Search Results (14)

Soil salinization threatens global agriculture, reducing crop productivity and food security. Developing strategies to improve salt tolerance is crucial for sustainable agriculture. This study examines the role of organic fertilizer in mitigating salt stress in rice (Oryza sativa L.) by integrating NDVI and metabolomics. Using salt-sensitive (19X) and salt-tolerant (HHZ) cultivars, we aimed to (1) evaluate changes in NDVI and metabolite content under salt stress, (2) assess the regulatory effects of organic fertilizer, and (3) identify key metabolites involved in stress response and fertilizer-induced regulation. Under salt stress, survival rate of the 19X plants dropped to 6%, while HHZ maintained 38%, with organic fertilizer increasing survival rate to 25% in 19X and 66% in HHZ. NDVI values declined sharply in 19X (from 0.56 to <0.25) but remained stable in HHZ (~0.56), showing a strong correlation with survival rate (R² = 0.87, p < 0.01). NDVI provided a dynamic, non-destructive assessment of rice health, offering a faster and more precise evaluation of salt tolerance than survival rate analysis. Metabolomic analysis identified 12 key salt-tolerant metabolites, including citric acid, which is well recognized for regulating salt tolerance. HTPA, pipecolic acid, maleamic acid, and myristoleic acid have previously been reported but require further study. Additionally, seven novel salt-tolerant metabolites—tridecylic acid, propentofylline, octadeca penten-3-one, 14,16-dihydroxy-benzoxacyclotetradecine-dione, cyclopentadecanolide, HpODE, and (±)8,9-DiHETE—were discovered, warranting further investigation. Organic fertilizer alleviated salt stress through distinct metabolic mechanisms in each cultivar. In 19X, it enhanced antioxidant defenses and energy metabolism, mitigating oxidative damage and improving fatty acid metabolism. In contrast, HHZ primarily benefitted from improved membrane stability and ion homeostasis, reducing lipid peroxidation and oxidative stress. These findings primarily support the identification and screening of salt-tolerant rice cultivars while also highlighting the need for cultivar-specific fertilization strategies to optimize stress resilience and crop performance. Based on the correlation analysis, 26 out of 53 differential metabolites were significantly correlated with NDVI, confirming a strong association between NDVI shifts and key metabolic changes in response to salt stress and organic fertilizer application. By integrating NDVI and metabolomics, this study provides a refined method for evaluating salt stress responses, capturing early NDVI changes and key salinity stress biomarkers. This approach may prove valuable for application in salt-tolerant variety screening, precision agriculture, and sustainable farming, contributing to scientific strategies for future crop improvement and agricultural resilience. Full article

Neonicotinoid resistance is increasingly prevalent in the agricultural pest Myzus persicae. Lipids play a critical role in insect defense systems, but their contribution to insect neonicotinoid resistance is disregarded. We conducted metabolomics and transcriptomics studies on M. persicae thiacloprid-resistant (THG-R) and -susceptible (FFJ-S) populations. A total of 149 lipid metabolites were identified, with 90 upregulated and 59 downregulated in THG-R compared to in FFJ-S. Metabolites in the arachidonic acid (AA) pathway substantially varied between THG-R and FFJ-S. For example, arachidonic acid, (±)11-HETE, and prostaglandin B1 were significantly upregulated, while prostaglandin A1, tetranor-PGDM, 8,15-diHETE, and (±)11(12)-EET were significantly decreased in THG-R. Transcriptomics profiles and qPCR indicated that lipid metabolic enzymes, including fatty acid synthase (FAS), the elongase of very-long-chain fatty acids (ELO), fatty acid desaturase (FAD), and phospholipase (PL) genes, were not overexpressed in THG-R. Among the twelve thioesterase genes, only MpTHEM6a was significantly upregulated in THG-R. Knocking down the expression of MpTHEM6a in THG-R significantly increased the toxicity of the three neonicotinoids, reduced the lifespan of adults, and decreased the number of nonviable nymphs produced by female adults. The metabolites AA, (±)11-HETE, and prostaglandin B1 are potential biomarkers in neonicotinoid-resistant M. persicae. MpTHEM6a may become a potential target for combating neonicotinoid-resistant M. persicae. Full article

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11–16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression. Full article

