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https://www.readbyqxmd.com/read/29309791/amelioration-of-streptozotocin-induced-type-2-diabetes-mellitus-in-wistar-rats-by-arachidonic-acid
#1
Naveen K V Gundala, Vegi G M Naidu, Undurti N Das
Traditionally arachidonic acid (AA, 20:4 n-6) is considered as a pro-inflammatory molecule since it forms precursor to prostaglandins (PGs), leukotrienes (LTs) and thromboxanes (TXs) that have pro-inflammatory actions. Type 2 diabetes mellitus (type 2 DM) is considered as a low-grade systemic inflammatory condition in which circulating PGs and LTs are increased. Streptozotocin (STZ)-induced type 2 DM is used as a model of human type 2 DM in which peripheral insulin resistance, increased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and hyperglycemia occurs...
January 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29228980/lipoxin-a4-reverses-mesenchymal-phenotypes-to-attenuate-invasion-and-metastasis-via-the-inhibition-of-autocrine-tgf-%C3%AE-1-signaling-in-pancreatic-cancer
#2
Liang Zong, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiguang Ma, Cancan Zhou, Qinhong Xu, Wanxing Duan, Liang Han, Jianjun Lei, Xuqi Li, Qingyong Ma, Zheng Wang
BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated. METHODS: Pancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays...
December 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29206462/lipidomics-reveals-dramatic-physiological-kinetic-isotope-effects-during-the-enzymatic-oxygenation-of-polyunsaturated-fatty-acids-i-ex-vivo-i
#3
Aaron R Navratil, Mikhail S Shchepinov, Edward A Dennis
Arachidonic acid (AA, 20:4) is an omega-6 polyunsaturated fatty acid (PUFA) and the main precursor to the class of lipid mediators known as eicosanoids. The enzymes that catalyze the oxygenation of AA begin by abstracting hydrogen from one of three bis-allylic carbons within 1,4- cis,cis-diene units. Substitution of deuterium for hydrogen has been shown to lead to massive kinetic isotope effects (KIE) for soybean lipoxygenase (sLOX) oxygenation of linoleic acid (LA, 18:2). Yet, experimental determination of the KIE during oxygenation of AA and LA by mammalian enzymes including cyclooxygenase (COX) and lipoxygenase (LOX) has revealed far lower values...
December 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29185103/unraveling-the-interaction-of-aspirin-ticagrelor-and-rosuvastatin-on-the-progression-of-atherosclerosis-and-inflammation-in-diabetic-mice
#4
Yumei Ye, Sven Nylander, Yochai Birnbaum
PURPOSE: We explored the effects of rosuvastatin, aspirin, ticagrelor, and clopidogrel, alone or in combinations on the progression of atherosclerosis and inflammasome activation in diabetic mice. Statins and ticagrelor increase the production of 15-epi-lipoxin A4 via cyclooxygenase-2. Aspirin alone increases 15-epi-lipoxin A4, but when combined with statins, cyclooxygenase-2 is completely blocked. METHODS: ApoE-/-/db+/db+ double-knockout mice received rosuvastatin (5 mg/kg/day), aspirin (25 mg/kg/day), ticagrelor (300 mg/kg/day), clopidogrel (75 mg/kg/day), or their combination for 14 weeks...
