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PloS One 2023Cannabis sativa is a global multi-billion-dollar cash crop with numerous industrial uses, including in medicine and recreation where its value is largely owed to the...
Cannabis sativa is a global multi-billion-dollar cash crop with numerous industrial uses, including in medicine and recreation where its value is largely owed to the production of pharmacological and psychoactive metabolites known as cannabinoids. Often underappreciated in this role, the lipoxygenase (LOX)-derived green leaf volatiles (GLVs), also known as the scent of cut grass, are the hypothetical origin of hexanoic acid, the initial substrate for cannabinoid biosynthesis. The LOX pathway is best known as the primary source of plant oxylipins, molecules analogous to the eicosanoids from mammalian systems. These molecules are a group of chemically and functionally diverse fatty acid-derived signals that govern nearly all biological processes including plant defense and development. The interaction between oxylipin and cannabinoid biosynthetic pathways remains to be explored. Despite their unique importance in this crop, there has not been a comprehensive investigation focusing on the genes responsible for oxylipin biosynthesis in any Cannabis species. This study documents the first genome-wide catalogue of the Cannabis sativa oxylipin biosynthetic genes and identified 21 LOX, five allene oxide synthases (AOS), three allene oxide cyclases (AOC), one hydroperoxide lyase (HPL), and five 12-oxo-phytodienoic acid reductases (OPR). Gene collinearity analysis found chromosomal regions containing several isoforms maintained across Cannabis, Arabidopsis, and tomato. Promoter, expression, weighted co-expression genetic network, and functional enrichment analysis provide evidence of tissue- and cultivar-specific transcription and roles for distinct isoforms in oxylipin and cannabinoid biosynthesis. This knowledge facilitates future targeted approaches towards Cannabis crop improvement and for the manipulation of cannabinoid metabolism.
Topics: Animals; Oxylipins; Cannabis; Gene Regulatory Networks; Arabidopsis; Oxides; Cannabinoids; Mammals
PubMed: 37099560
DOI: 10.1371/journal.pone.0272893 -
International Journal of Molecular... Jan 2022Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through...
Omega-6 and Omega-3 Fatty Acid-Derived Oxylipins from the Lipoxygenase Pathway in Maternal and Umbilical Cord Plasma at Delivery and Their Relationship with Infant Growth.
Omega-3 and omega-6 fatty acids are important for neonatal development and health. One mechanism by which omega-3 and omega-6 fatty acids exert their effects is through their metabolism into oxylipins and specialized pro-resolving mediators. However, the influence of oxylipins on fetal growth is not well understood. Therefore, the objective of this study was to identify oxylipins present in maternal and umbilical cord plasma and investigate their relationship with infant growth. Liquid chromatography-tandem mass spectrometry was used to quantify oxylipin levels in plasma collected at the time of delivery. Spearman's correlations highlighted significant correlations between metabolite levels and infant growth. They were then adjusted for maternal obesity (normal body mass index (BMI: ≤30 kg/m) vs. obese BMI (>30 kg/m) and smoking status (never vs. current/former smoker) using linear regression modeling. A -value < 0.05 was considered statistically significant. Our study demonstrated a diverse panel of oxylipins from the lipoxygenase pathway present at the time of delivery. In addition, both omega-3 and omega-6 oxylipins demonstrated potential influences on the birth length and weight percentiles. The oxylipins present during pregnancy may influence fetal growth and development, suggesting potential metabolites to be used as biomarkers for infant outcomes.
Topics: Adult; Chromatography, Liquid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Infant, Newborn; Lipoxygenases; Obesity; Oxylipins; Pregnancy; Tandem Mass Spectrometry; Umbilical Cord
PubMed: 35054892
DOI: 10.3390/ijms23020708 -
The Journal of Clinical Investigation Nov 2023This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant...
This study investigates a mechanistic link of bacterial biofilm-mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.
