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Journal of Obstetrics and Gynaecology :... Feb 2022We compared two combined methods for cervical ripening before induction of labour (IOL) Women (n = 150) were randomised into Foley's-misoprostol (n = 75) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of intracervical Foley catheter combined with a single dose of vaginal misoprostol tablet or intracervical dinoprostone gel for cervical ripening: a randomised study.
We compared two combined methods for cervical ripening before induction of labour (IOL) Women (n = 150) were randomised into Foley's-misoprostol (n = 75) and Foley's-dinoprostone (n = 75) groups. A single dose of vaginal misoprostol tablet (25 µg) or intracervical dinoprostone gel (0.5 mg) were used alongwith intracervical Foley's. The primary outcome was induction-delivery interval (IDI) and secondary outcomes were change in Bishop's score, oxytocin requirement, caesarean section (CS) rate, chorioamnionitis and neonatal outcome. The mean parity, gestation and indications for IOL were similar in the two groups. The IDI (19 h 37 min and 19 h 20 min; = .683), cervical ripening time, oxytocin requirement, CS rate (18.7 and 25.4%, = .322) and neonatal outcome were similar. Hyperstimulation developed in 2.7% women with Foley's-misoprostol and in 1.3% with Foley's-dinoprostone ( = .55). No woman had chorioamnionitis. Thus, these two combined methods of cervical ripening and IOL were observed to be similarly efficacious. A low incidence of hyperstimulation and no chorioamnionitis may be attributed to using a single dose of prostaglandins. Misoprostol may be substituted for dinoprostone in resource limited countries.Impact statement Combined methods for cervical ripening (intracervical Foley's plus prostaglandins) before induction of labour (IOL) may be similarly or more efficacious than individual methods. Most studies comparing various combined methods have used repeated doses of prostaglandins. A combined method using repetitive doses of prostaglandins may increase the risk of hyperstimulation and also of infection consequent to repeated vaginal examination to administer prostaglandins. These two concerns may be offset by combining a single dose of prostaglandin with intracervical Foley's catheter. Two combined methods for cervical ripening using a single dose of vaginal misoprostol (25 µg) or intracervical dinoprostone gel (0.5 mg) co-administered with intracervical Foley's catheter were found to be similarly efficacious. The IDI (19 h 37 min and 19 h 20 min; = .683), cervical ripening time, oxytocin requirement, CS rate (18.7 and 25.4%, = .322) and neonatal outcome were similar. The incidence of hyperstimulation was low (2.7 and 1.3% with Foley's-misoprostol and Foley's-dinoprostone, respectively) and no woman had chorioamnionitis. Combined methods for cervical ripening using a single dose of prostaglandins (misoprostol or dinoprostone) were observed to be similarly efficacious. Misoprostol is a cheaper alternative to dinoprostone and may be utilised in resource limited countries. These methods may be compared with each other in more number of women in order to identify which combined method is more efficient and safe. CTRI/2017/12/010738.
Topics: Administration, Intravaginal; Catheters; Cervical Ripening; Cesarean Section; Dinoprostone; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Oxytocics; Pregnancy; Tablets
PubMed: 34027782
DOI: 10.1080/01443615.2021.1904227 -
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 -
Biochemical Pharmacology Feb 2021Overactive bladder (OAB) syndrome is a prevalent condition of the lower urinary tract that causes symptoms, such as urinary frequency, urinary urgency, urge... (Review)
Review
Overactive bladder (OAB) syndrome is a prevalent condition of the lower urinary tract that causes symptoms, such as urinary frequency, urinary urgency, urge incontinence, and nocturia, and disproportionately affects women and the elderly. Current medications for OAB merely provide symptomatic relief with considerable limitations, as they are no more than moderately effective, not to mention that they may cause substantial adverse effects. Identifying novel molecular targets to facilitate the development of new medical therapies with higher efficacy and safety for OAB is in an urgent unmet need. Although the molecular mechanisms underlying the pathophysiology of OAB largely remain elusive and are likely multifactorial, mounting evidence from preclinical studies over the past decade reveals that the pro-inflammatory pathways engaging cyclooxygenases and their prostanoid products, particularly the prostaglandin E2 (PGE), may play essential roles in the progression of OAB. The goals of this review are to summarize recent progresses in our knowledge on the pathogenic roles of PGE in the OAB and to provide new mechanistic insights into the signaling pathways transduced by its four G-protein-coupled receptors (GPCRs), i.e., EP1-EP4, in the overactive detrusor smooth muscle. We also discuss the feasibility of targeting these GPCRs as an emerging strategy to treat OAB with better therapeutic specificity than the current medications.
