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Veterinary Ophthalmology Mar 2021Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to... (Review)
Review
Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti-glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti-glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose , Ocular Therapeutix's OTX-TIC travoprost implant, and Santen's polycaprolactone implant with PGE2-derivative DE-117. Other prostaglandin-based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX-TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856-isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT-501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals.
Topics: Animals; Cell- and Tissue-Based Therapy; Delayed-Action Preparations; Drug Implants; Forecasting; Genetic Therapy; Glaucoma; Humans; Intraocular Pressure; Nanotechnology; Prostaglandins, Synthetic
PubMed: 33164328
DOI: 10.1111/vop.12843 -
Marine Drugs Jul 2019Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of... (Review)
Review
Prostaglandins (PGs) are lipid mediators belonging to the eicosanoid family. PGs were first discovered in mammals where they are key players in a great variety of physiological and pathological processes, for instance muscle and blood vessel tone regulation, inflammation, signaling, hemostasis, reproduction, and sleep-wake regulation. These molecules have successively been discovered in lower organisms, including marine invertebrates in which they play similar roles to those in mammals, being involved in the control of oogenesis and spermatogenesis, ion transport, and defense. Prostaglandins have also been found in some marine macroalgae of the genera and and very recently the PGs pathway has been identified for the first time in some species of marine microalgae. In this review we report on the occurrence of prostaglandins in the marine environment and discuss the anti-inflammatory role of these molecules.
Topics: Animals; Anthozoa; Anti-Inflammatory Agents; Aquatic Organisms; Gracilaria; Laminaria; Microalgae; Prostaglandins; Thromboxanes
PubMed: 31340503
DOI: 10.3390/md17070428 -
Cells Jun 2021The prostaglandins constitute a family of lipids of 20 carbon atoms that derive from polyunsaturated fatty acids such as arachidonic acid. Traditionally, prostaglandins... (Review)
Review
The prostaglandins constitute a family of lipids of 20 carbon atoms that derive from polyunsaturated fatty acids such as arachidonic acid. Traditionally, prostaglandins have been linked to inflammation, female reproductive cycle, vasodilation, or bronchodilator/bronchoconstriction. Recent studies have highlighted the involvement of these lipids in cancer. In this review, existing information on the prostaglandins associated with different types of cancer and the advances related to the potential use of them in neoplasm therapies have been analyzed. We can conclude that the effect of prostaglandins depends on multiple factors, such as the target tissue, their plasma concentration, and the prostaglandin subtype, among others. Prostaglandin D2 (PGD) seems to hinder tumor progression, while prostaglandin E2 (PGE) and prostaglandin F2 alpha (PGF) seem to provide greater tumor progression and aggressiveness. However, more studies are needed to determine the role of prostaglandin I2 (PGI) and prostaglandin J2 (PGJ) in cancer due to the conflicting data obtained. On the other hand, the use of different NSAIDs (non-steroidal anti-inflammatory drugs), especially those selective of COX-2 (cyclooxygenase 2), could have a crucial role in the fight against different neoplasms, either as prophylaxis or as an adjuvant treatment. In addition, multiple targets, related to the action of prostaglandins on the intracellular signaling pathways that are involved in cancer, have been discovered. Thus, in depth research about the prostaglandins involved in different cancer and the different targets modulated by them, as well as their role in the tumor microenvironment and the immune response, is necessary to obtain better therapeutic tools to fight cancer.
Topics: Chemotherapy, Adjuvant; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Neoplasm Proteins; Neoplasms; Prostaglandins; Signal Transduction
PubMed: 34199169
DOI: 10.3390/cells10061487 -
Cancer Research Mar 2022Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development... (Review)
Review
Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development and progression. Understanding the molecular mechanisms of PG actions has potential clinical relevance for cancer prevention and therapy. This review focuses on the current status of PG signaling pathways in modulating cancer progression and aims to provide insights into the mechanistic actions of PGs and their receptors in influencing tumor progression. We also examine several small molecules identified as having anticancer activity that target prostaglandin receptors. The literature suggests that targeting PG pathways could provide opportunities for cancer prevention and therapy.
