Exploring oxylipins in processed foods: Understanding mechanisms, analytical perspectives, and enhancing quality with lipidomics.

Oxylipins are active lipid compounds formed through the oxidation of unsaturated fatty acids. These compounds have drawn considerable attention due to the potential impact on human health and processed food quality. Therefore, this study aimed to deepen current understanding and assess recent analytical advancements regarding the physiological roles of oxylipins in processed food products using lipidomics. The mechanisms behind oxylipins production in processed foods were extensively investigated, underscoring potential associations with chronic diseases. This indicates the need for innovative strategies to mitigate harmful oxylipins levels to enhance the safety and shelf life of processed food products. The results showed that mitigation methods, including the use of antioxidants and optimization of processing parameters, reduced oxylipins levels. The integration of lipidomics with food safety and quality control processes is evident in cutting-edge methods such as nuclear magnetic resonance and mass spectrometry for compliance and real-time evaluation. Aside from envisioning the future trajectory of food science and industry through prospective studies on oxylipins and processed foods, the results also provide the basis for future investigations, innovation, and advancements in the dynamic field of food science and technology.

The analgesic effects of Yu-Xue-Bi tablet (YXB) on mice with inflammatory pain by regulating LXA4-FPR2-TRPA1 pathway.

BACKGROUND: Oxylipins including lipoxin A4 (LXA4) facilitate the resolution of inflammation and possess analgesic properties by inhibiting macrophage infiltration and transient receptor potential (TRP) protein expression. Yu-Xue-Bi Tablet (YXB) is a traditional Chinese patent medicine used to relieve inflammatory pain. Our previous research has shown that the analgesic effect of YXB is related to inhibiting peripheral inflammation and regulating macrophage infiltration, but the mechanism is not yet clear. The purpose of this study is to explore the mechanisms of YXB on mice models with Complete Freund's Adjuvant (CFA)-induced inflammatory pain from the perspective at the resolution of inflammation. METHODS: Mechanical allodynia thresholds and heat hypersensitivity were measured using the Von Frey test and the hot plate test respectively. The open field test and the tail suspension test were employed to measure anxiety and depressive behaviors respectively. The expression of CD68+ and the proportion of F4/80+CD11b+ cells were measured by immunofluorescence staining and flow cytometry. The expression of transient receptor potential ankyrin 1(TRPA1) was measured by immunofluorescence staining and western blotting. Oxylipins omics analysis provided quantitative data on oxylipins in the paws, and enzyme linked immunosorbent assay (ELISA) was used to measure the levels of LXA4 there. Immunofluorescence staining was used to perform the expression of Leukotriene A4 hydroxylase (LTA4H) in the paws of mice. The impact of injecting the formyl peptide receptor 2(FPR2) antagonist WRW4 and the TRPA1 agonist AITC into the left paws was observed, focusing on the expression of mechanical allodynia thresholds, the expression of CD68+, TRPA1 in the paws, and Calcitonin gene-related peptide (CGRP) in the L5 spinal dorsal horn. RESULTS: YXB elevated mechanical allodynia thresholds, alleviated heat hypersensitivity and anxiety and depressive behaviors in CFA mice. It significantly reduced the number of CD68+ and proportion of F4/80+CD11b+ within the paws, thereby decreasing macrophage infiltration. Additionally, it diminished the expression of TRPA1 in the paws and TRPV1 in the DRG, leading to an inhibition of peripheral sensitization. Through quantitative analysis, it was found that YXB could modulate DHA-derived oxylipins and LXA4. ELISA results indicated that YXB elevated the levels of LXA4 and inhibited the expression of LAT4H in the paws. Furthermore, the pro-resolution and analgesic effects of YXB were hindered after administration of the FPR2 antagonist. Compared with the AITC group, YXB showed no significant improvement in anti-inflammatory and analgesic effects. CONCLUSIONS: YXB can regulate the oxylipins of paws in CFA mice to promote the resolution of inflammation. The LXA4-FPR2-TRPA1 pathway is a key mechanism for the resolution of inflammation and analgesic effects.

