Review
Pharmacology & Pharmacy
Timothy D. Bryson, Pamela Harding
Summary: This review article provides an update on the role of prostaglandin E2 receptors in cardiovascular disease, covering topics such as ischemia-reperfusion injury, arrhythmias, hypertension, and cardiac regeneration. Authors emphasize the importance of clinical studies, although the number of publications in this area is limited.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Noa Moshkovitz, Gali Epstein Shochet, David Shitrit
Summary: In this study, we investigated the effects of a PGE2 and PDE4 inhibitor, Roflumilast, in an IPF-CM system. The results showed that a combination of PGE2 and Roflumilast could block the large aggregate formation induced by IPF-CM and also inhibit cell migration, proliferation, and pro-fibrotic gene expression. Moreover, a review of patient records revealed a higher proportion of slow-progressing patients who were exposed to NSAIDs. These findings suggest the involvement of PGE2/PDE4 signaling in IPF progression and warrant further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anastasia Psarra, Maria A. Theodoropoulou, Martin Erhardt, Marina Mertiri, Christiana Mantzourani, Sofia Vasilakaki, Victoria Magrioti, Andrea Huwiler, George Kokotos
Summary: This study synthesized various alpha-ketoheterocycles and identified one alpha-ketobenzothiazole and one alpha-ketobenzoxazole that can suppress the generation of PGE(2) at a nanomolar level in stimulated mesangial cells.
Article
Genetics & Heredity
Naser Kakavandi, Shima Rezaee, Seyed Reza Hosseini-Fard, Ghasem Ghasempour, Mohsen Khosravi, Mohammad Shabani, Mohammad Najafi
Summary: The study revealed significantly increased levels of PTGES and 15-PGDH gene expression and serum 13,14-dihyro-15-keto-PGF2 alpha value in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520 and miR-34 on gene expression levels were confirmed. The findings suggest an active involvement of the monocyte PGE2 synthesis pathway in patients with stent no restenosis and stent restenosis, potentially related to miR-34 and miR-520 functions.
Article
Oncology
Jia Jiang, Anjie Li, Xiaolian Lai, Hanqun Zhang, Chonghong Wang, Huimin Wang, Libo Li, Yuncong Liu, Lu Xie, Can Yang, Cui Zhang, Shuoyan Lu, Yong Li
Summary: Colorectal cancer is a common and increasing malignancy. Elevated cyclooxygenase-2 is an important factor in inflammation-induced colorectal carcinogenesis. This study aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) levels and the risk of colorectal adenomas. The results showed that urinary PGE-M levels were significantly higher in the high-risk adenoma group compared to the control group, suggesting that urinary PGE-M may be a non-invasive indicator for estimating cancer risk.
FRONTIERS IN ONCOLOGY
(2023)
Article
Physiology
Karin J. Bosma, Monica Ghosh, Spencer R. Andrei, Lin Zhong, Jennifer C. Dunn, Valerie F. Ricciardi, Juliann B. Burkett, Antonis K. Hatzopoulos, Derek S. Damron, Maureen Gannon
Summary: This study found that systemic treatment with an EP3 antagonist improved cardiac function in a mouse model of diabetes. Additionally, blocking EP3 or activating EP4 enhanced contractility and calcium cycling in isolated cardiomyocytes. These findings suggest that modulation of EP3 and EP4 activity has beneficial effects on heart function.
PHYSIOLOGICAL REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Zita Kepes, Noemi Denes, Istvan Kertesz, Istvan Hajdu, Gyoergy Trencsenyi
Summary: As malignancies remain a major global health concern, early tumor identification is crucial. Targeting the COX-2/PGE2/EP axis could provide promising imaging probes for PGE2-positive tumors and anti-cancer drug design. Radiolabelled beta-cyclodextrins (CDs), such as RAMEB, have shown potential as vectors for molecular imaging of PGE2-related tumorigenesis. Preclinical studies using PET imaging with Ga-68 and Bi-205/206-labelled CD derivatives have evaluated their tumor-homing capability in PGE2-expressing tumors. This review highlights the importance of translating these findings into routine clinical usage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Zixuan Wang, Xinyuan Wei, Caili Ji, Wenhua Yu, Chuanwang Song, Caizhi Wang
Summary: Prostaglandin E2 (PGE2) inhibits the phagocytosis of bacteria by neutrophils through unique G protein-coupled receptors (EP receptors) and increased intracellular cyclic adenosine monophosphate (cAMP) production. Specific signaling pathways and enzymes, such as PTEN, contribute to the regulation of neutrophil phagocytic activity by PGE2.
