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Critical Reviews in Biochemistry and... Dec 2019Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is... (Review)
Review
Selenium (Se) is an essential trace element that functions in the form of the 21st amino acid, selenocysteine (Sec) in a defined set of proteins. Se deficiency is associated with pathological conditions in humans and animals, where incorporation of Sec into selenoproteins is reduced along with their expression and catalytic activity. Supplementation of Se-deficient population with Se has shown health benefits suggesting the importance of Se in physiology. An interesting paradigm to explain, in part, the health benefits of Se stems from the observations that selenoprotein-dependent modulation of inflammation and efficient resolution of inflammation relies on mechanisms involving a group of bioactive lipid mediators, prostanoids, which orchestrate a concerted action toward maintenance and restoration of homeostatic immune responses. Such an effect involves the interaction of various immune cells with these lipid mediators where cellular redox gatekeeper functions of selenoproteins further aid in not only dampening inflammation, but also initiating an effective and active resolution process. Here we have summarized the current literature on the multifaceted roles of Se/selenoproteins in the regulation of these bioactive lipid mediators and their immunomodulatory effects.
Topics: Animals; Humans; Inflammation; Lipid Metabolism; Prostaglandins; Randomized Controlled Trials as Topic; Selenium; Selenoproteins; Signal Transduction
PubMed: 31996052
DOI: 10.1080/10409238.2020.1717430 -
The Cochrane Database of Systematic... May 2020Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The aetiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularisation to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.This is an update of the review first published in 2016.
OBJECTIVES
To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 15 October 2019. The review authors searched LILACS, ISRCTN, Australian New Zealand Clinical Trials Registry, EU Clinical Trials Register, clincialtrials.gov and the OpenGrey Database to 5 January 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease.
DATA COLLECTION AND ANALYSIS
Two review authors, independently assessed the studies, extracted data and performed data analysis.
MAIN RESULTS
No new studies were identified for this update. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid. Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; 1 study; moderate-certainty evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; 1 study; moderate-certainty evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; 1 study; moderate-certainty evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; 2 studies; I² = 0%; very low-certainty evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; 1 study; low-certainty evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; 1 study; moderate-certainty evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; 1 study; moderate-certainty evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; 1 study; moderate-certainty evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; 1 study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; 1 study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low-certainty evidence). Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study. Overall, the certainty of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information (for example regarding baseline tobacco exposure).
AUTHORS' CONCLUSIONS
Moderate-certainty evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Very low and low-certainty evidence suggests there is no clear difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very low-certainty evidence suggests there is no clear difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. Further well designed RCTs assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.
Topics: Adult; Alprostadil; Amputation, Surgical; Aspirin; Epoprostenol; Folic Acid; Hematinics; Humans; Iloprost; Male; Middle Aged; Pain; Placebos; Platelet Aggregation Inhibitors; Prostaglandins; Randomized Controlled Trials as Topic; Thromboangiitis Obliterans; Ulcer
PubMed: 32364620
DOI: 10.1002/14651858.CD011033.pub4 -
Turkish Journal of Ophthalmology Feb 2023To report that the periorbital changes induced by prostaglandin analogue (PGA) eye drops are partially reversible after discontinuing treatment.
OBJECTIVES
To report that the periorbital changes induced by prostaglandin analogue (PGA) eye drops are partially reversible after discontinuing treatment.
MATERIALS AND METHODS
Nine patients with prostaglandin-associated periorbitopathy seen in a referral oculoplastic practice were included in this study, eight with unilateral glaucoma and one with bilateral open-angle glaucoma. All of them had been treated with topical PGA for at least one year, before the treatment was discontinued for cosmetic reasons.
RESULTS
In all cases, there were evident periocular differences between the treated eye and the fellow eye, consisting mainly of deepening of the upper eyelid sulcus and eyelid fat pad reduction. One year after discontinuing the PGA eye drops, improvement of these features was observed.
CONCLUSION
Clinicians and patients should be aware of the side effects of topical PGA therapy on periorbital tissues, and that these side effects can partially regress after discontinuation of the medication.
Topics: Humans; Glaucoma, Open-Angle; Eyelids; Glaucoma; Ophthalmic Solutions; Prostaglandins
PubMed: 36847619
DOI: 10.4274/tjo.galenos.2022.24365 -
International Journal of Molecular... Nov 2020Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the... (Review)
Review
Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D (PGD), prostaglandin-E, -E and E (PGE, PGE, PGE), prostaglandin F (PGF), prostacyclin (PGI) and thromboxane-A (TXA) on platelet activation and aggregation via their respective receptors.
Topics: Blood Platelets; Humans; Models, Biological; Platelet Aggregation; Prostaglandins; Receptors, Prostaglandin; Signal Transduction
PubMed: 33260972
DOI: 10.3390/ijms21239020 -
Communications Biology Aug 2021Prostaglandins are important lipids involved in mediating many physiological processes, such as allergic responses, inflammation, and pregnancy. However, technical...