Nickel-induced oxidative stress and phospholipid remodeling in cucumber leaves.

Nickel phytotoxicity has been attributed, among others, to oxidative stress. However, little is known about Ni-induced phospholipid modifications, including the oxidative ones. Accumulation of reactive oxygen species (ROS), antioxidative enzyme activities, malondialdehyde and the early lipid oxidation products contents, membrane permeability, phospholipid profile as well as phospholipid unsaturation degree were studied in the 1st and the 2nd leaves of hydroponically grown cucumber seedlings subjected to Ni stress. Compared to the 2nd leaf the 1st one showed stronger visual Ni toxicity symptoms, higher Ni, O2.- and H2O2 accumulation as well as greater enhancement in membrane permeability. Enzyme activities were differently influenced by Ni stress, however most pronounced changes were generally found in the 1st leaf. Ni treatment resulted in oxidation of leaf lipids, which was evidenced by appearance of increased contents of MDA and the early produced oxylipins. Among the latter 9-hydroxyoctadecatrienoic acid (9-HOTrE) and 13-hydroxyoctadecatrienoic acid (13-HOTrE) contents showed the most pronounced increase in response to Ni treatment. Exposure to the metal led to the changes in the leaf phospholipid profile and increased degree of phospholipid unsaturation. The obtained results have been discussed in relation to the difference in Ni stress severity between the 1st and the 2nd leaves.

9-HODE and 9-HOTrE alter mitochondrial metabolism, increase triglycerides, and perturb fatty acid uptake and synthesis associated gene expression in HepG2 cells.

Non-Alcoholic Fatty Liver Disease (NAFLD) prevalence is rising and can lead to detrimental health outcomes such as Non-Alcoholic Steatohepatitis (NASH), cirrhosis, and cancer. Recent studies have indicated that Cytochrome P450 2B6 (CYP2B6) is an anti-obesity CYP in humans and mice. Cyp2b-null mice are diet-induced obese, and human CYP2B6-transgenic (hCYP2B6-Tg) mice reverse the obesity or diabetes progression, but with increased liver triglyceride accumulation in association with an increase of several oxylipins. Notably, 9-hydroxyoctadecadienoic acid (9-HODE) produced from linoleic acid (LA, 18:2, ω-6) is the most prominent of these and 9-hydroxyoctadecatrienoic acid (9-HOTrE) from alpha-linolenic acid (ALA, 18:3, ω-3) is the most preferentially produced when controlling for substrate concentrations in vitro. Transactivation assays indicate that 9-HODE and 9-HOTrE activate PPARα and PPARγ. In Seahorse assays performed in HepG2 cells, 9-HOTrE increased spare respiratory capacity, slightly decreased palmitate metabolism, and increased non-glycolytic acidification in a manner consistent with slightly increased glutamine utilization; however, 9-HODE exhibited no effect on metabolism. Both compounds increased triglyceride and pyruvate concentrations, most strongly by 9-HOTrE, consistent with increased spare respiratory capacity. qPCR analysis revealed several perturbations in fatty acid uptake and metabolism gene expression. 9-HODE increased expression of CD36, FASN, PPARγ, and FoxA2 that are involved in lipid uptake and production. 9-HOTrE decreased ANGPTL4 expression and increased FASN expression consistent with increased fatty acid uptake, fatty acid production, and AMPK activation. Our findings support the hypothesis that 9-HODE and 9-HOTrE promote steatosis, but through different mechanisms as 9-HODE is directly involved in fatty acid uptake and synthesis; 9-HOTrE weakly inhibits mitochondrial fatty acid metabolism while increasing glutamine use.

Functional, Chemical, and Phytotoxic Characteristics of Cestrum parqui L'Herit: An Overview.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet, and now widely distributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anticancer, insecticidal, antifeedant, molluscicidal, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Various research groups are engaged in defining the chemical composition of the different parts of the plant and in defining its properties in view of important and promising commercial applications. To date, there are only a few incomplete reports on the potential applications of C. parqui extracts as selective natural pesticides and on their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui.

