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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 -
Biomolecules Sep 2023Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid...
Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid mediators is reported in the disease with a predominance of the inflammatory cascade derived from n-6 polyunsaturated fatty acids (n-6 PUFAs). Bioactive lipid mediators derived from arachidonic acid (AA) are involved in the inflammatory functions of T cells in psoriasis, whereas n-3 PUFAs' derivatives are anti-inflammatory metabolites. Here, we sought to evaluate the influence of a supplementation of the culture media with eicosapentaenoic acid (EPA) on the lipid profile of a psoriatic skin model produced with polarized T cells. Healthy and psoriatic skin substitutes were produced following the auto-assembly technique. Psoriatic skin substitutes produced with or without T cells presented increased epidermal and dermal linolenic acid (LA) and AA levels. N-6 PUFA lipid mediators were strongly measured in psoriatic substitutes, namely, 13-hydroxyoctadecadienoic acid (13-HODE), prostaglandin E (PGE) and 12-hydroxyeicosatetraenoic acid (12-HETE). The added EPA elevated the amounts of EPA, n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in the epidermal and dermal phospholipids. The EPA supplementation balanced the production of epidermal lipid mediators, with an increase in prostaglandin E (PGE), 12-hydroxyeicosapentaenoic acid (12-HEPE) and -eicosapentaenoyl-ethanolamine (EPEA) levels. These findings show that EPA modulates the lipid composition of psoriatic skin substitutes by encouraging the return to a cutaneous homeostatic state.
Topics: Humans; Eicosapentaenoic Acid; T-Lymphocytes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Eicosanoids; Arachidonic Acid; Skin Diseases; Psoriasis; Dinoprostone
PubMed: 37759812
DOI: 10.3390/biom13091413 -
American Journal of Perinatology May 2024This study aimed to conduct a systematic review and meta-analysis of all randomized and nonrandomized controlled trials (RCTs and NCTs, respectively) that explored... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to conduct a systematic review and meta-analysis of all randomized and nonrandomized controlled trials (RCTs and NCTs, respectively) that explored the maternal-neonatal outcomes of cervical osmotic dilators versus dinoprostone in promoting cervical ripening during labor induction.
STUDY DESIGN
Six major databases were screened until August 27, 2022. The quality of included studies was evaluated. The data were summarized as mean difference or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model.
RESULTS
Overall, 14 studies with 15 arms were analyzed ( = 2,380 patients). Ten and four studies were RCTs and NCTs, respectively. The overall quality for RCTs varied (low risk = 2, unclear risk = 7, and high risk = 1), whereas all NCTs had good quality ( = 4). For the primary endpoints, there was no significant difference between both groups regarding the rate of normal vaginal delivery (RR = 1.04, 95% CI: 0.95-1.14, = 0.41) and rate of cesarean delivery (RR = 1.04, 95% CI: 0.93-1.17, = 0.51). Additionally, there was no significant difference between both groups regarding the mean change in Bishop score and mean time from intervention to delivery. The rate of uterine hyperstimulation was significantly lower in the cervical osmotic dilator group. For the neonatal outcomes, during cervical ripening, the rate of fetal distress was significantly lower in the cervical osmotic dilator group. There was no significant difference between both groups regarding the mean Apgar scores, rate of meconium-stained amniotic fluid, rate of umbilical cord metabolic acidosis, rate of neonatal infection, and rate of neonatal intensive care unit admission.
CONCLUSION
During labor induction, cervical ripening with cervical osmotic dilators and dinoprostone had comparable maternal-neonatal outcomes. Cervical osmotic dilators had low risk of uterine hyperstimulation compared with dinoprostone. Overall, cervical osmotic dilators might be more preferred over dinoprostone in view of their analogous cervical ripening effects, comparable maternal-neonatal outcomes, and lack of drug-related adverse events.
