Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation

Lee, Bohae Rachel; Paing, May; Sharma-Walia, Neelam

doi:10.3389/fphys.2021.640374

Cited by 15 publications

(7 citation statements)

References 210 publications

(238 reference statements)

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“…Based on this chemical, the assay selected for the cluster was TOX21_PPARg_BLA_Agonist_ch2. While PPAR γ is not a direct target of prostaglandins, there is documented bidirectional communication between PPAR γ and different prostaglandin signaling pathways ( Koeffler, 2003 ; Fujimori, 2012 ; Evans et al, 2019 ; Lee et al, 2021 ) and 15-deoxy-Δ 12,14 -prostaglandin J 2 is the endogenous ligand for this receptor ( Kliewer et al, 1995 ; Lee et al, 2021 ). Beraprost is an analog for prostaglandin I or prostacyclin, which has been shown to modulate PPAR δ ( Forman et al, 1997 ; Lim et al, 1999 ).…”

Section: Resultsmentioning

confidence: 99%

Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements

et al. 2022

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Regulatory agencies around the world have committed to reducing or eliminating animal testing for establishing chemical safety. Adverse outcome pathways can facilitate replacement by providing a mechanistic framework for identifying the appropriate non-animal methods and connecting them to apical adverse outcomes. This study separated 11,992 chemicals with curated rat oral acute toxicity information into clusters of structurally similar compounds. Each cluster was then assigned one or more ToxCast/Tox21 assays by looking for the minimum number of assays required to record at least one positive hit call below cytotoxicity for all acutely toxic chemicals in the cluster. When structural information is used to select assays for testing, none of the chemicals required more than four assays and 98% required two assays or less. Both the structure-based clusters and activity from the associated assays were significantly associated with the GHS toxicity classification of the chemicals, which suggests that a combination of bioactivity and structural information could be as reproducible as traditional in vivo studies. Predictivity is improved when the in vitro assay directly corresponds to the mechanism of toxicity, but many indirect assays showed promise as well. Given the lower cost of in vitro testing, a small assay battery including both general cytotoxicity assays and two or more orthogonal assays targeting the toxicological mechanism could be used to improve performance further. This approach illustrates the promise of combining existing in silico approaches, such as the Collaborative Acute Toxicity Modeling Suite (CATMoS), with structure-based bioactivity information as part of an efficient tiered testing strategy that can reduce or eliminate animal testing for acute oral toxicity.

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Section: Resultsmentioning

confidence: 99%

Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements

et al. 2022

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“…Their expression increases during storage of SDA-PC but decreases significantly in SDA-PC with the occurrence of AR. PGA 1 is known as an inflammation regulator among other functions ( 45 ). 9-HODE increases adenylate cyclase in platelets as a partial agonist of PGE 1 and PGE 2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Bioactive lipids as biomarkers of adverse reactions associated with apheresis platelet concentrate transfusion

et al. 2023

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Platelet concentrate (PC) transfusion seeks to provide haemostasis in patients presenting severe central thrombocytopenia or severe bleeding. PCs may induce adverse reactions (AR) that can occasionally be severe (SAR). PCs contain active biomolecules such as cytokines and lipid mediators. The processing and storage of PCs creates so-called structural and biochemical storage lesions that accumulate when blood products reach their shelf life. We sought to investigate lipid mediators as bioactive molecules of interest during storage and review associations with adverse reactions post-transfusion. To facilitate understanding, we focused on single donor apheresis (SDA) PCs with approximately 31.8% of PCs being delivered in our setting. Indeed, pooled PCs are the most widely transfused products, but the study of a single donor lipid mediator is easier to interpret. We are investigating key lipid mediators involved in AR. Adverse reactions were closely monitored in accordance with current national and regional haemovigilance protocols. Residual PCs were analysed post-transfusion in a series of observations, both with and without severe reactions in recipients. A decrease in the lysophosphatidylcholine species to produce the lysophosphatidic acid species has been observed during storage and in the case of AR. Lysophosphatidic acid increased with primarily platelet-inhibitor lipids. Anti-inflammatory platelet-induced inhibition lipids were weakly expressed in cases of severe adverse reactions. We therefore propose that a decrease in lysophosphatidylcholine and an increase in lysophosphatidic acid can prospectively predict serious adverse transfusion reactions.

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“…Cyclopentenone prostaglandins (cyPGs), PGA 1 , PGA 2 , PGJ 2 , 15-Deoxy-Δ- 12,14 -Prostaglandin J 2 (15d-PGJ 2 ) and Δ 12 -PGJ 2 are a group of prostaglandins that increase apoptosis, resolve inflammation, have anti-metastatic and anti-angiogenic properties ( Lee et al, 2021 ). PGA 1 is produced from linoleic acid ( Whelan and Fritsche, 2013 ).…”

Section: Potential Therapeutic Strategies In Crc: New Trend and Futur...mentioning

confidence: 99%

A review on the role of fatty acids in colorectal cancer progression

Hoxha

Zappacosta

2022

Front. Pharmacol.

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Colorectal cancer (CRC) is the third leading cause of mortality in cancer patients. The role of fatty acids (FA) and their metabolism in cancer, particularly in CRC raises a growing interest. In particular, dysregulation of synthesis, desaturation, elongation, and mitochondrial oxidation of fatty acids are involved. Here we review the current evidence on the link between cancer, in particular CRC, and fatty acids metabolism, not only to provide insight on its pathogenesis, but also on the development of novel biomarkers and innovative pharmacological therapies that are based on FAs dependency of cancer cells.

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Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation

Cited by 15 publications

References 210 publications

Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements

Mapping Mechanistic Pathways of Acute Oral Systemic Toxicity Using Chemical Structure and Bioactivity Measurements

Bioactive lipids as biomarkers of adverse reactions associated with apheresis platelet concentrate transfusion

A review on the role of fatty acids in colorectal cancer progression

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