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive [T2DM(+)] HCC. A robust LC-MS/MS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MS/MS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM(+) HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM(+) HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM(+) HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC = 0.88) and early-stage (AUC = 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM(+) HCC from other T2DM(+) tumors, including pancreatic, gastric and colorectal cancer (AUC = 0.88) as well. In conclusion, our study develops a novel tool for early diagnosis of T2DM(+) HCC in T2DM patients. Full article

Hemodialysis patients (HDPs) have higher blood pressure, higher levels of inflammation, a higher risk of cardiovascular disease, and unusually low plasma n-3 polyunsaturated fatty acid (PUFA) levels compared to healthy subjects. The objective of our investigation was to examine the levels of endocannabinoids (eCBs) and oxylipins (OxLs) in female HDPs compared to healthy matched female controls, with the underlying hypothesis that differences in specific PUFA levels in hemodialysis patients would result in changes in eCBs and OxLs. Plasma phospholipid fatty acids were analyzed by gas chromatography. Plasma was extracted and analyzed using ultra-performance liquid chromatography followed by electrospray ionization and tandem MS for eCBs and OxLs. The global untargeted metabolite profiling of plasma was performed by GCTOF MS. Compared to the controls, HDPs showed lower levels of plasma EPA and the associated OxL metabolites 5- and 12-HEPE, 14,15-DiHETE, as well as DHA derived 19(20)-EpDPE. Meanwhile, no changes in arachidonylethanolamide or 2-arachidonylglycerol in the open circulation were detected. Higher levels of multiple N-acylethanolamides, monoacylglycerols, biomarkers of progressive kidney disease, the nitric oxide metabolism-linked citrulline, and the uremic toxins kynurenine and creatine were observed in HDP. These metabolic differences in cCBs and OxLs help explain the severe inflammatory and cardiovascular disease manifested by HDPs, and they should be explored in future studies. Full article

Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-β. Full article

High-altitude locations are fascinating for investigating biological and physiological responses in humans. In this work, we studied the high-altitude response in the plasma and urine of six healthy adult trekkers, who participated in a trek in Nepal that covered 300 km in 19 days along a route in the Kanchenjunga Mountain and up to a maximum altitude of 5140 m. Post-trek results showed an unbalance in redox status, with an upregulation of ROS (+19%), NOx (+28%), neopterin (+50%), and pro-inflammatory prostanoids, such as PGE₂ (+120%) and 15-deoxy-delta12,14-PGJ₂ (+233%). The isoprostane 15-F_2t-IsoP was associated with low levels of TAC (−18%), amino-thiols, omega-3 PUFAs, and anti-inflammatory CYP450 EPA-derived mediators, such as DiHETEs. The deterioration of antioxidant systems paves the way to the overload of redox and inflammative markers, as triggered by the combined physical and hypoxic stressors. Our data underline the link between oxidative stress and inflammation, which is related to the concept of OxInflammation into the altitude hypoxia fashion. Full article

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 μg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 μg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 μg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25–1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 μg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 μg/kg/day 5,6-DiHETE was slightly stronger than that by 150 μg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease. Full article

Lipid mediators, small molecules involved in regulating inflammation and its resolution, are a class of lipids of wide interest as their levels in blood and tissues may be used to monitor health and disease states or the effect of new treatments. These molecules are present at low levels in biological samples, and an enrichment step is often needed for their detection. We describe a rapid and selective method that uses new low-cost molecularly imprinted (MIP) and non-imprinted (NIP) polymeric sorbents for the extraction of lipid mediators from plasma and tissue samples. The extraction process was carried out in solid-phase extraction (SPE) cartridges, manually packed with the sorbents. After extraction, lipid mediators were quantified by liquid chromatography–tandem mass spectrometry (LC–MSMS). Various parameters affecting the extraction efficiency were evaluated to achieve optimal recovery and to reduce non-specific interactions. Preliminary tests showed that MIPs, designed using the prostaglandin biosynthetic precursor arachidonic acid, could effectively enrich prostaglandins and structurally related molecules. However, for other lipid mediators, MIP and NIP displayed comparable recoveries. Under optimized conditions, the recoveries of synthetic standards ranged from 62% to 100%. This new extraction method was applied to the determination of the lipid mediators concentration in human plasma and mouse tissues and compared to other methods based on commercially available cartridges. In general, the methods showed comparable performances. In terms of structural specificity, our newly synthesized materials accomplished better retention of prostaglandins (PGs), hydroxydocosahexaenoic acid (HDoHE), HEPE, hydroxyeicosatetraenoic acids (HETE), hydroxyeicosatrienoic acid (HETrE), and polyunsaturated fatty acid (PUFA) compounds, while the commercially available Strata-X showed a higher recovery for dihydroxyeicosatetraenoic acid (diHETrEs). In summary, our results suggest that this new material can be successfully implemented for the extraction of lipid mediators from biological samples. Full article

Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells—a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role. Full article

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO₂ (hypoxia-induced relaxation (HIR), 0% O₂) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO₂) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO₂ group (single HBO₂; 120 min of 100% O₂ at 2.0 bars); the 24H-HBO₂ group (examined 24 h after single exposure) and the 4D-HBO₂ group (four consecutive days of single HBO₂). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO₂ group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO₂ and 4D-HBO₂ groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO₂ group. HBO₂ affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO₂ and 4D-HBO₂ groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO₂ and 24H-HBO_2. An increased concentration of 8(9)-EET was observed in the A-HBO₂ and 24h-HBO₂ groups vs. the CTRL and 4D-HBO₂ groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO₂ group vs. the 4D-HBO₂ group. The 20-HETE concentration was increased in the A-HBO₂ group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes’ metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO₂. Full article

Oxygenated lipids, called “oxylipins,” serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer’s disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD. Full article

Hyaluronic acid (HA), a major glycosaminoglycan of the extracellular matrix, has cell signaling functions that are dependent on its molecular weight. Anti-inflammatory effects for high-molecular-weight (HMW) HA and pro-inflammatory effects for low-molecular-weight (LMW) HA effects were found for various myeloid cells, including microglia. Astrocytes are cells of ectodermal origin that play a pivotal role in brain inflammation, but the link between HA with different molecular weights and an inflammatory response in these cells is not clear. We tested the effects of LMW and HMW HA in rat primary astrocytes, stimulated with Poly:IC (PIC, TLR3 agonist) and lipopolysaccharide (LPS, TLR4 agonist). Oxylipin profiles were measured by the UPLC-MS/MS analysis and metabolites HDoHEs (from docosahexaenoic acid), -HETEs, prostaglandins (from arachidonic acid), DiHOMEs and HODEs (from linoleic acid) were detected. Both, HMW and LMW HA downregulated the cyclooxygenase-mediated polyunsaturated fatty acids metabolism, LMW also reduced lipoxygenase-mediated fatty acid metabolism. Taken together, the data show that both LMW and HMW (i) influence themselves on cytokines (TNFα, IL-6, IL-10), enzymes iNOS, COX-2, and oxylipin levels in extracellular medium of cultured astrocytes, (ii) induced cellular adaptations in long-term applications, (iii) modulate TLR4- and TLR3-signaling pathways. The effects of HMW and LMW HA are predominantly revealed in TLR4– and TLR3- mediated responses, respectively. Full article

Acute coronary syndrome (ACS) refers to ischemic conditions that occur as a result of atherosclerotic plaque rupture and thrombus formation. It has been shown that lipid peroxidation may cause plaque instability by inducing inflammation, apoptosis, and neovascularization. There is some evidence showing that these oxidized lipids may have a prognostic value in ACS. For instance, higher levels of oxidized phospholipids on apo B-100 lipoproteins (OxPL/apoB) predicted cardiovascular events independent of traditional risk factors, C-reactive protein (hsCRP), and the Framingham Risk Score (FRS). A recent cross-sectional study showed that levels of oxylipins, namely 8,9-DiHETrE and 16-HETE, were significantly associated with cardiovascular and cerebrovascular events, respectively. They found that with every 1 nmol/L increase in the concentrations of 8,9-DiHETrE, the odds of ACS increased by 454-fold. As lipid peroxidation makes heterogonous pools of secondary products, therefore, rapid multi-analyte quantification methods are needed for their assessment. Conventional lipid assessment methods such as chemical reagents or immunoassays lack specificity and sensitivity. Lipidomics may provide another layer of a detailed molecular level to lipid assessment, which may eventually lead to exploring novel biomarkers and/or new treatment options. Here, we will briefly review the lipidomics of bioactive lipids in ACS. Full article