Prostaglandins are important lipids involved in mediating many physiological processes, such as allergic responses, inflammation, and pregnancy. However, technical limitations of in-situ prostaglandin detection in tissue have led researchers to infer prostaglandin tissue distributions from localization of regulatory synthases, such as COX1 and COX2. Herein, we apply a novel mass spectrometry imaging method for direct in situ tissue localization of prostaglandins, and combine it with techniques for protein expression and RNA localization. We report that prostaglandin D, its precursors, and downstream synthases co-localize with the highest expression of COX1, and not COX2. Further, we study tissue with a conditional deletion of transformation-related protein 53 where pregnancy success is low and confirm that PG levels are altered, although localization is conserved. Our studies reveal that the abundance of COX and prostaglandin D synthases in cellular regions does not mirror the regional abundance of prostaglandins. Thus, we deduce that prostaglandins tissue localization and abundance may not be inferred by COX or prostaglandin synthases in uterine tissue, and must be resolved by an in situ prostaglandin imaging.
Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Embryo, Mammalian; Mass Spectrometry; Mice; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 34389796
DOI: 10.1038/s42003-021-02488-1 -
Life Science Alliance Sep 2022We investigated the relevance of the prostaglandin D2 pathway in Alzheimer's disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its...
We investigated the relevance of the prostaglandin D2 pathway in Alzheimer's disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer's disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer's disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer's disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer's disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer's disease.
Topics: Alzheimer Disease; Animals; Dinoprostone; Disease Models, Animal; Lipopolysaccharide Receptors; Male; Prostaglandin D2; Prostaglandins; Rats; Rats, Transgenic; Receptors, Immunologic; Receptors, Prostaglandin
PubMed: 36167438
DOI: 10.26508/lsa.202201555 -
Chest Apr 2020
Topics: Consensus; Epoprostenol; Familial Primary Pulmonary Hypertension; Humans; Prostaglandins I; Pulmonary Arterial Hypertension
PubMed: 32252927
DOI: 10.1016/j.chest.2019.11.017 -
Animal Reproduction Science May 2020Prostaglandins (PG) have primary functions in the reproductive tract, however, the mechanism of regulation of PG secretion in the endometrium is unclear. Estrogen as a...
Prostaglandins (PG) have primary functions in the reproductive tract, however, the mechanism of regulation of PG secretion in the endometrium is unclear. Estrogen as a predominant regulator of uterine functions during the mammalian estrous cycle and effects of estrogen on synthesis of PG and function in uterine tissues of cattle are not fully understood. In this study, there was evaluation of the concentration- and time-effects of 17β-estradiol on PG synthesis in endometrial explants of cattle, focusing on the secretion of prostaglandin E (PGE) and prostaglandin F (PGF) as well as relative abundance of mRNA transcript and protein for both the enzymes responsible for PGE and PGF synthesis, including prostaglandin-endoperoxide synthase 1 and 2 (PTGS1, PTGS2), PGE synthase (PGES), PGF synthase (PGFS), and carbonyl reductase (CBR1), and the receptors responsible for downstream PGE (PTGER2, PTGER4) and PGF (PTGFR) signaling. Results indicated that 17β-estradiol increased PGE and PGF production at concentrations ranging from 10 to 10 M. Furthermore, abundances of PTGS1, PTGS2, PGES, PGFS, PTGER2, PTGER4, and PTGFR mRNA transcripts and protein were greater immediately after 17β-estradiol treatment at almost all the concentrations, while these CBR1 abundances were less as a result of treatments with 17β-estradiol. These data support the hypothesis that estradiol modulates the synthesis and function of PG in the endometrium of cattle.
Topics: Animals; Cattle; Dinoprost; Dinoprostone; Endometrium; Estradiol; Female; Tissue Culture Techniques
PubMed: 32414468
DOI: 10.1016/j.anireprosci.2020.106466 -
Experimental & Molecular Medicine Jan 2021Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small... (Review)
Review
Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity. The cocrystallographic structure of Nurr1 bound to endogenous ligands such as prostaglandin E1/A1 and 5,6-dihydroxyindole contributed to clarifying the crucial roles of Nurr1 and opening new avenues for therapeutic interventions for neurodegenerative and/or inflammatory diseases related to Nurr1. This review introduces novel endogenous and synthetic Nurr1 agonists and discusses their potential effects in Nurr1-related diseases.
Topics: Animals; Anti-Inflammatory Agents; Humans; Indoles; Nuclear Receptor Subfamily 4, Group A, Member 2; Prostaglandins; Protein Binding
PubMed: 33479411
DOI: 10.1038/s12276-021-00555-5 -
Scientific Reports Mar 2023There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important... (Review)
Review
There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.
Topics: Animals; Female; Humans; Male; Cyclooxygenase 2; Pain; Prostaglandins; Sensory Receptor Cells; Sex Characteristics
PubMed: 36949072
DOI: 10.1038/s41598-023-31603-x