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As global pollution, microplastics pollution has aroused growing concerns. In our experiment, the effect of microplastics acute exposure on the liver of swordtail fish was investigated by using LC-MS metabolomics. Fishes treated with high concentration polystyrene microspheres (1 μm) for 72 h were divided into three concentration groups: (A) no microplastics, (B): 1 × 10

To provide a deep insight into the application of lipid in plant protein-based meat substitutes through high-moisture extrusion (HME) process, the effect of fatty acid saturation degree (stearic acid, oleic acid and linoleic acid) on the rheological and structural properties of pea protein isolate (PPI), and its relationship with the extrusion system parameters and extrudate qualities were investigated. The oleic acid and linoleic acid significantly decreased the apparent viscosity of PPI dispersion and thus reduced the die pressure and torque during HME processing. Electrophoresis and Fourier transform infrared spectroscopy results revealed that fatty acids inhibited the aggregation of legumin and vicilin subunits at 50 and 20 kDa, and promoted the conversion of α-helix and β-sheet to β-turn and random coil. The macro- and micro-structure observation and texture analysis suggested that the fatty acids with higher unsaturation degree were not advantageous for the pea protein fibrous structure improvement during HME process.

Characterisation of carcass traits and fat quality is important to effectively produce and genetically improve emus. We investigated carcass traits in 309 emus. The meat production of female emus showed a significantly higher value than that of males (P

The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine are lipids regulating many physiological processes, notably inflammation. Endocannabinoid hydrolysis inhibitors are now being investigated as potential anti-inflammatory agents. In addition to 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and N-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and N-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or N-acyl-ethanolamine levels, endocannabinoid hydrolysis inhibitors will likely increase the levels of their metabolites. Herein, we investigated whether 1-LG and LEA were substrates for the 15-lipoxygenase pathway, given that both possess a 1Z,4Z-pentadiene motif, near their omega end. We thus assessed how human eosinophils and neutrophils biosynthesized the 15-lipoxygenase metabolites of 1-LG and LEA. Linoleic acid (LA), a well-documented substrate of 15-lipoxygenases, was used as positive control. N-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G), the 15-lipoxygenase metabolites of LEA and 1-LG, were synthesized using Novozym 435 and soybean lipoxygenase. Eosinophils, which express the 15-lipoxygenase-1, metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was almost complete after five minutes. Substrate preference of eosinophils was LA > LEA > 1-LG in presence of 13-HODE-G hydrolysis inhibition with methyl-arachidonoyl-fluorophosphonate. Human neutrophils also metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was maximal after 15–30 s. Substrate preference was LA ≫ 1-LG > LEA. Importantly, 13-HODE-G was found in humans and mouse tissue samples. In conclusion, our data show that human eosinophils and neutrophils metabolize 1-LG and LEA into the novel endogenous 15-lipoxygenase metabolites 13-HODE-G and 13-HODE-EA. The full biological importance of 13-HODE-G and 13-HODE-EA remains to be explored.

Can exposure time to equilibration solutions during oocyte vitrification affect the lipid profile of oocytes and embryonic development? Could vitrification media supplemented with oleic, linoleic acids and L-carnitine effectively minimize damage induced by vitrification on embryo development and oocyte membrane lipid profile?Experimental study including 936 oocytes from C57BL/6J mice, randomly divided into fresh IVF (control) and equilibration solution groups. Oocytes were exposed to equilibration solution from Irvine Scientific, Tvitri-4 or Tvitri-4 supplemented with L-carnitine and fatty acids for 7 or 10 min, vitrified-warmed, and submitted to IVF. The lipid profile of oocytes immediately after equilibration solution exposure was also asessed using the same equilibration times and solution compositions.Longer equilibration time resulted in lower oocyte survival and blastocyst rates, and reduced relative abundance of structural lipids, i.e. phosphatidylcholines and sphingomyelins, varying according to equilibration solution composition. It also induced membrane disruptions resembling bubbles in the oocyte surface predominantly in equilibration solution from Irvine Scientific, rarely in Tvitri-4 and absent in Tvitri-4 supplemented with L-carnitine and fatty acids. To reveal the metabolic pathways associated with the equilibration phase of vitrification, lipid pathway analysis was conducted; both P-values and pathway impact values showed that the linoleic acid metabolism (P = 0.00223; impact =1) and alpha-Linolenic acid metabolism (P = 0.00084; impact = 0.33) were the most pathway perturbed, followed by glycerophospholipid metabolism (P = 0.0167; impact = 0.25) CONCLUSION: A longer equilibration phase pre-vitrification can influence embryo development and induce changes in oocyte lipid composition related to membrane integrity. The results suggest internalization of oleic and linoleic acids added to equilibration solution by the oocyte, which, to some extent, contributed to membrane phospholipids preservation, regardless of the equilibration times assessed.

Rigid polyurethane/polyisocyanurate (RPU/PIR) foam formulations were modified by evening primrose (Oenothera biennis) oil cake as a bio-filler in the amount of 5 to 50 wt.%. The obtained foams were tested in terms of processing parameters, cellular structure (SEM analysis), physico-mechanical properties (apparent density, compressive strength, brittleness, accelerated aging tests), thermal insulation properties (thermal conductivity coefficient, closed cells content, absorbability and water absorption), flammability, smoke emission, and thermal properties. The obtained results showed that the amount of bio-filler had a significant influence on the morphology of the modified foams. Thorough mixing of the polyurethane premix allowed better homogenization of the bio-filler in the polyurethane matrix, resulting in a regular cellular structure. This resulted in an improvement in the physico-mechanical and thermal insulation properties as well as a reduction in the flammability of the obtained materials. This research provided important information on the management of the waste product from the edible oil industry and the production process of fire-safe RPU/PIR foams with improved performance properties. Due to these beneficial effects, it was found that the use of evening primrose oil cake as a bio-filler for RPU/PIR foams opens a new way of waste management to obtain new “green” materials.

