Epoxyeicosatrienoic

OBJECTIVE: To investigate whether sEH inhibitor AUDA can mitigate postpartum depression (PPD)-like symptoms in the rat model and regulate the AA/NF-κB pathway to suppress the inflammatory response in the prefrontal lobes of PPD rats. METHODS: Five groups of Sprague Dawley rats were used: normal, sham operated, PPD model, AUDA, and paroxetine hydrochloride. During the 21-day treatment period, animals in all groups underwent assessments (open field test, forced swimming test, and sucrose consumption) for depression-like behavior...

Alveolar epithelial cell (AEC) senescence is considered to be a universal pathological feature of many chronic pulmonary diseases. Our previous study found that epoxyeicosatrienoic acids (EETs), produced from arachidonic acid (ARA) through the cytochrome P450 cyclooxygenase (CYP) pathway, have significant negative regulatory effects on cellular senescence in AECs. However, the exact mechanisms by which EETs alleviate the senescence of AECs still need to be further explored. In the present study, we observed that bleomycin (BLM) induced enhanced mitophagy accompanied by increased mitochondrial ROS (mito-ROS) content in the murine alveolar epithelial cell line MLE12...

Acid sphingomyelinase deficiency is a neurodegenerative lysosomal storage disorder caused by mutations in the sphingomyelin-degrading enzyme acid sphingomyelinase (ASM) gene. Upregulated neuroinflammation has been well-characterized in an ASM knockout mouse model of acid sphingomyelinase deficiency disease, but lipid mediator pathways involved in 'mediating' inflammation and inflammation-resolution have yet to be characterized. In this study, we 1) measured free (bioactive) and esterified (inactive) lipid mediators involved in inflammation and inflammation resolution in cerebellum and neuronal cultures of ASM knockout (ASMko) mice and wildtype (WT) controls, and 2) tested the incorporation of labeled pro-resolving free d11-14(15)-epoxyeicosatrienoic acid into culture neurons from ASMko and WT mice...

BACKGROUND: Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown. METHOD: 16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD...

BACKGROUND: Epoxyeicosatrienoic acids (EETs), which exert multiple endogenous protective effects, are hydrolyzed into less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). However, commercial drugs related to EETs or sEH are not yet in clinical use. METHODS: Firstly, the plasma concentration of EETs and DHETs of 316 patients with heart failure (HF) were detected and quantitated by liquid chromatography-tandem mass spectrometry. Then, transverse aortic constriction (TAC)-induced HF was introduced in cardiomyocyte-specific Ephx2-/- mice...

Arachidonic acid (AA), an n-6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers...

BACKGROUND: Recent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron's anti-breast carcinoma (BC) function. METHODS: Bioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays...

Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the brain. Herein, we demonstrate that brain-expressed FABPs (FABP3, FABP5, and FABP7) interact with epoxyeicosatrienoic acids (EETs) and the peroxisome proliferator-activated receptor gamma agonist 15-deoxy-Δ12,14 -Prostaglandin J2 (15d-PGJ2 )...

Human soluble epoxide hydrolase (sEH), a dual-functioning homodimeric enzyme with hydrolase and phosphatase activities, is known for its pivotal role in the hydrolysis of epoxyeicosatrienoic acids. Inhibitors targeting sEH have shown promising potential in the treatment of various life-threatening diseases. In this study, we employed a range of in silico modeling approaches to investigate a diverse dataset of structurally distinct sEH inhibitors. Our primary aim was to develop predictive and validated models while gaining insights into the structural requirements necessary for achieving higher inhibitory potential...

Myocarditis is a challenging inflammatory disease of the heart, and better understanding of its pathogenesis is needed to develop specific drug therapies. Epoxyeicosatrienoic acids (EETs), active molecules synthesized by CYP (cytochrome P450) enzymes from arachidonic acids and hydrolyzed to less active dihydroxyeicosatrienoic acids by sEH (soluble epoxide hydrolase), have been attributed anti-inflammatory activity. Here, we investigated whether EETs have immunomodulatory activity and exert protective effects on coxsackie B3 virus-induced myocarditis...

BACKGROUND: The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans...

BACKGROUND: Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism. METHODS: Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy...

OBJECTIVE: We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats. METHODS: Pregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d)...

Following the publication of the above article, an interested reader drew to the authors' attention that, for the cell migration assay experiments shown in Fig. 5 on p. 731, the 'TNF‑α' data panels in Fig. 5A and C appeared to be matching, where experiments performed under different conditions were intended to have been displayed. After having re‑examined their original data, the authors have realized that the data files were mislabelled, although they were able to retrieve the correct data for Fig...

In sporadic amyotrophic lateral sclerosis (sALS), IL-17A- and granzyme-positive cytotoxic T lymphocytes (CTL), IL-17A-positive mast cells, and inflammatory macrophages invade the brain and spinal cord. In some patients, the disease starts following a trauma or a severe infection. We examined cytokines and cytokine regulators over the disease course and found that, since the early stages, peripheral blood mononuclear cells (PBMC) exhibit increased expression of inflammatory cytokines IL-12A, IFN-γ, and TNF-α, as well as granzymes and the transcription factors STAT3 and STAT4...

In spite of unprecedented advances in modern cancer therapy, there is still a dearth of targeted therapy to circumvent triple-negative breast cancer (TNBC). Paclitaxel is the front-line therapy against TNBC, but the main constraints of its treatment are dose-related adverse effects and emerging chemoresistance. In this context, glabridin (phytoconstituent from Glycyrrhiza glabra) is reported to hit multiple signalling pathways at the in-vitro level, but hardly any information is known at the in-vivo level. We aimed here to elucidate glabridin potential with an underlying mechanism in combination with a low dose of paclitaxel using a highly aggressive mouse mammary carcinoma model...

Air pollution represented by particulate matter 2.5 (PM2.5) is closely related to diseases of the respiratory system. Although the understanding of its mechanism is limited, pulmonary inflammation is closely correlated with PM2.5-mediated lung injury. Soluble epoxide hydrolase (sEH) and epoxy fatty acids play a vital role in the inflammation. Herein, we attempted to use the metabolomics of oxidized lipids for analyzing the relationship of oxylipins with lung injury in a PM2.5-mediated mouse model, and found that the cytochrome P450 oxidases/sEH mediated metabolic pathway was involved in lung injury...

Alzheimer's disease (AD) is caused by a complex interaction between genetic and environmental factors. However, how the role of peripheral organ changes in response to environmental stimuli during aging in AD pathogenesis remains unknown. Hepatic soluble epoxide hydrolase (sEH) activity increases with age. Hepatic sEH manipulation bidirectionally attenuates brain amyloid-β (Aβ) burden, tauopathy, and cognitive deficits in AD mouse models. Moreover, hepatic sEH manipulation bidirectionally regulates the plasma level of 14,15-epoxyeicosatrienoic acid (-EET), which rapidly crosses the blood-brain barrier and modulates brain Aβ metabolism through multiple pathways...

Cytochrome P450 2J2 (CYP2J2) enzyme is widely expressed in aortic endothelial cells and cardiac myocytes and affects cardiac function, but the underlying mechanism is still unclear. Based on CYP2J knockout (KO) rats, we have directly studied the metabolic regulation of CYP2J on cardiac function during aging. The results showed that CYP2J deficiency significantly reduced the content of epoxyeicosatrienoic acids (EETs) in plasma, aggravated myocarditis, myocardial hypertrophy, as well as fibrosis, and inhibited the mitochondrial energy metabolism signal network Pgc-1α/Ampk/Sirt1...

AIM: To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women. METHODS: A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses...