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https://www.readbyqxmd.com/read/28214973/a-multifunctional-alanine-rich-anti-inflammatory-peptide-bcp61-showed-potent-inhibitory-effects-by-inhibiting-both-nf-%C3%AE%C2%BAb-and-mapk-expression
#1
Yun Hee Choi, Yoon Seok Choi, Young Kyun Kim, Md Saifur Rahman, G C Pradeep, Jin Cheol Yoo, Joo-Won Suh
The purified BCP61 was reported to be a unique low-molecular-weight (MW) anti-microbial peptide because of its non-identical alanine-rich N-terminal sequence. In this study, we investigated the anti-inflammatory effects of BCP61 on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells. The treatment with BCP61, with varying concentrations of 10, 50, and 100 μg/mL, inhibited levels of expression of LPS-induced NF-κB and MAPKs (extracellular signal-related kinases (ERKs), c-Jun NH2-terminal kinase (JNK), and mitogen-activated protein (p38)) as well as production of pro-inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)...
February 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28213942/pge2-ep4-attenuated-mucosal-injury-via-%C3%AE-arr1-src-egfr-mediated-proliferation-in-portal-hypertensive-gastropathy
#2
Siwei Tan, Xiaoliang Chen, Minyi Xu, Xiaoli Huang, Huiling Liu, Jie Jiang, Yu Lu, Xiaojie Peng, Bin Wu
BACKGROUND AND PURPOSE: Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients associated with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role of prostaglandin E2 (PGE2 ) and its E-type prostanoid 4 (EP4 ) receptor in the promotion of mucosal proliferation. However, whether β-arrestin1 (β-arr1), a well-established mediator of G-protein-coupled receptors (GPCRs), is involved in the PGE2 /EP4 -mediated mucosal proliferation complex in PHG remains unclear...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#3
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#4
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28212299/exogenous-and-endogenous-hydrogen-sulfide-protects-gastric-mucosa-against-the-formation-and-time-dependent-development-of-ischemia-reperfusion-induced-acute-lesions-progressing-into-deeper-ulcerations
#5
Marcin Magierowski, Katarzyna Magierowska, Magdalena Hubalewska-Mazgaj, Zbigniew Sliwowski, Robert Pajdo, Grzegorz Ginter, Slawomir Kwiecien, Tomasz Brzozowski
Hydrogen sulfide (H₂S) is an endogenous mediator, synthesized from l-cysteine by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H₂S-gastroprotection against ischemia/reperfusion (I/R) lesions and their time-dependent progression into deeper gastric ulcerations have been little studied. We determined the effect of l-cysteine, H₂S-releasing NaHS or slow H₂S releasing compound GYY4137 on gastric blood flow (GBF) and gastric lesions induced by 30 min of I followed by 3, 6, 24 and 48 h of R...
February 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28212021/discovery-and-development-of-1-2-bromophenyl-sulfonyl-5-methoxy-3-4-methyl-1-piperazinyl-methyl-1h-indole-dimesylate-monohydrate-suvn-502-a-novel-potent-selective-and-orally-active-serotonin-6-5-ht6-receptor-antagonist-for-potential-treatment-of-alzheimer-s
#6
Ramakrishna Nirogi, Anil Shinde, Rama Sastry Kambhampati, Abdul Rasheed Mohammed, Sangram Keshari Saraf, Rajesh Kumar Badange, Thrinath Reddy Bandyala, Venugopalarao Bhatta, Kumar Bojja, Veena Reballi, Ramkumar Subramanian, Vijay Benade, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Pradeep Jayarajan, Vinod Goyal, Venkat Jasti
Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (5al, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT6R (Ki = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28210256/transcriptomic-analysis-of-the-innate-antiviral-immune-response-in-porcine-intestinal-epithelial-cells-influence-of-immunobiotic-lactobacilli
#7
Leonardo Albarracin, Hisakazu Kobayashi, Hikaru Iida, Nana Sato, Tomonori Nochi, Hisashi Aso, Susana Salva, Susana Alvarez, Haruki Kitazawa, Julio Villena
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28203503/prostaglandin-e1-increases-microcirculation-in-random-pattern-flaps-on-rats-measured-with-laser-doppler-perfusion-imaging
#8
Kim Alexander Tønseth, Christian Sneistrup, Thomas Moe Berg
BACKGROUND: Reconstructive procedures with pedicled and free flaps are associated with a risk of ischemia. Prostaglandin E1 (PGE1) is a hormone-like substance with known antiischemic and tissue-protective effects. The aim of this study was to evaluate the effect of PGE1 on the microcirculation in random pattern skin flaps on rats. METHODS: Twenty-four rats were divided into 2 groups: an intervention group given PGE1 for 6 hours and a control group given saline. The flap (2 × 10 cm) was created on the back of the rats, and the microcirculation was monitored with laser Doppler perfusion imaging in 5 different zones (1, proximal; 5, distal) before surgery and after 60, 180, and 360 minutes postoperatively...