Decreased plasma docosahexaenoic acid concentration in chronic obstructive pulmonary disease patients with pulmonary Hypertension: Findings from human lipidomics and transcriptomics analysis.

Oxylipins derived from polyunsaturated fatty acids (PUFAs) are important endogenous signaling molecules, but are little characterized in pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD). In this study, we identified novel plasma oxylipins associated with PH risk in COPD patients. The plasma oxylipin profiles of COPD patients without PH (COPD-noPH) or with PH (COPD-PH) were obtained from discovery and validation cohort, using the process of LC-MS/MS analysis. There was a significant decrease in the plasma levels of both free docosahexaenoic acid (DHA) and DHA-derived oxylipins in the COPD-PH group. The multivariable logistic regression model identified DHA and four DHA-derived oxylipins (13-HDHA, 10-HDHA, 8-HDHA and 16-HDHA) exhibited significant differences between the two groups after adjusting for sex, BMI, FEV1% predicted, and smoking status. The diagnostic value of these metabolites was further evaluated through ROC curve analysis. The transcriptome profiles in peripheral blood mononuclear cells (PBMCs) of COPD-PH patients and COPD-PH patients were detected through high-throughput sequencing. The enrichment analysis revealed that the upregulated differentially expressed genes (DEGs) were highly enriched in the interferon signaling pathway. In addition, DHA supplementation proved that DHA may inhibit the development of pH by reducing the secretion of interferons derived from PBMCs. This conjecture was further confirmed by the higher level of serum interferon-γ and interferon-α2 of COPD-PH patients than that of COPD-noPH patients. The present study highlights that decreased DHA and DHA-derived oxylipins levels are suggestive of a higher risk of pH development in COPD cases.

Triazine herbicide prometryn alters epoxide hydrolase activity and increases cytochrome P450 metabolites in murine livers via lipidomic profiling.

Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging. The liver plays a crucial role in lipid metabolism and distribution throughout the organism. Long-term exposure to pesticides is suspected to contribute to hepatic carcinogenesis via notable disruption of lipid metabolism. Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. The amounts of prometryn documented in the environment, mainly waters, soil and plants used for human and domestic consumption are significantly high. Previous research revealed that prometryn decreased liver development during zebrafish embryogenesis. To understand the mechanisms by which prometryn could induce hepatotoxicity, the effect of prometryn (185 mg/kg every 48 h for seven days) was investigated on hepatic and plasma oxylipin levels in mice. Using an unbiased LC-MS/MS-based lipidomics approach, prometryn was found to alter oxylipins metabolites that are mainly derived from cytochrome P450 (CYP) and lipoxygenase (LOX) in both mice liver and plasma. Lipidomic analysis revealed that the hepatotoxic effects of prometryn are associated with increased epoxide hydrolase (EH) products, increased sEH and mEH enzymatic activities, and induction of oxidative stress. Furthermore, 9-HODE and 13-HODE levels were significantly increased in prometryn treated mice liver, suggesting increased levels of oxidation products. Together, these results support that sEH may be an important component of pesticide-induced liver toxicity.

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ2 mediated modification and control of HRas.

Senescent cells are characterized by multiple features such as increased expression of senescence-associated ß-galactosidase activity (SA ß-gal) and cell cycle inhibitors such as p21 or p16. They accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as Doxorubicin (Doxo) cause buildup of senescent cells, leading to the inhibition of tissue regeneration. Senescent cells influence the neighboring cells via numerous secreted factors which form the senescence-associated secreted phenotype (SASP). Lipids are emerging as a key component of SASP that can control tissue homeostasis. Arachidonic acid-derived lipids have been shown to accumulate within senescent cells, specifically 15d-PGJ2, which is an electrophilic lipid produced by the non-enzymatic dehydration of the prostaglandin PGD2. This study shows that 15d-PGJ2 is also released by Doxo-induced senescent cells as an SASP factor. Treatment of skeletal muscle myoblasts with the conditioned medium from these senescent cells inhibits myoblast fusion during differentiation. Inhibition of L-PTGDS, the enzyme that synthesizes PGD2, diminishes the release of 15d-PGJ2 by senescent cells and restores muscle differentiation. We further show that this lipid post-translationally modifies Cys184 of HRas in C2C12 mouse skeletal myoblasts, causing a reduction in the localization of HRas to the Golgi, increased HRas binding to Ras Binding Domain (RBD) of RAF Kinase (RAF-RBD), and activation of cellular Mitogen Activated Protein (MAP) kinase-Extracellular Signal Regulated Kinase (Erk) signaling (but not the Akt signaling). Mutating C184 of HRas prevents the ability of 15d-PGJ2 to inhibit the differentiation of muscle cells and control the activity of HRas. This work shows that 15d-PGJ2 released from senescent cells could be targeted to restore muscle homeostasis after chemotherapy.

