scholarly journals Short term supplementation of celecoxib shifted butyrate production on a simulated model of the gut microbial ecosystem and ameliorated in vitro inflammation

2019 ◽  
Author(s):  
Emma Hernandez-Sanabria ◽  
Evelien Heiremans ◽  
Marta Calatayud Arroyo ◽  
Ruben Props ◽  
Laurent Leclercq ◽  
...  
Keyword(s):  
Community Composition ◽  
Metabolic Activity ◽  
Bacterial Community Composition ◽  
Dependent Manner ◽  
Short Term ◽  
Acetyl Coa ◽  
Host Interactions ◽  
Cox 2 ◽  
Butyrate Production

ABSTRACTCelecoxib has been demonstrated effective in the prevention and treatment of chronic inflammatory disorders through inhibition of altered cyclooxygenase-2 (COX-2) pathways. Despite the benefits for preventing colorectal cancer (CRC), continuous administration may increase risk of cardiovascular events. Understanding microbiome-drug-host interactions is fundamental for improving drug disposition and safety responses of colon-targeted formulations, but little information is available on the bidirectional interaction between individual microbiomes and celecoxib. Here we conducted in vitro batch incubations of faecal microbiota to evaluate the short-term impact of celecoxib on activity and composition of colon bacterial communities. Celecoxib-exposed microbiota shifted metabolic activity and community composition, whereas total transcriptionally active bacterial population was not significantly changed. Butyrate production decreased by 50% in a donor-dependent manner, suggesting that celecoxib impacts in vitro fermentation. Microbiota-derived acetate has been associated with inhibition of cancer markers and our results suggest uptake of acetate for bacterial functions when celecoxib was supplied, which potentially favoured bacterial competition for acetyl-CoA. We further assessed whether colon microbiota modulates anti-inflammatory efficacy of celecoxib using both a simplified inflammation model, and a novel in vitro simulation of the enterohepatic metabolism. Celecoxib was responsible for only 5% of the variance in bacterial community composition but celecoxib-exposed microbiota preserved barrier function and decreased concentrations of IL-8 and CXCL16 in a donor-dependent manner in our two cell models simulating inflammatory milieu in the gut. Our results suggest that celecoxib-microbiome-host interactions may not only elicit adaptations in community composition but also in microbiota functionality and may need to be considered for guaranteeing efficient COX-2 inhibition.IMPORTANCEAs inter-individual changes in the microbiome composition and functionality may be a confounder on pharmacotherapy, we obtained mechanistic understanding on how short-term celecoxib exposure impacts the functional activities of colon communities. Celecoxib-exposed microbiota shifted metabolic activity without impacting numbers of total active bacteria, but only community composition. Thus, increased relative abundance of particular genera during celecoxib supplementation may just indicate changes in maintenance energy. Focus on the influence of acetyl-CoA on cancer cells and verifying whether changes in acetate:propionate:butyrate ratios rather than in taxonomic diversity can be used as markers of decreased inflammation may be the next frontiers for predicting successful NSAID therapy, and ultimately for developing microbiome-based therapies.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

Presynaptic Group II mGluR Inhibition of Short-Term Depression in the Medial Perforant Path of the Dentate Gyrus In Vitro

2001 ◽  
Vol 85 (6) ◽  
pp. 2509-2515 ◽  
Author(s):  
John Kilbride ◽  
Anthony M. Rush ◽  
Michael J. Rowan ◽  
Roger Anwyl
Keyword(s):  
Dentate Gyrus ◽  
Metabotropic Glutamate Receptors ◽  
State Level ◽  
Perforant Path ◽  
Dependent Manner ◽  
Short Term ◽  
Concentration Dependent Manner ◽  
Postsynaptic Response ◽  
Group Ii

Inhibition of short-term plasticity by activation of presynaptic group II metabotropic glutamate receptors (group II mGluR) was investigated in the medial perforant path of the dentate gyrus in the hippocampus in vitro. Brief trains of stimulation (10 stimuli at 1–200 Hz) evoked short-term depression of field excitatory postsynaptic potentials (EPSPs). The steady-state level of depression, measured after 10 stimuli, was frequency dependent, increasing between 1 and 200 Hz. Activation of group II mGluR by the selective agonist LY354740 did not alter short-term depression evoked by frequencies up to 10 Hz, but did inhibit short-term depression evoked at higher frequencies in a frequency- and concentration-dependent manner. The time-averaged postsynaptic response (EPSP per unit time) was found to increase linearly with frequency up to ∼20 Hz. At higher frequencies, the response plateaued, thereby becoming independent of frequency. Frequencies above this were differentiated only during the transient postsynaptic response that accompanies changes in firing rates. Activation of presynaptically located group II mGluR increased the frequency at which the EPSP per unit time plateaued up to 30–50 Hz.

scholarly journals P5375A default in acetyl-CoA carboxylase phosphorylation increases thrombus growth in vitro and in vivo, and in a collagen-dependent manner

2017 ◽  
Vol 38 (suppl_1) ◽  
Author(s):  
S. Lepropre ◽  
S. Kautbally ◽  
L. Bertrand ◽  
G.R. Steinberg ◽  
B.E. Kemp ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa

scholarly journals Extract of the Blood Circulation-Promoting Recipe-84 Can Protect Rat Retinas by Inhibiting the β-Catenin Signaling Pathway

2018 ◽  
Vol 19 (9) ◽  
pp. 2712 ◽  
Author(s):  
Qiu-Fang Qin ◽  
Min Liu ◽  
Gui-Hua Tian ◽  
Jian Chen ◽  
Yu-Sang Li
Keyword(s):  
Ganglion Cell ◽  
Signaling Pathway ◽  
Retinal Ganglion Cell ◽  
Blood Circulation ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Expression Levels ◽  
Cox 2 ◽  
Endothelial Growth Factor

Extract of the Blood Circulation-Promoting Recipe (EBR-84) from the Chinese Herbal medicine “Blood Circulation Promoting Recipe” could retard retinopathy development. This study investigated whether EBR-84 protects retinas by inhibiting the β-catenin pathway using a rat model of retinopathy and a retinal ganglion cell 5 (RGC-5) cell death model. RGC death was induced by either N-methyl-d-aspartic acid (NMDA) or TWS119 (an activator of the β-catenin pathway). After the corresponding treatment with EBR-84, RGC death and the protein expression levels of β-catenin, cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in rat retinas were examined. β-Catenin accumulated in the retinal ganglion cell layer (GCL) of NMDA-treated rats. EBR-84 (3.9, 7.8, and 15.6 g/kg) significantly attenuated the NMDA-induced RGC loss accompanying the reduction of β-catenin expression. Moreover, the expression levels of COX-2 and VEGF were decreased by EBR-84 in a dose-dependent manner. For the TWS119-treated rats, EBR-84 also ameliorated RGC loss and lowered the expression levels of β-catenin, COX-2, and VEGF. In vitro, EBR-84 increased the viability of NMDA-treated RGC-5 while decreased β-catenin expression. In conclusion, EBR-84 retarded ratretinopathy, and the β-catenin signaling pathway played an important role during this protective process.

scholarly journals Short-term supplementation of celecoxib-shifted butyrate production on a simulated model of the gut microbial ecosystem and ameliorated in vitro inflammation

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Emma Hernandez-Sanabria ◽  
Evelien Heiremans ◽  
Marta Calatayud Arroyo ◽  
Ruben Props ◽  
Laurent Leclercq ◽  
...  
Keyword(s):  
Short Term ◽  
Microbial Ecosystem ◽  
Simulated Model ◽  
Butyrate Production

Cow responses and evolution of the rumen bacterial and methanogen community following a complete rumen content transfer

2018 ◽  
Vol 156 (8) ◽  
pp. 1047-1058
Author(s):  
T. De Mulder ◽  
L. Vandaele ◽  
N. Peiren ◽  
A. Haegeman ◽  
T. Ruttink ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Community Composition ◽  
Bacterial Community Composition ◽  
Rumen Content ◽  
Short Term ◽  
Microbiome Composition ◽  
Nutritional Conditions ◽  
Microbiome Diversity ◽  
Methanogen Community ◽  
New Community

AbstractUnderstanding the rumen microbial ecosystem requires the identification of factors that influence the community structure, such as nutrition, physiological condition of the host and host–microbiome interactions. The objective of the current study was to describe the rumen microbial communities before, during and after a complete rumen content transfer. The rumen contents of one donor cow were removed completely and used as inoculum for the emptied rumen of the donor itself and three acceptor cows under identical physiological and nutritional conditions. Temporal changes in microbiome composition and rumen function were analysed for each of four cows over a period of 6 weeks. Shortly after transfer, the cows showed different responses to perturbation of their rumen content. Feed intake depression in the first 2 weeks after transfer resulted in short-term changes in milk production, methane emission, fatty acid composition and rumen bacterial community composition. These effects were more pronounced in two cows, whose microbiome composition showed reduced diversity. The fermentation metrics and microbiome diversity of the other two cows were not affected. Their rumen bacterial community initially resembled the composition of the donor but evolved to a new community profile that resembled neither the donor nor their original composition. Descriptive data presented in the current paper show that the rumen bacterial community composition can quickly recover from a reduction in microbiome diversity after a severe perturbation. In contrast to the bacteria, methanogenic communities were more stable over time and unaffected by stress or host effects.

scholarly journals Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

2014 ◽  
Vol 211 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Chenggang Li ◽  
Po-Shun Lee ◽  
Yang Sun ◽  
Xiaoxiao Gu ◽  
Erik Zhang ◽  
...  
Keyword(s):  
Exhaled Breath Condensate ◽  
Tumor Development ◽  
Exhaled Breath ◽  
Dependent Manner ◽  
Lipoxin A4 ◽  
Prostaglandin Biosynthesis ◽  
Cox 2 ◽  
Mtorc1 Activation

