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Advances in Anatomy, Embryology, and... 2015Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following... (Review)
Review
Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the conceptus undergoes an extended phase of mobility. Conceptus mobility is driven by conceptus-derived PGF2α and PGE2 that stimulate uterine contractions which in turn propel migration of the conceptus within the uterine lumen. Cessation of conceptus mobility is referred to as fixation and appears to be attributable to increasing size of the conceptus, preferential thickening of the endometrium near the mesometrial attachment referred to as encroachment, and a reduction in sialic acid content of the capsule. During maternal recognition of pregnancy, endometrial PGF2α release is attenuated, a consequence of reduced expression of key enzymes involved in prostaglandin production. Oxytocin responsiveness is altered during early pregnancy, and reduced expression of the oxytocin receptor appears to be regulated at the posttranscriptional level rather than the transcriptional level. Prostaglandin release is attenuated temporarily only during early pregnancy; during the third week of pregnancy, the endometrium resumes the ability to secrete PGF2α. The equine conceptus initiates steroidogenesis as early as Day 6 and synthesizes estrogens, androgens, and progesterone. Estrogens are metabolized locally, presumably regulating their bioavailability and actions. Results of experiments attempting to prove that conceptus-derived estrogens are responsible for extension of corpus luteum function have been inconclusive. By the fourth week of pregnancy, the chorionic girdle becomes visible on the trophoblast. Subsequent invasion of chorionic girdle cells leads to formation of endometrial cups which secrete equine chorionic gonadotropin. Equine chorionic gonadotropin has luteinizing hormone functions in the mare, causing luteinization of follicles resulting in the formation of secondary corpora lutea essential to production of progesterone and maintenance of pregnancy.
Topics: Animals; Dinoprostone; Embryo Implantation; Endometrium; Female; Horses; Pregnancy; Pregnancy, Animal; Receptors, Estrogen; Receptors, Progesterone
PubMed: 26450499
DOI: 10.1007/978-3-319-15856-3_9 -
Nutrients Oct 2022Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum condition characterized by excessive liver fat accumulation in people who do not abuse alcohol. There is no... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum condition characterized by excessive liver fat accumulation in people who do not abuse alcohol. There is no effective medical treatment for NAFLD; therefore, most important recommendations to reduce liver steatosis are diet and lifestyle, including proper physical activity. The aim of our study was to analyze the fatty acids and eicosanoids changes in the serum of patients who consumed high-fiber rolls for 8 weeks.
MATERIALS AND METHODS
The group of 28 Caucasian participants was randomly divided into two groups, those who received 24 g of fiber/day-from 2 buns of 12 g each (n = 14), and those who received 12 g of fiber/day-from 2 buns of 6 g (n = 14). At the beginning and on the last visit of the 8-week intervention, all patients underwent NAFLD evaluation, biochemical parameter measurements, and fatty acids and eicosanoids evaluation.
RESULTS
Patients who received 12 g of fiber had significantly reduced liver steatosis and body mass index. In the group who received 24 g of fiber/day, we observed a trend to liver steatosis reduction ( = 0.07) and significant decrease in aspartate aminotransferase ( = 0.03) and total cholesterol ( = 0.03). All changes in fatty acid and eicosanoids profile were similar. Fatty acids analysis revealed that extra fiber intake was associated with a significant increase in monounsaturated fatty acids and decrease in saturated fatty acids. Moreover, both groups showed increased concentration of gamma linoleic acid and docosahexaenoic acid. We also observed reduction in prostaglandin E.
CONCLUSIONS
Our study revealed that a high amount of fiber in the diet is associated with a reduction in fatty liver, although this effect was more pronounced in patients in the lower fiber group. However, regardless of the amount of fiber consumed, we observed significant changes in the profile of FAs, which may reflect the positive changes in the lipids liver metabolism. Regardless of the amount of fiber consumed, patients decreased the amount of PGE, which may indicate the lack of disease progression associated with the development of inflammation.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Fatty Acids; Docosahexaenoic Acids; Liver; Diet; Aspartate Aminotransferases; Fatty Acids, Monounsaturated; Dietary Fiber; Eicosanoids; Linoleic Acids; Prostaglandins E; Prostaglandins; Cholesterol
PubMed: 36296994
DOI: 10.3390/nu14204310 -
European Journal of Clinical Nutrition Jun 2023Autoimmune diseases are driven by T17 cells that secrete pro-inflammatory cytokines, especially IL-17. Under normal physiological conditions, autoreactive T cells are... (Review)
Review
Autoimmune diseases are driven by T17 cells that secrete pro-inflammatory cytokines, especially IL-17. Under normal physiological conditions, autoreactive T cells are suppressed by TGF-β and IL-10 secreted by microglia and dendritic cells. When this balance is upset due to injury, infection and other causes, leukocyte recruitment and macrophage activation occurs resulting in secretion of pro-inflammatory IL-6, TNF-α, IL-17 and PGE2, LTs (leukotrienes) accompanied by a deficiency of anti-inflammatory LXA4, resolvins, protecting, and maresins. PGE2 facilitates T1 cell differentiation and promotes immune-mediated inflammation through T17 expansion. There is evidence to suggest that autoimmune diseases can be suppressed by anti-inflammatory bioactive lipids LXA4, resolvins, protecting, and maresins. These results imply that systemic and/or local application of LXA4, resolvins, protecting, and maresins and administration of their precursors AA/EPA/DHA could form a potential therapeutic approach in the prevention and treatment of autoimmune diseases.
