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International Journal of Cosmetic... Jun 2022Skin ageing is a multifactorial process involving formation of reactive oxygen species, consecutive inflammation with reduced epidermal and dermal cell viability and...
OBJECTIVE
Skin ageing is a multifactorial process involving formation of reactive oxygen species, consecutive inflammation with reduced epidermal and dermal cell viability and resulting damage to the extracellular matrix. Effective dermocosmetic treatment modalities should ideally address these hallmarks in a holistic approach. Here, we determined the corresponding activity profile of bakuchiol, a plant-derived meroterpene, in an array of in vitro, ex vivo and in vivo studies and compared it to retinol, currently considered as gold standard in topical antiageing cosmetics.
METHODS
The antioxidative capacity and power of bakuchiol and retinol were analysed by measuring 2,2'-diphenyl-1-picrylhydrazyl (DPPH) reduction via its absorption decay and electron spin resonance spectroscopy, respectively. Effects on prostaglandin E2 (PGE2), macrophage migration inhibitory factor (MIF), fibroblast growth factor 7 (FGF7), collagen type I and VII (COL1A1, COL7A1), fibronectin (FN) levels as well as the metabolization of water-soluble tetrazolium 1 (WST-1) were determined in human dermal fibroblasts. Epidermal regeneration was assessed utilizing an in vitro wound healing model. FN protein levels were analysed ex vivo after treatment with a formulation containing bakuchiol, retinol or vehicle using suction blister fluid. Skin condition improvement was determined in vivo in a split-face comparison study after application of bakuchiol or vehicle.
RESULTS
In contrast to retinol, bakuchiol demonstrated high antioxidative efficacy. Levels of PGE2 and MIF were significantly decreased by both bakuchiol and retinol. Bakuchiol but not retinol significantly increased FGF7 protein levels. WST-1 metabolization levels were significantly augmented by bakuchiol and retinol. Bakuchiol and retinol application led to a significant augmentation of COL1A1, COL7A1 and FN protein levels. Wounds supplemented with bakuchiol but not retinol displayed a significant increase in epidermis regeneration. Clinically, areas treated with a bakuchiol-containing formulation showed a statistically significant increase in FN protein values after a 4-week application compared to untreated areas and areas treated with vehicle.
CONCLUSION
These data provide evidence for the multidirectional efficacy of bakuchiol against cellular hallmarks of skin ageing. Its activity profile shares some common features with retinol but demonstrates several hitherto unknown biopositive effects in our studies, namely stimulation of the critical extracellular matrix component FN, and accelerated epidermal regeneration and wound healing.
Topics: Collagen; Collagen Type VII; Dinoprostone; Humans; Phenols; Skin; Skin Aging; Vitamin A
PubMed: 35514037
DOI: 10.1111/ics.12784 -
Journal of Extracellular Vesicles Jun 2023Although inflammation is a vital defence response to infection, if left uncontrolled, it can lead to pathology. Macrophages are critical players both in driving the...
Although inflammation is a vital defence response to infection, if left uncontrolled, it can lead to pathology. Macrophages are critical players both in driving the inflammatory response and in the subsequent events required for restoring tissue homeostasis. Extracellular vesicles (EVs) are membrane-enclosed structures released by cells that mediate intercellular communication and are present in all biological fluids, including blood. Herein, we show that extracellular vesicles from plasma (pEVs) play a relevant role in the control of inflammation by counteracting PAMP-induced macrophage activation. Indeed, pEV-treatment of macrophages simultaneously with or prior to PAMP exposure reduced the secretion of pro-inflammatory IL-6 and TNF-α and increased IL-10 response. This anti-inflammatory activity was associated with the promotion of tissue-repair functions in macrophages, characterized by augmented efferocytosis and pro-angiogenic capacity, and increased expression of VEGFa, CD300e, RGS2 and CD93, genes involved in cell growth and tissue remodelling. We also show that simultaneous stimulation of macrophages with a PAMP and pEVs promoted COX2 expression and CREB phosphorylation as well as the accumulation of higher concentrations of PGE2 in cell culture supernatants. Remarkably, the anti-inflammatory activity of pEVs was abolished if cells were treated with a pharmacological inhibitor of COX2, indicating that pEV-mediated induction of COX2 is critical for the pEV-mediated inhibition of inflammation. Finally, we show that pEVs added to monocytes prior to their M-CSF-induced differentiation to macrophages increased efferocytosis and diminished pro-inflammatory cytokine responses to PAMP stimulation. In conclusion, our results suggest that pEVs are endogenous homeostatic modulators of macrophages, activating the PGE2/CREB pathway, decreasing the production of inflammatory cytokines and promoting tissue repair functions.