Multiple mucoceles of the minor salivary glands are rare in the mouth. Typically, the minor salivary glands of the soft palate are affected. We report two cases that responded entirely following systemic therapy with evening primrose oil. No recurrence was reported over a two-year follow-up period. Evening primrose oil is postulated to have an effect on the composition and/or viscosity of minor salivary gland secretions.

The unprecedented global demand for SARS-CoV-2 vaccines has demonstrated the need for highly effective vaccine candidates that are thermostable and amenable to large-scale manufacturing. Nanoparticle immunogens presenting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S) in repetitive arrays are being advanced as second-generation vaccine candidates, as they feature robust manufacturing characteristics and have shown promising immunogenicity in preclinical models. Here, we used previously reported deep mutational scanning (DMS) data to guide the design of stabilized variants of the RBD. The selected mutations fill a cavity in the RBD that has been identified as a linoleic acid binding pocket. Screening of several designs led to the selection of two lead candidates that expressed at higher yields than the wild-type RBD. These stabilized RBDs possess enhanced thermal stability and resistance to aggregation, particularly when incorporated into an icosahedral nanoparticle immunogen that maintained its integrity and antigenicity for 28 days at 35-40°C, while corresponding immunogens displaying the wild-type RBD experienced aggregation and loss of antigenicity. The stabilized immunogens preserved the potent immunogenicity of the original nanoparticle immunogen, which is currently being evaluated in a Phase I/II clinical trial. Our findings may improve the scalability and stability of RBD-based coronavirus vaccines in any format and more generally highlight the utility of comprehensive DMS data in guiding vaccine design.

PurposeThe inhibition of estrogen receptor alpha (ERα) or the activation of ERβ can inhibit papillary thyroid cancer (PTC), but the precise mechanism is not known. We aimed to explore the role of ERα and ERβ on the production of endogenous peroxisome proliferator-activated receptor gamma (PPARγ) ligands in PTC.Methods2 PTC cell lines, 32 pairs of PTC tissues and matched normal thyroid tissues were used in this study. The levels of endogenous PPARγ ligands 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), 13-S-hydroxyoctadecadienoic acid (13(S)-HODE), and15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) were measured by ELISA.ResultsThe levels of PGJ2 and 15(S)-HETE were significantly reduced in PTC, but 13(S)-HODE was not changed. Activation of ERα or inhibition of ERβ significantly downregulated the production of PGJ2, 15(S)-HETE and 13(S)-HODE, whereas inhibition of ERα or activation of ERβ markedly upregulated the production of these three ligands. Application of endogenous PPARγ ligands inhibited growth, induced apoptosis of cancer cells, and promoted the efficacy of chemotherapy.ConclusionThe levels of endogenous PPARγ ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. The inhibition of ERα or activation of ERβ can inhibit PTC by stimulating the production of endogenous PPARγ ligands to induce apoptosis in cancer cells.

Background: Under natural exposure conditions, pollen grains function as allergen carriers that release allergens from internal binding sites on contact with the aqueous phase of mucosa membranes. In addition, we recently demonstrated that pollen are a rich source of eicosanoid-like mediators, which are rapidly released on contact with the aqueous phase. Objective : The current study was designed to characterize the biochemical nature of pollen-derived lipid mediators in more detail and to delineate their biologic activity on polymorphonuclear granulocytes (PMNs). Methods : Aqueous and lipid extracts from Phleum pratense L and Betula alba L pollen were analyzed by means of HPLC. PMNs were exposed to aqueous extracts or lipid fractions from pollen or to HPLC-purified lipid mediators identified in pollen extracts. Effects on PMNs were tested with transwell migration, calcium mobilization, and surface expression of CD11b. Results : Aqueous pollen extracts (APEs) contained predominantly monohydroxylated products derived of linoleic acid and linolenic acid. In chemotaxis assays PMNs displayed significant migration to APEs. Lipid extracts from pollen and the HPLC fraction containing 13-hydroxy-octadecadienoic acid/hydroxy-linoleic acid and 13-hydroxy-octadecatrienoic acid/hydroxy-linolenic acid induced migratory responses, although to a lesser degree than the APEs. In addition, APE, as well as lipid, extracts induced PMN activation, as documented by means of calcium mobilization and upregulation of CD11b. Conclusion : Pollen grains release mediators that recruit and activate PMNs in vitro. Similar mechanisms may be effective in vivo, suggesting that pollen-derived lipid mediators may act as adjuvants in the elicitation phase of allergic reactions. (J Allergy Clin Immunol 2002;109:831-8.)

