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M Mezzelani, S Gorbi, D Fattorini, G d'Errico, M Benedetti, M Milan, L Bargelloni, F Regoli
The aim of the present investigation was to provide new insights on accumulation and possible adverse effects of various non-steroidal anti-inflammatory drugs (NSAIDs) in mussels, Mytilus galloprovincialis, exposed to an environmentally realistic concentration (0.5μg/L) of individual compounds, Acetaminophen (AMP), Diclofenac (DIC), Ibuprofen (IBU), Ketoprofen (KET) or Nimesulide (NIM). The measurement of drugs in mussel tissues was integrated with both functional alterations at cellular level and transcriptomic responses...
October 11, 2016: Aquatic Toxicology
Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov, David Attwell
Active neurons increase their energy supply by dilating nearby arterioles and capillaries. This neurovascular coupling underlies blood oxygen level-dependent functional imaging signals, but its mechanism is controversial. Canonically, neurons release glutamate to activate metabotropic glutamate receptor 5 (mGluR5) on astrocytes, evoking Ca(2+) release from internal stores, activating phospholipase A2 and generating vasodilatory arachidonic acid derivatives. However, adult astrocytes lack mGluR5, and knockout of the inositol 1,4,5-trisphosphate receptors that release Ca(2+) from stores does not affect neurovascular coupling...
October 24, 2016: Nature Neuroscience
Mahfoozur Rahman, Sarwar Beg, Amita Verma, Fahad A Al Abbasi, Firoz Anwar, Sumant Saini, Sohail Akhter, Vikas Kumar
OBJECTIVES: The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed. KEY FINDINGS: Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOXs) and arachidonic acid (AA)...
October 24, 2016: Journal of Pharmacy and Pharmacology
Xiangbing Wu, Chandler L Walker, Qingbo Lu, Wei Wu, Daniel B Eddelman, Jonathan M Parish, Xiao-Ming Xu
Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A2 (cPLA2), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level...
October 22, 2016: Molecular Neurobiology
S Zappavigna, M Scuotto, A M Cossu, D Ingrosso, M De Rosa, C Schiraldi, R Filosa, M Caraglia
BACKGROUND: Embelin is a potent dual inhibitor of 5-lipoxigenase (5-LOX) and microsomal prostaglandin E2 synthase (mPGES)-1 that suppresses proliferation of human glioma cells and induces apoptosis by inhibiting XIAP and NF-κB signaling pathway. Synthetic structural modification yielded the derivative 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), an embelin constrained analogue, with improved efficiency against 5-LOX in human neutrophils and anti-inflammatory activity in vivo...
October 22, 2016: Journal of Experimental & Clinical Cancer Research: CR
Paul A Gurbel, Kevin P Bliden, Rahul Chaudhary, Jeff Patrick, Fang Liu, Gailing Chen, Christopher McLeod, Udaya S Tantry
High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162...
September 20, 2016: American Journal of Cardiology
M Murakami, K Yamamoto, Y Miki, R Murase, H Sato, Y Taketomi
Within the phospholipase A2 (PLA2) family that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, secreted PLA2 (sPLA2) enzymes comprise the largest group containing 11 isoforms in mammals. Individual sPLA2s exhibit unique tissue or cellular distributions and enzymatic properties, suggesting their distinct biological roles. Although PLA2 enzymes, particularly cytosolic PLA2 (cPLA2α), have long been implicated in inflammation by driving arachidonic acid metabolism, the precise biological roles of sPLA2s have remained a mystery over the last few decades...
2016: Advances in Immunology
Nannan Wang, Ronghua Dai, Weihui Wang, Yan Peng, Xiaoning Zhao, Kaishun Bi
To evaluate the potential relationship between rheumatoid arthritis and arachidonic acid (AA) metabonomics via cyclooxygenase (COX) and lipoxygenase (LOX) pathways, a UPLC-MS/MS method has been developed and validated for simultaneous and quantitative profiling of eicosanoid metabolome in rat plasma. The analytes were extracted from plasma samples by protein precipitation procedure, and then separated on a Shim-pack XR-ODS column with mobile phase A (0.05% formic acid in water, pH=3.3 adjusted with dilute ammonium hydroxide) and mobile phase B [methanol: acetonitrile (20:80, v/v)]...