KEY POINTS
· This is the first analysis of cervical osmotic dilators versus PGE2 for cervical ripening during labor.. · There was no difference between both arms regarding the rates of normal vaginal/cesarean deliveries.. · There was no difference between both arms regarding the rates of neonatal adverse events.. · Cervical osmotic dilators had significant lower risk of uterine hyperstimulation compared with PGE2.. · Cervical osmotic dilators may be superior to PGE2 in view of their similar efficacy and better safety..
Topics: Humans; Labor, Induced; Cervical Ripening; Pregnancy; Female; Dinoprostone; Oxytocics; Cesarean Section; Infant, Newborn; Randomized Controlled Trials as Topic; Cervix Uteri; Delivery, Obstetric
PubMed: 37336231
DOI: 10.1055/s-0043-1770161 -
Journal of Biochemical and Molecular... Sep 2023The role and mechanism of Gremlin-1 in osteoarthritis (OA) were expected to be probed in this study. Firstly, an in vitro OA model was constructed by stimulating human...
The role and mechanism of Gremlin-1 in osteoarthritis (OA) were expected to be probed in this study. Firstly, an in vitro OA model was constructed by stimulating human chondrocyte cell line CHON-001 with IL-1β. Next, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were utilized for assessing the effect of IL-1β with different concentrations (5, 10, and 20 ng/mL) on the activity and Gremlin-1 messenger RNA of CHON-001 cells, respectively. Besides, the influence of knocking down/over-expressing Gremlin-1 on the inflammatory factors (IL-6, TNF-α, IL-18 and PGE2), oxidative stress-related substances (malondialdehyde [MDA]; superoxide dismutase [SOD]; lactate dehydrogenase [LDH]), extracellular matrix (ECM) degradation-related proteins, and mitogen-activated protein kinase (MAPK) pathway proteins in IL-1β-stimulated CHON-001 cells were tested by enzyme-linked immunosorbent assay, related kits, qRT-PCR, and western blot, respectively. IL-1β inhibited CHON-001 cell proliferation and upregulated Gremlin-1 expression in a concentration-dependent manner. Overexpression of Gremlin-1 increased the IL-6, TNF-α, IL-18, PGE2, and MDA levels, enhanced the LDH activity, and decreased the SOD activity in IL-1β-induced CHON-001 cells; while the effect of Gremlin-1 knockdown on the above factors was in contrast with that of the overexpression. Furthermore, overexpression of Gremlin-1 upregulated protein expression of matrix metalloproteinase (MMP)-3, MMP-13, and ADAMTS4 while downregulated protein expression of collagen III, aggrecan, and SOX-9 in IL-1β-stimulated CHON-001 cells. Besides, overexpression of Gremlin-1 increased the p-p38/p38 value while decreased the p-JNK/JNK value in L-1β-stimulated CHON-001 cells; however, knockdown of Gremlin-1 reversed the above results. Gremlin-1 may promote IL-1β-stimulated CHON-001 cell inflammation and ECM degradation by activating the MAPK signaling pathway.
Topics: Humans; Chondrocytes; Interleukin-18; Mitogen-Activated Protein Kinases; Tumor Necrosis Factor-alpha; Dinoprostone; Interleukin-6; Cells, Cultured; Inflammation; Signal Transduction; Osteoarthritis; Extracellular Matrix; Interleukin-1beta; MicroRNAs
PubMed: 37352019
DOI: 10.1002/jbt.23404 -
Journal of Reproductive Immunology Dec 2023Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana,...
Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1β and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1β levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.
Topics: Humans; Female; Rats; Animals; NF-kappa B; Toll-Like Receptor 4; Pelvic Inflammatory Disease; Interleukin-6; Dinoprostone; Interleukin-2; Tumor Necrosis Factor-alpha; Inflammation; Superoxide Dismutase
PubMed: 37774536
DOI: 10.1016/j.jri.2023.104154 -
Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats.Zhen Ci Yan Jiu = Acupuncture Research Dec 2023To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of...
OBJECTIVES
To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM.
METHODS
Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated.