The human soluble epoxide hydrolase (hsEH) is a key regulator of epoxy fatty acid (EpFA) metabolism. Inhibition of sEH can maintain endogenous levels of beneficial EpFAs and reduce the levels of their corresponding diol products, thus ameliorating a variety of pathological conditions including cardiovascular, central nervous system and metabolic diseases. The quest for orthosteric drugs that bind directly to the catalytic crevice of hsEH has been prolonged and sustained over the past decades, but the disappointing outcome of clinical trials to date warrants alternative pharmacological approaches. Previously, we have shown that hsEH can be allosterically inhibited by the endogenous electrophilic lipid 15-deoxy-Δ

Pancreatic ductal adenocarcinoma (PDAC), one of the worst prognosis types of tumors, is characterized by dense extracellular matrix, which compresses tumor vessels and forms a physical barrier to inhibit therapeutic drug penetration and efficacy. Herein, losartan, an antihypertension agent, is applied as a tumor stroma modulator and developed into a nanosystem. A series of lipophilic losartan prodrugs are constructed by esterification of the hydroxyl group on losartan to fatty acids. Based on the self-assembly ability and hydrodynamic diameter, the losartan-linoleic acid conjugate is selected for further investigation. To improve the stability in vivo, nanoassemblies are refined with PEGylation to form losartan nanoblocker (Los NB), and administered via intravenous injection for experiments. On murine models of pancreatic cancer, Los NB shows a greater ability to remodel the tumor microenvironment than free losartan, including stromal depletion, vessel perfusion increase, and hypoxia relief. Furthermore, Los NB pretreatment remarkably enhances the accumulation and penetration of 7-ethyl-10-hydroxycamptothecin (SN38)-loaded nanodrugs (SN38 NPs) in tumor tissues. Expectedly, overall therapeutic efficacy of SN38 NPs is significantly enhanced after Los NB pretreatment. Since losartan is one of the most commonly used antihypertension agents, this study may provide a potential for clinical transformation in stroma-rich PDAC treatment.

Lipid carriers of hydrophobic paclitaxel (PTX) are used in clinical trials for cancer chemotherapy. Improving their loading capacity requires enhanced PTX solubilization. We compared the time-dependence of PTX membrane solubility as a function of PTX content in cationic liposomes (CLs) with lipid tails containing one (oleoyl; DOPC/DOTAP) or two (linoleoyl; DLinPC/newly synthesized DLinTAP) cis double bonds by using microscopy to generate kinetic phase diagrams. The DLin lipids displayed significantly increased PTX membrane solubility over DO lipids. Remarkably, 8 mol% PTX in DLinTAP/DLinPC CLs remained soluble for approximately as long as 3 mol% PTX (the solubility limit, which has been the focus of most previous studies and clinical trials) in DOTAP/DOPC CLs. The increase in solubility is likely caused by enhanced molecular affinity between lipid tails and PTX, rather than by the transition in membrane structure from bilayers to inverse cylindrical micelles observed with small-angle X-ray scattering. Importantly, the efficacy of PTX-loaded CLs against prostate cancer cells (their IC50 of PTX cytotoxicity) was unaffected by changing the lipid tails, and toxicity of the CL carrier was negligible. Moreover, efficacy was approximately doubled against melanoma cells for PTX-loaded DLinTAP/DLinPC over DOTAP/DOPC CLs. Our findings demonstrate the potential of chemical modifications of the lipid tails to increase the PTX membrane loading while maintaining (and in some cases even increasing) the efficacy of CLs. The increased PTX solubility will aid the development of liposomal PTX carriers that require significantly less lipid to deliver a given amount of PTX, reducing side effects and costs.

Linoleic acid (LNA)-derived 13-hydroxyoctadecadienoic acid (13-HODE) is a bioactive lipid mediator that regulates multiple signaling processes in vivo. 13-HODE is also produced when LNA is oxidized during food processing. However, the absorption and incorporation kinetics of dietary 13-HODE into tissues is not known. The present study measured unesterified d4–13-HODE plasma bioavailability and incorporation of into rat liver, visceral adipose, heart and brain following gavage or intravenous (IV) injection (n=3 per group). Mass spectrometry analysis revealed that d4–13-HODE was absorbed within 20 minute of gavage, and continued to incorporate into plasma esterified lipid fractions throughout the 90 minute monitoring period. Following IV injection, unesterified d4–13-HODE was rapidly eliminated from plasma with a half-life of 1 minutes, whereas the gavaged tracer incorporated into esterified lipid pools and had a half-life of 71 min. Analysis of tracer incorporation kinetics into rat tissues following IV injection or gavage revealed that the esterified tracer preferentially incorporated into liver, adipose and heart compared to unesterified d4–13-HODE. No tracer was detected in the brain. This study provides new evidence that dietary 13-HODE is absorbed, and incorporated into peripheral tissues from esterified plasma pools. Understanding the chronic effects of dietary 13-HODE exposure on peripheral tissue physiology and metabolism merits future investigation.

