequency, including wide unregulated bandwidth, high security, and low cost. It is a promising complementary technique in 5G and beyond wireless communications, especially in indoor applications. However, lighting constraints have not been fully considered in the open literature when considering VLC system design, and its importance has been underestimated. That’s why this book—written by a team of experts with both academic research experience and industrial development experience in the field—is so welcome. To help readers u...

Cell-Intrinsic Roles for Autophagy in Modulating CD4 T Cell Functions

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Elise Jacquin

2018-05-01

Full Text Available The catabolic process of autophagy plays important functions in inflammatory and immune responses by modulating innate immunity and adaptive immunity. Over the last decade, a cell-intrinsic role for autophagy in modulating CD4 T cell functions and differentiation was revealed. After the initial observation of autophagosomes in effector CD4 T cells, further work has shown that not only autophagy levels are modulated in CD4 T cells in response to environmental signals but also that autophagy critically affects the biology of these cells. Mouse models of autophagy deletion in CD4 T cells have indeed shown that autophagy is essential for CD4 T cell survival and homeostasis in peripheral lymphoid organs. Furthermore, autophagy is required for CD4 T cell proliferation and cytokine production in response to T cell receptor activation. Recent developments have uncovered that autophagy controls CD4 T cell differentiation and functions. While autophagy is required for the maintenance of immunosuppressive functions of regulatory T cells, it restrains the differentiation of TH9 effector cells, thus limiting their antitumor and pro-inflammatory properties. We will here discuss these findings that collectively suggest that therapeutic strategies targeting autophagy could be exploited for the treatment of cancer and inflammatory diseases.

Category-selective attention modulates unconscious processes in the middle occipital gyrus.

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Tu, Shen; Qiu, Jiang; Martens, Ulla; Zhang, Qinglin

2013-06-01

Many studies have revealed the top-down modulation (spatial attention, attentional load, etc.) on unconscious processing. However, there is little research about how category-selective attention could modulate the unconscious processing. In the present study, using functional magnetic resonance imaging (fMRI), the results showed that category-selective attention modulated unconscious face/tool processing in the middle occipital gyrus (MOG). Interestingly, MOG effects were of opposed direction for face and tool processes. During unconscious face processing, activation in MOG decreased under the face-selective attention compared with tool-selective attention. This result was in line with the predictive coding theory. During unconscious tool processing, however, activation in MOG increased under the tool-selective attention compared with face-selective attention. The different effects might be ascribed to an interaction between top-down category-selective processes and bottom-up processes in the partial awareness level as proposed by Kouider, De Gardelle, Sackur, and Dupoux (2010). Specifically, we suppose an "excessive activation" hypothesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes.

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Rajasekhar, Pradeep; Poole, Daniel P; Veldhuis, Nicholas A

2017-01-01

Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein. © 2017 Elsevier Inc. All rights reserved.

Nuclear Technology. Course 28: Welding Inspection. Module 28-6, Process Controls.

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Espy, John

This sixth in a series of ten modules for a course titled Welding Inspection describes procedures review, process monitoring, and weld defect analysis. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject matter, (6)…

Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice

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Liu Zhihui

2008-08-01

Full Text Available Abstract Background Interleukin 1 beta (IL-1β plays an important role in a number of chronic and acute inflammatory diseases. To understand the role of IL-1β in disease processes and develop an in vivo screening system for anti-inflammatory drugs, a transgenic mouse line was generated which incorporated the transgene firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1β gene promoter. Luciferase gene expression was monitored in live mice under anesthesia using bioluminescence imaging in a number of inflammatory disease models. Results In a LPS-induced sepsis model, dramatic increase in luciferase activity was observed in the mice. This transgene induction was time dependent and correlated with an increase of endogenous IL-1β mRNA and pro-IL-1β protein levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced skin hypersensitivity reaction model, luciferase expression was locally induced in the zymosan injected knee joint and in the ear with oxazolone application, respectively. Dexamethasone suppressed the expression of luciferase gene both in the acute sepsis model and in the acute arthritis model. Conclusion Our data suggest that the transgenic mice model could be used to study transcriptional regulation of the IL-1β gene expression in the inflammatory process and evaluation the effect of anti-inflammatory drug in vivo.

Impact of weight loss on oxidative stress and inflammatory cytokines ...

African Journals Online (AJOL)

Background: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating ...

Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens

Directory of Open Access Journals (Sweden)

Cortés-Vieyra Ricarda

2012-06-01

Full Text Available Abstract Glycogen synthase kinase 3β (GSK3β plays a fundamental role during the inflammatory response induced by bacteria. Depending on the pathogen and its virulence factors, the type of cell and probably the context in which the interaction between host cells and bacteria takes place, GSK3β may promote or inhibit inflammation. The goal of this review is to discuss recent findings on the role of the inhibition or activation of GSK3β and its modulation of the inflammatory signaling in monocytes/macrophages and epithelial cells at the transcriptional level, mainly through the regulation of nuclear factor-kappaB (NF-κB activity. Also included is a brief overview on the importance of GSK3 in non-inflammatory processes during bacterial infection.

Mechanisms Modulating Inflammatory Osteolysis: A Review with Insights into Therapeutic Targets

OpenAIRE

Wei, Shi; Siegal, Gene P.

2008-01-01

Inflammatory osteolysis is a relatively frequent and incapacitating complication of rheumatoid arthritis and multiple other inflammation-associated bone diseases. It is thought to operate through an ultimate common pathway of accelerated osteoclast recruitment and activation under the control of cytokines produced in the inflammatory environment. Over the past decade, there have been major advances in our understanding of the mechanisms of osteoclastogenesis. It is now clear that the interact...

Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

Science.gov (United States)

Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

2015-11-01

Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

Science.gov (United States)

Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A

2006-07-01

Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

Science.gov (United States)

Basson, Abigail R; Lam, Minh; Cominelli, Fabio

2017-12-01

The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

Science.gov (United States)

Bagarolli, Renata A; Tobar, Natália; Oliveira, Alexandre G; Araújo, Tiago G; Carvalho, Bruno M; Rocha, Guilherme Z; Vecina, Juliana F; Calisto, Kelly; Guadagnini, Dioze; Prada, Patrícia O; Santos, Andrey; Saad, Sara T O; Saad, Mario J A

2017-12-01

Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

The time course of attentional modulation on emotional conflict processing.

Science.gov (United States)

Zhou, Pingyan; Yang, Guochun; Nan, Weizhi; Liu, Xun

2016-01-01

Cognitive conflict resolution is critical to human survival in a rapidly changing environment. However, emotional conflict processing seems to be particularly important for human interactions. This study examined whether the time course of attentional modulation on emotional conflict processing was different from cognitive conflict processing during a flanker task. Results showed that emotional N200 and P300 effects, similar to colour conflict processing, appeared only during the relevant task. However, the emotional N200 effect preceded the colour N200 effect, indicating that emotional conflict can be identified earlier than cognitive conflict. Additionally, a significant emotional N100 effect revealed that emotional valence differences could be perceived during early processing based on rough aspects of input. The present data suggest that emotional conflict processing is modulated by top-down attention, similar to cognitive conflict processing (reflected by N200 and P300 effects). However, emotional conflict processing seems to have more time advantages during two different processing stages.

Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

Science.gov (United States)

Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

2016-06-01

Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract.

Science.gov (United States)

Anahtar, Melis N; Byrne, Elizabeth H; Doherty, Kathleen E; Bowman, Brittany A; Yamamoto, Hidemi S; Soumillon, Magali; Padavattan, Nikita; Ismail, Nasreen; Moodley, Amber; Sabatini, Mary E; Ghebremichael, Musie S; Nusbaum, Chad; Huttenhower, Curtis; Virgin, Herbert W; Ndung'u, Thumbi; Dong, Krista L; Walker, Bruce D; Fichorova, Raina N; Kwon, Douglas S

2015-05-19

Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV. Copyright © 2015 Elsevier Inc. All rights reserved.

A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples

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Timothy M. D’Alfonso

2015-07-01

Full Text Available Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

A Review of Inflammatory Processes of the Breast with a Focus on Diagnosis in Core Biopsy Samples.

Science.gov (United States)

D'Alfonso, Timothy M; Ginter, Paula S; Shin, Sandra J

2015-07-01

Inflammatory and reactive lesions of the breast are relatively uncommon among benign breast lesions and can be the source of an abnormality on imaging. Such lesions can simulate a malignant process, based on both clinical and radiographic findings, and core biopsy is often performed to rule out malignancy. Furthermore, some inflammatory processes can mimic carcinoma or other malignancy microscopically, and vice versa. Diagnostic difficulty may arise due to the small and fragmented sample of a core biopsy. This review will focus on the pertinent clinical, radiographic, and histopathologic features of the more commonly encountered inflammatory lesions of the breast that can be characterized in a core biopsy sample. These include fat necrosis, mammary duct ectasia, granulomatous lobular mastitis, diabetic mastopathy, and abscess. The microscopic differential diagnoses for these lesions when seen in a core biopsy sample will be discussed.

Febrile syndrome of unknown origin: Indications for 18F-FDG PET/CT in inflammatory and infectious processes.

Science.gov (United States)

García, J R

Fever of unknown origin is defined as a body temperature greater than 38.3°C lasting more than three weeks for which the cause could not be found within one week of hospital admission. More than 200 causes have been reported, and these can be classified into four categories: infections, inflammatory diseases, oncologic processes, and miscellaneous conditions. Noninvasive diagnostic techniques are used in 69.2% of cases and invasive techniques in 30.8%. Structural imaging techniques show the morphological changes from infectious, inflammatory, and tumor-related processes, but they do not allow the detection of the early changes brought about by these processes. The metabolic information provided by 18 F-FDG PET/CT has a promising role in these patients. 18 F-FDG uptake is based on the cells' use of glucose as a source of energy, so it can be observed in infectious, inflammatory, and tumor-related processes. The established non-oncologic indications for 18 F-FDG PET/CT are sarcoidosis, osteomyelitis, spondylodiscitis, fever of unknown origin, and vasculitis, which together account for more than 85% of studies. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Structural Basis for Carbohydrate Recognition and Anti-inflammatory Modulation by Gastrointestinal Nematode Parasite Toxascaris leonina Galectin*

Science.gov (United States)

Hwang, Eun Young; Jeong, Mi Suk; Park, Sang Kyun; Ha, Sung Chul; Yu, Hak Sun; Jang, Se Bok

2016-01-01

Toxascaris leonina galectin (Tl-gal) is a galectin-9 homologue protein isolated from an adult worm of the canine gastrointestinal nematode parasite, and Tl-gal-vaccinated challenge can inhibit inflammation in inflammatory bowel disease-induced mice. We determined the first X-ray structures of full-length Tl-gal complexes with carbohydrates (lactose, N-acetyllactosamine, lacto-N-tetraose, sialyllactose, and glucose). Bonds were formed on concave surfaces of both carbohydrate recognition domains (CRDs) in Tl-gal. All binding sites were found in the HXXXR and WGXEER motifs. Charged Arg61/Arg196 and Glu80/Glu215 on the conserved motif of Tl-gal N-terminal CRD and C-terminal CRD are critical amino acids for recognizing carbohydrate binding, and the residues can affect protein folding and structure. The polar amino acids His, Asn, and Trp are also important residues for the interaction with carbohydrates through hydrogen bonding. Hemagglutination activities of Tl-gal were inhibited by interactions with carbohydrates and mutations. We found that the mutation of Tl-gal (E80A/E215A) at the carbohydrate binding region induced protein aggregation and could be caused in many diseases. The short linker region between the N-terminal and C-terminal CRDs of Tl-gal was very stable against proteolysis and maintained its biological activity. This structural information is expected to elucidate the carbohydrate recognition mechanism of Tl-gal and improve our understanding of anti-inflammatory mediators and modulators of immune response. PMID:27742836

Inflammatory process decrease by gallium-aluminium-arsenide (GaAlAs) low intensity laser irradiation on postoperative extraction of impacted lower third molar

International Nuclear Information System (INIS)

Atihe, Mauricio Martins

2002-01-01

This study aimed the observation of inflammatory process decrease by the use of GaAlAs Low Intensity Laser (λ=830 nm; 40 mW) irradiation. Five patients were selected and submitted to surgery of impacted lower third molars, both right and left sides at different occasions. On a first stage, a tooth of a random chosen side - right or left - was extracted by conventional surgery, without LILT. The inflammatory process was measured at postoperative on the first, third and seventh days. This side was then called 'control side'. After 21 days, period in which the inflammatory process of the first surgery was terminated, the other side surgery took place, this time using LILT (4 J at four spots) at postoperative, first and third days. As the previous surgery, the inflammatory process was also measured at postoperative on the first, third and seventh days. This side was called 'experimental or lased side'. The inflammatory process was evaluated by measuring its four characteristic signs: swelling, pain, color and temperature. It was clearly observed a decrease for swelling, pain and color on the lased side which presented significant inference and descriptive statistics. It can be concluded that GaAlAs Low Intensity Laser (λ=830 nm) can surely be used as an additional and important anti-inflammatory source on impacted lower third molar surgeries. (author)

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

Directory of Open Access Journals (Sweden)

Laura W. Engstrom

2010-01-01

Full Text Available The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/0.12% cholesterol (HF/CH or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM. Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF, stromal vascular fraction (SVF, and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6.

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

International Nuclear Information System (INIS)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

2014-01-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

Energy Technology Data Exchange (ETDEWEB)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

2014-10-01

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic

Myocarditis in auto-immune or auto-inflammatory diseases.

Science.gov (United States)

Comarmond, Cloé; Cacoub, Patrice

2017-08-01

Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Electroabsorption modulators used for all-optical signal processing and labelling

DEFF Research Database (Denmark)

Xu, Lin

2004-01-01

This thesis concerns the applications of semiconductor components, primarily electroabsorption modulators (EAMs), in optical signal processing and labelling for future all optical communication networks. An introduction to electroabsorption modulators is given and several mechanisms that form...... function of an EAM is frequency dependent and the main improvement from an EAM-based regenerator is the enhancement of the ER and the suppression of the noise in a space bit. Applications of EAMs in optical label processing using various orthogonal labelling schemes are discussed. Through EAM...... encoding are –25.6/-28.1 dBm and –23.7/-21 dBm, respectively. Using an EAM for optical label insertion and a MZ-SOA for optical label erasure and payload regeneration in the ASK(10 Gb/s)/ Frequency Shift Keying (312 Mb/s) orthogonal modulation format, the complete functionality of a network node including...

Pro-oxidant activity of indicaxanthin from Opuntia ficus indica modulates arachidonate metabolism and prostaglandin synthesis through lipid peroxide production in LPS-stimulated RAW 264.7 macrophages

OpenAIRE

M. Allegra; F. D’Acquisto; L. Tesoriere; A. Attanzio; M.A. Livrea

2014-01-01

Macrophages come across active prostaglandin (PG) metabolism during inflammation, shunting early production of pro-inflammatory towards anti-inflammatory mediators terminating the process. This work for the first time provides evidence that a phytochemical may modulate the arachidonate (AA) metabolism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, promoting the ultimate formation of anti-inflammatory cyclopentenone 15deoxy-PGJ2. Added 1 h before LPS, indicaxanthin from Opuntia ...

Role of Training and Detraining on Inflammatory and Metabolic Profile in Infarcted Rats: Influences of Cardiovascular Autonomic Nervous System

Science.gov (United States)

Santana, Aline Alves; Santamarina, Aline Boveto; Oyama, Lila Missae; Caperuto, Érico Chagas; de Souza, Cláudio Teodoro; Barboza, Catarina de Andrade; Rocha, Leandro Yanase; Figueroa, Diego; Mostarda, Cristiano; Irigoyen, Maria Cláudia; Lira, Fábio Santos

2014-01-01

The aim of this study was to evaluate the effects of exercise training (ET, 50–70% of VO2 max, 5 days/week) and detraining (DT) on inflammatory and metabolic profile after myocardial infarction (MI) in rats. Male Wistar rats were divided into control (C, n = 8), sedentary infarcted (SI, n = 9), trained infarcted (TI, n = 10; 3 months of ET), and detrained infarcted (DI, n = 11; 2 months of ET + 1 month of DT). After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis), and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI. PMID:25045207

Role of Training and Detraining on Inflammatory and Metabolic Profile in Infarcted Rats: Influences of Cardiovascular Autonomic Nervous System

Directory of Open Access Journals (Sweden)

Bruno Rodrigues

2014-01-01

Full Text Available The aim of this study was to evaluate the effects of exercise training (ET, 50–70% of VO2 max, 5 days/week and detraining (DT on inflammatory and metabolic profile after myocardial infarction (MI in rats. Male Wistar rats were divided into control (C, n=8, sedentary infarcted (SI, n=9, trained infarcted (TI,  n=10; 3 months of ET, and detrained infarcted (DI, n=11; 2 months of ET + 1 month of DT. After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis, and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI.

Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden

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Briones Teresita L

2012-10-01

Full Text Available Abstract Background Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function. Methods Male F344 rats aged 20 months (old and 6 months (young were used and randomly assigned to either vitamin D supplementation or no supplementation (control. A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3 42 I.U./Kg for 21 days. Control animals received equal volume of normal saline. Behavioral testing in water maze and spontaneous object recognition tasks started on day 14. Levels of interleukin (IL-1β and IL-10 were quantified to assess inflammatory state. Also, beta amyloid (Aβ clearance and Aβ load were measured. Results Our results show that: (1 aged rats demonstrated significant learning and memory impairment overall compared to younger animals. However, the age-related decline in learning and memory was ameliorated by the supplementation of vitamin D. No vitamin D effect on learning and memory was seen in the young animals; 2 the pro-inflammatory cytokine IL-1β is significantly increased while the anti-inflammatory cytokine IL-10 is significantly decreased in the aged rats compared to the young animals; but this age-related change in inflammatory state was mitigated by vitamin D supplementation. No effects of vitamin D were seen on the IL-1β and IL-10 expression in the young rats; (3 vitamin D increased Aβ clearance and decreased amyloid burden in the aged rats while no significant difference was seen between the young animal groups. Conclusions Our data suggest that vitamin D supplementation modulated age-related increase in pro-inflammatory state and amyloid burden. It is possible that these

Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases

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Tho X. Pham

2016-06-01

Full Text Available We previously demonstrated that the organic extract of Spirulina platensis (SPE, an edible blue-green alga, possesses potent anti-inflammatory effects. In this study, we investigated if the regulation of histone deacetylases (HDACs play a role in the anti-inflammatory effect of SPE in macrophages. Treatment of macrophages with SPE rapidly and dose-dependently reduced HDAC2, 3, and 4 proteins which preceded decreases in their mRNA levels. Degradation of HDAC4 protein was attenuated in the presence of inhibitors of calpain proteases, lysosomal acidification, and Ca2+/calmodulin-dependent protein kinase II, respectively, but not a proteasome inhibitor. Acetylated histone H3 was increased in SPE-treated macrophages to a similar level as macrophages treated with a pan-HDAC inhibitor, with concomitant inhibition of inflammatory gene expression upon LPS stimulation. Knockdown of HDAC3 increased basal and LPS-induced pro-inflammatory gene expression, while HDAC4 knockdown increased basal expression of interleukin-1β (IL-1β, but attenuated LPS-induced inflammatory gene expression. Chromatin immunoprecipitation showed that SPE decreased p65 binding and H3K9/K14 acetylation at the Il-1β and tumor necrosis factor α (Tnfα promoters. Our results suggest that SPE increased global histone H3 acetylation by facilitating HDAC protein degradation, but decreases histone H3K9/K14 acetylation and p65 binding at the promoters of Il-1β and Tnfα to exert its anti-inflammatory effect.

Vibrio cholerae cytolysin causes an inflammatory response in human intestinal epithelial cells that is modulated by the PrtV protease.

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Gangwei Ou

Full Text Available BACKGROUND: Vibrio cholerae is the causal intestinal pathogen of the diarrheal disease cholera. It secretes the protease PrtV, which protects the bacterium from invertebrate predators but reduces the ability of Vibrio-secreted factor(s to induce interleukin-8 (IL-8 production by human intestinal epithelial cells. The aim was to identify the secreted component(s of V. cholerae that induces an epithelial inflammatory response and to define whether it is a substrate for PrtV. METHODOLOGY/PRINCIPAL FINDINGS: Culture supernatants of wild type V. cholerae O1 strain C6706, its derivatives and pure V. cholerae cytolysin (VCC were analyzed for the capacity to induce changes in cytokine mRNA expression levels, IL-8 and tumor necrosis factor-alpha (TNF-alpha secretion, permeability and cell viability when added to the apical side of polarized tight monolayer T84 cells used as an in vitro model for human intestinal epithelium. Culture supernatants were also analyzed for hemolytic activity and for the presence of PrtV and VCC by immunoblot analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that VCC is capable of causing an inflammatory response characterized by increased permeability and production of IL-8 and TNF-alpha in tight monolayers. Pure VCC at a concentration of 160 ng/ml caused an inflammatory response that reached the magnitude of that caused by Vibrio-secreted factors, while higher concentrations caused epithelial cell death. The inflammatory response was totally abolished by treatment with PrtV. The findings suggest that low doses of VCC initiate a local immune defense reaction while high doses lead to intestinal epithelial lesions. Furthermore, VCC is indeed a substrate for PrtV and PrtV seems to execute an environment-dependent modulation of the activity of VCC that may be the cause of V. cholerae reactogenicity.

Anti-inflammatory activity of Momordica charantia in edema paw and in cortisol seric modulation

International Nuclear Information System (INIS)

Magnata, Simey S.L.P.; Correia, Marilia B.L.; Brandao, Jose Odinilson C.; Souza, Grace M.L.; Catanho, Maria Teresa J.A.; Terra, Daniele A.; Amorim, Lucia F.

2005-01-01

The first sources that the humanity disposed to disease's treatment was plants and herbs. The Momordica charantia, Melao de Sao Caetano (bitter melon), occur in South and Central America and in East, it has been used as an anti-diabetic agent, anti-tumor, anti-helmintic and anti-ulcerogenic. The objective of this study is to research the Momordica charantia's activity on inflammatory process and the change on cortisol hormone seric concentration. To evaluate the anti-inflammatory activity were used mice (n=5) in test groups (30,60,100,250 mg/kg of extract) and control (negative and positive) groups (AAS 250 mg/kg and NaCl 0,9%); the inflammatory agent (carrageenan 1% p/v, 0,1 mL) was injected into right hind paw planter surface, 30 min after, the groups received each dose IP of extract, AAS and solution saline respectively; 4 hour after the mice was sacrificed and the difference between right and left hind foot mass was measured. There was a significant reduction (p<0,05)in carrageenan-induced edema paw at test from control group, the best result was obtained at 60 mg/kg dose which inhibits edema formation by 50%. To determinate the cortisol concentrations male Wistar rats, were divided in three groups: control, test A (2 hours of treatment) and test B (4 hours of treatment). The control group received 0,25 mL of saline solution (NaCl) 0,9% and the test groups 0,25 mL of Momordica charantia's aqueous extract, obtained by decoction of green leaves, (31,16 mg/kg animal); all by via IP. After the treatment, the animals were sacrificed and the serum obtained for realization of dosages. The cortisol was determined through radioimmunoassay. The results showed a reduction on a average by 83,9% from control group. The Momordica charantia's extract showed a high anti-inflammatory effect and was capable of reducing the seric cortisol on normal rats. (author)

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases.

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Frey, Benjamin; Hehlgans, Stephanie; Rödel, Franz; Gaipl, Udo S

2015-11-28

Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

NPY2-receptor variation modulates iconic memory processes.

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Arning, Larissa; Stock, Ann-Kathrin; Kloster, Eugen; Epplen, Jörg T; Beste, Christian

2014-08-01

Sensory memory systems are modality-specific buffers that comprise information about external stimuli, which represent the earliest stage of information processing. While these systems have been the subject of cognitive neuroscience research for decades, little is known about the neurobiological basis of sensory memory. However, accumulating evidence suggests that the glutamatergic system and systems influencing glutamatergic neural transmission are important. In the current study we examine if functional promoter variations in neuropeptide Y (NPY) and its receptor gene NPY2R affect iconic memory processes using a partial report paradigm. We found that iconic memory decayed much faster in individuals carrying the rare promoter NPY2R G allele which is associated with increased expression of the Y2 receptor. Possibly this effect is due to altered presynaptic inhibition of glutamate release, known to be modulated by Y2 receptors. Altogether, our results provide evidence that the functionally relevant single nucleotide polymorphism (SNP) in the NPY2R promoter gene affect circumscribed processes of early sensory processing, i.e. only the stability of information in sensory memory buffers. This leads us to suggest that especially the stability of information in sensory memory buffers depends on glutamatergic neural transmission and factors modulating glutamatergic turnover. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Post-Lamination Manufacturing Process Automation for Photovoltaic Modules; Annual Technical Progress Report: 15 June 1999--14 July 2000

Energy Technology Data Exchange (ETDEWEB)

Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Lewis, E. R.; Hogan, S. J.

2000-09-29

Spire is addressing the PVMaT project goals of photovoltaic (PV) module cost reduction and improved module manufacturing process technology. New cost-effective automation processes are being developed for post-lamination PV module assembly, where post-lamination is defined as the processes after the solar cells are encapsulated. These processes apply to both crystalline and thin-film solar cell modules. Four main process areas are being addressed: (1) Module buffer storage and handling between steps; (2) Module edge trimming, edge sealing, and framing; (3) Junction-box installation; and (4) Testing for module performance, electrical isolation, and ground-path continuity.

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

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Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Post-Lamination Manufacturing Process Automation for Photovoltaic Modules: Final Subcontract Report, April 1998 - April 2002

Energy Technology Data Exchange (ETDEWEB)

Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Miller, D. C.; Moore, S. B.; Hogan, S. J.

2002-11-01

This report describes the automated systems developed for PV module assembly and testing processes after lamination. These processes are applicable to a broad range of module types, including those made with wafer-based and thin-film solar cells. Survey data and input from module manufacturers gathered during site visits were used to define system capabilities and process specifications. Spire completed mechanical, electrical, and software engineering for four automation systems: a module edge trimming system, the SPI-TRIM 350; an edge sealing and framing system, the SPI-FRAMER 350; an integrated module testing system, the SPI-MODULE QA 350; and a module buffer storage system, the SPI-BUFFER 350. A fifth system for junction-box installation, the SPI-BOXER 350, was nearly completed during the program. A new-size solar simulator, the SPI-SUN SIMULATOR 350i, was designed as part of the SPI-MODULE QA 350. This simulator occupies minimal production floor space, and its test area is large enough to handle most production modules. The automated systems developed in this program are designed for integration to create automated production lines.

Modulating the innate immune response to influenza A virus: potential therapeutic use of anti-inflammatory drugs

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Irene eRamos

2015-07-01

Full Text Available Infection by influenza A viruses (IAV is frequently characterized by robust inflammation that is usually more pronounced in the case of avian influenza. It is becoming clearer that the morbidity and pathogenesis caused by IAV is a consequence of this inflammatory response, with several components of the innate immune system acting as the main players. It has been postulated that using a therapeutic approach to limit the innate immune response in combination with antiviral drugs has the potential to diminish symptoms and tissue damage caused by IAV infection. Indeed, some anti-inflammatory agents have been shown to be effective in animal models at reducing IAV pathology as a proof of principle. The main challenge in developing such therapies is to selectively modulate signaling pathways that contribute to lung injury while maintaining the ability of the host cells to mount an antiviral response to control virus replication. However, the dissection of those pathways is very complex given the numerous components regulated by the same factors (i.e. NF kappa B transcription factors and the large number of players involved in this regulation, some of which may be undescribed or unknown. This article provides a comprehensive review of the current knowledge regarding the innate immune responses associated with tissue damage by IAV infection, the understanding of which is essential for the development of effective immunomodulatory drugs. Furthermore, we summarize the recent advances on the development and evaluation of such drugs as well as the lessons learned from those studies.