Topics: Humans; Interleukin-17; Dinoprostone; Inflammation; Autoimmune Diseases; Cytokines; Anti-Inflammatory Agents; Fatty Acids
PubMed: 35701524
DOI: 10.1038/s41430-022-01173-8 -
FASEB Journal : Official Publication of... Oct 2023Prostaglandin E (PGE ) has been implicated in counteracting fibroblast differentiation by TGFβ1 during pulmonary fibrosis. However, the precise mechanism is not well...
Prostaglandin E (PGE ) has been implicated in counteracting fibroblast differentiation by TGFβ1 during pulmonary fibrosis. However, the precise mechanism is not well understood. We show here that PGE via EP R and EP R inhibits the expression of mechanosensory molecules Lysyl Oxidase Like 2 (LOXL2), myocardin-related transcription factor A (MRTF-A), ECM proteins, plasminogen activation inhibitor 1 (PAI-1), fibronectin (FN), α-smooth muscle actin (α-SMA), and redox sensor (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)) required for TGFβ1-mediated fibroblast differentiation. We further demonstrate that PGE inhibits fibrotic signaling via Yes-associated protein (YAP) but does so independently from its actions on SMAD phosphorylation and conserved cylindromatosis (CYLD; deubiquitinase) expression. Mechanistically, PGE phosphorylates/inactivates YAP downstream of EP R/Gαs and restrains its translocation to the nucleus, thus inhibiting its interaction with TEA domain family members (TEADs) and transcription of fibrotic genes. Importantly, pharmacological or siRNA-mediated inhibition of YAP significantly downregulates TGFβ1-mediated fibrotic gene expression and myofibroblast formation. Notably, YAP expression is upregulated in the lungs of D. farinae-treated wild type (WT) mice relative to saline-treated WT mice. Our results unravel a unique role for PGE -YAP interactions in fibroblast differentiation, and that PGE /YAP inhibition can be used as a novel therapeutic target in the treatment of pathological conditions associated with myofibroblasts like asthma.
Topics: Animals; Mice; YAP-Signaling Proteins; Dinoprostone; Fibroblasts; Signal Transduction; Myofibroblasts
PubMed: 37732601
DOI: 10.1096/fj.202300745RR -
Nature Reviews. Rheumatology Mar 2019
Topics: Bone Density; Bone and Bones; Dinoprostone; Homeostasis
PubMed: 30728449
DOI: 10.1038/s41584-019-0181-2 -
Mediators of Inflammation 2015COX-2/mPGES-1/PGE2 cascade plays critical roles in modulating many physiological and pathological actions in different organs. In the kidney, this cascade is of high... (Review)
Review
COX-2/mPGES-1/PGE2 cascade plays critical roles in modulating many physiological and pathological actions in different organs. In the kidney, this cascade is of high importance in regulating fluid metabolism, blood pressure, and renal hemodynamics. Under some disease conditions, this cascade displays various actions in response to the different pathological insults. In the present review, the roles of this cascade in the pathogenesis of kidney injuries including diabetic and nondiabetic kidney diseases and acute kidney injuries were introduced and discussed. The new insights from this review not only increase the understanding of the pathological role of the COX-2/mPGES-1/PGE2 pathway in kidney injuries, but also shed new light on the innovation of the strategies for the treatment of kidney diseases.
Topics: Animals; Cyclooxygenase 2; Dinoprostone; Humans; Intramolecular Oxidoreductases; Kidney; Prostaglandin-E Synthases
PubMed: 25729216
DOI: 10.1155/2015/147894 -
ELife Jan 2023In organ regeneration, progenitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival,...
In organ regeneration, progenitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation, and differentiation. However, the types of cells that form the native microenvironment for renal progenitor cells (RPCs) have not been clarified. Here, single-cell sequencing of zebrafish kidney reveals as a principal marker of renal interstitial cells (RICs), which can be specifically labeled by GFP under the control of promoter in the transgenic zebrafish. During nephron regeneration, the formation of nephrons is supported by RICs that form a network to wrap the RPC aggregates. RICs that are in close contact with RPC aggregates express cyclooxygenase 2 (Cox2) and secrete prostaglandin E2 (PGE2). Inhibiting PGE2 production prevents nephrogenesis by reducing the proliferation of RPCs. PGE2 cooperates with Wnt4a to promote nephron maturation by regulating β-catenin stability of RPC aggregates. Overall, these findings indicate that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.
Topics: Animals; Dinoprostone; Zebrafish; Nephrons; Kidney; Animals, Genetically Modified
PubMed: 36645741
DOI: 10.7554/eLife.81438 -
International Journal of Biological... 2023Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which... (Review)
Review
Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from expression and activation is Prostaglandin E (PGE), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the -PGE signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.
Topics: Humans; Dinoprostone; Cyclooxygenase 2; Diabetes Mellitus, Type 1; Signal Transduction; Inflammation
PubMed: 37705740
DOI: 10.7150/ijbs.86492 -
American Journal of Respiratory and... Jul 2022
Topics: Alprostadil; Double-Blind Method; Extracorporeal Membrane Oxygenation; Humans; Pilot Projects; Vasodilator Agents
PubMed: 35579662
DOI: 10.1164/rccm.202204-0669ED -
Stem Cell Research & Therapy Jul 2023Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in...
BACKGROUND
Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs.
METHODS
Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems.
RESULTS
sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs.
CONCLUSIONS
We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.
Topics: Humans; Immunity, Innate; Dinoprostone; Interleukin-13; Leukocytes, Mononuclear; Lymphocytes; Extracellular Vesicles; Rhinitis, Allergic; Inflammation; Dendritic Cells
PubMed: 37488601
DOI: 10.1186/s13287-023-03408-2