Topics: Animals; Dinoprostone; Humans; Prostaglandin-Endoperoxide Synthases; Receptors, Prostaglandin E; Urinary Bladder; Urinary Bladder, Overactive
PubMed: 33309520
DOI: 10.1016/j.bcp.2020.114363 -
Frontiers in Immunology 2023For many years, surgery, adjuvant and combination chemotherapy have been the cornerstone of pancreatic cancer treatment. Although these approaches have improved patient...
INTRODUCTION
For many years, surgery, adjuvant and combination chemotherapy have been the cornerstone of pancreatic cancer treatment. Although these approaches have improved patient survival, relapse remains a common occurrence, necessitating the exploration of novel therapeutic strategies. CAR T cell therapies are now showing tremendous success in hematological cancers. However, the clinical efficacy of CAR T cells in solid tumors remained low, notably due to presence of an immunosuppressive tumor microenvironment (TME). Prostaglandin E2, a bioactive lipid metabolite found within the TME, plays a significant role in promoting cancer progression by increasing tumor proliferation, improving angiogenesis, and impairing immune cell's function. Despite the well-established impact of PGE2 signaling on cancer, its specific effects on CAR T cell therapy remain under investigation.
METHODS
To address this gap in knowledge the role of PGE2-related genes in cancer tissue and T cells of pancreatic cancer patients were evaluated . Through our study, we manufactured fully human functional mesoCAR T cells specific for pancreatic cancer and investigated the influence of PGE2-EP2/EP4 signaling on proliferation, cytotoxicity, and cytokine production of mesoCAR T cells against pancreatic cancer cells.
RESULTS
investigations uncovered a significant negative correlation between PGE2 expression and gene signature of memory T cells. Furthermore, experiments demonstrated that the activation of PGE2 signaling through EP2 and EP4 receptors suppressed the proliferation and major antitumor functions of mesoCAR T cells. Interestingly, the dual blockade of EP2 and EP4 receptors effectively reversed PGE2-mediated suppression of mesoCAR T cells, while individual receptor antagonists failed to mitigate the PGE2-induced suppression.
DISCUSSION
In summary, our findings suggest that mitigating PGE2-EP2/EP4 signaling may be a viable strategy for enhancing CAR T cell activity within the challenging TME, thereby improving the efficacy of CAR T cell therapy in clinical settings.
Topics: Humans; Dinoprostone; Receptors, Prostaglandin E, EP2 Subtype; Neoplasm Recurrence, Local; Receptors, Prostaglandin E, EP4 Subtype; Pancreatic Neoplasms; Immunosuppression Therapy; Tumor Microenvironment
PubMed: 37457723
DOI: 10.3389/fimmu.2023.1209572 -
Medical Science Monitor : International... Nov 2019BACKGROUND Dinoprostone is the recommended primary option for induction of labor (IOL) in late-term pregnancies (LTPs). However, oxytocin is used in developing and rural...
Comparison of Dinoprostone and Oxytocin for the Induction of Labor in Late-Term Pregnancy and the Rate of Cesarean Section: A Retrospective Study in Ten Centers in South China.
