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European Journal of Obstetrics,... Aug 2023A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods... (Review)
Review
Efficacy of pharmacological and mechanical cervical priming methods for induction of labour and their applicability for outpatient management: A systematic review of randomised controlled trials.
BACKGROUND
A systematic review to determine the efficacy and safety of prostaglandins (PG) and Foley catheter (FC) for cervical priming in the outpatient setting. Various methods are available to achieve cervical ripening prior to induction of labour (IOL). In this systematic review, we will report the literature to date, and investigate the efficacy and safety of using the Foley catheter balloon or prostaglandins for cervical ripening, comparing both methods with each other, and discuss the implications of these findings for midwifery led units.
METHODS
English peer-reviewed journals were systematically searched in the databases PubMed, MEDLINE, EMCARE, EMBASE and CINAHL, for studies investigating cervical ripening using the FC or PGs. Additional randomised controlled trials (RCTs) and non-RCTs were identified by a manual search. Search terms included: cervix dilatation effacement, cervix ripening, outpatient, ambulatory care, obstetric patients, pharmacological preparations, and Foley catheter. Only RCTs of FC versus PG or either intervention versus placebo or intervention in the in-patient Vs. outpatient setting were included. 15 RCTs were included.
RESULTS
The results of this review show that both FC and PG analogues are equally effective cervical ripening agents. When compared to FC, PGs lead to a reduced requirement for oxytocin augmentation and a shorter intervention to delivery interval. However, PG use is also associated with an increased risk of hyperstimulation, cardiotocographic monitoring abnormalities and negative neonatal outcomes.
CONCLUSIONS
FC cervical ripening is an effective method of outpatient cervical priming, which is safe, acceptable, and cost-effective and thus has a potential role in both resource-rich and resource-poor countries. With appropriate dosing, some PG analogues also appear to offer similar outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Dinoprostone; Outpatients; Cervix Uteri; Oxytocics; Labor, Induced; Prostaglandins; Abortifacient Agents, Nonsteroidal; Cervical Ripening
PubMed: 37300982
DOI: 10.1016/j.ejogrb.2023.05.037 -
The International Journal of... Oct 2023The aim of this study was to compare radiographic and clinical status and peri-implant sulcular fluid (PISF) prostaglandin E2 (PGE2) levels among patients with and...
The aim of this study was to compare radiographic and clinical status and peri-implant sulcular fluid (PISF) prostaglandin E2 (PGE2) levels among patients with and without peri-implant disease. Patients with peri-implant mucositis (PiM) (Group 1) and peri-implantitis (Group 2) and individuals without peri-implant disease (Group 3) were included. Demographic information was collected, and peri-implant modified plaque and bleeding indices (mPI and mBI), probing depth (PD), and crestal bone loss (CBL) were recorded. PISF samples were collected and PGE2 levels measured. Statistical significance was set at P < .01. A total of 22 patients with PiM, 22 with peri-implantitis, and 23 without peri-implant disease (controls) were included. Scores of mPI (P < .01), mBI (P < .01), and PD (P < .01) were higher in patients with PiM and peri-implantitis than the controls. The volumes of collected PISF were significantly higher in patients with peri-implantitis (P < .01) compared to patients with PiM and the controls. The PISF volume was significantly higher in PiM patients (P < .01) than in the controls. There was a significant correlation between peri-implant PD and PISF PGE2 levels in patients with peri-implantitis (P < .001). Raised PISF PGE2 levels indicate poor peri-implant health; therefore, PGE2 is a potential biomarker for the assessment of peri-implant health status.
Topics: Humans; Peri-Implantitis; Dinoprostone; Dental Implants; Mucositis; Dental Plaque Index
PubMed: 37879049
DOI: 10.11607/prd.6404 -
Sheng Li Xue Bao : [Acta Physiologica... Feb 2024Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the... (Review)
Review
Prostaglandin E (PGE2) is an important lipid molecule derived from arachidonic acid, which regulates a variety of physiological and pathological activities. Based on the inhibition of inflammatory PGE production, non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the most commonly used drugs to treat inflammatory diseases and to relieve fever and pain symptoms. PGE mediates its functions via four different G protein-coupled receptors, named EP1-EP4. Though the limited distribution and low PGE affinity of EP1, it plays important roles in the maintenance of many physiological functions and homeostasis. Moreover, EP1 is widely involved in the inflammatory response, pain perception and multisystem pathological function regulation. In this review, we will briefly summarize the recent advances on the physiological and pathophysiological function of EP1 and its targeted drugs development.
