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Raftlin and 8-iso-prostaglandin F2α levels and gene network analysis in patients with Modic changes.European Spine Journal : Official... Jul 2023Oxidative stress in the vertebral endplates of patients with low back pain and Modic changes (MCs) (types I, II, and III) endplate changes on magnetic resonance imaging....
PURPOSE
Oxidative stress in the vertebral endplates of patients with low back pain and Modic changes (MCs) (types I, II, and III) endplate changes on magnetic resonance imaging. 8-iso-prostaglandin F (8-iso-PGF) has been proposed as new indicator of oxidative stress. Raftlin, as an inflammatory biomarker, has been previously reported in inflammatory diseases. Oxidative stress plays an important role in various human diseases. This study was aimed to assess Raftlin and 8-iso-PGF levels in patients with MCs.
METHODS
Patients with MCI, II, and III (n = 45) and age- and sex matched controls subjects (n = 45) were enrolled in this study. 8-iso-PGF and Raftlin levels in the serum samples of both groups were measured with enzyme-linked immunosorbent assay.
RESULTS
In our study results, raftlin levels changed in parallel with prostaglandin levels (p < 0.05). Raftlin levels changed in parallel with prostaglandin levels (p < 0.05). The levels of 8-iso-PGF and Raftlin levels showed increase in patients with MCs and the control group (p < 0.05). In addition, a significant positive correlation was found between MC-I, MC-II, MC-III and Raftlin (r = 0.756, 0.733, 0.701 p < 0.001, respectively). A significant positive correlation was found between ISO (Respectively; r = 0.782, 0.712, 0.716 p < 0.001). In our evaluation between Raftlin and Iso, a significant positive relationship was determined. (r = 0.731, p < 0.001).
CONCLUSION
Our findings indicated that oxidative stress in patients with MC-I may be aggravated and it may cause an inflammation formation of the lesion areas in these patients. Also, the increased 8-iso-PGF and Raftlin levels in patients with MC-II and MC-III may be an adaptive response to against oxidative stress.
Topics: Humans; Biomarkers; Dinoprost; Gene Regulatory Networks; Inflammation; Oxidative Stress
PubMed: 37208489
DOI: 10.1007/s00586-023-07757-7 -
Frontiers in Immunology 2023Allergic inflammation of the airways such as allergic asthma is a major health problem with growing incidence world-wide. One cardinal feature in severe type 2-dominated...
Allergic inflammation of the airways such as allergic asthma is a major health problem with growing incidence world-wide. One cardinal feature in severe type 2-dominated airway inflammation is the release of lipid mediators of the eicosanoid family that can either promote or dampen allergic inflammation. Macrophages are key producers of prostaglandins and leukotrienes which play diverse roles in allergic airway inflammation and thus require tight control. Using RNA- and ATAC-sequencing, liquid chromatography coupled to mass spectrometry (LC-MS/MS), enzyme immunoassays (EIA), gene expression analysis and models, we show that the aryl hydrocarbon receptor (AhR) contributes to this control transcriptional regulation of lipid mediator synthesis enzymes in bone marrow-derived as well as in primary alveolar macrophages. In the absence or inhibition of AhR activity, multiple genes of both the prostaglandin and the leukotriene pathway were downregulated, resulting in lower synthesis of prostanoids, such as prostaglandin E2 (PGE), and cysteinyl leukotrienes, e.g., Leukotriene C4 (LTC). These AhR-dependent genes include encoding for the enzyme cyclooxygenase 1 (COX1) and encoding for the arachidonate 5-lipoxygenase (5-LO) both of which major upstream regulators of the prostanoid and leukotriene pathway, respectively. This regulation is independent of the activation stimulus and partially also detectable in unstimulated macrophages suggesting an important role of basal AhR activity for eicosanoid production in steady state macrophages. Lastly, we demonstrate that AhR deficiency in hematopoietic but not epithelial cells aggravates house dust mite induced allergic airway inflammation. These results suggest an essential role for AhR-dependent eicosanoid regulation in macrophages during homeostasis and inflammation.
Topics: Humans; Chromatography, Liquid; Dinoprostone; Eicosanoids; Inflammation; Leukotrienes; Macrophages, Alveolar; Prostaglandins; Receptors, Aryl Hydrocarbon; Tandem Mass Spectrometry
PubMed: 37081886
DOI: 10.3389/fimmu.2023.1157373 -
The Journal of Clinical Investigation Jul 2018Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting... (Review)
Review
Chronic inflammation is a risk factor for gastrointestinal cancer and other diseases. Most studies have focused on cytokines and chemokines as mediators connecting chronic inflammation to cancer, whereas the involvement of lipid mediators, including prostanoids, has not been extensively investigated. Prostanoids are among the earliest signaling molecules released in response to inflammation. Multiple lines of evidence suggest that prostanoids are involved in gastrointestinal cancer. In this Review, we discuss how prostanoids impact gastrointestinal cancer development. In particular, we highlight recent advances in our understanding of how prostaglandin E2 induces the immunosuppressive microenvironment in gastrointestinal cancers.