BACKGROUND Dinoprostone is the recommended primary option for induction of labor (IOL) in late-term pregnancies (LTPs). However, oxytocin is used in developing and rural areas, and studies have supported similar effectiveness for oxytocin and dinoprostone in reducing the rate of cesarean delivery of LTPs with a Bishop's score of between 4-6. This study aimed to compare dinoprostone and oxytocin for IOL in LTPs and the rate of cesarean section in ten centers in South China. MATERIAL AND METHODS A retrospective study included 1,408 women with LTP, with subgroups including a Bishop's score of 0-3 and 4-6. Rates of cesarean delivery were compared between women given vaginal dinoprostone and intravenous oxytocin for IOL. Secondary outcomes included the duration of labor, and maternal and fetal complications. RESULTS Comparison between women who received oxytocin (N=365) and dinoprostone (N=1,043) showed significantly lower rates of cesarean delivery with dinoprostone, but no significant difference between the subgroups with Bishop's scores of 0-3 and 4-6. The interval between induction to labor and duration of the active phase of labor were significantly reduced in the dinoprostone group with a Bishop's score of between 4-6. CONCLUSIONS For LTPs with a Bishop's score of 0-3, dinoprostone was superior to oxytocin for IOL with a lower rate of cesarean delivery, but both agents had a similar outcome for women with a Bishop's score of 4-6. These findings may have implications for the choice of agent used in IOL when dinoprostone is unavailable.
Topics: Adult; Cesarean Section; China; Dinoprostone; Female; Humans; Labor, Induced; Labor, Obstetric; Oxytocics; Oxytocin; Pregnancy; Pregnancy Trimester, Third; Retrospective Studies; Young Adult
PubMed: 31719513
DOI: 10.12659/MSM.918330 -
Free Radical Biology & Medicine Nov 2022Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in...
Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in the acute phase of SCI remains elusive. Here we quantified AA metabolomics by High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Method (LC-MS/MS) using spinal cord tissue collected at 4 h, 24 h and 48 h after contusive SCI in rats. Remarkably, Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) were significantly increased throughout the acute SCI. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the key enzymes involved in the production of PGE2 and LTB4, were elevated in the lesioned spinal cord tissue, validated by both western blot and immunofluorecnce. The spatial-temporal changes of COX-2 and 5-LOX mainly occurs in neurons both in epicenter and rostral and caudal spinal cord segments after SCI. Our study sheds light on the dynamic microenvironment changes in acute SCI by characterizing the profile of AA metabolism. The COX-2 and 5-LOX may be promising therapeutic target for SCI.
Topics: Rats; Animals; Cyclooxygenase 2; Chromatography, Liquid; Arachidonic Acid; Leukotriene B4; Dinoprostone; Tandem Mass Spectrometry; Up-Regulation; Metabolomics; Spinal Cord Injuries
PubMed: 36272669
DOI: 10.1016/j.freeradbiomed.2022.10.303 -
BJOG : An International Journal of... Jul 2022Increasingly, births around the world are started artificially using medications or other methods. This process is known as induction of labour. As it becomes more... (Review)
Review
Increasingly, births around the world are started artificially using medications or other methods. This process is known as induction of labour. As it becomes more common, methods are needed to meet the different clinical needs and birth preferences of women. Induction of labour typically includes a combination of the medication dinoprostone inserted into the vagina, artificial rupture of membranes ('releasing the waters'), and synthetic oxytocin (hormone given via a drip). This paper reviews some of the methods less commonly used for induction in the UK, namely a drug called misoprostol, which can be given orally or vaginally, and 'mechanical' methods, where labour is started by stretching the cervix (neck of the womb), most commonly with a soft silicone tube with a balloon near the tip, filled with water. Low-dose oral misoprostol tablets are now commercially available in the UK. Other methods for labour induction are not reviewed in detail in this paper. The evidence suggests mechanical induction of labour (using a balloon catheter) and misoprostol are both at least as safe and effective as using the standard drug, dinoprostone. There is evidence to suggest a balloon catheter may reduce the chance of serious negative outcomes for babies when compared with dinoprostone, and that giving low-dose oral misoprostol results in fewer caesarean births. Where possible and after informed consent, the method of induction of labour should be personalised to suit the individual woman, her clinical condition, and the setting in which she is giving birth. Local contexts and resources also need to be taken into account. To date, research into women's perspectives and experiences of induction of labour have been significantly lacking.