13-lipoxygenases (13-LOX) catalyze the dioxygenation of various polyunsaturated fatty acids (PUFAs), of which α-linolenic acid (LeA) is converted to 13-S-hydroperoxyoctadeca-9, 11, 15-trienoic acid (13-HPOT), the precursor for the prostaglandin-like plant hormones cis-(+)-12-oxophytodienoic acid (12-OPDA) and methyl jasmonate (MJ). This study aimed for characterizing the four annotated A. thaliana 13-LOX enzymes (LOX2, LOX3, LOX4, and LOX6) focusing on synthesis of 12-OPDA and 4Z,7Z,10Z)-12-[[-(1S,5S)-4-oxo-5-(2Z)-pent-2-en-1yl] cyclopent-2-en-1yl] dodeca-4,7,10-trienoic acid (OCPD). In addition, we performed interaction studies of 13-LOXs with ions and molecules to advance our understanding of 13-LOX. Cell imaging indicated plastid targeting of fluorescent proteins fused to 13-LOXs-N-terminal extensions, supporting the prediction of 13-LOX localization to plastids. The apparent maximal velocity (Vmax app) values for LOX-catalyzed LeA oxidation were highest for LOX4 (128 nmol·s−1·mg protein−1), with a Km value of 5.8 µM. A. thaliana 13-LOXs, in cascade with 12-OPDA pathway enzymes, synthesized 12-OPDA and OCPD from LeA and docosahexaenoic acid, previously shown only for LOX6. The activities of the four isoforms were differently affected by physiologically relevant chemicals, such as Mg2+, Ca2+, Cu2+ and Cd2+, and by 12-OPDA and MJ. As demonstrated for LOX4, 12-OPDA inhibited enzymatic LeA hydroperoxidation, with half-maximal enzyme inhibition at 48 µM. Biochemical interactions, such as the sensitivity of LOX toward thiol-reactive agents belonging to cyclopentenone prostaglandins, are suggested to occur in human LOX homologs. Furthermore, we conclude that 13-LOXs are isoforms with rather specific functional and regulatory enzymatic features.

N-Arachidonoyl-ethanolamine (AEA) is an endocannabinoid (eCB) and endogenous lipid mimicking many of the effects of Δ9-tetrahydrocannabinol, notably on brain functions, appetite, pain and inflammation. The eCBs and eCB-like compounds contain fatty acids, the main classes being the monoacylglycerols and the N-acyl-ethanolamines (NAEs). Thus, each long chain fatty acid likely exists under the form of a monoacylglycerol and NAE, as it is the case for arachidonic acid (AA) and linoleic acid (LA). Following their biosynthesis, AA and AEA can be further metabolized into additional eicosanoids, notably by the 15-lipoxygenase pathway. Thus, we postulated that NAEs possessing a 1Z,4Z-pentadiene motif, near their omega end, would be transformed into their 15-lipoxygenase metabolites. As a proof of concept, we investigated N-linoleoyl-ethanolamine (LAE). We successfully synthesized LEA and LEA-d4 as well as their 15-lipoxygenase-derived derivatives, namely 13-hydroxy-9Z,11E-octadecadienoyl-N-ethanolamine (13-HODE-EA) and 13-HODE-EA-d4, using Novozyme 435 immobilized on acrylic resin and soybean lipoxygenase respectively. We also show that both human 15-lipoxygenase-1 and -2 can biosynthesize 13-HODE-EA. Co-incubation of LEA and LA with either human 15-lipoxygenase led to the biosynthesis of 13-HODE-EA and 13-HODE in a ratio equal to or greater than 3:1, indicating that LEA is preferred to LA by these enzymes. Finally, we show that 13-HODE-EA is found in human saliva and skin and is a weak although selective TRPV1 agonist. The full biological importance of 13-HODE-EA remains to be explored.

Medicinal plants have been considered as an important source for the prevention and treatment of various diseases. The genus Arnica L. is a genus of Asteraceae family, many species of which are used in traditional medicine. Arnica chamissonis Less. and Arnica foliosa Nutt., which belong to plants of the genus Arnica L., are successfully grown in the culture. There is insufficient information in the literature on the biologically active substances of Arnica foliosa Nutt. The presence of sesquiterpene lactones in the leaves and inflorescences is indicated. The flowers contain polysaccharides, monosaccharides, which mainly contain D-glucose and D-xylose, as well as phenolic compounds (quercetin, luteolin, kaempferol) and essential oils. The aim.The aim of our study was to identify and determine the quantitative content of fatty acids by gas chromatography/mass spectrometry method (GC/MS) in Arnica foliosa Nutt. herb. Materials and methods.The determination of fatty acids composition of Arnica foliosa Nutt. was carried out by gas chromatograph Agilent 6890N with a mass detector 5973 inert (Agilent Technologies, USA). Results.The analysis of Arnica foliosa Nutt. herb showed a mixture of saturated (1.61 mg/g; 48.79 %) and unsaturated (1.69 mg/g; 51.21 % from total content acids) fatty acids. The main components of Arnica foliosa Nutt. herb were palmitic (1.02 mg/g; 30.91 % from total content acids), linolenic (0.96 mg/g; 29.09 % from total content acids) and linoleic (0.67 mg/g; 20.30 % from total content acids) acids. This raw material is a source of essential fatty acids, such as omega-3 (linolenic acid) and omega-6 (linoleic acid). Conclusions.As a result of Arnica foliosa Nutt. research, the presence of fatty acids is established in its raw material. The dominant fatty acids in the studied raw material were palmitic, linolenic and linoleic acids, the content of which was 30.91 % (1.02 mg/g), 29.09 % (0.96 mg/g) and 20.30 % (0.67 mg/g) from total content acids, respectively. The result shows that Arnica foliosa Nutt. is the source of fatty acids, so the use of this plant raw material for new remedies is possible in the future