RESULTS
Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(<0.01, <0.05), while contents of PGE2 in the serum and uterine tissue were reduced(<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(<0.05, <0.01), whereas the writhing latency was considerably prolonged in the EA group(<0.01), with elevated contents of PGE2 in the serum and uterine tissue(<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group.
CONCLUSIONS
EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.
Topics: Humans; Rats; Female; Animals; Rats, Sprague-Dawley; Dysmenorrhea; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Dinoprost; Dinoprostone; Acupuncture Points; Signal Transduction; Electroacupuncture; TOR Serine-Threonine Kinases; Edema; Mammals
PubMed: 38146249
DOI: 10.13702/j.1000-0607.20230007 -
Birth (Berkeley, Calif.) Sep 2023Outpatient induction of labor (IOL) is an alternative choice offered to pregnant women requiring cervical ripening. Outpatient IOL can provide solutions in terms of... (Review)
Review
Outpatient versus inpatient cervical ripening with a slow-release dinoprostone vaginal insert in term pregnancies on maternal, neonatal, and birth outcomes: A systematic review.
BACKGROUNDS
Outpatient induction of labor (IOL) is an alternative choice offered to pregnant women requiring cervical ripening. Outpatient IOL can provide solutions in terms of women empowerment, but most importantly promotes as normal labor as possible, within the medical context of the IOL. The objectives of this systematic review were to assess safety and effectiveness of cervical ripening performed with a slow-release dinoprostone vaginal insert in term pregnancies in two settings: the outpatient (home) versus the inpatient (hospital).
METHODS
The electronic databases Cinahl, Embase, Medline and Maternity and Infant Care were searched to detect studies that met the inclusion criteria. Both reviewers collected the data and assessed the quality of the studies and assessed the pooled odds ratio using a 95% confidence interval and a random-effects model. Primary outcomes were linked to maternal and neonatal morbidity. Secondary outcomes were related to birth outcomes.
RESULTS
No statistical difference was seen between the outpatient and inpatient setting in terms of maternal complications, neonatal morbidity, cesarean section, and labor onset <24 h. Women in the outpatient setting were significantly less likely to experience uterine hyperstimulation, and they were also significantly more likely to require oxytocin to augment or induce their labor than the women in the inpatient setting. Women in the outpatient setting were more satisfied with the cervical ripening experience.
CONCLUSIONS
Cervical ripening with a slow-release dinoprostone vaginal insert in term pregnancies in the outpatient setting appears as safe as the inpatient setting in terms of maternal, neonatal, and birth outcomes.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Dinoprostone; Oxytocics; Cesarean Section; Cervical Ripening; Outpatients; Inpatients; Labor, Induced
PubMed: 36332128
DOI: 10.1111/birt.12687 -
Minerva Obstetrics and Gynecology Jan 2024Induction of labor in women with unfavorable cervix can be started with cervical ripening by dinoprostone vaginal insert. In cases of unsuccessful response, management...
BACKGROUND
Induction of labor in women with unfavorable cervix can be started with cervical ripening by dinoprostone vaginal insert. In cases of unsuccessful response, management is unclear: a possible option is a repeated induction with prostaglandins. The aim of this study was to assess the results of a second induction by either dinoprostone or misoprostol, comparing those treatments.
METHODS
A retrospective analysis was carried out on a cohort of 109 women with unsuccesful response to a first attempt of induction with dinoprostone vaginal insert, who required a second stimulation by either dinoprostone vaginal gel (56 patients) or oral misoprostol (53 patients). The outcomes assessed where the rates of active labor and vaginal delivery, and secondarily maternal and perinatal adverse events.
RESULTS
Overall 70.6% of patients reached active labor and 62.4% had a vaginal delivery; the efficacy of the double induction was similar for dinoprostone vaginal gel and oral misoprostol, with active labor in 69.6% and 71.7% (P=0.83), and vaginal delivery in 62.5% and 62.3% of patients (P=0.99) respectively. The incidence of adverse events was low, with no perinatal complications and similar rates of maternal complications, notably major post-partum hemorrhage in 1.8% and 3.8% of patients (P=0.61) for dinoprostone and misoprostol respectively.
