Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils

The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine are lipids regulating many physiological processes, notably inflammation. Endocannabinoid hydrolysis inhibitors are now being investigated as potential anti-inflammatory agents. In addition to 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and N-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and N-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or N-acyl-ethanolamine levels, endocannabinoid hydrolysis inhibitors will likely increase the levels of their metabolites. Herein, we investigated whether 1-LG and LEA were substrates for the 15-lipoxygenase pathway, given that both possess a 1Z,4Z-pentadiene motif, near their omega end. We thus assessed how human eosinophils and neutrophils biosynthesized the 15-lipoxygenase metabolites of 1-LG and LEA. Linoleic acid (LA), a well-documented substrate of 15-lipoxygenases, was used as positive control. N-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G), the 15-lipoxygenase metabolites of LEA and 1-LG, were synthesized using Novozym 435 and soybean lipoxygenase. Eosinophils, which express the 15-lipoxygenase-1, metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was almost complete after five minutes. Substrate preference of eosinophils was LA > LEA > 1-LG in presence of 13-HODE-G hydrolysis with methyl-arachidonoyl-fluorophosphonate. Human neutrophils also metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was maximal after 15–30 s. Substrate preference was LA ≫ 1-LG > LEA. Importantly, 13-HODE-G was found in humans and mouse tissue samples. In conclusion, our data show that human eosinophils and neutrophils metabolize 1-LG and LEA into the novel endogenous 15-lipoxygenase metabolites 13-HODE-G and 13-HODE-EA. The full biological importance of 13-HODE-G and 13-HODE-EA remains to be explored.

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Insight on Ameliorative Role of Selenium Nanoparticles and Niacin in Wound Healing on Adult Female Albino Mice

Current Chemical Biology ◽

10.2174/2212796814666200818111849 ◽

2020 ◽

Vol 14 (3) ◽

pp. 169-186

Author(s):

Marwa Emam ◽

Akaber T. Keshta ◽

Yasser M.A. Mohamed ◽

Yasser A. Attia

Keyword(s):

Wound Healing ◽

Adult Female ◽

Vascular Endothelial Cell ◽

Skin Layer ◽

Positive Control ◽

Healing Time ◽

Selenium Nanoparticles ◽

Tissue Samples ◽

Liver And Kidney ◽

Albino Mice

Background: Wound healing is a complex process necessary for repairing damaged tissues and preventing infection. Selenium nanoparticles (Se NPs) were known due to their antioxidant and antimicrobial effects, also niacin has angiogenesis and antioxidant effects that are important in wound healing. Objective: The present study was conducted to investigate the effect of Se NPs and niacin in reducing and accelerating the wound healing time in mice. Methods: A simple wet chemical method has been modified to synthesize Se NPs in order to investigate their effect and niacin on reducing the wound healing in 80 adult female albino mice (250 mm2 full thickness open excision wound) that were divided into eight groups (10 mice/each). After 30-days, the mice were sacrificed, blood and tissue samples were taken for analysis. Results: The results showed that the percentage of wound area had been significantly reduced in Se NPs and niacin treated groups compared to the positive control. The level of Vascular Endothelial cell Growth Factor and Collagenase I in Se NPs and niacin groups significantly exceed those of other groups while Nitric Oxide (NO) was significantly decreased in treated groups. Liver and kidney functions showed the lower toxicity effect of Se NPs and niacin. Skin tissue showed the wound healing effect of Se NPs and niacin by regenerating skin layer compared to the positive group. Conclusion: Se NPs and niacin play an important role in accelerating and reducing the time of wound healing while they were antagonistic to each other.

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SPLUNC1 degradation by the cystic fibrosis mucosal environment drives airway surface liquid dehydration

European Respiratory Journal ◽

10.1183/13993003.00668-2018 ◽

2018 ◽

Vol 52 (4) ◽

pp. 1800668 ◽

Cited By ~ 10

Author(s):

Megan J. Webster ◽

Boris Reidel ◽

Chong D. Tan ◽

Arunava Ghosh ◽

Neil E. Alexis ◽

...

Keyword(s):

Cystic Fibrosis ◽

Airway Surface Liquid ◽

The Novel ◽

Pulmonary Tissue ◽

Tissue Samples ◽

Protein Levels ◽

Surface Liquid ◽

Protease Degradation ◽

Mucosal Secretions ◽

Cystic Fibrosis Transmembrane

The multi-organ disease cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane regulator gene (CFTR) that lead to diminished transepithelial anion transport. CF lungs are characterised by airway surface liquid (ASL) dehydration, chronic infection/inflammation and neutrophilia. Dysfunctional CFTR may upregulate the epithelial Na+ channel (ENaC), further exacerbating dehydration. We previously demonstrated that short palate lung and nasal epithelial clone 1 (SPLUNC1) negatively regulates ENaC in normal airway epithelia.Here, we used pulmonary tissue samples, sputum and human bronchial epithelial cells (HBECs) to determine whether SPLUNC1 could regulate ENaC in a CF-like environment.We found reduced endogenous SPLUNC1 in CF secretions, and rapid degradation of recombinant SPLUNC1 (rSPLUNC1) by CF secretions. Normal sputum, containing SPLUNC1 and SPLUNC1-derived peptides, inhibited ENaC in both normal and CF HBECs. Conversely, CF sputum activated ENaC, and rSPLUNC1 could not reverse this phenomenon. Additionally, we observed upregulation of ENaC protein levels in human CF bronchi. Unlike SPLUNC1, the novel SPLUNC1-derived peptide SPX-101 resisted protease degradation, bound apically to HBECs, inhibited ENaC and prevented ASL dehydration following extended pre-incubation with CF sputum.Our data indicate that CF mucosal secretions drive ASL hyperabsorption and that protease-resistant peptides, e.g. SPX-101, can reverse this effect to rehydrate CF ASL.

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Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against fleas in cats, under field conditions

Parasite ◽

10.1051/parasite/2021018 ◽

2021 ◽

Vol 28 ◽

pp. 22 ◽

Cited By ~ 2

Author(s):

Eric Tielemans ◽

Tomoko Otsuki ◽

Tara Cheesman ◽

Fiona Selmes ◽

Anthony Pfefferkorn ◽

...

Keyword(s):

United States ◽

Field Studies ◽

The United States ◽

Positive Control ◽

Control Group ◽

The Novel ◽

Domestic Cats ◽

Label Dose ◽

Treatment Tolerance ◽

Significant Health

Esafoxolaner is a purified afoxolaner enantiomer with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in a novel topical endectoparasiticide formulation for cats. This novel formulation was tested in four field studies, in the United States, Europe, Japan and Australia. In all studies, naturally flea-infested domestic cats were treated with the novel formulation at the label dose and conditions of use. The main objective, identical in the four studies, was to assess efficacy on fleas, based on comparison of mean number of fleas found on infested cats before and one month after treatment. Tolerance to the product was also evaluated in the four studies. Otherwise, the studies had some differences in their design and secondary objectives, for example testing for a reduction in flea infestation-related cutaneous signs, testing of one treatment or of three monthly treatments, and use of a positive control group. In the four studies, a total of 307 cats were treated with the novel formulation. The reduction of fleas one month after treatment was 97.7%, 98.8%, 100% and 99.7% in the United States, Europe, Japan and Australia, respectively. There were no significant health abnormalities attributed to treatment in any of the studies.

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Dilation catheter-guided mini-forceps biopsy improves the diagnostic accuracy of malignant biliary strictures

Endoscopy ◽

10.1055/a-0630-0878 ◽

2018 ◽

Vol 50 (08) ◽

pp. 809-812 ◽

Cited By ~ 2

Author(s):

Ying-Chun Ren ◽

Chun-Lan Huang ◽

Su-Min Chen ◽

Qiu-Yan Zhao ◽

Xin-Jian Wan ◽

...

Keyword(s):

Biliary Stricture ◽

The Novel ◽

Biliary Strictures ◽

Brush Cytology ◽

Accuracy Rate ◽

Endoscopic Retrograde ◽

Tissue Samples ◽

Forceps Biopsy ◽

Positive Rate ◽

Malignant Biliary Stricture

Abstract Background Tissue sampling for biliary stricture is important for differential diagnosis and further treatment. The aim of this study was to assess a novel dilation catheter-guided mini-forceps biopsy (DCMB) method in the diagnosis of malignant biliary strictures. Methods 42 patients with malignant biliary stricture who underwent both brush cytology and DCMB during endoscopic retrograde cholangiopancreatography between October 2014 and November 2015 were retrospectively included. During DCMB, the mini biopsy forceps was introduced into the biliary stricture through the dilation catheter, and then the position and direction of the forceps were adjusted to obtain tissue samples. Results The positive rate of DCMB was significantly higher than that of brush cytology (81.0 % [34/42] vs. 38.1 % [16/42]; P < 0.001). No severe complications occurred; three patients (7.1 %) experienced mild procedure-related acute pancreatitis. Conclusions The novel DCMB technique was a practical, safe, efficient, and low-costing method for diagnosing malignant biliary stricture with a high accuracy rate.