December 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29181388/early-production-of-the-neutrophil-derived-lipid-mediators-ltb4-and-lxa4-is-modulated-by-intracellular-infection-with-leishmania-major
#5
Michael Plagge, Tamás Laskay
Recruitment of neutrophil granulocytes to sites of infectious tissue damage is an early event in innate immune responses. Following chemotactic signals neutrophils establish a first line of defense in a swarm-like manner. Intracellular pathogens such as Leishmania major can, however, evade neutrophil-mediated killing and survive inside neutrophils. To achieve this the parasites evolved potent evasion mechanisms. Since neutrophils are a major source of inflammation regulating lipid mediators, we hypothesized that intracellular infection modifies the release of pro- and anti-inflammatory lipid mediators like leukotriene B4 (LTB4) and lipoxin A4 (LXA4), respectively...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29163531/impaired-resolution-of-inflammation-in-alzheimer-s-disease-a-review
#6
REVIEW
Robert A Whittington, Emmanuel Planel, Niccolò Terrando
Alzheimer's disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute inflammatory response is counterbalanced by an active process termed resolution. This process is designed to restore homeostasis and promote tissue healing by the activation of neutrophilic apoptosis, promotion of neutrophil clearance by macrophages, and increasing anti-inflammatory cytokine levels, while concurrently leading to a diminution in pro-inflammatory mediators...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29138268/n-acyl-amino-acids-elmiric-acids-endogenous-signaling-molecules-with-therapeutic-potential
#7
Sumner Burstein
The subject of N-acyl amino acid conjugates has been rapidly growing in recent years, especially with regard to their analgesic and anti-inflammatory actions. The field is comprised of a large family of lipid signaling molecules whose importance is only now being fully realized. The most widely studied member is N-arachidonoyl glycine (NAGly), which differs structurally from the endocannabinoid anandamide (N-arachidonoyl ethanolamide) by a single oxygen atom and the two are metabolically related. Topics that are covered in this mini review are: biosynthetic pathways for N-acyl amino acids, receptors for N-acyl amino acids, physiological actions of N-acyl amino acids, pharmacological effects of N-acyl amino acids and molecular mechanisms believed to be responsible for their effects...
November 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29137840/resolvin-d1-attenuates-imiquimod-induced-mice-psoriasiform-dermatitis-through-mapks-and-nf-%C3%AE%C2%BAb-pathways
#8
Juntao Xu, Xiaoru Duan, Feng Hu, Devesh Poorun, Xinxin Liu, Xin Wang, Song Zhang, Lu Gan, Mengwen He, Ke Zhu, Zhangyin Ming, Hongxiang Chen
BACKGROUND: Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported. OBJECTIVE: The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis. METHODS: Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29136768/lipoxin-a4-protects-against-spinal-cord-injury-via-regulating-akt-nuclear-factor-erythroid-derived-2-like-2-heme-oxygenase-1-signaling
#9
Tan Lu, Xuejian Wu, Na Wei, Xiaotan Liu, Yingfeng Zhou, Chunfeng Shang, Yongzhuang Duan, Yuzhen Dong
Spinal cord injury (SCI) is a devastating physical trauma worldwide. The mechanisms of SCI are still not clear and the effective treatment is limited. Lipoxin A4 (LXA4) possesses anti-inflammatory and neuroprotective effects. The present study was designed to further evaluate the molecular mechanisms of LXA4-induced protective effects in a rat model of SCI. We found that LXA4 increased Basso, Beattie and Bresnahan (BBB) scores, increased mechanical paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) to a radiant heat, reduced the lesion volume, decreased Bax mRNA expression and increased Bcl-2 expression after SCI...
November 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29126887/combined-administration-of-resolvin-e1-and-lipoxin-a4-resolves-inflammation-in-a-murine-model-of-alzheimer-s-disease
#10
Alpdogan Kantarci, Nurgul Aytan, Iro Palaska, Danielle Stephens, Leah Crabtree, Claudia Benincasa, Bruce G Jenkins, Isabel Carreras, Alpaslan Dedeoglu
Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aβ pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1...