Topics: Humans; Female; Mice; Animals; Breast Implants; Oxylipins; Biofilms; Immunity
PubMed: 38032740
DOI: 10.1172/JCI165644 -
Frontiers in Immunology 2022While animal aggregations can benefit the fitness of group members, the behaviour may also lead to higher risks of parasite infection as group density increases. Some...
While animal aggregations can benefit the fitness of group members, the behaviour may also lead to higher risks of parasite infection as group density increases. Some animals are known to moderate their investment in immunity relative to the risk of infection. These animals exhibit density-dependent prophylaxis (DDP) by increasing their immune investment as group density increases. Despite being documented in many taxa, the mechanisms of DDP remain largely unexplored. Snails are known to aggregate and experience large fluctuations in density and serve as required hosts for many parasites. Further, they are known to use chemical cues to aggregate. To test whether freshwater snails exhibit DDP and investigate the role that chemical signaling compounds may play in triggering this phenomenon, we performed four experiments on the freshwater snail , which is a common host for many trematode parasite species. First, we tested if DDP occurred in snails in laboratory-controlled conditions (control vs snail-conditioned water) and whether differences in exposure to chemical cues affected immune function. Second, we used gas chromatography to characterize fatty acids expressed in snail-conditioned water to determine if precursors for particular signaling molecules, such as oxylipins, were being produced by snails. Third, we characterized the oxylipins released by infected and uninfected field-collected snails, to better understand how differences in oxylipin cocktails may play a role in inducing DDP. Finally, we tested the immune response of snails exposed to four oxylipins to test the ability of specific oxylipins to affect DDP. We found that snails exposed to water with higher densities of snails and raised in snail-conditioned water had higher counts of haemocytes. Additionally, lipid analysis demonstrated that fatty acid molecules that are also precursors for oxylipins were present in snail-conditioned water. Trematode-infected snails emitted 50 oxylipins in higher amounts, with 24 of these oxylipins only detected in this group. Finally, oxylipins that were higher in infected snails induced naïve snails to increase their immune responses compared to sham-exposed snails. Our results provide evidence that snails exhibit DDP, and the changes in oxylipins emitted by infected hosts may be one of the molecular mechanisms driving this phenomenon.
Topics: Animals; Cues; Fresh Water; Oxylipins; Parasites; Snails; Trematoda
PubMed: 35173735
DOI: 10.3389/fimmu.2022.826500 -
Molecules (Basel, Switzerland) May 2021Cancer is a serious problem in modern medicine, mainly due to the insufficient effectiveness of currently available therapies. There is a particular interest in... (Review)
Review
Cancer is a serious problem in modern medicine, mainly due to the insufficient effectiveness of currently available therapies. There is a particular interest in compounds of natural origin, which can be used in the prophylaxis, as well as in the treatment and support of cancer treatment. One such compound is jasmonic acid (3-oxo-2-(pent-2'-enyl)cyclopentane acetic acid; isolated active form: -(-)-(3,7)- and -(+)-(3,7)-jasmonic acid) and its derivatives, which, due to their wide range of biological activities, are also proposed as potential therapeutic agents. Therefore, a review of literature data on the biological activity of jasmonates was prepared, with particular emphasis on the mechanisms of jasmonate action in neoplastic diseases. The anti-tumor activity of jasmonate compounds is based on altered cellular ATP levels; induction of re-differentiation through the action of Mitogen Activated Protein Kinases (MAPKs); the induction of the apoptosis by reactive oxygen species. Jasmonates can be used in anti-cancer therapy in combination with other known drugs, such as cisplatin, paclitaxel or doxorubicin, showing a synergistic effect. The structure-activity relationship of novel jasmonate derivatives with anti-tumor, anti-inflammatory and anti-aging effects is also shown.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cyclopentanes; Energy Metabolism; Humans; Neoplastic Processes; Oxylipins; Reactive Oxygen Species
PubMed: 34068337
DOI: 10.3390/molecules26102901 -
Journal of Microbiology (Seoul, Korea) Mar 2016Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While... (Review)
Review
Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter host-microbe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/host interactions.