Lymphangioleiomyomatosis (LAM) is a progressive neoplastic disorder that leads to lung destruction and respiratory failure primarily in women. LAM is typically caused by tuberous sclerosis complex 2 (TSC2) mutations resulting in mTORC1 activation in proliferative smooth muscle–like cells in the lung. The female predominance of LAM suggests that estradiol contributes to disease development. Metabolomic profiling identified an estradiol-enhanced prostaglandin biosynthesis signature in Tsc2-deficient (TSC−) cells, both in vitro and in vivo. Estradiol increased the expression of cyclooxygenase-2 (COX-2), a rate-limiting enzyme in prostaglandin biosynthesis, which was also increased at baseline in TSC-deficient cells and was not affected by rapamycin treatment. However, both Torin 1 treatment and Rictor knockdown led to reduced COX-2 expression and phospho-Akt-S473. Prostaglandin production was also increased in TSC-deficient cells. In preclinical models, both Celecoxib and aspirin reduced tumor development. LAM patients had significantly higher serum prostaglandin levels than healthy women. 15-epi-lipoxin-A4 was identified in exhaled breath condensate from LAM subjects and was increased by aspirin treatment, indicative of functional COX-2 expression in the LAM airway. In vitro, 15-epi-lipoxin-A4 reduced the proliferation of LAM patient–derived cells in a dose-dependent manner. Targeting COX-2 and prostaglandin pathways may have therapeutic value in LAM and TSC-related diseases, and possibly in other conditions associated with mTOR hyperactivation.

scholarly journals Microbial Community Composition Affects Soil Fungistasis

2003 ◽  
Vol 69 (2) ◽  
pp. 835-844 ◽  
Author(s):  
Wietse de Boer ◽  
Patrick Verheggen ◽  
Paulien J. A. Klein Gunnewiek ◽  
George A. Kowalchuk ◽  
Johannes A. van Veen
Keyword(s):  
Microbial Community ◽  
Community Composition ◽  
Bacterial Community Composition ◽  
Microbial Community Composition ◽  
Fusarium Culmorum ◽  
Community Analysis ◽  
Microbial Community Analysis ◽  
Carbon Limitation ◽  
Soil Fungistasis

ABSTRACT Most soils inhibit fungal germination and growth to a certain extent, a phenomenon known as soil fungistasis. Previous observations have implicated microorganisms as the causal agents of fungistasis, with their action mediated either by available carbon limitation (nutrient deprivation hypothesis) or production of antifungal compounds (antibiosis hypothesis). To obtain evidence for either of these hypotheses, we measured soil respiration and microbial numbers (as indicators of nutrient stress) and bacterial community composition (as an indicator of potential differences in the composition of antifungal components) during the development of fungistasis. This was done for two fungistatic dune soils in which fungistasis was initially fully or partly relieved by partial sterilization treatment or nutrient addition. Fungistasis development was measured as restriction of the ability of the fungi Chaetomium globosum, Fusarium culmorum, Fusarium oxysporum, and Trichoderma harzianum to colonize soils. Fungistasis did not always reappear after soil treatments despite intense competition for carbon, suggesting that microbial community composition is important in the development of fungistasis. Both microbial community analysis and in vitro antagonism tests indicated that the presence of pseudomonads might be essential for the development of fungistasis. Overall, the results lend support to the antibiosis hypothesis.

Effects of Celecoxib and Nimesulide on the Proliferation of Ectopic Endometrial Stromal Cells in vitro

2008 ◽  
Vol 36 (5) ◽  
pp. 1032-1038 ◽  
Author(s):  
B Kong ◽  
Y Tian ◽  
W Zhu ◽  
S Su ◽  
Y Kan
Keyword(s):  
Cell Cycle ◽  
Stromal Cells ◽  
Prostaglandin E ◽  
Apoptotic Cells ◽  
Dependent Manner ◽  
Selective Inhibitors ◽  
Endometrial Stromal Cells ◽  
Cox 2 ◽  
Dose Dependent

The effects of cyclooxygenase 2 (COX-2) selective inhibitors on the proliferation of ectopic endometrial stromal cells in vitro were investigated. Ectopic endometrial stromal cells were treated with either celecoxib or nimesulide for 24 and 48 h. The results showed that (i) both celecoxib and nimesulide inhibited the proliferation of ectopic endometrial stromal cells in vitro in a time- and dose-dependent manner; (ii) the expression of prostaglandin E2 was significantly inhibited by both celecoxib and nimesulide in a dose-dependent manner; (iii) the percentage of apoptotic cells was significantly higher for cells treated with celecoxib or nimesulide than for untreated cells; and (iv) the percentage of the cells in the G0/G1 phase increased after the cells were treated with either agent in a dose-dependent manner. These data suggest that celecoxib and nimesulide inhibited proliferation of ectopic endometrial stromal cells by inducing apoptosis and blocking the cell cycle at the G0/G1 phase.

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