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Evaluation of homogenization techniques for the preparation of mouse tissue samples to support drug discovery

Bioanalysis ◽

10.4155/bio.11.181 ◽

2011 ◽

Vol 3 (17) ◽

pp. 1923-1933 ◽

Cited By ~ 27

Author(s):

Xiaorong Liang ◽

Savita Ubhayakar ◽

Bianca M Liederer ◽

Brian Dean ◽

Ann Ran-Ran Qin ◽

...

Keyword(s):

Drug Discovery ◽

Mouse Tissue ◽

Tissue Samples

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Preparation of Polymerase Chain Reaction Templates from Embryonic and Adult Mouse Tissue Samples

Cold Spring Harbor Protocols ◽

10.1101/pdb.prot094391 ◽

2019 ◽

Vol 2019 (3) ◽

pp. pdb.prot094391

Author(s):

Janet Rossant ◽

Andras Nagy

Keyword(s):

Polymerase Chain Reaction ◽

Adult Mouse ◽

Mouse Tissue ◽

Chain Reaction ◽

Tissue Samples ◽

Polymerase Chain ◽

Adult Mouse Tissue

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Specific capture and whole-genome phylogeography of Dolphin morbillivirus

Scientific Reports ◽

10.1038/s41598-020-77835-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Francesco Cerutti ◽

Federica Giorda ◽

Carla Grattarola ◽

Walter Mignone ◽

Chiara Beltramo ◽

...

Keyword(s):

Illumina Miseq ◽

Whole Genome ◽

The Novel ◽

Target Enrichment ◽

Genome Sequences ◽

Tissue Samples ◽

Dolphin Morbillivirus ◽

Field Samples ◽

The Mediterranean ◽

Phylodynamic Analysis

AbstractDolphin morbillivirus (DMV) is considered an emerging threat having caused several epidemics worldwide. Only few DMV genomes are publicly available. Here, we report the use of target enrichment directly from cetacean tissues to obtain novel DMV genome sequences, with sequence comparison and phylodynamic analysis. RNA from 15 tissue samples of cetaceans stranded along the Italian and French coasts (2008–2017) was purified and processed using custom probes (by bait hybridization) for target enrichment and sequenced on Illumina MiSeq. Data were mapped against the reference genome, and the novel sequences were aligned to the available genome sequences. The alignment was then used for phylogenetic and phylogeographic analysis using MrBayes and BEAST. We herein report that target enrichment by specific capture may be a successful strategy for whole-genome sequencing of DMV directly from field samples. By this strategy, 14 complete and one partially complete genomes were obtained, with reads mapping to the virus up to 98% and coverage up to 7800X. The phylogenetic tree well discriminated the Mediterranean and the NE-Atlantic strains, circulating in the Mediterranean Sea and causing two different epidemics (2008–2015 and 2014–2017, respectively), with a limited time overlap of the two strains, sharing a common ancestor approximately in 1998.

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Effects of avilamycin and essential oils on mRNA expression of apoptotic and inflammatory markers and gut morphology of piglets

Czech Journal of Animal Science ◽

10.17221/338-cjas ◽

2008 ◽

Vol 53 (No. 9) ◽

pp. 377-387 ◽

Cited By ~ 24

Author(s):

A. Kroismayr ◽

J. Sehm ◽

M.W. Pfaffl ◽

K. Schedle ◽

C. Plitzner ◽

...

Keyword(s):

Essential Oils ◽

Negative Control Group ◽

Positive Control ◽

Negative Control ◽

Feed Additives ◽

Feed Additive ◽

Pcr Analysis ◽

Control Group ◽

Mesenteric Lymph Nodes ◽

Tissue Samples

In this study 120 piglets were allotted to 3 dietary treatments, negative control group, one group receiving a blend of essential oils (EO) derived from oregano, anise and citrus peels (40 mg/kg diet), and a positive control group treated with avilamycin as growth promoting feed additive (40 mg/kg diet). On day 22 of the experiment, 12 representative animals from each treatment group were sacrificed and tissue samples were collected for quantitative real time-PCR analysis and gut tissue morphology. EO and avilamycin decreased the gene expression of the transcriptional factor NFκB and the apoptotic marker TNFα significantly in the ileum and jejunum, respectively. The expression of the proliferation marker Cyclin D1 was also significantly decreased by both substances in the colon, mesenteric lymph nodes and spleen. The colonic crypt depth was reduced by avilamycin, and also numerically by the essential oils. These changes correlated with the up-regulation of the apoptosis factor Caspase 3. Histomorphometry revealed a smaller size of ileal Peyer’s patches through the use of both feed additives, which correlated significantly with lower expression rates of NFκB. In conclusion, the results suggest that EO and avilamycin relieved weaning piglets from an immune defence stress in a similar way.

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