Topics: Humans; Neoplasms; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Receptors, Prostaglandin; Signal Transduction
PubMed: 34949672
DOI: 10.1158/0008-5472.CAN-21-2297 -
Biological & Pharmaceutical Bulletin 2022Prostanoids are a group of typical lipid mediators that are biosynthesized from arachidonic acid by the actions of cyclooxygenases and their subsequent terminal... (Review)
Review
Prostanoids are a group of typical lipid mediators that are biosynthesized from arachidonic acid by the actions of cyclooxygenases and their subsequent terminal synthases. Prostanoids exert a wide variety of actions through their specific membrane receptors on target cells. In addition to their classical actions, including fever, pain, and inflammation, prostanoids have been shown to play pivotal roles in various biological processes, such as female reproduction and the maintenance of vascular and gut homeostasis. Moreover, recent research using mice deficient in each of the prostanoid receptors, or using agonists/antagonists specific for each receptor clarified novel actions of prostanoids that had long been unknown, and the mechanisms therein. In this review, we introduce recent advances in the fields of metabolic control by prostanoid receptors such as in adipocyte differentiation, lipolysis, and adipocyte browning in adipose tissues, and discuss the potential of prostanoid receptors as a treatment target for metabolic disorders.
Topics: Adipocytes; Animals; Female; Inflammation; Lipolysis; Mice; Prostaglandins; Receptors, Prostaglandin
PubMed: 35908909
DOI: 10.1248/bpb.b22-00270 -
Pharmacological Research Nov 2019Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links... (Review)
Review
Prostaglandins (PG) are pleiotropic bioactive lipids involved in the control of many physiological processes, including key roles in regulating inflammation. This links PG to the modulation of the quality and magnitude of immune responses. T cells, as a core part of the immune system, respond readily to inflammatory cues from their environment, and express a diverse array of PG receptors that contribute to their function and phenotype. Here we put in context our knowledge about how PG affect T cell biology, and review advances that bring light into how specific T cell functions that have been newly discovered are modulated through PG. We will also comment on drugs that target PG metabolism and sensing, their effect on T cell function during disease, and we will finally discuss how we can design new approaches that modulate PG in order to maximize desired therapeutic T cell effects.
Topics: Animals; Autoimmune Diseases; Cell Differentiation; Drug Discovery; Humans; Immunity; Inflammation; Prostaglandins; T-Lymphocytes
PubMed: 31553935
DOI: 10.1016/j.phrs.2019.104456 -
Prostaglandins, Leukotrienes, and... Apr 2021Cyclooxygenase (COX)-derived prostaglandin E (PGE) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from...
OBJECTIVE
Cyclooxygenase (COX)-derived prostaglandin E (PGE) is an important lipid mediator in colorectal carcinoma (CRC) pathogenesis. Other lipid mediators derived from lipoxygenases (LOX) have also been implicated in neoplastic processes in the colon. In this study we aimed to characterize lipid mediators, so called oxylipins, in human colon adenomatous polyps.
DESIGN
We quantified oxylipins in healthy colon tissue and colorectal adenoma tissue procured during routine colonoscopy examinations. Lipid metabolite profiles were analyzed by liquid chromatography-tandem mass spectrometry.
RESULTS
Adenoma tissue showed a distinct prostaglandin profile as compared to normal colon mucosa. Interestingly, PGE was not higher in adenoma tissue as compared to normal mucosa. In contrast, we found significantly lower levels of prostaglandin D, prostaglandin J, and prostaglandin D in adenoma tissue. Furthermore, levels of 5-LOX and 12-LOX pathway products were clearly increased in adenoma biopsy samples. We also investigated the effect of aspirin treatment on prostaglandin profiles in adenoma tissue in a subset of patients and found a trend towards decreased prostaglandin levels in response to aspirin.
CONCLUSION
The human data presented here show specific changes of oxylipin profiles in colon adenoma tissue with decreased prostaglandin D levels as well as increased 5- and 12-LOX metabolites.
Topics: Adenoma; Aged; Arachidonate 5-Lipoxygenase; Case-Control Studies; Colon; Colonic Neoplasms; Cyclooxygenase 2; Female; Humans; Male; Oxylipins; Pilot Projects; Prostaglandin D2; Prostaglandins D
PubMed: 33812217
DOI: 10.1016/j.plefa.2021.102269 -
Nature Communications May 2023Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation...
Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.78 Å, and 3.14 Å. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and G coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs.
Topics: Humans; Cryoelectron Microscopy; Ligands; GTP-Binding Proteins; Arachidonic Acid; Prostaglandins
PubMed: 37160891
DOI: 10.1038/s41467-023-38411-x -
Dermatologic Therapy Jan 2021Due to immune-mediated nature, medicines with immunomodulatory and anti-inflammatory effects can used to treat many dermatologic diseases. Phosphodiesterase and... (Review)
Review
Due to immune-mediated nature, medicines with immunomodulatory and anti-inflammatory effects can used to treat many dermatologic diseases. Phosphodiesterase and prostaglandins are involved in many inflammatory pathways that cause cutaneous disorders. Phosphodiesterase inhibitors (PDEIs) and prostaglandin analogues are currently employed to treat several dermatologic disorders. Given the few comprehensive reviews in this context, focusing on the dermatologic applications and efficacy of these medicines appears valuable. The present comprehensive review was, therefore, performed on the applications of PDEIs and prostaglandin analogues in different cutaneous disorders. All the relevant articles were selected to perform this review by searching databases such as Medline, Google Scholar, Scopus, and Web of Science. Oral PDEIs, especially apremilast, is an effective medicine in psoriasis and a number of other cutaneous disorders such as vitiligo. Topical PDEIs, including crisaborole ointment 2%, is a safe and effective treatment in atopic dermatitis. Prostaglandin analogues, especially their topical forms such as latanoprost and bimatoprost, have different applications in cutaneous disorders, including pigmentary disorders, especially vitiligo and hair repigmentation; for instance, bimatoprost is used for eyelash repigmentation. Prostaglandin analogues are also used in alopecia, including androgenetic alopecia and alopecia areata. Oral (apremilast) and topical (crisaborole) PDEIs and topical prostaglandin analogues, including latanoprost and bimatoprost, were found safe and effective in different skin diseases. In terms of efficiency and safety, these medicines compete with other medications of similar use even with higher efficacy and fewer side effects that necessitate further studies.
Topics: Bimatoprost; Dermatology; Humans; Latanoprost; Phosphodiesterase Inhibitors; Prostaglandins, Synthetic
PubMed: 33314552
DOI: 10.1111/dth.14669 -
European Journal of Clinical... Nov 2020COVID-19 is a highly contagious viral disease. In this study, we tried to define and discuss all the findings on the potential association between arachidonic acid (AA)... (Review)
Review
BACKGROUND AND OBJECTIVE
COVID-19 is a highly contagious viral disease. In this study, we tried to define and discuss all the findings on the potential association between arachidonic acid (AA) pathway and COVID-19 pathophysiology.
METHODS
A literature search across PubMed, Scopus, Embase, and Cochrane database was conducted. A total of 25 studies were identified.
RESULTS
The data elucidated that COX-2 and prostaglandins (PGs), particularly PGE, have pro-inflammatory action in COVID-19 pathophysiology. Arachidonic acid can act as endogenous antiviral compound. A deficiency in AA can make humans more susceptible to COVID-19. Targeting these pro-inflammatory mediators may help in decreasing the mortality and morbidity rate in COVID-19 patients.
CONCLUSIONS
PGE levels and other PGs levels should be measured in patients with COVID-19. Lowering the PGE levels through inhibition of human microsomal prostaglandin E synthase-1 (mPGES-1) can enhance the host immune response against COVID-19. In addition, the hybrid compounds, such as COX-2 inhibitors/TP antagonists, can be an innovative treatment to control the overall balance between AA mediators in patients with COVID-19.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Betacoronavirus; COVID-19; Coronavirus Infections; Cyclooxygenase 2; Humans; Inflammation; Pandemics; Phospholipases A2; Pneumonia, Viral; Prostaglandin-E Synthases; Prostaglandins; Protein-Lysine 6-Oxidase; SARS-CoV-2; Sex Factors
PubMed: 32583353
DOI: 10.1007/s00228-020-02941-w