CONCLUSIONS
Dinoprostone vaginal gel and oral misoprostol as a second cycle of induction appear to be both effective in achieving active labor and vaginal delivery after failure of dinoprostone vaginal insert, without a significant rate of adverse events.
PubMed: 38289253
DOI: 10.23736/S2724-606X.23.05414-3 -
Bioorganic Chemistry Aug 2023Type 2 diabetes mellitus (T2DM) is a rapidly growing epidemic that results in increased morbidity, mortality, and soaring medical costs. Prostaglandin E (PGE), a vital...
Type 2 diabetes mellitus (T2DM) is a rapidly growing epidemic that results in increased morbidity, mortality, and soaring medical costs. Prostaglandin E (PGE), a vital lipid mediator, has been reported to protect against hepatic steatosis, inflammation, endoplasmic reticulum (ER) stress, and insulin resistance, indicating its potential therapeutic role in T2DM. PGE can be degraded by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). SW033291, an inhibitor of 15-PGDH, has been reported to increase PGE levels, however, the effect of SW033291 in T2DM remains to be explored. This study aims to evaluate whether SW033291 protects against T2DM and explore its potential mechanisms. A T2DM mouse model was established through high-fat diet/streptozotocin injection, while palmitic acid-treated mouse primary hepatocytes were used as insulin-resistant cell models. SW033291 treatment reduced body weight, fat weight, fasting blood glucose, and improved impaired glucose tolerance and insulin resistance in T2DM mice. More importantly, SW033291 alleviated steatosis, inflammation, and ER stress in the liver of T2DM mice. Mechanistically, SW033291 decreased the expressions of SREBP-1c and ACC1, and increased the expression of PPARα in T2DM mice. Additionally, SW033291 inhibited NF-κB and eIF2α/CHOP signaling in T2DM mice. Further, we showed that the protective effects of SW033291 on the above-mentioned pathophysiological processes could be hindered by inhibition of the PGE receptor EP4. Overall, our study reveals a novel role of SW033291 in alleviating T2DM and suggests its potential as a new therapeutic strategy for T2DM.
Topics: Mice; Animals; Dinoprostone; Diabetes Mellitus, Type 2; Lipid Metabolism; Insulin Resistance; Liver; Inflammation; Fatty Liver
PubMed: 37285764
DOI: 10.1016/j.bioorg.2023.106646 -
Biomedicines Jul 2023(1) Background: Induction of labor is currently the most frequently performed procedure in modern obstetrics, referring to more than one in five women, and it is...
(1) Background: Induction of labor is currently the most frequently performed procedure in modern obstetrics, referring to more than one in five women, and it is postulated that the percentage of labor induction will increase. (2) Methods: In total, 2935 patients in uncomplicated full-term pregnancy fulfilled the study inclusion criteria and underwent induction of labor. Pregnant women were divided into three groups: IOL with Dinoprostone, Misoprostol vaginal suppositories, and Foley catheter. Outcomes, including cesarean section rates, time to delivery, and cesarean section indications, were analyzed. (3) Results: There was statistically significantly more cesarean sections within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups ( < 0.0001). The percentage of patients who had a cesarean section due to clinically diagnosed threatened fetal asphyxia was 63% in the Dinoprostone group, 81.3% in the Misoprostol group, and 55.3% in the Foley catheter group. There were statistically significantly more cesarean deliveries due to nonreassuring fetal heart rate patterns within 24 h in the Misoprostol group in comparison with the Dinoprostone and Foley catheter groups ( = 0.0031 and = 0.0363). (4) Conclusions: Misoprostol may cause a more turbulent and violent course of labor, with a higher rate of increased incidence of nonreassuring fetal heart rate patterns and cesarean deliveries. The use of a Dinoprostone vaginal insert or Foley catheter may provide longer labor, although still within 48 h, with a lower risk of cesarean section caused by nonreassuring fetal heart rate patterns.
PubMed: 37626622
DOI: 10.3390/biomedicines11082125