Topics: Humans; Arachidonic Acid; Dinoprostone; Homeostasis; Pain
PubMed: 38444136
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Jan 2024Hyperglycemia-a symptom that characterizes diabetes-is highly associated with atherothrombotic complications. However, the underlying mechanism by which hyperglycemia...
BACKGROUND
Hyperglycemia-a symptom that characterizes diabetes-is highly associated with atherothrombotic complications. However, the underlying mechanism by which hyperglycemia fuels platelet activation and arterial thrombus formation is still not fully understood.
METHODS
The profiles of polyunsaturated fatty acid metabolites in the plasma of patients with diabetes and healthy controls were determined with targeted metabolomics. FeCl-induced carotid injury model was used to assess arterial thrombus formation in mice with endothelial cell (EC)-specific YAP (yes-associated protein) deletion or overexpression. Flow cytometry and clot retraction assay were used to evaluate platelet activation. RNA sequencing and multiple biochemical analyses were conducted to unravel the underlying mechanism.
RESULTS
The plasma PGE (prostaglandin E) concentration was elevated in patients with diabetes with thrombotic complications and positively correlated with platelet activation. The PGE synthetases COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E synthase-1) were found to be highly expressed in ECs but not in other type of vessel cells in arteries from both patients with diabetes and hyperglycemic mice, compared with nondiabetic individuals and control mice, respectively. A combination of RNA sequencing and ingenuity pathway analyses indicated the involvement of YAP signaling. EC-specific deletion of YAP limited platelet activation and arterial thrombosis in hyperglycemic mice, whereas EC-specific overexpression of YAP in mice mimicked the prothrombotic state of diabetes, without affecting hemostasis. Mechanistically, we found that hyperglycemia/high glucose-induced endothelial YAP nuclear translocation and subsequently transcriptional expression of COX-2 and mPGES-1 contributed to the elevation of PGE and platelet activation. Blockade of EP3 (prostaglandin E receptor 3) activation by oral administration of DG-041 reversed the hyperactivity of platelets and delayed thrombus formation in both EC-specific YAP-overexpressing and hyperglycemic mice.
CONCLUSIONS
Collectively, our data suggest that hyperglycemia-induced endothelial YAP activation aggravates platelet activation and arterial thrombus formation via PGE/EP3 signaling. Targeting EP3 with DG-041 might be therapeutic for diabetes-related thrombosis.
Topics: Animals; Humans; Mice; Blood Platelets; Cyclooxygenase 2; Diabetes Mellitus; Dinoprostone; Hyperglycemia; Mice, Obese; Thrombosis
PubMed: 37916416
DOI: 10.1161/ATVBAHA.123.319835 -
Scientific Reports Nov 2023Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer...
Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 μM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-β, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Curcumin; Cyclooxygenase 2; Dinoprostone; Fibroblasts; Inflammation; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38008819
DOI: 10.1038/s41598-023-48073-w -
Journal of Molecular Medicine (Berlin,... Sep 2023Hirschsprung disease (HSCR) is a congenital disorder caused by the failure of enteric neural crest cells (ENCCs) to colonize the distal bowel, resulting in absence of...
Hirschsprung disease (HSCR) is a congenital disorder caused by the failure of enteric neural crest cells (ENCCs) to colonize the distal bowel, resulting in absence of enteric nervous system. While a range of molecules and signaling pathways have been found to contribute to HSCR development, the risk factors and pathogenesis of this disease in many patients remain unknown. We previously demonstrated that increased activity of the prostaglandin E2 (PGE2)/PGE2 receptor subtype EP2 pathway can be a risk factor for HSCR. In this study, an Ednrb-deficient mouse model of HSCR was generated and used to investigate if PGE2/EP2 pathway could be a potential therapeutic target for HSCR. We found that downregulation of PGE2/EP2 signaling by siRNA-mediated ablation of a PGE2 synthase or pharmacologic blockage of EP2 enhanced ENCC colonization in the distal bowel of Ednrb mice and alleviated their HSCR-like symptoms. Furthermore, blockage of EP2 was shown to promote ENCC migration through upregulating p38 mitogen-activated protein kinase activity, which was downregulated in the colon of Ednrb mice and in the distal aganglionic bowel of HSCR patients. These data provide evidence that maternal exposure during embryonic development to an environment with dysregulated activation of the PGE2/EP2 pathway may predispose genetically susceptible offspring to HSCR, and avoidance or early disruption of maternal events (e.g. inflammation) that possibly enhance PGE2/EP2 signaling during pregnancy would reduce the occurrence and severity of this disease. KEY MESSAGES : Knockdown of PTGES alleviates HSCR severity in Ednrb mice. Blockage of EP2-mediated PGE2 signaling alleviates HSCR severity in Ednrb mice. Blockage of EP2-mediated PGE2 signaling promotes ENCC migration via enhancing p38 activity.