Topics: Animals; Fungi; Host-Pathogen Interactions; Humans; Immunity, Active; Mycoses; Oxygenases; Oxylipins; Plant Diseases; Plants; Virulence
PubMed: 26920885
DOI: 10.1007/s12275-016-5620-z -
Journal of Dairy Science Mar 2021Our objective was to investigate the lipid content of uterus, blood plasma, and milk at early, mid, and late diestrus. Lactating cows (n = 30) had the estrous cycle and...
Our objective was to investigate the lipid content of uterus, blood plasma, and milk at early, mid, and late diestrus. Lactating cows (n = 30) had the estrous cycle and ovulation synchronized by administration of exogenous hormones. Cows were blocked by parity and assigned randomly to receive transcervical uterine flushing and biopsy on d 5 (early diestrus), 10 (mid diestrus) or 15 (late diestrus) of the estrous cycle. Flushing and endometrial biopsy were performed in the uterine horn ipsilateral to the corpus luteum. The recovered flushing was used for analyses of lipid composition by liquid chromatography-tandem mass spectrometry and the biopsy was used for investigation of lipid droplet abundance in endometrial cryosections using a neutral lipid fluorescent dye. In addition, blood and milk samples were collected from all cows on d 5, 10, and 15. All blood samples were used to measure the concentration of progesterone in plasma, and all milk samples were used to determine milk composition. Subsamples of blood plasma and milk were also used to evaluate the composition of fatty acids and oxylipins using the same methodology used for uterine flushing samples. The abundance of lipid droplets in the endometrium increased 1.9-fold from d 5 to 10, and 2-fold from d 10 to 15. Concentration of long-chain fatty acids and oxylipins in uterine flushing were, on average, 2.2 and 2.5 times greater in samples collected on d 15 compared with those collected on d 5 and 10. These differences were not observed in blood and milk, suggesting that accumulation of fatty acids and oxylipins in the uterus is regulated locally. In addition to concentration, the profile of individual fatty acids and oxylipins in uterine lumen changed substantially during diestrus. The main categories with increased abundance at late diestrus were mono- and polyunsaturated fatty acids, and oxylipins derived from arachidonic acid, dihomo-γ-linolenic acid, and docosahexaenoic acid. In conclusion, fatty acids and oxylipins accumulate in the uterine lumen during diestrus and might work as a mechanism to supply these lipids to the developing conceptus at late diestrus, when the onset of elongation occurs and substantial synthesis of biomass and cell signaling by lipid mediators are required.
Topics: Animals; Cattle; Diestrus; Endometrium; Fatty Acids; Female; Lactation; Lipid Droplets; Milk; Oxylipins; Pregnancy; Uterus
PubMed: 33455794
DOI: 10.3168/jds.2020-19196 -
The Plant Journal : For Cell and... Aug 2022Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting... (Review)
Review
Plants are able to construct lineage-specific natural products from a wide array of their core metabolic pathways. Considerable progress has been made toward documenting and understanding, for example, phenylpropanoid natural products derived from phosphoenolpyruvate via the shikimate pathway, terpenoid compounds built using isopentyl pyrophosphate, and alkaloids generated by the extensive modification of amino acids. By comparison, natural products derived from fatty acids have received little attention, except for unusual fatty acids in seed oils and jasmonate-like oxylipins. However, scattered but numerous reports show that plants are able to generate many structurally diverse compounds from fatty acids, including some with highly elaborate and unique structural features that have novel bioproduct functionalities. Furthermore, although recent work has shed light on multiple new fatty acid natural product biosynthesis pathways and products in diverse plant species, these discoveries have not been reviewed. The aims of this work, therefore, are to (i) review and systematize our current knowledge of the structures and biosynthesis of fatty acid-derived natural products that are not seed oils or jasmonate-type oxylipins, specifically, polyacetylenic, very-long-chain, and aromatic fatty acid-derived natural products, and (ii) suggest priorities for future investigative steps that will bring our knowledge of fatty acid-derived natural products closer to the levels of knowledge that we have attained for other phytochemical classes.
