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Cell Reports Jun 2022Prostaglandin E (PGE) promotes tumor cell proliferation, migration, and invasion, fostering an inflammation-enriched microenvironment that facilitates angiogenesis and...
Prostaglandin E (PGE) promotes tumor cell proliferation, migration, and invasion, fostering an inflammation-enriched microenvironment that facilitates angiogenesis and immune evasion. However, the PGE receptor subtype (EP1-EP4) involved in neuroblastoma (NB) growth remains elusive. Herein, we show that the EP2 receptor highly correlates with NB aggressiveness and acts as a predominant Gα-coupled receptor mediating PGE-initiated cyclic AMP (cAMP) signaling in NB cells with high-risk factors, including 11q deletion and MYCN amplification. Knockout of EP2 in NB cells blocks the development of xenografts, and its conditional knockdown prevents established tumors from progressing. Pharmacological inhibition of EP2 by our recently developed antagonist TG6-129 suppresses the growth of NB xenografts in nude mice and syngeneic allografts in immunocompetent hosts, accompanied by anti-inflammatory, antiangiogenic, and apoptotic effects. This proof-of-concept study suggests that the PGE/EP2 signaling pathway contributes to NB malignancy and that EP2 inhibition by our drug-like compounds provides a promising strategy to treat this deadly pediatric cancer.
Topics: Animals; Dinoprostone; Humans; Mice; Mice, Knockout; Mice, Nude; Neuroblastoma; Receptors, Prostaglandin E, EP2 Subtype; Tumor Microenvironment
PubMed: 35732130
DOI: 10.1016/j.celrep.2022.111000 -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2019Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological... (Review)
Review
Prostaglandin E2 (PGE2) is a cyclooxygenase metabolite of arachidonic acid. It acts as a bioactive lipid and plays an important role in regulating many biological processes. PGE2 binds to 4 different G protein-coupled receptors including prostaglandin E2 receptor subtypes EP1, EP2, EP3 and EP4. The EP4 receptor is widely expressed in most of human organs and tissues. Increasing evidence demonstrates that EP4 is essential for cardiovascular homeostasis and participates in the pathogenesis of many cardiovascular diseases. Here we summarize the role of EP4 in the regulation of cardiovascular function and discuss potential mechanisms by which EP4 is involved in the development of cardiovascular disorders with a focus on its effect on inflammation.
Topics: Cardiovascular Diseases; Cyclooxygenase 2; Dinoprostone; Humans; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 31008497
DOI: No ID Found -
Sheng Li Xue Bao : [Acta Physiologica... Apr 2024Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and... (Review)
Review
Chronic liver disease (CLD) is a major global health burden in terms of growing morbidity and mortality. Although many conditions can cause CLD, leading to cirrhosis and hepatocellular carcinoma (HCC), viral hepatitis, drug-induced liver injury (DILI), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the most common culprits. Prostaglandin E (PGE), produced in the liver, is an important lipid mediator derived from the ω-6 polyunsaturated fatty acid, arachidonic acid, and plays a critical role in hepatic homeostasis. The physiological effects of PGE are mediated through four classes of E-type prostaglandin (EP) receptors, namely EP1, EP2, EP3 and EP4. In recent years, an increasing number of studies has been done to clarify the effects of PGE and EP receptors in regulating liver function and the pathogenesis of CLD to create a new potential clinical impact. In this review, we overview the biosynthesis and regulation of PGE and discuss the role of its synthesizing enzymes and receptors in the maintenance of normal liver function and the development and progress of CLD. We also discuss the potential of the PGE-EP receptors system in treating CLD with various etiologies.
Topics: Humans; Dinoprostone; Receptors, Prostaglandin E; Liver Diseases; Chronic Disease; Animals; Liver; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease
PubMed: 38658381
DOI: No ID Found -
Dental Materials Journal May 2021This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine osteoblastic cells cultured on the 4-methacryloxyethyl trimellitate...
This study examined the effects of N-acetylcysteine (NAC) on the inflammatory reactions of murine osteoblastic cells cultured on the 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate (4-META/MMA)-based resin. Superbond C&B (SB) was used as the 4-META/MMA-based resin and placed in a 48-well cell culture plate. The cells were cultured in αMEM (control) as well as on SB and SB in αMEM with NAC (SB+NAC). They were examined using the WST-1 proliferation assay, real-time PCR, enzyme-linked immunosorbent assay (ELISA), intracellular reactive oxygen species (ROS) measurements, and cellular glutathione (GSH) detection. COX-2 and IL-6 gene expressions were upregulated in SB; however, they were suppressed by NAC. Furthermore, PGE production in the culture medium was increased in SB, whereas NAC decreased the PGE production. NAC lowered the ROS level in the culture medium and significantly increased the intracellular GSH level. The present in vitro study demonstrated that NAC might be effective for dental material detoxification.