IMMUNITY INFLAMMATION AND DISEASE
(2022)
Article
Microbiology
Savini Thrikawala, Mengyao Niu, Nancy P. Keller, Emily E. Rosowski
Summary: The study identified the importance of cyclooxygenase enzymes in controlling invasive aspergillosis, revealing that COX signaling promotes phagocyte-mediated inhibition of fungal growth. This mechanism contributes to reducing infection rates and increasing host survival.
Article
Cell Biology
Gibran Alejandro Estua-Acosta, Beatriz Buentello-Volante, Fatima Sofia Magana-Guerrero, Jose Eduardo-Aguayo Flores, Oscar Vivanco-Rojas, Ilse Castro-Salas, Karla Zarco-Avila, Mariana A. Garcia-Mejia, Yonathan Garfias
Summary: This research describes the impact of prostaglandin E-2 (PGE(2)) secreted by human amniotic membrane mesenchymal stem cells (hAM-MSCs) on neutrophil extracellular trap (NET) release and identifies the role of its receptors (EP2/EP4) in PAD-4 and NF kappa B activity in neutrophils.
Article
Biochemistry & Molecular Biology
Rachel J. Fenske, Alicia M. Weeks, Michael Daniels, Randall Nall, Samantha Pabich, Allison L. Brill, Darby C. Peter, Margaret Punt, Elizabeth D. Cox, Dawn Belt Davis, Michelle E. Kimple
Summary: More than half of patients with type 2 diabetes are unable to achieve blood glucose targets, and discovering ways to treat these individuals is crucial. PGE(2) has shown promise as a biomarker for beta-cell dysfunction in type 2 diabetes. A clinical cohort study found strong correlation between PGEM levels and therapeutic response, highlighting its potential as a predictive marker.
Article
Infectious Diseases
E. Yaneth Osorio, Ashanti Uscanga-Palomeque, Grace T. Patterson, Erika Cordova, Bruno L. Travi, Lynn Soong, Peter C. Melby
Summary: Malnutrition increases the risk of parasite dissemination from the skin to visceral organs, primarily driven by infected inflammatory monocytes. The production of PGE(2) promotes this process.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Health Care Sciences & Services
Yun Liu, Sixiu Ren, Hongjian Ji, Daonan Yan
Summary: Yangyin Shengji powder has anti-inflammatory and analgesic effects, is anti-oxidative stress, inhibits inflammatory response, and inhibits the COX-2/PGE2 signaling pathway, thus alleviating local inflammation of oral ulcer in mice after chemotherapy and promoting wound healing.
ANNALS OF PALLIATIVE MEDICINE
(2021)
Article
Behavioral Sciences
Gabrielle Rochefort, Veronique Provencher, Sophie Castonguay-Paradis, Julie Perron, Sebastien Lacroix, Cyril Martin, Nicolas Flamand, Vincenzo Di Marzo, Alain Veilleux
Summary: This study found that plasma levels of 2-EPG and 2-DPG were associated with higher intuitive eating scores independent of dietary intake, suggesting a role for these 2-monoacyl-glycerols in the regulation of intuitive eating.
Article
Cell Biology
Clara Depommier, Rosa Maria Vitale, Fabio Arturo Iannotti, Cristoforo Silvestri, Nicolas Flamand, Celine Druart, Amandine Everard, Rudy Pelicaen, Dominique Maiter, Jean-Paul Thissen, Audrey Loumaye, Michel P. Hermans, Nathalie M. Delzenne, Willem M. de Vos, Vincenzo Di Marzo, Patrice D. Cani
Summary: A. muciniphila is considered as a beneficial bacterium for obesity and metabolic disorders, and this study suggests that its effects may be mediated through modulation of certain endocannabinoid-related lipids. Specifically, the bacterium counteracted the decrease in 1-PG and 2-PG observed in overweight or obese individuals, which are endogenous activators of PPAR alpha, potentially explaining some of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.