Topics: Humans; Extracellular Vesicles; Dinoprostone; Cyclooxygenase 2; Macrophages; Cytokines; Inflammation
PubMed: 37272889
DOI: 10.1002/jev2.12331 -
The Journal of Clinical Investigation Jul 2020The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E2 (PGE2) secreted by...
The sensory nerve was recently identified as being involved in regulation of bone mass accrual. We previously discovered that prostaglandin E2 (PGE2) secreted by osteoblasts could activate sensory nerve EP4 receptor to promote bone formation by inhibiting sympathetic activity. However, the fundamental units of bone formation are active osteoblasts, which originate from mesenchymal stromal/stem cells (MSCs). Here, we found that after sensory denervation, knockout of the EP4 receptor in sensory nerves, or knockout of COX-2 in osteoblasts, could significantly promote adipogenesis and inhibit osteogenesis in adult mice. Furthermore, injection of SW033291 (a small molecule that locally increases the PGE2 level) or propranolol (a beta blocker) significantly promoted osteogenesis and inhibited adipogenesis. This effect of SW033291, but not propranolol, was abolished in conditional EP4-KO mice under normal conditions or in the bone repair process. We conclude that the PGE2/EP4 sensory nerve axis could regulate MSC differentiation in bone marrow of adult mice.
Topics: Adipogenesis; Animals; Cyclooxygenase 2; Dinoprostone; Gene Knockout Techniques; Mesenchymal Stem Cells; Mice; Mice, Knockout; Osteoblasts; Osteogenesis; Receptors, Prostaglandin E, EP4 Subtype; Sensory Receptor Cells
PubMed: 32191640
DOI: 10.1172/JCI131554 -
Archives of Gynecology and Obstetrics Jun 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer.... (Review)
Review
PURPOSE
Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer. However, concerning the adverse effects of NSAIDs and COXibs, it is still urgent and necessary to explore novel and specific anti-inflammation targets for potential chemoprevention. The signaling of cyclooxygenase 2-prostaglandin E-prostaglandin E receptors (COX-2-PGE-EPs) is the central inflammatory pathway involved in the gynecological carcinogenesis.
METHODS
Literature searches were performed to the function of COX-2-PGE-EPs in gynecological malignancies.
RESULTS
This review provides an overview of the current knowledge of COX-2-PGE-EPs signaling in endometrial cancer, ovarian cancer and cervical cancer. Many studies demonstrated the upregulated expression of the whole signaling pathway in gynecological malignancies and some focused on the function of COX-2 and cAMP-linked EP2/EP4 and EP3 signaling pathway in gynecological cancer. By contrast, roles of EP1 and the exact pathological mechanisms have not been completely clarified. The studies concerning EP receptors in gynecological cancers highlight the potential advantage of combining COX enzyme inhibitors with EP receptor antagonists as therapeutic agents in gynecological cancers.
CONCLUSION
EPs represent promising anti-inflammation biomarkers for gynecological cancer and may be novel treatment targets in the near future.
Topics: Cyclooxygenase 2; Dinoprostone; Female; Genital Neoplasms, Female; Humans
PubMed: 32363546
DOI: 10.1007/s00404-020-05559-6 -
Advanced Science (Weinheim,... Dec 2023Microgravity is the primary factor that affects human physiology in spaceflight, particularly bone loss and disturbances of the central nervous system. However, little...
Microgravity is the primary factor that affects human physiology in spaceflight, particularly bone loss and disturbances of the central nervous system. However, little is known about the cellular and molecular mechanisms of these effects. Here, it is reported that in mice hindlimb unloading stimulates expression of neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the hypothalamus, resulting in bone loss and altered fat metabolism. Enhanced expression of TH and NPY in the hypothalamus occurs downstream of a reduced prostaglandin E2 (PGE2)-mediated ascending interoceptive signaling of the skeletal interoception. Sympathetic antagonist propranolol or deletion of Adrb2 in osteocytes rescue bone loss in the unloading model. Moreover, depletion of TH sympathetic nerves or inhibition of norepinephrine release ameliorated bone resorption. Stereotactic inhibition of NPY expression in the hypothalamic neurons reduces the food intake with altered energy expenditure with a limited effect on bone, indicating hypothalamic neuroendocrine factor NPY in the facilitation of bone formation by sympathetic TH activity. These findings suggest that reduced PGE2-mediated interoceptive signaling in response to microgravity or unloading has impacts on the skeletal and central nervous systems that are reciprocally regulated.