In Vitro Anti-Inflammatory Effects of Three Fatty Acids from Royal Jelly

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Yi-Fan Chen

2016-01-01

Full Text Available Trans-10-hydroxy-2-decenoic acid (10-H2DA, 10-hydroxydecanoic acid (10-HDAA, and sebacic acid (SEA are the three major fatty acids in royal jelly (RJ. Previous studies have revealed several pharmacological activities of 10-H2DA and 10-HDAA, although the anti-inflammatory effects and underlying mechanisms by which SEA acts are poorly understood. In the present study, we evaluated and compared the in vitro anti-inflammatory effects of these RJ fatty acids in lipopolysaccharide-stimulated RAW 264.7 macrophages. The results showed that 10-H2DA, 10-HDAA, and SEA had potent, dose-dependent inhibitory effects on the release of the major inflammatory-mediators, nitric oxide, and interleukin-10, and only SEA decreased TNF-α production. Several key inflammatory genes have also been modulated by these RJ fatty acids, with 10-H2DA showing distinct modulating effects as compared to the other two FAs. Furthermore, we found that these three FAs regulated several proteins involved in MAPK and NF-κB signaling pathways. Taken together, these findings provide additional references for using RJ against inflammatory diseases.

Sigma-1 receptor and inflammatory pain.

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Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

2015-06-01

The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

Bone scan in diagnosis of inflammatory processes of the foot bones in diabetes mellitus

International Nuclear Information System (INIS)

Slavnov, V.M.; Markov, V.V.; Bolgars'ka, S.V.

2003-01-01

The radionuclide technique for early diagnosis of inflammatory process in the bones of the foot was developed for diabetes mellitus (DM) patients. The most important diagnostic criterion of the bone lesion in patients with DM is area asymmetry and total activity percentage between the lesion focus and symmetrical zone

Modulation, resolution and signal processing in radar, sonar and related systems

CERN Document Server

Benjamin, R; Costrell, L

1966-01-01

Electronics and Instrumentation, Volume 35: Modulation, Resolution and Signal Processing in Radar, Sonar and Related Systems presents the practical limitations and potentialities of advanced modulation systems. This book discusses the concepts and techniques in the radar context, but they are equally essential to sonar and to a wide range of signaling and data-processing applications, including seismology, radio astronomy, and band-spread communications.Organized into 15 chapters, this volume begins with an overview of the principal developments sought in pulse radar. This text then provides a

Apparel Research Network (ARN); Apparel Order Processing Module (AOPM): Field User Manual, Version 1

Science.gov (United States)

1997-09-30

changes. Cancel Button Closes the Site Information Screen, abandoning changes. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official...on the Ordering Official Information Screen. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official Information Screen (Jjj

Immune-modulating therapy in acute pancreatitis: Fact or fiction

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Akinosoglou, Karolina; Gogos, Charalambos

2014-01-01

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

Inflammatory bowel diseases: principles of nutritional therapy

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Campos Fábio Guilherme

2002-01-01

Full Text Available Inflammatory Bowel Diseases - ulcerative colitis and Crohn's disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn's disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants still need further evaluation through prospective and randomized trials.

Processing and characterization of device solder interconnection and module attachment for power electronics modules

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Haque, Shatil

This research is focused on the processing of an innovative three-dimensional packaging architecture for power electronics building blocks with soldered device interconnections and subsequent characterization of the module's critical interfaces. A low-cost approach termed metal posts interconnected parallel plate structure (MPIPPS) was developed for packaging high-performance modules of power electronics building blocks (PEBB). The new concept implemented direct bonding of copper posts, not wire bonding of fine aluminum wires, to interconnect power devices as well as joining the different circuit planes together. We have demonstrated the feasibility of this packaging approach by constructing PEBB modules (consisting of Insulated Gate Bipolar Transistors (IGBTs), diodes, and a few gate driver elements and passive components). In the 1st phase of module fabrication with IGBTs with Si3N 4 passivation, we had successfully fabricated packaged devices and modules using the MPIPPS technique. These modules were tested electrically and thermally, and they operated at pulse-switch and high power stages up to 6kW. However, in the 2nd phase of module fabrication with polyimide passivated devices, we experienced significant yield problems due to metallization difficulties of these devices. The under-bump metallurgy scheme for the development of a solderable interface involved sputtering of Ti-Ni-Cu and Cr-Cu, and an electroless deposition of Zn-Ni-Au metallization. The metallization process produced excellent yield in the case of Si3N4 passivated devices. However, under the same metallization schemes, devices with a polyimide passivation exhibited inconsistent electrical contact resistance. We found that organic contaminants such as hydrocarbons remain in the form of thin monolayers on the surface, even in the case of as-received devices from the manufacturer. Moreover, in the case of polyimide passivated devices, plasma cleaning introduced a few carbon constituents on the

Conceptual design for the Waste Receiving and Processing facility Module 2A

International Nuclear Information System (INIS)

1992-07-01

This is part of a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at Hanford Reservation. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated at WRAP Module 2A include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluenttreatment facilities, thermal treatment facility ash, other WRAP modules, and other miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume V, provides a comprehensive conceptual design level narrative description of the process, utility, ventilation, and plant control systems. The feeds and throughputs, design requirements, and basis for process selection are provided, as appropriate. Key DOE/WHC criteria and reference drawings are delineated

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

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Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Mouse mannose-binding lectin-A and ficolin-A inhibit lipopolysaccharide-mediated pro-inflammatory responses on mast cells

DEFF Research Database (Denmark)

Ma, Ying Jie; Kang, Hee Jung; Kim, Ji Yeon

2013-01-01

It is unknown how soluble pattern-recognition receptors in blood, such as mannose-binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow-derived mast cells (mBMMCs)-derived inflammatory response...... cytokine production by LPS-mediated TLR4 in mBMMCs appears to be down-regulated, indicating that mouse MBL and ficolin may have an inhibitory function toward mouse TLR4-mediated excessive inflammation on the mast cells.......It is unknown how soluble pattern-recognition receptors in blood, such as mannose-binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow-derived mast cells (mBMMCs)-derived inflammatory response...

The Pro-inflammatory Effects of Glucocorticoids in the Brain

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Duque, Erica de Almeida; Munhoz, Carolina Demarchi

2016-01-01

Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

The impact of maternal obesity on inflammatory processes and consequences for later offspring health outcomes.

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Segovia, S A; Vickers, M H; Reynolds, C M

2017-10-01

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.

Regulation of inflammatory gene expression in PBMCs by immunostimulatory botanicals.

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Karen L Denzler

Full Text Available Many hundreds of botanicals are used in complementary and alternative medicine for therapeutic use as antimicrobials and immune stimulators. While there exists many centuries of anecdotal evidence and few clinical studies on the activity and efficacy of these botanicals, limited scientific evidence exists on the ability of these botanicals to modulate the immune and inflammatory responses. Using botanogenomics (or herbogenomics, this study provides novel insight into inflammatory genes which are induced in peripheral blood mononuclear cells following treatment with immunomodulatory botanical extracts. These results may suggest putative genes involved in the physiological responses thought to occur following administration of these botanical extracts. Using extracts from immunostimulatory herbs (Astragalus membranaceus, Sambucus cerulea, Andrographis paniculata and an immunosuppressive herb (Urtica dioica, the data presented supports previous cytokine studies on these herbs as well as identifying additional genes which may be involved in immune cell activation and migration and various inflammatory responses, including wound healing, angiogenesis, and blood pressure modulation. Additionally, we report the presence of lipopolysaccharide in medicinally prepared extracts of these herbs which is theorized to be a natural and active component of the immunostimulatory herbal extracts. The data presented provides a more extensive picture on how these herbs may be mediating their biological effects on the immune and inflammatory responses.

IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity

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Lauren M.F. Merlo

2016-01-01

Full Text Available Indoleamine 2,3-dioxygenase 2 (IDO2, a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is expressed in antigen-presenting cells, including B cells and dendritic cells, but affects inflammatory responses in the autoimmune context specifically by acting in B cells to modulate T cell help in multiple model systems. Given that expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2 should be considered a potential therapeutic target for autoimmune disorders.

Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

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Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

2017-08-01

Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C LE ) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of C LE was determined at 24 and 72 h (h). Oxidant scavenging activity of C LE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. C LE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C LE and 72 h: 0.4-0.8 mg/ml C LE ) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C LE ) (p cachexia.

Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes

DEFF Research Database (Denmark)

Penkowa, Milena; hidalgo, juan; aschner, michael

2008-01-01

Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

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Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

2010-03-02

Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

Utility-based early modulation of processing distracting stimulus information.

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Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

2014-12-10

Humans are selective information processors who efficiently prevent goal-inappropriate stimulus information to gain control over their actions. Nonetheless, stimuli, which are both unnecessary for solving a current task and liable to cue an incorrect response (i.e., "distractors"), frequently modulate task performance, even when consistently paired with a physical feature that makes them easily discernible from target stimuli. Current models of cognitive control assume adjustment of the processing of distractor information based on the overall distractor utility (e.g., predictive value regarding the appropriate response, likelihood to elicit conflict with target processing). Although studies on distractor interference have supported the notion of utility-based processing adjustment, previous evidence is inconclusive regarding the specificity of this adjustment for distractor information and the stage(s) of processing affected. To assess the processing of distractors during sensory-perceptual phases we applied EEG recording in a stimulus identification task, involving successive distractor-target presentation, and manipulated the overall distractor utility. Behavioral measures replicated previously found utility modulations of distractor interference. Crucially, distractor-evoked visual potentials (i.e., posterior N1) were more pronounced in high-utility than low-utility conditions. This effect generalized to distractors unrelated to the utility manipulation, providing evidence for item-unspecific adjustment of early distractor processing to the experienced utility of distractor information. Copyright © 2014 the authors 0270-6474/14/3416720-06$15.00/0.

Multi-Gigahertz radar range processing of baseband and RF carrier modulated signals in Tm:YAG

International Nuclear Information System (INIS)

Merkel, K.D.; Krishna Mohan, R.; Cole, Z.; Chang, T.; Olson, A.; Babbitt, W.R.

2004-01-01

An optical device is described and demonstrated that uses a spatial-spectral holographic material to perform coherent signal processing operations on analog, high-bandwidth optical signals with large time-bandwidth-products. Signal processing is performed as the material records the coherent spectral interference (or cross-power spectrum) of modulated optical signals as a spatial-spectral population grating between electronic transition states. Multiple exposures of processing pulse sequences are integrated with increasing grating strength. The device, coined as the Spatial-Spectral Coherent Holographic Integrating Processor (or S 2 -CHIP), is described as currently envisioned for a broadband, mid-to-high pulse repetition frequency range-Doppler radar signal processing system. Experiments were performed in Tm:YAG (0.1 at% at 5 K) to demonstrate time delay variation, integration dynamics, and effects of coding as applied to a radar range processor. These demonstrations used baseband modulation with a 1 gigabit per second (GPBS) bit rate and code length of 512 bits (512 ns), where delays up to 1.0 μs were resolved with greater than a 40 dB peak to RMS sidelobe ratio after 800 processing shots. Multi-GHz processing was demonstrated using a bit rate of 2.5 GBPS (baseband modulation) and code length of 2048 bits (819.2 ns). Processing of double-sideband modulated signals on a radio frequency (RF) carrier was demonstrated, where 512 bit, 1.0 GBPS codes were modulated on a 1.75 GHz carrier and then modulated on the optical carrier

Renewal characterization of Markov modulated Poisson processes

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Marcel F. Neuts

1989-01-01

Full Text Available A Markov Modulated Poisson Process (MMPP M(t defined on a Markov chain J(t is a pure jump process where jumps of M(t occur according to a Poisson process with intensity λi whenever the Markov chain J(t is in state i. M(t is called strongly renewal (SR if M(t is a renewal process for an arbitrary initial probability vector of J(t with full support on P={i:λi>0}. M(t is called weakly renewal (WR if there exists an initial probability vector of J(t such that the resulting MMPP is a renewal process. The purpose of this paper is to develop general characterization theorems for the class SR and some sufficiency theorems for the class WR in terms of the first passage times of the bivariate Markov chain [J(t,M(t]. Relevance to the lumpability of J(t is also studied.

Effective Thermal Analysis of Using Peltier Module for Desalination Process

OpenAIRE

Hayder Al-Madhhachi

2018-01-01

The key objective of this study is to analyse the heat transfer processes involved in the evaporation and condensation of water in a water distillation system employing a thermoelectric module. This analysis can help to increase the water production and to enhance the system performance. For the analysis, a water distillation unit prototype integrated with a thermoelectric module was designed and fabricated. A theoretical model is developed to study the effect of the heat added, transferred a...

Intracellular Secretory Leukoprotease Inhibitor Modulates Inositol 1,4,5-Triphosphate Generation and Exerts an Anti-Inflammatory Effect on Neutrophils of Individuals with Cystic Fibrosis and Chronic Obstructive Pulmonary Disease

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Emer P. Reeves

2013-01-01

Full Text Available Secretory leukoprotease inhibitor (SLPI is an anti-inflammatory protein present in respiratory secretions. Whilst epithelial cell SLPI is extensively studied, neutrophil associated SLPI is poorly characterised. Neutrophil function including chemotaxis and degranulation of proteolytic enzymes involves changes in cytosolic calcium (Ca2+ levels which is mediated by production of inositol 1,4,5-triphosphate (IP3 in response to G-protein-coupled receptor (GPCR stimuli. The aim of this study was to investigate the intracellular function of SLPI and the mechanism-based modulation of neutrophil function by this antiprotease. Neutrophils were isolated from healthy controls (n=10, individuals with cystic fibrosis (CF (n=5 or chronic obstructive pulmonary disease (COPD (n=5. Recombinant human SLPI significantly inhibited fMet-Leu-Phe (fMLP and interleukin(IL-8 induced neutrophil chemotaxis (P<0.05 and decreased degranulation of matrix metalloprotease-9 (MMP-9, hCAP-18, and myeloperoxidase (MPO (P<0.05. The mechanism of inhibition involved modulation of cytosolic IP3 production and downstream Ca2+ flux. The described attenuation of Ca2+ flux was overcome by inclusion of exogenous IP3 in electropermeabilized cells. Inhibition of IP3 generation and Ca2+ flux by SLPI may represent a novel anti-inflammatory mechanism, thus strengthening the attractiveness of SLPI as a potential therapeutic molecule in inflammatory airway disease associated with excessive neutrophil influx including CF, non-CF bronchiectasis, and COPD.

Unified microprocessor CAMAC module for preliminary data processing

International Nuclear Information System (INIS)

Zaushitsin, V.L.; Kulik, O.V.; Repin, V.M.

1984-01-01

The UP-80 unified active module is described. It is made in the CAMAC standard on the base of the K580IK80 microprocessor allowing to increase the rate of large-volume experimental spectroscopic data processing by an order. Loading of 5 different programs for data processing is possible. Data from the operative storage with 1K capacity (8 bits) are recorded and read out trhough the CAMAC line (the regime of unit exchange is possible) or through the joint of the external line

Electromagnetic Field Devices and Their Effects on Nociception and Peripheral Inflammatory Pain Mechanisms.

Science.gov (United States)

Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

2016-03-01

Context • During cell-communication processes, endogenous and exogenous signaling affects normal and pathological developmental conditions. Exogenous influences, such as extra-low-frequency (ELF) electromagnetic fields (EMFs) have been shown to affect pain and inflammation by modulating G-protein coupling receptors (GPCRs), downregulating cyclooxygenase-2 (Cox-2) activity, and downregulating inflammatory modulators, such as tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) as well as the transcription factor nuclear factor kappa B (NF-κB). EMF devices could help clinicians who seek an alternative or complementary treatment for relief of patients chronic pain and disability. Objective • The research team intended to review the literature on the effects of EMFs on inflammatory pain mechanisms. Design • We used a literature search of articles published in PubMed using the following key words: low-frequency electromagnetic field therapy, inflammatory pain markers, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), opioid receptors, G-protein coupling receptors, and enzymes. Setting • The study took place at the Wake Forest School of Medicine in Winston-Salem, NC, USA. Results • The mechanistic pathway most often considered for the biological effects of EMF is the plasma membrane, across which the EMF signal induces a voltage change. Oscillating EMF exerts forces on free ions that are present on both sides of the plasma membrane and that move across the cell surface through transmembrane proteins. The ions create a forced intracellular vibration that is responsible for phenomena such as the influx of extracellular calcium (Ca2+) and the binding affinity of calmodulin (CaM), which is the primary transduction pathway to the secondary messengers, cAMP and cGMP, which have been found to influence inflammatory pain. Conclusions • An emerging body of evidence indicates the existence of a frequency

Quality control of roll-to-roll processed polymer solar modules by complementary imaging methods

DEFF Research Database (Denmark)

Rösch, R.; Krebs, Frederik C; Tanenbaum, D.M.

2012-01-01

We applied complementary imaging methods to investigate processing failures of roll-to-roll solution processed polymer solar modules based on polymer:fullerene bulk heterojunctions. For investigation of processing deficiencies in solar modules we employed dark lock-in thermography (DLIT......), electroluminescence (ELI) and photoluminescence/reflection imaging (PLI/RI) complemented by optical imaging (OI). The combination of all high resolution images allowed us to allocate the origin of processing errors to a specific deposition process, i.e. the insufficient coverage of an electrode interlayer...

Immune-modulating interventions in critically ill septic patients: pharmacological options

DEFF Research Database (Denmark)

Toft, Palle; Tønnesen, Else

2011-01-01

Critically ill patients with severe sepsis and septic shock are characterized by a systemic inflammatory response consisting of pro- and anti-inflammatory mediators. Owing to the high mortality of severe sepsis, great efforts have been undertaken within the last 30 years to develop an immune...... insulin therapy have been shown to improve survival in septic patients. However, in later studies, it has been difficult to reproduce these beneficial effects. There appears to be a discrepancy between the promising effects of immune-modulating interventions in animal studies and the effects seen......-modulating therapy to improve survival. Relatively few pharmacological immune-modulating interventions have demonstrated a beneficial impact on survival, while other studies have shown a detrimental effect of such interventions. Among the immune-modulating interventions tested, activated protein C and intensive...

Lemongrass (Cymbopogon flexuosus) essential oil demonstrated anti-inflammatory effect in pre-inflamed human dermal fibroblasts.

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Han, Xuesheng; Parker, Tory L

2017-06-01

Lemongrass ( Cymbopogon flexuosus ) essential oil (LEO), which has citral as its main component, has exhibited anti-inflammatory effect in both animal and human cells. In this study, we evaluated the anti-inflammatory activity of a commercially available LEO in pre-inflamed human dermal fibroblasts. We first studied the impact of LEO on 17 protein biomarkers that are critically associated with inflammation and tissue remodeling. LEO significantly inhibited production of the inflammatory biomarkers vascular cell adhesion molecule 1 (VCAM-1), interferon gamma-induced protein 10 (IP-10), interferon-inducible T-cell alpha chemoattractant (I-TAC), and monokine induced by gamma interferon (MIG); decreased levels of the tissue remodeling biomarkers collagen-I and III, epidermal growth factor receptor (EGFR), and plasminogen activator inhibitor (PAI-1); and inhibited the immunomodulatory biomarker macrophage colony-stimulating factor (M-CSF). Furthermore, we studied the impact of LEO on genome-wide gene expression profiles. LEO significantly modulated global gene expression and robustly impacted signaling pathways, many of which are critical for inflammation and tissue remodeling processes. This study provides the first evidence of the anti-inflammatory activity of LEO in human skin cells and indicates that it is a good therapeutic candidate for treating inflammatory conditions of the skin.

Oral fungal immunomodulatory protein-Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: A mouse model

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Po-Yu Chu

2017-06-01

Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering

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Sudhir H. Ranganath

2016-06-01

Full Text Available Mesenchymal stromal cells (MSCs are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-κB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction.

Bio-Electro-Fenton process for the degradation of Non-Steroidal Anti-Inflammatory Drugs in wastewater

DEFF Research Database (Denmark)

Nadais, Helena; Li, Xiaohu; Alves, Nadine

2018-01-01

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are ubiquitous municipal wastewater pollutants of which several are resistant to degradation in conventional wastewater treatment, and represent a major environmental health concern worldwide. An alternative treatment, the bio-electro-Fenton process......, has received increasing attention in past years. In this process the strong oxidant •HO is formed using the electrons derived from bacterial oxidation of organic substrate. In this work, a laboratory scale microbial electrolysis cell based bio-electro-Fenton process was developed for the treatment...

Modulation of the tissue regenerative process in fish by ß-glucans

DEFF Research Database (Denmark)

Nielsen, Michael Engelbrecht; Jiménez, Natalia Ivonne Vera; Przybylska, Dominika Alicja

the importance of fibroblasts, macrophages, reactive oxygen species (especially hydrogen peroxide) and certain cytokines during wound healing processes. In fish however, only a few studies have been devoted tissue regeneration and modulation of cell proliferation during wound healing, even though mechanical...... the immune response towards pathogen eradication or tissue repair....... but not in animals. are commonly used as immune modulators, but the mechanisms through which the modulation is achieved remains to be understood. Wound healing and tissue regeneration are essential mechanisms to ensure the survival and health of any organism. Studies from the mammalian systems have shown...

Mas-related G protein coupled receptor-X2: A potential new target for modulating mast cell-mediated allergic and inflammatory diseases.

Science.gov (United States)

Ali, Hydar

2016-12-01

Mast cells (MCs) are tissue resident immune cells that are best known for their roles in allergic and inflammatory diseases. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the most common targets of drug therapy. Neurokinin 1 receptor (NK-1R) is expressed on MCs and contributes to IgE and non-IgE-mediated responses in mice. Although NK-1R antagonists are highly effective in modulating experimental allergic and inflammatory responses in mice they lack efficacy in humans. This article reviews recent findings that demonstrate that while neuropeptides (NPs) activate murine MCs via NK-1R and Mas related G protein coupled receptor B2 (MrgprB2), they activate human MCs via Mas-related G protein coupled receptor X2 (MRGPRX2). Interestingly, conventional NK-1R antagonists have off-target activity against mouse MrgprB2 but not human MRGPRX2. These findings suggest that the failure to translate studies with NK-1R antagonists from in vivo mouse studies to the clinic likely reflects their lack of effect on human MRGPRX2. A unique feature of MRGPRX2 that distinguishes it from other GPCRs is that it is activated by a diverse group of ligands that include; neuropeptides, cysteine proteases, antimicrobial peptides and cationic proteins released from activated eosinophils. Thus, the development of small molecule MRGPRX2-specific antagonists or neutralizing antibodies may provide new targets for the treatment of MC-mediated allergic and inflammatory diseases.

Visualization of inflammatory processes using 'in vitro' and in vivo' labelled leucocytes

International Nuclear Information System (INIS)

Kostadinova, I.; Milanov, S.; Kovacheva, S.

1993-01-01

The labelled leucocytes have become a means of choice for the diagnosis of a variety of active inflammatory conditions. The aim of the study was to evaluate 'in vivo' and 'in vitro' methods for labelling of leucocytes. A total of 146 patients, suspected of having various inflammatory lesions were examined. In 95 of them 'in vitro' method with 99m Tc-HMPAO or 111 In-oxine was used, in 29 'in vivo' method with 99m Tc-MAB (BW 250/183) and in 22 both methods. The obtained results of sensitivity, specificity and accuracy were 87,3%, 96,5%, 89,5% for 'in vitro' method and 83,3%, 93,8%, 86,2% for 'in vivo' method. Taking into consideration the received data and comparable results, we think that in seriously ill patients and in cases of urgency, the use of easier 'in vivo' method is more suitable, while in chronic processes or in such with unclear localisation, 'in vitro' method is recommended, which sometimes gives images with better quality. (orig.) [de

Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

Science.gov (United States)

Vaz, Austin; Lisse, Jeffrey; Rizzo, Warren; Albani, Salvatore

2009-05-01

Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

Science.gov (United States)

Cai, Qing; Li, Yuanyuan; Pei, Gang

2017-03-24

Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia. The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta 42 (Aβ 42 ) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain. Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions. Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

Project T.E.A.M. (Technical Education Advancement Modules). Introduction to Statistical Process Control.

Science.gov (United States)

Billings, Paul H.

This instructional guide, one of a series developed by the Technical Education Advancement Modules (TEAM) project, is a 6-hour introductory module on statistical process control (SPC), designed to develop competencies in the following skill areas: (1) identification of the three classes of SPC use; (2) understanding a process and how it works; (3)…

A Versatile Multichannel Digital Signal Processing Module for Microcalorimeter Arrays

Science.gov (United States)

Tan, H.; Collins, J. W.; Walby, M.; Hennig, W.; Warburton, W. K.; Grudberg, P.

2012-06-01

Different techniques have been developed for reading out microcalorimeter sensor arrays: individual outputs for small arrays, and time-division or frequency-division or code-division multiplexing for large arrays. Typically, raw waveform data are first read out from the arrays using one of these techniques and then stored on computer hard drives for offline optimum filtering, leading not only to requirements for large storage space but also limitations on achievable count rate. Thus, a read-out module that is capable of processing microcalorimeter signals in real time will be highly desirable. We have developed multichannel digital signal processing electronics that are capable of on-board, real time processing of microcalorimeter sensor signals from multiplexed or individual pixel arrays. It is a 3U PXI module consisting of a standardized core processor board and a set of daughter boards. Each daughter board is designed to interface a specific type of microcalorimeter array to the core processor. The combination of the standardized core plus this set of easily designed and modified daughter boards results in a versatile data acquisition module that not only can easily expand to future detector systems, but is also low cost. In this paper, we first present the core processor/daughter board architecture, and then report the performance of an 8-channel daughter board, which digitizes individual pixel outputs at 1 MSPS with 16-bit precision. We will also introduce a time-division multiplexing type daughter board, which takes in time-division multiplexing signals through fiber-optic cables and then processes the digital signals to generate energy spectra in real time.

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 2: biochemical aspects.

Science.gov (United States)

Tomazoni, Shaiane Silva; Frigo, Lúcio; Dos Reis Ferreira, Tereza Cristina; Casalechi, Heliodora Leão; Teixeira, Simone; de Almeida, Patrícia; Muscara, Marcelo Nicolas; Marcos, Rodrigo Labat; Serra, Andrey Jorge; de Carvalho, Paulo de Tarso Camillo; Leal-Junior, Ernesto Cesar Pinto

2017-11-01

Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm 2 ; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm 2 ), 3 J (107.1 J/cm 2 ), and 9 J (321.4 J/cm 2 ) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p levels of COX-2 only in relation to the injury group (p levels of cytokines TNF-α, interleukin (IL)-1β, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.

HDAC inhibitors: modulating leukocyte differentiation, survival, proliferation and inflammation.

Science.gov (United States)

Sweet, Matthew J; Shakespear, Melanie R; Kamal, Nabilah A; Fairlie, David P

2012-01-01

Therapeutic effects of histone deacetylase (HDAC) inhibitors in cancer models were first linked to their ability to cause growth arrest and apoptosis of tumor cells. It is now clear that these agents also have pleiotropic effects on angiogenesis and the immune system, and some of these properties are likely to contribute to their anti-cancer activities. It is also emerging that inhibitors of specific HDACs affect the differentiation, survival and/or proliferation of distinct immune cell populations. This is true for innate immune cells such as macrophages, as well as cells of the acquired immune system, for example, T-regulatory cells. These effects may contribute to therapeutic profiles in some autoimmune and chronic inflammatory disease models. Here, we review our current understanding of how classical HDACs (HDACs 1-11) and their inhibitors impact on differentiation, survival and proliferation of distinct leukocyte populations, as well as the likely relevance of these effects to autoimmune and inflammatory disease processes. The ability of HDAC inhibitors to modulate leukocyte survival may have implications for the rationale of developing selective inhibitors as anti-inflammatory drugs.

Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

Energy Technology Data Exchange (ETDEWEB)

Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

2011-11-11

Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice

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Üçeyler Nurcan

2010-03-01

Full Text Available Abstract Background Although it has been largely demonstrated that nitric oxide synthase (NOS, a key enzyme for nitric oxide (NO production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results Intraperitoneal (i.p. pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor, aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor, L-N(G-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor, but not L-N(5-(1-iminoethyl-ornithine (L-NIO, a selective endothelial NOS inhibitor, significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl. injection of complete Freund's adjuvant (CFA. Real-time reverse transcription-polymerase chain reaction (RT-PCR revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF, interleukin-1 beta (IL-1β, and interleukin-10 (IL-10 gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO mice had lower gene expression of TNF, IL-1β, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

Cholinergic Modulation of Type 2 Immune Responses

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Goele Bosmans

2017-12-01

Full Text Available In recent years, the bidirectional relationship between the nervous and immune system has become increasingly clear, and its role in both homeostasis and inflammation has been well documented over the years. Since the introduction of the cholinergic anti-inflammatory pathway, there has been an increased interest in parasympathetic regulation of both innate and adaptive immune responses, including T helper 2 responses. Increasing evidence has been emerging suggesting a role for the parasympathetic nervous system in the pathophysiology of allergic diseases, including allergic rhinitis, asthma, food allergy, and atopic dermatitis. In this review, we will highlight the role of cholinergic modulation by both nicotinic and muscarinic receptors in several key aspects of the allergic inflammatory response, including barrier function, innate and adaptive immune responses, and effector cells responses. A better understanding of these cholinergic processes mediating key aspects of type 2 immune disorders might lead to novel therapeutic approaches to treat allergic diseases.