Article
Cell Biology
Clara Depommier, Nicolas Flamand, Rudy Pelicaen, Dominique Maiter, Jean-Paul Thissen, Audrey Loumaye, Michel P. Hermans, Amandine Everard, Nathalie M. Delzenne, Vincenzo Di Marzo, Patrice D. Cani
Summary: This study explores new associations between the eCBome and metabolic parameters related to obesity, using canonical correlation analysis and principal component analysis to identify connections between endogenous bioactive lipids and markers like leptin, lipopolysaccharide-binding protein, and NEFA. Predictive regression models show good performance, and analysis confirms higher levels of specific circulating endocannabinoids in individuals with elevated metabolic variables.
Article
Dermatology
Melissa Simard, Genevieve Rioux, Sophie Morin, Cyril Martin, Sylvain L. Guerin, Nicolas Flamand, Pierre Julien, Julie Fradette, Roxane Pouliot
Summary: Clinical studies have shown that diets enriched with omega-3 polyunsaturated fatty acids could alleviate psoriasis symptoms, but the mechanisms are poorly understood. This study investigated the effects of ALA on psoriatic keratinocytes in a 3D skin model. ALA supplementation decreased keratinocyte proliferation, improved epidermal differentiation, and altered levels of lipid mediators.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesco Tinto, Anne-Sophie Archambault, Elizabeth Dumais, Volatiana Rakotoarivelo, Magdalena Kostrzewa, Cyril Martin, Pier-Luc Plante, Yves Desjardins, Melissa Simard, Roxane Pouliot, Luciano De Petrocellis, Alessia Ligresti, Vincenzo Di Marzo, Nicolas Flamand
Summary: N-Arachidonoyl-ethanolamine (AEA) is an endocannabinoid mimicking the effects of Delta(9)-tetrahydrocannabinol, affecting brain functions, appetite, pain, and inflammation. Research on N-linoleoyl-ethanolamine (LAE) suggests that certain NAEs can be metabolized into 15-lipoxygenase-derived derivatives.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Anne-Sophie Archambault, Younes Zaid, Volatiana Rakotoarivelo, Caroline Turcotte, Etienne Dore, Isabelle Dubuc, Cyril Martin, Olivier Flamand, Youssef Amar, Amine Cheikh, Hakima Fares, Amine El Hassani, Youssef Tijani, Andreanne Cote, Michel Laviolette, Eric Boilard, Louis Flamand, Nicolas Flamand
Summary: The study found that severe COVID-19 patients have increased fatty acids and inflammatory lipid mediators in bronchoalveolar lavages (BALs), including thromboxane, leukotrienes, and monohydroxylated 15-lipoxygenase metabolites. Additionally, specialized pro-resolving mediators such as lipoxin A(4) and D-series resolvins are also increased, indicating a lipid mediator storm in the lungs of severe COVID-19 patients.
Article
Allergy
Younes Zaid, Etienne Dore, Isabelle Dubuc, Anne-Sophie Archambault, Olivier Flamand, Michel Laviolette, Nicolas Flamand, Eric Boilard, Louis Flamand
Summary: The study aimed to analyze and compare the presence of cytokines and lipid mediators of inflammation in the plasma and bronchoalveolar lavage (BAL) fluids of patients with severe COVID-19. The results showed high concentrations of numerous cytokines, chemokines, and lipid mediators in the BAL fluid of patients with severe COVID-19, indicating that hyperinflammation in the lungs of these patients is fueled by excessive production of chemokines and eicosanoids.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesco Suriano, Claudia Manca, Nicolas Flamand, Clara Depommier, Matthias Van Hul, Nathalie M. Delzenne, Cristoforo Silvestri, Patrice D. Cani, Vincenzo Di Marzo
Summary: The study revealed differential alterations in eCBome tone in the liver and adipose tissues between ob/ob and db/db mice, which may contribute to the impaired hepatic function and different inflammatory states observed in these two mouse models. Correlation studies suggested potential interactions with gut microbiota alterations in relation to the inflammatory phenotypes. The findings highlight the importance of bioactive lipids and eCBome molecules in maintaining tissue-dependent inflammatory states associated with obesity and diabetes.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Nutrition & Dietetics
Jerome Lamontagne-Proulx, Katherine Coulombe, Fadil Dahhani, Melissa Cote, Cedric Guyaz, Cyntia Tremblay, Vincenzo Di Marzo, Nicolas Flamand, Frederic Calon, Denis Soulet
Summary: The study demonstrates that dietary supplementation with DHA can protect enteric DAergic neurons in Thy1-alpha Syn mice, decrease microgliosis in the striatum, and promote the accumulation of eCB-like mediators, GLP-1, and Nrf2 in the ENS.