Topics: Animals; Carcinogens; Dinoprostone; Gastrointestinal Neoplasms; Humans; Immune Tolerance; Inflammation Mediators; Killer Cells, Natural; Macrophages; Metabolic Networks and Pathways; Models, Biological; Prostaglandins; T-Lymphocytes; Tumor Microenvironment
PubMed: 29733297
DOI: 10.1172/JCI97953 -
Anatomia, Histologia, Embryologia Jan 2024Prostaglandins are synthesized from arachidonic acid through the catalytic activities of cyclooxygenase, while the production of different prostaglandin types,... (Review)
Review
Prostaglandins are synthesized from arachidonic acid through the catalytic activities of cyclooxygenase, while the production of different prostaglandin types, prostaglandin F2 alpha (PGF) and prostaglandin E2 (PGE), are regulated by specific prostaglandin synthases (PGFS and PGES). Prostaglandin ligands (PGF and PGE) bind to specific high-affinity receptors and initiate biologically distinct signalling pathways. In the ovaries, prostaglandins are known to be important endocrine regulators of female reproduction, in addition to maintaining local function through autocrine and/or paracrine effect. Many research groups in different animal species have already identified a variety of factors and molecular mechanisms that are responsible for the regulation of prostaglandin functions. In addition, prostaglandins stimulate their intrafollicular and intraluteal production via the pathway of prostaglandin self-regulation in the ovary. Therefore, the objective of the review article is to discuss recent findings about local regulation patterns of prostaglandin ligands PGF and PGE during different physiological stages of ovarian function in domestic ruminants, especially in bovine. In conclusion, the discussed local regulation mechanisms of prostaglandins in the ovary may stimulate further research activities in different methodological approaches, especially during final follicle maturation and ovulation, as well as corpus luteum formation and function.
Topics: Female; Cattle; Animals; Prostaglandins; Ovary; Prostaglandin-Endoperoxide Synthases; Ruminants; Ovarian Follicle; Corpus Luteum
PubMed: 37788129
DOI: 10.1111/ahe.12980 -
Molecular Reproduction and Development Jul 2023Pregnancy establishment in mammals, including pigs, requires coordinated communication between developing conceptuses (embryos with associated membranes) and the... (Review)
Review
Pregnancy establishment in mammals, including pigs, requires coordinated communication between developing conceptuses (embryos with associated membranes) and the maternal organism. Porcine conceptuses signalize their presence by secreting multiple factors, of which estradiol-17β (E2) is considered the major embryonic signal initiating the maternal recognition of pregnancy. During this time, a limited supply of prostaglandin (PGF2α) to the corpora lutea and an increased secretion of luteoprotective factors (e.g., E2 and prostaglandin E2 [PGE2]) lead to the corpus luteum's maintained function of secreting progesterone, which in turn primes the uterus for implantation. Further, embryo implantation is related to establishing an appropriate proinflammatory environment coordinated by the secretion of proinflammatory mediators including cytokines, growth factors, and lipid mediators of both endometrial and conceptus origin. The novel, dual role of PGF2α has been underlined. Recent studies involving high-throughput technologies and sophisticated experimental models identified a number of novel factors and revealed complex relationships between these factors and those already established. Hence, it seems that early pregnancy should be regarded as a sequence of processes orchestrated by pleiotropic factors that are involved in redundancy and compensatory mechanisms that preserve the essential functions critical for implantation and placenta formation. Therefore, establishing the hierarchy between all molecules present at the embryo-maternal interface is now even more challenging.
Topics: Pregnancy; Female; Animals; Swine; Dinoprost; Pregnancy, Animal; Embryo Implantation; Prostaglandins; Dinoprostone; Mammals
PubMed: 35385215
DOI: 10.1002/mrd.23567 -
Pediatrics International : Official... Jan 2019The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to... (Review)
Review
The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and human breast milk is considered to provide the optimal source of nutrition for infants. Our previous studies examined the effect of feeding type on antioxidative properties, glucose and insulin metabolism, the lipid profile, metabolomics, and prostaglandin (PG) metabolism in term and preterm infants. A urinary marker of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine) was significantly lower in breast-fed term and preterm infants than in formula-fed infants. Markers of insulin sensitivity were significantly lower and atherosclerotic indices were significantly higher in breast-fed preterm infants than in mixed-fed infants at discharge. On urinary metabolomics analysis, choline, choline metabolites, and lactic acid were significantly lower in breast-fed term infants than in formula-fed infants. Urinary PGD metabolite level in breast-fed term infants was also significantly lower than in formula-fed term infants. This indicates that human breast milk affects biological metabolism in early infancy.