Guinea-pig interpubic joint (symphysis pubica relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

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Muñoz-de-Toro Mónica

2003-11-01

Full Text Available Abstract Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis. Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling

Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.

Directory of Open Access Journals (Sweden)

Mathieu Darsigny

Full Text Available BACKGROUND: Hnf4alpha, an epithelial specific transcriptional regulator, is decreased in inflammatory bowel disease and protects against chemically-induced colitis in mice. However, the precise role of this factor in maintaining normal inflammatory homeostasis of the intestine remains unclear. The aim of this study was to evaluate the sole role of epithelial Hnf4alpha in the maintenance of gut inflammatory homeostasis in mice. METHODOLOGY/PRINCIPAL FINDINGS: We show here that specific epithelial deletion of Hnf4alpha in mice causes spontaneous chronic intestinal inflammation leading to focal areas of crypt dropout, increased cytokines and chemokines secretion, immune cell infiltrates and crypt hyperplasia. A gene profiling analysis in diseased Hnf4alpha null colon confirms profound genetic changes in cell death and proliferative behaviour related to cancer. Among the genes involved in the immune protection through epithelial barrier function, we identify the ion transporter claudin-15 to be down-modulated early in the colon of Hnf4alpha mutants. This coincides with a significant decrease of mucosal ion transport but not of barrier permeability in young animals prior to the manifestation of the disease. We confirm that claudin-15 is a direct Hnf4alpha gene target in the intestinal epithelial context and is down-modulated in mouse experimental colitis and inflammatory bowel disease. CONCLUSION: Our results highlight the critical role of Hnf4alpha to maintain intestinal inflammatory homeostasis during mouse adult life and uncover a novel function for Hnf4alpha in the regulation of claudin-15 expression. This establishes Hnf4alpha as a mediator of ion epithelial transport, an important process for the maintenance of gut inflammatory homeostasis.

All-solution-processed PbS quantum dot solar modules

Science.gov (United States)

Jang, Jihoon; Shim, Hyung Cheoul; Ju, Yeonkyeong; Song, Jung Hoon; An, Hyejin; Yu, Jong-Su; Kwak, Sun-Woo; Lee, Taik-Min; Kim, Inyoung; Jeong, Sohee

2015-05-01

A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade-offs between power and the active area of the photovoltaic devices, which results in a low-cost power source, and which is scalable to larger areas.A rapid increase in power conversion efficiencies in colloidal quantum dot (QD) solar cells has been achieved recently with lead sulphide (PbS) QDs by adapting a heterojunction architecture, which consists of small-area devices associated with a vacuum-deposited buffer layer with metal electrodes. The preparation of QD solar modules by low-cost solution processes is required to further increase the power-to-cost ratio. Herein we demonstrate all-solution-processed flexible PbS QD solar modules with a layer-by-layer architecture comprising polyethylene terephthalate (PET) substrate/indium tin oxide (ITO)/titanium oxide (TiO2)/PbS QD/poly(3-hexylthiophene) (P3HT)/poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS)/Ag, with an active area of up to 30 cm2, exhibiting a power conversion efficiency (PCE) of 1.3% under AM 1.5 conditions (PCE of 2.2% for a 1 cm2 unit cell). Our approach affords trade

Oxidized low-density lipoproteins induced inflammatory process during atherogenesis with aging

International Nuclear Information System (INIS)

Larbi, Anis; Khalil, Abdelouahed; Douziech, Nadine; Guerard, Karl-Philippe; Fueloep, Tamas

2005-01-01

Atherosclerosis is a chronic disease developing through decades with two life-threatening complications: myocardial infarction and stroke. Oxidized low-density lipoproteins (oxLDL) produced by oxidative modifications of LDL in the subendothelial space have been demonstrated to be critically involved in atherogenesis through their intensive pro-inflammatory activity. Recently, it was shown that oxLDL have an apoptosis-inducing effect in T cells depending on time and degree of oxidation. The goal of the current study is to elucidate the molecular mechanisms underlying the apoptotic-inducing effects of oxLDL on T lymphocytes. T cells of young and elderly subjects were incubated for various periods of time with LDL oxidized to various degrees. The proliferation, the apoptosis, the MAPK ERK1/2 activation and the expression of the Bcl-2 protein family members were measured upon different LDL treatments. Thus, more the LDL are oxidized more they induce apoptosis and this effect is highly accentuated with aging. The oxLDL decrease the activation of the surviving molecule ERK1/2 and modulate the ratio of Bax/Bcl-2 towards a pro-apoptotic profile, which is also accentuated with aging. These results partly explain why atherosclerosis is increasing with aging concomitantly to its complications

The hormonal Zeitgeber melatonin: Role as a circadian modulator in memory processing

Directory of Open Access Journals (Sweden)

Oliver eRawashdeh

2012-03-01

Full Text Available The neuroendocrine substance melatonin is a hormone synthesized rhythmically by the pineal gland under the influence of the circadian system and alternating light/dark cycles. Melatonin has been shown to have broad applications, and consequently becoming a molecule of great controversy. Undoubtedly, however, melatonin plays an important role as a time cue for the endogenous circadian system. This review focuses on melatonin as a regulator in the circadian modulation of memory processing. Memory processes (acquisition, consolidation and retrieval are modulated by the circadian system. However, the mechanism by which the biological clock is rhythmically influencing cognitive processes remains unknown. We also discuss, how the circadian system by generating cycling melatonin levels can implant information about daytime into memory processing, depicted as day and nighttime differences in acquisition, memory consolidation and/or retrieval.

The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

OpenAIRE

Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

2009-01-01

Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

Conceptual design for the Waste Receiving and Processing facility Module 2A

International Nuclear Information System (INIS)

1992-07-01

This is a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at Hanford Reservation. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated at WRAP Module 2A include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluent treatment facilities, thermal treatment facility ash, other WRAP modules, and other, miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume 1 provides a narrative of the project background, objective and justification. A description of the WRAP 2A mission, operations and project scope is also included. Significant project requirements such as security, health, safety, decontamination and decomissioning, maintenance, data processing, and quality are outlined. Environmental compliance issues and regulatory permits are identified, and a preliminary safety evaluation is provided

Computer tomography of inflammatory rheumatic degenerative and reparative affections and transformation processes in the region of the sacroiliac joints

International Nuclear Information System (INIS)

Heller, M.; Guertler, K.F.; Dihlmann, W.; Allgemeines Krankenhaus Barmbek, Hamburg

1980-01-01

Inflammatory rheumatic, degenerative and reparative affections and transformation processes in the region of the sacroiliac joints can be demonstrated via computer tomography and/or conventinal roentgenology. It is found that computer tomography is superior to plain roentgenography diagnosis, including tomography, in respect of malpositioning of the articulating bones and reparative phenomena. On the other hand, early diagnosis of inflammatory rheumatic changes does not yield any additional information via computer tomography. (orig.) [de

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

Science.gov (United States)

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway

International Nuclear Information System (INIS)

Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Béliveau, Richard

2012-01-01

Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention.

Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway

Energy Technology Data Exchange (ETDEWEB)

Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Beliveau, Richard, E-mail: oncomol@nobel.si.uqam.ca

2012-08-01

Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6R{alpha}) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention.

External and internal limitations in amplitude-modulation processing

DEFF Research Database (Denmark)

Ewert, Stephan; Dau, Torsten

2004-01-01

Three experiments are presented to explore the relative role of "external" signal variability and "internal" resolution limitations of the auditory system in the detection and discrimination of amplitude modulations (AM). In the first experiment, AM-depth discrimination performance was determined......-filterbank models. The predictions revealed that AM-depth discrimination and AM detection are limited by a combination of the external signal variability and an internal "Weber-fraction" noise process....

Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its Anti-Inflammatory Activity In Vitro.

Science.gov (United States)

Liao, Jingzhu; Li, Chanyi; Huang, Jing; Liu, Wuping; Chen, Hongce; Liao, Shuangye; Chen, Hongyuan; Rui, Wen

2018-01-15

Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey by a traditional Chinese medicine processing method which strengthens the tonic effect. Astragalus polysaccharide (APS), perform its immunomodulatory effects by relying on the tonic effect of Radix Astragalus , therefore, the improved pharmacological activity of honey-processed Astragalus polysaccharide (HAPS) might be due to structural changes during processing. The molecular weights of HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high performance gel filtration chromatography combined with evaporative light scattering detection (HPGFC-ELSD). The monosaccharide composition was determined by ultra-performance liquid chromatogram quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) after pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP). The results showed that the essential components were mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56, respectively. FT-IR and NMR analysis of HAPS results showed the presence of uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more effective than those of APS according to the NO contents and the expression of IFN-γ, IL-1β, IL-22 and TNF-α in lipopolysaccharide (LPS)-induced RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity improvement might be associated with molecular structure changes, bearing on the potential immunomodulatory action.

Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its Anti-Inflammatory Activity In Vitro

Directory of Open Access Journals (Sweden)

Jingzhu Liao

2018-01-01

Full Text Available Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey by a traditional Chinese medicine processing method which strengthens the tonic effect. Astragalus polysaccharide (APS, perform its immunomodulatory effects by relying on the tonic effect of Radix Astragalus, therefore, the improved pharmacological activity of honey-processed Astragalus polysaccharide (HAPS might be due to structural changes during processing. The molecular weights of HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high performance gel filtration chromatography combined with evaporative light scattering detection (HPGFC-ELSD. The monosaccharide composition was determined by ultra-performance liquid chromatogram quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS after pre-column derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP. The results showed that the essential components were mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56, respectively. FT-IR and NMR analysis of HAPS results showed the presence of uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more effective than those of APS according to the NO contents and the expression of IFN-γ, IL-1β, IL-22 and TNF-α in lipopolysaccharide (LPS-induced RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity improvement might be associated with molecular structure changes, bearing on the potential immunomodulatory action.

Atorvastatin attenuates contrast-induced nephropathy by modulating inflammatory responses through the regulation of JNK/p38/Hsp27 expression

Directory of Open Access Journals (Sweden)

Xuyu He

2016-05-01

Our study demonstrates that high-dosage atorvastatin treatment attenuates both the inflammatory processes and apoptosis in contrast-induced acute kidney injury, and that the JNK/p38 MAPK pathway participates in the contrast-induced apoptosis of renal tubular cells. Finally, atorvastatin reduces CIN by suppression of apoptosis, which may be through inhibition of JNK/p38 MAPK pathways.

Anti-inflammatory effects of polyphenols in arthritis.

Science.gov (United States)

Oliviero, Francesca; Scanu, Anna; Zamudio-Cuevas, Yessica; Punzi, Leonardo; Spinella, Paolo

2018-03-01

Polyphenols have been extensively investigated with regard to their antioxidant, anti-inflammatory, and immunomodulant properties in many inflammatory chronic conditions. The aim of this review is to summarise how these compounds can modulate the inflammatory pathways which characterise the most prevalent arthropathies including osteoarthritis, rheumatoid arthritis and crystal-induced arthritis. Among polyphenols, epigallocatechin gallate, carnosol, hydroxytyrosol, curcumin, resveratrol, kaempferol and genistein have been the most widely investigated in arthritis. The most important results of the studies outlined in this article show how polyphenolic compounds are able to inhibit the expression and the release of a number of pro-inflammatory mediators and proteolytic enzymes, the activity of different transcriptional factors and the production of reactive oxygen species in vitro. Studies on animal models of rheumatoid arthritis, osteoarthritis and gout show interesting results in terms of reduced tissue damage, restored cartilage homeostasis, and decreased levels of uric acid, respectively. Despite the multiple protective effects of polyphenols, there are no dietary recommendations for patients affected by rheumatic diseases. Future studies, including intervention trials, should be conducted to determine the relevance of polyphenols consumption or supplementation in arthritis. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Batching alternatives for Phase I retrieval wastes to be processed in WRAP Module 1

International Nuclear Information System (INIS)

Mayancsik, B.A.

1994-01-01

During the next two decades, the transuranic (TRU) waste now stored in the 200 Area burial trenches and storage buildings is to be retrieved, processed in the Waste Receiving and Processing (WRAP) Module 1 facility, and shipped to a final disposal facility. The purpose of this document is to identify the criteria that can be used to batch suspect TRU waste, currently in retrievable storage, for processing through the WRAP Module 1 facility. These criteria are then used to generate a batch plan for Phase 1 Retrieval operations, which will retrieve the waste located in Trench 4C-04 of the 200 West Area burial ground. The reasons for batching wastes for processing in WRAP Module 1 include reducing the exposure of workers and the environment to hazardous material and ionizing radiation; maximizing the efficiency of the retrieval, processing, and disposal processes by reducing costs, time, and space throughout the process; reducing analytical sampling and analysis; and reducing the amount of cleanup and decontamination between process runs. The criteria selected for batching the drums of retrieved waste entering WRAP Module 1 are based on the available records for the wastes sent to storage as well as knowledge of the processes that generated these wastes. The batching criteria identified in this document include the following: waste generator; type of process used to generate or package the waste; physical waste form; content of hazardous/dangerous chemicals in the waste; radiochemical type and quantity of waste; drum weight; and special waste types. These criteria were applied to the waste drums currently stored in Trench 4C-04. At least one batching scheme is shown for each of the criteria listed above

Depression: An Immuno-Inflammatory Cascade

Directory of Open Access Journals (Sweden)

Vivek Sharma

2016-06-01

Full Text Available Major depressive disorder also known as clinical depression, unipolar depression or depression is associated with significant morbidity, mortality, high suicidal tendencies and deaths. Preclinical and clinical studies suggest that psychiatric illnesses like MDD, are associated with inflammatory processes. While it is unlikely that major depressive disorder is a primary and lsquo;inflammatory' disorder, there is now evidence to suggest that inflammation play a subtle role in the pathophysiology of major depressive disorder. The inflammation in depression cascade pin points to the origin from immune hyperactivity and thus a new theory that explains role of immune system mediated inflammation has been accepted and researched upon. widely. This theory states that depression is accompanied by altered immune function and activation of the inflammatory response system. This theory is strengthened form the fact that the current therapeutic options which mainly target neurotransmitters, are not effective in many patients and these patients has been found to be associated with elevated levels of inflammatory mediators specifically cytokines. It is reported more recently that other risk factors for depression, including psychosocial stress, psychological trauma, sleep disturbance and pain, also increases inflammatory processes. Thus the intervention in the immune system originated from inflammatory cytokines seems a therapeutically viable option in the field of depression research. [Archives Medical Review Journal 2016; 25(2.000: 223-240

Method for Signal Processing of Electric Field Modulation Sensor in a Conductive Environment

Directory of Open Access Journals (Sweden)

O. I. Miseyk

2015-01-01

Full Text Available In investigating the large waters and deep oceans the most promising are modulation sensors for measuring electric field in a conducting environment in a very low frequency range in devices of autonomous or non-autonomous vertical sounding. When using sensors of this type it is necessary to solve the problem of enhancement and measurement of the modulated signal from the baseband noise.The work analyses hydrodynamic and electromagnetic noise at the input of transducer with "rotating" sensitive axis. By virtue of matching the measuring electrodes with the signal processing circuit a conclusion has been drawn that the proposed basic model of a transducer with "rotating” sensitive axis is the most efficient in terms of enhancement and measurement of modulated signal from the baseband noise. It has been shown that it is undesirable for transducers to have the rotation of electrodes resulting, in this case, in arising noise to be synchronously changed with transducer rotation frequency (modulation frequency. This will complicate the further signal-noise enhancement later in their processing.The paper justifies the choice of demodulation output signal, called synchronous demodulation using a low-pass filter with a cutoff frequency much lower than the carrier frequency to provide an output signal in the range of very low frequency and dc electric fields.The paper offers an original circuit to process the signals taken from the modulation sensor with "rotating" measurement base. This circuit has advantages over the earlier known circuits for measuring electric fields in a conducting (marine environment in the ultralow frequency range of these fields in terms of sensitivity and measuring accuracy of modulation sensors.

Neuroendocrine modulation of the inflammatory response in common carp: adrenaline regulates leukocyte profile and activity

NARCIS (Netherlands)

Kepka, M.; Verburg-van Kemenade, B.M.L.; Chadzinska, M.K.

2013-01-01

Inflammatory responses have to be carefully controlled, as high concentrations and/or prolonged action of inflammation-related molecules (e.g. reactive oxygen species, nitric oxide and pro-inflammatory cytokines) can be detrimental to host tissue and organs. One of the potential regulators of the

Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

Directory of Open Access Journals (Sweden)

Joanna Balding

2004-01-01

Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

Breastfeeding in infancy is not associated with inflammatory status in healthy adolescents.

Science.gov (United States)

Vérier, Caroline M P; Duhamel, Alain; Béghin, Laurent; Diaz, Ligia-Esperanza; Warnberg, Julia; Marcos, Ascensión; Gómez-Martínez, Sonia; Manios, Yannis; De Henauw, Stefaan; Sjöström, Michael; Moreno, Luis A; Kersting, Mathilde; Breidenassel, Christina; Molnar, Dènes; Artero, Enrique G; Ferrari, Marika; Widhalm, Kurt; Turck, Dominique; Gottrand, Frédéric

2011-03-01

It has been suggested that breast-feeding (BF) may be associated with a decreased risk of cardiovascular disease in adulthood. A low-grade inflammation is associated with an increased risk of cardiovascular disease, even in apparently healthy children. The objective of this study was to assess the potential modulating effect of BF on the inflammatory status of healthy adolescents. Information on BF (duration) was obtained from parental records in 484 of 1040 healthy European urban adolescents (56.4% females) that had a blood sample obtained as part of the Healthy Lifestyle in Europe by Nutrition and Adolescence study. Blood serum inflammatory markers were measured, including high sensitivity C-reactive protein, complement factors 3 and 4, ceruloplasmin, adhesion molecules (L-selectin and soluble endothelial selectin, soluble vascular cell adhesion molecule 1, and intercellular adhesion molecule 1), cytokines, TGFβ1, and white blood cells. After univariate analysis, a propensity score, including the potential confounding factors, was computed and used to assess the association between BF and selected inflammatory markers. BF was not significantly associated with any of the selected inflammatory markers after adjustment for gender and propensity score. In our study, BF was not associated with low-grade inflammatory status in healthy adolescents, suggesting that the potential cardiovascular benefits of BF are related to other mechanisms than modulation of inflammation or might become relevant at a later age. Groups at high risk for cardiovascular disease should be a target for further research concerning the effects of BF.

Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission

Directory of Open Access Journals (Sweden)

Mário A. C. Silva-Neto

2012-01-01

Full Text Available Lysophosphatidylcholine is a bioactive lipid that regulates a large number of cellular processes and is especially present during the deposition and infiltration of inflammatory cells and deposition of atheromatous plaque. Such molecule is also present in saliva and feces of the hematophagous organism Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts as a powerful chemoattractant for inflammatory cells at the site of the insect bite, which will provide a concentrated population of cells available for parasite infection. Also, LPC increases macrophage intracellular calcium concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits NO production by macrophages stimulated by live T. cruzi, and thus interferes with the immune system of the vertebrate host. In the present paper, we discuss the main signaling mechanisms that are likely used by such molecule and their eventual use as targets to block parasite transmission and the pathogenesis of Chagas disease.

Lysophosphatidylcholine: A Novel Modulator of Trypanosoma cruzi Transmission

Science.gov (United States)

Silva-Neto, Mário A. C.; Carneiro, Alan B.; Silva-Cardoso, Livia; Atella, Georgia C.

2012-01-01

Lysophosphatidylcholine is a bioactive lipid that regulates a large number of cellular processes and is especially present during the deposition and infiltration of inflammatory cells and deposition of atheromatous plaque. Such molecule is also present in saliva and feces of the hematophagous organism Rhodnius prolixus, a triatominae bug vector of Chagas disease. We have recently demonstrated that LPC is a modulator of Trypanosoma cruzi transmission. It acts as a powerful chemoattractant for inflammatory cells at the site of the insect bite, which will provide a concentrated population of cells available for parasite infection. Also, LPC increases macrophage intracellular calcium concentrations that ultimately enhance parasite invasion. Finally, LPC inhibits NO production by macrophages stimulated by live T. cruzi, and thus interferes with the immune system of the vertebrate host. In the present paper, we discuss the main signaling mechanisms that are likely used by such molecule and their eventual use as targets to block parasite transmission and the pathogenesis of Chagas disease. PMID:22132309

The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells

Directory of Open Access Journals (Sweden)

Sara V. Maurer

2017-11-01

Full Text Available Degeneration of central cholinergic neurons impairs memory, and enhancement of cholinergic synapses improves cognitive processes. Cholinergic signaling is also anti-inflammatory, and neuroinflammation is increasingly linked to adverse memory, especially in Alzheimer’s disease. Much of the evidence surrounding cholinergic impacts on the neuroimmune system focuses on the α7 nicotinic acetylcholine (ACh receptor, as stimulation of this receptor prevents many of the effects of immune activation. Microglia and astrocytes both express this receptor, so it is possible that some cholinergic effects may be via these non-neuronal cells. Though the presence of microglia is required for memory, overactivated microglia due to an immune challenge overproduce inflammatory cytokines, which is adverse for memory. Blocking these exaggerated effects, specifically by decreasing the release of tumor necrosis factor α (TNF-α, interleukin 1β (IL-1β, and interleukin 6 (IL-6, has been shown to prevent inflammation-induced memory impairment. While there is considerable evidence that cholinergic signaling improves memory, fewer studies have linked the “cholinergic anti-inflammatory pathway” to memory processes. This review will summarize the current understanding of the cholinergic anti-inflammatory pathway as it relates to memory and will argue that one mechanism by which the cholinergic system modulates hippocampal memory processes is its influence on neuroimmune function via the α7 nicotinic ACh receptor.

Identification of inflammatory processes in temporomandibular joint (TMJ) by 99mTc-HMPAO in animal model

International Nuclear Information System (INIS)

Brasileiro, Claudia Borges; Cardoso, Valbert Nascimento; Lima, Carla Flavia de; Campos, Tarcisio Passos Ribeiro de

2005-01-01

Temporomandibular joint (TMJ) is a synovial joint that represents the junction of mandible with skull. TMJ and mastication muscles are affected by temporomandibular disorders (TMDs). During the last two decades the advances in imaging diagnostic of TMJ have greatly contributed to the assessment of the TMJ disorders. Labelled leukocytes with technetium- 99m hexamethyl propylene amine oxime ( 99m Tc-HMPAO) represent an efficient method that generates images based in physiological and/or biochemical changes related to inflammation. The aim of this study was to investigate the potential usefulness of technetium-99m labelled leukocytes scintigraphy in the diagnosis of TMJ inflammatory process applying a rabbit TMJ arthritis model. Arthritis was induced unilaterally with an intra-articular injection of ovalbumin in left ATM. On the contra-lateral side, the same dose of saline was injected. After five days, leukocytes were labeled with HMPAO and 99m Tc-HMPAO TMJ scintigraphic images were made. After twelve days a computed tomography was realized. Scintigraphic images obtained five days after induction of TMJ inflammation showed the localization of inflammatory process. The results were expressed as cpm of activity found in left ATM and contra-lateral side. Significant differences of activity were found between inflamed articulation and contra-lateral side (P = 0,0073). In conclusion, the method of leukocytes labeled with 99m Tc showed to be sensitive in detection of inflammatory disorders of TMJ and can be of great value in early diagnostic of these disorders. (author)

Ureaplasma Species Differentially Modulate Pro- and Anti-Inflammatory Cytokine Responses in Newborn and Adult Human Monocytes Pushing the State Toward Pro-Inflammation

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Glaser, Kirsten; Silwedel, Christine; Fehrholz, Markus; Waaga-Gasser, Ana M.; Henrich, Birgit; Claus, Heike; Speer, Christian P.

2017-01-01

Background: Ureaplasma species have been associated with chorioamnionitis and preterm birth and have been implicated in the pathogenesis of neonatal short and long-term morbidity. However, being mostly commensal bacteria, controversy remains on the pro-inflammatory capacity of Ureaplasma. Discussions are ongoing on the incidence and impact of prenatal, perinatal, and postnatal infection. The present study addressed the impact of Ureaplasma isolates on monocyte-driven inflammation. Methods: Cord blood monocytes of term neonates and adult monocytes, either native or LPS-primed, were cultured with Ureaplasma urealyticum (U. urealyticum) serovar 8 (Uu8) and Ureaplasma parvum serovar 3 (Up3). Using qRT-PCR, cytokine flow cytometry, and multi-analyte immunoassay, we assessed mRNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-12p40, IL-10, and IL-1 receptor antagonist (IL-1ra) as well as Toll-like receptor (TLR) 2 and TLR4. Results: Uu8 and Up3 induced mRNA expression and protein release of TNF-α, IL-1β and IL-8 in term neonatal and adult monocytes (p Ureaplasma-stimulated cells paralleled those results. Ureaplasma-induced cytokine levels did not significantly differ from LPS-mediated levels except for lower intracellular IL-1β in adult monocytes (Uu8: p ureaplasmas did not induce IL-12p40 response and promoted lower amounts of anti-inflammatory IL-10 and IL-1ra than LPS, provoking a cytokine imbalance more in favor of pro-inflammation (IL-1β/IL-10, IL-8/IL-10 and IL-8/IL-1ra: p Ureaplasma isolates in human monocytes. Stimulating pro-inflammatory cytokine responses while hardly inducing immunomodulatory and anti-inflammatory cytokines, ureaplasmas might push monocyte immune responses toward pro-inflammation. Inhibition of LPS-induced cytokines in adult monocytes in contrast to sustained inflammation in term neonatal monocytes indicates a differential modulation of host immune responses to a second stimulus. Modification of

Cognate antigen stimulation generates potent CD8+ inflammatory effector T cells.

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Hsueh-Cheng eSung

2013-12-01

Full Text Available Inflammatory reactions are believed to be triggered by innate signals and have a major protective role by recruiting innate immunity cells, favoring lymphocyte activation and differentiation, and thus contributing to the sequestration and elimination of the injurious stimuli. Although certain lymphocyte types such as TH17 cells co-participate in inflammatory reactions, their generation from the naïve pool requires the pre-existence of an inflammatory milieu. In this context, inflammation is always regarded as beginning with an innate response that may be eventually perpetuated and amplified by certain lymphocyte types. In contrast, we here show that even in sterile immunizations or in MyD88 deficient mice, CD8 T cells produce a burst of pro-inflammatory cytokines and chemokines. These functions follow opposite rules to the classic CD8 effector functions since they are generated prior to cell expansion and decline before antigen elimination. As few as 56 CD8+ inflammatory effector cells in a lymph node can mobilize 107 cells in 24h, including lymphocytes, natural killer cells and several accessory cell types involved in inflammatory reactions. Thus, although inflammation modulates cognate responses, CD8 cognate responses also initiate local inflammatory reactions.

The anti-inflammatory effects of the tellurium redox modulating compound, AS101, are associated with regulation of NFκB signaling pathway and nitric oxide induction in macrophages

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Sredni Benjamin

2010-01-01

Full Text Available Abstract Background LPS-activated macrophages produce mediators which are involved in inflammation and tissue injury, and especially those associated with endotoxic shock. The non toxic tellurium compound ammonium tri-chloro(dioxoethylene-O,O'-tellurate, AS101, has been recently shown to exert profound anti-inflammatory properties in animal models, associated with its Te(IV redox chemistry. This study explores the anti-inflammatory properties of AS101 with respect to modulation of inflammatory cytokines production and regulation of iNOS transcription and expression in activated macrophages via targeting the NFkB complex. Results AS101 decreased production of IL-6 and in parallel down-regulated LPS-induced iNOS expression and NO secretion by macrophages. AS101 reduced IkB phosphorylation and degradation, and reduced NFkB nuclear translocalization, albeit these effects were exerted at different kinetics. Chromatin immunoprecipitation assays showed that AS101 treatment attenuated p50-subunit ability to bind DNA at the NFkB consensus site in the iNOS promotor following LPS induction. Conclusions Besides AS101, the investigation of therapeutic activities of other tellurium(IV compounds is scarce in the literature, although tellurium is the fourth most abundant trace element in the human body. Since IKK and NFkB may be regulated by thiol modifications, we may thus envisage, inview of our integrated results, that Te(IV compounds, may have important roles in thiol redox biological activity in the human body and represent a new class of anti-inflammatory compounds.