Medicinal plants have been considered as an important source for the prevention and treatment of various diseases. The genus Arnica L. is a genus of Asteraceae family, many species of which are used in traditional medicine. Arnica chamissonis Less. and Arnica foliosa Nutt., which belong to plants of the genus Arnica L., are successfully grown in the culture. There is insufficient information in the literature on the biologically active substances of Arnica foliosa Nutt. The presence of sesquiterpene lactones in the leaves and inflorescences is indicated. The flowers contain polysaccharides, monosaccharides, which mainly contain D-glucose and D-xylose, as well as phenolic compounds (quercetin, luteolin, kaempferol) and essential oils.The aim. The aim of our study was to identify and determine the quantitative content of fatty acids by gas chromatography/mass spectrometry method (GC/MS) in Arnica foliosa Nutt. herb.Materials and methods. The determination of fatty acids composition of Arnica foliosa Nutt. was carried out by gas chromatograph Agilent 6890N with a mass detector 5973 inert (Agilent Technologies, USA).Results. The analysis of Arnica foliosa Nutt. herb showed a mixture of saturated (1.61 mg/g; 48.79 %) and unsaturated (1.69 mg/g; 51.21 % from total content acids) fatty acids. The main components of Arnica foliosa Nutt. herb were palmitic (1.02 mg/g; 30.91 % from total content acids), linolenic (0.96 mg/g; 29.09 % from total content acids) and linoleic (0.67 mg/g; 20.30 % from total content acids) acids. This raw material is a source of essential fatty acids, such as omega-3 (linolenic acid) and omega-6 (linoleic acid).Conclusions. As a result of Arnica foliosa Nutt. research, the presence of fatty acids is established in its raw material. The dominant fatty acids in the studied raw material were palmitic, linolenic and linoleic acids, the content of which was 30.91 % (1.02 mg/g), 29.09 % (0.96 mg/g) and 20.30 % (0.67 mg/g) from total content acids, respectively. The result shows that Arnica foliosa Nutt. is the source of fatty acids, so the use of this plant raw material for new remedies is possible in the future, Лікарські рослини стали важливим джерелом для профілактики та лікування різних захворювань. Рід Arnica L. – рід родини айстрових, багато видів якого використовують у традиційній медицині. Arnica chamissonis Less. та Arnica foliosa Nutt., що належать до рослин роду Arnica L., добре культивуються. У літературі недостатньо інформації про біологічно активні речовини Arnica foliosa Nutt. Указано про наявність у листках та суцвіттях сесквітерпенових лактонів. Квітки містять полісахариди, моносахариди, переважно D-глюкозу та D-ксилозу, а також фенольні сполуки (кверцетин, лютеолін, кемпферол) та ефірні олії.Мета. Метою нашого дослідження була ідентифікація та визначення кількісного вмісту жирних кислот методом газової хромато-мас-спектрометрії (ГХ/МС) у траві Arnica foliosa Nutt.Матеріали і методи. Визначення жирнокислотного складу Arnica foliosa Nutt. проводили на газовому хроматографом Agilent 6890N із мас-детектором 5973 inert (Agilent Technologies, США).Результати. Аналіз трави Arnica foliosa Nutt. показав наявність насичених (1,61 мг / г; 48,79 % від загальної кількості усіх кислот) та ненасичених (1,69 мг / г; 51,21 % від загальної кількості усіх кислот) жирних кислот. Основними компонентами Arnica foliosa Nutt. були пальмітинова (1,02 мг / г; 30,91 % від загальної кількості усіх кислот), ліноленова (0,96 мг / г; 29,09 % від загальної кількості усіх кислот) та лінолева (0,67 мг / г; 20,30 % від загальної кількості усіх кислот) кислоти. Ця сировина може бути джерелом незамінних жирних кислот, таких як омега-3 (ліноленова кислота) та омега-6 (лінолева кислота).Висновки. У результаті дослідження, в сировині Arnica foliosa Nutt., встановлено наявність жирних кислот. Домінуючими жирними кислотами у досліджуваній сировині були пальмітинова, ліноленова та лінолева кислоти, вміст яких становив 30,91 % (1,02 мг/г), 29,09 % (0,96 мг/г) та 20,30 % (0,67 мг/г) від загальної кількості усіх кислот, відповідно. Результат дослідження показує, що трава Arnica foliosa Nutt. може бути джерелом жирних кислот, тому перспективним є використання цієї рослинної сировини для одержання нових лікарських засобів у майбутньому, Лекарственные растения стали важным источником для профилактики и лечения различных заболеваний. Род Arnica L. – род семейства астровых, многие виды которого используются в традиционной медицине. Arnica chamissonis Less. и Arnica foliosa Nutt., принадлежащие к растениям рода Arnica L., успешно выращиваются в культуре. В литературе недостаточно информации о биологически активных веществах Arnica foliosa Nutt. Показано наличие сесквитерпеновых лактонов в листьях и соцветиях. Цветки содержат полисахариды, моносахариды, которые в основном содержат D-глюкозу и D-ксилозу, а также фенольные соединения (кверцетин, лютеолин, кемпферол) и эфирные масла.Цель. Целью нашего исследования была идентификация и определение количественного содержания жирных кислот методом газовой хромато-масс-спектрометрии (ГХ/МС) в траве Arnica foliosa Nutt.Материалы и методы. Определение жирнокислотного состава Arnica foliosa Nutt. проводили на газовом хроматографе Agilent 6890N с масс-детектором 5973 inert (Agilent Technologies, США).Результаты. Анализ травы Arnica foliosa Nutt. показал наличие насыщенных (1,61 мг/г; 48,79 % от общего количества всех кислот) и ненасыщенных (1,69 мг/г; 51,21 % от общего количества всех кислот) жирных кислот. Основными компонентами Arnica foliosa Nutt. были пальмитиновая (1,02 мг/г; 30,91 % от общего количества всех кислот), линоленовая (0,96 мг/г; 29,09 % от общего количества всех кислот) и линолевая (0,67 мг/г; 20,30 % от общего количества всех кислот) кислоты. Это сырье может быть источником незаменимых жирных кислот, таких как омега-3 (линоленовая кислота) и омега-6 (линолевая кислота).Выводы. В результате исследования, в сырье Arnica foliosa Nutt., установлено наличие жирных кислот. Доминирующими жирными кислотами в исследуемом сырье были пальмитиновая, линоленовая и линолевая кислоты, содержание которых составляло 30,91 % (1,02 мг/г), 29,09 % (0,96 мг/г) и 20,30 % (0,67 мг/г) от общего количества всех кислот, соответственно. Результат исследования показывает, что Arnica foliosa Nutt. может быть источником жирных кислот, поэтому перспективно использование этого растительного сырья для получения новых лекарственных средств в будущем

Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC(50) ≈ 20–300 nM) towards the recombinant mouse, rat and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1–5, 8–12) at therapeutically relevant total concentrations (≥ 3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC(50) ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics, but it effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.

It is well known that consumption of a high-fat diet (HFD) promotes intestinal inflammation despite little being known about causative factors. Recent evidence implicates dietary peroxidized lipids (POLs), which are typically formed from the oxidation of polyunsaturated fatty acid double bonds, as potential contributors due to their enrichment in HFDs, ability to be formed during gastrointestinal transit, and immunogenic and cytotoxic properties. 13-HPODE, the most common dietary POL, demonstrates pro-inflammatory activity in a variety of immune cells, especially Natural Killer (NK) cells whose role in mediating intestinal inflammation remains unclear. Therefore, we set out to investigate how 13-HPODE and other POLs modulate NK-cell activity in the context of intestinal inflammation. We not only found that NK cells fully decompose exogenous 13-HPODE, but that direct treatment stimulates TNF-α and MCP1 expression as well as Granzyme B (GZMB) secretion in a dose-dependent manner. Similar results were observed upon incubation of NK cells with oxidized, but not-unoxidized, low-density lipoproteins. Secretory products from 13-HPODE-treated NK cells were able to induce Caco2 intestinal cell inflammation in the same way as exogenous GZMB with greater sensitivity in undifferentiated compared to differentiated cells. Results were recapitulated in 13-HPODE-fed mice, demonstrating both spatial and temporal patterns of elevated GZMB expression that favored acute treatments in the distal intestinal epithelium. Collectively, our results suggest that that HFD-derived POLs, like 13-HPODE, potentially contribute to intestinal inflammation by stimulating the secretion of pro-inflammatory granzymes by resident NK cells, ultimately revealing a more direct role for diet in modulating gut homeostasis and the immune environment.

Neuroblastoma is the leading cause of cancer death in children aged 1 to 4 years. Particularly, five-year overall survival for high-risk neuroblastoma is below 50% with no curative options when refractory or relapsed. Most of current therapies target cell division and proliferation, thereby inducing DNA damage and programmed cell death. However, aggressive tumours often present alterations of these processes and are resistant to therapy. Therefore, exploring alternative pathways to induce tumour cell death will provide new therapeutic opportunities for these patients. In this study we aimed at testing the therapeutic potential of ABTL0812, a novel anticancer drug that induces cytotoxic autophagy to eliminate cancer cells, which is currently in phase II clinical trials of adult tumours. Here, we show that ABTL0812 impaired the viability of clinical representative neuroblastoma cell lines regardless of genetic alterations associated to bad prognosis and resistance to therapy. Oral administration of ABTL0812 to mice bearing neuroblastoma xenografts impaired tumour growth. Furthermore, our findings revealed that, in neuroblastoma, ABTL0812 induced cancer cell death via induction of endoplasmic reticulum stress, activation of the unfolded protein response, autophagy and apoptosis. Remarkably, ABTL0812 potentiated the antitumour activity of chemotherapies and differentiating agents such as irinotecan and 13-cis-retinoic acid. In conclusion, ABTL0812 distinctive mechanism of action makes it standout to be used alone or in combination in high-risk neuroblastoma patients.

Schistosomiasis is an infectious disease caused by helminth parasites of the genus Schistosoma; it is transmitted in over 78 countries. The main strategy for schistosomiasis control is treatment of infected people with praziquantel (PZQ). As PZQ-resistant strains have emerged, new anti-schistosomal agents have become necessary. We evaluated the in vitro and in vivo effect of P-MAPA, an aggregated polymer of protein magnesium ammonium phospholinoleate-palmitoleate anhydride with immunomodulatory properties; it is produced by Aspergillus oryzae fermentation. In vitro, P-MAPA (5, 50, and 100 µg/mL) damaged the Schistosoma mansoni tegument, causing thorn losses and tuber destruction in male worms and peeling and erosion in females after 24-h incubation. In vivo, P-MAPA (5 and 100 mg/kg, alone and combined with PZQ – 50 mg/kg) reduced the number of eggs by up to 69.20% in the liver and 88.08% in the intestine. Furthermore, granulomas were reduced up to 83.13%, and there was an increase in the number of dead eggs and a reduction of serum aspartate aminotransferase levels. These data suggest that P-MAPA activity can help improve schistosomiasis treatment and patients’ quality of life.

