scholarly journals Differential Lipid Mediator Involvement in the Different Forms of Genetic Frontotemporal Dementia: Novel Insights into Neuroinflammation

2021 ◽  
pp. 1-7
Author(s):  
Aitana Sogorb-Esteve ◽  
Romain A. Colas ◽  
Jesmond Dalli ◽  
Jonathan D. Rohrer
Keyword(s):  
Frontotemporal Dementia ◽  
Docosapentaenoic Acid ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
C9orf72 Expansion ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Mapt Mutation ◽  
Homeostatic State

Background: The pathophysiology of frontotemporal dementia (FTD) is poorly understood but recent studies implicate neuroinflammation as an important factor. However, little is known so far about the role of the resolution pathway, the response to inflammation that allows tissue to return to a homeostatic state. Objective: We aimed to measure the concentrations of lipid mediators including specialized proresolving mediators (SPMs) and proinflammatory eicosanoids in the cerebrospinal fluid (CSF) of people with FTD. Methods: 15 people with genetic FTD (5 with C9orf72 expansions, 5 with GRN mutations, and 5 with MAPT mutations) were recruited to the study along with 15 age- and sex-matched healthy controls. Targeted liquid chromatography-tandem mass spectrometry techniques were used to measure the CSF concentrations of lipid mediators in the docosahexaenoic acid (DHA), n-3 docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid (AA) metabolomes. Results: Only the C9orf72 expansion carriers had higher concentrations of SPMs (DHA-derived maresins and DHA-derived resolvins) compared with controls. In contrast, GRN and MAPT mutation carriers had normal concentrations of SPMs but significantly higher concentrations of the proinflammatory AA-derived leukotrienes and AA-derived thromboxane compared with controls. Additionally, the C9orf72 expansion carriers also had significantly higher concentrations of AA-derived leukotrienes. Conclusion: This initial pilot study of lipid mediators provides a window into a novel biological pathway not previously investigated in FTD, showing differential patterns of alterations between those with C9orf72 expansions (where SPMs are higher) and GRN and MAPT mutations (where only proinflammatory eicosanoids are higher).

scholarly journals Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 746
Author(s):  
Kehong Zhang ◽  
Simona Pace ◽  
Paul M. Jordan ◽  
Lukas K. Peltner ◽  
Alexander Weber ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Monocyte ◽  
Ultra Performance Liquid Chromatography ◽  
Innate Immune ◽  
Lipid Mediator ◽  
Tripterygium Wilfordii ◽  
Direct Inhibition ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Lox Products

Tripterygium wilfordii glycosides (TWG) is a traditional Chinese medicine with effectiveness against rheumatoid arthritis (RA), supported by numerous clinical trials. Lipid mediators (LM) are biomolecules produced from polyunsaturated fatty acids mainly by cyclooxygenases (COX) and lipoxygenases (LOX) in complex networks which regulate inflammation and immune responses and are strongly linked to RA. The mechanism by which TWG affects LM networks in RA treatment remains elusive. Employing LM metabololipidomics using ultra-performance liquid chromatography-tandem mass spectrometry revealed striking modulation of LM pathways by TWG in human monocyte-derived macrophage (MDM) phenotypes. In inflammatory M1-MDM, TWG (30 µg/mL) potently suppressed agonist-induced formation of 5-LOX products which was confirmed in human PMNL and traced back to direct inhibition of 5-LOX (IC50 = 2.9 µg/mL). TWG also efficiently blocked thromboxane formation in M1-MDM without inhibiting other prostanoids and COX enzymes. Importantly, in anti-inflammatory M2-MDM, TWG (30 µg/mL) induced pronounced formation of specialized pro-resolving mediators (SPM) and related 12/15-LOX-derived SPM precursors, without COX and 5-LOX activation. During MDM polarization, TWG (1 µg/mL) decreased the capacity to generate pro-inflammatory 5-LOX and COX products, cytokines and markers for M1 phenotypes. Together, suppression of pro-inflammatory LM but SPM induction may contribute to the antirheumatic properties of TWG.

scholarly journals Methodologies and Procedures Employed in the Identification and Quantitation of Lipid Mediators via LC-MS/MS

2020 ◽  
Author(s):  
Roman A. Colas ◽  
Esteban A Gomez ◽  
Jesmond Dalli
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Solid Phase ◽  
Lipid Mediators ◽  
Tandem Mass ◽  
Phase Extraction ◽  
Robust Approach ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract Liquid chromatography tandem mass spectrometry (LC-MS/MS) is a sensitive and robust approach for the identification and quantitation of lipid mediators including the specialized pro-resolving mediators (resolvins, maresins, protectins and lipoxins), and the classic eicosanoids. Due to the relatively low concentration of these molecules in biological samples, this methodology is classically coupled with solid phase extraction (SPE) techniques that enhance the sensitivity of the assay. Herein, we provide a step-by-step description of instrumentation employed in the both SPE and LC-MS/MS and detailed methodologies employed in the extraction of these lipid mediators and their identification and quantitation using LC-MS/MS.

scholarly journals Association between plasma betaine levels and dysglycemia in patients with coronary artery disease

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Fei Guo ◽  
Xueting Qiu ◽  
Yuanting Zhu ◽  
Zhirong Tan ◽  
Zhenyu Li ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Metabolic Disorders ◽  
Glycated Hemoglobin ◽  
Fasting Glucose ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Traditional Risk Factors ◽  
Artery Disease

Abstract Background: Dietary betaine intake was reported to associate with favorable profile of metabolic disorders. However, the role of circulating betaine in coronary artery disease (CAD) patients with dysglycemia is still unknown. The present study aimed to investigate the potential associations between plasma betaine levels and dysglycemia in CAD patients. Methods: Total 307 subjects were enrolled in the present study with 165 CAD patients (57 with dysglycemia and 108 with normal glycemia) and 142 age- and sex-matched controls (CON). Fasting plasma betaine was detected using liquid chromatography tandem mass spectrometry. Results: Plasma betaine was lower in normal glycemia CAD patients (28.29 (22.38–35.73) μM) compared with healthy controls (29.75 (25.32–39.15) μM), and was further decreased in CAD patients with dysglycemia (24.14 (20.84–30.76) μM, P<0.01). Betaine levels were inversely correlated with fasting glucose, glycated hemoglobin% (HbA1c), diastolic blood pressure (DBP), triglyceride (TG) and alanine aminotransferase (ALT) levels (all, P≤0.05). Subjects in the highest betaine tertile group had lowest frequency of CAD and dysglycemia (all, P<0.01). Increased betaine levels were independently associated with low risk of dysglycemia in CAD after adjustment for multiple traditional risk factors (OR = 0.04, 95% CI: 0–0.37, P=0.01). Furthermore, betaine had good performance at distinguishing CAD with dysglycemia from normal glycemia CAD (AUC = 0.62, P<0.01). Conclusion: Plasma betaine levels are independently and inversely associated with dysglycemia in CAD after adjustment for multiple factors, and may be useful for risk stratification of dysglycemia in CAD.

scholarly journals A Role for Lipid Mediators in Acute Myeloid Leukemia

2019 ◽  
Vol 20 (10) ◽  
pp. 2425 ◽  
Author(s):  
Andreas Loew ◽  
Thomas Köhnke ◽  
Emma Rehbeil ◽  
Anne Pietzner ◽  
Karsten-H. Weylandt
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Therapy ◽  
Hematologic Malignancies ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Immune Mechanisms ◽  
Acute Myeloid

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.

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