Role of oxylipins in ovarian function and disease: A comprehensive review.

Ovaries are essential for healthy female reproduction, with the follicles as their fundamental functional units, which consist of an oocyte and surrounding granulosa cells. The development and formation of follicles in the ovaries are closely linked to reproductive health. Oxylipins refer to oxidative metabolites produced from the oxidation of polyunsaturated fatty acids, either through automatic oxidation or with the help of specific enzymes. They play crucial regulatory roles in the immune system, oxidative stress, and inflammatory reactions and are intimately linked to the development of numerous illnesses, such as diabetes, heart disease, asthma, and Alzheimer's disease. Furthermore, oxylipins have a complex relationship with ovarian function, and both prostaglandins and leukotrienes produced by arachidonic acid affect processes such as follicle growth and development, ovulation, and hormone regulation. The synthesis and metabolism of oxylipins in the ovaries are finely regulated. Oxylipin dysregulation has been linked to various ovarian diseases, including endometriosis, polycystic ovary syndrome, ovarian cancer, and premature ovarian insufficiency. In addition, potential therapeutic targets and interventions targeting the oxylipin pathway for the treatment of ovarian diseases have become a prominent research focus, including regulating the enzymes responsible for oxylipin synthesis, using anti-inflammatory agents, and regulating lipid metabolism. Recent research has been directed towards improving the reproductive outcomes of women with ovarian diseases through this series of interventions. An overview of the role of oxylipins in ovarian function and disease is provided in this article, which will aid researchers in understanding the current state of the field and in identifying future directions.

Assessment of Fatty Acid and Oxylipin Profile of Resprouting Olive Trees Positive to Xylella fastidiosa subsp. pauca in Salento (Apulia, Italy).

Xylella fastidiosa subsp. pauca ST53 (XFP), the causal agent of olive quick decline syndrome (OQDS), was thoroughly investigated after a 2013 outbreak in the Salento region of Southern Italy. Some trees from Ogliarola Salentina and Cellina di Nardò, susceptible cultivars in the Gallipoli area, the first XFP infection hotspot in Italy, have resprouted crowns and are starting to flower and yield fruits. Satellite imagery and Normalized Difference Vegetation Index analyses revealed a significant improvement in vegetation health and productivity from 2018 to 2022 of these trees. Lipid molecules have long been recognized as plant defense modulators, and recently, we investigated their role in XFP-positive hosts and in XFP-resistant as well as in XFP-susceptible cultivars of olive trees. Here, we present a case study regarding 36 olive trees (12 XFP-positive resprouting, 12 XFP-positive OQDS-symptomatic, and 12 XFP-negative trees) harvested in 2022 within the area where XFP struck first, killing millions of trees in a decade. These trees were analyzed for some free fatty acid, oxylipin, and plant hormones, in particular jasmonic and salicylic acid, by targeted LC-MS/MS. Multivariate analysis revealed that lipid markers of resistance (e.g., 13-HpOTrE), along with jasmonic and salicylic acid, were accumulated differently in the XFP-positive resprouting trees from both cultivars with respect to XFP-positive OQDS symptomatic and XFP-negative trees, suggesting a correlation of lipid metabolism with the resprouting, which can be an indication of the resiliency of these trees to OQDS. This is the first report concerning the resprouting of OQDS-infected olive trees in the Salento area.