Physiological Aspects of Aging. Module A-5. Block A. Basic Knowledge of the Aging Process.

Science.gov (United States)

Harvey, Dexter; Cap, Orest

This instructional module on physiological aspects of aging is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Nine sections present…

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

Science.gov (United States)

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

Leucocytes labelled with In-111-oxine in acute inflammatory processes

International Nuclear Information System (INIS)

Herranz, R.; Lomena, F.; Fernandez, R.M.; Del Rio, L.; Piera, C.; Vida, F.; Setoain, J.

1982-01-01

We used autologous leucocytes labelled with In-111-Oxine to diagnose inflammatory processes, located or scattered, in 60 patients. In 46 there was suspected located infection focus. Gammagraphy was abnormal in 38 cases (83%), 28 abdominally located (87%), 5 thorax located (71%) and 5 of several locations. In other 14 cases there was clinic suspicion of infection without located septic focus. In 5 of them gammagraphy was interpreted as positive but only in 3 patients it was found abdominal located abscess. The two other cases are considered as false positive ones. In the 9 remaining, with negative gammagraphy there was no clinic confirmation nor other diagnostic methods of abscess existence. In this paper we checked high sensitivity of leucocytes In-111-Oxine to diagnose and locate infectious focuses. In our casuistry there was only a false negative and two false positive ones

Matrix Metalloproteinases: Inflammatory Regulators of Cell Behaviors in Vascular Formation and Remodeling

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Qishan Chen

2013-01-01

Full Text Available Abnormal angiogenesis and vascular remodeling contribute to pathogenesis of a number of disorders such as tumor, arthritis, atherosclerosis, restenosis, hypertension, and neurodegeneration. During angiogenesis and vascular remodeling, behaviors of stem/progenitor cells, endothelial cells (ECs, and vascular smooth muscle cells (VSMCs and its interaction with extracellular matrix (ECM play a critical role in the processes. Matrix metalloproteinases (MMPs, well-known inflammatory mediators are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and non-ECM molecules mediating tissue remodeling in both physiological and pathological processes. MMPs including MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MT1-MMP, are stimulated and activated by various stimuli in vascular tissues. Once activated, MMPs degrade ECM proteins or other related signal molecules to promote recruitment of stem/progenitor cells and facilitate migration and invasion of ECs and VSMCs. Moreover, vascular cell proliferation and apoptosis can also be regulated by MMPs via proteolytically cleaving and modulating bioactive molecules and relevant signaling pathways. Regarding the importance of vascular cells in abnormal angiogenesis and vascular remodeling, regulation of vascular cell behaviors through modulating expression and activation of MMPs shows therapeutic potential.

Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management.

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McIlroy, J; Ianiro, G; Mukhopadhya, I; Hansen, R; Hold, G L

2018-01-01

The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics. To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics. A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed. Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice. Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option. © 2017 John Wiley & Sons Ltd.

T cells in vascular inflammatory diseases

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Lucas L Lintermans

2014-10-01

Full Text Available Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4+ T cells termed effector memory T cells. This expanded population of effector memory T cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, NK cells, B cells and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of effector memory T cells in uniquely dependent on the voltage-gated Kv1.3 potassium channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic effector memory T cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation.

ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity

Energy Technology Data Exchange (ETDEWEB)

Liu, Xin-Hua [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Bauman, William A. [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Cardozo, Christopher, E-mail: chris.cardozo@va.gov [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

2015-08-14

Transcription factors of the nuclear factor-kappa B (NF-κB) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-κB also regulates the processes of muscle atrophy. NF-κB activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-κB mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 in NF-κB mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-κB activity and determined the interactions between AnkrD1 expression and NF-κB signaling induced by TNFα in differentiating C2C12 myoblasts. TNFα upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNFα-induced transcriptional activation of NF-κB, whereas overexpression of AnkrD1 inhibited TNFα-induced NF-κB activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-κB and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-κB binding site in the AnrkD2 promoter and required NF-κB to do so. These results provide evidence of signaling integration between AnkrD1 and NF-κB pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-κB transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. - Highlights: • AnkrD1 is upregulated by TNFα and represses NF-κB-induced transcriptional activity. • AnkrD1 binds to p50 subunit of NF-κB and is recruited to NF-κB bound to chromatin. • AnkrD1 mediates a feed-back inhibitory loop

Arrays of surface-normal electroabsorption modulators for the generation and signal processing of microwave photonics signals

NARCIS (Netherlands)

Noharet, Bertrand; Wang, Qin; Platt, Duncan; Junique, Stéphane; Marpaung, D.A.I.; Roeloffzen, C.G.H.

2011-01-01

The development of an array of 16 surface-normal electroabsorption modulators operating at 1550nm is presented. The modulator array is dedicated to the generation and processing of microwave photonics signals, targeting a modulation bandwidth in excess of 5GHz. The hybrid integration of the

Conceptual design for the Waste Receiving And Processing facility Module 2A

International Nuclear Information System (INIS)

1992-07-01

This Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility. The mission of the WRAP Module 2A facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. This volume provides the detailed cost estimate for the WRAP 2A facility. Included in this volume is the project construction schedule

Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway.

Science.gov (United States)

Lamy, Sylvie; Akla, Naoufal; Ouanouki, Amira; Lord-Dufour, Simon; Béliveau, Richard

2012-08-01

Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

Engineering structure design and fabrication process of small sized China helium-cooled solid breeder test blanket module

International Nuclear Information System (INIS)

Wang Zeming; Chen Lu; Hu Gang

2014-01-01

Preliminary design and analysis for china helium-cooled solid breeder (CHHC-SB) test blanket module (TBM) have been carried out recently. As partial verification that the original size module was reasonable and the development process was feasible, fabrication work of a small sized module was to be carried out targetedly. In this paper, detailed design and structure analysis of small sized TBM was carried out based on preliminary design work, fabrication process and integrated assembly process was proposed, so a fabrication for the trial engineering of TBM was layed successfully. (authors)

Distortions caused by the signal processing in analog AM modulators

International Nuclear Information System (INIS)

Njau, E.C.

1988-08-01

Complete analytical expressions for distortions caused by signal processing in analog AM modulators are developed. The salient features in these expressions are shown to be consistent with displays of actual spectra of AM signals. Finally suggestions are given on how the distortions may be practically minimized. (author). 6 refs, 3 figs

High throughput diffractive multi-beam femtosecond laser processing using a spatial light modulator

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Kuang Zheng [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)], E-mail: z.kuang@liv.ac.uk; Perrie, Walter [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Leach, Jonathan [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Sharp, Martin; Edwardson, Stuart P. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom); Padgett, Miles [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Dearden, Geoff; Watkins, Ken G. [Laser Group, Department of Engineering, University of Liverpool Brownlow Street, Liverpool L69 3GQ (United Kingdom)

2008-12-30

High throughput femtosecond laser processing is demonstrated by creating multiple beams using a spatial light modulator (SLM). The diffractive multi-beam patterns are modulated in real time by computer generated holograms (CGHs), which can be calculated by appropriate algorithms. An interactive LabVIEW program is adopted to generate the relevant CGHs. Optical efficiency at this stage is shown to be {approx}50% into first order beams and real time processing has been carried out at 50 Hz refresh rate. Results obtained demonstrate high precision surface micro-structuring on silicon and Ti6Al4V with throughput gain >1 order of magnitude.

Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation.

Science.gov (United States)

Lagadec, Patricia; Balaguer, Thierry; Boukhechba, Florian; Michel, Grégory; Bouvet-Gerbettaz, Sébastien; Bouler, Jean-Michel; Scimeca, Jean-Claude; Rochet, Nathalie

2017-07-15

Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction. Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms

Modeling auditory processing of amplitude modulation I. Detection and masking with narrow-band carriers

NARCIS (Netherlands)

Dau, T.; Kollmeier, B.; Kohlrausch, A.G.

1997-01-01

This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615–3622 (1996)]. The new element in the

Offspring of parents with Balkan Endemic Nephropathy have higher C-reactive protein levels suggestive of inflammatory processes: a longitudinal study

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Tsolova Svetla

2009-04-01

Full Text Available Abstract Background Despite the characteristic extensive tubulointerstitial fibrosis, Balkan Endemic Nephropathy (BEN is usually considered a non-inflammatory disease. Methods We examined a marker of inflammation, C-reactive protein (CRP, in the offspring of patients with BEN, a population at risk for BEN, prior to development of established disease to determine if an inflammatory process could be identified in the early stages of the disease. In 2003/04, 102 adult offspring whose parents had BEN and a control group of 99 adult offspring of non-BEN patients were enrolled in this prospective study. This cohort was re-examined yearly for four consecutive years. Levels of serum CRP were measured in years 3 and 4 and compared between groups. The data were analyzed with mixed models. Results Compared to controls, offspring of BEN parents had statistically higher CRP levels in two consecutive years, suggestive of early inflammatory reactivity. Whenever the mother was affected by BEN (both parents, or mother only, serum CRP was significantly increased, but not if only the father had BEN. CRP was inversely related to kidney cortex width but not to markers or renal function. Conclusion Early stages of BEN may involve inflammatory processes. The observation of a maternal involvement supports the concept of fetal programming, which has been implicated in the pathogenesis of other chronic kidney diseases.

Caspase-12 and the inflammatory response to Yersinia pestis.

Science.gov (United States)

Ferwerda, Bart; McCall, Matthew B B; de Vries, Maaike C; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A B; Tissingh, Rudi A; Reubsaet, Frans A G; Sauerwein, Robert; van der Meer, Jos W M; van der Ven, André J A M; Netea, Mihai G

2009-09-01

Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.

Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats.

Science.gov (United States)

Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

2017-09-01

Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48 + cells) at days 1 and 3 post implantation and CD11b + cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on

Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model

NARCIS (Netherlands)

Koopman, F. A.; Vosters, J. L.; Roescher, N.; Broekstra, N.; Tak, P. P.; Vervoordeldonk, M. J.

2015-01-01

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's

Edge sealing for low cost stability enhancement of roll-to-roll processed flexible polymer solar cell modules

DEFF Research Database (Denmark)

Tanenbaum, David M.; Dam, Henrik Friis; Rösch, R.

2012-01-01

Fully roll-to-roll processed polymer solar cell modules were prepared, characterized, and laminated. Cell modules were cut from the roll and matched pairs were selected, one module with exposed cut edges, the other laminated again with the same materials and adhesive sealing fully around the cut...... edges. The edge sealing rim was 10 mm wide. Cell modules were characterized by periodic measurements of IV curves over extended periods in a variety of conditions, as well as by a variety of spatial imaging techniques. Data show significant stability benefits of the edge sealing process. The results...

Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

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Ashlee B. Carter

2009-01-01

Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

Bioactive dietary peptides and amino acids in inflammatory bowel disease.

Science.gov (United States)

Zhang, Hua; Hu, Chien-An A; Kovacs-Nolan, Jennifer; Mine, Yoshinori

2015-10-01

Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-α and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-α, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.

Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii.

Science.gov (United States)

Pothoulakis, C

2009-10-15

Saccharomyces boulardii, a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as inflammatory bowel disease (IBD), and bacterially mediated or enterotoxin-mediated diarrhoea and inflammation. To discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii. Review of the literature related to the anti-inflammatory effects of this probiotic. Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted-protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor kappaB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that protects from gut inflammation and IBD. S. boulardii also suppresses 'bacteria overgrowth' and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states.

Review article: Anti-inflammatory mechanisms of action of Saccharomyces boulardii

Science.gov (United States)

Pothoulakis, C.

2009-01-01

SUMMARY Background Saccharomyces boulardii (S. boulardii), a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as Inflammatory Bowel Disease (IBD), and bacterially – or enterotoxin-mediated diarrhea and inflammation. Aim Discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii Methods Review of the literature related to the anti-inflammatory effects of this probiotic. Results Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor κB, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) that protects from gut inflammation and IBD. S. boulardii also suppresses “bacteria overgrowth” and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor, and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. Conclusions The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states. PMID:19706150

Transcranial alternating current stimulation: A review of the underlying mechanisms and modulation of cognitive processes

Directory of Open Access Journals (Sweden)

Christoph S Herrmann

2013-06-01

Full Text Available Brain oscillations of different frequencies have been associated with a variety of cognitive functions. Convincing evidence supporting those associations has been provided by studies using intracranial stimulation, pharmacological interventions and lesion studies. The emergence of novel non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS and transcranial alternating current stimulation (tACS now allows to modulate brain oscillations directly. Particularly, tACS offers the unique opportunity to causally link brain oscillations of a specific frequency range to cognitive processes, because it uses sinusoidal currents that are bound to one frequency only. Using tACS allows to modulate brain oscillations and in turn to influence cognitive processes, thereby demonstrating the causal link between the two. Here, we review findings about the physiological mechanism of tACS and studies that have used tACS to modulate basic motor and sensory processes as well as higher cognitive processes like memory, ambiguous perception, and decision making.

Involvement of Visceral Adipose Tissue in Immunological Modulation of Inflammatory Cascade in Preeclampsia

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Katsuhiko Naruse

2015-01-01

Full Text Available Objectives. The pathophysiology of preeclampsia is characterized by abnormal placentation, an exaggerated inflammatory response, and generalized dysfunction of the maternal endothelium. We investigated the effects of preeclampsia serum on the expression of inflammation-related genes by adipose tissue. Materials and Methods. Visceral adipose tissue was obtained from the omentum of patients with early ovarian cancer without metastasis. Adipose tissue was incubated with sera obtained from either five women affected with severe preeclampsia or five women from control pregnant women at 37°C in a humidified incubator at 5% CO2 for 24 hours. 370 genes in total mRNA were analyzed with quantitative RT-PCR (Inflammatory Response & Autoimmunity gene set. Results. Gene expression analysis revealed changes in the expression levels of 30 genes in adipose tissue treated with preeclampsia sera. Some genes are related to immune response, oxidative stress, insulin resistance, and adipogenesis, which plays a central role in excessive systemic inflammatory response of preeclampsia. In contrast, other genes have shown beneficial effects in the regulation of Th2 predominance, antioxidative stress, and insulin sensitivity. Conclusion. In conclusion, visceral adipose tissue offers protection against inflammation, oxidative insults, and other forms of cellular stress that are central to the pathogenesis of preeclampsia.

GH activity and markers of inflammation

DEFF Research Database (Denmark)

Andreassen, Mikkel; Frystyk, Jan; Faber, Jens

2012-01-01

The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated.......The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated....

Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses.

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Chowdhury, Sayantani; Sinha, Krishnendu; Banerjee, Sharmistha; Sil, Parames C

2016-11-12

Oxidative stress, ER stress, inflammation, and apoptosis results in the pathogenesis of cisplatin-induced cardiotoxicity. The present study was designed to investigate the signaling mechanisms involved in the ameliorating effect of taurine, a conditionally essential amino acid, against cisplatin-mediated cardiac ER stress dependent apoptotic death and inflammation. Mice were simultaneously treated with taurine (150 mg kg -1 body wt, i.p.) and cisplatin (10 mg kg -1 body wt, i.p.) for a week. Cisplatin exposure significantly altered serum creatine kinase and troponin T levels. In addition, histological studies revealed disintegration in the normal radiation pattern of cardiac muscle fibers. However, taurine administration could abate such adverse effects of cisplatin. Taurine administration significantly mitigated the reactive oxygen species production, alleviated the overexpression of nuclear factor-κB (NF-κB), and inhibited the elevation of proinflammatoy cytokines, adhesion molecules, and chemokines. Cisplatin exposure resulted in the unfolded protein response (UPR)-regulated CCAAT/enhancer binding protein (CHOP) up-regulation, induction of GRP78: a marker of ER stress and eIF2α signaling. Increase in calpain-1 expression level, activation of caspase-12 and caspase-3, cleavage of the PARP protein as well as the inhibition of antiapoptotic protein Bcl-2 were reflected on cisplatin-triggered apoptosis. Taurine could, however, combat against such cisplatin induced cardiac-abnormalities. The above mentioned findings suggest that taurine plays a beneficial role in providing protection against cisplatin-induced cardiac damage by modulating inflammatory responses and ER stress. © 2016 BioFactors, 42(6):647-664, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes.

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Marta Molero-Luis

Full Text Available OBJECTIVE: A high level of cerebrospinal fluid (CSF neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. METHODS: To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A, acquired/unknown etiologic neurologic diseases (B and inflammatory-immune mediated processes (C. RESULTS: The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. CONCLUSIONS: Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes.

Serotonergic and dopaminergic modulation of attentional processes.

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Boulougouris, Vasileios; Tsaltas, Eleftheria

2008-01-01

Disturbances in attentional processes are a common feature of several psychiatric disorders such as schizophrenia, attention deficit/hyperactivity disorder and Huntington's disease. The use of animal models has been useful in defining various candidate neural systems thus enabling us to translate basic laboratory science to the clinic and vice-versa. In this chapter, a comparative and integrated account is provided on the neuroanatomical and neurochemical modulation of basic behavioural operations such as selective attention, vigilance, set-shifting and executive control focusing on the comparative functions of the serotonin and dopamine systems in the cognitive control exerted by the prefrontal cortex. Specifically, we have reviewed evidence emerging from several behavioural paradigms in experimental animals and humans each of which centres on a different aspect of the attentional function. These paradigms offering both human and animal variants include the five-choice serial reaction time task (5CSRTT), attentional set-shifting and stop-signal reaction time task. In each case, the types of operation that are measured by the given paradigm and their neural correlates are defined. Then, the role of the ascending dopaminergic and serotonergic systems in the neurochemical modulation of its behavioural output are examined, and reference is made to clinical implications for neurological and neuropsychiatric disorders which exhibit deficits in these cognitive tests.

Value conditioning modulates visual working memory processes.

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Thomas, Paul M J; FitzGibbon, Lily; Raymond, Jane E

2016-01-01

Learning allows the value of motivationally salient events to become associated with stimuli that predict those events. Here, we asked whether value associations could facilitate visual working memory (WM), and whether such effects would be valence dependent. Our experiment was specifically designed to isolate value-based effects on WM from value-based effects on selective attention that might be expected to bias encoding. In a simple associative learning task, participants learned to associate the color of tinted faces with gaining or losing money or neither. Tinted faces then served as memoranda in a face identity WM task for which previously learned color associations were irrelevant and no monetary outcomes were forthcoming. Memory was best for faces with gain-associated tints, poorest for faces with loss-associated tints, and average for faces with no-outcome-associated tints. Value associated with 1 item in the WM array did not modulate memory for other items in the array. Eye movements when studying faces did not depend on the valence of previously learned color associations, arguing against value-based biases being due to differential encoding. This valence-sensitive value-conditioning effect on WM appears to result from modulation of WM maintenance processes. (c) 2015 APA, all rights reserved).

Extracorporeal shock wave therapy in inflammatory diseases: molecular mechanism that triggers anti-inflammatory action.

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Mariotto, Sofia; de Prati, Alessandra Carcereri; Cavalieri, Elisabetta; Amelio, Ernesto; Marlinghaus, Ernst; Suzuki, Hisanori

2009-01-01

Shock waves (SW), defined as a sequence of single sonic pulses characterised by high peak pressure (100 MPa), a fast rise in pressure (conveyed by an appropriate generator to a specific target area at an energy density ranging from 0.03 to 0.11 mJ/mm(2). Extracorporeal SW (ESW) therapy was first used on patients in 1980 to break up kidney stones. During the last ten years, this technique has been successfully employed in orthopaedic diseases such as pseudoarthosis, tendinitis, calcarea of the shoulder, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. In particular, treatment of the tendon and muscle tissues was found to induce a long-time tissue regeneration effect in addition to having a more immediate anthalgic and anti-inflammatory outcome. In keeping with this, an increase in neoangiogenesis in the tendons of dogs was observed after 4-8 weeks of ESW treatment. Furthermore, clinical observations indicate an immediate increase in blood flow around the treated area. Nevertheless, the biochemical mechanisms underlying these effects have yet to be fully elucidated. In the present review, we briefly detail the physical properties of ESW and clinical cases treated with this therapy. We then go on to describe the possible molecular mechanism that triggers the anti-inflammatory action of ESW, focusing on the possibility that ESW may modulate endogenous nitric oxide (NO) production either under normal or inflammatory conditions. Data on the rapid enhancement of endothelial NO synthase (eNOS) activity in ESW-treated cells suggest that increased NO levels and the subsequent suppression of NF-kappaB activation may account, at least in part, for the clinically beneficial action on tissue inflammation.

Emotion processing in the aging brain is modulated by semantic elaboration

OpenAIRE

Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M.; Cabeza, Roberto

2010-01-01

The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs’ capacity for controlled elaboration. However, the role of semantic elaboration...

P-glycoprotein Modulates Morphine Uptake into the CNS: A Role for the Non-steroidal Anti-inflammatory Drug Diclofenac

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Sanchez-Covarrubias, Lucy; Slosky, Lauren M.; Thompson, Brandon J.; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M.; Ronaldson, Patrick T.; Davis, Thomas P.

2014-01-01

Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction. PMID:24520393

P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

Science.gov (United States)

Sanchez-Covarrubias, Lucy; Slosky, Lauren M; Thompson, Brandon J; Zhang, Yifeng; Laracuente, Mei-Li; DeMarco, Kristin M; Ronaldson, Patrick T; Davis, Thomas P

2014-01-01

Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

P-glycoprotein modulates morphine uptake into the CNS: a role for the non-steroidal anti-inflammatory drug diclofenac.

Directory of Open Access Journals (Sweden)

Lucy Sanchez-Covarrubias

Full Text Available Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP, induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp that is endogenously expressed at the blood-brain barrier (BBB. The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h, as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.

Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro

DEFF Research Database (Denmark)

Midttun, Helene L. E.; Acevedo, Nathalie; Skallerup, Per

2018-01-01

similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro......Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using...... transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed...

Silicon dioxide etching process for fabrication of micro-optics employing pulse-modulated electron-beam-excited plasma

International Nuclear Information System (INIS)

Takeda, Keigo; Ohta, Takayuki; Ito, Masafumi; Hori, Masaru

2006-01-01

Silicon dioxide etching process employing a pulse-modulated electron-beam-excited plasma (EBEP) has been developed for a fabrication process of optical micro-electro-mechanical systems (MEMSs). Nonplanar dielectric materials were etched by using self-bias induced by the electron beam generating the plasma. In order to investigate the effect of pulse modulation on electron beam, plasma diagnostics were carried out in the EBEP employing C 4 F 8 gas diluted with Ar gas by using a Langmuir single probe and time resolved optical emission spectroscopy. It was found that the pulse-modulated EBEP has an excellent potential to reduce the plasma-induced thermal damage on a photoresist film on a substrate to get the uniform etching and the anisotropic SiO 2 etching in comparison with the conventional EBEP. The pulse-modulated EBEP enabled us to get the high etch rate of SiO 2 of 375 nm/min without any additional bias power supply. Furthermore, the microfabrication on the core area of optical fiber was realized. These results indicate that the pulse-modulated EBEP will be a powerful tool for the application to optical MEMS process

Optical signal processing techniques and applications of optical phase modulation in high-speed communication systems

Science.gov (United States)

Deng, Ning

In recent years, optical phase modulation has attracted much research attention in the field of fiber optic communications. Compared with the traditional optical intensity-modulated signal, one of the main merits of the optical phase-modulated signal is the better transmission performance. For optical phase modulation, in spite of the comprehensive study of its transmission performance, only a little research has been carried out in terms of its functions, applications and signal processing for future optical networks. These issues are systematically investigated in this thesis. The research findings suggest that optical phase modulation and its signal processing can greatly facilitate flexible network functions and high bandwidth which can be enjoyed by end users. In the thesis, the most important physical-layer technology, signal processing and multiplexing, are investigated with optical phase-modulated signals. Novel and advantageous signal processing and multiplexing approaches are proposed and studied. Experimental investigations are also reported and discussed in the thesis. Optical time-division multiplexing and demultiplexing. With the ever-increasing demand on communication bandwidth, optical time division multiplexing (OTDM) is an effective approach to upgrade the capacity of each wavelength channel in current optical systems. OTDM multiplexing can be simply realized, however, the demultiplexing requires relatively complicated signal processing and stringent timing control, and thus hinders its practicability. To tackle this problem, in this thesis a new OTDM scheme with hybrid DPSK and OOK signals is proposed. Experimental investigation shows this scheme can greatly enhance the demultiplexing timing misalignment and improve the demultiplexing performance, and thus make OTDM more practical and cost effective. All-optical signal processing. In current and future optical communication systems and networks, the data rate per wavelength has been approaching

Glycine regulates the production of pro-inflammatory cytokines in lean and monosodium glutamate-obese mice.

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Alarcon-Aguilar, F J; Almanza-Perez, Julio; Blancas, Gerardo; Angeles, Selene; Garcia-Macedo, Rebeca; Roman, Ruben; Cruz, Miguel

2008-12-03

Fat tissue plays an important role in the regulation of inflammatory processes. Increased visceral fat has been associated with a higher production of cytokines that triggers a low-grade inflammatory response, which eventually may contribute to the development of insulin resistance. In the present study, we investigated whether glycine, an amino acid that represses the expression in vitro of pro-inflammatory cytokines in Kupffer and 3T3-L1 cells, can affect in vivo cytokine production in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Our data demonstrate that glycine treatment in lean mice suppressed TNF-alpha transcriptional expression in fat tissue, and serum protein levels of IL-6 were suppressed, while adiponectin levels were increased. In MSG/Ob mice, glycine suppressed TNF-alpha and IL-6 gene expression in fat tissue and significantly reduced protein levels of IL-6, resistin and leptin. To determine the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the modulation of this inflammatory response evoked by glycine, we examined its expression levels in fat tissue. Glycine clearly increased PPAR-gamma expression in lean mice but not in MSG/Ob mice. Finally, to identify alterations in glucose metabolism by glycine, we also examined insulin levels and other biochemical parameters during an oral glucose tolerance test. Glycine significantly reduced glucose tolerance and raised insulin levels in lean but not in obese mice. In conclusion, our findings suggest that glycine suppresses the pro-inflammatory cytokines production and increases adiponectin secretion in vivo through the activation of PPAR-gamma. Glycine might prevent insulin resistance and associated inflammatory diseases.

Rational modulation of neuronal processing with applied electric fields.

Science.gov (United States)

Bikson, Marom; Radman, Thomas; Datta, Abhishek

2006-01-01

Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.

Treadmill walking exercise modulates bone mineral status and ...

African Journals Online (AJOL)

Treadmill walking exercise modulates bone mineral status and inflammatory cytokines in obese asthmatic patients with long term intake of corticosteroids. Shehab M. Abd El-Kader, Osama H. Al-Jiffri, Eman M. Ashmawy, Riziq Allah M. Gaowgzeh ...

Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells

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Vaibhav Shinde

2016-04-01

Full Text Available Background/Aims: Embryonic developmental studies under microgravity conditions in space are very limited. To study the effects of altered gravity on the embryonic development processes we established an in vitro methodology allowing differentiation of mouse embryonic stem cells (mESCs under simulated microgravity within a fast-rotating clinostat (clinorotation and capture of microarray-based gene signatures. Methods: The differentiating mESCs were cultured in a 2D pipette clinostat. The microarray and bioinformatics tools were used to capture genes that are deregulated by simulated microgravity and their impact on developmental biological processes. Results: The data analysis demonstrated that differentiation of mESCs in pipettes for 3 days resultet to early germ layer differentiation and then to the different somatic cell types after further 7 days of differentiation in the Petri dishes. Clinorotation influences differentiation as well as non-differentiation related biological processes like cytoskeleton related 19 genes were modulated. Notably, simulated microgravity deregulated genes Cyr61, Thbs1, Parva, Dhrs3, Jun, Tpm1, Fzd2 and Dll1 are involved in heart morphogenesis as an acute response on day 3. If the stem cells were further cultivated under normal gravity conditions (1 g after clinorotation, the expression of cardiomyocytes specific genes such as Tnnt2, Rbp4, Tnni1, Csrp3, Nppb and Mybpc3 on day 10 was inhibited. This correlated well with a decreasing beating activity of the 10-days old embryoid bodies (EBs. Finally, we captured Gadd45g, Jun, Thbs1, Cyr61and Dll1 genes whose expressions were modulated by simulated microgravity and by real microgravity in various reported studies. Simulated microgravity also deregulated genes belonging to the MAP kinase and focal dhesion signal transduction pathways. Conclusion: One of the most prominent biological processes affected by simulated microgravity was the process of cardiomyogenesis. The

Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

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Gui-Lin Jin

2018-01-01

Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index.