December 1, 2016: Talanta
Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
James A Shayman
Prostaglandins have been characterized as the metabolic products of arachidonic acid released from glycerophospholipids following hydrolysis by phospholipase A2s and enzymatic oxidation by the COX1 and COX2. In this issue of Cell Chemical Biology, Liu et al. (2016) examine the metabolism of 2-arachidonoyl-lyso-phosphatidylcholine and 2-arachidonoyl-lyso-phosphatidylethanolamine by COX2 and conversion to glycerolipid linked prostanoids, raising a series of interesting and important questions.
October 20, 2016: Cell Chemical Biology
K Denise Apperson, Gita Cherian
Flax seed is a rich source of α-linolenic acid (18:3 n-3). Feeding broiler birds flax seed can increase n-3 fatty acids in meat tissues. However, non-starch polysaccharides in flax seed decrease nutrient digestibility and can have a negative impact on bird performance and muscle fatty acid content. Addition of carbohydrase enzymes to flax-based broiler diets can decrease the anti-nutritive effects of non-starch polysaccharides. An experiment was conducted to investigate on the effect of flax seed and carbohydrase enzyme foregut morphology, muscle tissue, fatty acids, and bird performance...
October 19, 2016: Poultry Science
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
October 17, 2016: Toxicology and Applied Pharmacology
Matías Hernández, Susana Wicz, Ricardo S Corral
BACKGROUND: Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca(2+)/NFAT cascade in cardiomyocytes, leading to cyclooxygenase type 2 (COX-2) induction and increased release of prostanoids and prohypertrophic peptides. PURPOSE: To determine whether the well-known cardioprotective and anti-inflammatory effects of curcumin (Cur) could be helpful to interfere with this key machinery for pathogenesis of Chagas myocarditis...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Jih-Jung Chen, Tung-Han Tsai, Hsiang-Ruei Liao, Li-Chai Chen, Yueh-Hsiung Kuo, Ping-Jyun Sung, Chun-Lin Chen, Chun-Sheng Wei
Two new sesquiterpenoids-13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)-have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3-15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mojtaba Shafiekhani, Pouya Faridi, Javad Kojuri, Soha Namazi
OBJECTIVE: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. MATERIALS AND METHODS: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0...
September 2016: Avicenna Journal of Phytomedicine
Liang Dong, Chong Yuan, Benjamin J Orlando, Michael G Malkowski, William L Smith
Prostaglandin endoperoxide H synthase-2 (PGHS-2), also called cyclooxygenase-2 (COX-2), converts arachidonic acid to PGH2. PGHS-2 is a conformational heterodimer comprised of allosteric (Eallo) and catalytic (Ecat) subunits. Fatty acids (FAs) bind to Arg-120 of Eallo increasing to different degrees, depending on the FA, the Vmax of its Ecat partner. We report here that movement of helical residues 120-122 and loop residues 123-129 of Eallo underlie the allosteric effects of FAs and allosteric COX-2 inhibitors including naproxen and flurbiprofen...
October 18, 2016: Journal of Biological Chemistry
L De Rooy, H Hamdallah, S C Dyall
BACKGROUND & AIMS: Adequate supply of arachidonic (ARA) and docosahexaenoic (DHA) acids is essential for brain development, and extremely preterm infants may be at risk of deficiency. Current levels of ARA and DHA given to extremely preterm infants and the amounts available for accretion have not been established, although recent evidence suggests DHA intake is at a level likely to lead to severe deficits. This study quantified the omega-6 and omega-3 polyunsaturated fatty acid (PUFA) intakes from all sources in the first six weeks of life of preterm infants in standard care...
October 8, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Zhi Chen, Hao Wu, Guohua Wang, Ye Feng
BACKGROUND: This study was aimed to explore the molecular mechanisms of hypertensive nephropathy (HTN). METHODS: Gene expression profile of GSE37460, which based on 27 healthy living donor samples (HTN group) and 15 hypertensive nephropathy samples (control group), were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between two groups were identified. STRING database was used to reveal protein-protein interaction (PPI) network of DEGs, followed by the functional enrichment analysis of the PPI network...
October 18, 2016: BMC Nephrology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
X R Feng, M L Liu, F Liu, Y Fan, Q P Tian
OBJECTIVE: To assess the consequences of switching aspirin dosage from 100 mg/d to 40 mg/d on cardiovascular benefit, bleeding risk and platelet aggregation in very elderly patients. METHODS: Arachidonic acid induced platelet aggregation(AA-Ag) was measured in 537 patients aged 80 or older treated with aspirin (100 mg/d). In the study, 100 patients with low on-treatment platelet aggregation and at high risk of bleeding and low risk of cardiovascular events, were switched to aspirin (40 mg/d) and their platelet aggregation was measured again 7 days later...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
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