Effect of FADS1 SNPs rs174546, rs174547 and rs174550 on blood fatty acid profiles and plasma free oxylipins.

Introduction: Previous studies have indicated that activity of fatty acid desaturase 1 (FADS1), is involved in cardiometabolic risk. Recent experimental data have shown that FADS1 knockdown can promote lipid accumulation and lipid droplet formation in liver cells. In this study, we aimed to characterize whether different FADS1 genotypes affect liver fat content, essential fatty acid content and free oxylipin mediators in the blood. Methods: We analyzed the impact of FADS1 single-nucleotide polymorphisms (SNPs) rs174546, rs174547, and rs174550 on blood fatty acids and free oxylipins in a cohort of 85 patients from an academic metabolic medicine outpatient center. Patients were grouped based on their genotype into the homozygous major (derived) allele group, the heterozygous allele group, and the homozygous minor (ancestral) allele group. Omega-3 polyunsaturated fatty acids (n-3 PUFA) and omega-6 polyunsaturated fatty acids (n-6 PUFA) in the blood cell and plasma samples were analyzed by gas chromatography. Free Oxylipins in plasma samples were analyzed using HPLC-MS/MS. Liver fat content and fibrosis were evaluated using Fibroscan technology. Results: Patients with the homozygous ancestral (minor) FADS1 genotype exhibited significantly lower blood levels of the n-6 PUFA arachidonic acid (AA), but no significant differences in the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There were no significant differences in liver fat content or arachidonic acid-derived lipid mediators, such as thromboxane B2 (TXB2), although there was a trend toward lower levels in the homozygous ancestral genotype group. Discussion: Our findings suggest that FADS1 genotypes influence the blood levels of n-6 PUFAs, while not significantly affecting the n-3 PUFAs EPA and DHA. The lack of significant differences in liver fat content and arachidonic acid-derived lipid mediators suggests that the genotype-related variations in fatty acid levels may not directly translate to differences in liver fat or inflammatory lipid mediators in this cohort. However, the trend towards lower levels of certain lipid mediators in the homozygous ancestral genotype group warrants further investigation to elucidate the underlying mechanisms of different FADS1 genotypes and potential implications for cardiometabolic risk.

Microalgae as a New Source of Oxylipins: A Comprehensive LC-MS-Based Analysis Using Conventional and Green Extraction Methods.

Microalgae are promising sources of essential lipids, including omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFA) and novel lipid metabolites like oxylipins. However, limited data exist on the oxylipin profile, its characterization, and the potential impact of the extraction process on these metabolites in microalgae. Thus, our study aimed to investigate the fatty acid and oxylipin profile of four microalgal species of interest (Microchloropsis gaditana, Tisochrysis lutea, Phaeodactylum tricornutum, and Porphyridium cruentum) while also examining the impact of the extraction method, with a focus on developing a greener process using ultrasound-assisted extraction (UAE) and ethanol. The UAE method showed similar oxylipin profiles, generally yielding concentrations comparable to those of the conventional Folch method. In total, 68 oxylipins derived from n-3 and n-6 PUFA were detected, with the highest concentrations of n-3 oxylipins found in P. tricornutum and T. lutea and of n-6 oxylipins in P. cruentum. This study provides the most extensive oxylipin characterization of these microalgae species to date, offering insights into alternative extraction methods and opening new avenues for further investigation of the significance of oxylipins in microalgae.

Resolvins D5 and D1 undergo phase II metabolism by uridine 5'-diphospho-glucuronosyltransferases.