Science.gov (United States)

van Lierop, Marie-José C; Alkema, Wynand; Laskewitz, Anke J; Dijkema, Rein; van der Maaden, Hans M; Smit, Martin J; Plate, Ralf; Conti, Paolo G M; Jans, Christan G J M; Timmers, C Marco; van Boeckel, Constant A A; Lusher, Scott J; McGuire, Ross; van Schaik, Rene C; de Vlieg, Jacob; Smeets, Ruben L; Hofstra, Claudia L; Boots, Annemieke M H; van Duin, Marcel; Ingelse, Benno A; Schoonen, Willem G E J; Grefhorst, Aldo; van Dijk, Theo H; Kuipers, Folkert; Dokter, Wim H A

2012-01-01

Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.

Criticality classification of waste receiving and processing module 2A

International Nuclear Information System (INIS)

Boothe, G.F.

1994-10-01

The purpose of this document is to evaluate the criticality potential of the Waste Receiving and Processing Module 2A (WRAP 2A) and to demonstrate that the facility is an exempt facility, under the provisions of the Nuclear Criticality Safety Manual. The WRAP 2A maximum potential transuranic (TRU) contents of feedstreams and product inventories are discussed. Total plant fissionable materials are estimated and compared with the fissionable material exempt quantity. The WRAP 2A operations and processes are also described, relative to the potential for concentrating or accumulating fissionable material within the facility

Effect of Probiotic Administration on Acute Inflammatory Pain

Directory of Open Access Journals (Sweden)

Shadnoush

2016-11-01

Full Text Available Background Acute inflammatory pain causes by direct stimulation of nociceptors and release of inflammatory mediators and cytokines. Probiotics are capable to modulate the immune system, down regulate the inflammatory mediators, and increase regulatory and anti-inflammatory cytokines. Objectives The aim of this study was to examine the effect of oral administration of probiotics on behavioral, cellular and molecular aspects of acute inflammatory pain in male rats. Methods Adult male Wistar rats (200 - 220 g were selected and randomly divided into 7 experimental groups (CFA, CFA control, CFA + vehicle (distilled water, CFA + 3 doses of probiotics, CFA + indomethacin and each group was divided into 3 subgroups based on different time points (days 0, 3, and 7 (n = 6 rats, each group. Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by a single subcutaneous injection of CFA into the rats’ left hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 (109 CFU/g was administered daily (gavage after the CFA injection. Blood samples were taken from the vessel retro-orbital corners of rat’s eyes. After behavioral and inflammatory tests, the lumbar segments of rat’s spinal cord (L1 - L5 were removed. Hyperalgesia, edema, serum TNF-α and IL-1β levels and NF-κB expression were assessed on days 0, 3, and 7 of the study. Results The results of this study showed the role of effective dose of probiotics (1/500 in reducing edema (P = 0.0009, hyperalgesia (P = 0.0002, serum levels of TNF-α (P = 0.0004 and IL-1β (P = 0.0004 and NF-κB expression (P = 0.0007 during the acute phase of inflammatory pain caused by CFA. Conclusions It seems that an effective dose of probiotics due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain in the acute phase.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

International Nuclear Information System (INIS)

Rödel, Franz; Frey, Benjamin; Manda, Katrin; Hildebrandt, Guido; Hehlgans, Stephanie; Keilholz, Ludwig; Seegenschmiedt, M. Heinrich; Gaipl, Udo S.; Rödel, Claus

2012-01-01

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Rödel, Franz [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Frey, Benjamin [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Manda, Katrin; Hildebrandt, Guido [Department of Radiotherapy and Radiation Oncology, University of Rostock, Rostock (Germany); Hehlgans, Stephanie [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany); Keilholz, Ludwig [Department of Radiotherapy, Clinical Center Bayreuth, Bayreuth (Germany); Seegenschmiedt, M. Heinrich [Strahlenzentrum Hamburg Medizinisches Versorgungszentrum, Hamburg (Germany); Gaipl, Udo S. [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen (Germany); Rödel, Claus, E-mail: franz.roedel@kgu.de [Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Johann Wolfgang-Goethe Universität, Frankfurt am Main (Germany)

2012-09-25

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

Science.gov (United States)

Martínez, Willington; Ospina, Luis Fernando; Granados, Diana; Delgado, Gabriela

2010-03-01

The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

Growth modulation of fibroblasts by chitosan-polyvinyl pyrrolidone ...

Indian Academy of Sciences (India)

elicit inflammatory reactions which severely limit their use. (Ekholm et al 1999). ... modulation by a chitosan-PVP hydrogel, and suggest that the phenomenon may prove to be of ... All other chemicals or reagents used were of analytical grade.

Apparel Research Network (ARN) Apparel Order Processing Module (AOPM). Application Program for Management of Special Measurement Clothing Orders

Science.gov (United States)

1997-09-30

Screen, abandoning changes. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official Screens The Ordering Official Screens are provided for...currendy selected Ordering Official will appear on the Ordering Official Information Screen. APPAREL ORDER PROCESSING MODULE FIELD USER MANUAL Ordering Official

Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis.

LENUS (Irish Health Repository)

Aherne, Carol M

2009-10-01

Expression of the orphan nuclear receptor NR4A2 is controlled by pro-inflammatory mediators, suggesting that NR4A2 may contribute to pathological processes in the inflammatory lesion. This study identifies the chemoattractant protein, interleukin 8 (IL-8\\/CXCL8), as a molecular target of NR4A2 in human inflammatory arthritis and examines the mechanism through which NR4A2 modulates IL-8 expression. In TNF-alpha-activated human synoviocyte cells, enhanced expression of IL-8 mRNA and protein correspond to temporal changes in NR4A2 transcription and nuclear distribution. Ectopic expression of NR4A2 leads to robust changes in endogenous IL-8 mRNA levels and co-treatment with TNF-alpha results in significant (p<0.001) secretion of IL-8 protein. Transcriptional effects of NR4A2 on the human IL-8 promoter are enhanced in the presence of TNF-alpha, suggesting molecular crosstalk between TNF-alpha signalling and NR4A2. A dominant negative IkappaB kinase antagonizes the combined effects of NR4A2 and TNF-alpha on IL-8 promoter activity. Co-expression of NR4A2 and the p65 subunit of NF-kappaB enhances IL-8 transcription and functional studies indicate that transactivation occurs independently of NR4A2 binding to DNA or heterodimerization with additional nuclear receptors. The IL-8 minimal promoter region is sufficient to support NR4A2 and NF-kappaB\\/p65 co-operative activity and NR4A2 can interact with NF-kappaB\\/p65 on a 39bp sequence within this region. In patients treated with methotrexate for active inflammatory arthritis, a reduction in NR4A2 synovial tissue levels correlate significantly (n=10, r=0.73, p=0.002) with changes in IL-8 expression. Collectively, these data delineate an important role for NR4A2 in modulating IL-8 expression and reveal novel transcriptional responses to TNF-alpha in human inflammatory joint disease.

Design of the 12-bit Delta-Sigma Modulator using SC Technique for Vibration Sensor Output Processing

Directory of Open Access Journals (Sweden)

M. Pavlik

2012-04-01

Full Text Available The work deals with the design of the 12-bit Delta-Sigma modulator using switched capacitors (SC technique. The modulator serves to vibration sensor output processing. The first part describes the Delta-Sigma modulator parameters definition. Results of the proposed topology ideal model were presented as well. Next, the Delta-Sigma modulator circuitry on the transistor level was done. The ONSemiconductor I2T100 0.7 um CMOS technology was used for design. Then, the Delta-Sigma modulator nonidealities were simulated and implemented into the MATLAB ideal model of the modulator. The model of real Delta-Sigma modulator was derived. Consequently, modulator coefficients were optimized. Finally, the corner analysis of the Delta-Sigma modulator with the optimized coefficients was simulated. The value of SNDR = 82.2 dB (ENOB = 13.4 bits was achieved.

Inflammatory and apoptotic remodeling in autonomic nervous system following myocardial infarction.

Directory of Open Access Journals (Sweden)

Chen Gao

Full Text Available Chronic myocardial infarction (MI triggers pathological remodeling in the heart and cardiac nervous system. Abnormal function of the autonomic nervous system (ANS, including stellate ganglia (SG and dorsal root ganglia (DRG contribute to increased sympathoexcitation, cardiac dysfunction and arrythmogenesis. ANS modulation is a therapeutic target for arrhythmia associated with cardiac injury. However, the molecular mechanism involved in the pathological remodeling in ANS following cardiac injury remains to be established.In this study, we performed transcriptome analysis by RNA-sequencing in thoracic SG and (T1-T4 DRG obtained from Yorkshire pigs following either acute (3 to 5 hours or chronic (8 weeks myocardial infarction. By differential expression and weighted gene co-expression network analysis (WGCNA, we identified significant transcriptome changes and specific gene modules in the ANS tissues in response to myocardial infarction at either acute or chronic phases. Both differential expressed genes and the member genes of the WGCNA gene module associated with post-infarct condition were significantly enriched for inflammatory signaling and apoptotic cell death. Targeted validation analysis supported a significant induction of inflammatory and apoptotic signal in both SG and DRG following myocardial infarction, along with cellular evidence of apoptosis induction based on TUNEL analysis. Importantly, these molecular changes were observed specifically in the thoracic segments but not in their counterparts obtained from lumbar sections.Myocardial injury leads to time-dependent global changes in gene expression in the innervating ANS. Induction of inflammatory gene expression and loss of neuron cell viability in SG and DRG are potential novel mechanisms contributing to abnormal ANS function which can promote cardiac arrhythmia and pathological remodeling in myocardium.

Selective modulation of nociceptive processing due to noise distraction.

Science.gov (United States)

Boyle, Yvonne; El-Deredy, Wael; Martínez Montes, Eduardo; Bentley, Deborah E; Jones, Anthony K P

2008-09-15

This study investigates the effects of noise distraction on the different components and sources of laser-evoked potentials (LEPs) whilst attending to either the spatial component (localisation performance task) or the affective component (unpleasantness rating task) of pain. LEPs elicited by CO2 laser stimulation of the right forearm were recorded from 64 electrodes in 18 consenting healthy volunteers. Subjects reported either pain location or unpleasantness, in the presence and absence of distraction by continuous 85 dBa white noise. Distributed sources of the LEP peaks were identified using Low Resolution Electromagnetic Tomography (LORETA). Pain unpleasantness ratings and P2 (430 ms) peak amplitude were significantly reduced by distraction during the unpleasantness task, whereas the localisation ability and the corresponding N1/N2 (310 ms) peak amplitude remained unchanged. Noise distraction (at 310 ms) reduced activation in the anterior cingulate cortex (ACC) and precuneus during attention to localisation and unpleasantness, respectively. This suggests a complimentary role for these two areas in the control of attention to pain. In contrast, activation of the occipital pole and SII were enhanced by noise during the localisation and unpleasantness task, respectively, suggesting that the presence of noise was associated with increased spatial attentional load. This study has shown selective modulation of affective pain processing by noise distraction, indicated by a reduction in the unpleasantness ratings and P2 peak amplitude and associated activity within the medial pain system. These results show that processing of the affective component of pain can be differentially modulated by top-down processes, providing a potential mechanism for therapeutic intervention.

Characterization and modulation of canine mast cell derived eicosanoids

Science.gov (United States)

Lin, Tzu-Yin; London, Cheryl A.

2013-01-01

Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl®) and deracoxib (Deramaxx®) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin®), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs. PMID:20036014

Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

LENUS (Irish Health Repository)

Bergin, David A

2012-04-01

Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

Lung inflammatory pseudo tumor

International Nuclear Information System (INIS)

Veliz, Elizabeth; Leone, Gaetano; Cano, Fernando; Sanchez, Jaime

2005-01-01

The inflammatory pseudo tumor is a non neoplastic process characterized by an irregular growth of inflammatory cells. We described the case of a 38 year-old patient, she went to our institute for a in situ cervix cancer and left lung nodule without breathing symptoms; valued by neumology who did bronchoscopy with biopsy whose result was negative for malignancy. She went to surgery in where we find intraparenquima nodule in felt lingula of approximately 4 cms, we remove it; the result was: Inflammatory pseudotumor. This pathology is a not very frequent, it can develop in diverse regions of the organism, it is frequent in lung. The image tests are not specific for the diagnose, which it is possible only with the biopsy. The treatment is the complete resection. (The author)

Harm avoidance in adolescents modulates late positive potentials during affective picture processing.

Science.gov (United States)

Zhang, Wenhai; Lu, Jiamei; Ni, Ziyin; Liu, Xia; Wang, Dahua; Shen, Jiliang

2013-08-01

Research in adults has shown that individual differences in harm avoidance (HA) modulate electrophysiological responses to affective stimuli. To determine whether HA in adolescents modulates affective information processing, we collected event-related potentials from 70 adolescents while they viewed 90 pictures from the Chinese affective picture system. Multiple regressions revealed that HA negatively predicted late positive potential (LPP) for positive pictures and positively predicted for negative pictures; however, HA did not correlate with LPP for neutral pictures. The results suggest that at the late evaluative stage, high-HA adolescents display attentional bias to negative pictures while low-HA adolescents display attentional bias to negative pictures. Moreover, these dissociable attentional patterns imply that individual differences in adolescents' HA modulate the late selective attention mechanism of affective information. Copyright © 2013. Published by Elsevier Ltd.

Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation.

Science.gov (United States)

Kourtzelis, Ioannis; Kotlabova, Klara; Lim, Jong-Hyung; Mitroulis, Ioannis; Ferreira, Anaisa; Chen, Lan-Sun; Gercken, Bettina; Steffen, Anja; Kemter, Elisabeth; Klotzsche-von Ameln, Anne; Waskow, Claudia; Hosur, Kavita; Chatzigeorgiou, Antonios; Ludwig, Barbara; Wolf, Eckhard; Hajishengallis, George; Chavakis, Triantafyllos

2016-04-01

Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation.

The role of trophic factors and inflammatory processes in physical activity-induced neuroprotection in Parkinson’s disease

Directory of Open Access Journals (Sweden)

Ewelina Pałasz

2017-01-01

Full Text Available Glial cells and neurotrophins play an important role in maintaining homeostasis of the CNS. Disturbances of their function can lead to a number of nervous system diseases, including Parkinson’s disease (PD. Current clinical studies provide evidence that moderate physical activity adapted to the health status of PD patients can support pharmacological treatment, slow down the onset of motor impairments, and extend the patients period of independence. Physical activity, by stimulating the production and release of endogenous trophic factors, prevents the neurodegeneration of dopaminergic neurons via inhibition of inflammatory processes and the reduction of oxidative stress. The aim of this study is to present the current state of knowledge for the anti-inflammatory and neuroprotective properties of physical activity as a supportive therapy in Parkinson’s disease.

Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages.

Directory of Open Access Journals (Sweden)

Wan-Kyu Ko

Full Text Available The aim of this study was to investigate the anti-inflammatory effects of Ursodeoxycholic acid (UDCA in lipopolysaccharide (LPS-stimulated RAW 264.7 macrophages.We induced an inflammatory process in RAW 264.7 macrophages using LPS. The anti-inflammatory effects of UDCA on LPS-stimulated RAW 264.7 macrophages were analyzed using nitric oxide (NO. Pro-inflammatory and anti-inflammatory cytokines were analyzed by quantitative real time polymerase chain reaction (qRT-PCR and enzyme-linked immunosorbent assay (ELISA. The phosphorylations of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and p38 in mitogen-activated protein kinase (MAPK signaling pathways and nuclear factor kappa-light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα signaling pathways were evaluated by western blot assays.UDCA decreased the LPS-stimulated release of the inflammatory mediator NO. UDCA also decreased the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α, interleukin 1-α (IL-1α, interleukin 1-β (IL-1β, and interleukin 6 (IL-6 in mRNA and protein levels. In addition, UDCA increased an anti-inflammatory cytokine interleukin 10 (IL-10 in the LPS-stimulated RAW 264.7 macrophages. UDCA inhibited the expression of inflammatory transcription factor nuclear factor kappa B (NF-κB in LPS-stimulated RAW 264.7 macrophages. Furthermore, UDCA suppressed the phosphorylation of ERK, JNK, and p38 signals related to inflammatory pathways. In addition, the phosphorylation of IκBα, the inhibitor of NF-κB, also inhibited by UDCA.UDCA inhibits the pro-inflammatory responses by LPS in RAW 264.7 macrophages. UDCA also suppresses the phosphorylation by LPS on ERK, JNK, and p38 in MAPKs and NF-κB pathway. These results suggest that UDCA can serve as a useful anti-inflammatory drug.

Systemic Inflammatory Response and Adhesion Molecules

Directory of Open Access Journals (Sweden)

L. V. Molchanova

2005-01-01

Full Text Available The lecture presents the materials of foreign studies on the mechanisms responsible for the formation of a systemic inflammatory response syndrome (SIRS. The hypotheses accounting for the occurrence of SIRS in emergencies are described. Adhesion molecules (AM and endothelial dysfunction are apparent to be involved in the inflammatory process, no matter what the causes of SIRS are. The current classification of AM and adhesion cascades with altered blood flow is presented. There are two lines in the studies of AM. One line is to measure the concentration of AM in the plasma of patients with emergencies of various etiology. The other is to study the impact of antiadhesion therapy on the alleviation of the severity of terminal state and its outcome. The studies provide evidence for that an adhesive process is a peculiar prelude to a systemic inflammatory response.

Sapucaia nuts ( Lecythis pisonis ) modulate the hepatic ...

African Journals Online (AJOL)

Sapucaia nuts ( Lecythis pisonis ) modulate the hepatic inflammatory and antioxidant metabolism activity in rats fed high-fat diets. ... that “sapucaia” could serve as a potential source of antioxidants and as a protector agent for the examined animals. Keywords: Sapucaia nuts, inflammation, oxidative stress, gene expression ...

Modulating Spatial Processes and Navigation via Transcranial Electrical Stimulation: A Mini Review

Directory of Open Access Journals (Sweden)

Tad T. Brunyé

2018-01-01

Full Text Available Transcranial electrical stimulation (tES uses low intensity current to alter neuronal activity in superficial cortical regions, and has gained popularity as a tool for modulating several aspects of perception and cognition. This mini-review article provides an overview of tES and its potential for modulating spatial processes underlying successful navigation, including spatial attention, spatial perception, mental rotation and visualization. Also considered are recent advances in empirical research and computational modeling elucidating several stable cortical-subcortical networks with dynamic involvement in spatial processing and navigation. Leveraging these advances may prove valuable for using tES, particularly transcranial direct and alternating current stimulation (tDCS/tACS, to indirectly target subcortical brain regions by altering neuronal activity in distant yet functionally connected cortical areas. We propose future research directions to leverage these advances in human neuroscience.

Project T.E.A.M. (Technical Education Advancement Modules). Advanced Statistical Process Control.

Science.gov (United States)

Dunlap, Dale

This instructional guide, one of a series developed by the Technical Education Advancement Modules (TEAM) project, is a 20-hour advanced statistical process control (SPC) and quality improvement course designed to develop the following competencies: (1) understanding quality systems; (2) knowing the process; (3) solving quality problems; and (4)…

On stochastic integration for volatility modulated Brownian-driven Volterra processes via white noise analysis

DEFF Research Database (Denmark)

E. Barndorff-Nielsen, Ole; Benth, Fred Espen; Szozda, Benedykt

This paper generalizes the integration theory for volatility modulated Brownian-driven Volterra processes onto the space G* of Potthoff-Timpel distributions. Sufficient conditions for integrability of generalized processes are given, regularity results and properties of the integral are discussed...

On stochastic integration for volatility modulated Brownian-driven Volterra processes via white noise analysis

DEFF Research Database (Denmark)

Barndorff-Nielsen, Ole E.; Benth, Fred Espen; Szozda, Benedykt

This paper generalizes the integration theory for volatility modulated Brownian-driven Volterra processes onto the space G∗ of Potthoff--Timpel distributions. Sufficient conditions for integrability of generalized processes are given, regularity results and properties of the integral are discusse...

Emotion processing in the aging brain is modulated by semantic elaboration

Science.gov (United States)

Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M.; Cabeza, Roberto

2010-01-01

The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs’ capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. FMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation. PMID:20869375

Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

NARCIS (Netherlands)

Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P.J.; Liu, Daisy J.X.; Wiele, Van de Tom; Eeckhaut, Venessa; Immerseel, Van Filip; Maele, Van de Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

2016-01-01

Background: Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear

High power n-type metal-wrap-through cells and modules using industrial processes

Energy Technology Data Exchange (ETDEWEB)

Guillevin, N.; Heurtault, B.J.B.; Geerligs, L.J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, P.O. Box 1, NL-1755 ZG Petten (Netherlands); Jianming, Wang; Ziqian, Wang; Jinye, Zhai; Zhiliang, Wan; Shuquan, Tian; Wenchao, Zhao; Zhiyan, Hu; Gaofei, Li; Bo, Yu; Jingfeng, Xiong [Yingli Green Energy Holding Co.,Ltd. 3399 North Chaoyang Avenue, Baoding (China)

2013-10-15

This paper reviews our recent progress in the development of metal wrap through (MWT) cells and modules, produced from n-type Czochralski silicon wafers. The use of n-type silicon as base material allows for high efficiencies: for front emitter-contacted industrial cells, efficiencies above 20% have been reported. N-type MWT (nMWT) cells produced by industrial process technologies allow even higher efficiency due to reduced front metal coverage. Based on the same industrial technology, the efficiency of the bifacial n-MWT cells exceeds the efficiency of the n-type front-and-rear contact and bifacial 'Pasha' technology (n-Pasha) by 0.1-0.2% absolute, with a maximum nMWT efficiency of 20.1% so far. Additionally, full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. In a direct 60-cell module performance comparison, the n-MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter-contacted n-Pasha module. Thanks to reduced resistive losses in copper circuitry on the backfoil compared to traditional tabs, the CTM FF loss of the MWT module was reduced by about 2.2%abs. compared to the tabbed front emitter contact module. A full-size module made using MWT cells of 19.6% average efficiency resulted in a power output close to 280W. Latest results of the development of the n-MWT technology at cell and module level are discussed in this paper, including a recent direct comparison run between n-MWT and n-Pasha cells and results of n-MWT cells from 140{mu}m thin mono-crystalline wafers, with only very slight loss (1% of Isc) for the thin cells. Also reverse characteristics and effects of reverse bias for extended time at cell and module level are reported, where we find a higher tolerance of MWT modules than tabbed front contact modules for hotspots.

Inflammatory injury to the neonatal brain – what can we do?

Directory of Open Access Journals (Sweden)

Noa eOfek-shlomai

2014-04-01

Full Text Available Abstract Perinatal brain damage is one of the leading causes of life long disability. This damage could be hypoxic-ischemic, inflammatory or both.This mini-review discusses different interventions aiming at minimizing inflammatory processes in the neonatal brain, both before and after insult. Current options of anti-inflammatory measures for neonates remain quite limited. We describe current anti-inflammatory intervention strategies such as avoiding perinatal infection and inflammation, and reducing exposure to inflammatory processes. We describe the known effects of anti-inflammatory drugs such as steroids, antibiotics, and indomethacin, and the possible anti-inflammatory role of other substances such as IL-1receptor antagonists, erythropoietin, caffeine, estradiol, insulin like growth factor and melatonin as well as endogenous protectors, and genetic regulation of inflammation. If successful, these may decrease mortality and long term morbidity among term and preterm infants.

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides

Science.gov (United States)

van Dijk, Albert; van Eldik, Mandy; Veldhuizen, Edwin J. A.; Tjeerdsma-van Bokhoven, Hanne L. M.; de Zoete, Marcel R.; Bikker, Floris J.; Haagsman, Henk P.

2016-01-01

Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives. PMID:26848845

Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.

Directory of Open Access Journals (Sweden)

Albert van Dijk

Full Text Available Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11 we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS. N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives.

Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

Directory of Open Access Journals (Sweden)

Gina M Coudriet

2010-11-01

Full Text Available The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR. To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS-stimulation of bone marrow derived macrophages (BMM. BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274 or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

Collagenous mucosal inflammatory diseases of the gastrointestinal tract.

Science.gov (United States)

Freeman, Hugh J

2005-07-01

Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.

Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

Science.gov (United States)

Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

2017-08-01

Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

International Nuclear Information System (INIS)

Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M

2006-01-01

In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions

A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

Energy Technology Data Exchange (ETDEWEB)

Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M [Signal and Imaging Processing and Tele-Medicine Technology Research Group, Department of Electrical and Electronics Engineering, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia)

2006-04-01

In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

Modulating Neuroinflammation to Treat Neuropsychiatric Disorders

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Franziska A. Radtke

2017-01-01

Full Text Available Neuroinflammation is recognised as one of the potential mechanisms mediating the onset of a broad range of psychiatric disorders and may contribute to nonresponsiveness to current therapies. Both preclinical and clinical studies have indicated that aberrant inflammatory responses can result in altered behavioral responses and cognitive deficits. In this review, we discuss the role of inflammation in the pathogenesis of neuropsychiatric disorders and ask the question if certain genetic copy-number variants (CNVs associated with psychiatric disorders might play a role in modulating inflammation. Furthermore, we detail some of the potential treatment strategies for psychiatric disorders that may operate by altering inflammatory responses.

PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

International Nuclear Information System (INIS)

Bernards, Nicholas

2014-01-01

The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [ 18 F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [ 18 F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [ 18 F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [ 18 F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [ 18 F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [ 18 F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author) [fr

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

Science.gov (United States)

Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin

2013-01-01

Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

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Hulya Uzkeser

2012-01-01

Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis

NARCIS (Netherlands)

Levine, Yaakov A.; Koopman, Frieda A.; Faltys, Michael; Caravaca, April; Bendele, Alison; Zitnik, Ralph; Vervoordeldonk, Margriet J.; Tak, Paul Peter

2014-01-01

The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis

Toward Eco Product Development with Qualitative and CAE Design Process - Case Study of Flame Guiding Module

Science.gov (United States)

Chen, W. L.; Chao, F. L.

2018-04-01

Sustainable products become increasingly important for company in addressing eco-performance to satisfy global environmental regulations. Case study of flame guiding module reviewed design process and concerns related to the torch design. For enhancing flame height, the torch was embedded with an airflow guidance structure. The design process and design methodologies were investigated as an eco-design case study. Combine qualitative and CAE simulation were proposed to fulfil its main and auxiliary functions including reduction of impact during use. The design guidelines help prevent mistake arrangements, CAE helps understand combustion phenomenon. The flow field simulation enables fine tune of geometric design. Functional test and measurement are carried out to confirm the product features. On Eco-performance, we choose 5 items for evaluation the status of previous and redesign module, namely function need, low impact material, few manufacturing steps, low energy consumption, and safety. The radar diagram indicates that eco-performance of redesign module is better. Life cycle assessment calculated the carbon footprint of the manufacturing and processing stage with Eco-it. By using recycled steel in the flame module, it reduces raw material stage carbon footprint significantly.

Markov-modulated infinite-server queues driven by a common background process

OpenAIRE

Mandjes , Michel; De Turck , Koen

2016-01-01

International audience; This paper studies a system with multiple infinite-server queues which are modulated by a common background process. If this background process, being modeled as a finite-state continuous-time Markov chain, is in state j, then the arrival rate into the i-th queue is λi,j, whereas the service times of customers present in this queue are exponentially distributed with mean µ −1 i,j ; at each of the individual queues all customers present are served in parallel (thus refl...

Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

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Stephanie A. Amici

2017-11-01

Full Text Available Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

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Paola Maura Tricarico

2014-04-01

Full Text Available Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD. One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3, cytokines and nitric oxide (NO]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.

Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

Science.gov (United States)

Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

2016-09-15

Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti-inflammatory

Emotion processing in the aging brain is modulated by semantic elaboration.