November 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29111541/lipoxin-a4-improves-erectile-dysfunction-in-rats-with-type-i-diabetes-by-inhibiting-oxidative-stress-and-corporal-fibrosis
#11
Kai Cui, Zhe Tang, Chuan-Chang Li, Tao Wang, Ke Rao, Shao-Gang Wang, Ji-Hong Liu, Zhong Chen
Previous studies have shown that oxidative stress and corporal fibrosis in penile tissues of rats were key pathological factors of erectile dysfunction induced by diabetic mellitus (DMED). Lipoxin A4 (LXA4) was reported to inhibit oxidative stress and fibrosis diseases, while whether it could exert a protective role on erectile function was not clear. Type I diabetic mellitus (DM) was induced in thirty male 10-week-old Sprague-Dawley rats using streptozotocin. Ten weeks later, twenty-two rats with DMED confirmed by an apomorphine test were divided into two groups: the DMED group (n = 11) and the DMED + LXA4 group (n = 11; LXA4 injection daily for 4 weeks)...
November 7, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29110146/atherosclerosis-periodontal-disease-and-treatment-with-resolvins
#12
REVIEW
James A Hamilton, Hatice Hasturk, Alpdogan Kantarci, Charles N Serhan, Thomas Van Dyke
PURPOSE OF REVIEW: This review aims to discuss the existing evidence on the link between atherosclerosis and periodontitis by particularly presenting new findings that link the pathology and therapy of these diseases. Acute vascular ischemic events that can lead to stroke or myocardial infarction are initiated by inflammatory processes leading to rupture or erosion of plaques susceptible to thrombosis ("high risk" or "vulnerable"). These are highly inflamed plaques residing in the media and adventitia that may not be detected by angiography measurments of luminal narrowing...
November 6, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29106385/astrocyte-derived-lipoxins-a4-and-b4-promote-neuroprotection-from-acute-and-chronic-injury
#13
Izhar Livne-Bar, Jessica Wei, Hsin-Hua Liu, Samih Alqawlaq, Gah-Jone Won, Alessandra Tuccitto, Karsten Gronert, John G Flanagan, Jeremy M Sivak
Astrocytes perform critical non-cell autonomous roles following CNS injury that involve either neurotoxic or neuroprotective effects. Yet the nature of potential prosurvival cues has remained unclear. In the current study, we utilized the close interaction between astrocytes and retinal ganglion cells (RGCs) in the eye to characterize a secreted neuroprotective signal present in retinal astrocyte conditioned medium (ACM). Rather than a conventional peptide neurotrophic factor, we identified a prominent lipid component of the neuroprotective signal through metabolomics screening...
November 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29053142/resolution-of-inflammation-and-sepsis-survival-are-improved-by-dietary-%C3%AE-3-fatty-acids
#14
Andreas Körner, Martin Schlegel, Julia Theurer, Hannes Frohnmeyer, Michael Adolph, Marieke Heijink, Martin Giera, Peter Rosenberger, Valbona Mirakaj
Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration...
October 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29044225/microrna-181b-is-increased-in-cystic-fibrosis-cells-and-impairs-lipoxin-a4-receptor-dependent-mechanisms-of-inflammation-resolution-and-antimicrobial-defense
#15
Anna Maria Pierdomenico, Sara Patruno, Marilina Codagnone, Felice Simiele, Veronica Cecilia Mari, Roberto Plebani, Antonio Recchiuti, Mario Romano
The involvement of microRNA (miR) in cystic fibrosis (CF) pathobiology is rapidly emerging. We previously documented that miR-181b controls the expression of the ALX/FPR2 receptor, which is recognized by the endogenous proresolution ligand, lipoxin (LX)A4. Here, we examined whether the miR-181b-ALX/FPR2 circuit was altered in CF. We examined human airways epithelial cells, normal (16HBE14o-), carrying the ΔF508 mutation (CFBE41o-) or corrected for this mutation (CFBE41o-/CEP-CFTR wt 6.2 kb), as well as monocyte-derived macrophages (MΦs) from CF patients...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021582/novel-mechanism-of-regulation-of-the-5-lipoxygenase-leukotriene-b4-pathway-by-high-density-lipoprotein-in-macrophages