Different fatty acids have distinct effects on the survival of breast cancer cells, which could be mediated by fatty acid binding proteins (FABPs), a family of lipid chaperones. Due to the diverse structures of the members of FABP family, each FABP demonstrates distinct binding affinities to different fatty acids. Of note, FABP7 is predominantly expressed in triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer. Yet, the role of FABP7 in modulating the effects of fatty acids on TNBC survival was unclear. In contrast to the high expression of FABP7 in human TNBC tumours, FABP7 protein was undetectable in TNBC cell lines. Hence, a FABP7 overexpression model was used for this study, in which the transduced TNBC cell lines (MDA-MB-231 and Hs578T) were treated with various mono- and polyunsaturated fatty acids. Oleic acid (OA), docosahexaenoic acid (DHA) and arachidonic acid (AA) inhibited TNBC cell growth at high concentrations, with no differences resulted from FABP7 overexpression. Interestingly, overexpression of FABP7 augmented linoleic acid-induced cell death in MDA-MB-231 cells. The increased cell death may be explained by a decrease in 13-HODE, a pro-tumorigenic oxidation product of linoleic acid. The phenotype was, however, attenuated with a rescue treatment using 25 nM 13-HODE. The decrease in 13-HODE was potentially due to fatty acid partitioning modulated by FABP7, as demonstrated by a 3-fold increase in fatty acid oxidation. Our findings suggest that linoleic acid could be a potential therapeutic strategy for FABP7-overexpressing TNBC patients.

A study was carried out to evaluate oil contents, fatty acid composition and tocopherol contents of several walnut types in relation to roasting process. The major fatty acid identified was linoleic acid in both roasted and unroasted walnut oils. Linoleic acid contents of unroasted walnut oil varied from 46.44 (Type 9) and 63.59% (Type 7), while the linoleic acid contents of roasted walnut oils at 120 degrees C/h ranged from 55.95% (Type 3) to 64.86% (Type 10). Interestingly, linolenic acid contents of both roasted and unroasted oils changed between 9.43 (Type 10) and 16.29% (Type 8) to 9.64 (Type 10) and 16.58% (Type 8), respectively and were significant (p < 0.05) different. gamma-tocopherol content of unroasted walnut oils varied between 6.3 (Type 3) and 11.4 mg/100g (Type 1) and gamma-tocopherol contents of roasted walnut oils ranged between 28.1 (Type 8) and 38.2 mg/100g (Type 3). The oil could be useful for industrial applications owing to good physicochemical properties. Fatty acid values for oil obtained from roasted walnut were slightly higher than those reported for unroasted walnut oils. Deanship of Scientific Research at King Saud UniversityKing Saud University [RG-1439-016] The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group no.(RG-1439-016).

The seed of five fruits and vegetables, which are often eaten by Chinese people, were selected as research objects to study the physicochemical properties, nutritional ingredients and antioxidant capacity of their seed oils. The fatty acid results indicated that the oleic acid was the main unsaturated fatty acid in almond oil and celery seed oil (content of 64.10% and 62.96%, respectively), and the wax gourd seed oil, watermelon seed oil and pumpkin seed oil were linoleic acid as the main unsaturated fatty acid (content of 72.45%, 76.77% and 47.35%, respectively). Unsaturated fatty acids are mainly located at the sn-2 position of the triacylglycerol (TAG), whereas saturated fatty acids are mainly located at the sn-1, 3 positions for the five seed oils. The pumpkin seed oil had certain advantages in terms of phytosterols and squalene (3716 and 2732 mg/kg, respectively). The high content of polyphenol for celery seed oil exhibits higher medicinal value. Polyphenols, and brassicasterols were have significant correlation with antioxidant capacity (p < 0.05, r = 0.890-0.998). The significant differences in nutrient composition between these fruits and vegetables seed oils indicate their unique value as food.

Background: Evidence suggests that inflammation increases risk for ovarian cancer. Aspirin has been shown to decrease ovarian cancer risk, though the mechanism is unknown. Studies of inflammatory markers, lipid molecules such as arachidonic acid, linoleic acid, and alpha-linoleic acid metabolites, and development of ovarian cancer are essential to understand the potential mechanisms. Methods: We conducted a nested case–control study (157 cases/156 matched controls) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Unconditional logistic regression was used to estimate the association between prediagnostic serum levels of 31 arachidonic acid/linoleic acid/alpha-linoleic acid metabolites and risk of ovarian cancer. Results: Five of the 31 arachidonic acid/linoleic acid/alpha-linoleic acid (free fatty acids) metabolites were positively associated with ovarian cancer risk: 8-HETE [tertile 3 vs. 1: OR 2.53 (95% confidence interval [CI] 1.18–5.39), Ptrend 0.02], 12,13-DHOME [2.49 (1.29–4.81), 0.01], 13-HODE [2.47 (1.32–4.60), 0.005], 9-HODE [1.97 (1.06–3.68), 0.03], 9,12,13-THOME [2.25 (1.20–4.21), 0.01]. In analyses by subtype, heterogeneity was suggested for 8-HETE [serous OR (95% CI): 2.53 (1.18–5.39) vs. nonserous OR (95% CI): 1.15 (0.56–2.36), Phet 0.1] and 12,13-EpOME [1.95 (0.90–4.22) vs. 0.82 (0.39–1.73), 0.05]. Conclusions: Women with increased levels of five fatty acid metabolites (8-HETE, 12,13-DHOME, 13-HODE, 9-HODE, and 9,12,13-THOME) were at increased risk of developing ovarian cancer in the ensuing decade. All five metabolites are derived from either arachidonic acid (8-HETE) or linoleic acid (12,13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME) via metabolism through the LOX/cytochrome P450 pathway. Impact: The identification of these risk-related fatty acid metabolites provides mechanistic insights into the etiology of ovarian cancer and indicates the direction for future research.

Hydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.