Topics: Acetylcysteine; Animals; Cells, Cultured; Dinoprostone; Methacrylates; Mice; Reactive Oxygen Species
PubMed: 33642448
DOI: 10.4012/dmj.2020-275 -
Skin Research and Technology : Official... Aug 2023Mesenchymal stem cells (MSCs) can promote burn wound healing, skin appearance, and function recovery by promoting the differentiation and migration of fibroblasts of a...
PURPOSE
Mesenchymal stem cells (MSCs) can promote burn wound healing, skin appearance, and function recovery by promoting the differentiation and migration of fibroblasts of a wound. The burn environment can activate the autophagy of MSCs. However, it is not clear whether this autophagy can affect the proliferation and migration of fibroblasts.
METHODS
In this study, pretreated MSCs with rapamycin and 3-methyladenine modulated autophagy and co-cultured with fibroblasts of burn. Cell migration was detected by immunofluorescence chemical staining. Western blot analysis and enzyme-linked immunosorbent assay were performed to detect 2,3-Dioxygenase (IDO), cytokine synthesis inhibitory factor 10 (IL-10), cytokine synthesis inhibitory factor 6 (IL-6), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-β1) proteins levels, and the autophagy proteins p62 and microtubule-associated protein LC3-II/I.
RESULTS
We demonstrated that autophagy regulates MSCs survival and proliferation in burn wound transplants and found that autophagy inhibition with 3-methyladenine reduced MSCs-mediated, fibroblast proliferation and migration in burn environment. However, rapamycin-induced autophagy had the opposite effect and increased the TGF-β1 expression. Therefore, we speculate that MSCs may promote fibroblast proliferation and migration by secreting TGF-β1 via the AKT/mTOR (RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin) pathway.
CONCLUSION
Autophagy of MSCs regulates burn wound fibroblast proliferation and migration by affecting TGF-β1 and prostaglandin E2 production adjacent to MSCs transplanted on the burn wound. The results of this study provide a potential strategy for promoting MSCs treatment of burns.
Topics: Humans; Interleukin-10; Transforming Growth Factor beta1; Dinoprostone; Burns; Fibroblasts
PubMed: 37632175
DOI: 10.1111/srt.13431 -
Journal of Neuroimmune Pharmacology :... Sep 2023Post-traumatic stress disorder (PTSD) is a chronic incapacitating condition with recurrent experience of trauma-related memories, negative mood, altered cognition, and... (Review)
Review
Post-traumatic stress disorder (PTSD) is a chronic incapacitating condition with recurrent experience of trauma-related memories, negative mood, altered cognition, and hypervigilance. Agglomeration of preclinical and clinical evidence in recent years specified that alterations in neural networks favor certain characteristics of PTSD. Besides the disruption of hypothalamus-pituitary-axis (HPA) axis, intensified immune status with elevated pro-inflammatory cytokines and arachidonic metabolites of COX-2 such as PGE2 creates a putative scenario in worsening the neurobehavioral facet of PTSD. This review aims to link the Diagnostic and Statistical Manual of mental disorders (DSM-V) symptomology to major neural mechanisms that are supposed to underpin the transition from acute stress reactions to the development of PTSD. Also, to demonstrate how these intertwined processes can be applied to probable early intervention strategies followed by a description of the evidence supporting the proposed mechanisms. Hence in this review, several neural network mechanisms were postulated concerning the HPA axis, COX-2, PGE2, NLRP3, and sirtuins to unravel possible complex neuroinflammatory mechanisms that are obscured in PTSD condition.
Topics: Humans; Stress Disorders, Post-Traumatic; Hypothalamo-Hypophyseal System; Cyclooxygenase 2; Dinoprostone; Pituitary-Adrenal System
PubMed: 37097603
DOI: 10.1007/s11481-023-10064-z -
Yakugaku Zasshi : Journal of the... 2021Prostanoids [prostaglandins (PGs) and thromboxanes (TXs)] are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G... (Review)
Review
Prostanoids [prostaglandins (PGs) and thromboxanes (TXs)] are a series of bioactive lipid metabolites that function in an autacoid manner via activation of cognate G protein-coupled receptors (GPCRs). The nine subtypes of prostanoid receptors (DP1, DP2, EP1, EP2, EP3, EP4, FP, IP, TP) are involved in a wide range of functions, including inflammation, immune response, reproduction, and homeostasis of the intestinal mucosa and cardiovascular system. Among the prostanoid receptors, the structure of antagonist-bound DP2, which belongs to the chemoattractant receptor family, was previously determined. However, the mechanisms of prostanoid recognition and receptor activation remained elusive. To address this issue, we determined the crystal structures of antagonist-bound EP4 and PGE-bound EP3. The EP3-PGE complex exhibits an active-like conformation, including outward movement of the cytoplasmic end of transmembrane (TM) 6 relative to the cytoplasmic end of TM6 of the EP4 complex. The carboxyl moiety of PGE is recognized through three hydrogen bonds formed by highly conserved residues: Y114, T206, and R333 (superscripts denote Ballesteros-Weinstein numbering). In addition, the ω-chain of PGE orients toward TM6, which appears to contribute to receptor activation. The structure reveals important insights into the activation mechanism of prostanoid receptors and provides a molecular basis for the binding modes of endogenous ligands. These findings should facilitate the development of subtype-selective and non-PG-like ligands.