Science.gov (United States)

Ritchey, Maureen; Bessette-Symons, Brandy; Hayes, Scott M; Cabeza, Roberto

2011-03-01

The neural correlates of emotion processing have been shown to vary with age: older adults (OAs) exhibit increased frontal activations and, under some circumstances, decreased amygdala activations relative to young adults (YAs) during emotion processing. Some of these differences are additionally modulated by valence, with age-related biases toward positive versus negative stimuli, and are thought to depend on OAs' capacity for controlled elaboration. However, the role of semantic elaboration in mediating valence effects in the aging brain has not yet been explicitly tested. In the present study, YAs and OAs were scanned while they viewed negative, neutral, and positive pictures during either a deep, elaborative task or a shallow, perceptual task. fMRI results reveal that emotion-related activity in the amygdala is preserved in aging and insensitive to elaboration demands. This study provides novel evidence that differences in valence processing are modulated by elaboration: relative to YAs, OAs show enhanced activity in the medial prefrontal cortex (PFC) and ventrolateral PFC in response to positive versus negative stimuli, but only during elaborative processing. These positive valence effects are predicted by individual differences in executive function in OAs for the deep but not shallow task. Finally, psychophysiological interaction analyses reveal age effects on valence-dependent functional connectivity between medial PFC and ventral striatum, as well as age and task effects on medial PFC-retrosplenial cortex interactions. Altogether, these findings provide support for the hypothesis that valence shifts in the aging brain are mediated by controlled processes such as semantic elaboration, self-referential processing, and emotion regulation. Copyright © 2010 Elsevier Ltd. All rights reserved.

The NJOY nuclear data processing system: Volume 2, The NJOY, RECONR, BROADR, HEATR, and THERMR modules

International Nuclear Information System (INIS)

MacFarlane, R.E.; Muir, D.W.; Boicourt, R.M.

1982-05-01

The NJOY nuclear data processing system is a comprehensive computer code package for producing cross sections and related nuclear parameters from ENDF/B evaluated nuclear data. This volume provides detailed descriptions of the NJOY module, which contains the executive program and utility subroutines used by the other modules, and it discusses the theory and computational methods of four of the modules used for producing pointwise cross sections: RECONR, BROADR, HEATR, and THERMR

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

Science.gov (United States)

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review.

Science.gov (United States)

Melo, A D B; Silveira, H; Luciano, F B; Andrade, C; Costa, L B; Rostagno, M H

2016-01-01

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

MicroRNAs in inflammatory lung disease - master regulators or target practice?

LENUS (Irish Health Repository)

Oglesby, Irene K

2010-10-28

Abstract MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs with immense significance in numerous biological processes. When aberrantly expressed miRNAs have been shown to play a role in the pathogenesis of several disease states. Extensive research has explored miRNA involvement in the development and fate of immune cells and in both the innate and adaptive immune responses whereby strong evidence links miRNA expression to signalling pathways and receptors with critical roles in the inflammatory response such as NF-κB and the toll-like receptors, respectively. Recent studies have revealed that unique miRNA expression profiles exist in inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and lung cancer. Evaluation of the global expression of miRNAs provides a unique opportunity to identify important target gene sets regulating susceptibility and response to infection and treatment, and control of inflammation in chronic airway disorders. Over 800 human miRNAs have been discovered to date, however the biological function of the majority remains to be uncovered. Understanding the role that miRNAs play in the modulation of gene expression leading to sustained chronic pulmonary inflammation is important for the development of new therapies which focus on prevention of disease progression rather than symptom relief. Here we discuss the current understanding of miRNA involvement in innate immunity, specifically in LPS\\/TLR4 signalling and in the progression of the chronic inflammatory lung diseases cystic fibrosis, COPD and asthma. miRNA in lung cancer and IPF are also reviewed.

MicroRNAs in inflammatory lung disease--master regulators or target practice?

LENUS (Irish Health Repository)

Oglesby, Irene K

2010-01-01

MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs with immense significance in numerous biological processes. When aberrantly expressed miRNAs have been shown to play a role in the pathogenesis of several disease states. Extensive research has explored miRNA involvement in the development and fate of immune cells and in both the innate and adaptive immune responses whereby strong evidence links miRNA expression to signalling pathways and receptors with critical roles in the inflammatory response such as NF-κB and the toll-like receptors, respectively. Recent studies have revealed that unique miRNA expression profiles exist in inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and lung cancer. Evaluation of the global expression of miRNAs provides a unique opportunity to identify important target gene sets regulating susceptibility and response to infection and treatment, and control of inflammation in chronic airway disorders. Over 800 human miRNAs have been discovered to date, however the biological function of the majority remains to be uncovered. Understanding the role that miRNAs play in the modulation of gene expression leading to sustained chronic pulmonary inflammation is important for the development of new therapies which focus on prevention of disease progression rather than symptom relief. Here we discuss the current understanding of miRNA involvement in innate immunity, specifically in LPS\\/TLR4 signalling and in the progression of the chronic inflammatory lung diseases cystic fibrosis, COPD and asthma. miRNA in lung cancer and IPF are also reviewed.

Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment

Science.gov (United States)

Kim, Yong Sook; Jeong, Hye-yun; Kim, Ah Ra; Kim, Woong-Hee; Cho, Haaglim; Um, JungIn; Seo, Youngha; Kang, Wan Seok; Jin, Suk-Won; Kim, Min Chul; Kim, Yong-Chul; Jung, Da-Woon; Williams, Darren R.; Ahn, Youngkeun

2016-01-01

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI. PMID:27510556

Fermented non-digestible fraction from combined nixtamalized corn (Zea mays L.)/cooked common bean (Phaseolus vulgaris L.) chips modulate anti-inflammatory markers on RAW 264.7 macrophages.

Science.gov (United States)

Luzardo-Ocampo, I; Campos-Vega, R; Cuellar-Nuñez, M L; Vázquez-Landaverde, P A; Mojica, L; Acosta-Gallegos, J A; Loarca-Piña, G

2018-09-01

Chronic non-communicable diseases (NCDs) are low-level inflammation processes affected by several factors including diet. It has been reported that mixed whole grain and legume consumption, e.g. corn and common bean, might be a beneficial combination due to its content of bioactive compounds. A considerable amount would be retained in the non-digestible fraction (NDF), reaching the colon, where microbiota produce short-chain fatty acids (SCFAs) and phenolic compounds (PC) with known anti-inflammatory effect. The aim of this study was to estimate the anti-inflammatory potential of fermented-NDF of corn-bean chips (FNDFC) in RAW 264.7 macrophages. After 24 h, FNDFC produced SCFAs (0.156-0.222 mmol/l), inhibited nitric oxide production > 80% and H 2 O 2  > 30%, up-regulated anti-inflammatory cytokines (I-TAC, TIMP-1) > 2-fold, and produced angiostatic and protective factors against vascular/tissue damage, and amelioration of tumor necrosis factor signalling and inflammatory bowel disease. These results confirm the anti-inflammatory potential derived from healthy corn-bean chips. Copyright © 2018. Published by Elsevier Ltd.

The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease.

Science.gov (United States)

Iijima, Hideki; Shinzaki, Shinichiro; Takehara, Tetsuo

2012-11-01

This review summarizes the recent literature about the roles of vitamins D and K in bone metabolism and immunity-mediated inflammatory processes in inflammatory bowel diseases (IBDs). The levels of vitamins D and K are lower than normal in patients with IBD, especially in Crohn's disease. Although vitamins D and K are important for the maintenance of bone mineral density in non-IBD patients, an association between vitamins D or K and bone metabolism is not apparent in IBD patients. Recent studies showed that vitamins D and K are suggested to have immune-suppressive effects, both in animal models of colitis and human trials. In particular, vitamin D suppresses dendritic and T-cell functions by inhibiting the production of proinflammatory cytokines. Insufficiency of vitamin D is associated with the activated phenotype of IBD. Vitamins D and K potentially contribute to the maintenance of bone health in IBD, but this effect may be diminished by other factors such as steroid use, reduced exposure to sunlight, and inflammatory cytokines. Vitamin D and possibly vitamin K are suggested to be involved in the suppression of immune-mediated inflammation and modulation of disease activity.

Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

Science.gov (United States)

Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

2015-04-01

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

SLPI and inflammatory lung disease in females.

LENUS (Irish Health Repository)

McKiernan, Paul J

2012-02-01

During the course of certain inflammatory lung diseases, SLPI (secretory leucoprotease inhibitor) plays a number of important roles. As a serine antiprotease it functions to protect the airways from proteolytic damage due to neutrophil and other immune cell-derived serine proteases. With respect to infection it has known antimicrobial and anti-viral properties that are likely to contribute to host defence. Another of its properties is the ability to control inflammation within the lung where it can interfere with the transcriptional induction of pro-inflammatory gene expression induced by NF-kappaB (nuclear factor kappaB). Thus, factors that regulate the expression of SLPI in the airways can impact on disease severity and outcome. Gender represents once such idiosyncratic factor. In females with CF (cystic fibrosis), it is now thought that circulating oestrogen contributes, in part, to the observed gender gap whereby females have worse disease and poorer prognosis than males. Conversely, in asthma, sufferers who are females have more frequent exacerbations at times of low-circulating oestrogen. In the present paper, we discuss how SLPI participates in these events and speculate on whether regulatory mechanisms such as post-transcriptional modulation by miRNAs (microRNAs) are important in the control of SLPI expression in inflammatory lung disease.

Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: A review.

Science.gov (United States)

Zhu, Fengmei; Du, Bin; Xu, Baojun

2018-05-24

Inflammation is the first biological response of the immune system to infection, injury or irritation. Evidence suggests that the anti-inflammatory effect is mediated through the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ as well as noncytokine mediator, prostaglandin E 2 . Fruits, vegetables, and food legumes contain high levels of phytochemicals that show anti-inflammatory effect, but their mechanisms of actions have not been completely identified. The aim of this paper was to summarize the recent investigations and findings regarding in vitro and animal model studies on the anti-inflammatory effects of fruits, vegetables, and food legumes. Specific cytokines released for specific type of physiological event might shed some light on the specific use of each source of phytochemicals that can benefit to counter the inflammatory response. As natural modulators of proinflammatory gene expressions, phytochemical from fruits, vegetables, and food legumes could be incorporated into novel bioactive anti-inflammatory formulations of various nutraceuticals and pharmaceuticals. Finally, these phytochemicals are discussed as the natural promotion strategy for the improvement of human health status. The phenolics and triterpenoids in fruits and vegetables showed higher anti-inflammatory activity than other compounds. In food legumes, lectins and peptides had anti-inflammatory activity in most cases. However, there are lack of human study data on the anti-inflammatory activity of phytochemicals from fruits, vegetables, and food legumes.

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

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Giuditta Gambino

2018-05-01

Full Text Available Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

Science.gov (United States)

Gambino, Giuditta; Allegra, Mario; Sardo, Pierangelo; Attanzio, Alessandro; Tesoriere, Luisa; Livrea, Maria A.; Ferraro, Giuseppe; Carletti, Fabio

2018-01-01

Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could

Curcumin and Inflammatory Bowel Disease: Potential and Limits of Innovative Treatments

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Liza Vecchi Brumatti

2014-12-01

Full Text Available Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD, a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn’s disease (CD and Ulcerative Colitis (UC, depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB modulating immune response. This review summarizes literature data of curcumin as anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.

Towards large-scale production of solution-processed organic tandem modules based on ternary composites: Design of the intermediate layer, device optimization and laser based module processing

DEFF Research Database (Denmark)

Li, Ning; Kubis, Peter; Forberich, Karen

2014-01-01

on commercially available materials, which enhances the absorption of poly(3-hexylthiophene) (P3HT) and as a result increase the PCE of the P3HT-based large-scale OPV devices; 3. laser-based module processing, which provides an excellent processing resolution and as a result can bring the power conversion...... efficiency (PCE) of mass-produced organic photovoltaic (OPV) devices close to the highest PCE values achieved for lab-scale solar cells through a significant increase in the geometrical fill factor. We believe that the combination of the above mentioned concepts provides a clear roadmap to push OPV towards...

Effect of mineral trioxide aggregates and Portland cements on inflammatory cells.

Science.gov (United States)

Shahi, Shahriar; Rahimi, Saeed; Yavari, Hamid Reza; Mokhtari, Hadi; Roshangar, Leila; Abasi, Mehran Mesgary; Sattari, Sahar; Abdolrahimi, Majid

2010-05-01

Recently, some studies have compared mineral trioxide aggregate (MTA) with Portland cements, concluding that the principal ingredients of Portland cements are similar to those of MTA. The purpose of the present study was to evaluate the effect of gray MTA, white MTA, and gray and white Portland cements on inflammatory cells in rats. Fresh mixtures mixed with distilled water were placed in polyethylene tubes, which were implanted in the dorsal subcutaneous connective tissue of 60 Sprague-Dawley rats along with empty tubes as controls. Tissue specimens were collected after the rats were sacrificed after 7, 15, 30, 60, and 90 days. The specimens were fixed, stained, processed, and histologically evaluated under a light microscope. Inflammatory reactions were classified as grade 0: without inflammatory cells, grade I: sporadic infiltration of inflammatory cells, grade II: moderate infiltration (125 cells). Data were analyzed with the nonparametric (two factor) analysis of variance and Kruskal-Wallis H-test. All the groups showed grade III inflammation after 7 and 15 days; there was a decrease in the inflammatory process after 30, 60, and 90 days. After 90 days, gray MTA, white MTA, and control groups had grade 0 inflammatory process, but gray Portland cement and white Portland cement groups showed grade 0 to grade I inflammatory processes. MTAs were more biocompatible; however, more studies are required. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

Science.gov (United States)

Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

2014-12-01

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Validity of Scientific Based Chemistry Android Module to Empower Science Process Skills (SPS) in Solubility Equilibrium

Science.gov (United States)

Antrakusuma, B.; Masykuri, M.; Ulfa, M.

2018-04-01

Evolution of Android technology can be applied to chemistry learning, one of the complex chemistry concept was solubility equilibrium. this concept required the science process skills (SPS). This study aims to: 1) Characteristic scientific based chemistry Android module to empowering SPS, and 2) Validity of the module based on content validity and feasibility test. This research uses a Research and Development approach (RnD). Research subjects were 135 s1tudents and three teachers at three high schools in Boyolali, Central of Java. Content validity of the module was tested by seven experts using Aiken’s V technique, and the module feasibility was tested to students and teachers in each school. Characteristics of chemistry module can be accessed using the Android device. The result of validation of the module contents got V = 0.89 (Valid), and the results of the feasibility test Obtained 81.63% (by the student) and 73.98% (by the teacher) indicates this module got good criteria.

Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

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Amy Llewellyn

2017-10-01

Full Text Available There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.

Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

Science.gov (United States)

Llewellyn, Amy; Foey, Andrew

2017-01-01

There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology. PMID:29065562

Integrin-directed modulation of macrophage responses to biomaterials.

Science.gov (United States)

Zaveri, Toral D; Lewis, Jamal S; Dolgova, Natalia V; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2014-04-01

Macrophages are the primary mediator of chronic inflammatory responses to implanted biomaterials, in cases when the material is either in particulate or bulk form. Chronic inflammation limits the performance and functional life of numerous implanted medical devices, and modulating macrophage interactions with biomaterials to mitigate this response would be beneficial. The integrin family of cell surface receptors mediates cell adhesion through binding to adhesive proteins nonspecifically adsorbed onto biomaterial surfaces. In this work, the roles of integrin Mac-1 (αMβ2) and RGD-binding integrins were investigated using model systems for both particulate and bulk biomaterials. Specifically, the macrophage functions of phagocytosis and inflammatory cytokine secretion in response to a model particulate material, polystyrene microparticles were investigated. Opsonizing proteins modulated microparticle uptake, and integrin Mac-1 and RGD-binding integrins were found to control microparticle uptake in an opsonin-dependent manner. The presence of adsorbed endotoxin did not affect microparticle uptake levels, but was required for the production of inflammatory cytokines in response to microparticles. Furthermore, it was demonstrated that integrin Mac-1 and RGD-binding integrins influence the in vivo foreign body response to a bulk biomaterial, subcutaneously implanted polyethylene terephthalate. A thinner foreign body capsule was formed when integrin Mac-1 was absent (~30% thinner) or when RGD-binding integrins were blocked by controlled release of a blocking peptide (~45% thinner). These findings indicate integrin Mac-1 and RGD-binding integrins are involved and may serve as therapeutic targets to mitigate macrophage inflammatory responses to both particulate and bulk biomaterials. Copyright © 2014 Elsevier Ltd. All rights reserved.

Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.

Science.gov (United States)

Regan, Andrew D; Cohen, Rebecca D; Whittaker, Gary R

2009-02-05

Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.

Experimentally Investigating the Effect of Temperature Differences in the Particle Deposition Process on Solar Photovoltaic (PV Modules

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Yu Jiang

2016-10-01

Full Text Available This paper reports an experimental investigation of the dust particle deposition process on solar photovoltaic (PV modules with different surface temperatures by a heating plate to illustrate the effect of the temperature difference (thermophoresis between the module surface and the surrounding air on the dust accumulation process under different operating temperatures. In general, if the temperature of PV modules is increased, the energy conversion efficiency of the modules is decreased. However, in this study, it is firstly found that higher PV module surface temperature differences result in a higher energy output compared with those modules with lower temperature differences because of a reduced accumulation of dust particles. The measured deposition densities of dust particles were found to range from 0.54 g/m2 to 0.85 g/m2 under the range of experimental conditions and the output power ratios were found to increase from 0.861 to 0.965 with the increase in the temperature difference from 0 to 50 °C. The PV module with a higher temperature difference experiences a lower dust density because of the effect of the thermophoresis force arising from the temperature gradient between the module surface and its surrounding air. In addition, dust particles have a significant impact on the short circuit current, as well as the output power. However, the influence of particles on open circuit voltage can be negligible.

Modulation of Autophagy-Like Processes by Tumor Viruses

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Karl Munger

2012-06-01

Full Text Available Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.

Multi-channel logical circuit module used for high-speed, low amplitude signals processing and QDC gate signals generation

International Nuclear Information System (INIS)

Su Hong; Li Xiaogang; Zhu Haidong; Ma Xiaoli; Yin Weiwei; Li Zhuyu; Jin Genming; Wu Heyu

2001-01-01

A new kind of logical circuit will be introduced in brief. There are 16 independent channels in the module. The module receives low amplitude signals(≥40 mV), and processes them to amplify, shape, delay, sum and etc. After the processing each channel produces 2 pairs of ECL logical signal to feed the gate of QDC as the gate signal of QDC. The module consists of high-speed preamplifier unit, high-speed discriminate unit, delaying and shaping unit, summing unit and trigger display unit. The module is developed for 64 CH. 12 BIT Multi-event QDC. The impedance of QDC is 110 Ω. Each gate signal of QDC requires a pair of differential ECL level, Min. Gate width 30 ns and Max. Gate width 1 μs. It has showed that the outputs of logical circuit module satisfy the QDC requirements in experiment. The module can be used on data acquisition system to acquire thousands of data at high-speed ,high-density and multi-parameter, in heavy particle nuclear physics experiment. It also can be used to discriminate multi-coincidence events

Intestinal epithelium in inflammatory bowel disease

DEFF Research Database (Denmark)

Coskun, Mehmet

2014-01-01

The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

Modifications to the composition of the hyphal outer layer of Aspergillus fumigatus modulates HUVEC proteins related to inflammatory and stress responses.

Science.gov (United States)

Neves, Gabriela Westerlund Peixoto; Curty, Nathália de Andrade; Kubitschek-Barreira, Paula Helena; Fontaine, Thierry; Souza, Gustavo Henrique Martins Ferreira; Cunha, Marcel Lyra; Goldman, Gustavo H; Beauvais, Anne; Latgé, Jean-Paul; Lopes-Bezerra, Leila M

2017-01-16

Aspergillus fumigatus, the main etiologic agent causing invasive aspergillosis, can induce an inflammatory response and a prothrombotic phenotype upon contact with human umbilical vein endothelial cells (HUVECs). However, the fungal molecules involved in this endothelial response remain unknown. A. fumigatus hyphae produce an extracellular matrix composed of galactomannan, galactosaminogalactan and α-(1,3)-glucan. In this study, we investigated the consequences of UGM1 gene deletion in A. fumigatus, which produces a mutant with increased galactosaminogalactan production. The ∆ugm1 mutant exhibited an HUVEC-hyperadhesive phenotype and induced increased endothelial TNF-α secretion and tissue factor mRNA overexpression in this "semi-professional" immune host cell. Using a shotgun proteomics approach, we show that the A. fumigatus ∆ugm1 strain can modulate the levels of proteins in important endothelial pathways related to the inflammatory response mediated by TNF-α and to stress response pathways. Furthermore, a purified galactosaminogalactan fraction was also able to induce TNF-α secretion and the coincident HUVEC pathways regulated by the ∆ugm1 mutant, which overexpresses this component, as demonstrated by fluorescence microscopy. This work contributes new data regarding endothelial mechanisms in response to A. fumigatus infection. Invasive aspergillosis is the main opportunistic fungal infection described in neutropenic hematologic patients. One important clinical aspect of this invasive fungal infection is vascular thrombosis, which could be related, at least in part, to the activation of endothelial cells, as shown in previous reports from our group. It is known that direct contact between the A. fumigatus hyphal cell wall and the HUVEC cell surface is necessary to induce an endothelial prothrombotic phenotype and secretion of pro-inflammatory cytokines, though the cell surface components of this angioinvasive fungus that trigger this endothelial

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

Directory of Open Access Journals (Sweden)

Hwan-Jin Hwang

Full Text Available OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. METHOD AND RESULTS: Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α and monocyte chemo-attractant protein-1 (MCP-1, the crucial inflammatory molecules known to aggravate atherosclerosis. CONCLUSION: Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

Growth Hormone Resistance—Special Focus on Inflammatory Bowel Disease

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Christoffer Soendergaard

2017-05-01

Full Text Available Growth hormone (GH plays major anabolic and catabolic roles in the body and is important for regulating several aspects of growth. During an inflammatory process, cells may develop a state of GH resistance during which their response to GH stimulation is limited. In this review, we will emphasize specific mechanisms governing the formation of GH resistance in the active phase of inflammatory bowel disease. The specific molecular effects mediated through individual inflammatory mediators and processes will be highlighted to provide an overview of the transcriptional, translational and post-translational inflammation-mediated impacts on the GH receptor (GHR along with the impacts on GH-induced intracellular signaling. We also will review GH’s effects on mucosal healing and immune cells in the context of experimental colitis, human inflammatory bowel disease and in patients with short bowel syndrome.

Vacuumed gap membrane distillation (vagmed) module, multi-stage vagmed systems, and vagmed processes

KAUST Repository

Ghaffour, Noreddine

2016-06-30

Vacuumed gap membrane distillation (VAGMED) modules, and multi-stage VAGMED systems and processes using the modules are provided. In an embodiment, the membrane distillation modules (10) can comprise: a) a condenser (12) including a condensation surface (15); b) a first passageway (13) having an inlet for receiving a first feed stream (14) and an outlet through which the first stream can pass out of the first passageway, the first passageway configured to bring the first feed stream into thermal communication with the condensation surface; c) an evaporator (17) including a permeable evaporation surface allowing condensable gas to pass there through; d) a second passageway (18) having an inlet for receiving a second feed stream (19) and an outlet through which the second feed stream can pass out of the second passageway, the second passageway configured to bring the second feed stream into communication with the permeable evaporation surface; and e) an enclosure (24) providing a vacuum compartment within which the condenser, the evaporator and the first and second passageways of the module are contained.

Vacuumed gap membrane distillation (vagmed) module, multi-stage vagmed systems, and vagmed processes

KAUST Repository

Ghaffour, NorEddine; Alsaadi, Ahmad Salem; Francis, Lijo

2016-01-01

Vacuumed gap membrane distillation (VAGMED) modules, and multi-stage VAGMED systems and processes using the modules are provided. In an embodiment, the membrane distillation modules (10) can comprise: a) a condenser (12) including a condensation surface (15); b) a first passageway (13) having an inlet for receiving a first feed stream (14) and an outlet through which the first stream can pass out of the first passageway, the first passageway configured to bring the first feed stream into thermal communication with the condensation surface; c) an evaporator (17) including a permeable evaporation surface allowing condensable gas to pass there through; d) a second passageway (18) having an inlet for receiving a second feed stream (19) and an outlet through which the second feed stream can pass out of the second passageway, the second passageway configured to bring the second feed stream into communication with the permeable evaporation surface; and e) an enclosure (24) providing a vacuum compartment within which the condenser, the evaporator and the first and second passageways of the module are contained.

Sleep and inflammatory markers in different psychiatric disorders.

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Krysta, Krzysztof; Krzystanek, Marek; Bratek, Agnieszka; Krupka-Matuszczyk, Irena

2017-02-01

Many psychiatric disorders, like schizophrenia, affective disorders, addictions and different forms of dementia are associated with sleep disturbances. In the etiology and course of those diseases inflammatory processes are regarded to be an increasingly important factor. They are also a frequently discussed element of the pathology of sleep. In this literature review reports on correlations between poor sleep and inflammatory responses in various psychiatric conditions are discussed. The link between schizophrenia, affective disorders and inflammatory cytokines is a complex phenomenon, which has been already confirmed in a number of studies. However, the presence of sleep deficits in those conditions, being a common symptom of depression and psychoses, can be an additional factor having a considerable impact on the immunological processes in mental illnesses. In the analyzed data, a number of studies are presented describing the role of inflammatory markers in sleep disturbances and psychopathological symptoms of affective, psychotic, neurogenerative and other disorders. Also attention is drawn to possible implications for their treatment. Efforts to use, e.g., anti-inflammatory agents in psychiatry in the context of their impact on sleep are reported. The aspect of inflammatory markers in the role of sleep deprivation as the treatment method in major depressive disorder is also discussed. A general conclusion is drawn that the improvement of sleep quality plays a crucial role in the care for psychiatric patients.

Wound healing modulators in a tracheoplasty canine model.

Science.gov (United States)

Olmos-Zúñiga, J Raúl; Hernández-Jiménez, Claudia; Díaz-Martínez, Emmanuel; Jasso-Victoria, Rogelio; Sotres-Vega, Avelina; Gaxiola-Gaxiola, Miguel O; Villalba-Caloca, Jaime; Baltazares-Lipp, Matilde; Santillán-Doherty, Patricio; Santibáñez-Salgado, J Alfredo

2007-01-01

Postsurgical tracheal stenosis results from fibrosis formation due to ischemia. There are healing modulators, hyaluronic acid (HA) and collagen polyvinylpyrrolidone (CPVP), which reduce collagen fibers formation. Thus we can hypothesize that the topical application of one of these modulators can diminish postsurgical tracheal scarring and stenosis. The aim of this work was to evaluate the macroscopic, microscopic, and biochemical changes of tracheal healing after the application of HA or CPVP in a canine tracheoplasty model. The study design was prospective experimental investigation in a canine model. Eighteen mongrel dogs underwent three cervical tracheal rings resection and end-to-end anastomosis. They were randomized into three groups according to treatment: group I (control group) (n = 6), topical application of saline solution on tracheal anastomosis; group II (n = 6), topical application of 15 microg HA on tracheal anastomosis; and group III (n = 6), topical application of 2.5 mg CPVP on tracheal anastomosis. They were evaluated clinical, radiological and tracheoscopically during 4 weeks. They were euthanized at the end of the study time. Macroscopic, microscopic, and biochemical changes of tracheal anastomosis healing were analyzed. Collagen formation was quantified by the Woessner method. All the animals survived the surgical procedure and study period. Macroscopic, radiologic, and endoscopic studies showed that animals in group I developed tracheal stenosis, inflammation, and firm fibrous tissue formation, and histological studies also showed severe inflammatory reaction and fibrosis formation. Groups II (HA) and III (CPVP) showed well-organized thin collagen fibers with minimal inflammatory response. Biochemical evaluation revealed a higher collagen concentration in group I animals (analysis of variance [ANOVA] p anastomosis diminished the degree of stenosis and inflammatory reaction. Both modulators improved tracheal healing.

Interactions between amplitude modulation and frequency modulation processing: Effects of age and hearing loss.

Science.gov (United States)

Paraouty, Nihaad; Ewert, Stephan D; Wallaert, Nicolas; Lorenzi, Christian

2016-07-01

Frequency modulation (FM) and amplitude modulation (AM) detection thresholds were measured for a 500-Hz carrier frequency and a 5-Hz modulation rate. For AM detection, FM at the same rate as the AM was superimposed with varying FM depth. For FM detection, AM at the same rate was superimposed with varying AM depth. The target stimuli always contained both amplitude and frequency modulations, while the standard stimuli only contained the interfering modulation. Young and older normal-hearing listeners, as well as older listeners with mild-to-moderate sensorineural hearing loss were tested. For all groups, AM and FM detection thresholds were degraded in the presence of the interfering modulation. AM detection with and without interfering FM was hardly affected by either age or hearing loss. While aging had an overall detrimental effect on FM detection with and without interfering AM, there was a trend that hearing loss further impaired FM detection in the presence of AM. Several models using optimal combination of temporal-envelope cues at the outputs of off-frequency filters were tested. The interfering effects could only be predicted for hearing-impaired listeners. This indirectly supports the idea that, in addition to envelope cues resulting from FM-to-AM conversion, normal-hearing listeners use temporal fine-structure cues for FM detection.

