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https://www.readbyqxmd.com/read/29138268/n-acyl-amino-acids-elmiric-acids-endogenous-signaling-molecules-with-therapeutic-potential
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28919798/comparative-effects-of-the-%C3%AF-3-polyunsaturated-fatty-acid-derivatives-resolvins-e1-and-d1-and-protectin-dx-in-models-of-inflammation-and-pain
#15
Flávia Cs Fonseca, Ricardo M Orlando, Regina Mm Turchetti-Maia, Janetti Nogueira de Francischi
PURPOSE: Specialized pro-resolving lipid mediators (SPMs), also known as lipoxins, resolvins (Rvs), protectins and maresins, have been implicated in the resolution of the inflammatory process. However, a systematic comparison of their activity in the relief of inflammation and pain models is still lacking. MATERIALS AND METHODS: The effects of Rvs E1 and D1 and protectin DX (PDX) were assessed in rat paws inflamed by the standard proinflammatory stimulus carrageenan or by histamine, 5-hydroxytryptamine, substance P or prostaglandin E2...
2017: Journal of Inflammation Research
https://www.readbyqxmd.com/read/28869373/lipoxin-a4-alleviates-cerebral-ischemia-reperfusion-injury-through-up-regulating-nrf2
#16
Yan Guo, Chenglong Dong, Jiao Tang, Xiaolei Deng, Guodong Wang, Weizhen Wang, Hanrong Xu
No abstract text is available yet for this article.
September 4, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28855632/resolution-agonist-15-epi-lipoxin-a4-programs-early-activation-of-resolving-phase-in-post-myocardial-infarction-healing
#17
Vasundhara Kain, Fei Liu, Veronika Kozlovskaya, Kevin A Ingle, Subhashini Bolisetty, Anupam Agarwal, Santosh Khedkar, Sumanth D Prabhu, Eugenia Kharlampieva, Ganesh V Halade
Following myocardial infarction (MI), overactive inflammation remodels the left ventricle (LV) leading to heart failure coinciding with reduced levels of 15-epi-Lipoxin A4 (15-epi LXA4). However, the role of 15-epi LXA4 in post-MI acute inflammatory response and resolving phase is unclear. We hypothesize that liposomal fusion of 15-epi-LXA4 (Lipo-15-epi-LXA4) or free 15-epi-LXA4 will expedite the resolving phase in post-MI inflammation. 8 to 12-week-old male C57BL/6 mice were subjected to permanent coronary artery ligation...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822808/bml-111-equilibrated-ace-angii-at1r-and-ace2-ang-1-7-mas-axis-to-protect-hepatic-fibrosis-in-rats
#18
Quandong Hu, Zhenzhen Hu, Qiongfeng Chen, Yonghong Huang, Zi Mao, Fangyun Xu, Xiaoyan Zhou
BACKGROUND: It was recently reported Lipoxins (LXs) had protective effects on fibrous diseases, and renin-angiotensin-aldosterone system (RAAS) had played vital and bidirectional roles in hepatic fibrosis. In this paper, a hepatic fibrosis model, induced by carbon tetrachloride (CCL4) in rats, was used to observe the relations between RAAS and LXs, as well as to further explore the alternative anti-fibrosis mechanisms of LXs. METHODS: The model was evaluated by morphological observations and biochemical assays...
August 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28819748/lipoxin-a4-attenuates-bronchopulmonary-dysplasia-via-upregulation-of-let-7c-and-downregulation-of-tgf-%C3%AE-1-signaling-pathway
#19
Xiao-Qing Chen, Sheng-Hua Wu, Yan-Yan Luo, Bing-Jie Li, Shu-Jun Li, Hong-Yan Lu, Rui Jin, Zhong-Yi Sun
Transforming growth factor-β (TGF-β) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF-β antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF-β antibodies, and let-7c mimic/anti-microRNA transfections...
December 2017: Inflammation
https://www.readbyqxmd.com/read/28809482/structural-dynamics-of-15-lipoxygenase-2-via-hydrogen-deuterium-exchange
#20
Kristin D Droege, Mary E Keithly, Charles R Sanders, Richard N Armstrong, Matthew K Thompson
Eicosanoids are inflammatory signaling lipids that are biosynthesized in response to cellular injury or threat. They were originally thought to be pro-inflammatory molecules, but members of at least one subclass, the lipoxins, are able to resolve inflammation. One step in lipoxin synthesis is the oxygenation of arachidonic acid by 15-lipoxygenase (15-LOX). 15-LOX contains two domains: a Ca(2+) binding PLAT domain and a catalytic domain. 15-LOX is a soluble cytosolic protein until binding of Ca(2+) to the PLAT domain promotes translocation to the membrane surface...
September 26, 2017: Biochemistry
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