Topics: Administration, Intravaginal; Dinoprostone; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy
PubMed: 35478481
DOI: 10.1111/1471-0528.17136 -
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 -
Phytomedicine : International Journal... Dec 2023Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore,...
BACKGROUND
Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis.
PURPOSE
The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway.
STUDY DESIGN
The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O.
METHOD
In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun.
RESULTS
The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner (p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT (p < 0.05).
CONCLUSION
Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
Topics: Animals; Mice; Carcinoma, Hepatocellular; Dinoprostone; Liver Neoplasms; Cyclooxygenase 2; Esters; Ginsenosides; Cell Line, Tumor
PubMed: 37806155
DOI: 10.1016/j.phymed.2023.155131 -
Journal of Advanced Research Apr 2024Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone...
INTRODUCTION
Rheumatoid arthritis (RA) is a systemic autoimmune disease with limited treatment success, characterized by chronic inflammation and progressive cartilage and bone destruction. Accumulating evidence has shown that neutrophil extracellular traps (NETs) released by activated neutrophils are important for initiating and perpetuating synovial inflammation and thereby could be a promising therapeutic target for RA. K/B × N serum transfer-induced arthritis (STIA) is a rapidly developed joint inflammatory model that somehow mimics the inflammatory response in patients with RA. Human gingival-derived mesenchymal stem cells (GMSCs) have been previously shown to possess immunosuppressive effects in arthritis and humanized animal models. However, it is unknown whether GMSCs can manage neutrophils in autoimmune arthritis.
OBJECTIVES
To evaluate whether infusion of GMSCs can alleviate RA by regulating neutrophils and NETs formation. If this is so, we will explore the underlying mechanism(s) in an animal model of inflammatory arthritis.
METHODS
The effects of GMSCs on RA were assessed by comparing the symptoms of the K/B × N serum transfer-induced arthritis (STIA) model administered either with GMSCs or with control cells. Phenotypes examined included clinical scores, rear ankle thickness, paw swelling, inflammation, synovial cell proliferation, and immune cell frequency. The regulation of GMSCs on NETs was examined through immunofluorescence and immunoblotting in GMSCs-infused STIA mice and in an in vitro co-culture system of neutrophils with GMSCs. The molecular mechanism(s) by which GMSCs regulate NETs was explored both in vitro and in vivo by silencing experiments.
RESULTS
We found in this study that adoptive transfer of GMSCs into STIA mice significantly ameliorated experimental arthritis and reduced neutrophil infiltration and NET formation. In vitro studies also showed that GMSCs inhibited the generation of NETs in neutrophils. Subsequent investigations revealed that GMSCs secreted prostaglandin E2 (PGE2) to activate protein kinase A (PKA), which ultimately inhibited the downstream extracellular signal-regulated kinase (ERK) pathway that is essential for NET formation.
CONCLUSION
Our results demonstrate that infusion of GMSCs can ameliorate inflammatory arthritis mainly by suppressing NET formation via the PGE2-PKA-ERK signaling pathway. These findings further support the notion that the manipulation of GMSCs is a promising stem cell-based therapy for patients with RA and other autoimmune and inflammatory diseases.
Topics: Humans; Animals; Mice; Extracellular Traps; Dinoprostone; Extracellular Signal-Regulated MAP Kinases; Cyclic AMP-Dependent Protein Kinases; Arthritis, Rheumatoid; Inflammation
PubMed: 37169220
DOI: 10.1016/j.jare.2023.05.001