Specialized pro-resolving mediators (SPMs) are oxidized lipid mediators that have been shown to resolve inflammation in cellular and animal models as well as humans. SPMs and their biological precursors are even commercially available as dietary supplements. It has been understood for more than forty years that pro-inflammatory oxidized lipid mediators, including prostaglandins and leukotrienes, are rapidly inactivated via metabolism. Studies on the metabolism of SPMs are, however, limited. Herein, we report that resolvin D5 (RvD5) and resolvin D1 (RvD1), well-studied SPMs, are readily metabolized by human liver microsomes (HLM) to glucuronide conjugated metabolites. We further show that this transformation is catalyzed by specific uridine 5'-diphospho-glucuronosyltransferase (UGT) isoforms. Additionally, we demonstrate that RvD5 and RvD1 metabolism by HLM is influenced by non-steroidal anti-inflammatory drugs (NSAIDs), which can act as UGT inhibitors through cyclooxygenase-independent mechanisms. The results from these studies highlight the importance of considering metabolism, as well as factors that influence metabolic enzymes, when seeking to quantify SPMs in vivo.

Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

A MEPS-UHPLC-MS/MS analytical platform to detect isoprostanoids and specialized pro-resolving mediators in the urinary extracellular vesicles of mountain ultramarathon runners.

Oxylipins are powerful signalling compounds derived from polyunsaturated fatty acids (PUFAs) and involved in regulating the immune system response. A mass spectrometry-based method was developed and validated for the targeted profiling of 52 oxylipins (e.g., isoprostanoids, prostaglandins, epoxy- and hydroxy-fatty acids, specialized pro-resolving mediators) and 4 PUFAs in small urinary extracellular vesicles (uEVs). Ultrasound-assisted extraction using a 50:50 v/v MeOH:H2O mixture ensured optimal analytical performances. Limits of detection ranged between 10 and 400 pg/mL for oxylipins and 0.10-3 ng/mL for PUFAs. Satisfactory recoveries (85-116 %) and good intra- and inter-day precisions (RSD ≤15 %) were obtained for all the analytes. The reliability of the procedure was tested in a real case scenario by monitoring ultramarathon runners during the world Tor des Géants® (TDG) race. Both F2- and E2-isoprostanes were detected in small uEVs of the ultramarathon runners, suggesting the onset of an oxidant insult. 5-F2t-IsoP exhibited significant pre- to post-race variations, thus potentially representing a non-invasive marker of in-vivo lipid peroxidation. The presence of specialized pro-resolving mediators suggests the activation of pro-resolution signalling cascade resolving inflammation. These outcomes may help manage post-exercise recovery and improve training.

Physiological changes associated with aging: Identification of novel biomarkers for frailty syndrome in women.

This study explores the physiological changes associated with aging that lead to frailty syndrome, characterized by reduced vitality and degeneration across multiple bodily systems, increasing susceptibility to various pathologies. While established scales like the Fried Phenotype and Frailty Trait Scale (FTS) are commonly used for assessing frailty, incorporating biomarkers is crucial for accurate diagnosis and prognosis. Our research examines plasma oxylipin levels in frail elderly individuals to identify novel biomarkers. Diagnostic criteria for frailty included assessments using the Fried Phenotype and FTS-5, with blood samples collected from 71 elderly participants (50 women and 21 men) with mean ages of 73.6 ± 5.9 and 76.2 ± 6.2 years, respectively. Women exhibited elevated platelet counts (p-value 0.0035). The significant differences in oxylipin concentrations associated with the Fried Phenotype were particularly noteworthy, predominantly observed in women. Specifically, in women, decreased grip strength (<15 kg) and slow gait speed (<0.8 m/s) correlated with increased levels of thromboxane B2 (TxB2) and 7-HDoHE (p-values 0.0404, 0.0300, 0.0033, and 0.0033, respectively). Additionally, elevated 7-HDoHE levels correlated with a BMI exceeding 28 kg/m2 (p-value 0.0123) and Physical Activity Scale for the Elderly (PASE) scores surpassing 5 points (p-value 0.0134) in women. In summary, our findings emphasize that frail older individuals, particularly women, exhibit higher levels of TxB2 and 7-HDoHE compared to their non-frail counterparts, aligning with established frailty classification and scale parameters, suggesting their potential as indicative biomarkers.

Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases.

We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.

Stearidonic acid improves eicosapentaenoic acid status: studies in humans and cultured hepatocytes.