Fatty acids, especially polyunsaturated, and their metabolites (eicosanoids) play many pivotal roles in human body, influencing various physiological and pathological processes. The aim of the study was to evaluate the effect of supplementation with edible oils diverse in terms of fatty acid composition on fatty acid contents, activities of converting their enzymes, and on lipoxygenase metabolites of arachidonic and linoleic acids (eicosanoids) in rat serum. Female Sprague-Dawley rats divided into seven groups were used in the study. Animals from six groups were fed one of oils daily (carotino oil, made up by combining of red palm oil and canola oil, linseed oil, olive oil, rice oil, sesame oil, or sunflower oil). One group received a standard diet only. Fatty acids were determined using gas chromatography with flame ionization detection. Eicosanoids&mdash, hydroxyeicosatetraenoic (HETE) and hydroxyoctadecadienoic acids (HODE) were extracted using a solid-phase extraction method and analyzed with HPLC. Vegetable oils given daily to rats caused significant changes in serum fatty acid profile and eicosanoid concentrations. Significant differences were also found in desaturases&rsquo, activity, with the linseed and olive oil supplemented groups characterized by the highest D6D and D5D activity. These findings may play a significant role in various pathological states.

Type 2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase-1 (15LO1) is induced by the type 2 cytokine IL-13 in human airway epithelial cells (HAECs) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15-HETE-phosphatidylethanolamine (15-HETE-PE), and 13-hydroxyoctadecadienoic acid (13-HODE). In this study, we investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, as well as its influence on goblet cell differentiation in HAECs. Primary HAECs obtained from bronchial brushings of asthmatic and healthy subjects were cultured under air-liquid interface culture supplemented with arachidonic acid and linoleic acid (10 μM each) and exposed to IL-13 for 7 days. Short interfering RNA transfection and 15LO1 inhibition were applied to suppress 15LO1 expression and activity. IL-13 stimulation induced expression of 15LO1 and preferentially generated 15-HETE-PE in vitro, both of which persisted after removal of IL-13. 15LO1 inhibition (by short interfering RNA and chemical inhibitor) decreased IL-13-induced forkhead box protein A3 (FOXA3) expression and enhanced FOXA2 expression. These changes were associated with reductions in both mucin 5AC and periostin. Exogenous 15-HETE-PE stimulation (alone) recapitulated IL-13-induced FOXA3, mucin 5AC, and periostin expression. The results of this study confirm the central importance of 15LO1 and its primary product, 15-HETE-PE, for epithelial cell remodeling in HAECs.

Nonalcoholic fatty liver disease (NAFLD) is becoming a major public health problem worldwide. The study aimed to evaluate the concentration of eicosanoids in serum and liver tissue during steatosis progression and to assess whether eicosanoid change scores may predict liver tissue remodeling. Thirty six eight-week-old male Sprague Dawley rats were enrolled and sacrificed at different stages of NAFLD. Eicosanoid concentrations, namely lipoxin A4, hydroxyeicosatetraenoic acids (HETE), hydroxyloctadecadienoic acids (HODE), protectin DX, Maresine1, leucotriene B4, prostaglandin E2, and resolvin D1 measurement in serum and liver tissue with Agilent Technologies 1260 liquid chromatography were evaluated. For the liver and serum concentrations of 9-HODE and 13-HODE, the correlations were found to be strong and positive (r &gt, 0.7, p &lt, 0.05). Along with NAFLD progression, HODE concentration significantly increased, and change scores were more abundant in the liver. The moderate positive correlation between liver and serum (r = 0.52, p &lt, 0.05) was also observed for resolvin E1. The eicosanoid concentration decreased during NAFLD progression, but mostly in serum. There were significant correlations between HETE concentrations in liver and serum, but their associations were relatively low and changes the most in liver tissue. Eicosanoids profile, predominantly 9-HODE and 13-HODE, may serve as a potential biomarker for NAFLD development.

Salinity is linked to poor plant growth and a reduction in global food output. Therefore, there is an essential need for plant adaptation and mitigation of salinity stress conditions. Plants combat salinity stress influences by promoting a set of physiological, biochemical, and molecular actions. Tremendous mechanisms are being applied to induce plant stress tolerance, involving amino acid application. For evaluating the growth and productivity of Moringa oleifera trees grown under salt stress conditions, moringa has been cultivated under different levels of salinity and subjected to a foliar spray of proline (Pro) and phenylalanine (Phe) amino acids. Moringa plants positively responded to the lowest level of salinity as the leaves, inflorescences, seeds, and oil yields have been increased, but the growth and productivity slightly declined with increasing salinity levels after that. However, Pro and Phe applications significantly ameliorate these effects, particularly, Pro-treatments which decelerated chlorophyll and protein degradation and enhanced vitamin C, polyphenols, and antioxidant activity. A slight reduction in mineral content was observed under the high levels of salinity. Higher osmoprotectants (proline, protein, and total soluble sugars) content was given following Pro treatment in salted and unsalted plants. A significant reduction in oil yield was obtained as affected by salinity stress. Additionally, salinity exhibited a reduction in oleic acid (C18:1), linoleic (C18:2), and linolenic (C18:3) acids, and an increase in stearic (C18:0), palmitic (C16:0), eicosenoic (C20:2), and behenic (C22:0) acids. Generally, Pro and Phe treatments overcome the harmful effects of salinity in moringa trees by stimulating the osmoprotectants, polyphenols, and antioxidant activity, causing higher dry matter accumulation and better defense against salinity stress.