Topics: Antioxidants; Breast Feeding; Humans; Infant; Infant, Newborn; Metabolic Syndrome; Metabolomics; Milk, Human; Oxidative Stress; Prostaglandins
PubMed: 30194786
DOI: 10.1111/ped.13693 -
European Journal of Immunology Oct 2021Type 2 immunity is critical for the protective and repair responses that mediate resistance to parasitic helminth infection. This immune response also drives aberrant... (Review)
Review
Type 2 immunity is critical for the protective and repair responses that mediate resistance to parasitic helminth infection. This immune response also drives aberrant inflammation during atopic diseases. Prostaglandins are a class of critical lipid mediators that are released during type 2 inflammation and are integral in controlling the initiation, activation, maintenance, effector functions, and resolution of Type 2 inflammation. In this review, we explore the roles of the different prostaglandin family members and the receptors they bind to during allergen- and helminth-induced Type 2 inflammation and the mechanism through which prostaglandins promote or suppress Type 2 inflammation. Furthermore, we discuss the potential role of prostaglandins produced by helminth parasites in the regulation of host-pathogen interactions, and how prostaglandins may regulate the inverse relationship between helminth infection and allergy. Finally, we discuss opportunities to capitalize on our understanding of prostaglandin pathways to develop new therapeutic options for humans experiencing Type 2 inflammatory disorders that have a significant prostaglandin-driven component including allergic rhinitis and asthma.
Topics: Animals; Biomarkers; Disease Management; Disease Susceptibility; Energy Metabolism; Gene Expression Regulation; Host-Parasite Interactions; Host-Pathogen Interactions; Humans; Inflammation; Prostaglandins; Receptors, Prostaglandin; Signal Transduction
PubMed: 34396535
DOI: 10.1002/eji.202048909 -
American Journal of Respiratory and... Sep 2022
Topics: Biomarkers; F2-Isoprostanes; Fibroblasts; Humans; Oxidative Stress; Prostaglandins; Pulmonary Fibrosis; Receptors, Prostaglandin; Receptors, Thromboxane; Thromboxanes
PubMed: 35763804
DOI: 10.1164/rccm.202205-0914ED -
Critical Reviews in Biochemistry and... Dec 2019Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is... (Review)
Review
Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is associated with pathological conditions in humans and animals, where incorporation of Sec into selenoproteins is reduced along with their expression and catalytic activity. Supplementation of Se-deficient population with Se has shown health benefits suggesting the importance of Se in physiology. An interesting paradigm to explain, in part, the health benefits of Se stems from the observations that selenoprotein-dependent modulation of inflammation and efficient resolution of inflammation relies on mechanisms involving a group of bioactive lipid mediators, prostanoids, which orchestrate a concerted action toward maintenance and restoration of homeostatic immune responses. Such an effect involves the interaction of various immune cells with these lipid mediators where cellular redox gatekeeper functions of selenoproteins further aid in not only dampening inflammation, but also initiating an effective and active resolution process. Here we have summarized the current literature on the multifaceted roles of Se/selenoproteins in the regulation of these bioactive lipid mediators and their immunomodulatory effects.
Topics: Animals; Humans; Inflammation; Lipid Metabolism; Prostaglandins; Randomized Controlled Trials as Topic; Selenium; Selenoproteins; Signal Transduction
PubMed: 31996052
DOI: 10.1080/10409238.2020.1717430 -
Bioscience, Biotechnology, and... 2015Lipid-derived electrophilic molecules are endogenously generated and are causally involved in many pathophysiological effects. Prostaglandin D2, a major cyclooxygenase... (Review)
Review
Lipid-derived electrophilic molecules are endogenously generated and are causally involved in many pathophysiological effects. Prostaglandin D2, a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the J-series PGs such as 15-deoxy-Δ(12,14)-PGJ2 (15d-PGJ2). Because of the electrophilic α,β-unsaturated ketone moiety present in its cyclopentenone ring, 15d-PGJ2 acts as an endogenous electrophile. 15d-PGJ2 can covalently react via the Michael addition reaction with critical cellular nucleophiles, such as the free cysteine residues of proteins that play a key role in the regulation of the intracellular signaling pathways. Covalent modification of cellular proteins by 15d-PGJ2 may be one of the most important mechanisms by which 15d-PGJ2 induces many biological responses involved in the pathophysiological effects associated with inflammation. This current review is intended to provide a comprehensive summary of 15d-PGJ2 as an endogenous electrophilic mediator of biological activities.
Topics: Animals; Antioxidants; Apoptosis; Humans; Inflammation; Oxidation-Reduction; Oxidative Stress; Prostaglandin D2; Proteins; Signal Transduction
PubMed: 26011133
DOI: 10.1080/09168451.2015.1012149