January 2017: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#9
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28202546/identification-of-a-novel-series-of-anti-inflammatory-and-anti-oxidative-phospholipid-oxidation-products-containing-cyclopentenone-moiety-in-vitro-and-in-vivo-implication-in-atherosclerosis
#10
Jianhong Lu, Shuyuan Guo, Xinli Xue, Qun Chen, Jing Ge, Yujuan Zhuo, Huiqin Zhong, Buxing Chen, Mingming Zhao, Wei Han, Takashi Suzuki, Mingjiang Zhu, Lin Xia, Claus Schneider, Timothy S Blackwell, Ned A Porter, Lemin Zheng, Sotirios Tsimikas, Huiyong Yin
Oxidative stress and inflammation are two major contributing factors to atherosclerosis, a leading cause for cardiovascular diseases (CVDs). Oxidation of phospholipids on the surface of low density lipoprotein (LDL) particles generated under oxidative stress has been associated with the progression of atherosclerosis but the underlying molecular mechanisms remain poorly defined. We identified a novel series of oxidation products containing cyclopentenone moiety, termed deoxy-A2/J2-isoprostanes-phosphocholine (deoxy-A2/J2-IsoP-PC), from 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) in vivo using mass spectrometry and by comparison to a chemically synthesized standard...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28197966/signaling-pathway-involved-in-the-inhibitory-effect-of-fty720p-on-the-na-k-atpase-in-hepg2-cells
#11
Nadine Al Alam, Sawsan Ibrahim Kreydiyyeh
The Na(+)/K(+) ATPase modulates the activity of many transporters in the liver, and maintains the ionic constancy of the intracellular milieu, preserving thus normal functioning of hepatocytes. Previous work showed that FTY720P, a sphingosine one phosphate receptor agonist used in the treatment of multiple sclerosis, exerts in HepG2 cells, an inhibitory effect on the activity of the ATPase, mediated via PGE2. This study is an attempt to identify the signaling molecules involved downstream of the prostaglandin...
February 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28197210/orientin-ameliorates-lps-induced-inflammatory-responses-through-the-inhibitory-of-the-nf-%C3%AE%C2%BAb-pathway-and-nlrp3-inflammasome
#12
Qingfei Xiao, Zhihui Qu, Ying Zhao, Liming Yang, Pujun Gao
Inflammation is a complex response to diverse pathological conditions, resulting in negative rather than protective effects when uncontrolled. Orientin (Ori), a flavonoid component isolated from natural plants, possesses abundant properties. Thus, we aimed to discover the potential therapeutic effects of orientin on lipopolysaccharide- (LPS-) induced inflammation in RAW 264.7 cells and the underlying mechanisms. In our studies, we evaluated the effects of Ori on proinflammatory mediator production stimulated by LPS, including tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-18, and IL-1β, along with prostaglandin E2 (PGE2) and NO...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28195470/total-synthesis-confirms-the-molecular-structure-proposed-for-oxidized-levuglandin-d2
#13
Yu-Shiuan Cheng, Wenyuan Yu, Yunfeng Xu, Robert G Salomon
Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aβ1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins...