Topics: Female; Mice; Animals; Hirschsprung Disease; Dinoprostone; p38 Mitogen-Activated Protein Kinases; Enteric Nervous System
PubMed: 37522903
DOI: 10.1007/s00109-023-02353-0 -
Annals of Biomedical Engineering Dec 2023Low-level Laser Therapy (LLLT) was widely used in clinical practice for tendon disorders. However, the underlying mechanisms and effectiveness of LLLT in treating tendon... (Review)
Review
Low-level Laser Therapy (LLLT) was widely used in clinical practice for tendon disorders. However, the underlying mechanisms and effectiveness of LLLT in treating tendon injury remain unclear. Therefore, the present study was conducted aiming to summarize the evidence regarding the histological, physiological, and biomechanical effects of LLLT on tendon healing in animal and human models. Four databases were searched for relevant literature. Four independent reviewers screened abstracts and full-text articles, extracted relevant data, evaluated the risk of bias, and quantified the quality of evidence. Database searches yielded 1400 non-duplicated citations. Fifty-five studies were included (50 animal and five human studies). Animal studies revealed that LT had stimulating effects on collagen organization, collagen I and collagen II formation, matrix metalloproteinase (MMP)-8, transforming growth factor β1, vascular endothelial growth factor, hydroxyproline, maximum load, maximum elongation before breaking, and tendon stiffness. However, LLLT had inhibitory effects on the number of inflammatory cells, histological scores, relative amount of collagen III, cyclooxygenase-2, prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α, MMP-1, and MMP-3. Although one human study found that LLLT reduced the concentration of PGE2 in peritendinous tissue of the Achilles tendon, other human studies revealed that the effects of LLLT on the physiology and biomechanics of human tendons remained uncertain. LLLT facilitates tendon healing through various histological, physiological, and biomechanical effects in animal models. Only post-LLLT anti-inflammatory effects were found in human studies.
Topics: Humans; Rats; Animals; Low-Level Light Therapy; Rats, Wistar; Tendinopathy; Dinoprostone; Vascular Endothelial Growth Factor A; Collagen; Achilles Tendon
PubMed: 37899380
DOI: 10.1007/s10439-023-03364-1 -
EBioMedicine Nov 2023Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is characterized by predominant pro-tumor Th2-type inflammation. T follicular helper (Tfh) cells...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and it is characterized by predominant pro-tumor Th2-type inflammation. T follicular helper (Tfh) cells are relevant immunoregulators in cancer, and often correlate with better survival. How the Th2-skewed microenvironment in PDAC modulates the differentiation of Tfh cells and their immunoregulatory function is unknown.
METHODS
We carried out high-dimensional flow cytometry and T-cell receptor- and RNA-sequencing, as well as bioinformatics, immunohistochemistry and in vitro mechanistic studies.
FINDINGS
We identified Tfh1-, Tfh2-, and Tfh17-like cell clusters in the blood, tumors and tumor-draining lymph-nodes (TDLNs) of chemo-naïve PDAC patients and showed that high percentages of Tfh2 cells within the tumor tissue and TDLNs correlated with reduced patient survival. Moreover, only Tfh2 cells were highly activated and were reduced in frequency in patients who responded to neoadjuvant chemotherapy. RNA-sequencing analysis of immunoglobulin expression showed that tumor and TDLN samples expressed all immunoglobulin (IGH) isotypes apart from IGHE. Consistent with these findings, Tfh2 cells differentiated in vitro by tumor microenvironment-conditioned dendritic cells promoted the production of anti-inflammatory IgG4 antibodies by co-cultured B cells, dependent on IL-13. Moreover, unexpectedly, Tfh2 cells inhibited the secretion of pro-inflammatory IgE, dependent on prostaglandin E.
INTERPRETATION
Our results indicate that in PDAC, highly activated pro-tumor Tfh2 favor anti-inflammatory IgG4 production, while inhibit pro-inflammatory IgE. Thus, targeting the circuits that drive Tfh2 cells, in combination with chemotherapy, may re-establish beneficial anti-tumor Tfh-B cell interactions and facilitate more effective treatment.
FUNDING
Research grants from the Italian Association for Cancer Research (AIRC) IG-19119 to MPP and the AIRC Special Program in Metastatic disease: the key unmet need in oncology, 5 per Mille no. 22737 to CB, MF, CD, MR and MPP; the ERA-NET EuroNanoMed III (a collaborative european grant financed by the Italian Ministry of Health, Italy) project PANIPAC (JTC2018/041) to MPP; the Fondazione Valsecchi to SC.