Topics: Biological Products; Fatty Acids; Oxylipins; Plant Oils; Plants
PubMed: 35749584
DOI: 10.1111/tpj.15878 -
Plant & Cell Physiology Jun 2019The moss Physcomitrella patens receives increased scientific interest since its genome was sequenced a decade ago. As a bryophyte, it represents the first group of... (Review)
Review
The moss Physcomitrella patens receives increased scientific interest since its genome was sequenced a decade ago. As a bryophyte, it represents the first group of plants that evolved in a terrestrial habitat still without a vascular system that developed later in tracheophytes. It is easily transformable via homologous recombination, which enables the formation of targeted loss-of-function mutants. Even though genetics, development and life cycle in Physcomitrella are well studied nowadays, research on lipids in Physcomitrella is still underdeveloped. This review aims on presenting an overview on the state of the art of lipid research with a focus on membrane lipids, surface lipids and oxylipins. We discuss in this review that Physcomitrella possesses very interesting features regarding its membrane lipids. Here, the presence of very-long-chain polyunsaturated fatty acids (VLC-PUFA) still shows a closer similarity to marine microalgae than to vascular plants. Unlike algae, Physcomitrella has a cuticle comparable to vascular plants composed of cutin and waxes. The presence of VLC-PUFA in Physcomitrella also leads to a greater variability of signaling lipids even though the phytohormone jasmonic acid is not present in this organism, which is different to vascular plants. In summary, the research on lipids in Physcomitrella is still in its infancy, especially considering membrane lipids. We hope that this review will help to promote the further advancement of lipid research in this important model organism in the future, so we can better understand how lipids are involved in the evolution of land plants.
Topics: Bryopsida; Fatty Acids, Unsaturated; Membrane Lipids; Oxylipins; Waxes
PubMed: 30698763
DOI: 10.1093/pcp/pcz006 -
Rheumatology (Oxford, England) May 2023Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and...
OBJECTIVE
Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and identified new oxylipin biomarkers for clinical use in differentiating gout from hyperuricaemia.
MATERIAL AND METHODS
Oxylipin profiling was performed in 90 men (30 very early onset gout, 30 asymptomatic hyperuricaemia [HU] and 30 normouricaemia [NU], all aged <20 years) divided into discovery and validation sample sets. The dataset was analysed based on orthogonal projection to latent structure-discriminant analysis. Correlation network and pathway enrichment were conducted to reveal potential oxylipin-involved pathways of gout. Candidate oxylipins were further evaluated and optimized in the validation cohort, and differential oxylipin biomarkers combined with or without serum urate were applied to construct diagnostic models.
RESULTS
In discovery stage, 21 differential oxylipins in the gout vs HU comparisons and 14 differential oxylipins in the gout vs NU comparisons were discovered. Correlation network analysis was performed and 14(S)-HDHA (14S-hydroxy-4Z,7Z,10Z,12E,16Z,19Z-docosahexaenoic acid) was identified as a hub metabolite in both comparisons. Seven down-regulated oxylipins in the gout vs HU group and five down-regulated oxylipins in the gout vs NU group were validated. Diagnostic models were constructed with the above oxylipins, with 14(S)-HDHA alone having an area under the curve of 1 (95% CI, 1, 1) in both comparisons.
CONCLUSIONS
Young men with very early onset gout have distinct oxylipin spectrums, especially those derived from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Differential oxylipins could serve as candidate serum biomarkers in differentiating gout from hyperuricaemia.
Topics: Male; Humans; Adolescent; Oxylipins; Docosahexaenoic Acids; Hyperuricemia; Biomarkers; Gout
PubMed: 36111871
DOI: 10.1093/rheumatology/keac507