February 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28195067/the-effect-of-short-term-treatment-with-probiotic-vsl-3-on-various-clinical-and-biochemical-parameters-in-patients-with-liver-cirrhosis
#14
W Marlicz, E Wunsch, M Mydlowska, M Milkiewicz, K Serwin, M Mularczyk, P Milkiewicz, J Raszeja-Wyszomirska
The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28194409/a-variant-in-cox-2-gene-is-associated-with-left-main-coronary-artery-disease-and-clinical-outcomes-of-coronary-artery-bypass-grafting
#15
Hanning Liu, Zhengxi Xu, Cheng Sun, Dachuan Gu, Xiao Teng, Yan Zhao, Zhe Zheng
As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#16
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28192731/isotrifoliol-inhibits-pro-inflammatory-mediators-by-suppression-of-tlr-nf-%C3%AE%C2%BAb-and-tlr-mapk-signaling-in-lps-induced-raw264-7-cells
#17
Hua Li, Jeong-Hyun Yoon, Hyo-Jun Won, Hyeon-Seon Ji, Heong Joo Yuk, Ki Hun Park, Ho-Yong Park, Tae-Sook Jeong
Soybeans, produced by Glycine max (L.) Merr., contain high levels of isoflavones, such as genistein and daidzein. However, soy leaves contain more diverse and abundant flavonol glycosides and coumestans, as compared to the soybean. This study investigated the anti-inflammatory effects of the major coumestans present in soy leaf (coumestrol, isotrifoliol, and phaseol) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Coumestans significantly reduced LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS) production; isotrifoliol had the most potent anti-inflammatory activity...
February 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28192229/hne-as-an-inducer-of-cox-2
#18
REVIEW
Koji Uchida
Cyclooxygenase-2 (COX-2), an inducible isoform responsible for high levels of prostaglandin (PG) production during inflammation and immune responses, mediate a variety of biological actions involved in vascular pathophysiology. COX-2 is induced by various stimuli, including proinflammatory cytokines, to result in PG synthesis associated with inflammation and carcinogenesis. 4-Hydroxy-2-nonenal (HNE) is one of a group of small molecules that can induce COX-2 expression. The mechanistic studies have revealed that the HNE-induced COX-2 expression results from the stabilization of COX-2 mRNA mediated by the p38 mitogen-activated protein kinase signaling pathway and uniquely requires a serum component, which is eventually identified to be modified low-density lipoproteins (LDLs), such as the oxidized form of LDLs...
February 9, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28190634/discovery-and-characterization-of-cyclopentyl-ethyl-benzoic-acid-inhibitors-of-microsomal-prostaglandin-e-synthase-1
#19
Katherine M Partridge, Stephen Antonysamy, Shobha N Bhattachar, Srinivasan Chandrasekhar, Matthew J Fisher, Adrian Fretland, Karen Gooding, Anita Harvey, Norman E Hughes, Steven L Kuklish, John G Luz, Peter R Manninen, James E McGee, Daniel R Mudra, Antonio Navarro, Bryan H Norman, Steven J Quimby, Matthew A Schiffler, Ashley V Sloan, Alan M Warshawsky, Jennifer M Weller, Jeremy S York, Xiao-Peng Yu
We describe a novel class of acidic mPGES-1 inhibitors with nanomolar enzymatic and human whole blood (HWB) potency. Rational design in conjunction with structure-based design led initially to the identification of anthranilic acid 5, an mPGES-1 inhibitor with micromolar HWB potency. Structural modifications of 5 improved HWB potency by over 1000×, reduced CYP2C9 single point inhibition, and improved rat clearance, which led to the selection of [(cyclopentyl)ethyl]benzoic acid compound 16 for clinical studies...
November 7, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28190472/gastroprotective-and-anti-secretory-mechanisms-of-2-phenylquinoline-an-alkaloid-isolated-from-galipea-longiflora
#20
Eduardo Breviglieri, Luisa Mota da Silva, Thaise Boeing, Lincon Bordignon Somensi, Benhur Judah Cury, Alberto Gimenez, Valdir Cechinel Filho, Sérgio Faloni de Andrade
BACKGROUND: We previously described the gastroprotective effect of 2-phenylquinoline (2-PQ), the main alkaloid isolated from the bark of Galipea longiflora (Rutaceae). However, despite the significant and promising results, the pharmacological mechanisms of the gastroprotection induced by 2-PQ have not been investigated. PURPOSE: To evaluate the mechanisms underlying the gastroprotective effects of 2-PQ. STUDY DESIGN: We used an in vivo mouse ulcer model and in vitro methodologies involving H⁺/K⁺-ATPase and L929 murine fibroblasts...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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