Background: Ahiflower oil from the seeds of Buglossoides arvensis is rich in α-linolenic acid (ALA) and stearidonic acid (SDA). ALA and SDA are potential precursor fatty acids for the endogenous synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are n3-long chain polyunsaturated fatty acids (n3-LC-PUFAS), in humans. Since taurine, an amino sulfonic acid, is often associated with tissues rich in n3-LC-PUFAS (e.g., in fatty fish, human retina), taurine may play a role in EPA- and DHA-metabolism. Objective: To examine the capacity of the plant-derived precursor fatty acids (ALA and SDA) and of the potential fatty acid metabolism modulator taurine to increase n3-LC-PUFAS and their respective oxylipins in human plasma and cultivated hepatocytes (HepG2 cells). Methods: In a monocentric, randomized crossover study 29 healthy male volunteers received three sequential interventions, namely ahiflower oil (9 g/day), taurine (1.5 g/day) and ahiflower oil (9 g/day) + taurine (1.5 g/day) for 20 days. In addition, cultivated HepG2 cells were treated with isolated fatty acids ALA, SDA, EPA, DHA as well as taurine alone or together with SDA. Results: Oral ahiflower oil intake significantly improved plasma EPA levels (0.2 vs. 0.6% of total fatty acid methyl esters (FAMES)) in humans, whereas DHA levels were unaffected by treatments. EPA-levels in SDA-treated HepG2 cells were 65% higher (5.1 vs. 3.0% of total FAMES) than those in ALA-treated cells. Taurine did not affect fatty acid profiles in human plasma in vivo or in HepG2 cells in vitro. SDA-rich ahiflower oil and isolated SDA led to an increase in EPA-derived oxylipins in humans and in HepG2 cells, respectively. Conclusion: The consumption of ahiflower oil improves the circulating levels of EPA and EPA-derived oxylipins in humans. In cultivated hepatocytes, EPA and EPA-derived oxylipins are more effectively increased by SDA than ALA.

Oxylipin Dynamics Following A Single Bout of Yoga Exercise: A Pilot Randomized Controlled Trial Secondary Analysis.

Background: Yoga may promote health via a complex modulation of inflammation. Little is known about oxylipins, a class of circulating mediators involved in inflammation resolution. Objective: To explore the acute effects of yoga exercise on systemic levels of oxylipins. Methods: This is a secondary analysis of a three-arm (high-intensity-yoga: HY, n = 10); moderate-intensity-yoga: MY, n = 10; and no-intervention-control: CON, n = 10) pilot randomized controlled trial employing a single bout of yoga exercise. Blood samples (baseline and 4-timepoint post-intervention) were used for an unbiased metabolipidomic profiling analysis. Net Areas Under the Curve per oxylipin were evaluated for each group. Results: Lipoxin(LX)B4, prostaglandin(PG)D2, and resolvin(Rv)D3 exhibited a greater magnitude of change in HY compared with MY and CON. Conclusion: Findings inform the design of future trials exploring the acute effects of yoga exercise on oxylipins' systemic levels.

Lipids and Lipid-Mediated Signaling in Plant-Pathogen Interactions.

Plant lipids are essential cell constituents with many structural, storage, signaling, and defensive functions. During plant-pathogen interactions, lipids play parts in both the preexisting passive defense mechanisms and the pathogen-induced immune responses at the local and systemic levels. They interact with various components of the plant immune network and can modulate plant defense both positively and negatively. Under biotic stress, lipid signaling is mostly associated with oxygenated natural products derived from unsaturated fatty acids, known as oxylipins; among these, jasmonic acid has been of great interest as a specific mediator of plant defense against necrotrophic pathogens. Although numerous studies have documented the contribution of oxylipins and other lipid-derived species in plant immunity, their specific roles in plant-pathogen interactions and their involvement in the signaling network require further elucidation. This review presents the most relevant and recent studies on lipids and lipid-derived signaling molecules involved in plant-pathogen interactions, with the aim of providing a deeper insight into the mechanisms underpinning lipid-mediated regulation of the plant immune system.