#16
Shigeyasu Tsuda, Masakazu Shinohara, Toshihiko Oshita, Manabu Nagao, Nobuaki Tanaka, Takeshige Mori, Tetsuya Hara, Yasuhiro Irino, Ryuji Toh, Tatsuro Ishida, Ken-Ichi Hirata
High-density lipoprotein (HDL) interacts with various cells, particularly macrophages, in functional cell-HDL interactions. Here, we found that HDL protein quality and lipid quality play critical roles in HDL functions. HDL fractions from healthy volunteers (HDLHealthy) and patients with recurrent coronary atherosclerotic disease (HDLCAD) were prepared. To analyse functional HDL-macrophage interactions, macrophages were co-incubated with each HDL, and lipid mediator production was assessed by liquid chromatography/mass spectrometry-based metabololipidomics...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28987723/low-dose-aspirin-increases-15-epi-lipoxin-a4-levels-in-diabetic-chronic-kidney-disease-patients
#17
Marian Goicoechea, Maria Dolores Sanchez-Niño, Alberto Ortiz, Soledad García de Vinuesa, Borja Quiroga, Carmen Bernis, Enrique Morales, Gema Fernández-Juarez, Patricia de Sequera, Ursula Verdalles, Eduardo Verde, José Luño
BACKGROUND: Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients. STUDY DESIGN: Open label randomized clinical trial. SETTING AND PARTICIPANTS: 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months...
October 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28982736/an-epoxide-hydrolase-secreted-by-pseudomonas-aeruginosa-decreases-mucociliary-transport-and-hinders-bacterial-clearance-from-the-lung
#18
Kelli L Hvorecny, Emily Dolben, Sophie Moreau-Marquis, Thomas H Hampton, Tamer B Shabaneh, Becca A Flitter, Christopher D Bahl, Jennifer M Bomberger, Bruce D Levy, Bruce A Stanton, Deborah A Hogan, Dean R Madden
The opportunistic pathogen Pseudomonas aeruginosa colonizes the lungs of susceptible individuals by deploying virulence factors targeting host defenses. The secreted CFTR inhibitory factor (Cif) dysregulates the endocytic recycling of CFTR and thus reduces CFTR abundance in host epithelial membranes. We have postulated that the decrease in ion secretion mediated by Cif would slow mucociliary transport and decrease bacterial clearance from the lungs. To test this hypothesis, we explored the effects of Cif in cultured epithelia and in the lungs of mice...
October 5, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28978222/the-eicosanoids-redox-regulated-lipid-mediators-in-immunometabolic-disorders
#19
Ana Carolina Araujo, Craig E Wheelock, Jesper Z Haeggström
SIGNIFICANCE: The oxidation of arachidonic acid via cyclooxygenase and lipoxygenase activity to produce eicosanoids during inflammation is a well-known biosynthetic pathway. These lipid mediators are involved in fever, pain and thrombosis and are generated from a variety of cell types as well as through interactions between immune cells and epithelial/endothelial cells. Metabolic disorders including hyperlipidemia, hypertension, and diabetes are associated with chronic low-grade inflammation, impacting the immune system and promoting a variety of chronic diseases...
October 5, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28962156/pilot-application-of-lipoxin-a4-analog-and-lipoxin-a4-receptor-agonist-in-asthmatic-children-with-acute-episodes
#20
Xia Kong, Sheng-Hua Wu, Li Zhang, Xiao-Qing Chen
Previous studies have demonstrated that lipoxin A4 (LXA4) analogs blocked both airway hyper-responsiveness and pulmonary inflammation in a murine model of asthma. The present pilot study investigated the initial efficacy and safety of inhaled 5(S),6(R)-LXA4 methyl ester and BML-111, a LXA4 agonist, in the treatment of asthmatic children with acute episodes. A total of 50 asthmatic children diagnosed with acute moderate asthma were randomly assigned into groups and subjected to an inhalation challenge with pulmicort (n=10), ventolin (n=10), 5(S),6(R)-LXA4 methyl ester (n=10), BML-111 (n=10) or normal saline as a placebo (n=10)...
September 2017: Experimental and Therapeutic Medicine
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