Topics: Humans; Mice; Animals; Dinoprostone; Interoception; Neuropeptide Y; Hypothalamus; Neurons
PubMed: 37880864
DOI: 10.1002/advs.202305042 -
European Journal of Obstetrics,... Jul 2023To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in...
OBJECTIVES
To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in twin pregnancies.
STUDY DESIGN
Retrospective cohort study of twin pregnancies > 34 + 0 weeks gestation that underwent induction of labour (IOL) with DG, MVI or DVI between December 2016 and November 2019 in a Tertiary NHS hospital, North West England, UK. Delivery characteristics, maternal complications and neonatal outcomes were compared between the three groups.
RESULTS
A total of 87 twin pregnancies were included for analysis. 27 women received DG, 34 received MVI and 26 DVI. The MVI cohort had a higher proportion of nulliparous women (55.9%) compared to the DG and DVI cohorts, 29.6% and 38.5% respectively. No other differences amongst demographic characteristics were considered clinically significant. DG demonstrated a significantly quicker time to delivery (minutes) compared to DVI (1021 ± 556 versus 1649 ± 852; P = 0.0026). Significantly fewer women required terbutaline for hyperstimulation/tachysystole in the DG group compared to MVI (0% vs 32%; RR 0.05; 95% CI 0.003-0.88). Both DG and MVI groups required significantly less oxytocin following artificial rupture of membranes compared to DVI (33% vs 65%; RR 0.51; 95% CI 0.28-0.93) and (29% vs 65%; RR 0.45; 95% CI 0.25-0.81). There were no significant differences in mode of delivery, maternal complications and neonatal outcomes.
CONCLUSION
Our data suggests that for women with a twin pregnancy considering a planned labour that induction with DG, MVI and DVI appear to be equally safe and effective IOL methods. These results should be interpreted with caution due to the study being underpowered to detect significant adverse outcomes. In order to determine the optimal method of IOL in twins, direct randomised comparison is needed.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Administration, Intravaginal; Dinoprostone; Labor, Induced; Misoprostol; Oxytocics; Pregnancy, Twin; Retrospective Studies
PubMed: 37167810
DOI: 10.1016/j.ejogrb.2023.04.024 -
Archives of Gynecology and Obstetrics Jan 2019To assess the efficacy and safety of a double-balloon catheter versus dinoprostone insert for labour induction. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of a double-balloon catheter versus dinoprostone insert for labour induction.
STUDY DESIGN
PubMed, MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Central Register of Clinical Trials databases were searched from 1985 to April 2018. Randomized controlled trials that compared a double-balloon catheter and dinoprostone insert for cervical ripening were identified. Eligible study populations consisted of women with singleton pregnancies that had any indication for labour induction and were randomly assigned to undergo induction with a double-balloon catheter or dinoprostone insert. The main outcomes were incidence of vaginal delivery within 24 h and caesarean section, and neonatal outcomes.
RESULTS
Five randomized trials (603 women; 305 with a double-balloon catheter and 298 with a dinoprostone insert) were eligible for inclusion. No differences were observed between the two groups in terms of vaginal delivery within 24 h [relative risk (RR) 1.21, 95% confidence interval (CI) 0.93-1.59] and incidence of caesarean section (RR 0.99, 95% CI 0.77-1.27). Compared with the double-balloon catheter, the dinoprostone insert was associated with a reduced need for oxytocin administration in the process of labour induction (RR 1.95, 95% CI 1.45-2.62). However, there was a higher incidence of excessive uterine activity (RR 0.17, 95% CI 0.06-0.54) and neonatal umbilical cord arterial blood pH < 7.1 (RR 0.36, 95% CI 0.15-0.84) in the dinoprostone insert group.
CONCLUSION
This review showed that the efficacy of labour induction using both the double-balloon catheter and dinoprostone insert was similar. However, the double-balloon catheter seemed to be a safer method.