Topics: Humans; Immunoglobulin G; Dinoprostone; Pancreatic Neoplasms; Immunoglobulin E; Anti-Inflammatory Agents; RNA; Tumor Microenvironment
PubMed: 37776595
DOI: 10.1016/j.ebiom.2023.104819 -
British Journal of Cancer Mar 2024Many urothelial bladder carcinoma (UBC) patients don't respond to immune checkpoint blockade (ICB) therapy, possibly due to tumor-associated neutrophils (TANs)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many urothelial bladder carcinoma (UBC) patients don't respond to immune checkpoint blockade (ICB) therapy, possibly due to tumor-associated neutrophils (TANs) suppressing lymphocyte immune response.
METHODS
We conducted a meta-analysis on the predictive value of neutrophil-lymphocyte ratio (NLR) in ICB response and investigated TANs' role in UBC. We used RNA-sequencing, HALO spatial analysis, single-cell RNA-sequencing, and flow cytometry to study the impacts of TANs and prostaglandin E2 (PGE2) on IDO1 expression. Animal experiments evaluated celecoxib's efficacy in targeting PGE2 synthesis.
RESULTS
Our analysis showed that higher TAN infiltration predicted worse outcomes in UBC patients receiving ICB therapy. Our research revealed that TANs promote IDO1 expression in cancer cells, resulting in immunosuppression. We also found that PGE2 synthesized by COX-2 in neutrophils played a key role in upregulating IDO1 in cancer cells. Animal experiments showed that targeting PGE2 synthesis in neutrophils with celecoxib enhanced the efficacy of ICB treatment.
CONCLUSIONS
TAN-secreted PGE2 upregulates IDO1, dampening T cell function in UBC. Celecoxib targeting of PGE2 synthesis represents a promising approach to enhance ICB efficacy in UBC.
Topics: Animals; Humans; Dinoprostone; Celecoxib; Neutrophils; Cyclooxygenase 2; Urinary Bladder; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; CD8-Positive T-Lymphocytes; RNA
PubMed: 38233491
DOI: 10.1038/s41416-023-02552-z -
The Journal of Allergy and Clinical... Sep 2023Aspirin-exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and respiratory reactions to COX-1 inhibitors. Overproduction of cysteinyl...
BACKGROUND
Aspirin-exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and respiratory reactions to COX-1 inhibitors. Overproduction of cysteinyl leukotrienes and underproduction of prostaglandin E (PGE) are hallmarks of AERD. A mouse model predicted a key role for the thromboxane-prostanoid (TP) receptor in AERD.
OBJECTIVE
Our aim was to determine whether ifetroban, a TP receptor antagonist, attenuates aspirin-induced respiratory symptoms in patients with AERD.
METHODS
A total of 35 patients with AERD completed a 4-week double-blinded, placebo-controlled trial of ifetroban and underwent an oral aspirin challenge. The primary outcome was change in the provocative dose of aspirin that caused a 2-point increase in Total Nasal Symptom Score. Changes in lung function, eicosanoid levels, and platelet and mast cell activation were assessed. Cultured human nasal fibroblasts were stimulated with or without the TP agonist U46619 and assayed for prostanoid production.
RESULTS
Ifetroban was well tolerated in AERD and did not change the mean 2-point increase in Total Nasal Symptom Score (P = .763). Participants taking ifetroban had greater aspirin-induced nasal symptoms and a greater decline in FEV value than did participants receiving placebo (-18.8% ± 3.6% with ifetroban vs -8.4% ± 2.1% with placebo [P = .017]). Four weeks of ifetroban significantly increased urinary leukotriene E levels and decreased nasal PGE levels compared with placebo. Peak aspirin-induced urinary thromboxane levels correlated with peak urinary leukotriene E and prostaglandin D metabolite levels in participants taking ifetroban. U46119 significantly potentiated the production of PGE by cultured nasal fibroblasts from subjects with AERD but not by cultured nasal fibroblasts from controls without polypoid sinusitis.
CONCLUSION
Contrary to our hypothesis, TP receptor blockade worsened aspirin-induced reactions in AERD, possibly by exacerbating dysregulation of the eicosanoid system. TP signaling on stromal cells may be critical to maintaining PGE production when COX-2 function is low.
Topics: Animals; Mice; Humans; Prostaglandins; Thromboxanes; Leukotriene E4; Receptors, Thromboxane; Asthma, Aspirin-Induced; Aspirin; Eicosanoids; Dinoprostone; Homeostasis; Sinusitis
PubMed: 37068712
DOI: 10.1016/j.jaci.2023.03.030