Article
Pharmacology & Pharmacy
Melissa Simard, Volatiana Rakotoarivelo, Vincenzo Di Marzo, Nicolas Flamand
Summary: The CB2 receptor is expressed in a wide range of leukocytes and its activation has potential therapeutic effects for inflammatory and autoimmune diseases. Current research focuses on identifying immune cells expressing CB2 receptors and studying the consequences of receptor activation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Anne-Sophie Archambault, Julyanne Brassard, Emilie Bernatchez, Cyril Martin, Vincenzo Di Marzo, Michel Laviolette, Louis-Philippe Boulet, Marie-Renee Blanchet, Nicolas Flamand
Summary: High eosinophil counts are an important feature of eosinophilic asthma. This study compared the ability of human and mouse eosinophils to synthesize key lipid mediators. The results showed that human and mouse eosinophils can synthesize the same lipid mediators, but in different amounts, indicating potential differences in their impact on asthma.
Article
Medicine, Research & Experimental
Etienne Dore, Charles Joly-Beauparlant, Satoshi Morozumi, Alban Mathieu, Tania Levesque, Isabelle Allaeys, Anne-Claire Duchez, Nathalie Cloutier, Mickael Leclercq, Antoine Bodein, Christine Payre, Cyril Martin, Agnes Petit-Paitel, Michael H. Gelb, Manu Rangachari, Makoto Murakami, Laetitia Davidovic, Nicolas Flamand, Makoto Arita, Gerard Lambeau, Arnaud Droit, Eric Boilard
Summary: sPLA(2)-IIA exerts its effects on the immune system by acting on the intestinal microbiota and its lipidome. Changes in the composition of the intestinal microbiota and bacterial-derived lipid mediators are potentially involved in this process.
Article
Engineering, Biomedical
Melissa Simard, Andrea Tremblay, Sophie Morin, Cyril Martin, Pierre Julien, Julie Fradette, Nicolas Flamand, Roxane Pouliot
Summary: Polyunsaturated fatty acids (PUFAs) play a vital role in the establishment and maintenance of the skin barrier function. This study found that supplementation with alpha-linolenic acid (ALA) and linoleic acid (LA) in the culture medium improved the barrier function of a tissue-engineered skin model. The exogenously provided fatty acids were incorporated into phospholipid and triglyceride fractions of the skin substitutes, and further modulated the levels of bioactive lipid mediators. These findings highlight the importance of optimizing the supply of PUFAs in the culture media for the establishment of an improved barrier function in vitro.
ACTA BIOMATERIALIA
(2022)
Review
Pharmacology & Pharmacy
Nils Helge Schebb, Hartmut Kuehn, Astrid S. Kahnt, Katharina M. Rund, Valerie B. O'Donnell, Nicolas Flamand, Marc Peters-Golden, Per-Johan Jakobsson, Karsten H. Weylandt, Nadine Rohwer, Robert C. Murphy, Gerd Geisslinger, Garret A. FitzGerald, Julien Hanson, Claes Dahlgren, Mohamad Wessam Alnouri, Stefan Offermanns, Dieter Steinhilber
Summary: This paper critically evaluates the biosynthetic pathways of specialized pro-resolving lipid mediators (SPMs), their receptors and signaling cascades, and the analytical methods used to quantify these mediators. It concludes that there is limited biosynthetic capacity for SPMs in human leukocytes, the identity and signaling of proposed SPM receptors need further validation, SPM levels are not related to dietary supplementation or resolution of inflammation, and the commonly reported methodology for quantification of SPMs is unreliable.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Melissa Shen, Claudia Manca, Francesco Suriano, Nayudu Nallabelli, Florent Pechereau, Benedicte Allam-Ndoul, Fabio Arturo Iannotti, Nicolas Flamand, Alain Veilleux, Patrice D. Cani, Cristoforo Silvestri, Vincenzo Di Marzo
Summary: The endocannabinoidome-gut microbiome axis plays a fundamental role in controlling energy intake and metabolism. The liver-expressed antimicrobial peptide 2 (LEAP2) is a molecule that affects energy metabolism in the gastrointestinal system. This study investigates the role of this axis in the expression of LEAP2 in the liver and intestines, and suggests that LEAP2 from the small intestine may have an impact on food intake and energy metabolism.