Topics: Crystallography, X-Ray; Dinoprostone; Ligands; Molecular Conformation; Protein Binding; Receptors, G-Protein-Coupled; Receptors, Prostaglandin; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 33790113
DOI: 10.1248/yakushi.20-00202 -
Mediators of Inflammation 2021Prostaglandin E2 (PGE) is a lipid mediator derived from the fatty acid arachidonic acid. As an essential inflammatory factor, PGE has a critical impact on immune... (Review)
Review
Prostaglandin E2 (PGE) is a lipid mediator derived from the fatty acid arachidonic acid. As an essential inflammatory factor, PGE has a critical impact on immune regulation through the prostanoid E (EP) receptor pathway. T cells, including CD4 and CD8 T cell subsets, play crucial roles in the adaptive immune response. Previous studies have shown that PGE is involved in regulating CD4 T cell differentiation and inflammatory cytokine production via the EP receptor pathway, thereby affecting the development of diseases mediated by CD4 T cells. In this review, we summarize the signaling pathway of PGE and describe the relationship between PGE and T cell differentiation. Hence, this review may provide important evidence for immune therapies and may even promote the development of biomedicines.
Topics: Cell Differentiation; Dinoprostone; Humans; Receptors, Prostaglandin E; Signal Transduction; T-Lymphocytes
PubMed: 34867083
DOI: 10.1155/2021/9087816 -
Scientific Reports Apr 2021Induction of labour (IOL) is increasingly used in obstetric practice. For patients with unfavourable cervix, we are constantly looking for an optimal, in terms of... (Comparative Study)
Comparative Study Observational Study
Induction of labour (IOL) is increasingly used in obstetric practice. For patients with unfavourable cervix, we are constantly looking for an optimal, in terms of effectiveness and safety, ripening of cervix protocol. It was retrospective cohort study. We analyzed obstetrical results in 481 patients undergoing IOL in one center using two different vaginal inserts that release prostaglandins at a constant rate for 24 h-misoprostol vaginal insert (MVI) with 200 µg of misoprostol (n = 367) and dinoprostone vaginal insert (DVI) with 10 mg of dinoprostone (n = 114). Full-term, single pregnancy patients with intact fetal membranes and the cervix evaluated in Bishop score ≤ 6 were included in the analysis. In the group of MVI patients, the labour ended with caesarean section more often (OR 2.71 95% CI 1.63-4.47) and more frequent unreassuring cardiotocographic trace indicating the surgical delivery occurred (OR 2.38 95% CI 1.10-5.17). We did not notice any differences in the percentage of vacuum extraction and patients in whom the use of oxytocin was necessary during labour induction. The clinical status of newborns after birth and the pH of cord blood did not differ between groups.The use of MVI 200 μg in patients with an unriped cervix is associated with a greater chance of completing delivery by caesarean section and increased chance of abnormal intrapartum CTG trace compared to the use of DVI 10 mg. These differences do not affect the clinical and biochemical status of the newborn.
Topics: Administration, Intravaginal; Adult; Cesarean Section; Dinoprostone; Female; Fetal Blood; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy; Retrospective Studies; Treatment Outcome
PubMed: 33907254
DOI: 10.1038/s41598-021-88723-5 -
Journal of the Formosan Medical... Aug 2023The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between dinoprostone slow-release pessary (Propess) and dinoprostone tablet (Prostin) for labour induction at term in nulliparous women.
METHODS
This was a prospective single-blind randomized controlled trial conducted in a tertiary medical centre in Taiwan from September 1, 2020 to February 28, 2021. We recruited nulliparous women at term with a singleton pregnancy, fetus in cephalic presentation, an unfavourable cervix, and the cervical length had been measured by transvaginal sonography three times during labour induction. The main outcomes are duration from induction of labour to vaginal delivery, vaginal delivery rate, maternal and neonatal complication rates.
RESULTS
In both groups, Prostin and Propess, 30 pregnant women were enrolled. The Propess group had higher vaginal delivery rate but it did not meet statistically significant difference. The Prostin group had significantly higher rate of adding oxytocin for augmentation (p = 0.0002). No significant difference was observed in either labouring course, maternal or neonatal outcomes. The probability of vaginal delivery was independently related to the cervical length measured by transvaginal sonography 8 h after Prostin or Propess administration as well as neonatal birth weight.
CONCLUSION
Both Prostin and Propess can be used as cervical ripening agents with similar efficacy and without significant morbidity. Propess administration was associated with higher vaginal delivery rate and less need to add oxytocin. Intrapartum measurement of cervical length is helpful in predicting successful vaginal delivery.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Dinoprostone; Oxytocics; Oxytocin; Prospective Studies; Single-Blind Method; Labor, Induced
PubMed: 36907791
DOI: 10.1016/j.jfma.2023.02.006