Topics: Adult; Catheters; Cervical Ripening; Cesarean Section; Delivery, Obstetric; Dinoprostone; Female; Humans; Labor, Induced; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome; Uterus
PubMed: 30315411
DOI: 10.1007/s00404-018-4929-8 -
Journal of Medicinal Chemistry Jul 2023Cyclooxygenase-1 and -2 (COX1 and COX2) derived endogenous ligand prostaglandin-E (PGE) triggers several physiological and pathological conditions. It mediates signaling... (Review)
Review
Cyclooxygenase-1 and -2 (COX1 and COX2) derived endogenous ligand prostaglandin-E (PGE) triggers several physiological and pathological conditions. It mediates signaling through four G-protein coupled receptors, EP1, EP2, EP3, and EP4. Among these, EP2 is expressed throughout the body including the brain and uterus. The functional role of EP2 has been extensively studied using EP2 gene knockout mice, cellular models, and selective small molecule agonists and antagonists for this receptor. The efficacy data from in vitro and in vivo animal models indicate that EP2 receptor is a major proinflammatory mediator with deleterious functions in a variety of diseases suggesting a path forward for EP2 inhibitors as the next generation of selective anti-inflammatory and antiproliferative agents. Interestingly in certain diseases, EP2 action is beneficial; therefore, EP2 agonists seem to be clinically useful. Here, we highlight the strengths, weaknesses, opportunities, and potential threats (SWOT analysis) for targeting EP2 receptor for therapeutic development for a variety of unmet clinical needs.
Topics: Animals; Mice; Receptors, Prostaglandin E; Dinoprostone; Cyclooxygenase 2; Drug Discovery; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 37458373
DOI: 10.1021/acs.jmedchem.3c00655 -
Pharmacology & Therapeutics May 2018The body is exposed to foreign pathogens every day, but remarkably, most pathogens are effectively cleared by the innate immune system without the need to invoke the... (Review)
Review
The body is exposed to foreign pathogens every day, but remarkably, most pathogens are effectively cleared by the innate immune system without the need to invoke the adaptive immune response. Key cellular components of the innate immune system include macrophages and neutrophils and the recruitment and function of these cells are tightly regulated by chemokines and cytokines in the tissue space. Innate immune responses are also known to regulate development of adaptive immune responses often via the secretion of various cytokines. In addition to these protein regulators, numerous lipid mediators can also influence innate and adaptive immune functions. In this review, we cover one particular lipid regulator, prostaglandin E (PGE) and describe its synthesis and signaling and what is known about the ability of this lipid to regulate immunity and host defense against viral, fungal and bacterial pathogens.
Topics: Adaptive Immunity; Animals; Autophagy; Dinoprostone; Extracellular Traps; Humans; Immunity, Innate; Infections; Interleukin-1beta; Toll-Like Receptors
PubMed: 29274705
DOI: 10.1016/j.pharmthera.2017.12.008 -
Expert Opinion on Pharmacotherapy 2015Induction of labor remains one of the most commonly performed procedures in the US and in other developed countries around the world. Various agents for cervical... (Review)
Review
INTRODUCTION
Induction of labor remains one of the most commonly performed procedures in the US and in other developed countries around the world. Various agents for cervical ripening are used prior to induction; the most commonly used are prostaglandins and oxytocin. The ideal agent is one that decreases time to vaginal delivery without compromising maternal and/or fetal safety.
AREAS COVERED
This article reviews the current pharmacologic methods available for induction of labor. Although these agents have been extensively studied and their safety and efficacy profile are well accepted, there is still ongoing research to determine the safest and most effective method. The article discusses the impact of pharmacogenomics as it relates to the most common induction agents. The dosing, route of administration, and side effects of these agents are reviewed.
EXPERT OPINION
Prostaglandins and oxytocin have been proven to be safe and effective methods of induction. However, the optimal medication for induction is yet to be determined. Although there are currently no pharmacogenomic findings that affect dosing of either prostaglandins or oxytocin, this is a growing area of research. In the near future, it may become clear that there is no 'one regimen for all' when selecting an induction or cervical ripening agent, or any other pharmaceutical altogether.
Topics: Cervical Ripening; Dinoprostone; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy
PubMed: 26149629
DOI: 10.1517/14656566.2015.1060960