Evaluation of the effect of Punica granatum juice and punicalagin on NFκB modulation in inflammatory bowel disease.

Science.gov (United States)

Shah, Tanmay A; Parikh, Mihir; Patel, Kirti V; Patel, Kalpana G; Joshi, Chaitanya G; Gandhi, Tejal R

2016-08-01

Punica granatum L. (Lythraceae) inhibits cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. No pharmacological work is reported on the effects of P. granatum juice on the cellular signaling pathways involved in initiation and progression of inflammation. The present investigation evaluates the effect of P. granatum juice (PJ) and purified punicalagin (PW) on nuclear factor kappa B (NFκB) and the signaling pathways leading to its expression in colon inflammation. Male Sprague-Dawley rats were divided into six groups: positive and negative control, vehicle (50 % ethanol), standard (5-ASA 100 mg/kg, p.o.), PJ (400 mg/kg, p.o.), PW (4 mg/kg, p.o.). Colitis was induced with 2,4-dinitrobenzene sulfonic acid and animals were euthanized on 18th day. Colon samples collected were subjected to various histological assessment (CMDI, DAI), and biochemical parameters (MPO, MDA, SOD, NO). Gene expression study was carried out using RT-PCR for cytokines (TNF-α, IL-1β, IL-18 and NF-κβ). Pretreatment with PJ and PW significantly (p granatum juice is more biologically active over punicalagin alone and can be potentially used for the treatment of inflammatory bowel disease.

A synthetic NCAM-derived mimetic peptide, FGL, exerts anti-inflammatory properties via IGF-1 and interferon-gamma modulation

DEFF Research Database (Denmark)

Downer, Eric J; Cowley, Thelma R; Cox, Fionnuala

2009-01-01

activation and subsequent pro-inflammatory cytokine production. The aim of the current study was to determine if FGL corrects the age-related imbalance in hippocampal levels of insulin-like growth factor-1 (IGF-1) and pro-inflammatory interferon-gamma (IFNgamma), and subsequently attenuates the glial...

Modulations of the processing of line discontinuities under selective attention conditions?

Science.gov (United States)

Giersch, Anne; Fahle, Manfred

2002-01-01

We examined whether the processing of discontinuities involved in figure-ground segmentation, like line ends, can be modulated under selective attention conditions. Subjects decided whether a gap in collinear or parallel lines was located to the right or left. Two stimuli were displayed in immediate succession. When the gaps were on the same side, reaction times (RTs) for the second stimulus increased when collinear lines followed parallel lines, or the reverse, but only when the two stimuli shared the same orientation and location. The effect did not depend on the global form of the stimuli or on the relative orientation of the gaps. A frame drawn around collinear elements affected the results, suggesting a crucial role of the "amodal" orthogonal lines produced when line ends are aligned. Including several gaps in the first stimulus also eliminated RT variations. By contrast, RT variations remained stable across several experimental blocks and were significant for interstimulus intervals from 50 to 600 msec between the two stimuli. These results are interpreted in terms of a modulation of the processing of line ends or the production of amodal lines, arising when attention is selectively drawn to a gap.

Markov modulated Poisson process models incorporating covariates for rainfall intensity.

Science.gov (United States)

Thayakaran, R; Ramesh, N I

2013-01-01

Time series of rainfall bucket tip times at the Beaufort Park station, Bracknell, in the UK are modelled by a class of Markov modulated Poisson processes (MMPP) which may be thought of as a generalization of the Poisson process. Our main focus in this paper is to investigate the effects of including covariate information into the MMPP model framework on statistical properties. In particular, we look at three types of time-varying covariates namely temperature, sea level pressure, and relative humidity that are thought to be affecting the rainfall arrival process. Maximum likelihood estimation is used to obtain the parameter estimates, and likelihood ratio tests are employed in model comparison. Simulated data from the fitted model are used to make statistical inferences about the accumulated rainfall in the discrete time interval. Variability of the daily Poisson arrival rates is studied.

Antioxidant and anti-inflammatory activities of Arbutus unedo aqueous extract

Directory of Open Access Journals (Sweden)

Idir Moualek

2016-11-01

Conclusions: A. unedo showed in vitro anti-inflammatory activity by inhibiting the heat induced albumin denaturation and red blood cells membrane stabilization. Our results show that aqueous leaf extract of A. unedo has good antioxidant activity and interesting anti-inflammatory properties. A. unedo aqueous extract can be used to prevent oxidative and inflammatory processes.

Pro- and Anti-Inflammatory Cytokines Release in Mice Injected with Crotalus durissus terrificus Venom

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A. Hernández Cruz

2008-01-01

Full Text Available The effects of Crotalus durissus terrificus venom (Cdt were analyzed with respect to the susceptibility and the inflammatory mediators in an experimental model of severe envenomation. BALB/c female mice injected intraperitoneally presented sensibility to Cdt, with changes in specific signs, blood biochemical and inflammatory mediators. The venom induced reduction of glucose and urea levels and an increment of creatinine levels in serum from mice. Significant differences were observed in the time-course of mediator levels in sera from mice injected with Cdt. The maximum levels of IL-6, NO, IL-5, TNF, IL-4 and IL-10 were observed 15 min, 30 min, 1, 2 and 4 hours post-injection, respectively. No difference was observed for levels of IFN-γ. Taken together, these data indicate that the envenomation by Cdt is regulated both pro- and anti-inflammatory cytokine responses at time-dependent manner. In serum from mice injected with Cdt at the two first hours revealed of pro-inflammatory dominance. However, with an increment of time an increase of anti-inflammatory cytokines was observed and the balance toward to anti-inflammatory dominance. In conclusion, the observation that Cdt affects the production of pro- and anti-inflammatory cytokines provides further evidence for the role played by Cdt in modulating pro/anti-inflammatory cytokine balance.

Mucosal Interactions Between Genetics, Diet And Microbiome In Inflammatory Bowel Diseases

Directory of Open Access Journals (Sweden)

Abigail Basson

2016-08-01

Full Text Available Numerous reviews have discussed gut microbiota composition changes during inflammatory bowel diseases (IBD, particularly Crohn’s disease (CD. However, most studies address the observed effects by focusing on studying the univariate connection between disease and dietary-induced alterations to gut microbiota composition. The possibility that these effects may reflect a number of other interconnected (i.e. pantropic mechanisms, activated in parallel, particularly concerning various bacterial metabolites, is in the process of been elucidated. Progress seems however hampered by various difficult-to-study factors interacting at the mucosal level. Here we highlight some of such factors that merit consideration, namely; 1 the contribution of host genetics and diet in altering gut microbiome, and in turn, the crosstalk among secondary metabolic pathways; 2 the interdependence between the amount of dietary fat, the fatty acid composition, the effects of timing and route of administration on gut microbiota community, and the impact of microbiota-derived fatty acids; 3 the effect of diet on bile acid composition, and the modulator role of bile acids on the gut microbiota; 4 the impact of endogenous and exogenous intestinal micronutrients and metabolites, and 5 the need to consider food associated toxins and chemicals which can introduce confounding immune modulating elements (e.g., antioxidant and phytochemicals in oils and proteins. These concepts, which are not mutually exclusive, are herein illustrated paying special emphasis on physiologically inter-related processes.

Ground processing of the McDonnell Douglas Payload Assist Module (PAM)

Science.gov (United States)

Bryan, C. E.; Maclean, D. A.

1985-01-01

The payload assist module (PAM) ground processing operations which have evolved since they were started in 1982 are described. The objective of the changes was to reduce the prelaunch testing of the airborne support equipment to increase the throughput of PAM systems while not compromising the reliability of the system when functioned on-orbit. The changes that resulted from the initial cargo element ground processing, the on-orbit performance of the systems, plus the postflight refurbishment and recertification of the airborne support equipment resulted in significant reductions in labor expenditures and work shifts required to prepare a PAM system for flight.

The NJOY nuclear data processing system: The MICROR module

International Nuclear Information System (INIS)

Mathews, D.R.; Stepanek, J.; Pelloni, S.; Higgs, C.E.

1984-12-01

The NJOY nuclear data processing system is a comprehensive computer code package for producing pointwise and multigroup neutron and photon cross sections and related nuclear parameters from ENDF/B-IV and V evaluated nuclear data. The MICROR overlay is a reformatting module that produces cross sections library files for the MICROX, MICROX-2 and MICROBURN postprocessor codes. Using the data on the pointwise and groupwise NJOY tapes, MICROR produces the tapes containing basic nuclear data, FDTAPE, GAR and GGTAPE used by two-region spectrum codes MICROX and MICROX-2 and by two-region spectrum burn-up code MICROBURN. (author)

Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis

Directory of Open Access Journals (Sweden)

Alessia ePiermattei

2016-05-01

Full Text Available Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2, by exploiting a previously characterized Tlr2 variant (Met82Ile. Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

Proteomic and Metabolomic Analyses Reveal Contrasting Anti-Inflammatory Effects of an Extract of Mucor Racemosus Secondary Metabolites Compared to Dexamethasone.

Science.gov (United States)

Meier, Samuel M; Muqaku, Besnik; Ullmann, Ronald; Bileck, Andrea; Kreutz, Dominique; Mader, Johanna C; Knasmüller, Siegfried; Gerner, Christopher

2015-01-01

Classical drug assays are often confined to single molecules and targeting single pathways. However, it is also desirable to investigate the effects of complex mixtures on complex systems such as living cells including the natural multitude of signalling pathways. Evidence based on herbal medicine has motivated us to investigate potential beneficial health effects of Mucor racemosus (M rac) extracts. Secondary metabolites of M rac were collected using a good-manufacturing process (GMP) approved production line and a validated manufacturing process, in order to obtain a stable product termed SyCircue (National Drug Code USA: 10424-102). Toxicological studies confirmed that this product does not contain mycotoxins and is non-genotoxic. Potential effects on inflammatory processes were investigated by treating stimulated cells with M rac extracts and the effects were compared to the standard anti-inflammatory drug dexamethasone on the levels of the proteome and metabolome. Using 2D-PAGE, slight anti-inflammatory effects were observed in primary white blood mononuclear cells, which were more pronounced in primary human umbilical vein endothelial cells (HUVECs). Proteome profiling based on nLC-MS/MS analysis of tryptic digests revealed inhibitory effects of M rac extracts on pro-inflammatory cytoplasmic mediators and secreted cytokines and chemokines in these endothelial cells. This finding was confirmed using targeted proteomics, here treatment of stimulated cells with M rac extracts down-regulated the secretion of IL-6, IL-8, CXCL5 and GROA significantly. Finally, the modulating effects of M rac on HUVECs were also confirmed on the level of the metabolome. Several metabolites displayed significant concentration changes upon treatment of inflammatory activated HUVECs with the M rac extract, including spermine and lysophosphatidylcholine acyl C18:0 and sphingomyelin C26:1, while the bulk of measured metabolites remained unaffected. Interestingly, the effects of M rac

Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

Science.gov (United States)

Donzis, Elissa J; Tronson, Natalie C

2014-11-01

This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

The human metapneumovirus matrix protein stimulates the inflammatory immune response in vitro.

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Audrey Bagnaud-Baule

Full Text Available Each year, during winter months, human Metapneumovirus (hMPV is associated with epidemics of bronchiolitis resulting in the hospitalization of many infants. Bronchiolitis is an acute illness of the lower respiratory tract with a consequent inflammation of the bronchioles. The rapid onset of inflammation suggests the innate immune response may have a role to play in the pathogenesis of this hMPV infection. Since, the matrix protein is one of the most abundant proteins in the Paramyxoviridae family virion, we hypothesized that the inflammatory modulation observed in hMPV infected patients may be partly associated with the matrix protein (M-hMPV response. By western blot analysis, we detected a soluble form of M-hMPV released from hMPV infected cell as well as from M-hMPV transfected HEK 293T cells suggesting that M-hMPV may be directly in contact with antigen presenting cells (APCs during the course of infection. Moreover, flow cytometry and confocal microscopy allowed determining that M-hMPV was taken up by dendritic cells (moDCs and macrophages inducing their activation. Furthermore, these moDCs enter into a maturation process inducing the secretion of a broad range of inflammatory cytokines when exposed to M-hMPV. Additionally, M-hMPV activated DCs were shown to stimulate IL-2 and IFN-γ production by allogeneic T lymphocytes. This M-hMPV-mediated activation and antigen presentation of APCs may in part explain the marked inflammatory immune response observed in pathology induced by hMPV in patients.

Project management plan, Waste Receiving and Processing Facility, Module 1, Project W-026

Energy Technology Data Exchange (ETDEWEB)

Starkey, J.G.

1993-05-01

The Hanford Waste Receiving and Processing Facility Module 1 Project (WRAP 1) has been established to support the retrieval and final disposal of approximately 400K grams of plutonium and quantities of hazardous components currently stored in drums at the Hanford Site.

Project management plan, Waste Receiving and Processing Facility, Module 1, Project W-026

International Nuclear Information System (INIS)

Starkey, J.G.

1993-05-01

The Hanford Waste Receiving and Processing Facility Module 1 Project (WRAP 1) has been established to support the retrieval and final disposal of approximately 400K grams of plutonium and quantities of hazardous components currently stored in drums at the Hanford Site

Detection and processing of phase modulated optical signals at 40 Gbit/s and beyond

DEFF Research Database (Denmark)

Geng, Yan

the amplitude regeneration capability based on FWM in a highly nonlinear fiber (HNLF). The first reported experimental demonstration of amplitude equalization of 40 Gbit/s RZ-DPSK signals using a 500 m long HNLF is presented. Using four possible phase levels to carry the information, DQPSK allows generation......This thesis addresses demodulation in direct detection systems and signal processing of high speed phase modulated signals in future all-optical wavelength division multiplexing (WDM) communication systems where differential phase shift keying (DPSK) or differential quadrature phase shift keying...... (DQPSK) are used to transport information. All-optical network functionalities -such as optical labeling, wavelength conversion and signal regeneration- are experimentally investigated. Direct detection of phase modulated signals requires phase-to-intensity modulation conversion in a demodulator...

The NJOY Nuclear Data Processing System: Volume 3, The GROUPR, GAMINR, and MODER modules

International Nuclear Information System (INIS)

MacFarlane, R.E.; Muir, D.W.

1987-10-01

The NJOY Nuclear Data Processing System is a comprehensive computer code package for producing pointwise and multigroup cross sections and related quantities from ENDF/B-IV, V, or VI evaluated nuclear data. A concise description of the code system and references to the ancestors of NJOY are given in Vol. 1 of this report. This volume describes the GROUPR module, which produces multigroup neutron interaction cross sections and group-to-group production cross sections for neutrons and photons; the GAMINR module, which produces multigroup photon-interaction cross sections and group-to-group matrices; and the MODER module, which converts ENDF/B and NJOY interface files back and forth between formatted (i.e., BCD, ASCII) and binary modes and performs several associated editing functions. 34 refs., 13 figs

Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators.

Science.gov (United States)

Wieseler, Julie; Ellis, Amanda; McFadden, Andrew; Stone, Kendra; Brown, Kimberley; Cady, Sara; Bastos, Leandro F; Sprunger, David; Rezvani, Niloofar; Johnson, Kirk; Rice, Kenner C; Maier, Steven F; Watkins, Linda R

2017-06-01

Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown. Here we tested if trigeminal nucleus caudalis (Sp5C) glial and/or immune cells are activated following supradural inflammatory soup, and if putative glial/immune inhibitors suppress the consequent facial allodynia. Inflammatory soup was administered via bilateral indwelling supradural catheters in freely moving rats, inducing robust and reliable facial allodynia. Gene expression for microglial/macrophage activation markers, interleukin-1β, and tumor necrosis factor-α increased following inflammatory soup along with robust expression of facial allodynia. This provided the basis for pursuing studies of the behavioral effects of 3 diverse immunomodulatory drugs on facial allodynia. Pretreatment with either of two compounds broadly used as putative glial/immune inhibitors (minocycline, ibudilast) prevented the development of facial allodynia, as did treatment after supradural inflammatory soup but prior to the expression of facial allodynia. Lastly, the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone likewise blocked development of facial allodynia after supradural inflammatory soup. Taken together, these exploratory data support that activated glia and/or immune cells may drive the development of facial allodynia in response to supradural inflammatory soup in unanesthetized male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

A shift toward T helper 2 responses and an increase in modulators of innate immunity in depressed patients treated with escitalopram.

Science.gov (United States)

Ho, Pei-Shen; Yeh, Yi-Wei; Huang, San-Yuan; Liang, Chih-Sung

2015-03-01

Depression is hypothesized to involve inflammatory processes, and identifying the key cytokines targeted by antidepressant drugs is critical for tailoring treatment to specific cases. However, investigating a limited number of cytokines at one time cannot provide a broad picture of antidepressant-associated immunomodulation. Cytokines act in a network where one could demonstrate pleiotropism, redundancy, synergy, and antagonism with other cytokine functions. This study was aimed at determining whether escitalopram functions as an anti-inflammatory agent and, if so, how it influences cytokine networks. A total of 24 healthy controls and 26 patients with clinical depression requiring inpatient treatment were recruited. A multiplex assay, an efficient tool to simultaneously measure 27 cytokines, was applied in patients with depression before and after 4-week escitalopram treatment. Healthy controls did not take escitalopram and completed cytokine analyses once. We demonstrated that escitalopram increased the levels of interleukin (IL)-1 receptor antagonist and IL-2. Moreover, escitalopram contributed to a shift toward T helper 2 responses and an increase in modulators of innate immunity, leading to a decrease of immune system activation, both innate and adaptive. We suggest that escitalopram modulates the balance of IL-1 and IL-1 receptor antagonist and improves the function and number of T regulatory cells. However, diverse conclusions could be drawn if only a few cytokines were assessed or different significance levels were used. Further studies should investigate a wide range of cytokines in a reliable and valid way, which is key to disentangling the effects of different antidepressants on inflammatory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Science.gov (United States)

Rasuo, Biljana; Hock, Jennifer Vanessa Phi; Kweider, Nisreen; Fragoulis, Athanassios; Sönmez, Tolga Taha; Jahr, Holger; Pufe, Thomas; Lippross, Sebastian

2017-01-01

The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP). The main objective of this work is to examine the influences of platelet-released growth factor (PRGF) on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes. PMID:29348703

Platelet-Released Growth Factors Modulate the Secretion of Cytokines in Synoviocytes under Inflammatory Joint Disease

Directory of Open Access Journals (Sweden)

Mersedeh Tohidnezhad

2017-01-01

Full Text Available The etiology and pathogenesis of rheumatoid arthritis (RA are marked by a complex interplay of various cell populations and is mediated by different signaling pathways. Traditionally, therapies have primarily focused on pain relief, reducing inflammation and the recovery of joint function. More recently, however, researchers have discussed the therapeutic efficacy of autologous platelet-rich plasma (PRP. The main objective of this work is to examine the influences of platelet-released growth factor (PRGF on human synoviocytes under inflammatory conditions. Additionally, it is checked to which extend treatment with platelet concentrate influences the release of cytokines form synoviocytes. For this purpose, an in vitro RA model was created by stimulating the cells with the TNF-α. The release of cytokines was measured by ELISA. The cytokine gene expression was analyzed by real-time PCR. It has been observed that the stimulation concentration of 10 ng/ml TNF-α resulted in a significantly increased endogenous secretion and gene expression of IL-6 and TNF-α. The anti-inflammatory effect of PRGF could be confirmed through significant reduction of TNF-α and IL-1β. An induced inflammatory condition seems to cause PRGF to inhibit the release of proinflammatory cytokines. Further study is required to understand the exact effect mechanism of PRGF on synoviocytes.

Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles

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Marta Machado-Pereira

2017-01-01

Full Text Available Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2. RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state, promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.

Waste Receiving and Processing Facility Module 1 Data Management System software requirements specification

International Nuclear Information System (INIS)

Rosnick, C.K.

1996-01-01

This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-0126). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

International Nuclear Information System (INIS)

Brann, E.C. II.

1994-01-01

This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

Energy Technology Data Exchange (ETDEWEB)

Brann, E.C. II

1994-09-09

This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

Effect of recombinant erythropoietin on inflammatory markers in patients with affective disorders

DEFF Research Database (Denmark)

Vinberg, Maj; Weikop, Pia; Olsen, Niels Vidiendal

2016-01-01

Aim: This study investigated the effect of repeated infusions of recombinant human erythropoietin (EPO) on markers of inflammation in patients with affective disorders and whether any changes in inflammatory markers were associated with improvements on verbal memory. Methods: In total, 83 patients......). In both sub-studies, patients were randomised in a double-blind, parallel-group design to receive eight weekly intravenous infusions of EPO (Eprex; 40,000 IU/ml) or saline (0.9% NaCl). Plasma concentrations of interleukin 6 (IL-6), interleukin 18 (IL-18) and high sensitive c-reactive protein (hsCRP) were...... and change in verbal memory. Conclusions: Repeated EPO infusions had no effect on IL-6 and IL-18 levels but produced a modest increase in hsCRP levels in patients with TRD. Changes over time in inflammatory markers were not correlated with changes in cognition suggesting that modulation of the inflammatory...

Synthesis of pro-inflammatory cytokines and adhesion molecules expression by the irradiated human monocyte/macrophage

International Nuclear Information System (INIS)

Pons, I.

1997-09-01

As lesions induced by ionizing radiations are essentially noticed in organs the functional and structural organisation of which depend on the highly proliferative stem cell pool, the author reports an in-vivo investigation of the effect of a gamma irradiation on the expression and secretion of pro-inflammatory cytokines par human monocytes/macrophages. In order to study the role of the cell environment in the radiation-induced inflammation, the author studied whether a co-stimulation of monocytes/macrophages by gamma irradiation, or the exposure of co-cultures of monocytes/macrophages and lymphocytes, could modulate the regulation of inflammatory cytokines. The author also studied the modulation of the expression of adhesion molecules mainly expressed by the monocyte/macrophage, and the membrane density of the CD14 receptor after irradiation of monocytes/macrophages during 24 hours, and of totally differentiated macrophages after seven days of culture

Self-reflection modulates the outcome evaluation process: Evidence from an ERP study.

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Zhu, Xiangru; Gu, Ruolei; Wu, Haiyan; Luo, Yuejia

2015-12-01

Recent research demonstrated structural overlap between reward and self processing, but the functional relationship that explains how self processing influences reward processing remains unclear. The present study used an experimentally constrained reflection task to investigate whether individuals' outcome evaluations in a gambling task are modulated by task-unrelated self- and other-reflection processes. The self- and other-reflection task contained descriptions of the self or others, and brain event-related potentials (ERPs) were recorded while 16 normal adults performed a gambling task. The ERP analysis focused on the feedback-related negativity (FRN) component. We found that the difference wave of FRN increased in the self-reflection condition compared with the other-reflection condition. The present findings provide direct evidence that self processing can influence reward processing. Copyright © 2015 Elsevier B.V. All rights reserved.

Close interpersonal proximity modulates visuomotor processing of object affordances in shared, social space.

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Saccone, Elizabeth J; Szpak, Ancret; Churches, Owen; Nicholls, Michael E R

2018-01-01

Research suggests that the human brain codes manipulable objects as possibilities for action, or affordances, particularly objects close to the body. Near-body space is not only a zone for body-environment interaction but also is socially relevant, as we are driven to preserve our near-body, personal space from others. The current, novel study investigated how close proximity of a stranger modulates visuomotor processing of object affordances in shared, social space. Participants performed a behavioural object recognition task both alone and with a human confederate. All object images were in participants' reachable space but appeared relatively closer to the participant or the confederate. Results revealed when participants were alone, objects in both locations produced an affordance congruency effect but when the confederate was present, only objects nearer the participant elicited the effect. Findings suggest space is divided between strangers to preserve independent near-body space boundaries, and in turn this process influences motor coding for stimuli within that social space. To demonstrate that this visuomotor modulation represents a social phenomenon, rather than a general, attentional effect, two subsequent experiments employed nonhuman joint conditions. Neither a small, Japanese, waving cat statue (Experiment 2) nor a metronome (Experiment 3) modulated the affordance effect as in Experiment 1. These findings suggest a truly social explanation of the key interaction from Experiment 1. This study represents an important step toward understanding object affordance processing in real-world, social contexts and has implications broadly across fields of social action and cognition, and body space representation.

Inflammatory single nucleotide polymorphisms and the risk of atrial fibrillation: a case control study

DEFF Research Database (Denmark)

Henningsen, Kristoffer M; Olesen, Morten S; Ravn, Lasse S

2011-01-01

Systemic inflammation is associated with atrial fibrillation (AF) and inflammatory processes are involved in the pathophysiology of AF. We hypothesized that genetic polymorphisms, which determine the rate of inflammatory cytokines, are associated with increased risk of AF.......Systemic inflammation is associated with atrial fibrillation (AF) and inflammatory processes are involved in the pathophysiology of AF. We hypothesized that genetic polymorphisms, which determine the rate of inflammatory cytokines, are associated with increased risk of AF....

Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

International Nuclear Information System (INIS)

Fernandes, Cláudia A.; Fievez, Laurence; Neyrinck, Audrey M.; Delzenne, Nathalie M.; Bureau, Fabrice; Vanbever, Rita

2012-01-01

Highlights: ► Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. ► Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. ► Cambinol decreased NF-κB activity but had no impact on p38 MAPK activation. ► Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-α) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-κB) activity and inhibitor kappa B alpha (IκBα) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.

Occurrence and fate of antibiotic, analgesic/anti-inflammatory, and antifungal compounds in five wastewater treatment processes.

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Guerra, P; Kim, M; Shah, A; Alaee, M; Smyth, S A

2014-03-01

The presence of pharmaceuticals and personal care products (PPCPs) in the aquatic environment as a result of wastewater effluent discharge is a concern in many countries. In order to expand our understanding on the occurrence and fate of PPCPs during wastewater treatment processes, 62 antibiotic, analgesic/anti-inflammatory, and antifungal compounds were analyzed in 72 liquid and 24 biosolid samples from six wastewater treatment plants (WWTPs) during the summer and winter seasons of 2010-2012. This is the first scientific study to compare five different wastewater treatment processes: facultative and aerated lagoons, chemically-enhanced primary treatment, secondary activated sludge, and advanced biological nutrient removal. PPCPs were detected in all WWTP influents at median concentrations of 1.5 to 92,000 ng/L, with no seasonal differences. PPCPs were also found in all final effluents at median levels ranging from 3.6 to 4,200 ng/L with higher values during winter (pRemoval efficiencies ranged between -450% and 120%, depending on the compound, WWTP type, and season. Mass balance showed that the fate of analgesic/anti-inflammatory compounds was predominantly biodegradation during biological treatment, while antibiotics and antifungal compounds were more likely to sorb to sludge. However, some PPCPs remained soluble and were detected in effluent samples. Overall, this study highlighted the occurrence and behavior of a large set of PPCPs and determined how their removal is affected by environmental/operational factors in different WWTPs. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Predicting speech intelligibility based on the signal-to-noise envelope power ratio after modulation-frequency selective processing

DEFF Research Database (Denmark)

Jørgensen, Søren; Dau, Torsten

2011-01-01

A model for predicting the intelligibility of processed noisy speech is proposed. The speech-based envelope power spectrum model has a similar structure as the model of Ewert and Dau [(2000). J. Acoust. Soc. Am. 108, 1181-1196], developed to account for modulation detection and masking data. The ...... process provides a key measure of speech intelligibility. © 2011 Acoustical Society of America.......A model for predicting the intelligibility of processed noisy speech is proposed. The speech-based envelope power spectrum model has a similar structure as the model of Ewert and Dau [(2000). J. Acoust. Soc. Am. 108, 1181-1196], developed to account for modulation detection and masking data....... The model estimates the speech-to-noise envelope power ratio, SNR env, at the output of a modulation filterbank and relates this metric to speech intelligibility using the concept of an ideal observer. Predictions were compared to data on the intelligibility of speech presented in stationary speech...

Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats

Directory of Open Access Journals (Sweden)

Roussel Anne M

2007-01-01

Full Text Available Abstract Background Tristetraprolin (TTP/ZFP36 family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. We hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. Methods Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3, pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2, and Elavl1/Hua/Hur and Vegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. Results Ttp and Zfp36l1 mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle. Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid extract/kg diet increased Ttp mRNA levels by 50–140% but Tnf mRNA levels decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in the muscle. Tea (2 g solid extract/kg diet increased Elavl1/Hua/Hur mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. Conclusion These results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases.

The importance of vitamin D in the pathology of bone metabolism in inflammatory bowel diseases.

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Krela-Kaźmierczak, Iwona; Szymczak, Aleksandra; Łykowska-Szuber, Liliana; Eder, Piotr; Stawczyk-Eder, Kamila; Klimczak, Katarzyna; Linke, Krzysztof; Horst-Sikorska, Wanda

2015-10-12

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

Safety Assessment of Commonly Used Nanoparticles in Biomedical Applications: Impact on Inflammatory Processes

Science.gov (United States)

Alnasser, Yossef

Nanotechnology offers great promise in the biomedical field. Current knowledge of nanoparticles' (NPs) safety and possible mechanisms of various particle types' toxicity is insufficient. The role of particle properties and the route of particles administration in toxic reactions remain unexplored. In this thesis, we aimed to inspect the interrelationship between particle size, chemical composition and toxicological effects of four candidate NPs for drug delivery systems: gold (Au), chitosan, silica, and poly (lactide-co-glycolide) (PLGA). Mice model was combined with in vitro study to explore NPs' safety. We investigated mice survival, weight, behavior, and pro-inflammatory changes. NF-kappaB induction was assessed in vitro using the Luciferase Assay System. As observed in mice, Au NPs had a higher toxicity profile at a shorter duration than the other NPs. This was significantly in concordance with pro-inflammatory changes which may be the key routes of Au NPs toxicity. Although silica NPs induced NF-kappaB, they were less toxic to the mice than Au NPs and did not lead to the pro-inflammatory changes. Chitosan NPs were toxic to the mice but failed to cause significant NF-kappaB induction and pro-inflammatory changes. These findings indicate that chitosan NPs might not have the same pathophysiologic mechanism as the Au NPs. Comparative analysis in this model demonstrated that PLGA NPs is the safest drug delivery candidate to be administered subcutaneously.

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

Science.gov (United States)

Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

Science.gov (United States)

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Evolutionary conserved mechanisms pervade structure and transcriptional modulation of allograft inflammatory factor-1 from sea anemone Anemonia viridis.

Science.gov (United States)

Cuttitta, Angela; Ragusa, Maria Antonietta; Costa, Salvatore; Bennici, Carmelo; Colombo, Paolo; Mazzola, Salvatore; Gianguzza, Fabrizio; Nicosia, Aldo

2017-08-01

Gene family encoding allograft inflammatory factor-1 (AIF-1) is well conserved among organisms; however, there is limited knowledge in lower organisms. In this study, the first AIF-1 homologue from cnidarians was identified and characterised in the sea anemone Anemonia viridis. The full-length cDNA of AvAIF-1 was of 913 bp with a 5' -untranslated region (UTR) of 148 bp, a 3'-UTR of 315 and an open reading frame (ORF) of 450 bp encoding a polypeptide with149 amino acid residues and predicted molecular weight of about 17 kDa. The predicted protein possesses evolutionary conserved EF hand Ca 2+ binding motifs, post-transcriptional modification sites and a 3D structure which can be superimposed with human members of AIF-1 family. The AvAIF-1 transcript was constitutively expressed in all tested tissues of unchallenged sea anemone, suggesting that AvAIF-1 could serve as a general protective factor under normal physiological conditions. Moreover, we profiled the transcriptional activation of AvAIF-1 after challenges with different abiotic/biotic stresses showing induction by warming conditions, heavy metals exposure and immune stimulation. Thus, mechanisms associated to inflammation and immune challenges up-regulated AvAIF-1 mRNA levels. Our results suggest its involvement in the inflammatory processes and immune response of A. viridis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of glutamine, taurine and their association on inflammatory pathway markers in macrophages.

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Sartori, Talita; Galvão Dos Santos, Guilherme; Nogueira-Pedro, Amanda; Makiyama, Edson; Rogero, Marcelo Macedo; Borelli, Primavera; Fock, Ricardo Ambrósio

2018-06-01

The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated in the presence of glutamine and taurine and proliferation rates, cell viability, cell cycle phases, IL-1α, IL-6, IL-10 and TNF-α as well as H 2 O 2 production and the expression of the transcription factor, NFκB, and its inhibitor, IκBα, were evaluated. Our results showed an increase in viable cells and increased proliferation rates of cells treated with glutamine concentrations over 2 mM, as well as cells treated with both glutamine and taurine. The cell cycle showed a higher percentage of cells in the phases S, G2 and M when they were treated with 2 or 10 mM glutamine, or with glutamine and taurine in cells stimulated with lipopolysaccharide. The pNFκB/NFκB showed reduced ratio expression when cells were treated with 10 mM of glutamine or with glutamine in association with taurine. These conditions also resulted in reduced TNF-α, IL-1α and H 2 O 2 production, and higher production of IL-10. These findings demonstrate that glutamine and taurine are able to modulate macrophages inflammatory pathways, and that taurine can potentiate the effects of glutamine, illustrating their immunomodulatory properties.

Cholinergic enhancement modulates neural correlates of selective attention and emotional processing.

Science.gov (United States)

Bentley, Paul; Vuilleumier, Patrik; Thiel, Christiane M; Driver, Jon; Dolan, Raymond J

2003-09-01

Neocortical cholinergic afferents are proposed to influence both selective attention and emotional processing. In a study of healthy adults we used event-related fMRI while orthogonally manipulating attention and emotionality to examine regions showing effects of cholinergic modulation by the anticholinesterase physostigmine. Either face or house pictures appeared at task-relevant locations, with the alternative picture type at irrelevant locations. Faces had either neutral or fearful expressions. Physostigmine increased relative activity within the anterior fusiform gyrus for faces at attended, versus unattended, locations, but decreased relative activity within the posterolateral occipital cortex for houses in attended, versus unattended, locations. A similar pattern of regional differences in the effect of physostigmine on cue-evoked responses was also present in the absence of stimuli. Cholinergic enhancement augmented the relative neuronal response within the middle fusiform gyrus to fearful faces, whether at attended or unattended locations. By contrast, physostigmine influenced responses in the orbitofrontal, intraparietal and cingulate cortices to fearful faces when faces occupied task-irrelevant locations. These findings suggest that acetylcholine may modulate both selective attention and emotional processes through independent, region-specific effects within the extrastriate cortex. Furthermore, cholinergic inputs to the frontoparietal cortex may influence the allocation of attention to emotional information.

Functional Role of Milk Fat Globule-Epidermal Growth Factor VIII in Macrophage-Mediated Inflammatory Responses and Inflammatory/Autoimmune Diseases

Directory of Open Access Journals (Sweden)

Young-Su Yi

2016-01-01

Full Text Available Inflammation involves a series of complex biological processes mediated by innate immunity for host defense against pathogen infection. Chronic inflammation is considered to be one of the major causes of serious diseases, including a number of autoimmune/inflammatory diseases, cancers, cardiovascular diseases, and neurological diseases. Milk fat globule-epidermal growth factor 8 (MFG-E8 is a secreted protein found in vertebrates and was initially discovered as a critical component of the milk fat globule. Previously, a number of studies have reported that MFG-E8 contributes to various biological functions including the phagocytic removal of damaged and apoptotic cells from tissues, the induction of VEGF-mediated neovascularization, the maintenance of intestinal epithelial homeostasis, and the promotion of mucosal healing. Recently, emerging studies have reported that MFG-E8 plays a role in inflammatory responses and inflammatory/autoimmune diseases. This review describes the characteristics of MFG-E8-mediated signaling pathways, summarizes recent findings supporting the roles of MFG-E8 in inflammatory responses and inflammatory/autoimmune diseases, and discusses MFG-E8 targeting as a potential therapeutic strategy for the development of anti-inflammatory/autoimmune disease drugs.

The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis.

Science.gov (United States)

Jackson, J K; Higo, T; Hunter, W L; Burt, H M

2006-04-01

Curcumin and quercetin are antioxidant molecules with anti-proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these agents using four assays of inflammatory aspects of arthritis. Crystal-induced neutrophil activation was measured by luminol-dependent chemiluminescence. Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of the matrix metalloproteinases collagenase and stromelysin was measured by Northern Blot analysis. Angiogenesis was measured using the chorioallantoic membrane of the chick embryo. Both agents inhibited neutrophil activation, synoviocyte proliferation and angiogenesis. Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay. These studies suggest that curcumin and to a lesser extent quercetin may offer therapeutic potential for the treatment of crystal-induced arthritis or rheumatoid arthritis.

Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

International Nuclear Information System (INIS)

Arab, Hany H.; El-Sawalhi, Maha M.

2013-01-01

Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE 2 and LTB 4 ) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of arthritic rats

Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

Energy Technology Data Exchange (ETDEWEB)

Arab, Hany H., E-mail: hany_h_arab@yahoo.com [Biochemistry Division, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt); El-Sawalhi, Maha M. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt)

2013-04-15

Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

Inhibitory effects of bee venom on mast cell-mediated allergic inflammatory responses.

Science.gov (United States)

Kang, Yun-Mi; Chung, Kyung-Sook; Kook, In-Hoon; Kook, Yoon-Bum; Bae, Hyunsu; Lee, Minho; An, Hyo-Jin

2018-06-01

Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune‑associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC‑1 cells were treated with BV prior to stimulation with phorbol‑12‑myristate 13‑acetate plus calcium ionophore A23187 (PMACI). The production of allergy‑associated pro‑inflammatory mediators was examined, and the underlying mechanisms were investigated. Furthermore, to investigate whether BV exhibits anti‑inflammatory effects associated with anti‑allergic effects in vivo, a compound 48/80‑induced anaphylaxis model was used. BV inhibited histamine release, mRNA expression and production of cytokines in the PMACI‑stimulated HMC‑1 cells. Furthermore, the inhibitory effects of BV on mitogen‑activated protein kinase (MAPK), MAPK kinase, signal transducer and activator of transcription 3 (STAT3) and Akt were demonstrated. The present study also investigated the ability of BV to inhibit compound 48/80‑induced systemic anaphylaxis in vivo. BV protected the mice against compound 48/80‑induced anaphylactic‑associated mortality. Furthermore, BV suppressed the mRNA expression levels of pro‑inflammatory cytokines, and suppressed the activation of MAPK and STAT3 in this model. These results provide novel insights into the possible role of BV as a modulator for mast cell‑mediated allergic inflammatory disorders.

Waste Receiving and Processing Facility, Module 1: Volume 7, Project design criteria

International Nuclear Information System (INIS)

1992-03-01

This Project Design Criteria document for the WRAP facility at the Hanford Site is presented within a systems format. The WRAP Module 1 facility has been categorized into eight (8) engineering systems for design purposes. These systems include: receiving, shipping and storage, nondestructive assay/nondestructive examination (NDA/NDE), waste process, internal transportation, building, heating ventilation and air conditioning (HVAC), process control, and utilities. Within each system section of this document, the system-specific requirements are identified. The scope of the system is defined, the design goals are identified and the functional requirements are detailed

Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

Science.gov (United States)

Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

2011-01-01

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

Modulation of human time processing by subthalamic deep brain stimulation.

Science.gov (United States)

Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

2011-01-01

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

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Ji Wang

2016-06-01

Full Text Available Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

Anti-inflammatory effects of chronic aspirin on brain arachidonic acid metabolites

Science.gov (United States)

Basselin, Mireille; Ramadan, Epolia; Chen, Mei; Rapoport, Stanley I.

2010-01-01

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) to lipoxin A4 (LXA4) and 15-epi-LXA4. However it is unknown whether chronic therapeutic doses of ASA are anti-inflammatory in the brain. We hypothesized that ASA would dampen increases in brain concentrations of AA metabolites in a rat model of neuroinflammation, produced by a 6-day intracerebroventricular infusion of bacterial lipopolysaccharide (LPS). In rats infused with LPS (0.5 ng/h) and given ASA-free water to drink, concentrations in high-energy microwaved brain of PGE2, TXB2 and leukotriene B4 (LTB4) were elevated. In rats infused with artificial cerebrospinal fluid, 6 weeks of treatment with a low (10 mg/kg/day) or high (100 mg/kg/day) ASA dose in drinking water decreased brain PGE2, but increased LTB4, LXA4 and 15-epi-LXA4 concentrations. Both doses attenuated the LPS effects on PGE2, and TXB2. The increments in LXA4 and 15-epi-LXA4 caused by high-dose ASA were significantly greater in LPS-infused rats. The ability of ASA to increase anti-inflammatory LXA4 and 15-epi-LXA4 and reduce pro-inflammatory PGE2 and TXB2 suggests considering aspirin further for treating clinical neuroinflammation. PMID:20981485

Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines

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Sanaa M. Abd El-Twab

2016-08-01

Full Text Available Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. It has also been shown to reduce suicidal risk and short term mortality. Few experimental studies have demonstrated the thyroid toxicity caused by lithium as well as the possible protective effect of curcumin. Twenty four male albino rats were divided into three groups; group I (control group, group II received lithium carbonate daily for 6 weeks and group III received the same dose of lithium carbonate as group II concomitantly with curcumin for 6 weeks. The specimens were prepared for histopathological, immunohistochemical and biochemical examination. Lithium-induced thyroid dysfunction evidenced by the histopathological and immunohistochemical changes represented by detached cells and vacuolated cytoplasm of some follicular cells and highly significant increase in positive immunostained of thyroglobulin and caspase-3 respectively. Moreover, a significant decrease in serum free triiodothyonine (FT3, free thyroxine (FT4 concomitant with significantly increased thyroid stimulating hormone (TSH and pro-inflammatory cytokines, and thyroid lipid peroxidation (MDA and nitric oxide (NO levels. Curcumin counteracted lithium-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines and improvements in the degenerative changes of the thyroid gland. In conclusion, the present study provides evidence that curcumin exerts thyroprotective effects against lithium carbonate mediated by its antioxidant, anti-inflammatory and anti-apoptotic effect as indicated by caspase-3. This report also confers that the use of this drug should be justified for long treatment under direct medical supervision.

Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds.

Science.gov (United States)

Tezuka, Hiroyuki; Imai, Shinjiro

2015-01-01

Inflammation is an immune response against both internal and external antigens in organisms, particularly in mammals, and includes both uncontrolled chronic and low-grade inflammations. Uncontrolled chronic inflammation often leads to severe diseases such as vascular disease, arthritis, cancer, diabete, allergy, and autoimmunity. On the other hand, low-grade inflammation is recognized as a relationship between obesity and risk of metabolic syndrome. Elevated production of pro-inflammatory cytokines and mediators is commonly observed in patients with uncontrolled or low-grade inflammation-associated diseases. Plants have been generated phytochemicals to overcome inflammations and infections through evolution. Phytochemicals belong to alkaloids, polyphenols, flavonoids, coumarins, and terpenoids. The consumption of soybeans plays a role in immune modulation through their components such as isoflavones, saponins, and anthocyanins. Recently, it was reported that the application of phytochemicals into patients with inflammatory diseases improves their symptoms. Therefore, it is important to identify novel phytochemicals with immunomodulatory activities. This review introduces and discusses recent advances and patents regarding soybean or processed soy food compounds which exhibit immunomodulatory activity in immune diseases, particularly allergy, by mediating the suppression of inflammatory pathways.

Corticofugal modulation of initial neural processing of sound information from the ipsilateral ear in the mouse.

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Xiuping Liu

2010-11-01

Full Text Available Cortical neurons implement a high frequency-specific modulation of subcortical nuclei that includes the cochlear nucleus. Anatomical studies show that corticofugal fibers terminating in the auditory thalamus and midbrain are mostly ipsilateral. Differently, corticofugal fibers terminating in the cochlear nucleus are bilateral, which fits to the needs of binaural hearing that improves hearing quality. This leads to our hypothesis that corticofugal modulation of initial neural processing of sound information from the contralateral and ipsilateral ears could be equivalent or coordinated at the first sound processing level.With the focal electrical stimulation of the auditory cortex and single unit recording, this study examined corticofugal modulation of the ipsilateral cochlear nucleus. The same methods and procedures as described in our previous study of corticofugal modulation of contralateral cochlear nucleus were employed simply for comparison. We found that focal electrical stimulation of cortical neurons induced substantial changes in the response magnitude, response latency and receptive field of ipsilateral cochlear nucleus neurons. Cortical stimulation facilitated auditory response and shortened the response latency of physiologically matched neurons whereas it inhibited auditory response and lengthened the response latency of unmatched neurons. Finally, cortical stimulation shifted the best frequencies of cochlear neurons towards those of stimulated cortical neurons.Our data suggest that cortical neurons enable a high frequency-specific remodelling of sound information processing in the ipsilateral cochlear nucleus in the same manner as that in the contralateral cochlear nucleus.

NJOY nuclear data processing system. Volume IV. The ERRORR and COVR modules

International Nuclear Information System (INIS)

Muir, D.W.; MacFarlane, R.E.

1985-12-01

The NJOY nuclear data processing system is a comprehensive computer code package for producing cross sections and related nuclear parameters from ENDF/B evaluated nuclear data. This volume provides detailed descriptions of the NJOY modules ERRORR and COVR, which are concerned with the covariances (uncertainties and correlations) of multigroup cross sections and fission neutron yield (anti nu) values. 17 refs

Natural Modulators of Amyloid-Beta Precursor Protein Processing

Science.gov (United States)

Zhang, Can; Tanzi, Rudolph E.

2013-01-01

Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the primary cause of dementia, with no cure currently available. The pathogenesis of AD is believed to be primarily driven by Aβ, the principal component of senile plaques. Aβ is an ~4 kDa peptide generated from the amyloid-β precursor protein (APP) through proteolytic secretases. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have a long history alleviating common clinical disorders, including dementia. However, the cell/molecular pathways mediated by these natural products are largely unknown until recently when the underlying molecular mechanisms of the disorders begin to be elucidated. Here, the mechanisms with which natural products modulate the pathogenesis of AD are discussed, in particular, by focusing on their roles in the processing of APP. PMID:22998566

WISP3 (CCN6 Is a Secreted Tumor-Suppressor Protein that Modulates IGF Signaling in Inflammatory Breast Cancer

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Celina G. Kleer

2004-03-01

Full Text Available Inflammatory breast cancer (IBC is the most lethal form of locally advanced breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that belongs to the CCN family. It contains a signal peptide at the N-terminus and four highly conserved motifs. Here, for the first time, we investigate the function of WISP3 protein in relationship to its structural features. We found that WISP3 is secreted into the conditioned media and into the lumens of normal breast ducts. Once secreted, WISP3 was able to decrease, directly or through induction of other molecule(s, the IGF-1-induced activation of the IGF-IR, and two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC cells. Furthermore, WISP3 containing conditioned media decreased the growth rate of SUM149 cells. This work sheds light into the mechanism of WISP3 function by demonstrating that it is secreted and that, once in the extracellular media, it induces a series of molecular events that leads to modulation of IGF-IR signaling pathways and cellular growth in IBC cells.

Inflammatory myofibroblastic tumor

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Sangeeta Palaskar

2011-01-01

Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

A High Density Low Cost Digital Signal Processing Module for Large Scale Radiation Detectors

International Nuclear Information System (INIS)

Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson T.; Grudberg, Peter M.; Warburton, William K.

2013-06-01

A 32-channel digital spectrometer PIXIE-32 is being developed for nuclear physics or other radiation detection applications requiring digital signal processing with large number of channels at relatively low cost. A single PIXIE-32 provides spectrometry and waveform acquisition for 32 input signals per module whereas multiple modules can be combined into larger systems. It is based on the PCI Express standard which allows data transfer rates to the host computer of up to 800 MB/s. Each of the 32 channels in a PIXIE-32 module accepts signals directly from a detector preamplifier or photomultiplier. Digitally controlled offsets can be individually adjusted for each channel. Signals are digitized in 12-bit, 50 MHz multi-channel ADCs. Triggering, pile-up inspection and filtering of the data stream are performed in real time, and pulse heights and other event data are calculated on an event-by event basis. The hardware architecture, internal and external triggering features, and the spectrometry and waveform acquisition capability of the PIXIE- 32 as well as its capability to distribute clock and triggers among multiple modules, are presented. (authors)

Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands.

Science.gov (United States)

Kaur, Gaganpreet; Kaur, Maninder; Silakari, Om

2014-01-01

The recent research area endeavors to discover ultimate multi-target ligands, an increasingly feasible and attractive alternative to existing mono-targeted drugs for treatment of complex, multi-factorial inflammation process which underlays plethora of debilitated health conditions. In order to improvise this option, exploration of relevant chemical core scaffold will be an utmost need. Privileged benzimidazole scaffold being historically versatile structural motif could offer a viable starting point in the search for novel multi-target ligands against multi-factorial inflammation process since, when appropriately substituted, it can selectively modulate diverse receptors, pathways and enzymes associated with the pathogenesis of inflammation. Despite this remarkable capability, the multi-target capacity of the benzimidazole scaffold remains largely unexploited. With this in focus, the present review article attempts to provide synopsis of published research to exemplify the valuable use of benzimidazole nucleus and focus on their suitability as starting scaffold to develop multi-targeted anti-inflammatory ligands.

Conceptual design for the Waste Receiving and Processing facility Module 2A

International Nuclear Information System (INIS)

1992-07-01

This is part of a Conceptual Design Report (CDR) for the Waste Receiving and Processing (WRAP) Module 2A facility at the Hanford Reservation. The mission of the facility is to receive, process, package, certify, and ship for permanent burial at the Hanford site disposal facilities those contact handled (CH) low-level radioactive mixed wastes (LLMW) that: (1) are currently in retrievable storage at the Hanford Central Waste Complex (HCWC) awaiting a treatment capability to permit permanent disposal compliant with the Land Disposal Restrictions and; (2) are forecasted to be generated over the next 30 years. The primary sources of waste to be treated include the currently stored waste from the 183-H solar basin evaporators, secondary solids from the future Hanford site liquid effluent treatment facilities, thermal treatment facility ash, other WRAP modules, and other miscellaneous waste from storage and onsite/offsite waste generators consisting of compactible and non-compactible solids, contaminated soils, and metals. This volume, Volume III is a compilation of the outline specifications that will form the basis for development of the Title design construction specifications. This volume contains abbreviated CSI outline specifications for equipment as well as non-equipment related construction and material items. For process and mechanical equipment, data sheets are provided with the specifications which indicate the equipment overall design parameters. This volume also includes a major equipment list

Anti-Inflammatory Effect of Dialyzable Leukocyte Extract in Autoimmune Prostatitis: Evaluation in Animal Model

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Carlos Pérez-Alvarado

2017-01-01

Full Text Available Objective. To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS. Methods. Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF-α, IFN-γ, IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone. Results. Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups. Conclusion. DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP.

Development of Automated Production Line Processes for Solar Brightfield Modules: Final Annual Technical Progress Report, 1 July 2004 -- 15 October 2005

Energy Technology Data Exchange (ETDEWEB)

Nowlan, M. J.; Murach, J. M.; Sutherland, S. F.; Miller, D. C.; Moore S. B.; Hogan, S. J.

2006-08-01

Spire Corporation is addressing the Photovoltaic Manufacturing R&D project goals of improving photovoltaic (PV) manufacturing processes and products while reducing costs and providing a technology foundation that supports significant manufacturing scale-up. To accomplish this, we are focusing our efforts on the design of a large-area utility-scale module and the development of the necessary manufacturing techniques and equipment to manufacture such a module in a high-volume production environment. A three-phase program is under way for developing and demonstrating new automated systems for fabricating very large PV modules ideal for use in multi-megawatt grid-connected applications. We designed a large-area (1.57 m x 3.68 m) 800-W module, and we are developing associated module production equipment that will minimize the total installed system cost for utility-scale PV arrays. Activities in Phase 2 focused on the development of automation for module materials lay-up, cell string busing, and module lamination; enhancements to the cell stringing and lamination processes; and performance testing of large-area modules.

Macrophage elastase (MMP-12: a pro-inflammatory mediator?

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Soazig Nénan

2005-03-01

Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

A Module Experimental Process System Development Unit (MEPSDU). [flat plate solar arrays

Science.gov (United States)

1981-01-01

The development of a cost effective process sequence that has the potential for the production of flat plate photovoltaic modules which meet the price goal in 1986 of 70 cents or less per Watt peak is described. The major accomplishments include (1) an improved AR coating technique; (2) the use of sand blast back clean-up to reduce clean up costs and to allow much of the Al paste to serve as a back conductor; and (3) the development of wave soldering for use with solar cells. Cells were processed to evaluate different process steps, a cell and minimodule test plan was prepared and data were collected for preliminary Samics cost analysis.

Inflammation in Depression and the Potential for Anti-Inflammatory Treatment

DEFF Research Database (Denmark)

Kohler, Ole; Krogh, Jesper; Mors, Ole

2016-01-01

Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular......, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity...... of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we review...

Anti-Inflammatory and Antiarthritic Activity of Anthraquinone Derivatives in Rodents

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Ajay D. Kshirsagar

2014-01-01

Full Text Available Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2 in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund’s adjuvant induced arthritis in rats. The AE (aloe emodin and AEC significantly P<0.001 reduced carrageenan induced paw edema at 50 and 75 mg/kg. Complete Freund’s adjuvant induced arthritis model showed significant P<0.001 decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10 mg/kg showed significant P<0.001 inhibition in inflammation and arthritis.

CCS mRNA transcripts and serum CCS protein as copper marker in adults suffering inflammatory processes.

Science.gov (United States)

Araya, Magdalena; Gutiérrez, Ricardo; Arredondo, Miguel

2014-08-01

The chaperone to Zn-Cu superoxide dismutase (CCS) has been postulated as a candidate copper indicator, changing in a consistent manner in induced and recovered copper deficiency, in experimental cell and animal models. In real life people have various conditions that may modify molecules acting as acute phase proteins, such as serum ceruloplasmin and copper concentration and could alter CCS responses. With the hypothesis that CCS mRNA transcripts and protein would be different in individuals suffering inflammatory processes in comparison to healthy individuals, we assessed adult individuals who, although not ill had conditions known to induce variable degrees of inflammation. Screening of 600 adults resulted in two study groups, formed on the basis of their clinical history and levels of serum C reactive protein (CRP): Group 1 (n = 61, mean (range) CRP = 0.9 (0.3-2.0 mg/dL) and Group 2 (n = 150, mean (range) CRP = 6.1 (4.3-8.7 mg/dL). Results showed that mRNA transcripts relative abundance was not different for CCS, MTIIA, TNF-alpha and Cu-Zn-SOD by group (p > 0.05, one way Anova), nor between sexes (p > 0.05, one way Anova). Distribution of CCS mRNA transcripts and CCS protein in serum did not show any differences or trends. Results disproved our hypothesis that CCS abundance of transcripts and CCS protein would be different in individuals suffering inflammatory processes, adding further support to the idea that CCS may be a copper marker.

Synaptic Homeostasis and Allostasis in the Dentate Gyrus Caused by Inflammatory and Neuropathic Pain Conditions

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Rui-Rui Wang

2018-01-01

Full Text Available It has been generally accepted that pain can cause imbalance between excitation and inhibition (homeostasis at the synaptic level. However, it remains poorly understood how this imbalance (allostasis develops in the CNS under different pain conditions. Here, we analyzed the changes in both excitatory and inhibitory synaptic transmission and modulation of the dentate gyrus (DG under two pain conditions with different etiology and duration. First, it was revealed that the functions of the input-output (I/O curves for evoked excitatory postsynaptic currents (eEPSCs following the perforant path (PP stimulation were gained under both acute inflammatory and chronic neuropathic pain conditions relative to the controls. However, the functions of I/O curves for the PP-evoked inhibitory postsynaptic currents (eIPSCs differed between the two conditions, namely it was greatly gained under inflammatory condition, but was reduced under neuropathic condition in reverse. Second, both the frequency and amplitude of miniature IPSCs (mIPSCs were increased under inflammatory condition, however a decrease in frequency of mIPSCs was observed under neuropathic condition. Finally, the spike discharge of the DG granule cells in response to current injection was significantly increased by neuropathic pain condition, however, no different change was found between inflammatory pain condition and the control. These results provide another line of evidence showing homeostatic and allostatic modulation of excitatory synaptic transmission by inhibitory controls under different pathological pain conditions, hence implicating use of different therapeutic approaches to maintain the homeostasis between excitation and inhibition while treating different conditions of pathological pain.